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Sample records for myocardial alterations due

  1. Death Due to Myocardial Bridging.

    PubMed

    Ural, M Numan; Eren, Filiz; Inanir, Nursel Türkmen; Eren, Bülent; Vojtisek, Tomas; Gürses, Murat Serdar

    2015-06-01

    Myocardial bridging is a congenital coronary pathology described as a segment of coronary artery which courses through the myocardial wall beneath the muscle bridge. Although the myocardial bridging prognosis is benign, have been also reported sudden death in medical literature. ¬A 30-year-old married woman was found dead at her home. After local prosecutors' investigation the death was declared as suspicious and forensic autopsy was obliged. The left anterior descending coronary artery was detected embedded deeply in the myocardium 2 cm from its coronary ostial origin. There were no other pathology to explain death. We analyzed sudden death case occurred because of myocardial bridging and the pathophysiological mechanisms in the light of medico-legal literature.

  2. Type 2 myocardial infarction due to supply-demand mismatch.

    PubMed

    Mihatov, Nino; Januzzi, James L; Gaggin, Hanna K

    2017-08-01

    The best-accepted definition of myocardial infarction (MI) is provided by statements from the Universal Definition of MI Global Task force. This article, now in its third iteration, defines MI as myocardial cell death due to prolonged myocardial ischemia. It further delineates an increasingly incident subclassification of MI known as type 2 MI (T2MI). T2MI identifies instances of myocardial necrosis in which an imbalance between myocardial oxygen supply and/or demand occurs for reasons other than atherosclerotic plaque disruption. While associated with considerable risk (comparable to that of type 1 MI, which has well-defined management strategies), the spectrum of potential etiologies for T2MI makes development of precise diagnostic criteria and therapeutic implications of the diagnosis challenging. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Cardiovascular collapse after myocardial infarction due to centipede bite.

    PubMed

    Üreyen, Çağin Mustafa; Arslan, Şakir; Baş, Cem Yunus

    2015-07-01

    Centipede bites have been reported to cause localized and/or systemic symptoms including local pain, erythema and edema, nausea and vomiting, palpitations, headache, lymphadenopathy, and rhabdomyolysis. However, acute myocardial infarction due to centipede envenomation is reported in only three cases in English medical literature.We present a case of 31-year-old male bitten by a golden colored centipede leading to myocardial infarction and cardiopulmonary arrest which is seen very rarely. The patient was admitted to emergency department with a swollen and painful right foot. However, typical chest pain became the major complaint and cardiopulmonary arrest developed while electrocardiography was being obtained. The patient was resuscitated successfully for 5 min and acute infero-posterolateral myocardial infarction was detected on electrocardiography.

  4. Myocardial Cx43 expression in the cases of sudden death due to dilated cardiomyopathy.

    PubMed

    Chen, Xinshan; Zhang, Yigu

    2006-10-16

    Probing into myocardial connexin (Cx) 43 expression in the cases of sudden death due to dilated cardiomyopathy (DCM) and relationship between Cx43 expression and sudden death. Myocardial Cx43 was detected with immunohistochemical staining in the cases of 11 sudden death caused by DCM and 14 cases of control group who died of violent reasons and other diseases, which were autopsied in our department from 1997 to 2003. Of 11 cases of DCM, there were 10 men and 1 woman with ranging in age from 7 to 49 years old (x (37.8) years old for 9 adult cases). Of 14 cases in the control group, there were 10 men and 4 women with ranging in age from 11 to 53 years old (x (29.9) years old for 11 adult cases). Myocardial Cx43 expression was obviously decreased in DCM group. Positive dyeing spots were different in size, distribution, color and disparity, some of them were distributed in the form of particle. Obvious change had not been observed in the cases of control group or with only slight changes in coloring degree and expressive area. The quantitative data showed that there was significant difference between two groups (p=0.0075) about Cx43 expressive area, but there was no difference between the left and right ventricles (p>0.05) in each group itself. And there was not difference between the two groups about average optical density of expression. Myocardial Cx43 expression is obviously reduced in the patients with DCM who die suddenly. The alteration of quantity and distribution of myocardial Cx43 expression is probably related to sudden death of the patients with DCM.

  5. Acrolein inhalation alters myocardial synchrony and performance at and below exposure concentrations that cause ventilatory responses

    EPA Science Inventory

    Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we ...

  6. Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve

    PubMed Central

    Dal-Bianco, Jacob P.; Aikawa, Elena; Bischoff, Joyce; Guerrero, J. Luis; Hjortnaes, Jesper; Beaudoin, Jonathan; Szymanski, Catherine; Bartko, Philipp E.; Seybolt, Margo M.; Handschumacher, Mark D.; Sullivan, Suzanne; Garcia, Michael L.; Mauskapf, Adam; Titus, James S.; Wylie-Sears, Jill; Irvin, Whitney S.; Chaput, Miguel; Messas, Emmanuel; Hagège, Albert A.; Carpentier, Alain; Levine, Robert A.

    2016-01-01

    BACKGROUND In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that experimental tethering alone increases mitral valve area in association with endothelial-to-mesenchymal transition. OBJECTIVES This study explored the clinically relevant situation of tethering and MI, testing the hypothesis that ischemic milieu modifies MV adaptation. METHODS Twenty-three adult sheep were examined. Under cardiopulmonary bypass, the PM tips in 6 sheep were retracted apically to replicate tethering, short of producing MR (tethered-alone). PM retraction was combined with apical MI created by coronary ligation in another 6 sheep (tethered + MI), and left ventricular (LV) remodeling was limited by external constraint in 5 additional sheep (LV constraint). Six sham-operated sheep were controls. Diastolic MV surface area was quantified by 3-dimensional echocardiography at baseline and after 58 ± 5 days, followed by histopathology and flow cytometry of excised leaflets. RESULTS Tethered + MI leaflets were markedly thicker than tethered-alone valves and sham controls. Leaflet area also increased significantly. EMT, detected as α-smooth muscle actin-positive endothelial cells, significantly exceeded that in tethered-alone and control valves. Transforming growth factor-β, matrix metalloproteinase expression, and cellular proliferation were markedly increased. Uniquely, tethering + MI showed endothelial activation with vascular adhesion molecule expression, neovascularization, and cells positive for CD45, considered a hematopoietic cell marker. Tethered + MI findings were comparable with external ventricular constraint. CONCLUSIONS MI altered leaflet adaptation, including a profibrotic increase in valvular cell activation, CD45-positive cells, and matrix turnover

  7. Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats

    PubMed Central

    van den Brom, Charissa E.; Boly, Chantal A.; Bulte, Carolien S. E.; van den Akker, Rob F. P.; Kwekkeboom, Rick F. J.; Loer, Stephan A.; Boer, Christa; Bouwman, R. Arthur

    2016-01-01

    Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state. PMID:26824042

  8. Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats.

    PubMed

    van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur

    2016-01-01

    Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state.

  9. Nitrendipine binding in congestive heart failure due to myocardial infarction

    SciTech Connect

    Dixon, I.M.; Lee, S.L.; Dhalla, N.S. )

    1990-03-01

    Depressed cardiac pump function is the hallmark of congestive heart failure, and it is suspected that decreased influx of Ca2+ into the cardiac cell is responsible for depressed contractile function. Since Ca2+ channels in the sarcolemmal membrane are considered to be an important route for the entry of Ca2+, we examined the status of Ca2+ receptors/channels in failing rat hearts after myocardial infarction of the left ventricular free wall. For this purpose, the left coronary artery was ligated and hearts were examined 4, 8, and 16 weeks later; sham-operated animals served as controls. Hemodynamic assessment revealed decreased total mechanical energy (left ventricular systolic pressure x heart rate), increased left ventricular diastolic pressure, and decreased positive and negative dP/dt in experimental animals at 4, 8, and 16 weeks. Although accumulation of ascites in the abdominal cavity was evident at 4 weeks, other clinical signs of congestive heart failure in experimental rats were evident from the presence of lung congestion and cardiac dilatation at 8 and 16 weeks after induction of myocardial infarction. The density of Ca2+ receptors/channels in crude membranes, as assessed by (3H)nitrendipine binding assay, was found to be decreased in the uninfarcted experimental left ventricle at 8 and 16 weeks; however, no change in the affinity of nitrendipine was evident. A similar depression in the specific binding of another dihydropyridine compound, (3H)PN200-110, was also evident in failing hearts. Brain and skeletal muscle crude membrane preparations, unlike those of the right ventricle and liver, revealed a decrease in Ca2+ receptors/channels density in experimental animals at 16 weeks.

  10. Altered phosphate metabolism in myocardial infarction: P-31 MR spectroscopy

    SciTech Connect

    Bottomley, P.A.; Herfkens, R.J.; Smith, L.S.; Bashore, T.M.

    1987-12-01

    The high-energy myocardial phosphate metabolism of four patients with acute anterior myocardial infarction after coronary angioplasty and drug therapy was evaluated with cardiac-gated phosphorus magnetic resonance (MR) depth-resolved surface coil spectroscopy (DRESS) 5-9 days after the onset of symptoms. Significant reductions (about threefold) in the phosphocreatine (PCr) to inorganic phosphate (Pi) ratio and elevations in the Pi to adenosine triphosphate (ATP) ratio were observed in endocardially or transmurally derived MR spectra when compared with values from epicardially displaced spectra and values from seven healthy volunteers (P less than .05). High-energy phosphate metabolites and Pi ratios did not vary significantly during the cardiac cycle in healthy volunteers. However, contamination of Pi resonances by phosphomonoester components, including blood 2,3-diphosphoglycerate, precluded accurate spectral quantification of Pi and pH. The results indicate that localized P-31 MR spectroscopy may be used to directly assess cellular energy reserve in clinical myocardial infarction and to evaluate metabolic response to interventions.

  11. Differentiation of hemopericardium due to ruptured myocardial infarction or aortic dissection on unenhanced postmortem computed tomography.

    PubMed

    Ampanozi, Garyfalia; Flach, Patricia M; Ruder, Thomas D; Filograna, Laura; Schweitzer, Wolf; Thali, Michael J; Ebert, Lars C

    2017-03-28

    The aim of the study was to evaluate unenhanced postmortem computed tomography (PMCT) in cases of non-traumatic hemopericardium by establishing the sensitivity, specificity and accuracy of diagnostic criteria for the differentiation between aortic dissection and myocardial wall rupture due to infarction. Twenty six cases were identified as suitable for evaluation, of which ruptured aortic dissection could be identified as the underlying cause of hemopericardium in 50% of the cases, and myocardial wall rupture also in 50% of the cases. All cases underwent a PMCT and 24 of the cases also underwent one or more additional examinations: a subsequent autopsy, or a postmortem magnetic resonance (PMMR), or a PMCT angiography (PMCTA), or combinations of the above. Two radiologists evaluated the PMCT images and classified each case as "aortic dissection", "myocardial wall rupture" or "undetermined". Quantification of the pericardial blood was carried out using segmentation techniques. 17 of 26 cases were correctly identified, either as aortic dissections or myocardial ruptures, by both readers. 7 of 13 myocardial wall ruptures were identified by both readers, whereas both readers identified correctly 10 of 13 aortic dissection cases. Taking into account the responses of both readers, specificity was 100% for both causes of hemopericardium and sensitivity as well as accuracy was higher for aortic dissections than myocardial wall ruptures (72.7% and 87.5% vs 53.8% and 75% respectively). Pericardial blood volumes were constantly higher in the aortic dissection group, but a statistical significance of these differences could not be proven, since the small count of cases did not allow for statistical tests. This study showed that diagnostic criteria for the differentiation between ruptured aortic dissection and myocardial wall rupture due to infarction are highly specific and accurate.

  12. Myocardial alterations during hemodialysis: insights from new noninvasive technology.

    PubMed

    Singh, N; Langer, A; Freeman, M R; Goldstein, M B

    1994-01-01

    Eighteen patients with chronic renal failure had their cardiac status monitored during hemodialysis (HD). Ten studies were carried out using an ambulatory nuclear vest to assess ejection fraction (EF), heart rate (HR), relative end-systolic (ESV) and end-diastolic (EDV) volumes every 60 s. A total of 36 episodes of EF falls occurred in 9 patients, all asymptomatic. These EF falls were associated with a rise in ESV, while HR, BP, and EDV remained unchanged. The EF falls correlated best with the volume of ultrafiltrate removed. Ten patients had on-line ST-segment monitoring with sestamibi injection either at the time of ST depression (STD) or at the end of dialysis, if no STD occurred, in order to detect the presence of transient ischemia. Seven of ten patients had perfusion defects after dialysis, with STD occurring in 3 of 10 patients. Predialysis imaging was available in only 8 of 10 patients, and 6 of these patients had perfusion defects. Changes in perfusion defects were not significantly different in the 3 patients with STD compared with those without STD. EF falls and perfusion defects are common in HD patients even in the absence of known coronary artery disease; however, ST segment monitoring is not a sensitive tool for its detection. These changes in function and perfusion may represent myocardial ischemia and contribute to the high incidence of cardiovascular morbidity and mortality in this patient population.

  13. Finite-Element Extrapolation of Myocardial Structure Alterations Across the Cardiac Cycle in Rats

    PubMed Central

    David Gomez, Arnold; Bull, David A.; Hsu, Edward W.

    2015-01-01

    Myocardial microstructures are responsible for key aspects of cardiac mechanical function. Natural myocardial deformation across the cardiac cycle induces measurable structural alteration, which varies across disease states. Diffusion tensor magnetic resonance imaging (DT-MRI) has become the tool of choice for myocardial structural analysis. Yet, obtaining the comprehensive structural information of the whole organ, in 3D and time, for subject-specific examination is fundamentally limited by scan time. Therefore, subject-specific finite-element (FE) analysis of a group of rat hearts was implemented for extrapolating a set of initial DT-MRI to the rest of the cardiac cycle. The effect of material symmetry (isotropy, transverse isotropy, and orthotropy), structural input, and warping approach was observed by comparing simulated predictions against in vivo MRI displacement measurements and DT-MRI of an isolated heart preparation at relaxed, inflated, and contracture states. Overall, the results indicate that, while ventricular volume and circumferential strain are largely independent of the simulation strategy, structural alteration predictions are generally improved with the sophistication of the material model, which also enhances torsion and radial strain predictions. Moreover, whereas subject-specific transversely isotropic models produced the most accurate descriptions of fiber structural alterations, the orthotropic models best captured changes in sheet structure. These findings underscore the need for subject-specific input data, including structure, to extrapolate DT-MRI measurements across the cardiac cycle. PMID:26299478

  14. Correlation between oxidative stress and alteration of intracellular calcium handling in isoproterenol-induced myocardial infarction.

    PubMed

    Díaz-Muñoz, Mauricio; Alvarez-Pérez, Marco Antonio; Yáñez, Lucía; Vidrio, Susana; Martínez, Lidia; Rosas, Gisele; Yáñez, Mario; Ramírez, Sotero; de Sánchez, Victoria Chagoya

    2006-09-01

    Myocardial Ca(2+) overload and oxidative stress are well documented effects associated to isoproterenol (ISO)-induced myocardial necrosis, but information correlating these two issues is scarce. Using an ISO-induced myocardial infarction model, 3 stages of myocardial damage were defined: pre-infarction (0-12 h), infarction (12-24 h) and post-infarction (24-96 h). Alterations in Ca(2+) homeostasis and oxidative stress were studied in mitochondria, sarcoplasmic reticulum and plasmalemma by measuring the Ca(2+) content, the activity of Ca(2+) handling proteins, and by quantifying TBARs, nitric oxide (NO) and oxidative protein damage (changes in carbonyl and thiol groups). Free radicals generated system, antioxidant enzymes and oxidative stress (GSH/GSSG ratio) were also monitored at different times of ISO-induced cardiotoxicity. The Ca(2+) overload induced by ISO was counterbalanced by a diminution in the ryanodine receptor activity and the Na(+)-Ca(+2) exchanger as well as by the increase in both calcium ATPases activities (vanadate- and thapsigargine-sensitive) and mitochondrial Ca(2+) uptake during pre-infarction and infarction stages. Pro-oxidative reactions and antioxidant defences during the 3 stages of cardiotoxicity were observed, with maximal oxidative stress during the infarction. Significant correlations were found among pro-oxidative reactions with plasmalemma and sarcoplasmic reticulum Ca(2+) ATPases, and ryanodine receptor activities at the onset and development of ISO-induced infarction. These findings could be helpful in the design of antioxidant therapies in this pathology.

  15. Warming can boost denitrification disproportionately due to altered oxygen dynamics.

    PubMed

    Veraart, Annelies J; de Klein, Jeroen J M; Scheffer, Marten

    2011-03-31

    Global warming and the alteration of the global nitrogen cycle are major anthropogenic threats to the environment. Denitrification, the biological conversion of nitrate to gaseous nitrogen, removes a substantial fraction of the nitrogen from aquatic ecosystems, and can therefore help to reduce eutrophication effects. However, potential responses of denitrification to warming are poorly understood. Although several studies have reported increased denitrification rates with rising temperature, the impact of temperature on denitrification seems to vary widely between systems. We explored the effects of warming on denitrification rates using microcosm experiments, field measurements and a simple model approach. Our results suggest that a three degree temperature rise will double denitrification rates. By performing experiments at fixed oxygen concentrations as well as with oxygen concentrations varying freely with temperature, we demonstrate that this strong temperature dependence of denitrification can be explained by a systematic decrease of oxygen concentrations with rising temperature. Warming decreases oxygen concentrations due to reduced solubility, and more importantly, because respiration rates rise more steeply with temperature than photosynthesis. Our results show that denitrification rates in aquatic ecosystems are strongly temperature dependent, and that this is amplified by the temperature dependencies of photosynthesis and respiration. Our results illustrate the broader phenomenon that coupling of temperature dependent reactions may in some situations strongly alter overall effects of temperature on ecological processes.

  16. Warming Can Boost Denitrification Disproportionately Due to Altered Oxygen Dynamics

    PubMed Central

    Veraart, Annelies J.; de Klein, Jeroen J. M.; Scheffer, Marten

    2011-01-01

    Background Global warming and the alteration of the global nitrogen cycle are major anthropogenic threats to the environment. Denitrification, the biological conversion of nitrate to gaseous nitrogen, removes a substantial fraction of the nitrogen from aquatic ecosystems, and can therefore help to reduce eutrophication effects. However, potential responses of denitrification to warming are poorly understood. Although several studies have reported increased denitrification rates with rising temperature, the impact of temperature on denitrification seems to vary widely between systems. Methodology/Principal Findings We explored the effects of warming on denitrification rates using microcosm experiments, field measurements and a simple model approach. Our results suggest that a three degree temperature rise will double denitrification rates. By performing experiments at fixed oxygen concentrations as well as with oxygen concentrations varying freely with temperature, we demonstrate that this strong temperature dependence of denitrification can be explained by a systematic decrease of oxygen concentrations with rising temperature. Warming decreases oxygen concentrations due to reduced solubility, and more importantly, because respiration rates rise more steeply with temperature than photosynthesis. Conclusions/Significance Our results show that denitrification rates in aquatic ecosystems are strongly temperature dependent, and that this is amplified by the temperature dependencies of photosynthesis and respiration. Our results illustrate the broader phenomenon that coupling of temperature dependent reactions may in some situations strongly alter overall effects of temperature on ecological processes. PMID:21483809

  17. Prior exercise training does not prevent acute cardiac alterations after myocardial infarction in female rats

    PubMed Central

    Veiga, Eduardo C A; Antonio, Ednei L; Bocalini, Danilo S; Murad, Neif; Abreu, Luiz C; Tucci, Paulo J F; Sato, Monica A

    2011-01-01

    OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week) or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean ± SEM) were analyzed using a two-way ANOVA model followed by Tukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58±3.04 vs. 37.59±3.07). In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73±1.52 vs. 45.48±3.49). The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36±2% and 39±3%, respectively) were smaller than those for the exercise sham surgery (ES, 67±1%) and sedentary sham surgery (SS, 69±2%) groups. The E/A was higher in the sedentary myocardial infarction (4.4±0.3) and exercised myocardial infarction (5.5±0.3) rats than in the SS (2.4±0.1) and ES (2.2±0.1) rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model. PMID:21789396

  18. Ischemia-induced alterations in myocardial (Na+ + K+)-ATPase and cardiac glycoside binding.

    PubMed Central

    Beller, G A; Conroy, J; Smith, T W

    1976-01-01

    The effects of ischemia on the canine myocardial (Na+ + K+)-ATPase complex were examined in terms of alterations in cardiac glycoside binding and enzymatic activity. Ability of the myocardial cell to bind tritiated ouabain in vivo was assessed after 1, 2, and 6 h of coronary occlusion followed by 45 min of reperfusion, and correlated with measurements of in vitro (Na+ + K+)-ATPase activity and in vitro [3H]ouabain binding after similar periods of ischemia. Regional blood flow alterations during occlusion and reperfusion were simultaneously determined utilizing 15 mum radioactive microspheres to determine the degree to which altered binding of ouabain might be flow related. Anterior wall infarction was produced in 34 dogs by snaring of confluent branches of the left coronary system. Epicardial electrograms delineated ischemic and border zone areas. Coronary reperfusion after 2 and 6 h of occlusion was associated with impaired reflow of blood and markedly impaired uptake of [3H]ouabain in ischemic myocardium. In both groups, in vivo [3H]ouabain binding by ischemic tissue was reduced out of proportion to the reduction in flow. Despite near-complete restoration of flow in seven dogs occluded for 1 h and reperfused, [3H]ouabain remained significantly reduced to 58 +/- 9% of nonischemic uptake in subendocardial layers of the central zone of ischemia. Thus, when coronary flow was restored to areas of myocardium rendered acutely ischemia for 1 or more hours, ischemic zones demonstrated progressively diminished ability to bind ouabain. To determine whether ischemia-induced alteration in myocardial (Na+ + K+)-ATPase might underlie these changes, (Na+ + K+)-ATPase activity and [3H]ouabain binding were measured in microsomal fractions from ischemic myocardium after 1, 2, and 6 h of coronary occlusion. In animals occluded for 6 h, (Na+ + K+)-ATPase activity was significantly reduced by 40% in epicardial and by 35% in endocardial layers compared with nonischemic myocardium

  19. Myocardial reloading after extracorporeal membrane oxygenation alters substrate metabolism while promoting protein synthesis.

    PubMed

    Kajimoto, Masaki; O'Kelly Priddy, Colleen M; Ledee, Dolena R; Xu, Chun; Isern, Nancy; Olson, Aaron K; Des Rosiers, Christine; Portman, Michael A

    2013-08-19

    Extracorporeal membrane oxygenation (ECMO) unloads the heart, providing a bridge to recovery in children after myocardial stunning. ECMO also induces stress which can adversely affect the ability to reload or wean the heart from the circuit. Metabolic impairments induced by altered loading and/or stress conditions may impact weaning. However, cardiac substrate and amino acid requirements upon weaning are unknown. We assessed the hypothesis that ventricular reloading with ECMO modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis. Sixteen immature piglets (7.8 to 15.6 kg) were separated into 2 groups based on ventricular loading status: 8-hour ECMO (UNLOAD) and postwean from ECMO (RELOAD). We infused into the coronary artery [2-(13)C]-pyruvate as an oxidative substrate and [(13)C6]-L-leucine as an indicator for amino acid oxidation and protein synthesis. Upon RELOAD, each functional parameter, which were decreased substantially by ECMO, recovered to near-baseline level with the exclusion of minimum dP/dt. Accordingly, myocardial oxygen consumption was also increased, indicating that overall mitochondrial metabolism was reestablished. At the metabolic level, when compared to UNLOAD, RELOAD altered the contribution of various substrates/pathways to tissue pyruvate formation, favoring exogenous pyruvate versus glycolysis, and acetyl-CoA formation, shifting away from pyruvate decarboxylation to endogenous substrate, presumably fatty acids. Furthermore, there was also a significant increase of tissue concentrations for all CAC intermediates (≈80%), suggesting enhanced anaplerosis, and of fractional protein synthesis rates (>70%). RELOAD alters both cytosolic and mitochondrial energy substrate metabolism, while favoring leucine incorporation into protein synthesis rather than oxidation in the CAC. Improved understanding of factors governing these metabolic perturbations may serve as a basis for interventions and thereby improve

  20. Myocardial Reloading After Extracorporeal Membrane Oxygenation Alters Substrate Metabolism While Promoting Protein Synthesis

    PubMed Central

    Kajimoto, Masaki; O'Kelly Priddy, Colleen M.; Ledee, Dolena R.; Xu, Chun; Isern, Nancy; Olson, Aaron K.; Rosiers, Christine Des; Portman, Michael A.

    2013-01-01

    Background Extracorporeal membrane oxygenation (ECMO) unloads the heart, providing a bridge to recovery in children after myocardial stunning. ECMO also induces stress which can adversely affect the ability to reload or wean the heart from the circuit. Metabolic impairments induced by altered loading and/or stress conditions may impact weaning. However, cardiac substrate and amino acid requirements upon weaning are unknown. We assessed the hypothesis that ventricular reloading with ECMO modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis. Methods and Results Sixteen immature piglets (7.8 to 15.6 kg) were separated into 2 groups based on ventricular loading status: 8‐hour ECMO (UNLOAD) and postwean from ECMO (RELOAD). We infused into the coronary artery [2‐13C]‐pyruvate as an oxidative substrate and [13C6]‐L‐leucine as an indicator for amino acid oxidation and protein synthesis. Upon RELOAD, each functional parameter, which were decreased substantially by ECMO, recovered to near‐baseline level with the exclusion of minimum dP/dt. Accordingly, myocardial oxygen consumption was also increased, indicating that overall mitochondrial metabolism was reestablished. At the metabolic level, when compared to UNLOAD, RELOAD altered the contribution of various substrates/pathways to tissue pyruvate formation, favoring exogenous pyruvate versus glycolysis, and acetyl‐CoA formation, shifting away from pyruvate decarboxylation to endogenous substrate, presumably fatty acids. Furthermore, there was also a significant increase of tissue concentrations for all CAC intermediates (≈80%), suggesting enhanced anaplerosis, and of fractional protein synthesis rates (>70%). Conclusions RELOAD alters both cytosolic and mitochondrial energy substrate metabolism, while favoring leucine incorporation into protein synthesis rather than oxidation in the CAC. Improved understanding of factors governing these metabolic perturbations may

  1. Hydrological Alterations Due to Climate-Induced Regional Vegetation Change

    NASA Astrophysics Data System (ADS)

    White, A. B.; Vivoni, E. R.; Springer, E. P.

    2010-12-01

    An extended, severe drought in the southwestern U.S. from 2000 to 2003 was accompanied by increased temperatures and bark beetle infestations, inducing the large-scale mortality of woody overstory (Pinus edulis). The consequential redistribution of water, radiation, and nutrient availability modified the ecosystem phenology, species composition, and forced the ecosystem to transition into a new state. We hypothesize that the hydrological processes in the ecosystem were also altered due to the mortality. Thus, our objective is to investigate changes in the soil-vegetation-atmosphere continuum at the watershed scale. The Rio Ojo Caliente Basin is a subbasin of the Upper Rio Grande, located mostly in New Mexico, and is approximately 1,000 km2. Examining a remotely-sensed vegetation index (1-km AVHRR NDVI from 1990 to 2006), there is an increasing trend in the NDVI from 1989 to 1999 (pre-mortality period), a decreasing trend from 2000 to 2003 (mortality period), and a dramatic increasing trend from 2004 to 2006 (post-mortality period) in which the NDVI rebounds to nearly pre-mortality magnitudes. This pattern exists across varying spatial scales (plot to watershed to region) and signifies a profound alteration in the ecosystem, for while the vegetation composition was altered to a great degree, the system rapidly returned to a homeostatic state balancing resource supply and use during the post-mortality period. To investigate hydrological changes due to the mortality, we employ a physically-based, distributed hydrologic model, tRIBS (TIN-based Real-Time Integrated Basin Simulator) for the Rio Ojo Caliente Basin. STATSGO 1-km soils data, 10-meter National Elevation Dataset DEMs, Carson National Forest vegetation species data, and MM5-downscaled NCEP/NCAR Reanalysis-I meteorologic data are used as model inputs. A combination of MODIS and AVHRR remote-sensing data, values from the literature, and field data from a long-term, pi {n}on-juniper (PJ) observation site in Los

  2. Acrolein Inhalation Alters Myocardial Synchrony and Performance at and Below Exposure Concentrations that Cause Ventilatory Responses.

    PubMed

    Thompson, Leslie C; Ledbetter, Allen D; Haykal-Coates, Najwa; Cascio, Wayne E; Hazari, Mehdi S; Farraj, Aimen K

    2017-04-01

    Acrolein is an irritating aldehyde generated during combustion of organic compounds. Altered autonomic activity has been documented following acrolein inhalation, possibly impacting myocardial synchrony and function. Given the ubiquitous nature of acrolein in the environment, we sought to better define the immediate and delayed functional cardiac effects of acrolein inhalation in vivo. We hypothesized that acrolein inhalation would increase markers of cardiac mechanical dysfunction, i.e., myocardial dyssynchrony and performance index in mice. Male C57Bl/6J mice were exposed to filtered air (FA) or acrolein (0.3 or 3.0 ppm) for 3 h in whole-body plethysmography chambers (n = 6). Echocardiographic analyses were performed 1 day before exposure and at 1 and 24 h post-exposure. Speckle tracking echocardiography revealed that circumferential strain delay (i.e., dyssynchrony) was increased at 1 and 24 h following exposure to 3.0 ppm, but not 0.3 ppm, when compared to pre-exposure and/or FA exposure. Pulsed wave Doppler of transmitral blood flow revealed that acrolein exposure at 0.3 ppm, but not 3.0 ppm, increased the Tei index of myocardial performance (i.e., decreased global heart performance) at 1 and 24 h post-exposure compared to pre-exposure and/or FA exposure. We conclude that short-term inhalation of acrolein can acutely modify cardiac function in vivo and that echocardiographic evaluation of myocardial synchrony and performance following exposure to other inhaled pollutants could provide broader insight into the health effects of air pollution.

  3. Variability of myocardial perfusion dark rim Gibbs artifacts due to sub-pixel shifts

    PubMed Central

    Ferreira, Pedro; Gatehouse, Peter; Kellman, Peter; Bucciarelli-Ducci, Chiara; Firmin, David

    2009-01-01

    Background Gibbs ringing has been shown as a possible source of dark rim artifacts in myocardial perfusion studies. This type of artifact is usually described as transient, lasting a few heart beats, and localised in random segments of the myocardial wall. Dark rim artifacts are known to be unpredictably variable. This article aims to illustrate that a sub-pixel shift, i.e. a small displacement of the pixels with respect to the endocardial border, can result in different Gibbs ringing and hence different artifacts. Therefore a hypothesis for one cause of dark rim artifact variability is given based on the sub-pixel position of the endocardial border. This article also demonstrates the consequences for Gibbs artifacts when two different methods of image interpolation are applied (post-FFT interpolation, and pre-FFT zero-filling). Results Sub-pixel shifting of in vivo perfusion studies was shown to change the appearance of Gibbs artifacts. This effect was visible in the original uninterpolated images, and in the post-FFT interpolated images. The same shifted data interpolated by pre-FFT zero-filling exhibited much less variability in the Gibbs artifact. The in vivo findings were confirmed by phantom imaging and numerical simulations. Conclusion Unless pre-FFT zero-filling interpolation is performed, Gibbs artifacts are very dependent on the position of the subendocardial wall within the pixel. By introducing sub-pixel shifts relative to the endocardial border, some of the variability of the dark rim artifacts in different myocardial segments, in different patients and from frame to frame during first-pass perfusion due to cardiac and respiratory motion can be explained. Image interpolation by zero-filling can be used to minimize this dependency. PMID:19473492

  4. Primary percutaneous coronary intervention for acute myocardial infarction in a pediatric patient with giant coronary aneurysm due to Kawasaki disease.

    PubMed

    Mongiovì, Maurizio; Alaimo, Annalisa; Vernuccio, Federica; Pieri, Daniele

    2014-01-01

    We report a case of acute myocardial infarction in an 8-year-old boy with a history of Kawasaki disease and giant coronary aneurysms in the right and left coronary arteries. We performed coronary angiography and percutaneous coronary intervention 4 hours after the onset of symptoms. This case suggests that primary percutaneous coronary intervention might be safe and effective in the long-term treatment of acute myocardial infarction due to coronary sequelae of Kawasaki. © 2013 Wiley Periodicals, Inc.

  5. Myocardial Structural Alteration and Systolic Dysfunction in Preclinical Hypertrophic Cardiomyopathy Mutation Carriers

    PubMed Central

    Yiu, Kai Hang; Atsma, Douwe E.; Delgado, Victoria; Ng, Arnold C. T.; Witkowski, Tomasz G.; Ewe, See Hooi; Auger, Dominique; Holman, Eduard R.; van Mil, Anneke M.; Breuning, Martijn H.; Tse, Hung Fat; Bax, Jeroen J.; Schalij, Martin J.; Marsan, Nina Ajmone

    2012-01-01

    Background To evaluate the presence of myocardial structural alterations and subtle myocardial dysfunction during familial screening in asymptomatic mutation carriers without hypertrophic cardiomyopathy (HCM) phenotype. Methods and Findings Sixteen HCM families with pathogenic mutation were studied and 46 patients with phenotype expression (Mut+/Phen+) and 47 patients without phenotype expression (Mut+/Phen−) were observed. Twenty-five control subjects, matched with the Mut+/Phen− group, were recruited for comparison. Echocardiography was performed to evaluate conventional parameters, myocardial structural alteration by calibrated integrated backscatter (cIBS) and global and segmental longitudinal strain by speckle tracking analysis. All 3 groups had similar left ventricular dimensions and ejection fraction. Basal anteroseptal cIBS was the highest in Mut+/Phen+ patients (−14.0±4.6 dB, p<0.01) and was higher in Mut+/Phen− patients as compared to controls (−17.0±2.3 vs. −22.6±2.9 dB, p<0.01) suggesting significant myocardial structural alterations. Global and basal anteroseptal longitudinal strains (−8.4±4.0%, p<0.01) were the most impaired in Mut+/Phen+ patients as compared to the other 2 groups. Although global longitudinal strain was similar between Mut+/Phen− group and controls, basal anteroseptal strain was lower in Mut+/Phen− patients (−14.1±3.8%, p<0.01) as compared to controls (−19.9±2.9%, p<0.01), suggesting a subclinical segmental systolic dysfunction. A combination of >−19.0 dB basal anteroseptal cIBS or >−18.0% basal anteroseptal longitudinal strain had a sensitivity of 98% and a specificity of 72% in differentiating Mut+/Phen− group from controls. Conclusion The use of cIBS and segmental longitudinal strain can differentiate HCM Mut+/Phen− patients from controls with important clinical implications for the family screening and follow-up of these patients. PMID:22574137

  6. Protective effect of lidocaine during regional myocardial ischemia: an altered pathophysiologic response assessed by NADH fluorescence

    SciTech Connect

    Baron, D.W.; Walls, J.T.; Anderson, R.E.; Harrison, C.E. Jr.

    1982-07-01

    Studies were undertaken to determine the effects of lidocaine on ischemic myocardium, which was induced by coronary artery constriction in open-chested dogs. A real-time epicardial fluorescent technique to detect in vivo-reduced nicotinamide adenine dinucleotide (NADH) during 60 seconds of ischemia was used. Blood flow of ischemic myocardium was measured by using radioactive microspheres of 9 +/- 1 micrometers (mean +/- SE) and was compared with that of normal myocardium, shown by injection of alpha-zurine blue dye. Lidocaine effectively reduced peak NADH fluorescence by 18.6%, from 93.9 +/- 7.2 to 76.4 +/-4.1 mV (p less than 0.005). Lidocaine delayed the onset of fluorescence (2.2 +/- 0.2 versus 1.3 +/- 0.1 s p less than 0.002) and facilitated the recovery from ischemia (38.4 +/- 2.9 versus 54.8 +/- 2.9 s p less than 0.001). Increase in NADH concentration during ischemia correlated (r.0.76, p less than 0.006) with ischemic fluorescence. These findings were independent of altered hemodynamics or change in myocardial blood flow. Results indicate that lidocaine provides myocardial cellular protection during transient ischemia; there is an altered NADH fluorescent response to coronary artery occlusion.

  7. Unilateral pulmonary edema: a rare initial presentation of cardiogenic shock due to acute myocardial infarction.

    PubMed

    Shin, Jeong Hun; Kim, Seok Hwan; Park, Jinkyu; Lim, Young-Hyo; Park, Hwan-Cheol; Choi, Sung Il; Shin, Jinho; Kim, Kyung-Soo; Kim, Soon-Gil; Hong, Mun K; Lee, Jae Ung

    2012-02-01

    Cardiogenic unilateral pulmonary edema (UPE) is a rare clinical entity that is often misdiagnosed at first. Most cases of cardiogenic UPE occur in the right upper lobe and are caused by severe mitral regurgitation (MR). We present an unusual case of right-sided UPE in a patient with cardiogenic shock due to acute myocardial infarction (AMI) without severe MR. The patient was successfully treated by percutaneous coronary intervention and medical therapy for heart failure. Follow-up chest Radiography showed complete resolution of the UPE. This case reminds us that AMI can present as UPE even in patients without severe MR or any preexisting pulmonary disease affecting the vasculature or parenchyma of the lung.

  8. [Markers for early detection of alterations in carbohydrate metabolism after acute myocardial infarction].

    PubMed

    de Gea-García, J H; Benali, L; Galcerá-Tomás, J; Padilla-Serrano, A; Andreu-Soler, E; Melgarejo-Moreno, A; Alonso-Fernández, N

    2014-03-01

    Undiagnosed abnormal glucose metabolism is often seen in patients admitted with acute myocardial infarction, although there is no consensus on which patients should be studied with a view to establishing an early diagnosis. The present study examines the potential of certain variables obtained upon admission to diagnose abnormal glucose metabolism. A prospective cohort study was carried out. The Intensive Care Unit of Arrixaca University Hospital (Murcia), Spain. A total of 138 patients admitted to the Intensive Care Unit with acute myocardial infarction and without known or de novo diabetes mellitus. After one year, oral glucose tolerance testing was performed. Clinical and laboratory test parameters were recorded upon admission and one year after discharge. Additionally, after one year, oral glucose tolerance tests were made, and a study was made of the capacity of the variables obtained at admission to diagnose diabetes, based on the ROC curves and multivariate analysis. Of the 138 patients, 112 (72.5%) had glucose metabolic alteration, including 16.7% with diabetes. HbA1c was independently associated with a diagnosis of diabetes (RR: 7.28, 95%CI 1.65 to 32.05, P = .009), and showed the largest area under the ROC curve for diabetes (0.81, 95%CI 0.69 to 0.92, P = .001). In patients with acute myocardial infarction, HbA1c helps identify those individuals with abnormal glucose metabolism after one year. Thus, its determination in this group of patients could be used to identify those subjects requiring a more exhaustive study in order to establish an early diagnosis. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  9. Ultrastructural alterations in allylamine cardiovascular toxicity. Late myocardial and vascular lesions.

    PubMed Central

    Boor, P. J.; Ferrans, V. J.

    1985-01-01

    The late myocardial and vascular ultrastructural changes in rat hearts following consumption of the cardiovascular toxin allylamine were studied. Rats were given 0.1% allylamine HCl in drinking water for 10-104 days. From 10 to 21 days, there was organization of acute myocardial necrosis by macrophages and scattered polymorphonuclear leukocytes with prominent interstitial-cell proliferation. Alterations at 21-104 days included extensive scarring with formation of dense mature collagen with scattered fibroblasts present, grossly evident left-ventricular aneurysm, and gross and microscopic changes similar to those observed in the secondary form of endocardial fibroelastosis. Areas of scar contained highly cellular foci of smooth-muscle cells, myofibroblasts, and abundant extracellular elastin. Cardiac myocytes frequently showed markedly disorganized myofilaments, bizarrely distorted mitochondria with condensed cristae, and other severe degenerative changes. Small vessels within and adjacent to scar showed proliferation of intimal smooth-muscle cells. Endothelial lesions or recent or organized thrombi were not seen. Focal endocardial metaplasia, consisting of both chondroid and osseous tissue, was found in areas of transmural scarring, or ventricular aneurysm. Chondrocytes had the overall nuclear and cellular morphology, abundant rough endoplasmic reticulum, and surrounding lacunae typical of mature fibrocartilage. In some areas, the collagen matrix was undergoing calcification with the typical cross-banded pattern of calcifying connective tissue. Osteocytes were located in a densely calcified bone matrix and displayed characteristic cellular extensions into surrounding canaliculi. These findings indicate a severe myocardial, small-vessel, and endocardial injury during the course of chronic allylamine intoxication. Images Figure 13 Figure 14 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 15 Figure

  10. Predictive Factors of Hospital Mortality Due to Myocardial Infarction: A Multilevel Analysis of Iran's National Data

    PubMed Central

    Ahmadi, Ali; Soori, Hamid; Mehrabi, Yadollah; Etemad, Koorosh; Sajjadi, Homeira; Sadeghi, Mehraban

    2015-01-01

    Background: Regarding failure to establish the statistical presuppositions for analysis of the data by conventional approaches, hierarchical structure of the data as well as the effect of higher-level variables, this study was conducted to determine the factors independently associated with hospital mortality due to myocardial infarction (MI) in Iran using a multilevel analysis. Methods: This study was a national, hospital-based, and cross-sectional study. In this study, the data of 20750 new MI patients between April, 2012 and March, 2013 in Iran were used. The hospital mortality due to MI was considered as the dependent variable. The demographic data, clinical and behavioral risk factors at the individual level and environmental data were gathered. Multilevel logistic regression models with Stata software were used to analyze the data. Results: Within 1-year of study, the frequency (%) of hospital mortality within 30 days of admission was derived 2511 (12.1%) patients. The adjusted odds ratio (OR) of mortality with (95% confidence interval [CI]) was derived 2.07 (95% CI: 1.5–2.8) for right bundle branch block, 1.5 (95% CI: 1.3–1.7) for ST-segment elevation MI, 1.3 (95% CI: 1.1–1.4) for female gender, and 1.2 (95% CI: 1.1–1.3) for humidity, all of which were considered as risk factors of mortality. But, OR of mortality was 0.7 for precipitation (95% CI: 0.7–0.8) and 0.5 for angioplasty (95% CI: 0.4–0.6) were considered as protective factors of mortality. Conclusions: Individual risk factors had independent effects on the hospital mortality due to MI. Variables in the province level had no significant effect on the outcome of MI. Increasing access and quality to treatment could reduce the mortality due to MI. PMID:26730342

  11. Hydrologic property alterations due to elevated temperatures at Yucca Mountain

    SciTech Connect

    Flint, A.L.; Nash, M.H.; Nash, M.S.

    1994-12-31

    Yucca Mountain is currently being evaluated as a potential site for a high level nuclear waste repository. The pre-emplacement hydrologic properties of the rock are important in determining the suitability of the site; however, post emplacement thermal loads and associated drying may permanently alter the character of the rock. A preliminary study was undertaken to determine the effects of elevated temperatures on hydrologic properties of the welded Topopah Spring member of the Paintbrush Tuff and a zeolitic, nonwelded tuff from the Tuffaceous Beds of Calico Hills. Rock outcrop samples were collected and dried in the laboratory at different temperatures (up to 400 degrees C). Hydrologic and physical properties -were tested before and after each of the drying cycles.

  12. Disruption of pdgfra alters endocardial and myocardial fusion during zebrafish cardiac assembly

    PubMed Central

    El-Rass, Suzan; Eisa-Beygi, Shahram; Khong, Edbert; Brand-Arzamendi, Koroboshka; Mauro, Antonio; Zhang, Haibo; Clark, Karl J.; Ekker, Stephen C.

    2017-01-01

    ABSTRACT Cardiac development in vertebrates is a finely tuned process regulated by a set of conserved signaling pathways. Perturbations of these processes are often associated with congenital cardiac malformations. Platelet-derived growth factor receptor α (PDGFRα) is a highly conserved tyrosine kinase receptor, which is essential for development and organogenesis. Disruption of Pdgfrα function in murine models is embryonic lethal due to severe cardiovascular defects, suggesting a role in cardiac development, thus necessitating the use of alternative models to explore its precise function. In this study, we generated a zebrafish pdgfra mutant line by gene trapping, in which the Pdgfra protein is truncated and fused with mRFP (Pdgfra-mRFP). Our results demonstrate that pdgfra mutants have defects in cardiac morphology as a result of abnormal fusion of myocardial precursors. Expression analysis of the developing heart at later stages suggested that Pdgfra-mRFP is expressed in the endocardium. Further examination of the endocardium in pdgfra mutants revealed defective endocardial migration to the midline, where cardiac fusion eventually occurs. Together, our data suggests that pdgfra is required for proper medial migration of both endocardial and myocardial precursors, an essential step required for cardiac assembly and development. PMID:28167492

  13. Disruption of pdgfra alters endocardial and myocardial fusion during zebrafish cardiac assembly.

    PubMed

    El-Rass, Suzan; Eisa-Beygi, Shahram; Khong, Edbert; Brand-Arzamendi, Koroboshka; Mauro, Antonio; Zhang, Haibo; Clark, Karl J; Ekker, Stephen C; Wen, Xiao-Yan

    2017-03-15

    Cardiac development in vertebrates is a finely tuned process regulated by a set of conserved signaling pathways. Perturbations of these processes are often associated with congenital cardiac malformations. Platelet-derived growth factor receptor α (PDGFRα) is a highly conserved tyrosine kinase receptor, which is essential for development and organogenesis. Disruption of Pdgfrα function in murine models is embryonic lethal due to severe cardiovascular defects, suggesting a role in cardiac development, thus necessitating the use of alternative models to explore its precise function. In this study, we generated a zebrafish pdgfra mutant line by gene trapping, in which the Pdgfra protein is truncated and fused with mRFP (Pdgfra-mRFP). Our results demonstrate that pdgfra mutants have defects in cardiac morphology as a result of abnormal fusion of myocardial precursors. Expression analysis of the developing heart at later stages suggested that Pdgfra-mRFP is expressed in the endocardium. Further examination of the endocardium in pdgfra mutants revealed defective endocardial migration to the midline, where cardiac fusion eventually occurs. Together, our data suggests that pdgfra is required for proper medial migration of both endocardial and myocardial precursors, an essential step required for cardiac assembly and development.

  14. Electrocardiographic alterations suggestive of myocardial injury elicited by rapid pressure lowering in hypertension.

    PubMed

    Pepi, M; Alimento, M; Maltagliati, A; Tosi, E; Guazzi, M D

    1988-08-01

    In hypertensive cardiac hypertrophy, the elevated coronary perfusion pressure compensates importantly for the raised coronary resistance. An imbalance between perfusion and left ventricular (LV) mass, such as that occurring with rapid or excessive blood pressure lowering, may result in an inadequate oxygen supply. In 28 primary hypertensives (Group A) with LV mass index within the mean + 1 SD (96 + 19 g m-2) of 145 controls, and in 26 patients whose LV mass exceeded these values (Group B), we lowered the diastolic blood pressure rapidly to 85-90 mmHg, using both s.l. nifedipine and i.v. nitroprusside. During each test, eight patients in Group B had inversion of T waves in lead I, aVL, V3-V6, which waxed and waned in parallel with the pressure fall and recovery, and was independent of conduction disturbances, variations or group differences in the QRS axis, QTc interval, heart rate, LV fractional shortening and wall stress. A 'coronary steal phenomenon' or passive collapse in compliant lesions consequent to vasodilatation may trigger acute myocardial ischaemia in the presence of severe coronary disease. Patients developing the ECG alterations, however, were free from angina and four, who were subjected to coronary angiography, had normal arteriograms. Patients with the myocardial injury pattern showed greater LV mass indices and larger falls in diastolic pressure for it to reach normal levels. The supply of energy to the hypertrophied hypertensive heart seems to depend importantly on the coronary perfusion pressure, suggesting the cautious use of rapid acting drugs.

  15. Varying Definitions for Periprocedural Myocardial Infarction Alter Event Rates and Prognostic Implications

    PubMed Central

    Idris, Hanan; Lo, Sidney; Shugman, Ibrahim M.; Saad, Yousef; Hopkins, Andrew P.; Mussap, Christian; Leung, Dominic; Thomas, Liza; Juergens, Craig P.; French, John K.

    2014-01-01

    Background Periprocedural myocardial infarction (PMI) has had several definitions in the last decade, including the Society for Cardiovascular Angiography and Interventions (SCAI) definition, that requires marked biomarker elevations congruent with surgical PMI criteria. Methods and Results The aim of this study was to examine the definition‐based frequencies of PMI and whether they influenced the reported association between PMI and increased rates of late death/ myocardial infarction (MI). We studied 742 patients; 492 (66%) had normal troponin T (TnT) levels and 250 (34%) had elevated, but stable or falling, TnT levels. PMI, using the 2007 and the 2012 universal definition, occurred in 172 (23.2%) and in 99 (13.3%) patients, respectively, whereas 19 (2.6%) met the SCAI PMI definition (P<0.0001). Among patients with PMI using the 2012 definition, occlusion of a side branch ≤1 mm occurred in 48 patients (48.5%) and was the most common angiographic finding for PMI. The rates of death/MI at 2 years in patients with, compared to those without, PMI was 14.7% versus 10.1% (P=0.087) based on the 2007 definition, 16.9% versus 10.3% (P=0.059) based on the 2012 definition, and 29.4% versus 10.7% (P=0.015) based on the SCAI definition. Conclusion In this study, PMI, according to the SCAI definition, was associated with more‐frequent late death/MI, with ≈20% of all patients, who had PMI using the 2007 universal MI definition, not having SCAI‐defined PMI. Categorizing these latter patients as SCAI‐defined no PMI did not alter the rate of death/MI among no‐PMI patients. PMID:25359403

  16. Varying definitions for periprocedural myocardial infarction alter event rates and prognostic implications.

    PubMed

    Idris, Hanan; Lo, Sidney; Shugman, Ibrahim M; Saad, Yousef; Hopkins, Andrew P; Mussap, Christian; Leung, Dominic; Thomas, Liza; Juergens, Craig P; French, John K

    2014-10-30

    Periprocedural myocardial infarction (PMI) has had several definitions in the last decade, including the Society for Cardiovascular Angiography and Interventions (SCAI) definition, that requires marked biomarker elevations congruent with surgical PMI criteria. The aim of this study was to examine the definition-based frequencies of PMI and whether they influenced the reported association between PMI and increased rates of late death/ myocardial infarction (MI). We studied 742 patients; 492 (66%) had normal troponin T (TnT) levels and 250 (34%) had elevated, but stable or falling, TnT levels. PMI, using the 2007 and the 2012 universal definition, occurred in 172 (23.2%) and in 99 (13.3%) patients, respectively, whereas 19 (2.6%) met the SCAI PMI definition (P<0.0001). Among patients with PMI using the 2012 definition, occlusion of a side branch ≤1 mm occurred in 48 patients (48.5%) and was the most common angiographic finding for PMI. The rates of death/MI at 2 years in patients with, compared to those without, PMI was 14.7% versus 10.1% (P=0.087) based on the 2007 definition, 16.9% versus 10.3% (P=0.059) based on the 2012 definition, and 29.4% versus 10.7% (P=0.015) based on the SCAI definition. In this study, PMI, according to the SCAI definition, was associated with more-frequent late death/MI, with ≈20% of all patients, who had PMI using the 2007 universal MI definition, not having SCAI-defined PMI. Categorizing these latter patients as SCAI-defined no PMI did not alter the rate of death/MI among no-PMI patients. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  17. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs.

    PubMed Central

    Heyndrickx, G R; Millard, R W; McRitchie, R J; Maroko, P R; Vatner, S F

    1975-01-01

    The time relationship for recovery of mechanical function, the intramyocardial electrogram and coronary flow after brief periods of regional myocardial ischemia, was studied in conscious dogs. Total left vemtricular (LV) function was assessed with measurements of LV systolic and diastolic pressures, rate of change of LV pressure (dP/dt), and dP/dt/P. Regional LV function was assessed with measurements of regional segment length and velocity of shortening. An implanted hydraulic occluder on either the left anterior descending or circumflex coronary artery was inflated for 5- and 15-min periods on separate days. A 5-min occlusion depressed overall LV function transiently, but just before release of occlusion overall function had nearly returned to control. At this time regional function in the ischemic zone was still depressed to the point of absent shorteining or paradoxical motion during systole and was associated with marked ST segment elevation (+ 10 +/- 2.2 mV) at the site where function was measured. With release of occlusion and reperfusion the intramyocardial electrogram returned to normal within 1 min, and reactive hyperemia subsided by 5-10 min. In contrast to the rapid return to preocclusion levels for coronary flow and the electrogram, regional mechanical function remained depressed for over 3 h. A 15-min coronary occlusion resulted in an even more prolonged (greater than 6 h) derangement of function in the ischemic zone. Thus, brief periods of coronary occlusion result in prolonged impairement of regional myocardial function which could not have been predicted from the rapid return of the electrogram and coronary flow. These observations indicate that brief interruptions of coronary flow result either in a prolonged period of local ischemia or that alterations of mechanical induced by ischemia far outlast the repayment of the oxygen debt. PMID:1159098

  18. Intraventricular flow alterations due to dyssynchronous wall motion

    NASA Astrophysics Data System (ADS)

    Pope, Audrey M.; Lai, Hong Kuan; Samaee, Milad; Santhanakrishnan, Arvind

    2015-11-01

    Roughly 30% of patients with systolic heart failure suffer from left ventricular dyssynchrony (LVD), in which mechanical discoordination of the ventricle walls leads to poor hemodynamics and suboptimal cardiac function. There is currently no clear mechanistic understanding of how abnormalities in septal-lateral (SL) wall motion affects left ventricle (LV) function, which is needed to improve the treatment of LVD using cardiac resynchronization therapy. We use an experimental flow phantom with an LV physical model to study mechanistic effects of SL wall motion delay on LV function. To simulate mechanical LVD, two rigid shafts were coupled to two segments (apical and mid sections) along the septal wall of the LV model. Flow through the LV model was driven using a piston pump, and stepper motors coupled to the above shafts were used to locally perturb the septal wall segments relative to the pump motion. 2D PIV was used to examine the intraventricular flow through the LV physical model. Alterations to SL delay results in a reduction in the kinetic energy (KE) of the flow field compared to synchronous SL motion. The effect of varying SL motion delay from 0% (synchronous) to 100% (out-of-phase) on KE and viscous dissipation will be presented. This research was supported by the Oklahoma Center for Advancement of Science and Technology (HR14-022).

  19. Acute Myocardial Infarction Due to Spontaneous Dissection of the Right Coronary Artery in a Young Male

    SciTech Connect

    Papadopoulos, Dimitris P. Moyssakis, Ioannis; Perakis, Alexandros; Athanasiou, Andreas; Anagnostopoulou, Sophia; Benos, Ioannis; Votteas, Vassilios E.

    2004-09-15

    Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction. We report a case of a 33-year-old male who presented with an acute inferior myocardial infarction. Coronary arteriography performed 3 hours after the episode revealed a dissection involving the middle segment of right coronary artery. Because of a spiral form of dissection and the TIMI 3 flow grade, our patient was treated medically and repeat coronary angiography 6 months later was decided.

  20. Acute myocardial infarction following blunt chest trauma due to sea traffic accident.

    PubMed

    Vincelj, Josip; Sokol, Ivan; Samodol, Ante; Grubisić-Cabo, Robert

    2007-09-14

    Myocardial infarction as a complication of blunt chest trauma has been reported most commonly in victims of car accidents. Other cases have been very rarely reported. To our knowledge, sea traffic accident as the cause of coronary artery injury has not been described. The authors report on a rare case of acute anterior wall myocardial infarction in a 60-year-old woman following blunt chest trauma caused by sea traffic accident.

  1. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994.

    PubMed

    Rosamond, W D; Chambless, L E; Folsom, A R; Cooper, L S; Conwill, D E; Clegg, L; Wang, C H; Heiss, G

    1998-09-24

    To clarify the determinants of contemporary trends in mortality from coronary heart disease (CHD), we conducted surveillance of hospital admissions for myocardial infarction and of in-hospital and out-of-hospital deaths due to CHD among 35-to-74-year-old residents of four communities of varying size in the United States (a total of 352,481 persons in 1994). Between 1987 and 1994, we estimate that there were 11,869 hospitalizations for myocardial infarction (on the basis of 8572 hospitalizations sampled) and 3407 fatal coronary events (3023 sampled). The largest average annual decrease in mortality due to CHD occurred among white men (change in mortality, -4.7 percent; 95 percent confidence interval, -2.2 to -7.1 percent), followed by white women (-4.5 percent; 95 percent confidence interval, -0.7 to -8.2 percent), black women (-4.1 percent; 95 percent confidence interval, -10.3 to +2.5 percent), and black men (-2.5 percent; 95 percent confidence interval, -6.9 to +2.2 percent). Overall, in-hospital mortality from CHD fell by 5.1 percent per year, whereas out-of-hospital mortality declined by 3.6 percent per year. There was no evidence of a decline in the incidence of hospitalization for a first myocardial infarction among either men or women; in fact, such hospital admissions increased by 7.4 percent per year (95 percent confidence interval for the change, +0.5 to +14.8 percent) among black women and 2.9 percent per year (95 percent confidence interval, -3.6 to +9.9 percent) among black men. Rates of recurrent myocardial infarction decreased, and survival after myocardial infarction improved. From 1987 to 1994, we observed a stable or slightly increasing incidence of hospitalization for myocardial infarction. Nevertheless, there were significant annual decreases in mortality from CHD. The decline in mortality in the four communities we studied may be due largely to improvements in the treatment and secondary prevention of myocardial infarction.

  2. Cardiac-specific overexpression of catalase attenuates paraquat-induced myocardial geometric and contractile alteration: role of ER stress.

    PubMed

    Ge, Wei; Ge, We; Zhang, Yingmei; Han, Xuefeng; Ren, Jun

    2010-12-15

    Paraquat, a quaternary nitrogen herbicide, is a highly toxic pro-oxidant that causes multiorgan failure including that of the heart via generation of reactive oxygen species, although the underlying mechanism has not been well elucidated. This study examined the influence of cardiac-specific overexpression of catalase, an antioxidant detoxifying H(2)O(2), on paraquat-induced myocardial geometric and functional alterations, with a focus on ER stress. FVB and catalase transgenic mice were administered paraquat for 48h. Myocardial geometry, contractile function, apoptosis, and ER stress were evaluated using echocardiography, edge detection, caspase-3 activity, and immunoblotting. Our results revealed that paraquat treatment significantly enlarged left ventricular (LV) end diastolic and systolic diameters; increased LV mass and resting myocyte length; reduced fractional shortening, cardiomyocyte peak shortening, and maximal velocity of shortening/relengthening; and prolonged relengthening duration in the FVB group. Whereas the catalase transgene itself did not alter myocardial geometry and function, it mitigated or significantly attenuated paraquat-elicited myocardial geometric and functional changes. Paraquat promoted overt apoptosis and ER stress as evidenced by increased caspase-3 activity, apoptosis, and ER stress markers including Bax, Bcl-2, GADD153, calregulin, and phosphorylated JNK, IRE1α, and eIF2α; all were ablated by the catalase transgene. Paraquat-induced cardiomyocyte dysfunction was mitigated by the ER stress inhibitor tauroursodeoxycholic acid. Moreover, the JNK inhibitor SP600125 reversed paraquat-induced ER stress as evidenced by enhanced GADD153 and IRE1α phosphorylation. Taken together, these data revealed that catalase may rescue paraquat-induced myocardial geometric and functional alteration possibly by alleviating JNK-mediated ER stress.

  3. Cardiac-Specific Overexpression of Catalase Attenuates Paraquat-Induced Myocardial Geometric and Contractile Alteration: Role of ER Stress

    PubMed Central

    Ge, We; Zhang, Yingmei; Han, Xuefeng; Ren, Jun

    2010-01-01

    Paraquat, a quarternary nitrogen herbicide, is a highly toxic prooxidant resulting in multi-organ failure including the heart via generation of reactive oxygen species although the underlying mechanism has not been well elucidated. This study examined the influence of cardiac-specific overexpression of catalase, an antioxidant detoxifying H2O2, on paraquat-induced myocardial geometric and functional alterations, with a focus on ER stress. FVB and catalase transgenic mice were administrated paraquat for 48 hrs. Myocardial geometry, contractile function, apoptosis, and ER stress were evaluated using echocardiography, edge-detection, caspase-3 activity and immunoblotting. Our results revealed that paraquat treatment significantly enlarged LV end-diastolic and systolic diameters, increased LV mass and resting myocyte length, reduced fractional shortening, cardiomyocyte peak shortening, maximal velocity of shortening/relengthening and prolonged relengthening duration in FVB group. While catalase transgene itself did not alter myocardial geometry and function, it mitigated or significantly attenuated paraquat-elicited myocardial geometric and functional changes. Paraquat promoted overt apoptosis and ER stress as evidenced by increased caspase-3 activity, apoptosis and ER stress markers including Bax, Bcl-2, GADD153, calregulin and phosphorylation of JNK, IRE1α and eIF2α, all were ablated by catalase transgene. Paraquat-induced cardiomyocyte dysfunction was mitigated by the ER stress inhibitor tauroursodeoxycholic acid. Moreover, the JNK inhibitor SP600125 reversed paraquat-induced ER stress as evidenced by enhanced GADD153 and IRE1α phosphorylation. Taken together, these data revealed that catalase may rescue paraquat-induced myocardial geometric and functional alteration possibly via alleviating JNK-mediated ER stress. PMID:20937379

  4. Atlas-based quantification of cardiac remodeling due to myocardial infarction.

    PubMed

    Zhang, Xingyu; Cowan, Brett R; Bluemke, David A; Finn, J Paul; Fonseca, Carissa G; Kadish, Alan H; Lee, Daniel C; Lima, Joao A C; Suinesiaputra, Avan; Young, Alistair A; Medrano-Gracia, Pau

    2014-01-01

    Myocardial infarction leads to changes in the geometry (remodeling) of the left ventricle (LV) of the heart. The degree and type of remodeling provides important diagnostic information for the therapeutic management of ischemic heart disease. In this paper, we present a novel analysis framework for characterizing remodeling after myocardial infarction, using LV shape descriptors derived from atlas-based shape models. Cardiac magnetic resonance images from 300 patients with myocardial infarction and 1991 asymptomatic volunteers were obtained from the Cardiac Atlas Project. Finite element models were customized to the spatio-temporal shape and function of each case using guide-point modeling. Principal component analysis was applied to the shape models to derive modes of shape variation across all cases. A logistic regression analysis was performed to determine the modes of shape variation most associated with myocardial infarction. Goodness of fit results obtained from end-diastolic and end-systolic shapes were compared against the traditional clinical indices of remodeling: end-diastolic volume, end-systolic volume and LV mass. The combination of end-diastolic and end-systolic shape parameter analysis achieved the lowest deviance, Akaike information criterion and Bayesian information criterion, and the highest area under the receiver operating characteristic curve. Therefore, our framework quantitatively characterized remodeling features associated with myocardial infarction, better than current measures. These features enable quantification of the amount of remodeling, the progression of disease over time, and the effect of treatments designed to reverse remodeling effects.

  5. Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts.

    PubMed

    Rorabaugh, Boyd R; Seeley, Sarah L; Bui, Albert D; Sprague, Lisanne; D'Souza, Manoranjan S

    2016-02-15

    Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg(-1)·day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart. Copyright © 2016 the American Physiological Society.

  6. Exploring spatial trends in Canadian incidence of hospitalization due to myocardial infarction with additional determinants of health.

    PubMed

    Caswell, J M

    2016-11-01

    To explore the presence of spatial trends among rates of hospitalization due to myocardial infarction across health regions of Canada and the associated role of additional health determinants. An ecological study was conducted using aggregate data from the Canadian Institute for Health Information for age-standardized rates of myocardial infarction hospitalizations by health region in 2013. Exploratory spatial data analyses were applied to myocardial infarction hospitalization rates including Moran's I for detecting global spatial autocorrelation. Local spatial dependence was examined using local indicators of spatial autocorrelation (LISA) to better identify the location of potential regional clusters. Linear and spatial regressions were applied to examine the role of additional health determinants. Significant spatial autocorrelation was observed for hospitalizations due to myocardial infarction for both sexes, independently and combined. This was largely present in the form of geographic disparities with cold spot clusters of low rates in the west, particularly British Columbia, and hot spot clusters of high rates moving east, especially in Ontario, Quebec, and New Brunswick. Additional disparities were observed with high rates clustered in Northern Ontario compared to clusters of low rates in Southern Ontario. Significant predictors included smoking, average income, education, and overweight or obesity and, after controlling for these, the central cold spot of low rates shifted east to Saskatchewan. The identification of spatial homogeneity suggests a necessity for better geographic-based preventive measures as determined by the varied needs of particular regions' communities. The demonstration that space matters in this context further indicates that spatial dependence should be included in additional investigations of myocardial infarction incidence and associated hospitalizations. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier

  7. Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction.

    PubMed

    Park, Ju Yeon; Lee, Sang-Hak; Shin, Min-Jeong; Hwang, Geum-Sook

    2015-01-01

    Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.

  8. Acute myocardial infarction due to coronary artery embolism in a patient with atrial fibrillation.

    PubMed

    Camaro, C; Aengevaeren, W R M

    2009-08-01

    A 66-year-old female was referred for primary coronary intervention because of acute inferior STelevation myocardial infarction. Electrocardiography also showed atrial fibrillation. Coronary angiography showed a distal occlusion of the right coronary artery. Two different wires did not pass the occlusion, but dislodged the apparent thrombus more distally. No abnormalities were seen in the course of the recanalised part of the vessel. The sequential angiographic images together with the presence of atrial fibrillation are highly suggestive of coronary embolism as the cause of the myocardial infarction. Anticoagulation and rate control strategy was initiated. The patient was discharged in good condition. (Neth Heart J 2009;17:297-9.).

  9. Acute myocardial infarction due to coronary artery embolism in a patient with atrial fibrillation

    PubMed Central

    Camaro, C.; Aengevaeren, W.R.M.

    2009-01-01

    A 66-year-old female was referred for primary coronary intervention because of acute inferior STelevation myocardial infarction. Electrocardiography also showed atrial fibrillation. Coronary angiography showed a distal occlusion of the right coronary artery. Two different wires did not pass the occlusion, but dislodged the apparent thrombus more distally. No abnormalities were seen in the course of the recanalised part of the vessel. The sequential angiographic images together with the presence of atrial fibrillation are highly suggestive of coronary embolism as the cause of the myocardial infarction. Anticoagulation and rate control strategy was initiated. The patient was discharged in good condition. (Neth Heart J 2009;17:297-9.19789700) PMID:19789700

  10. Time course alterations of myocardial endothelin-1 production during the formation of exercise training-induced cardiac hypertrophy.

    PubMed

    Iemitsu, Motoyuki; Maeda, Seiji; Otsuki, Takeshi; Goto, Katsutoshi; Miyauchi, Takashi

    2006-06-01

    Endothelin (ET)-1 is produced by endothelial cells and cardiac myocytes. ET-1 has positive inotropic and chronotropic effects on the heart and causes myocardial cell hypertrophy. Exercise training induces a physiologic cardiac hypertrophy. To study whether myocardial ET-1 is involved in the formation of exercise training-induced cardiac hypertrophy, we investigated time-course alterations of myocardial ET-1 gene expression and ET-1 peptide level in the heart of rats during a formative process of exercise training-induced cardiac hypertrophy. We used the hearts of rats that had been exercise-trained for 4 weeks (4WT) or 8 weeks (8WT) and sedentary control rats for 4 weeks (4WC) or 8 weeks (8WC). Exercise-trained rats performed treadmill running for 5 days/week (60 mins/day). Left ventricular mass index and wall thickness and stroke volume index, measured using echocardiography, in the 8WT group were significantly greater than in the 8WC group, although there were no differences between the 4WC and 4WT groups in these parameters. These results indicated that the 8WT rats developed physiologic cardiac hypertrophy, whereas the 4WT rats did not yet have cardiac hypertrophy. Myocardial ET-1 gene expression and tissue ET-1 concentration in the heart were significantly higher in the 8WT group than in the 8WC group, whereas these values did not differ between the 4WC and 4WT groups. The present study suggests that an alternation of myocardial ET-1 production corresponds with the formation of exercise training-induced cardiac hypertrophy. Therefore, the exercise training-induced change in myocardial ET-1 production may participate in a mechanism of exercise training-induced cardiac adaptation (e.g., cardiac hypertrophy).

  11. Myocardial infarction in a 17-year-old patient due to neurofibromatosis-associated coronary aneurysm.

    PubMed

    Evrengul, Harun; Kilic, Dogu I; Zungur, Mustafa; Alihanoglu, Yusuf I; Tanriverdi, Halil

    2013-06-01

    Neurofibromatosis is an autosomal dominant multi-system genetic disorder. Extra-cardiac vascular manifestations of neurofibromatosis have been previously described in many reports. However, coronary arterial involvements have been rarely described. A 17-year-old girl with neurofibromatosis presented to our institute with subacute myocardial infarction. Coronary angiogram revealed an aneurysm with thrombus in the left anterior descending artery.

  12. Pseudo-acute myocardial infarction due to transient apical ventricular dysfunction syndrome (Takotsubo syndrome).

    PubMed

    Maciel, Bruno Araújo; Cidrão, Alan Alves de Lima; Sousa, Italo Bruno Dos Santos; Ferreira, José Adailson da Silva; Messias Neto, Valdevino Pedro

    2013-03-01

    Takotsubo syndrome is characterized by predominantly medial-apical transient left ventricular dysfunction, which is typically triggered by physical or emotional stress. The present article reports the case of a 61-year-old female patient presenting with dizziness, excessive sweating, and sudden state of ill feeling following an episode involving intense emotional stress. The physical examination and electrocardiogram were normal upon admission, but the troponin I and creatine kinase-MB concentrations were increased. Acute myocardial infarction without ST segment elevation was suspected, and coronary angiography was immediately performed, which showed severe diffuse left ventricular hypokinesia, medial-apical systolic ballooning, and a lack of significant coronary injury. The patient was referred to the intensive care unit and was successfully treated with supportive therapy. As this case shows, Takotsubo syndrome might simulate the clinical manifestations of acute myocardial infarction, and coronary angiography is necessary to distinguish between both myocardial infarction and myocardial infarction in the acute stage. The present patient progressed with spontaneous resolution of the ventricular dysfunction without any sequelae.

  13. Pseudo-acute myocardial infarction due to transient apical ventricular dysfunction syndrome (Takotsubo syndrome)

    PubMed Central

    Maciel, Bruno Araújo; Cidrão, Alan Alves de Lima; Sousa, Ítalo Bruno dos Santos; Ferreira, José Adailson da Silva; Messias Neto, Valdevino Pedro

    2013-01-01

    Takotsubo syndrome is characterized by predominantly medial-apical transient left ventricular dysfunction, which is typically triggered by physical or emotional stress. The present article reports the case of a 61-year-old female patient presenting with dizziness, excessive sweating, and sudden state of ill feeling following an episode involving intense emotional stress. The physical examination and electrocardiogram were normal upon admission, but the troponin I and creatine kinase-MB concentrations were increased. Acute myocardial infarction without ST segment elevation was suspected, and coronary angiography was immediately performed, which showed severe diffuse left ventricular hypokinesia, medial-apical systolic ballooning, and a lack of significant coronary injury. The patient was referred to the intensive care unit and was successfully treated with supportive therapy. As this case shows, Takotsubo syndrome might simulate the clinical manifestations of acute myocardial infarction, and coronary angiography is necessary to distinguish between both myocardial infarction and myocardial infarction in the acute stage. The present patient progressed with spontaneous resolution of the ventricular dysfunction without any sequelae. PMID:23887762

  14. In-hospital mortality due to acute myocardial infarction. relevance of type of hospital and care provided. RECALCAR study.

    PubMed

    Bertomeu, Vicente; Cequier, Ángel; Bernal, José L; Alfonso, Fernando; Anguita, Manuel P; Muñiz, Javier; Barrabés, José A; García-Dorado, David; Goicolea, Javier; Elola, Francisco J

    2013-12-01

    To investigate the relationship between in-hospital mortality due to acute myocardial infarction and type of hospital, discharge service, and treatment provided. Retrospective analysis of 100 993 hospital discharges with a principal diagnosis of myocardial infarction in hospitals of the Spanish National Health Service. In-hospital mortality was adjusted for risk following the models of the Institute for Clinical Evaluative Sciences (Canada) and the Centers for Medicare & Medicaid Services (United States). Hospital characteristics are relevant to explain the variation in the individual probability of dying from myocardial infarction (median odds ratio: 1.3561). The risk-adjusted in-hospital mortality in cluster 3 and especially in cluster 4 hospitals (500 beds to 1000 beds and medium-high complexity) was significantly lower than in hospitals with less than 200 beds. Cluster 5 (more than 1000 beds), which includes a diverse group of hospitals, had a higher mortality rate than clusters 3 and 4. The adjusted mortality in the groups with the best and worst outcomes was 6.74% (cluster 4) and 8.49% (cluster 1), respectively. Mortality was also lower when the cardiology unit was responsible for the discharge or when angioplasty had been performed. The typology of the hospital, treatment in a cardiology unit, and percutaneous coronary intervention are significantly associated with the survival of a patient hospitalized for myocardial infarction. We recommend that the Spanish National Health Service establish health care networks that favor percutaneous coronary intervention and the participation of cardiology units in the management of patients with acute myocardial infarction. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  15. Catecholamines and myocardial contractile function during hypodynamia and with an altered thyroid hormone balance

    NASA Technical Reports Server (NTRS)

    Pruss, G. M.; Kuznetsov, V. I.; Zhilinskaya, A. A.

    1980-01-01

    The dynamics of catecholamine content and myocardial contractile function during hypodynamia were studied in 109 white rats whose motor activity was severely restricted for up to 30 days. During the first five days myocardial catecholamine content, contractile function, and physical load tolerance decreased. Small doses of thyroidin counteracted this tendency. After 15 days, noradrenalin content and other indices approached normal levels and, after 30 days, were the same as control levels, although cardiac functional reserve was decreased. Thyroidin administration after 15 days had no noticeable effect. A detailed table shows changes in 17 indices of myocardial contractile function during hypodynamia.

  16. Acute inferior myocardial infarction due to cannabis smoking in a young man.

    PubMed

    Kocabay, Gonenc; Yildiz, Mustafa; Duran, Nilufer Eksi; Ozkan, Mehmet

    2009-09-01

    Cannabis smoking, which has euphoric effects, is consistently increasing in Europe. Smoking cannabis is a rare trigger of acute myocardial infarction (MI) by inducing coronary artery spasm. Some cases who have thrombus formation in acute coronary artery and no serious atherosclerotic lesions have been reported in the literature. These cases had involved the left coronary artery. Although some cases were reported with MI after cannabis smoking, only two case reports with inferior MI after cannabis smoking were reported in the literature. The present report is of a young male patient who was affected by acute inferior MI half an hour after cannabis smoking.

  17. ST segment elevation myocardial infarction due to slow coronary flow occurring after cannabis consumption.

    PubMed

    Karabulut, Ahmet; Cakmak, Mahmut

    2010-11-01

    Slow coronary flow (SCF) is an angiographic finding defined as the slow movement of contrast throughout the coronary lumen in the absence of epicardial coronary stenosis. It has been reported that SCF can on rare occasions cause ST elevated myocardial infarction (MI). Recent studies have shown that cannabis consumption can increase the risk of coronary heart disease and can trigger acute coronary syndromes, especially in young individuals without common risk factors. Here, we present a case of inferior MI in a patient who had consumed cannabis regularly over a long period and whose coronary angiography revealed SCF.

  18. Acute Myocardial Infarction due to Polyarteritis Nodosa in a Young Female Patient.

    PubMed

    Wi, Jin; Choi, Hyun Hee; Lee, Chan Joo; Kim, Taehoon; Shin, Sanghoon; Ko, Young-Guk; Jang, Yangsoo; Park, Yong Bum; Kwon, Young Joo

    2010-04-01

    Coronary artery aneurysms are uncommon, are usually associated with atherosclerosis, and rarely involve all three major coronary arteries. The present report describes a rare case of a young female patient presenting with acute myocardial infarction (AMI). Coronary angiography revealed multiple severe aneurysmal and stenotic changes. Based on clinical feature and angiographic findings, it was strongly suspected that the patient had polyarteritis nodosa (PAN) complicated by AMI. The patient was treated with standard cardiac medications and immunosuppressive agents and has remained stable without further complications during a follow-up period of 6 months.

  19. Identifying cancer patients who alter care or lifestyle due to treatment-related financial distress.

    PubMed

    Nipp, Ryan D; Zullig, Leah L; Samsa, Gregory; Peppercorn, Jeffrey M; Schrag, Deborah; Taylor, Donald H; Abernethy, Amy P; Zafar, S Yousuf

    2016-06-01

    Cancer patients may experience financial distress as a side effect of their care. Little is known about which patients are at greatest risk for altering their care or lifestyle due to treatment-related financial distress. We conducted a cross-sectional survey study to determine which patients are at greatest risk for altering their care or lifestyle due to treatment-related financial distress. Eligible patients were adults receiving cancer treatment enrolled between June 2010 and May 2011. We grouped coping strategies as lifestyle altering or care altering. We assessed coping strategies and relationships between covariates using descriptive statistics and analysis of variance. Among 174 participants, 89% used at least one lifestyle-altering coping strategy, while 39% used a care-altering strategy. Care-altering coping strategies adopted by patients included the following: not filling a prescription (28%) and taking less medication than prescribed (23%). Lifestyle-altering strategies included the following: spending less on leisure activities (77%), spending less on basics like food and clothing (57%), borrowing money (54%), and spending savings (50%). Younger patients were more likely than older patients to use coping strategies (p < 0.001). Lower-income patients adopted care-altering strategies more than higher-income patients (p = 0.03). Participants with more education and shorter duration of chemotherapy used lifestyle-altering strategies more than their counterparts (both p < 0.05). As a means of coping with treatment-related financial distress, patients were more likely to use lifestyle-altering approaches, but more than one-third adopted potentially harmful care-altering strategies. Younger age, lower income, higher education, and shorter duration of chemotherapy were characteristics associated with greater use of coping strategies. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Prognostic Significance of Remote Myocardium Alterations Assessed by Quantitative Noncontrast T1 Mapping in ST-Segment Elevation Myocardial Infarction.

    PubMed

    Reinstadler, Sebastian J; Stiermaier, Thomas; Liebetrau, Johanna; Fuernau, Georg; Eitel, Charlotte; de Waha, Suzanne; Desch, Steffen; Reil, Jan-Christian; Pöss, Janine; Metzler, Bernhard; Lücke, Christian; Gutberlet, Matthias; Schuler, Gerhard; Thiele, Holger; Eitel, Ingo

    2017-06-09

    This study assessed the prognostic significance of remote zone native T1 alterations for the prediction of clinical events in a population with ST-segment elevation myocardial infarction (STEMI) who were treated by primary percutaneous coronary intervention (PPCI) and compared it with conventional markers of infarct severity. The exact role and incremental prognostic relevance of remote myocardium native T1 mapping alterations assessed by cardiac magnetic resonance (CMR) after STEMI remains unclear. We included 255 consecutive patients with STEMI who were reperfused within 12 h after symptom onset. CMR core laboratory analysis was performed to assess left ventricular (LV) function, standard infarct characteristics, and native T1 values of the remote, noninfarcted myocardium. The primary endpoint was a composite of death, reinfarction, and new congestive heart failure within 6 months (major adverse cardiac events [MACE]). Patients with increased remote zone native T1 values (>1,129 ms) had significantly larger infarcts (p = 0.012), less myocardial salvage (p = 0.002), and more pronounced LV dysfunction (p = 0.011). In multivariable analysis, remote zone native T1 was independently associated with MACE after adjusting for clinical risk factors (p = 0.001) or other CMR variables (p = 0.007). In C-statistics, native T1 of remote myocardium provided incremental prognostic information beyond clinical risk factors, LV ejection fraction, and other markers of infarct severity (all p < 0.05). The addition of remote zone native T1 to a model of prognostic CMR parameters (ejection fraction, infarct size, and myocardial salvage index) led to net reclassification improvement of 0.82 (95% confidence interval: 0.46 to 1.17; p < 0.001) and to an integrated discrimination improvement of 0.07 (95% confidence interval: 0.02 to 0.13; p = 0.01). In STEMI patients treated by PPCI, evaluation of remote zone alterations by quantitative noncontrast T1 mapping provided independent

  1. Acute myocardial infarction due to coronary thrombosis caused by blunt chest trauma.

    PubMed

    Treuth, Gregory M; Baibars, Motaz; Alraiyes, Abdul Hamid; Alraies, M Chadi

    2014-04-25

    A 65-year-old man presented to the emergency department following an anterior chest trauma. He had significant chest pain and chest X-ray was significant for revealed multiple rib fractures and negative. CT scan of the chest ruled out pulmonary embolism or aortic dissection. However, few hours later he developed hypotension requiring admission to medical intensive care unit and intravenous vasopressors. Further workup showed ST elevation myocardial infarction involving the anterior ECG leads. Emergent coronary angiography was performed with intervention to the mid-left anterior descending occlusion. Cardiogenic shock resolved and patient was discharged few days later. One-year follow-up with echocardiogram showed stable ischaemic cardiomyopathy with improved left ventricular ejection fraction to 50%.

  2. Impaired myocardial development resulting in neonatal cardiac hypoplasia alters postnatal growth and stress response in the heart.

    PubMed

    Drenckhahn, Jörg-Detlef; Strasen, Jette; Heinecke, Kirsten; Langner, Patrick; Yin, Kom Voy; Skole, Friederike; Hennig, Maria; Spallek, Bastian; Fischer, Robert; Blaschke, Florian; Heuser, Arnd; Cox, Timothy C; Black, Mary Jane; Thierfelder, Ludwig

    2015-04-01

    Foetal growth has been proposed to influence cardiovascular health in adulthood, a process referred to as foetal programming. Indeed, intrauterine growth restriction in animal models alters heart size and cardiomyocyte number in the perinatal period, yet the consequences for the adult or challenged heart are largely unknown. The aim of this study was to elucidate postnatal myocardial growth pattern, left ventricular function, and stress response in the adult heart after neonatal cardiac hypoplasia in mice. Utilizing a new mouse model of impaired cardiac development leading to fully functional but hypoplastic hearts at birth, we show that myocardial mass is normalized until early adulthood by accelerated physiological cardiomyocyte hypertrophy. Compensatory hypertrophy, however, cannot be maintained upon ageing, resulting in reduced organ size without maladaptive myocardial remodelling. Angiotensin II stress revealed aberrant cardiomyocyte growth kinetics in adult hearts after neonatal hypoplasia compared with normally developed controls, characterized by reversible overshooting hypertrophy. This exaggerated growth mainly depends on STAT3, whose inhibition during angiotensin II treatment reduces left ventricular mass in both groups but causes contractile dysfunction in developmentally impaired hearts only. Whereas JAK/STAT3 inhibition reduces cardiomyocyte cross-sectional area in the latter, it prevents fibrosis in control hearts, indicating fundamentally different mechanisms of action. Impaired prenatal development leading to neonatal cardiac hypoplasia alters postnatal cardiac growth and stress response in vivo, thereby linking foetal programming to organ size control in the heart. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  3. The Frequency and Significance of Silent Myocardial Ischemia Due to Hyoscine Butylbromide Use in Peripheral Angiography

    SciTech Connect

    Maher, Richard; Phillips-Hughes, Jane; Banning, Adrian; Boardman, Philip

    1999-09-15

    Purpose: Hyoscine-N-butylbromide (HB) is an anticholinergic drug used in digital subtraction angiography of the aortoiliac region because it decreases bowel gas movement artifact. HB also causes an increase in heart rate. We investigated whether this could cause silent myocardial ischemia (SMI) in susceptible patients during peripheral angiography. Methods: Thirty-six patients undergoing peripheral angiography were randomized into two groups, with 17 patients receiving 20 mg HB intraarterially during the angiogram and 19 patients receiving no drug. All patients were fitted with a Holter monitor that recorded the electrocardiogram before, during, and after the angiogram. Heart rate trends and ST segments were then analyzed. Results: Patients given HB had a statistically significant rise in heart rate compared with the control group. Although the difference was not statistically significant, two (12%) patients receiving HB had procedural ST depression compared with none in the control group. Pre- and postprocedural episodes of ST depression were common, occurring in 41% of patients receiving HB and 37% of patients receiving no drug, and were associated with an increase in heart rate. Conclusion: The infrequent episodes of procedural SMI, potentially caused by the positive chronotropic effects of HB, are probably insignificant when compared with the high frequency of SMI episodes occurring outside the procedure.

  4. Sudden death due to ventricular double rupture as a complication of inferior acute myocardial infarction

    PubMed Central

    Chen, Shi-Jian; Zhang, Chen; Meng, Qing-Tao; Peng, Yong; Chen, Mao

    2016-01-01

    Abstract Rationale: Ventricular double rupture (VDR) is a rare but lethal mechanical complication of acute myocardial infarction (AMI). The early identification and timely treatment of VDR remain challenging problems. We present a case of AMI with VDR and briefly review the characteristics and prognosis of this life-threatening disease. Patient concerns and Diagnoses: A 77-year-old male presented to our hospital with a 4-day history of severe dizziness, mild chest tightness, and dyspnea. An inferior AMI was diagnosed. Interventions and Outcomes: On the second hospital day, hypotension and a new cardiac murmur was found. The emergency echocardiographic study disclosed a ventricular septal defect. Soon after that the patient suddenly died of ventricular free-wall rupture. Lessons: In patients with AMI complicated by a septal perforation in the apical region, close to the septum-free wall junction, special attention should be paid to the great risk of VDR. Other high risk factors included advanced age, delayed reperfusion, and inferior infarction. Sufficient evaluation of the risk factors, close monitoring of vital signs, early identification of the specific symptoms, and timely treatment are the key points for the effective prediction and prevention of VDR. PMID:28033290

  5. Human immunodeficiency virus-infected subjects have no altered myocardial perfusion.

    PubMed

    Catzin-Kuhlmann, Andres; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Colín-Ramírez, Eloisa; Asz, Daniel; Aguirre, Víctor H; Herrera, Luis E; Valles, Victoria; Aguilar-Salinas, Carlos A; Sierra, Juan; Calva, Juan J

    2007-10-31

    We assessed myocardial perfusion (blinded interpretation of a single-photon emission computed tomography) and known risk factors for atherosclerosis in 105 randomly selected human immunodeficiency virus (HIV)-infected patients in a clinic in Mexico City and in a community sample of 105 age and gender-matched infection-free subjects. An abnormal scan was obtained in 4.8% of the infected and in 7.6% of the non-infected subjects. Severity of scintigraphic abnormalities was similar in both groups. In these Mexican HIV-infected patients, despite a long time of infection and of exposure to combined antiretroviral therapy and to other classical risk factors for atherosclerosis, there was no evidence of increased risk for abnormal myocardial perfusion. Dissimilar magnitude in the hazard of coronary heart disease may occur among infected populations with different frequencies of traditional predisposing factors for cardiovascular illness.

  6. Myocardial Reloading after Extracorporeal Membrane Oxygenation Alters Substrate Metabolism While Promoting Protein Synthesis

    SciTech Connect

    Kajimoto, Masaki; Priddy, Colleen M.; Ledee, Dolena; Xu, Chun; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-08-19

    Extracorporeal membrane oxygenation (ECMO) unloads the heart providing a bridge to recovery in children after myocardial stunning. Mortality after ECMO remains high.Cardiac substrate and amino acid requirements upon weaning are unknown and may impact recovery. We assessed the hypothesis that ventricular reloading modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis. Fourteen immature piglets (7.8-15.6 kg) were separated into 2 groups based on ventricular loading status: 8 hour-ECMO (UNLOAD) and post-wean from ECMO (RELOAD). We infused [2-13C]-pyruvate as an oxidative substrate and [13C6]-L-leucine, as a tracer of amino acid oxidation and protein synthesis into the coronary artery. RELOAD showed marked elevations in myocardial oxygen consumption above baseline and UNLOAD. Pyruvate uptake was markedly increased though RELOAD decreased pyruvate contribution to oxidative CAC metabolism.RELOAD also increased absolute concentrations of all CAC intermediates, while maintaining or increasing 13C-molar percent enrichment. RELOAD also significantly increased cardiac fractional protein synthesis rates by >70% over UNLOAD. Conclusions: RELOAD produced high energy metabolic requirement and rebound protein synthesis. Relative pyruvate decarboxylation decreased with RELOAD while promoting anaplerotic pyruvate carboxylation and amino acid incorporation into protein rather than to the CAC for oxidation. These perturbations may serve as therapeutic targets to improve contractile function after ECMO.

  7. Altered regional myocardial metabolism in congestive cardiomyopathy detected by positron tomography

    SciTech Connect

    Geltman, E.M.; Smith, J.L.; Beecher, D.; Ludbrook, P.A.; Ter-Pogossian, M.M.; Sobel, B.E.

    1983-05-01

    The present study was performed to determine whether positron emission tomography performed after intravenous injection of /sup 11/C-palmitate permits detection and characterization of congestive cardiomyopathy. Positron emission tomography was performed after the intravenous injection of /sup 11/C-palmitate in 13 normal subjects, 17 patients with congestive cardiomyopathy, and six patients with initial transmural myocardial infarction (defined electrocardiographically). Regionally depressed accumulation of /sup 11/C-palmitate was assessed, characterized, and quantified in seven parallel transaxial reconstructions in each patient. Patients with cardiomyopathy exhibited a larger number of discrete noncontiguous regions of accumulation of palmitate within the myocardium than either control subjects or patients with transmural infarction (17.4 +/- 0.6 (SEM) versus 11.8 +/- 0.7 versus 10.3 +/- 0.6, p less than 0.005). Similarly, regions of accumulation of palmitate were irregularly shaped in patients with cardiomyopathy, with a longer normalized perimeter than either control subjects or patients with transmural infarction (2.0 +/- 0.05 versus 1.8 +/- 0.06 versus 1.9 +/- 0.09, p less than 0.05). Regional abnormalities of the accumulation of 11C-palmitate could not be explained by regional differences in left ventricular wall motion or myocardial perfusion. Thus, marked heterogeneity of regional myocardial accumulation of 11C-palmitate is detectable and quantifiable in patients with congestive cardiomyopathy by positron emission tomography and may be particularly valuable for early detection and characterization of cardiomyopathy.

  8. Experimental Myocardial Infarction Induces Altered Regulatory T Cell Hemostasis, and Adoptive Transfer Attenuates Subsequent Remodeling

    PubMed Central

    Sharir, Rinat; Semo, Jonathan; Shimoni, Sara; Ben-Mordechai, Tamar; Landa-Rouben, Natalie; Maysel-Auslender, Sofia; Shaish, Aviv; Entin–Meer, Michal; Keren, Gad; George, Jacob

    2014-01-01

    Background Ischemic cardiac damage is associated with upregulation of cardiac pro-inflammatory cytokines, as well as invasion of lymphocytes into the heart. Regulatory T cells (Tregs) are known to exert a suppressive effect on several immune cell types. We sought to determine whether the Treg pool is influenced by myocardial damage and whether Tregs transfer and deletion affect cardiac remodeling. Methods and Results The number and functional suppressive activity of Tregs were assayed in mice subjected to experimental myocardial infarction. The numbers of splenocyte-derived Tregs in the ischemic mice were significantly higher after the injury than in the controls, and their suppressive properties were significantly compromised. Compared with PBS, adoptive Treg transfer to mice with experimental infarction reduced infarct size and improved LV remodeling and functional performance by echocardiography. Treg deletion with blocking anti-CD25 antibodies did not influence infarct size or echocardiographic features of cardiac remodeling. Conclusion Treg numbers are increased whereas their function is compromised in mice with that underwent experimental infarction. Transfer of exogeneous Tregs results in attenuation of myocardial remodeling whereas their ablation has no effect. Thus, Tregs may serve as interesting potential interventional targets for attenuating left ventricular remodeling. PMID:25436994

  9. Pronounced alterations of cellular metabolism and structure due to hyper- or hypo-osmosis.

    PubMed

    Mao, Lei; Hartl, Daniela; Nolden, Tobias; Koppelstätter, Andrea; Klose, Joachim; Himmelbauer, Heinz; Zabel, Claus

    2008-09-01

    Cell volume alteration represents an important factor contributing to the pathology of late-onset diseases. Previously, it was reported that protein biosynthesis and degradation are inversely (trans) regulated during cell volume regulation. Upon cell shrinkage, protein biosynthesis was up-regulated and protein degradation down-regulated. Cell swelling showed opposite regulation. Recent evidence suggests a decrease of protein biodegradation activity in many neurodegenerative diseases and even during aging; both also show prominent cell shrinkage. To clarify the effect of cell volume regulation on the overall protein turnover dynamics, we investigated mouse embryonic stem cells under hyper- and hypotonic osmotic conditions using a 2-D gel based proteomics approach. These conditions cause cell swelling and shrinkage, respectively. Our results demonstrate that the adaption to altered osmotic conditions and therefore cell volume alterations affects a broad spectrum of cellular pathways, including stress response, cytoskeleton remodeling and importantly, cellular metabolism and protein degradation. Interestingly, protein synthesis and degradation appears to be cis-regulated (same direction) on a global level. Our findings also support the hypothesis that protein alterations due to osmotic stress contribute to the pathology of neurodegenerative diseases due to a 60% expression overlap with proteins found altered in Alzheimer's, Huntington's, or Parkinson's disease. Eighteen percent of the proteins altered are even shared with all three disorders.

  10. Acute myocardial infarction due to left main coronary artery disease in men and women: does ST-segment elevation matter?

    PubMed Central

    Gutkowski, Wojciech; Raczyński, Grzegorz; Janion-Sadowska, Agnieszka; Gierlotka, Marek; Poloński, Lech

    2015-01-01

    Introduction Gender-specific issues regarding ST-segment elevation (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) due to unprotected left main coronary artery (ULMCA) disease were not sufficiently studied. We assessed the value of STEMI/NSTEMI initial classification on the management of men and women with acute MI due to critical stenosis or occlusion of the ULMCA. Material and methods The study group consisted of 643 consecutive patients with acute MI with the ULMCA as the infarct-related artery. Data derive from an ongoing, nationwide, multicenter, prospective, observational registry. Results Isolated ULMCA disease was more frequent in women and multivessel disease was more frequent in men in the NSTEMI group. The incidence of cardiogenic shock or pulmonary edema and cardiac arrest was higher in the STEMI group. Totally occluded ULMCA was more frequent in the STEMI group. Although the majority of patients underwent percutaneous coronary intervention (PCI), it was less frequently used in NSTEMI women and NSTEMI men. Although in-hospital and long-term mortality rates were higher in the STEMI group, there were no gender-related differences within groups. The initial ST-segment elevation was an independent predictor of in-hospital (OR = 2.37, 95% CI: 1.14–4.91, p = 0.02) and 12-month (OR = 1.52, 95% CI: 1.01–2.27, p = 0.045) mortality. Conclusions There were no gender-related differences in the management within the STEMI or NSTEMI group. Although acute myocardial infarction due to ULMCA disease is associated with high mortality in both genders, STEMI was a negative prognostic factor of in-hospital and 12-month mortality. Despite poor baseline characteristics and clinical presentation in women, female gender itself did not influence mortality. PMID:26788080

  11. Evidence Report: Risk of Crew Adverse Health Event Due to Altered Immune Response

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Sams, Clarence F.

    2013-01-01

    The Risk of Crew Adverse Health Event Due to Altered Immune Response is identified by the National Aeronautics and Space Administration (NASA) Human Research Program (HRP) as a recognized risk to human health and performance in space. The HRP Program Requirements Document (PRD) defines these risks. This Evidence Report provides a summary of the evidence that has been used to identify and characterize this risk. It is known that human immune function is altered in- and post-flight, but it is unclear at present if such alterations lead to increased susceptibility to disease. Reactivation of latent viruses has been documented in crewmembers, although this reactivation has not been directly correlated with immune changes or with observed diseases. As described in this report, further research is required to better characterize the relationships between altered immune response and susceptibility to disease during and after spaceflight. This is particularly important for future deep-space exploration missions.

  12. Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

    PubMed

    Roy, Abhro Jyoti; Stanely Mainzen Prince, P

    2013-10-01

    The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats.

  13. Transmural stretch-dependent regulation of contractile properties in rat heart and its alteration after myocardial infarction.

    PubMed

    Cazorla, Olivier; Szilagyi, Szabolcs; Le Guennec, Jean-Yves; Vassort, Guy; Lacampagne, Alain

    2005-01-01

    The "stretch-sensitization" response is essential to the regulation of heart contractility. An increase in diastolic volume improves systolic contraction. The cellular mechanisms of this modulation, the Frank-Starling law, are still uncertain. Moreover, their alterations in heart failure remains controversial. Here, using left ventricular skinned rat myocytes, we show a nonuniform stretch-sensitization of myofilament activation across the ventricular wall. Stretch-dependent Ca2+ sensitization of myofilaments increases from sub-epicardium to sub-endocardium and is correlated with an increase in passive tension. This passive tension-dependent component of myofibrillar activation is not associated with expression of titin isoforms, changes in troponin I level, and phosphorylation status. Instead, we observe that stretch induces phosphorylation of ventricular myosin light chain 2 isoform (VLC2b) in sub-endocardium specifically. Thus, VLC2b phosphorylation could act as a stretch-dependent modulator of activation tuned within normal heart. Moreover, in postmyocardial infarcted rat, the gradient of stretch-dependent Ca2+ sensitization disappears associated with a lack of VLC2b phosphorylation in sub-endocardium. In conclusion, nonuniformity is a major characteristic of the normal adult left ventricle (LV). The heterogeneous myocardial deformation pattern might be caused not only by the morphological heterogeneity of the tissue in the LV wall, but also by the nonuniform contractile properties of the myocytes across the wall. The loss of a contractile transmural gradient after myocardial infarction should contribute to the impaired LV function.

  14. Myocardial stiffness is attributed to alterations in cross-linked collagen rather than total collagen or phenotypes in spontaneously hypertensive rats.

    PubMed

    Norton, G R; Tsotetsi, J; Trifunovic, B; Hartford, C; Candy, G P; Woodiwiss, A J

    1997-09-16

    The relative contributions of increases in myocardial collagen, collagen cross-linking, and the ratio of type I to type III collagen to the stiff myocardium in hypertension were determined. We compared the action of hydralazine (0.07 mmol x kg(-1) x d(-1)) with that of captopril (0.22 mmol x kg(-1) x d(-1)) on the left ventricular end-diastolic (LVED) myocardial stiffness constant, k (g x cm(-2)) and LV myocardial interstitial characteristics in spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) control rats. LVED k (SHR, 27.9+/-1; WKY, 19.5+/-1.2; P<.01), myocardial hydroxyproline concentrations (HPRO; microg/mg dry wt) (SHR, 4.19+/-0.16; WKY, 3.17+/-0.09; P<.001), and collagen type I/III ratios (SHR, 7.1+/-0.7; WKY, 2.1+/-0.2; P<.001) were increased, whereas the percentage of myocardial collagen extracted after cyanogen bromide digestion (an index of cross-linked collagen) was decreased (SHR, 17+/-3; WKY, 41+/-4; P<.001) in SHRs compared with WKY controls. Captopril therapy reduced LVED k, myocardial HPRO, collagen type I/III, and augmented collagen solubility (43+/-4) in SHRs to values similar to those measured in WKY controls. Hydralazine therapy, despite a favorable effect on LVED k in SHRs (20.+/-1.6, P<.01 compared with untreated SHRs), failed to influence either myocardial HPRO (4.18+/-0.18) or collagen type I/III (8+/-1) but did improve collagen solubility (31+/-2). An association between alterations in LVED k and collagen solubility but not between changes in LVED k and total collagen or phenotype ratios after antihypertensive therapy in SHRs suggests that myocardial stiffness in hypertension is the consequence of an enhanced myocardial collagen cross-linking rather than of an increase in total collagen or type I phenotype concentrations.

  15. Comprehensive analysis of myocardial infarction due to left circumflex artery occlusion: comparison with infarction due to right coronary artery and left anterior descending artery occlusion

    SciTech Connect

    Huey, B.L.; Beller, G.A.; Kaiser, D.L.; Gibson, R.S.

    1988-11-01

    Forty consecutive patients with creatine kinase-MB confirmed myocardial infarction due to circumflex artery occlusion (Group 1) were prospectively evaluated and compared with 107 patients with infarction due to right coronary artery occlusion (Group 2) and 94 with left anterior descending artery occlusion (Group 3). All 241 patients underwent exercise thallium-201 scintigraphy, radionuclide ventriculography, 24 h Holter electrocardiographic (ECG) monitoring and coronary arteriography before hospital discharge and were followed up for 39 +/- 18 months. There were no significant differences among the three infarct groups in age, gender, number of risk factors, prevalence and type of prior infarction, Norris index, Killip class and frequency of in-hospital complications. Acute ST segment elevation was present in only 48% of patients in Group 1 versus 71 and 72% in Groups 2 and 3, respectively (p = 0.012), and 38% of patients with a circumflex artery-related infarct had no significant ST changes (that is, elevation or depression) on admission (versus 21 and 20% for patients in Groups 2 and 3, respectively) (p = 0.001). Abnormal R waves in lead V1 were more common in Group 1 than in Group 2 (p less than 0.003) as was ST elevation in leads I, aVL and V4 to V6 (p less than or equal to 0.048). These differences in ECG findings between Group 1 and 2 patients correlated with a significantly higher prevalence of posterior and lateral wall asynergy in the group with a circumflex artery-related infarct. Infarct size based on peak creatine kinase levels and multiple radionuclide variables was intermediate in Group 1 compared with that in Group 2 (smallest) and Group 3 (largest). During long-term follow-up, the probability of recurrent cardiac events was similar in the three infarct groups.

  16. Reduction of death rate due to acute myocardial infarction in subjects with cancers through systemic restoration of impaired nitric oxide.

    PubMed

    Ghosh, Rajeshwary; Ray, Udayan; Jana, Pradipta; Bhattacharya, Rabindra; Banerjee, Debipriya; Sinha, Asru

    2014-01-01

    Excessive aggregation of platelets at the site of plaque rupture on the coronary artery led to the formation of thrombus which is reported to precipitate acute myocardial infarction (AMI). Nitric oxide (NO) has been reported to inhibit platelet aggregation and induce thrombolysis through the in situ formation of plasmin. As the plasma NO level in AMI patients from two different ethnic groups was reduced to 0 µM (median) compared to 4.0 µM (median) in normal controls, the effect of restoration of the NO level to normal ranges on the rate of death due to AMI was determined. The restoration of plasma NO level was achieved by a sticking small cotton pad (10×25 mm) containing 0.28 mmol sodium nitroprusside (SNP) in 0.9% NaCl to the abdominal skin of the participants using non-toxic adhesive tape which was reported to normalize the plasma NO level. The participants (8,283) were volunteers in an independent study who had different kinds of cancers and did not wish to use any conventional therapy for their condition but opted to receive SNP "pad" for their condition for 3 years. The use of SNP "pad" which normalized (≈4.0 µM) the plasma NO level that in consequence reduced the death rate due to AMI, among the participants, was found to be significantly reduced compared to the death due to AMI in normal population. Our data suggested that the use of SNP "pad" significantly reduced the death due to AMI. www.ctri.nic.in CTRI/2013/12/004236.

  17. Image reconstruction in higher dimensions: myocardial perfusion imaging of tracer dynamics with cardiac motion due to deformation and respiration

    DOE PAGES

    Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.; ...

    2015-10-09

    Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variationmore » of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. We find these results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Finally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images.« less

  18. Image Reconstruction in Higher Dimensions: Myocardial Perfusion Imaging of Tracer Dynamics with Cardiac Motion Due to Deformation and Respiration

    PubMed Central

    Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.; Gullberg, Grant T.

    2015-01-01

    Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variation of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. These results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases due to redistribution of the counts over the cardiac-respiratory gates. However, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images. PMID:26450115

  19. Image reconstruction in higher dimensions: myocardial perfusion imaging of tracer dynamics with cardiac motion due to deformation and respiration

    SciTech Connect

    Shrestha, Uttam M.; Seo, Youngho; Botvinick, Elias H.; Gullberg, Grant T.

    2015-10-09

    Myocardial perfusion imaging (MPI) using slow rotating large field of view cameras requires spatiotemporal reconstruction of dynamically acquired data to capture the time variation of the radiotracer concentration. In vivo, MPI contains additional degrees of freedom involving unavoidable motion of the heart due to quasiperiodic beating and the effects of respiration, which can severely degrade the quality of the images. This work develops a technique for a single photon emission computed tomography (SPECT) that reconstructs the distribution of the radiotracer concentration in the myocardium using a tensor product of different sets of basis functions that approximately describe the spatiotemporal variation of the radiotracer concentration and the motion of the heart. In this study the temporal B-spline basis functions are chosen to reflect the dynamics of the radiotracer, while the intrinsic deformation and the extrinsic motion of the heart are described by a product of a discrete set of Gaussian basis functions. Reconstruction results are presented showing the dynamics of the tracer in the myocardium as it deforms due to cardiac beating, and is displaced due to respiratory motion. We find these results are compared with the conventional 4D-spatiotemporal reconstruction method that models only the temporal changes of the tracer activity. The higher dimensional reconstruction method proposed here improves bias, yet the signal-to-noise ratio (SNR) decreases slightly due to redistribution of the counts over the cardiac-respiratory gates. Additionally, there is a trade-off between the number of gates and the number of projections per gate to achieve high contrast images.

  20. Thyroid-induced alterations in myocardial sodium-potassium-activated adenosine triphosphatase, monovalent cation active transport, and cardiac glycoside binding.

    PubMed Central

    Curfman, G D; Crowley, T J; Smith, T W

    1977-01-01

    The effects of thyroid hormone on guinea pig myocardial NaK-ATPase activity, transmembrane monovalent cation active transport, and cardiac glycoside binding were were examined. NaK-ATPase activities of left atrial and left ventricular homogenates of control and triiodothyronine (T3)-treated animals were determined, and compared to activities of skeletal muscle and liver. T3 administration was associated with a significant increase of 18% in left atrial and left ventricular NaK-ATPase specific activities. This increment was less than that noted in skeletal muscle (+42%) and liver (+30%). To determine if enhanced NaK-ATPase activity was accompanied by increased monovalent cation active transport, in vitro 86Rb+ uptake by left atrial strips and hemidiaphragms was measured. Transition from the euthyroid to the hyperthyroid state resulted in a 68% increase in active 86Rb+ uptake by left atrium, and a 62% increase in active uptake by diaphragm. Passive 86Rb+ uptake was not affected in either tissue. Ouabain binding by atrial and ventricular homogenates of T3-treated animals was increased by 19 and 17%, respectively, compared to controls, in close agreement with thyroid-induced increments in NaK-ATPase activiey. Taken together, these results are consistent with enhanced myocardial NaK-ATPase activity and monovalent cation activt transport due to an increase in the number of functional enzyme complexes. PMID:138689

  1. Global-scale analysis of river flow alterations due to water withdrawals and reservoirs

    NASA Astrophysics Data System (ADS)

    Döll, P.; Fiedler, K.; Zhang, J.

    2009-12-01

    Global-scale information on natural river flows and anthropogenic river flow alterations is required to identify areas where aqueous ecosystems are expected to be strongly degraded. Such information can support the identification of environmental flow guidelines and a sustainable water management that balances the water demands of humans and ecosystems. This study presents the first global assessment of the anthropogenic alteration of river flow regimes, in particular of flow variability, by water withdrawals and dams/reservoirs. Six ecologically relevant flow indicators were quantified using an improved version of the global water model WaterGAP. WaterGAP simulated, with a spatial resolution of 0.5 degree, river discharge as affected by human water withdrawals and dams around the year 2000, as well as naturalized discharge without this type of human interference. Compared to naturalized conditions, long-term average global discharge into oceans and internal sinks has decreased by 2.7% due to water withdrawals, and by 0.8% due to dams. Mainly due to irrigation, long-term average river discharge and statistical low flow Q90 (monthly river discharge that is exceeded in 9 out of 10 months) have decreased by more than 10% on one sixth and one quarter of the global land area (excluding Antarctica and Greenland), respectively. Q90 has increased significantly on only 5% of the land area, downstream of reservoirs. Due to both water withdrawals and reservoirs, seasonal flow amplitude has decreased significantly on one sixth of the land area, while interannual variability has increased on one quarter of the land area mainly due to irrigation. It has decreased on only 8% of the land area, in areas downstream of reservoirs where consumptive water use is low. The impact of reservoirs is likely underestimated by our study as small reservoirs are not taken into account. Areas most affected by anthropogenic river flow alterations are the Western and Central USA, Mexico, the

  2. Longitudinal structural, functional, and cellular myocardial alterations with chronic centrifugal continuous-flow left ventricular assist device support.

    PubMed

    Muthiah, Kavitha; Humphreys, David T; Robson, Desiree; Dhital, Kumud; Spratt, Phillip; Jansz, Paul; Macdonald, Peter S; Hayward, Christopher S

    2017-07-01

    Left ventricular assist device (LVAD) support triggers adaptations within failing hearts. The HeartWare (HeartWare International, Inc., Framingham, MA) LVAD exhibits different flow profiles and afterload dependence compared with previous-generation devices, which may alter remodelling patterns. We sought to characterize myocardial adaptation to third-generation centrifugal-flow LVADs at a functional, hemodynamic, and structural level in addition to profiling transcriptomal changes using next-generation sequencing platforms. We studied 37 patients supported with the HeartWare device with paired measurements of invasive hemodynamics, serial longitudinal left ventricular (LV) and right ventricular (RV) 3-dimensional echocardiography, and N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) measurements. Paired samples for comparison of histologic myocardial cellular size and transcriptomal profiling were performed on specimens taken at pump implant and transplantation. The mean support duration was 280 ± 163 days. Mechanical unloading after HeartWare support resulted in reduced filling pressures (mean pulmonary capillary wedge pressure 27.1 ± 6.6 to 14.8 ± 5.1 mm Hg, p < 0.0001). Mean LV cardiomyocyte cell size decreased from 2,789.7 ± 671.8 to 2,290.8 ± 494.2 μm(2) (p = 0.02). LV and RV ejection fractions improved significantly (24% ± 8% to 35% ± 9% [p < 0.001] and 35% ± 11% to 40% ± 8% [p < 0.02], respectively). NT-proBNP levels fell 4.8-fold by Day 90 after support, consistent with a decrease in LV wall stress. Despite these concordant beneficial findings, the microRNA transcriptome did not change significantly across the group. Reverse remodelling is evident at multiple levels with chronic HeartWare support in the absence of changes in the microRNA transcriptome. Successful myocardial unloading is associated with a decrease in wall stress, regression of cardiomyocyte hypertrophy, and an improvement in LV and RV ejection fractions. Crown

  3. Air pollution and admissions due to ST elevation myocardial infarction-a time-series study from northwest of Iran.

    PubMed

    Ghaffari, Samad; Hajizadeh, Reza; Pourafkari, Leili; Shokouhi, Behrouz; Tajlil, Arezou; Mazani, Sarvin; Kavandi, Hadiseh; Ansari, Hosein; Nader, Nader D

    2017-10-04

    We investigated the association between the levels of air pollutants and the number of daily admissions due to ST segment elevation myocardial infarction (STEMI) in a metropolitan in the northwest of Iran. Daily concentrations of common air pollutants were obtained for the greater city of Tabriz for a period of 2 years. These reports included sulfur dioxide (SO2), nitrogen dioxide (NO2), nitric oxide (NO), nitrogen byproducts (NOx), carbon monoxide (CO), ozone (O3), and particulate matters < 10 μm (PM10). The census of admissions for STEMI was retrieved for the same period from hospital registries. The association of daily variations in air pollutant levels and the daily number of STEMI admissions were investigated in a time-series analysis. In the multi-pollutant model adjusting for long-term trend, seasonality, and temperature, a significant association was found for 1-h [NO2] and 24-h [CO]. A marginally significant association was observed for 24-h [NO2] and 8-h [CO]. The 24-h [CO] had the strongest association with the number of admissions with STEMI. Maximum 1-h concentrations of NO2 on the same day and on the prior day as well as 24-h concentrations of CO on the prior day were independently associated with increased number of STEMI admissions. However, daily concentrations of SO2, NO, O3, and PM10 were not associated with the frequency of hospital admissions for STEMI.

  4. Cardiogenic shock due to myocardial infarction: diagnosis, monitoring and treatment: a German-Austrian S3 Guideline.

    PubMed

    Werdan, Karl; Ruß, Martin; Buerke, Michael; Delle-Karth, Georg; Geppert, Alexander; Schöndube, Friedrich A

    2012-05-01

    Infarction-related cardiogenic shock (ICS) is usually due to left-ventricular pump failure. With a mortality of 30% to 80%, ICS is the most common cause of death from acute myocardial infarction. The S3 guideline presented here characterizes the current evidence-based treatment of ICS: early revascularization, treatment of shock, and intensive care treatment of multi-organ dysfunction syndrome (MODS) if it arises. The success or failure of treatment for MODS determines the outcome in ICS. Experts from eight German and Austrian specialty societies analyzed approximately 3600 publications that had been retrieved by a systematic literature search. Three interdisciplinary consensus conferences were held, resulting in the issuing of 111 recommendations and algorithms for this S3 guideline. Early revascularization of the occluded vessel, usually with a percutaneous coronary intervention (PCI), is of paramount importance. The medical treatment of shock consists of dobutamine as the inotropic agent and norepinephrine as the vasopressor of choice and is guided by a combination of pressure and flow values, or by the cardiac power index. Levosimendan can be given in addition to treat catecholamine-resistant shock. For patients with ICS who are treated with PCI, the current S3 guideline differs from the European and American myocardial infarction guidelines with respect to the recommendation for intra-aortic balloon pulsation (IABP): Whereas the former guidelines give a class I recommendation for IABP, this S3 guideline states only that IABP "can" be used in this situation, in view of the poor state of the evidence. Only for patients being treated with systemic fibrinolysis is IABP weakly recommended (IABP "should" be used in such cases). With regard to the optimal intensive-care interventions for the prevention and treatment of MODS, recommendations are given concerning ventilation, nutrition, erythrocyte-concentrate transfusion, prevention of thrombosis and stress ulcers

  5. Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.

    PubMed

    Peliciari-Garcia, Rodrigo A; Goel, Mehak; Aristorenas, Jonathan A; Shah, Krishna; He, Lan; Yang, Qinglin; Shalev, Anath; Bailey, Shannon M; Prabhu, Sumanth D; Chatham, John C; Gamble, Karen L; Young, Martin E

    2016-10-01

    A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Global-scale analysis of river flow alterations due to water withdrawals and reservoirs

    NASA Astrophysics Data System (ADS)

    Döll, P.; Fiedler, K.; Zhang, J.

    2009-07-01

    Global-scale information on natural river flows and anthropogenic river flow alterations is required to identify areas where aqueous ecosystems are expected to be strongly degraded. Such information can support the identification of environmental flow guidelines and a sustainable water management that balances the water demands of humans and ecosystems. This study presents the first global assessment of the anthropogenic alteration of river flow regimes by water withdrawals and dams, focusing in particular on the change of flow variability. Six ecologically relevant flow indicators were quantified using an improved version of the global water model WaterGAP. WaterGAP simulated, with a spatial resolution of 0.5 degree, river discharge as affected by human water withdrawals and dams, as well as naturalized discharge without this type of human interference. Mainly due to irrigation, long-term average river discharge and statistical low flow Q90 (monthly river discharge that is exceeded in 9 out of 10 months) have decreased by more than 10% on one sixth and one quarter of the global land area (excluding Antarctica and Greenland), respectively. Q90 has increased significantly on only 5% of the land area, downstream of reservoirs. Due to both water withdrawals and dams, seasonal flow amplitude has decreased significantly on one sixth of the land area, while interannual variability has increased on one quarter of the land area mainly due to irrigation. It has decreased on only 8% of the land area, in areas with little consumptive water use that are downstream of dams. Areas most affected by anthropogenic river flow alterations are the western and central USA, Mexico, the western coast of South America, the Mediterranean rim, Southern Africa, the semi-arid and arid countries of the Near East and Western Asia, Pakistan and India, Northern China and the Australian Murray-Darling Basin, as well as some Arctic rivers. Due to a large number of uncertainties related e.g. to the

  7. Myocardial perfusion and adrenergic innervation in patients with RBBB and LAfB: the effect of altering the activation sequence with right ventricular apical pacing.

    PubMed

    Simantirakis, Emmanuel N; Prassopoulos, Vasilios K; Marketou, Maria E; Chrysostomakis, Stavros I; Koukouraki, Sophia I; Lekakis, John P; Karkavitsas, Nikolaos S; Vardas, Panos E

    2003-05-01

    The aim of this study was to investigate myocardial perfusion and adrenergic innervation in patients with intraventricular conduction disturbances and to detect any changes caused by alteration of the ventricular activation sequence as a result of right ventricular apical pacing. We studied 15 patients with right bundle branch block (RBBB) and left anterior fascicular block (LAFB), while 15 healthy individuals served as controls. All patients underwent planar and single-photon emission computed tomography (SPECT) myocardial imaging after intravenous infusion of 5mCi 123I-metaiodobenzylguanidine (123I-MIBG) and a SPECT thallium201 myocardial perfusion study before and 3 months after pacemaker implantation. The heart to mediastinum ratio was calculated during the 123I-MIBG study in order to assess the global cardiac sympathetic activity and was significantly smaller in patients than in controls (P < 0.001). Patients with RBBB and LAFB revealed regional adrenergic innervation defects, mostly in the inferior and posterior walls. After a medium-term pacing period, a redistribution of 123I-MIBG uptake was detected, with aggravation of adrenergic innervation defects in the apical and posterior walls and amelioration in septal and anterior walls. Five patients showed perfusion defects that remained unchanged after pacing. Two others displayed mild myocardial perfusion defects that did not exist before pacing. In conclusion, patients with RBBB and LAFB reveal global and regional disturbances of myocardial adrenergic innervation, which shows redistribution as a result of the altered propagation of the ventricular electrical activation. To a smaller degree these patients reveal myocardial perfusion disturbances in which pacing has a limited medium-term effect.

  8. Increased mortality and morbidity due to acute myocardial infarction in a public hospital, in Feira de Santana, Bahia.

    PubMed

    Ferreira, Graça Maria Tavares de Melo; Correia, Luis Cláudio; Reis, Helena; Ferreira Filho, Carlos Brandão; Freitas, Francisco; Ferreira, Guilherme Melo; Júnior, Ivan; Oliveira, Nelson; Guimarães, Armênio Costa

    2009-08-01

    Factors related to socioeconomic status and health care quality and management may influence mortality and morbidity rates due to acute myocardial infarction (AMI). To compare mortality and morbidity in patients with AMI hospitalized in public and private hospitals. An observational study, with comparison groups. Clinical evaluation on admission, and recording of diagnostic, therapeutic and evolution data until discharge or death. Comparison of clinical characteristics by univariate analysis followed by bivariate analysis, evaluating the combination of predictors with death and morbidity (Killip> I), SPSS, version 13.0. 150 patients were evaluated, 63 (42.0%) of private hospitals and 87 (58.0%) of public hospitals, with 63.1% and 62.1% of males, aged 61.1 +/- 13.8 and 60.0 +/- 11.6 years, respectively. The mortality from AMI was 19.5% in public hospitals vs 4.8% in private hospitals (p = 0.001), and morbidity (Killip class> I) was 34.3% in public hospitals vs 15.0% in private hospitals (p = 0.012). There was a significant difference between public and private patients, due to lower family income and education (70.1% with one to two salaries vs 19.0%, p <0.001, and 49.4% of illiterates vs 6.3%, p <0.001, respectively ); late arrival at the hospital (HAT> 1 hour: 76.9% vs 48.6%, p = 0.003); and a longer period of time before being medicated (AMT > 15 minutes: 47.1% vs 8.0%; p <0.001); ICU for 8% of the patients in public hospitals vs 94% in private hospitals; and thrombolysis for 20.6% vs 54.0%, respectively (p <0.001). Mortality and morbidity were greater among public patients, which presented more serious conditions, arrived later at the hospital and received lower quality treatment.

  9. Alterations in myocardial thallium-201 distribution in patients with chronic systemic hypertension undergoing single-photon emission computed tomography

    SciTech Connect

    DePuey, E.G.; Guertler-Krawczynska, E.; Perkins, J.V.; Robbins, W.L.; Whelchel, J.D.; Clements, S.D.

    1988-08-01

    To characterize thallium-201 distribution in single-photon emission computed tomography (SPECT) cardiac images and polar bullseye maps, 100 patients with chronic systemic hypertension due to end-stage renal disease were studied and the results compared with those in 35 normotensive control subjects. Thallium-201 SPECT was performed after exercise in all control subjects and 70 hypertensive patients, and after intravenous dipyridamole in 30 patients. A frequent finding in hypertensive patients was a fixed decrease in the normal lateral-to-septal count density ratio in immediate thallium-201 SPECT images (1.02 +/- 0.10 vs 1.17 +/- 0.08 in control subjects, p less than 0.00001) and in 3-hour delayed images (1.02 +/- 0.11 vs 1.11 +/- 0.08 in control subjects, p less than 0.00001). No significant difference in count density ratio was present in patients undergoing treadmill versus diypridamole intervention. In 35 patients the count density ratio was greater than 2.0 standard deviations below the normal mean, creating the false impression of a fixed lateral defect (i.e., myocardial infarction). In 12 patients, myocardial wall thickness was measured at end-diastole by 2-dimensional echocardiography. Wall thickness was increased (greater than 11 mm) in all patients. The mean lateral-to-septal wall thickness ratio was 1.08 +/- 1.11; in no patient was the ratio less than 0.76 to indicate selective septal hypertrophy. The lateral-to-septal wall thickness and lateral-to-septal thallium-201 count density ratios correlated poorly (r = 0.43).

  10. Is the effect of job strain on myocardial infarction risk due to interaction between high psychological demands and low decision latitude? Results from Stockholm Heart Epidemiology Program (SHEEP).

    PubMed

    Hallqvist, J; Diderichsen, F; Theorell, T; Reuterwall, C; Ahlbom, A

    1998-06-01

    The objectives are to examine if the excess risk of myocardial infarction from exposure to job strain is due to interaction between high demands and low control and to analyse what role such an interaction has regarding socioeconomic differences in risk of myocardial infarction. The material is a population-based case-referent study having incident first events of myocardial infarction as outcome (SHEEP: Stockholm Heart Epidemiology Program). The analysis is restricted to males 45-64 yr of age with a more detailed analysis confined to those still working at inclusion. In total, 1047 cases and 1450 referents were included in the analysis. Exposure categories of job strain were formed from self reported questionnaire information. The results show that high demands and low decision latitude interact with a synergy index of 7.5 (95% C.I.: 1.8-30.6) providing empirical support for the core mechanism of the job strain model. Manual workers are more susceptible when exposed to job strain and its components and this increased susceptibility explains about 25-50% of the relative excess risk among manual workers. Low decision latitude may also, as a causal link, explain about 30% of the socioeconomic difference in risk of myocardial infarction. The distinction between the interaction and the causal link mechanisms identifies new etiologic questions and intervention alternatives. The specific causes of the increased susceptibility among manual workers to job strain and its components seem to be an interesting and important research question.

  11. Low recruitment due to altered settlement substrata as primary constraint for coral communities under ocean acidification.

    PubMed

    Fabricius, Katharina E; Noonan, Sam H C; Abrego, David; Harrington, Lindsay; De'ath, Glenn

    2017-09-13

    The future of coral reefs under increasing CO2 depends on their capacity to recover from disturbances. To predict the recovery potential of coral communities that are fully acclimatized to elevated CO2, we compared the relative success of coral recruitment and later life stages at two volcanic CO2 seeps and adjacent control sites in Papua New Guinea. Our field experiments showed that the effects of ocean acidification (OA) on coral recruitment rates were up to an order of magnitude greater than the effects on the survival and growth of established corals. Settlement rates, recruit and juvenile densities were best predicted by the presence of crustose coralline algae, as opposed to the direct effects of seawater CO2 Offspring from high CO2 acclimatized parents had similarly impaired settlement rates as offspring from control parents. For most coral taxa, field data showed no evidence of cumulative and compounding detrimental effects of high CO2 on successive life stages, and three taxa showed improved adult performance at high CO2 that compensated for their low recruitment rates. Our data suggest that severely declining capacity for reefs to recover, due to altered settlement substrata and reduced coral recruitment, is likely to become a dominant mechanism of how OA will alter coral reefs. © 2017 The Author(s).

  12. Experimental hyperleptinemia in neonatal rats leads to selective leptin responsiveness, hypertension, and altered myocardial function.

    PubMed

    Samuelsson, Anne-Maj; Clark, James; Rudyk, Olena; Shattock, Michael J; Bae, Sung Eun; South, Timothy; Pombo, Joaquim; Redington, Kathrine; Uppal, Esna; Coen, Clive W; Poston, Lucilla; Taylor, Paul D

    2013-09-01

    The prevalence of obesity among pregnant women is increasing. Evidence from human cohort studies and experimental animals suggests that offspring cardiovascular and metabolic function is compromised through early life exposure to maternal obesity. Previously, we reported that juvenile offspring of obese rats develop sympathetically mediated hypertension associated with neonatal hyperleptinemia. We have now addressed the hypothesis that neonatal exposure to raised leptin in the immediate postnatal period plays a causal role. Pups from lean Sprague-Dawley rats were treated either with leptin (3 mg/kg IP) or with saline twice daily from postnatal day 9 to 15 to mimic the exaggerated postnatal leptin surge observed in offspring of obese dams. Cardiovascular function was assessed by radiotelemetry at 30 days, and 2 and 12 months. In juvenile (30 days) leptin-treated rats, hearts were heavier and night-time (active period) systolic blood pressure was raised (mm Hg; mean ± SEM: male leptin-treated, 132 ± 1 versus saline-treated, 119 ± 1, n=6, P<0.05; female leptin-treated, 132 ± 2 versus saline-treated, 119 ± 1, n=6, P<0.01), and the pressor response to restraint stress and leptin challenge increased compared with saline-treated rats. Heart rate variability demonstrated an increased low:high frequency ratio in 30-day leptin-treated animals, indicative of heightened sympathetic efferent tone. Echocardiography showed altered left ventricular structure and systolic function in 30-day female leptin versus saline-treated rats. These disorders persisted to adulthood. In isolated hearts, contractile function was impaired at 5 months in male leptin-treated rats. Exogenously imposed hyperleptinemia in neonatal rats permanently influences blood pressure and cardiac structure and function.

  13. Percutaneous coronary intervention for acute myocardial infarction in a pediatric patient with coronary aneurysm and stenosis due to Kawasaki disease.

    PubMed

    Drossner, David M; Chappell, Clay; Rab, Tanveer; Kim, Dennis

    2012-06-01

    We report the case of an acutely ill 3-year-old female, with a previous medical history of Kawasaki disease, who presented to care with an acute myocardial infarction. We describe the coordinated therapies employed by pediatric and adult cardiologists aimed to establish coronary revascularization.

  14. Low-level laser irradiation alters cardiac cytokine expression following acute myocardial infarction: a potential mechanism for laser therapy.

    PubMed

    Yang, Zhikai; Wu, Yihe; Zhang, Hao; Jin, Peifeng; Wang, Wei; Hou, Jianfeng; Wei, Yingjie; Hu, Shengshou

    2011-06-01

    Low-level laser irradiation (LLLI) has the potential of exerting cardioprotective effect following myocardial infarction (MI). The authors hypothesized that LLLI could influence the expression of cardiac cytokines and contribute to the reversal of ventricular remodeling. LLLI regulates the expression of cytokines after tissue damage. However, little is known concerning the alteration of the cardiac cytokine expression profile after LLLI. MI was created by coronary ligation. The surviving rats were divided randomly into laser and control groups. 33 rats were exposed to a diode laser (635  nm, 5  mW, CW, laser, beam spot size 0.8  cm(2), 6  mW/cm(2), 150  sec, 0.8  J, 1J/cm(2)) as laser group. Another 33 rats received only coronary ligation and served as control group. 28 rats received a thoracotomy without coronary ligation (sham group). One day after laser irradiation, 5 rats from each group were sacrificed and the heart tissues were analyzed by cytokine antibody arrays. Enzyme-linked immunosorbent assay (ELISA) was performed to confirm its reliability. Two weeks after MI, cardiac function and structure were evaluated by echocardiography and histological study. Cytokine antibody array indicated 4 cytokines were significantly changed after laser therapy. ELISA confirmed that granulocyte-macrophage colony stimulating factor and fractalkine were the cytokines involved in the response to therapeutic laser irradiation. However, there was no difference in cytokine release between various groups at 2 weeks after MI. Although LLLI did not improve the damaged heart function, it did reduce the infarct area expansion. The antibody-based protein array technology was applied for screening the cytokine expression profile following MI, with or without laser irradiation. The expression of multiple cytokines was regulated in the acute phase after LLLI. Our results revealed a potential novel mechanism for applying laser therapy to the treatment of heart disease.

  15. Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction

    PubMed Central

    Teren, A.; Kirsten, H.; Beutner, F.; Scholz, M.; Holdt, L. M.; Teupser, D.; Gutberlet, M.; Thiery, J.; Schuler, G.; Eitel, I.

    2017-01-01

    Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15–25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 × 10−5), and regulation of inflammatory response (p = 1.86 × 10−3). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction. PMID:28155873

  16. [Chronic Heart Failure Due to Formation of Giant Left Ventricular Pseudoaneurysm After Painless Myocardial Infarction in a Female Patient With Diabetes].

    PubMed

    Katkova, L A; Furman, N V; Dolotovskaya, P V; Dovgalevsky, Ya P; Sakharova, N K; Panteleeva, E A; Parshina, E A

    2016-09-01

    Rupture of the free wall of the left ventricle with the formation of a false aneurysm (pseudoaneurysm, PA) - is a rare complication of acute myocardial infarction. Given the high risk of rupture of the PA and other life-threatening consequences (progressive heart failure, thromboembolic events), as well as the absence of pathognomonic signs and the difficulty in determining treatment strategy (feasibility and timing of surgery), early diagnosis of this complication appears to be especially important. We present here an overview of literature data on prevalence, specific features of diagnostics, and problems related to selection of method of treatment of PA. A case f congestive heart failure due to PA of the left ventricle as a result of painless myocardial infarction in 65-year-old patient with diabetes is also presented.

  17. Evaluation of myocardial blood flow reserve in patients with chronic congestive heart failure due to idiopathic dilated cardiomyopathy.

    PubMed

    Canetti, Menahem; Akhter, Mohammed W; Lerman, Amir; Karaalp, Ilyas S; Zell, Jason A; Singh, Harpreet; Mehra, Anilkumar; Elkayam, Uri

    2003-11-15

    This study demonstrates a significant impairment in coronary blood flow reserve in most patients with idiopathic dilated cardiomyopathy despite normal epicardial coronary arteries. This change may prevent appropriate increases in coronary blood flow and thus lead to myocardial ischemia and progression of disease. An association between decreased response to adenosine and acetylcholine supports previous observations indicating that adenosine-induced vasodilation of coronary microcirculation is dependent on endothelial nitric oxide production.

  18. ST Segment Elevation Myocardial Infarction Due to Severe Ostial Left Main Stem Stenosis in a Patient with Syphilitic Aortitis.

    PubMed

    Predescu, L M; Zarma, L; Platon, P; Postu, M; Bucsa, A; Croitoru, M; Prodan, B; Chioncel, O; Deleanu, D

    2016-01-01

    Cardiovascular manifestations of tertiary syphilis infections are uncommon, but represent an important cause of mortality and morbidity. Syphilitic aortitis is characterized by aortic regurgitation, dilatation of ascending aorta and ostial coronary artery lesions. We report a case of 36 years old man admitted to our hospital for acute anterior ST segment elevation myocardial infarction complicated with cardiogenic shock (hypotension 75/50 mmHg). Transthoracic echocardiography revealed a dilated left ventricle with severe systolic dysfunction (ejection fraction = 25%), severe mitral regurgitation, moderate aortic regurgitation and mildly dilated ascending aorta. Coronary angiography showed a severe ostial lesion of left main coronary artery which was treated by urgent stent implantation and an intra-aortic contrapulsation balloon was implanted. Blood tests for syphilitic infection were positive. The patient was discharged with treatment including benzathine penicillin. In our case, we present an acute manifestation of a syphilitic ostial left main stenosis treated by primary percutaneous coronary intervention in acute myocardial infarction. Long term follow-up of the patient is crucial as a result of potential rapid in-stent restenosis caused by continuous infection of the ascending aorta. This case is particular because it shows that syphilitic aortitis can be diagnosed in acute settings, like ST segment elevation myocardial infarction.

  19. Bark beetle-induced tree mortality alters stand energy budgets due to water budget changes

    NASA Astrophysics Data System (ADS)

    Reed, David E.; Ewers, Brent E.; Pendall, Elise; Frank, John; Kelly, Robert

    2016-10-01

    Insect outbreaks are major disturbances that affect a land area similar to that of forest fires across North America. The recent mountain pine bark beetle (D endroctonus ponderosae) outbreak and its associated blue stain fungi (Grosmannia clavigera) are impacting water partitioning processes of forests in the Rocky Mountain region as the spatially heterogeneous disturbance spreads across the landscape. Water cycling may dramatically change due to increasing spatial heterogeneity from uneven mortality. Water and energy storage within trees and soils may also decrease, due to hydraulic failure and mortality caused by blue stain fungi followed by shifts in the water budget. This forest disturbance was unique in comparison to fire or timber harvesting because water fluxes were altered before significant structural change occurred to the canopy. We investigated the impacts of bark beetles on lodgepole pine (Pinus contorta) stand and ecosystem level hydrologic processes and the resulting vertical and horizontal spatial variability in energy storage. Bark beetle-impacted stands had on average 57 % higher soil moisture, 1.5 °C higher soil temperature, and 0.8 °C higher tree bole temperature over four growing seasons compared to unimpacted stands. Seasonal latent heat flux was highly correlated with soil moisture. Thus, high mortality levels led to an increase in ecosystem level Bowen ratio as sensible heat fluxes increased yearly and latent heat fluxes varied with soil moisture levels. Decline in canopy biomass (leaf, stem, and branch) was not seen, but ground-to-atmosphere longwave radiation flux increased, as the ground surface was a larger component of the longwave radiation. Variability in soil, latent, and sensible heat flux and radiation measurements increased during the disturbance. Accounting for stand level variability in water and energy fluxes will provide a method to quantify potential drivers of ecosystem processes and services as well as lead to greater

  20. Timescales of stream bed stabilization due to altered flow and sediment regimes below dams

    NASA Astrophysics Data System (ADS)

    Salant, N.; Renshaw, C.; Magilligan, F.

    2005-12-01

    Altered flow and sediment transport regimes due to impoundment can result in significant channel bed composition changes which exacerbate the geomorphic and ecological effects of flow regulation. Using long-term discharge and cross-sectional data in combination with a two-fraction sediment transport model, we assess changes in the downstream bed of two flow-regulated rivers with equivalent dam-induced changes in flow but opposite changes in sediment flux. Supply limitation has led to incision and armoring in one case while supply excess has led to aggradation and embeddedness in the other. Under limited sediment supply, bed elevation variability decreases soon after impoundment, while excess sediment supply results in a decades-long gradual decrease in both bed elevation variability and depth of incision. Although the balance of sediment supply and transport differs between dam managements styles, both the immediate and more gradual changes can be explained within the framework of a two-fraction sediment transport model. Our results demonstrate the importance of considering bed composition on sediment transport predictions and the development of management strategies for ecosystem maintenance.

  1. Altered Local Coherence in the Default Mode Network due to Sevoflurane Anesthesia

    PubMed Central

    Deshpande, Gopikrishna; Kerssens, Chantal; Sebel, Peter Simon; Hu, Xiaoping

    2010-01-01

    Recently we introduced a robust measure, integrated local correlation (ILC), of local connectivity in the brain using fMRI data which reflects the temporal correlation of brain activity in every voxel neighborhood. The current work studies ILC in fMRI data obtained in the absence and presence of sevoflurane anesthesia (0%, 2%, and 1% end-tidal concentration, respectively) administered to healthy volunteers. ILC was determined specifically in regions of the default mode network (DMN) to address local changes in each state. In addition, a potential confound in analyses based on correlations due to signal-to-noise variations was addressed by wavelet denoising. This accommodated decreases in signal power commonly seen during anesthesia without artificially reducing derived correlations. Results showed that ILC was significantly reduced in the entire DMN during 2% sevoflurane yet recovered in the posterior and anterior cingulate cortices as well as inferior parietal cortex during 1% sevoflurane. By contrast, ILC remained attenuated prefrontally in the 1% condition, which indicates uncoupling of the frontal areas of DMN during light anesthesia. These results confirm widespread anesthetic-induced cortical suppression but also demonstrate that the local connectivity of the prefrontal cortex is rapidly reduced by sevoflurane. It remains to be seen whether these alterations arise locally as a direct consequence of anesthetic action on local neurons or are driven by distant changes in oscillations and activity elsewhere in the brain. PMID:20059988

  2. Brain death provokes very acute alteration in myocardial morphology detected by echocardiography: preventive effect of beta-blockers.

    PubMed

    Ferrera, René; Hadour, Guylaine; Tamion, Fabienne; Henry, Jean-Paul; Mulder, Paul; Richard, Vincent; Thuillez, Christian; Ovize, Michel; Derumeaux, Geneviève

    2011-03-01

    Our objective was to evaluate immediate acute changes in myocardial function during the autonomic storm of brain death (BD). Wistar rats were divided into four groups (n = 8/group): controls without any treatment, β-blocker (Esmolol®, 10 mg/kg), calcium channel blocker (Diltiazem®, 10 mg/kg), or alpha-blocker (Prazosin®, 0.3 mg/kg). Treatments were administered intravenously 5 min before BD induction. Echocardiography (ATL-5000, 8 MHz) was performed to measure left ventricular (LV) dimensions and fractional shortening at baseline, during BD induction and 5 min and 15 min after BD. In controls, BD was immediately associated with an increase in wall thickness and a decrease in LV cavity dimension. This myocardial wall hypertrophy was completely prevented by β-blockers, but not with calcium- and alpha-blockers. Extensive myocardial interstitial edema was found in all groups, except in the β-blocker group. Myocardial wall hypertrophy was also prevented during a longer follow-up of 180 min after BD in β-blocker group as opposed to controls. In conclusion, BD is associated with an immediate and severe myocardial damage related to an important interstitial edema which is prevented by β-blockers.

  3. Myocardial viability.

    PubMed Central

    Birnbaum, Y; Kloner, R A

    1996-01-01

    Left ventricular function is a major predictor of outcome in patients with coronary artery disease. Acute ischemia, postischemic dysfunction (stunning), myocardial hibernation, or a combination of these 3 are among the reversible forms of myocardial dysfunction. In myocardial stunning, dysfunction occurs despite normal myocardial perfusion, and function recovers spontaneously over time. In acute ischemia and hibernation, there is regional hypoperfusion. Function improves only after revascularization. Evidence of myocardial viability usually relies on the demonstration of uptake of various metabolic tracers, such as thallium (thallous chloride TI 201) or fludeoxyglucose F 18, by dysfunctional myocardium or by the demonstration of contractile reserve in a dysfunctional region. This can be shown as an augmentation of function during the infusion of various sympathomimetic agents. The response of ventricular segments to increasing doses of dobutamine may indicate the underlying mechanism of dysfunction. Stunned segments that have normal perfusion show dose-dependent augmentation of function. If perfusion is reduced as in hibernating myocardium, however, a biphasic response usually occurs: function improves at low doses of dobutamine, whereas higher doses may induce ischemia and, hence, dysfunction. But in patients with severely impaired perfusion, even low doses may cause ischemia. Myocardial regions with subendocardial infarction or diffuse scarring may also have augmented contractility during catecholamine infusion due to stimulation of the subepicardial layers. In these cases, augmentation of function after revascularization is not expected. Because the underlying mechanism, prognosis, and therapy may differ among these conditions, it is crucial to differentiate among dysfunctional myocardial segments that are nonviable and have no potential to regain function, hibernating or ischemic segments in which recovery of function occurs only after revascularization, and

  4. Assessing river regime alteration due to flood detention structures in dry and semi-dry regions

    NASA Astrophysics Data System (ADS)

    Yaraghi, Navid; Torabihaghighi, Ali; Ronkanen, Anna-Kaisa; Fazel, Nasim; Rossi, Pekka. M.; Klöve, Björn

    2017-04-01

    In dry and semi-dry climate, flood detention structures are used for flood control and managed aquifer recharge. These damps basin runoff response decreasing the maximum flows and increasing the runoff duration through wet seasons. In this study, a framework to quantify the role of flood detention dams in headwater tributaries on total water balance of major basin and alteration of flow pattern in the main river has been presented. The study contains four main subroutines: rainfall-runoff model, reservoir flood routing, river analysis system and seepage analysis. The flood hydrographs with different return periods are estimated based on the climatic data and geomorphology of headwater basin. River flow analysis below the flood detention structure is carried out for two unsteady flow scenarios, first with the hydrographs of natural system (as pre-impact: quick flood with significant peak flow) and second the routed hydrographs due to detention process in the reservoir (as post-impact: damped flood lower peak with longer duration time). Two sets of dynamic water surface along the river (from the location of detention structure (x=0) to the confluence point with main river (x=L) are developed based on two hydrologic conditions as results of river analysis system. The results of framework define the impact of flood detention structure by comparing the timing, magnitude and variability of flow. The Kamal Abad artificial groundwater recharge in Mahrloo Lake basin in Southern Iran was selected as case study to demonstrate the application of the created framework. Through the probability analysis, the return period for hydrological drought would be compared in pre and post impact condition. The results clearly showed how embankments influence floods in tributaries and in some cases the flow reduced significantly and disappears in tributaries.

  5. Hypercholesterolemia abrogates sevoflurane-induced delayed preconditioning against myocardial infarct in rats by alteration of nitric oxide synthase signaling.

    PubMed

    Zhang, Feng-Jiang; Ma, Lei-Lei; Wang, Wen-Na; Qian, Ling-Bo; Yang, Mei-Juan; Yu, Jing; Chen, Gang; Yu, Li-Na; Yan, Min

    2012-05-01

    The aim of the current study was to determine whether hypercholesterolemia affects the delayed sevoflurane preconditioning against myocardial ischemia-reperfusion (IR) injury and, if so, the underlying mechanism. Male Sprague-Dawley rats fed 2% cholesterol-enriched chow for 8 weeks were subjected to sevoflurane preconditioning (2.4% vol/vol, 1 h) 24 h before myocardial ischemia was induced by occluding the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. The hemodynamic parameters left ventricular developed pressure, left ventricular end-diastolic pressure, and maximal rise/fall rate of left ventricular pressure were continuously monitored, and myocardial infarct size was determined at the end of reperfusion. The protein expression of myocardial nitric oxide synthase (NOS), Bcl-2, and Bad was assessed before ischemia. We found that the left ventricular hemodynamic parameters during the whole IR procedure and the myocardial infarct size did not significantly differ between the normocholesterolemic and hypercholesterolemic control groups. The hemodynamic parameters were all markedly improved during the reperfusion period, and the myocardial infarct size was significantly reduced by delayed sevoflurane preconditioning in normocholesterolemic rats, but all of these improvements were reversed by N-(3-(aminomethyl)benzyl) acetamidine (1400W, 1 mg/kg; i.v., 10 min before ischemia), a selective inducible NOS (iNOS) inhibitor, and 5-hydroxy decanoate sodium (5 mg/kg, i.v., 10 min before ischemia), a mitochondrial ATP-dependent K⁺ channel blocker. Such cardiac improvement induced by delayed sevoflurane preconditioning did not occur in hypercholesterolemic rats and was not exacerbated by 1400W or 5-hydroxy decanoate sodium. The expression of myocardial iNOS was markedly enhanced by delayed sevoflurane preconditioning in normocholesterolemic, but not in hypercholesterolemic rats. The expression of endothelial NOS and Bad did not differ

  6. Geochemical alteration of shallow groundwater due to injection of CO2

    NASA Astrophysics Data System (ADS)

    Peter, A.; Hornbruch, G.; Beyer, M.; Lamert, H.; Heinrich, B.; Geistlinger, H. W.; Werban, U.; Dietrich, P.; Grossmann, J.; Garbe-Schoenberg, C.; Dahmke, A.

    2011-12-01

    Leakage from subsurface storage sites is one of the main concerns connected with CCS technology. One potential risk associated with CO2 leaking from storage sites is the geochemical alteration of shallow groundwater systems causing pH decrease, mineral dissolution and potential mobilization of heavy metals. As on the one hand leakages into drinking water aquifers within pilot scale CCS projects seem to be very unlikely, but on the other hand a sound risk assessment before implementing CCS is absolutely necessary, the aim of the presented project is to emulate a leakage of CO2 by injecting gaseous CO2 into a shallow aquifer. Two main objectives were pursued by the injection test: firstly, to gain insight into potential geochemical reactions taking place in groundwater systems due to CO2 leakage, especially under the focus whether reactive transport models are capable to predict these reactions. Secondly, to develop and apply different monitoring methods. The focus of the present paper is on the first objective. The test site is located at a former military air field in northeastern Germany. Geologically, the subsurface consists of pleistocene sediments including sandur deposits as well as moraine and basin sediments. The aquifer of concern extends between 10 and 19m below surface and consists mainly of medium to coarse sands free of carbonates. Groundwater flow velocities vary locally within <0.1m/d up to 0.3m/d. At three injection wells at distances of 5m 30L CO2/min (i.e. 54g CO2/min) in total were injected at a depth of 18m below surface. The injection was operated continuously for 10 days in March and April 2011. Groundwater monitoring was performed at 34 monitoring wells covering an area of 80m x 40m. 16 multi-level wells allow for groundwater sampling at three different depths. Ten groundwater sampling campaigns were carried out, two before, three during and five after the injection test. The main results obtained so far concerning the geochemical alteration

  7. DETECTING STREAM INVERTEBRATE COMMUNITY ALTERATION DUE TO MID TO LOW LEVELS OF WATERSHED LANDSCAPE MODIFICATION

    EPA Science Inventory

    As part of an investigation into the effects of watershed landscape alteration on stream ecosystems, quantitative invertebrate samples were collected from riffles in 26 second and third order south shore Lake Superior streams. Nonmetric multidimensional scaling (NMDS) ordination ...

  8. Alteration of dentin-enamel mechanical properties due to dental whitening treatments.

    PubMed

    Zimmerman, B; Datko, L; Cupelli, M; Alapati, S; Dean, D; Kennedy, M

    2010-05-01

    The mechanical properties of dentin and enamel affect the reliability and wear properties of a tooth. This study investigated the influence of clinical dental treatments and procedures, such as whitening treatments or etching prior to restorative procedures. Both autoclaved and non-autoclaved teeth were studied in order to allow for both comparison with published values and improved clinical relevance. Nanoindentation analysis with the Oliver-Pharr model provided elastic modulus and hardness across the dentin-enamel junction (DEJ). Large increases were observed in the elastic modulus of enamel in teeth that had been autoclaved (52.0 GPa versus 113.4 GPa), while smaller increases were observed in the dentin (17.9 GPa versus 27.9 GPa). Likewise, there was an increase in the hardness of enamel (2.0 GPa versus 4.3 GPa) and dentin (0.5 GPa versus 0.7 GPa) with autoclaving. These changes suggested that the range of elastic modulus and hardness values previously reported in the literature may be partially due to the sterilization procedures. Treatment of the exterior of non-autoclaved teeth with Crest Whitestrips, Opalescence or UltraEtch caused changes in the mechanical properties of both the enamel and dentin. Those treated with Crest Whitestrips showed a reduction in the elastic modulus of enamel (55.3 GPa to 32.7 GPa) and increase in the elastic modulus of dentin (17.2 GPa to 24.3 GPa). Opalescence treatments did not significantly affect the enamel properties, but did result in a decrease in the modulus of dentin (18.5 GPa to 15.1 GPa). Additionally, as expected, UltraEtch treatment decreased the modulus and hardness of enamel (48.7 GPa to 38.0 GPa and 1.9 GPa to 1.5 GPa, respectively) and dentin (21.4 GPa to 15.0 GPa and 1.9 GPa to 1.5 GPa, respectively). Changes in the mechanical properties were linked to altered protein concentration within the tooth, as evidenced by fluorescence microscopy and Fourier transform infrared spectroscopy.

  9. Alteration of Dentin-Enamel Mechanical Properties Due to Dental Whitening Treatments

    PubMed Central

    Zimmerman, B.; Datko, L.; Cupelli, M.; Alapati, S.; Dean, D.; Kennedy, M.

    2010-01-01

    The mechanical properties of dentin and enamel affect the reliability and wear properties of a tooth. This study investigated the influence of clinical dental treatments and procedures, such as whitening treatments or etching prior to restorative procedures. Both autoclaved and non-autoclaved teeth were studied in order to allow for both comparison with published values and improved clinical relevance. Nanoindentation analysis with the Oliver-Pharr model provided elastic modulus and hardness across the dentin-enamel junction (DEJ). Large increases were observed in the elastic modulus of enamel in teeth that had been autoclaved (52.0GPa versus 113.4GPa), while smaller increases were observed in the dentin (17.9GPa versus 27.9GPa). Likewise, there was an increase in the hardness of enamel (2.0GPa versus 4.3GPa) and dentin (0.5GPa versus 0.7GPa) with autoclaving. These changes suggested that the range of elastic modulus and hardness values previously reported in literature may be partially due to the sterilization procedures. Treatment of the exterior of non-autoclaved teeth with Crest Whitestrips™, Opalescence™ or UltraEtch™ caused changes in the mechanical properties of both the enamel and dentin. Those treated with Crest Whitestrips™ showed a reduction in the elastic modulus of enamel (55.3GPa to 32.7GPa) and increase in the elastic modulus of dentin (17.2GPa to 24.3GPa). Opalescence™ treatments did not significantly affect the enamel properties, but did result in a decrease in modulus of dentin (18.5GPa to 15.1GPa). Additionally, as expected, UltraEtch™ treatment decreased the modulus and hardness of enamel (48.7GPa to 38.0GPa and 1.9GPa to 1.5GPa, respectively) and dentin (21.4GPa to 15.0GPa and 1.9GPa to 1.5GPa, respectively). Changes in the mechanical properties were linked to altered protein concentration within the tooth, as evidenced by fluorescence microscopy and Fourier transform infrared spectroscopy. PMID:20346902

  10. Are Amygdalar Volume Alterations in Children with Tourette Syndrome Due to ADHD Comorbidity?

    ERIC Educational Resources Information Center

    Ludolph, Andrea G.; Pinkhardt, Elmar H.; van Elst, Ludger Tebartz; Libal, Gerhard; Ludolph, Albert C.; Fegert, Jorg M.; Kassubek, Jan

    2008-01-01

    Recent studies have shown that changes in the basal ganglia circuitry and limbic loops may play an important role both in Tourette syndrome (TS) and attention-deficit-hyperactivity disorder (ADHD). This study aimed to investigate in vivo possible morphological alterations of the amygdala as a key component of the limbic system. Amygdalar and total…

  11. Are Amygdalar Volume Alterations in Children with Tourette Syndrome Due to ADHD Comorbidity?

    ERIC Educational Resources Information Center

    Ludolph, Andrea G.; Pinkhardt, Elmar H.; van Elst, Ludger Tebartz; Libal, Gerhard; Ludolph, Albert C.; Fegert, Jorg M.; Kassubek, Jan

    2008-01-01

    Recent studies have shown that changes in the basal ganglia circuitry and limbic loops may play an important role both in Tourette syndrome (TS) and attention-deficit-hyperactivity disorder (ADHD). This study aimed to investigate in vivo possible morphological alterations of the amygdala as a key component of the limbic system. Amygdalar and total…

  12. Alterations in myocardial perfusion during exercise after isosorbide dinitrate infusion in patients with coronary disease: assessment by thallium-201 scintigraphy

    SciTech Connect

    Tono, I.; Satoh, S.; Kanaya, T.; Komatani, A.; Takahashi, K.; Tsuiki, K.; Yasui, S.

    1986-03-01

    We studied the effect of intravenous isosorbide dinitrate (ISDN) on myocardial perfusion of patients with coronary artery disease, by using exercise thallium-201 (TI-201) myocardial scintigraphy. A control study was conducted initially to assess regional myocardial perfusion rate. Left ventricular myocardium was divided into six parts: anterior, lateral, apical, inferior, posterior, and septal segments. The segmental myocardial perfusion was characterized according to TI-201 initial uptake index (IUI) of relative distribution and redistribution index (RDI) of TI-201 washout. The normal limit of IUI and RDI was established from the data of 17 persons with normal coronary arteries, and then the IUI less than or equal to 84% and the RDI greater than or equal to 1.12 was defined as abnormal. Based on IUI and RDI, each segment was characterized into three types: A type = IUI less than or equal to 84%, RDI greater than or equal to 1.12; B type = IUI less than or equal to 84%, RDI less than 1.12; and C type = IUI greater than 84%, RDI less than 1.12. ISDN was given as a dose of 0.1 mg/kg/hr, and then treadmill testing was repeated for the same duration of exercise time using the same protocol as in the control period. The segments of A type showed a significant improvement in IUI and RDI after receiving ISDN infusion, while the B and C type segments showed no change. It was also shown that the improvement of IUI and RDI of the A type segments was not as marked in multivessel disease as in cases of single-vessel disease.

  13. Quantitative proteomic changes during post myocardial infarction remodeling reveals altered cardiac metabolism and Desmin aggregation in the infarct region.

    PubMed

    Datta, Kaberi; Basak, Trayambak; Varshney, Swati; Sengupta, Shantanu; Sarkar, Sagartirtha

    2017-01-30

    Myocardial infarction is one of the leading causes of cardiac dysfunction, failure and sudden death. Post infarction cardiac remodeling presents a poor prognosis, with 30%-45% of patients developing heart failure, in a period of 5-25years. Oxidative stress has been labelled as the primary causative factor for cardiac damage during infarction, however, the impact it may have during the process of post infarction remodeling has not been well probed. In this study, we have implemented iTRAQ proteomics to catalogue proteins and functional processes, participating both temporally (early and late phases) and spatially (infarct and remote zones), during post myocardial infarction remodeling of the heart as functions of the differential oxidative stress manifest during the remodeling process. Cardiac metabolism was the dominant network to be affected during infarction and the remodeling time points considered in this study. A distinctive expression pattern of cytoskeletal proteins was also observed with increased remodeling time points. Further, it was found that the cytoskeletal protein Desmin, aggregated in the infarct zone during the remodeling process, mediated by the protease Calpain1. Taken together, all of these data in conjunction may lay the foundation to understand the effects of oxidative stress on the remodeling process and elaborate the mechanism behind the compromised cardiac function observed during post myocardial infarction remodeling.

  14. Alterations in lung clearance mechanisms due to single and repeated nitrogen dioxide exposures in the rabbit

    SciTech Connect

    Vollmuth, T.A.

    1986-01-01

    Tracheobronchial mucociliary clearance was assessed following single, two-hour exposures to either 0.3, 1.0, 3.0, or 10.0 ppm NO/sub 2/, or 14 daily two hour exposures to 0.3, 1.0, 3.0 ppm NO/sub 2/. No significant changes in the mean residence time of tracer particles in the tracheobronchial region were produced under any exposure condition, indicating no effect upon mucociliary clearance. Macrophage functional properties were examined in vitro at select times following single, two hour in vivo exposures to 1.0 and 10.0 ppm NO/sub 2/. Macrophage number and viability were not affected; however, significant dose-related differences in phagocytosis and mobility were observed. These changes were associated with altered in vivo alveolar clearance patterns. Additional studies examined the effects of in vitro exposure to nitrite and hydrogen ion, two known NO/sub 2/ reaction products in the lung, on macrophage phagocytosis. While hydrogen ion had no effect at the levels used, nitrate was shown to enhance phagocytosis. These results demonstrate that alveolar clearance and macrophage function are altered by short-term NO/sub 2/ exposure at realistic, environmental levels. These data also provide insight into the mechanisms of NO/sub 2/-induced alteration in lung clearance pathways.

  15. Risk of Crew Adverse Health Event Due to Altered Immune Response

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Kunz, Hawley; Sams, Clarence F.

    2015-01-01

    Determining the effect of space travel on the human immune system has proven to be extremely challenging. Limited opportunities for in-flight studies, varying mission durations, technical and logistical obstacles, small subject numbers, and a broad range of potential assays have contributed to this problem. Additionally, the inherent complexity of the immune system, with its vast array of cell populations, sub-populations, diverse regulatory molecules, and broad interactions with other physiological systems, makes determining precise variables to measure very difficult. There is also the challenge of determining the clinical significance of any observed immune alterations. Will such a change lead to disease, or is it a transient subclinical observation related to short-term stress? The effect of this problem may be observed by scanning publications associated with immunity and spaceflight, which began to appear during the 1970s. Although individually they are each valid studies, the comprehensive literature to date suffers from widely varying sampling methods and assay techniques, low subject counts, and sometimes a disparate focus on narrow aspects of immunity. The most clinically relevant data are derived from in-flight human studies, which have demonstrated altered cell-mediated immunity and reactivation of latent herpes viruses. Much more data are available from post-flight testing of humans, with clear evidence of altered cytokine production patterns, altered leukocyte distribution, continued latent viral reactivation, and evidence of dramatically altered virus-specific immunity. It is unknown if post-flight assessments relate to the in-flight condition or are a response to landing stress and readaptation. In-flight culture of cells has clearly demonstrated that immune cells are gravity-sensitive and display altered functional characteristics. It is unknown if these data are related to in vivo immune cell function or are an artifact of microgravity culture

  16. Alteration of interleaflet coupling due to compounds displaying rapid translocation in lipid membranes

    PubMed Central

    Reigada, Ramon

    2016-01-01

    The spatial coincidence of lipid domains at both layers of the cell membrane is expected to play an important role in many cellular functions. Competition between the surface interleaflet tension and a line hydrophobic mismatch penalty are conjectured to determine the transversal behavior of laterally heterogeneous lipid membranes. Here, by a combination of molecular dynamics simulations, a continuum field theory and kinetic equations, I demonstrate that the presence of small, rapidly translocating molecules residing in the lipid bilayer may alter its transversal behavior by favoring the spatial coincidence of similar lipid phases. PMID:27596355

  17. Phenotypic reversion in analbuminemic rats due to an altered splicing mechanism

    PubMed Central

    Esumi, Hiroyasu; Sugimura, Takashi

    2007-01-01

    Serum albumin is regarded as an important and indispensable protein, but analbuminemic rats established by Sumi Nagase in 1977 seems to exhibit few symptoms in spite of an almost total lack of albumin in the serum. The albumin gene of analbuminemic rats was found to have a seven-base-pair deletion in an intron, close to exon-intron junction, resulting in the formation of non-functional mRNA in hepatocytes. Immunostaining for albumin was negative in young analbuminemic rat hepatocytes, but a significant number of immunoreactive hepatocytes were observed in aged rats. The incidence of immunoreactive hepatocytes increased with aging. Surprisingly, many immunoreactive hepatocytes were observed after hepatocarcinogen treatment sometimes in large clusters. Albumin transcripts in analbuminemic rat liver after treatment with carcinogen, showed an altered pattern of exon-skipping. The altered albumin molecules thus synthesized accumulated in cellular organelles. Analbuminemic rats exhibited a high sensitivity in various organs to different types of carcinogens. Further challenges remain regarding the biology of analbuminemic rats. PMID:24019588

  18. Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction

    PubMed Central

    Martin, Kenneth; Turner, Elizebeth C.; Kumar, Arun H.; Browne, Tara; Caplice, Noel M.

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1lo and F4/80hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function. PMID:26407006

  19. Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction.

    PubMed

    Leblond, Anne-Laure; Klinkert, Kerstin; Martin, Kenneth; Turner, Elizebeth C; Kumar, Arun H; Browne, Tara; Caplice, Noel M

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1lo and F4/80hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function.

  20. Alteration of platelet GPVI signaling in ST-elevation myocardial infarction patients demonstrated by a combination of proteomic, biochemical, and functional approaches.

    PubMed

    Vélez, Paula; Ocaranza-Sánchez, Raymundo; López-Otero, Diego; Grigorian-Shamagian, Lilian; Rosa, Isaac; Guitián, Esteban; García-Acuña, José María; González-Juanatey, José Ramón; García, Ángel

    2016-12-22

    The platelet-specific collagen receptor glycoprotein VI (GPVI) is critical for the formation of arterial thrombosis in vivo. We analyzed GPVI-activated platelets from ST-elevation myocardial infarction (STEMI) patients and matched stable coronary artery disease (SCAD) controls in order to provide novel clues on the degree of involvement of GPVI signaling in the acute event. Firstly, platelets were isolated from systemic venous blood and activated with the GPVI specific agonist CRP (collagen-related peptide). STEMI and SCAD samples were compared by a phosphoproteomics approach. Validations were by immunoblotting in systemic and intracoronary blood from independent cohorts of patients. Twenty-six differentially regulated proteins were identified when comparing CRP-activated systemic platelets from STEMI and SCAD patients, 4 of which were selected for validation studies: PLCɣ2, G6f, SLP-76, and Dok-2. Immunoblot analyses showed these four proteins had higher tyrosine phosphorylation levels in response to CRP in platelets from STEMI patients, being these levels more pronounced at the culprit site of coronary artery occlusion. Moreover, platelet aggregation studies showed a higher response to GPVI agonists in STEMI patients compared to SCAD controls. In conclusion, we show an altered activation state of GPVI signaling in STEMI patients, confirming this receptor as a promising anti-thrombotic target for myocardial infarction.

  1. Alteration of platelet GPVI signaling in ST-elevation myocardial infarction patients demonstrated by a combination of proteomic, biochemical, and functional approaches

    PubMed Central

    Vélez, Paula; Ocaranza-Sánchez, Raymundo; López-Otero, Diego; Grigorian-Shamagian, Lilian; Rosa, Isaac; Guitián, Esteban; García-Acuña, José María; González-Juanatey, José Ramón; García, Ángel

    2016-01-01

    The platelet-specific collagen receptor glycoprotein VI (GPVI) is critical for the formation of arterial thrombosis in vivo. We analyzed GPVI-activated platelets from ST-elevation myocardial infarction (STEMI) patients and matched stable coronary artery disease (SCAD) controls in order to provide novel clues on the degree of involvement of GPVI signaling in the acute event. Firstly, platelets were isolated from systemic venous blood and activated with the GPVI specific agonist CRP (collagen-related peptide). STEMI and SCAD samples were compared by a phosphoproteomics approach. Validations were by immunoblotting in systemic and intracoronary blood from independent cohorts of patients. Twenty-six differentially regulated proteins were identified when comparing CRP-activated systemic platelets from STEMI and SCAD patients, 4 of which were selected for validation studies: PLCɣ2, G6f, SLP-76, and Dok-2. Immunoblot analyses showed these four proteins had higher tyrosine phosphorylation levels in response to CRP in platelets from STEMI patients, being these levels more pronounced at the culprit site of coronary artery occlusion. Moreover, platelet aggregation studies showed a higher response to GPVI agonists in STEMI patients compared to SCAD controls. In conclusion, we show an altered activation state of GPVI signaling in STEMI patients, confirming this receptor as a promising anti-thrombotic target for myocardial infarction. PMID:28004756

  2. Degeneration of Dopaminergic Neurons Due to Metabolic Alterations and Parkinson’s Disease

    PubMed Central

    Song, Juhyun; Kim, Jongpil

    2016-01-01

    The rates of metabolic diseases, such as type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease (CVD), markedly increase with age. In recent years, studies have reported an association between metabolic changes and various pathophysiological mechanisms in the central nervous system (CNS) in patients with metabolic diseases. Oxidative stress and hyperglycemia in metabolic diseases lead to adverse neurophysiological phenomena, including neuronal loss, synaptic dysfunction, and improper insulin signaling, resulting in Parkinson’s disease (PD). In addition, several lines of evidence suggest that alterations of CNS environments by metabolic changes influence the dopamine neuronal loss, eventually affecting the pathogenesis of PD. Thus, we reviewed recent findings relating to degeneration of dopaminergic neurons during metabolic diseases. We highlight the fact that using a metabolic approach to manipulate degeneration of dopaminergic neurons can serve as a therapeutic strategy to attenuate pathology of PD. PMID:27065205

  3. Altered myocardial glucose utilization and the reverse mismatch pattern on rubidium-82 perfusion/F-18-FDG PET during the sub-acute phase following reperfusion of acute anterior myocardial infarction.

    PubMed

    Anselm, Daniel D; Anselm, Anjali H; Renaud, Jennifer; Atkins, Harold L; de Kemp, Robert; Burwash, Ian G; Williams, Kathryn A; Guo, Ann; Kelly, Cathy; Dasilva, Jean; Beanlands, Rob S B; Glover, Christopher A

    2011-08-01

    Reperfused myocardium post-acute myocardial infarction (AMI) may have altered metabolism with implications for therapy response and function recovery. We explored glucose utilization and the "reverse mismatch" (RMM) pattern (decreased F-18-fluorodeoxyglucose (FDG) uptake relative to perfusion) in patients who underwent mechanical reperfusion with percutaneous coronary intervention (PCI) for AMI. Thirty-one patients with anterior wall AMI treated with acute reperfusion, with left ventricular ejection fraction ≤45%, underwent rest rubidium-82 (Rb-82) and FDG PET 2-10 days post-AMI. Resting echocardiograms were used to assess wall motion abnormalities. Significant RMM occurred in 15 (48%) patients and was associated with a shorter time to PCI of 2.9 hours (2.2, 13.3 hours) compared to patients without significant RMM: 11.4 hours (3.9, 22.4 hours) (P = .03). Within the peri-infarct regions, segments with significant RMM were more likely to have wall motion abnormalities (OR = 2.3 (1.1, 4.7), P = .02) compared to segments without significant RMM. RMM is a common pattern on perfusion/FDG PET during the sub-acute phase following reperfusion of AMI and is associated with shorter times to PCI. Within the peri-infarct region, RMM occurs frequently and is more often associated with wall motion abnormalities than segments without RMM. Whether this represents a myocardial metabolic shift during the sub-acute phase of recovery warrants further study.

  4. Sap flow is Underestimated by Thermal Dissipation Sensors due to Alterations of Wood Anatomy

    NASA Astrophysics Data System (ADS)

    Marañón-Jiménez, S.; Wiedemann, A.; van den Bulcke, J.; Cuntz, M.; Rebmann, C.; Steppe, K.

    2014-12-01

    The thermal dissipation technique (TD) is one of the most commonly adopted methods for sap flow measurements. However, underestimations of up to 60% of the tree transpiration have been reported with this technique, although the causes are not certainly known. The insertion of TD sensors within the stems causes damage of the wood tissue and subsequent healing reactions, changing wood anatomy and likely the sap flow path. However, the anatomical changes in response to the insertion of sap flow sensors and the effects on the measured flow have not been assessed yet. In this study, we investigate the alteration of vessel anatomy on wounds formed around TD sensors. Our main objectives were to elucidate the anatomical causes of sap flow underestimation for ring-porous and diffuse-porous species, and relate these changes to sap flow underestimations. Successive sets of TD probes were installed in early, mid and end of the growing season in Fagus sylvatica (diffuse-porous) and Quercus petraea (ring-porous) trees. They were logged after the growing season and additional sets of sensors were installed in the logged stems with presumably no healing reaction. The wood tissue surrounding each sensor was then excised and analysed by X-ray computed microtomography (X-ray micro CT). This technique allowed the quantification of vessel anatomical characteristics and the reconstruction of the 3-D internal microstructure of the xylem vessels so that extension and shape of the altered area could be determined. Gels and tyloses clogged the conductive vessels around the sensors in both beech and oak. The extension of the affected area was larger for beech although these anatomical changes led to similar sap flow underestimations in both species. The higher vessel size in oak may explain this result and, therefore, larger sap flow underestimation per area of affected conductive tissue. The wound healing reaction likely occurred within the first weeks after sensor installation, which

  5. Moderate ischemic mitral regurgitation after postero-lateral myocardial infarction in sheep alters left ventricular shear but not normal strain in the infarct and infarct borderzone

    PubMed Central

    Ge, Liang; Wu, Yife; Soleimani, Mehrdad; Khazalpour, Michael; Takaba, Kiyoaki; Tartibi, Mehrzad; Zhang, Zhihong; Acevedo-Bolton, Gabriel; Saloner, David A.; Wallace, Arthur W.; Mishra, Rakesh; Grossi, Eugene A.; Guccione, Julius M.; Ratcliffe, Mark B.

    2016-01-01

    Background Chronic ischemic mitral regurgitation (CIMR: MR) is associated with poor outcome. Left ventricular (LV) strain after postero-lateral myocardial infarction (MI) may drive LV remodeling. Although moderate CIMR has been previously shown to effect LV remodeling, the effect of CIMR on LV strain after postero-lateral MI remains unknown. We tested the hypothesis that moderate CIMR alters LV strain after postero-lateral MI. Methods/Results Postero-lateral MI was created in 10 sheep. Cardiac MRI with tags was performed 2 weeks before and 2, 8 and 16 weeks after MI. LV and right ventricular (RV) volumes were measured and regurgitant volume indexed to body surface area (BSA; RegurgVolume Index) calculated as the difference between LV and RV stroke volumes / BSA. Three-dimensional strain was calculated. Circumferential (Ecc)and longitudinal (Ell) strains were reduced in the infarct proper, MI borderzone (BZ) and remote myocardium 16 weeks after MI. In addition, radial circumferential (Erc) and radial longitudinal (Erl) shear strains were reduced in remote myocardium but increased in the infarct and BZ 16 weeks after MI. Of all strain components, however, only Erc was effected by RegurgVolume Index (p=0.0005). There was no statistically significant effect of RegurgVolume Index on Ecc, Ell, Erl, or circumferential longitudinal shear strain (Ecl). Conclusions Moderate CIMR alters radial circumferential shear strain after postero-lateral MI in the sheep. Further studies are needed to determine the effect of shear strain on myocyte hypertrophy and the effect of mitral repair on myocardial strain. PMID:26857634

  6. Oral mucosa alterations in chronic hepatitis and cirrhosis due to HBV or HCV infection.

    PubMed

    Sulka, Agnieszka; Simon, Krzysztof; Piszko, Paweł; Kalecińska, Ewa; Dominiak, Marzena

    2006-03-01

    The aim of the study was to evaluate the character of lesions within oral mucosa in patients suffering from chronic hepatitis and cirrhosis of the liver due to either HBV or HCV infection. A total of 74 patients treated at the Clinic of Infectious Diseases in Wrocław for chronic hepatitis B (20 patients, group I) and for chronic hepatitis C (23 patients group III) and cirrhosis of the liver due to HBV (15 patients , group II) and HCV (16 patients, group IV) infection. The control group comprised 29 healthy subjects. Lesions within the oral mucosa found on clinical examinations were confirmed with a histopathological evaluation. Patients suffering from chronic hepatitis B revealed leukoplakia (1/20), melanoplakia (1/20), petechiae (1/20), 17 patients from this group did not show any changes. Patients suffering from chronic hepatitis C revealed leukoplakia (6/23), Delbanco's disease (2/23), melanoplakia (1/23), lichen planus (1/23), petechiae (1/23), 12 patients from this group did not show any changes. Patients suffering from cirrhosis of the liver due of HBV infection revealed leukoplakia (3/15) petechiae (2/15), Delbanco's disease (1/15), angular cheilitis (1/15), aphthae (1/15), 7 patients from this group did not reveal any changes. Patients suffering from cirrhosis of the liver due of HCV infection revealed petechiae (2/16), melanoplakia (1/16), candidosis (1/16), labial herpes (1/16), 11 patients from this group did not reveal any changes. In control group we observed leukoplakia (3/29), Delbanco's disease (1/29), labial herpes (1/29), petechiae (1/29), and 23 subjects did not present pathological lesions within the oral mucosa. Results indicate the lack of connection between chronic HBV and HCV infection as well as the stage of the disease with the incidence and character of oral lesions in oral mucosa.

  7. Respiratory alterations due to urban air pollution: An experimental study in rats

    SciTech Connect

    Saldiva, P.H.N.; King, M.; Delmonte, V.L.C.; Macchione, M.; Parada, M.A.C.; Daliberto, M.L.; Sakae, R.S.; Criado, P.M.P.; Silveira, P.L.P.; Zin, W.A.; Boehm, G.M. Univ. of Alberta, Edmonton )

    1992-02-01

    In order to assess the adverse effects of urban levels of air pollution, rats were used as biological indicators in a chronic exposure experiment. Animals were housed for 6 months in the center of Sao Paulo and were compared to controls kept for the same period in a clean area. Pollution levels were obtained from a State air pollution monitoring station, 200 m distant from the exposure place, which provided the levels of CO, SO{sub 2}, particulates, and ozone. The animals were submitted to several tests focusing on the respiratory system, comprising pulmonary function tests, studies on mucociliary clearance and mucus rheology, histochemical evaluation of airways, bronchoalveolar lavage, and ultrastructural studies of the epithelium of the airways. Rats exposed to air pollution developed secretory cell hyperplasia in the airways, ultrastructural ciliary alterations, and a more rigid mucus, changes that caused mucociliary clearance impairment. In addition, nasal resistance and the number of inflammatory cells recovered by bronchoalveolar lavage were increased in air pollution exposed animals. The results obtained in the present investigation suggest that chronic exposure to urban levels of air pollution may cause respiratory lesions in rats.

  8. Oxidative stress and some biochemical alterations due to scorpion (Leiurus quinquestriatus) crude venom in rats.

    PubMed

    Salman, Muhammad M A; Hammad, Seddik

    2017-07-01

    Scorpion envenomation is a common medical problem in many countries; it is an important cause of morbidity and mortality. The venom of Leiurus quinquestriatus (LQ) is responsible for a number of deaths in children and adults. It has been stated that specific pathophysiological conditions such as generation of oxygen free radicals may trigger the onset of multiple organ dysfunction; therefore, the present study aimed to assess the oxidative stress mediated by LQ crude venom and its effect on the biochemical parameters in rats. Adult male Albino rats (250±30g body weight) were divided into three groups (n=5). In control group, rats were intraperitoneally (ip) injected with 50μL saline solution. Groups 2 and 3 were ip injected with 0.1mg/kg and 0.2mg/kg body weight of crude venom, respectively. Blood samples and liver tissues were harvested 1, 2 and 4h post-injection. Serum levels of glucose, cholesterol, creatinine, urea, uric acid and malondialdehyde increased significantly in envenomed animals within 1, 2 and 4h post-injection, compared to controls. However, the levels of total serum protein, albumin, globulin and triglycerides as well as catalase, glutathione peroxidase and super oxide dismutase in envenomed rats were significantly decreased compared to controls. We can conclude that LQ crude venom induces oxidative stress via reduction of antioxidant systems and alters some biochemical parameters of envenomed rats. Copyright © 2017. Published by Elsevier Masson SAS.

  9. Dynamic alterations in wellbore cement integrity due to geochemical reactions in CO2-rich environments

    NASA Astrophysics Data System (ADS)

    Cao, Peilin; Karpyn, Zuleima T.; Li, Li

    2013-07-01

    The interaction between wellbore cement and CO2 has the potential to alter cement properties and form preferential leakage pathways during geological carbon sequestration. This work investigates changes in wellbore cement integrity during continuous flooding of CO2-saturated brine. We created composite cement-sandstone core samples with a continuous gap in the cement zone in order to represent defects such as fractures and voids in wellbore cement. Volumetric and structural changes in the cement zone were monitored and quantified using X-ray Micro-Computed Tomography imaging. During an 8 day dynamic flow-through period, the fracture/void aperture increased significantly, whereas the host sandstone remained unaltered. The void volume increased at a faster rate in the early stage of the flow-through period than it did toward the end of the period. Compared to the apertures close to the core outlet, those located near the core inlet experienced more severe cement degradation, accompanied by a decrease in specific surface area, constituting evidence of a smoothing effect. Contrary to previous observations of the self-healing behavior of cement fractures, the in situ permeability on a parallel experiment increased by a factor of 8 after 10 days of flooding. Findings from this work will provide valuable insights applicable to the development of predictive models and for risk assessment under conditions relevant to CO2 sequestration.

  10. Spatial and Temporal Alterations on Carbon and Water Cycles Due to Grazing

    NASA Astrophysics Data System (ADS)

    Maksimowicz, M. M.; Brunsell, N. A.; Ham, J. M.

    2009-05-01

    Grasslands are vital in the carbon cycle, as large amounts of carbon are stored in the soils of the prairie. As climate change affects the carbon cycle, it is essential for the agricultural communities to understand the impacts of these changes on farming practices such as grazing and meat production. The objective of this study is to determine the effect of grazing on the carbon cycle by characterizing the surface boundary layer of both a grazed field and an ungrazed field. Data were collected from open path eddy covariance systems over Rannells Flint Hills Prairie Preserve in north-central Kansas, one over an ungrazed field and one over a grazed field. Cospectra of fluxes of CO2, heat, water, and momentum for July 2007 were compared to assess the size of eddies contributing energy to each field. For CO2, the cospectra for both the ungrazed and the ungrazed field were similar. For all of the other fluxes, lower frequency eddies contributed more energy in the grazed field than the ungrazed field. By using a footprint model, the contributing source areas were determined for fluxes from May through October of 2007. The grazed field had a larger distance of contribution in both stable and unstable atmospheric conditions. Implications of this study include the alterations on fields and impacts on the carbon and water cycles as a result of grazing.

  11. Baseline Perfusion Alterations Due to Acute Application of Quetiapine and Pramipexole in Healthy Adults.

    PubMed

    Michels, Lars; Scherpiet, Sigrid; Stämpfli, Philipp; Herwig, Uwe; Brühl, Annette B

    2016-11-01

    The dopaminergic system is implicated in many mental processes and neuropsychiatric disorders. Pharmacologically, drugs with dopamine receptor antagonistic and agonistic effects are used, but their effects on functional brain metabolism are not well known. In this randomized crossover, placebo-controlled, and rater-blinded study, 25 healthy adults received an acute dose placebo substance (starch), quetiapine (dopamine receptor antagonist), or pramipexole (dopamine agonist of the nonergoline class) 1 hour before the experiment. Background-suppressed 2D pseudo-continuous arterial spin labeling was used to examine whole-brain baseline cerebral blood flow differences induced by the 3 substances. We found that quetiapine reduced perfusion in the occipital (early visual areas) and bilateral cerebellar cortex relative to placebo. In contrast, quetiapine enhanced cerebral blood flow (relative to placebo) in the striatal system (putamen and caudate nucleus) but also in the supplementary motor area, insular-, prefrontal- as well as in the pre- and postcentral cortex. Pramipexole increased cerebral blood flow compared with placebo in the caudate nucleus, putamen, middle frontal, supplementary motor area, and brainstem (substantia nigra), but reduced cerebral blood flow in the posterior thalamus, cerebellum, and visual areas. Pramipexole administration resulted in stronger cerebral blood flow relative to quetiapine in the hypothalamus, cerebellum, and substantia nigra. Our results indicate that quetiapine and pramipexole differentially modulate regional baseline cerebral blood flow. Both substances act on the dopaminergic system, although they affect distinct regions. Quetiapine altered dopaminergic function in frontal, striatal, and motor regions. In contrast, pramipexole affected cerebral blood flow of the nigrostriatal (striatum and substantia nigra) dopaminergic, but less the fronto-insular system. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  12. Baseline Perfusion Alterations Due to Acute Application of Quetiapine and Pramipexole in Healthy Adults

    PubMed Central

    Scherpiet, Sigrid; Stämpfli, Philipp; Herwig, Uwe; Brühl, Annette B.

    2016-01-01

    Background: The dopaminergic system is implicated in many mental processes and neuropsychiatric disorders. Pharmacologically, drugs with dopamine receptor antagonistic and agonistic effects are used, but their effects on functional brain metabolism are not well known. Methods: In this randomized crossover, placebo-controlled, and rater-blinded study, 25 healthy adults received an acute dose placebo substance (starch), quetiapine (dopamine receptor antagonist), or pramipexole (dopamine agonist of the nonergoline class) 1 hour before the experiment. Background-suppressed 2D pseudo-continuous arterial spin labeling was used to examine whole-brain baseline cerebral blood flow differences induced by the 3 substances. Results: We found that quetiapine reduced perfusion in the occipital (early visual areas) and bilateral cerebellar cortex relative to placebo. In contrast, quetiapine enhanced cerebral blood flow (relative to placebo) in the striatal system (putamen and caudate nucleus) but also in the supplementary motor area, insular-, prefrontal- as well as in the pre- and postcentral cortex. Pramipexole increased cerebral blood flow compared with placebo in the caudate nucleus, putamen, middle frontal, supplementary motor area, and brainstem (substantia nigra), but reduced cerebral blood flow in the posterior thalamus, cerebellum, and visual areas. Pramipexole administration resulted in stronger cerebral blood flow relative to quetiapine in the hypothalamus, cerebellum, and substantia nigra. Conclusions: Our results indicate that quetiapine and pramipexole differentially modulate regional baseline cerebral blood flow. Both substances act on the dopaminergic system, although they affect distinct regions. Quetiapine altered dopaminergic function in frontal, striatal, and motor regions. In contrast, pramipexole affected cerebral blood flow of the nigrostriatal (striatum and substantia nigra) dopaminergic, but less the fronto-insular system. PMID:27466220

  13. The Asthenosphere Melting Regimes Alteration due to Changing Conditions of Upper Mantle

    NASA Astrophysics Data System (ADS)

    Perepechko, Y. V.; Sharapov, V. N.; Sorokin, K., Jr.

    2014-12-01

    Analyzed in the article are different asthenosphere magma generation regimes above the upper mantle hot spots as thermodynamic and geometric parameters of the upper mantle and the conditions on its boundaries vary. The two-layer mantle model is applied to consider the formation of decompression melting areas. The thickness of metasomatically altered lithospheric mantle is determined by the mantle substance rheology and the location of the upper boundary of asthenosphere. We also take into consideration the principal solid state phase transitions by using the mantle substance state equation. The sizes and distribution of hot spots as well as their maximal temperature were defined by the thermodynamic conditions of the perovskite transition existence. The numerical analysis results demonstrate the manifestation of three main mantle dynamics modes; the conditions necessary to form the partial melting zones are not reached; some melting areas with the 30 to 65 Ma existence time do occur; the melting areas that are formed exist permanently. The permanently existing asthenosphere zones are marked by quasiperiodical variation in thickness and the degree of melting. The typical temperatures of a hot spot sharing these modes are the 1740°С and 2020°С correspondingly. The originally presupposed heating degree and the temperature ratio of the upper mantle do influence the decompression melting degree substantially and - to a lesser extent - they influence the size of melting zones. The primary evolution of the second mode is described by the development of a complex system of asthenosphere zones that lead to the occurrence of additional convectional cells dividing the partial melting zone. The variation in the rheological properties of the mantle substance also contributes to the manifestation of the complex structure of asthenosphere zone. The work was made with support of the Russian Foundation for Basic Research grant #12-05-00625.

  14. Relationship between risk factors and in-hospital mortality due to myocardial infarction by educational level: a national prospective study in Iran.

    PubMed

    Ahmadi, Ali; Khaledifar, Arsalan; Sajjadi, Homeira; Soori, Hamid

    2014-11-27

    Since no hospital-based, nationwide study has been yet conducted on the association between risk factors and in-hospital mortality due to myocardial infarction (MI) by educational level in Iran, the present study was conducted to investigate relationship between risk factors and in-hospital mortality due to MI by educational level. In this nationwide hospital-based, prospective analysis, follow-up duration was from definite diagnosis of MI to death. The cohort of the patients was defined in view of the date at diagnosis, hospitalization and the date at discharge (recovery or in-hospital death due to MI). 20750 patients hospitalized for newly diagnosed MI between April, 2012 and March, 2013 comprised sample size. Totally, 2511 deaths due to MI were obtained. The data on education level (four-level) were collected based on years of schooling. To determine in-hospital mortality rate and the associated factors with mortality, seven statistical models were developed using Cox proportional hazards models. Of the studied patients, 9611 (6.1%) had no education. in-hospital mortality rate was 8.36 (95% CI: 7.81-8.9) in women and 6.12 (95% CI: 5.83-6.43) in men per 100 person-years. This rate was 5.56 in under 65-year-old patients and 8.37 in over 65-year-old patients. This rate in the patients with no, primary, high school, and academic education was respectively 8.11, 6.11, 4.85 and 5.81 per 100 person-years. Being woman, chest pain prior to arriving in hospital, lack of thrombolytic therapy, right bundle branch block, ventricular tachycardia, smoking and ST-segment elevation myocardial infarction were significantly associated with increased hazard ratio (HR) of death. The adjusted HR of mortality was 1.27 (95% CI: 1.06-1.52), 0.93 (95% CI: 0.77-1.13), 0.72 (95% CI: 0.57-0.91) and 0.82 (95% CI: 0.66-1.01) in the patients with respectively illiterate, primary, secondary and high school education compared to academic education. A disparity was noted in post-MI mortality

  15. Assessing Receiving Water Quality Impacts due to Flow Path Alteration in Residential Catchments, using the Stormwater and Wastewater Management Model

    NASA Astrophysics Data System (ADS)

    Wolosoff, S. E.; Duncan, J.; Endreny, T.

    2001-05-01

    The Croton water supply system, responsible for supplying approximately 10% of New York City's water, provides an opportunity for exploration into the impacts of significant terrestrial flow path alteration upon receiving water quality. Natural flow paths are altered during residential development in order to allow for construction at a given location, reductions in water table elevation in low lying areas and to provide drainage of increased overland flow volumes. Runoff conducted through an artificial drainage system, is prevented from being attenuated by the natural environment, thus the pollutant removal capacity inherent in most natural catchments is often limited to areas where flow paths are not altered by development. By contrasting the impacts of flow path alterations in two small catchments in the Croton system, with different densities of residential development, we can begin to identify appropriate limits to the re-routing of runoff in catchments draining into surface water supplies. The Stormwater and Wastewater Management Model (SWMM) will be used as a tool to predict the runoff quantity and quality generated from two small residential catchments and to simulate the potential benefits of changes to the existing drainage system design, which may improve water quality due to longer residence times.

  16. Correcting oral contraceptive pharmacokinetic alterations due to obesity. A randomized controlled trial

    PubMed Central

    Edelman, Alison B; Cherala, Ganesh; Munar, Myrna Y.; McInnis, Martha; Stanczyk, Frank Z.; Jensen, Jeffrey T

    2014-01-01

    Objective To determine if increasing the hormone dose or eliminating the hormone-free interval improves key pharmacokinetic (PK) alterations caused by obesity during oral contraceptive (OC) use. Study design Obese (BMI ≥ 30 kg/m2), ovulatory, otherwise healthy, women received an OC containing 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) dosed cyclically (21 days active pills with 7-day placebo week) for two cycles and then were randomized for two additional cycles to: Continuous Cycling [CC, a dose neutral arm using the same OC with no hormone-free interval] or Increased Dose [ID, a dose escalation arm using an OC containing 30 mcg EE/150 mcg LNG cyclically]. During Cycle 2, 3, and 4, outpatient visits were performed to assess maximum serum concentration (Cmax), area under the curve (AUC0-∞), and time to steady state as well as pharmacodynamics. These key PK parameters were calculated and compared within groups between baseline and treatment cycles. Results A total of 31 women enrolled and completed the study (CC group n = 16; ID group n = 15). Demographics were similar between groups [mean BMI: CC 38kg/m2 (SD 5.1), ID 41kg/m2 (SD 7.6)]. At baseline, the key LNG PK parameters were no different between groups; average time to reach steady-state was 12 days in both groups; Cmax were CC: 3.82 ± 1.28 ng/mL and ID: 3.13 ± 0.87 ng/mL; and AUC0-∞ were CC: 267 ± 115 hr*ng/mL and ID: 199±75 hr*ng/mL. Following randomization, the CC group maintained steady-state serum levels whereas the ID group had a significantly higher Cmax (p< 0.001) but again required 12 days to achieve steady-state. However, AUC was not significantly different between CC (412 ± 255 hr*ng/mL) and ID (283 ± 130 hr*ng/mL). Forty-five percent (14/31) of the study population had evidence of an active follicle-like structure prior to randomization and afterwards this decreased to 9% (3/31). Conclusion Both increasing the OC dose and continuous dosing appear to counteract the impact

  17. Streptococcus pneumoniae in biofilms are unable to cause invasive disease due to altered virulence determinant production.

    PubMed

    Sanchez, Carlos J; Kumar, Nikhil; Lizcano, Anel; Shivshankar, Pooja; Dunning Hotopp, Julie C; Jorgensen, James H; Tettelin, Hervé; Orihuela, Carlos J

    2011-01-01

    It is unclear whether Streptococcus pneumoniae in biofilms are virulent and contribute to development of invasive pneumococcal disease (IPD). Using electron microscopy we confirmed the development of mature pneumococcal biofilms in a continuous-flow-through line model and determined that biofilm formation occurred in discrete stages with mature biofilms composed primarily of dead pneumococci. Challenge of mice with equal colony forming units of biofilm and planktonic pneumococci determined that biofilm bacteria were highly attenuated for invasive disease but not nasopharyngeal colonization. Biofilm pneumococci of numerous serotypes were hyper-adhesive and bound to A549 type II pneumocytes and Detroit 562 pharyngeal epithelial cells at levels 2 to 11-fold greater than planktonic counterparts. Using genomic microarrays we examined the pneumococcal transcriptome and determined that during biofilm formation S. pneumoniae down-regulated genes involved in protein synthesis, energy production, metabolism, capsular polysaccharide (CPS) production, and virulence. We confirmed these changes by measuring CPS by ELISA and immunoblotting for the toxin pneumolysin and the bacterial adhesins phosphorylcholine (ChoP), choline-binding protein A (CbpA), and Pneumococcal serine-rich repeat protein (PsrP). We conclude that biofilm pneumococci were avirulent due to reduced CPS and pneumolysin production along with increased ChoP, which is known to bind C-reactive protein and is opsonizing. Likewise, biofilm pneumococci were hyper-adhesive due to selection for the transparent phase variant, reduced CPS, and enhanced production of PsrP, CbpA, and ChoP. These studies suggest that biofilms do not directly contribute to development of IPD and may instead confer a quiescent mode of growth during colonization.

  18. Experimental investigation of injectivity alteration due to salt precipitation during CO2 sequestration in saline aquifers

    NASA Astrophysics Data System (ADS)

    Jeddizahed, Javad; Rostami, Behzad

    2016-10-01

    Injection of CO2 into saline aquifers causes the geochemical reaction of rock-fluid and salt precipitation due to the evaporation of water as a physical process. Well injectivity is an important issue in carbon capture and storage (CCS) projects because large volumes of CO2 must be stored for a long time and salt precipitation can significantly reduce injectivity by reducing the permeability. The impact of salt precipitation on the injectivity must therefore be specified in order to maintain the security of CCS projects and enable them to perform at a high level of practicality. The objective of this work is to investigate the influence of the injection rate and brine salinity on injectivity reduction due to evaporation and salt precipitation. In this study, we injected supercritical CO2 into a sandstone rock sample fully saturated with NaCl brine to characterize the salt precipitation induced by the evaporation process. Evaporation is investigated by mass measurement of the water and vapor produced. The extension in time of salt precipitation and the precipitation profile are analyzed by drying rate measurement, Capillary number and Peclet number. The consequences of salt precipitation on injectivity are specified by permeability and relative permeability analysis. The results show that a high drying rate in the early stage of injection induces rapid salt precipitation. The level of salt precipitation increases with salinity, within a permeability reduction range of 21-66%, and decreases with the injection rate, within a permeability reduction range of 43-62%. The relative permeability of CO2 is affected by both the injection rate and salinity.

  19. Adaptation to altered balance conditions in unilateral amputees due to atherosclerosis: a randomized controlled study

    PubMed Central

    2011-01-01

    Background Amputation impairs the ability to balance. We examined adaptation strategies in balance following dysvascularity-induced unilateral tibial amputation in skilled prosthetic users (SPU) and first fitted amputees (FFA) (N = 28). Methods Excursions of center of pressure (COP) were determined during 20 s quiet standing using a stabilometry system with eyes-open on both legs or on the non-affected leg(s). Main measures: COP trajectories and time functions; distribution of reaction forces between the two legs; inclination angles obtained through second order regression analysis using stabilogram data. Results FFA vs SPU demonstrated 27.8% greater postural sway in bilateral stance (p = 0.0004). Postural sway area was smaller in FFA standing on the non-affected leg compared with SPU (p = 0.028). The slope of the regression line indicating postural stability was nearly identical in FFA and SPU and the direction of regression line was opposite for the left and right leg amputees. Conclusion Of the two adaptation strategies in balance, the first appears before amputation due to pain and fatigue in the affected leg. This strategy appears in the form of reduced postural sway while standing on the non-affected leg. The second adaptation occurs during rehabilitation and regular use of the prosthesis resulting in normal weightbearing associated with reduced postural sway on two legs and return to the normal postural stability on one leg. PMID:21619618

  20. Effects on MRI due to altered rf polarization near conductive implants or instruments.

    PubMed

    Graf, Hansjörg; Steidle, Günter; Martirosian, Petros; Lauer, Ulrike A; Schick, Fritz

    2006-01-01

    In magnetic resonance imaging near metal parts variations in radio frequency (rf)-amplitude and of receive sensitivity must be considered. For loop structures, e.g., vascular stents, B1 produces rf eddy currents in accordance to Faraday's law; the B1-related electrical rf field E1 injects directly to elongated structures (e.g., wires). Locally, the rf magnetic field Bl,ind (induced B1) is superimposed onto the rf field from the transmitter coil, which near the metal can dominate spin excitation. Geometry and arrangement of the parts determine the polarization of B(1,ind). Components parallel to B0 are of special interest. A copper sheet (100 mm x 15 mm, 3 mm thick) and a 27 cm long copper wire were examined in a water phantom using the spin-echo (SE) technique. In addition to rf-amplitude amplification, rf-phase shift due to z components of B(1,ind) could be detected near the metallic objects. Periodic rf-amplitude instabilities had an amplified effect for phase-shifted regions. Phase-encoding artifacts occurred as distinct ghosts (TR=200 ms) or band-like smearing (TR=201 ms) from affected spin ensembles. SE phase imaging can potentially be used in interventional magnetic resonance imaging for background-free localization of metallic markers.

  1. Alteration of the oxygen-dependent reactivity of de novo Due Ferri proteins

    NASA Astrophysics Data System (ADS)

    Reig, Amanda J.; Pires, Marcos M.; Snyder, Rae Ana; Wu, Yibing; Jo, Hyunil; Kulp, Daniel W.; Butch, Susan E.; Calhoun, Jennifer R.; Szyperski, Thomas G.; Solomon, Edward I.; Degrado, William F.

    2012-11-01

    De novo proteins provide a unique opportunity to investigate the structure-function relationships of metalloproteins in a minimal, well-defined and controlled scaffold. Here, we describe the rational programming of function in a de novo designed di-iron carboxylate protein from the Due Ferri family. Originally created to catalyse the O2-dependent, two-electron oxidation of hydroquinones, the protein was reprogrammed to catalyse the selective N-hydroxylation of arylamines by remodelling the substrate access cavity and introducing a critical third His ligand to the metal-binding cavity. Additional second- and third-shell modifications were required to stabilize the His ligand in the core of the protein. These structural changes resulted in at least a 106-fold increase in the relative rate between the arylamine N-hydroxylation and hydroquinone oxidation reactions. This result highlights the potential for using de novo proteins as scaffolds for future investigations of the geometric and electronic factors that influence the catalytic tuning of di-iron active sites.

  2. Alteration of Fractured Rocks Due to Coupled Chemical and Mechanical Processes: High-Resolution Simulations and Experimental Observations

    NASA Astrophysics Data System (ADS)

    Ameli, Pasha

    Engineering activities such as enhanced geothermal energy production and improved oil recovery techniques are heavily dependent on the permeability of the subsurface, while others such as CO2 sequestration and nuclear waste disposal rely on the efficiency of rock formations as transport barriers. In either case fractures provide the main pathways for fluid flow and transport, especially in rocks with lower matrix porosity. Laboratory experiments aimed at quantifying the chemo-mechanical responses of fractures have shown a range of results, some of which contradict simple conceptual models. For example, under conditions favoring mineral dissolution, where one would expect an overall increase in permeability, experiments show that permeability increases under some conditions and decreases under others. Recent experiments have attempted to link these core-scale observations to the relevant small-scale processes occurring within fractures. Results suggest that the loss of mechanical strength in asperities due to chemical alteration may cause non-uniform deformation and alteration of fracture apertures. However, due to the lack of direct micro-scale measurements of the coupled chemical and mechanical processes that lead to alteration of contacting fracture surfaces, our ability to predict the long-term evolution of fractures is still limited. To explore the processes that control permeability evolution, I developed a computational model that uses micro-scale surface roughness and explicitly couples dissolution and elastic deformation to calculate local alterations in fracture aperture under chemical and mechanical stresses. A depth-averaged algorithm of fracture flow is used to model reactive transport and chemical alteration of the fracture surfaces. Then, I deform the resulting altered fracture-surfaces using an algorithm that calculates the elastic deformation. The results of the model are compared with flow-through experiments conducted on fractured limestone. The

  3. Altered combustion characteristics of metallized energetics due to stable secondary material inclusion

    NASA Astrophysics Data System (ADS)

    Terry, Brandon C.

    Though metals and metalloids have been widely considered as reactive fuels, the ability to tune their ignition and combustion characteristics remains challenging. One means to accomplish this may be through low-level inclusion of secondary materials into the metallized fuel. While there are several potential methods to stably introduce secondary inclusion materials, this work focuses on the use of mechanical activation (MA) and metal alloys. Recent work has shown that low-level inclusion of fluoropolymers into aluminum particles can have a substantial effect on their combustion characteristics. The reflected shock ignition of mechanically activated aluminum/polytetrafluoroethylene (MA Al/PTFE) is compared to a physical mixture (PM) of Al/PTFE, neat spherical aluminum, and flake aluminum. It was found that the powders with higher specific surface areas ignited faster than the spherical particles of the same size, and had ignition delay times comparable to agglomerates of aluminum particles that were two orders of magnitude smaller in size. Flake aluminum powder had the same ignition delay as MA Al/PTFE, indicating that any initial aluminum/fluoropolymer reactions did not yield an earlier onset of aluminum oxidation. However, MA Al/PTFE did have a shorter total burn time. The PM of Al/PTFE powder had a shorter ignition delay than neat spherical aluminum due to the rapid decomposition of PTFE into reactive fluorocarbon compounds, but the subsequent fluorocarbon reactions also created a secondary luminosity profile that significantly increased the total burn time of the system. The explosive shock ignition of aluminum and aluminum-silicon eutectic alloy compacts was evaluated with and without polymer inclusions. A statistical analysis was completed, investigating the effects of: detonation train orientation (into or not into a hard surface); the high explosive driver; whether the metal/polymer system is mechanically activated; particle size; particle morphology

  4. Does the presence of heart failure alter prescribing of drug therapy after myocardial infarction? A multicentre study.

    PubMed

    Krum, Henry; Meehan, Adam; Varigos, John; Loane, Philippa R; Billah, Baki

    2006-08-21

    To evaluate the use of cardiovascular medications in patients with and without heart failure after myocardial infarction (MI). Multicentre study of drug therapy for patients with MI in 16 major metropolitan teaching hospitals in Australia over a 1-month period at each hospital in the period November 2004 - March 2005. 479 patients admitted consecutively to the individual hospitals. Proportion of patients with and without heart failure who were prescribed key cardiovascular medications after MI. 116 of the 479 patients admitted for MI (24.2%) had heart failure at some point during their hospitalisation. Patients with heart failure were older (68 v 63 years; P < 0.05), more likely to be women (34% v 24%; P < 0.05) and a higher proportion had diabetes (26% v 21%). There was significantly reduced prescribing of beta-blockers, clopidogrel and statins for patients with heart failure compared with those without heart failure. Mineralocorticoid receptor antagonist use was low (< 10%) in the former group. We found reduced prescribing of some prognostically relevant medications for patients with heart failure. For beta-blockers, this may be explained by the greater clinical instability in patients with heart failure. Given the absolute benefit of drug therapy in patients with heart failure after MI, our findings suggest suboptimal prescribing in Australian teaching hospital practice.

  5. Alterations in myocardial metabolism and function at rest in stable angina pectoris: relations with the amount of exercise-induced thallium-201 perfusion defect

    SciTech Connect

    De Kock, M.; Melin, J.A.; Pouleur, H.; Rousseau, M.F.

    1986-01-01

    The relation between the amount of exercise-induced ischemia and alterations in left ventricular (LV) function and metabolism at rest was studied in 18 coronary patients with stable angina pectoris. An ischemic defect area score was computed from quantitative exercise thallium-201 (Tl-201) scintigraphy; this estimation of the amount of ischemic myocardium was used to classify the patients in group I (n = 8; score less than 15%, mean 6.7 +/- 2.5%) and II (n = 10; score greater than 15%; mean 27.2 +/- 8.9%). Hemodynamics and metabolism were studied in basal state. No patient had anginal pain during the study, and the extent of angiographic coronary artery disease (CAD) was comparable in the two groups. Heart rate, aortic pressure, coronary blood flow, and myocardial oxygen uptake were also similar in both groups. However, ejection fraction was reduced in group II (51 +/- 13 vs 63 +/- 5%; p less than 0.01) and LV relaxation was impaired as shown by the increase in time-constant of isovolumic pressure fall (55 +/- 16 vs 44 +/- 6 ms in group I; p less than 0.05); the LV end-diastolic pressure was also increased in group II (19 +/- 8 vs 10 +/- 4 mmHg in group l; p less than 0.05). Furthermore, in group II, myocardial lactate uptake was reduced (4 +/- 19 vs 30 +/- 29 mumole/min in group I; p less than 0.01) and the productions of alanine and glutamine were augmented (-7.5 +/- 4.4 vs -4.6 +/- 1.6 mumole/min in group I; p less than 0.05).

  6. Pressure-overload cardiac hypertrophy is associated with distinct alternative splicing due to altered expression of splicing factors.

    PubMed

    Kim, Taeyong; Kim, Jin Ock; Oh, Jae Gyun; Hong, Seong-Eui; Kim, Do Han

    2014-01-01

    Chronic pressure-overload cardiac hypertrophy is associated with an increased risk of morbidity/mortality, largely due to maladaptive remodeling and dilatation that progresses to dilated cardiomyopathy. Alternative splicing is an important biological mechanism that generates proteomic complexity and diversity. The recent development of next-generation RNA sequencing has improved our understanding of the qualitative signatures associated with alternative splicing in various biological conditions. However, the role of alternative splicing in cardiac hypertrophy is yet unknown. The present study employed RNA-Seq and a bioinformatic approach to detect the RNA splicing regulatory elements involved in alternative splicing during pressure-overload cardiac hypertrophy. We found GC-rich exonic motifs that regulate intron retention in 5' UTRs and AT-rich exonic motifs that are involved in exclusion of the AT-rich elements that cause mRNA instability in 3' UTRs. We also identified motifs in the intronic regions involved in exon exclusion and inclusion, which predicted splicing factors that bind to these motifs. We found, through Western blotting, that the expression levels of three splicing factors, ESRP1, PTB and SF2/ASF, were significantly altered during cardiac hypertrophy. Collectively, the present results suggest that chronic pressure-overload hypertrophy is closely associated with distinct alternative splicing due to altered expression of splicing factors.

  7. Gliadin-Mediated Proliferation and Innate Immune Activation in Celiac Disease Are Due to Alterations in Vesicular Trafficking

    PubMed Central

    Barone, M. Vittoria; Zanzi, Delia; Maglio, Mariantonia; Nanayakkara, Merlin; Santagata, Sara; Lania, Giuliana; Miele, Erasmo; Ribecco, Maria Teresa Silvia; Maurano, Francesco; Auricchio, Renata; Gianfrani, Carmen; Ferrini, Silvano; Troncone, Riccardo; Auricchio, Salvatore

    2011-01-01

    Background and Objectives Damage to intestinal mucosa in celiac disease (CD) is mediated both by inflammation due to adaptive and innate immune responses, with IL-15 as a major mediator of the innate immune response, and by proliferation of crypt enterocytes as an early alteration of CD mucosa causing crypts hyperplasia. We have previously shown that gliadin peptide P31-43 induces proliferation of cell lines and celiac enterocytes by delaying degradation of the active epidermal growth factor receptor (EGFR) due to delayed maturation of endocytic vesicles. IL-15 is increased in the intestine of patients affected by CD and has pleiotropic activity that ultimately results in immunoregulatory cross-talk between cells belonging to the innate and adaptive branches of the immune response. Aims of this study were to investigate the role of P31-43 in the induction of cellular proliferation and innate immune activation. Methods/Principal Findings Cell proliferation was evaluated by bromodeoxyuridine (BrdU) incorporation both in CaCo-2 cells and in biopsies from active CD cases and controls. We used real-time PCR to evaluate IL-15 mRNA levels and FACS as well as ELISA and Western Blot (WB) analysis to measure protein levels and distribution in CaCo-2 cells. Gliadin and P31-43 induce a proliferation of both CaCo-2 cells and CD crypt enterocytes that is dependent on both EGFR and IL-15 activity. In CaCo-2 cells, P31-43 increased IL-15 levels on the cell surface by altering intracellular trafficking. The increased IL-15 protein was bound to IL15 receptor (IL-15R) alpha, did not require new protein synthesis and functioned as a growth factor. Conclusion In this study, we have shown that P31-43 induces both increase of the trans-presented IL-15/IL5R alpha complex on cell surfaces by altering the trafficking of the vesicular compartments as well as proliferation of crypt enterocytes with consequent remodelling of CD mucosa due to a cooperation of IL-15 and EGFR. PMID:21364874

  8. Gliadin-mediated proliferation and innate immune activation in celiac disease are due to alterations in vesicular trafficking.

    PubMed

    Barone, M Vittoria; Zanzi, Delia; Maglio, Mariantonia; Nanayakkara, Merlin; Santagata, Sara; Lania, Giuliana; Miele, Erasmo; Ribecco, Maria Teresa Silvia; Maurano, Francesco; Auricchio, Renata; Gianfrani, Carmen; Ferrini, Silvano; Troncone, Riccardo; Auricchio, Salvatore

    2011-02-25

    Damage to intestinal mucosa in celiac disease (CD) is mediated both by inflammation due to adaptive and innate immune responses, with IL-15 as a major mediator of the innate immune response, and by proliferation of crypt enterocytes as an early alteration of CD mucosa causing crypts hyperplasia. We have previously shown that gliadin peptide P31-43 induces proliferation of cell lines and celiac enterocytes by delaying degradation of the active epidermal growth factor receptor (EGFR) due to delayed maturation of endocytic vesicles. IL-15 is increased in the intestine of patients affected by CD and has pleiotropic activity that ultimately results in immunoregulatory cross-talk between cells belonging to the innate and adaptive branches of the immune response. Aims of this study were to investigate the role of P31-43 in the induction of cellular proliferation and innate immune activation. Cell proliferation was evaluated by bromodeoxyuridine (BrdU) incorporation both in CaCo-2 cells and in biopsies from active CD cases and controls. We used real-time PCR to evaluate IL-15 mRNA levels and FACS as well as ELISA and Western Blot (WB) analysis to measure protein levels and distribution in CaCo-2 cells. Gliadin and P31-43 induce a proliferation of both CaCo-2 cells and CD crypt enterocytes that is dependent on both EGFR and IL-15 activity. In CaCo-2 cells, P31-43 increased IL-15 levels on the cell surface by altering intracellular trafficking. The increased IL-15 protein was bound to IL15 receptor (IL-15R) alpha, did not require new protein synthesis and functioned as a growth factor. In this study, we have shown that P31-43 induces both increase of the trans-presented IL-15/IL5R alpha complex on cell surfaces by altering the trafficking of the vesicular compartments as well as proliferation of crypt enterocytes with consequent remodelling of CD mucosa due to a cooperation of IL-15 and EGFR.

  9. Reverse and pseudo redistribution of thallium-201 in healed myocardial infarction and normal and negative thallium-201 washout in ischemia due to background oversubtraction

    SciTech Connect

    Lear, J.L.; Raff, U.; Jain, R.

    1988-09-15

    While the interpolative background subtraction used in quantitative planar thallium scanning can significantly overestimate the background overlying the heart, the effects of background oversubtraction on quantitative analysis have not been well defined. A mathematical model that relates myocardial washout determined using interpolative background subtraction to true myocardial washout is presented. The model was validated using phantoms and applied to myocardial and pulmonary thallium kinetic data in 100 patients, 85 with and 15 without coronary artery disease. The model showed that when using interpolative background subtraction, measured washout equals true washout in normally perfused myocardium; however, depending on the relation between myocardial and pulmonary thallium clearance, myocardial washout in ischemic regions and areas of infarction can be substantially over- or underestimated. Based on generally accepted quantitative criteria, this incorrect washout determination can at times lead to misdiagnosis of infarction as ischemia and ischemia as normally perfused tissue. It can also cause both ''reverse redistribution'' and ''pseudo redistribution'' of thallium in myocardial infarction in the absence of a physiologic basis.

  10. Modeling of the relationship between the environmental air pollution, clinical risk factors, and hospital mortality due to myocardial infarction in Isfahan, Iran

    PubMed Central

    Sadeghi, Mehraban; Ahmadi, Ali; Baradaran, Azar; Masoudipoor, Neda; Frouzandeh, Soleiman

    2015-01-01

    Background: This study aimed to determine the relationship between the environmental factor, clinical risk factors, and individual variables with mortality due to acute myocardial infarction (MI) in Isfahan. Materials and Methods: This cross-sectional study was performed between April 2012 and March 2013. The data on the patients’ mortality due to MI in Isfahan were obtained from the MI National Registry. The international classification system (ICD10: I21-I22) was used to diagnose MI. The air quality indicators and environmental variables were used to measure the air pollution. Multilevel logistic regression in the Stata software was used to determine the factors associated with mortality in patients and odds ratios (ORs) were calculated. Results: Six hundred eleven patients with MI were studied during 1-year. 444 (72.2%) patients were male and the rest were female. 4.7% of the patients died due to MI. The mean age at MI incidence was 62.2 ± 13 years. Of the air pollution parameters, PM10 had the maximum mean concentration (49.113 ppm), followed by NOX, NO, NO2, CO, SO2, and O3. The adjusted OR of mortality was derived 2.07 (95% CI: 1.5-2.85) for right bundle branch block, 1.5 (95% CI: 1.3-1.7) for ST-segment elevation MI, 1.84 (95% CI: 1.13-3) for age, 1.06 (95% CI: 1.01-1.20) for CO, 1.1 (95% CI: 1.03-1.30) for O3, and 1.04 (95% CI: 1.01-1.4) for SO2, all of which were considered as the risk factors of mortality. However, OR of mortality was 0.79 for precipitation (95% CI: 0.74-0.84) and 0.52 for angioplasty (95% CI: 0.4-0.68) were considered as protective factors of mortality. The individual characteristics including age, history of MI in the immediate family, hypertension, and diabetes were significantly associated with mortality from MI. The indices of air pollution including SO2, CO, O3, and environmental factors such as the precipitation and temperature were the determinants of mortality in patients with MI. Conclusion: With regards to the factors

  11. CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice

    PubMed Central

    Benjamin, Ivor J.; Guo, Yiru; Srinivasan, Sathyanarayanan; Boudina, Sihem; Taylor, Ryan P.; Rajasekaran, Namakkal S.; Gottlieb, Roberta; Wawrousek, Eric F.; Abel, E. Dale; Bolli, Roberto

    2013-01-01

    The abundantly expressed small molecular weight proteins, CRYAB and HSPB2, have been implicated in cardioprotection ex vivo. However, the biological roles of CRYAB/HSPB2 coexpression for either ischemic preconditioning and/or protection in situ remain poorly defined. Wild-type (WT) and age-matched (~5–9 mo) CRYAB/HSPB2 double knockout (DKO) mice were subjected either to 30 min of coronary occlusion and 24 h of reperfusion in situ or preconditioned with a 4-min coronary occlusion/4-min reperfusion × 6, before similar ischemic challenge (ischemic preconditioning). Additionally, WT and DKO mice were subjected to 30 min of global ischemia in isolated hearts ex vivo. All experimental groups were assessed for area at risk and infarct size. Mitochondrial respiration was analyzed in isolated permeabilized cardiac skinned fibers. As a result, DKO mice modestly altered heat shock protein expression. Surprisingly, infarct size in situ was reduced by 35% in hearts of DKO compared with WT mice (38.8 ± 17.9 vs. 59.8 ± 10.6% area at risk, P < 0.05). In DKO mice, ischemic preconditioning was additive to its infarct-sparing phenotype. Similarly, infarct size after ischemia and reperfusion ex vivo was decreased and the production of superoxide and creatine kinase release was decreased in DKO compared with WT mice (P < 0.05). In permeabilized fibers, ADP-stimulated respiration rates were modestly reduced and calcium-dependent ATP synthesis was abrogated in DKO compared with WT mice. In conclusion, contrary to expectation, our findings demonstrate that CRYAB and HSPB2 deficiency induces profound adaptations that are related to 1) a reduction in calcium-dependent metabolism/respiration, including ATP production, and 2) decreased superoxide production during reperfusion. We discuss the implications of these disparate results in the context of phenotypic responses reported for CRYAB/HSPB2-deficient mice to different ischemic challenges. PMID:17873008

  12. [Improvement of laboratory diagnostics of cholera due to genetically altered (hybrid) variants of cholera Vibrio biovar El Tor].

    PubMed

    Savel'eva, I V; Khatsukov, K X; Savel'eva, E I; Moskvitina, S I; Kovalev, D A; Savel'ev, V N; Kulichenko, A N; Antonenko, A D; Babenyshev, B V

    2015-01-01

    Improvement of laboratory diagnostics of cholera taking into the account appearance of hybrid variants of cholera vibrio El Tor biovar in the 1990s. Phenotypic and molecular-genetic properties of typical toxigenic (151 strains) and hybrid (102 strains) variants of El Tor biovar cholera vibrios, isolated in the Caucuses in 1970-1990 and 1993-1998, respectively, were studied. Toxigenicity gene DNA fragments, inherent to El Tor biovars or classic, were detected by using a reagent kit "Genes of Vibrio cholerae variant ctxB-rstR-rstC, REF" developed by us. Reagent kit "Genes of V. cholerae variant ctxB-rstR-rstC, REF" is proposed to be used for laboratory diagnostics of cholera during study of material from humans or environmental objects and for identification of V. cholerae 01 on genome level in PCR-analysis as a necessary addition to the classic scheme of bacteriological analysis. Laboratory diagnostics of cholera due to genetically altered (hybrid) variants of cholera vibrio El Tor biovar is based on a complex study of material from humans and environmental objects by routine bacteriologic and PCR-analysis methods with the aim of detection of gene DNA fragments in the studied material, that determine biovar (classic or El Tor), identification of V. cholerae O1 strains with differentiation of El Tor vibrios into typical and altered, as well as determination of enterotoxin, produced by the specific cholera vibrio strain (by the presence ctxB(El) or ctxB(Cl) gene DNA fragment, coding biosynthesis of CT-2 or CT-1, respectively).

  13. A Case of Acute Myocardial Infarction due to Left Main Trunk Occlusion Complicated With Aortic Dissection as Diagnosed by Intravascular Ultrasound

    PubMed Central

    Okamoto, Masashi; Amano, Tomonori; Matsuoka, Shunzo; Hirai, Hideki; Masuda, Kazunori; Nakajima, Kanta; Sueyoshi, Atsushi

    2012-01-01

    A 52-year-old man was transferred to our hospital with a sudden onset of severe chest pains. His electrocardiogram revealed ST-segment elevation suggestive of acute myocardial infarction. Emergency coronary angiography showed subtotal occlusion of left main trunk (LMT) with delayed coronary flow. Because intravascular ultrasound revealed a large intimal flap, we diagnosed aortic dissection involving the LMT. After stenting of the LMT, the patient underwent surgical repair of the aortic dissection. Although it is difficult to obtain a correct diagnosis of aortic dissection complicated with myocardial ischemia, we succeeded in diagnosing this rare condition by use of a intravascular ultrasound.

  14. [Depression and myocardial infaction].

    PubMed

    Testuz, A

    2009-03-04

    Several works show an association between depression and the occurence of a first myocardial infarction. Depression after myocardial infarction seems to be a marker of poorer outcome, regardless of other risk factors or severity of the myocardial infarction. Dysautonomia and alteration of platelet activation are a few physiopathological changes shared by both affections, through which they might be related. Treatment of depression is not associated with better cardiovascular outcome, but selective serotonin reuptake inhibitors have been shown safe and efficient among patients with coronary heart disease. Cognitivo-comportemental approach and cardiovascular rehabilitation program after myocardial infarction also play a role in improving quality of life of the depressed patient with coronary heart disease.

  15. Myocardial Ischemia

    MedlinePlus

    ... pectoris: Chest pain caused by myocardial ischemia. www.uptodate.com/home. Accessed June 1, 2015. Deedwania PC. Silent myocardial ischemia: Epidemiology and pathogenesis. www.uptodate.com/home. Accessed June 1, 2015. Mann DL, ...

  16. Increased Symmetric Dimethylarginine Level Is Associated with Worse Hospital Outcomes through Altered Left Ventricular Ejection Fraction in Patients with Acute Myocardial Infarction

    PubMed Central

    Lorin, Julie; Guilland, Jean-Claude; Stamboul, Karim; Guenancia, Charles; Cottin, Yves; Rochette, Luc; Vergely, Catherine; Zeller, Marianne

    2017-01-01

    Objectives We aimed to investigate whether SDMA- symmetric dimethylarginine -the symmetrical stereoisomer of ADMA- might be a marker of left ventricular function in AMI. Background Asymmetric dimethylarginine (ADMA) has been implicated in the prognosis after acute myocardial infarction (AMI) and heart failure (HF). Methods Cross sectional prospective study from 487 consecutive patients hospitalized <24 hours after AMI. Patients with HF on admission were excluded. Serum levels of ADMA, SDMA and L-arginine were determined using HPLC. Glomerular filtration rate (eGFR) was estimated based on creatinine levels. Outcomes were in-hospital severe HF, as defined by Killip class >2, and death. Results Patients were analysed based on SDMA tertiles. Sex, diabetes, dyslipidemia, and prior MI were similar for all tertiles. In contrast, age and hypertension increased across the tertiles (p<0.001). From the first to the last tertile, GRACE risk score was elevated while LVEF and eGFR was reduced. The rate of severe HF and death were gradually increased across the SDMA tertiles (from 0.6% to 7.4%, p = 0.006 and from 0.6% to 5.0%, p = 0.034, respectively). Backward logistic multivariate analysis showed that SDMA was an independent estimate of developing severe HF, even when adjusted for confounding (OR(95%CI): 8.2(3.0–22.5), p<0.001). Further, SDMA was associated with mortality, even after adjustment for GRACE risk score (OR(95%CI): 4.56(1.34–15.52), p = 0.015). Conclusions Our study showed for the first time that SDMA is associated with hospital outcomes, through altered LVEF and may have biological activity beyond renal function. PMID:28125604

  17. Alterations in heart sarcolemmal Ca2(+)-ATPase and Ca2(+)-binding activities due to oxygen free radicals.

    PubMed

    Kaneko, M; Singal, P K; Dhalla, N S

    1990-01-01

    Effects of oxygen free radicals on Ca2+/Mg2+ ATPase and ATP-independent Ca2(+)-binding activities were examined in rat heart sarcolemma. Membranes were incubated with different oxygen radical generating media such as xanthine + xanthine oxidase, hydrogen peroxide, and hydrogen peroxide + Fe2+. In the presence of xanthine + xanthine oxidase, Ca2+ ATPase activity was stimulated and this effect was prevented by the addition of superoxide dismutase. Hydrogen peroxide also showed a significant increase in Ca2(+)-ATPase activity in a dose-dependent manner and this effect was blocked by catalase. On the other hand, a combination of hydrogen peroxide + Fe2+ decreased Ca2(+)-ATPase activity; this depression was prevented by the addition of D-mannitol. The observed change in Ca2(+)-ATPase activity due to oxygen free radicals was associated with changes in Vmax, whereas Ka remained unaffected. Both xanthine + xanthine oxidase and hydrogen peroxide increased whereas, hydrogen peroxide + Fe2+ inhibited the ATP-independent Ca2(+)-binding activities. It is suggested that oxygen free radicals may influence Ca2+ movements in the cell by altering the Ca2+/Mg2+ ATPase and Ca2(+)-binding activities of the membrane and these effects may be oxygen-radical species specific.

  18. Rapid increases in permeability and porosity of bentonite-sand mixtures due to alteration by water vapor

    SciTech Connect

    Couture, R.A.

    1984-01-01

    Packed columns of canister packing material containing 25% bentonite and 75% quartz or basalt sand, were exposed to water vapor at temperatures up t 260/sup 0/C. The permeabilities of the columns were subsequently measured after complete saturation with liquid water in a pressurized system. Exposure to water vapor caused irreversible increases in permeability by factors of up to 10/sup 5/. After saturation with liquid water, the permeability was nearly independent of temperature. The increases in permeability were due to a large decrease in the ability of the bentonite to swell in water. Calculations suggest that swelling of bentonite altered at 250/sup 0/C was not sufficient to fill the pore spaces. If the pore spaces are filled, the mixture will form an effective barrier against flow, diffusion, and transport of colloids. The results suggest that if bentonite-based canister packing material is exposed even briefly to water vapor at high temperatures in a high-level nuclear waste repository, its performance will be seriously impaired. The problem is less severe if the proportion of bentonite is high and the material is highly compacted. Previous results show significant degradation of bentonite by water vapor at temperatures as low as 150/sup 0/C. This suggests that in some repositories, backfill in tunnels and drifts may also be affected. 9 references, 5 figures, 1 table.

  19. Hydrogeochemical alteration of groundwater due to a CO2 injection test into a shallow aquifer in Northeast Germany

    NASA Astrophysics Data System (ADS)

    Dethlefsen, Frank; Peter, Anita; Hornbruch, Götz; Lamert, Hendrik; Garbe-Schönberg, Dieter; Beyer, Matthias; Dietrich, Peter; Dahmke, Andreas

    2014-05-01

    The accidental release of CO2 into potable aquifers, for instance as a consequence of a leakage out of a CO2 store site, can endanger drinking water resources due to the induced geochemical processes. A 10-day CO2 injection experiment into a shallow aquifer was carried out in Wittstock (Northeast Germany) in order to investigate the geochemical impact of a CO2 influx into such an aquifer and to test different monitoring methods. Information regarding the site investigation, the injection procedure monitoring setup, and first geochemical monitoring results are described in [1]. Apart from the utilization of the test results to evaluate monitoring approaches [2], further findings are presented on the evaluation of the geophysical monitoring [3], and the monitoring of stable carbon isotopes [4]. This part of the study focuses of the hydrogeochemical alteration of groundwater due to the CO2 injection test. As a consequence of the CO2 injection, major cations were released, i.e. concentrations increased, whereas major anion concentrations - beside bicarbonate - decreased, probably due to increased anion sorption capacity at variably charged exchange sites of minerals. Trace element concentrations increased as well significantly, whereas the relative concentration increase was far larger than the relative concentration increase of major cations. Furthermore, geochemical reactions show significant spatial heterogeneity, i.e. some elements such as Cr, Cu, Pb either increased in concentration or remained at stable concentrations with increasing TIC at different wells. Statistical analyses of regression coefficients confirm the different spatial reaction patterns at different wells. Concentration time series at single wells give evidence, that the trace element release is pH dependent, i.e. trace elements such as Zn, Ni, Co are released at pH of around 6.2-6.6, whereas other trace elements like As, Cd, Cu are released at pH of 5.6-6.4. [1] Peter, A., et al., Investigation of

  20. Validity of estimates of myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography despite altered patterns of substrate utilization

    SciTech Connect

    Brown, M.A.; Myears, D.W.; Bergmann, S.R.

    1989-02-01

    We recently demonstrated that the myocardial turnover rate constant (k) measured noninvasively with positron emission tomography (PET) after intravenous administration of (/sup 11/C)acetate provides a reliable index of myocardial oxidative metabolism (MVO/sub 2/) theoretically independent of the pattern of myocardial substrate use. However, because estimates of metabolism with other metabolic tracers are sensitive to substrate use, we measured k in 12 dogs during baseline conditions and again after infusion of either glucose (n = 8) or Intralipid (n = 4), interventions that raised arterial glucose or fatty acids by more than fivefold with concomitant changes in myocardial substrate use. Following glucose administration k increased, but no difference was detected after compensation for changes in hemodynamics and myocardial work induced by the infusion (0.18 +/- 0.03 min-1) (t1/2 = 3.9 min) at baseline compared with 0.22 +/- 0.06 min-1 (t1/2 = 3.2 min, p = N.S.). k was not affected by Intralipid infusion (k = 0.15 +/- 0.06 min-1 at baseline and 0.14 +/- 0.04 min-1 during infusion), and correlated closely with MVO/sub 2/ measured directly (n = 19 comparisons, r = 0.89). The results indicate that estimates of MVO/sub 2/ using (/sup 11/C)acetate and PET are valid despite changes in the pattern of myocardial substrate utilization.

  1. Alteration of the Carbon and Nitrogen Isotopic Composition in the Martian Surface Rocks Due to Cosmic Ray Exposure

    NASA Technical Reports Server (NTRS)

    Pavlov, A. A.; Pavlov, A. K.; Ostryakov, V. M.; Vasilyev, G. I.; Mahaffy, P.; Steele, A.

    2014-01-01

    C-13/C-12 and N-15/N-14 isotopic ratios are pivotal for our understanding of the Martian carbon cycle, history of the Martian atmospheric escape, and origin of the organic compounds on Mars. Here we demonstrate that the carbon and nitrogen isotopic composition of the surface rocks on Mars can be significantly altered by the continuous exposure of Martian surface to cosmic rays. Cosmic rays can effectively produce C-13 and N-15 isotopes via spallation nuclear reactions on oxygen atoms in various Martian rocks. We calculate that in the top meter of the Martian rocks, the rates of production of both C-13 and N-15 due to galactic cosmic rays (GCRs) exposure can vary within 1.5-6 atoms/cm3/s depending on rocks' depth and chemical composition. We also find that the average solar cosmic rays can produce carbon and nitrogen isotopes at a rate comparable to GCRs in the top 5-10 cm of the Martian rocks. We demonstrate that if the total carbon content in a surface Martian rock is <10 ppm, then the "light," potentially "biological" C-13/C-12 ratio would be effectively erased by cosmic rays over 3.5 billion years of exposure. We found that for the rocks with relatively short exposure ages (e.g., 100 million years), cosmogenic changes in N-15/N-14 ratio are still very significant. We also show that a short exposure to cosmic rays of Allan Hills 84001 while on Mars can explain its high-temperature heavy nitrogen isotopic composition (N-15/N-14). Applications to Martian meteorites and the current Mars Science Laboratory mission are discussed.

  2. Alteration of the carbon and nitrogen isotopic composition in the Martian surface rocks due to cosmic ray exposure

    NASA Astrophysics Data System (ADS)

    Pavlov, A. A.; Pavlov, A. K.; Ostryakov, V. M.; Vasilyev, G. I.; Mahaffy, P.; Steele, A.

    2014-06-01

    13C/12C and 15N/14N isotopic ratios are pivotal for our understanding of the Martian carbon cycle, history of the Martian atmospheric escape, and origin of the organic compounds on Mars. Here we demonstrate that the carbon and nitrogen isotopic composition of the surface rocks on Mars can be significantly altered by the continuous exposure of Martian surface to cosmic rays. Cosmic rays can effectively produce 13C and 15N isotopes via spallation nuclear reactions on oxygen atoms in various Martian rocks. We calculate that in the top meter of the Martian rocks, the rates of production of both 13C and 15N due to galactic cosmic rays (GCRs) exposure can vary within 1.5-6 atoms/cm3/s depending on rocks' depth and chemical composition. We also find that the average solar cosmic rays can produce carbon and nitrogen isotopes at a rate comparable to GCRs in the top 5-10 cm of the Martian rocks. We demonstrate that if the total carbon content in a surface Martian rock is <10 ppm, then the "light," potentially "biological" 13C/12C ratio would be effectively erased by cosmic rays over 3.5 billion years of exposure. We found that for the rocks with relatively short exposure ages (e.g., 100 million years), cosmogenic changes in 15N/14N ratio are still very significant. We also show that a short exposure to cosmic rays of Allan Hills 84001 while on Mars can explain its high-temperature heavy nitrogen isotopic composition (15N/14N). Applications to Martian meteorites and the current Mars Science Laboratory mission are discussed.

  3. Alteration of the Carbon and Nitrogen Isotopic Composition in the Martian Surface Rocks Due to Cosmic Ray Exposure

    NASA Technical Reports Server (NTRS)

    Pavlov, A. A.; Pavlov, A. K.; Ostryakov, V. M.; Vasilyev, G. I.; Mahaffy, P.; Steele, A.

    2014-01-01

    C-13/C-12 and N-15/N-14 isotopic ratios are pivotal for our understanding of the Martian carbon cycle, history of the Martian atmospheric escape, and origin of the organic compounds on Mars. Here we demonstrate that the carbon and nitrogen isotopic composition of the surface rocks on Mars can be significantly altered by the continuous exposure of Martian surface to cosmic rays. Cosmic rays can effectively produce C-13 and N-15 isotopes via spallation nuclear reactions on oxygen atoms in various Martian rocks. We calculate that in the top meter of the Martian rocks, the rates of production of both C-13 and N-15 due to galactic cosmic rays (GCRs) exposure can vary within 1.5-6 atoms/cm3/s depending on rocks' depth and chemical composition. We also find that the average solar cosmic rays can produce carbon and nitrogen isotopes at a rate comparable to GCRs in the top 5-10 cm of the Martian rocks. We demonstrate that if the total carbon content in a surface Martian rock is <10 ppm, then the "light," potentially "biological" C-13/C-12 ratio would be effectively erased by cosmic rays over 3.5 billion years of exposure. We found that for the rocks with relatively short exposure ages (e.g., 100 million years), cosmogenic changes in N-15/N-14 ratio are still very significant. We also show that a short exposure to cosmic rays of Allan Hills 84001 while on Mars can explain its high-temperature heavy nitrogen isotopic composition (N-15/N-14). Applications to Martian meteorites and the current Mars Science Laboratory mission are discussed.

  4. Alterations in Atrial Electrophysiology and Tissue Structure in a Canine Model of Chronic Atrial Dilatation Due to Mitral Regurgitation

    PubMed Central

    Verheule, Sander; Wilson, Emily; Everett, Thomas; Shanbhag, Sujata; Golden, Catherine; Olgin, Jeffrey

    2007-01-01

    Background Clinically, chronic atrial dilatation is associated with an increased incidence of atrial fibrillation (AF), but the underlying mechanism is not clear. We have investigated atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation (MR). Methods and Results Thirteen control and 19 MR dogs (1 month after partial mitral valve avulsion) were studied. Dogs in the MR group were monitored using echocardiography and Holter recording. In open-chest follow-up experiments, electrode arrays were placed on the atria to investigate conduction patterns, effective refractory periods, and inducibility of AF. Alterations in tissue structure and ultrastructure were assessed in atrial tissue samples. At follow-up, left atrial length in MR dogs was 4.09±0.45 cm, compared with 3.25±0.28 at baseline (P<0.01), corresponding to a volume of 205±61% of baseline. At follow-up, no differences in atrial conduction pattern and conduction velocities were noted between control and MR dogs. Effective refractory periods were increased homogeneously throughout the left and right atrium. Sustained AF (>1 hour) was inducible in 10 of 19 MR dogs and none of 13 control dogs (P<0.01). In the dilated MR left atrium, areas of increased interstitial fibrosis and chronic inflammation were accompanied by increased glycogen ultrastructurally. Conclusions Chronic atrial dilatation in the absence of overt heart failure leads to an increased vulnerability to AF that is not based on a decrease in wavelength. PMID:12732604

  5. Diurnal Alterations of Refraction, Anterior Segment Biometrics, and Intraocular Pressure in Long-Time Dehydration due to Religious Fasting.

    PubMed

    Baser, Gonen; Cengiz, Hakan; Uyar, Murat; Seker Un, Emine

    2016-01-01

    To investigate the effects of dehydration due to fasting on diurnal changes of intraocular pressure, anterior segment biometrics, and refraction. The intraocular pressures, anterior segment biometrics (axial length: AL; Central corneal thickness: CCT; Lens thickness: LT; Anterior chamber depth: ACD), and refractive measurements of 30 eyes of 15 fasting healthy male volunteers were recorded at 8:00 in the morning and 17:00 in the evening in the Ramadan of 2013 and two months later. The results were compared and the statistical analyses were performed using the Rstudio software version 0.98.501. The variables were investigated using visual (histograms, probability plots) and analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk test) to determine whether or not they were normally distributed. The refractive values remained stable in the fasting as well as in the control period (p = 0.384). The axial length measured slightly shorter in the fasting period (p = 0.001). The corneal thickness presented a diurnal variation, in which the cornea measured thinner in the evening. The difference between the fasting and control period was not statistically significant (p = 0.359). The major differences were observed in the anterior chamber depth and IOP. The ACD was shallower in the evening during the fasting period, where it was deeper in the control period. The diurnal IOP difference was greater in the fasting period than the control period. Both were statistically significant (p = 0.001). The LT remained unchanged in both periods. The major difference was shown in the anterior chamber shallowing in the evening hours and IOP. Our study contributes the hypothesis that the posterior segment of the eye is more responsible for the axial length alterations and normovolemia has a more dominant influence on diurnal IOP changes.

  6. Declines in Soil pH due to Anthropogenic Nitrogen Inputs Alter Buffering and Exchange Reactions in Tropical Forest Soils

    NASA Astrophysics Data System (ADS)

    Lohse, K. A.

    2003-12-01

    Anthropogenic nitrogen (N) inputs may alter tropical soil buffering and exchange reactions that have important implications for nutrient cycling, forest productivity, and downstream ecosystems. In contrast to relatively young temperate soils that are typically buffered from N inputs by base cation reactions, aluminum reactions may serve to buffer highly weathered tropical soils and result in immediate increases in aluminum mobility and toxicity. Increased nitrate losses due to chronic N inputs may also deplete residual base cations in already weathered base cation-poor soils, further acidify soils, and thereby reduce nitrate mobility through pH-dependent anion exchange reactions. To test these hypotheses, I determined soil pH and cation and anion exchange capacity (CEC and AEC) and measured base cation and aluminum soil solution losses following first-time and long-term experimental N additions from two Hawaiian tropical forest soils, a 300 year old Andisol and a 4.1 million year old Oxisol. I found that elevated base cation losses accompanied increased nitrate losses after first time N additions to the young Andisol whereas immediate and large aluminum losses were associated with increased nitrate losses from the Oxisol. In the long-term, base cation and aluminum losses increased in proportion to nitrate losses. Long-term N additions at both sites resulted in significant declines in soil pH, decreased CEC and increased AEC. These results suggest that even chronic N inputs resulting in small but elevated nitrate losses may deplete residual base cations, increase mobility and toxicity of aluminum, and potentially lead to declines in forest productivity and acidification of downstream ecosystems. These findings also suggest that AEC may provide a long-term mechanism to delay nitrate losses in tropical forests with significant variable charge that are experiencing chronic anthropogenic N inputs.

  7. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    SciTech Connect

    Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  8. Evaluate the early changes of myocardial fibers in rhesus monkey during sub-acute stage of myocardial infarction using diffusion tensor magnetic resonance imaging.

    PubMed

    Wang, Yuqing; Cai, Wei; Wang, Lei; Xia, Rui

    2016-05-01

    The deterioration of cardiac mechanical function starts from the micro-alterations in the myocardial fibers after myocardial infarction (MI) due to the heart beats derived from the systole and diastole of the myocardial fibers. So, we want to evaluate quantitatively the early changes of myocardial fibers in rhesus monkey during sub-acute MI stage. Three fixed hearts with infarction after left anterior descending coronary artery ligation for 7days and eight age-matched intact controls were scanned by ex-vivo diffusion tensor magnetic resonance imaging (DT-MRI) to measure apparent diffusion coefficient (ADC), fractional anisotropy (FA) and helix angle (HA). In comparison with healthy controls, FA and transmural range of HA in MI regions showed a significant reduction whereas ADC showed a significant increment (p<0.01). The double-helix myocardial fibers shifted further to left-handed helix around the infarcted and adjacent myocardium but shifted further to right-handed helix in remote myocardium. HA is sensitive to evaluate quantitatively the early changes of myocardial fibers in sub-acute MI rhesus monkeys. The myocardial fibers in normal monkeys are similar to those in normal humans, suggesting that early changes of myocardial fibers in sub-acute MI monkeys can contribute to more accurately understand those in patients suffering sub-acute MI. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Acute Myocardial Infarction Due to Coronary Artery Embolism in a 22-Year-Old Woman with Mitral Stenosis with Atrial Fibrillation Under Warfarinization: Successful Management with Anticoagulation.

    PubMed

    Sinha, Santosh Kumar; Jha, Mukesh Jitendra; Razi, Mahmadula; Chaturvedi, Vikash; Erappa, Yatish Besthenahalli; Singh, Shravan; Mishra, Vikas; Khanra, Dibbendhu; Singh, Karandeep

    2017-04-07

    BACKGROUND Coronary artery embolization is an exceedingly rare cause of myocardial infarction, but a few cases in association with prosthetic mechanical valves have been reported. We report a case of embolic myocardial infarction caused by a thrombus in the left atrium with deranged coagulation profile in a patient with critical mitral stenosis under warfarinization. CASE REPORT A 22-year-old woman was taken to the catheterization lab for early coronary intervention in lieu of non-ST elevation myocardial infarction. Electrocardiography showed T↓ in V1 to V4, and atrial fibrillation with controlled ventricular rate. Coronary angiography showed total occlusion of the mid-left anterior descending artery with thrombus. After upstream treatment with tirofiban, the apparent thrombus was dislodged distally while passing a BMW wire. No abnormalities were seen by intravascular ultrasound study. Echocardiography revealed critical mitral stenosis, and left atrial clot with mild left ventricular dysfunction. Coagulation profile revealed sub-therapeutic international normalized ratio levels. The sequential angiographic images, normal intravascular ultrasound study, and presence of atrial fibrillation are confirmatory of coronary embolism as the cause of myocardial infarction. Anticoagulation and treatment of acute coronary syndrome were initiated and she was referred for closed mitral valvulotomy. CONCLUSIONS Coronary artery thromboembolism as a nonatherosclerotic cause of acute coronary syndrome is rare. The treatment consists of aggressive anticoagulation, antiplatelet therapy, and interventional options, including simple wiring when possible. In this context, primary prevention in the form of patient education on optimal anticoagulation with oral vitamin K antagonist and medical advice about imminent thromboembolic risks are of extreme importance.

  10. Potential for quantification of regionally altered myocardial perfusion by analysis of rubidium and thallium mean transit times in the rabbit heart

    SciTech Connect

    Marshall, R.C.; Taylor, S.E.; Powers-Risius, P.

    1995-05-01

    Quantitative estimation of regionally altered perfusion could result in improved clinical care for patients with coronary artery disease. We hypothesized that myocardial blood flow (F) and mean transit time (T{sub mtt}) should vary reciprocally for potassium analogs, such as rubidium and thallium, based on the relationship V{sub d}/F=T{sub mtt}. Twelve isolated blood-perfused rabbit hearts were studied at flows ranging from 0.7 to 2.92 ml/gm min{sup -1}. Bolus injections of Rb-83, Tl-201 and I-125 albumin were followed by subsequent venous ampling for 20 to 30 minutes. T{sub mtt} was estimated using two methods which compensate for the dispersion of the bolus in the blood vessels. In Method A, the I-125 albumin venous concentration curve was convolved with a Dirac delta function and one or more exponentials, and fit to the Rb-83 and Tl-201 venous concentration curves. Mean transit times of the Rb-83 and Tl-201 were computed as the weighted sums of the fitted components. In B, all three venous concentration curves were extrapolated by fitting a straight line to the tail of the semi-log plot of each curve. Extrapolated curves were then normalized to unit area, weighted by time, and numerically integrated to obtain gross mean transit times. Net mean transit times for Rb-83 and Tl-201 were then obtained by subtracting the gross mean transit time for I-125 albumin from those for Rb-83 and Tl-201. T{sub mtt} ranged from 4.0 to 15.5 min for Rb-83 and 6.0 to 29.7 min for Tl-=201. Correlations between 1/T{sub mtt} and F for Tl-201 were y = 0.064x - 0.005, r = 0.87 (Method A) and y = 0.049x + 0.011, r = 0.80 (Method B). The correlation for Rb-83 and Method B was y = 0.07x + 0.03, r = 0.89 which was significantly superior to Method A. Results are consistent with the hypothesis that F and T{sub mtt} vary inversely and suggest that T{sub mtt} could be used to quantitatively estimate regional perfusion in vivo after subtraction of the mean transit time of the input function.

  11. ST-elevation acute myocardial infarction due to arterial thrombosis in a 29-year-old woman with normal coronary arteries

    PubMed Central

    Male, Eneida; Morton, Talitha; Farber, Adam

    2017-01-01

    Acute myocardial infarction (AMI) is rare in young adults. We present a case of a 29-year-old black woman who presented with an acute onset of chest pain while sleeping. Anterior wall ST-elevation AMI was diagnosed based on clinical presentation, electrocardiographic findings, and elevated cardiac biomarkers. Coronary angiography revealed a totally occluded proximal left anterior descending artery. The obstructing lesion, thrombus, was removed. There was no evidence of atherosclerotic disease or dissection. An evaluation for a hypercoagulable state was unrevealing. Echocardiography 1 year later revealed normal left ventricular wall motion and systolic function. PMID:28127135

  12. Prefrontal Compensatory Engagement in TBI is due to Altered Functional Engagement Of Existing Networks and not Functional Reorganization.

    PubMed

    Turner, Gary R; McIntosh, Anthony R; Levine, Brian

    2011-01-01

    Functional neuroimaging studies of traumatic brain injury (TBI) have demonstrated altered neural recruitment, specifically within prefrontal cortex (PFC). This is manifest typically as increased recruitment of homologous regions of PFC (e.g., right ventrolateral PFC during performance of a verbal working memory task, possibly in response to damage involving the left PFC). The behavioral correlates of these functional changes are poorly understood. We used fMRI and multivariate analytic methods to investigate changes in spatially distributed activity patterns and their behavioral correlates in a sample of TBI patients with diffuse axonal injury (DAI, but without focal injury) and matched healthy controls. Participants performed working memory tasks with varying memory load and executive demand. We identified networks within left and right PFC that uniquely and positively correlated with performance in our control and TBI samples respectively, providing evidence of compensatory functional recruitment. Next we combined brain-behavior and functional connectivity analyses to investigate whether compensatory brain changes were facilitated by functional reorganization (i.e., recruitment of brain regions not engaged by our control sample) or altered functional engagement (i.e., differential recruitment of similar brain regions between the two groups based on task demands). In other words, does altered recruitment represent the instantiation of novel neural networks to support working memory performance after injury or the unmasking of extant, but behaviorally latent, functional connectivity? Our results support an altered functional engagement hypothesis. Areas within PFC that are normally coactivated during working memory are behaviorally relevant at an earlier stage of difficulty for TBI patients as compared to controls. This altered functional engagement, also evident in the aging literature, is attributable to distributed changes owing to significant DAI.

  13. Implantable cardioverter defibrillator and survival after out-of-hospital cardiac arrest due to acute myocardial infarction in Denmark in the years 2001-2012, a nationwide study.

    PubMed

    Winther-Jensen, Matilde; Kjaergaard, Jesper; Lassen, Jens F; Køber, Lars; Torp-Pedersen, Christian; Hansen, Steen M; Lippert, Freddy; Kragholm, Kristian; Christensen, Erika F; Hassager, Christian

    2017-03-01

    The purpose of this study was to describe the implantation of implantable cardioverter defibrillator after out-of-hospital cardiac arrest caused by myocardial infarction in Denmark 2001-2012 and subsequent survival. The Danish Cardiac Arrest Registry was used to identify patients ⩾18 years surviving to discharge without prior implantable cardioverter defibrillator. Information on cardioverter defibrillator implantation was obtained from the National Patient Registry. We identified 974 myocardial infarction-out-of-hospital cardiac arrest patients surviving to hospital discharge, 130 of these patients (13%) had a cardioverter defibrillator implanted early (⩽40 days post-out-of-hospital cardiac arrest), 58 patients (6%) had late implantable cardioverter defibrillator (41-365 days post-out-of-hospital cardiac arrest). Odds of implantable cardioverter defibrillator implantation within one year were higher in patients receiving cardiopulmonary resuscitation (odds ratio (OR)CPR: 1.99, confidence interval (CI): 1.23-3.22, p=0.01), and Charlson Comorbidity Index level 1, (ORCCI1: 2.10, CI:1.25-3.49, p<0.01). Odds of a late implantable cardioverter defibrillator was higher in patients undergoing percutaneous coronary intervention (PCI) (ORPCI: 3.67, CI: 1.35-9.97, p=0. 01). An early, but not late implantable cardioverter defibrillator was associated with increased survival (event time ratioEarly ICD: 1.45, CI: 1.11-1.90, p=0.01). Chronic heart failure, higher age groups, Charlson Comorbidity Index levels 1 to ⩾3 and male sex were associated with lower survival. Highest income was associated with higher survival. Cardioverter defibrillator implantation rates in patients surviving an myocardial infarction-out-of-hospital cardiac arrest increased from 14% to 19% over the period. Of the total patient population, 13% had implantation earlier than recommended by guidelines, presumably as primary prevention of sudden cardiac death. Acute PCI and arrest later in the study

  14. Structural alterations in rat liver proteins due to streptozotocin-induced diabetes and the recovery effect of selenium: Fourier transform infrared microspectroscopy and neural network study

    NASA Astrophysics Data System (ADS)

    Bozkurt, Ozlem; Haman Bayari, Sevgi; Severcan, Mete; Krafft, Christoph; Popp, Jürgen; Severcan, Feride

    2012-07-01

    The relation between protein structural alterations and tissue dysfunction is a major concern as protein fibrillation and/or aggregation due to structural alterations has been reported in many disease states. In the current study, Fourier transform infrared microspectroscopic imaging has been used to investigate diabetes-induced changes on protein secondary structure and macromolecular content in streptozotocin-induced diabetic rat liver. Protein secondary structural alterations were predicted using neural network approach utilizing the amide I region. Moreover, the role of selenium in the recovery of diabetes-induced alterations on macromolecular content and protein secondary structure was also studied. The results revealed that diabetes induced a decrease in lipid to protein and glycogen to protein ratios in diabetic livers. Significant alterations in protein secondary structure were observed with a decrease in α-helical and an increase in β-sheet content. Both doses of selenium restored diabetes-induced changes in lipid to protein and glycogen to protein ratios. However, low-dose selenium supplementation was not sufficient to recover the effects of diabetes on protein secondary structure, while a higher dose of selenium fully restored diabetes-induced alterations in protein structure.

  15. Magnetic resonance imaging dynamic contrast enhancement (DCE) characteristics of healed myocardial infarction differ from viable myocardium.

    PubMed

    Goldfarb, James W; Zhao, Wenguo

    2014-12-01

    To determine whether healed myocardial infarction alters dynamic contrast-enhancement (DCE) curve shapes as well as late gadolinium-enhancement (LGE). Twenty patients with chronic myocardial infarction underwent MR imaging at 1.5 T with blood and myocardial T1 measurements before and after contrast administration for forty minutes. Viable and infarcted myocardial partition coefficients were calculated using multipoint slope methods for ten different DCE sampling intervals and windows. Partition coefficients and coefficients of determination were compared with paired statistical tests to assess the linearity of DCE curve shapes over the 40 min time period. Calculated partition coefficients did not vary significantly between methods (p=0.325) for viable myocardium but did differ for infarcted myocardium (p<0.001), indicating a difference in infarcted DCE. There was a significant difference between viable and infarcted myocardial partition coefficients estimates for all methods with the exception of methods that included measurements during the first 10 min after contrast agent administration. Myocardial partition coefficients calculated from a slope calculation vary in healed myocardial infarction based on the selection of samples due to non-linear DCE curve shapes. Partition coefficient calculations are insensitive to data sampling effects in viable myocardium due to linear DCE curve shapes. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Cardiac remodeling and physical training post myocardial infarction

    PubMed Central

    Garza, Michael A; Wason, Emily A; Zhang, John Q

    2015-01-01

    After myocardial infarction (MI), the heart undergoes extensive myocardial remodeling through the accumulation of fibrous tissue in both the infarcted and noninfarcted myocardium, which distorts tissue structure, increases tissue stiffness, and accounts for ventricular dysfunction. There is growing clinical consensus that exercise training may beneficially alter the course of post-MI myocardial remodeling and improve cardiac function. This review summarizes the present state of knowledge regarding the effect of post-MI exercise training on infarcted hearts. Due to the degree of difficulty to study a viable human heart at both protein and molecular levels, most of the detailed studies have been performed by using animal models. Although there are some negative reports indicating that post-MI exercise may further cause deterioration of the wounded hearts, a growing body of research from both human and animal experiments demonstrates that post-MI exercise may beneficially alter the course of wound healing and improve cardiac function. Furthermore, the improved function is likely due to exercise training-induced mitigation of renin-angiotensin-aldosterone system, improved balance between matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, favorable myosin heavy chain isoform switch, diminished oxidative stress, enhanced antioxidant capacity, improved mitochondrial calcium handling, and boosted myocardial angiogenesis. Additionally, meta-analyses revealed that exercise-based cardiac rehabilitation has proven to be effective, and remains one of the least expensive therapies for both the prevention and treatment of cardiovascular disease, and prevents re-infarction. PMID:25717353

  17. Apparent partial resetting of U-Th-Pb systems in experimentally altered monazite resulting from nano-mixtures due to incomplete replacement.

    NASA Astrophysics Data System (ADS)

    Grand'homme, Alexis; Janots, Emilie; Seydoux-Guillaume, Anne-Magali; Guillaume, Damien; Bosse, Valérie; Magnin, Valérie

    2016-04-01

    Hydrothermal alteration experiments of natural monazite crystals (Manangotry, Madagascar; 555 Ma) under alkali conditions (NaOH 1M in 18O doped solution) at low temperature conditions (300, 400, 500 and 600°C), 200 MPa, were conducted to clarify the origin of unsupported Pb (radiogenic or not) in altered monazite (Seydoux-Guillaume et al., 2012). At 300°C, no evidence of monazite replacement was observed. From 400 to 600°C, experimental products show a replacement texture with pristine monazite (Mnz1) surrounded by an alteration rim with a different composition (SEM and EPMA). In the altered domains, in-situ isotopic and chemical U-Th-Pb dating yields intermediate ages between original monazite (555 Ma) and complete experimental resetting (0 Ma). Incomplete resetting is due to the systematic presence of Pb in altered domains, whose concentration decreases with increasing temperature. Transmission Electron Microscope (TEM) observations reveal an incomplete replacement of Mnz1 by a secondary monazite (Mnz2), free of Pb, within the altered domain. The latter domain, apparently homogeneous in BSE images, is in fact constituted by closely associated nano-mixtures of Mnz1 and Mnz2. Furthermore, the volume of Mnz2 within the altered domain, i.e. the efficiency of replacement, increases with increasing temperature. Apparent partial resetting of U-Th-Pb systems results from the unavoidable nano-mixture of different proportion of Mnz1 and Mnz2 within the analytical microvolume (EPMA, LA-ICP-MS). This study therefore indicates that the micrometric resolution (even the 5 μm3 for EPMA) of in-situ dating techniques may be not sufficient to solve such nano-replacement domains, especially when alteration occurs at low-temperature. Ref: Seydoux-Guillaume, A.-M., Montel, J.-M., Bingen, B., Bosse, V., de Parseval, P., Paquette, J.-L., Janots, E., and Wirth, R., (2012). Chemical Geology, v. 330-331, p. 140-158.

  18. Neuronal and glial alterations due to focal cortical hypoxia induced by direct cobalt chloride (CoCl2) brain injection.

    PubMed

    Caltana, Laura; Merelli, Amalia; Lazarowski, Alberto; Brusco, Alicia

    2009-05-01

    Ischemic brain injury is a dynamic process that involves oxidative stress, inflammation, and cell death, as well as activation of endogenous adaptive and regenerative mechanisms depending on activation of transcription factors such as hypoxia inducible factor 1-alpha (HIF-1alpha). Because CoCl2 activates HIF-1alpha, we described a new focal-hypoxia model by direct intracerebral CoCl2 injection. Adult male Wistar rats were intracerebrally injected with CoCl2 (2 microl-50 mM), in frontoparietal cortex of right hemisphere, and saline (2 microl) in the contralateral hemisphere. In slides of fixed brains at 1, 6, 9, 24 h or 5 day after treatment, TTC, histochemistry (toluidine blue, Hoescht-33342, TUNEL), immunostaining (HIF-1alpha, GFAP), Lycopersicon esculentum lectin staining, and electron microscopy (EM) were performed. Immediately after 1 h post CoCl2 injection, HIF-1alpha stabilization and neuronal nuclear shrinkage and cromathin condensation were observed by immunostaining and EM, respectively. Neuronal apoptotic nuclear morphology and GFAP immunoreactivity and lectin maximal reactivity were detected during 6-9 h. Ultrastructural alterations of morphology included edematous perinuclear cytoplasm, organelles and endoplasmic reticulum (RE) enlargement, mitochondrial swelling with increased matrix density, and deposits of electron-dense material. Neurons showed particular nuclear indentations. Astrocytes and oligodendrocytes presented alterations in both nuclei and RE with dilated lumen and altered mitochondrias, and all these ultrastructural changes became detectable at day 5. CoCl2 cortical injection mimics focal brain ischemia, inducing neuronal death and glial activation. This model brings the opportunity to develop focal ischemia in selected brain areas to study their functional consequences and potential pharmacological therapies for in vivo models of stroke.

  19. A graphical approach to characterize sub-daily flow regimes and evaluate its alterations due to hydropeaking.

    PubMed

    Alonso, Carlos; Román, Alfonso; Bejarano, Maria Dolores; Garcia de Jalon, Diego; Carolli, Mauro

    2017-01-01

    Most flow regime characterizations focus on long time scale flow patterns, which are not precise enough to capture key components of short-term flow fluctuations. Recent proposed methods describing sub-daily flow fluctuations are focused on limited components of the flow regime being unable to fully represent it, or on the identification of peaking events based on subjectively defined thresholds, being unsuitable for evaluations of short-term flow regime alterations through comparisons between regulated and free-flowing rivers. This study aims to launch an innovative approach based on the visual display of quantitative information to address the challenge of the short-term hydrologic characterization and evaluation of alteration resulting from hydropeaking. We propose a graphical method to represent a discrete set of ecologically relevant indices that characterize and evaluate the alteration of sub-daily flow regimes. The frequency of occurrence of classified values of a descriptive hydrological variable is represented in a map-like graph where longitude, latitude and altitude represent the Julian day, the value of the variable and the frequency of occurrence, respectively. Subsequently, we tested the method on several rivers, both free-flowing and subjected to hydropower production. The advantages of our approach compared to other analytical methods are: (i) it displays a great amount of information without oversimplification; (ii) it takes into account changes in the intensity, timing and frequency of the sub-daily flows, without needing a priori defined thresholds to identify hydropeaking events; and (iii) it supports the Water Framework Directive goal. Specifically, results from applications of our graphical method agree with Sauterleute and Charmasson (2014) analytical method.

  20. Alterations in the metabolism of endogenous trace metals due to cadmium, manganese and nickel - effect of partial hepatectomy

    SciTech Connect

    Srivastava, R.C.; Ahmad, I.; Kaur, G.; Hasan, S.K.

    1988-01-01

    The effect of cadmium, manganese and nickel on the levels of copper, manganese, iron and zinc in liver was studied in sham operated and partially hepatectomized rats, 72 hrs after metal administration. Partial hepatectomy produced significant increase in the level of zinc and decrease in the levels of copper, iron and manganese. The metabolic disposition of these essential micronutrients were significantly altered as a result of cadmium administration in both the groups. Manganese and nickel had little effect and only induced the level of zinc.

  1. The altered expression profile of microRNAs in cardiopulmonary bypass canine models and the effects of mir-499 on myocardial ischemic reperfusion injury

    PubMed Central

    2013-01-01

    Background MicroRNAs were enrolled in various cardiovascular disease especially ischemic heart diseases, but the microRNA changes during myocardial ischemia reperfusion injury underwent cardiopulmonary bypass are still unknown. This study screens the microRNA differences in CPB canines and evaluates the relationship of microRNAs with myocardial ischemia reperfusion injury. Methods 13 healthy canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest, followed by 90 minutes reperfusion. Left ventricular myocardial samples, blood samples and hemodynamic data were taken at different time points. We performed microRNAs microarray experiments upon the left ventricle myocardium tissue of canines before CPB and after reperfusion for 90 minutes by pooling 3 tissue samples together and used qRT-PCR for confirmation. Results Statistically significant difference was found in mir-499 level before CPB and after reperfusion (T1 vs. T4, p = 0.041). We further examined the mir-499 levels by using qRT-PCR in all 13 canines at 4 different time points (T1 vs. T4, p = 0.029). Mir-499 expression was negatively correlated with cardiac troponin T (cTnT) and creatine kinase- MB (CK-MB) levels of canines in all time points samples (r = 0.469, p < 0.001 and r = 0.273, p = 0.050 respectively). Moreover, higher mir-499 expression level was associated with higher dP/dtmax at 25 minutes and 90 minutes after reperfusion. Conclusion Myocardial ischemic reperfusion injury with cardiopulmonary bypass results in declining level of mir-499 expression in left ventricle myocardium of canines, suggesting mir-499 would be a potential therapeutic target in cardiac protection during open heart surgery. PMID:23800236

  2. Myocardial Tissue Doppler Velocity in Child Growth

    PubMed Central

    Choi, Sun-Ha; Kim, Nam Kyun; Jung, Jo Won; Choi, Jae Young

    2016-01-01

    Background In adults, tissue Doppler imaging (TDI) is a recommended component of routine echocardiography. However, TDI velocities are less accepted in pediatrics, due to their strong variability and age dependence in children. This study examines the distribution of myocardial tissue Doppler velocities in healthy children to assess the effect of age with cardiac growth on the various echocardiographic measurements. Methods Total 144 healthy children were enrolled in this study. They were recruited from the pediatric outpatient clinic for routine well-child visits. The statistical relationships between age and TDI values were analyzed. Also, the statistical relationships between body surface area (BSA) and TDI values, left ventricle end-diastolic dimension (LVEDD) and TDI values were analyzed. Also, we conducted multivariate analysis of cardiac growth parameters such as, age, BSA, LVEDD and TDI velocity data. Results All of the age, BSA, and LVEDD had positive correlations with deceleration time (DT), pressure half-time (PHT), peak early diastolic myocardial velocity, peak systolic myocardial velocity, and had negative correlations with peak late diastolic velocity (A) and the ratio of trans-mitral inflow velocity to early diastolic velocity of mitral annulus (E/E'). In the multivariate analysis, all of the age, BSA, and LVEDD had positive correlations with DT, PHT, and negative correlations with A and E/E'. Conclusion The cardiac growth parameters related alterations of E/E' may suggest that diastolic myocardial velocities are cardiac growth dependent, and diastolic function has positive correlation with cardiac growth in pediatric group. This cardiac growth related myocardial functional variation would be important for assessment of cardiac involvement either in healthy and sick child. PMID:27081443

  3. Alteration of Mesoscopic Properties and Mechanical Behavior of Sandstone Due to Hydro-Physical and Hydro-Chemical Effects

    NASA Astrophysics Data System (ADS)

    Qiao, Liping; Wang, Zhechao; Huang, Anda

    2017-02-01

    The hydro-physical and hydro-chemical interactions between groundwater and a rock mass can lead to changes in the mineral composition and structure of the rock (e.g., generation of voids and dissolution pores and an increase in the porosity), thereby altering the macroscopic mechanical characteristics of the rock mass. Sandstone specimens were saturated with distilled water and five aqueous solutions characterized by various ion concentrations and pH values for several months, and their porosity was measured in real time. Simultaneously, the concentration and pH of each aqueous solution were monitored every 30 days. The results indicate that after immersion in the aqueous solutions for 180 days, the porosity of the sandstone specimens and the ion concentrations and pH of the aqueous solutions tended to stabilize. Then, the immersed sandstone specimens were analyzed in thin section and subjected to computerized tomography scanning. It turns out that the mineral composition and structure of the specimens had all changed to various degrees. Finally, the uniaxial compression tests were conducted on the sandstone specimens to analyze the effects of the hydro-physical and hydro-chemical alteration on the macroscopic mechanical characteristics of the rock (e.g., the stress-strain relationship, elastic modulus, and peak strength). The results of this study can serve as a reference for investigations into theories and applications of water-rock interactions and for research in related fields.

  4. Bentonite alteration due to thermal-hydro-chemical processes during the early thermal period in a nuclear waste repository

    SciTech Connect

    Xu, T.; Senger, R.; Finsterle, S.

    2011-02-01

    After closure of an underground nuclear waste repository, the decay of radionuclides will raise temperature in the repository, and the bentonite buffer will resaturate by water inflow from the surrounding host rock. The perturbations from these thermal and hydrological processes are expected to dissipate within hundreds to a few thousand years. Here, we investigate coupled thermal-hydro-chemical processes and their effects on the short-term performance of a potential nuclear waste repository located in a clay formation. Using a simplified geometric configuration and abstracted hydraulic parameters of the clayey formation, we examine geochemical processes, coupled with thermo-hydrologic phenomena, and potential changes in porosity near the waste container during the early thermal period. The developed models were used for evaluating the mineral alterations and potential changes in porosity of the buffer, which can affect the repository performance. The results indicate that mineral alteration and associated changes in porosity induced by early thermal and hydrological processes are relatively small and are expected to not significantly affect flow and transport properties. Chlorite precipitation was obtained in all simulation cases. A maximum of one percent volume fraction of chlorite could be formed, whose process may reduce swelling and sorption capacity of bentonite clay, affecting the performance of the repository. llitisation process was not obtained from the present simulations.

  5. Myocardial diseases of animals.

    PubMed Central

    Van Vleet, J. F.; Ferrans, V. J.

    1986-01-01

    In this review we have attempted a comprehensive compilation of the cardiac morphologic changes that occur in spontaneous and experimental myocardial diseases of animals. Our coverage addresses diseases of mammals and birds and includes these diseases found in both domesticated and wild animals. A similar review of the myocardial diseases in this broad range of animal species has not been attempted previously. We have summarized and illustrated the gross, microscopic, and ultrastructural alterations for these myocardial diseases; and, whenever possible, we have reviewed their biochemical pathogenesis. We have arranged the myocardial diseases for presentation and discussion according to an etiologic classification with seven categories. These include a group of idiopathic or primary cardiomyopathies recognized in man (hypertrophic, dilated, and restrictive types) and a large group of secondary cardiomyopathies with known causes, such as inherited tendency; nutritional deficiency; toxicity; physical injury and shock; endocrine disorders, and myocarditides of viral, bacterial, and protozoal causation. Considerable overlap exists between each of the etiologic groups in the spectrum of pathologic alterations seen in the myocardium. These include various degenerative changes, myocyte necrosis, and inflammatory lesions. However, some diseases show rather characteristic myocardial alterations such as vacuolar degeneration in anthracycline cardiotoxicity, myofibrillar lysis in furazolidone cardiotoxicity, calcification in calcinosis of mice, glycogen accumulation in the glycogenoses, lipofuscinosis in cattle, fatty degeneration in erucic acid cardiotoxicity, myofiber disarray in hypertrophic cardiomyopathy, and lymphocytic inflammation with inclusion bodies in canine parvoviral myocarditis. The myocardial diseases represent the largest group in the spectrum of spontaneous cardiac diseases of animals. Pericardial and endocardial diseases and congential cardiac diseases are

  6. Alterations in the coupling functions between cortical and cardio-respiratory oscillations due to anaesthesia with propofol and sevoflurane

    PubMed Central

    Petkoski, Spase; Raeder, Johan; Smith, Andrew F.; McClintock, Peter V. E.; Stefanovska, Aneta

    2016-01-01

    The precise mechanisms underlying general anaesthesia pose important and still open questions. To address them, we have studied anaesthesia induced by the widely used (intravenous) propofol and (inhalational) sevoflurane anaesthetics, computing cross-frequency coupling functions between neuronal, cardiac and respiratory oscillations in order to determine their mutual interactions. The phase domain coupling function reveals the form of the function defining the mechanism of an interaction, as well as its coupling strength. Using a method based on dynamical Bayesian inference, we have thus identified and analysed the coupling functions for six relationships. By quantitative assessment of the forms and strengths of the couplings, we have revealed how these relationships are altered by anaesthesia, also showing that some of them are differently affected by propofol and sevoflurane. These findings, together with the novel coupling function analysis, offer a new direction in the assessment of general anaesthesia and neurophysiological interactions, in general. PMID:27045000

  7. Alterations in the coupling functions between cortical and cardio-respiratory oscillations due to anaesthesia with propofol and sevoflurane

    NASA Astrophysics Data System (ADS)

    Stankovski, Tomislav; Petkoski, Spase; Raeder, Johan; Smith, Andrew F.; McClintock, Peter V. E.; Stefanovska, Aneta

    2016-05-01

    The precise mechanisms underlying general anaesthesia pose important and still open questions. To address them, we have studied anaesthesia induced by the widely used (intravenous) propofol and (inhalational) sevoflurane anaesthetics, computing cross-frequency coupling functions between neuronal, cardiac and respiratory oscillations in order to determine their mutual interactions. The phase domain coupling function reveals the form of the function defining the mechanism of an interaction, as well as its coupling strength. Using a method based on dynamical Bayesian inference, we have thus identified and analysed the coupling functions for six relationships. By quantitative assessment of the forms and strengths of the couplings, we have revealed how these relationships are altered by anaesthesia, also showing that some of them are differently affected by propofol and sevoflurane. These findings, together with the novel coupling function analysis, offer a new direction in the assessment of general anaesthesia and neurophysiological interactions, in general.

  8. Altered joint tribology in osteoarthritis: Reduced lubricin synthesis due to the inflammatory process. New horizons for therapeutic approaches.

    PubMed

    Szychlinska, M A; Leonardi, R; Al-Qahtani, M; Mobasheri, A; Musumeci, G

    2016-06-01

    Osteoarthritis (OA) is the most common form of joint disease. This review aimed to consolidate the current evidence that implicates the inflammatory process in the attenuation of synovial lubrication and joint tissue homeostasis in OA. Moreover, with these findings, we propose some evidence for novel therapeutic strategies for preventing and/or treating this complex disorder. The studies reviewed support that inflammatory mediators participate in the onset and progression of OA after joint injury. The flow of pro-inflammatory cytokines following an acute injury seems to be directly associated with altered lubricating ability in the joint tissue. The latter is associated with reduced level of lubricin, one of the major joint lubricants. Future research should focus on the development of new therapies that attenuate the inflammatory process and restore lubricin synthesis and function. This approach could support joint tribology and synovial lubrication leading to improved joint function and pain relief.

  9. HANAC Col4a1 Mutation in Mice Leads to Skeletal Muscle Alterations due to a Primary Vascular Defect.

    PubMed

    Guiraud, Simon; Migeon, Tiffany; Ferry, Arnaud; Chen, Zhiyong; Ouchelouche, Souhila; Verpont, Marie-Christine; Sado, Yoshikazu; Allamand, Valérie; Ronco, Pierre; Plaisier, Emmanuelle

    2017-03-01

    Collagen IV is a major component of basement membranes (BMs). The α1(IV) chain, encoded by the COL4A1 gene, is expressed ubiquitously and associates with the α2(IV) chain to form the α1α1α2(IV) heterotrimer. Several COL4A1 mutations affecting a conformational domain containing integrin-binding sites are responsible for the systemic syndrome of hereditary angiopathy, nephropathy, aneurysms, and cramps (HANAC). To analyze the pathophysiology of HANAC, Col4a1 mutant mice bearing the p.Gly498Val mutation were generated. Analysis of the skeletal muscles of Col4a1(G498V) mutant animals showed morphologic characteristics of a muscular dystrophy phenotype with myofiber atrophy, centronucleation, focal inflammatory infiltrates, and fibrosis. Abnormal ultrastructural aspects of muscle BMs was associated with reduced extracellular secretion of the mutant α1α1α2(IV) trimer. In addition to muscular dystrophic features, endothelial cell defects of the muscle capillaries were observed, with intracytoplasmic accumulation of the mutant α1α1α2(IV) molecules, endoplasmic reticulum cisternae dilation, and up-regulation of endoplasmic reticulum stress markers. Induction of the unfolded protein response in Col4a1 mutant muscle tissue resulted in an excess of apoptosis in endothelial cells. HANAC mutant animals also presented with a muscular functional impairment and increased serum creatine kinase levels reflecting altered muscle fiber sarcolemma. This extensive description of the muscular phenotype of the Col4a1 HANAC murine model suggests a potential contribution of primary endothelial cell defects, together with muscle BM alterations, to the development of COL4A1-related myopathy.

  10. In situ characterization of wettability alteration and displacement mechanisms governing recovery enhancement due to low-salinity waterflooding

    NASA Astrophysics Data System (ADS)

    Khishvand, M.; Alizadeh, A. H.; Oraki Kohshour, I.; Piri, M.; Prasad, R. S.

    2017-05-01

    A series of micro-scale core-flooding experiments were performed on reservoir core samples at elevated temperature and pressure conditions to develop better insights into wettability alteration and pore-scale displacement mechanisms taking place during low-salinity waterflooding (LSWF). Two individual miniature core samples were cut from a preserved reservoir whole core, saturated to establish initial reservoir fluid saturation conditions, and subsequently waterflooded with low-salinity and high-salinity brines. A third miniature sister core sample was also cut, solvent-cleaned, and subjected to a dynamic wettability restoration process (to reestablish native state wettability) and then a low-salinity waterflood. All samples were imaged during the experiments using a micro-CT scanner to obtain fluid occupancy maps and measure in situ oil-water contact angles. The results of the experiments performed on the preserved core samples show a significantly improved performance of low-salinity waterflooding compared to that of high-salinity waterflooding (HSWF). Pore-scale contact angle measurements provide direct evidence of wettability alteration from weakly oil-wet toward weakly water-wet conditions during LSWF, whereas contact angles measured during HSWF remain unchanged. We believe that the reduction in oil-water contact angles toward increased water-wetness lowers the threshold water pressure needed to displace oil from some medium-sized pore elements. Contact angles measured during the dynamic wettability restoration process show an equilibrium wettability state very similar to the initial one observed in the preserved samples. This indicates that drilling fluid contaminants had a negligible effect on the reservoir rock wettability. The experimental results also reveal similarities between saturation trends for the preserved-LSWF and restored-LSWF tests.

  11. Contributions of altered sensation and feedback responses to changes in coordination of postural control due to aging.

    PubMed

    Speers, R A; Kuo, A D; Horak, F B

    2002-08-01

    We used multivariate kinematics and joint torque measurements during dynamic posturography to determine the relative contributions of changes in overall control gain, relative weighting of sensors, and noise-like effects on posture control in the elderly. Our results show that sway coordination and amplitude both change with age, but that changes in overall feedback gains do not explain these differences. We propose that increased sway of elderly subjects in platform sway-referenced conditions is due to sensory noise or decreased ability to detect small motions of the platform, while increased sway during visual sway-referencing is due to re-weighting of the various sensors. Copyright 2002 Elsevier Science B.V.

  12. The testis of the mice C57/BL6 offspring in adulthood have alterations due to maternal caffeine consumption.

    PubMed

    Cavalcante, Fernanda Silveira; Aiceles, Verônica; Moraes, Diana de Freitas Serapião; Alves-Pereira, Jorge Luiz; Faria, Tatiane Silva; Ramos, Cristiane da Fonte

    2014-01-01

    To investigate the effects of the maternal caffeine consumption during pregnancy to adult male testis mice offspring. Twenty pregnant mice were divided into control group (c) and caffeine group (cf). dams received daily saline or 20 mg/kg of caffeine subcutaneously. Male offspring were monitored daily until 13th week. The testis were used to evaluate both the proliferation (pcna) and apoptosis (bax); leptin receptor (ob-r); aromatase; follicle stimulating hormone (fshr), luteinizing hormone (lhr) and androgen receptors (ar); steroidogenic acute regulatory protein (star); vascular endothelial growth factor (vegf) and estrogen receptors (erα and erβ) by western blotting. Serum concentrations of testosterone, estradiol and leptin were measured. There was a significant reduction in food intake and the body mass gain (p<0.05) in the cf ; pcna (p=0.01), fshr (p=0.02), star (p=0.0007), vegf (p=0.009), ar (p=0.03) in the cf. while an increase were note in bax (p=0.01), ob-r (p=0.02), lhr (p=0.04) and in the aromatase (p=0.03) in the cf. only erα and erβ were not changed by maternal caffeine. The serum testosterone levels in the cf offspring were 90% lower than in the c offspring (p=0.04). Maternal caffeine consumption has a role and alters the testis of the offspring in adulthood.

  13. Altered Hematopoiesis in Mice Lacking DNA Polymerase μ Is Due to Inefficient Double-Strand Break Repair

    PubMed Central

    Lucas, Daniel; Escudero, Beatriz; Ligos, José Manuel; Segovia, Jose Carlos; Estrada, Juan Camilo; Terrados, Gloria; Blanco, Luis; Samper, Enrique; Bernad, Antonio

    2009-01-01

    Polymerase mu (Polμ) is an error-prone, DNA-directed DNA polymerase that participates in non-homologous end-joining (NHEJ) repair. In vivo, Polμ deficiency results in impaired Vκ-Jκ recombination and altered somatic hypermutation and centroblast development. In Polμ−/− mice, hematopoietic development was defective in several peripheral and bone marrow (BM) cell populations, with about a 40% decrease in BM cell number that affected several hematopoietic lineages. Hematopoietic progenitors were reduced both in number and in expansion potential. The observed phenotype correlates with a reduced efficiency in DNA double-strand break (DSB) repair in hematopoietic tissue. Whole-body γ-irradiation revealed that Polμ also plays a role in DSB repair in non-hematopoietic tissues. Our results show that Polμ function is required for physiological hematopoietic development with an important role in maintaining early progenitor cell homeostasis and genetic stability in hematopoietic and non-hematopoietic tissues. PMID:19229323

  14. Thickness alterations of retinal nerve fiber layer in children with sleep-disordered breathing due to adenotonsillar hypertrophy.

    PubMed

    Cinici, Emine; Tatar, Arzu

    2015-08-01

    This study is designed to assess whether hypoxia which is caused by apnea and hypopnea episodes, has an effect on retinal nerve fiber layer (RNFL) thickness, using optical coherence tomography (OCT) in pediatric patients with Adenotonsillar hypertrophy (ATH). Fifty-seven children patient with AHT, and 31 healthy non-AHT children (between 6 and 12 ages) were enrolled in this study. Obstructive symptoms of the patients with ATH were assessed by using OSA-18 survey. The patients were divided into 2 groups as mild (>60 and <80) and severe (>80) OSAS patients, according to OSA-18 survey total scores. RNFL thickness, in the four quadrants (superior, nasal, inferior and temporal) patient's both eyes, was measured by optical coherence tomography. RNFL parameters of control and patient groups were compared. Correlation between OSA survey scores and RNFL thickness of the patient groups were examined. A positive correlation was found between ages and RNLF thickness of all subjects enrolled in this study (r=+0.107, p<0.05). And also a poor correlation was found between OSA-18 survey scores and RNFL parameters in patient group (between -0.031 and +0.016 at right and left eyes, p>0.05). No statistically significant alteration in RNFL thickness was found between the patient and control groups (p>0.05). Age range (6-12) of the patients with ATH in our study considers that possible OSAS time was not long enough to affect RNLF thickness. Remembering the risk of optic injury development in children with ATH (in a long term), tonsillectomy and/or adenoidectomy operations shouldn't be delayed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Pathogen and Pest Responses Are Altered Due to RNAi-Mediated Knockdown of GLYCOALKALOID METABOLISM 4 in Solanum tuberosum.

    PubMed

    Paudel, Jamuna Risal; Davidson, Charlotte; Song, Jun; Maxim, Itkin; Aharoni, Asaph; Tai, Helen H

    2017-09-06

    Steroidal glycoalkaloids (SGAs) are major secondary metabolites constitutively produced in cultivated potato Solanum tuberosum, and α-solanine and α-chaconine are the most abundant SGAs. SGAs are toxic to humans at high levels but their role in plant protection against pests and pathogens is yet to be established. In this study, levels of SGAs in potato were reduced by RNA interference (RNAi)-mediated silencing of GLYCOALKALOID METABOLISM 4 (GAME4)-a gene encoding cytochrome P450, involved in an oxidation step in the conversion of cholesterol to SGA aglycones. Two GAME4 RNAi lines, T8 and T9, were used to investigate the effects of manipulation of the SGA biosynthetic pathway in potato. Growth and development of an insect pest, Colorado potato beetle (CPB), were affected in these lines. While no effect on CPB leaf consumption or weight gain was observed, early instar larval death and accelerated development of the insect was found while feeding on leaves of GAME4 RNAi lines. Modulation of SGA biosynthetic pathway in GAME4 RNAi plants was associated with a larger alteration to the metabolite profile, including increased levels of one or both the steroidal saponins or phytoecdysteroids, which could affect insect mortality as well as development time. Colonization by Verticillium dahliae on GAME4 RNAi plants was also tested. There were increased pathogen levels in the T8 GAME4 RNAi line but not in the T9. Metabolite differences between T8 and T9 were found and may have contributed to differences in V. dahliae infection. Drought responses created by osmotic stress were not affected by modulation of SGA biosynthetic pathway in potato.

  16. Temporal variation in epidermal flavonoids due to altered solar UV radiation is moderated by the leaf position in Betula pendula.

    PubMed

    Morales, Luis O; Tegelberg, Riitta; Brosché, Mikael; Lindfors, Anders; Siipola, Sari; Aphalo, Pedro J

    2011-11-01

    The physiological mechanisms controlling plant responses to dynamic changes in ambient solar ultraviolet (UV) radiation are not fully understood: this information is important to further comprehend plant adaptation to their natural habitats. We used the fluorimeter Dualex to estimate in vivo the epidermal flavonoid contents by measuring epidermal UV absorbance (A(375) ) in Betula pendula Roth (silver birch) leaves of different ages under altered UV. Seedlings were grown in a greenhouse for 15 days without UV and transferred outdoors under three UV treatments (UV-0, UV-A and UV-A+B) created by three types of plastic film. After 7 and 13 days, Dualex measurements were taken at adaxial and abaxial epidermis of the first three leaves (L1, L2 and L3) of the seedlings. After 14 days, some of the seedlings were reciprocally swapped amongst the treatments to study the accumulation of epidermal flavonoids in the youngest unfolded leaves (L3) during leaf expansion under changing solar UV environments. A(375) of the leaves responded differently to the UV treatment depending on their position. UV-B increased the A(375) in the leaves independently of leaf position. L3 quickly adjusted A(375) in their epidermis according to the UV they received and these adjustments were affected by previous UV exposure. The initial absence of UV-A+B or UV-A, followed by exposure to UV-A+B, particularly enhanced leaf A(375) . Silver birch leaves modulate their protective pigments in response to changes in the UV environment during their expansion, and their previous UV exposure history affects the epidermal-absorbance achieved during later UV exposure. Copyright © Physiologia Plantarum 2011.

  17. Reduced phototropism in pks mutants may be due to altered auxin-regulated gene expression or reduced lateral auxin transport.

    PubMed

    Kami, Chitose; Allenbach, Laure; Zourelidou, Melina; Ljung, Karin; Schütz, Frédéric; Isono, Erika; Watahiki, Masaaki K; Yamamoto, Kotaro T; Schwechheimer, Claus; Fankhauser, Christian

    2014-02-01

    Phototropism allows plants to orient their photosynthetic organs towards the light. In Arabidopsis, phototropins 1 and 2 sense directional blue light such that phot1 triggers phototropism in response to low fluence rates, while both phot1 and phot2 mediate this response under higher light conditions. Phototropism results from asymmetric growth in the hypocotyl elongation zone that depends on an auxin gradient across the embryonic stem. How phototropin activation leads to this growth response is still poorly understood. Members of the phytochrome kinase substrate (PKS) family may act early in this pathway, because PKS1, PKS2 and PKS4 are needed for a normal phototropic response and they associate with phot1 in vivo. Here we show that PKS proteins are needed both for phot1- and phot2-mediated phototropism. The phototropic response is conditioned by the developmental asymmetry of dicotyledonous seedlings, such that there is a faster growth reorientation when cotyledons face away from the light compared with seedlings whose cotyledons face the light. The molecular basis for this developmental effect on phototropism is unknown; here we show that PKS proteins play a role at the interface between development and phototropism. Moreover, we present evidence for a role of PKS genes in hypocotyl gravi-reorientation that is independent of photoreceptors. pks mutants have normal levels of auxin and normal polar auxin transport, however they show altered expression patterns of auxin marker genes. This situation suggests that PKS proteins are involved in auxin signaling and/or lateral auxin redistribution. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  18. Alterations of domains in the plasmatic membrane due to damages of the perinuclear theca of pig preserved spermatozoa.

    PubMed

    Orozco Benítez, María Guadalupe; Lemus Flores, Clemente; Hernández Ballesteros, Juan Antonio; Navarrete Méndez, Raúl; Juárez-Mosqueda, María de Lourdes

    2008-05-15

    Samples of semen from 12 pigs, three from Yorkshire, Landrace, Duroc and Mexican Hairless each where obtained to study cryopreservation methods. Three stages of boar semen cryopreservation were evaluated: none (fresh stage), cooling at 5 degrees C and freezing at -196 degrees C then thawing to 56 degrees C for 12 sec. Perinuclear theca damage and domain alterations were selected as indices of seminal quality, as measured by electronic and fluorescence microcopy, respectively according to two lineal models considering by separately the effect of semen preservation and breed. Integrity and absence of perinuclear theca significantly (p < 0.001) decreased and increased, respectively according to a decrease in temperature of cryopreservation, from 87.4 to 58.8% and from 0.8 to 26.2%, respectively. This same significant (p < 0.001) effect was found for acrosomal and post-acrosomal membrane distribution of domains, from 92.1 to 76.8% and from 3.1 to 13.1% in this same order. Slight but highly significant (p < 0.001) differences were observed when theca integrity was evaluated as affected by breed, with highest and lowest values for Yorkshire and Pel6n Mexicano pigs, respectively. No breed effect was encountered for presence of acrosomal domains. A strong interdependence was found between perinuclear theca damage and domain distribution. In this connection, a highly significant (p < 0.001) positive, interdependence was observed between the theca damage and acrosomal domain (r = 0.87), while this same relationship was although highly significant (p < 0.001), negative in nature for equatorial and post-acrosonal domains (r = -0.77 and -0.85, respectively). This experiment confirmed that cryopreservation methods may severely affect semen quality of pigs and that genotype may further influence these same indices. More research is needed for improving methods of preservation of pig semen quality, from the point of view of perinuclear theca and domain characteristics of

  19. 96 h LC50, behavioural alterations and histopathological effects due to wastewater toxicity in a freshwater fish Channa punctatus.

    PubMed

    Kaur, Rajbir; Dua, Anish

    2015-04-01

    The aim of the study was to evaluate the toxic impact of wastewater from sites 1 and 2 of Tung Dhab drain in the state of Punjab, India, on fish behaviour, morphology and gill histopathological biomarkers in comparison to control group. Static non-renewal tests were conducted for 96 h to determine LC50 of the wastewater for both sites using five concentrations (6.25-100%). Fish were regularly noticed for any deviation in behaviour and external morphology. Physico-chemical analysis of wastewater was done using standard methods recommended by APHA/AWWA/WEF (2005). Chronic toxicity tests were conducted for 15 and 30 days with sublethal concentrations of wastewater (50-90% of LC50) and gill histopathology was assessed. Wastewater near a paper mill was more toxic as observed from LC50 values of 72.45%. There was evident deterioration of water quality as the recorded values of some parameters were higher than the standard discharge limits. The test fish exhibited increased air gulping and surfacing, erratic movements initially and decreased opercular movements as the exposure period increased. Morphological observations include increased body colouration, mucus secretion, scale loss and haemorrhages on the skin and lower lip. Alterations in the gill histology such as complete lamellar fusion, epithelial lifting and intraepithelial oedema, haemorrhages, lamellar necrosis and aneurysm were noted in the test fish. Results demonstrate that the fish exposed to wastewater from both sites showed significantly greater change in gill organ index (IG) as compared to control fish for 15 and 30 days.

  20. Geomorphic Framework to assess changes to aquatic habitat due to flow regulation and channel and floodplain alteration, Cedar River, Washington

    USGS Publications Warehouse

    Gendaszek, Andrew S.; Magirl, Christopher S.; Czuba, Christiana R.; Konrad, Christopher P.; Little, Rand

    2010-01-01

    Flow regulation, bank armoring, and floodplain alteration since the early 20th century have contributed to significant changes in the hydrologic regime and geomorphic processes of the Cedar River in Washington State. The Cedar River originates in the Cascade Range, provides drinking water to the Seattle metropolitan area, and supports several populations of anadromous salmonids. Flow regulation currently has limited influence on the magnitude, duration, and timing of high-flow events, which affect the incubation of salmonids as well as the production and maintenance of their habitat. Unlike structural changes to the channel and floodplain, flow regulation may be modified in the short-term to improve the viability of salmon populations. An understanding of the effects of flow regulation on those populations must be discerned over a range of scales from individual floods that affect the size of individual year classes to decadal high flow regime that influences the amount and quality of channel and off-channel habitat available for spawning and rearing. We present estimates of reach-scale sediment budgets and changes to channel morphology derived from historical orthoimagery, specific gage analyses at four long-term streamflow-gaging stations to quantify trends in aggradation, and hydrologic statistics of the magnitude and duration of peak streamflows. These data suggest a gradient of channel types from unconfined, sediment-rich segments to confined, sediment-poor segments that are likely to have distinct responses to high flows. Particle-size distribution data and longitudinal water surface and streambed profiles for the 56 km downstream of Chester Morse Lake measured in 2010 show the spatial extent of preferred salmonid habitat along the Cedar River. These historical and current data constitute a geomorphic framework to help assess different river management scenarios for salmonid habitat and population viability. PDF version of a presentation on changes to aquatic

  1. Altered state of primordial follicles in neonatal and early infantile rats due to maternal hypothyroidism: Light and electron microscopy approach.

    PubMed

    Danilović Luković, Jelena; Korać, Aleksandra; Milošević, Ivan; Lužajić, Tijana; Puškaš, Nela; Kovačević Filipović, Milica; Radovanović, Anita

    2016-11-01

    altered morphology in both groups of hypothyroid pups was increased. Apoptosis markers have not shown significant difference between groups but PCNA had an increased expression in the oocytes and granulosa cells in primordial follicles of hypothyroid rats. Light and electron microscopy analysis indicate that previously detected premature ovarian follicular atresia in pre-pubertal and pubertal hypothyroid rats is preceded with premature formation of primordial follicles followed by slight changes on sER and mitochondria in examined oocytes, and increased expression of PCNA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Inhibition of tomato (Solanum lycopersicum L.) root growth by cyanamide is due to altered cell division, phytohormone balance and expansin gene expression.

    PubMed

    Soltys, Dorota; Rudzińska-Langwald, Anna; Gniazdowska, Agnieszka; Wiśniewska, Anita; Bogatek, Renata

    2012-11-01

    Cyanamide (CA) has been reported as a natural compound produced by hairy vetch (Vicia villosa Roth.) and it was shown also to be an allelochemical, responsible for strong allelopathic potential in this species. CA phytotoxicity has been demonstrated on various plant species, but to date little is known about its mode of action at cellular level. Treatment of tomato (Solanum lycopersicum L.) roots with CA (1.2 mM) resulted in inhibition of growth accompanied by alterations in cell division, and imbalance of plant hormone (ethylene and auxin) homeostasis. Moreover, the phytotoxic effect of CA was also manifested by modifications in expansin gene expression, especially in expansins responsible for cell wall remodeling after the cytokinesis (LeEXPA9, LeEXPA18). Based on these results the phytotoxic activity of CA on growth of roots of tomato seedlings is likely due to alterations associated with cell division.

  3. Computational Study of Hippocampal-Septal Theta Rhythm Changes Due to Beta-Amyloid-Altered Ionic Channels

    PubMed Central

    Zou, Xin; Coyle, Damien; Wong-Lin, KongFatt; Maguire, Liam

    2011-01-01

    Electroencephagraphy (EEG) of many dementia patients has been characterized by an increase in low frequency field potential oscillations. One of the characteristics of early stage Alzheimer’s disease (AD) is an increase in theta band power (4–7 Hz). However, the mechanism(s) underlying the changes in theta oscillations are still unclear. To address this issue, we investigate the theta band power changes associated with β-Amyloid (Aβ) peptide (one of the main markers of AD) using a computational model, and by mediating the toxicity of hippocampal pyramidal neurons. We use an established biophysical hippocampal CA1-medial septum network model to evaluate four ionic channels in pyramidal neurons, which were demonstrated to be affected by Aβ. They are the L-type Ca2+ channel, delayed rectifying K+ channel, A-type fast-inactivating K+ channel and large-conductance Ca2+-activated K+ channel. Our simulation results demonstrate that only the Aβ inhibited A-type fast-inactivating K+ channel can induce an increase in hippocampo-septal theta band power, while the other channels do not affect theta rhythm. We further deduce that this increased theta band power is due to enhanced synchrony of the pyramidal neurons. Our research may elucidate potential biomarkers and therapeutics for AD. Further investigation will be helpful for better understanding of AD-induced theta rhythm abnormalities and associated cognitive deficits. PMID:21720560

  4. Magnified visual feedback exacerbates positional variability in older adults due to altered modulation of the primary agonist muscle

    PubMed Central

    Baweja, Harsimran S.; Kwon, MinHyuk

    2013-01-01

    The purpose of this study was to determine whether magnified visual feedback during position-holding contractions exacerbates the age-associated differences in motor output variability due to changes in the neural activation of the agonist muscle in the upper and lower limb. Twelve young (18–35 years) and ten older adults (65–85 years) were instructed to accurately match a target position at 5° of index finger abduction and ankle dorsiflexion while lifting 10 % of their 1 repetition maximum (1RM) load. Position was maintained at three different visual angles (0.1°, 1°, and 4°) that varied across trials. Each trial lasted 25 s and visual feedback of position was removed from 15 to 25 s. Positional error was quantified as the root mean square error (RMSE) of the subject’s performance from the target. Positional variability was quantified as the standard deviation of the position data. The neural activation of the first dorsal interosseus and tibialis anterior was measured with surface electromyography (EMG). Older adults were less accurate compared with young adults and the RMSE decreased significantly with an increase in visual gain. As expected, and independent of limb, older adults exhibited significantly greater positional variability compared with young adults that was exacerbated with magnification of visual feedback (1° and 4°). This increase in variability at the highest magnification of visual feedback was predicted by a decrease in power from 12 to 30 Hz of the agonist EMG signal. These findings demonstrate that motor control in older adults is impaired by magnified visual feedback during positional tasks. PMID:22948735

  5. Altered bioavailability due to changes in the formulation of a commercial preparation of levothyroxine in patients with differentiated thyroid carcinoma.

    PubMed

    Olveira, G; Almaraz, M C; Soriguer, F; Garriga, M J; Gonzalez-Romero, S; Tinahones, F; Ruiz de Adana, M S

    1997-06-01

    after the changeover to Dexnon were due to its greater bioavailability. Simple changes in the manufacture of levothyroxine tablets may produce important variations in their bioavailability, having an adverse effect on the clinical control of the patients, and causing extra expense by the need for repeated patient visits and thyroid function tests.

  6. 2013 Immune Risk Standing Review Panel Evidence Review for: The Risk of Crew Adverse Health Event Due to Altered Immune Response

    NASA Technical Reports Server (NTRS)

    Steinberg, Susan

    2014-01-01

    The 2013 Immune Risk Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on February 3-4, 2014. The SRP reviewed the new Evidence Report for the Risk of Crew Adverse Health Event Due to Altered Immune Response (from here on referred to as the 2013 Immune Evidence Report), as well as the Research Plan for this Risk that is in the current version of the Human Research Program’s (HRP) Integrated Research Plan (IRP).

  7. A Mouse Model Suggests Two Mechanisms for Thyroid Alterations in Infantile Cystinosis: Decreased Thyroglobulin Synthesis Due to Endoplasmic Reticulum Stress/Unfolded Protein Response and Impaired Lysosomal Processing

    PubMed Central

    Gaide Chevronnay, H. P.; Janssens, V.; Van Der Smissen, P.; Liao, X. H.; Abid, Y.; Nevo, N.; Antignac, C.; Refetoff, S.; Cherqui, S.; Pierreux, C. E.

    2015-01-01

    Thyroid hormones are released from thyroglobulin (Tg) in lysosomes, which are impaired in infantile/nephropathic cystinosis. Cystinosis is a lysosomal cystine storage disease due to defective cystine exporter, cystinosin. Cystinotic children develop subclinical and then overt hypothyroidism. Why hypothyroidism is the most frequent and earliest endocrine complication of cystinosis is unknown. We here defined early alterations in Ctns−/− mice thyroid and identified subcellular and molecular mechanisms. At 9 months, T4 and T3 plasma levels were normal and TSH was moderately increased (∼4-fold). By histology, hyperplasia and hypertrophy of most follicles preceded colloid exhaustion. Increased immunolabeling for thyrocyte proliferation and apoptotic shedding indicated accelerated cell turnover. Electron microscopy revealed endoplasmic reticulum (ER) dilation, apical lamellipodia indicating macropinocytic colloid uptake, and lysosomal cystine crystals. Tg accumulation in dilated ER contrasted with mRNA down-regulation. Increased expression of ER chaperones, glucose-regulated protein of 78 kDa and protein disulfide isomerase, associated with alternative X-box binding protein-1 splicing, revealed unfolded protein response (UPR) activation by ER stress. Decreased Tg mRNA and ER stress suggested reduced Tg synthesis. Coordinated increase of UPR markers, activating transcription factor-4 and C/EBP homologous protein, linked ER stress to apoptosis. Hormonogenic cathepsins were not altered, but lysosome-associated membrane protein-1 immunolabeling disclosed enlarged vesicles containing iodo-Tg and impaired lysosomal fusion. Isopycnic fractionation showed iodo-Tg accumulation in denser lysosomes, suggesting defective lysosomal processing and hormone release. In conclusion, Ctns−/− mice showed the following alterations: 1) compensated primary hypothyroidism and accelerated thyrocyte turnover; 2) impaired Tg production linked to ER stress/UPR response; and 3) altered

  8. Wave Propagation of Myocardial Stretch: Correlation with Myocardial Stiffness

    PubMed Central

    Pislaru, Cristina; Pellikka, Patricia A.; Pislaru, Sorin V.

    2015-01-01

    The mechanism of flow propagation during diastole in the left ventricle (LV) has been well described. Little is known about the associated waves propagating along the heart wall s. These waves may have a mechanism similar to pulse wave propagation in arteries. The major goal of the study was to evaluate the effect of myocardial stiffness and preload on this wave transmission. Methods Longitudinal late diastolic deformation and wave speed (Vp) of myocardial stretch in the anterior LV wall were measured using sonomicrometry in sixteen pigs. Animals with normal and altered myocardial stiffness (acute myocardial infarction) were studied with and without preload alterations. Elastic modulus estimated from Vp (EVP; Moens-Korteweg equation) was compared to incremental elastic modulus obtained from exponential end -diastolic stress-strain relation (ESS). Myocardial distensibility and α-and β-coefficients of stress-strain relations were calculated. Results Vp was higher at reperfusion compared to baseline (2.6±1.3 m/s vs. 1.3±0.4 m/s; p=0.005) and best correlated with ESS (r 2=0.80, p<0.0001), β-coefficient (r2=0.78, p<0.0001), distensibility (r2=0.47, p=0.005), and wall thickness/diameter ratio (r2=0.42, p=0.009). Elastic moduli (EVP and ESS) were strongly correlated (r2=0.83, p<0.0001). Increasing preload increased Vp and EVP and decreased distensibility. At multivariate analysis, ESS, wall thickness, and end-diastolic and systolic LV pressures were independent predictors of Vp (r2model=0.83, p<0.0001). Conclusions The main determinants of wave propagation of longitudinal myocardial stretch were myocardial stiffness and LV geometry and pressure. This local wave speed could potentially be measured noninvasively by echocardiography. PMID:25193091

  9. Wave propagation of myocardial stretch: correlation with myocardial stiffness.

    PubMed

    Pislaru, Cristina; Pellikka, Patricia A; Pislaru, Sorin V

    2014-01-01

    The mechanism of flow propagation during diastole in the left ventricle (LV) has been well described. Little is known about the associated waves propagating along the heart walls. These waves may have a mechanism similar to pulse wave propagation in arteries. The major goal of the study was to evaluate the effect of myocardial stiffness and preload on this wave transmission. Longitudinal late diastolic deformation and wave speed (Vp) of myocardial stretch in the anterior LV wall were measured using sonomicrometry in 16 pigs. Animals with normal and altered myocardial stiffness (acute myocardial infarction) were studied with and without preload alterations. Elastic modulus estimated from Vp (E VP; Moens-Korteweg equation) was compared to incremental elastic modulus obtained from exponential end-diastolic stress-strain relation (E SS). Myocardial distensibility and α- and β-coefficients of stress-strain relations were calculated. Vp was higher at reperfusion compared to baseline (2.6 ± 1.3 vs. 1.3 ± 0.4 m/s; p = 0.005) and best correlated with E SS (r2 = 0.80, p < 0.0001), β-coefficient (r2 = 0.78, p < 0.0001), distensibility (r2 = 0.47, p = 0.005), and wall thickness/diameter ratio (r2 = 0.42, p = 0.009). Elastic moduli (E VP and E SS) were strongly correlated (r2 = 0.83, p < 0.0001). Increasing preload increased Vp and E VP and decreased distensibility. At multivariate analysis, E SS, wall thickness, and end-diastolic and systolic LV pressures were independent predictors of Vp (r2 model = 0.83, p < 0.0001). In conclusion, the main determinants of wave propagation of longitudinal myocardial stretch were myocardial stiffness and LV geometry and pressure. This local wave speed could potentially be measured noninvasively by echocardiography.

  10. Antiplatelet efficacy of P2Y12 inhibitors (prasugrel, ticagrelor, clopidogrel) in patients treated with mild therapeutic hypothermia after cardiac arrest due to acute myocardial infarction.

    PubMed

    Bednar, Frantisek; Kroupa, Josef; Ondrakova, Martina; Osmancik, Pavel; Kopa, Milos; Motovska, Zuzana

    2016-05-01

    Survivors after cardiac arrest (CA) due to AMI undergo PCI and then receive dual antiplatelet therapy. Mild therapeutic hypothermia (MTH) is recommended for unconscious patients after CA to improve neurological outcomes. MTH can attenuate the effectiveness of P2Y12 inhibitors by reducing gastrointestinal absorption and metabolic activation. The combined effect of these conditions on the efficacy of P2Y12 inhibitors is unknown. We compared the antiplatelet efficacies of new P2Y12 inhibitors in AMI patients after CA treated with MTH. Forty patients after CA for AMI treated with MTH and received one P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) were enrolled in a prospective observational single-center study. Platelet inhibition was measured by VASP (PRI) on days 1, 2, and 3 after drug administration. In-hospital clinical data and 1-year survival data were obtained. The proportion of patients with ineffective platelet inhibition (PRI > 50 %, high on-treatment platelet reactivity) for clopidogrel, prasugrel, and ticagrelor was 77 vs. 19 vs. 1 % on day 1; 77 vs. 17 vs. 0 % on day 2; and 85 vs. 6 vs. 0 % on day 3 (P < 0.001). The platelet inhibition was significantly worse in clopidogrel group than in prasugrel or ticagrelor group. Prasugrel and ticagrelor are very effective for platelet inhibition in patients treated with MTH after CA due to AMI, but clopidogrel is not. Using prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients.

  11. Myocardial thallium-201 kinetics and regional flow alterations with 3 hours of coronary occlusion and either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis

    SciTech Connect

    Granato, J.E.; Watson, D.D.; Flanagan, T.L.; Beller, G.A.

    1987-01-01

    Myocardial thallium-201 kinetics and regional blood flow alterations were examined in a canine model using 3 hours of coronary occlusion and different methods of reperfusion. Group I comprised 10 dogs undergoing a 3 hour left anterior descending artery occlusion and no reperfusion. Group II comprised seven dogs undergoing 3 hours of left anterior descending artery occlusion and rapid reperfusion through a totally patent vessel. Group III comprised 10 dogs undergoing 3 hours of left anterior descending artery occlusion and slow reperfusion through a residual stenosis. All dogs received 1.5 mCi of thallium-201 after 40 minutes of coronary occlusion. During occlusion and 2 hours of reperfusion, serial hemodynamic, blood flow and myocardial thallium-201 activity measurements were made. The relative thallium-201 gradient (normal zone minus ischemic zone activity when initial normal activity is expressed as 100%) during left anterior descending coronary occlusion was similar in all groups. Group I, 87 +/- 3%; Group II, 78 +/- 6%; Group III, 83 +/- 6% (p = NS). After 2 hours of either method of reperfusion, the final relative gradient had decreased to a similar level (Group II, 51 +/- 9%; Group III, 42 +/- 6%). These values were not significantly different from the final relative thallium-201 gradient seen in dogs undergoing a sustained 3 hour occlusion (Group I, 55 +/- 5%). After 2 hours of reperfusion, both methods of reflow were associated with similar degrees of ''no reflow.'' Transmural flows in the central ischemic zone were 89 +/- 10% of normal in Group II and 71 +/- 6% of normal in Group III after reperfusion, with both flows substantially higher than the relative thallium-201 activities in these dogs.

  12. Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions

    PubMed Central

    Pannek, Kerstin; Boyd, Roslyn N.; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E.

    2014-01-01

    in FA in unilateral CP, and that these alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention. PMID:25003031

  13. Assessment of the structural brain network reveals altered connectivity in children with unilateral cerebral palsy due to periventricular white matter lesions.

    PubMed

    Pannek, Kerstin; Boyd, Roslyn N; Fiori, Simona; Guzzetta, Andrea; Rose, Stephen E

    2014-01-01

    alterations in FA are related to clinical function. Application of this connectome-based analysis to investigate alterations in connectivity following treatment may elucidate the neurological correlates of improved functioning due to intervention.

  14. Targeted Injection of a Biocomposite Material Alters Macrophage and Fibroblast Phenotype and Function following Myocardial Infarction: Relation to Left Ventricular Remodeling

    PubMed Central

    McGarvey, Jeremy R.; Pettaway, Sara; Shuman, James A.; Novack, Craig P.; Zellars, Kia N.; Freels, Parker D.; Echols, Randall L.; Burdick, Jason A.; Gorman, Joseph H.; Gorman, Robert C.

    2014-01-01

    A treatment target for progressive left ventricular (LV) remodeling prevention following myocardial infarction (MI) is to affect structural changes directly within the MI region. One approach is through targeted injection of biocomposite materials, such as calcium hydroxyapatite microspheres (CHAM), into the MI region. In this study, the effects of CHAM injections upon key cell types responsible for the MI remodeling process, the macrophage and fibroblast, were examined. MI was induced in adult pigs before randomization to CHAM injections (20 targeted 0.1-ml injections within MI region) or saline. At 7 or 21 days post-MI (n = 6/time point per group), cardiac magnetic resonance imaging was performed, followed by macrophage and fibroblast isolation. Isolated macrophage profiles for monocyte chemotactic macrophage inflammatory protein-1 as measured by real-time polymerase chain reaction increased at 7 days post-MI in the CHAM group compared with MI only (16.3 ± 6.6 versus 1.7 ± 0.6 cycle times values, P < 0.05), and were similar by 21 days post-MI. Temporal changes in fibroblast function and smooth muscle actin (SMA) expression relative to referent control (n = 5) occurred with MI. CHAM induced increases in fibroblast proliferation, migration, and SMA expression—indicative of fibroblast transformation. By 21 days, CHAM reduced LV dilation (diastolic volume: 75 ± 2 versus 97 ± 4 ml) and increased function (ejection fraction: 48 ± 2% versus 38 ± 2%) compared with MI only (both P < 0.05). This study identified that effects on macrophage and fibroblast differentiation occurred with injection of biocomposite material within the MI, which translated into reduced adverse LV remodeling. These unique findings demonstrate that biomaterial injections impart biologic effects upon the MI remodeling process over any biophysical effects. PMID:25022514

  15. Altered myocardial perfusion in patients with angina pectoris or silent ischemia during exercise as assessed by quantitative thallium-201 single-photon emission computed tomography

    SciTech Connect

    Mahmarian, J.J.; Pratt, C.M.; Cocanougher, M.K.; Verani, M.S. )

    1990-10-01

    The extent of abnormally perfused myocardium was compared in patients with and without chest pain during treadmill exercise from a large, relatively low-risk consecutive patient population (n = 356) referred for quantitative thallium-201 single-photon emission computed tomography (SPECT). All patients had concurrent coronary angiography. Patients were excluded if they had prior coronary angioplasty or bypass surgery. Tomographic images were assessed visually and from computer-generated polar maps. Chest pain during exercise was as frequent in patients with normal coronary arteries (12%) as in those with significant (greater than 50% stenosis) coronary artery disease (CAD) (14%). In the 219 patients with significant CAD, silent ischemia was fivefold more common than symptomatic ischemia (83% versus 17%, p = 0.0001). However, there were no differences in the extent, severity, or distribution of coronary stenoses in patients with silent or symptomatic ischemia. Our major observation was that the extent of quantified SPECT perfusion defects was nearly identical in patients with (20.9 +/- 15.9%) and without (20.5 +/- 15.6%) exertional chest pain. The sensitivity for detecting the presence of CAD was significantly improved with quantitative SPECT compared with stress electrocardiography (87% versus 65%, p = 0.0001). Although scintigraphic and electrocardiographic evidence of exercise-induced ischemia were comparable in patients with chest pain (67% versus 73%, respectively; p = NS), SPECT was superior to stress electrocardiography for detecting silent myocardial ischemia. The majority of patients in this study with CAD who developed ischemia during exercise testing were asymptomatic, although they exhibited an angiographic profile and extent of abnormally perfused myocardium similar to those of patients with symptomatic ischemia.

  16. Molecular Characterization of Reactive Oxygen Species in Myocardial Ischemia-Reperfusion Injury.

    PubMed

    Zhou, Tingyang; Chuang, Chia-Chen; Zuo, Li

    2015-01-01

    Myocardial ischemia-reperfusion (I/R) injury is experienced by individuals suffering from cardiovascular diseases such as coronary heart diseases and subsequently undergoing reperfusion treatments in order to manage the conditions. The occlusion of blood flow to the tissue, termed ischemia, can be especially detrimental to the heart due to its high energy demand. Several cellular alterations have been observed upon the onset of ischemia. The danger created by cardiac ischemia is somewhat paradoxical in that a return of blood to the tissue can result in further damage. Reactive oxygen species (ROS) have been studied intensively to reveal their role in myocardial I/R injury. Under normal conditions, ROS function as a mediator in many cell signaling pathways. However, stressful environments significantly induce the generation of ROS which causes the level to exceed body's antioxidant defense system. Such altered redox homeostasis is implicated in myocardial I/R injury. Despite the detrimental effects from ROS, low levels of ROS have been shown to exert a protective effect in the ischemic preconditioning. In this review, we will summarize the detrimental role of ROS in myocardial I/R injury, the protective mechanism induced by ROS, and potential treatments for ROS-related myocardial injury.

  17. Altered growth, pigmentation, and antimicrobial susceptibility properties of Staphylococcus aureus due to loss of the major cold shock gene cspB.

    PubMed

    Duval, Brea D; Mathew, Anselmo; Satola, Sarah W; Shafer, William M

    2010-06-01

    An insertional mutation made in the major cold shock gene cspB in Staphylococcus aureus strain COL, a methicillin-resistant clinical isolate, yielded a mutant that displayed a reduced capacity to respond to cold shock and many phenotypic characteristics of S. aureus small-colony variants: a growth defect at 37 degrees C, a reduction in pigmentation, and altered levels of susceptibility to many antimicrobials. In particular, a cspB null mutant displayed increased resistance to aminoglycosides, trimethoprim-sulfamethoxazole, and paraquat and increased susceptibility to daptomycin, teicoplanin, and methicillin. With the exception of the increased susceptibility to methicillin, which was due to a complete loss of the type I staphylococcal cassette chromosome mec element, these properties were restored to wild-type levels by complementation when cspB was expressed in trans. Taken together, our results link a stress response protein (CspB) of S. aureus to important phenotypic properties that include resistance to certain antimicrobials.

  18. The conductive hearing loss due to an experimentally induced middle ear effusion alters the interaural level and time difference cues to sound location.

    PubMed

    Thornton, Jennifer L; Chevallier, Keely M; Koka, Kanthaiah; Lupo, J Eric; Tollin, Daniel J

    2012-10-01

    Otitis media with effusion (OME) is a pathologic condition of the middle ear that leads to a mild to moderate conductive hearing loss as a result of fluid in the middle ear. Recurring OME in children during the first few years of life has been shown to be associated with poor detection and recognition of sounds in noisy environments, hypothesized to result due to altered sound localization cues. To explore this hypothesis, we simulated a middle ear effusion by filling the middle ear space of chinchillas with different viscosities and volumes of silicone oil to simulate varying degrees of OME. While the effects of middle ear effusions on the interaural level difference (ILD) cue to location are known, little is known about whether and how middle ear effusions affect interaural time differences (ITDs). Cochlear microphonic amplitudes and phases were measured in response to sounds delivered from several locations in azimuth before and after filling the middle ear with fluid. Significant attenuations (20-40 dB) of sound were observed when the middle ear was filled with at least 1.0 ml of fluid with a viscosity of 3.5 Poise (P) or greater. As expected, ILDs were altered by ~30 dB. Additionally, ITDs were shifted by ~600 μs for low frequency stimuli (<4 kHz) due to a delay in the transmission of sound to the inner ear. The data show that in an experimental model of OME, ILDs and ITDs are shifted in the spatial direction of the ear without the experimental effusion.

  19. Prediction of Altered Bile Acid Disposition Due to Inhibition of Multiple Transporters: An Integrated Approach Using Sandwich-Cultured Hepatocytes, Mechanistic Modeling, and Simulation

    PubMed Central

    Guo, Cen; Yang, Kyunghee; Brouwer, Kenneth R.; St. Claire, Robert L.

    2016-01-01

    Transporter-mediated alterations in bile acid disposition may have significant toxicological implications. Current methods to predict interactions are limited by the interplay of multiple transporters, absence of protein in the experimental system, and inaccurate estimates of inhibitor concentrations. An integrated approach was developed to predict altered bile acid disposition due to inhibition of multiple transporters using the model bile acid taurocholate (TCA). TCA pharmacokinetic parameters were estimated by mechanistic modeling using sandwich-cultured human hepatocyte data with protein in the medium. Uptake, basolateral efflux, and biliary clearance estimates were 0.63, 0.034, and 0.074 mL/min/g liver, respectively. Cellular total TCA concentrations (Ct,Cells) were selected as the model output based on sensitivity analysis. Monte Carlo simulations of TCA Ct,Cells in the presence of model inhibitors (telmisartan and bosentan) were performed using inhibition constants for TCA transporters and inhibitor concentrations, including cellular total inhibitor concentrations ([I]t,cell) or unbound concentrations, and cytosolic total or unbound concentrations. For telmisartan, the model prediction was accurate with an average fold error (AFE) of 0.99–1.0 when unbound inhibitor concentration ([I]u) was used; accuracy dropped when total inhibitor concentration ([I]t) was used. For bosentan, AFE was 1.2–1.3 using either [I]u or [I]t. This difference was evaluated by sensitivity analysis of the cellular unbound fraction of inhibitor (fu,cell,inhibitor), which revealed higher sensitivity of fu,cell,inhibitor for predicting TCA Ct,Cells when inhibitors exhibited larger ([I]t,cell/IC50) values. In conclusion, this study demonstrated the applicability of a framework to predict hepatocellular bile acid concentrations due to drug-mediated inhibition of transporters using mechanistic modeling and cytosolic or cellular unbound concentrations. PMID:27233294

  20. Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space flight

    NASA Technical Reports Server (NTRS)

    Bloomberg, Jacob J.; Reschke, Millard F.; Clement, Gilles R.; Mulavara, Ajitkumar P.; Taylor, Laura C..

    2015-01-01

    Control of vehicles and other complex systems is a high-level integrative function of the central nervous system (CNS). It requires well-functioning subsystem performance, including good visual acuity, eye-hand coordination, spatial and geographic orientation perception, and cognitive function. Evidence from space flight research demonstrates that the function of each of these subsystems is altered by removing gravity, a fundamental orientation reference, which is sensed by vestibular, proprioceptive, and haptic receptors and used by the CNS for spatial orientation, posture, navigation, and coordination of movements. The available evidence also shows that the degree of alteration of each subsystem depends on a number of crew- and mission-related factors. There is only limited operational evidence that these alterations cause functional impacts on mission-critical vehicle (or complex system) control capabilities. Furthermore, while much of the operational performance data collected during space flight has not been available for independent analysis, those that have been reviewed are somewhat equivocal owing to uncontrolled (and/or unmeasured) environmental and/or engineering factors. Whether this can be improved by further analysis of previously inaccessible operational data or by development of new operational research protocols remains to be seen. The true operational risks will be estimable only after we have filled the knowledge gaps and when we can accurately assess integrated performance in off-nominal operational settings (Paloski et al. 2008). Thus, our current understanding of the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Space flight is limited primarily to extrapolation of scientific research findings, and, since there are limited ground-based analogs of the sensorimotor and vestibular changes associated with space flight, observation of their functional

  1. Alterations in Cardiac Deformation, Timing of Contraction and Relaxation, and Early Myocardial Fibrosis Accompany the Apparent Recovery of Acute Stress-Induced (Takotsubo) Cardiomyopathy: An End to the Concept of Transience.

    PubMed

    Schwarz, Konstantin; Ahearn, Trevor; Srinivasan, Janaki; Neil, Christopher J; Scally, Caroline; Rudd, Amelia; Jagpal, Baljit; Frenneaux, Michael P; Pislaru, Cristina; Horowitz, John D; Dawson, Dana K

    2017-08-01

    Takotsubo syndrome is an increasingly recognized cause of chest pain and occasionally of cardiogenic shock. Despite rapid improvement of the left ventricular (LV) ejection fraction, recent registry data raise concerns about long-term prognosis. The aim of this study was to test the hypothesis that restoration of normal ejection fraction after acute takotsubo syndrome is not equivalent to full functional recovery. Fifty-two patients with takotsubo syndrome (according to the Mayo Clinic criteria plus cardiac magnetic resonance imaging to exclude myocardial infarction) and 44 healthy control subjects of the same age, gender, and cardiovascular comorbidity distribution were prospectively recruited. The focus of the investigation was on patients with takotsubo syndrome presenting with ST-segment elevation-type electrocardiographic findings or malignant arrhythmias and with LV apical ballooning variant, and a 4-month recovery endpoint was assessed. Patients underwent echocardiographic assessment of LV myocardial deformation (global longitudinal, radial, and circumferential strain; LV twist, torsion, and untwist; and time to peak twist and untwist) and assessment of LV myocardial structure by pre- and post-contrast-enhanced cardiac magnetic resonance by T1 mapping acutely and at 4-month follow-up. Control subjects underwent a single-time-point investigation. Data were analyzed using paired or unpaired tests, as appropriate for their distribution, and corrected for multiple comparisons. The patients' mean age was 66 years (range, 28-87 years), and 92% were women. All abnormal echocardiographic indices observed acutely in patients with takotsubo syndrome improved (but did not necessarily normalize) at follow-up. Significant mechanotemporal alterations characterizing both systole (global longitudinal strain and apical circumferential strain, P < .01 for both; LV twist, twist rate, and torsion, P < .0001 for all) and diastole (untwist rate and time to peak untwisting

  2. [Vectorcardiographic diagnosis of the myocardial inactivatable zone].

    PubMed

    de Micheli, A; Medrano, G A

    1989-01-01

    Clinical importance of the vectorcardiographic exploration (distant and spatial) of the myocardial electrical phenomenon is emphasized. This technique constitutes a useful integration of electrocardiographic exploration (near and analytical). The more characteristic morphological and chronological changes due to an inactivatable area are discussed in the light of ventricular myocardial depolarization. Some typical vectorcardiographic features corresponding to the presence of a myocardial inactivatable zone are presented. The utility of the complementary elements which vectorcardiography can bring to electrocardiography is emphasized. Both of these procedures integrate a rational exploration of electrical activity of the myocardium, the solid base of prognostic and therapeutic decisions in cases of myocardial infarction.

  3. Acute haemolytic crisis due to concomitant presence of infection and possible altered acetaminophen catabolism in a Philipino child carrying the G6PD-Vanua Lava mutation.

    PubMed

    Minucci, Angelo; De Luca, Daniele; Torti, Eleonora; Concolino, Paola; Maurizi, Palma; Giardina, Bruno; Zuppi, Cecilia; Capoluongo, Ettore

    2011-05-01

    Glucose-6-phosphate dehydrogenase (G6PD), an X-linked hereditary deficiency, is the most common of all clinically significant enzyme defects. While many drugs are responsible for haemolytic anaemia in G6PD-deficient patients, acetaminophen's imputability is still under debate, although an overdose of this drug can provoke acute haemolytic events. We report a case of a Philipino child carrying the G6PD-Vanua Lava mutation with acute haemolytic crisis related to infection in progress and acetaminophen's administration. Fever and concomitant infection, through an increment of erythrocyte glutathione depletion, sensitized the infant to the haemolytic event. In this condition, acetaminophen (or paracetamol [PCM]) was capable of inducing a haemolytic crisis in our G6PD-deficient patient although administered under standard conditions. PCM seems to have induced the haemolytic event, probably by the alteration of its catabolism due to dehydration and fever. The enzymatic G6PD instability associated to the presence of the G6PD-Vanua Lava mutation could have led to an increment of red blood cells' sensitivity to lysis; hence, it is possible that PCM toxicity may also be due to the presence of this particular mutation. Finally, we propose a new biochemical classification of this G6PD variant.

  4. Myocardial Tagging With SSFP

    PubMed Central

    Herzka, Daniel A.; Guttman, Michael A.; McVeigh, Elliot R.

    2007-01-01

    This work presents the first implementation of myocardial tagging with refocused steady-state free precession (SSFP) and magnetization preparation. The combination of myocardial tagging (a noninvasive method for quantitative measurement of regional and global cardiac function) with the high tissue signal-to-noise ratio (SNR) obtained with SSFP is shown to yield improvements in terms of the myocardium–tag contrast-to-noise ratio (CNR) and tag persistence when compared to the current standard fast gradient-echo (FGRE) tagging protocol. Myocardium–tag CNR and tag persistence were studied using numerical simulations as well as phantom and human experiments. Both quantities were found to decrease with increasing imaging flip angle (α) due to an increased tag decay rate and a decrease in myocardial steady-state signal. However, higher α yielded better blood–myocardium contrast, indicating that optimal α is dependent on the application: higher α for better blood–myocardium boundary visualization, and lower α for better tag persistence. SSFP tagging provided the same myocardium–tag CNR as FGRE tagging when acquired at four times the bandwidth and better tag– and blood–myocardium CNRs than FGRE tagging when acquired at equal or twice the receiver bandwidth (RBW). The increased acquisition efficiency of SSFP allowed decreases in breath-hold duration, or increases in temporal resolution, as compared to FGRE. PMID:12541254

  5. Altered spacing of promoter elements due to the dodecamer repeat expansion contributes to reduced expression of the cystatin B gene in EPM1.

    PubMed

    Lalioti, M D; Scott, H S; Antonarakis, S E

    1999-09-01

    Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1; MIM 254800) is an autosomal recessive disorder characterized by seizures, myoclonus and progression to cerebellar ataxia. EPM1 arises due to mutations in the cystatin B (CSTB) gene which encodes a cysteine proteinase inhibitor. Only a minority of EPM1 alleles carry point mutations, while the majority contain large expansions of the dodecamer CCCCGCCCCGCG repeat which is present at two to three copies in normal individuals. The dodecamer repeat is located in the 5' flanking region of the CSTB gene, presumably in its promoter. The pathological repeat expansion results in a reduction in CSTB mRNA, which may be cell specific. To elucidate the mechanism of this reduction of gene expression, we have studied the putative CSTB promoter in vitro. A 3.8 kb fragment, containing the putative promoter with a 600 bp repeat expansion, showed a 2- to 4-fold reduction in luciferase activity compared with an identical fragment with a normal repeat; this reduction was observed only in certain cell types. Introduction of heterologous DNA fragments of 730 and 1000 bp into the normal promoter, instead of the repeat expansion, showed similarly reduced activity. Terminal deletions of the promoter implicate a putative AP-1 binding site, upstream of the repeat, in CSTB transcription activation. We propose that a novel mechanism of pathogenesis, the altering of the spacing of transcription factor binding sites from each other and/or the transcription initiation site due to repeat expansion, is among the causes of reduction in CSTB expression and thus EPM1.

  6. Mice deficient in mitochondrial glycerol-3-phosphate acyltransferase-1 have diminished myocardial triacylglycerol accumulation during lipogenic diet and altered phospholipid fatty acid composition

    PubMed Central

    Lewin, Tal M.; de Jong, Hendrik; Schwerbrock, Nicole J. M.; Hammond, Linda E.; Watkins, Steven M.; Combs, Terry P.; Coleman, Rosalind A.

    2008-01-01

    Glycerol-3-phosphate acyltransferase-1 (GPAT1), which is located on the outer mitochondrial membrane comprises up to 30% of total GPAT activity in the heart. It is one of at least four mammalian GPAT isoforms known to catalyze the initial, committed, and rate limiting step of glycerolipid synthesis. Because excess triacylglycerol (TAG) accumulates in cardiomyocytes in obesity and type 2 diabetes, we determined whether lack of GPAT1 would alter the synthesis of heart TAG and phospholipids after a 2-week high sucrose diet or a 3-month high fat diet. Even in the absence of hypertriglyceridemia, TAG increased 2-fold with both diets in hearts from wildtype mice. In contrast, hearts from Gpat1−/− mice contained 20–80% less TAG than the wildtype controls. In addition, hearts from Gpat1−/− mice fed the high-sucrose diet incorporate 60% less [14C]palmitate into heart TAG as compared to wildtype mice. Because GPAT1 prefers 16:0-CoA to other long chain acyl-CoA substrates, we determined the fatty acid composition of heart phospholipids. Compared to wildtype littermate controls, hearts from Gpat1−/− mice contained a lower amount of 16:0 in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine/phosphatidylinositol and significantly more C20:4n6. Phosphatidylcholine and phosphatidylethanolamine from Gpat1−/− hearts also contained higher amounts of 18:0 and 18:1. Although at least three other GPAT isoforms are expressed in the heart, our data suggest that GPAT1 contributes significantly to cardiomyocyte TAG synthesis during lipogenic or high fat diets and influences the incorporation of 20:4n6 into heart phospholipids. PMID:18522808

  7. Age-associated impairement in endpoint accuracy of goal-directed contractions performed with two fingers is due to altered activation of the synergistic muscles.

    PubMed

    Chen, Yen-Ting; Pinto Neto, Osmar; de Miranda Marzullo, Ana Carolina; Kennedy, Deanna M; Fox, Emily J; Christou, Evangelos A

    2012-07-01

    The purpose of this study was to determine whether older adults compared with young adults exhibit impaired end-point accuracy during a two-finger task due to altered activation of the contributing synergistic muscles. Nine young (21.3 years ± 1.6 years, 4 men) and 9 older (73.1 years ± 6.4 years, 5 men) were instructed to accurately match the center of a target with concurrent abduction of the index and little fingers (synergistic two-finger task). The target comprised of 20% MVC and 200 ms. Visual feedback of the force trajectory and target was provided 1s after each trial. Subjects completed 40 trials and the last 10 were used for analysis. Endpoint accuracy was quantified as the normalized deviation from the target in terms of peak force (peak force error), time-to-peak force (time-to-peak force error), and a combination of the two (overall error). Motor output variability was quantified as the standard deviation and coefficient of variation (CV) of peak force and time to peak force. The neural activation of the involved synergist muscles (first dorsal interosseus (FDI) and abductor digiti minimi (ADM)) was quantified with the electromyography (EMG) amplitude (root mean square) and its frequency structure (wavelet analysis). Older adults exhibited significantly greater peak force (46.7 ± 10% vs. 24.9 ± 3.2%) and overall endpoint error (68.5 ± 9.7% vs. 41.7 ± 4.3%), whereas the time to peak force error was similar for the two age groups. Older adults also exerted greater peak force variability than young adults, as quantified by the CV of peak force (34.3 ± 3.5% vs. 24.1 ± 2.3%). The greater peak force error in older adults was associated with changes in the activation of the ADM muscle but not the FDI. Specifically, greater peak force error was associated with greater power from 13-30 Hz and lesser power from 30-60 Hz. These results, therefore, suggest that older adults compared with young adults exhibit impaired endpoint force accuracy during a two

  8. Smoking ban in public areas is associated with a reduced incidence of hospital admissions due to ST-elevation myocardial infarctions in non-smokers. Results from the Bremen STEMI Registry.

    PubMed

    Schmucker, J; Wienbergen, H; Seide, S; Fiehn, E; Fach, A; Würmann-Busch, B; Gohlke, H; Günther, K; Ahrens, W; Hambrecht, R

    2014-09-01

    Laws banning tobacco smoking from public areas have been passed in several countries, including the region of Bremen, Germany at the end of 2007. The present study analyses the incidence of hospital admissions due to ST-elevation myocardial infarctions (STEMIs) before and after such a smoking ban was implemented, focusing on differences between smokers and non-smokers. In this respect, data of the Bremen STEMI Registry (BSR) give a complete epidemiological overview of a region in northwest Germany with approximately 800,000 inhabitants since all STEMIs are admitted to one central heart centre. Between January 2006 and December 2010, data from the BSR was analysed focusing on date of admission, age, gender, and prior nicotine consumption. A total of 3545 patients with STEMI were admitted in the Bremen Heart Centre during this time period. Comparing 2006-2007 vs. 2008-2010, hence before and after the smoking ban, a 16% decrease of the number of STEMIs was observed: from a mean of 65 STEMI/month in 2006-2007 to 55/month in 2008-2010 (p < 0.01). The group of smokers showed a constant number of STEMIs: 25/month in 2006-2007 to 26/month in 2008-2010 (+4%, p = 0.8). However, in non-smokers, a significant reduction of STEMIs over time was found: 39/month in 2006-2007 to 29/month in 2008-2010 (-26%, p < 0.01). The decline of STEMIs in non-smokers was consistently observed in all age groups and both sexes. Adjusting for potentially confounding factors like hypertension, obesity, and diabetes mellitus did not explain the observed decline. In the BSR, a significant decline of hospital admissions due to STEMIs in non-smokers was observed after the smoking ban in public areas came into force. No reduction of STEMI-related admissions was found in smokers. These results may be explained by the protection of non-smokers from passive smoking and the absence of such an effect in smokers by the dominant effect of active smoking. © The Author(s) 2013 Reprints and

  9. Doxorubicin In Vivo Rapidly Alters Expression and Translation of Myocardial Electron Transport Chain Genes, Leads to ATP Loss and Caspase 3 Activation

    PubMed Central

    Pointon, Amy V.; Walker, Tracy M.; Phillips, Kate M.; Luo, Jinli; Riley, Joan; Zhang, Shu-Dong; Parry, Joel D.; Lyon, Jonathan J.; Marczylo, Emma L.; Gant, Timothy W.

    2010-01-01

    Background Doxorubicin is one of the most effective anti-cancer drugs but its use is limited by cumulative cardiotoxicity that restricts lifetime dose. Redox damage is one of the most accepted mechanisms of toxicity, but not fully substantiated. Moreover doxorubicin is not an efficient redox cycling compound due to its low redox potential. Here we used genomic and chemical systems approaches in vivo to investigate the mechanisms of doxorubicin cardiotoxicity, and specifically test the hypothesis of redox cycling mediated cardiotoxicity. Methodology/Principal Findings Mice were treated with an acute dose of either doxorubicin (DOX) (15 mg/kg) or 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) (25 mg/kg). DMNQ is a more efficient redox cycling agent than DOX but unlike DOX has limited ability to inhibit gene transcription and DNA replication. This allowed specific testing of the redox hypothesis for cardiotoxicity. An acute dose was used to avoid pathophysiological effects in the genomic analysis. However similar data were obtained with a chronic model, but are not specifically presented. All data are deposited in the Gene Expression Omnibus (GEO). Pathway and biochemical analysis of cardiac global gene transcription and mRNA translation data derived at time points from 5 min after an acute exposure in vivo showed a pronounced effect on electron transport chain activity. This led to loss of ATP, increased AMPK expression, mitochondrial genome amplification and activation of caspase 3. No data gathered with either compound indicated general redox damage, though site specific redox damage in mitochondria cannot be entirely discounted. Conclusions/Significance These data indicate the major mechanism of doxorubicin cardiotoxicity is via damage or inhibition of the electron transport chain and not general redox stress. There is a rapid response at transcriptional and translational level of many of the genes coding for proteins of the electron transport chain complexes. Still

  10. Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction.

    PubMed

    Askari, Arman T; Brennan, Marie-Luise; Zhou, Xiaorong; Drinko, Jeanne; Morehead, Annitta; Thomas, James D; Topol, Eric J; Hazen, Stanley L; Penn, Marc S

    2003-03-03

    Left ventricular (LV) remodeling after myocardial infarction (MI) results in LV dilation, a major cause of congestive heart failure and sudden cardiac death. Ischemic injury and the ensuing inflammatory response participate in LV remodeling, leading to myocardial rupture and LV dilation. Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function. We studied acute myocardial infarction (AMI) in a chronic coronary artery ligation model in MPO null mice (MPO(-/-)). MPO(-/-) demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function. The mechanism appears to be due to decreased oxidative inactivation of plasminogen activator inhibitor 1 (PAI-1) in the MPO(-/-), leading to decreased tissue plasmin activity. MPO and PAI-1 are shown to have a critical role in the LV response immediately after MI, as demonstrated by markedly delayed myocardial rupture in the MPO(-/-) and accelerated rupture in the PAI-1(-/-). These data offer a mechanistic link between inflammation and LV remodeling by demonstrating a heretofore unrecognized role for MPO and PAI-1 in orchestrating the myocardial response to AMI.

  11. 2013 Immune Risk Standing Review Panel Research Plan Review for: The Risk of Crew Adverse Health Event Due to Altered Immune Response

    NASA Technical Reports Server (NTRS)

    Steinberg, Susan

    2014-01-01

    The 2013 Immune Risk Standing Review Panel (from here on referred to as the SRP) participated in a meeting with representatives from the Human Research Program (HRP) Human Health Countermeasures (HHC) Element and HRP management on February 3-4, 2014 in Houston, TX to review the updated Research Plan for the Risk of Crew Adverse Health Event Due to Altered Immune Response in the HRP Integrated Research Plan. The SRP is impressed with the work the immune discipline has done since the 2012 SRP review and agrees with the new wording of the Gaps, no longer questions, now statements. The SRP also likes the addition of adding targets for closing the Gaps, but it is not clear how they got to some of the interim stages (interval percentages). A major concern that the SRP has mentioned since the initial 2009 SRP meeting is that there is still not enough emphasis on the interdisciplinary aspect of the immune risk associated with other risks (i.e., nutrition, radiation, etc.). The SRP recommends that a "translational SRP" or advisory group be developed that is composed of members from all of the HRP SRPs. The SRP also thinks that the immune discipline should consider a more systems biology approach. Lastly, the SRP is concerned that the risks observed in research from low Earth orbit (LEO) missions may not accurately reflect all the risks of longer duration flight beyond LEO. Also, there does not seem to be a concern for immune responses that may occur when someone is in space longer than six months, for example, a Mars mission would take three years. The absence of disease in past and current flight scenarios does not mean the risk may not be there in future flight settings.

  12. SBDS-Deficient Cells Have an Altered Homeostatic Equilibrium due to Translational Inefficiency Which Explains their Reduced Fitness and Provides a Logical Framework for Intervention.

    PubMed

    Calamita, Piera; Miluzio, Annarita; Russo, Arianna; Pesce, Elisa; Ricciardi, Sara; Khanim, Farhat; Cheroni, Cristina; Alfieri, Roberta; Mancino, Marilena; Gorrini, Chiara; Rossetti, Grazisa; Peluso, Ivana; Pagani, Massimiliano; Medina, Diego L; Rommens, Johanna; Biffo, Stefano

    2017-01-01

    Ribosomopathies are a family of inherited disorders caused by mutations in genes necessary for ribosomal function. Shwachman-Diamond Bodian Syndrome (SDS) is an autosomal recessive disease caused, in most patients, by mutations of the SBDS gene. SBDS is a protein required for the maturation of 60S ribosomes. SDS patients present exocrine pancreatic insufficiency, neutropenia, chronic infections, and skeletal abnormalities. Later in life, patients are prone to myelodisplastic syndrome and acute myeloid leukemia (AML). It is unknown why patients develop AML and which cellular alterations are directly due to the loss of the SBDS protein. Here we derived mouse embryonic fibroblast lines from an SbdsR126T/R126T mouse model. After their immortalization, we reconstituted them by adding wild type Sbds. We then performed a comprehensive analysis of cellular functions including colony formation, translational and transcriptional RNA-seq, stress and drug sensitivity. We show that: 1. Mutant Sbds causes a reduction in cellular clonogenic capability and oncogene-induced transformation. 2. Mutant Sbds causes a marked increase in immature 60S subunits, limited impact on mRNA specific initiation of translation, but reduced global protein synthesis capability. 3. Chronic loss of SBDS activity leads to a rewiring of gene expression with reduced ribosomal capability, but increased lysosomal and catabolic activity. 4. Consistently with the gene signature, we found that SBDS loss causes a reduction in ATP and lactate levels, and increased susceptibility to DNA damage. Combining our data, we conclude that a cell-specific fragile phenotype occurs when SBDS protein drops below a threshold level, and propose a new interpretation of the disease.

  13. SBDS-Deficient Cells Have an Altered Homeostatic Equilibrium due to Translational Inefficiency Which Explains their Reduced Fitness and Provides a Logical Framework for Intervention

    PubMed Central

    Miluzio, Annarita; Russo, Arianna; Ricciardi, Sara; Khanim, Farhat; Cheroni, Cristina; Alfieri, Roberta; Mancino, Marilena; Gorrini, Chiara; Peluso, Ivana; Pagani, Massimiliano; Medina, Diego L.

    2017-01-01

    Ribosomopathies are a family of inherited disorders caused by mutations in genes necessary for ribosomal function. Shwachman-Diamond Bodian Syndrome (SDS) is an autosomal recessive disease caused, in most patients, by mutations of the SBDS gene. SBDS is a protein required for the maturation of 60S ribosomes. SDS patients present exocrine pancreatic insufficiency, neutropenia, chronic infections, and skeletal abnormalities. Later in life, patients are prone to myelodisplastic syndrome and acute myeloid leukemia (AML). It is unknown why patients develop AML and which cellular alterations are directly due to the loss of the SBDS protein. Here we derived mouse embryonic fibroblast lines from an SbdsR126T/R126T mouse model. After their immortalization, we reconstituted them by adding wild type Sbds. We then performed a comprehensive analysis of cellular functions including colony formation, translational and transcriptional RNA-seq, stress and drug sensitivity. We show that: 1. Mutant Sbds causes a reduction in cellular clonogenic capability and oncogene-induced transformation. 2. Mutant Sbds causes a marked increase in immature 60S subunits, limited impact on mRNA specific initiation of translation, but reduced global protein synthesis capability. 3. Chronic loss of SBDS activity leads to a rewiring of gene expression with reduced ribosomal capability, but increased lysosomal and catabolic activity. 4. Consistently with the gene signature, we found that SBDS loss causes a reduction in ATP and lactate levels, and increased susceptibility to DNA damage. Combining our data, we conclude that a cell-specific fragile phenotype occurs when SBDS protein drops below a threshold level, and propose a new interpretation of the disease. PMID:28056084

  14. T1, T2 Mapping and Extracellular Volume Fraction (ECV): Application, Value and Further Perspectives in Myocardial Inflammation and Cardiomyopathies.

    PubMed

    Roller, F C; Harth, S; Schneider, C; Krombach, G A

    2015-09-01

    Cardiac magnetic resonance imaging (CMRI) is a versatile diagnostic tool. One of its main advantages is the possibility of tissue characterization. T1-weighted images for scar and T2-weighted images for edema visualization are key methods for tissue characterization. Otherwise these sequences are strongly limited for the detection of diffuse myocardial pathologies. Recently, rapid technical innovations have generated new techniques. T1, T2 mapping and evaluation of the extracellular volume fraction (ECV) allow quantification of diffuse myocardial pathologies and showed great potential in the visualization of fibrosis, edema, amyloid, iron overload and lipid. In the future these techniques might enable the detection of early cardiac involvement, even act as a prognosticator. Moreover, therapy monitoring and follow-up might be possible due to versatile parameter quantification with these new techniques. CMR allows for tissue characterization via T1- and T2-weighted sequences. In cases of diffuse, global myocardial pathologies, correct image interpretation with traditional CMR sequences might be difficult. T1, T2 mapping and ECV can quantify diffuse, global myocardial pathologies. Alterations of myocardial T1 and T2 relaxation times occur in various myocardial diseases (e.g. acute myocarditis). In the future mapping might act as a prognosticator or therapy monitoring tool. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Effect of eating on thallium myocardial imaging

    SciTech Connect

    Wilson, R.A.; Sullivan, P.J.; Okada, R.D.; Boucher, C.A.; Morris, C.; Pohost, G.M.; Strauss, H.W.

    1986-02-01

    To determine if eating between initial and delayed thallium images alters the appearance of the delayed thallium scan, a prospective study was performed; 184 subjects sent for routine thallium imaging were randomized into two groups, those who ate a meal high in carbohydrates between initial and delayed thallium myocardial images (n = 106), and those who fasted (n = 78). The /sup 201/Tl images were interpreted in blinded fashion for global myocardial and pulmonary clearance of /sup 201/Tl myocardial defects. The eating group had a significantly lower incidence of transient myocardial defects compared to the noneating group (7 percent vs 18 percent, respectively; p less than 0.05). The time between initial and delayed images and the incidence of exercise-induced ischemic ST-segment depression or pathologic Q waves on the electrocardiogram were not significantly different between the two groups. These data suggest that eating a high-carbohydrate meal between initial and delayed /sup 201/Tl images causes increased /sup 201/Tl myocardial clearance rates and may alter /sup 201/Tl myocardial redistribution over time.

  16. Postmortem detection of inapparent myocardial infarction

    PubMed Central

    McVie, J. G.

    1970-01-01

    Two methods of detecting early inapparent myocardial infarcts have been studied and their value in diagnostic practice compared. The better method proved to be the determination of the potassium to sodium ratio (ionic ratio) which falls in infarcted tissue within minutes of the onset of anoxia. The second method was nitro blue tetrazolium staining of gross sections of myocardium which revealed any infarct older than three and a half hours. As staining is dependent upon enzyme activity, the latter method is disturbed by autolysis. It was shown, on the other hand, that the ionic ratio (K+/Na+) was not affected by autolysis and was therefore well suited to forensic practice. Sixteen non-infarcted control hearts, plus the nine from cases of sudden death due to causes other than myocardial infarction, all yielded high ionic ratios (K+/Na+), average 1·4, and stained normally with tetrazolium (the normal controls). Positive control was provided by 20 histologically proven infarcts of which the ionic ratios (K+/Na+) were all low (average 0·7). Histochemical staining with tetrazolium delineated infarcted areas in each case. In a series of 29 sudden deaths, a cause of death other than myocardial infarction was found at necropsy in nine, mentioned above as normal controls. The remaining 20 hearts were not infarcted histologically, but were shown to be infarcted by examination of the ionic ratios (K+/Na+). These ratios were low (average 0·8) including three borderline ratios. Confirmatory evidence of infarction included nitro blue tetrazolium staining which revealed infarcts in 10 of the 20 cases, and clinical and necropsy observations. The ionic ratio (K+/Na+) decreases as the age of the infarct increases for at least 24 hours. Thereafter as healing proceeds, the ratio gradually reverts to normal. Thus, previous infarction and replacement fibrosis do not significantly alter the ionic ratio (K+/Na+). Nor is it changed by left ventricular hypertrophy, the presence of

  17. Invasion of a semi-arid shrubland by annual grasses increases autotrophic and heterotrophic soil respiration rates due to altered soil moisture and temperature patterns

    NASA Astrophysics Data System (ADS)

    Mauritz, M.; Hale, I.; Lipson, D.

    2010-12-01

    Shrub <-> grassland conversions are a globally occurring phenomenon altering habitat structure, quality and nutrient cycling. Grasses and shrubs differ in their above and belowground biomass allocation, root architecture, phenology, litter quality and quantity. Conversion affects soil microbial communities, soil moisture and temperature and carbon (C) allocation patterns. However, the effect of conversion on C storage is regionally variable and there is no consistent direction of change. In Southern California invasion by annual grasses is a major threat to native shrub communities and it has been proposed that grass invasion increases NPP and ecosystem C storage (Wolkovich et al, 2009). In order to better understand how this shrub <-> grassland conversion changes ecosystem C storage it is important to understand the partitioning of soil respiration into autotrophic and heterotrophic components. Respiration was measured in plots under shrubs and grasses from February when it was cold and wet to July when it was hot and dry, capturing seasonal transitions in temperature and water availability. Roots were excluded under shrubs and grasses with root exclusion cores to quantify heterotrophic respiration. Using total soil respiration (Rt) = autotrophic respiration (root) (Ra)+ heterotrophic respiration (microbial) (Rh) the components contributing to total soil respiration can be evaluated. Respiration, soil moisture and temperature were measured daily at four hour intervals using Licor 8100 automated chamber measurements. Throughout the measurement period, Rt under grasses exceeded Rt under shrubs. Higher Rt levels under grasses were mainly due to higher Ra in grasses rather than changes in Rh. On average grass Ra was almost double shrub Ra. Higher grass respiration levels are partially explained by differences in soil moisture and temperature between shrubs and grasses. Respiration rates responded similarly to seasonal transitions regardless of treatment although Ra

  18. Myocardial imaging. Coxsackie myocarditis

    SciTech Connect

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  19. Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer.

    PubMed

    Mather, K J; Hutchins, G D; Perry, K; Territo, W; Chisholm, R; Acton, A; Glick-Wilson, B; Considine, R V; Moberly, S; DeGrado, T R

    2016-03-15

    Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[(18)F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([(11)C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m(-2)·min(-1)) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption (P = 0.04) and perfusion (P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids (P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions (P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups (P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM (P = 0.003). Myocardial work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM. Copyright © 2016 the American Physiological Society.

  20. Does cancer start in the womb? altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors.

    PubMed

    Soto, Ana M; Brisken, Cathrin; Schaeberle, Cheryl; Sonnenschein, Carlos

    2013-06-01

    We are now witnessing a resurgence of theories of development and carcinogenesis in which the environment is again being accepted as a major player in phenotype determination. Perturbations in the fetal environment predispose an individual to disease that only becomes apparent in adulthood. For example, gestational exposure to diethylstilbestrol resulted in clear cell carcinoma of the vagina and breast cancer. In this review the effects of the endocrine disruptor bisphenol-A (BPA) on mammary development and tumorigenesis in rodents is used as a paradigmatic example of how altered prenatal mammary development may lead to breast cancer in humans who are also widely exposed to it through plastic goods, food and drink packaging, and thermal paper receipts. Changes in the stroma and its extracellular matrix led to altered ductal morphogenesis. Additionally, gestational and lactational exposure to BPA increased the sensitivity of rats and mice to mammotropic hormones during puberty and beyond, thus suggesting a plausible explanation for the increased incidence of breast cancer.

  1. Magnetic resonance imaging for characterizing myocardial diseases.

    PubMed

    Saeed, Maythem; Liu, Hui; Liang, Chang-Hong; Wilson, Mark W

    2017-03-31

    The National Institute of Health defined cardiomyopathy as diseases of the heart muscle. These myocardial diseases have different etiology, structure and treatment. This review highlights the key imaging features of different myocardial diseases. It provides information on myocardial structure/orientation, perfusion, function and viability in diseases related to cardiomyopathy. The standard cardiac magnetic resonance imaging (MRI) sequences can reveal insight on left ventricular (LV) mass, volumes and regional contractile function in all types of cardiomyopathy diseases. Contrast enhanced MRI sequences allow visualization of different infarct patterns and sizes. Enhancement of myocardial inflammation and infarct (location, transmurality and pattern) on contrast enhanced MRI have been used to highlight the key differences in myocardial diseases, predict recovery of function and healing. The common feature in many forms of cardiomyopathy is the presence of diffuse-fibrosis. Currently, imaging sequences generating the most interest in cardiomyopathy include myocardial strain analysis, tissue mapping (T1, T2, T2*) and extracellular volume (ECV) estimation techniques. MRI sequences have the potential to decode the etiology by showing various patterns of infarct and diffuse fibrosis in myocarditis, amyloidosis, sarcoidosis, hypertrophic cardiomyopathy due to aortic stenosis, restrictive cardiomyopathy, arrythmogenic right ventricular dysplasia and hypertension. Integrated PET/MRI system may add in the future more information for the diagnosis and progression of cardiomyopathy diseases. With the promise of high spatial/temporal resolution and 3D coverage, MRI will be an indispensible tool in diagnosis and monitoring the benefits of new therapies designed to treat myocardial diseases.

  2. Myocardial factor revisited: The importance of myocardial fibrosis in adults with congenital heart disease.

    PubMed

    Broberg, Craig S; Burchill, Luke J

    2015-06-15

    Pioneers in congenital heart surgery observed that exercise capacity did not return to normal levels despite successful surgical repair, leading some to cite a "myocardial factor" playing a role. They conjectured that residual alterations in myocardial function would be significant for patients' long-term outlook. In fulfillment of their early observations, today's adult congenital heart disease (ACHD) population shows well-recognized features of heart failure, even among patients without clear residual anatomic or hemodynamic abnormalities, demonstrating the vital role of the myocardium in their morbidity and mortality. Whereas the 'myocardial factor' was an elusive concept in the early history of congenital heart care, we now have imaging techniques to detect and quantify one such factor--myocardial fibrosis. Understanding the importance of myocardial fibrosis as a final common pathway in a variety of congenital lesions provides a framework for both the study and treatment of clinical heart failure in this context. While typical heart failure pharmacology should reduce or attenuate fibrogenesis, efforts to show meaningful improvements with standard pharmacotherapy in ACHD repeatedly fall short. This paper considers the importance of myocardial fibrosis and function, the current body of evidence for myocardial fibrosis in ACHD, and its implications for research and treatment.

  3. Myocardial Factor Revisited: The Importance of Myocardial Fibrosis in Adults with Congenital Heart Disease

    PubMed Central

    Broberg, Craig S.; Burchill, Luke J.

    2015-01-01

    Pioneers in congenital heart surgery observed that exercise capacity did not return to normal levels despite successful surgical repair, leading some to cite a “myocardial factor” playing a role. They conjectured that residual alterations in myocardial function would be significant for patients’ long-term outlook. In fulfillment of their early observations, today’s adult congenital heart disease (ACHD) population shows well-recognized features of heart failure, even among patients without clear residual anatomic or hemodynamic abnormalities, demonstrating the vital role of the myocardium in their morbidity and mortality. Whereas the ‘myocardial factor’ was an elusive concept in the early history of congenital heart care, we now have imaging techniques to detect and quantify one such factor – myocardial fibrosis. Understanding the importance of myocardial fibrosis as a final common pathway in a variety of congenital lesions provides a framework for both the study and treatment of clinical heart failure in this context. While typical heart failure pharmacology should reduce or attenuate fibrogenesis, efforts to show meaningful improvements with standard pharmacotherapy in ACHD repeatedly fall short. This paper considers the importance of myocardial fibrosis and function, the current body of evidence for myocardial fibrosis in ACHD, and its implications for research and treatment. PMID:25897907

  4. Effect of Curcuma longa and Ocimum sanctum on myocardial apoptosis in experimentally induced myocardial ischemic-reperfusion injury

    PubMed Central

    Mohanty, Ipseeta; Arya, Dharamvir Singh; Gupta, Suresh Kumar

    2006-01-01

    Background In the present investigation, the effect of Curcuma longa (Cl) and Ocimum sanctum (Os) on myocardial apoptosis and cardiac function was studied in an ischemia and reperfusion (I-R) model of myocardial injury. Methods Wistar albino rats were divided into four groups and orally fed saline once daily (sham, control IR) or Cl (100 mg/kg; Cl-IR) or Os (75 mg/kg; Os-IR) respectively for 1 month. On the 31st day, in the rats of the control IR, Cl-IR and Os-IR groups LAD occlusion was undertaken for 45 min, and reperfusion was allowed for 1 h. The hemodynamic parameters{mean arterial pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak positive (+) LVdP/dt (rate of pressure development) and negative (-) LVdP/dt (rate of pressure decline)} were monitored at pre-set points throughout the experimental duration and subsequently, the animals were sacrificed for immunohistopathological (Bax, Bcl-2 protein expression & TUNEL positivity) and histopathological studies. Results Chronic treatment with Cl significantly reduced TUNEL positivity (p < 0.05), Bax protein (p < 0.001) and upregulated Bcl-2 (p < 0.001) expression in comparison to control IR group. In addition, Cl demonstrated mitigating effects on several myocardial injury induced hemodynamic {(+)LVdP/dt, (-) LVdP/dt & LVEDP} and histopathological perturbations. Chronic Os treatment resulted in modest modulation of the hemodynamic alterations (MAP, LVEDP) but failed to demonstrate any significant antiapoptotic effects and prevent the histopathological alterations as compared to control IR group. Conclusion In the present study, significant cardioprotection and functional recovery demonstrated by Cl may be attributed to its anti-apoptotic property. In contrast to Os, Cl may attenuate cell death due to apoptosis and prevent the impairment of cardiac performance. PMID:16504000

  5. Alterations of physiology and gene expression due to long-term magnesium-deficiency differ between leaves and roots of Citrus reticulata.

    PubMed

    Jin, Xiao-Lin; Ma, Cui-Lan; Yang, Lin-Tong; Chen, Li-Song

    2016-07-01

    Seedlings of Ponkan (Citrus reticulata) were irrigated with nutrient solution containing 0 (Mg-deficiency) or 1mM MgSO4 (control) every two day for 16 weeks. Thereafter, we examined magnesium (Mg)-deficiency-induced changes in leaf and root gas exchange, total soluble proteins and gene expression. Mg-deficiency lowered leaf CO2 assimilation, and increased leaf dark respiration. However, Mg-deficient roots had lower respiration. Total soluble protein level was not significantly altered by Mg-deficiency in roots, but was lower in Mg-deficient leaves than in controls. Using cDNA-AFLP, we obtained 70 and 71 differentially expressed genes from leaves and roots. These genes mainly functioned in signal transduction, stress response, carbohydrate and energy metabolism, cell transport, cell wall and cytoskeleton metabolism, nucleic acid, and protein metabolisms. Lipid metabolism (Ca(2+) signals)-related Mg-deficiency-responsive genes were isolated only from roots (leaves). Although little difference existed in the number of Mg-deficiency-responsive genes between them both, most of these genes only presented in Mg-deficient leaves or roots, and only four genes were shared by them both. Our data clearly demonstrated that Mg-deficiency-induced alterations of physiology and gene expression greatly differed between leaves and roots. In addition, we focused our discussion on the causes for photosynthetic decline in Mg-deficient leaves and the responses of roots to Mg-deficiency. Copyright © 2016 Elsevier GmbH. All rights reserved.

  6. Alterations in mechanical behaviour of articular cartilage due to changes in depth varying material properties--a nonhomogeneous poroelastic model study.

    PubMed

    Li, L P; Shirazi-Adl, A; Buschmann, M D

    2002-02-01

    The depth dependence of the material properties is present in normal adult cartilage and is believed to have significant implications in its normal mechanical function. Cartilage pathology may alter the depth dependence, e.g. a reduced depth dependence of the fibril stiffness has been observed in osteoarthritic cartilage. The objective of the present study is to investigate the alterations in the mechanical response of articular cartilage when the depth dependence of the material properties is varied to simulate healthy and pathological situations. This study is made possible by a recently developed nonhomogeneous poroelastic model. Depth variations of the strains and stresses for individual material phases (collagen, proteoglycan and fluid) are obtained for cartilage disks in unconfined compression using the finite element method. The mean nominal axial strain considered is up to 15%, while the axial strain at the articular surface can reach 33%. This paper demonstrates how the mechanical behaviours of cartilage are affected by individual depth dependent cartilage properties, while such observations are not fully available in experimental investigations. This study suggests the possibility of diagnosing cartilage health by analysing its mechanical behaviours.

  7. Altered sediment biota and lagoon habitat carbonate dynamics due to sea cucumber bioturbation in a high-pCO2 environment.

    PubMed

    Wolfe, Kennedy; Vidal-Ramirez, Francisco; Dove, Sophie; Deaker, Dione; Byrne, Maria

    2017-07-20

    The effects of global change on biological systems and functioning are already measurable, but how ecological interactions are being altered is poorly understood. Ecosystem resilience is strengthened by ecological functionality, which depends on trophic interactions between key species and resilience generated through biogenic buffering. Climate-driven alterations to coral reef metabolism, structural complexity and biodiversity are well documented, but the feedbacks between ocean change and trophic interactions of non-coral invertebrates are understudied. Sea cucumbers, some of the largest benthic inhabitants of tropical lagoon systems, can influence diel changes in reef carbonate dynamics. Whether they have the potential to exacerbate or buffer ocean acidification over diel cycles depends on their relative production of total alkalinity (AT ) through the dissolution of ingested calcium carbonate (CaCO3 ) sediments and release of dissolved inorganic carbon (CT ) through respiration and trophic interactions. In this study, the potential for the sea cucumber, Stichopus herrmanni, a bêche-de-mer (fished) species listed as vulnerable to extinction, to buffer the impacts of ocean acidification on reef carbonate chemistry was investigated in lagoon sediment mesocosms across diel cycles. Stichopus herrmanni directly reduced the abundance of meiofauna and benthic primary producers through its deposit-feeding activity under present-day and near-future pCO2 . These changes in benthic community structure, as well as AT (sediment dissolution) and CT (respiration) production by S. herrmanni, played a significant role in modifying seawater carbonate dynamics night and day. This previously unappreciated role of tropical sea cucumbers, in support of ecosystem resilience in the face of global change, is an important consideration with respect to the bêche-de-mer trade to ensure sea cucumber populations are sustained in a future ocean. © 2017 John Wiley & Sons Ltd.

  8. Shifts in the climate space of temperate cyprinid fishes due to climate change are coupled with altered body sizes and growth rates.

    PubMed

    Ruiz-Navarro, Ana; Gillingham, Phillipa K; Britton, J Robert

    2016-09-01

    Predictions of species responses to climate change often focus on distribution shifts, although responses can also include shifts in body sizes and population demographics. Here, shifts in the distributional ranges ('climate space'), body sizes (as maximum theoretical body sizes, L∞) and growth rates (as rate at which L∞ is reached, K) were predicted for five fishes of the Cyprinidae family in a temperate region over eight climate change projections. Great Britain was the model area, and the model species were Rutilus rutilus, Leuciscus leuciscus, Squalius cephalus, Gobio gobio and Abramis brama. Ensemble models predicted that the species' climate spaces would shift in all modelled projections, with the most drastic changes occurring under high emissions; all range centroids shifted in a north-westerly direction. Predicted climate space expanded for R. rutilus and A. brama, contracted for S. cephalus, and for L. leuciscus and G. gobio, expanded under low-emission scenarios but contracted under high emissions, suggesting the presence of some climate-distribution thresholds. For R. rutilus, A. brama, S. cephalus and G. gobio, shifts in their climate space were coupled with predicted shifts to significantly smaller maximum body sizes and/or faster growth rates, aligning strongly to aspects of temperature-body size theory. These predicted shifts in L∞ and K had considerable consequences for size-at-age per species, suggesting substantial alterations in population age structures and abundances. Thus, when predicting climate change outcomes for species, outputs that couple shifts in climate space with altered body sizes and growth rates provide considerable insights into the population and community consequences, especially for species that cannot easily track their thermal niches. © 2016 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

  9. Potential alteration of fjordal circulation due to a large floating structure—Numerical investigation with application to Hood Canal basin in Puget Sound

    SciTech Connect

    Khangaonkar, Tarang; Wang, Taiping

    2013-01-02

    Circulation in typical fjords is characterized by a shallow brackish layer at the surface over a deep long and narrow saltwater column. This surface layer is responsible for the outflow of water from the fjord, is easily disrupted by external forces, such as wind, and is influenced by freshwater inflow. In this paper, we postulate that the stability of fjordal circulation may also be vulnerable to impacts from anthropogenic alterations, such as floating structures, that could constrict the mixing and transport in the upper layers of the water column. The potential for alteration of circulation in Hood Canal, a silled-fjord located inside Puget Sound, Washington, has been examined. Using classical analytical treatments along the lines formulated by Hansen and Rattray [1965], Rattray [1967], Dyer [1973] and more recently, MacCready [2004], we develop a solution applicable to a range of estuary classifications varying from a partially mixed estuary regime to classical fjord conditions. Both estuary types exist in the Puget Sound system, and we compare our analytical solution with observed data. The analysis is based on an exponential variation of eddy viscosity with depth, and it has been extended further with modifications of the free surface boundary conditions to develop a solution representing the presence of a floating bridge at the estuary/fjord entrance. The model results show that tidally averaged mean circulation under the influence of such a constraint could reduce by as much as 30 to 50 percent. The overall water quality of fjords and narrow estuaries is dependent on net circulation and flushing. A potential decrease in residual flow or a corresponding increase in residence time of this magnitude merits further study.

  10. Myocardial mechanics in cardiomyopathies.

    PubMed

    Modesto, Karen; Sengupta, Partho P

    2014-01-01

    Cardiomyopathies are a heterogeneous group of diseases that can be phenotypically recognized by specific patterns of ventricular morphology and function. The authors summarize recent clinical observations that mechanistically link the multidirectional components of left ventricular (LV) deformation with morphological phenotypes of cardiomyopathies for offering key insights into the transmural heterogeneity of myocardial function. Subendocardial dysfunction predominantly alters LV longitudinal shortening, lengthening and suction performance and contributes to the phenotypic patterns of heart failure (HF) with preserved ejection fraction (EF) seen with hypertrophic and restrictive patterns of cardiomyopathy. On the other hand, a more progressive transmural disease results in reduction of LV circumferential and twist mechanics leading to the phenotypic pattern of dilated cardiomyopathy and the clinical syndrome of HF with reduced (EF). A proper characterization of LV transmural mechanics, energetics, and space-time distributions of pressure and shear stress may allow recognition of early functional changes that can forecast progression or reversal of LV remodeling. Furthermore, the interactions between LV muscle and fluid mechanics hold the promise for offering newer mechanistic insights and tracking impact of novel therapies.

  11. Evaluation in dogs of a new double-dose technique for imaging changes in myocardial perfusion

    SciTech Connect

    Rothendler, J.A.; Okada, R.D.; Strauss, H.W.; Chesler, D.A.; Pohost, G.M.

    1984-06-01

    Assessment of myocardial perfusion with thallium immediately before and after an intervention that alters blood flow has been difficult due to presence of residual activity from the first tracer dose at the time of the second imaging. In a canine model the authors investigated a technique using two separate thallium injections during an intervention and after its reversal. Images were obtained after each injection, and a difference image was obtained by subtracting the first from the second image to correct for tracer persisting from the first injection. Interventions on coronary blood flow included: transient occlusion, subcritical stenosis with dipyridamole infusion, and permanent occlusion. The first images showed defects corresponding to the occlusion or stenosis, while the ''difference'' images correlated with myocardial perfusion at the time of the second injection.

  12. Abnormal Myocardial Function Is Related to Myocardial Steatosis and Diffuse Myocardial Fibrosis in HIV-Infected Adults.

    PubMed

    Thiara, Diana K; Liu, Chia Ying; Raman, Fabio; Mangat, Sabrina; Purdy, Julia B; Duarte, Horacio A; Schmidt, Nancyanne; Hur, Jamie; Sibley, Christopher T; Bluemke, David A; Hadigan, Colleen

    2015-11-15

    Impaired cardiac function persists in the era of effective human immunodeficiency virus (HIV) therapy, although the etiology is unclear. We used magnetic resonance imaging (MRI) to measure intramyocardial lipid levels and fibrosis as possible contributors to HIV-associated myocardial dysfunction. A cross-sectional study of 95 HIV-infected and 30 matched-healthy adults, without known cardiovascular disease (CVD) was completed. Intramyocardial lipid levels, myocardial fibrosis, and cardiac function (measured on the basis of strain) were quantified by MRI. Systolic function was significantly decreased in HIV-infected subjects as compared to controls (mean radial strain [±SD], 21.7 ± 8.6% vs 30.5 ± 14.2%; P = .004). Intramyocardial lipid level and fibrosis index were both increased in HIV-infected subjects as compared to controls (P ≤ .04 for both) and correlated with the degree of myocardial dysfunction measured by strain parameters. Intramyocardial lipid levels correlated positively with antiretroviral therapy duration and visceral adiposity. Further, impaired myocardial function was strongly correlated with increased monocyte chemoattractant protein 1 levels (r = 0.396, P = .0002) and lipopolysaccharide binding protein levels (r = 0.25, P = .02). HIV-infected adults have reduced myocardial function as compared to controls in the absence of known CVD. Decreased cardiac function was associated with abnormal myocardial tissue composition characterized by increased lipid levels and diffuse myocardial fibrosis. Metabolic alterations related to antiretroviral therapy and chronic inflammation may be important targets for optimizing long-term cardiovascular health in HIV-infected individuals. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  13. Inferior ST-Elevation Myocardial Infarction Associated with Takotsubo Cardiomyopathy

    PubMed Central

    Koeth, Oliver; Zeymer, Uwe; Schiele, Rudolf; Zahn, Ralf

    2010-01-01

    Takotsubo cardiomyopathy (TCM) is usually characterized by transient left ventricular apical ballooning. Due to the clinical symptoms which include chest pain, electrocardiographic changes, and elevated myocardial markers, Takotsubo cardiomyopathy is frequently mimicking ST-elevation myocardial infarction in the absence of a significant coronary artery disease. Otherwise an acute occlusion of the left anterior descending coronary artery can produce a typical Takotsubo contraction pattern. ST-elevation myocardial infarction (STEMI) is frequently associated with emotional stress, but to date no cases of STEMI triggering TCM have been reported. We describe a case of a female patient with inferior ST-elevation myocardial infarction complicated by TCM. PMID:20811565

  14. Impaired Protofibril Formation in Fibrinogen γN308K Is Due to Altered D:D and "A:a" Interactions

    SciTech Connect

    Bowley, S.; Okumura, N; Lord, S

    2009-01-01

    'A:a' knob-hole interactions and D:D interfacial interactions are important for fibrin polymerization. Previous studies with recombinant ?N308K fibrinogen, a substitution at the D:D interface, showed impaired polymerization. We examined the molecular basis for this loss of function by solving the crystal structure of ?N308K fragment D. In contrast to previous fragment D crystals, the ?N308K crystals belonged to a tetragonal space group with an unusually long unit cell (a = b = 95 Angstroms, c = 448.3 Angstroms). Alignment of the normal and ?N308K structures showed the global structure of the variant was not changed and the knob 'A' peptide GPRP was bound as usual to hole 'a'. The substitution introduced an elongated positively charged patch in the D:D region. The structure showed novel, symmetric D:D crystal contacts between ?N308K molecules, indicating the normal asymmetric D:D interface in fibrin would be unstable in this variant. We examined GPRP binding to ?N308K in solution by plasmin protection assay. The results showed weaker peptide binding, suggesting that 'A:a' interactions were altered. We examined fibrin network structures by scanning electron microscopy and found the variant fibers were thicker and more heterogeneous than normal fibers. Considered together, our structural and biochemical studies indicate both 'A:a' and D:D interactions are weaker. We conclude that stable protofibrils cannot assemble from ?N308K monomers, leading to impaired polymerization.

  15. Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors.

    PubMed

    Li, Wei; Xu, Xin; Pozzo-Miller, Lucas

    2016-03-15

    Deficits in long-term potentiation (LTP) at central excitatory synapses are thought to contribute to cognitive impairments in neurodevelopmental disorders associated with intellectual disability and autism. Using the methyl-CpG-binding protein 2 (Mecp2) knockout (KO) mouse model of Rett syndrome, we show that naïve excitatory synapses onto hippocampal pyramidal neurons of symptomatic mice have all of the hallmarks of potentiated synapses. Stronger Mecp2 KO synapses failed to undergo LTP after either theta-burst afferent stimulation or pairing afferent stimulation with postsynaptic depolarization. On the other hand, basal synaptic strength and LTP were not affected in slices from younger presymptomatic Mecp2 KO mice. Furthermore, spine synapses in pyramidal neurons from symptomatic Mecp2 KO are larger and do not grow in size or incorporate GluA1 subunits after electrical or chemical LTP. Our data suggest that LTP is occluded in Mecp2 KO mice by already potentiated synapses. The higher surface levels of GluA1-containing receptors are consistent with altered expression levels of proteins involved in AMPA receptor trafficking, suggesting previously unidentified targets for therapeutic intervention for Rett syndrome and other MECP2-related disorders.

  16. Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors

    PubMed Central

    Li, Wei; Xu, Xin

    2016-01-01

    Deficits in long-term potentiation (LTP) at central excitatory synapses are thought to contribute to cognitive impairments in neurodevelopmental disorders associated with intellectual disability and autism. Using the methyl-CpG-binding protein 2 (Mecp2) knockout (KO) mouse model of Rett syndrome, we show that naïve excitatory synapses onto hippocampal pyramidal neurons of symptomatic mice have all of the hallmarks of potentiated synapses. Stronger Mecp2 KO synapses failed to undergo LTP after either theta-burst afferent stimulation or pairing afferent stimulation with postsynaptic depolarization. On the other hand, basal synaptic strength and LTP were not affected in slices from younger presymptomatic Mecp2 KO mice. Furthermore, spine synapses in pyramidal neurons from symptomatic Mecp2 KO are larger and do not grow in size or incorporate GluA1 subunits after electrical or chemical LTP. Our data suggest that LTP is occluded in Mecp2 KO mice by already potentiated synapses. The higher surface levels of GluA1-containing receptors are consistent with altered expression levels of proteins involved in AMPA receptor trafficking, suggesting previously unidentified targets for therapeutic intervention for Rett syndrome and other MECP2-related disorders. PMID:26929363

  17. Acute posteroinferior wall myocardial infarction secondary to football chest trauma.

    PubMed

    Espinosa, R; Badui, E; Castaño, R; Madrid, R

    1985-12-01

    Myocardial infarction secondary to nonpenetrating chest trauma is rare. We present the case of a sportsman who developed an acute transmural posteroinferior wall myocardial infarction due to chest trauma by a football. The angiographic study revealed total obstruction of the proximal right coronary artery.

  18. Optimization of myocardial function.

    PubMed

    Alpert, N R; Mulieri, L A; Hasenfuss, G; Holubarsch, C

    1993-01-01

    Under normal conditions the cardiac output is designed to meet the metabolic needs of the organism. Thus, the demands imposed on the heart muscle can range from low values at rest to an order of magnitude greater values during exercise. The heart uses a number of strategies to meet the short- and long-term changes in demand. These strategies are of general biological interest and employ similar mechanisms to those responsible for the differences in muscle performance seen between muscle from various species and diverse muscle types within a given animal. This review deals with the heart's utilization of these strategies to meet a broad range of requirements. Tortoise (TM) and rat soleus (RS) muscles are slow, have high economy and develop low power. In contrast (FM) and rat extensor digitorum longus (REDL) are fast, have low economy and have a high power output. These differences are explainable in terms of the characteristics of the myosin head cross-bridge cycle (Cross-bridge tension-time integral: FM/FT = 0.024; REDL/RS = 0.16. Myosin ATPase activity: FM/TM = 15; RDEL/RS = 2.3) and excitation contraction coupling system (time to peak tension: FM/TM = 0.2; REDL/RS = 0.4). Heart muscle employs similar strategies (cross-bridge cycle; excitation contraction coupling) to meet short (catecholamine) and long (hypertrophy secondary to pressure overload or thyrotoxicosis) term changes in demand. In the presence of catecholamine power is increased while economy is decreased. This difference between control (C) and isoproterenol treated hearts (I) is explainable in terms of the contractile and excitation contraction coupling systems (Cross-bridge tension-time integral: I/C = 0.4. Tension independent heat: I/C = 2.0. Tension independent heat rate: I/C = 2.5). A persistent increase in the demand on the heart results in myocardial hypertrophy that is associated with intracellular reorganization. Hyperthyroidism (T) and pressure overload (PO) were used to produce myocardial

  19. [Methylphenidate induced ST elevation acute myocardial infarction].

    PubMed

    Ruwald, Martin Huth; Ruwald, Anne-Christine Huth; Tønder, Niels

    2012-03-05

    Adult attention deficit and hyperkinetic disorder (ADHD) is increasingly diagnosed and treated with methylphenidate. We present the case of an 20 year-old man, who was diagnosed with ADHD and suffered a ST elevation acute myocardial infarction due to coronary vasospasm related to an overdose, and subsequent episodes of myocardial injury due to the use and misuse of methylphenidate over a period of two years. We recommend an increased attention to the subscription of methylphenidate to patients, who are at risk of misuse and patients, who have a cardiovascular history.

  20. Rapid loss of adiponectin-stimulated fatty acid oxidation in skeletal muscle of rats fed a high fat diet is not due to altered muscle redox state.

    PubMed

    Ritchie, Ian R W; Dyck, David J

    2012-01-01

    A high fat (HF) diet rapidly impairs the ability of adiponectin (Ad) to stimulate fatty acid (FA) oxidation in oxidative soleus muscle, but the underlying mechanism remains elusive. Mere days of HF feeding also increase the muscle's production and accumulation of reactive oxygen species (ROS) and shift cellular redox to a more oxidized state. It seems plausible that this shift towards a more oxidized state might act as negative feedback to suppress the ability of Ad to stimulate FA oxidation and generate more ROS. Therefore, we sought to determine whether i) a shift towards a more oxidized redox state (reduction in GSH/2GSSG) coincided with impaired Ad-stimulated palmitate oxidation in oxidative and glycolytic rodent muscle after 5 days of HF feeding (60% kCal), and ii) if supplementation with the antioxidant, N-acetylcysteine (NAC) could prevent the HF-diet induced impairment in Ad-response. Globular Ad (gAd) increased palmitate oxidation in isolated soleus and EDL muscles by 42% and 34%, respectively (p<0.05) but this was attenuated with HF feeding in both muscles. HF feeding decreased total GSH (-26%, p<0.05) and GSH/2GSSG (-49%, p<0.05) in soleus, but not EDL. Supplementation with NAC prevented the HF diet-induced reductions in GSH and GSH/2GSSG in soleus, but did not prevent the loss of Ad response in either muscle. Furthermore, direct incubations with H(2)O(2) did not impair Ad-stimulated FA oxidation in either muscle. In conclusion, our data indicates that skeletal muscle Ad resistance is rapidly induced in both oxidative and glycolytic muscle, independently of altered cellular redox state.

  1. Full-gestational exposure to nicotine and ethanol augments nicotine self-administration by altering ventral tegmental dopaminergic function due to NMDA receptors in adolescent rats.

    PubMed

    Roguski, Emily E; Sharp, Burt M; Chen, Hao; Matta, Shannon G

    2014-03-01

    In adult rats, we have shown full-gestational exposure to nicotine and ethanol (Nic + EtOH) augmented nicotine self-administration (SA) (increased nicotine intake) compared to pair-fed (PF) offspring. Therefore, we hypothesized that full-gestational exposure to Nic + EtOH disrupts control of dopaminergic (DA) circuitry by ventral tegmental area (VTA) NMDA receptors, augmenting nicotine SA and DA release in nucleus accumbens (NAcc) of adolescents. Both NAcc DA and VTA glutamate release were hyper-responsive to intra-VTA NMDA in Nic + EtOH offspring versus PF (p = 0.03 and 0.02, respectively). Similarly, DA release was more responsive to i.v. nicotine in Nic + EtOH offspring (p = 0.02). Local DL-2-Amino-5-phosphonopentanoic acid sodium salt (AP5) (NMDA receptor antagonist) infusion into the VTA inhibited nicotine-stimulated DA release in Nic + EtOH and PF offspring. Nicotine SA was augmented in adolescent Nic + EtOH versus PF offspring (p = 0.000001). Daily VTA microinjections of AP5 reduced nicotine SA by Nic + EtOH offspring, without affecting PF (p = 0.000032). Indeed, nicotine SA in Nic + EtOH offspring receiving AP5 was not different from PF offspring. Both VTA mRNA transcripts and NMDA receptor subunit proteins were not altered in Nic + EtOH offspring. In summary, adolescent offspring exposed to gestational Nic + EtOH show markedly increased vulnerability to become dependent on nicotine. This reflects the enhanced function of a subpopulation of VTA NMDA receptors that confer greater nicotine-induced DA release in NAcc. We hypothesized that concurrent gestational exposure to nicotine and ethanol would disrupt the control of VTA dopaminergic circuitry by NMDA receptors. Resulting in the augmented nicotine self-administration (SA) in adolescent offspring.

  2. NSAID-induced acute phase response is due to increased intestinal permeability and characterized by early and consistent alterations in hepatic gene expression.

    PubMed

    Tugendreich, Stuart; Pearson, Cecelia I; Sagartz, John; Jarnagin, Kurt; Kolaja, Kyle

    2006-01-01

    Toxicogenomics using a reference database can provide a better understanding and prediction of toxicity, largely by creating biomarkers that tie gene expression to actual pathology events. During the course of building a toxicogenomic database, an observation was made that a number of non-steroidal anti-inflammatory compounds (NSAIDs) at supra-pharmacologic doses induced an acute phase response (APR) and displayed hepatic gene expression patterns similar to that of intravenous lipopolysaccharide (LPS). Since NSAIDs are known to cause injury along the gastrointestinal tract, it has been suggested that NSAIDs increase intestinal permeability, allowing LPS and/or bacteria into the systemic circulation and stimulating an APR detectable in the liver. A short term study was subsequently conducted examining the effects of aspirin, indomethacin, ibuprofen, and rofecoxib to rats and a variety of endpoints were examined that included serum levels of inflammatory cytokines, histologic evaluation, and hepatic gene expression. Both indomethacin and ibuprofen injured the gastrointestinal tract, induced an APR, and increased serum levels of LPS, while rofecoxib and aspirin did not affect the GI tract or induce an APR. In treatments that eventually showed a systemic inflammatory response, hepatic expression of many inflammatory genes was noted as early as 6 hours after treatment well before alterations in traditional clinical pathology markers were detected. This finding led to the creation of a hepatic gene expression biomarker of APR that was effectively shown to be an early identifier of imminent inflammatory injury. In terms of the relative gastrointestinal safety and the NSAIDs studied, an important safety distinction can be made between the presumptive efficacious dose and the APR-inducing dose for indomethacin (1-2-fold), ibuprofen (5-fold), and rofecoxib (approximately 250-fold). Our data support the notion that NSAID-induced intestinal injury results in leakage of

  3. A geomorphic framework to assess changes to aquatic habitat due to flow regulation and channel and floodplain alteration of the Cedar River, Washington

    NASA Astrophysics Data System (ADS)

    Gendaszek, A. S.; Magirl, C. S.; Barnas, C. R.; Konrad, C. P.; Little, R.

    2010-12-01

    Flow regulation, bank armoring, and floodplain alteration since the early 20th century have contributed to significant changes in the hydrologic regime and geomorphic processes of the Cedar River in Washington State. The Cedar River originates in the Cascade Range, provides drinking water to the Seattle metropolitan area, and supports several populations of anadromous salmonids. Flow regulation currently has limited influence on the magnitude, duration, and timing of high-flow events, which affect the incubation of salmonids as well as the production and maintenance of their habitat. Unlike structural changes to the channel and floodplain, flow regulation may be modified in the short-term to improve the viability of salmon populations. An understanding of the effects of flow regulation on those populations must be discerned over a range of scales from individual floods that affect the size of individual year classes to decadal high flow regime that influences the amount and quality of channel and off-channel habitat available for spawning and rearing. We present estimates of reach-scale sediment budgets and changes to channel morphology derived from historical orthoimagery, specific gage analyses at four long-term streamflow-gaging stations to quantify trends in aggradation, and hydrologic statistics of the magnitude and duration of peak streamflows. These data suggest a gradient of channel types from unconfined, sediment-rich segments to confined, sediment-poor segments that are likely to have distinct responses to high flows. Particle-size distribution data and longitudinal water surface and streambed profiles for the 56 km downstream of Chester Morse Lake measured in 2010 show the spatial extent of preferred salmonid habitat along the Cedar River. These historical and current data constitute a geomorphic framework to help assess different river management scenarios for salmonid habitat and population viability.

  4. Channel widening due to urbanization and a major flood can alter bed particle organization and bed stability in an urban boulder-bed channel

    NASA Astrophysics Data System (ADS)

    Prestegaard, K. L.; Behrns, K.; Blanchet, Z.; Hankin, E.

    2007-12-01

    The Anacostia River is a tributary of the Potomac River north of Washington D.C. that has become progressively more urbanized in the past 50 years. Bankfull discharge and bankfull width in the Anacostia have increased by 3- 4x in the past 50 years. Nearby watersheds of similar size and geology, but without significant urbanization, contain threshold gravel-bed streams. The Anacostia, however, is not a threshold channel; it exhibits break-up of boulder-bed channels in upstream reaches and significant gravel bar formation in downstream reaches. These gravel bars have grown and migrated considerably in the past 10-15 years, contributing significantly to local channel widening that can be twice that of adjacent reaches. The purpose of this study is to determine bedload transport rates and grain size distributions and their relationship to discharge, bed organization and sediment supply. Bed mobility data come from both bedload transport measurements and measurements of channel bed changes. Channel bed changes were obtained from a) repeated channel cross section surveys, b) surface and subsurface size distributions, and c) bed particle organization measurements (measurements of location of particles within reaches). These measurements were made prior to and after the floods of 2006, which equalled the largest floods on record for most parts of the Anacostia River. In some boulder bed reaches, boulders were removed from the center of the channel and deposited along and on the channel banks. The mid-channel boulders were replaced by sheets of gravel and cobbles, significantly altering the bed mobility of the channels.

  5. [Microscopic myocardial changes and their significance for forensic medical diagnosis].

    PubMed

    Kapustin, A V

    2006-01-01

    Morphological myocardial changes essential for diagnosis in forensic medical medicine are listed as well as alterations in the vessels of the myocardium, cardiac muscular fibers and cardiomyocytes important for diagnosis of death of ischemic heart disease, acute alcohol poisoning, alcohol cardiomyopathy, closed cardiac lesions. Changes induced by reflex impacts on the heart and postmortem alterations are also shown.

  6. Assessment and classification of patients with myocardial injury and infarction in clinical practice

    PubMed Central

    Chapman, Andrew R; Adamson, Philip D

    2017-01-01

    Myocardial injury is common in patients without acute coronary syndrome, and international guidelines recommend patients with myocardial infarction are classified by aetiology. The universal definition differentiates patients with myocardial infarction due to plaque rupture (type 1) from those due to myocardial oxygen supply-demand imbalance (type 2) secondary to other acute illnesses. Patients with myocardial necrosis, but no symptoms or signs of myocardial ischaemia, are classified as acute or chronic myocardial injury. This classification has not been widely adopted in practice, because the diagnostic criteria for type 2 myocardial infarction encompass a wide range of presentations, and the implications of the diagnosis are uncertain. However, both myocardial injury and type 2 myocardial infarction are common, occurring in more than one-third of all hospitalised patients. These patients have poor short-term and long-term outcomes with two-thirds dead in 5 years. The classification of patients with myocardial infarction continues to evolve, and future guidelines are likely to recognise the importance of identifying coronary artery disease in type 2 myocardial infarction. Clinicians should consider whether coronary artery disease has contributed to myocardial injury, as selected patients are likely to benefit from further investigation and in these patients targeted secondary prevention has the potential to improve outcomes. PMID:27806987

  7. Gsα activity is reduced in erythrocyte membranes of patients with psedohypoparathyroidism due to epigenetic alterations at the GNAS locus.

    PubMed

    Zazo, Celia; Thiele, Susanne; Martín, Cesar; Fernandez-Rebollo, Eduardo; Martinez-Indart, Lorea; Werner, Ralf; Garin, Intza; Hiort, Olaf; Perez de Nanclares, Guiomar

    2011-08-01

    In pseudohypoparathyroidism (PHP), PTH resistance results from impairment of signal transduction of G protein-coupled receptors caused by a deficiency of the Gsα-cAMP signaling cascade due to diminished Gsα activity in maternally imprinted tissues. In PHP-Ia, inactivating mutations of the GNAS gene lead to haploinsufficiency in some tissues with biallelic expression, so in addition to PHP, Albright's hereditary osteodystrophy (AHO) is also present. In PHP-Ib, caused by methylation defects at the GNAS locus, diminished Gsα activity was thought to be limited to maternally imprinted tissues, such as the renal proximal tubule and the thyroid, leading to a lack of AHO. Recently, we demonstrated methylation defects in patients with AHO signs, indicating a connection between epigenetic changes and AHO. Our objective was to determine Gsα activity in erythrocyte membranes in patients with epigenetic defects at the GNAS locus compared to normal controls and patients with inactivating GNAS mutations. Gsα activity and expression, mutation of the GNAS locus, and methylation status were studied in patients with PHP and mild signs of AHO (PHP-Ia: 12; PHP-Ib: 17, of which 8 had some features of AHO). Then, we statistically compared the Gsα activity of the different PHP subtypes. Patients with methylation defects at the GNAS locus show a significant decrease in erythrocyte Gsα activity compared to normal controls (PHP-Ib versus controls, p < .001). This was significantly lower in patients with AHO signs (PHP-Ib + mild-AHO versus PHP-Ib, p < .05). Our research shows that PHP-Ia and PHP-Ib classification is not only overlapped genetically, as reported, but also in terms of Gsα activity. Reduced expression of GNAS due to methylation defects could downregulate Gsα activity in other tissues beyond those described and could also be causative of AHO.

  8. Elevated Accumulation of Proline in NaCl-Adapted Tobacco Cells Is Not Due to Altered Δ1-Pyrroline-5-Carboxylate Reductase 1

    PubMed Central

    LaRosa, P. Christopher; Rhodes, David; Rhodes, Judith C.; Bressan, Ray A.; Csonka, Laszlo N.

    1991-01-01

    Tobacco (Nicotiana tabacum L. var Wisconsin 38) cells that are adapted to 428 millimolar NaCl accumulate proline mainly due to increased synthesis from glutamate. These cells were used to evaluate the possible role of Δ1-pyrroline-5-carboxylate reductase in the regulation of proline biosynthesis. No increase in the specific activity of Δ1-pyrroline-5-carboxylate reductase in crude extracts throughout the growth cycle was observed in NaCl-adapted cells compared to unadapted cells. The enzyme from both cell types was purified extensively. On the basis of affinity for the substrates NADPH, NADH, and Δ1-pyrroline-5-carboxylate, pH profiles, chromatographic behavior during purification, and electrophoretic mobility of the native enzyme, the activities of the enzyme from the two sources were similar. These data suggest that the NaCl-dependent regulation of proline synthesis in tobacco cells does not involve induction of pyrroline-5-carboxylate isozymes or changes in its kinetic properties. ImagesFigure 1 PMID:16668159

  9. Increase in mean platelet volume in patients with myocardial bridge.

    PubMed

    Bilen, Emine; Tanboga, Ibrahim Halil; Kurt, Mustafa; Kocak, Umran; Ayhan, Huseyin; Keles, Telat; Bozkurt, Engin

    2013-01-01

    Myocardial bridge is associated with atherosclerosis altered in shear stress and endothelial dysfunction. Mean platelet volume (MPV), a determinant of platelet activation, is shown to be related with atherosclerosis and endothelial dysfunction. In this study, we aimed to evaluate platelet function assessed by MPV in patients with myocardial bridge. Forty-two patients with myocardial bridge in the left anterior descending artery (LAD) and 43 age- and gender-matched healthy participants were included in the study. Myocardial bridging was defined as an intramyocardial systolic compression or milking of a segment of an epicardial coronary artery on angiography. For the entire study population, MPV was measured using an automatic blood counter. The study population consisted of 42 patients with myocardial bridge (52.7 ± 10.2, 76.2% male) and 43 age- and sex-matched healthy control participants (52.1 ± 10.4, 74.4% male). Compared to the control group, MPV value was significantly higher in patients with myocardial bridge (8.9 ± 1.24 vs 8.3 ± 0.78; P = .01). Further, there were no significant differences between groups regarding hemoglobin level, platelet count, fasting blood glucose, and creatinine levels. Our study findings indicated that myocardial bridge is associated with elevated MPV values. Our results might partly explain the increased cardiovascular events in patients with myocardial bridge.

  10. Identification of Temporal and Region-Specific Myocardial Gene Expression Patterns in Response to Infarction in Swine

    PubMed Central

    Nonell, Lara; Puigdecanet, Eulàlia; Astier, Laura; Solé, Francesc; Bayes-Genis, Antoni

    2013-01-01

    Molecular mechanisms associated with pathophysiological changes in ventricular remodelling due to myocardial infarction (MI) remain poorly understood. We analyzed changes in gene expression by microarray technology in porcine myocardial tissue at 1, 4, and 6 weeks post-MI. MI was induced by coronary artery ligation in 9 female pigs (30–40 kg). Animals were randomly sacrificed at 1, 4, or 6 weeks post-MI (n = 3 per group) and 3 healthy animals were also included as control group. Total RNA from myocardial samples was hybridized to GeneChip® Porcine Genome Arrays. Functional analysis was obtained with the Ingenuity Pathway Analysis (IPA) online tool. Validation of microarray data was performed by quantitative real-time PCR (qRT-PCR). More than 8,000 different probe sets showed altered expression in the remodelling myocardium at 1, 4, or 6 weeks post-MI. Ninety-seven percent of altered transcripts were detected in the infarct core and 255 probe sets were differentially expressed in the remote myocardium. Functional analysis revealed 28 genes de-regulated in the remote myocardial region in at least one of the three temporal analyzed stages, including genes associated with heart failure (HF), systemic sclerosis and coronary artery disease. In the infarct core tissue, eight major time-dependent gene expression patterns were recognized among 4,221 probe sets commonly altered over time. Altered gene expression of ACVR2B, BID, BMP2, BMPR1A, LMNA, NFKBIA, SMAD1, TGFB3, TNFRSF1A, and TP53 were further validated. The clustering of similar expression patterns for gene products with related function revealed molecular footprints, some of them described for the first time, which elucidate changes in biological processes at different stages after MI. PMID:23372767

  11. Mechanisms for altered carnitine content in hypertrophied rat hearts

    SciTech Connect

    Reibel, D.K.; O'Rourke, B.; Foster, K.A.

    1987-03-01

    Carnitine levels are reduced in hypertrophied hearts of rats subjected to aortic constriction (banding) and evaluated in hypertrophied hearts of spontaneously hypertensive rats (SHR). In an attempt to determine the mechanisms for these alterations, L-(/sup 14/C)carnitine transport was examined in isolated perfused hearts. Total carnitine uptake was significantly reduced by approx.20% in hypertrophied hearts of banded rats at all perfusate carnitine concentrations employed. The reduction in total uptake was due to a 40% reduction in carrier-mediated carnitine uptake with no difference in uptake by diffusion. In contrast, carnitine uptake was not altered in isolated hypertrophied hearts of SHR. However, serum carnitine levels were elevated in SHR, which could result in increased myocardial carnitine uptake in vivo. The data suggest that altered carnitine content in hypertrophied hearts of aortic-banded rats is due to an alteration in the carrier-mediated carnitine transport system in the myocardium. However, altered carnitine content in hypertrophied hearts of SHR is not due to a change in the carnitine transport system per se but may rather be due to a change in serum carnitine levels.

  12. Periodontitis and myocardial hypertrophy.

    PubMed

    Suzuki, Jun-Ichi; Sato, Hiroki; Kaneko, Makoto; Yoshida, Asuka; Aoyama, Norio; Akimoto, Shouta; Wakayama, Kouji; Kumagai, Hidetoshi; Ikeda, Yuichi; Akazawa, Hiroshi; Izumi, Yuichi; Isobe, Mitsuaki; Komuro, Issei

    2017-04-01

    There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

  13. Combretastatin A4 disodium phosphate-induced myocardial injury

    PubMed Central

    Tochinai, Ryota; Nagata, Yuriko; Ando, Minoru; Hata, Chie; Suzuki, Tomo; Asakawa, Naoyuki; Yoshizawa, Kazuhiko; Uchida, Kazumi; Kado, Shoichi; Kobayashi, Toshihide; Kaneko, Kimiyuki; Kuwahara, Masayoshi

    2016-01-01

    Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner. PMID:27559241

  14. Immune status alters the probability of apparent illness due to dengue virus infection: Evidence from a pooled analysis across multiple cohort and cluster studies.

    PubMed

    Clapham, Hannah E; Cummings, Derek A T; Johansson, Michael A

    2017-09-27

    sensitivity over time due to the interaction between previous incidence and the symptomatic proportion, as shown here. Nonetheless the underlying incidence of infection is critical to understanding susceptibility of the population and estimating the true burden of disease, key factors for effectively targeting interventions. The estimates shown here help clarify the link between past infection, observed disease, and current transmission intensity.

  15. Altered pathogenicity of a tl/CH/LDT3/03 genotype infectious bronchitis coronavirus due to natural recombination in the 5'- 17kb region of the genome.

    PubMed

    Han, Zongxi; Zhang, Tingting; Xu, Qianqian; Gao, Mengying; Chen, Yuqiu; Wang, Qiuling; Zhao, Yan; Shao, Yuhao; Li, Huixin; Kong, Xiangang; Liu, Shengwang

    2016-02-02

    An infectious bronchitis coronavirus, designated as ck/CH/LGX/130530, was isolated from an IBV strain H120-vaccinated chicken in this study. Analysis of the S1 gene showed that isolate ck/CH/LGX/130530 was a tl/CH/LDT3/03-like virus, with a nucleotide sequence similarity of 99%. However, a complete genomic sequence analysis showed that ck/CH/LGX/130530 was more closely related to a Massachusetts type strain (95% similarity to strain H120) than to the tl/CH/LDT3/03 strain (86%), suggesting that recombination might have occurred during the origin of the virus. A SimPlot analysis of the complete genomic sequence confirmed this hypothesis, and it showed that isolate ck/CH/LGX/130530 emerged from a recombination event between parental IBV H120 strain and pathogenic tl/CH/LDT3/03-like virus. The results obtained from the pairwise comparison and nucleotide similarity showed that the recombination breakpoint was located in the nsp14 gene at nucleotides 17055-17083. In line with the high S1 gene sequence similarity, the ck/CH/LGX/130530 isolate was serotypically close to that of the tl/CH/LDT3/03 strain (73% antigenic relatedness). Furthermore, vaccination with the LDT3-A vaccine, which was derived from the tl/CH/LDT3/03 strain by serial passaging in chicken eggs, provided good protection against challenge with the tl/CH/LDT3/03 strain, in contrast to the poor protection offered with the H120 vaccine. Interestingly, isolate ck/CH/LGX/130530 exhibited low pathogenicity toward specific-pathogen-free chickens compared with the nephropathogenic tl/CH/LDT3/03 strain, which was likely due to natural recombination in the 5' 17-kb region of the genome. Our results also indicate that the replicase gene of IBV isolate ck/CH/LGX/130530 is associated with viral pathogenicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Alterations in platelet Ca2+ signalling in diabetic patients is due to increased formation of superoxide anions and reduced nitric oxide production.

    PubMed

    Schaeffer, G; Wascher, T C; Kostner, G M; Graier, W F

    1999-02-01

    enhanced by excessive superoxide production and an attenuated negative direct or indirect feedback control by nitric oxide, due to its reduced production.

  17. Ultrastructural and cellular basis for the development of abnormal myocardial mechanics during the transition from hypertension to heart failure.

    PubMed

    Shah, Sanjiv J; Aistrup, Gary L; Gupta, Deepak K; O'Toole, Matthew J; Nahhas, Amanda F; Schuster, Daniel; Chirayil, Nimi; Bassi, Nikhil; Ramakrishna, Satvik; Beussink, Lauren; Misener, Sol; Kane, Bonnie; Wang, David; Randolph, Blake; Ito, Aiko; Wu, Megan; Akintilo, Lisa; Mongkolrattanothai, Thitipong; Reddy, Mahendra; Kumar, Manvinder; Arora, Rishi; Ng, Jason; Wasserstrom, J Andrew

    2014-01-01

    Although the development of abnormal myocardial mechanics represents a key step during the transition from hypertension to overt heart failure (HF), the underlying ultrastructural and cellular basis of abnormal myocardial mechanics remains unclear. We therefore investigated how changes in transverse (T)-tubule organization and the resulting altered intracellular Ca(2+) cycling in large cell populations underlie the development of abnormal myocardial mechanics in a model of chronic hypertension. Hearts from spontaneously hypertensive rats (SHRs; n = 72) were studied at different ages and stages of hypertensive heart disease and early HF and were compared with age-matched control (Wistar-Kyoto) rats (n = 34). Echocardiography, including tissue Doppler and speckle-tracking analysis, was performed just before euthanization, after which T-tubule organization and Ca(2+) transients were studied using confocal microscopy. In SHRs, abnormalities in myocardial mechanics occurred early in response to hypertension, before the development of overt systolic dysfunction and HF. Reduced longitudinal, circumferential, and radial strain as well as reduced tissue Doppler early diastolic tissue velocities occurred in concert with T-tubule disorganization and impaired Ca(2+) cycling, all of which preceded the development of cardiac fibrosis. The time to peak of intracellular Ca(2+) transients was slowed due to T-tubule disruption, providing a link between declining cell ultrastructure and abnormal myocardial mechanics. In conclusion, subclinical abnormalities in myocardial mechanics occur early in response to hypertension and coincide with the development of T-tubule disorganization and impaired intracellular Ca(2+) cycling. These changes occur before the development of significant cardiac fibrosis and precede the development of overt cardiac dysfunction and HF.

  18. Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography. [Dogs

    SciTech Connect

    Schelbert, H.R.; Phelps, M.E.

    1980-06-01

    While the results of regional myocardial glucose metabolism measurements using positron emission computed tomography (/sup 13/N-ammonia) are promising, their utility and value remains to be determined in man. If this technique can be applied to patients with acute myocardial ischemia or infarction it may permit delineation of regional myocardial segments with altered, yet still active metabolism. Further, it may become possible to evaluate the effects of interventions designed to salvage reversibly injured myocardium by this technique.

  19. Myocardial infarction in Antigua. 1990 to 1995.

    PubMed

    Martin, T C; Van Longhuyzen, H W; Amaraswamy, R; Tangutoori, R; Bennett, B

    1997-09-01

    Between January 1990 and May 1995, 117 patients were admitted to the Intensive Care Unit at Holberton Hospital, Antigua, for chest pain due to suspected acute myocardial infarction. 39 (45%) of 86 patients whose records were available for retrospective review had confirmed (27 patients) or probable (12 patients) acute myocardial infarction. Risk factors identified among the patients included hypertension, diabetes, tobacco smoking, hypercholesterolaemia and obesity. On admission, 82% were Killip class I and 18% were Killip class II. Medications in the Intensive Care Unit included nitrates, aspirin, calcium channel blockers, beta-adrenergic blockers, heparin and angiotensin converting enzyme inhibitors (21%). No thrombolytic agents were available. The average hospital stay was 10 days and the in-hospital mortality rate was 13%. These data indicate that early mortality from acute myocardial infarction can be reduced in developing countries by early admission to an Intensive Care Unit and use of drugs known to be effective in its treatment.

  20. Biochemical assessment of acute myocardial ischaemia.

    PubMed Central

    Perez-Cárceles, M D; Osuna, E; Vieira, D N; Martínez, A; Luna, A

    1995-01-01

    AIMS--To evaluate the efficacy of biochemical parameters in different fluids in the diagnosis of myocardial infarction of different causes, analysed after death. METHODS--The myoglobin concentration and total creatine kinase (CK) and creatine kinase MB isoenzyme (CK-MB) activities were measured in serum, pericardial fluid, and vitreous humour from seven diagnostic groups of cadavers classified according to the severity of myocardial ischaemia and cause of death. Lactate dehydrogenase (LDH) and myosin were measured only in serum and pericardial fluid, and cathepsin D only in pericardial fluid. Routine haematoxylin and eosin and acridine orange staining were used for microscopy studies of heart tissue. RESULTS--In pericardial fluid there were substantial differences between the different groups with respect to CK, CK-MB, and LDH activities and myosin concentrations. The highest values were found in cases with morphological evidence of myocardial ischaemia. CONCLUSIONS--Biochemical parameters, which reach the pericardial fluid via passive diffusion and ultrafiltration due to a pressure gradient, were thus detectable in this fluid earlier than in serum in cases with myocardial ischaemia. These biochemical parameters may be of use for ruling out myocardial ischaemia in those controversial cases in which reliable morphological findings are lacking. PMID:7745110

  1. Myocardial Noncompaction Presenting With Myocardial Bridge

    PubMed Central

    Shen, Yuechun; Li, Xinchun; Lu, Dongfeng; Xiao, Aiyi; Li, Jun

    2015-01-01

    Abstract Myocardial noncompaction, namly isolated noncompaction of the left ventricular myocardium (NVM), is a rare congenital disease. It can be either seen in the absence of other cardiac anomalies, or associated with other congenital cardiac defects, mostly stenotic lesions of the left ventricular outflow tract. A myocardial bridge (MB) is thought being associated with coronary heart disease, such as coronary spasm, arrhythmia, and so on. The significance of MB in association with other congenital cardiac conditions is unknown. We report a novel case who was presented NVM and MB. A 34-year-old man complained of chest prickling-like pain and dizzy for 1 year. His blood pressure was 110/70 mm Hg. Echocardiograph revealed increased trabeculations below the level of papillary muscle of left ventricle (LV); deep intertrabecular recesses in the endocardial wall of LV particularly in apex free wall; and LV ejection fraction of 57%. A coronary computerized tomography scan showed that part, 38.9 cm, of left descending artery tunnel was surrounding by cardiac muscles rather than resting on top of the myocardium. The therapeutics interventions included lifestyle cares, agents of anti-ischemia and improvement myocardial cell metabolism. The patient was followed up for 2.6 years, and his general condition was stable. This case indicates that NVM can be developed with MB, and the complete diagnosis of NVM and MB should be made by different image studies. PMID:26356695

  2. Myocardial revascularization with both internal thoracic arteries 25 years after delayed repair for aortic coarctation.

    PubMed

    Gaudino, Mario; Farina, Piero; Cammertoni, Federico; Massetti, Massimo

    2015-02-01

    Aortic coarctation has been reported to cause alterations in the internal thoracic arteries that make these vessels unsuitable to be used as grafts for myocardial revascularization, especially if coarctation repair was performed in adulthood. This is the first reported bilateral internal thoracic grafting for myocardial revascularization in a patient who had undergone aortic coarctation repair 25 years earlier.

  3. Formation of binucleated myocardial cells in the neonatal rat. An index for growth hypertrophy

    SciTech Connect

    Clubb, F.J. Jr.; Bishop, S.P.

    1984-05-01

    The purposes of this study were to characterize myocardial cell growth in neonatal rats and investigate the mechanism of binucleation in myocardial cells. To test the hypothesis that binucleated myocardial cells result from karyokinesis without cytokinesis, experiments were designed to measure the rate of DNA synthesis and the percentage of binucleated myocardial cells in neonatal rats during growth. Estimates of myocardial cell nuclear divisions were obtained from rats pulsed with tritiated thymidine at 17 days of gestation. Autoradiograms were prepared from isolated myocardial cells of rats killed at various ages postpartum, and the number of developed silver halide grains over myocardial cell nuclei was calculated. This estimated the mitotic activity of nuclei. To determine myocardial cell DNA synthesis postpartum, another set of rats were injected at various time periods with 4 hourly doses of tritiated thymidine, and hearts were fixed by perfusion 1 hour later. Labeling index of myocardial cells was calculated (labeled/total myocardial cells) from autoradiograms. Results indicated that the growth of myocardial cells in period can be divided into three phases: (a) a hyperplastic phase, (b) a transitional phase, and (c) a hypertrophic phase. Binucleation of myocardial cells was not due to fusion of mononucleated cells.

  4. Quantitative myocardial perfusion SPECT.

    PubMed

    Tsui, B M; Frey, E C; LaCroix, K J; Lalush, D S; McCartney, W H; King, M A; Gullberg, G T

    1998-01-01

    In recent years, there has been much interest in the clinical application of attenuation compensation to myocardial perfusion single photon emission computed tomography (SPECT) with the promise that accurate quantitative images can be obtained to improve clinical diagnoses. The different attenuation compensation methods that are available create confusion and some misconceptions. Also, attenuation-compensated images reveal other image-degrading effects including collimator-detector blurring and scatter that are not apparent in uncompensated images. This article presents basic concepts of the major factors that degrade the quality and quantitative accuracy of myocardial perfusion SPECT images, and includes a discussion of the various image reconstruction and compensation methods and misconceptions and pitfalls in implementation. The differences between the various compensation methods and their performance are demonstrated. Particular emphasis is directed to an approach that promises to provide quantitative myocardial perfusion SPECT images by accurately compensating for the 3-dimensional (3-D) attenuation, collimator-detector response, and scatter effects. With advances in the computer hardware and optimized implementation techniques, quantitatively accurate and high-quality myocardial perfusion SPECT images can be obtained in clinically acceptable processing time. Examples from simulation, phantom, and patient studies are used to demonstrate the various aspects of the investigation. We conclude that quantitative myocardial perfusion SPECT, which holds great promise to improve clinical diagnosis, is an achievable goal in the near future.

  5. Formation of binucleated myocardial cells in the neonatal rat. An index for growth hypertrophy.

    PubMed

    Clubb, F J; Bishop, S P

    1984-05-01

    The purposes of this study were to characterize myocardial cell growth in neonatal rats and investigate the mechanism of binucleation in myocardial cells. To test the hypothesis that binucleated myocardial cells result from karyokinesis without cytokinesis, experiments were designed to measure the rate of DNA synthesis and the percentage of binucleated myocardial cells in neonatal rats during growth. Estimates of myocardial cell nuclear divisions were obtained from rats pulsed with tritiated thymidine at 17 days of gestation. Autoradiograms were prepared from isolated myocardial cells of rats killed at various ages postpartum, and the number of developed silver halide grains over myocardial cell nuclei was calculated. This estimated the mitotic activity of nuclei. To determine myocardial cell DNA synthesis postpartum, another set of rats were injected at various time periods with 4 hourly doses of tritiated thymidine, and hearts were fixed by perfusion 1 hour later. Labeling index of myocardial cells was calculated (labeled/total myocardial cells) from autoradiograms prepared on 1 micron thick, methacrylate-embedded heart cross-sections. Results of this study indicated that the growth of myocardial cells in the neonatal period can be divided into three phases: (a) a hyperplastic phase, (b) a transitional phase, and (c) a hypertrophic phase. Binucleation of myocardial cells was not due to fusion of mononucleated cells, because there was continued DNA synthesis in the neonatal hearts, reflected by continued incorporation of tritiated thymidine; in addition, the grain counts per nucleus of the binucleated myocardial cells were half that of mononucleated cells; nor was binucleation due to amitotic splitting of single nuclei, since binucleated myocardial cells had similar grain counts over each nucleus. We conclude that the formation of binucleated myocardial cells is an early indicator of growth hypertrophy in the neonatal rat and a result of mitosis without

  6. Myocardial Lineage Development

    PubMed Central

    Evans, Sylvia M.; Yelon, Deborah; Conlon, Frank L.; Kirby, Margaret L.

    2010-01-01

    The myocardium of the heart is composed of multiple highly specialized myocardial lineages, including those of the ventricular and atrial myocardium, and the specialized conduction system. Specification and maturation of each of these lineages during heart development is a highly ordered, ongoing process involving multiple signaling pathways and their intersection with transcriptional regulatory networks. Here, we attempt to summarize and compare much of what we know about specification and maturation of myocardial lineages from studies in several different vertebrate model systems. To date, most research has focused on early specification, and while there is still more to learn, less is known about factors that promote subsequent maturation of myocardial lineages required to build the functioning adult heart. PMID:21148449

  7. Compensatory mechanisms for cardiac dysfunction in myocardial infarction.

    PubMed

    Ertl, G; Gaudron, P; Eilles, C; Schorb, W; Kochsiek, K

    1991-01-01

    Loss of contractile myocardial tissue by myocardial infarction would result in depressed cardiac output if compensatory mechanisms would not be operative. Frank-Straub-Starling-mechanism and increased heart rate and contractility due to sympathetic stimulation are unlikely to chronically compensate for cardiac dysfunction. Structural left ventricular dilatation may be compensatory, but results in increased wall stress and, ultimately, in progressive dilatation and heart failure. In patients with myocardial infarction, we have shown left-ventricular dilatation in dependence of infarct size and time after infarction. Dilatation is compensatory first and normalizes stroke volume. However, left ventricular dilatation progresses without further hemodynamic profit and, thus, may participate in development of heart failure.

  8. Platelet activation and thrombus formation relates to the presence of myocardial inflammation in patients with cardiomyopathy.

    PubMed

    Bobbert, Peter; Weikert, Ulf; Schmidt-Lucke, Caroline; Skurk, Carsten; Meyer, Alexander; Steffens, Daniel; Schultheiss, Heinz Peter; Rauch, Ursula

    2014-05-01

    Patients with cardiomyopathy show a significantly increased risk for thromboembolic events due to a hypercoagulable state and platelet dysfunction. The pathophysiologic mechanism underlying the increasing platelet activity in patients with cardiomyopathy remains unclear. We performed a clinical study to elucidate the link between myocardial tissue alterations and platelet activation in patients with cardiomyopathy. A total of 30 patients with suspected cardiomyopathy and 10 healthy control patients were included in our study. Hemodynamic parameters were measured by catheterization and echocardiography. Endomyocardial biopsies were taken to determine myocardial inflammation. Flow cytometry was performed to examine the platelet activation by quantification of p-selectin and thrombospondin expression on platelets. The p-selectin (8.46 ± 3.67 AU) and thrombospondin (26.56 ± 23.21 AU) expression was significantly correlated with the amount of CD3+ T cells (p-selectin: r=0.573, p<0.05; thrombospondin: r=0.488, p<0.05) and the endothelial/interstitial activation (p-selectin: r=0.521, p<0.05; thrombospondin: r=0.39, p<0.05). This was found to be independent of hemodynamic parameters, age, and gender. The platelet activation of patients (n=3) with echocardiographically documented ventricular thrombi was significantly increased (p-selectin: 12.57 ± 5.5 AU vs. 8.1 ± 3.2 AU, p<0.05) and this was associated with elevated myocardial inflammation scores. Myocardial inflammation is associated with a significant increase in platelet activation and ventricular thrombus formation independently of the hemodynamic conditions. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  9. Inhalation of decomposed chlorodifluoromethane (freon-22) and myocardial infarction.

    PubMed

    Sjögren, Bengt; Gunnare, Sara; Sandler, Håkan

    2002-06-01

    After exposure to decomposed chlorodifluoromethane (freon-22), a 65-year-old man developed respiratory symptoms such as cough, blood-stained sputum, and increasing dyspnea. Three weeks later, his family doctor diagnosed infectious bronchitis. Another week later he died due to myocardial infarction. The discussion focuses on an inflammatory process caused by the inhalation of decomposed freon and its possible association with myocardial infarction.

  10. [Indications for percutaneous myocardial revascularization].

    PubMed

    Sganzerla, Paolo; Centonze, Fabrizio; Tavasci, Emanuela

    2012-10-01

    Indications and timing of myocardial revascularization procedures are discussed based on the case of a 78-year-old woman suffering from effort angina due to three-vessel coronary artery disease with normal left ventricular function. At present, atherosclerotic patients have a relatively long history of their disease, so that physicians should organize therapeutic strategies resulting from a right trade-off between guidelines of international scientific societies and the peculiar clinical requirements of the individual patient in the particular stage of his/her disease. This kind of tailored therapy may result from a multidisciplinary approach (heart team), which should involve many specialists as comorbidities and frailty of the patients are numerous and significant.

  11. Myocardial perfusion and left ventricular function indices assessed by gated myocardial perfusion SPECT in methamphetamine abusers.

    PubMed

    Dadpour, Bita; Dabbagh Kakhki, Vahid R; Afshari, Reza; Dorri-Giv, Masoumeh; Mohajeri, Seyed A R; Ghahremani, Somayeh

    2016-12-01

    Methamphetamine (MA) is associated with alterations of cardiac structure and function, although it is less known. In this study, we assessed possible abnormality in myocardial perfusion and left ventricular function using gated myocardial perfusion SPECT. Fifteen patients with MA abuse, on the basis of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) MA dependency determined by Structured Clinical Interview for DSM-IV, underwent 2-day dipyridamole stress/rest Tc-sestamibi gated myocardial perfusion SPECT. An average daily dose of MA use was 0.91±1.1 (0.2-4) g. The duration of MA use was 3.4±2.1 (1-7) years. In visual and semiquantitative analyses, all patients had normal gated myocardial perfusion SPECT, with no perfusion defects. In all gated SPECT images, there was no abnormality in left ventricular wall motion and thickening. All summed stress scores and summed rest scores were below 3. Calculated left ventricular functional indices including the end-diastolic volume, end-systolic volume, and left ventricular ejection fraction were normal. Many cardiac findings because of MA mentioned in previous reports are less likely because of significant epicardial coronary artery stenosis.

  12. [Percutaneous myocardial laser revascularization (PMR)].

    PubMed

    Lauer, B; Stahl, F; Bratanow, S; Schuler, G

    2000-09-01

    In patients with severe angina pectoris due to coronary artery disease, who are not candidates for either percutaneous coronary angioplasty or coronary artery bypass surgery, transmyocardial laser revascularization (TMR) often leads to improvement of clinical symptoms and increased exercise capacity. One drawback of TMR is the need for surgical thoracotomy in order to gain access to the epicardial surface of the heart. Therefore, a catheter-based system has been developed, which allows creation of laser channels into the myocardium from the left ventricular cavity. Between January 1997 and November 1999, this "percutaneous myocardial laser revascularization" (PMR) has been performed in 101 patients at the Herzzentrum Leipzig. In 63 patients, only 1 region of the heart (anterior, lateral, inferior or septal) was treated with PMR, in 38 patients 2 or 3 regions were treated in 1 session. There were 12.3 +/- 4.5 (range 4 to 22) channels/region created into the myocardium. After 3 months, the majority of patients reported significant improvement of clinical symptoms (CCS class at baseline: 3.3 +/- 0.4, after 6 months: 1.6 +/- 0.8) (p < 0.001) and an increased exercise capacity (baseline: 397 +/- 125 s, after 6 months: 540 +/- 190 s) (p < 0.05). After 2 years, the majority of patients had experienced sustained clinical benefit after PMR, the CCS class after 2 years was 1.3 +/- 0.7, exercise capacity was 500 +/- 193 s. However, thallium scintigraphy failed to show increased perfusion in the PMR treated regions. The pathophysiologic mechanisms of myocardial laser revascularization is not yet understood. Most of the laser channels are found occluded after various time intervals after intervention. Other possible mechanisms include myocardial denervation or angioneogenesis after laser revascularization, however, unequivocal evidence for these theories is not yet available. In conclusion, PMR seems to be a safe and feasible new therapeutic option for patients with refractory

  13. Steroid-induced recurrent myocardial ischemia.

    PubMed

    Yildirim, Ufuk; Gulel, Okan; Soylu, Korhan; Yuksel, Serkan; Sahin, Mahmut

    2014-01-01

    We report the case of a female patient under oral prednisolone therapy due to a diagnosis of idiopathic intracranial hypertension with papilledema. Unfortunately, short-term treatment with prednisolone caused an unusual complication in the patient, i.e., recurrent myocardial ischemia. Possible mechanisms leading to this complication were evaluated in the light of current knowledge. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  14. Perioperative Assessment of Myocardial Deformation

    PubMed Central

    Duncan, Andra E.; Alfirevic, Andrej; Sessler, Daniel I.; Popovic, Zoran B.; Thomas, James D.

    2014-01-01

    Evaluation of left ventricular performance improves risk assessment and guides anesthetic decisions. However, the most common echocardiographic measure of myocardial function, the left ventricular ejection fraction (LVEF), has important limitations. LVEF is limited by subjective interpretation which reduces accuracy and reproducibility, and LVEF assesses global function without characterizing regional myocardial abnormalities. An alternative objective echocardiographic measure of myocardial function is thus needed. Myocardial deformation analysis, which performs quantitative assessment of global and regional myocardial function, may be useful for perioperative care of surgical patients. Myocardial deformation analysis evaluates left ventricular mechanics by quantifying strain and strain rate. Strain describes percent change in myocardial length in the longitudinal (from base to apex) and circumferential (encircling the short-axis of the ventricle) direction and change in thickness in the radial direction. Segmental strain describes regional myocardial function. Strain is a negative number when the ventricle shortens longitudinally or circumferentially and is positive with radial thickening. Reference values for normal longitudinal strain from a recent meta-analysis using transthoracic echocardiography are (mean ± SD) −19.7 ± 0.4%, while radial and circumferential strain are 47.3 ± 1.9 and −23.3 ± 0.7%, respectively. The speed of myocardial deformation is also important and is characterized by strain rate. Longitudinal systolic strain rate in healthy subjects averages −1.10 ± 0.16 sec−1. Assessment of myocardial deformation requires consideration of both strain (change in deformation), which correlates with LVEF, and strain rate (speed of deformation), which correlates with rate of rise of left ventricular pressure (dP/dt). Myocardial deformation analysis also evaluates ventricular relaxation, twist, and untwist, providing new and noninvasive methods to

  15. Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis

    PubMed Central

    Maya, Lisandro; Villarreal, Francisco J.

    2009-01-01

    In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies is termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, it is imperative the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies. Currently, there is no single diagnostic method for the identification of diabetic cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition. Early changes in cardiac function are typically manifested as abnormal diastolic function that with time leads to loss of contractile function. Echocardiography based methods currently stands as the preferred diagnostic approach for diabetic cardiomyopathy, due to its wide availability and economical use. In addition to conventional techniques, magnetic resonance imaging and spectroscopy along with contrast agents are now leading new approaches in the diagnosis of myocardial fibrosis, and cardiac and hepatic metabolic changes. These strategies can be complemented with serum biomarkers so they can offer a clear picture as to diabetes-induced changes in cardiac structure/function even at very early stages of the disease. This review article intends to provide a summary of experimental and routine tools currently available to diagnose diabetic cardiomyopathy induced changes in cardiac structure/function. These tools can be reliably used in either experimental models of diabetes or for clinical applications. PMID:19595694

  16. Idiopathic massive myocardial calcification: a case report and review of the literature.

    PubMed

    Shackley, Brit S; Nguyen, Thao P; Shivkumar, Kalyanam; Finn, Paul J; Fishbein, Michael C

    2011-01-01

    We report a rare case of massive myocardial calcification in a 42-year-old male who presented with symptoms of congestive heart failure and arrhythmia. Myocardial calcification is most commonly associated with myocardial infarction or, less commonly, hypercalcemia. This case is particularly unusual due to the lack of any known predisposing risk factors, including normal coronary arteries, normal renal function, and normal serum calcium levels. Alternative etiologies are discussed accompanied by a review of the literature.

  17. Litsea Deccanensis Ameliorates Myocardial Infarction in Wistar Rats: Evidence from Biochemical and Histological Studies

    PubMed Central

    Kumar, Bharath P; Kannan, Mari M; Quine, Darlin S

    2011-01-01

    The present study was designed to evaluate the cardioprotective effects of methanolic extract of Litsea deccanensis (MELD) against isoproterenol-induced myocardial infarction in rats by studying cardiac markers, lipid peroxidation, lipid profile, and histological changes. Male Wistar rats were treated orally with MELD (100 and 200 mg/kg) daily for a period of 21 days. After 21 days of pretreatment, isoproterenol (100 mg/kg) was injected subcutaneously to rats at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol-induced rats showed significant (P < 0.05) increase in the levels of serum creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances, and lipid hydro peroxides. The serum lipid levels were altered in the isoproterenol-induced myocardial infarcted rats. The histopathological findings of the myocardial tissue evidenced myocardial damage in isoproterenol-induced rats. The oral pretreatment with MELD restored the pathological alterations in the isoproterenol-induced myocardial infarcted rats. The MELD pretreatment significantly reduced the levels of biochemical markers, lipid peroxidation and regulated the lipid profile of the antioxidant system in the isoproterenol-induced rats. An inhibited myocardial necrosis was evidenced by the histopathological findings in MELD pretreated isoproterenol-induced rats. Our study shows that oral pretreatment with MELD prevents isoproterenol-induced oxidative stress in myocardial infarction. The presence of phenolic acid and flavonoid contents were confirmed by preliminary phytochemical tests. The reducing power and free radical scavenging activities of the MELD may be the possible reason for it pharmacological actions. PMID:22224035

  18. Litsea deccanensis ameliorates myocardial infarction in wistar rats: evidence from biochemical and histological studies.

    PubMed

    Kumar, Bharath P; Kannan, Mari M; Quine, Darlin S

    2011-10-01

    The present study was designed to evaluate the cardioprotective effects of methanolic extract of Litsea deccanensis (MELD) against isoproterenol-induced myocardial infarction in rats by studying cardiac markers, lipid peroxidation, lipid profile, and histological changes. Male Wistar rats were treated orally with MELD (100 and 200 mg/kg) daily for a period of 21 days. After 21 days of pretreatment, isoproterenol (100 mg/kg) was injected subcutaneously to rats at an interval of 24 h for 2 days to induce myocardial infarction. Isoproterenol-induced rats showed significant (P < 0.05) increase in the levels of serum creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances, and lipid hydro peroxides. The serum lipid levels were altered in the isoproterenol-induced myocardial infarcted rats. The histopathological findings of the myocardial tissue evidenced myocardial damage in isoproterenol-induced rats. The oral pretreatment with MELD restored the pathological alterations in the isoproterenol-induced myocardial infarcted rats. The MELD pretreatment significantly reduced the levels of biochemical markers, lipid peroxidation and regulated the lipid profile of the antioxidant system in the isoproterenol-induced rats. An inhibited myocardial necrosis was evidenced by the histopathological findings in MELD pretreated isoproterenol-induced rats. Our study shows that oral pretreatment with MELD prevents isoproterenol-induced oxidative stress in myocardial infarction. The presence of phenolic acid and flavonoid contents were confirmed by preliminary phytochemical tests. The reducing power and free radical scavenging activities of the MELD may be the possible reason for it pharmacological actions.

  19. Contractile analysis with kriging based on MR myocardial velocity imaging.

    PubMed

    Lee, Su-Lin; Huntbatch, Andrew; Yang, Guang-Zhong

    2008-01-01

    Diagnosis and treatment of coronary artery disease requires a full understanding of the intrinsic contractile mechanics of the heart. MR myocardial velocity imaging is a promising technique for revealing intramural cardiac motion but its ability to depict 3D strain tensor distribution is constrained by anisotropic voxel coverage of velocity imaging due to limited imaging slices and the achievable SNR in patient studies. This paper introduces a novel Kriging estimator for simultaneously improving the tracking and dense inter-slice estimation of the myocardial velocity data. A harmonic embedding technique is employed to determine point correspondence between left ventricle models between subjects, allowing for a statistical shape model to be reconstructed. The use of different semivariograms is investigated for optimal deformation reconstruction. Results from in vivo data demonstrate a marked improvement in tracking myocardial deformation, thus enhancing the potential clinical value of MR myocardial velocity imaging.

  20. Acute myocardial infarction and sudden death in Sioux Indians.

    PubMed

    Hrabovsky, S L; Welty, T K; Coulehan, J L

    1989-04-01

    While some Indian tribes have low rates of acute myocardial infarction, Northern Plains Indians, including the Sioux, have rates of morbidity and mortality from acute myocardial infarction higher than those reported for the United States population in general. In a review of diagnosed cases of acute myocardial infarction over a 3-year period in 2 hospitals serving predominantly Sioux Indians, 8% of cases were found misclassified, and 22% failed to meet rigorous diagnostic criteria, although the patients did indeed have ischemic heart disease. Patients had high frequencies of complications and risk factors and a fatality rate of 16% within a month of admission. Sudden deaths likely due to ischemic heart disease but in persons not diagnosed as having acute myocardial infarction by chart review occurred 3 times more frequently than deaths occurring within a month of clinical diagnosis.

  1. The Influence of Diabetes Mellitus in Myocardial Ischemic Preconditioning.

    PubMed

    Rezende, Paulo Cury; Rahmi, Rosa Maria; Hueb, Whady

    Ischemic preconditioning (IP) is a powerful mechanism of protection discovered in the heart in which ischemia paradoxically protects the myocardium against other ischemic insults. Many factors such as diseases and medications may influence IP expression. Although diabetes poses higher cardiovascular risk, the physiopathology underlying this condition is uncertain. Moreover, although diabetes is believed to alter intracellular pathways related to myocardial protective mechanisms, it is still controversial whether diabetes may interfere with ischemic preconditioning and whether this might influence clinical outcomes. This review article looks at published reports with animal models and humans that tried to evaluate the possible influence of diabetes in myocardial ischemic preconditioning.

  2. Acute myocardial infarction.

    PubMed

    Boersma, Eric; Mercado, Nestor; Poldermans, Don; Gardien, Martin; Vos, Jeroen; Simoons, Maarten L

    2003-03-08

    Acute myocardial infarction is a common disease with serious consequences in mortality, morbidity, and cost to the society. Coronary atherosclerosis plays a pivotal part as the underlying substrate in many patients. In addition, a new definition of myocardial infarction has recently been introduced that has major implications from the epidemiological, societal, and patient points of view. The advent of coronary-care units and the results of randomised clinical trials on reperfusion therapy, lytic or percutaneous coronary intervention, and chronic medical treatment with various pharmacological agents have substantially changed the therapeutic approach, decreased in-hospital mortality, and improved the long-term outlook in survivors of the acute phase. New treatments will continue to emerge, but the greatest challenge will be to effectively implement preventive actions in all high-risk individuals and to expand delivery of acute treatment in a timely fashion for all eligible patients.

  3. Myocardial gene therapy

    NASA Astrophysics Data System (ADS)

    Isner, Jeffrey M.

    2002-01-01

    Gene therapy is proving likely to be a viable alternative to conventional therapies in coronary artery disease and heart failure. Phase 1 clinical trials indicate high levels of safety and clinical benefits with gene therapy using angiogenic growth factors in myocardial ischaemia. Although gene therapy for heart failure is still at the pre-clinical stage, experimental data indicate that therapeutic angiogenesis using short-term gene expression may elicit functional improvement in affected individuals.

  4. Vitexin exerts cardioprotective effect on chronic myocardial ischemia/reperfusion injury in rats via inhibiting myocardial apoptosis and lipid peroxidation

    PubMed Central

    Che, Xia; Wang, Xin; Zhang, Junyan; Peng, Chengfeng; Zhen, Yilan; Shao, Xu; Zhang, Gongliang; Dong, Liuyi

    2016-01-01

    Purpose: The aim of this study was to explore the cardioprotective effect of vitexin on chronic myocardial ischemia/reperfusion injury in rats and potential mechanisms. Methods: A chronic myocardial ischemia/reperfusion injury model was established by ligating left anterior descending coronary for 60 minutes, and followed by reperfusion for 14 days. After 2 weeks ischemia/reperfusion, cardiac function was measured to assess myocardial injury. The level of ST segment was recorded in different periods by electrocardiograph. The change of left ventricular function and myocardial reaction degree of fibrosis of heart was investigated by hematoxylin and eosin (HE) staining and Sirius red staining. Endothelium-dependent relaxations due to acetylcholine were observed in isolated rat thoracic aortic ring preparation. The blood samples were collected to measure the levels of MDA, the activities of SOD and NADPH in serum. Epac1, Rap1, Bax and Bcl-2 were examined by using Western Blotting. Results: Vitexin exerted significant protective effect on chronic myocardial ischemia/reperfusion injury, improved obviously left ventricular diastolic function and reduced myocardial reactive fibrosis degree in rats of myocardial ischemia. Medium and high-dose vitexin groups presented a significant decrease in Bax, Epac1 and Rap1 production and increase in Bcl-2 compared to the I/R group. It may be related to preventing myocardial cells from apoptosis, improving myocardial diastolic function and inhibiting lipid peroxidation. Conclusions: Vitexin is a cardioprotective herb, which may be a promising useful complementary and alternative medicine for patients with coronary heart disease. PMID:27648122

  5. Myocardial injury due to lightning strike--a case report.

    PubMed

    Alyan, Omer; Ozdemir, Ozcan; Tufekcioglu, Omaç; Geyik, Bilal; Aras, Dursun; Demirkan, Deniz

    2006-01-01

    Lightning strike is a natural phenomenon with potentially devastating effects and represents one of the leading causes of cardiac arrest and death from environmental phenomena. Almost every organ system may be impaired as lightning passes through the human body taking the shortest pathways between the contact points. In this paper, the authors report a 38-year-old man who was injured by lightning, a typical example of ;;side splash,'' and had transient electrocardiographic changes.

  6. Effect of NO synthase inhibition on myocardial metabolism during moderate ischemia.

    PubMed

    Martin, Claus; Schulz, Rainer; Post, Heiner; Gres, Petra; Heusch, Gerd

    2003-06-01

    Nitric oxide (NO) is involved in the control of myocardial metabolism. In normoperfused myocardium, NO synthase inhibition shifts myocardial metabolism from free fatty acid (FFA) toward carbohydrate utilization. Ischemic myocardium is characterized by a similar shift toward preferential carbohydrate utilization, although NO synthesis is increased. The importance of NO for myocardial metabolism during ischemia has not been analyzed in detail. We therefore assessed the influence of NO synthase inhibition with N(G)-nitro-l-arginine (l-NNA) on myocardial metabolism during moderate ischemia in anesthetized pigs. In control animals, the increase in left ventricular pressure with l-NNA was mimicked by aortic constriction. Before ischemia, l-NNA decreased myocardial FFA consumption (MV(FFA); P < 0.05), while consumption of carbohydrate and O(2) (MVo(2)) remained constant. ATP equivalents [calculated with the assumption of complete oxidative substrate decomposition (ATP(eq))] decreased with l-NNA (P < 0.05), associated with a decrease of regional myocardial function (P < 0.05). In contrast, aortic constriction had no effect on MV(FFA), while MVo(2) increased (P < 0.05) and ATP(eq) and regional myocardial function remained constant. During ischemia, alterations in myocardial metabolism were similar in control and l-NNA-treated animals: MV(FFA) decreased (P < 0.05) and net lactate consumption was reversed to net lactate production (P < 0.05). Regional myocardial function was decreased (P < 0.05), although more markedly in animals receiving l-NNA (P < 0.05). We conclude that the efficiency of oxidative metabolism was impaired by l-NNA per se, paralleled by impaired regional myocardial function. During ischemia, l-NNA had no effect on myocardial substrate consumption, indicating that NO synthases were no longer effectively involved in the control of myocardial metabolism.

  7. Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis.

    PubMed

    Tuo, Qin-Hui; Zeng, Heng; Stinnett, Amanda; Yu, Heidi; Aschner, Judy L; Liao, Daun-Fang; Chen, Jian-Xiong

    2008-06-01

    Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are the two ligands of the Tie-2 receptor, a receptor tyrosine kinase that is expressed on the endothelium. A balanced angiopoietin/Tie-2 system is critical for the maintenance of vascular integrity. We investigated the potential role of a disrupted angiopoietin/Tie-2 system on hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Using streptozotocin (STZ) mice subjected to myocardial ischemia, we examined the effects of shifting the Ang-2-to-Ang-1 ratio on myocardial infarction size, apoptosis, bone marrow (BM) cell-endothelial progenitor cell (EPC) differentiation, and angiogenesis. In control mice, myocardial ischemia increased expression of both Ang-2 and Tie-2. In STZ mice, Ang-2 expression was elevated, whereas Tie-2 expression was reduced, and neither was significantly altered by ischemia. Myocardial infarct size and apoptosis were increased in STZ compared with control mice. Using in vivo administration of an adenovirus containing Ang-1 or Ang-2, we found that shifting the Ang-2-to-Ang-1 ratio to favor Ang-1 reduced myocardial apoptosis and infarct size in STZ mice, while shifting the Ang-2-to-Ang-1 ratio to favor Ang-2 resulted in a significant increase in myocardial infarct size and apoptosis in control mice. Myocardial ischemia-stimulated BM cell-EPC differentiation was inhibited and myocardial angiogenesis was reduced in STZ mice. Systemic administration of Ad-Ang-1 restored BM cell-EPC differentiation and increased myocardial VEGF expression and angiogenesis in STZ mice. Our data demonstrate that disturbed angiopoietin/Tie-2 signaling contributes to the hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis. Restoration of the Ang-2-to-Ang-1 ratio may be a novel therapeutic strategy for the treatment of diabetic myocardial ischemic diseases.

  8. Myocardial fibrosis in an veteran endurance athlete

    PubMed Central

    Wilson, Mathew; O'Hanlon, Rory; Prasad, Sanjay; Basavarajaiah, Sandeep; Stephens, Nigel; Senior, Roxy; Shaw, Anthony; Sharma, Sanjay; Whyte, Gregory

    2009-01-01

    This study reports the cardiac structure and function of a lifelong male endurance athlete, who has run over 148 000 miles, who presented with symptoms of chest discomfort, dyspnoea and loss of competitive running performance. Importantly, the athlete documented several periods of regular intensive endurance activity while suffering with flu-like symptoms. Cardiovascular MRI demonstrated a pattern of late gadolinium enhancement, which indicated myocardial scarring as a result of previous myocarditis. Myocarditis is a non-ischaemic inflammatory disease of the myocardium associated with cardiac dysfunction and arrhythmogenic substrate. The clinical course of viral myocarditis is mostly insidious with limited cardiac inflammation and dysfunction. However, as in the present case, overwhelming inflammation may occur in a subset of patients leading to myocardial fibrosis due to recurrent inflammation. PMID:21847425

  9. Myocardial tissue engineering using electrospun nanofiber composites.

    PubMed

    Kim, Pyung-Hwan; Cho, Je-Yoel

    2016-01-01

    Emerging trends for cardiac tissue engineering are focused on increasing the biocompatibility and tissue regeneration ability of artificial heart tissue by incorporating various cell sources and bioactive molecules. Although primary cardiomyocytes can be successfully implanted, clinical applications are restricted due to their low survival rates and poor proliferation. To develop successful cardiovascular tissue regeneration systems, new technologies must be introduced to improve myocardial regeneration. Electrospinning is a simple, versatile technique for fabricating nanofibers. Here, we discuss various biodegradable polymers (natural, synthetic, and combinatorial polymers) that can be used for fiber fabrication. We also describe a series of fiber modification methods that can increase cell survival, proliferation, and migration and provide supporting mechanical properties by mimicking micro-environment structures, such as the extracellular matrix (ECM). In addition, the applications and types of nanofiber-based scaffolds for myocardial regeneration are described. Finally, fusion research methods combined with stem cells and scaffolds to improve biocompatibility are discussed.

  10. Perioperative myocardial infarction in patients undergoing myocardial revascularization surgery

    PubMed Central

    Pretto, Pericles; Martins, Gerez Fernandes; Biscaro, Andressa; Kruczan, Dany David; Jessen, Barbara

    2015-01-01

    Introduction Perioperative myocardial infarction adversely affects the prognosis of patients undergoing coronary artery bypass graft and its diagnosis was hampered by numerous difficulties, because the pathophysiology is different from the traditional instability atherosclerotic and the clinical difficulty to be characterized. Objective To identify the frequency of perioperative myocardial infarction and its outcome in patients undergoing coronary artery bypass graft. Methods Retrospective cohort study performed in a tertiary hospital specialized in cardiology, from May 01, 2011 to April 30, 2012, which included all records containing coronary artery bypass graft records. To confirm the diagnosis of perioperative myocardial infarction criteria, the Third Universal Definition of Myocardial Infarction was used. Results We analyzed 116 cases. Perioperative myocardial infarction was diagnosed in 28 patients (24.1%). Number of grafts and use and cardiopulmonary bypass time were associated with this diagnosis and the mean age was significantly higher in this group. The diagnostic criteria elevated troponin I, which was positive in 99.1% of cases regardless of diagnosis of perioperative myocardial infarction. No significant difference was found between length of hospital stay and intensive care unit in patients with and without this complication, however patients with perioperative myocardial infarction progressed with worse left ventricular function and more death cases. Conclusion The frequency of perioperative myocardial infarction found in this study was considered high and as a consequence the same observed average higher troponin I, more cases of worsening left ventricular function and death. PMID:25859867

  11. Myocardial infarction - a rare complication in Henoch-Schönlein purpura.

    PubMed Central

    Abdel-Hadi, O.; Greenstone, M. A.; Hartley, R. B.; Kidner, P. H.

    1981-01-01

    A 29-year-old man with previous Henoch-Schönlein disease presented with multiple systemic emboli and a myocardial infarction. Subsequent investigation by angiography showed normal coronary arteries. This appears to be the first reported case of Henoch-Schönlein disease and myocardial infarction probably due to coronary vasculitis. Images Fig. 1 PMID:7301688

  12. Left ventricular remodeling after experimental myocardial cryoinjury in rats.

    PubMed

    Ciulla, Michele M; Paliotti, Roberta; Ferrero, Stefano; Braidotti, Paola; Esposito, Arturo; Gianelli, Umberto; Busca, Giuseppe; Cioffi, Ugo; Bulfamante, Gaetano; Magrini, Fabio

    2004-01-01

    The standard coronary ligation, the most studied model of experimental myocardial infarction in rats, is limited by high mortality and produces unpredictable areas of necrosis. To standardize the location and size of the infarct and to elucidate the mechanisms of myocardial remodeling and its progression to heart failure, we studied the functional, structural, and ultrastructural changes of myocardial infarction produced by experimental myocardial cryoinjury. The cryoinjury was successful in 24 (80%) of 30 male adult CD rats. A subepicardial infarct was documented on echocardiograms, with an average size of about 21%. Macroscopic examination reflected closely the stamp of the instrument used, without transition zones to viable myocardium. Histological examination, during the acute setting, revealed an extensive area of coagulation necrosis and hemorrhage in the subepicardium. An inflammatory infiltrate was evident since the 7th hour, whereas the reparative phase started within the first week, with proliferation of fibroblasts, endothelial cells, and myocytes. From the 7th day, deposition of collagen fibers was reported with a reparative scar completed at the 30th day. Ultrastructural study revealed vascular capillary damage and irreversible alterations of the myocytes in the acute setting and confirmed the histological findings of the later phases. The damage was associated with a progressive left ventricular (LV) remodeling, including thinning of the infarcted area, hypertrophy of the noninfarcted myocardium, and significant LV dilation. This process started from the 60th day and progressed over the subsequent 120 days period; at 180 days, a significant increase in LV filling pressure, indicative of heart failure, was found. In conclusion, myocardial cryodamage, although different in respect to ischemic damage, causes a standardized injury reproducing the cellular patterns of coagulation necrosis, early microvascular reperfusion, hemorrhage, inflammation

  13. Heroin-associated myocardial damages--conventional and immunohistochemical investigations.

    PubMed

    Dettmeyer, R; Friedrich, K; Schmidt, P; Madea, B

    2009-05-30

    Well-known complications related to drug abuse are myocardial insufficiency, myocardial infarction, endocarditis, myocarditis, aortic dissection, neurologic damages, ischemic colitis, thrombotic phenomenons, renal infarction and acute liver failure. Furthermore, microfocal fibrosis of the myocardium is found in stimulant abuse. The origin of myocardial fibrosis associated with opiate abuse (endocarditis, myocarditis, embolism) is still unclear. This question shall be investigated using immunohistochemical staining for early diagnosis of myocarditis. A quantification of myocardial interstitial leucocytic infiltrates was accomplished in 21 chronic drug abusers who died of heroin/morphine intoxication and compared to 15 normal subjects who died suddenly due to non-cardiac causes of death without intoxication (e.g. traffic accidents, head trauma). Toxicological investigations were performed and in addition, blood samples were checked to clarify the status of HIV, hepatitis A, B and C in both groups. To verify signs of inflammation, myocardial specimen from different locations were investigated with conventional histological stainings and immunohistochemical techniques for characterization and quantification of interstitial myocardial leucocytes, T-lymphocytes and macrophages. The number of cells were found up to fivefold increased in heroin addicts compared to the control group without reaching the cut-off values for immunohistochemically based diagnosis of myocarditis.

  14. Stochastic modeling for magnetic resonance quantification of myocardial blood flow

    NASA Astrophysics Data System (ADS)

    Seethamraju, Ravi T.; Muehling, Olaf; Panse, Prasad M.; Wilke, Norbert M.; Jerosch-Herold, Michael

    2000-10-01

    Quantification of myocardial blood flow is useful for determining the functional severity of coronary artery lesions. With advances in MR imaging it has become possible to assess myocardial perfusion and blood flow in a non-invasive manner by rapid serial imaging following injection of contrast agent. To date most approaches reported in the literature relied mostly on deriving relative indices of myocardial perfusion directly from the measured signal intensity curves. The central volume principle on the other hand states that it is possible to derive absolute myocardial blood flow from the tissue impulse response. Because of the sensitivity involved in deconvolution due to noise in measured data, conventional methods are sub-optimal, hence, we propose to use stochastic time series modeling techniques like ARMA to obtain a robust impulse response estimate. It is shown that these methods when applied for the optical estimation of the transfer function give accurate estimates of myocardial blood flow. The most significant advantage of this approach, compared with compartmental tracer kinetic models, is the use of a minimum set of prior assumptions on data. The bottleneck in assessing myocardial blood flow, does not lie in the MRI acquisition, but rather in the effort or time for post processing. It is anticipated that the very limited requirements for user input and interaction will be of significant advantage for the clinical application of these methods. The proposed methods are validated by comparison with mean blood flow measurements obtained from radio-isotope labeled microspheres.

  15. Stem cell therapy for the treatment of myocardial infarction.

    PubMed

    Dauwe, D F; Janssens, S P

    2011-10-01

    Despite timely reperfusion and subsequent optimal postinfarct pharmacotherapy and device-based treatment, the outcome in patients with severe myocardial infarction remains unfavourable. Myocardial salvage is incomplete, resulting in adverse left ventricular remodeling with concomitant morbidity and mortality. The combined risk of recurrent myocardial infarction, death or readmission for heart failure amounts to 25 % within the first year, highlighting the need for additional treatment strategies. Recent and rapidly evolving insights in cardiac biology, recognizing endogenous repair capabilities of the adult human heart, paved the path towards progenitor or stem cell based cardiac protection and repair strategies following ischemic injury. We critically report on the major randomized controlled clinical trials published so far concerning intracoronary transfer of autologous bone marrow cells in the setting of acute myocardial infarction. Moreover, underlying mechanisms, practical aspects, remaining questions and future challenges are highlighted. Taken together, these trials confirm the safety and feasibility of intracoronary progenitor cell transfer in the setting of myocardial infarction. Efficacy data suggests its potential to improve left ventricular function recovery beyond current state of the art therapy, but results are mixed, modest at best and do not support true cardiomyogenesis. Hence, due to its complexity, costs and remaining uncertainties, it is still too early to implement progenitor cell therapy in its current form in standard treatment strategies for ischemic heart disease. Future studies on strategies for cardiomyocyte regeneration in combination with myocardial protection are needed.

  16. Hearts deficient in both Mfn1 and Mfn2 are protected against acute myocardial infarction

    PubMed Central

    Hall, A R; Burke, N; Dongworth, R K; Kalkhoran, S B; Dyson, A; Vicencio, J M; Dorn II, G W; Yellon, D M; Hausenloy, D J

    2016-01-01

    Mitochondria alter their shape by undergoing cycles of fusion and fission. Changes in mitochondrial morphology impact on the cellular response to stress, and their interactions with other organelles such as the sarcoplasmic reticulum (SR). Inhibiting mitochondrial fission can protect the heart against acute ischemia/reperfusion (I/R) injury. However, the role of the mitochondrial fusion proteins, Mfn1 and Mfn2, in the response of the adult heart to acute I/R injury is not clear, and is investigated in this study. To determine the effect of combined Mfn1/Mfn2 ablation on the susceptibility to acute myocardial I/R injury, cardiac-specific ablation of both Mfn1 and Mfn2 (DKO) was initiated in mice aged 4–6 weeks, leading to knockout of both these proteins in 8–10-week-old animals. This resulted in fragmented mitochondria (electron microscopy), decreased mitochondrial respiratory function (respirometry), and impaired myocardial contractile function (echocardiography). In DKO mice subjected to in vivo regional myocardial ischemia (30 min) followed by 24 h reperfusion, myocardial infarct size (IS, expressed as a % of the area-at-risk) was reduced by 46% compared with wild-type (WT) hearts. In addition, mitochondria from DKO animals had decreased MPTP opening susceptibility (assessed by Ca2+-induced mitochondrial swelling), compared with WT hearts. Mfn2 is a key mediator of mitochondrial/SR tethering, and accordingly, the loss of Mfn2 in DKO hearts reduced the number of interactions measured between these organelles (quantified by proximal ligation assay), attenuated mitochondrial calcium overload (Rhod2 confocal microscopy), and decreased reactive oxygen species production (DCF confocal microscopy) in response to acute I/R injury. No differences in isolated mitochondrial ROS emissions (Amplex Red) were detected in response to Ca2+ and Antimycin A, further implicating disruption of mitochondria/SR tethering as the protective mechanism. In summary, despite apparent

  17. Myocardial revascularisation after acute myocardial infarction.

    PubMed

    Bana, A; Yadava, O P; Ghadiok, R; Selot, N

    1999-05-15

    One hundred and twenty-three patients had coronary artery bypass grafting (CABG) within 30 days of acute myocardial infarction (AMI) from May 1992 to November 1997. Commonest infarct was anterior transmural (61.8%) and commonest indication of surgery was post-infarct persistent or recurrent angina (69.1%). Ten patients were operated within 48 h and 36 between 48 h to 2 weeks of having MI. Out of these, nine patients were having infarct extension and cardiogenic shock at the time of surgery. Pre-operatively fourteen patients were on inotropes of which six also had intra-aortic balloon pump (IABP) support. All patients had complete revascularisation with 3.8+/-1.2 distal anastomoses per patient. By multivariate analysis, we found that independent predictors of post-operative morbidity [inotropes >48 h, use of IABP, ventilation >24 h, ICU stay >5 days] and complications [re-exploration, arrhythmias, pulmonary complications, wound infection, cerebrovascular accident (CVA)] were left ventricular ejection fraction (LVEF) <30%, Q-wave MI, surgery <48 h after AMI, presence of pre-operative cardiogenic shock and age >60 years (P < or = 0.01). Mortality at 30 days was 3.3%. LVEF <30%, Q-wave MI, surgery <48 h after AMI, presence of pre-operative cardiogenic shock and age >60 years were found to be independent predictors of 30 days mortality (P < or = 0.01). Ninety patients were followed up for a mean duration of 33 months (1 to 65 months). There were three late deaths and five patients developed recurrence of angina. To conclude, CABG can be carried out with low risk following AMI in stable patients for post-infarct angina. Patients who undergo urgent or emergent surgery and who have pre-operative cardiogenic shock, IABP, poor left ventricular functions, age >60 years and Q-wave MI are at increased risk.

  18. Dipyridamole thallium-201 myocardial scintigraphy

    SciTech Connect

    Not Available

    1988-09-01

    Thallium-201 (/sup 201/Tl) myocardial scintigraphy is a sensitive technique for detecting coronary artery disease. Standardized exercise testing is the most common method for inducing myocardial stress for /sup 201/Tl imaging. Unfortunately, a significant number of patients are unable to undergo adequate treadmill or bicycle exercise. In these patients, pharmacologic stress with dipyridamole provides a safe, efficacious, and reliable alternative.

  19. Diurnal variations in myocardial metabolism

    USDA-ARS?s Scientific Manuscript database

    The heart is challenged by a plethora of extracellular stimuli over the course of a normal day, each of which distinctly influences myocardial contractile function. It is therefore not surprising that myocardial metabolism also oscillates in a time-of-day dependent manner. What is becoming increasin...

  20. 2015 Sensorimotor Risk Standing Review Panel Evidence and Status Review For: the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight

    NASA Technical Reports Server (NTRS)

    Steinberg, Susan

    2015-01-01

    The 2015 Sensorimotor Risk Standing Review Panel (from here on referred to as the SRP) participated in a WebEx/teleconference with members of the Human Health Countermeasures (HHC) Element, representatives from the Human Research Program (HRP), NASA Headquarters, and NASA Research and Education Support Services (NRESS) on December 17, 2015 (list of participants is in Section VI of this report). The SRP reviewed the new Evidence Report for the Risk of Impaired Control of Spacecraft/Associated Systems and Decreased Mobility Due to Vestibular/Sensorimotor Alterations Associated with Spaceflight (from here on referred to as the 2015 Sensorimotor Evidence Report), and also received a status review of the Risk. The opening section of the 2015 Sensorimotor Evidence Report provides written descriptions of various incidents that have occurred during space missions. In most of these incidents, the main underlying contributing factors are not easy to identify unambiguously. For example, in section 1.9, a number of falls occurred while astronauts were walking on the moon. It is not clear to the SRP, however, why they fell. It is only possible to extrapolate from likely specific psychophysical or physiological abnormalities, but how these abnormalities were determined, and how they were directly responsible for the falls is unclear to the SRP. Section 2.1.2 on proprioception is very interesting, but the functional significance of the abnormalities detected is not clear. The SRP sees this as a problem throughout the report: a mapping between the component abnormalities identified and the holistic behaviors that are most relevant, for example, controlling the vehicle, and locomotion during egress, is generally lacking. The SRP thinks the cognitive section is too strongly focused on vestibular functioning. The SRP questions the notion that the main cognitive effects are mainly attributable to reversible vestibular changes induced by spaceflight. The SRP thinks that there can also

  1. Left ventricular hypertrophy: an initial response to myocardial injury.

    PubMed

    Francis, G S; McDonald, K M

    1992-06-04

    The prevailing wisdom generally has been that the failing heart hypertrophies in response to increased wall stress. The increase in myocardial mass observed in heart failure is therefore a relatively late compensatory event geared to normalize wall stress. Although this is undoubtedly true, especially for heart failure resulting from a large anterior myocardial infarction accompanied by rapid left ventricular expansion, it is possible that an important form of hypertrophy occurs much earlier as an initial response to myocardial injury. One can hypothesize that the initial response to injury is a nonspecific phenotypic alteration of the cardiac myocyte to one of growth and development. Such changes may be driven by both trophic and mechanical forces and may be important in altering the architecture of the myocardial cell and surrounding cardiac interstitium. Preliminary data from a variety of models support the concept that neuroendocrine activity is an important component in the ventricular remodeling process, and that pharmacologic interventions designed to block systemic and tissue neuroendocrine activity may prevent excessive cardiac enlargement and its ultimate consequences. Because this concept has important implications for preventive cardiology, the results of several prevention trials, including the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), Studies of Left Ventricular Dysfunction (SOLVD), and Survival and Ventricular Enlargement (SAVE) are awaited eagerly.

  2. Noninvasive estimation of regional myocardial oxygen consumption by positron emission tomography with carbon-11 acetate in patients with myocardial infarction

    SciTech Connect

    Walsh, M.N.; Geltman, E.M.; Brown, M.A.; Henes, C.G.; Weinheimer, C.J.; Sobel, B.E.; Bergmann, S.R. )

    1989-11-01

    We previously demonstrated in experimental studies that myocardial oxygen consumption (MVO2) can be estimated noninvasively with positron emission tomography (PET) from analysis of the myocardial turnover rate constant (k) after administration of carbon-11 (11C) acetate. To determine regional k in healthy human subjects and to estimate alterations in MVO2 accompanying myocardial ischemia, we administered (11C)acetate to five healthy human volunteers and to six patients with myocardial infarction. Extraction of (11C)acetate by the myocardium was avid and clearance from the blood-pool rapid yielding myocardial images of excellent quality. Regional k was homogeneous in myocardium of healthy volunteers (coefficient variation = 11%). In patients, k in regions remote from the area of infarction was not different from values in myocardium of healthy human volunteers (0.061 +/- 0.025 compared with 0.057 +/- 0.008 min-1). In contrast, MVO2 in the center of the infarct region was only 6% of that in remote regions (p less than 0.01). In four patients studied within 48 hr of infarction and again more than seven days after the acute event, regional k and MVO2 did not change. The approach developed should facilitate evaluation of the efficacy of interventions designed to enhance recovery of jeopardized myocardium and permit estimation of regional MVO2 and metabolic reserve underlying cardiac disease of diverse etiologies.

  3. Myocardial Upregulation of Cathepsin D by Ischemic Heart Disease Promotes Autophagic Flux and Protects Against Cardiac Remodeling and Heart Failure.

    PubMed

    Wu, Penglong; Yuan, Xun; Li, Faqian; Zhang, Jianhua; Zhu, Wei; Wei, Meng; Li, Jingbo; Wang, Xuejun

    2017-07-01

    Lysosomal dysfunction is implicated in human heart failure for which ischemic heart disease is the leading cause. Altered myocardial expression of CTSD (cathepsin D), a major lysosomal protease, was observed in human heart failure, but its pathophysiological significance has not been determined. Western blot analyses revealed an increase in the precursor but not the mature form of CTSD in myocardial samples from explanted human failing hearts with ischemic heart disease, which is recapitulated in chronic myocardial infarction produced via coronary artery ligation in Ctsd(+/+) but not Ctsd(+/-) mice. Mice deficient of Ctsd displayed impaired myocardial autophagosome removal, reduced autophagic flux, and restrictive cardiomyopathy. After induction of myocardial infarction, weekly serial echocardiography detected earlier occurrence of left ventricle chamber dilatation, greater decreases in ejection fraction and fractional shortening, and lesser wall thickening throughout the first 4 weeks; pressure-volume relationship analyses at 4 weeks revealed greater decreases in systolic and diastolic functions, stroke work, stroke volume, and cardiac output; greater increases in the ventricular weight to body weight and the lung weight to body weight ratios and larger scar size were also detected in Ctsd(+/-) mice compared with Ctsd(+/+) mice. Significant increases of myocardial autophagic flux detected at 1 and 4 weeks after induction of myocardial infarction in the Ctsd(+/+) mice were diminished in the Ctsd(+/-) mice. Myocardial CTSD upregulation induced by myocardial infarction protects against cardiac remodeling and malfunction, which is at least in part through promoting myocardial autophagic flux. © 2017 American Heart Association, Inc.

  4. Living Without Creatine: Unchanged Exercise Capacity and Response to Chronic Myocardial Infarction in Creatine-Deficient Mice

    PubMed Central

    Lygate, Craig A.; Aksentijevic, Dunja; Dawson, Dana; Hove, Michiel ten; Phillips, Darci; de Bono, Joseph P.; Medway, Debra J.; Sebag-Montefiore, Liam; Hunyor, Imre; Channon, Keith M.; Clarke, Kieran; Zervou, Sevasti; Watkins, Hugh; Balaban, Robert S.; Neubauer, Stefan

    2014-01-01

    Rationale Creatine is thought to be involved in the spatial and temporal buffering of ATP in energetic organs such as heart and skeletal muscle. Creatine depletion affects force generation during maximal stimulation, while reduced levels of myocardial creatine are a hallmark of the failing heart, leading to the widely held view that creatine is important at high workloads and under conditions of pathological stress. Objective We therefore hypothesised that the consequences of creatine-deficiency in mice would be impaired running capacity, and exacerbation of heart failure following myocardial infarction. Methods and Results Surprisingly, mice with whole-body creatine deficiency due to knockout of the biosynthetic enzyme (guanidinoacetate N-methyltransferase – GAMT) voluntarily ran just as fast and as far as controls (>10km/night) and performed the same level of work when tested to exhaustion on a treadmill. Furthermore, survival following myocardial infarction was not altered, nor was subsequent LV remodelling and development of chronic heart failure exacerbated, as measured by 3D-echocardiography and invasive hemodynamics. These findings could not be accounted for by compensatory adaptations, with no differences detected between WT and GAMT−/− proteomes. Alternative phosphotransfer mechanisms were explored; adenylate kinase activity was unaltered, and although GAMT−/− hearts accumulated the creatine pre-cursor guanidinoacetate, this had negligible energy-transfer activity, while mitochondria retained near normal function. Conclusions Creatine-deficient mice show unaltered maximal exercise capacity and response to chronic myocardial infarction, and no obvious metabolic adaptations. Our results question the paradigm that creatine is essential for high workload and chronic stress responses in heart and skeletal muscle. PMID:23325497

  5. Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion.

    PubMed

    Liu, Jian; Wang, Peipei; Douglas, Samuel L; Tate, Joshua M; Sham, Simon; Lloyd, Steven G

    2016-07-01

    High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulin-ketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels.

  6. Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion

    PubMed Central

    Liu, Jian; Wang, Peipei; Douglas, Samuel L.; Tate, Joshua M.; Sham, Simon

    2016-01-01

    High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulin-ketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels. PMID:27199129

  7. Computational Modeling of the Effects of Myocardial Infarction on Left Ventricular Hemodynamics

    NASA Astrophysics Data System (ADS)

    Vedula, Vijay; Seo, Jung Hee; Mittal, Rajat; Fortini, Stefania; Querzoli, Giorgio

    2012-11-01

    Most in-vivo and modeling studies on myocardial infarction and ischemia have been directed towards understanding the left ventricular wall mechanics including stress-strain behavior, end systolic pressure-volume correlations, ejection fraction and stroke work. Fewer studies have focused on the alterations in the intraventricular blood flow behavior due to local infarctions. Changes in the motion of the endocardium can cause local circulation and stagnation regions; these increase the blood cell residence time in the left ventricle and may eventually be implicated in thrombus formation. In the present study, we investigate the effects of myocardial infarction on the ventricular hemodynamics in simple models of the left ventricle using an immersed-boundary flow solver. Apart from the Eulerian flow features such as vorticity and velocity flow fields, pressure distribution, shear stress, viscous dissipation and pump work, we also examine the Lagrangian dynamics of the flow to gain insights into the effect of flow dynamics on thrombus formation. The study is preceded by a comprehensive validation study which is based on an in-vitro experimental model of the left ventricle and this study is also described. This research is supported by the U.S. National Science Foundation through (NSF) CDI-Type II grant IOS-1124804. Computational resources for some of the simulations were also provided in part through the NSF grant NSF-OCI-108849.

  8. Left ventricular dilatation and failure post-myocardial infarction: pathophysiology and possible pharmacologic interventions.

    PubMed

    Firth, B G; Dunnmon, P M

    1990-10-01

    An important antecedent to the development of late congestive heart failure is left ventricular dilatation and remodeling following myocardial infarction, which occurs in 30-40% of acute anterior transmural infarcts. Dilatation and remodeling commence within the first 24 hours following myocardial infarction and may be steadily progressive over months to years. Both the infarcted and uninfarcted regions of the myocardium are equally involved in the process. The remodeling process comprises left ventricular wall thinning (mainly due to cell slippage), chamber dilatation, and compensatory hypertrophy of the uninfarcted segment of the myocardium. The hypertrophy may initially be physiologic but may ultimately become a pathologic process, and thereby contribute to pump dysfunction. The possible reasons why the ventricular hypertrophy may ultimately be dysfunctional include alterations in local architecture and their sequelae alone or in concert with local changes in the beta-adrenergic, alpha-adrenergic, or renin angiotensin systems. At the present time, there are encouraging data to suggest that nitroglycerin, or the angiotensin converting enzyme inhibitor captopril, may ameliorate this process.

  9. Leukocyte CD11a expression and granulocyte activation during experimental myocardial ischemia and long lasting reperfusion

    PubMed Central

    Lantos, János; Grama, László; Orosz, Tamás; Temes, Gyula; Rőth, Elizabeth

    2001-01-01

    BACKGROUND: Myocardial ischemia and reperfusion are accompanied by leukocyte activation and expression of surface adhesion molecules, which induce pathological interactions between endothelial cells and circulating neutrophils, leading to tissue damage. While the dynamics of these processes have been well defined during acute reperfusion, there is very little information regarding long lasting reperfusion. OBJECTIVES: To investigate neutrophil granulocyte (PMN) activation and the CD11a expression of leukocytes during myocardial ischemia and reperfusion for four weeks. ANIMALS AND METHODS: The left anterior descending coronary artery was occluded for 1 h in six dogs, followed by reperfusion for four weeks. Peripheral blood samples were collected before the operation, at the end of ischemia, at 5 and 60 min of reperfusion, and on postoperative days 1, 2, 3, 7, 14, 21 and 28. Sham operation on four dogs served as control. Leukocyte expression of CD11a was measured by flow cytometry. Superoxide radical production of isolated PMNs was determined spectrophotometrically. RESULTS: Granulocyte CD11a expression increased while the superoxide radical-producing capacity decreased significantly by the third postoperative day. Sham operation produced similar alterations in these parameters during the first postoperative week. From the second postoperative week, however, granulocyte radical production and adhesion molecule expression were higher in the ischemic animals. CONCLUSIONS: The exhaustion of PMN radical production and maximal CD11a expression during the first postoperative week are probably due to the surgical trauma caused by thoracotomy, but increased granulocyte function during later reperfusion indicates prolonged healing of injured myocardium. PMID:20428266

  10. Regulation of myocardial amino acid balance in the conscious dog.

    PubMed Central

    Schwartz, R G; Barrett, E J; Francis, C K; Jacob, R; Zaret, B L

    1985-01-01

    between myocardial uptake and arterial concentration of leucine, isoleucine, valine, and total BCAA (r = 0.98, 0.98, 0.92, and 0.97, respectively); P less than 0.001 for each). In vivo, BCAA are the principal amino acids taken up by the myocardium basally and during amino acid infusion. Plasma BCAA concentration and not insulin determines the rate of myocardial BCAA uptake. Insulin stimulates myocardial alanine uptake. Neither insulin nor amino acid infusion alters myocardial glutamine release. PMID:2859300

  11. Genetic analysis in post-mortem samples with micro-ischemic alterations.

    PubMed

    Campuzano, Oscar; Sanchez-Molero, Olallo; Mademont-Soler, Irene; Coll, Monica; Allegue, Catarina; Ferrer-Costa, Carles; Mates, Jesus; Perez-Serra, Alexandra; Del Olmo, Bernat; Iglesias, Anna; Sarquella-Brugada, Georgia; Brugada, Josep; Borondo, Juan Carlos; Castella, Josep; Medallo, Jordi; Brugada, Ramon

    2017-02-01

    Sudden cardiac arrest is a leading cause of death worldwide. Most cardiac arrests happen in patients who have previously suffered a myocardial infarct. The risk of sudden death after infarction may increase in people who carry a pathogenic genetic alteration in cardiac ion channels. We hypothesized that micro-ischemia could trigger lethal arrhythmogenesis, thus we sought to identify genetic alterations in cardiac ion channels in patients with micro-ischemic disease. We studied a cohort of 56 post-mortem samples. Autopsy studies identified myocardial infarction as the cause of death in each case. We used both Sanger sequencing and next-generation sequencing to screen candidate genes associated with sudden cardiac death. We identified six rare missense genetic variations in five unrelated patients. Two variants have been previously reported; one is associated with atrial fibrillation (SCN5A_p.H445D), and the other is predicted to be benign (ANK2_p.T2059M). The novel variants were predicted in silico as benign, except for one (RyR2_p.M4019T), which was classified as deleterious. Our post-mortem, micro-infarction cohort displayed a rate of nearly 10% non-common genetic variants. However, the clinical significance of most of the identified variants remains unknown due to lack of family assessment. Further analyses should be performed in large cohorts to clarify the role of ion-channel gene analysis in samples showing microscopic ischemic alterations.

  12. Prevention of myocardial infarction.

    PubMed

    Adams, M R

    2002-12-01

    Despite the rapid advances that have been made in the treatment of coronary artery disease, myocardial infarction remains the major cause of death in the developed world and a growing problem for developing countries. To address this growing problem, a strategy aimed at prevention of events in high-risk individuals is required. This involves assessment of cardiovascular risk followed by risk reduction. At present there is no perfect technique available for risk prediction, although computed tomography and magnetic resonance imaging scanning, along with serum markers of inflammation, offer the greatest potential. The applicability of these techniques at present is also limited by cost and accessibility. Risk reduction is possible through lifestyle changes and drug therapy, and effective risk assessment is essential in selecting those most likely to benefit from these interventions.

  13. Delayed diagnosis of Fabry disease presenting as myocardial ischaemia.

    PubMed

    Marcì, Marcello; Duro, Giovanni; Tuttolomondo, Antonino; Tuttolomondo, Bruno; Pinto, Antonio; Cirrincione, Vincenzo; Sanfilippo, Nicola

    2012-01-01

    Cardiovascular complications due to the accumulation of globotriaosylceramide in cardiac cells occur in almost all patients affected by Anderson-Fabry disease. Cardiac manifestations include left ventricular hypertrophy, mitral regurgitation, conduction disturbances and myocardial ischaemia. We report a case of Fabry's disease diagnosed several years after the onset of early cardiac symptoms.

  14. Does exercise training alter myocardial creatine kinase MB isoenzyme content?

    PubMed

    Miller, T D; Rogers, P J; Bauer, B A; O'Brien, J F; Squires, R W; Bailey, K R; Bove, A A

    1989-08-01

    Skeletal muscle biopsies from highly trained endurance athletes have been shown to contain an increased percentage of the creatine kinase MB (CK-MB) isoenzyme, which has been attributed to continuous regeneration of the skeletal muscle fibers in response to exercise-induced injury. The purpose of this study was to determine whether myocardium undergoes a similar degenerative-regenerative process as a result of exercise training. Fifteen mongrel dogs underwent a 12-wk period of training (N = 8) or cage confinement (N = 7). The animals were then sacrificed, and samples of left and right ventricular myocardium were analyzed for total CK activity and CK-MB isoenzyme content. Percentages of CK-MB were slightly but insignificantly higher from both ventricles of exercise-trained as compared with cage-confined dogs: left ventricle, 4.6 +/- 0.6% vs 3.3 +/- 0.6%, respectively (P = 0.15); right ventricle, 4.0 +/- 0.4% vs 3.0 +/- 0.8%, respectively (P = 0.29). We conclude that chronic exercise training does not induce physiologically important degenerative changes in myocardium.

  15. Intestinal microbiota determine severity of myocardial infarction in rats

    PubMed Central

    Lam, Vy; Su, Jidong; Koprowski, Stacy; Hsu, Anna; Tweddell, James S.; Rafiee, Parvaneh; Gross, Garrett J.; Salzman, Nita H.; Baker, John E.

    2012-01-01

    Signals from the intestinal microbiota are important for normal host physiology; alteration of the microbiota (dysbiosis) is associated with multiple disease states. We determined the effect of antibiotic-induced intestinal dysbiosis on circulating cytokine levels and severity of ischemia/reperfusion injury in the heart. Treatment of Dahl S rats with a minimally absorbed antibiotic vancomycin, in the drinking water, decreased circulating leptin levels by 38%, resulted in smaller myocardial infarcts (27% reduction), and improved recovery of postischemic mechanical function (35%) as compared with untreated controls. Vancomycin altered the abundance of intestinal bacteria and fungi, measured by 16S and 18S ribosomal DNA quantity. Pretreatment with leptin (0.12 μg/kg i.v.) 24 h before ischemia/reperfusion abolished cardioprotection produced by vancomycin treatment. Dahl S rats fed the commercially available probiotic product Goodbelly, which contains the leptin-suppressing bacteria Lactobacillus plantarum 299v, also resulted in decreased circulating leptin levels by 41%, smaller myocardial infarcts (29% reduction), and greater recovery of postischemic mechanical function (23%). Pretreatment with leptin (0.12 μg/kg i.v.) abolished cardioprotection produced by Goodbelly. This proof-of-concept study is the first to identify a mechanistic link between changes in intestinal microbiota and myocardial infarction and demonstrates that a probiotic supplement can reduce myocardial infarct size.—Lam, V., Su, J., Koprowski, S., Hsu, A., Tweddell, J. S., Rafiee, P., Gross, G. J., Salzman, N. H., Baker, J. E. Intestinal microbiota determine severity of myocardial infarction in rats. PMID:22247331

  16. Acute myocardial infarction in young adults: causes and management

    PubMed Central

    Osula, S; Bell, G; Hornung, R

    2002-01-01

    The case report in this review illustrates an acute myocardial infarction in a young adult probably due to arterial thrombosis that can be attributed to a hypercoagulable state resulting from the nephrotic syndrome. Although rare, acute myocardial infarction should be considered in young adults presenting with chest pain. A detailed clinical history may help to identify the aetiology, and guide subsequent management, but diagnostic coronary angiography is essential. Careful risk factor modification and treatment of the underlying cause should reduce the incidence of recurrent cardiac events. PMID:11796868

  17. [Acute traumatic myocardial infarction with cardiogenic shock in severe polytrauma--a case report].

    PubMed

    Rohe, G; Feyerherd, F; Möx, B; Hachenberg, T

    2000-04-01

    A 41-year-old man suffered severe polytrauma and developed a traumatic myocardial infarction with cardiogenic shock. Thrombolysis as well as coronary bypass grafting was contraindicated due to accompanying injuries. An attempted early coronary revascularization by percutaneous transluminal coronary angioplasty (PTCA) failed due to dissection of the left interventricular coronary artery. Treatment of cardiac insufficiency was complicated by intraabdominal haemorrhage enforcing emergency laparotomy. Intraaortic balloon counterpulsation proved to be efficient in supporting circulation in these circumstances. The case report documents the practicability and importance of treating both myocardial ischaemia and attending injuries in an equivalent and coordinated manner in traumatic myocardial infarction.

  18. Myocardial perfusion as assessed by thallium-201 scintigraphy during the discontinuation of mechanical ventilation in ventilator-dependent patients

    SciTech Connect

    Hurford, W.E.; Lynch, K.E.; Strauss, H.W.; Lowenstein, E.; Zapol, W.M. )

    1991-06-01

    Patients who cannot be separated from mechanical ventilation (MV) after an episode of acute respiratory failure often have coexisting coronary artery disease. The authors hypothesized that increased left ventricular (LV) wall stress during periods of spontaneous ventilation (SV) could alter myocardial perfusion in these patients. Using thallium-201 (201TI) myocardial scintigraphy, the authors studied the occurrence of myocardial perfusion abnormalities during periods of SV in 15 MV-dependent patients (nine women, six men; aged 71 {plus minus} 7 yr, mean {plus minus} SD). Fourteen of these patients were studied once with 201TI myocardial scintigraphy during intermittent mechanical ventilation (IMV) and again on another day, after at least 10 min of SV through a T-piece. One patient was studied during SV only. Thirteen of 14 of the patients (93%) studied during MV had abnormal patterns of initial myocardial 201TI uptake, but only 1 patient demonstrated redistribution of 201TI on delayed images. The remainder of the abnormalities observed during MV were fixed defects. SV produced significant alterations of myocardial 201TI distribution or transient LV dilation, or both, in 7 of the 15 patients (47%). Four patients demonstrated new regional decreases of LV myocardial thallium concentration with redistribution of the isotope on delayed images. The patient studied only during SV also had myocardial 201TI defects with redistribution. Five patients (3 also having areas of 201TI redistribution) had transient LV dilation during SV.

  19. [Valvular surgical treatment concurrent with myocardial revascularization].

    PubMed

    Lavítola, P de L; Dallan, L A; Tarasoutchi, F; Grinberg, M; da Luz, P L; Pileggi, F; Jatene, A D

    1992-12-01

    To study the morbidity and mortality due to valvar surgical treatment performed concomitantly to myocardial revascularization. From 1650 patients submitted to mitral or aortic valve surgical treatment, 103 (6.24%) had it associated to myocardial revascularization. Coronary insufficiency was associated to aortic valvar lesion in 66 (64.0%) patients, group I, with mean age of 62.3 +/- 8 years; and in 37 (35.9%) patients with mitral valve lesion, group II, with mean age of 57.8 +/- 5.8 years. Diagnosis was based upon the anamnesis, physical examination and confirmed by cine-coronarographic findings. I-Complications at the immediate postoperative; a) mortality 11 (10.6%) patients, 6 (9.09%) from group I: by low cardiac output 3, uncontrolled arrhythmia 1, mediastinitis 1; acute infarction with cardiogenic shock 1, and 5 (134.5%) of group II: uncontrolled hemorrhage 2, sudden death 1, saphenous vein graft occlusion, respiratory insufficiency and sepsis 2; b) controlled intercurrences that increased the time of hospitalization: mental disorder 5 patients; CVA 7, diabetes decompensation 2, worsening of chronic renal insufficiency 1, upper level digestive hemorrhage 1 and respiratory insufficiency 3 patients. II-late postoperative complications of 77 (83.6%) patients which could be followed up during a period of 60 months: 1) mortality: 3 (3.89%) patients; 2 due to cardiomyopathy and 1 by acute myocardial infarction; 2) late evolution-functional capacity III (NYHA) by cardiomyopathy 6; I/II 68 patients; mild angina 6 patients, 2 underwent revascularization at the end of final 36-42 months. The clinical improvement and mortality indexes statistically similar to the isolate surgical acts stimulate us to keep up with such associate procedures.

  20. Infection and inflammation as risk factors for myocardial infarction.

    PubMed

    Nieminen, M S; Mattila, K; Valtonen, V

    1993-12-01

    Recent studies have illustrated that in addition to the well known risk factors, such as lipoproteins, smoking, hypertension, there are others that cause atherosclerosis and myocardial infarction. Our knowledge of atherosclerotic lesions has increased. We now know that atherosclerotic changes are due to inflammatory cell infiltration as well as to increases in migration of vascular smooth muscle cells. Endothelial cells play a major role in the pathology of vascular changes. In recent years a new risk factor for coronary artery disease has been discovered: chlamydia pneumonial infections. Herpes class viruses have also been associated with pathology of atherosclerotic lesions. Studies show that dental status and bacterial infections are also related to the risk of myocardial infarction. This review discusses the possible mechanisms of infection and inflammation and whether they are major or modifying risk factors for atherosclerosis and myocardial infarction.

  1. Amphetamine Containing Dietary Supplements and Acute Myocardial Infarction

    PubMed Central

    Hritani, Abdulwahab; Antoun, Patrick

    2016-01-01

    Weight loss is one of the most researched and marketed topics in American society. Dietary regimens, medications that claim to boost the metabolism, and the constant pressure to fit into society all play a role in our patient's choices regarding new dietary products. One of the products that are well known to suppress appetite and cause weight loss is amphetamines. While these medications suppress appetite, most people are not aware of the detrimental side effects of amphetamines, including hypertension, tachycardia, arrhythmias, and in certain instances acute myocardial infarction. Here we present the uncommon entity of an acute myocardial infarction due to chronic use of an amphetamine containing dietary supplement in conjunction with an exercise regimen. Our case brings to light further awareness regarding use of amphetamines. Clinicians should have a high index of suspicion of use of these substances when young patients with no risk factors for coronary artery disease present with acute arrhythmias, heart failure, and myocardial infarctions. PMID:27516911

  2. Histopathological study on myocardial hypertrophy associated with ischemic heart disease.

    PubMed

    Ishijima, M

    1990-06-01

    The mode and causes of myocardial hypertrophy occurring in association with ischemic heart disease were studied. The investigation involved autopsied hearts (15 cases of subendocardial infarction, 27 of transmural infarction, 20 of non-infarcted three vessel disease and 17 controls) and biopsied materials obtained during coronary-aorta bypass graft surgery (23 patients with angina pectoris and 46 with myocardial infarction). The subendocardial infarction group showed most marked myocardial hypertrophy that reflected extensive infarction and fibrosis, dilatation of the left ventricular cavity and the loss of myocytes. Despite a marked decrease in the number of myocyte layers, the residual myocardium of the left ventricle was uniformly hypertrophic, accompanied by an increase in the heart weight. The larger the area of fibrosis, the more marked was myocardial hypertrophy irrespective of the luminal diameter of the responsible coronary artery. These findings indicate that myocardial hypertrophy associated with ischemic heart disease is enhanced by the compensatory mechanisms for a decrease in the contractile myocardium due to fibrosis.

  3. In-vivo measurement of swine myocardial resistivity.

    PubMed

    Tsai, Jang-Zern; Will, James A; Hubbard-Van Stelle, Scott; Cao, Hong; Tungjitkusolmun, Supan; Choy, Young Bin; Haemmerich, Dieter; Vorperian, Vicken R; Webster, John G

    2002-05-01

    We used a four-terminal plunge probe to measure myocardial resistivity in two directions at three sites from the epicardial surface of eight open-chest pigs in-vivo at eight frequencies ranging from 1 Hz to 1 MHz. We calibrated the plunge probe to minimize the error due to stray capacitance between the measured subject and ground. We calibrated the probe in saline solutions contained in a metal cup situated near the heart that had an electrical connection to the pig's heart. The mean of the measured myocardial resistivity was 319 ohm x cm at 1 Hz down to 166 ohm x cm at 1 MHz. Statistical analysis showed the measured myocardial resistivity of two out of eight pigs was significantly different from that of other pigs. The myocardial resistivity measured with the resistivity probe oriented along and across the epicardial fiber direction was significantly different at only one out of the eight frequencies. There was no significant difference in the myocardial resistivity measured at different sites.

  4. Nitroglycerin Use in Myocardial Infarction Patients: Risks and Benefits

    PubMed Central

    Ferreira, Julio C.B.; Mochly-Rosen, Daria

    2012-01-01

    Acute myocardial infarction and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin remains a first-line treatment for angina pectoris and acute myocardial infarction. Nitroglycerin achieves its benefit by giving rise to nitric oxide, which causes vasodilation and increases blood flow to the myocardium. However, continuous delivery of nitroglycerin results in tolerance, limiting the use of this drug. Nitroglycerin tolerance is due, at least in part, to inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme that converts nitroglycerin to the vasodilator, nitric oxide. We have recently found that, in addition to nitroglycerin’s effect on the vasculature, sustained treatment with nitroglycerin negatively affects cardiomyocyte viability following ischemia, thus resulting in increased infarct size in a myocardial infarction model in animals. Co-administration of Alda-1, an activator of ALDH2, with nitroglycerin improves metabolism of reactive aldehyde adducts and prevents the nitroglycerin-induced increase in cardiac dysfunction following myocardial infarction. In this review, we describe the molecular mechanisms associated with the benefits and risks of nitroglycerin administration in myocardial infarction. (167 of 200). PMID:22040938

  5. 3D cardiac wall thickening assessment for acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Khalid, A.; Chan, B. T.; Lim, E.; Liew, Y. M.

    2017-06-01

    Acute myocardial infarction (AMI) is the most severe form of coronary artery disease leading to localized myocardial injury and therefore irregularities in the cardiac wall contractility. Studies have found very limited differences in global indices (such as ejection fraction, myocardial mass and volume) between healthy subjects and AMI patients, and therefore suggested regional assessment. Regional index, specifically cardiac wall thickness (WT) and thickening is closely related to cardiac function and could reveal regional abnormality due to AMI. In this study, we developed a 3D wall thickening assessment method to identify regional wall contractility dysfunction due to localized myocardial injury from infarction. Wall thickness and thickening were assessed from 3D personalized cardiac models reconstructed from cine MRI images by fitting inscribed sphere between endocardial and epicardial wall. The thickening analysis was performed in 5 patients and 3 healthy subjects and the results were compared against the gold standard 2D late-gadolinium-enhanced (LGE) images for infarct localization. The notable finding of this study is the highly accurate estimation and visual representation of the infarct size and location in 3D. This study provides clinicians with an intuitive way to visually and qualitatively assess regional cardiac wall dysfunction due to infarction in AMI patients.

  6. Carbon nanotube facilitation of myocardial ablation with radiofrequency energy.

    PubMed

    Nguyen, Duy T; Barham, Waseem; Zheng, Lijun; Shillinglaw, Benjamin; Tzou, Wendy S; Neltner, Bonnie; Mestroni, Luisa; Bosi, Susanna; Ballerini, Laura; Prato, Maurizio; Sauer, William H

    2014-12-01

    The use of carbon nanotubes (CNTs) in oncology has been proposed for the purpose of sensitizing tumors to radiofrequency (RF) ablation. We hypothesize that myocardial tissue infiltrated with CNTs will improve thermal conductivity of RF heating and lead to altered ablation lesion characteristics. An ex vivo model consisting of viable bovine myocardium, a circulating saline bath at 37 °C, a submersible load cell, and a deflectable sheath was assembled. A 4-mm nonirrigated ablation catheter was positioned with 10 gm of force over bovine myocardium infiltrated with CNTs, 0.9% saline, or sham injections. A series of ablation lesions were delivered at 20 and 50 W, and lesion volumes were acquired by analyzing tissue sections with a digital micrometer. Tissue temperature analyses at 3 and 5 mm depths were also performed. Myocardial tissue treated with CNTs resulted in significantly larger lesions at both low and high power settings. The electrical impedance was increased in CNT treated tissue with a greater impedance change observed in the CNT infiltrated myocardium. The thermal conductivity of heat generated by application of RF in the tissue was altered by the presence of CNTs, resulting in higher temperatures at 3 and 5 mm depths for both 20 and 50 W. Myocardial tissue treated with CNTs resulted in significantly larger lesions at both low and high power settings. The electrical and thermal conductivity of heat generated by application of RF in myocardial tissue was altered by the presence of CNTs. Further research is needed to assess the in vivo applicability for this concept of facilitated ablation with CNTs. © 2014 Wiley Periodicals, Inc.

  7. Heart rate variability as a marker of myocardial perfusion.

    PubMed

    Schechter, D; Sapoznikov, D; Luria, M H; Mendelson, S; Bocher, M; Chisin, R

    1998-01-01

    RR variability (HRV), an independent predictor of death following myocardial infarction, may also be related to other features of coronary artery disease. We evaluated its ability to differentiate among sedentary patients with chest pain >/=45 years of age demonstrating either normal or abnormal myocardial perfusion with rest and exercise thallium-210 tomographic imaging. The major HRV difference between 48 men and 50 women with normal perfusion was a significantly higher high frequency power in women. No significant differences in mean HRV values were found between the 57 men with abnormal perfusion scans and the 48 men with normal perfusion. In both men and women with normal perfusion scans, duration of exercise was significantly related to age. In men with abnormal scans, impaired myocardial perfusion alters the relationship between exercise duration and age, and a group of individuals with diminished HRV and low levels of physical fitness, regardless of age, can be identified. Despite these latter selective findings, we conclude that HRV is not a sensitive indicator to differentiate patients with normal and abnormal myocardial perfusion.

  8. Effect of ribose on thallium-201 myocardial redistribution

    SciTech Connect

    Angello, D.A.; Wilson, R.A.; Gee, D.

    1988-12-01

    Myocardial S Tl redistribution after transient ischemia may be too slow to allow identification of a reversible myocardial defect within the routine S Tl imaging period. To determine whether S Tl redistribution could be affected by a metabolic intervention, intravenous ribose was administered postischemia. Seventeen domestic swine were subjected to a 10-min ischemic period followed by either a 30-min i.v. ribose (n = 8) or saline (n = 9) infusion. Thallium-201 was injected during ischemia and myocardial S Tl activity was continuously monitored in ischemic and nonischemic regions with miniature CdTe radiation detection probes. Coronary flow in the ischemic region was reduced to 25% of that in the nonischemic regions in both saline and ribose groups. The S Tl time-activity curves demonstrated a significant enhancement of % S Tl redistribution in the ribose-treated animals at the end of ribose infusion: Ribose (48 +/- 11%), Saline (20 +/- 4%), p less than 0.05. Alteration of S Tl kinetics by ribose may permit earlier recognition of S Tl myocardial redistribution after transient ischemia.

  9. [Is secondary myocardial hypertrophy a physiological or pathological adaptive mechanism?].

    PubMed

    Krayenbühl, H P

    1982-08-01

    Physiological hypertrophy is present when the increase in myocardial mass resulting from chronic mechanical loading is associated with normal or enhanced myocardial function and myosin ATPase activity. Morphological alterations occurring during the formation of hypertrophy are fully reversible in physiological hypertrophy. In pathological hypertrophy myocardial function and myosin ATPase activity are depressed and morphological changes do not or only incompletely regress following the elimination of the stimulus of hypertrophy. In the experimental animal myocardial hypertrophy resulting from exercise conditioning or slight to moderate ventricular pressure overload fulfills the criteria of physiological hypertrophy. More severe sudden pressure overload is accompanied by depression of contractile function. These pressure overload models have however, little analogy to the more progressive development of pressure loading in humans. In young dogs and in cats with a gradually increasing pressure load, in vivo ventricular ejection fraction remained within normal limits 37 to 60 weeks after banding of the ventricular outflow vessel. In vitro myocardial function evaluated in the hypertrophied papillary muscle was, however, at least in part depressed, notably when hydroxyproline concentration was augmented. Following debanding in rats with aortic constriction hydroxyproline content did not regress suggesting that fibrosis once established is not reversible. In man myocardial hypertrophy from exercise conditioning is associated with normal ventricular function except in older athletes, who may show a subtle reduction in ventricular shortening. Patients with chronic pressure overload from aortic stenosis or volume overload from aortic insufficiency in whom the angiographic muscle mass is severely increased (greater than or equal to 180 g/m2) elicit a depressed left ventricular contractile function. Preserved left ventricular ejection performance in aortic valve disease is

  10. Myocardial Salvaging Effects of Berberine in Experimental Diabetes Co-Existing with Myocardial Infarction

    PubMed Central

    Borde, Manjusha K.; Mohanty, Ipseeta Ray; Maheshwari, Ujwala; Deshmukh, Y.A.

    2016-01-01

    Introduction Berberine, an isoquinoline alkaloid isolated from the Berberis aristata, has been shown to display a wide array of pharmacological activities (hypoglycaemic and hypolipidemic). Aim The present study was designed to investigate whether these pharmacological properties translate into the cardioprotective effects of Berberine in the setting of diabetes mellitus. Materials and Methods Necessary approval from the Institutional Animal Ethics Committee was taken for the study. Experimental diabetes was produced with single dose of Streptozotocin (STZ): 45mg/kg ip and myocardial infarction was induced by administering Isoproterenol (ISP): 85mg/kg, sc to rats on 35th & 36th day. After the confirmation of diabetes on 7th day (>200mg/dl), Berberine (100 mg/kg) was administered orally to experimental rats from day 8 and continued for 30 days thereafter. Various anti-diabetic (Glucose, HbA1c), cardioprotective (CPK-MB), metabolic (lipid profile), safety {liver function (SGPT, kidney function (Creatinine)} and histopathological indices of injury were evaluated in Healthy Control, Diabetic Control and Berberine treated groups. Results Administration of STZ-ISP resulted in a significant decrease in body weight (p<0.001), diabetic changes (increase in blood glucose, HbA1c), cardiac injury (leakage of myocardial CPK-MB), altered lipid profile, SGPT, creatinine levels (p<0.001) in the diabetic control group rats as compared to healthy control. Berberine treatment demonstrated significant antidiabetic as well as myocardial salvaging effects as indicated by restoration of blood glucose, HbA1c and CPK-MB levels (p<0.001) compared to diabetic control group. In addition, Berberine favourably modulated the lipid parameters (total cholesterol, triglycerides, HDL, LDL). Subsequent to ISP challenge, histopathological assessment of heart, pancreas and biochemical indices of injury confirmed the cardioprotective effects of Berberine in setting of diabetes. In addition, Berberine

  11. Rat myocardial protein degradation.

    PubMed

    Steer, J H; Hopkins, B E

    1981-07-01

    1. Myocardial protein degradation rates were determined by following tyrosine release from rat isolated left hemi-atria in vitro. 2. After two 20 min preincubations the rate of tyrosine release from hemi-atria was constant for 4 h. 3. Skeletal muscle protein degradation was determined by following tyrosine release from rat isolated hemi-diaphragm (Fulks, Li & Goldberg, 1975). 4. Insulin (10(-7) M) inhibited tyrosine release from hemi-atria and hemi-diaphragm to a similar extent. A 48 h fast increased tyrosine release rate from hemi-diaphragm and decreased tyrosine release rate from hemi-atria. Hemi-diaphragm tyrosine release was inhibited by 15 mmol/l D-glucose but a variety of concentrations of D-glucose (0, 5, 15 mmol/l) had no effect on tyrosine release from hemi-atria. Five times the normal plasma levels of the branched-chain amino acids leucine, isoleucine and valine had no effect on tyrosine release from either hemi-atria or hemi-diaphragm.

  12. Myocardial complications of immunisations.

    PubMed

    Helle, E P; Koskenvuo, K; Heikkilä, J; Pikkarainen, J; Weckström, P

    1978-10-01

    Immunisation may induce myocardial complications. In this pilot study clinical, electrocardiographic, chemical and immunological findings have been studied during a six weeks' follow-up after routine immunisation (mumps, polio, tetanus, smallpox, diphtheria and type A meningococcal disease) among 234 Finnish conscripts at the beginning of their military service. Serial pattern of ECG changes suggestive of myocarditis was recorded in eight of the 234 conscripts one to two weeks after vaccination against smallpox and diphtheria. Changes were mainly minor ST segment elevations and T wave inversions and usually they disappeared in a few weeks. The ECG positives more often had a history of atopy, and their mean body temperatures and heart rates after the vaccinations were higher than among the other subjects (p less than 0.01). However, clinical myocarditis was never noted, nor were immunological or enzymological changes different among the ECG positives. Thus in 3% of the study population, evidence of postvaccinal myocarditis was noted, based on serial ECG patterns, but without any other evidence of cardiac disease.

  13. CAD of myocardial perfusion

    NASA Astrophysics Data System (ADS)

    Storm, Corstiaan J.; Slump, Cornelis H.

    2007-03-01

    Our purpose is in the automated evaluation of the physiological relevance of lesions in coronary angiograms. We aim to extract as much as possible quantitative information about the physiological condition of the heart from standard angiographic image sequences. Coronary angiography is still the gold standard for evaluating and diagnosing coronary abnormalities as it is able to locate precisely the coronary artery lesions. The dimensions of the stenosis can be assessed nowadays successfully with image processing based Quantitative Coronary Angiography (QCA) techniques. Our purpose is to assess the clinical relevance of the pertinent stenosis. We therefore analyze the myocardial perfusion as revealed in standard angiographic image sequences. In a Region-of-Interest (ROI) on the angiogram (without an overlaying major blood vessel) the contrast is measured as a function of time (the so-called time-density curve). The required hyperemic state of exercise is induced artificially by the injection of a vasodilator drug e.g. papaverine. In order to minimize motion artifacts we select based on the recorded ECG signal end-diastolic images in both a basal and a hyperemic run in the same projection to position the ROI. We present the development of the algorithms together with results of a small study of 20 patients which have been catheterized following the standard protocol.

  14. Lipid, Oxidative and Inflammatory Profile and Alterations in the Enzymes Paraoxonase and Butyrylcholinesterase in Plasma of Patients with Homocystinuria Due CBS Deficiency: The Vitamin B12 and Folic Acid Importance.

    PubMed

    Vanzin, Camila Simioni; Mescka, Caroline Paula; Donida, Bruna; Hammerschimidt, Tatiane Grazieli; Ribas, Graziela S; Kolling, Janaína; Scherer, Emilene B; Vilarinho, Laura; Nogueira, Célia; Coitinho, Adriana Simon; Wajner, Moacir; Wyse, Angela T S; Vargas, Carmen Regla

    2015-08-01

    Cystathionine-β-synthase (CBS) deficiency is the main cause of homocystinuria. Homocysteine (Hcy), methionine, and other metabolites of Hcy accumulate in the body of affected patients. Despite the fact that thromboembolism represents the major cause of morbidity in CBS-deficient patients, the mechanisms of cardiovascular alterations found in homocystinuria remain unclear. In this work, we evaluated the lipid and inflammatory profile, oxidative protein damage, and the activities of the enzymes paraoxonase (PON1) and butyrylcholinesterase (BuChE) in plasma of CBS-deficient patients at diagnosis and during the treatment (protein-restricted diet supplemented with pyridoxine, folic acid, betaine, and vitamin B12). We also investigated the effect of folic acid and vitamin B12 on these parameters. We found a significant decrease in HDL cholesterol and apolipoprotein A1 (ApoA-1) levels, as well as in PON1 activity in both untreated and treated CBS-deficient patients when compared to controls. BuChE activity and IL-6 levels were significantly increased in not treated patients. Furthermore, significant positive correlations between PON1 activity and sulphydryl groups and between IL-6 levels and carbonyl content were verified. Moreover, vitamin B12 was positively correlated with PON1 and ApoA-1 levels, while folic acid was inversely correlated with total Hcy concentration, demonstrating the importance of this treatment. Our results also demonstrated that CBS-deficient patients presented important alterations in biochemical parameters, possibly caused by the metabolites of Hcy, as well as by oxidative stress, and that the adequate adherence to the treatment is essential to revert or prevent these alterations.

  15. The Chinese version of the Myocardial Infarction Dimensional Assessment Scale (MIDAS): Mokken scaling

    PubMed Central

    2012-01-01

    Background Hierarchical scales are very useful in clinical practice due to their ability to discriminate precisely between individuals, and the original English version of the Myocardial Infarction Dimensional Assessment Scale has been shown to contain a hierarchy of items. The purpose of this study was to analyse a Mandarin Chinese translation of the Myocardial Infarction Dimensional Assessment Scale for a hierarchy of items according to the criteria of Mokken scaling. Data from 180 Chinese participants who completed the Chinese translation of the Myocardial Infarction Dimensional Assessment Scale were analysed using the Mokken Scaling Procedure and the 'R' statistical programme using the diagnostics available in these programmes. Correlation between Mandarin Chinese items and a Chinese translation of the Short Form (36) Health Survey was also analysed. Findings Fifteen items from the Mandarin Chinese Myocardial Infarction Dimensional Assessment Scale were retained in a strong and reliable Mokken scale; invariant item ordering was not evident and the Mokken scaled items of the Chinese Myocardial Infarction Dimensional Assessment Scale correlated with the Short Form (36) Health Survey. Conclusions Items from the Mandarin Chinese Myocardial Infarction Dimensional Assessment Scale form a Mokken scale and this offers further insight into how the items of the Myocardial Infarction Dimensional Assessment Scale relate to the measurement of health-related quality of life people with a myocardial infarction. PMID:22221696

  16. Lidocaine Enhances Contractile Function of Ischemic Myocardial Regions in Mouse Model of Sustained Myocardial Ischemia

    PubMed Central

    Kania, Gabriela; Osto, Elena; Jakob, Philipp; Krasniqi, Nazmi; Beck-Schimmer, Beatrice; Blyszczuk, Przemyslaw; Eriksson, Urs

    2016-01-01

    Rationale Perioperative myocardial ischemia is common in high-risk patients. The use of interventional revascularisation or even thrombolysis is limited in this patient subset due to exceedingly high bleeding risks. Blockade of voltage-gated sodium channels (VGSC) with lidocaine had been suggested to reduce infarct size and cardiomyocyte cell death in ischemia/reperfusion models. However, the impact of lidocaine on cardiac function during sustained ischemia still remains unclear. Methods Sustained myocardial ischemia was induced by ligation of the left anterior descending artery in 12–16 weeks old male BALB/c mice. Subcutaneous lidocaine (30 mg/kg) was used to block VGSC. Cardiac function was quantified at baseline and at 72h by conventional and speckle-tracking based echocardiography to allow high-sensitivity in vivo phenotyping. Infarct size and cardiomyocyte cell death were assessed post mortem histologically and indirectly using troponin measurements. Results Ischemia strongly impaired both, global systolic and diastolic function, which were partially rescued in lidocaine treated in mice. No differences regarding infarct size and cardiomyocyte cell death were observed. Mechanistically, and as shown with speckle-tracking analysis, lidocaine specifically improves residual contractility in the ischemic but not in the remote, non-ischemic myocardium. Conclusion VGSC blockade with lidocaine rescues function of ischemic myocardium as a potential bridging to revascularisation in the setting of perioperative myocardial ischemia. PMID:27140425

  17. Intracoronary delivery of recombinant TIMP-3 after myocardial infarction: effects on myocardial remodeling and function.

    PubMed

    Barlow, Shayne C; Doviak, Heather; Jacobs, Julia; Freeburg, Lisa A; Perreault, Paige E; Zellars, Kia N; Moreau, Karen; Villacreses, Camila F; Smith, Stephen; Khakoo, Aarif Y; Lee, TaeWeon; Spinale, Francis G

    2017-10-01

    Ischemia-reperfusion (IR) and myocardial infarction (MI) cause adverse left ventricular (LV) remodeling and heart failure and are facilitated by an imbalance in matrix metalloproteinase (MMP) activation and the endogenous tissue inhibitors of metalloproteinase (TIMPs). We have identified that myocardial injections of recombinant TIMP-3 (rTIMP-3; human full length) can interrupt post-MI remodeling. However, whether and to what degree intracoronary delivery of rTIMP-3 post-IR is feasible and effective remained to be established. Pigs (25 kg) underwent coronary catheterization and balloon occlusion of the left anterior descending coronary artery (LAD) for 90 min whereby at the final 4 min, rTIMP-3 (30 mg, n = 9) or saline was infused in the distal LAD. LV echocardiography was performed at 3-28 days post-IR, and LV ejection fraction (EF) and LV end-diastolic volume were measured. LV EF fell and LV end-diastolic volume increased from baseline (pre-IR) values (66 ± 1% and 40 ± 1 ml, respectively, means ± standard deviation) in both groups; however, the extent of LV dilation was reduced in the rTIMP-3 group by 40% at 28 days post-IR (P < 0.05) and the fall in LV EF was attenuated. Despite equivalent plasma troponin levels (14 ± 3 ng/ml), computed MI size at 28 days was reduced by over 45% in the rTIMP-3 group (P < 0.05), indicating that rTIMP-3 treatment abrogated MI expansion post-IR. Plasma NH2-terminal pro-brain natriuretic peptide levels, an index of heart failure progression, were reduced by 25% in the rTIMP-3 group compared with MI saline values (P < 0.05). Although the imbalance between MMPs and TIMPs has been recognized as a contributory factor for post-MI remodeling, therapeutic strategies targeting this imbalance have not been forthcoming. This study is the first to demonstrate that a relevant delivery approach (intracoronary) using rTIMP can alter the course of post-MI remodeling.NEW & NOTEWORTHY Myocardial ischemia and reperfusion injury

  18. Myocardial perfusion imaging for detection of silent myocardial ischemia

    SciTech Connect

    Beller, G.A.

    1988-04-21

    Despite the widespread use of the exercise stress test in diagnosing asymptomatic myocardial ischemia, exercise radionuclide imaging remains useful for detecting silent ischemia in numerous patient populations, including those who are totally asymptomatic, those who have chronic stable angina, those who have recovered from an episode of unstable angina or an uncomplicated myocardial infarction, and those who have undergone angioplasty or received thrombolytic therapy. Studies show that thallium scintigraphy is more sensitive than exercise electrocardiography in detecting ischemia, i.e., in part, because perfusion defects occur more frequently than ST depression and before angina in the ischemic cascade. Thallium-201 scintigraphy can be performed to differentiate a true- from a false-positive exercise electrocardiographic test in patients with exercise-induced ST depression and no angina. The development of technetium-labeled isonitriles may improve the accuracy of myocardial perfusion imaging. 11 references.

  19. Myocardial Infarction: Symptoms and Treatments.

    PubMed

    Lu, Lei; Liu, Min; Sun, RongRong; Zheng, Yi; Zhang, Peiying

    2015-07-01

    Myocardial infarction (MI) is a term used for an event of heart attack which is due to formation of plaques in the interior walls of the arteries resulting in reduced blood flow to the heart and injuring heart muscles because of lack of oxygen supply. The symptoms of MI include chest pain, which travels from left arm to neck, shortness of breath, sweating, nausea, vomiting, abnormal heart beating, anxiety, fatigue, weakness, stress, depression, and other factors. The immediate treatment of MI include, taking aspirin, which prevents blood from clotting, and nitro-glycerin to treat chest pain and oxygen. The heart attack can be prevented by taking an earlier action to lower those risks by controlling diet, fat, cholesterol, salt, smoking, nicotine, alcohol, drugs, monitoring of blood pressure every week, doing exercise every day, and loosing body weight. The treatment of MI includes, aspirin tablets, and to dissolve arterial blockage injection of thrombolytic or clot dissolving drugs such as tissue plasminogen activator, streptokinase or urokinase in blood within 3 h of the onset of a heart attack. The painkillers such as morphine or meperidine can be administered to relieve pain. Nitroglycerin and antihypertensive drugs such as beta-blockers, ACE inhibitors or calcium channel blockers may also be used to lower blood pressure and to improve the oxygen demand of heart. The ECG, coronary angiography and X-ray of heart and blood vessels can be performed to observe the narrowing of coronary arteries. In this article the causes, symptoms and treatments of MI are described.

  20. Low birth weight in response to salt restriction during pregnancy is not due to alterations in uterine-placental blood flow or the placental and peripheral renin-angiotensin system.

    PubMed

    Leandro, Sandra Márcia; Furukawa, Luzia Naôko Shinohara; Shimizu, Maria Heloisa Massola; Casarini, Dulce Elena; Seguro, Antonio Carlos; Patriarca, Giuliana; Coelho, Michella Soares; Dolnikoff, Miriam Sterman; Heimann, Joel Claudio

    2008-09-03

    A number of studies conducted in humans and in animals have observed that events occurring early in life are associated with the development of diseases in adulthood. Salt overload and restriction during pregnancy and lactation are responsible for functional (hemodynamic and hormonal) and structural alterations in adult offspring. Our group observed that lower birth weight and insulin resistance in adulthood is associated with salt restriction during pregnancy. On the other hand, perinatal salt overload is associated with higher blood pressure and higher renal angiotensin II content in adult offspring. Therefore, we hypothesised that renin-angiotensin system (RAS) function is altered by changes in sodium intake during pregnancy. Such changes may influence fetoplacental blood flow and thereby fetal nutrient supply, with effects on growth in utero and, consequently, on birth weight. Female Wistar rats were fed low-salt (LS), normal-salt (NS), or high-salt (HS) diet, starting before conception and continuing until day 19 of pregnancy. Blood pressure, heart rate, fetuses and dams' body weight, placentae weight and litter size were measured on day 19 of pregnancy. Cardiac output, uterine and placental blood flow were also determined on day 19. Expressions of renin-angiotensin system components and of the TNF-alpha gene were evaluated in the placentae. Plasma renin activity (PRA) and plasma and tissue angiotensin-converting enzyme (ACE) activity, as well as plasma and placental levels of angiotensins I, II, and 1-7 were measured. Body weight and kidney mass were greater in HS than in NS and LS dams. Food intake did not differ among the maternal groups. Placental weight was lower in LS dams than in NS and HS dams. Fetal weight was lower in the LS group than in the NS and HS groups. The PRA was greater in LS dams than in NS and HS dams, although ACE activity (serum, cardiac, renal, and placental) was unaffected by the level of sodium intake. Placental levels of

  1. MYOCARDIAL AKT: THE OMNIPRESENT NEXUS

    PubMed Central

    Sussman, Mark A.; Völkers, Mirko; Fischer, Kimberlee; Bailey, Brandi; Cottage, Christopher T.; Din, Shabana; Gude, Natalie; Avitabile, Daniele; Alvarez, Roberto; Sundararaman, Balaji; Quijada, Pearl; Mason, Matt; Konstandin, Mathias H.; Malhowski, Amy; Cheng, Zhaokang; Khan, Mohsin; McGregor, Michael

    2013-01-01

    One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses. PMID:21742795

  2. Diurnal variations in myocardial metabolism.

    PubMed

    Bray, Molly S; Young, Martin E

    2008-07-15

    The heart is challenged by a plethora of extracellular stimuli over the course of a normal day, each of which distinctly influences myocardial contractile function. It is therefore not surprising that myocardial metabolism also oscillates in a time-of-day dependent manner. What is becoming increasingly apparent is that the heart exhibits diurnal variations in its intrinsic properties, including responsiveness to extracellular stimuli. This article summarizes our current knowledge regarding the mechanism(s) mediating diurnal variations in myocardial metabolism. Particular attention is focused towards the intramyocardial circadian clock, a cell autonomous molecular mechanism that appears to regulate myocardial metabolism both directly (e.g. triglyceride and glycogen metabolism) and indirectly (through modulation of the responsiveness of the myocardium to workload, insulin, and fatty acids). In doing so, the circadian clock within the cardiomyocyte allows the heart to anticipate environmental stimuli (such as changes in workload, feeding status) prior to their onset. This synchronization between the myocardium and its environment is enhanced by regular feeding schedules. Conversely, loss of synchronization may occur through disruption of the circadian clock and/or diurnal variations in neurohumoral factors (as observed during diabetes mellitus). Here, we discuss the possibility that loss of synchronization between the heart and its environment predisposes the heart to metabolic maladaptation and subsequent myocardial contractile dysfunction.

  3. Regional myocardial downregulation of the inhibitory guanosine triphosphate-binding protein (Gi alpha 2) and beta-adrenergic receptors in a porcine model of chronic episodic myocardial ischemia.

    PubMed Central

    Hammond, H K; Roth, D A; McKirnan, M D; Ping, P

    1993-01-01

    Regional myocardial ischemia is associated with increased levels of adenosine and norepinephrine, factors that may alter activation of the beta-adrenergic receptor (beta AR)-G protein-adenylyl cyclase pathway in the heart. We have used the ameroid constrictor model to determine whether alterations in myocardial signal transduction through the beta AR-G protein-adenylyl cyclase pathway occur in the setting of chronic episodes of reversible ischemia. Pigs were instrumented with ameroid occluders placed around the left circumflex coronary artery. 5 wk later, after ameroid closure, flow and function were normal in the ischemic bed, but flow (P = 0.001) and function (P < 0.03) were abnormal when metabolic demands were increased. The ischemic bed showed a reduction in myocardial beta AR number (P < 0.005). Despite regional downregulation of myocardial beta AR number, adenylyl cyclase activity was similar in the ischemic and control beds. Quantitative immunoblotting showed that the cardiac inhibitory GTP-binding protein, Gi alpha 2, was decreased in the ischemic bed (P = 0.02). In contrast, the cardiac stimulatory GTP-binding protein, Gs alpha, was increased in endocardial sections from the ischemic bed (P = < 0.05). Decreased Gi alpha 2 content was associated with decreased inhibition of adenylyl cyclase. Reduced Gi alpha 2 content, in conjunction with increased Gs alpha content in the endocardium, may provide a means by which adrenergic activation is maintained in the setting of chronic episodic myocardial ischemia. Images PMID:8254020

  4. Acute inferior myocardial infarction in a patient with a prosthetic aortic valve and high international normalized ratio

    PubMed Central

    Sari, Ibrahim; Delil, Kenan; Ileri, Cigdem; Samadov, Fuad

    2014-01-01

    ST elevation acute myocardial infarction in patients with a mechanical prosthetic valve is rare and usually due to inadequate anticoagulation. We present a case of acute inferior myocardial infarction in a patient with a prosthetic aortic valve and high international normalized ratio, which has not been reported previously. PMID:24799934

  5. How reliable is myocardial imaging in the diagnosis of acute myocardial infarction

    SciTech Connect

    Willerson, J.T.

    1983-01-01

    Myocardial scintigraphic techniques available presently allow a sensitive and relatively specific diagnosis of acute myocardial infarction when they are used correctly, although every technique has definite limitations. Small myocardial infarcts (less than 3 gm.) may be missed, and there are temporal limitations in the usefulness of the scintigraphic techniques. The development of tomographic methodology that may be used with single-photon radionuclide emitters (including technetium and /sup 201/Tl will allow the detection of relatively small abnormalities in myocardial perfusion and regions of myocardial infarction and will help to provide a more objective interpretation of the myocardial scintigrams. The use of overlay techniques allowing simultaneous assessment of myocardial perfusion, infarct-avid imaging, and radionuclide ventriculograms will provide insight into the relevant aspects of the extent of myocardial damage, the relationship of damage to myocardial perfusion, and the functional impact of myocardial infarction on ventricular performance.

  6. Attention Alters Perceived Attractiveness.

    PubMed

    Störmer, Viola S; Alvarez, George A

    2016-04-01

    Can attention alter the impression of a face? Previous studies showed that attention modulates the appearance of lower-level visual features. For instance, attention can make a simple stimulus appear to have higher contrast than it actually does. We tested whether attention can also alter the perception of a higher-order property-namely, facial attractiveness. We asked participants to judge the relative attractiveness of two faces after summoning their attention to one of the faces using a briefly presented visual cue. Across trials, participants judged the attended face to be more attractive than the same face when it was unattended. This effect was not due to decision or response biases, but rather was due to changes in perceptual processing of the faces. These results show that attention alters perceived facial attractiveness, and broadly demonstrate that attention can influence higher-level perception and may affect people's initial impressions of one another.

  7. Myocardial Architecture, Mechanics, and Fibrosis in Congenital Heart Disease

    PubMed Central

    Ghonim, Sarah; Voges, Inga; Gatehouse, Peter D.; Keegan, Jennifer; Gatzoulis, Michael A.; Kilner, Philip J.; Babu-Narayan, Sonya V.

    2017-01-01

    Congenital heart disease (CHD) is the most common category of birth defect, affecting 1% of the population and requiring cardiovascular surgery in the first months of life in many patients. Due to advances in congenital cardiovascular surgery and patient management, most children with CHD now survive into adulthood. However, residual and postoperative defects are common resulting in abnormal hemodynamics, which may interact further with scar formation related to surgical procedures. Cardiovascular magnetic resonance (CMR) has become an important diagnostic imaging modality in the long-term management of CHD patients. It is the gold standard technique to assess ventricular volumes and systolic function. Besides this, advanced CMR techniques allow the acquisition of more detailed information about myocardial architecture, ventricular mechanics, and fibrosis. The left ventricle (LV) and right ventricle have unique myocardial architecture that underpins their mechanics; however, this becomes disorganized under conditions of volume and pressure overload. CMR diffusion tensor imaging is able to interrogate non-invasively the principal alignments of microstructures in the left ventricular wall. Myocardial tissue tagging (displacement encoding using stimulated echoes) and feature tracking are CMR techniques that can be used to examine the deformation and strain of the myocardium in CHD, whereas 3D feature tracking can assess the twisting motion of the LV chamber. Late gadolinium enhancement imaging and more recently T1 mapping can help in detecting fibrotic myocardial changes and evolve our understanding of the pathophysiology of CHD patients. This review not only gives an overview about available or emerging CMR techniques for assessing myocardial mechanics and fibrosis but it also describes their clinical value and how they can be used to detect abnormalities in myocardial architecture and mechanics in CHD patients. PMID:28589126

  8. Myocardial contrast echo effect: the dilemma of coronary blood flow and volume.

    PubMed

    Rovai, D; DeMaria, A N; L'Abbate, A

    1995-07-01

    Despite the useful information provided by myocardial contrast echocardiography, the meaning of myocardial contrast intensity remains elusive. This review is meant to define the contribution of physical and biologic factors in producing myocardial contrast and to elucidate the relative roles of coronary blood flow and intramyocardial blood volume in determining contrast effect. The main physical factors influencing the contrast echo effect include the properties of microbubbles as scattering elements (mainly their radius, compressibility, stability and concentration), electronic signal processing, instrument setting and contrast-induced signal attenuation. The effect of these factors can be limited by an appropriate experimental or clinical setup. Biologic factors are less easily controllable, and changes in coronary blood flow and alterations in myocardial blood volume appear to be the main determinants of myocardial contrast intensity. Moreover, these factors influence contrast intensity in opposite directions. Both the area under the time-intensity curve and the mean transit time of myocardial contrast are inversely related to coronary blood flow but directly related to myocardial vascularity and blood volume. Therefore, an increase in coronary flow not accompanied by an increase in myocardial vascularity and volume is accompanied by a decrease in the area under the curve and mean transit time of contrast. Conversely, an increase in coronary flow mediated by augmented myocardial vascularity and volume will produce an increase in the area under the curve and mean transit time. A better understanding of the physical and biologic determinants of contrast echo intensity will be fundamental in the clinical application of new agents and technologies.

  9. Morphological aspects of myocardial bridges.

    PubMed

    Lujinović, Almira; Kulenović, Amela; Kapur, Eldan; Gojak, Refet

    2013-11-01

    Although some myocardial bridges can be asymptomatic, their presence often causes coronary disease either through direct compression of the "tunnel" segment or through stimulation and accelerated development of atherosclerosis in the segment proximally to the myocardial bridge. The studied material contained 30 human hearts received from the Department of Anatomy. The hearts were preserved 3 to 5 days in 10% formalin solution. Thereafter, the fatty tissue was removed and arterial blood vessels prepared by careful dissection with special reference to the presence of the myocardial bridges. Length and thickness of the bridges were measured by the precise electronic caliper. The angle between the myocardial bridge fibre axis and other axis of the crossed blood vessel was measured by a goniometer. The presence of the bridges was confirmed in 53.33% of the researched material, most frequently (43.33%) above the anterior interventricular branch. The mean length of the bridges was 14.64 ± 9.03 mm and the mean thickness was 1.23 ± 1.32 mm. Myocardial bridge fibres pass over the descending blood vessel at the angle of 10-90 degrees. The results obtained on a limited sample suggest that the muscular index of myocardial bridge is the highest for bridges located on RIA, but that the difference is not significant in relation to bridges located on other branches. The results obtained suggest that bridges located on other branches, not only those on RIA, could have a great contractive power and, consequently, a great compressive force, which would be exerted on the wall of a crossed blood vessel.

  10. Morphological aspects of myocardial bridges

    PubMed Central

    Lujinović, Almira; Kulenović, Amela; Kapur, Eldan; Gojak, Refet

    2013-01-01

    Although some myocardial bridges can be asymptomatic, their presence often causes coronary disease either through direct compression of the “tunnel” segment or through stimulation and accelerated development of atherosclerosis in the segment proximally to the myocardial bridge. The studied material contained 30 human hearts received from the Department of Anatomy. The hearts were preserved 3 to 5 days in 10% formalin solution. Thereafter, the fatty tissue was removed and arterial blood vessels prepared by careful dissection with special reference to the presence of the myocardial bridges. Length and thickness of the bridges were measured by the precise electronic caliper. The angle between the myocardial bridge fibre axis and other axis of the crossed blood vessel was measured by a goniometer. The presence of the bridges was confirmed in 53.33% of the researched material, most frequently (43.33%) above the anterior interventricular branch. The mean length of the bridges was 14.64±9.03 mm and the mean thickness was 1.23±1.32 mm. Myocardial bridge fibres pass over the descending blood vessel at the angle of 10-90 degrees. The results obtained on a limited sample suggest that the muscular index of myocardial bridge is the highest for bridges located on RIA, but that the difference is not significant in relation to bridges located on other branches. The results obtained suggest that bridges located on other branches, not only those on RIA, could have a great contractive power and, consequently, a great compressive force, which would be exerted on the wall of a crossed blood vessel. PMID:24289755

  11. Multifunctional MR monitoring of the healing process after myocardial infarction.

    PubMed

    Bönner, Florian; Jacoby, Christoph; Temme, Sebastian; Borg, Nadine; Ding, Zhaoping; Schrader, Jürgen; Flögel, Ulrich

    2014-01-01

    Healing of the myocardium after infarction comprises a variety of local adaptive processes which contribute to the functional outcome after the insult. Therefore, we aimed to establish a setting for concomitant assessment of regional alterations in contractile function, morphology, and immunological state to gain prognostic information on cardiac recovery after infarction. For this, mice were subjected to myocardial ischemia/reperfusion (I/R) and monitored for 28 days by cine MRI, T2 mapping, late gadolinium enhancement (LGE), and (19)F MRI. T2 values were calculated from gated multi-echo sequences. (19)F-loaded nanoparticles were injected intravenously for labelling circulating monocytes and making them detectable by (19)F MRI. In-house developed software was used for regional analysis of cine loops, T2 maps, LGE, and (19)F images to correlate local wall movement, tissue damage as well as monocyte recruitment over up to 200 sectors covering the left ventricle. This enabled us to evaluate simultaneously zonal cardiac necrosis, oedema, and inflammation patterns together with sectional fractional shortening (FS) and global myocardial function. Oedema, indicated by a rise in T2, showed a slightly better correlation with FS than LGE. Regional T2 values increased from 19 ms to above 30 ms after I/R. In the course of the healing process oedema resolved within 28 days, while myocardial function recovered. Infiltrating monocytes could be quantitatively tracked by (19)F MRI, as validated by flow cytometry. Furthermore, (19)F MRI proved to yield valuable insight on the outcome of myocardial infarction in a transgenic mouse model. In conclusion, our approach permits a comprehensive surveillance of key processes involved in myocardial healing providing independent and complementary information for individual prognosis.

  12. Acute Myocardial Ischemia: Cellular Mechanisms Underlying ST Segment Elevation

    PubMed Central

    Di Diego, José M.; Antzelevitch, Charles

    2014-01-01

    The electrocardiogram (ECG) is an essential tool for the diagnosis of acute myocardial ischemia in the emergency department, as well as for that of an evolving acute myocardial infarction (AMI). Changes in the surface ECG in leads whose positive poles face the ischemic region are known to be related to injury currents flowing across the boundaries between the ischemic and the surrounding normal myocardium. Although experimental studies have also shown an endocardium to epicardium differential sensitivity to the effect of acute ischemia, the important contribution of this transmural heterogeneous response to the changes observed in the surface ECG are less appreciated by the clinical cardiologist. This review briefly discusses our current knowledge regarding the electrophysiology of the ischemic myocardium focusing primarily on the electrophysiologic changes underlying the ECG alterations observed at the onset of a transmural AMI. PMID:24742586

  13. In vivo heat shock protects rat myocardial mitochondria.

    PubMed

    Bornman, L; Steinmann, C M; Gericke, G S; Polla, B S

    1998-05-29

    Heat shock (HS)/stress proteins (HSP) provide protection from a variety of stresses other than HS, including oxidative stress and mitochondria have been implicated as the target of HS-related protection in stressed cultured cells. Here we investigated whether mitochondria also are targets for the HS-mediated protection in vivo. Sprague Dawley rats were exposed, or not, to HS (41 degrees C, 15 min). After a 21 h recovery period, hearts were excised and perfused with or without H2O2 (0.15 mM). Myocardial mitochondria were then isolated, and their oxygen consumption was analyzed. HS prevented H2O2-induced alterations in state 3 respiration while increasing the expression of Hsp70 and heme oxygenase (HO). Thus, in vivo HS protects rat myocardial mitochondrial respiration against the deleterious effects of oxidative injury, a protection relating to Hsp70 and/or HO and targeting state 3 respiration.

  14. Paraganglioma causing a myocardial infarction

    PubMed Central

    DeMers, Gerard; Portouw, Steve

    2012-01-01

    Paragangliomas, extra-adrenal pheochromocytomas, are rare and classically associated with sustained or paroxysmal hypertension, headache, perspiration, palpitations, and anxiety. A 49-year-old male, parachute instructor, likely developed a hypertensive emergency when deploying his parachute leading to a myocardial infarction. A para-aortic tumor was incidentally discovered during the patient's emergency department work-up and was eventually surgically resected. He had no evidence of coronary disease during his evaluation. This case shows that a myocardial infarction may be the initial manifestation of these neuroendocrine tumors. Hypertensive emergency, much less elevated blood pressure may not be present at time of presentation. PMID:22787353

  15. Myocardial Mapping With Cardiac Magnetic Resonance: The Diagnostic Value of Novel Sequences.

    PubMed

    Sanz, Javier; LaRocca, Gina; Mirelis, Jesús G

    2016-09-01

    Cardiac magnetic resonance has evolved into a crucial modality for the evaluation of cardiomyopathy due to its ability to characterize myocardial structure and function. In the last few years, interest has increased in the potential of "mapping" techniques that provide direct and objective quantification of myocardial properties such as T1, T2, and T2* times. These approaches enable the detection of abnormalities that affect the myocardium in a diffuse fashion and/or may be too subtle for visual recognition. This article reviews the current state of myocardial T1 and T2-mapping in both health and disease.

  16. Myocardial tissue engineering using electrospun nanofiber composites

    PubMed Central

    Kim, Pyung-Hwan; Cho, Je-Yoel

    2016-01-01

    Emerging trends for cardiac tissue engineering are focused on increasing the biocompatibility and tissue regeneration ability of artificial heart tissue by incorporating various cell sources and bioactive molecules. Although primary cardiomyocytes can be successfully implanted, clinical applications are restricted due to their low survival rates and poor proliferation. To develop successful cardiovascular tissue regeneration systems, new technologies must be introduced to improve myocardial regeneration. Electrospinning is a simple, versatile technique for fabricating nanofibers. Here, we discuss various biodegradable polymers (natural, synthetic, and combinatorial polymers) that can be used for fiber fabrication. We also describe a series of fiber modification methods that can increase cell survival, proliferation, and migration and provide supporting mechanical properties by mimicking micro-environment structures, such as the extracellular matrix (ECM). In addition, the applications and types of nanofiber-based scaffolds for myocardial regeneration are described. Finally, fusion research methods combined with stem cells and scaffolds to improve biocompatibility are discussed. [BMB Reports 2016; 49(1): 26-36] PMID:26497579

  17. Thallium-201 myocardial scintigraphy in acute myocardial infarction and ischemia

    SciTech Connect

    Wackers, F.J.

    1982-04-01

    Thallium-201 scintigraphy provides a sensitive and reliable method of detecting acute myocardial infarction and ischemia when imaging is performed with understanding of the temporal characteristics and accuracy of the technique. The results of scintigraphy are related to the time interval between onset of symptoms and time of imaging. During the first 6 hr after chest pain almost all patients with acute myocardial infarction and approximately 50% of the patients with unstable angina will demonstrate /sup 201/TI pefusion defects. Delayed imaging at 2-4 hr will permit distinction between ischemia and infarction. In patients with acute myocardial infarction, the size of the perfusion defect accurately reflects the extent of the infarcted and/or jeopardized myocardium, which may be used for prognostic stratification. In view of the characteristics of /sup 201/TI scintigraphy, the most practical application of this technique is in patients in whom myocardial infarction has to be ruled out, and for early recognition of patients at high risk for complications.

  18. Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.

    PubMed

    Nishijo, Muneko; Tai, Pham The; Anh, Nguyen Thi Nguyet; Nghi, Tran Ngoc; Nakagawa, Hideaki; Van Luong, Hoang; Anh, Tran Hai; Morikawa, Yuko; Waseda, Tomoo; Kido, Teruhiko; Nishijo, Hisao

    2015-01-01

    In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that

  19. Urinary Amino Acid Alterations in 3-Year-Old Children with Neurodevelopmental Effects due to Perinatal Dioxin Exposure in Vietnam: A Nested Case-Control Study for Neurobiomarker Discovery

    PubMed Central

    Nishijo, Muneko; Tai, Pham The; Anh, Nguyen Thi Nguyet; Nghi, Tran Ngoc; Nakagawa, Hideaki; Van Luong, Hoang; Anh, Tran Hai; Morikawa, Yuko; Waseda, Tomoo; Kido, Teruhiko; Nishijo, Hisao

    2015-01-01

    In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that

  20. Regional myocardial three-dimensional principal strains during postinfarction remodeling.

    PubMed

    Pilla, James J; Koomalsingh, Kevin J; McGarvey, Jeremy R; Witschey, Walter R T; Dougherty, Larry; Gorman, Joseph H; Gorman, Robert C

    2015-03-01

    The purpose of this study was to quantify myocardial three-dimensional (3D) principal strains as the left ventricle (LV) remodels after myocardial infarction (MI). Serial quantification of myocardial strains is important for understanding the mechanical response of the LV to MI. Principal strains convert the 3D LV wall-based strain matrix with three normal and three shear elements, to a matrix with three nonzero normal elements, thereby eliminating the shear elements, which are difficult to physically interpret. The study was designed to measure principal strains of the remote, border zone, and infarct regions in a porcine model of post-MI LV remodeling. Magnetic resonance imaging was used to measure function and strain at baseline, 1 week, and 4 weeks after infarct. Principal strain was measured using 3D acquisition and the optical flow method for displacement tracking. Principal strains were altered as the LV remodeled. Maximum principal strain magnitude decreased in all regions, including the noninfarcted remote, while maximum principal strain angles rotated away from the radial direction in the border zone and infarct. Minimum principal strain magnitude followed a similar pattern; however, strain angles were altered in all regions. Evolution of principal strains correlated with adverse LV remodeling. Using a state-of-the-art imaging and optical flow method technique, 3D principal strains can be measured serially after MI in pigs. Results are consistent with progressive infarct stretching as well as with decreased contractile function in the border zone and remote myocardial regions. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Regional heterogeneity in cardiac sympathetic innervation in acute myocardial infarction: relationship with myocardial oedema on magnetic resonance.

    PubMed

    Gimelli, Alessia; Masci, Pier Giorgio; Liga, Riccardo; Grigoratos, Chrysanthos; Pasanisi, Emilio Maria; Lombardi, Massimo; Marzullo, Paolo

    2014-09-01

    To assess the relationships between myocardial structure and function on cardiac magnetic resonance (CMR) imaging and sympathetic tone on (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy early after myocardial infarction (MI). Ten patients underwent (123)I-MIBG and (99m)Tc-tetrofosmin rest cadmium zinc telluride scintigraphy 4 ± 1 days after MI. The segmental left ventricular (LV) relative radiotracer uptake of both (99m)Tc-tetrofosmin and early (123)I-MIBG was calculated. The day after scintigraphy, on CMR imaging, the extent of ischaemia-related oedema and of myocardial fibrosis (late gadolinium enhancement, LGE) was assessed. Accordingly, the extent of oedema and LGE was evaluated for each segment and segmental wall thickening determined. Based on LGE distribution, LV segments were categorized as "infarcted" (56 segments), "adjacent" (66 segments) or "remote" (48 segments). Infarcted segments showed a more depressed systolic wall thickening and greater extent of oedema than adjacent segments (p < 0.001) and remote segments (p < 0.001). Interestingly, while uptake of (99m)Tc-tetrofosmin was significantly depressed only in infarcted segments (p < 0.001 vs. both adjacent and remote segments), uptake of (123)I-MIBG was impaired not only in infarcted segments (p < 0.001 vs. remote) but also in adjacent segments (p = 0.024 vs. remote segments). At the regional level, after correction for (99m)Tc-tetrofosmin and LGE distribution, segmental (123)I-MIBG uptake (p < 0.001) remained an independent predictor of ischaemia-related oedema. After acute MI the regional impairment of sympathetic tone extends beyond the area of altered myocardial perfusion and is associated with myocardial oedema.

  2. Carnosic acid promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress and apoptosis in mice.

    PubMed

    Sahu, Bidya Dhar; Putcha, Uday Kumar; Kuncha, Madhusudana; Rachamalla, Shyam Sunder; Sistla, Ramakrishna

    2014-09-01

    Carnosic acid is a well-known antioxidant. Recently, it has been identified as modulator of nuclear factor erythroid 2-related factor 2 (Nrf2). The effect of carnosic acid in the context of cardiovascular disorders has not been studied. In the present study, we investigated the beneficial effect and the underlying cardioprotective mechanism of carnosic acid by using mouse model of isoproterenol (ISO)-induced myocardial stress. Elevated serum levels of Troponin I, CK-MB, LDH, SGOT and SGPT, and myofibrillar degeneration with necrotic damage, and the presence of epicardial inflammatory infiltrate (H & E staining) confirmed the ISO-induced myocardial stress. Myocardial content of vitamin C, reduced glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, quinine oxidoreductase 1, superoxide dismutase, catalase, nuclear translocation of Nrf2 and protein expression heme oxygenase-1 were evaluated. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and myocardial expression of cleaved caspase-3, caspase-9, p53, Bax, and Bcl-2 were investigated to assess the apoptotic cell death. Pretreatment with carnosic acid attenuated ISO-induced elevated serum levels of Troponin I, CK-MB, LDH, SGOT and SGPT, and histopathological alterations in heart. Moreover, carnosic acid enhanced the nuclear translocation of Nrf2 and up-regulated the phase II/antioxidant enzyme activities. Furthermore, TUNEL assay and apoptosis-related protein analysis indicated that carnosic acid prevented ISO-induced cardiomyocyte apoptosis. Isoproterenol-induced myocardial lipid peroxidation and protein oxidation were also significantly decreased by carnosic acid pretreatment. The overall results clearly indicate that therapeutic application of carnosic acid might be beneficial in treating cardiovascular disorders.

  3. Coupled agent-based and finite-element models for predicting scar structure following myocardial infarction.

    PubMed

    Rouillard, Andrew D; Holmes, Jeffrey W

    2014-08-01

    Following myocardial infarction, damaged muscle is gradually replaced by collagenous scar tissue. The structural and mechanical properties of the scar are critical determinants of heart function, as well as the risk of serious post-infarction complications such as infarct rupture, infarct expansion, and progression to dilated heart failure. A number of therapeutic approaches currently under development aim to alter infarct mechanics in order to reduce complications, such as implantation of mechanical restraint devices, polymer injection, and peri-infarct pacing. Because mechanical stimuli regulate scar remodeling, the long-term consequences of therapies that alter infarct mechanics must be carefully considered. Computational models have the potential to greatly improve our ability to understand and predict how such therapies alter heart structure, mechanics, and function over time. Toward this end, we developed a straightforward method for coupling an agent-based model of scar formation to a finite-element model of tissue mechanics, creating a multi-scale model that captures the dynamic interplay between mechanical loading, scar deformation, and scar material properties. The agent-based component of the coupled model predicts how fibroblasts integrate local chemical, structural, and mechanical cues as they deposit and remodel collagen, while the finite-element component predicts local mechanics at any time point given the current collagen fiber structure and applied loads. We used the coupled model to explore the balance between increasing stiffness due to collagen deposition and increasing wall stress due to infarct thinning and left ventricular dilation during the normal time course of healing in myocardial infarcts, as well as the negative feedback between strain anisotropy and the structural anisotropy it promotes in healing scar. The coupled model reproduced the observed evolution of both collagen fiber structure and regional deformation following coronary

  4. Detection of Phosphomonoester Signals in Proton-Decoupled 31P NMR Spectra of the Myocardium of Patients with Myocardial Hypertrophy

    NASA Astrophysics Data System (ADS)

    Jung, Wulf-Ingo; Sieverding, Ludger; Breuer, Johannes; Schmidt, Oliver; Widmaier, Stefan; Bunse, Michael; van Erckelens, Franz; Apitz, Jürgen; Dietze, Guenther J.; Lutz, Otto

    1998-07-01

    Proton-decoupled31P NMR spectroscopy at 1.5 T of the anterior left ventricular myocardium was used to monitor myocardial phosphate metabolism in asymptomatic patients with hypertrophic cardiomyopathy (HCM,n= 14) and aortic stenosis (AS,n= 12). In addition to the well-known phosphorus signals a phosphomonoester (PME) signal was detected at about 6.9 ppm in 7 HCM and 2 AS patients. This signal was not observed in the spectra of normal controls (n= 11). We suggest that in spectra of patients with myocardial hypertrophy the presence of a PME signal reflects alterations in myocardial glucose metabolism.

  5. In vivo induction of antioxidant response and oxidative stress associated with genotoxicity and histopathological alteration in two commercial fish species due to heavy metals exposure in northern India (Kali) river.

    PubMed

    Fatima, Mahino; Usmani, Nazura; Firdaus, Fakiha; Zafeer, Mohammad Faraz; Ahmad, Shafeeque; Akhtar, Kafil; Dawar Husain, S M; Ahmad, Mir Hilal; Anis, Ehraz; Mobarak Hossain, M

    2015-01-01

    Heavy metals can significantly bioaccumulate in fish tissues. The step wise mechanism of heavy metal toxicities on fish health is still limited. The present study assessed the tissue-specific antioxidant response and oxidative stress biomarkers of commercially important fish species namely, Channa striatus and Heteropneustes fossilis inhabiting Kali River of northern India where heavy-metal load is beyond the World Health Organisation - maximum permissible limits. Heavy metals chromium (Cr), nickel (Ni), lead (Pb) and cadmium (Cd) were elevated in both fish species compared to recommended values of the Federal Environmental Protection Agency (FEPA), 1999 for edible fishes. Reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CATA) activities in all tissues (brachial, neural, renal and hepatic) were altered. Cellular lipid and protein compromisation in both fishes induced by heavy metals was determined by lipid peroxidation (LPO) and protein carbonylation (PC) assays. Micronucleus (MN) test of erythrocytes and comet assay of liver cells confirmed genotoxicity. Histopathology of the liver, kidney and brain of affected fishes was distorted significantly with its reference fishes thereby affecting the quality and quantity of these fish stocks. This raises a serious concern as these fishes are consumed by the local population which would ultimately affect human health.

  6. Pathophysiology of technetium-99m stannous pyrophosphate and thallium-201 scintigraphy of acute anterior myocardial infarcts in dogs.

    PubMed Central

    Buja, L M; Parkey, R W; Stokely, E M; Bonte, F J; Willerson, J T

    1976-01-01

    In 17 dogs with acute myocardial infarcts produced by ligation of the proximal left anterior descending coronary artery, a comparative study was made of myocardial scintigrams obtained with technetium-99m stannous pyrophosphate (99mTc-PYP) and thallium-201 (201T1), tissue levels of 99mTc-PYP and 201T1 uptake, histopathologic alterations, and regional myocardial perfusion measured with radioactive microspheres. 9 of the 10 hearts examined histologically had transmural infarcts with outer peripheral, inner peripheral, and central zones characterized by distinctive histopathologic features. A progressive reduction in myocardial blood flow was demonstrated between normal myocardium and the centers of the infarcts, and correlated well with progressive reduction in 201T1 upatke in the same regions. Marked 99mTc-PYP concentration occurred in areas with partial to homogeneous myocardial necrosis and residual perfusion located in the outer peripheral regions of the infarcts. The latter areas also were characterized by the presence of muscle cell calcification. The patterns of distribution of 99mTc-PYP and 201T1 explained the filling defects on 201T1 myocardial scintigrams and the doughnut patterns on 99mTc-PYP myocardial scintigrams in dogs with transmural infarcts. One dog with a subendocardial infarct had a small homogeneous area of activity on the 99mTc-PYP myocardial scintigram, and showed marked uptake of 99mTc-PYP in subendocardial areas of extensive necrosis and calcification still receiving some coronary perfusion. Thus, the data indicate that the status of regional myocardial perfusion is a key determinant for the occurrence of distinctive patterns of myocardial necrosis and for the scintigraphic detection of acute myocardial infarcts with 99mTc-PYP and 201T1. Images PMID:180053

  7. Cardiac rehabilitation improves coronary endothelial function in patients with heart failure due to dilated cardiomyopathy: A positron emission tomography study.

    PubMed

    Legallois, Damien; Belin, Annette; Nesterov, Sergey V; Milliez, Paul; Parienti, J-J; Knuuti, Juhani; Abbas, Ahmed; Tirel, Olivier; Agostini, Denis; Manrique, Alain

    2016-01-01

    Endothelial dysfunction is common in patients with heart failure and is associated with poor clinical outcome. Cardiac rehabilitation is able to enhance peripheral endothelial function but its impact on coronary vasomotion remains unknown. We aimed to evaluate the effect of cardiac rehabilitation on coronary vasomotion in patients with heart failure. We prospectively enrolled 29 clinically stable heart failure patients from non-ischaemic dilated cardiomyopathy and without coronary risk factors. Myocardial blood flow was quantified using (15)-O water positron emission tomography at rest and during a cold pressor test, before and after 12 weeks of cardiac rehabilitation and optimization of medical therapy. Rest myocardial blood flow was significantly improved after the completion of rehabilitation compared to baseline (1.31 ± 0.38 mL/min/g vs. 1.16 ± 0.41 mL/min/g, p = 0.04). The endothelium-related change in myocardial blood flow from rest to cold pressor test and the percentage of myocardial blood flow increase during the cold pressor test were both significantly improved after cardiac rehabilitation (respectively from -0.03 ± 0.22 mL/min/g to 0.19 ± 0.22 mL/min/g, p < 0.001 and from 101.5 ± 16.5% to 118.3 ± 24.4%, p < 0.001). Left ventricular ejection fraction, plasma levels of brain natriuretic peptide, maximal oxygen consumption and the Minnesota Living with Heart Failure Questionnaire score were also significantly improved. The improvement was not related to uptitration of medical therapy. Coronary endothelial function is altered in patients with heart failure due to non-ischaemic dilated cardiomyopathy. In these patients, cardiac rehabilitation significantly improves coronary vasomotion. © The European Society of Cardiology 2014.

  8. Over-Expression of Catalase in Myeloid Cells Confers Acute Protection Following Myocardial Infarction

    PubMed Central

    Cabigas, E. Bernadette; Somasuntharam, Inthirai; Brown, Milton E.; Che, Pao Lin; Pendergrass, Karl D.; Chiang, Bryce; Taylor, W. Robert; Davis, Michael E.

    2014-01-01

    Cardiovascular disease is the leading cause of death in the United States and new treatment options are greatly needed. Oxidative stress is increased following myocardial infarction and levels of antioxidants decrease, causing imbalance that leads to dysfunction. Therapy involving catalase, the endogenous scavenger of hydrogen peroxide (H2O2), has been met with mixed results. When over-expressed in cardiomyocytes from birth, catalase improves function following injury. When expressed in the same cells in an inducible manner, catalase showed a time-dependent response with no acute benefit, but a chronic benefit due to altered remodeling. In myeloid cells, catalase over-expression reduced angiogenesis during hindlimb ischemia and prevented monocyte migration. In the present study, due to the large inflammatory response following infarction, we examined myeloid-specific catalase over-expression on post-infarct healing. We found a significant increase in catalase levels following infarction that led to a decrease in H2O2 levels, leading to improved acute function. This increase in function could be attributed to reduced infarct size and improved angiogenesis. Despite these initial improvements, there was no improvement in chronic function, likely due to increased fibrosis. These data combined with what has been previously shown underscore the need for temporal, cell-specific catalase delivery as a potential therapeutic option. PMID:24853285

  9. Over-expression of catalase in myeloid cells confers acute protection following myocardial infarction.

    PubMed

    Cabigas, E Bernadette; Somasuntharam, Inthirai; Brown, Milton E; Che, Pao Lin; Pendergrass, Karl D; Chiang, Bryce; Taylor, W Robert; Davis, Michael E

    2014-05-21

    Cardiovascular disease is the leading cause of death in the United States and new treatment options are greatly needed. Oxidative stress is increased following myocardial infarction and levels of antioxidants decrease, causing imbalance that leads to dysfunction. Therapy involving catalase, the endogenous scavenger of hydrogen peroxide (H2O2), has been met with mixed results. When over-expressed in cardiomyocytes from birth, catalase improves function following injury. When expressed in the same cells in an inducible manner, catalase showed a time-dependent response with no acute benefit, but a chronic benefit due to altered remodeling. In myeloid cells, catalase over-expression reduced angiogenesis during hindlimb ischemia and prevented monocyte migration. In the present study, due to the large inflammatory response following infarction, we examined myeloid-specific catalase over-expression on post-infarct healing. We found a significant increase in catalase levels following infarction that led to a decrease in H2O2 levels, leading to improved acute function. This increase in function could be attributed to reduced infarct size and improved angiogenesis. Despite these initial improvements, there was no improvement in chronic function, likely due to increased fibrosis. These data combined with what has been previously shown underscore the need for temporal, cell-specific catalase delivery as a potential therapeutic option.

  10. Long-term obesity promotes alterations in diastolic function induced by reduction of phospholamban phosphorylation at serine-16 without affecting calcium handling

    PubMed Central

    Leopoldo, André S.; da Silva, Danielle C. T.; do Nascimento, André F.; de Campos, Dijon H. S.; Luvizotto, Renata A. M.; de Deus, Adriana F.; Freire, Paula P.; Medeiros, Alessandra; Okoshi, Katashi; Cicogna, Antonio C.

    2014-01-01

    Few studies have evaluated the relationship between the duration of obesity, cardiac function, and the proteins involved in myocardial calcium (Ca2+) handling. We hypothesized that long-term obesity promotes cardiac dysfunction due to a reduction of expression and/or phosphorylation of myocardial Ca2+-handling proteins. Thirty-day-old male Wistar rats were distributed into two groups (n = 10 each): control (C; standard diet) and obese (Ob; high-fat diet) for 30 wk. Morphological and histological analyses were assessed. Left ventricular cardiac function was assessed in vivo by echocardiographic evaluation and in vitro by papillary muscle. Cardiac protein expression of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), calsequestrin, L-type Ca2+ channel, and phospholamban (PLB), as well as PLB serine-16 phosphorylation (pPLB Ser16) and PLB threonine-17 phosphorylation (pPLB Thr17) were determined by Western blot. The adiposity index was higher (82%) in Ob rats than in C rats. Obesity promoted cardiac hypertrophy without alterations in interstitial collagen levels. Ob rats had increased endocardial and midwall fractional shortening, posterior wall shortening velocity, and A-wave compared with C rats. Cardiac index, early-to-late diastolic mitral inflow ratio, and isovolumetric relaxation time were lower in Ob than in C. The Ob muscles developed similar baseline data and myocardial responsiveness to increased extracellular Ca2+. Obesity caused a reduction in cardiac pPLB Ser16 and the pPLB Ser16/PLB ratio in Ob rats. Long-term obesity promotes alterations in diastolic function, most likely due to the reduction of pPLB Ser16, but does not impair the myocardial Ca2+ entry and recapture to SR. PMID:24970855

  11. [Myocardial infarction after butane inhalation in a 14-year-old boy].

    PubMed

    Godlewski, Krzysztof; Werner, Bozena; Sterliński, Maciej; Pytkowski, Mariusz; Szwed, Hanna; Domagała, Marek; Koc, Lucyna

    2006-03-01

    Myocardial infarction is a rare disease in children. Among many reasons the toxic damage of myocardium should be taken into consideration. The authors present the case of a 14-year-old boy with sudden cardiac arrest due to ventricular fibrillation and myocardial infarction as a result of butane gas inhalation. Coronary angiography revealed normal coronary arteries. Cardioverter-defibrillator was implanted as a secondary prophylaxis of sudden cardiac death.

  12. Disappearing signs of acute myocardial infarction in a patient with viral myocarditis

    PubMed Central

    Bullón, F. Sarnago; Falzgraf, Sharon; Pedrero, Agustin Camacho; Jimenez, Manuel Abeytua

    1980-01-01

    A case of acute viral myocarditis with the rapid appearance and disappearance of clinical, laboratory, electrocardiographic, and vectorcardiographic signs of acute myocardial infarction is described in this report. Although segmentary alterations in contractility were demonstrated by ventriculography, coronary angiography revealed normal coronary arteries. Images PMID:15216283

  13. Spousal Adjustment to Myocardial Infarction.

    ERIC Educational Resources Information Center

    Ziglar, Elisa J.

    This paper reviews the literature on the stresses and coping strategies of spouses of patients with myocardial infarction (MI). It attempts to identify specific problem areas of adjustment for the spouse and to explore the effects of spousal adjustment on patient recovery. Chapter one provides an overview of the importance in examining the…

  14. Myocardial revascularization in Jehovah Witnesses.

    PubMed

    Seifert, P E; Auer, J E; Hohensee, P

    1989-04-01

    The refusal of certain patients to accept blood transfusions need not be a deterrent to surgery. We report on nine Jehovah's Witnesses who over a one-year period underwent myocardial revascularization without significant blood loss or decrease in hematocrit values.

  15. Imaging techniques for myocardial inflammation

    SciTech Connect

    O'Connell, J.B.; Henkin, R.E.; Robinson, J.A.

    1986-03-01

    Dilated cardiomyopathy (DC) represents a heterogeneous group of disorders which results in morbidity and mortality in young individuals. Recent evidence suggests that a subset of these patients have histologic evidence of myocarditis which is potentially treatable with immunosuppression. The identification of myocardial inflammation may therefore lead to development of therapeutic regimens designed to treat the cause rather than the effect of the myocardial disease. Ultimately, this may result in improvement in the abysmal prognosis of DC. The currently accepted technique for identification of active myocardial inflammation is endomyocardial biopsy. This technique is not perfect, however, since pathologic standards for the diagnosis of myocarditis have not been established. Furthermore, focal inflammation may give rise to sampling error. The inflammation-avid radioisotope gallium-67 citrate has been used as an adjunct to biopsy improving the yield of myocarditis from 7 percent to 36 percent. Serial imaging correlates well to biopsy results. Future studies are designed to study the applicability of lymphocyte labelling techniques to myocardial inflammatory disease.

  16. Severe Hypokalemia Masquerading Myocardial Ischemia

    PubMed Central

    Petrov, Daniel Bogdanov; Sardovski, Svetlozar Ivanov; Milanova, Maria Hristova

    2012-01-01

    An advanced degree of body potassium deficit may produce striking changes in the electrocardiogram (ECG). These changes can result in incidental findings on the 12-lead ECG or precipitate potentially life-threatening dysrhythmias. Although usually readily recognized, at times these abnormalities may be confused with myocardial ischemia. The object was to report a case of severe hypokalemia mimicking myocardial ischemia. A 33-year-old, previously healthy man, presented to the Emergency Department (ED) with a progressive weakness and chest discomfort. The electrocardiogram showed a marked ST-segment depression in leads II, III, aVF, V1-V6. The initial diagnosis was non ST-elevation myocardial infarction. Echocardiography was normal and troponin levels were within normal limits. A more detailed history revealed that the patient had an episode of acute gastroenteritis with diarrhea and vomiting. Serum chemistries were notable for a potassium concentration of 1,8 mmol per liter. With aggressive electrolyte correction, the ECG abnormalities reverted as potassium levels normalized. Hypokalemia induced ST-segment depression may simulate myocardial ischemia. The differential diagnosis might be difficult, especially in the cases when ST changes are accompanied with chest discomfort.

  17. Provoking conditions, management and outcomes of type 2 myocardial infarction and myocardial necrosis.

    PubMed

    Smilowitz, Nathaniel R; Weiss, Matthew C; Mauricio, Rina; Mahajan, Asha M; Dugan, Kaitlyn E; Devanabanda, Arvind; Pulgarin, Claudia; Gianos, Eugenia; Shah, Binita; Sedlis, Steven P; Radford, Martha; Reynolds, Harmony R

    2016-09-01

    Type 2 myocardial infarction (MI) is defined as myocardial necrosis (myonecrosis) due to an imbalance in supply and demand with clinical evidence of ischemia. Some clinical scenarios of supply-demand mismatch predispose to myonecrosis but limit the identification of symptoms and ECG changes referable to ischemia; therefore, the MI definition may not be met. Factors that predispose to type 2 MI and myonecrosis without definite MI, approaches to treatment, and outcomes remain poorly characterized. Patients admitted to an academic medical center with an ICD-9 diagnosis of secondary myocardial ischemia or non-primary diagnosis of non-ST-elevation MI were retrospectively reviewed. Cases were classified as either MI (n=255) or myonecrosis without definite MI (n=220) based on reported symptoms, ischemic ECG changes, and new wall motion abnormalities. Conditions associated with type 2 MI or myonecrosis included non-cardiac surgery (38%), anemia or bleeding requiring transfusion (32%), sepsis (31%), tachyarrhythmia (23%), hypotension (22%), respiratory failure (23%), and severe hypertension (8%). Inpatient mortality was 5%, with no difference between patients with MI and those with myonecrosis (6% vs. 5%, p=0.41). At discharge, only 43% of patients received aspirin and statin therapy. Type 2 MI and myonecrosis occur frequently in the setting of supply-demand mismatch due to non-cardiac surgery, sepsis, or anemia. Myonecrosis without definite MI is associated with similar in-hospital mortality as type 2 MI; both groups warrant further workup for cardiovascular disease. Antiplatelet and statin prescriptions were infrequent at discharge, reflecting physician uncertainty about the role of secondary prevention in these patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Relationship between myocardial viability and the predischarge electrocardiographic pattern in patients with first anterior wall acute myocardial infarction.

    PubMed

    Atak, Ramazan; Turhan, Hasan; Senen, Kubilay; Ileri, Mehmet; Yetkin, Ertan; Ozbakir, Cemal; Demirkan, Deniz

    2003-10-01

    The assessment of residual viability in the infarcted area after an acute myocardial infarction is relevant to subsequent management and prognosis. The aim of this study was to investigate the correlation between myocardial viability after an acute anterior myocardial infarction (AMI) as assessed by low dose dobutamine stress echocardiography (LDDSE) and the electrocardiographic patterns of ST segment and T wave abnormalities at the end of the first week of the acute event. Sixty-nine consecutive patients (51 men, 18 women, mean age+/-standard deviation=57+/-11 years) who admitted to our clinic due to a first episode of transmural AMI were included in this study. Two-dimensional echocardiography was performed to all patients during rest and low dose dobutamine administration at the end of the first week of admission (7+/-2 days). Patients were classified into four groups according to ST segment and T wave morphology: group A, ST elevation < or =0.1 mV and negative T waves; group B, ST elevation < or =0.1 mV and positive T waves; group C, ST elevation > or =0.1 mV and negative T waves and group D, ST elevation > or =0.1 mV and positive T waves. Myocardial viability was detected more often in patients with isoelectric ST segments (22/24, 92%) than those with elevated ST segments (21/45, 47%) (P<0.001). Similarly patients with negative T waves had myocardial viability more frequently compared to those with positive T waves (32/45, 71% vs. 11/24, 46%, P<0.01). Seventeen (94%) of 18 patients in group A and 5 (83%) of six patients in group B had viable myocardium (P>0.05). Myocardial viability was found in 15 (56%) of 27 patients in group C and six (33%) of 18 patients in group D (P<0.01). As a marker of viable myocardium, isoelectricity of ST segment was specific (92%) but only moderately sensitive (51%), with a 92% positive predictive accuracy and a poor (53%) negative predictive value. T wave negativity was less specific but more sensitive than isoelectricity of ST

  19. Myocardial protection in heart surgery.

    PubMed

    Mentzer, Robert M

    2011-01-01

    One of the unmet clinical needs in heart surgery is the prevention of myocardial stunning and necrosis that occurs as a result of ischemia-reperfusion. Myocardial stunning, a frequent consequence after heart surgery, is characterized by a requirement for postoperative inotropic support despite a technically satisfactory heart operation. In high-risk patients with marginal cardiac reserve, stunning is a major cause of prolonged critical care and may be associated with as much as a 5-fold increase in mortality. In contrast, the frequency of myocardial necrosis (myocardial infarction [MI]) after cardiac surgery is less appreciated and its consequences are much more subtle. The consequences may not be apparent for months to years. While we now have a much better understanding of the molecular mechanisms underlying myocardial stunning and MI, we still have no effective way to prevent these complications, nor a consistently effective means to engage the well-studied endogenous mechanisms of cardioprotection. The failure to develop clinically effective interventions is multifactorial and can be attributed to reliance on findings obtained from subcellular and cellular studies, to drawing conclusions from preclinical large animal studies that have been conducted in a disease-free state, and to accepting less than robust surrogate markers of injury in phase II clinical trials. These factors also explain the disappointing failure to identify effective adjuvant therapy in the setting of percutaneous coronary revascularization for acute MI (AMI) and reperfusion injury. These issues have contributed to the disappointing outcomes of large and costly phase III trials, resulting in a lack of enthusiasm on the part of the pharmaceutical industry to engage in further drug development for this indication. The purpose of this review is to (1) define the scope of the clinical problem; (2) summarize the outcomes of selected phases II and III clinical trials; and (3) identify the gap that

  20. Myocardial disarray. A critical review.

    PubMed Central

    Becker, A E; Caruso, G

    1982-01-01

    Myocardial disarray or disorganisation is at present a contentious topic, not least because its value as a clinical marker for hypertrophic cardiomyopathy has changed considerably over the years. Initially observed as one of the features of asymmetric septal hypertrophy, disarray has since been promoted as its pathognomonic histological feature, regarded by some observers as the morphological manifestation of a genetically transmitted myocardial defect. Recently, however, it has become evident that myocardial disarray is not limited to hypertrophic cardiomyopathy, but is encountered in hearts with both congenital and acquired conditions, and is also observed in normal hearts. The specificity of disarray for hypertrophic cardiomyopathy is thus seriously questioned. Latterly, it has been suggested that disarray, judged from through-and-through sections of the ventricular midseptum is a highly specific and sensitive marker of hypertrophic cardiomyopathy when considered in quantitative rather than qualitative fashion. The present study sets out to answer the question whether disarray could be the histological expression of the normal but intricate fibre architecture of the heart, a consideration also initiated by debatable definitions of normality and abnormality of myocardial histology. Gross fibre dissections in five normal hearts showed that many sites occurred in which disarray was a natural phenomenon. In five more hearts it was found that the plane of section of a tissue block might profoundly influence the histology. In fact, tissue cubicles sampled from different faces showed a change in histology in the vast majority. Thus the diagnostic significance of myocardial disarray as a marker of hypertrophic cardiomyopathy in the clinical setting almost vanishes; a change in orientation of a tissue section may actually turn "normality" into "disarray". Images PMID:7044398

  1. Myocardial metabolism during hypoxia: Maintained lactate oxidation during increased glycolysis

    SciTech Connect

    Mazer, C.D.; Stanley, W.C.; Hickey, R.F.; Neese, R.A.; Cason, B.A.; Demas, K.A.; Wisneski, J.A.; Gertz, E.W. )

    1990-09-01

    In the intact animal, myocardial lactate utilization and oxidation during hypoxia are not well understood. Nine dogs were chronically instrumented with flow probes on the left anterior descending coronary artery and with a coronary sinus sampling catheter. ({sup 14}C)lactate and ({sup 13}C)glucose tracers, or ({sup 13}C)lactate and ({sup 14}C)glucose were administered to quantitate lactate and glucose oxidation, lactate conversion to glucose, and simultaneous lactate extraction and release. The animals were anesthetized and exposed to 90 minutes of severe hypoxia (PO2 = 25 +/- 4 torr). Hypoxia resulted in significant increases in heart rate, cardiac output and myocardial blood flow, but no significant change in myocardial oxygen consumption. The arterial/coronary sinus differences for glucose and lactate did not change from normoxia to hypoxia; however, the rate of glucose uptake increased significantly due to the increase in myocardial blood flow. Tracer-measured lactate extraction did not decrease with hypoxia, despite a 250% increase in lactate release. During hypoxia, 90% +/- 4% of the extracted {sup 14}C-lactate was accounted for by the appearance of {sup 14}CO{sub 2} in the coronary sinus, compared with 88% +/- 4% during normoxia. Thus, in addition to the expected increase in glucose uptake and lactate production, we observed an increase in lactate oxidation during hypoxia.

  2. Antioxidant enzymes attenuate myocardial stunning in the conscious dog

    SciTech Connect

    Triana, J.F.; Unisa, A.; Bolli, R. )

    1990-02-26

    Several studies have shown that postischemic myocardial dysfunction (myocardial stunning) is attenuated by antioxidants, implying a pathogenetic role of oxy-radicals in this phenomenon. However, since all these studies have been performed in open-chest preparations, artifacts due to anesthesia, trauma, and other nonphysiologic conditions cannot be excluded. Accordingly, chronically instrumented dogs underwent a 15-minute occlusion (o) of the left anterior descending artery followed by reperfusion. Dogs received i.v. either saline or superoxide dismutase (SOD) plus catalase (CAT) (16,000 U/kg and 55,000 U/kg, respectively, over 1 hour starting 15 minutes before O). Regional myocardial function was assessed as systolic wall thickening (WTh) using a pulsed Doppler probe. WTh after reperfusion was significantly greater in treated dogs, and this difference could not be ascribed to differences in collateral flow or hemodynamics. The authors conclude that SOD plus catalase attenuate myocardial stunning in the conscious dog, indicating that oxy-radicals play a pathogenetic role in this phenomenon under physiologic conditions.

  3. Matching coronary blood flow to myocardial oxygen consumption.

    PubMed

    Tune, Johnathan D; Gorman, Mark W; Feigl, Eric O

    2004-07-01

    At rest the myocardium extracts approximately 75% of the oxygen delivered by coronary blood flow. Thus there is little extraction reserve when myocardial oxygen consumption is augmented severalfold during exercise. There are local metabolic feedback and sympathetic feedforward control mechanisms that match coronary blood flow to myocardial oxygen consumption. Despite intensive research the local feedback control mechanism remains unknown. Physiological local metabolic control is not due to adenosine, ATP-dependent K(+) channels, nitric oxide, prostaglandins, or inhibition of endothelin. Adenosine and ATP-dependent K(+) channels are involved in pathophysiological ischemic or hypoxic coronary dilation and myocardial protection during ischemia. Sympathetic beta-adrenoceptor-mediated feedforward arteriolar vasodilation contributes approximately 25% of the increase in coronary blood flow during exercise. Sympathetic alpha-adrenoceptor-mediated vasoconstriction in medium and large coronary arteries during exercise helps maintain blood flow to the vulnerable subendocardium when cardiac contractility, heart rate, and myocardial oxygen consumption are high. In conclusion, several potential mediators of local metabolic control of the coronary circulation have been evaluated without success. More research is needed.

  4. Myocardial depression in sepsis: from pathogenesis to clinical manifestations and treatment.

    PubMed

    Antonucci, Elio; Fiaccadori, Enrico; Donadello, Katia; Taccone, Fabio Silvio; Franchi, Federico; Scolletta, Sabino

    2014-08-01

    The cardiovascular system plays a key role in sepsis, and septic myocardial depression is a common finding associated with increased morbidity and mortality. Myocardial depression during sepsis is not clearly defined, but it can perhaps be best described as a global (systolic and diastolic) dysfunction of both the left and right sides of the heart. The pathogenesis of septic myocardial depression involves a complex mix of systemic (hemodynamic) factors and genetic, molecular, metabolic, and structural alterations. Pulmonary artery catheterization and modern echo-Doppler techniques are important diagnostic tools in this setting. There are no specific therapies for septic myocardial depression, and the cornerstone of management is control of the underlying infectious process (adequate antibiotic therapy, removal of the source) and hemodynamic stabilization (fluids, vasopressor and inotropic agents). In this review, we will summarize the pathogenesis, diagnosis, and treatment of myocardial depression in sepsis. Additional studies are needed in order to improve diagnosis and identify therapeutic targets in septic myocardial dysfunction. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. ET-receptor antagonism, myocardial gene expression, and ventricular remodeling during CHF in rats.

    PubMed

    Oie, E; Bjønerheim, R; Grogaard, H K; Kongshaug, H; Smiseth, O A; Attramadal, H

    1998-09-01

    Both myocardial and plasma endothelin-1 (ET-1) are elevated in congestive heart failure (CHF). However, the role played by endogenous ET-1 in the progression of CHF remains unknown. The aim of the present study was to investigate and correlate myocardial gene expression programs and left ventricular (LV) remodeling during chronic ET-receptor antagonism in CHF rats. After ligation of the left coronary artery, rats were randomized to oral treatment with a nonselective ET-receptor antagonist (bosentan, 100 mg . kg-1 . day-1, n = 11) or vehicle (saline, n = 13) for 15 days, starting 24 h after induction of myocardial infarction. Bosentan substantially attenuated LV dilatation during postinfarction failure as evaluated by echocardiography. Furthermore, bosentan decreased LV systolic and end-diastolic pressures and increased fractional shortening. Myocardial expression of preproET-1 mRNA and a fetal gene program characteristic of myocardial hypertrophy were increased in the CHF rats and were not affected by bosentan. Consistently, right ventricular-to-body weight ratios, diameters of cardiomyocytes, and echocardiographic analysis demonstrated a sustained hypertrophic response and a normalized relative wall thickness after intervention with bosentan. Thus the modest reduction of preload and afterload provided by bosentan substantially attenuates LV dilatation, causing improved pressure-volume relationships. However, the compensatory hypertrophic response was not altered by ET-receptor antagonism. Therefore, ET-1 does not appear to play a crucial role in the mechanisms of myocardial hypertrophy during the early phase of postinfarction failure.

  6. Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart.

    PubMed Central

    Bani, D.; Masini, E.; Bello, M. G.; Bigazzi, M.; Sacchi, T. B.

    1998-01-01

    Myocardial injury caused by ischemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, platelet and mast cell activation, and peroxidation of cell membrane lipids, which are followed by myocardial cell alterations resulting eventually in cell necrosis. The current study was designed to test the possible cardioprotective effect of the hormone relaxin, which has been found to cause coronary vessel dilation and to inhibit platelet and mast cell activation. Ischemia (for 30 minutes) was induced in rat hearts in vivo by ligature of the left anterior descending coronary artery; reperfusion (for 60 minutes or less if the rats died before this predetermined time) was induced by removal of the ligature. Relaxin (100 ng) was given intravenously 30 minutes before ischemia. The results obtained showed that relaxin strongly reduces 1) the extension of the myocardial areas affected by ischemia-reperfusion-induced damage, 2) ventricular arrhythmias, 3) mortality, 4) myocardial neutrophil number, 5) myeloperoxidase activity, a marker of neutrophil accumulation, 6) production of malonyldialdehyde, an end product of lipid peroxidation, 7) mast cell granule release, 8) calcium overload, and 9) morphological signs of myocardial cell injury. This study shows that relaxin can be regarded as an agent with a marked cardioprotective action against ischemia-reperfusion-induced myocardial injury. Images Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:9588905

  7. [Rupture of the free wall of the heart as cause of death in acute myocardial infarct].

    PubMed

    Hurtado Buen Abad, L; De la Ree, R; Contreras, M; González-Hermosillo, J A; Salinas, L; Cárdenas, M

    1978-01-01

    Twenty four cases with myocardial rupture among 259 patients with autopsy after death due to myocardial infarction, were compared with patients with acute myocardial infarction and death secondary to other causes. Myocardial rupture occured during the first 72 hours in 58% of the patients and all cases within the first five days. Two thirds of the patients were males and 46% were 70 years of age. There were 24 myocardial ruptures (9.5%). Previous history of arterial hypertension and un-remittent anginal pain were predisposing factors for rupture (p=0.05). Other previously reported bad prognostic factors such as persistent hipertension after acute infarction, severe exercise before infarction and history of Diabetes Mellitus were not statistically significant in this study. Ruptured myocardium was not influenced by a previous history of myocardial infarction, hospitalization delay in the C.C.U., administration of anticoagulants, digitalis or pressor amines. There was no significant difference among the groups compared in enzyme curves or magnitude of leucocytosis. Electromechanic dissociation, sinus bradycardia, nodal rhythm followed by idioventricular rhythm and asystole, were observed following myocardial rupture.

  8. Acute myocardial infarction: the first manifestation of ischemic heart disease and relation to risk factors.

    PubMed

    Manfroi, Waldomiro Carlos; Peukert, Carolina; Berti, Clarissa Bacha; Noer, Clarissa; Gutierres, Danielle de Avila; Silva, Felipe Theodoro Bezerra Gaspar Carvalho da

    2002-04-01

    To assess the association between cardiovascular risk factors and acute myocardial infarction as the first manifestation of ischemic heart disease, correlating them with coronary angiographic findings. We carried out a cross-sectional study of 104 patients with previous acute myocardial infarction, who were divided into 2 groups according to the presence or absence of angina prior to acute myocardial infarction. We assessed the presence of angina preceding acute myocardial infarction and risk factors, such as age >55 years, male sex, smoking, systemic arterial hypertension, lipid profile, diabetes mellitus, obesity, sedentary lifestyle, and familial history of ischemic heart disease. On coronary angiography, the severity of coronary heart disease and presence of left ventricular hypertrophy were assessed. Of the 104 patients studied, 72.1% were males, 90.4% were white, 73.1% were older than 55 years, and 53.8% were hypertensive. Acute myocardial infarction was the first manifestation of ischemic heart disease in 49% of the patients. The associated risk factors were systemic arterial hypertension (RR=0.19; 95% CI=0.06-0.59; P=0.04) and left ventricular hypertrophy (RR=0.27; 95% CI=0,.8-0.88; P=0.03). The remaining risk factors were not statistically significant. Prevalence of acute myocardial infarction as the first manifestation of ischemic heart disease is high, approximately 50%. Hypertensive individuals more frequently have symptoms preceding acute myocardial infarction, probably due to ventricular hypertrophy associated with high blood pressure levels.

  9. [The influence of halogenated anesthetic agents on the hemodynamics and myocardial metabolism in ischemic heart disease].

    PubMed

    Vasil'ev, A V; Nesterova, Iu V; Brand, Ia B

    2007-01-01

    The authors studied the effects of anesthesia with equipotential concentrations of halothane, enflurane, and isoflurane plus 33% O2 on central hemodynamics, coronary flow, and myocardial metabolism in 60 patients undergoing myocardial revascularization surgery. The study found that halothane and isoflurane with 33% O2 caused dose-dependent and well-controlled arterial hypotension and decreased left ventricular (LV) stroke work index, myocardial consumption of O2 MCO2), total peripheral vascular resistance, and coronary vascular resistance (CVR), which increased coronary volume flow. Monoanesthesia with enflurane lowered myocardial contractility and did not change LV work; MCO2 decreased, while coronary sinus flow increased due to a decrease in CVR. Thus, the comparison of hemodynamic and myocardial effects of the three potent inhaled anesthetics--halothane, enflurane, and isoflurane - demonstrated their positive effects on myocardial oxygen balance in a form of dosed and controlled decrease in its work in cardiological patients with preserved LV contractility. The imported anesthetics enflurane and isoflurane do not have any significant advantage over the Russian-made halothane in this category of patients. At the same time, halothane vs. enflurane has a more noticeable "unloading" effect on afterload and does not cause convulsive episodes and periods of cerebral activity depression; in contrast to isoflurane, halothane dose not cause metabolic disturbances in a compromised myocardium; halothane is used in lower inhaled concentrations to achieve the same degree of myocardial work decrease without a substantial decrease in cardiac efficiency. These facts suggest that halothane has a practical advantage over the other anesthetics.

  10. Aqueous extract of Saussurea lappa root ameliorate oxidative myocardial injury induced by isoproterenol in rats.

    PubMed

    Saleem, T S Mohamed; Lokanath, N; Prasanthi, A; Madhavi, M; Mallika, G; Vishnu, M N

    2013-04-01

    Saussurea lappa Clarke (Compositae), is commonly known as Kushta. In Ayurvedha, it is mentioned that the aqueous extract of the root S. lappa was used for treatment of angina pectoris. The present study was designed to investigate the cardioprotective effect of aqueous extract of root of S. lappa against isoproterenol induced myocardial injury. Myocardial injury in rat was induced by the administration of isoproterenol at a dose of 85 mg/kg, i.p., The rats were pretreated with the aqueous extract of S. lappa (AESL) in three different doses (100, 200 and 300 mg/kg, p.o.) through the oral route. Isoproterenol alone-treated rats showed increased serum concentration of lactate dehydrogenase (LDH), creatinine kinase (CK), and aspartate transaminase (AST), increased myocardial thiobarbituric acid reactive substances (TBARS) level, and decreased myocardial glutathione (GSH) level due to myocardial damage produced by isoproterenol. This is further conformed by histopathological changes. Chronic oral administration of AESL in three different doses significantly restored the level of myocardial LDH, CK, AST, TBARS, and GSH. The extract effect was compared with the reference standard α-tocopherol which also offered similar protection in biochemical and histopathological changes. The overall beneficial effect which was observed with the dose of 200 mg/kg indicated that AESL produced significant dose-dependent activity against isoproterenol induced myocardial injury.

  11. Aqueous extract of Saussurea lappa root ameliorate oxidative myocardial injury induced by isoproterenol in rats

    PubMed Central

    Saleem, T. S. Mohamed; Lokanath, N.; Prasanthi, A.; Madhavi, M.; Mallika, G.; Vishnu, M. N.

    2013-01-01

    Saussurea lappa Clarke (Compositae), is commonly known as Kushta. In Ayurvedha, it is mentioned that the aqueous extract of the root S. lappa was used for treatment of angina pectoris. The present study was designed to investigate the cardioprotective effect of aqueous extract of root of S. lappa against isoproterenol induced myocardial injury. Myocardial injury in rat was induced by the administration of isoproterenol at a dose of 85 mg/kg, i.p., The rats were pretreated with the aqueous extract of S. lappa (AESL) in three different doses (100, 200 and 300 mg/kg, p.o.) through the oral route. Isoproterenol alone-treated rats showed increased serum concentration of lactate dehydrogenase (LDH), creatinine kinase (CK), and aspartate transaminase (AST), increased myocardial thiobarbituric acid reactive substances (TBARS) level, and decreased myocardial glutathione (GSH) level due to myocardial damage produced by isoproterenol. This is further conformed by histopathological changes. Chronic oral administration of AESL in three different doses significantly restored the level of myocardial LDH, CK, AST, TBARS, and GSH. The extract effect was compared with the reference standard α-tocopherol which also offered similar protection in biochemical and histopathological changes. The overall beneficial effect which was observed with the dose of 200 mg/kg indicated that AESL produced significant dose-dependent activity against isoproterenol induced myocardial injury. PMID:23833749

  12. Phellinus linteus Mycelium Alleviates Myocardial Ischemia-Reperfusion Injury through Autophagic Regulation.

    PubMed

    Su, Hsing-Hui; Chu, Ya-Chun; Liao, Jiuan-Miaw; Wang, Yi-Hsin; Jan, Ming-Shiou; Lin, Chia-Wei; Wu, Chiu-Yeh; Tseng, Chin-Yin; Yen, Jiin-Cherng; Huang, Shiang-Suo

    2017-01-01

    The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly increasing around the world and this disease is a major contributor to global morbidity and mortality. It is known that regulation of programmed cell death including apoptosis and autophagy reduces the impact of myocardial IR injury. In this study, the cardioprotective effects and underlying mechanisms of Phellinus linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal mushroom, were examined in rats subjected to myocardial IR injury. The left main coronary artery of rats was ligated for 1 h and reperfused for 3 h. The arrhythmia levels were monitored during the entire process and the infarct size was evaluated after myocardial IR injury. Furthermore, the expression levels of proteins in apoptotic and autophagic pathways were observed. Pretreatment with PL mycelium (PLM) significantly reduced ventricular arrhythmia and mortality due to myocardial IR injury. PLM also significantly decreased myocardial infarct size and plasma lactate dehydrogenase level after myocardial IR injury. Moreover, PLM administration resulted in decreased caspase 3 and caspase 9 activation and increased Bcl-2/Bax ratio. Phosphorylation level of AMPK was elevated while mTOR level was reduced. Becline-1 and p62 levels decreased. These findings suggest that PLM is effective in protecting the myocardium against IR injury. The mechanism involves mediation through suppressed pro-apoptotic signaling and regulation of autophagic signaling, including stimulation of AMPK-dependent pathway and inhibition of beclin-1-dependent pathway, resulting in enhancement of protective autophagy and inhibition of excessive autophagy.

  13. Phellinus linteus Mycelium Alleviates Myocardial Ischemia-Reperfusion Injury through Autophagic Regulation

    PubMed Central

    Su, Hsing-Hui; Chu, Ya-Chun; Liao, Jiuan-Miaw; Wang, Yi-Hsin; Jan, Ming-Shiou; Lin, Chia-Wei; Wu, Chiu-Yeh; Tseng, Chin-Yin; Yen, Jiin-Cherng; Huang, Shiang-Suo

    2017-01-01

    The incidence of myocardial ischemia-reperfusion (IR) injury is rapidly increasing around the world and this disease is a major contributor to global morbidity and mortality. It is known that regulation of programmed cell death including apoptosis and autophagy reduces the impact of myocardial IR injury. In this study, the cardioprotective effects and underlying mechanisms of Phellinus linteus (Berk. and Curt.) Teng, Hymenochaetaceae (PL), a type of medicinal mushroom, were examined in rats subjected to myocardial IR injury. The left main coronary artery of rats was ligated for 1 h and reperfused for 3 h. The arrhythmia levels were monitored during the entire process and the infarct size was evaluated after myocardial IR injury. Furthermore, the expression levels of proteins in apoptotic and autophagic pathways were observed. Pretreatment with PL mycelium (PLM) significantly reduced ventricular arrhythmia and mortality due to myocardial IR injury. PLM also significantly decreased myocardial infarct size and plasma lactate dehydrogenase level after myocardial IR injury. Moreover, PLM administration resulted in decreased caspase 3 and caspase 9 activation and increased Bcl-2/Bax ratio. Phosphorylation level of AMPK was elevated while mTOR level was reduced. Becline-1 and p62 levels decreased. These findings suggest that PLM is effective in protecting the myocardium against IR injury. The mechanism involves mediation through suppressed pro-apoptotic signaling and regulation of autophagic signaling, including stimulation of AMPK-dependent pathway and inhibition of beclin-1-dependent pathway, resulting in enhancement of protective autophagy and inhibition of excessive autophagy. PMID:28420993

  14. Myocardial Tissue Remodeling in Adolescent Obesity

    PubMed Central

    Shah, Ravi V.; Abbasi, Siddique A.; Neilan, Tomas G.; Hulten, Edward; Coelho‐Filho, Otavio; Hoppin, Alison; Levitsky, Lynne; de Ferranti, Sarah; Rhodes, Erinn T.; Traum, Avram; Goodman, Elizabeth; Feng, Henry; Heydari, Bobak; Harris, William S.; Hoefner, Daniel M.; McConnell, Joseph P.; Seethamraju, Ravi; Rickers, Carsten; Kwong, Raymond Y.; Jerosch‐Herold, Michael

    2013-01-01

    Background Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue‐level markers within the myocardium that precede organ‐level alterations have not been described. Methods and Results We studied 21 obese adolescents (mean age, 17.7±2.6 years; mean body mass index [BMI], 41.9±9.5 kg/m2, including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1±4.5 years; BMI, 20.1±3.5 kg/m2) using biomarkers of cardiometabolic risk and cardiac magnetic resonance imaging (CMR) to phenotype cardiac structure, function, and interstitial matrix remodeling by standard techniques. Although left ventricular ejection fraction and left atrial volumes were similar in healthy volunteers and obese patients (and within normal body size‐adjusted limits), interstitial matrix expansion by CMR extracellular volume fraction (ECV) was significantly different between healthy volunteers (median, 0.264; interquartile range [IQR], 0.253 to 0.271), obese adolescents without T2D (median, 0.328; IQR, 0.278 to 0.345), and obese adolescents with T2D (median, 0.376; IQR, 0.336 to 0.407; P=0.0001). ECV was associated with BMI for the entire population (r=0.58, P<0.001) and with high‐sensitivity C‐reactive protein (r=0.47, P<0.05), serum triglycerides (r=0.51, P<0.05), and hemoglobin A1c (r=0.76, P<0.0001) in the obese stratum. Conclusions Obese adolescents (particularly those with T2D) have subclinical alterations in myocardial tissue architecture associated with inflammation and insulin resistance. These alterations precede significant left ventricular hypertrophy or decreased cardiac function. PMID:23963758

  15. Myocardial Energy Substrate Metabolism in Heart Failure : from Pathways to Therapeutic Targets.

    PubMed

    Fukushima, Arata; Milner, Kenneth; Gupta, Abhishek; Lopaschuk, Gary D

    2015-01-01

    Despite recent advances in therapy, heart failure remains a major cause of mortality and morbidity and is a growing healthcare burden worldwide. Alterations in myocardial energy substrate metabolism are a hallmark of heart failure, and are associated with an energy deficit in the failing heart. Previous studies have shown that a metabolic shift from mitochondrial oxidative metabolism to glycolysis, as well as an uncoupling between glycolysis and glucose oxidation, plays a crucial role in the development of cardiac inefficiency and functional impairment in heart failure. Therefore, optimizing energy substrate utilization, particularly by increasing mitochondrial glucose oxidation, can be a potentially promising approach to decrease the severity of heart failure by improving mechanical cardiac efficiency. One approach to stimulating myocardial glucose oxidation is to inhibit fatty acid oxidation. This review will overview the physiological regulation of both myocardial fatty acid and glucose oxidation in the heart, and will discuss what alterations in myocardial energy substrate metabolism occur in the failing heart. Furthermore, lysine acetylation has been recently identified as a novel post-translational pathway by which mitochondrial enzymes involved in all aspects of cardiac energy metabolism can be regulated. Thus, we will also discuss the effect of acetylation of metabolic enzymes on myocardial energy substrate preference in the settings of heart failure. Finally, we will focus on pharmacological interventions that target enzymes involved in fatty acid uptake, fatty acid oxidation, transcriptional regulation of fatty acid oxidation, and glucose oxidation to treat heart failure.

  16. Monocyte chemoattractant proteins mediate myocardial microvascular dysfunction in swine renovascular hypertension.

    PubMed

    Lin, Jing; Zhu, Xiangyang; Chade, Alejandro R; Jordan, Kyra L; Lavi, Ronit; Daghini, Elena; Gibson, Matthew E; Guglielmotti, Angelo; Lerman, Amir; Lerman, Lilach O

    2009-11-01

    Monocyte chemoattractant proteins (MCPs) play an important role in mediating inflammatory processes. Hypertension (HTN) is associated with inflammation as well as impaired cardiac microcirculatory function and structure, but the contribution of MCPs to these alterations remained unclear. This study tested the hypothesis that MCPs regulate cardiac microvascular function and structure in experimental HTN. Pigs (n=6 per group) were studied after 10 weeks of normal, renovascular HTN, or renovascular HTN+ bindarit (MCPs inhibitor, 50 mg/kg/d PO). Left ventricular (LV) function, myocardial microvascular permeability, and fractional vascular volume were assessed by fast computed tomography before and after adenosine infusion (400 microg/kg/min). Myocardial fibrosis, inflammation, and microvascular remodeling were determined ex vivo. Hypertension was not altered by bindarit, but LV hypertrophy and diastolic function were improved. In response to adenosine, myocardial microvascular permeability increased in HTN (from 0.0083+/-0.0009 to 0.0103+/-0.0011 AU, P=0.038 versus baseline) and fractional vascular volume decreased, whereas both remained unchanged in normal and HTN+bindarit pigs. HTN upregulated endothelin-1 expression, myocardial inflammation, and microvascular wall thickening, which were inhibited by bindarit. MCPs partly mediate myocardial inflammation, fibrosis, vascular remodeling, and impaired vascular integrity induced by hypertension. Inhibition of MCPs could potentially be a therapeutic target in hypertensive cardiomyopathy.

  17. Green tea extract protects rats against myocardial infarction associated with left anterior descending coronary artery ligation.

    PubMed

    Hsieh, Shih-Rong; Tsai, Dan-Chin; Chen, Jan-Yow; Tsai, Sen-Wei; Liou, Ying-Ming

    2009-08-01

    There is increasing evidence that green tea polyphenols can protect against myocardial damage. Recently, we showed that they bind to cardiac troponin C and alter myofilament Ca(2+) sensitivity in cardiac muscle. In the present study, we examined whether green tea extract (GTE) could prevent the progressive remodeling seen in ischemic myocardium and improve cardiac function by modulation of the contractile apparatus utilizing a myocardial infarction (MI) model in the rat involving ligation of the left anterior descending branch. Using this model, severe myocardial injury was found, including altered cardiac performance and the appearance of extensive fibrosis and left ventricular (LV) enlargement. Supplementation with 400 mg/kg/day of GTE for 4, 18, or 46 days had beneficial effects in preventing the hemodynamic changes. Histopathological studies showed that GTE attenuated the progressive remodeling seen after myocardial injury. Echocardiography confirmed that GTE prevented LV enlargement and improved LV performance in post-MI rats. In addition, we showed that GTE supplementation for 18 or 46 days increased the myofilament Ca(2+) sensitivity of the ischemic myocardium in post-MI rats. These results validate the novel action of green tea polyphenols in protecting against myocardial damage and enhancing cardiac contractility by modulating myofilament Ca(2+) sensitivity in post-MI rats.

  18. Hemorrhagic shock impairs myocardial cell volume regulation and membrane integrity in dogs

    SciTech Connect

    Horton, J.W.

    1987-06-01

    An in vitro myocardial slice technique was used to quantitate alterations in cell volume regulation and membrane integrity after 2 h or hemorrhagic shock. After in vitro incubation in Krebs-Ringer-phosphate medium containing trace (/sup 14/C)inulin, values (ml H/sub 2/O/g dry wt) for control nonshocked myocardial slices were 4.03 /plus minus/ 0.11 (SE) for total water, 2.16 /plus minus/ 0.07 for inulin impermeable space, and 1.76 /plus minus/ 0.15 for inulin diffusible space. Shocked myocardial slices showed impaired response to cold incubation. After 2 h of in vivo shock, total tissue water, inulin diffusible space, and inulin impermeable space increased significantly for subendocardium, whereas changes in subepicardium parameters were minimal. Shock-induced cellular swelling was accompanied by an increased total tissue sodium, but no change in tissue potassium. Calcium entry blockade in vivo significantly reduced subendocardial total tissue water as compared with shock-untreated dogs. In addition, calcium entry blockade reduced shock-induced increases in inulin diffusible space. In vitro myocardial slice studies confirm alterations in subendocardial membrane integrity after 2 h of in vivo hemorrhagic shock. Shock-induced abnormalities in myocardial cell volume regulation are reduced by calcium entry blockade in vivo.

  19. Regenerating functional heart tissue for myocardial repair

    PubMed Central

    Alcon, Andre; Bozkulak, Esra Cagavi; Qyang, Yibing

    2012-01-01

    Heart disease is one of the leading causes of death worldwide and the number of patients with the disease is likely to grow with the continual decline in health for most of the developed world. Heart transplantation is one of the only treatment options for heart failure due to an acute myocardial infarction, but limited donor supply and organ rejection limit its widespread use. Cellular cardiomyoplasty, or cellular implantation, combined with various tissue-engineering methods aims to regenerate functional heart tissue. This review highlights the numerous cell sources that have been used to regenerate the heart as well as cover the wide range of tissue-engineering strategies that have been devised to optimize the delivery of these cells. It will probably be a long time before an effective regenerative therapy can make a serious impact at the bedside. PMID:22388688

  20. Caffeine reduces myocardial blood flow during exercise.

    PubMed

    Higgins, John P; Babu, Kavita M

    2013-08-01

    Caffeine consumption has been receiving increased interest from both the medical and lay press, especially given the increased amounts now available in energy products. Acute ingestion of caffeine usually increases cardiac work; however, caffeine impairs the expected proportional increase in myocardial blood flow to match this increased work of the heart, most notably during exercise. This appears to be mainly due to caffeine's effect on blocking adenosine-induced vasodilatation in the coronary arteries in normal healthy subjects. This review summarizes the available medical literature specifically relating to pure caffeine tablet ingestion and reduced exercise coronary blood flow, and suggests possible mechanisms. Further studies are needed to evaluate this effect for other common caffeine-delivery systems, including coffee, energy beverages, and energy gels, which are often used for exercise performance enhancement, especially in teenagers and young athletes.

  1. An unusual presentation of mad honey poisoning: acute myocardial infarction.

    PubMed

    Akinci, Sinan; Arslan, Uğur; Karakurt, Kamber; Cengel, Atiye

    2008-09-26

    An unusual type of food poisoning is commonly seen in the Black Sea coast of Turkey due to grayanotoxin containing toxic honey so called "mad honey" ingestion. In cases of toxication bradycardia and rhythm disturbances are commonly observed. Herein, we present a case of a patient who was admitted to the hospital because of acute myocardial infarction with normal coronary arteries after "mad honey" ingestion.

  2. Acute Myocardial Infarction following Naltrexone Consumption; a Case Report

    PubMed Central

    Dadpour, Bita; Gholoobi, Arash; Tajoddini, Shahrad; Habibi, Amir

    2017-01-01

    Cardiovascular effects of opioid withdrawal have long been studied. It was reported that patients with underlying ischemic heart disease and atherosclerotic vessels may be complicated by a sudden physical and emotional stress due to withdrawal syndrome. But some other believes sudden increase in catecholamine level as a sympathetic overflow might effect on heart with and without underlying ischemia. In the current study, a patient on methadone maintenance therapy (MMT) who experienced myocardial infarction (MI) after taking naltrexone was described. PMID:28286852

  3. Recovery of regional myocardial dysfunction after successful coronary angioplasty early after a non-Q wave myocardial infarction

    SciTech Connect

    Suryapranata, H.; Serruys, P.W.; Beatt, K.; De Feyter, P.J.; van den Brand, M.; Roelandt, J. )

    1990-08-01

    More aggressive therapy has been suggested for patients who have a non-Q wave myocardial infarction (MI) because of the frequency of subsequent unstable angina, recurrent MI, and high mortality rate compared to patients with Q wave MI. The present study was undertaken to investigate the effect of coronary angioplasty on regional myocardial function of the infarct zone in patients with angina early after a non-Q wave MI. The study population consisted of 36 patients undergoing successful coronary angioplasty within 30 days of a non-Q wave MI, in whom sequential left ventricular angiograms of adequate quality were obtained before the initial procedure and at follow-up angiography. The global ejection fraction increased significantly from 60 +/- 9% to 67 +/- 6% (p = 0.0003). This significant increase in the global ejection fraction was primarily due to a significant improvement in the regional myocardial function of the infarct zone. The results of the present study show not only that ischemic attacks early after a non-Q wave MI may lead to prolonged regional myocardial dysfunction but more important that this depressed myocardium has the potential to achieve normal contraction after successful coronary angioplasty.

  4. In vivo effects of myocardial creatine depletion on left ventricular function, morphology, and energy metabolism--consequences in acute myocardial infarction.

    PubMed

    Lorentzon, Malin; Råmunddal, Truls; Bollano, Entela; Soussi, Bassam; Waagstein, Finn; Omerovic, Elmir

    2007-04-01

    (P < .05). Similarly, LV dimensions were increased in the BGP group (P < .05). Induction of acute MI resulted in markedly increased incidence of MVA and higher mortality in the BGP group (P < .01). Myocardial Cr depletion results in functional and structural LV alterations associated with lower myocardial energy reserve. Intact myocardial Cr metabolism is important for normal LV function during basal and stress conditions. Acute MI in the setting of myocardial Cr depletion leads to excessive mortality from ventricular arrhythmias and progressive heart failure.

  5. Pseudo-myocardial infarction in diabetic ketoacidosis with hyperkalemia.

    PubMed

    Bellazzini, Marc A; Meyer, Tom

    2010-10-01

    Hyperkalemia-induced electrocardiogram changes such as dysrhythmias and altered T wave morphology are well described in the medical literature. Pseudo-infarction hyperkalemia-induced changes are less well known, but present a unique danger for the clinician treating these critically ill patients. This article describes a case of pseudo anteroseptal myocardial infarction in a type 1 diabetic with hyperkalemia. The most common patterns of pseudo-infarct and their associated potassium concentrations are then summarized from a literature review of 24 cases.

  6. Reducing myocardial injury by minimizing imbalance between oxygen supply and demand.

    PubMed

    Braunwald, Eugene

    2007-07-01

    The purpose of this study was to determine whether hemodynamic and pharmacologic factors can influence the extent and severity of myocardial necrosis produced by coronary occlusion. In 48 dogs, 10 to 14 epicardial leads were recorded on the anterior surface of the left ventricle in the distribution and vicinity of the site of occlusion of a branch of the left anterior descending coronary artery. The average S-T segment elevation for each animal was determined at 5-min intervals after occlusion. This elevation was used as an index of the presence and severity of myocardial ischemic injury. Isoproterenol, ouabain, glucagon, bretylium, and tachycardia given prior to a repeated occlusion each increased the severity and extent of ischemic injury, while propranolol decreased it. Elevation of arterial pressure with methoxamine reduced the occlusion-induced S-T segment elevation, and lowering of the mean arterial pressure by hemorrhage had the opposite effect. In 19 additional experiments, propranolol, isoproterenol, and alterations in arterial pressure produced similar alterations in S-T segment elevation when these interventions were applied as long as 3 hr after ligation. Myocardial creatine phosphokinase (CPK) activity determined 24 hr after coronary artery ligation correlated well with S-T segment elevation at the same sites recorded 15 min after ligation. Moreover, isoproterenol increased and propranolol decreased the area of depression of myocardial CPK activity. We conclude that the hemodynamic status and neurohumoral background at the time of coronary occlusion and for at least 3 hr thereafter can alter the extent and severity of myocardial ischemic injury and myocardial necrosis.

  7. Exercise training with ageing protects against ethanol induced myocardial glutathione homeostasis.

    PubMed

    Kakarla, Pushpalatha; Kesireddy, Sathyavelureddy; Christiaan, Leeuwenburgh

    2008-05-01

    Glutathione plays a central role in the maintenance of cellular antioxidant defense. The alterations in the glutathione and associated recyclic enzymes caused by both exercise training and ethanol are well documented; however, their interactive effects with age are not well understood. Therefore, the influence of ageing and the interactive effects of exercise training and ethanol on the myocardial glutathione system in 3 months and 18 months old rats were examined. The results showed a significant (p<0.01) reduction in GSH content, Se and non-Se GSH-Px, GR and GST activities in the myocardium of rat with age. A significant increase (p<0.05) in the activities of these enzymes was observed in both age groups of rats in response to exercise training. This exercise-induced elevation of Se and non-Se GSH-Px and GR activities was more pronounced in the 18 months old rats when compared to 3 months old rats. Ethanol consumption significantly (p<0.05) reduced the GSH content, Se and non-Se GSH-Px and GR activities in both age groups of rats. In contrast, ethanol consumption significantly (p<0.05) increased the activity of GST. The combined action of exercise plus ethanol significantly (p<0.05) elevated the GSH content, Se and non-Se GSH-Px, GR and GST activities when compared to the ethanol treated rats in both age groups, indicating the suppression of ethanol-induced oxidative stress by exercise training. In conclusion, there was a compensatory myocardial response lessening ethanol-induced oxidative stress by exercise training, which seemed to result from the higher activity of glutathione recycling and utilizing enzymes, which may be critical for preventing chronic oxidative damage to the myocardium during ageing and even due to ethanol consumption.

  8. No Myocardial Vulnerability to Mental Stress in Takotsubo Stress Cardiomyopathy

    PubMed Central

    Collste, Olov; Tornvall, Per; Sundin, Örjan; Alam, Mahbubul; Frick, Mats

    2014-01-01

    Objectives Due to the frequent use of coronary angiography the awareness of Takotsubo stress cardiomyopathy (TSC) has increased although the exact pathophysiology of TSC is still largely unknown. Our objective was to investigate the effects of mental stress on myocardial function, heart rate variability (HRV) and salivary cortisol (SC) in TSC patients. Design This study is a case-control study and a sub-study of the Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study. Setting Mental stress test was performed more than 6 months after the acute event in TSC patients and age- and sex-matched controls. Standard echocardiography and tissue Doppler imaging (TDI) - derived time-phases of cardiac cycle were recorded to calculate myocardial performance index (MPI) to assess ventricular function before and during mental stress. Holter-ECG recording was made to estimate HRV before, during and after mental stress. SC was measured at baseline, before and 20 minutes after mental stress. Subjects Twenty-two TSC patients and 22 sex-and age-matched controls were recruited from the SMINC-study and investigated with a mental stress test. All TSC patients had a previous normal cardiovascular magnetic resonance investigation. Results There were no significant differences at rest or during mental stress for left and right ventricular MPI or other standard diastolic variables between TSC patients and controls. HRV did not differ between TSC patients and controls. There was a trend towards less increase in SC after mental stress in TSC patients compared to controls. Conclusion Mental stress did not induce a significant difference in myocardial function or HRV response between TSC and controls. Moreover, no significant difference could be seen in SC response at baseline, during or after mental stress. This study indicates that myocardial vulnerability to mental stress does not persist in TSC patients. PMID:24695370

  9. [Assessment of myocardial vitality with dobutamine echocardiography: current review].

    PubMed

    Völler, H; Nixdorff, U; Flachskampf, F A

    2000-10-01

    Myocardial stunning (contractile dysfunction in the presence of normalized perfusion) and myocardial hibernation (contractile dysfunction matching reduced perfusion) have represented separate concepts of viable, but dyssynergic myocardium in the past. However, in vivo experimental and clinical work suggests that repetitive ischemia due to coronary artery disease may induce a gradual transition between stunned and hibernating myocardium. Myocardial hibernation itself can result from a spectrum of ischemic conditions ranging from impaired myocardial blood flow reserve to frank hypoperfusion. With increasing severity and duration of ischemia, degeneration of cardiac myocytes, accumulation of glycogen and cell death ensue. Additionally, there is an increase of extracellular matrix protein content leading to reparative fibrosis, which in turn limits functional recovery. In the light of these structural features, the available methods for detection of viable myocardium, in particular dobutamine echocardiography and nuclear imaging techniques, offer complementary rather than contradictory information. Dobutamine echo has satisfactory sensitivity, excellent specificity, and high diagnostic accuracy for the detection of viable dyssynergic myocardium. While in the past only its predictive accuracy for segmental recovery has been validated, newer data show an improved survival after revascularization if at least four viable dyssynergic left ventricular segments in a 16 segment model can be identified by dobutamine echocardiography. The complete (low and high dose) dobutamine protocol can elicit several types of contractile responses (sustained improvement in contraction or monophasic response, biphasic response, new wall motion abnormality) which should be interpreted in view of other clinical data including a previous infarction. The test protocol can be used safely at the end of the first week after myocardial infarction. If ischemia or viability is documented

  10. Low-Intensity Pulsed Ultrasound Enhances Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Mouse Model of Acute Myocardial Infarction.

    PubMed

    Shindo, Tomohiko; Ito, Kenta; Ogata, Tsuyoshi; Hatanaka, Kazuaki; Kurosawa, Ryo; Eguchi, Kumiko; Kagaya, Yuta; Hanawa, Kenichiro; Aizawa, Kentaro; Shiroto, Takashi; Kasukabe, Sachie; Miyata, Satoshi; Taki, Hirofumi; Hasegawa, Hideyuki; Kanai, Hiroshi; Shimokawa, Hiroaki

    2016-06-01

    Left ventricular (LV) remodeling after acute myocardial infarction still remains an important issue in cardiovascular medicine. We have recently demonstrated that low-intensity pulsed ultrasound (LIPUS) therapy improves myocardial ischemia in a pig model of chronic myocardial ischemia through enhanced myocardial angiogenesis. In the present study, we aimed to demonstrate whether LIPUS also ameliorates LV remodeling after acute myocardial infarction and if so, to elucidate the underlying molecular mechanisms involved in the beneficial effects of LIPUS. We examined the effects of LIPUS on LV remodeling in a mouse model of acute myocardial infarction, where the heart was treated with either LIPUS or no-LIPUS 3 times in the first week (days 1, 3, and 5). The LIPUS improved mortality and ameliorated post-myocardial infarction LV remodeling in mice. The LIPUS upregulated the expression of vascular endothelial growth factor, endothelial nitric oxide synthase, phosphorylated ERK, and phosphorylated Akt in the infarcted area early after acute myocardial infarction, leading to enhanced angiogenesis. Microarray analysis in cultured human endothelial cells showed that a total of 1050 genes, including those of the vascular endothelial growth factor signaling and focal adhesion pathways, were significantly altered by the LIPUS. Knockdown with small interfering RNA of either β1-integrin or caveolin-1, both of which are known to play key roles in mechanotransduction, suppressed the LIPUS-induced upregulation of vascular endothelial growth factor. Finally, in caveolin-1-deficient mice, the beneficial effects of LIPUS on mortality and post-myocardial infarction LV remodeling were absent. These results indicate that the LIPUS therapy ameliorates post-myocardial infarction LV remodeling in mice in vivo, for which mechanotransduction and its downstream pathways may be involved. © 2016 American Heart Association, Inc.

  11. The PPAR-α activator fenofibrate fails to provide myocardial protection in ischemia and reperfusion in pigs

    PubMed Central

    Xu, Ya; Lu, Li; Greyson, Clifford; Rizeq, Mona; Nunley, Karin; Wyatt, Beata; Bristow, Michael R.; Long, Carlin S.; Schwartz, Gregory G.

    2010-01-01

    Rodent studies suggest that peroxisome proliferator-activated receptor-α (PPAR-α) activation reduces myocardial ischemia-reperfusion (I/R) injury and infarct size; however, effects of PPAR-α activation in large animal models of myocardial I/R are unknown. We determined whether chronic treatment with the PPAR-α activator fenofibrate affects myocardial I/R injury in pigs. Domestic farm pigs were assigned to treatment with fenofibrate 50 mg·kg−1 ·day−1 orally or no drug treatment, and either a low-fat (4% by weight) or a high-fat (20% by weight) diet. After 4 wk, 66 pigs underwent 90 min low-flow regional myocardial ischemia and 120 min reperfusion under anesthetized open-chest conditions, resulting in myocardial stunning. The high-fat group received an infusion of triglyceride emulsion and heparin during this terminal experiment to maintain elevated arterial free fatty acid (FFA) levels. An additional 21 pigs underwent 60 min no-flow ischemia and 180 min reperfusion, resulting in myocardial infarction. Plasma concentration of fenofibric acid was similar to the EC50 for activation of PPAR-α in vitro and to maximal concentrations achieved in clinical use. Myocardial expression of PPAR-α mRNA was prominent but unaffected by fenofibrate treatment. Fenofibrate increased expression of carnitine palmitoyltransferase (CPT)-I mRNA in liver and decreased arterial FFA and lactate concentrations (each P < 0.01). However, fenofibrate did not affect myocardial CPT-I expression, substrate uptake, lipid accumulation, or contractile function during low-flow I/R in either the low- or high-fat group, nor did it affect myocardial infarct size. Despite expression of PPAR-α in porcine myocardium and effects of fenofibrate on systemic metabolism, treatment with this PPAR-α activator does not alter myocardial metabolic or contractile responses to I/R in pigs. PMID:16339839

  12. [Premonitory sign of myocardial rupture].

    PubMed

    Lauten, A; Dittrich, P

    1975-10-01

    It is reported on 14 cases in which a rupture of the myocardium occurred following a myocardial infarction. The moment of the appearance as well as anamnestic and clinical peculiarities are examined. As the only usable symptom of the rupture the symptomatology of the electromechanic dissociation must be taken into consideration. Finally it is referred to the on principle possible operative consequences of the rupture of the myocardium (oversewing or infarctetomy).

  13. Myocardial structure and matrix metalloproteinases.

    PubMed

    Aggeli, C; Pietri, P; Felekos, I; Rautopoulos, L; Toutouzas, K; Tsiamis, E; Stefanadis, C

    2012-01-01

    Metalloproteinases (MMPs) are enzymes which enhance proteolysis of extracellular matrix proteins. The pathophysiologic and prognostic role of MMPs has been demonstrated in numerous studies. The present review covers a wide a range of topics with regards to MMPs structural and functional properties, as well as their role in myocardial remodeling in several cardiovascular diseases. Moreover, the clinical and therapeutic implications from their assessment are highlighted.

  14. Tachyarrhythmias in acute myocardial infarction.

    PubMed

    McLean, K H; Bett, J N; Saltups, A

    1975-02-01

    In 1505 patients with acute myocardial infarction (MI) serious ventricular arrhythmias were commoner in those with transmural ECG changes, and were associated with an increase in mortality and in the incidence of left ventricular failure (LVF) as well as higher peak serum lactic dehydrogenase (LDH) levels. Atrial fibrillation (AF) occurred more often in older patients and in those with LVF and clinical evidence of pericarditis.

  15. Functional tests for myocardial ischemia

    SciTech Connect

    Levinson, J.R.; Guiney, T.E.; Boucher, C.A. )

    1991-01-01

    Functional tests for myocardial ischemia are numerous. Most depend upon a combination of either exercise or pharmacologic intervention with analysis of the electrocardiogram, of regional perfusion with radionuclide imaging, or of regional wall motion with radionuclide imaging or echocardiography. While each test has unique features, especially at the research level, they are generally quite similar in clinical practice, so the clinician is advised to concentrate on one or two in which local expertise is high.22 references.

  16. [Psychiatric disorders following myocardial infarction].

    PubMed

    Meincke, Ulrich; Hoff, Paul

    2006-05-15

    The number of patients who survive acute myocardial infarction has increased during recent decades. In addition, demographic development results in a rising incidence of cardiovascular diseases. Based on these facts, also the significance of psychiatric disorders is growing that may occur after myocardial infarction, such as depression, posttraumatic stress and anxiety disorders. Physicians are faced with the challenge to identify these clinical entities, that show a syndromal overlap with somatic complaints after myocardial infarction. After differentiation prompt start of adequate psychiatric-psychotherapeutic interventions is of relevance, not only regarding the patient's quality of life, but also in terms of cardiovascular prognosis. Indeed, depressive and anxiety disorders are known to be associated with a poor compliance as for rehabilitation and secondary prevention of cardiovascular disorders. Moreover, some studies suggest depression to be an independent risk factor of coronary heart disease. Consequently, early recognition and treatment, most often primarily in the hands of internists and cardiologists, are of enormous importance for the course and prognosis of the psychiatric disorder but also of cardiovascular disease.

  17. Myocardial Infarction in the Elderly

    PubMed Central

    Carro, Amelia; Kaski, Juan Carlos

    2011-01-01

    Advances in pharmacological treatment and effective early myocardial revascularization have –in recent years- led to improved clinical outcomes in patients with acute myocardial infarction (AMI). However, it has been suggested that compared to younger subjects, elderly AMI patients are less likely to receive evidence-based treatment, including myocardial revascularization therapy. Several reasons have been postulated to explain this trend, including uncertainty regarding the true benefits of the interventions commonly used in this setting as well as increased risk mainly associated with comorbidities. The diagnosis, management, and post-hospitalization care of elderly patients presenting with an acute coronary syndrome pose many difficulties at present. A complex interplay of variables such as comorbidities, functional and socioeconomic status, side effects associated with multiple drug administration, and individual biologic variability, all contribute to creating a complex clinical scenario. In this complex setting, clinicians are often required to extrapolate evidence-based results obtained in cardiovascular trials from which older patients are often, implicitly or explicitly, excluded. This article reviews current recommendations regarding management of AMI in the elderly. PMID:22396870

  18. Mucosal tolerance induction in autoimmune myocarditis and myocardial infarction.

    PubMed

    Li, Jin; Göser, Stefan; Leuschner, Florian; Volz, H Christian; Buss, Sebastian; Andrassy, Martin; Öttl, Renate; Pfitzer, Gabriele; Katus, Hugo A; Kaya, Ziya

    2013-01-20

    Antigen-specific therapy is a compelling approach for the treatment of autoimmune conditions. Primary goal is to induce the specific tolerization of self-reactive immune cells without altering host immunity against pathogens. We studied the effects of mucosal tolerance induction on cTnI-induced experimental autoimmune myocarditis (EAM) and post-infarct remodeling. Mucosal tolerance was induced by intranasal application of cTnI, alternatively anti-CD3 p.o. Protocols varied in frequency, dosage and time point of application before EAM. We then applied the most effective regimen to mice undergoing myocardial infarction in order to verify its effectiveness in post-infarct cardiac remodeling. The myocardium was evaluated on histological slides and for the cytokine secretion pattern, while echocardiography determined cardiac function. A single dose of 100 μg of cTnI 7 days prior to myocarditis appeared to be most effective in suppressing inflammation and fibrosis (p = 0.03), while improving fractional shortening (p = 0.02). Treatment with intranasal cTnI upregulated IL-10 expression. On the other hand, frequent intranasal application of high doses of cTnI increased myocardial inflammation. Anti-CD3 p.o. showed the propensity to reduce myocardial inflammation and improve cardiac function. The single dose regimen of i.n. cTnI applied 7 days before a myocardial infarction reduced inflammation by trend (p=0.07) and improved heart function (p=0.002). Moreover, expression of matrix metalloproteinases 9 and 14 significantly decreased when treated with intranasal cTnI (p<0.01). Depending on the optimal amount, the time period and the choice of antigen, effective mucosal tolerance can be achieved and represents an appealing therapeutic approach in the inflammatory process of cardiac remodeling. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Myocardialization of the cardiac outflow tract

    NASA Technical Reports Server (NTRS)

    van den Hoff, M. J.; Moorman, A. F.; Ruijter, J. M.; Lamers, W. H.; Bennington, R. W.; Markwald, R. R.; Wessels, A.

    1999-01-01

    During development, the single-circuited cardiac tube transforms into a double-circuited four-chambered heart by a complex process of remodeling, differential growth, and septation. In this process the endocardial cushion tissues of the atrioventricular junction and outflow tract (OFT) play a crucial role as they contribute to the mesenchymal components of the developing septa and valves in the developing heart. After fusion, the endocardial ridges in the proximal portion of the OFT initially form a mesenchymal outlet septum. In the adult heart, however, this outlet septum is basically a muscular structure. Hence, the mesenchyme of the proximal outlet septum has to be replaced by cardiomyocytes. We have dubbed this process "myocardialization." Our immunohistochemical analysis of staged chicken hearts demonstrates that myocardialization takes place by ingrowth of existing myocardium into the mesenchymal outlet septum. Compared to other events in cardiac septation, it is a relatively late process, being initialized around stage H/H28 and being basically completed around stage H/H38. To unravel the molecular mechanisms that are responsible for the induction and regulation of myocardialization, an in vitro culture system in which myocardialization could be mimicked and manipulated was developed. Using this in vitro myocardialization assay it was observed that under the standard culture conditions (i) whole OFT explants from stage H/H20 and younger did not spontaneously myocardialize the collagen matrix, (ii) explants from stage H/H21 and older spontaneously formed extensive myocardial networks, (iii) the myocardium of the OFT could be induced to myocardialize and was therefore "myocardialization-competent" at all stages tested (H/H16-30), (iv) myocardialization was induced by factors produced by, most likely, the nonmyocardial component of the outflow tract, (v) at none of the embryonic stages analyzed was ventricular myocardium myocardialization-competent, and finally

  20. Imaging of myocardial perfusion with magnetic resonance.

    PubMed

    Barkhausen, Jörg; Hunold, Peter; Jochims, Markus; Debatin, Jörg F

    2004-06-01

    Coronary artery disease (CAD) is currently the leading cause of death in developed nations. Reflecting the complexity of cardiac function and morphology, noninvasive diagnosis of CAD represents a major challenge for medical imaging. Although coronary artery stenoses can be depicted with magnetic resonance (MR) and computed tomography (CT) techniques, its functional or hemodynamic impact frequently remains elusive. Therefore, there is growing interest in other, target organ-specific parameters such as myocardial function at stress and first-pass myocardial perfusion imaging to assess myocardial blood flow. This review explores the pathophysiologic background, recent technical developments, and current clinical status of first-pass MR imaging (MRI) of myocardial perfusion.

  1. Myocardial bridges: Overview of diagnosis and management.

    PubMed

    Rogers, Ian S; Tremmel, Jennifer A; Schnittger, Ingela

    2017-09-01

    A myocardial bridge is a segment of a coronary artery that travels into the myocardium instead of the normal epicardial course. Although it is general perception that myocardial bridges are normal variants, patients with myocardial bridges can present with symptoms, such as exertional chest pain, that cannot be explained by a secondary etiology. Such patients may benefit from individualized medical/surgical therapy. This article describes the prevalence, clinical presentation, classification, evaluation, and management of children and adults with symptomatic myocardial bridges. © 2017 The Authors Congenital Heart Disease published by Wiley Periodicals, Inc.

  2. Arrhythmias in Post-Myocardial Infarction Patients

    ClinicalTrials.gov