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Sample records for cardiac activity detected

  1. Detection of cardiac activity changes from human speech

    NASA Astrophysics Data System (ADS)

    Tovarek, Jaromir; Partila, Pavol; Voznak, Miroslav; Mikulec, Martin; Mehic, Miralem

    2015-05-01

    Impact of changes in blood pressure and pulse from human speech is disclosed in this article. The symptoms of increased physical activity are pulse, systolic and diastolic pressure. There are many methods of measuring and indicating these parameters. The measurements must be carried out using devices which are not used in everyday life. In most cases, the measurement of blood pressure and pulse following health problems or other adverse feelings. Nowadays, research teams are trying to design and implement modern methods in ordinary human activities. The main objective of the proposal is to reduce the delay between detecting the adverse pressure and to the mentioned warning signs and feelings. Common and frequent activity of man is speaking, while it is known that the function of the vocal tract can be affected by the change in heart activity. Therefore, it can be a useful parameter for detecting physiological changes. A method for detecting human physiological changes by speech processing and artificial neural network classification is described in this article. The pulse and blood pressure changes was induced by physical exercises in this experiment. The set of measured subjects was formed by ten healthy volunteers of both sexes. None of the subjects was a professional athlete. The process of the experiment was divided into phases before, during and after physical training. Pulse, systolic, diastolic pressure was measured and voice activity was recorded after each of them. The results of this experiment describe a method for detecting increased cardiac activity from human speech using artificial neural network.

  2. Active cardiac model and its application on structure detection from early fetal ultrasound sequences.

    PubMed

    Deng, Yinhui; Wang, Yuanyuan; Shen, Yuzhong; Chen, Ping

    2012-04-01

    The structure of an early fetal heart provides vital information for the diagnosis of fetus defects. However, early fetal hearts are difficult to detect due to their relatively small size and the low signal-to-noise ratio of ultrasound images. In this paper, a novel method is proposed for automatic detection of early fetal cardiac structure from ultrasound images. The proposed method consists of two major parts which are the preprocessing phase and the active cardiac model: (1) The preprocessing phase consists of two sub-steps. (a) The region of interest is first automatically selected based on an accumulated motion image, which is able to represent the motion information of the fetal heart more accurately. (b) Then by combining Rayleigh-trimmed filter and anisotropic diffusion in 3-dimensional space, a despeckling method is developed to suppress the speckle noise and emphasize the motion information for subsequent cardiac structure detection. (2) The active cardiac model is proposed for the detection of fetal heart structure, which is a key contribution of this paper. It takes into account both the structure and motion information of fetal hearts simultaneously. Both learning and inference of the active cardiac model are described in the paper. Experiments on seven ultrasound sequences demonstrate the effectiveness of the proposed method. PMID:21620676

  3. Detecting cardiac involvement with magnetic resonance in patients with active eosinophilic granulomatosis with polyangiitis.

    PubMed

    Yune, Sehyo; Choi, Dong-Chull; Lee, Byung-Jae; Lee, Jin-Young; Jeon, Eun-Seok; Kim, Sung Mok; Choe, Yeon Hyeon

    2016-06-01

    Cardiac involvement is the most important prognostic factor in eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). The aims of this study were to describe findings of cardiac magnetic resonance (CMR) in patients with active EGPA and to find factors associated with cardiac involvement detected by CMR that could help identify patients who would benefit from the examination. Medical records and CMR images in 16 consecutive EGPA patients (8 women and 8 men, median age of 47 years ranging from 34 to 68 years) were reviewed. Clinical features and results of laboratory tests were compared according to the presence of myocardial late gadolinium enhancement (LGE) on CMR images. The patients were followed for the development of cardiac symptoms and signs (mean follow up duration, 40.5 ± 12.8 months). Among the total of 16 patients, 8 (50 %) had myocardial LGE according to CMR, located in the subendocardial layer in 7 of them (87.5 %). The extent of LGE had a significant negative correlation with left ventricular ejection fraction (LVEF, ρ = -0.723, p = 0.043). The presence of LGE was associated with larger end-systolic left ventricle internal dimension (34 vs. 28 mm, p = 0.027) and presence of diastolic dysfunction (75 vs. 0 %, p = 0.008) on echocardiography, elevated NT-proBNP (75 vs. 12.5 %, p = 0.012), and elevated CK-MB (62.5 vs. 0 %, p = 0.010) compared to the group without LGE. Only one patient (6.3 %) had cardiac symptoms before CMR and another patient (6.3 %) developed heart failure 4 years later during remission. The other 14 patients remained free from cardiac signs and symptoms during the follow-up period. In patients with active EGPA, CMR enables detection of cardiac involvement when cardiac symptoms are not present. Echocardiographic diastolic dysfunction and elevated NT-proBNP or CK-MB may help identify active EGPA patients who can benefit from CMR to detect cardiac involvement without cardiac symptoms. PMID

  4. Detection of abnormal cardiac activity using principal component analysis--a theoretical study.

    PubMed

    Greisas, Ariel; Zafrir, Zohar; Zlochiver, Sharon

    2015-01-01

    Electrogram-guided ablation has been recently developed for allowing better detection and localization of abnormal atrial activity that may be the source of arrhythmogeneity. Nevertheless, no clear indication for the benefit of using electrograms guided ablation over empirical ablation was established thus far, and there is a clear need of improving the localization of cardiac arrhythmogenic targets for ablation. In this paper, we propose a new approach for detection and localization of irregular cardiac activity during ablation procedures that is based on dimension reduction algorithms and principal component analysis (PCA). Using an 8×8 electrode array, our method produces manifolds that allow easy visualization and detection of possible arrhythmogenic ablation targets characterized by irregular conduction. We employ mathematical modeling and computer simulations to demonstrate the feasibility of the new approach for two well established arrhythmogenic sources for irregular conduction--spiral waves and patchy fibrosis. Our results show that the PCA method can differentiate between focal ectopic activity and spiral wave activity, as these two types of activity produce substantially different manifold shapes. Moreover, the technique allows the detection of spiral wave cores and their general meandering and drifting pattern. Fibrotic patches larger than 2 mm(2) could also be visualized using the PCA method, both for quiescent atrial tissue and for tissue exhibiting spiral wave activity. We envision that this method, contingent to further numerical and experimental validation studies in more complex, realistic geometrical configurations and with clinical data, can improve existing atrial ablation mapping capabilities, thus increasing success rates and optimizing arrhythmia management. PMID:25073163

  5. Detecting cardiac contractile activity in the early mouse embryo using multiple modalities

    PubMed Central

    Chen, Chiann-Mun; Miranda, António M. A.; Bub, Gil; Srinivas, Shankar

    2015-01-01

    The heart is one of the first organs to develop during mammalian embryogenesis. In the mouse, it starts to form shortly after gastrulation, and is derived primarily from embryonic mesoderm. The embryonic heart is unique in having to perform a mechanical contractile function while undergoing complex morphogenetic remodeling. Approaches to imaging the morphogenesis and contractile activity of the developing heart are important in understanding not only how this remodeling is controlled but also the origin of congenital heart defects (CHDs). Here, we describe approaches for visualizing contractile activity in the developing mouse embryo, using brightfield time lapse microscopy and confocal microscopy of calcium transients. We describe an algorithm for enhancing this image data and quantifying contractile activity from it. Finally we describe how atomic force microscopy can be used to record contractile activity prior to it being microscopically visible. PMID:25610399

  6. Blu-ray Technology-Based Quantitative Assays for Cardiac Markers: From Disc Activation to Multiplex Detection.

    PubMed

    Weng, Samuel; Li, Xiaochun; Niu, Michelle; Ge, Bixia; Yu, Hua-Zhong

    2016-07-01

    Acute myocardial infarction (AMI) is the leading cause of mortality and morbidity globally. To reduce the number of mortalities, reliable and rapid point-of-care (POC) diagnosis of AMI is extremely critical. We herein present a Blu-ray technology-based assay platform for multiplex cardiac biomarker detection; not only off-the-shelf Blu-ray discs (BDs) were adapted as substrates to prepare standard immunoassays and DNA aptamer/antibody hybrid assays for the three key cardiac marker proteins (myoglobin, troponin I, and C-creative protein) but also an unmodified optical drive was directly employed to read the assay results digitally. In particular, we have shown that all three cardiac markers can be quantitated in their respective physiological ranges of interest, and the detection limits achieved are comparable with conventional enzyme-linked immunosorbent assay (ELISA) kits. The Blu-ray assay platform was further validated by measuring real-world samples and establishing a linear correlation with the simultaneously obtained ELISA data. Without the need to modify either the hardware (Blu-ray discs and optical drives) or the software driver, this assay-on-a-BD technique promises to be a low-cost user-friendly quantitative tool for on-site chemical analysis and POC medical diagnosis. PMID:27268387

  7. Coronary thrombus detected by cardiac CT angiography before cardiac catheterization.

    PubMed

    Slim, Ahmad M; Slim, Jennifer N; Haney, Brian R; Shry, Eric A

    2010-11-01

    A patient presented with a complaint of pleuritic chest discomfort with elevated cardiac biomarkers. After a cardiac magnetic resonance imaging scan for the suspicion of myopericarditis showed a potential myocardial infarct, a coronary CT scan was performed. This revealed a thrombus of the left anterior descending artery. Cardiac catheterization confirmed the findings, and a small clot was removed. To our knowledge, this is the first reported case of coronary thrombus being detected by CT angiography with cardiac catheterization correlation. Coronary CT angiography has been increasingly used to evaluate acute chest pain with a negative predictive value close to 100%. In a young patient with suspicion of myopericarditis, CT angiography proved to be useful in diagnosing thrombus in the coronary tree. PMID:20463613

  8. Automatic basal slice detection for cardiac analysis

    NASA Astrophysics Data System (ADS)

    Paknezhad, Mahsa; Marchesseau, Stephanie; Brown, Michael S.

    2016-03-01

    Identification of the basal slice in cardiac imaging is a key step to measuring the ejection fraction (EF) of the left ventricle (LV). Despite research on cardiac segmentation, basal slice identification is routinely performed manually. Manual identification, however, has been shown to have high inter-observer variability, with a variation of the EF by up to 8%. Therefore, an automatic way of identifying the basal slice is still required. Prior published methods operate by automatically tracking the mitral valve points from the long-axis view of the LV. These approaches assumed that the basal slice is the first short-axis slice below the mitral valve. However, guidelines published in 2013 by the society for cardiovascular magnetic resonance indicate that the basal slice is the uppermost short-axis slice with more than 50% myocardium surrounding the blood cavity. Consequently, these existing methods are at times identifying the incorrect short-axis slice. Correct identification of the basal slice under these guidelines is challenging due to the poor image quality and blood movement during image acquisition. This paper proposes an automatic tool that focuses on the two-chamber slice to find the basal slice. To this end, an active shape model is trained to automatically segment the two-chamber view for 51 samples using the leave-one-out strategy. The basal slice was detected using temporal binary profiles created for each short-axis slice from the segmented two-chamber slice. From the 51 successfully tested samples, 92% and 84% of detection results were accurate at the end-systolic and the end-diastolic phases of the cardiac cycle, respectively.

  9. Detection of cardiac transplant rejection with radiolabeled lymphocytes. [Rats

    SciTech Connect

    Bergmann, S.R.; Lerch, R.A.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-03-01

    To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy.

  10. Cardiac phase detection in intravascular ultrasound images

    NASA Astrophysics Data System (ADS)

    Matsumoto, Monica M. S.; Lemos, Pedro Alves; Yoneyama, Takashi; Furuie, Sergio Shiguemi

    2008-03-01

    Image gating is related to image modalities that involve quasi-periodic moving organs. Therefore, during intravascular ultrasound (IVUS) examination, there is cardiac movement interference. In this paper, we aim to obtain IVUS gated images based on the images themselves. This would allow the reconstruction of 3D coronaries with temporal accuracy for any cardiac phase, which is an advantage over the ECG-gated acquisition that shows a single one. It is also important for retrospective studies, as in existing IVUS databases there are no additional reference signals (ECG). From the images, we calculated signals based on average intensity (AI), and, from consecutive frames, average intensity difference (AID), cross-correlation coefficient (CC) and mutual information (MI). The process includes a wavelet-based filter step and ascendant zero-cross detection in order to obtain the phase information. Firstly, we tested 90 simulated sequences with 1025 frames each. Our method was able to achieve more than 95.0% of true positives and less than 2.3% of false positives ratio, for all signals. Afterwards, we tested in a real examination, with 897 frames and ECG as gold-standard. We achieved 97.4% of true positives (CC and MI), and 2.5% of false positives. For future works, methodology should be tested in wider range of IVUS examinations.

  11. Noninvasive ambulatory measurement system of cardiac activity.

    PubMed

    Pino, Esteban J; Chavez, Javier A P; Aqueveque, Pablo

    2015-08-01

    This work implements a noninvasive system that measures the movements caused by cardiac activity. It uses unobtrusive Electro-Mechanical Films (EMFi) on the seat and on the backrest of a regular chair. The system detects ballistocardiogram (BCG) and respiration movements. Real data was obtained from 54 volunteers. 19 of them were measured in the laboratory and 35 in a hospital waiting room. Using a BIOPAC acquisition system, the ECG was measured simultaneously to the BCG for comparison. Wavelet Transform (WT) is a better option than Empirical Mode Decomposition (EMD) for signal extraction and produces higher effective measurement time. In the laboratory, the best results are obtained on the seat. The correlation index was 0.9800 and the Bland-Altman limits of agreement were 0.7136 ± 4.3673 [BPM]. In the hospital waiting room, the best results are also from the seat sensor. The correlation index was 0.9840, and the limits of agreement were 0.4386 ± 3.5884 [BPM]. The system is able to measure BCG in an unobtrusive way and determine the cardiac frequency with high precision. It is simple to use, which means the system can easily be used in non-standard settings: resting in a chair or couch, at the gym, schools or in a hospital waiting room, as shown. PMID:26738057

  12. Cardiac motion compensation and resolution modeling in simultaneous PET-MR: a cardiac lesion detection study

    NASA Astrophysics Data System (ADS)

    Petibon, Y.; Ouyang, J.; Zhu, X.; Huang, C.; Reese, T. G.; Chun, S. Y.; Li, Q.; El Fakhri, G.

    2013-04-01

    Cardiac motion and partial volume effects (PVE) are two of the main causes of image degradation in cardiac PET. Motion generates artifacts and blurring while PVE lead to erroneous myocardial activity measurements. Newly available simultaneous PET-MR scanners offer new possibilities in cardiac imaging as MRI can assess wall contractility while collecting PET perfusion data. In this perspective, we develop a list-mode iterative reconstruction framework incorporating both tagged-MR derived non-rigid myocardial wall motion and position dependent detector point spread function (PSF) directly into the PET system matrix. In this manner, our algorithm performs both motion ‘deblurring’ and PSF deconvolution while reconstructing images with all available PET counts. The proposed methods are evaluated in a beating non-rigid cardiac phantom whose hot myocardial compartment contains small transmural and non-transmural cold defects. In order to accelerate imaging time, we investigate collecting full and half k-space tagged MR data to obtain tagged volumes that are registered using non-rigid B-spline registration to yield wall motion information. Our experimental results show that tagged-MR based motion correction yielded an improvement in defect/myocardium contrast recovery of 34-206% as compared to motion uncorrected studies. Likewise, lesion detectability improved by respectively 115-136% and 62-235% with MR-based motion compensation as compared to gating and no motion correction and made it possible to distinguish non-transmural from transmural defects, which has clinical significance given the inherent limitations of current single modality imaging in identifying the amount of residual ischemia. The incorporation of PSF modeling within the framework of MR-based motion compensation significantly improved defect/myocardium contrast recovery (5.1-8.5%, p < 0.01) and defect detectability (39-56%, p < 0.01). No statistical difference was found in PET contrast and lesion

  13. Functiogenesis of cardiac pacemaker activity.

    PubMed

    Sakai, Tetsuro; Kamino, Kohtaro

    2016-07-01

    Throughout our investigations on the ontogenesis of the electrophysiological events in early embryonic chick hearts, using optical techniques to record membrane potential probed with voltage-sensitive dyes, we have introduced a novel concept of "functiogenesis" corresponding to "morphogenesis". This article gives an account of the framework of "functiogenesis", focusing on the cardiac pacemaker function and the functional organization of the pacemaking area. PMID:26719289

  14. Display of cardiac activation pathways with echocardiography

    NASA Astrophysics Data System (ADS)

    Olstad, Bjoern; Brodin, Lars A.; Berg, Sevald

    1997-05-01

    The study of cardiac activation dynamics is an important factor in the characterization of the cardiac function. One such example is the localization of WPW-pathways inside the myocardium. Accurate localization of these pathways can be used to determine if the patient should be treated with catheter techniques or surgical techniques. This paper analyzes the temporal information in tissue velocity imaging with both qualitative and quantitative methods. The clinical experiments indicate that echocardiography can become an alternative technique for non-invasive electrophysiology in these kinds of applications.

  15. Cardiac motion compensation and resolution modeling in simultaneous PET-MR: a cardiac lesion detection study

    PubMed Central

    Petibon, Y; Ouyang, J; Zhu, X; Huang, C; Reese, T G; Chun, S Y; Li, Q; El Fakhri, G

    2013-01-01

    Cardiac motion and Partial Volume Effects (PVE) are two of the main causes of image degradation in cardiac PET. Motion generates artifacts and blurring while PVE lead to erroneous myocardial activity measurements. Newly available simultaneous PET-MR scanners offer new possibilities in cardiac imaging as MRI can assess wall contractility while collecting PET perfusion data. In this perspective, we develop a list-mode iterative reconstruction framework incorporating both tagged-MR derived non-rigid myocardial wall motion and position dependent detector Point Spread Function (PSF) directly into the PET system matrix. In this manner, our algorithm performs both motion “deblurring” and PSF deconvolution while reconstructing images with all available PET counts. The proposed methods are evaluated in a beating non-rigid cardiac phantom whose hot myocardial compartment contains small transmural and non-transmural cold defects. In order to accelerate imaging time, we investigate collecting full and half k-space tagged MR data to obtain tagged volumes that are registered using non-rigid B-spline registration to yield wall motion information. Our experimental results show that tagged-MR based motion correction yielded an improvement in defect/myocardium contrast recovery of 34-206% as compared to motion uncorrected studies. Likewise, lesion detectability improved by respectively 115-136% and 62-235% with MR-based motion compensation as compared to gating and no motion correction and made it possible to distinguish non-transmural from transmural defects, which has clinical significance given inherent limitations of current single modality imaging in identifying the amount of residual ischemia. The incorporation of PSF modeling within the framework of MR-based motion compensation significantly improved defect/myocardium contrast recovery (5.1-8.5%, p<0.01) and defect detectability (39-56%, p<0.01). No statistical difference was found in PET contrast and lesion detectability

  16. Cardiac cAMP: production, hydrolysis, modulation and detection.

    PubMed

    Boularan, Cédric; Gales, Céline

    2015-01-01

    Cyclic adenosine 3',5'-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability. PMID:26483685

  17. Cardiac cAMP: production, hydrolysis, modulation and detection

    PubMed Central

    Boularan, Cédric; Gales, Céline

    2015-01-01

    Cyclic adenosine 3′,5′-monophosphate (cAMP) modulates a broad range of biological processes including the regulation of cardiac myocyte contractile function where it constitutes the main second messenger for β-adrenergic receptors' signaling to fulfill positive chronotropic, inotropic and lusitropic effects. A growing number of studies pinpoint the role of spatial organization of the cAMP signaling as an essential mechanism to regulate cAMP outcomes in cardiac physiology. Here, we will briefly discuss the complexity of cAMP synthesis and degradation in the cardiac context, describe the way to detect it and review the main pharmacological arsenal to modulate its availability. PMID:26483685

  18. Molecular candidates for cardiac stretch-activated ion channels

    PubMed Central

    Reed, Alistair; Kohl, Peter; Peyronnet, Rémi

    2014-01-01

    The heart is a mechanically-active organ that dynamically senses its own mechanical environment. This environment is constantly changing, on a beat-by-beat basis, with additional modulation by respiratory activity and changes in posture or physical activity, and further overlaid with more slowly occurring physiological (e.g. pregnancy, endurance training) or pathological challenges (e.g. pressure or volume overload). Far from being a simple pump, the heart detects changes in mechanical demand and adjusts its performance accordingly, both via heart rate and stroke volume alteration. Many of the underlying regulatory processes are encoded intracardially, and are thus maintained even in heart transplant recipients. Over the last three decades, molecular substrates of cardiac mechanosensitivity have gained increasing recognition in the scientific and clinical communities. Nonetheless, the processes underlying this phenomenon are still poorly understood. Stretch-activated ion channels (SAC) have been identified as one contributor to mechanosensitive autoregulation of the heartbeat. They also appear to play important roles in the development of cardiac pathologies – most notably stretch-induced arrhythmias. As recently discovered, some established cardiac drugs act, in part at least, via mechanotransduction pathways suggesting SAC as potential therapeutic targets. Clearly, identification of the molecular substrate of cardiac SAC is of clinical importance and a number of candidate proteins have been identified. At the same time, experimental studies have revealed variable–and at times contrasting–results regarding their function. Further complication arises from the fact that many ion channels that are not classically defined as SAC, including voltage and ligand-gated ion channels, can respond to mechanical stimulation. Here, we summarise what is known about the molecular substrate of the main candidates for cardiac SAC, before identifying potential further

  19. Automated detection of cardiac phase from intracoronary ultrasound image sequences.

    PubMed

    Sun, Zheng; Dong, Yi; Li, Mengchan

    2015-01-01

    Intracoronary ultrasound (ICUS) is a widely used interventional imaging modality in clinical diagnosis and treatment of cardiac vessel diseases. Due to cyclic cardiac motion and pulsatile blood flow within the lumen, there exist changes of coronary arterial dimensions and relative motion between the imaging catheter and the lumen during continuous pullback of the catheter. The action subsequently causes cyclic changes to the image intensity of the acquired image sequence. Information on cardiac phases is implied in a non-gated ICUS image sequence. A 1-D phase signal reflecting cardiac cycles was extracted according to cyclical changes in local gray-levels in ICUS images. The local extrema of the signal were then detected to retrieve cardiac phases and to retrospectively gate the image sequence. Results of clinically acquired in vivo image data showed that the average inter-frame dissimilarity of lower than 0.1 was achievable with our technique. In terms of computational efficiency and complexity, the proposed method was shown to be competitive when compared with the current methods. The average frame processing time was lower than 30 ms. We effectively reduced the effect of image noises, useless textures, and non-vessel region on the phase signal detection by discarding signal components caused by non-cardiac factors. PMID:26406038

  20. Estrogen receptor profiling and activity in cardiac myocytes.

    PubMed

    Pugach, Emily K; Blenck, Christa L; Dragavon, Joseph M; Langer, Stephen J; Leinwand, Leslie A

    2016-08-15

    Estrogen signaling appears critical in the heart. However a mechanistic understanding of the role of estrogen in the cardiac myocyte is lacking. Moreover, there are multiple cell types in the heart and multiple estrogen receptor (ER) isoforms. Therefore, we studied expression, localization, transcriptional and signaling activity of ERs in isolated cardiac myocytes. We found only ERα RNA (but no ERβ RNA) in cardiac myocytes using two independent methods. The vast majority of full-length ERα protein (ERα66) localizes to cardiac myocyte nuclei where it is competent to activate transcription. Alternate isoforms of ERα encoded by the same genomic locus (ERα46 and ERα36) have differential transcriptional activity in cardiac myocytes but also primarily localize to nuclei. In contrast to other reports, no ERα isoform is competent to activate MAPK or PI3K signaling in cardiac myocytes. Together these data support a role for ERα at the level of transcription in cardiac myocytes. PMID:27164442

  1. Using outdoor activities in cardiac recovery.

    PubMed

    McNish, Hugh

    Evidence suggests that green spaces next to hospitals can be used to promote health. This article reports on a pilot study to determine how hospital green spaces can be used for patients with cardiac problems and their rehabilitation programmes. Over a six-week period, patients spent one hour per week taking part in activities, including tai chi, photography and willow sculpting, as part of their rehabilitation programme. Patients showed improved physical health, less social isolation, a better overall mood and increased positivity. They were also more likely to choose to exercise than at the start of the rehabilitation programme, and valued the new skills and knowledge that they gained. PMID:24915682

  2. Sonication of Explanted Cardiac Implants Improves Microbial Detection in Cardiac Device Infections

    PubMed Central

    Oliva, Alessandra; Nguyen, Bich Lien; Mascellino, Maria T.; D'Abramo, Alessandra; Iannetta, Marco; Ciccaglioni, Antonio; Vullo, Vincenzo

    2013-01-01

    The sonication technique has been shown to be a promising tool for microbiological diagnosis of device-related infections. We evaluated the usefulness of the sonication method for pathogen detection in 80 explanted cardiac components collected from 40 patients, and the results were compared with those of conventional cultures. Forty subjects undergoing cardiac device removal were studied: 20 had cardiac device infection, and 20 subjects underwent elective generator replacement or revision in the absence of infection. Sonication of explanted devices was more sensitive than traditional culture for microbial detection (67% and 50%, respectively; P = 0.0005). The bacterial count detected in sonication fluid culture was significantly higher than that detected in traditional culture in both infected (P = 0.019) and uninfected (P = 0.029) devices. In the infected patients, sonication fluid culture yielded a significantly higher rate of pathogen detection in explanted electrodes than traditional culture (65% versus 45%; P = 0.02), while no differences were found in the generators. Ten strains were detected only through sonication fluid culture: 6 Staphylococcus epidermidis strains, 1 Staphylococcus hominis strain, 2 Corynebacterium striatum strains, and 1 Brevundimonas sp. Neither the type nor the duration of antimicrobial therapy before device removal had an effect on the diagnostic performance of sonication fluid culture (P = 0.75 and P = 0.56, respectively). In the patients without infection, sonication fluid culture was positive in 8 cases (40%), whereas conventional culture was positive in only 4 (20%). In summary, the sonication technique improves the microbiological diagnosis of explanted cardiac devices. PMID:23196364

  3. Remote health monitoring system for detecting cardiac disorders.

    PubMed

    Bansal, Ayush; Kumar, Sunil; Bajpai, Anurag; Tiwari, Vijay N; Nayak, Mithun; Venkatesan, Shankar; Narayanan, Rangavittal

    2015-12-01

    Remote health monitoring system with clinical decision support system as a key component could potentially quicken the response of medical specialists to critical health emergencies experienced by their patients. A monitoring system, specifically designed for cardiac care with electrocardiogram (ECG) signal analysis as the core diagnostic technique, could play a vital role in early detection of a wide range of cardiac ailments, from a simple arrhythmia to life threatening conditions such as myocardial infarction. The system that the authors have developed consists of three major components, namely, (a) mobile gateway, deployed on patient's mobile device, that receives 12-lead ECG signals from any ECG sensor, (b) remote server component that hosts algorithms for accurate annotation and analysis of the ECG signal and (c) point of care device of the doctor to receive a diagnostic report from the server based on the analysis of ECG signals. In the present study, their focus has been toward developing a system capable of detecting critical cardiac events well in advance using an advanced remote monitoring system. A system of this kind is expected to have applications ranging from tracking wellness/fitness to detection of symptoms leading to fatal cardiac events. PMID:26577166

  4. HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation

    PubMed Central

    Lin, Shenglan; Wang, Yana; Zhang, Xiaojin; Kong, Qiuyue; Li, Chuanfu; Li, Yuehua; Ding, Zhengnian

    2016-01-01

    Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation. PMID:27110324

  5. Prevention, Detection, and Management of Chemotherapy-Related Cardiac Dysfunction.

    PubMed

    Abdel-Qadir, Husam; Amir, Eitan; Thavendiranathan, Paaladinesh

    2016-07-01

    Cancer treatment-related cardiac dysfunction (CTRCD) occurs with many agents used in the treatment of cancer. This is most relevant in patients receiving cancer treatment with curative intent as opposed to those treated with a palliative intent where lifespan is more likely to be limited by the cancer diagnosis. Clinicians need to be aware of methods to prevent, detect, and manage CTRCD. This article frames an approach to CTCRD based on the American College of Cardiology/American Heart Association stages of heart failure (HF). In patients who are at risk for CTRCD (stage A HF), risk reduction methods may be warranted, including management of cardiovascular risk factors, modification of cancer treatment, and universal preventive therapy. Once cancer therapy begins, it is prudent to detect and promptly treat myocardial dysfunction (stage B HF). This can be achieved by careful monitoring during therapy using echocardiography, multigated acquisition scans, or cardiac MRI. Subclinical myocardial systolic dysfunction (ie, without a drop in ejection fraction) can be identified using either echocardiography measured peak systolic global longitudinal strain or cardiac troponin I. At present, there is insufficient evidence to institute preventive interventions based on changes in these preclinical markers. Finally, in patients with stage C/D HF, management strategies should follow existing guidelines. Advanced treatment including cardiac transplantation and mechanical circulatory support may be considered in appropriate circumstances. PMID:27118058

  6. Comparative Analysis of Telomerase Activity in CD117+CD34+ Cardiac Telocytes with Bone Mesenchymal Stem Cells, Cardiac Fibroblasts and Cardiomyocytes

    PubMed Central

    Li, Yuan-Yuan; Lu, Shan-Shan; Xu, Ting; Zhang, Hong-Qi; Li, Hua

    2015-01-01

    Background: This study characterized the cardiac telocyte (TC) population both in vivo and in vitro, and investigated its telomerase activity related to mitosis. Methods: Using transmission electron microscopy and a phase contrast microscope, the typical morphological features of cardiac TCs were observed; by targeting the cell surface proteins CD117 and CD34, CD117+CD34+ cardiac TCs were sorted via flow cytometry and validated by immunofluorescence based on the primary cell culture. Then the optimized basal nutrient medium for selected population was examined with the cell counting kit 8. Under this conditioned medium, the process of cell division was captured, and the telomerase activity of CD117+CD34+ cardiac TCs was detected in comparison with bone mesenchymal stem cells (BMSCs), cardiac fibroblasts (CFBs), cardiomyocytes (CMs). Results: Cardiac TCs projected characteristic telopodes with thin segments (podomers) in alternation with dilation (podoms). In addition, 64% of the primary cultured cardiac TCs were composed of CD117+CD34+ cardiac TCs; which was verified by immunofluorescence. In a live cell imaging system, CD117+CD34+ cardiac TCs were observed to enter into cell division in a short time, followed by an significant invagination forming across the middle of the cell body. Using a real-time quantitative telomeric-repeat amplification assay, the telomerase concentration in CD117+CD34+ cardiac TCs was obviously lower than in BMSCs and CFBs, and significantly higher than in CMs. Conclusions: Cardiac TCs represent a unique cell population and CD117+CD34+ cardiac TCs have relative low telomerase activity that differs from BMSCs, CFBs and CMs and thus they might play an important role in maintaining cardiac homeostasis. PMID:26168836

  7. Structure-cardiac activity relationship of C19-diterpenoid alkaloids.

    PubMed

    Jian, Xi-Xian; Tang, Pei; Liu, Xiu-Xiu; Chao, Ruo-Bing; Chen, Qiao-Hong; She, Xue-Ke; Chen, Dong-Lin; Wang, Feng-Peng

    2012-06-01

    Thirty three C19-diterpenoid alkaloids, twenty-two prepared from known C19-diterpenoid alkaloids and eleven isolated from Aconitum and Delphinium spp. were evaluated for their cardiac activity in the isolated bullfrog heart assay. Among them, eleven compounds exhibited cardiac activity, with average rate of amplitude increase in the range of 16-118%. Compound 7, mesaconine (17), hypaconine (25), and beiwutinine (26) exhibited strong cardiac activities relative to the reference drug. The structure-activity relationship data acquired indicated that an alpha-hydroxyl group at C-15, a hydroxyl group at C-8, an alpha-methoxyl or hydroxyl group at C-1, and a secondary amine or N-methyl group in ring A are important structure features necessary for the cardiac activities of the aconitine-type C19-diterpenoid alkaloids without any ester groups. In addition, an alpha-hydroxyl group at C-3 is also helpful for the cardiac activity of these alkaloids. PMID:22816290

  8. Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

    SciTech Connect

    Eisen, H.J.; Rosenbloom, M.; Laschinger, J.C.; Saffitz, J.E.; Cox, J.L.; Sobel, B.E.; Bolman, R.M. III; Bergmann, S.R.

    1988-07-01

    Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed.

  9. Early detection of acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Jefferies, John Lynn; Devarajan, Prasad

    2016-01-01

    Acute kidney injury (AKI) is increasingly recognized as a common problem in children undergoing cardiac surgery, with well documented increases in morbidity and mortality in both the short and the long term. Traditional approaches to the identification of AKI such as changes in serum creatinine have revealed a large incidence in this population with significant negative impact on clinical outcomes. However, the traditional diagnostic approaches to AKI diagnosis have inherent limitations that may lead to under-diagnosis of this pathologic process. There is a dearth of randomized controlled trials for the prevention and treatment of AKI associated with cardiac surgery, at least in part due to the paucity of early predictive biomarkers. Novel non-invasive biomarkers have ushered in a new era that allows for earlier detection of AKI. With these new diagnostic tools, a more consistent approach can be employed across centers that may facilitate a more accurate representation of the actual prevalence of AKI and more importantly, clinical investigation that may minimize the occurrence of AKI following pediatric cardiac surgery. A thoughtful management approach is necessary to mitigate the effects of AKI after cardiac surgery, which is best accomplished in close collaboration with pediatric nephrologists. Long-term surveillance for improvement in kidney function and potential development of chronic kidney disease should also be a part of the comprehensive management strategy. PMID:27429538

  10. Mitogen-activated protein kinase (MAPK) in cardiac tissues.

    PubMed

    Page, C; Doubell, A F

    Mitogen-activated protein kinase (MAPK) has recently emerged as a prominent role player in intracellular signalling in the ventricular myocyte with attention being focussed on its possible role in the development of ventricular hypertrophy. It is becoming clear that MAPK is also active in other cells of cardiac origin such as cardiac fibroblasts and possible functions of this signalling pathway in the heart have yet to be explored. In this report the mammalian MAPK pathway is briefly outlined, before reviewing current knowledge of the MAPK pathway in cardiac tissue (ventricular myocytes, vascular smooth muscle cells and cardiac fibroblasts). New data is also presented on the presence and activity of MAPK in two additional cardiac celltypes namely atrial myocytes and vascular endothelial cells from the coronary microcirculation. PMID:8739228

  11. Towards robust specularity detection and inpainting in cardiac images

    NASA Astrophysics Data System (ADS)

    Alsaleh, Samar M.; Aviles, Angelica I.; Sobrevilla, Pilar; Casals, Alicia; Hahn, James

    2016-03-01

    Computer-assisted cardiac surgeries had major advances throughout the years and are gaining more popularity over conventional cardiac procedures as they offer many benefits to both patients and surgeons. One obvious advantage is that they enable surgeons to perform delicate tasks on the heart while it is still beating, avoiding the risks associated with cardiac arrest. Consequently, the surgical system needs to accurately compensate the physiological motion of the heart which is a very challenging task in medical robotics since there exist different sources of disturbances. One of which is the bright light reflections, known as specular highlights, that appear on the glossy surface of the heart and partially occlude the field of view. This work is focused on developing a robust approach that accurately detects and removes those highlights to reduce their disturbance to the surgeon and the motion compensation algorithm. As a first step, we exploit both color attributes and Fuzzy edge detector to identify specular regions in each acquired image frame. These two techniques together work as restricted thresholding and are able to accurately identify specular regions. Then, in order to eliminate the specularity artifact and give the surgeon a better perception of the heart, the second part of our solution is dedicated to correct the detected regions using inpainting to propagate and smooth the results. Our experimental results, which we carry out in realistic datasets, reveal how efficient and precise the proposed solution is, as well as demonstrate its robustness and real-time performance.

  12. Social stress, autonomic neural activation, and cardiac activity in rats.

    PubMed

    Sgoifo, A; Koolhaas, J; De Boer, S; Musso, E; Stilli, D; Buwalda, B; Meerlo, P

    1999-11-01

    Animal models of social stress represent a useful experimental tool to investigate the relationship between psychological stress, autonomic neural activity and cardiovascular disease. This paper summarizes the results obtained in a series of experiments performed on rats and aimed at verifying whether social challenges produce specific modifications in the autonomic neural control of heart rate and whether these changes can be detrimental for cardiac electrical stability. Short-term electrocardiographic recordings were performed via radiotelemetry and the autonomic input to the heart evaluated by means of time-domain heart rate variability measures. Compared to other stress contexts, a social defeat experience produces a strong shift of autonomic balance toward sympathetic dominance, poorly antagonized by vagal rebound, and associated with the occurrence of cardiac tachyarrhythmias. These effects were particularly severe when a wild-type strain of rats was studied. The data also suggest that the cardiac autonomic responses produced by different types of social contexts (dominant-subordinate interaction, dominant-dominant confrontation, social defeat) are related to different degrees of emotional activation, which in turn are likely modulated by the social rank of the experimental animal and the opponent, the prior experience with the stressor, and the level of controllability over the stimulus. PMID:10580306

  13. Speckle Tracking Based Strain Analysis Is Sensitive for Early Detection of Pathological Cardiac Hypertrophy.

    PubMed

    An, Xiangbo; Wang, Jingjing; Li, Hao; Lu, Zhizhen; Bai, Yan; Xiao, Han; Zhang, Youyi; Song, Yao

    2016-01-01

    Cardiac hypertrophy is a key pathological process of many cardiac diseases. However, early detection of cardiac hypertrophy is difficult by the currently used non-invasive method and new approaches are in urgent need for efficient diagnosis of cardiac malfunction. Here we report that speckle tracking-based strain analysis is more sensitive than conventional echocardiography for early detection of pathological cardiac hypertrophy in the isoproterenol (ISO) mouse model. Pathological hypertrophy was induced by a single subcutaneous injection of ISO. Physiological cardiac hypertrophy was established by daily treadmill exercise for six weeks. Strain analysis, including radial strain (RS), radial strain rate (RSR) and longitudinal strain (LS), showed marked decrease as early as 3 days after ISO injection. Moreover, unlike the regional changes in cardiac infarction, strain analysis revealed global cardiac dysfunction that affects the entire heart in ISO-induced hypertrophy. In contrast, conventional echocardiography, only detected altered E/E', an index reflecting cardiac diastolic function, at 7 days after ISO injection. No change was detected on fractional shortening (FS), E/A and E'/A' at 3 days or 7 days after ISO injection. Interestingly, strain analysis revealed cardiac dysfunction only in ISO-induced pathological hypertrophy but not the physiological hypertrophy induced by exercise. Taken together, our study indicates that strain analysis offers a more sensitive approach for early detection of cardiac dysfunction than conventional echocardiography. Moreover, multiple strain readouts distinguish pathological cardiac hypertrophy from physiological hypertrophy. PMID:26871457

  14. Speckle Tracking Based Strain Analysis Is Sensitive for Early Detection of Pathological Cardiac Hypertrophy

    PubMed Central

    An, Xiangbo; Wang, Jingjing; Li, Hao; Lu, Zhizhen; Bai, Yan; Xiao, Han; Zhang, Youyi; Song, Yao

    2016-01-01

    Cardiac hypertrophy is a key pathological process of many cardiac diseases. However, early detection of cardiac hypertrophy is difficult by the currently used non-invasive method and new approaches are in urgent need for efficient diagnosis of cardiac malfunction. Here we report that speckle tracking-based strain analysis is more sensitive than conventional echocardiography for early detection of pathological cardiac hypertrophy in the isoproterenol (ISO) mouse model. Pathological hypertrophy was induced by a single subcutaneous injection of ISO. Physiological cardiac hypertrophy was established by daily treadmill exercise for six weeks. Strain analysis, including radial strain (RS), radial strain rate (RSR) and longitudinal strain (LS), showed marked decrease as early as 3 days after ISO injection. Moreover, unlike the regional changes in cardiac infarction, strain analysis revealed global cardiac dysfunction that affects the entire heart in ISO-induced hypertrophy. In contrast, conventional echocardiography, only detected altered E/E’, an index reflecting cardiac diastolic function, at 7 days after ISO injection. No change was detected on fractional shortening (FS), E/A and E’/A’ at 3 days or 7 days after ISO injection. Interestingly, strain analysis revealed cardiac dysfunction only in ISO-induced pathological hypertrophy but not the physiological hypertrophy induced by exercise. Taken together, our study indicates that strain analysis offers a more sensitive approach for early detection of cardiac dysfunction than conventional echocardiography. Moreover, multiple strain readouts distinguish pathological cardiac hypertrophy from physiological hypertrophy. PMID:26871457

  15. Wnt1/βcatenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair

    PubMed Central

    Duan, Jinzhu; Gherghe, Costin; Liu, Dianxin; Hamlett, Eric; Srikantha, Luxman; Rodgers, Laurel; Regan, Jenna N; Rojas, Mauricio; Willis, Monte; Leask, Andrew; Majesky, Mark; Deb, Arjun

    2012-01-01

    Wnts are required for cardiogenesis but the role of specific Wnts in cardiac repair remains unknown. In this report, we show that a dynamic Wnt1/βcatenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair. Acute ischaemic cardiac injury upregulates Wnt1 that is initially expressed in the epicardium and subsequently by cardiac fibroblasts in the region of injury. Following cardiac injury, the epicardium is activated organ-wide in a Wnt-dependent manner, expands, undergoes epithelial–mesenchymal transition (EMT) to generate cardiac fibroblasts, which localize in the subepicardial space. The injured regions in the heart are Wnt responsive as well and Wnt1 induces cardiac fibroblasts to proliferate and express pro-fibrotic genes. Disruption of downstream Wnt signalling in epicardial cells decreases epicardial expansion, EMT and leads to impaired cardiac function and ventricular dilatation after cardiac injury. Furthermore, disruption of Wnt/βcatenin signalling in cardiac fibroblasts impairs wound healing and decreases cardiac performance as well. These findings reveal that a pro-fibrotic Wnt1/βcatenin injury response is critically required for preserving cardiac function after acute ischaemic cardiac injury. PMID:22085926

  16. Detection of Cardiac Abnormalities from Multilead ECG using Multiscale Phase Alternation Features.

    PubMed

    Tripathy, R K; Dandapat, S

    2016-06-01

    The cardiac activities such as the depolarization and the relaxation of atria and ventricles are observed in electrocardiogram (ECG). The changes in the morphological features of ECG are the symptoms of particular heart pathology. It is a cumbersome task for medical experts to visually identify any subtle changes in the morphological features during 24 hours of ECG recording. Therefore, the automated analysis of ECG signal is a need for accurate detection of cardiac abnormalities. In this paper, a novel method for automated detection of cardiac abnormalities from multilead ECG is proposed. The method uses multiscale phase alternation (PA) features of multilead ECG and two classifiers, k-nearest neighbor (KNN) and fuzzy KNN for classification of bundle branch block (BBB), myocardial infarction (MI), heart muscle defect (HMD) and healthy control (HC). The dual tree complex wavelet transform (DTCWT) is used to decompose the ECG signal of each lead into complex wavelet coefficients at different scales. The phase of the complex wavelet coefficients is computed and the PA values at each wavelet scale are used as features for detection and classification of cardiac abnormalities. A publicly available multilead ECG database (PTB database) is used for testing of the proposed method. The experimental results show that, the proposed multiscale PA features and the fuzzy KNN classifier have better performance for detection of cardiac abnormalities with sensitivity values of 78.12 %, 80.90 % and 94.31 % for BBB, HMD and MI classes. The sensitivity value of proposed method for MI class is compared with the state-of-art techniques from multilead ECG. PMID:27118009

  17. Theoretical considerations for mapping activation in human cardiac fibrillation

    NASA Astrophysics Data System (ADS)

    Rappel, Wouter-Jan; Narayan, Sanjiv M.

    2013-06-01

    Defining mechanisms for cardiac fibrillation is challenging because, in contrast to other arrhythmias, fibrillation exhibits complex non-repeatability in spatiotemporal activation but paradoxically exhibits conserved spatial gradients in rate, dominant frequency, and electrical propagation. Unlike animal models, in which fibrillation can be mapped at high spatial and temporal resolution using optical dyes or arrays of contact electrodes, mapping of cardiac fibrillation in patients is constrained practically to lower resolutions or smaller fields-of-view. In many animal models, atrial fibrillation is maintained by localized electrical rotors and focal sources. However, until recently, few studies had revealed localized sources in human fibrillation, so that the impact of mapping constraints on the ability to identify rotors or focal sources in humans was not described. Here, we determine the minimum spatial and temporal resolutions theoretically required to detect rigidly rotating spiral waves and focal sources, then extend these requirements for spiral waves in computer simulations. Finally, we apply our results to clinical data acquired during human atrial fibrillation using a novel technique termed focal impulse and rotor mapping (FIRM). Our results provide theoretical justification and clinical demonstration that FIRM meets the spatio-temporal resolution requirements to reliably identify rotors and focal sources for human atrial fibrillation.

  18. Detection of quiescent cardiac phases in echocardiography data using nonlinear filtering and boundary detection techniques.

    PubMed

    Ravichandran, Lakshminarayan; Wick, Carson A; McClellan, James H; Liu, Tian; Tridandapani, Srini

    2014-10-01

    We describe an algorithm to detect cardiac quiescence within a heartbeat using nonlinear filtering and boundary detection techniques in echocardiography images. The motivation for detection of these quiescent phases is to provide improved cardiac gating to obtain motion-artifact-free images of the heart at cardiac computed tomography (CT). Currently, cardiac gating is provided through electrocardiography (ECG), which does not provide information about the instantaneous mechanical state of the heart. Our goal is to test if information about the actual mechanical motion of the heart obtained from B-mode echocardiographic data could potentially be used for gating purposes. The nonlinear filtering algorithm presented involves anisotropic diffusion to smoothen the homogeneous regions of the B-mode images while preserving image edges that represent myocardial boundaries. Following this, we detect the boundary of a particular region of interest (ROI) using a thresholding step. The positional changes of this ROI are then observed for quiescent phases over multiple cardiac cycles using the ECG's R-R interval. In a pilot study, seven subjects were imaged in the apical, four-chamber view, and quiescence of the interventricular septum was primarily observed in the diastolic region of the ECG signal. However, the position and length of quiescence vary across multiple heartbeats for the same individual and for different individuals as well. The center of quiescence for the seven patients ranged from 51 to 84 % and did not show a trend with heart rates, which ranged from 54 to 83 beats per minute. The gating intervals based on such analysis of echocardiographic signals could potentially optimize cardiac CT gating. PMID:24859726

  19. Detection and Prevention of Cardiac Arrhythmias During Space Flight

    NASA Technical Reports Server (NTRS)

    Pillai, Dilip; Rosenbaum, David S.; Liszka, Kathy J.; York, David W.; Mackin, Michael A.; Lichter, Michael J.

    2004-01-01

    There have been reports suggesting that long-duration space flight might lead to an increased risk of potentially serious heart rhythm disturbances. If space flight does, in fact, significantly decrease cardiac electrical stability, the effects could be catastrophic, potentially leading to sudden cardiac death. It will be important to determine the mechanisms underlying this phenomenon in order to prepare for long-term manned lunar and interplanetary missions and to develop appropriate countermeasures. Our hypothesis is that prolonged exposure to microgravity will alter T wave alternans measurements, decrease heart rate variance, increase QT dispersion, decrease heart rate recovery and alter QT restitution curve. A recently published study has shown that long duration spaceflights prolong cardiac conduction and repolarization. They concluded that long duration flight is associated with QT interval prolongation and may increase arrhythmia susceptibility. We propose using computer technology as a noninvasive clinical tool to detect and study clinically significant TWA during standard exercise testing using electrode systems specifically adapted for the purpose of obtaining and measuring TWA. A population of approximately 15 healthy men and 5 healthy women subjects, representative of the astronaut cohort will be asked to voluntarily participate in this study. Their blood pressure and ECG/TWA will be measured pre-flight and in-flight. Prior to flight, subjects will be asked to participate in an orientation session. Still photos will be taken of the skin where the conductive gel is used for the multi-segment sensors. Photos will be recorded preflight, immediately postflight, and several times during the proceeding week until it has been determined that any skin reaction has disappeared or that no rash is present and will not appear.

  20. Ubiquitous health monitoring and real-time cardiac arrhythmias detection: a case study.

    PubMed

    Li, Jian; Zhou, Haiying; Zuo, Decheng; Hou, Kun-Mean; De Vaulx, Christophe

    2014-01-01

    As the symptoms and signs of heart diseases that cause sudden cardiac death, cardiac arrhythmia has attracted great attention. Due to limitations in time and space, traditional approaches to cardiac arrhythmias detection fail to provide a real-time continuous monitoring and testing service applicable in different environmental conditions. Integrated with the latest technologies in ECG (electrocardiograph) analysis and medical care, the pervasive computing technology makes possible the ubiquitous cardiac care services, and thus brings about new technical challenges, especially in the formation of cardiac care architecture and realization of the real-time automatic ECG detection algorithm dedicated to care devices. In this paper, a ubiquitous cardiac care prototype system is presented with its architecture framework well elaborated. This prototype system has been tested and evaluated in all the clinical-/home-/outdoor-care modes with a satisfactory performance in providing real-time continuous cardiac arrhythmias monitoring service unlimitedly adaptable in time and space. PMID:24211993

  1. Noninvasive Cardiac Quantum Spectrum Technology Effectively Detects Myocardial Ischemia.

    PubMed

    Li, Ke; Xue, Qiao; Liu, Mohan; Zheng, Xiaoqin; Chen, Rui; Li, Yufeng; Dan, Qing; Fang, Danqun

    2016-01-01

    BACKGROUND A standard resting electrocardiogram (ECG) shows limited sensitivity and specificity for the detection of coronary artery disease (CAD). Several analytic methods exist to enhance the sensitivity and specificity of resting ECG for diagnosis of CAD. We compared a new computer-enhanced, resting ECG analysis device, the cardiac quantum spectrum (CQS) technique, with coronary angiography in the detection of CAD. MATERIAL AND METHODS A consecutive sample of 93 patients with a history of suspected CAD scheduled for coronary angiography was evaluated with CQS before coronary angiography. The sensitivity and specificity of CQS and standard 12-lead ECG for detecting hemodynamically relevant coronary stenosis were compared, using coronary angiography as the reference standard. Kappa analysis was performed to assess the agreement between CQS severity scores and the level of stenosis determined by coronary angiography. RESULTS The CQS system identified 78 of 82 patients with hemodynamically relevant stenosis (sensitivity, 95.1%; specificity, 63.6%; accuracy, 91.4%; positive predictive value, 95.1%; negative predictive value, 63.6%). Sensitivity and accuracy were much higher for CQS analysis than for the standard ECG. The Kappa value, assessing the level of agreement between CQS and coronary angiography, was 0.376 (P<0.001). CONCLUSIONS CQS analysis of resting ECG data detects hemodynamically relevant CAD with high sensitivity and specificity. PMID:27351755

  2. Noninvasive Cardiac Quantum Spectrum Technology Effectively Detects Myocardial Ischemia

    PubMed Central

    Li, Ke; Xue, Qiao; Liu, Mohan; Zheng, Xiaoqin; Chen, Rui; Li, Yufeng; Dan, Qing; Fang, Danqun

    2016-01-01

    Background A standard resting electrocardiogram (ECG) shows limited sensitivity and specificity for the detection of coronary artery disease (CAD). Several analytic methods exist to enhance the sensitivity and specificity of resting ECG for diagnosis of CAD. We compared a new computer-enhanced, resting ECG analysis device, the cardiac quantum spectrum (CQS) technique, with coronary angiography in the detection of CAD. Material/Methods A consecutive sample of 93 patients with a history of suspected CAD scheduled for coronary angiography was evaluated with CQS before coronary angiography. The sensitivity and specificity of CQS and standard 12-lead ECG for detecting hemodynamically relevant coronary stenosis were compared, using coronary angiography as the reference standard. Kappa analysis was performed to assess the agreement between CQS severity scores and the level of stenosis determined by coronary angiography. Results The CQS system identified 78 of 82 patients with hemodynamically relevant stenosis (sensitivity, 95.1%; specificity, 63.6%; accuracy, 91.4%; positive predictive value, 95.1%; negative predictive value, 63.6%). Sensitivity and accuracy were much higher for CQS analysis than for the standard ECG. The Kappa value, assessing the level of agreement between CQS and coronary angiography, was 0.376 (P<0.001). Conclusions CQS analysis of resting ECG data detects hemodynamically relevant CAD with high sensitivity and specificity. PMID:27351755

  3. Sensitivity of scintigraphy with /sup 111/In-lymphocytes for detection of cardiac allograft rejection

    SciTech Connect

    Eisenberg, S.B.; Eisen, H.J.; Sobel, B.E.; Bergmann, S.R.; Bolman, R.M. 3d.

    1988-12-01

    We recently demonstrated the feasibility of noninvasive detection of cardiac allograft rejection after administration of indium-111-labeled lymphocytes. To determine the sensitivity and specificity of the technique, as well as its value for delineating the severity of rejection, we studied 16 dogs with heterotopic thoracic cardiac allografts. Five animals were evaluated while exposed to immunosuppressive agents. Animals were scanned sequentially after administration of 100-400 microCi of indium-111-labeled autologous lymphocytes. Myocardial lymphocyte infiltration was expressed as the indium excess (IE), defined as the ratio of indium activity of the transplant or native heart compared with that in blood. Scintigraphic results were compared with characteristics of simultaneously obtained endomyocardial biopsies. Among 17 biopsy documented episodes of rejection, 16 were detected scintigraphically. Among 18 biopsies with no evidence of rejection, scintigraphy was uniformly negative. Thus, the sensitivity and specificity of scintigraphy were 94 and 100%, respectively. Biopsies graded as showing no rejection were associated with an IE of 0.3 +/- 0.5 (+/- SD); those graded as mild, 2.8 +/- 1.7; those as moderate, 10.7 +/- 7.2; and those graded as indicative of severe rejection, 14.2 +/- 4.5. Thus, scintigraphy with indium-111-labeled lymphocytes sensitively and specifically detects cardiac allograft rejection and delineates the intensity of the rejection process. It should be useful clinically for assessing potential allograft rejection noninvasively.

  4. Time delay between cardiac and brain activity during sleep transitions

    NASA Astrophysics Data System (ADS)

    Long, Xi; Arends, Johan B.; Aarts, Ronald M.; Haakma, Reinder; Fonseca, Pedro; Rolink, Jérôme

    2015-04-01

    Human sleep consists of wake, rapid-eye-movement (REM) sleep, and non-REM (NREM) sleep that includes light and deep sleep stages. This work investigated the time delay between changes of cardiac and brain activity for sleep transitions. Here, the brain activity was quantified by electroencephalographic (EEG) mean frequency and the cardiac parameters included heart rate, standard deviation of heartbeat intervals, and their low- and high-frequency spectral powers. Using a cross-correlation analysis, we found that the cardiac variations during wake-sleep and NREM sleep transitions preceded the EEG changes by 1-3 min but this was not the case for REM sleep transitions. These important findings can be further used to predict the onset and ending of some sleep stages in an early manner.

  5. Ultrasound Current Source Density Imaging of the Cardiac Activation Wave Using a Clinical Cardiac Catheter

    PubMed Central

    Qin, Yexian; Li, Qian; Ingram, Pier; Barber, Christy; Liu, Zhonglin

    2015-01-01

    Ultrasound current source density imaging (UCSDI), based on the acoustoelectric (AE) effect, is a noninvasive method for mapping electrical current in 4-D (space + time). This technique potentially overcomes limitations with conventional electrical mapping procedures typically used during treatment of sustained arrhythmias. However, the weak AE signal associated with the electrocardiogram is a major challenge for advancing this technology. In this study, we examined the effects of the electrode configuration and ultrasound frequency on the magnitude of the AE signal and quality of UCSDI using a rabbit Langendorff heart preparation. The AE signal was much stronger at 0.5 MHz (2.99 μV/MPa) than 1.0 MHz (0.42 μV/MPa). Also, a clinical lasso catheter placed on the epicardium exhibited excellent sensitivity without penetrating the tissue. We also present, for the first time, 3-D cardiac activation maps of the live rabbit heart using only one pair of recording electrodes. Activation maps were used to calculate the cardiac conduction velocity for atrial (1.31 m/s) and apical (0.67 m/s) pacing. This study demonstrated that UCSDI is potentially capable of real-time 3-D cardiac activation wave mapping, which would greatly facilitate ablation procedures for treatment of arrhythmias. PMID:25122512

  6. SPR detection of cardiac troponin T for acute myocardial infarction.

    PubMed

    Pawula, Maria; Altintas, Zeynep; Tothill, Ibtisam E

    2016-01-01

    A surface plasmon resonance (SPR) sensor developed for the rapid, sensitive and specific detection of cardiac troponin T (cTnT) in serum samples is reported in this work. An extensive optimisation of assay parameters was conducted to achieve optimal detection strategy. Both direct and sandwich immunoassay formats were investigated and optimised. The response obtained was enhanced further by the use of gold nanoparticles (AuNPs) conjugated to the anti-cTnT detection antibody. A regeneration method was developed to enable the reuse of the SPR sensor for multiple sample application. The SPR immunosensor showed good reproducibility for cTnT detection in the concentration range of 25-1000 ng mL(-1) and 5-400 ng mL(-1) for the direct and sandwich assays in buffer, respectively. The linear regression analysis was performed and R(2) value was found as 0.99 for both assays. In order to optimise the sensor for serum analysis, nonspecific binding of serum proteins was reduced through the use of additives in the dilution buffer. To achieve greater sensitivity, the performance of the cTnT immunosensor sandwich assay in human serum was evaluated using non-modified and AuNP modified detector antibodies. A detection limit (LOD) for the immunosensor in 50% serum was assessed as 5 ng mL(-1) cTnT for the standard sandwich assay and 0.5 ng mL(-1) cTnT when using AuNP conjugated detector antibodies with a linear dynamic range of 0.5-40 ng mL(-1). The dissociation constant was found as 3.28 × 10(-9) M using Langmuir binding model which indicates high affinity between cTnT and its antibody. The proposed SPR immunosensor has a promising potential to be developed for point-of-care testing for the early diagnosis of acute myocardial infarction (AMI). This method can also be used for the rapid detection of biomarkers in central nervous system diseases. PMID:26695335

  7. Cardiac parasympathetic activity in severe uncomplicated coronary artery disease.

    PubMed Central

    Nolan, J.; Flapan, A. D.; Reid, J.; Neilson, J. M.; Bloomfield, P.; Ewing, D. J.

    1994-01-01

    BACKGROUND--Previous studies have suggested that coronary artery disease is independently associated with reduced cardiac parasympathetic activity, and that this is important in its pathophysiology. These studies included many patients with complications that might be responsible for the reported autonomic abnormalities. OBJECTIVE--To measure cardiac parasympathetic activity in patients with uncomplicated coronary artery disease. PATIENTS AND METHODS--44 patients of mean (SD) age 56 (8) with severe uncomplicated coronary artery disease (symptoms uncontrolled on maximal medical treatment; > 70% coronary stenosis at angiography; normal ejection fraction; no evidence of previous infarction, diabetes, or hypertension). Heart rate variability was measured from 24 hour ambulatory electrocardiograms by counting the number of times successive RR intervals exceeded the preceding RR interval by > 50 ms, a previously validated sensitive and specific index of cardiac parasympathetic activity. RESULTS--Mean (range) of counts were: waking 112 (range 6-501)/h, sleeping 198 (0-812)/h, and total 3912 (151-14 454)/24 h. These mean results were unremarkable, and < 10% of patients fell below the lower 95% confidence interval for waking, sleeping, or total 24 hour counts in normal people. There was no relation between the severity of coronary artery disease or the use of concurrent antianginal drug treatment and cardiac parasympathetic activity. CONCLUSION--In contrast with previous reports no evidence of a specific independent association between coronary artery disease and reduced cardiac parasympathetic activity was found. The results of previous studies may reflect the inclusion of patients with complications and not the direct effect of coronary artery disease itself. PMID:7913823

  8. PP2 prevents isoproterenol stimulation of cardiac pacemaker activity.

    PubMed

    Huang, Jianying; Lin, Yen-Chang; Hileman, Stan; Martin, Karen H; Hull, Robert; Yu, Han-Gang

    2015-02-01

    Increasing evidence has demonstrated the potential risks of cardiac arrhythmias (such as prolonged QT interval) using tyrosine kinase inhibitors for cancer therapy. We report here that a widely used selective inhibitor of Src tyrosine kinases, PP2, can inhibit and prevent isoproterenol stimulation of cardiac pacemaker activity. In dissected rat sinus node, PP2 inhibited and prevented isoproterenol stimulation of spontaneous beating rate. In isolated sinus node myocytes, PP2 suppressed the hyperpolarization-activated "funny" current (If) by negatively shifting the activation curve and decelerating activation kinetics, associated with decreased cell surface expression and reduced tyrosine phosphorylation of hyperpolarization-activated cyclic nucleotide-modulated channel 4 (HCN4) channel proteins. In human embryonic kidney 293 cells overexpressing recombinant human HCN4 channels, PP2 reversed isoproterenol stimulation of HCN4 and inhibited HCN4-573x, a cAMP-insensitive human HCN4 mutant. Isoprotenrenol had little effects on HCN4-573x. These results demonstrated that inhibition of presumably tyrosine Src kinase activity in heart by PP2 decreased and prevented the potential β-adrenergic stimulation of cardiac pacemaker activity. These effects are mediated, at least partially, by a cAMP-independent attenuation of channel activity and cell surface expression of HCN4, the key channel protein that controls the heart rate. PMID:25658311

  9. Automatic detection of atrial fibrillation in cardiac vibration signals.

    PubMed

    Brueser, C; Diesel, J; Zink, M D H; Winter, S; Schauerte, P; Leonhardt, S

    2013-01-01

    We present a study on the feasibility of the automatic detection of atrial fibrillation (AF) from cardiac vibration signals (ballistocardiograms/BCGs) recorded by unobtrusive bedmounted sensors. The proposed system is intended as a screening and monitoring tool in home-healthcare applications and not as a replacement for ECG-based methods used in clinical environments. Based on BCG data recorded in a study with 10 AF patients, we evaluate and rank seven popular machine learning algorithms (naive Bayes, linear and quadratic discriminant analysis, support vector machines, random forests as well as bagged and boosted trees) for their performance in separating 30 s long BCG epochs into one of three classes: sinus rhythm, atrial fibrillation, and artifact. For each algorithm, feature subsets of a set of statistical time-frequency-domain and time-domain features were selected based on the mutual information between features and class labels as well as first- and second-order interactions among features. The classifiers were evaluated on a set of 856 epochs by means of 10-fold cross-validation. The best algorithm (random forests) achieved a Matthews correlation coefficient, mean sensitivity, and mean specificity of 0.921, 0.938, and 0.982, respectively. PMID:23086532

  10. Changes in the cardiac muscle electric activity as a result of Coronary Artery Bypass Graft operation

    NASA Astrophysics Data System (ADS)

    Grajek, Magdalena; Krzyminiewski, Ryszard; Kalawski, Ryszard; Kulczak, Mariusz

    2008-01-01

    Many bioelectric signals have a complex internal structure that can be a rich source of information on the tissue or cell processes. The structure of such signals can be analysed in detail by applying digital methods of signal processing. Therefore, of substantial use in diagnosis of the coronary arterial disease is the method of digital enhancement of increasing signal resolution ECG (NURSE-ECG), permitting detection of temporary changes in the electric potentials in the cardiac muscle in the process of depolarisation. Thanks to the application of NURSE-ECG it has become possible to detect relatively small changes in the electric activity of particular fragments of the cardiac muscle undetectable by the standard ECG method, caused by ischemia, the effect of a drug or infarct. The aim of this study was to identify and analyse changes in the electric activity of the cardiac muscle as a result of the Coronary Artery Bypass Graft (CABG) operation. In this study the method of NURSE-ECG has been applied in order to identify and analyse changes in the electric activity of the cardiac muscle as a result of the CABG operation. In the study performed in cooperation of the Institute of Physics Adam Mickiewicz University and the Strus Hospital, Cardiac Surgery Ward, 37 patients with advanced coronary arterial disease were asked to participate. The patients were examined prior to the operation, on the day after the operation and two months after the operation and a year after the operation. The ECG recordings were subjected to a numerical procedure of resolution enhancement by a NURSE-ECG program to reveal the tentative changes in the electric potential of the cardiac muscle on its depolarisation. Results of the study have shown that the NURSE ECG method can be applied to monitor changes in the electric activity of the cardiac muscle occurring as a result of CABG operation. One the second day after the operation in the majority of patients (70%) a rapid decrease of the total

  11. A voltage-activated proton current in human cardiac fibroblasts

    SciTech Connect

    El Chemaly, Antoun; Guinamard, Romain; Demion, Marie; Fares, Nassim; Jebara, Victor; Faivre, Jean-Francois; Bois, Patrick . E-mail: patrick.bois@univ-poitiers.fr

    2006-02-10

    A voltage-activated proton current in human cardiac fibroblasts, measured using the whole-cell recording configuration of the patch-clamp technique, is reported. Increasing the pH of the bathing solution shifted the current activation threshold to more negative potentials and increased both the current amplitude and its rate of activation. Changing the pH gradient by one unit caused a 51 mV shift in the reversal potential of the current, demonstrating a high selectivity for protons of the channel carrying the current. Extracellularly applied Zn{sup 2+} reversibly inhibited the current. Activation of the current contributes to the resting membrane conductance under conditions of intracellular acidosis. It is proposed that this current in cardiac fibroblasts is involved in the regulation of the intracellular pH and the membrane potential under physiological conditions as well as in response to pathological conditions such as ischemia.

  12. Cardiac repolarization abnormalities and increased sympathetic activity in scleroderma.

    PubMed Central

    Ciftci, Orcun; Onat, Ahmet Mesut; Yavuz, Bunyamin; Akdogan, Ali; Aytemir, Kudret; Tokgozoglu, Lale; Sahiner, Levent; Deniz, Ali; Ureten, Kemal; Kizilca, Guler; Calguneri, Meral; Oto, Ali

    2007-01-01

    BACKGROUND: Cardiac involvement in scleroderma is a poor prognostic sign and is usually underdiagnosed, particularly in asymptomatic patient. This paper focuses on QT dynamicity and heart rate variability (HRV) in patients with scleroderma and controls in an attempt to investigate the cardiac autonomic system and ventricular repolarization. METHODS: Sixty patients with scleroderma and 30 age- and sex-matched healthy controls who had no cardiovascular risk factors were included in this study. All patients and the controls underwent a 24-hour holter recording as well as a transthoracic echocardiography. HRV and QT dynamicity parameters were calculated. RESULTS: In HRV analysis, autonomic balance was changed in favor of the sympathetic system in patients with diffuse scleroderma. In QT dynamicity analysis, QT/RR slopes were significantly steeper in patients with diffuse scleroderma compared to patients with limited scleroderma and controls (QTapex/RR: 0.24 +/- 0.16, 0.15 +/- 0.03, 0.14 +/- 0.03 respectively p < 0.001; QTend/RR: 0.26 +/- 0.17, 0.14 +/- 0.04, 0.13 +/- 0.05, respectively p < 0.001). CONCLUSIONS: Patients with diffuse scleroderma may have asymptomatic cardiac repolarization abnormalities and autonomic dysfunction. Our results may indicate that QT dynamicity and HRV can be useful noninvasive methods that may detect impaired state of autonomic balance and cardiac repolarization in patients with diffuse scleroderma. PMID:17393947

  13. Diagnostic utility of cardiac magnetic resonance for detection of cardiac involvement in female carriers of Duchenne muscular dystrophy

    PubMed Central

    Iwase, Takashi; Takao, Shoichiro; Akaike, Masashi; Adachi, Katsuhito; Sumitomo-Ueda, Yuka; Yagi, Shusuke; Niki, Toshiyuki; Kusunose, Kenya; Tomita, Noriko; Hirata, Yoichiro; Yamaguchi, Koji; Koshiba, Kunihiko; Taketani, Yoshio; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Aihara, Ken-ichi; Harada, Masafumi; Nishitani, Hiromu; Sata, Masataka

    2010-01-01

    Background Cardiac involvement is a recognised complication in female carriers of Duchenne muscular dystrophy (DMD). Since segmental or global left ventricle (LV) wall motion abnormalities in DMD carriers can arise even without apparent muscle weakness, it is difficult to differentiate cardiac involvement of a DMD carrier from other heart diseases in a non-invasive manner. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) enables assessment of regional wall motion abnormality and myocardial damage with high spatial resolution. Objective To assess the utility of CMR for detection of myocardial damage in female carriers of DMD. Methods and results Gadolinium-enhanced CMR was performed in seven female DMD carriers. Physical examination, electrocardiography, chest radiograph, measurements of total creatinine kinase and brain natriuretic peptide levels, and two-dimensional echocardiography were also performed. Four (57%) of the seven carriers had LGE, and LGE was frequently observed at the subepicardial layer in the inferolateral segment. Two carriers had a focal LGE at the LV inferolateral wall without LV dilation or wall motion abnormalities. Conclusion CMR findings of DMD carriers were characterised by subepicardial LGE, which was localised at inferolateral segments. CMR may be a useful modality for detecting cardiac involvement in DMD carriers.

  14. Interactions between cardiac, respiratory, and brain activity in humans

    NASA Astrophysics Data System (ADS)

    Musizza, Bojan; Stefanovska, Aneta

    2005-05-01

    The electrical activity of the heart (ECG), respiratory function and electric activity of the brain (EEG) were simultaneously recorded in conscious, healthy humans. Instantaneous frequencies of the heart beat, respiration and α-waves were then determined from 30-minutes recordings. The instantaneous cardiac frequency was defined as the inverse value of the time interval between two consecutive R-peaks. The instantaneous respiratory frequency was obtained from recordings of the excursions of thorax by application of the Hilbert transform. To obtain the instantaneous frequency of α-waves, the EEG signal recorded from the forehead was first analysed using the wavelet transform. Then the frequency band corresponding to α-waves was extracted and the Hilbert transform applied. Synchronization analysis was performed and the direction of coupling was ascertained, using pairs of instantaneous frequencies in each case. It is shown that the systems are weakly bidirectionally coupled. It was confirmed that, in conscious healthy humans, respiration drives cardiac activity. We also demonstrate from these analyses that α-activity drives both respiration and cardiac activity.

  15. Activation of GPR30 inhibits cardiac fibroblast proliferation.

    PubMed

    Wang, Hao; Zhao, Zhuo; Lin, Marina; Groban, Leanne

    2015-07-01

    The incidence of left ventricular diastolic dysfunction significantly increases in postmenopausal women suggesting the association between estrogen loss and diastolic dysfunction. The in vivo activation of G protein-coupled estrogen receptor (GPR30) attenuates the adverse effects of estrogen loss on cardiac fibrosis and diastolic dysfunction in mRen2.Lewis rats. This study was designed to address the effects of GPR30 on cardiac fibroblast proliferation in rats. The expression of GPR30 in cardiac fibroblasts isolated from adult Sprague-Dawley rats was confirmed by RT-PCR, Western blot analysis, and immunofluorescence staining. Results from BrdU incorporation assays, cell counting, carboxyfluorescein diacetate succinimidyl ester labeling in conjunction with flow cytometry, and Ki-67 staining showed that treatment with G1, a specific agonist of GPR30, inhibited cardiac fibroblast proliferation in a dose-dependent manner, which was associated with decreases in CDK1 and cyclin B1 protein expressions. In the GPR30-KO cells, BrdU incorporation, and CDK1 and cyclin B1 expressions significantly increased when compared to GPR30-intact cells. G1 had no effect on BrdU incorporation, CDK1 and cyclin B1 mRNA levels in GPR30-KO cells. In vivo studies showed increases in CDK1 and cyclin B1 mRNA levels, Ki-67-positive cells, and the immunohistochemistry staining of vimentin, a fibroblast marker, in the left ventricles from ovariectomized mRen2.Lewis rats versus hearts from ovary-intact littermates; 2 weeks of G1 treatment attenuated these adverse effects of estrogen loss. This study demonstrates that GPR30 is expressed in rat cardiac fibroblasts, and activation of GPR30 limits proliferation of these cells likely via suppression of the cell cycle proteins, cyclin B1, and CDK1. PMID:25893735

  16. Visualization of cardiac dipole using a current density map: detection of cardiac current undetectable by electrocardiography using magnetocardiography.

    PubMed

    Ikefuji, Hiroyuki; Nomura, Masahiro; Nakaya, Yutaka; Mori, Toshifumi; Kondo, Noriyasu; Ieishi, Kiyoshi; Fujimoto, Sayuri; Ito, Susumu

    2007-02-01

    A close relationship exists between electric current and the magnetic field. However, electricity and magnetism have different physical characteristics, and magnetocardiography (MCG) may provide information on cardiac current that is difficult to obtain by electrocardiography (ECG). In the present study, we investigated the issue of whether the current density map method, in which cardiac current is estimated from the magnetic gradient, facilitates the visualization of cardiac current undetectable by ECG. The subjects were 50 healthy adults (N group), 40 patients with left ventricular overloading (LVO group), 15 patients with right ventricular overloading (RVO group), 10 patients with an old inferior myocardial infarction (OMI group), and 30 patients with diabetes mellitus (DM group). MCGs were recorded with a second derivative superconducting quantum interference device (SQUID) gradiometer using liquid helium. Isopotential maps and current density maps from unipolar precordial ECG leads and MCGs, respectively, were prepared, and the cardiac electric current was examined. The current density map at the ventricular depolarization phase showed one peak of current density in the N group. However, in the OMI group, the current density map showed multiple peaks of current density areas. In the RVO group, two peaks of current densities were detected at the right superior region and left thoracic region and these two diploles appeared to be from the right and left ventricular derived cardiac currents, respectively. Moreover, there was a significant correlation between the magnitude of the current density from the right ventricle and the systolic pulmonary arterial pressure. The current density map at the ventricular repolarization phase in the N group showed only a single current source. However, abnormal current sources in the current density maps were frequently detected even in patients showing no abnormalities on isopotential maps in the LVO, DM, and OMI groups. The

  17. Early detection of cardiac involvement in thalassemia: From bench to bedside perspective

    PubMed Central

    Koonrungsesomboon, Nut; Chattipakorn, Siriporn C; Fucharoen, Suthat; Chattipakorn, Nipon

    2013-01-01

    Myocardial siderosis is known as the major cause of death in thalassemia major (TM) patients since it can lead to iron overload cardiomyopathy. Although this condition can be prevented if timely effective intensive chelation is given to patients, the mortality rate of iron overload cardiomyopathy still remains high due to late detection of this condition. Various direct and indirect methods of iron assessment, including serum ferritin level, echocardiogram, non-transferrin-bound iron, cardiac magnetic resonance T2*, heart rate variability, and liver biopsy and myocardial biopsy, have been proposed for early detection of cardiac iron overload in TM patients. However, controversial evidence and limitations of their use in clinical practice exist. In this review article, all of these iron assessment methods that have been proposed or used to directly or indirectly determine the cardiac iron status in TM reported from both basic and clinical studies are comprehensively summarized and presented. Since there has been growing evidence in the past decades that cardiac magnetic resonance imaging as well as cardiac autonomic status known as the heart rate variability can provide early detection of cardiac involvement in TM patients, these two methods are also presented and discussed. The existing controversy regarding the assessment of cardiac involvement in thalassemia is also discussed. PMID:24009816

  18. Influence of computer work under time pressure on cardiac activity.

    PubMed

    Shi, Ping; Hu, Sijung; Yu, Hongliu

    2015-03-01

    Computer users are often under stress when required to complete computer work within a required time. Work stress has repeatedly been associated with an increased risk for cardiovascular disease. The present study examined the effects of time pressure workload during computer tasks on cardiac activity in 20 healthy subjects. Heart rate, time domain and frequency domain indices of heart rate variability (HRV) and Poincaré plot parameters were compared among five computer tasks and two rest periods. Faster heart rate and decreased standard deviation of R-R interval were noted in response to computer tasks under time pressure. The Poincaré plot parameters showed significant differences between different levels of time pressure workload during computer tasks, and between computer tasks and the rest periods. In contrast, no significant differences were identified for the frequency domain indices of HRV. The results suggest that the quantitative Poincaré plot analysis used in this study was able to reveal the intrinsic nonlinear nature of the autonomically regulated cardiac rhythm. Specifically, heightened vagal tone occurred during the relaxation computer tasks without time pressure. In contrast, the stressful computer tasks with added time pressure stimulated cardiac sympathetic activity. PMID:25614130

  19. Cardiac rate detection method based on the beam splitter prism

    NASA Astrophysics Data System (ADS)

    Yang, Lei; Liu, Xiaohua; Liu, Ming; Zhao, Yuejin; Dong, Liquan; Zhao, Ruirui; Jin, Xiaoli; Zhao, Jingsheng

    2013-09-01

    A new cardiac rate measurement method is proposed. Through the beam splitter prism, the common-path optical system of transmitting and receiving signals is achieved. By the focusing effect of the lens, the small amplitude motion artifact is inhibited and the signal-to-noise is improved. The cardiac rate is obtained based on the PhotoPlethysmoGraphy (PPG). We use LED as the light source and use photoelectric diode as the receiving tube. The LED and the photoelectric diode are on the different sides of the beam splitter prism and they form the optical system. The signal processing and display unit is composed by the signal processing circuit, data acquisition device and computer. The light emitted by the modulated LED is collimated by the lens and irradiates the measurement target through the beam splitter prism. The light reflected by the target is focused on the receiving tube through the beam splitter prism and another lens. The signal received by the photoelectric diode is processed by the analog circuit and obtained by the data acquisition device. Through the filtering and Fast Fourier Transform, the cardiac rate is achieved. We get the real time cardiac rate by the moving average method. We experiment with 30 volunteers, containing different genders and different ages. We compare the signals captured by this method to a conventional PPG signal captured concurrently from a finger. The results of the experiments are all relatively agreeable and the biggest deviation value is about 2bmp.

  20. Three-dimensional active shape model matching for left ventricle segmentation in cardiac CT

    NASA Astrophysics Data System (ADS)

    van Assen, Hans C.; van der Geest, Rob J.; Danilouchkine, Mikhail G.; Lamb, Hildo J.; Reiber, Johan H. C.; Lelieveldt, Boudewijn P. F.

    2003-05-01

    Manual quantitative analysis of cardiac left ventricular function using multi-slice CT is labor intensive because of the large datasets. We present an automatic, robust and intrinsically three-dimensional segmentation method for cardiac CT images, based on 3D Active Shape Models (ASMs). ASMs describe shape and shape variations over a population as a mean shape and a number of eigenvariations, which can be extracted by e.g. Principal Component Analysis (PCA). During the iterative ASM matching process, the shape deformation is restricted within statistically plausible constraints (+/-3σ). Our approach has two novel aspects: the 3D-ASM application to volume data of arbitrary planar orientation, and the application to image data from another modality than which was used to train the model, without the necessity of retraining it. The 3D-ASM was trained on MR data and quantitatively evaluated on 17 multi-slice cardiac CT data sets, with respect to calculated LV volume (blood pool plus myocardium) and endocardial volume. In all cases, model matching was convergent and final results showed a good model performance. Bland-Altman analysis however, showed that bloodpool volume was slightly underestimated and LV volume was slightly overestimated by the model. Nevertheless, these errors remain within clinically acceptable margins. Based on this evaluation, we conclude that our 3D-ASM combines robustness with clinically acceptable accuracy. Without retraining for cardiac CT, we could adapt a model trained on cardiac MR data sets for application in cardiac CT volumes, demonstrating the flexibility and feasibility of our matching approach. Causes for the systematic errors are edge detection, model constraints, or image data reconstruction. For all these categories, solutions are discussed.

  1. CpG-ODN Attenuates Pathological Cardiac Hypertrophy and Heart Failure by Activation of PI3Kα-Akt Signaling

    PubMed Central

    Yang, Liang; Cai, Xiangyu; Liu, Jie; Jia, Zhe; Jiao, Jinjin; Zhang, Jincai; Li, Changlin; Li, Jing; Tang, Xiang D.

    2013-01-01

    Phosphoinositide-3-kinase α (PI3Kα) represents a potential novel drug target for pathological cardiac hypertrophy (PCH) and heart failure. Oligodeoxynucleotides containing CpG motifs (CpG-ODN) are classic agonists of Toll-like receptor 9 (TLR9), which typically activates PI3K-Akt signaling in immune cells; however, the role of the nucleotide TLR9 agonists in cardiac myocytes is largely unknown. Here we report that CpG-ODN C274 could both attenuate PCH and improve cardiac dysfunction by activating PI3Kα-Akt signaling cascade. In vitro studies indicated that C274 could blunt reactivation of fetal cardiac genes and cell enlargement induced by a hypertrophic agent, isoproterenol. The anti-hypertrophic effect of C274 was suppressed by a pan-PI3K inhibitor, LY294002, or a small interfering RNA targeting PI3Kα. In vivo studies demonstrated that PCH, as marked by increased heart weight (HW) and cardiac ANF mRNA, was normalized by pre-administration with C274. In addition, Doppler echocardiography detected cardiac ventricular dilation, and contractile dysfunction in isoproterenol-treated animals, consistent with massive replacement fibrosis, reflecting cardiac cell death. As expected, pre-treatment of mice with C274 could prevent cardiac dysfunction associated with diminished cardiac cell death and fibrosis. In conclusion, CpG-ODNs are novel cardioprotective agents possessing antihypertrophic and anti-cell death activity afforded by engagement of the PI3Kα-Akt signaling. CpG-ODNs may have clinical use curbing the progression of PCH and preventing heart failure. PMID:23638055

  2. Gated cardiac NMR imaging and 2D echocardiography in the detection of intracardial neoplasm

    SciTech Connect

    Go, R.T.; O'Donnell, J.K.; Salcedo, E.E.; Feiglin, D.H.; Underwood, D.A.; MacIntyre, W.J.; Meaney, T.F.

    1985-05-01

    Noninvasive 2D echocardiography has replaced contrast angiography as the procedure of choice in the diagnosis of intracardiac neoplasm. The purpose of this study was to determine whether intracardiac neoplasm can be detected as well by gated cardiac NMR. Four patients with known intracardiac neoplasm previously diagnosed by 2D echocardiography had gated cardiac NMR imaging using a superconductive 0.6 Tesla magnet. All patients were performed using a Tl weighted spin echo pulse sequence with a TE of 30 msec and TR of one R-R interval. Two-dimensional planar single or multiple slice techniques were used. In one patient, imaging at different times along the R-R interval were performed for cine display. The results of the present study show detection of the intracardiac neoplasm in all four cases by gated cardiac NMR imaging and the results were comparable to 2D echocardiography. The former imaging technique showed superior spatial resolution. Despite its early stage of development, gated cardiac NMR imaging appears at least equal to 2D echocardiography in the detection of intracardiac neoplasm. The availability of multislice coupled with multiframe acquisition techniques now being developed will provide a cinematic display that will be more effective in the display of the tumor in motion within the cardiac chamber involved and facilitate visualization of the relationship of the tumor to adjacent cardiac structures.

  3. Evaluation of transesophageal echocardiography in detecting cardiac sources of emboli in ischemic stroke patients

    PubMed Central

    Toodeji, Mohammad Amin; Izadi, Sadegh; Shariat, Abdolhamid; Nikoo, Mohamad Hosin

    2015-01-01

    Background: Embolus is one of the causes of ischemic stroke that can be due to cardiac sources such as valvular heart diseases and atrial fibrillation and atheroma of the aorta. Transesophageal echocardiography (TEE) is superior in identifying potential cardiac sources of emboli. Due to insufficient data on TEE findings in ischemic stroke in Iran, the present study was done to evaluate TEE in detecting cardiac sources of emboli. The main aim of this study was to describe the cardiogenic sources of emboli using TEE in the ischemic stroke patients. Methods: This is a cross-sectional study conducted during a 13-month period from January 2012 to February 2013 in Shiraz Nemazee teaching hospital. Patients admitted with stroke diagnosis were included; but hemorrhagic stroke cases were excluded. 229 patients with ischemic stroke diagnosis were included and underwent TEE. Results: Causes of cardiac emboli were detected in 65 cases (40.7%) and categorized to high-risk (29.7%) and potential risk (11%). High risk cardiac sources included atrial fibrillation (8.7%), mitral valve disease (MS or MI) 11 cases (4.75%), aortic valve disease (AS or AI) 8 (3.5%), prosthetic valve 3 (1.35%), dilated cardiomyopathy 45 (19.65%) and congestive heart failure with ejection fraction < 30% in 8 cases (3.5%). Potential cardiac sources of emboli comprised 7 cases (3.05%) of septal aneurysm, 4 (1.75%) left ventricular hypokinesia, 13 (5.7%) mitral annular calcification and 9 cases (3.95%) complex atheroma in the ascending aorta or proximal arch. Conclusion: Our study showed that high risk cardiac sources of emboli can be detected using TEE in a considerable percentage of ischemic stroke patients. The most common high risk cardiac etiologies were dilated cardiomyopathy and valvular heart diseases. PMID:26793628

  4. Tetrandrine reverses human cardiac myofibroblast activation and myocardial fibrosis.

    PubMed

    Teng, Guoqi; Svystonyuk, Daniyil; Mewhort, Holly E M; Turnbull, Jeannine D; Belke, Darrell D; Duff, Henry J; Fedak, Paul W M

    2015-06-15

    Tetrandrine (TTD) is a calcium channel blocker with documented antifibrotic actions. In this study, for the first time, we identified that TTD can directly prevent in vitro human cardiac myofibroblast activation and limit in vivo myocardial fibrosis. In vitro, cardiac myofibroblasts from human atrial biopsies (N = 10) were seeded in three-dimensional collagen matrices. Cell-collagen constructs were exposed to transforming growth factor-β1 (10 ng/ml), with or without TTD (1 and 5 μM) for 48 h. Collagen gel contraction, myofibroblast activation (α-smooth muscle actin expression), expression of profibrotic mRNAs, and rate of collagen protein synthesis were compared. TTD decreased collagen gel contraction (79.7 ± 1.3 vs 60.1 ± 8.9%, P < 0.01), α-smooth muscle actin expression (flow cytometry), collagen synthesis ([(3)H]proline incorporation), and collagen mRNA expression. Cell viability was similar between groups (annexin positive cells: 1.7 vs. 1.4%). TTD inhibited collagen gel contraction in the presence of T-type and L-type calcium channel blockers, and the intracellular calcium chelator BAPTA-AM (15 μM), suggesting that the observed effects are not mediated by calcium homeostasis. In vivo, Dahl salt-sensitive hypertensive rats were treated with variable doses of TTD (by intraperitoneal injection over 4 wk) and compared with untreated controls (N = 12). Systemic blood pressure was monitored by tail cuff. Myocardial fibrosis and left ventricular compliance were assessed by histology and passive pressure-volume analysis. Myocardial fibrosis was attenuated compared with untreated controls (%collagen area: 9.4 ± 7.3 vs 2.1 ± 1.0%, P < 0.01). Left ventricular compliance was preserved. In conclusion, TTD reverses human cardiac myofibroblast activation and myocardial fibrosis, independent of calcium channel blockade. PMID:25862829

  5. Dominance in cardiac parasympathetic activity during real recreational SCUBA diving.

    PubMed

    Chouchou, Florian; Pichot, Vincent; Garet, Martin; Barthélémy, Jean-Claude; Roche, Frédéric

    2009-06-01

    It was already established that exposure to hyperbaric conditions induces vagal-depended bradycardia but field study on autonomic nervous system (ANS) activity during self-contained underwater breathing apparatus (SCUBA) diving is lacking. The aim of the present study was to evaluate ANS modifications during real recreational SCUBA diving using heart rate variability analysis (timedomain, frequency-domain and Poincaré plot) in 10 experienced and volunteers recreational divers. Mean RR, root mean square of successive differences of interval (rMSSD), high frequency of spectral analysis and standard deviation 1 of Poincaré Plot increased (P < 0.05) during dive. Low frequency/high frequency ratio decreased during dive (P < 0.05) but increased after (P < 0.05). Recreational SCUBA diving induced a rise in vagal activity and a decrease in cardiac sympathetic activity. Conversely, sympathetic activity increases (P < 0.05) during the recovery. PMID:19277697

  6. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    SciTech Connect

    Cros, C.; Skinner, M.; Moors, J.; Lainee, P.; Valentin, J.P.

    2012-12-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two

  7. Detection and Prevention of Cardiac Arrhythmias During Space Flight

    NASA Technical Reports Server (NTRS)

    Pillai, Dilip; Rosenbaum, David S.; Liszka, Kathy J.; York, David W.; Mackin, Michael A.; Lichter, Michael J.

    2004-01-01

    There have been reports suggesting that long-duration space flight might lead to an increased risk of potentially serious heart rhythm disturbances. If space flight does, in fact, significantly decrease cardiac electrical stability, the effects could be catastrophic, potentially leading to sudden cardiac death. It will be important to determine the mechanisms underlying this phenomenon in order to prepare for long-term manned lunar and interplanetary missions and to develop appropriate countermeasures. Electrical alternans affecting the ST segment and T-wave have been demonstrated to be common among patients at increased risk for ventricular arrhythmias. Subtle electrical alternans on the ECG may serve as a noninvasive marker of vulnerability to ventricular arrhythmias. We are studying indices of electrical instability in the heart for long term space missions by non-invasively measuring microvolt level T-wave alternans in a reduced gravity environment. In this investigation we are using volunteer subjects on the KC-135 aircraft as an initial study of the effect of electrical adaptation of the heart to microgravity. T-wave alternans will be analyzed for heart rate variability and QT restitution curve plotting will be compared for statistical significance.

  8. Activity performance problems of patients with cardiac diseases and their impact on quality of life

    PubMed Central

    Duruturk, Neslihan; Tonga, Eda; Karatas, Metin; Doganozu, Ersin

    2015-01-01

    [Purpose] To describe the functional consequences of patients with cardiac diseases and analyze associations between activity limitations and quality of life. [Subjects and Methods] Seventy subjects (mean age: 60.1±12.0 years) were being treated by Physical Medicine and Rehabilitation and Cardiology Departments were included in the study. Activity limitations and participation restrictions as perceived by the individual were measured by the Canadian Occupational Performance Measure (COPM). The Nottingham Extended Activities of Daily Living (NEADL) Scale was used to describe limitations in daily living activities. To detect the impact of activity limitations on quality of life the Nottingham Health Profile (NHP) was used. [Results] The subjects described 46 different types of problematic activities. The five most identified problems were walking (45.7%), climbing up the stairs (41.4%), bathing (30%), dressing (28.6%) and outings (27.1%). The associations between COPM performance score with all subgroups of NEADL and NHP; total, energy, physical abilities subgroups, were statistically significant. [Conclusion] Our results showed that patients with cardiac diseases reported problems with a wide range of activities, and that also quality of life may be affected by activities of daily living. COPM can be provided as a patient-focused outcome measure, and it may be a useful tool for identifying those problems. PMID:26311919

  9. Activity performance problems of patients with cardiac diseases and their impact on quality of life.

    PubMed

    Duruturk, Neslihan; Tonga, Eda; Karatas, Metin; Doganozu, Ersin

    2015-07-01

    [Purpose] To describe the functional consequences of patients with cardiac diseases and analyze associations between activity limitations and quality of life. [Subjects and Methods] Seventy subjects (mean age: 60.1±12.0 years) were being treated by Physical Medicine and Rehabilitation and Cardiology Departments were included in the study. Activity limitations and participation restrictions as perceived by the individual were measured by the Canadian Occupational Performance Measure (COPM). The Nottingham Extended Activities of Daily Living (NEADL) Scale was used to describe limitations in daily living activities. To detect the impact of activity limitations on quality of life the Nottingham Health Profile (NHP) was used. [Results] The subjects described 46 different types of problematic activities. The five most identified problems were walking (45.7%), climbing up the stairs (41.4%), bathing (30%), dressing (28.6%) and outings (27.1%). The associations between COPM performance score with all subgroups of NEADL and NHP; total, energy, physical abilities subgroups, were statistically significant. [Conclusion] Our results showed that patients with cardiac diseases reported problems with a wide range of activities, and that also quality of life may be affected by activities of daily living. COPM can be provided as a patient-focused outcome measure, and it may be a useful tool for identifying those problems. PMID:26311919

  10. A visible light imaging device for cardiac rate detection with reduced effect of body movement

    NASA Astrophysics Data System (ADS)

    Jiang, Xiaotian; Liu, Ming; Zhao, Yuejin

    2014-09-01

    A visible light imaging system to detect human cardiac rate is proposed in this paper. A color camera and several LEDs, acting as lighting source, were used to avoid the interference of ambient light. From people's forehead, the cardiac rate could be acquired based on photoplethysmography (PPG) theory. The template matching method was used after the capture of video. The video signal was discomposed into three signal channels (RGB) and the region of interest was chosen to take the average gray value. The green channel signal could provide an excellent waveform of pulse wave on the account of green lights' absorptive characteristics of blood. Through the fast Fourier transform, the cardiac rate was exactly achieved. But the research goal was not just to achieve the cardiac rate accurately. With the template matching method, the effects of body movement are reduced to a large extent, therefore the pulse wave can be detected even while people are in the moving state and the waveform is largely optimized. Several experiments are conducted on volunteers, and the results are compared with the ones gained by a finger clamped pulse oximeter. The contrast results between these two ways are exactly agreeable. This method to detect the cardiac rate and the pulse wave largely reduces the effects of body movement and can probably be widely used in the future.

  11. The Evaluation of Cardiac Sarcoidosis with 18F-FDG PET.

    PubMed

    Al-Faham, Zaid; Jolepalem, Prashant; Oliver Wong, Ching Yee

    2016-06-01

    Cardiac involvement in sarcoidosis is associated with poor prognosis. (18)F-FDG PET can detect the presence of cardiac sarcoidosis, assess disease activity, and serve as a means to monitor treatment response in patients with cardiac sarcoidosis. PMID:26271805

  12. Sudden Cardiac Arrest During Sports Activity in Middle Age

    PubMed Central

    Marijon, Eloi; Uy-Evanado, Audrey; Reinier, Kyndaron; Teodorescu, Carmen; Narayanan, Kumar; Jouven, Xavier; Gunson, Karen; Jui, Jonathan; Chugh, Sumeet S.

    2015-01-01

    Background Sports-associated sudden cardiac arrests (SCAs) occur mostly during middle age. We sought to determine burden, characteristics, and outcomes of SCA during sports among middle aged residents of a large US community. Methods and Results SCA cases aged 35–65 years were identified in a large, prospective, population-based study (2002–2013), with systematic and comprehensive assessment of their lifetime medical history. Of the 1,247 SCA cases, 63 (5%) occurred during sports activities at a mean age of 51.1±8.8 years, yielding an incidence of 21.7 (95%CI 8.1–35.4) per million per year. The incidence varied significantly based on sex, with a higher incidence among men (RR 18.68 95%CI 2.50–139.56) for sports SCA, as compared to all other SCA (RR 2.58, 95%CI 2.12–3.13). Sports SCA was also more likely to be a witnessed event (87 vs. 53%, P<0.001), with cardiopulmonary resuscitation (44 vs. 25%, P=0.001) and ventricular fibrillation (84 vs. 51%, P<0.0001). Survival to hospital discharge was higher for sports-associated SCA (23.2 vs. 13.6%, P=0.04). Sports SCA cases presented with known pre-existing cardiac disease in 16%, ≥1 cardiovascular risk factor in 56%, and overall, 36% of cases had typical cardiovascular symptoms during the week preceding SCA. Conclusions Sports-associated SCA in middle age represents a relatively small proportion of the overall SCA burden, reinforcing the idea of the high benefit-low risk nature of sports activity. Especially in light of current population aging trends, our findings emphasize that targeted education could maximize both safety and acceptance of sports activity in the older athlete. PMID:25847988

  13. Integrin activation and focal complex formation in cardiac hypertrophy

    NASA Technical Reports Server (NTRS)

    Laser, M.; Willey, C. D.; Jiang, W.; Cooper, G. 4th; Menick, D. R.; Zile, M. R.; Kuppuswamy, D.

    2000-01-01

    Cardiac hypertrophy is characterized by both remodeling of the extracellular matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show increased expression and cytoskeletal association of the ECM proteins fibronectin and vitronectin in pressure-overloaded feline myocardium. These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter proteins p130(Cas), Shc, and Nck, and activation of the extracellular-regulated kinases ERK1/2. A synthetic peptide containing the Arg-Gly-Asp (RGD) motif of fibronectin and vitronectin was used to stimulate adult feline cardiomyocytes cultured on laminin or within a type-I collagen matrix. Whereas cardiocytes under both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded cells exhibited cytoskeletal assembly of FAK, c-Src, Nck, and Shc. In RGD-stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and c-Src association occurred without Tyr-416 phosphorylation and p130(Cas) association. Therefore, c-Src activation is not required for its cytoskeletal binding but may be important for additional phosphorylation of FAK. Overall, our study suggests that multiple signaling pathways originate in pressure-overloaded heart following integrin engagement with ECM proteins, including focal complex formation and ERK1/2 activation, and many of these pathways can be activated in cardiomyocytes via RGD-stimulated integrin activation.

  14. Differential and Conditional Activation of PKC-Isoforms Dictates Cardiac Adaptation during Physiological to Pathological Hypertrophy

    PubMed Central

    Naskar, Shaon; Datta, Kaberi; Mitra, Arkadeep; Pathak, Kanchan; Datta, Ritwik; Bansal, Trisha; Sarkar, Sagartirtha

    2014-01-01

    A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac function analysis. PKC-δ was significantly induced during pathological hypertrophy while PKC-α was exclusively activated during physiological hypertrophy in our study. PKC-δ activation during pathological hypertrophy resulted in cardiomyocyte apoptosis leading to compromised cardiac function and on the other hand, activation of PKC-α during physiological hypertrophy promoted cardiomyocyte growth but down regulated cellular apoptotic load resulting in improved cardiac function. Reversal in PKC-isoform with induced activation of PKC-δ and simultaneous inhibition of phospho-PKC-α resulted in an efficient myocardium to deteriorate considerably resulting in compromised cardiac function during physiological hypertrophy via augmentation of apoptotic and fibrotic load. This is the first report where PKC-α and -δ have been shown to play crucial role in cardiac adaptation during physiological and pathological hypertrophy respectively thereby rendering compromised cardiac function to an otherwise efficient heart by conditional reversal of their activation. PMID:25116170

  15. Current cardiac imaging techniques for detection of left ventricular mass

    PubMed Central

    2010-01-01

    Estimation of left ventricular (LV) mass has both prognostic and therapeutic value independent of traditional risk factors. Unfortunately, LV mass evaluation has been underestimated in clinical practice. Assessment of LV mass can be performed by a number of imaging modalities. Despite inherent limitations, conventional echocardiography has fundamentally been established as most widely used diagnostic tool. 3-dimensional echocardiography (3DE) is now feasible, fast and accurate for LV mass evaluation. 3DE is also superior to conventional echocardiography in terms of LV mass assessment, especially in patients with abnormal LV geometry. Cardiovascular magnetic resonance (CMR) and cardiovascular computed tomography (CCT) are currently performed for LV mass assessment and also do not depend on cardiac geometry and display 3-dimensional data, as well. Therefore, CMR is being increasingly employed and is at the present standard of reference in the clinical setting. Although each method demonstrates advantages over another, there are also disadvantages to receive attention. Diagnostic accuracy of methods will also be increased with the introduction of more advanced systems. It is also likely that in the coming years new and more accurate diagnostic tests will become available. In particular, CMR and CCT have been intersecting hot topic between cardiology and radiology clinics. Thus, good communication and collaboration between two specialties is required for selection of an appropriate test. PMID:20515461

  16. A viscoplastic model for the active component in cardiac muscle.

    PubMed

    Rubin, M B

    2016-08-01

    The HMK model (Hunter et al. in Prog Biophys Mol Biol 69:289-331, 1998) proposes mechanobiological equations for the influence of intracellular calcium concentration [Formula: see text] on the evolution of bound calcium concentration [Formula: see text] and the tropomyosin kinetics parameter z, which model processes in the active component of the tension in cardiac muscle. The inelastic response due to actin-myosin crossbridge kinetics is modeled in the HMK model with a function Q that depends on the history of the rate of total stretch of the muscle fiber. Here, an alternative model is proposed which models the active component of the muscle fiber as a viscoplastic material. In particular, an evolution equation is proposed for the elastic stretch [Formula: see text] in the active component. Specific forms of the constitutive equations are proposed and used to match experimental data. The proposed viscoplastic formulation allows for separate modeling of three processes: the high rate deactivation of crossbridges causing rapid reduction in active tension; the high but lower rate reactivation of crossbridges causing recovery of active tension; and the low rate relaxation effects characterizing the Hill model of muscles. PMID:26476735

  17. Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships.

    PubMed

    Nyhan, D P; Clougherty, P W; Goll, H M; Murray, P A

    1987-07-01

    Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3114215

  18. Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation

    PubMed Central

    Cao, Ke; Xu, Jie; Pu, Wenjun; Dong, Zhizhong; Sun, Lei; Zang, Weijin; Gao, Feng; Zhang, Yong; Feng, Zhihui; Liu, Jiankang

    2015-01-01

    Obesity is associated with an increasing prevalence of cardiovascular diseases and metabolic syndrome. It is of paramount importance to reduce obesity-associated cardiac dysfunction and impaired energy metabolism. In this study, the activation of the AMP-activated protein kinase (AMPK) pathway by punicalagin (PU), a major ellagitannin in pomegranate was investigated in the heart of a rat obesity model. In male SD rats, eight-week administration of 150 mg/kg pomegranate extract (PE) containing 40% punicalagin sufficiently prevented high-fat diet (HFD)-induced obesity associated accumulation of cardiac triglyceride and cholesterol as well as myocardial damage. Concomitantly, the AMPK pathway was activated, which may account for prevention of mitochondrial loss via upregulating mitochondrial biogenesis and amelioration of oxidative stress via enhancing phase II enzymes in the hearts of HFD rats. Together with the normalized expression of uncoupling proteins and mitochondrial dynamic regulators, PE significantly prevented HFD-induced cardiac ATP loss. Through in vitro cultures, we showed that punicalagin was the predominant component that activated AMPK by quickly decreasing the cellular ATP/ADP ratio specifically in cardiomyocytes. Our findings demonstrated that punicalagin, the major active component in PE, could modulate mitochondria and phase II enzymes through AMPK pathway to prevent HFD-induced cardiac metabolic disorders. PMID:26369619

  19. Noninvasive detection of human cardiac transplant rejection with indium-111 antimyosin (Fab) imaging

    SciTech Connect

    Frist, W.; Yasuda, T.; Segall, G.; Khaw, B.A.; Strauss, H.W.; Gold, H.; Stinson, E.; Oyer, P.; Baldwin, J.; Billingham, M.

    1987-11-01

    Diagnosis of rejection after cardiac transplantation is currently made by right ventricular endomyocardial biopsy. To evaluate antimyosin imaging as a noninvasive means of detecting human cardiac rejection, the Fab fragment of murine monoclonal antimyosin antibodies was labeled with indium-111 and given intravenously to 18 patients (age 45 +/- 12 years) in 20 studies 7 days to 9 years after transplantation. Endomyocardial biopsy specimens were obtained at the time of each imaging study. Eight patients had positive scans confirmed by biopsy as rejection, and eight patients had negative scans and no evidence of rejection on biopsy. Discordance was observed in four studies, two with positive scans and no rejection on biopsy and two with negative scans and positive biopsy. The sensitivity, specificity, and overall accuracy of the technique were each 80%. Imaging with radiolabeled antimyosin antibody Fab fragments may be of value in the noninvasive identification of rejection in the cardiac transplant recipient.

  20. Ricin detection: tracking active toxin.

    PubMed

    Bozza, William P; Tolleson, William H; Rosado, Leslie A Rivera; Zhang, Baolin

    2015-01-01

    Ricin is a plant toxin with high bioterrorism potential due to its natural abundance and potency in inducing cell death. Early detection of the active toxin is essential for developing appropriate countermeasures. Here we review concepts for designing ricin detection methods, including mechanism of action of the toxin, advantages and disadvantages of current detection assays, and perspectives on the future development of rapid and reliable methods for detecting ricin in environmental samples. PMID:25481398

  1. Activity detection in scientific visualization.

    PubMed

    Ozer, Sedat; Silver, Deborah; Bemis, Karen; Martin, Pino

    2014-03-01

    For large-scale simulations, the data sets are so massive that it is sometimes not feasible to view the data with basic visualization methods, let alone explore all time steps in detail. Automated tools are necessary for knowledge discovery, i.e., to help sift through the data and isolate specific time steps that can then be further explored. Scientists study patterns and interactions and want to know when and where interesting things happen. Activity detection, the detection of specific interactions of objects which span a limited duration of time, has been an active research area in the computer vision community. In this paper, we introduce activity detection to scientific simulations and show how it can be utilized in scientific visualization. We show how activity detection allows a scientist to model an activity and can then validate their hypothesis on the underlying processes. Three case studies are presented. PMID:24434219

  2. The influence of motor activity on the development of cardiac arrhythmias during experimental emotional stress

    NASA Technical Reports Server (NTRS)

    Ulyaninskiy, L. S.; Urmancheyeva, T. G.; Stepanyan, Y. P.; Fufacheva, A. A.; Gritsak, A. V.; Kuznetsova, B. A.; Kvitka, A. A.

    1982-01-01

    Experimental emotional stress which can produce various disorders of cardiac rhythm: sinus tachycardia, atrial fibrillation, ventricular, extrasystoles and paroxysmal ventricular tachysystoles was studied. In these conditions the adrenalin content in the blood and myocardium is increased 3 to 4 times. It is found that moderate motor activity leads to a relative decrease of adrenalin in the myocardium and arrest of cardiac arrhythmias.

  3. Fetal cardiac arrhythmia detection and in utero therapy

    PubMed Central

    Strasburger, Janette F.; Wakai, Ronald T.

    2010-01-01

    The human fetal heart develops arrhythmias and conduction disturbances in response to ischemia, inflammation, electrolyte disturbances, altered load states, structural defects, inherited genetic conditions, and many other causes. Yet sinus rhythm is present without altered rate or rhythm in some of the most serious electrophysiological diseases, which makes detection of diseases of the fetal conduction system challenging in the absence of magnetocardiographic or electrocardiographic recording techniques. Life-threatening changes in QRS or QT intervals can be completely unrecognized if heart rate is the only feature to be altered. For many fetal arrhythmias, echocardiography alone can assess important clinical parameters for diagnosis. Appropriate treatment of the fetus requires awareness of arrhythmia characteristics, mechanisms, and potential associations. Criteria to define fetal bradycardia specific to gestational age are now available and may allow detection of ion channelopathies, which are associated with fetal and neonatal bradycardia. Ectopic beats, once thought to be entirely benign, are now recognized to have important pathologic associations. Fetal tachyarrhythmias can now be defined precisely for mechanism-specific therapy and for subsequent monitoring of response. This article reviews the current and future diagnostic techniques and pharmacologic treatments for fetal arrhythmia. PMID:20418904

  4. Bisphenol A, an environmental estrogen-like toxic chemical, induces cardiac fibrosis by activating the ERK1/2 pathway.

    PubMed

    Hu, Yingying; Zhang, Li; Wu, Xianxian; Hou, Liangyu; Li, Zhange; Ju, Jin; Li, Qian; Qin, Wei; Li, Jiamin; Zhang, Qingwei; Zhou, Tong; Zhang, Longyin; Xu, Chaoqian; Fang, Zhiwei; Zhang, Yong

    2016-05-27

    Bisphenol A (BPA) is a widely studied typical endocrine-disrupting chemical. The present study aimed to verify whether BPA could induce proliferation of cardiac fibroblasts and collagen production leading to cardiac interstitial fibrosis. After exposure to BPA for 30 consecutive days, decreased cardiac function was observed in rats using echocardiography, and the deposition of collagen was detected by Masson's trichrome staining and electron microscope. BPA remarkably stimulated proliferation and migration of cultured cardiac fibroblasts and collagen production in a concentration-dependent manner, as revealed by MTT, wound healing assay and collagen assay. Meanwhile, BPA treatment also enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In contrast, pretreatment with estrogen receptor inhibitor ICI182780 or ERK inhibitor PD98059 prevented the enhanced phosphorylation of ERK1/2, and subsequently inhibited the up-regulation of transforming growth factor-β1 (TGF-β1) expression induced by BPA. As a consequence, these inhibitors also decreased proliferation and collagen production, as well as the fibrosis-related genes expression. Taken together, our results indicated that BPA may act as a promoting factor in proliferative process and collagen production of cardiac fibroblasts via activating ERK1/2. PMID:27025157

  5. Moderate Physical Activity in Healthy Adults Is Associated With Cardiac Remodeling

    PubMed Central

    Dawes, Timothy J.W.; Corden, Ben; Cotter, Sorcha; de Marvao, Antonio; Walsh, Roddy; Ware, James S.; Cook, Stuart A.

    2016-01-01

    Background— Cardiac mass and volumes are often elevated in athletes, but it is not known whether moderate physical activity is also associated with cardiac dilatation and hypertrophy in a healthy adult population. Methods and Results— In total, 1096 adults (54% female, median age 39 years) without cardiovascular disease or cardiomyopathy-associated genetic variants underwent cardiac magnetic resonance imaging to determine biventricular volumes and function. Physical activity was assessed using a validated activity questionnaire. The relationship between cardiac parameters and activity was assessed using multiple linear regression adjusting for age, sex, race, and systolic blood pressure. Logistic regression was performed to determine the effect of activity on the likelihood of subjects having cardiac dilatation or hypertrophy according to standard cardiac magnetic resonance normal ranges. Increasing physical activity was associated with greater left ventricular (LV) mass (β=0.23; P<0.0001) and elevated LV and right ventricular volumes (LV: β=0.26, P<0.0001; right ventricular: β=0.26, P<0.0001). Physical activity had a larger effect on cardiac parameters than systolic blood pressure (0.06≤β≤0.21) and a similar effect to age (−0.20≤β≤−0.31). Increasing physical activity was a risk factor for meeting imaging criteria for LV hypertrophy (adjusted odds ratio 2.1; P<0.0001), LV dilatation (adjusted odds ratio 2.2; P<0.0001), and right ventricular dilatation (adjusted odds ratio 2.2; P<0.0001). Conclusions— Exercise-related cardiac remodeling is not confined to athletes, and there is a risk of overdiagnosing cardiac dilatation or hypertrophy in a proportion of active, healthy adults. PMID:27502059

  6. Pellino1-mediated TGF-β1 synthesis contributes to mechanical stress induced cardiac fibroblast activation.

    PubMed

    Song, Juan; Zhu, Yun; Li, Jiantao; Liu, Jiahao; Gao, Yun; Ha, Tuanzhu; Que, Linli; Liu, Li; Zhu, Guoqing; Chen, Qi; Xu, Yong; Li, Chuanfu; Li, Yuehua

    2015-02-01

    Activation of cardiac fibroblasts is a key event in the progression of cardiac fibrosis that leads to heart failure. However, the molecular mechanisms underlying mechanical stress-induced cardiac fibroblast activation are complex and poorly understood. This study demonstrates that Pellino1, an E3 ubiquitin ligase, was activated in vivo in pressure overloaded rat hearts and in cultured neonatal rat cardiac fibroblasts (NRCFs) exposed to mechanical stretch in vitro. Suppression of the expression and activity of Pellino1 by adenovirus-mediated delivery of shPellino1 (adv-shpeli1) attenuated pressure overload-induced cardiac dysfunction and cardiac hypertrophy and decreased cardiac fibrosis in rat hearts. Transfection of adv-shpeli1 also significantly attenuated mechanical stress-induced proliferation, differentiation and collagen synthesis in NRCFs. Pellino1 silencing also abrogated mechanical stretch-induced polyubiquitination of tumor necrosis factor-alpha receptor association factor-6 (TRAF6) and receptor-interacting protein 1 (RIP1) and consequently decreased the DNA binding activity of nuclear factor-kappa B (NF-κB) in NRCFs. In addition, Pellino1 silencing prevented stretch-induced activation of p38 and activator protein 1 (AP-1) binding activity in NRCFs. Chromatin Immunoprecipitation (ChIP) and luciferase reporter assays showed that Pellino1 silencing prevented the binding of NF-κB and AP-1 to the promoter region of transforming growth factor-β1 (TGF-β1) thus dampening TGF-β1 transactivation. Our data reveal a previously unrecognized role of Pellino1 in extracellular matrix deposition and cardiac fibroblast activation in response to mechanical stress and provides a novel target for treatment of cardiac fibrosis and heart failure. PMID:25446187

  7. Improving the performance of cardiac abnormality detection from PCG signal

    NASA Astrophysics Data System (ADS)

    Sujit, N. R.; Kumar, C. Santhosh; Rajesh, C. B.

    2016-03-01

    The Phonocardiogram (PCG) signal contains important information about the condition of heart. Using PCG signal analysis prior recognition of coronary illness can be done. In this work, we developed a biomedical system for the detection of abnormality in heart and methods to enhance the performance of the system using SMOTE and AdaBoost technique have been presented. Time and frequency domain features extracted from the PCG signal is input to the system. The back-end classifier to the system developed is Decision Tree using CART (Classification and Regression Tree), with an overall classification accuracy of 78.33% and sensitivity (alarm accuracy) of 40%. Here sensitivity implies the precision obtained from classifying the abnormal heart sound, which is an essential parameter for a system. We further improve the performance of baseline system using SMOTE and AdaBoost algorithm. The proposed approach outperforms the baseline system by an absolute improvement in overall accuracy of 5% and sensitivity of 44.92%.

  8. Non-contact detection of cardiac rate based on visible light imaging device

    NASA Astrophysics Data System (ADS)

    Zhu, Huishi; Zhao, Yuejin; Dong, Liquan

    2012-10-01

    We have developed a non-contact method to detect human cardiac rate at a distance. This detection is based on the general lighting condition. Using the video signal of human face region captured by webcam, we acquire the cardiac rate based on the PhotoPlethysmoGraphy theory. In this paper, the cardiac rate detecting method is mainly in view of the blood's different absorptivities of the lights various wavelengths. Firstly, we discompose the video signal into RGB three color signal channels and choose the face region as region of interest to take average gray value. Then, we draw three gray-mean curves on each color channel with time as variable. When the imaging device has good fidelity of color, the green channel signal shows the PhotoPlethysmoGraphy information most clearly. But the red and blue channel signals can provide more other physiological information on the account of their light absorptive characteristics of blood. We divide red channel signal by green channel signal to acquire the pulse wave. With the passband from 0.67Hz to 3Hz as a filter of the pulse wave signal and the frequency spectrum superimposed algorithm, we design frequency extracted algorithm to achieve the cardiac rate. Finally, we experiment with 30 volunteers, containing different genders and different ages. The results of the experiments are all relatively agreeable. The difference is about 2bmp. Through the experiment, we deduce that the PhotoPlethysmoGraphy theory based on visible light can also be used to detect other physiological information.

  9. Blunt cardiac rupture with prehospital pulseless electrical activity: a rare successful experience.

    PubMed

    Lu, Li-Hua; Choi, Wai-Mau; Wu, Hsueh-Ru; Liu, Hung-Chang; Chiu, Wen-Ta; Tsai, Shin-Han

    2005-12-01

    Blunt cardiac rupture is highly associated with mortality. In the recent literature, the reported mortality rates of cardiac rupture ranged from 59.7% to 100%. The probability of survival for those with prehospital pulseless electrical activity was extremely low. This case report describes a rare example of survival of a female patient with life-threatening cardiac rupture and cardiac tamponade after a major car accident. The victim developed pulseless electrical activity at admission. She recovered from the accident, however, without developing any signs of neurologic deficits. This case study emphasizes the value of the primary survey of patients and prompt and accurate interventions, including focused abdominal sonography for trauma, pericardiocentesis, and an urgent thoracotomy in the operating room for primary repair of cardiac rupture without applying a cardiopulmonary bypass system. The study showed that early diagnosis and aggressive interventions are crucial factors to the successful outcome of patient's survival. PMID:16394928

  10. Incidence of Sudden Cardiac Death in a Young Active Population

    PubMed Central

    Farioli, Andrea; Christophi, Costas A; Quarta, Candida Cristina; Kales, Stefanos N

    2015-01-01

    Background Little is known about the burden of sudden cardiac death (SCD) among active, presumably healthy persons. We investigated the incidence of SCD among US male career firefighters. Methods and Results All on-duty SCDs among US male career firefighters between 1998 and 2012 were identified from the US Fire Administration and the US National Institute for Occupational Safety and Health databases. Age-specific incidence rates (IRs) of SCD with 95% CIs were computed. A joinpoint model was fitted to analyze the trend in IR and to help estimate the annual percentage change of SCD rates over the years. The effects of seasonality were assessed through a Poisson regression model. We identified 182 SCDs; based on 99 available autopsy reports, the leading underlying cause of death was coronary heart disease (79%). The overall IR was 18.1 SCDs per 100 000 person-years. The age-specific IRs of SCD ranged between 3.8 (for those aged 18 to 24 years) and 45.2 (for those aged 55 to 64 years) per 100 000 person-years. The annual rate of SCD steadily declined over time (annual percentage change −3.9%, 95% CI −5.8 to −2.0). SCD events were more frequent during January (peak-to-low ratio 1.70; 95% CI 1.09 to 2.65). In addition, the IR was 3 times higher during high-risk duties compared with low-risk duties. IRs among firefighters were lower than those observed among the US general population and US military personnel. Conclusions SCD risk in this active working population is overestimated using statistics from the general population. To address public health questions among these subpopulations, more specific studies of active adults should be conducted. PMID:26066031

  11. Lipoprotein lipase activity is required for cardiac lipid droplet production.

    PubMed

    Trent, Chad M; Yu, Shuiqing; Hu, Yunying; Skoller, Nathan; Huggins, Lesley A; Homma, Shunichi; Goldberg, Ira J

    2014-04-01

    The rodent heart accumulates TGs and lipid droplets during fasting. The sources of heart lipids could be either FFAs liberated from adipose tissue or FAs from lipoprotein-associated TGs via the action of lipoprotein lipase (LpL). Because circulating levels of FFAs increase during fasting, it has been assumed that albumin transported FFAs are the source of lipids within heart lipid droplets. We studied mice with three genetic mutations: peroxisomal proliferator-activated receptor α deficiency, cluster of differentiation 36 (CD36) deficiency, and heart-specific LpL deletion. All three genetically altered groups of mice had defective accumulation of lipid droplet TGs. Moreover, hearts from mice treated with poloxamer 407, an inhibitor of lipoprotein TG lipolysis, also failed to accumulate TGs, despite increased uptake of FFAs. TG storage did not impair maximal cardiac function as measured by stress echocardiography. Thus, LpL hydrolysis of circulating lipoproteins is required for the accumulation of lipids in the heart of fasting mice. PMID:24493834

  12. Robust cardiac event change detection method for long-term healthcare monitoring applications.

    PubMed

    Satija, Udit; Ramkumar, Barathram; Manikandan, M Sabarimalai

    2016-06-01

    A long-term continuous cardiac health monitoring system highly demands more battery power for real-time transmission of electrocardiogram (ECG) signals and increases bandwidth, treatment costs and traffic load of the diagnostic server. In this Letter, the authors present an automated low-complexity robust cardiac event change detection (CECD) method that can continuously detect specific changes in PQRST morphological patterns and heart rhythms and then enable transmission/storing of the recorded ECG signals. The proposed CECD method consists of four stages: ECG signal quality assessment, R-peak detection and beat waveform extraction, temporal and RR interval feature extraction and cardiac event change decision. The proposed method is tested and validated using both normal and abnormal ECG signals including different types of arrhythmia beats, heart rates and signal quality. Results show that the method achieves an average sensitivity of 99.76%, positive predictivity of 94.58% and overall accuracy of 94.32% in determining the changes in heartbeat waveforms of the ECG signals. PMID:27382480

  13. Fourier transform infrared spectroscopic imaging of cardiac tissue to detect collagen deposition after myocardial infarction

    NASA Astrophysics Data System (ADS)

    Cheheltani, Rabee; Rosano, Jenna M.; Wang, Bin; Sabri, Abdel Karim; Pleshko, Nancy; Kiani, Mohammad F.

    2012-05-01

    Myocardial infarction often leads to an increase in deposition of fibrillar collagen. Detection and characterization of this cardiac fibrosis is of great interest to investigators and clinicians. Motivated by the significant limitations of conventional staining techniques to visualize collagen deposition in cardiac tissue sections, we have developed a Fourier transform infrared imaging spectroscopy (FT-IRIS) methodology for collagen assessment. The infrared absorbance band centered at 1338 cm-1, which arises from collagen amino acid side chain vibrations, was used to map collagen deposition across heart tissue sections of a rat model of myocardial infarction, and was compared to conventional staining techniques. Comparison of the size of the collagen scar in heart tissue sections as measured with this methodology and that of trichrome staining showed a strong correlation (R=0.93). A Pearson correlation model between local intensity values in FT-IRIS and immuno-histochemical staining of collagen type I also showed a strong correlation (R=0.86). We demonstrate that FT-IRIS methodology can be utilized to visualize cardiac collagen deposition. In addition, given that vibrational spectroscopic data on proteins reflect molecular features, it also has the potential to provide additional information about the molecular structure of cardiac extracellular matrix proteins and their alterations.

  14. Cardiac Tissue Injury and Remodeling Is Dependent Upon MR Regulation of Activation Pathways in Cardiac Tissue Macrophages.

    PubMed

    Shen, Jimmy Z; Morgan, James; Tesch, Greg H; Rickard, Amanda J; Chrissobolis, Sophocles; Drummond, Grant R; Fuller, Peter J; Young, Morag J

    2016-08-01

    Macrophage mineralocorticoid receptor (MR) signaling is an important mediator of cardiac tissue inflammation and fibrosis. The goal of the present study was to determine the cellular mechanisms of MR signaling in macrophages that promote cardiac tissue injury and remodeling. We sought to identify specific markers of MR signaling in isolated tissue macrophages (cardiac, aortic) vs splenic mononuclear cells from wild-type and myeloid MR-null mice given vehicle/salt or deoxycorticosterone (DOC)/salt for 8 weeks. Cardiac tissue fibrosis in response to 8 weeks of DOC/salt treatment was found in the hearts from wild-type but not myeloid MR-null mice. This was associated with an increased expression of the profibrotic markers TGF-β1 and matrix metalloproteinase-12 and type 1 inflammatory markers TNFα and chemokine (C-X-C motif) ligand-9 in cardiac macrophages. Differential expression of immunomodulatory M2-like markers (eg, arginase-1, macrophage scavenger receptor 1) was dependent on the tissue location of wild-type and MR-null macrophages. Finally, intact MR signaling is required for the phosphorylation of c-Jun NH2-terminal kinase in response to a proinflammatory stimulus in bone marrow monocytes/macrophages in culture. These data suggest that the activation of the c-Jun NH2-terminal kinase pathway in macrophages after a tissue injury and inflammatory stimuli in the DOC/salt model is MR dependent and regulates the transcription of downstream profibrotic factors, which may represent potential therapeutic targets in heart failure patients. PMID:27253999

  15. Further Studies on Structure-Cardiac Activity Relationships of Diterpenoid Alkaloids.

    PubMed

    Zhang, Zhong-Tang; Jian, Xi-Xian; Ding, Jia-Yu; Deng, Hong-Ying; Chao, Ruo-Bing; Chen, Qiao-Hong; Chen, Dong-Lin; Wang, Feng-Peng

    2015-12-01

    The cardiac effect of thirty-eight diterpenoid alkaloids was evaluated on the isolated bullfrog heart model. Among them, twelve compounds exhibited appreciable cardiac activity, with compounds 3 and 35 being more active than the reference drug lanatoside. The structure-cardiac activity relationships of the diterpenoid alkaloids were summarized based on our present and previous studies [2]: i) 1α-OMe or 1α-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C19-diterpenoid alkaloids without any esters. C18-diterpenoid alkaloids, lycoctonine-type C19-diterpenoid alkaloids, and the veatchine- and denudatine-type C20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3α-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6α-OMe, 13-OH, 15α-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom. PMID:26882669

  16. Functionalized SnO₂ nanobelt field-effect transistor sensors for label-free detection of cardiac troponin.

    PubMed

    Cheng, Yi; Chen, Kan-Sheng; Meyer, Nancy L; Yuan, Jing; Hirst, Linda S; Chase, P Bryant; Xiong, Peng

    2011-07-15

    Real-time label-free electrical detection of proteins, including cardiac troponin (cTn), is demonstrated using functionalized SnO₂ nanobelt field-effect transistors (FETs) with integrated microfluidics. Selective biomolecular functionalization of the active SnO₂ nanobelt channel and effective passivation of the substrate surface were realized and verified through fluorescence microscopy. The validation/verification of the sensing scheme was initially demonstrated via detection of biotin-streptavidin binding: devices with single biotinylated SnO₂ nanobelts showed pronounced conductance changes in response to streptavidin binding. Importantly, the pH-dependence of the conductance changes was fully consistent with the charged states of streptavidin at different pH. Moreover, the specificity of the sensors' electrical responses was confirmed by co-labeling with quantum dots. Finally, the sensing platform was successfully applied for detection of the cardiac troponin I (cTnI) subunit within cTn, a clinically important protein marker for myocardial infarction. PMID:21652197

  17. Semi-automated scar detection in delayed enhanced cardiac magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Morisi, Rita; Donini, Bruno; Lanconelli, Nico; Rosengarden, James; Morgan, John; Harden, Stephen; Curzen, Nick

    2015-06-01

    Late enhancement cardiac magnetic resonance images (MRI) has the ability to precisely delineate myocardial scars. We present a semi-automated method for detecting scars in cardiac MRI. This model has the potential to improve routine clinical practice since quantification is not currently offered due to time constraints. A first segmentation step was developed for extracting the target regions for potential scar and determining pre-candidate objects. Pattern recognition methods are then applied to the segmented images in order to detect the position of the myocardial scar. The database of late gadolinium enhancement (LE) cardiac MR images consists of 111 blocks of images acquired from 63 patients at the University Hospital Southampton NHS Foundation Trust (UK). At least one scar was present for each patient, and all the scars were manually annotated by an expert. A group of images (around one third of the entire set) was used for training the system which was subsequently tested on all the remaining images. Four different classifiers were trained (Support Vector Machine (SVM), k-nearest neighbor (KNN), Bayesian and feed-forward neural network) and their performance was evaluated by using Free response Receiver Operating Characteristic (FROC) analysis. Feature selection was implemented for analyzing the importance of the various features. The segmentation method proposed allowed the region affected by the scar to be extracted correctly in 96% of the blocks of images. The SVM was shown to be the best classifier for our task, and our system reached an overall sensitivity of 80% with less than 7 false positives per patient. The method we present provides an effective tool for detection of scars on cardiac MRI. This may be of value in clinical practice by permitting routine reporting of scar quantification.

  18. Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin.

    PubMed

    Zhang, Shujuan; Zhang, Feng; Sun, Haijian; Zhou, Yebo; Han, Ying

    2012-11-01

    Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure (CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex. Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks (15 mg/kg). Six weeks after the first injection, the rats underwent anesthesia with urethane and α-chloralose. After vagotomy and baroreceptor denervation, cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure (MAP) response to epicardial application of capsaicin (1.0 nmol). The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity. The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats. Bilateral PVN microinjection of angiotensin II (Ang II) caused larger responses of the cardiac sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats. These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure. PMID:23554781

  19. Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin

    PubMed Central

    Zhang, Shujuan; Zhang, Feng; Sun, Haijian; Zhou, Yebo; Han, Ying

    2012-01-01

    Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure (CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex. Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks (15 mg/kg). Six weeks after the first injection, the rats underwent anesthesia with urethane and α-chloralose. After vagotomy and baroreceptor denervation, cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure (MAP) response to epicardial application of capsaicin (1.0 nmol). The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity. The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats. Bilateral PVN microinjection of angiotensin II (Ang II) caused larger responses of the cardiac sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats. These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure. PMID:23554781

  20. Effects of short-term food deprivation on interoceptive awareness, feelings and autonomic cardiac activity.

    PubMed

    Herbert, Beate M; Herbert, Cornelia; Pollatos, Olga; Weimer, Katja; Enck, Paul; Sauer, Helene; Zipfel, Stephan

    2012-01-01

    The perception of internal bodily signals (interoception) plays a relevant role for emotion processing and feelings. This study investigated changes of interoceptive awareness and cardiac autonomic activity induced by short-term food deprivation and its relationship to hunger and affective experience. 20 healthy women were exposed to 24h of food deprivation in a controlled setting. Interoceptive awareness was assessed by using a heartbeat tracking task. Felt hunger, cardiac autonomic activity, mood and subjective appraisal of interoceptive sensations were assessed before and after fasting. Results show that short-term fasting intensifies interoceptive awareness, not restricted to food cues, via changes of autonomic cardiac and/or cardiodynamic activity. The increase of interoceptive awareness was positively related to felt hunger. Additionally, the results demonstrate the role of cardiac vagal activity as a potential index of emotion related self-regulation, for hunger, mood and the affective appraisal of interoceptive signals during acute fasting. PMID:21958594

  1. Beat-by-Beat Quantification of Cardiac Cycle Events Detected From Three-Dimensional Precordial Acceleration Signals.

    PubMed

    Paukkunen, Mikko; Parkkila, Petteri; Hurnanen, Tero; Pankaala, Mikko; Koivisto, Tero; Nieminen, Tuomo; Kettunen, Raimo; Sepponen, Raimo

    2016-03-01

    The vibrations produced by the cardiovascular system that are coupled to the precordium can be noninvasively detected using accelerometers. This technique is called seismocardiography. Although clinical applications have been proposed for seismocardiography, the physiology underlying the signal is still not clear. The relationship of seismocardiograms of on the back-to-front axis and cardiac events is fairly well known. However, the 3-D seismocardiograms detectable with modern accelerometers have not been quantified in terms of cardiac cycle events. A major reason for this might be the degree of intersubject variability observed in 3-D seismocardiograms. We present a method to quantify 3-D seismocardiography in terms of cardiac cycle events. First, cardiac cycle events are identified from the seismocardiograms, and then, assigned a number based on the location in which the corresponding event was found. 396 cardiac cycle events from 9 healthy subjects and 120 cardiac cycle events from patients suffering from atrial flutter were analyzed. Despite the weak intersubject correlation of the waveforms (0.05, 0.27, and 0.15 for the x-, y-, and z-axes, respectively), the present method managed to find latent similarities in the seismocardiograms of healthy subjects. We observed that in healthy subjects the distribution of cardiac cycle event coordinates was centered on specific locations. These locations were different in patients with atrial flutter. The results suggest that spatial distribution of seismocardiographic cardiac cycle events might be used to discriminate healthy individuals and those with a failing heart. PMID:25594987

  2. Effects of microgravity on liposome-reconstituted cardiac gap junction channeling activity

    NASA Technical Reports Server (NTRS)

    Claassen, D. E.; Spooner, B. S.

    1989-01-01

    Effects of microgravity on cardiac gap junction channeling activity were investigated aboard NASA zero-gravity aircraft. Liposome-reconstituted gap junctions were assayed for channel function during free-fall, and the data were compared with channeling at 1 g. Control experiments tested for 0 g effects on the structural stability of liposomes, and on the enzyme-substrate signalling system of the assay. The results demonstrate that short periods of microgravity do not perturb reconstituted cardiac gap junction channeling activity.

  3. Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest

    PubMed Central

    Li, Duan; Mabrouk, Omar S.; Liu, Tiecheng; Tian, Fangyun; Xu, Gang; Rengifo, Santiago; Choi, Sarah J.; Mathur, Abhay; Crooks, Charles P.; Kennedy, Robert T.; Wang, Michael M.; Ghanbari, Hamid; Borjigin, Jimo

    2015-01-01

    The mechanism by which the healthy heart and brain die rapidly in the absence of oxygen is not well understood. We performed continuous electrocardiography and electroencephalography in rats undergoing experimental asphyxia and analyzed cortical release of core neurotransmitters, changes in brain and heart electrical activity, and brain–heart connectivity. Asphyxia stimulates a robust and sustained increase of functional and effective cortical connectivity, an immediate increase in cortical release of a large set of neurotransmitters, and a delayed activation of corticocardiac functional and effective connectivity that persists until the onset of ventricular fibrillation. Blocking the brain’s autonomic outflow significantly delayed terminal ventricular fibrillation and lengthened the duration of detectable cortical activities despite the continued absence of oxygen. These results demonstrate that asphyxia activates a brainstorm, which accelerates premature death of the heart and the brain. PMID:25848007

  4. Daytime cardiac autonomic activity during one week of continuous night shift.

    PubMed

    Holmes, A L; Burgess, H J; McCulloch, K; Lamond, N; Fletcher, A; Dorrian, J; Roach, G; Dawson, D

    2001-12-01

    Shift workers encounter an increased risk of cardiovascular disease compared to their day working counterparts. To explore this phenomenon, the effects of one week of simulated night shift on cardiac sympathetic (SNS) and parasympathetic (PNS) activity were assessed. Ten (5m; 5f) healthy subjects aged 18-29 years attended an adaptation and baseline night before commencing one week of night shift (2300-0700 h). Sleep was recorded using a standard polysomnogram and circadian phase was tracked using salivary melatonin data. During sleep, heart rate (HR), cardiac PNS activity (RMSSD) and cardiac SNS activity (pre-ejection period) were recorded. Night shift did not influence seep quality, but reduced sleep duration by a mean of 52 +/- 29 min. One week of night shift evoked a small chronic sleep debt of 5 h 14 +/- 56 min and a cumulative circadian phase delay of 5 h +/- 14 min. Night shift had no significant effect on mean HR, but mean cardiac SNS activity during sleep was consistently higher and mean cardiac PNS activity during sleep declined gradually across the week. These results suggest that shiftwork has direct and unfavourable effects on cardiac autonomic activity and that this might be one mechanism via which shiftwork increases the risk of cardiovascular disease. It is postulated that sleep loss could be one mediator of the association between shiftwork and cardiovascular health. PMID:14564886

  5. Noninvasive Imaging of Activated Complement in Ischemia-Reperfusion Injury Post–Cardiac Transplant

    PubMed Central

    Sharif-Paghaleh, E; Yap, M L; Meader, L L; Chuamsaamarkkee, K; Kampmeier, F; Badar, A; Smith, R A; Sacks, S; Mullen, G E

    2015-01-01

    Ischemia-reperfusion injury (IRI) is inevitable in solid organ transplantation, due to the transplanted organ being ischemic for prolonged periods prior to transplantation followed by reperfusion. The complement molecule C3 is present in the circulation and is also synthesized by tissue parenchyma in early response to IRI and the final stable fragment of activated C3, C3d, can be detected on injured tissue for several days post-IRI. Complement activation post-IRI was monitored noninvasively by single photon emission computed tomography (SPECT) and CT using 99mTc-recombinant complement receptor 2 (99mTc-rCR2) in murine models of cardiac transplantation following the induction of IRI and compared to 99mTc-rCR2 in C3−/− mice or with the irrelevant protein 99mTc-prostate–specific membrane antigen antibody fragment (PSMA). Significant uptake with 99mTc-rCR2 was observed as compared to C3−/− or 99mTc-PSMA. In addition, the transplanted heart to muscle ratio of 99mTc-rCR2 was significantly higher than 99mTc-PSMA or C3−/−. The results were confirmed by histology and autoradiography. 99mTc-rCR2 can be used for noninvasive detection of activated complement and in future may be used to quantify the severity of transplant damage due to complement activation postreperfusion. PMID:25906673

  6. Curcumin attenuates cardiac fibrosis in spontaneously hypertensive rats through PPAR-γ activation

    PubMed Central

    Meng, Zhe; Yu, Xin-hui; Chen, Jun; Li, Ling; Li, Sheng

    2014-01-01

    Aim: To investigate the effects of curcumin (Cur) on cardiac fibrosis in spontaneously hypertensive rats (SHRs) and the mechanisms underlying the anti-fibrotic effect of Cur in rat cardiac fibroblasts (CFs) in vitro. Methods: SHRs were orally treated with Cur (100 mg·kg−1·d−1) or Cur (100 mg·kg−1·d−1) plus the PPAR-γ antagonist GW9662 (1 mg·kg−1·d−1) for 12 weeks. Cultured CFs were treated with angiotensin II (Ang II, 0.1 μmol/L) in vitro. The expression of relevant proteins and mRNAs was analyzed using Western blotting and real-time PCR, respectively. The expression and activity of peroxisome proliferator-activated receptor-γ (PPAR-γ) were detected using Western blotting and a DNA-binding assay, respectively. Results: Treatment of SHRs with Cur significantly decreased systolic blood pressure, blood Ang II concentration, heart weight/body weight ratio and left ventricle weight/body weight ratio, with concurrently decreased expression of connective tissue growth factor (CTGF), plasminogen activator inhibitor (PAI)-1, collagen III (Col III) and fibronectin (FN), and increased expression and activity of PPAR-γ in the left ventricle. Co-treatment with GW9662 partially abrogated the anti-fibrotic effects of Cur in SHRs. Pretreatment of CFs with Cur (5, 10, 20 μmol/L) dose-dependently inhibited Ang II-induced expression of CTGF, PAI-1, Col III and FN, and increased the expression and binding activity of PPAR-γ. Pretreatment with GW9662 partially reversed anti-fibrotic effects of Cur in vitro. Furthermore, pretreatment of CFs with Cur inhibited Ang II-induced expression of transforming growth factor-β1 (TGF-β1) and phosphorylation of Smad2/3, which were reversed by GW9662. Conclusion: Cur attenuates cardiac fibrosis in SHRs and inhibits Ang II-induced production of CTGF, PAI-1 and ECM in CFs in vitro. The crosstalk between PPAR-γ and TGF-β1/Smad2/3 signaling is involved in the anti-fibrotic and anti-proliferative effects of Cur. PMID:25132338

  7. The effect of space microgravity on the physiological activity of mammalian resident cardiac stem cells

    NASA Astrophysics Data System (ADS)

    Belostotskaya, Galina; Zakharov, Eugeny

    Prolonged exposure to weightlessness during space flights is known to cause depression of heart function in mammals. The decrease in heart weight and its remodeling under the influence of prolonged weightlessness (or space microgravity) is assumed to be due to both morphological changes of working cardiomyocytes and their progressive loss, as well as to possible depletion of resident cardiac stem cells (CSCs) population, or their inability to self-renewal and regeneration of muscle tissue under conditions of weightlessness. We have previously shown that the presence of different maturity clones formed by resident CSCs not only in culture but also in the mammalian myocardium can be used as an indicator of the regenerative activity of myocardial cells [Belostotskaya, et al., 2013: 2014]. In this study, we were interested to investigate whether the 30-day near-Earth space flight on the spacecraft BION-M1 affects the regenerative potential of resident CSCs. Immediately after landing of the spacecraft, we had examined the presence of resident c-kit+, Sca-1+ and Isl1+ CSCs and their development in suspension of freshly isolated myocardial cells of C57BL mice in comparison to controls. Cardiac cell suspension was obtained by enzymatic digestion of the heart [Belostotskaya and Golovanova, 2014]. Immunocytochemically stained preparations of fixed cells were analyzed with confocal microscope Leica TCS SP5 (Germany) in the Resource Center of St-Petersburg State University. CSCs were labeled with appropriate antibodies. CSCs differentiation into mature cardiomyocytes was verified using antibodies to Sarcomeric α-Actinin and Cardiac Troponin T. Antibodies to Connexin43 were used to detect cell-cell contacts. All antibodies were conjugated with Alexa fluorochromes (488, 532, 546, 568, 594 and/or 647 nm), according to Zenon-technology (Invitrogen). It has been shown that, under identical conditions of cell isolation, more complete digestion of heart muscle was observed in

  8. Detection and putative effect of GATA4 gene variants in patients with congenital cardiac septal defects.

    PubMed

    Al-Azzouny, M A; El Ruby, M O; Issa, H A; Behiry, E G; Elsayed, N R; Fayez, A G

    2016-01-01

    The zinc finger transcription factor GATA4, located on chromosome 8p23.1-p22, has been implicated as a critical regulator of cardiac development during embryogenesis. Mutations of GATA4 appear to be responsible for some cardiac septal defects. The aim of this work was to screen for mutations in the GATA4 gene in sample of Egyptian patients affected by isolated and non-isolated cardiac septal defects. We examined 20 patients with atrial septal defect (ASD), ventricle septal defect (VSD), atrioventricular septal defects (AVSD) and A-V canal disturbance defect and compared with examined 10 unaffected individuals as normal control. The patients were referred from Congenital Heart Disease Clinic of the Clinical Genetics department at the National Research Centre. All patients were subjected to clinical evaluation, echocardiography and karyotyping. Genomic DNA was extracted from all cases and subjected to PCR followed by direct sequencing. The predicted effect of variants was done by a variety of proper prediction tools. We detected six variants in GATA4 gene, two of them are novel variants. Predicted functional analysis of the relevant variants was performed by In silico analysis. Further confirmatory studies on familial segregation and in vitro / in vivo functional analysis are recommended to support our results. PMID:27064867

  9. Improving vagal activity ameliorates cardiac fibrosis induced by angiotensin II: in vivo and in vitro

    PubMed Central

    Liu, Jin-Jun; Huang, Ning; Lu, Yi; Zhao, Mei; Yu, Xiao-Jiang; Yang, Yang; Yang, Yong-hua; Zang, Wei-Jin

    2015-01-01

    Cardiac remodeling is characterized by overactivity of the renin–angiotensin system (RAS) and withdrawal of vagal activity. We hypothesized that improving vagal activity could attenuate cardiac fibrosis induced by angiotensin II (Ang II) in vivo and in vitro. Rats were subjected to abdominal aorta constriction (AAC) with or without pyridostigmine (PYR) (31 mg/kg/d). After 8 weeks, PYR significantly decreased Ang II level, AT1 protein expression, and collagen deposition in cardiac tissue and improved heart rate variability, baroreflex sensitivity and cardiac function, which were abolished by atropine. In vitro, treatment of cardiac fibroblasts (CFs) with Ang II (10−7 M) increased cell proliferation, migration, transformation, and secretory properties, which were significantly diminished by acetylcholine (ACh, 10−6 M). Subsequently, Ang II significantly increased collagen type I expression as well as metalloproteinase (MMP)-2 expression and activity. Transforming growth factor (TGF)-β1 expression and Smad3 phosphorylation presented a similar trend. Notably, the knockdown of the acetylcholine M2 receptor by siRNA could abolish ACh anti-fibrotic action. These data implicated cholinesterase inhibitor can increase vagal activity and reduce local Ang II level, and ACh inhibit Ang II pro-fibrotic effects. Our findings suggested that the parasympathetic nervous system can serve as a promising target for cardiac remodeling treatment. PMID:26596640

  10. Dnmt2/Trdmt1 as Mediator of RNA Polymerase II Transcriptional Activity in Cardiac Growth

    PubMed Central

    Polo, Beatrice; Baudouy, Delphine; Kiani, Jafar; Michiels, Jean-François; Cuzin, François; Rassoulzadegan, Minoo

    2016-01-01

    Dnmt2/Trdmt1 is a methyltransferase, which has been shown to methylate tRNAs. Deficient mutants were reported to exhibit various, seemingly unrelated, defects in development and RNA-mediated epigenetic heredity. Here we report a role in a distinct developmental regulation effected by a noncoding RNA. We show that Dnmt2-deficiency in mice results in cardiac hypertrophy. Echocardiographic measurements revealed that cardiac function is preserved notwithstanding the increased dimensions of the organ due to cardiomyocyte enlargement. Mechanistically, activation of the P-TEFb complex, a critical step for cardiac growth, results from increased dissociation of the negatively regulating Rn7sk non-coding RNA component in Dnmt2-deficient cells. Our data suggest that Dnmt2 plays an unexpected role for regulation of cardiac growth by modulating activity of the P-TEFb complex. PMID:27270731

  11. Detecting geyser activity with infrasound

    NASA Astrophysics Data System (ADS)

    Johnson, J. B.; Anderson, J. F.; Anthony, R. E.; Sciotto, M.

    2013-04-01

    We monitored geyser activity in the Lower Geyser Basin (LGB) of Yellowstone National Park with dual four-element microphone arrays separated by ~ 600 m. The arrays were independently used to identify incident coherent plane wave energy, then conjoint cross beam back-azimuths from the two arrays were used to precisely locate signal sources. During a week in August 2011 we located repeating infrasound events, peaked in energy between 1 and 10 Hz, originating from at least five independent geothermal features, including the episodically erupting Great Fountain, Fountain and Kaleidoscope Geysers, as well as periodic infrasound from nearby Botryoidal and persistent sound from Firehole Spring. Although activity from nearby cone-type geysers was not detected in the infrasound band up through 50 Hz, the major fountain-type geysers (i.e., with columns greater than 10 m) could be detected at several kilometers, and two minor geysers (i.e., a few meters in eruption height) could be tracked at distances up to a few hundred meters. Detection of geyser activity was especially comprehensive at night when ambient noise was low. We conclude that infrasound monitoring of fountain-type geysers permits convenient tracking of geyser activity, episodicity, signal duration, energy content, and spectral content. These parameters enable objective statistical quantification of geyser behavior and changes over time that may be due to external forcing. Infrasonic study of geyser activity in an individual basin has great monitoring utility and can be reasonably accomplished with two or more distributed sensor arrays.

  12. Novel role for caspase-activated DNase in the regulation of pathological cardiac hypertrophy.

    PubMed

    Gao, Lu; Huang, Kun; Jiang, Ding-Sheng; Liu, Xiaoxiong; Huang, Dan; Li, Hongliang; Zhang, Xiao-Dong; Huang, Kai

    2015-04-01

    Caspase-activated DNase (CAD) is a double-strand-specific endonuclease that is responsible for the cleavage of nucleosomal spacer regions and subsequent chromatin condensation during apoptosis. Given that several endonucleases (eg, DNase I, DNase II, and Endog) have been shown to regulate pathological cardiac hypertrophy, we questioned whether CAD, which is critical for the induction of DNA fragmentation, plays a pivotal role in pressure overload-elicited cardiac hypertrophy. A CAD-knockout mouse model was generated and subjected to aortic banding for 8 weeks. The extent of cardiac hypertrophy was evaluated by echocardiography and pathological and molecular analyses. Our results demonstrated that the disruption of CAD attenuated pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction. Conversely, transgenic mice with cardiac-specific overexpression of CAD showed an aggravated cardiac hypertrophic response to chronic pressure overload. Mechanistically, we discovered that the expression and activation of mitogen-activated protein kinase-extracellular signal-regulated kinase 1/2 was significantly reduced in the CAD-knockout hearts compared with the control hearts; however, they were greatly increased in the CAD-overexpressing hearts after aortic banding. Similar results were observed in ex vivo cultured neonatal rat cardiomyocytes after treatment with angiotensin II for 48 hours. These data indicate that CAD functions as a necessary modulator of the hypertrophic response by regulating the mitogen-activated protein kinase-extracellular signal-regulated kinase 1/2 signaling pathway in the heart. Our study suggests that CAD might be a novel target for the treatment of pathological cardiac hypertrophy and heart failure. PMID:25646292

  13. 1,25 Dihydroxyvitamin D3 Inhibits TGFβ1-Mediated Primary Human Cardiac Myofibroblast Activation

    PubMed Central

    Meredith, Anna; Boroomand, Seti; Carthy, Jon; Luo, Zongshu; McManus, Bruce

    2015-01-01

    Aims Epidemiological and interventional studies have suggested a protective role for vitamin D in cardiovascular disease, and basic research has implicated vitamin D as a potential inhibitor of fibrosis in a number of organ systems; yet little is known regarding direct effects of vitamin D on human cardiac cells. Given the critical role of fibrotic responses in end stage cardiac disease, we examined the effect of active vitamin D treatment on fibrotic responses in primary human adult ventricular cardiac fibroblasts (HCF-av), and investigated the relationship between circulating vitamin D (25(OH)D3) and cardiac fibrosis in human myocardial samples. Methods and Results Interstitial cardiac fibrosis in end stage HF was evaluated by image analysis of picrosirius red stained myocardial sections. Serum 25(OH)D3 levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)β1 to induce activation, in the presence or absence of active vitamin D (1,25(OH)2D3). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)2D3 treatment significantly inhibited TGFβ1-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation. Conclusions Our results demonstrate that active vitamin D can prevent TGFβ1-mediated biochemical and functional pro-fibrotic changes in human primary cardiac fibroblasts. An inverse relationship between vitamin D status and cardiac fibrosis in end stage heart failure was observed. Collectively, our data support an inhibitory role for vitamin D in cardiac fibrosis. PMID:26061181

  14. Efficacy of antimicrobial activity of slow release silver nanoparticles dressing in post-cardiac surgery mediastinitis.

    PubMed

    Totaro, Pasquale; Rambaldini, Manfredo

    2009-01-01

    We report our preliminary experience in post-cardiac surgery mediastinitis using a recently introduced silver-releasing dressing claiming prompt antibacterial activity. Acticoat, a silver nanoparticles slow release dressing was used in four patients with documented post-cardiac surgery mediastinitis and persistently positive microbiological cultures despite vacuum-assisted closure (VAC) therapy. In all four patients negative cultures were obtained within a maximum of 72 h and patients were discharged within a maximum of 20 days. PMID:18948308

  15. The Impact of Antibody Selection on the Detection of Cardiac Troponin I

    PubMed Central

    Guy, Moltu J.; Chen, Yi-Chen; Clinton, Laura; Zhang, Han; Zhang, Jiang; Dong, Xintong; Xu, Qingge; Ayaz-Guner, Serife; Ge, Ying

    2012-01-01

    Background Cardiac troponin I (cTnI) is the current standard biomarker for diagnosing acute myocardial infarction and for risk-stratification of acute coronary syndromes in patients. However it remains unclear how the epitope specificity of antibodies in immunoassays influences the detection of various modified forms of cTnI. Methods Four mouse anti-human cTnI monoclonal antibodies targeting different regions of human cTnI were chosen for immunoaffinity purification of cTnI from human and swine cardiac tissue. High-resolution intact protein mass spectrometry was employed to assess the comparative performance of these four antibodies in detecting modified forms of cTnI. Results Our data revealed that antibody selection significantly impacts the relative protein yield of cTn from immunoaffinity purification. Remarkably, a single amino acid variation in cTnI (G->S) in the epitope region completely abolished the binding between monoclonal antibody 560 and swine cTnI in solution. Moreover, proteolytic degradation around the epitope region severely compromised the detection of proteolytic fragment forms of cTnI by monoclonal antibodies. In contrast, the phosphorylation status near the epitope region did not significantly affect the antibody recognition of cTnI. Conclusion Caution needs to be taken in the interpretation of the data produced by immuno-assays with monoclonal antibodies against various epitopes of cTnI. PMID:23107929

  16. Label-free Detection of Cardiac Troponin I with a Photonic Crystal Biosensor

    PubMed Central

    Zhang, Bailin; Morales, Andres W.; Peterson, Ralph; Tang, Liang; Ye, Jing Yong

    2014-01-01

    A biosensor has been developed with a photonic crystal structure used in a total-internal-reflection (PC-TIR) configuration for label-free detection of a cardiac biomarker: Troponin I (cTnI). In contrast to a conventional optical microcavity that has a closed structure with its cavity layer sandwiched between two high-reflection surfaces, the PC-TIR configuration creates a unique open microcavity, which allows its cavity layer (sensing layer) to be easily functionalized and directly exposed to analyte molecules for bioassays. In this study, a PC-TIR sensor has been used for the label-free measurements of cardiac biomarkers by monitoring the changes in the resonant condition of the cavity due to biomolecular binding processes. Antibodies against cTnI are immobilized on the sensor surface for specific detection of cTnI with a wide range of concentrations. Detection limit of cTnI with a concentration as low as 0.1 ng mL−1 has been achieved. PMID:24632136

  17. Electrochemical biosensors based on nanofibres for cardiac biomarker detection: A comprehensive review.

    PubMed

    Rezaei, Babak; Ghani, Mozhdeh; Shoushtari, Ahmad Mousavi; Rabiee, Mohammad

    2016-04-15

    The vital importance of early and accurate diagnosis of cardiovascular diseases (CVDs) to prevent the irreversible damage or even death of patients has driven the development of biosensor devices for detection and quantification of cardiac biomarkers. Electrochemical biosensors offer rapid sensing, low cost, portability and ease of use. Over the past few years, nanotechnology has contributed to a tremendous improvement in the sensitivity of biosensors. In this review, the authors summarise the state-of-the-art of the application of one particular type of nanostructured material, i.e. nanofibres, for use in electrochemical biosensors for the ultrasensitive detection of cardiac biomarkers. A new way of classifying the nanofibre-based electrochemical biosensors according to the electrical conductance and the type of nanofibres is presented. Some key data from each article reviewed are highlighted, including the mechanism of detection, experimental conditions and the response range of the biosensor. The primary aim of this review is to emphasise the prospects for nanofibres for the future development of biosensors in diagnosis of CVDs as well as considering how to improve their characteristics for application in medicine. PMID:26657595

  18. A sensitive algorithm for automatic detection of space-time alternating signals in cardiac tissue

    PubMed Central

    Bien, Harold; Entcheva, Emilia

    2011-01-01

    Alternans, a beat-to-beat alternation in cardiac signals, may serve as a precursor to lethal cardiac arrhythmias, including ventricular tachycardia and ventricular fibrillation. Therefore, alternans is a desirable target of early arrhythmia prediction/detection. For long-term records and in the presence of noise, the definition of alternans is qualitative and ambiguous. This makes their automatic detection in large spatiotemporal data sets almost impossible. We present here a quantitative combinatorics-derived definition of alternans in the presence of random noise and a novel algorithm for automatic alternans detection using criteria like temporal persistence (TP), representative phase (RP) and alternans ratio (AR). This technique is validated by comparison to theoretically-derived probabilities and by test data sets with white noise. Finally, the algorithm is applied to ultra-high resolution optical mapping data from cultured cell monolayers, exhibiting calcium alternans. Early fine-scale alternans, close to the noise level, were revealed and linked to the later formation of larger regions and evolution of spatially discordant alternans (SDA). This robust new technique can be useful in quantification and better understanding of the onset of arrhythmias and in general analysis of space-time alternating signals. PMID:19162616

  19. Detection and prediction of sudden cardiac death (SCD) for personal healthcare.

    PubMed

    Shen, Tsu-Wang; Shen, Hsiao-Ping; Lin, Ching-Heng; Ou, Yi-Ling

    2007-01-01

    Sudden Cardiac Death (SCD) is one of continuing challenges to the modern clinician. It is responsible for an estimated 400,000 deaths per year in the United States and millions of deaths worldwide. This research developed a personal cardiac homecare system by sensing Lead-I ECG signals for detecting and predicting SCD events, which also builds in ECG identity verification. A MIT/BIH SCD Holter Database plus our ECG database were investigated. The system includes a self-made ECG amplifier, a NI DAQ card, a laptop computer, LabView and MatLab programs. The wavelet analysis was applied to detect SCD and the overall performance is 87.5% correct detection rate. In addition, artificial neural networks (ANN) were used to predict SCD events. The correct prediction rates by applying least mean square (LMS), decision based neural network (DBNN), and back propagation (BP) neural network were 67.44%, 58.14% and 55.81% respectively. PMID:18002521

  20. Increased Efferent Cardiac Sympathetic Nerve Activity and Defective Intrinsic Heart Rate Regulation in Type 2 Diabetes.

    PubMed

    Thaung, H P Aye; Baldi, J Chris; Wang, Heng-Yu; Hughes, Gillian; Cook, Rosalind F; Bussey, Carol T; Sheard, Phil W; Bahn, Andrew; Jones, Peter P; Schwenke, Daryl O; Lamberts, Regis R

    2015-08-01

    Elevated sympathetic nerve activity (SNA) coupled with dysregulated β-adrenoceptor (β-AR) signaling is postulated as a major driving force for cardiac dysfunction in patients with type 2 diabetes; however, cardiac SNA has never been assessed directly in diabetes. Our aim was to measure the sympathetic input to and the β-AR responsiveness of the heart in the type 2 diabetic heart. In vivo recording of SNA of the left efferent cardiac sympathetic branch of the stellate ganglion in Zucker diabetic fatty rats revealed an elevated resting cardiac SNA and doubled firing rate compared with nondiabetic rats. Ex vivo, in isolated denervated hearts, the intrinsic heart rate was markedly reduced. Contractile and relaxation responses to β-AR stimulation with dobutamine were compromised in externally paced diabetic hearts, but not in diabetic hearts allowed to regulate their own heart rate. Protein levels of left ventricular β1-AR and Gs (guanine nucleotide binding protein stimulatory) were reduced, whereas left ventricular and right atrial β2-AR and Gi (guanine nucleotide binding protein inhibitory regulatory) levels were increased. The elevated resting cardiac SNA in type 2 diabetes, combined with the reduced cardiac β-AR responsiveness, suggests that the maintenance of normal cardiovascular function requires elevated cardiac sympathetic input to compensate for changes in the intrinsic properties of the diabetic heart. PMID:25784543

  1. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling.

    PubMed

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj; Schönberger, Tanja; Noegel, Angelika A; Gawaz, Meinrad; Lang, Florian

    2014-02-28

    Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca(2+) signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7(-/-)) and wild-type mice (anxa7(+/+)) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7(-/-) mice than in anxa7(+/+) mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions. PMID:24508799

  2. Effect of Long-Term Physical Activity Practice after Cardiac Rehabilitation on Some Risk Factors

    ERIC Educational Resources Information Center

    Freyssin, Celine, Jr.; Blanc, Philippe; Verkindt, Chantal; Maunier, Sebastien; Prieur, Fabrice

    2011-01-01

    The objective of this study was to evaluate the effects of long-term physical activity practice after a cardiac rehabilitation program on weight, physical capacity and arterial compliance. The Dijon Physical Activity Score was used to identify two groups: sedentary and active. Weight, distance at the 6-min walk test and the small artery elasticity…

  3. Monitoring plasma cardiac troponin I for the detection of myocardial injury after percutaneous transluminal coronary angioplasty.

    PubMed

    Ricchiuti, V; Shear, W S; Henry, T D; Paulsen, P R; Miller, E A; Apple, F S

    2000-12-01

    The objective of this study was to detect myocardial injury defined by an increase of plasma cardiac troponin I (cTnI) following percutaneous transluminal coronary angioplasty (PTCA) and compare plasma cTnI with the risk of cardiac complications at 30 days. Plasma cTnI, creatine kinase (CK) MB, and total CK were determined in 83 patients before (baseline) and 6, 12 and 24 h after PTCA. Thirty-eight patients underwent conventional PTCA, 39 PTCA-stent and six rotational atherectomy. Patients with acute myocardial infarction (AMI) and increased pre-procedural cTnI >0.8 microg/l were categorized into group 1 (n=23). The remaining 60 patients (pre-procedural cTnI=0.8 microg/l) were categorized as follows: group 2 (n=15) AMI; group 3 (n=20) unstable angina (UA); group 4 (n=25) coronary artery disease (CAD). Twelve hours post-procedure, all three cardiac markers were more frequently increased over baseline in group 2 patients (40-60%) compared to patients in group 3 (5-29%, P<0.03) or group 4 (0.5-5%, P<0.01). This was also true for patients undergoing PTCA-stent compared to conventional PTCA or rotational atherectomy (27-40 vs. 4-14%, P<0.02). cTnI was more sensitive (60%) to detect release of myocardial protein after PTCA compared to total CK (47%) or CKMB (43%). A moderate increase of cTnI (0.8-1.5 microg/l) in groups 2, 3 and 4 was associated with higher risk of complications 30 days post-procedure. PMID:11074073

  4. Efficient Generation of Cardiac Purkinje Cells from ESCs by Activating cAMP Signaling

    PubMed Central

    Tsai, Su-Yi; Maass, Karen; Lu, Jia; Fishman, Glenn I.; Chen, Shuibing; Evans, Todd

    2015-01-01

    Summary Dysfunction of the specialized cardiac conduction system (CCS) is associated with life-threatening arrhythmias. Strategies to derive CCS cells, including rare Purkinje cells (PCs), would facilitate models for mechanistic studies and drug discovery and also provide new cellular materials for regenerative therapies. A high-throughput chemical screen using CCS:lacz and Contactin2:egfp (Cntn2:egfp) reporter embryonic stem cell (ESC) lines was used to discover a small molecule, sodium nitroprusside (SN), that efficiently promotes the generation of cardiac cells that express gene profiles and generate action potentials of PC-like cells. Imaging and mechanistic studies suggest that SN promotes the generation of PCs from cardiac progenitors initially expressing cardiac myosin heavy chain and that it does so by activating cyclic AMP signaling. These findings provide a strategy to derive scalable PCs, along with insight into the ontogeny of CCS development. PMID:26028533

  5. Cardiac myocyte–secreted cAMP exerts paracrine action via adenosine receptor activation

    PubMed Central

    Sassi, Yassine; Ahles, Andrea; Truong, Dong-Jiunn Jeffery; Baqi, Younis; Lee, Sang-Yong; Husse, Britta; Hulot, Jean-Sébastien; Foinquinos, Ariana; Thum, Thomas; Müller, Christa E.; Dendorfer, Andreas; Laggerbauer, Bernhard; Engelhardt, Stefan

    2014-01-01

    Acute stimulation of cardiac β-adrenoceptors is crucial to increasing cardiac function under stress; however, sustained β-adrenergic stimulation has been implicated in pathological myocardial remodeling and heart failure. Here, we have demonstrated that export of cAMP from cardiac myocytes is an intrinsic cardioprotective mechanism in response to cardiac stress. We report that infusion of cAMP into mice averted myocardial hypertrophy and fibrosis in a disease model of cardiac pressure overload. The protective effect of exogenous cAMP required adenosine receptor signaling. This observation led to the identification of a potent paracrine mechanism that is dependent on secreted cAMP. Specifically, FRET-based imaging of cAMP formation in primary cells and in myocardial tissue from murine hearts revealed that cardiomyocytes depend on the transporter ABCC4 to export cAMP as an extracellular signal. Extracellular cAMP, through its metabolite adenosine, reduced cardiomyocyte cAMP formation and hypertrophy by activating A1 adenosine receptors while delivering an antifibrotic signal to cardiac fibroblasts by A2 adenosine receptor activation. Together, our data reveal a paracrine role for secreted cAMP in intercellular signaling in the myocardium, and we postulate that secreted cAMP may also constitute an important signal in other tissues. PMID:25401477

  6. Fetal cardiac activity analysis during twin pregnancy using a multi-channel SQUID system

    NASA Astrophysics Data System (ADS)

    Costa Monteiro, E.; Schleussner, E.; Kausch, S.; Grimm, B.; Schneider, A.; Hall Barbosa, C.; Haueisen, J.

    2001-05-01

    The use of SQUID magnetometers for non-invasive in utero assessment of cardiac electrical disturbances has already been shown to be a valuable clinical tool. In this way, its applicability also for the complicated case of twin pregnancy, in which the proximity of the cardiac magnetic source of each fetus can hamper the individual analysis of cardiac electrical activity, is of clinical interest. In this paper, we present fetal magnetocardiography performed on a mother pregnant of twins with 26 weeks gestational age, measured inside a magnetically shielded room, by using two identical 31-channel low- Tc SQUID magnetometer systems. Each sensor array has been positioned over one of the fetuses, according to its heart position previously assessed with the aid of ultrasound measurements. The raw data is initially averaged in time and, afterwards, analyzed by means of time plots and isofield maps. The time recordings allow the study of the morphology of each fetus’ cardiac signal and the cardiac time intervals. The resultant equivalent dipole obtained from the isofield maps indicates the position and orientation of each fetus heart. The results agree with the ultrasound analysis performed immediately before the measurements and used to obtain the approximate location of the fetuses’ hearts. Since a distinct analysis of the cardiac electrical activity of each fetus could be achieved, the results indicate the potential of the fetal magnetocardiography in the individual antenatal diagnosis of each one of the fetuses of a twin pregnancy.

  7. Mild hypothermia inhibits systemic and cerebral complement activation in a swine model of cardiac arrest

    PubMed Central

    Gong, Ping; Zhao, Hong; Hua, Rong; Zhang, Mingyue; Tang, Ziren; Mei, Xue; Cui, Juan; Li, Chunsheng

    2015-01-01

    Complement activation has been implicated in ischemia/reperfusion injury. This study aimed to determine whether mild hypothermia (HT) inhibits systemic and cerebral complement activation after resuscitation from cardiac arrest. Sixteen minipigs resuscitated from 8 minutes of untreated ventricular fibrillation were randomized into two groups: HT group (n=8), treated with HT (33°C) for 12 hours; and normothermia group (n=8), treated similarly as HT group except for cooling. Blood samples were collected at baseline and 0.5, 6, 12, and 24 hours after return of spontaneous circulation (ROSC). The brain cortex was harvested 24 hours after ROSC. Complement and pro-inflammatory markers were detected using enzyme-linked immunosorbent assay. Neurologic deficit scores were evaluated 24 hours after ROSC. C1q, Bb, mannose-binding lectin (MBL), C3b, C3a, C5a, interleukin-6, and tumor necrosis factor-α levels were significantly increased under normothermia within 24 hours after ROSC. However, these increases were significantly reduced by HT. Hypothermia decreased brain C1q, MBL, C3b, and C5a contents 24 hours after ROSC. Hypothermic pigs had a better neurologic outcome than normothermic pigs. In conclusion, complement is activated through classic, alternative, and MBL pathways after ROSC. Hypothermia inhibits systemic and cerebral complement activation, which may provide an additional mechanism of cerebral protection. PMID:25757755

  8. Activation of mitochondrial calpain and increased cardiac injury: beyond AIF release.

    PubMed

    Thompson, Jeremy; Hu, Ying; Lesnefsky, Edward J; Chen, Qun

    2016-02-01

    Calpain 1 (CPN1) is a ubiquitous cysteine protease that exists in both cytosol and cardiac mitochondria. Mitochondrial CPN1 (mit-CPN1) is located in the intermembrane space and matrix. Activation of mit-CPN1 within the intermembrane space increases cardiac injury by releasing apoptosis-inducing factor from mitochondria during ischemia-reperfusion (IR). We asked if activation of mit-CPN1 is involved in mitochondrial injury during IR. MDL-28170 (MDL) was used to inhibit CPN1 in buffer-perfused hearts following 25-min ischemia and 30-min reperfusion. MDL treatment decreased the release of lactate dehydrogenase into coronary effluent compared with untreated hearts, indicating that inhibition of CPN1 decreases cardiac injury. MDL also prevented the cleavage of spectrin (a substrate of CPN1) in cytosol during IR, supporting that MDL treatment decreased cytosolic calpain activation. In addition, MDL markedly improved calcium retention capacity compared with untreated heart, suggesting that MDL treatment decreases mitochondrial permeability transition pore opening. In addition, we found that IR led to decreased complex I activity, whereas inhibition of mit-CPN1 using MDL protected complex I. Pyruvate dehydrogenase content was decreased following IR. However, pyruvate dehydrogenase content was preserved in MDL-treated mitochondria. Taken together, MDL treatment decreased cardiac injury during IR by inhibiting both cytosolic and mit-CPN1. Activation of mit-CPN1 increases cardiac injury during IR by sensitizing mitochondrial permeability transition pore opening and impairing mitochondrial metabolism through damage of complex I. PMID:26637561

  9. Activation of the Cardiac Renin-Angiotensin System in High Oxygen-Exposed Newborn Rats: Angiotensin Receptor Blockade Prevents the Developmental Programming of Cardiac Dysfunction.

    PubMed

    Bertagnolli, Mariane; Dios, Anne; Béland-Bonenfant, Sarah; Gascon, Gabrielle; Sutherland, Megan; Lukaszewski, Marie-Amélie; Cloutier, Anik; Paradis, Pierre; Schiffrin, Ernesto L; Nuyt, Anne Monique

    2016-04-01

    Newborn rats exposed to high oxygen (O2), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin-angiotensin system activation in O2-exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O2 exposure), P5, P10 (end of O2), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O2-exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-β/SMAD3 pathway, and upregulation of cardiac angiotensin-converting enzyme 2. In conclusion, short-term Ang II blockade during neonatal high O2 prevents the development of cardiac alterations later in life in rats. These findings highlight the key role of neonatal renin-angiotensin system activation in the developmental programming of cardiac dysfunction induced by deleterious neonatal conditions. PMID:26857347

  10. Activated c-Kit receptor in the heart promotes cardiac repair and regeneration after injury

    PubMed Central

    Di Siena, S; Gimmelli, R; Nori, S L; Barbagallo, F; Campolo, F; Dolci, S; Rossi, P; Venneri, M A; Giannetta, E; Gianfrilli, D; Feigenbaum, L; Lenzi, A; Naro, F; Cianflone, E; Mancuso, T; Torella, D; Isidori, A M; Pellegrini, M

    2016-01-01

    The role of endogenous c-Kit receptor activation on cardiac cell homeostasis and repair remains largely unexplored. Transgenic mice carrying an activating point mutation (TgD814Y) in the kinase domain of the c-Kit gene were generated. c-KitTgD814Y receptor was expressed in the heart during embryonic development and postnatal life, in a similar timing and expression pattern to that of the endogenous gene, but not in the hematopoietic compartment allowing the study of a cardiac-specific phenotype. c-KitTgD814Y mutation produced a constitutive active c-Kit receptor in cardiac tissue and cells from transgenic mice as demonstrated by the increased phosphorylation of ERK1/2 and AKT, which are the main downstream molecular effectors of c-Kit receptor signaling. In adult transgenic hearts, cardiac morphology, size and total c-Kit+ cardiac cell number was not different compared with wt mice. However, when c-KitTgD814Y mice were subjected to transmural necrotic heart damage by cryoinjury (CI), all transgenic survived, compared with half of wt mice. In the sub-acute phase after CI, transgenic and wt mice showed similar heart damage. However, 9 days after CI, transgenic mice exhibited an increased number of c-Kit+CD31+ endothelial progenitor cells surrounding the necrotic area. At later follow-up, a consistent reduction of fibrotic area, increased capillary density and increased cardiomyocyte replenishment rate (as established by BrdU incorporation) were observed in transgenic compared with wt mice. Consistently, CD45−c-Kit+ cardiac stem cells isolated from transgenic c-KitTgD814Y mice showed an enhanced endothelial and cardiomyocyte differentiation potential compared with cells isolated from the wt. Constitutive activation of c-Kit receptor in mice is associated with an increased cardiac myogenic and vasculogenic reparative potential after injury, with a significant improvement of survival. PMID:27468693

  11. Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling

    SciTech Connect

    Voelkl, Jakob; Alesutan, Ioana; Pakladok, Tatsiana; Viereck, Robert; Feger, Martina; Mia, Sobuj; Schönberger, Tanja; Noegel, Angelika A.; Gawaz, Meinrad; Lang, Florian

    2014-02-28

    Highlights: • Cardiac Anxa7 expression was up-regulated following TAC. • The hypertrophic response following TAC was augmented in Anxa7-deficient mice. • Silencing of Anxa7 increased indicators of HL-1 cardiomyocytes hypertrophy. • Silencing of Anxa7 induced Nfatc1 nuclear translocation. • Silencing of Anxa7 enhanced NFAT-dependent transcriptional activity. - Abstract: Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca{sup 2+} signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7{sup −/−}) and wild-type mice (anxa7{sup +/+}) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7{sup −/−} mice than in anxa7{sup +/+} mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions.

  12. Enhanced fluorescence anisotropy assay for human cardiac troponin I and T detection.

    PubMed

    Qiao, Yanling; Tang, Hongmin; Munske, Gerhard R; Dutta, Prashanta; Ivory, Cornelius F; Dong, Wen-Ji

    2011-11-01

    Human cardiac troponin I (hcTnI) and troponin T (hcTnT) are the biomarkers of choice for the diagnosis of cardiac diseases. In an effort to improve assay sensitivity, in this study we developed a novel approach to simultaneously detect hcTnI and hcTnT in homogenous solutions by monitoring enhanced-fluorescence-anisotropy changes. Specifically, our design was based on a competition assay by measuring anisotropy change of fluorophore-labeled peptides bound to primary monoclonal antibodies in the presence of nano-gold-modified secondary antibody in response to the presence of target proteins. Enhanced-fluorescence-anisotropy resulted from interaction between the primary antibody and the nano-gold-labeled secondary antibody, which significantly increased the size and decreased tumbling motion of the complex of peptide-antibodies. The measurements were performed to detect hcTnI and hcTnT either individually or simultaneously in a homogenous buffer solution and in the solutions containing human plasma. Our results showed that when fluorescence emission was monitored at a single wavelength selected by a monochromator the assay at all experimental conditions had excellent linear response to the target proteins within the concentration range of 0.5-40 nM. The detection limit is 0.5 nM for both hcTnI and hcTnT in the presence of human plasma. However, when fluorescence emission was monitored using a cutoff filter, the linear response of the assay to the target proteins is within 15-500 pM. The detection limit is 15 pM which is close to the recommended 99th percentile cutoff point for concentrations of hcTnI and hcTnT tests to discriminate healthy and diseased conditions. Homogenous nature, rapid response time, and easy implementation of our assay design make it a useful tool for disease biomarker and protein sensing. PMID:21647606

  13. Enhanced Fluorescence Anisotropy Assay for Human Cardiac Troponin I and T Detection

    PubMed Central

    Qiao, Yanling; Tang, Hongmin; Munske, Gerhard R.; Dutta, Prashanta; Ivory, Cornelius F.

    2012-01-01

    Human cardiac troponin I (hcTnI) and troponin T (hcTnT) are the biomarkers of choice for the diagnosis of cardiac diseases. In an effort to improve assay sensitivity, in this study we developed a novel approach to simultaneously detect hcTnI and hcTnT in homogenous solutions by monitoring enhanced-fluorescence-anisotropy changes. Specifically, our design was based on a competition assay by measuring anisotropy change of fluorophore-labeled peptides bound to primary monoclonal antibodies in the presence of nano-gold-modified secondary antibody in response to the presence of target proteins. Enhanced-fluorescence-anisotropy resulted from interaction between the primary antibody and the nano-gold-labeled secondary antibody, which significantly increased the size and decreased tumbling motion of the complex of peptide-antibodies. The measurements were performed to detect hcTnI and hcTnT either individually or simultaneously in a homogenous buffer solution and in the solutions containing human plasma. Our results showed that when fluorescence emission was monitored at a single wavelength selected by a monochromator the assay at all experimental conditions had excellent linear response to the target proteins within the concentration range of 0.5–40 nM. The detection limit is 0.5 nM for both hcTnI and hcTnT in the presence of human plasma. However, when fluorescence emission was monitored using a cutoff filter, the linear response of the assay to the target proteins is within 15–500 pM. The detection limit is 15 pM which is close to the recommended 99th percentile cutoff point for concentrations of hcTnI and hcTnT tests to discriminate healthy and diseased conditions. Homogenous nature, rapid response time, and easy implementation of our assay design make it a useful tool for disease biomarker and protein sensing. PMID:21647606

  14. Exendin-4 attenuates cardiac hypertrophy via AMPK/mTOR signaling pathway activation.

    PubMed

    Zhou, Yue; He, Xin; Chen, Yili; Huang, Yiyi; Wu, Lingling; He, Jiangui

    Diabetes mellitus is a prominent risk factor for cardiovascular diseases. Diabetic cardiomyopathy is an important complication of the heart independent of hypertension and coronary artery disease and is accompanied by cardiac hypertrophy. Cardiac hypertrophy easily leads to heart failure, which is a leading cause of morbidity and mortality. Glucagon-like peptide 1 (GLP-1) is an incretin hormone, which has various beneficial roles in the cardiovascular system, and exendin-4 is a highly potent glucagon-like peptide 1 receptor agonist. However, the role of GLP-1 in cardiac hypertrophy remains unknown. Our study revealed that exendin-4 treatment ameliorated phenylephrine (PE)-induced cardiac hypertrophy, which presented as decreased cardiac hypertrophic markers (ANP, BNP, and β-MHC) and cell surface area. This condition was significantly reversed upon treatment with the GLP-1 receptor antagonist exendin9-39. We also discovered that Erk1/2 and AMPK signaling pathways were involved in this process. Furthermore, our data demonstrate that the AMPK inhibitor compound C inhibited the anti-hypertrophic effect of exendin-4, which is associated with the mTOR/p70S6K/4-EBP1 signaling pathway. Finally, exendin-4 enhanced the anti-hypertrophic effect of rapamycin. In summary, our study disclosed that exedin-4 inhibits cardiac hypertrophy by upregulating GLP-1 receptor expression and activating the AMPK/mTOR signaling pathway. PMID:26519882

  15. Inappropriate shocks delivered by implantable cardiac defibrillators during oversensing of activity of diaphagmatic muscle

    PubMed Central

    Babuty, D; Fauchier, L; Cosnay, P

    1999-01-01

    Two cases are reported (both men, one 72 and one 54 years old) of inappropriate shocks delivered by an implantable cardiac defibrillator (ICD) device, which oversensed the myopotentials induced by deep breathing and Valsalva manoeuvre. No damage to leads was associated with the oversensing of myopotentials. The mechanism of the inappropriate shocks was determined using real time electrograms. Modification of the duration of ventricular detection and decrease in sensitivity made it possible to avoid the oversensing of myopotentials and to deliver ICD treatment.

 Keywords: implantable cardiac defibrillator;  inappropriate shocks;  myopotentials PMID:10220554

  16. The impact of cardiac gating on the detection of coronary calcifications in dual-energy chest radiography: a phantom study

    NASA Astrophysics Data System (ADS)

    Sabol, John M.; Liu, Ray; Saunders, Rowland; Markley, Jonathan; Moreno, Nery; Seamans, John; Wiese, Scott; Jabri, Kadri; Gilkeson, Robert C.

    2006-03-01

    The detection of coronary calcifications with CT is generally accepted as a useful method for predicting early onset of coronary artery disease. Film-screen X-ray and fluoroscopy have also been shown to have high predictive value for coronary disease diagnosis, but have minimal sensitivity. Recently, flat-panel detectors capable of dual-energy techniques have enabled the separation of soft-tissue and bone from images. Clinical studies report substantially improved sensitivity for the detection of coronary calcifications using these techniques. However, heart motion causes minor artefacts from misregistration of both calcified and soft-tissue structures, resulting in inconsistent detection of calcifications. This research examines whether cardiac gating improves the reliability of calcification detection. Single-energy, gated, and non-gated dual-energy imaging techniques are examined in a dynamic phantom model. A gating system was developed to synchronize two dual-energy exposures to a specified phase of the cardiac cycle. The performance and repeatability of the gating system was validated with the use of a cyclical phantom. An anthropomorphic phantom was developed to simulate both cardiac and soft-tissue motion, and generate ECG-like output signals. The anthropomorphic phantom and motion artefact accuracy was verified by comparison with clinical images of patients with calcifications. The ability of observers to detect calcifications in non-gated, and gated techniques was compared through the use of an ROC experiment. Gating visibly reduces the effect of motion artifacts in the dual-energy images. Without gating, motion artefacts cause greater variability in calcification detection. Comparison of the average area-under-the-curve of the ROC curves show that gating significantly increases the accuracy of calcification detection. The effects of motion and gating on DE cardiac calcification detection have been demonstrated and characterized in a phantom model that

  17. Asiatic Acid Protects against Cardiac Hypertrophy through Activating AMPKα Signalling Pathway

    PubMed Central

    Ma, Zhen-Guo; Dai, Jia; Wei, Wen-Ying; Zhang, Wen-Bin; Xu, Si-Chi; Liao, Hai-Han; Yang, Zheng; Tang, Qi-Zhu

    2016-01-01

    Background: AMPactivated protein kinase α (AMPKα) is closely involved in the process of cardiac hypertrophy. Asiatic acid (AA), a pentacyclic triterpene, was found to activate AMPKα in our preliminary experiment. However, its effects on the development of cardiac hypertrophy remain unclear. The present study was to determine whether AA could protect against cardiac hypertrophy. Methods: Mice subjected to aortic banding were orally given AA (10 or 30mg/kg) for 7 weeks. In the inhibitory experiment, Compound C was intraperitoneally injected for 3 weeks after surgery. Results: Our results showed that AA markedly inhibited hypertrophic responses induced by pressure overload or angiotensin II. AA also suppressed cardiac fibrosis in vivo and accumulation of collagen in vitro. The protective effects of AA were mediated by activation of AMPKα and inhibition of the mammalian target of rapamycin (mTOR) pathway and extracellular signal-regulated kinase (ERK) in vivo and in vitro. However, AA lost the protective effects after AMPKα inhibition or gene deficiency. Conclusions: AA protects against cardiac hypertrophy by activating AMPKα, and has the potential to be used for the treatment of heart failure. PMID:27313499

  18. Real-time detection of pathological cardiac events in the electrocardiogram.

    PubMed

    Iliev, Ivo; Krasteva, Vessela; Tabakov, Serafim

    2007-03-01

    The development of accurate and fast methods for real-time electrocardiogram (ECG) analysis is mandatory in handheld fully automated monitoring devices for high-risk cardiac patients. The present work describes a simple software method for fast detection of pathological cardiac events. It implements real-time procedures for QRS detection, interbeat RR-intervals analysis, QRS waveform evaluation and a decision-tree beat classifier. Two QRS descriptors are defined to assess (i) the RR interval deviation from the mean RR interval and (ii) the QRS waveform deviation from the QRS pattern of the sustained rhythm. The calculation of the second parameter requires a specific technique, in order to satisfy the demand for straight signal processing with minimum iterations and small memory size. This technique includes fast and resource efficient estimation of a histogram matrix, which accumulates dynamically the amplitude-temporal distribution of the successive QRS pattern waveforms. The pilot version of the method is developed in Matlab and it is tested with internationally recognized ECG databases. The assessment of the online single lead QRS detector showed sensitivity and positive predictivity of above 99%. The classification rules for detection of pathological ventricular beats were defined empirically by statistical analysis. The attained specificity and sensitivity are about 99.5% and 95.7% for all databases and about 99.81% and 98.87% for the noise free dataset. The method is applicable in low computational cost systems for long-term ECG monitoring, such as intelligent holters, automatic event/alarm recorders or personal devices with intermittent wireless data transfer to a central terminal. PMID:17322591

  19. Activation of MEK/ERK Signaling by PACAP in Guinea Pig Cardiac Neurons.

    PubMed

    Clason, Todd A; Girard, Beatrice M; May, Victor; Parsons, Rodney L

    2016-06-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) signaling can increase guinea pig cardiac neuron excitability in part through extracellular signal-regulated kinase (ERK) activation. The present study examined the PACAP receptors and signaling cascades that stimulate guinea pig cardiac neuron ERK signaling using confocal microscopy to quantify PACAP-induced neuronal phosphorylated ERK (pERK) immunoreactivity. PACAP and maxadilan, but not vasoactive intestinal polypeptide (VIP), increased cardiac neuron pERK, implicating primary roles for PACAP-selective PAC1 receptor (Adcyap1r1) signaling rather than VPAC receptors (Vipr1 and Vipr2) in the generation of cardiac neuron pERK. The adenylyl cyclase (AC) activator forskolin, but not the protein kinase C (PKC) activator phorbol myristate acetate (PMA), increased pERK. Also, Bim1 did not blunt PACAP activation of pERK. Together, the results suggest PAC1 receptor signal transduction via Gs/adenylyl cyclase (AC)/cAMP rather than Gq/phospholipase C (PLC) generated neuronal pERK. Activator and inhibitor studies suggested that the PACAP-mediated pERK activation was PKA-dependent rather than an exchange protein directly activated by a cAMP (EPAC), PKA-independent mechanism. The PACAP-induced pERK was inhibited by the clathrin inhibitor Pitstop2 to block receptor internalization and endosomal signaling. We propose that the PACAP-mediated MEK/ERK activation in cardiac neurons involves both AC/cAMP/PKA signaling and PAC1 receptor internalization/activation of signaling endosomes. PMID:27194157

  20. Endogenous bradykinin activates ischaemically sensitive cardiac visceral afferents through kinin B2 receptors in cats

    PubMed Central

    Tjen-A-Looi, Stephanie C; Pan, Hui-Lin; Longhurst, John C

    1998-01-01

    Activity of ischaemically sensitive cardiac visceral afferents during myocardial ischaemia induces both angina and cardiovascular reflexes. Increased production of bradykinin (BK) and cyclo-oxygenase products (i.e. prostaglandins (PGs)) occurs during myocardial ischaemia. However, the role of these agents in activation of ischaemically sensitive cardiac afferents has not been established. The present study tested the hypothesis that BK produced during ischaemia activates cardiac afferents through kinin B2 receptors. Single-unit activity of cardiac afferents innervating the left ventricle was recorded from the left thoracic sympathetic chain (T1–T4) of anaesthetized cats. Ischaemically sensitive cardiac afferents were identified according to their response to 5 min of myocardial ischaemia. The mechanism of BK in activation of ischaemically sensitive cardiac afferents was determined by injection of BK (1 μg kg−1 i.a.), des-Arg9-BK (1 μg kg−1 i.a., a specific kinin B1 receptor agonist), kinin B2 receptor antagonists: HOE140 (30 μg kg−1 i.v.) and NPC-17731 (40 μg kg−1 i.v.), cyclo-oxygenase inhibition with indomethacin (5 mg kg−1 i.v.) and NPC-17731 (40 μg kg−1 i.v.) after pretreatment with indomethacin (5 mg kg−1 i.v.). We observed that BK increased the discharge rate of all eleven ischaemically sensitive cardiac afferents from 0.39 ± 0.12 to 1.47 ± 0.37 impulses s−1 (P < 0.05). Conversely, des-Arg9-BK did not significantly increase the activity of eleven ischaemically sensitive fibres (0.58 ± 0.02 vs. 0.50 ± 0.18 impulses s−1). HOE140 significantly attenuated the response of twelve afferents to ischaemia (0.61 ± 0.22 to 1.85 ± 0.5 vs. 0.53 ± 0.16 to 1.09 ± 0.4 impulses s−1). NPC-17731, another kinin B2 receptor antagonist, had similar inhibitory effects on six other ischaemically sensitive cardiac afferents (0.35 ± 0.14 to 1.19 ± 0.29 vs. 0.22 ± 0.08 to 0.23 ± 0.07 impulses s−1). Indomethacin significantly reduced the

  1. RyR2 Modulates a Ca2+-Activated K+ Current in Mouse Cardiac Myocytes

    PubMed Central

    Mu, Yong-hui; Zhao, Wen-chao; Duan, Ping; Chen, Yun; Zhao, Wei-da; Wang, Qian; Tu, Hui-yin; Zhang, Qian

    2014-01-01

    In cardiomyocytes, Ca2+ entry through voltage-dependent Ca2+ channels (VDCCs) binds to and activates RyR2 channels, resulting in subsequent Ca2+ release from the sarcoplasmic reticulum (SR) and cardiac contraction. Previous research has documented the molecular coupling of small-conductance Ca2+-activated K+ channels (SK channels) to VDCCs in mouse cardiac muscle. Little is known regarding the role of RyRs-sensitive Ca2+ release in the SK channels in cardiac muscle. In this study, using whole-cell patch clamp techniques, we observed that a Ca2+-activated K+ current (IK,Ca) recorded from isolated adult C57B/L mouse atrial myocytes was significantly decreased by ryanodine, an inhibitor of ryanodine receptor type 2 (RyR2), or by the co-application of ryanodine and thapsigargin, an inhibitor of the sarcoplasmic reticulum calcium ATPase (SERCA) (p<0.05, p<0.01, respectively). The activation of RyR2 by caffeine increased the IK,Ca in the cardiac cells (p<0.05, p<0.01, respectively). We further analyzed the effect of RyR2 knockdown on IK,Ca and Ca2+ in isolated adult mouse cardiomyocytes using a whole-cell patch clamp technique and confocal imaging. RyR2 knockdown in mouse atrial cells transduced with lentivirus-mediated small hairpin interference RNA (shRNA) exhibited a significant decrease in IK,Ca (p<0.05) and [Ca2+]i fluorescence intensity (p<0.01). An immunoprecipitated complex of SK2 and RyR2 was identified in native cardiac tissue by co-immunoprecipitation assays. Our findings indicate that RyR2-mediated Ca2+ release is responsible for the activation and modulation of SK channels in cardiac myocytes. PMID:24747296

  2. Label-Free Detection of Cardiac Troponin-I Using Carbon Nanofiber Based Nanoelectrode Arrays

    NASA Technical Reports Server (NTRS)

    Periyakaruppan, Adaikkappan; Koehne, Jessica Erin; Gandhiraman, Ram P.; Meyyappan, M.

    2013-01-01

    A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. A carbon nanofiber (CNF) multiplexed array has been fabricated with 9 sensing pads, each containing 40,000 carbon nanofibers as nanoelectrodes. Here, we report the use of vertically aligned CNF nanoelectrodes for the detection of cardiac Troponin-I for the early diagnosis of myocardial infarction. Antibody, antitroponin, probe immobilization and subsequent binding to human cardiac troponin-I were characterized using electrochemical impedance spectroscopy and cyclic voltammetry techniques. Each step of the modification process resulted in changes in electrical capacitance or resistance to charge transfer due to the changes at the electrode surface upon antibody immobilization and binding to the specific antigen. This sensor demonstrates high sensitivity, down to 0.2 ng/mL, and good selectivity making this platform a good candidate for early stage diagnosis of myocardial infarction.

  3. Automated detection of the left ventricular region in gated nuclear cardiac imaging.

    PubMed

    Boudraa, A E; Arzi, M; Sau, J; Champier, J; Hadj-Moussa, S; Besson, J E; Sappey-Marinier, D; Itti, R; Mallet, J J

    1996-04-01

    An approach to automated outlining the left ventricular contour and its bounded area in gated isotopic ventriculography is proposed. Its purpose is to determine the ejection fraction (EF), an important parameter for measuring cardiac function. The method uses a modified version of the fuzzy C-means (MFCM) algorithm and a labeling technique. The MFCM algorithm is applied to the end diastolic (ED) frame and then the (FCM) is applied to the remaining images in a "box" of interest. The MFCM generates a number of fuzzy clusters. Each cluster is a substructure of the heart (left ventricle,...). A cluster validity index to estimate the optimum clusters number present in image data point is used. This index takes account of the homogeneity in each cluster and is connected to the geometrical property of data set. The labeling is only performed to achieve the detection process in the ED frame. Since the left ventricle (LV) cluster has the greatest area of the cardiac images sequence in ED phase, a framing operation is performed to obtain, automatically, the "box" enclosing the LV cluster. THe EF assessed in 50 patients by the proposed method and a semi-automatic one, routinely used, are presented. A good correlation between the two methods EF values is obtained (R = 0.93). The LV contour found has been judged very satisfactory by a team of trained clinicians. PMID:8626193

  4. [Drug with a high metabolic activity, cocarnit, in the treatment of diabetic cardiac autonomic neuropathy].

    PubMed

    Popov, S V; Melekhovets', O K; Demikhova, N V; Vynnychenko, L B

    2012-01-01

    Left ventricular diastolic dysfunction in patients with diabetes is formed in the absence of atherosclerotic changes as a consequence of diabetic cardiac autonomic neuropathy in the early stages of diabetes. Progression of autonomic cardiac neuropathy in cardio-vascular type is associated with the violation of energy supply of cells, protein synthesis, electrolyte exchange, the exchange of trace elements, oxidation reduction processes, oxygen-transport function of blood, so that metabolic therapy is carried out to optimize the processes of formation and energy costs. The drug cocarnit activates processes of aerobic oxidation of glucose, as well as providing regulatory influence on the oxidation of fatty acids. Applying of cocarnit in complex therapy in patients with diabetic cardiac autonomic neuropathy found improvement of left ventricular diastolic function, and positive dynamics in the efferent activity balance of the sympathetic and parasympathetic control of heart rate variability, which provides the regression of clinical symptoms. PMID:23356142

  5. Verification of cardiac mechanics software: benchmark problems and solutions for testing active and passive material behaviour

    PubMed Central

    Gurev, Viatcheslav; Arens, Sander; Augustin, Christoph M.; Baron, Lukas; Blake, Robert; Bradley, Chris; Castro, Sebastian; Crozier, Andrew; Favino, Marco; Fastl, Thomas E.; Fritz, Thomas; Gao, Hao; Gizzi, Alessio; Griffith, Boyce E.; Hurtado, Daniel E.; Krause, Rolf; Luo, Xiaoyu; Nash, Martyn P.; Pezzuto, Simone; Plank, Gernot; Rossi, Simone; Ruprecht, Daniel; Seemann, Gunnar; Smith, Nicolas P.; Sundnes, Joakim; Rice, J. Jeremy; Trayanova, Natalia; Wang, Dafang; Jenny Wang, Zhinuo; Niederer, Steven A.

    2015-01-01

    Models of cardiac mechanics are increasingly used to investigate cardiac physiology. These models are characterized by a high level of complexity, including the particular anisotropic material properties of biological tissue and the actively contracting material. A large number of independent simulation codes have been developed, but a consistent way of verifying the accuracy and replicability of simulations is lacking. To aid in the verification of current and future cardiac mechanics solvers, this study provides three benchmark problems for cardiac mechanics. These benchmark problems test the ability to accurately simulate pressure-type forces that depend on the deformed objects geometry, anisotropic and spatially varying material properties similar to those seen in the left ventricle and active contractile forces. The benchmark was solved by 11 different groups to generate consensus solutions, with typical differences in higher-resolution solutions at approximately 0.5%, and consistent results between linear, quadratic and cubic finite elements as well as different approaches to simulating incompressible materials. Online tools and solutions are made available to allow these tests to be effectively used in verification of future cardiac mechanics software. PMID:26807042

  6. Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture.

    PubMed

    Maruyama, Sonomi; Nakamura, Kazuto; Papanicolaou, Kyriakos N; Sano, Soichi; Shimizu, Ippei; Asaumi, Yasuhide; van den Hoff, Maurice J; Ouchi, Noriyuki; Recchia, Fabio A; Walsh, Kenneth

    2016-01-01

    Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area compared to cardiac myocytes. The conditional ablation of Fstl1 in S100a4-expressing fibroblast lineage cells (Fstl1-cfKO mice) led to a reduction in injury-induced Fstl1 expression and increased mortality due to cardiac rupture during the acute phase. Cardiac rupture was associated with a diminished number of myofibroblasts and decreased expression of extracellular matrix proteins. The infarcts of Fstl1-cfKO mice displayed weaker birefringence, indicative of thin and loosely packed collagen. Mechanistically, the migratory and proliferative capabilities of cardiac fibroblasts were attenuated by endogenous Fstl1 ablation. The activation of cardiac fibroblasts by Fstl1 was mediated by ERK1/2 but not Smad2/3 signaling. This study reveals that Fstl1 is essential for the acute repair of the infarcted myocardium and that stimulation of early fibroblast activation is a novel function of Fstl1. PMID:27234440

  7. The modulation of cardiac progenitor cell function by hydrogel-dependent Notch1activation

    PubMed Central

    Boopathy, Archana V.; Che, Pao Lin; Somasuntharam, Inthirai; Fiore, Vincent F.; Cabigas, E. Bernadette; Ban, Kiwon; Brown, Milton E.; Narui, Yoshie; Barker, Thomas H.; Yoon, Young-sup; Salaita, Khalid; García, Andrés J.; Davis, Michael E.

    2014-01-01

    Myocardial infarction is the leading cause of death worldwide and phase I clinical trials utilizing cardiac progenitor cells (CPCs) have shown promising outcomes. Notch1 signaling plays a critical role in cardiac development and in the survival, cardiogenic lineage commitment, and differentiation of cardiac stem/progenitor cells. In this study, we functionalized self-assembling peptide (SAP) hydrogels with a peptide mimic of the Notch1 ligand Jagged1 (RJ) to evaluate the therapeutic benefit of CPC delivery in the hydrogels in a rat model of myocardial infarction. The behavior of CPCs cultured in the 3D hydrogels in vitro including gene expression, proliferation, and growth factor production was evaluated. Interestingly, we observed Notch1 activation to be dependent on hydrogel polymer density/stiffness with synergistic increase in presence of RJ. Our results show that RJ mediated Notch1 activation depending on hydrogel concentration differentially regulated cardiogenic gene expression, proliferation, and growth factor production in CPCs in vitro. In rats subjected to experimental myocardial infarction, improvement in acute retention and cardiac function was observed following cell therapy in RJ hydrogels compared to unmodified or scrambled peptide containing hydrogels. This study demonstrates the potential therapeutic benefit of functionalizing SAP hydrogels with RJ for CPC based cardiac repair. PMID:24974008

  8. Detection of pulsus paradoxus by pulse oximetry in pediatric patients after cardiac surgery.

    PubMed

    Amoozgar, Hamid; Ghodsi, Hossein; Borzoee, Mohammad; Amirghofran, Ahmad Ali; Ajami, Gholamhossein; Serati, Zahra

    2009-01-01

    The presence or absence of pulsus paradoxus (PP), defined as an inspiratory decrease greater than 10 mmHg in systolic blood pressure, can have significant diagnostic and therapeutic implications for many clinical conditions including acute asthma, pericardial tamponade, heart failure, hypovolemia, shock states, and the like. However, PP may be difficult to measure in children. Indwelling arterial catheters facilitate the measurement of PP, but this invasive technique generally is reserved for critically ill patients. This study aimed to assess the use of the pulse oximetry plethysmographic waveform (POPW) for the detection of PP in pediatric patients after cardiac surgery. The study enrolled 40 pediatric patients 18 years of age and younger who had invasive blood pressure monitoring with an intraarterial cannula. Systolic pressure variability (SPV) and changes in POPW amplitude (DeltaPOPW%), calculated using five consecutive snapshots from every patient's monitor, were compared using linear regression, Pearson product-moment correlation, the Spearman rank method, and receiver operating characteristic (ROC) curve analysis. A strong correlation existed between respiratory SPV and DeltaPOPW% for the detection of PP (r = 0.682; p < 0.0001). A respiratory variation in DeltaPOPW% exceeding 25.44% (about one-fourth the amplitude of the tallest POP waveform) allowed detection of PP with a sensitivity of 86.7% and a specificity of 88%. Pulse oximetry is a readily available and easily performed noninvasive means for detecting PP in children. PMID:18665417

  9. Regular exercise improves cardiac contractile activation by modulating MHC isoforms and SERCA activity in orchidectomized rats.

    PubMed

    Vutthasathien, Pavarana; Wattanapermpool, Jonggonnee

    2015-10-01

    Data from the trial known as Testosterone in Older Men with Mobility Limitations (TOM) has indicated an association between testosterone administration and a greater risk for adverse cardiovascular events. We therefore propose that regular exercise is a cardioprotective alternative that prevents detrimental changes in contractile activation when a deficiency in male sex hormones exists. Ten-week-old orchidectomized (ORX) rats were subjected to a 9-wk treadmill running program at moderate intensity starting 1 wk after surgery. Although exercise-induced cardiac hypertrophy was observed both in rats that underwent ORX and sham surgery, regular exercise enhanced cardiac myofilament Ca(2+) sensitivity and myosin light-chain 2 phosphorylation only in rats that underwent a sham operation. Although the rats that had sham surgery and and given exercise exhibited no change in maximum developed tension, regular running prevented the suppression of maximum active tension in the hearts of ORX rats. Regular exercise also prevented a shift in myosin heavy chain (MHC) isoforms toward β-MHC, a reduction in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) activity, and an increase in SERCA sensitivity in the hearts of ORX rats. Neither SERCA content nor its modulating component, phospholamban (PLB), was altered by exercise in either sham-operated or ORX rats. However, decreases in the phosphorylated Thr(17) form of PLB and the phosphorylated Thr(287) form of Ca(2+)/calmodulin-dependent kinase II in the hearts of ORX rats were abolished after regular exercise. These results thus support the use of regular running as a cardioprotective alternative to testosterone replacement in hypogonadal conditions. PMID:26272317

  10. Cardiac screening of young athletes prior to participation in sports: difficulties in detecting the fatally flawed among the fabulously fit.

    PubMed

    Sharma, Sanjay; Merghani, Ahmed; Gati, Sabiha

    2015-01-01

    Deaths of young athletes from cardiac disease are uncommon but receive considerable media attention and intermittently galvanize debates about cardiac screening prior to participation in sports. Both the American Heart Association (AHA) and European Society of Cardiology (ESC) endorse preparticipation screening in athletes; however, there is disagreement about the best approach. The AHA recommends history and physical examination; this approach is pragmatic and relatively inexpensive but has poor sensitivity because most athletes are asymptomatic and physical examination identifies only a minority of those at risk of sudden cardiac death. The inclusion of the electrocardiogram in accordance with the recommendations of the ESC improves sensitivity for detection of serious cardiac disease but is associated with an unacceptably high false-positive rate, in part because of the overlap between the electrical manifestations of athletic training and the cardiomyopathies. For young athletes with normal electrocardiogram results, echocardiography contributes minimally to the diagnosis of serious cardiac diseases. Given all the complexities, cardiac screening of young athletes should be voluntary not mandatory and conducted by highly experienced physicians who fully understand the cardiovascular adaptation to intensive exercise. PMID:25384176

  11. Cardiac Patients’ Walking Activity Determined by a Step Counter in Cardiac Telerehabilitation: Data From the Intervention Arm of a Randomized Controlled Trial

    PubMed Central

    Hansen, John; Grønkjær, Mette; Andreasen, Jan Jesper; Nielsen, Gitte; Sørensen, Erik Elgaard; Dinesen, Birthe Irene

    2016-01-01

    Background Walking represents a large part of daily physical activity. It reduces both overall and cardiovascular diseases and mortality and is suitable for cardiac patients. A step counter measures walking activity and might be a motivational tool to increase and maintain physical activity. There is a lack of knowledge about both cardiac patients’ adherence to step counter use in a cardiac telerehabilitation program and how many steps cardiac patients walk up to 1 year after a cardiac event. Objective The purpose of this substudy was to explore cardiac patients’ walking activity. The walking activity was analyzed in relation to duration of pedometer use to determine correlations between walking activity, demographics, and medical and rehabilitation data. Methods A total of 64 patients from a randomized controlled telerehabilitation trial (Teledi@log) from Aalborg University Hospital and Hjoerring Hospital, Denmark, from December 2012 to March 2014 were included in this study. Inclusion criteria were patients hospitalized with acute coronary syndrome, heart failure, and coronary artery bypass grafting or valve surgery. In Teledi@log, the patients received telerehabilitation technology and selected one of three telerehabilitation settings: a call center, a community health care center, or a hospital. Monitoring of steps continued for 12 months and a step counter (Fitbit Zip) was used to monitor daily steps. Results Cardiac patients walked a mean 5899 (SD 3274) steps per day, increasing from mean 5191 (SD 3198) steps per day in the first week to mean 7890 (SD 2629) steps per day after 1 year. Adherence to step counter use lasted for a mean 160 (SD 100) days. The patients who walked significantly more were younger (P=.01) and continued to use the pedometer for a longer period (P=.04). Furthermore, less physically active patients weighed more. There were no significant differences in mean steps per day for patients in the three rehabilitation settings or in the

  12. Multichannel SQUID system detecting tangential components of the cardiac magnetic field

    NASA Astrophysics Data System (ADS)

    Tsukada, Keiji; Haruta, Yasuhiro; Adachi, Akira; Ogata, Hisanao; Komuro, Takanori; Ito, Tsuyoshi; Takada, Youichi; Kandori, Akihiko; Noda, Yasunaga; Terada, Yasushi; Mitsui, Toshio

    1995-10-01

    The 32-channel SQUID system described here is used for diagnosing heart disease by measuring the x and y components of the cardiac magnetic field. To detect a magnetic field parallel to the body surface, it uses a compact hybrid superconducting quantum interference device (SQUID) gradiometer consisting of a planar pickup coil (fabricated using thin-film techniques) and a square double-washer dc-SQUID having large voltage-flux transfer function. The SQUIDs are operated in a flux-locked mode using simple readout circuits connected directly to the preamplifier without additional positive feedback. The system is installed in a magnetically shielded room in a hospital. A low noise characteristics lower than 10 ft/√ Hz in a white noise is obtained in the hospital. Examples of tangential magnetocardiogram (MCG) measurements presented here show that the MCG obtained using this gradiometer makes it easy to visually estimate the electrophysiological behavior of the heart.

  13. Automatic cardiac arrhythmia detection and classification using vectorcardiograms and complex networks.

    PubMed

    Queiroz, Vinícius; Luz, Eduardo; Moreira, Gladston; Guarda, Álvaro; Menotti, David

    2015-01-01

    This paper intends to bring new insights in the methods for extracting features for cardiac arrhythmia detection and classification systems. We explore the possibility for utilizing vectorcardiograms (VCG) along with electrocardiograms (ECG) to get relevant informations from the heartbeats on the MIT-BIH database. For this purpose, we apply complex networks to extract features from the VCG. We follow the ANSI/AAMI EC57:1998 standard, for classifying the beats into 5 classes (N, V, S, F and Q), and de Chazal's scheme for dataset division into training and test set, with 22 folds validation setup for each set. We used the Support Vector Machinhe (SVM) classifier and the best result we chose had a global accuracy of 84.1%, while still obtaining relatively high Sensitivities and Positive Predictive Value and low False Positive Rates, when compared to other papers that follows the same evaluation methodology that we do. PMID:26737464

  14. Environmental Resources in Maintenance of Physical Activity 6 Months Following Cardiac Rehabilitation.

    PubMed

    Perez, Adriana; Fleury, Julie; Belyea, Michael

    2016-08-01

    This study examined differences in weekly time spent in physical activity by level of perceived environmental resources, 6 months following graduation from cardiac rehabilitation. A descriptive, longitudinal design used standardized measures to evaluate perceived environmental resources and physical activity levels. Repeated measures analysis of variance was used to examine mean differences in weekly time spent in physical activity by level of perceived environmental resources. Adults 51 to 86 years old (N = 150) diagnosed with coronary heart disease were included. There was a significant change over time in physical activity as measured by minutes per week, F(2, 148) = 7.915, p = .001, where activity increased between baseline and 3 months, and then dropped slightly at 6 months. This change over time differed by the level of perceived neighborhood resources, F(2, 148) = 3.545, p = .032. Home and neighborhood resources may positively influence physical activity maintenance following cardiac rehabilitation. PMID:26826141

  15. The influence of sleep onset on the diurnal variation in cardiac activity and cardiac control.

    PubMed

    Carrington, Melinda; Walsh, Michelle; Stambas, Thalia; Kleiman, Jan; Trinder, John

    2003-09-01

    Heart rate (HR), blood pressure (BP) and autonomic nervous system (ANS) activity vary diurnally, with a reduction in HR and BP, and a shift to vagal dominance during the dark phase. However, the cause of these changes, particularly the relative influence of sleep and circadian mechanisms, remains uncertain. The present study assessed the effect of sleep onset on HR, BP, high frequency (HF) component of heart rate variability (HRV), low frequency/high frequency (LF/HF) ratio and pre-ejection period (PEP). Sleep onset was dissociated from circadian influences by having subjects go to sleep at two different circadian phases, their normal time of sleep onset (normal sleep onset, NSO), and after a delay of 3 h (delayed sleep onset, DSO). The assumption was that changes caused by sleep onset would occur in association with sleep onset, irrespective of its timing, while circadian effects would have a consistent circadian phase and be independent of when sleep onset occurred. Thirteen and 17 subjects were run in the NSO and DSO conditions, respectively. Following a 1-h adaptation period, data collection began 2 h before subjects' normal time of sleep onset and continued until morning awakening. The lights were turned out after 2 h in the NSO condition and 5 h in the DSO condition. Subjects were required to maintain a supine position throughout the experimental sessions. The night-time decrease in HR was found to be due to both sleep onset and a circadian influence, with the circadian component being more prominent. In contrast, the fall in BP was largely due to a sleep onset effect. Increased vagal activity, as reflected in the HF component and a shift to vagal dominance in the LF/HF ratio, appeared to be primarily a function of the sleep system, while sympathetic activity, as assessed by PEP, reflected a circadian influence. PMID:12941060

  16. ALTERATION OF CARDIAC ELECTRICAL ACTIVITY BY WATER-LEACHABLE COMPONENTS OF RESIDUAL OIL FLY ASH (ROFA)

    EPA Science Inventory

    Alteration of cardiac electrical activity by water-leachable components
    of residual oil fly ash (ROFA)

    Desuo Wang, Yuh-Chin T. Huang*, An Xie, Ting Wang

    *Human Studies Division, NHEERL, US EPA
    104 Mason Farm Road, Chapel Hill, NC 27599
    Department of Basic ...

  17. Effects of active chronic cocaine use on cardiac sympathetic neuronal function assessed by carbon-11-hydroxyephedrine

    SciTech Connect

    Melon, P.G.; Boyd, C.J.; McVey, S. |

    1997-03-01

    Cardiac toxicity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by sympathetic nerve terminals of the heart. Carbon-11-hydroxyephedrine is a positron-emitting tracer that has been validated as a highly specific marker for norepinephrine transporter activity of the sympathetic nerve terminals and thus makes possible in vivo assessment of the effect of cocaine on norepinephrine reuptake and storage in the cardiac sympathetic nerve terminals. The aim of the study was to use the catecholamine analog {sup 11}C-hydroxyephedrine with PET to determine whether active chronic use of cocaine in women modifies the function of sympathetic nerve terminals of the heart. Six normal female volunteers and nine female active chronic cocaine users were studied. Cardiac regional {sup 11}C-hydroxyephedrine uptake and blood flow, as assessed with {sup 13}N-ammonia, were determined using semi-quantitative polar map analysis of myocardial tracer distribution. Carbon-11-hydroxyephedrine cardiac retention was quantified using dynamic data acquisition and kinetic analysis of blood and tissue activity. 27 refs., 4 figs., 3 tabs.

  18. Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial SIRT3

    PubMed Central

    Pillai, Vinodkumar B.; Samant, Sadhana; Sundaresan, Nagalingam R.; Raghuraman, Hariharasundaram; Kim, Gene; Bonner, Michael Y.; Arbiser, Jack L.; Walker, Douglas I.; Jones, Dean P.; Gius, David; Gupta, Mahesh P.

    2015-01-01

    Honokiol (HKL) is a natural biphenolic compound derived from the bark of magnolia trees with anti-inflammatory, anti-oxidative, anti-tumor and neuroprotective properties. Here we show that HKL blocks agonist-induced and pressure overload-mediated, cardiac hypertrophic responses, and ameliorates pre-existing cardiac hypertrophy, in mice. Our data suggest that the anti-hypertrophic effects of HKL depend on activation of the deacetylase SIRT3. We demonstrate that HKL is present in mitochondria, enhances SIRT3 expression nearly two-fold and suggest that HKL may bind to SIRT3 to further increase its activity. Increased SIRT3 activity is associated with reduced acetylation of mitochondrial SIRT3 substrates, MnSOD and OSCP. HKL-treatment increases mitochondrial rate of oxygen consumption and reduces ROS synthesis in wild-type, but not in SIRT3-KO cells. Moreover, HKL-treatment blocks cardiac fibroblast proliferation and differentiation to myofibroblasts in SIRT3-dependent manner. These results suggest that HKL is a pharmacological activator of SIRT3 capable of blocking, and even reversing, the cardiac hypertrophic response. PMID:25871545

  19. Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3.

    PubMed

    Pillai, Vinodkumar B; Samant, Sadhana; Sundaresan, Nagalingam R; Raghuraman, Hariharasundaram; Kim, Gene; Bonner, Michael Y; Arbiser, Jack L; Walker, Douglas I; Jones, Dean P; Gius, David; Gupta, Mahesh P

    2015-01-01

    Honokiol (HKL) is a natural biphenolic compound derived from the bark of magnolia trees with anti-inflammatory, anti-oxidative, anti-tumour and neuroprotective properties. Here we show that HKL blocks agonist-induced and pressure overload-mediated, cardiac hypertrophic responses, and ameliorates pre-existing cardiac hypertrophy, in mice. Our data suggest that the anti-hypertrophic effects of HKL depend on activation of the deacetylase Sirt3. We demonstrate that HKL is present in mitochondria, enhances Sirt3 expression nearly twofold and suggest that HKL may bind to Sirt3 to further increase its activity. Increased Sirt3 activity is associated with reduced acetylation of mitochondrial Sirt3 substrates, MnSOD and oligomycin-sensitivity conferring protein (OSCP). HKL-treatment increases mitochondrial rate of oxygen consumption and reduces ROS synthesis in wild type, but not in Sirt3-KO cells. Moreover, HKL-treatment blocks cardiac fibroblast proliferation and differentiation to myofibroblasts in a Sirt3-dependent manner. These results suggest that HKL is a pharmacological activator of Sirt3 capable of blocking, and even reversing, the cardiac hypertrophic response. PMID:25871545

  20. Activators of PPARgamma antagonize protection of cardiac myocytes by endothelin-1.

    PubMed

    Ehara, Natsuhiko; Hasegawa, Koji; Ono, Koh; Kawamura, Teruhisa; Iwai-Kanai, Eri; Morimoto, Tatsuya; Akao, Masaharu; Adachi, Souichi; Kita, Toru

    2004-08-20

    Endothelin-1 (ET-1) is a potent survival factor against myocardial cell apoptosis. This anti-apoptotic effect of ET-1 is mediated in part through calcineurin/NFATc-dependent induction of bcl-2 expression. Since it has been reported that peroxisome proliferator-activated receptor-gamma (PPARgamma) interacts with NFATc, we investigated the effects of PPARgamma ligands on anti-apoptotic effects of ET-1 in cardiac myocytes. In primary cardiac myocytes from neonatal rats, administration of PPARgamma activators (15-deoxy-delta12,14-prostaglandin J2 and troglitazone) attenuated the anti-apoptotic effects of ET-1. These activators abolished the ET-1-stimulated increase in bcl-2 expression and in binding of cardiac NFATc to the bcl-2 NFAT site. These findings demonstrate that activators of PPARgamma perturb the anti-apoptotic effects of ET-1 in cardiac myocytes and that this perturbation is, in part, based on functional transcriptional cross-talk between NFATc and PPARgamma. PMID:15358182

  1. Vortex shedding as a precursor of turbulent electrical activity in cardiac muscle.

    PubMed Central

    Cabo, C; Pertsov, A M; Davidenko, J M; Baxter, W T; Gray, R A; Jalife, J

    1996-01-01

    In cardiac tissue, during partial blockade of the membrane sodium channels, or at high frequencies of excitation, inexcitable obstacles with sharp edges may destabilize the propagation of electrical excitation waves, causing the formation of self-sustained vortices and turbulent cardiac electrical activity. The formation of such vortices, which visually resembles vortex shedding in hydrodynamic turbulent flows, was observed in sheep epicardial tissue using voltage-sensitive dyes in combination with video-imaging techniques. Vortex shedding is a potential mechanism leading to the spontaneous initiation of uncontrolled high-frequency excitation of the heart. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 7 PMID:8785270

  2. Cardiac activity in marine invertebrates in response to pollutants: Automated interpulse duration assessment

    SciTech Connect

    Lundebye, A.K.; Curtis, T.; Depledge, M.H.

    1995-12-31

    The updated method of the Computer-Aided Physiological Monitoring (CAPMON) system was used to study the effects of copper exposure on cardiac activity in the shore crab (Carcinus maenas) and the common mussel (Mytilus edulis). This new Automated Interpulse Duration Assessment (AIDA) system measures the time interval between heart beats, and was found to be a more sensitive tool for evaluating cardiac responses to pollutant exposure than other techniques. In addition to information regarding heart rate, also obtained by the CAPMON system (as beats per minute), the new system enables frequency distribution analysis of interpulse duration. An experiment involving C. maenas examined the effects of short term (24 h) and chronic exposure (4 weeks) to copper concentrations 0, 0.2, 0.4, 0.6 and 0.8 mgl{sup {minus}1} Cu. Subsequent recovery (6 weeks) of cardiac activity was also examined. In a second experiment mussels were exposed to one of five copper concentrations (in the range of 0--0.1 mgl{sup {minus}1} Cu) and `normal` cardiac activity was compared with activity after copper exposure. A dose-response relationship was established between copper concentration and heart rate in crabs. The control group had the longest mean inter-pulse duration, and mean interpulse duration decreased in a concentration-dependent manner for the copper treatments, reflecting an increase in heart rate. Distribution of interpulse duration changed from a variable, rather wide distribution in control crabs, to a sharp-peaked normal distribution in exposed crabs. Results after 4 weeks exposure were not significantly different from those found after 24 h. Return to normal cardiac activity was evident after a 6 week `recovery` period. Results from the mussel experiment showed burst activity followed by a decline in heart rate in response to copper exposure.

  3. Silicon nanowire biosensors for detection of cardiac troponin I (cTnI) with high sensitivity.

    PubMed

    Kim, Kihyun; Park, Chanoh; Kwon, Donghoon; Kim, Donghoon; Meyyappan, M; Jeon, Sangmin; Lee, Jeong-Soo

    2016-03-15

    We have demonstrated highly sensitive and label-free detection of cardiac troponin I (cTnI), a biomarker for diagnosis of acute myocardial infarction, using silicon nanowire field-effect transistors. A honeycomb-like structure is utilized for nanowire configuration to offer improved electrical performance and increased sensing area. The fabricated devices show n-type behavior with a relatively high ON-OFF current ratio, small sub-threshold swing and low gate leakage current. Monoclonal antibodies for cTnI were covalently immobilized on the nanowire surface and the attachment of antibodies is clearly visualized by atomic force microscope. The sensitivity with various concentrations of buffer solution was also investigated in order to determine the optimal buffer condition. The devices exhibit highest sensitivity under buffer solutions with low ion concentration. In addition, the detection limit of the sensor is as low as ~5 pg/mL, the lowest reported in the literature to date and nearly an order of magnitude smaller than the suggested threshold limit. The fabricated devices demonstrate a good selectivity for detecting cTnI. PMID:26496224

  4. Real-time detection of transient cardiac ischemic episodes from ECG signals.

    PubMed

    Dranca, L; Goñi, A; Illarramendi, A

    2009-09-01

    We propose a new algorithm to detect and classify transient cardiac ischemia episodes, designed with the goal of providing a real-time execution without penalizing the classifier accuracy much. The algorithm is based on a novel mixture of time-domain analysis and machine learning techniques, specifically bagging of decision trees, and it has been developed using a well-recognized and freely distributed database, namely the long-term ST database. The ST episode detection sensitivity/positive predictivity using the annotation protocol A for this database is 68.26%/74.91%. The sensitivity result increases until 93.97% for the most dangerous episodes in terms of duration and magnitude (annotated according to protocol C). The test of the algorithm over the freely distributed part of the European Society of Cardiology database has shown results of sensitivity and positive predictivity of 83.33% and 77.31%, respectively. Those results are close to the results obtained by related works that present approaches to detect ischemia episodes off-line, which is remarkable if we take into account that in our real-time approach, less information is available during the classification process. PMID:19696464

  5. In-Hospital Cardiac Arrest: An Update on Pulseless Electrical Activity and Asystole.

    PubMed

    Attin, Mina; Tucker, Rebecca G; Carey, Mary G

    2016-09-01

    Nonshockable rhythms, including pulseless electrical activity (PEA) and asystole, precede more than 70% of in-hospital cardiac arrests (I-HCA). Compared with shockable rhythms (ventricular fibrillation and ventricular tachycardia), nonshockable rhythms have higher mortality and morbidity. Therefore, investigating the underlying mechanisms of these arrhythmias to improve the quality of care and outcome for patients who suffer cardiac arrest is a priority. As the first responders to I-HCA, nurses must have the proper knowledge and training to provide timely and efficient cardiopulmonary resuscitation therapy. This article provides an overview of nonshockable cardiac arrhythmias preceding I-HCA as a means of addressing the gap between science and clinical practice. PMID:27484665

  6. Erbb2 Is Required for Cardiac Atrial Electrical Activity during Development

    PubMed Central

    Tenin, Gennadiy; Clowes, Christopher; Wolton, Kathryn; Krejci, Eliska; Wright, Jayne A.; Lovell, Simon C.; Sedmera, David; Hentges, Kathryn E.

    2014-01-01

    The heart is the first organ required to function during embryonic development and is absolutely necessary for embryo survival. Cardiac activity is dependent on both the sinoatrial node (SAN), which is the pacemaker of heart's electrical activity, and the cardiac conduction system which transduces the electrical signal though the heart tissue, leading to heart muscle contractions. Defects in the development of cardiac electrical function may lead to severe heart disorders. The Erbb2 (Epidermal Growth Factor Receptor 2) gene encodes a member of the EGF receptor family of receptor tyrosine kinases. The Erbb2 receptor lacks ligand-binding activity but forms heterodimers with other EGF receptors, stabilising their ligand binding and enhancing kinase-mediated activation of downstream signalling pathways. Erbb2 is absolutely necessary in normal embryonic development and homozygous mouse knock-out Erbb2 embryos die at embryonic day (E)10.5 due to severe cardiac defects. We have isolated a mouse line, l11Jus8, from a random chemical mutagenesis screen, which carries a hypomorphic missense mutation in the Erbb2 gene. Homozygous mutant embryos exhibit embryonic lethality by E12.5-13. The l11Jus8 mutants display cardiac haemorrhage and a failure of atrial function due to defects in atrial electrical signal propagation, leading to an atrial-specific conduction block, which does not affect ventricular conduction. The l11Jus8 mutant phenotype is distinct from those reported for Erbb2 knockout mouse mutants. Thus, the l11Jus8 mouse reveals a novel function of Erbb2 during atrial conduction system development, which when disrupted causes death at mid-gestation. PMID:25269082

  7. Preventive health care, 1999 update: 2. Echocardiography for the detection of a cardiac source of embolus in patients with stroke

    PubMed Central

    Kapral, M K; Silver, F L

    1999-01-01

    OBJECTIVE: To develop guidelines for the use of echocardiography in the investigation of patients with stroke. OPTIONS: (1) Routine transthoracic echocardiography (TTE); (2) routine transesophageal echocardiography (TEE); (3) routine TTE followed by TEE if the TTE findings are noncontributory; (4) selective TTE or TEE in patients with cardiac disease who would not otherwise receive anticoagulant therapy. OUTCOMES: This article reviews the available evidence on the yield of TTE and TEE in detecting cardiac sources of cerebral emboli in patients with stroke, the effectiveness of treatment for cardiac sources of emboli and the effectiveness of screening echocardiography for secondary stroke prevention. EVIDENCE: MEDLINE was searched for relevant articles published from January 1966 to April 1998; also reviewed were additional articles identified from the bibliographies and citations obtained from experts. BENEFITS, HARMS AND COSTS: Echocardiography can detect intracardiac masses (thrombus, vegetation or tumour) in about 4% (with TTE) to 11% (with TEE) of stroke patients. The yield is lower among patients without clinical evidence of cardiac disease by history, physical examination, electrocardiography or chest radiography (less than 2%) than among patients with clinical evidence of cardiac disease (less than 19%). The risks of echocardiography to patients are small. TTE has virtually no risks, and TEE is associated with cardiac, pulmonary and bleeding complications in 0.18%. Patients with an identified intracardiac thrombus are at increased risk for embolic events (absolute risk uncertain, range 0%-38%), and this appears to be reduced with anticoagulant therapy (absolute risk reduction uncertain). Anticoagulant therapy carries a risk of major hemorrhage of 1% to 3% per year. The overall effectiveness of echocardiography in the prevention of recurrent stroke is unknown. VALUES: The strength of evidence was evaluated using the methods of the Canadian Task Force on

  8. Tai Chi as an adjunct physical activity for adults aged 45 years and older enrolled in phase III cardiac rehabilitation

    PubMed Central

    Taylor-Piliae, Ruth E; Silva, Edna; Sheremeta, Sharon Peachey

    2015-01-01

    Background Cardiac rehabilitation improves physical, cognitive and psychosocial functioning, yet services are greatly underutilized with increasing patterns of attrition over time. Tai Chi has been suggested as a possible adjunct to cardiac rehabilitation exercise training. Aim To describe differences in physical, cognitive and psychosocial functioning among adults ≥ 45 years old attending phase III cardiac rehabilitation, who have or have not self-selected Tai Chi exercise as an adjunct physical activity. Methods A cross-sectional design compared subjects attending group-based Wu style Tai Chi classes plus cardiac rehabilitation, with cardiac rehabilitation only. Subjects had a battery of physical and cognitive functioning tests administered to examine aerobic endurance, balance, strength, and flexibility, verbal retrieval/recall, attention, concentration and tracking. Subjects completed a health survey to ascertain cardiac event information, medical history, and psychosocial functioning (i.e. health-related quality of life, stress, depressive symptoms, social support, and Tai Chi self-efficacy). Results A total of 51 subjects (75% married, 84% college-educated, 96% White/European-American) participated. Subjects were on average 70 (± 8) years old and had attended cardiac rehabilitation for 45 (± 37) months. Approximately 45% (n = 23) attended Tai Chi classes plus cardiac rehabilitation, while 55% (n = 28) attended cardiac rehabilitation only. Subjects attending Tai Chi plus cardiac rehabilitation had better balance, perceived physical health, and Tai Chi self-efficacy compared to those attending cardiac rehabilitation only (p ≤ 0.03). Conclusion Tai Chi can be easily implemented in any community/cardiac rehabilitation facility, and may offer adults additional options after a cardiac event. PMID:21095159

  9. Channelized relevance vector machine as a numerical observer for cardiac perfusion defect detection task

    NASA Astrophysics Data System (ADS)

    Kalayeh, Mahdi M.; Marin, Thibault; Pretorius, P. Hendrik; Wernick, Miles N.; Yang, Yongyi; Brankov, Jovan G.

    2011-03-01

    In this paper, we present a numerical observer for image quality assessment, aiming to predict human observer accuracy in a cardiac perfusion defect detection task for single-photon emission computed tomography (SPECT). In medical imaging, image quality should be assessed by evaluating the human observer accuracy for a specific diagnostic task. This approach is known as task-based assessment. Such evaluations are important for optimizing and testing imaging devices and algorithms. Unfortunately, human observer studies with expert readers are costly and time-demanding. To address this problem, numerical observers have been developed as a surrogate for human readers to predict human diagnostic performance. The channelized Hotelling observer (CHO) with internal noise model has been found to predict human performance well in some situations, but does not always generalize well to unseen data. We have argued in the past that finding a model to predict human observers could be viewed as a machine learning problem. Following this approach, in this paper we propose a channelized relevance vector machine (CRVM) to predict human diagnostic scores in a detection task. We have previously used channelized support vector machines (CSVM) to predict human scores and have shown that this approach offers better and more robust predictions than the classical CHO method. The comparison of the proposed CRVM with our previously introduced CSVM method suggests that CRVM can achieve similar generalization accuracy, while dramatically reducing model complexity and computation time.

  10. Peptide Functionalized Gold Nanorods for the Sensitive Detection of a Cardiac Biomarker Using Plasmonic Paper Devices

    PubMed Central

    Tadepalli, Sirimuvva; Kuang, Zhifeng; Jiang, Qisheng; Liu, Keng-Ku; Fisher, Marilee A.; Morrissey, Jeremiah J.; Kharasch, Evan D.; Slocik, Joseph M.; Naik, Rajesh R.; Singamaneni, Srikanth

    2015-01-01

    The sensitivity of localized surface plasmon resonance (LSPR) of metal nanostructures to adsorbates lends itself to a powerful class of label-free biosensors. Optical properties of plasmonic nanostructures are dependent on the geometrical features and the local dielectric environment. The exponential decay of the sensitivity from the surface of the plasmonic nanotransducer calls for the careful consideration in its design with particular attention to the size of the recognition and analyte layers. In this study, we demonstrate that short peptides as biorecognition elements (BRE) compared to larger antibodies as target capture agents offer several advantages. Using a bioplasmonic paper device (BPD), we demonstrate the selective and sensitive detection of the cardiac biomarker troponin I (cTnI). The smaller sized peptide provides higher sensitivity and a lower detection limit using a BPD. Furthermore, the excellent shelf-life and thermal stability of peptide-based LSPR sensors, which precludes the need for special storage conditions, makes it ideal for use in resource-limited settings. PMID:26552720

  11. Peptide Functionalized Gold Nanorods for the Sensitive Detection of a Cardiac Biomarker Using Plasmonic Paper Devices

    NASA Astrophysics Data System (ADS)

    Tadepalli, Sirimuvva; Kuang, Zhifeng; Jiang, Qisheng; Liu, Keng-Ku; Fisher, Marilee A.; Morrissey, Jeremiah J.; Kharasch, Evan D.; Slocik, Joseph M.; Naik, Rajesh R.; Singamaneni, Srikanth

    2015-11-01

    The sensitivity of localized surface plasmon resonance (LSPR) of metal nanostructures to adsorbates lends itself to a powerful class of label-free biosensors. Optical properties of plasmonic nanostructures are dependent on the geometrical features and the local dielectric environment. The exponential decay of the sensitivity from the surface of the plasmonic nanotransducer calls for the careful consideration in its design with particular attention to the size of the recognition and analyte layers. In this study, we demonstrate that short peptides as biorecognition elements (BRE) compared to larger antibodies as target capture agents offer several advantages. Using a bioplasmonic paper device (BPD), we demonstrate the selective and sensitive detection of the cardiac biomarker troponin I (cTnI). The smaller sized peptide provides higher sensitivity and a lower detection limit using a BPD. Furthermore, the excellent shelf-life and thermal stability of peptide-based LSPR sensors, which precludes the need for special storage conditions, makes it ideal for use in resource-limited settings.

  12. Rapidly detecting disorder in rhythmic biological signals: A spectral entropy measure to identify cardiac arrhythmias

    NASA Astrophysics Data System (ADS)

    Staniczenko, Phillip P. A.; Lee, Chiu Fan; Jones, Nick S.

    2009-01-01

    We consider the use of a running measure of power spectrum disorder to distinguish between the normal sinus rhythm of the heart and two forms of cardiac arrhythmia: atrial fibrillation and atrial flutter. This spectral entropy measure is motivated by characteristic differences in the power spectra of beat timings during the three rhythms. We plot patient data derived from ten-beat windows on a “disorder map” and identify rhythm-defining ranges in the level and variance of spectral entropy values. Employing the spectral entropy within an automatic arrhythmia detection algorithm enables the classification of periods of atrial fibrillation from the time series of patients’ beats. When the algorithm is set to identify abnormal rhythms within 6s , it agrees with 85.7% of the annotations of professional rhythm assessors; for a response time of 30s , this becomes 89.5%, and with 60s , it is 90.3%. The algorithm provides a rapid way to detect atrial fibrillation, demonstrating usable response times as low as 6s . Measures of disorder in the frequency domain have practical significance in a range of biological signals: the techniques described in this paper have potential application for the rapid identification of disorder in other rhythmic signals.

  13. Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

    PubMed Central

    Weisbrod, David; Khun, Shiraz Haron; Bueno, Hanna; Peretz, Asher; Attali, Bernard

    2016-01-01

    The proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. The sinoatrial node (SAN) in human right atrium generates an electrical stimulation approximately 70 times per minute, which propagates from a conductive network to the myocardium leading to chamber contractions during the systoles. Although the SAN and other nodal conductive structures were identified more than a century ago, the mechanisms involved in the generation of cardiac automaticity remain highly debated. In this short review, we survey the current data related to the development of the human cardiac conduction system and the various mechanisms that have been proposed to underlie the pacemaker activity. We also present the human embryonic stem cell-derived cardiomyocyte system, which is used as a model for studying the pacemaker. Finally, we describe our latest characterization of the previously unrecognized role of the SK4 Ca2+-activated K+ channel conductance in pacemaker cells. By exquisitely balancing the inward currents during the diastolic depolarization, the SK4 channels appear to play a crucial role in human cardiac automaticity. PMID:26725737

  14. Using Visual Methods to Understand Physical Activity Maintenance following Cardiac Rehabilitation.

    PubMed

    Hardcastle, Sarah J; McNamara, Keira; Tritton, Larette

    2015-01-01

    Few studies have explored the factors associated with long-term maintenance of exercise following cardiac rehabilitation. The present study used auto-photography and interviews to explore the factors that influence motivation and continued participation in physical activity among post cardiac rehabilitation patients. Twenty-three semi-structured interviews were conducted alongside participant-selected photographs or drawings with participants that had continued participation in physical activity for at least two years following the cardiac rehabilitation programme. Participants were recruited from circuit training classes in East Sussex in the UK. Thematic content analysis revealed seven main themes: fear of death and ill health avoidance, critical incidents, overcoming aging, social influences, being able to enjoy life, provision of routine and structure, enjoyment and psychological well-being. Fear of death, illness avoidance, overcoming aging, and being able to enjoy life were powerful motives for continued participation in exercise. The social nature of the exercise class was also identified as a key facilitator of continued participation. Group-based exercise suited those that continued exercise participation post cardiac rehabilitation and fostered adherence. PMID:26381147

  15. Using Visual Methods to Understand Physical Activity Maintenance following Cardiac Rehabilitation

    PubMed Central

    Hardcastle, Sarah J.

    2015-01-01

    Few studies have explored the factors associated with long-term maintenance of exercise following cardiac rehabilitation. The present study used auto-photography and interviews to explore the factors that influence motivation and continued participation in physical activity among post cardiac rehabilitation patients. Twenty-three semi-structured interviews were conducted alongside participant-selected photographs or drawings with participants that had continued participation in physical activity for at least two years following the cardiac rehabilitation programme. Participants were recruited from circuit training classes in East Sussex in the UK. Thematic content analysis revealed seven main themes: fear of death and ill health avoidance, critical incidents, overcoming aging, social influences, being able to enjoy life, provision of routine and structure, enjoyment and psychological well-being. Fear of death, illness avoidance, overcoming aging, and being able to enjoy life were powerful motives for continued participation in exercise. The social nature of the exercise class was also identified as a key facilitator of continued participation. Group-based exercise suited those that continued exercise participation post cardiac rehabilitation and fostered adherence. PMID:26381147

  16. Activation of GATA4 gene expression at the early stage of cardiac specification

    NASA Astrophysics Data System (ADS)

    Yilbas, Ayse; Hamilton, Alison; Wang, Yingjian; Mach, Hymn; Lacroix, Natascha; Davis, Darryl; Chen, Jihong; LI, Qiao

    2014-03-01

    Currently, there are no effective treatments to directly repair damaged heart tissue after cardiac injury since existing therapies focus on rescuing or preserving reversibly damaged tissue. Cell-based therapies using cardiomyocytes generated from stem cells present a promising therapeutic approach to directly replace damaged myocardium with new healthy tissue. However, the molecular mechanisms underlying the commitment of stem cells into cardiomyocytes are not fully understood and will be critical to guide this new technology into the clinic. Since GATA4 is a critical regulator of cardiac differentiation, we examined the molecular basis underlying the early activation of GATA4 gene expression during cardiac differentiation of pluripotent stem cells. Our studies demonstrate the direct involvement of histone acetylation and transcriptional coactivator p300 in the regulation of GATA4 gene expression. More importantly, we show that histone acetyltransferase (HAT) activity is important for GATA4 gene expression with the use of curcumin, a HAT inhibitor. In addition, the widely used histone deacetylase inhibitor valproic acid enhances both histone acetylation and cardiac specification.

  17. P-selectin increases angiotensin II-induced cardiac inflammation and fibrosis via platelet activation

    PubMed Central

    LIU, GAIZHEN; LIANG, BIN; SONG, XIAOSU; BAI, RUI; QIN, WEIWEI; SUN, XU; LU, YAN; BIAN, YUNFEI; XIAO, CHUANSHI

    2016-01-01

    Platelet activation is important in hypertension-induced cardiac inflammation and fibrosis. P-selectin expression significantly (P<0.05) increases when platelets are activated during hypertension. Although P-selectin recruits leukocytes to sites of inflammation, the role of P-selectin in cardiac inflammation and fibrosis remains to be elucidated. The present study aimed to investigate whether platelet-derived P-selectin promotes hypertensive cardiac inflammation and fibrosis. P-selectin knockout (P-sel KO) mice and wild-type (WT) C57BL/6 littermates were infused with angiotensin II (Ang II) at 1,500 ng/kg/min for 7 days and then cross-transplanted with platelets originating from either WT or P-sel KO mice. P-selectin expression was increased in the myocardium and plasma of hypertensive mice, and the P-sel KO mice exhibited significantly (P<0.05) reduced cardiac fibrosis. The fibrotic areas were markedly smaller in the hearts of P-sel KO mice compared with WT mice, as assessed by Masson's trichrome staining. In addition, α-smooth muscle actin and transforming growth factor β1 (TGF-β1) expression levels were decreased in the P-sel KO mice, as assessed by immunohistochemistry. Following platelet transplantation into P-sel KO mice, the number of Mac-2 (galectin-3)- and TGF-β1-positive cells was increased in mice that received WT platelets compared with those that received P-sel KO platelets, and the mRNA expression levels of collagen I and TGF-β1 were also increased. The results from the present study suggest that activated platelets secrete P-selectin to promote cardiac inflammation and fibrosis in Ang II-induced hypertension. PMID:27121797

  18. P‑selectin increases angiotensin II‑induced cardiac inflammation and fibrosis via platelet activation.

    PubMed

    Liu, Gaizhen; Liang, Bin; Song, Xiaosu; Bai, Rui; Qin, Weiwei; Sun, Xu; Lu, Yan; Bian, Yunfei; Xiao, Chuanshi

    2016-06-01

    Platelet activation is important in hypertension‑induced cardiac inflammation and fibrosis. P-selectin expression significantly (P<0.05) increases when platelets are activated during hypertension. Although P‑selectin recruits leukocytes to sites of inflammation, the role of P‑selectin in cardiac inflammation and fibrosis remains to be elucidated. The present study aimed to investigate whether platelet‑derived P‑selectin promotes hypertensive cardiac inflammation and fibrosis. P‑selectin knockout (P‑sel KO) mice and wild‑type (WT) C57BL/6 littermates were infused with angiotensin II (Ang II) at 1,500 ng/kg/min for 7 days and then cross‑transplanted with platelets originating from either WT or P‑sel KO mice. P‑selectin expression was increased in the myocardium and plasma of hypertensive mice, and the P‑sel KO mice exhibited significantly (P<0.05) reduced cardiac fibrosis. The fibrotic areas were markedly smaller in the hearts of P‑sel KO mice compared with WT mice, as assessed by Masson's trichrome staining. In addition, α‑smooth muscle actin and transforming growth factor β1 (TGF‑β1) expression levels were decreased in the P‑sel KO mice, as assessed by immunohistochemistry. Following platelet transplantation into P‑sel KO mice, the number of Mac‑2 (galectin‑3)‑ and TGF‑β1‑positive cells was increased in mice that received WT platelets compared with those that received P‑sel KO platelets, and the mRNA expression levels of collagen I and TGF‑β1 were also increased. The results from the present study suggest that activated platelets secrete P‑selectin to promote cardiac inflammation and fibrosis in Ang II‑induced hypertension. PMID:27121797

  19. How are arrhythmias detected by implanted cardiac devices managed in Europe? Results of the European Heart Rhythm Association Survey.

    PubMed

    Todd, Derick; Hernandez-Madrid, Antonio; Proclemer, Alessandro; Bongiorni, Maria Grazia; Estner, Heidi; Blomström-Lundqvist, Carina

    2015-09-01

    The management of arrhythmias detected by implantable cardiac devices can be challenging. There are no formal international guidelines to inform decision-making. The purpose of this European Heart Rhythm Association (EHRA) survey was to assess the management of various clinical scenarios among members of the EHRA electrophysiology research network. There were 49 responses to the questionnaire. The survey responses were mainly (81%) from medium-high volume device implanting centres, performing more than 200 total device implants per year. Clinical scenarios were described focusing on four key areas: the implantation of pacemakers for bradyarrhythmia detected on an implantable loop recorder (ILR), the management of patients with ventricular arrhythmia detected by an ILR or pacemaker, the management of atrial fibrillation in patients with pacemakers and cardiac resynchronization therapy devices and the management of ventricular tachycardia in patients with implantable cardioverter-defibrillators. PMID:26443791

  20. Techniques for automated local activation time annotation and conduction velocity estimation in cardiac mapping

    PubMed Central

    Cantwell, C.D.; Roney, C.H.; Ng, F.S.; Siggers, J.H.; Sherwin, S.J.; Peters, N.S.

    2015-01-01

    Measurements of cardiac conduction velocity provide valuable functional and structural insight into the initiation and perpetuation of cardiac arrhythmias, in both a clinical and laboratory context. The interpretation of activation wavefronts and their propagation can identify mechanistic properties of a broad range of electrophysiological pathologies. However, the sparsity, distribution and uncertainty of recorded data make accurate conduction velocity calculation difficult. A wide range of mathematical approaches have been proposed for addressing this challenge, often targeted towards specific data modalities, species or recording environments. Many of these algorithms require identification of activation times from electrogram recordings which themselves may have complex morphology or low signal-to-noise ratio. This paper surveys algorithms designed for identifying local activation times and computing conduction direction and speed. Their suitability for use in different recording contexts and applications is assessed. PMID:25978869

  1. Techniques for automated local activation time annotation and conduction velocity estimation in cardiac mapping.

    PubMed

    Cantwell, C D; Roney, C H; Ng, F S; Siggers, J H; Sherwin, S J; Peters, N S

    2015-10-01

    Measurements of cardiac conduction velocity provide valuable functional and structural insight into the initiation and perpetuation of cardiac arrhythmias, in both a clinical and laboratory context. The interpretation of activation wavefronts and their propagation can identify mechanistic properties of a broad range of electrophysiological pathologies. However, the sparsity, distribution and uncertainty of recorded data make accurate conduction velocity calculation difficult. A wide range of mathematical approaches have been proposed for addressing this challenge, often targeted towards specific data modalities, species or recording environments. Many of these algorithms require identification of activation times from electrogram recordings which themselves may have complex morphology or low signal-to-noise ratio. This paper surveys algorithms designed for identifying local activation times and computing conduction direction and speed. Their suitability for use in different recording contexts and applications is assessed. PMID:25978869

  2. Hypoxia-activated apoptosis of cardiac myocytes requires reoxygenation or a pH shift and is independent of p53

    PubMed Central

    Bishopric, Nanette H.; Discher, Daryl J.; Kaiser, Shari; Hernandez, Olga; Sato, Barbara; Zang, Jie; Webster, Keith A.

    1999-01-01

    Ischemia and reperfusion activate cardiac myocyte apoptosis, which may be an important feature in the progression of ischemic heart disease. The relative contributions of ischemia and reperfusion to apoptotic signal transduction have not been established. We report here that severe chronic hypoxia alone does not cause apoptosis of cardiac myocytes in culture. When rapidly contracting cardiac myocytes were exposed to chronic hypoxia, apoptosis occurred only when there was a decrease in extracellular pH ([pH]o). Apoptosis did not occur when [pH]o was neutralized. Addition of acidic medium from hypoxic cultures or exogenous lactic acid stimulated apoptosis in aerobic myocytes. Hypoxia-acidosis–mediated cell death was independent of p53: equivalent apoptosis occurred in cardiac myocytes isolated from wild-type and p53 knockout mice, and hypoxia caused no detectable change in p53 abundance or p53-dependent transcription. Reoxygenation of hypoxic cardiac myocytes induced apoptosis in 25–30% of the cells and was also independent of p53 by the same criteria. Finally, equivalent levels of apoptosis, as demonstrated by DNA fragmentation, were induced by ischemia-reperfusion, but not by ischemia alone, of Langendorff-perfused hearts from wild-type and p53 knockout mice. We conclude that acidosis, reoxygenation, and reperfusion, but not hypoxia (or ischemia) alone, are strong stimuli for programmed cell death that is substantially independent of p53. J. Clin. Invest. 104:239–252 (1999). PMID:10430605

  3. Ca2+-calcineurin signaling is involved in norepinephrine-induced cardiac fibroblasts activation

    PubMed Central

    Tian, Chun-Jing; Pang, Xiao

    2015-01-01

    Cardiac fibroblasts (CFs) activation plays a vital role in cardiac fibrosis. There are some studies demonstrate that norepinephrine (NE, an α1-adrenoceptor agonist) induced CFs proliferation. But whether Ca2+-calcineurin, a signaling concerned with growth and differentiation in various cell types, is participated in NE-induced CFs activation is unclear. In present study, we determined NE-induced CFs proliferation and differentiation, synthesis of collagen, and calcineurin (CaN) activity, and the effects of phentolamine (Phen, an α1-adrenoceptor antagonist), verapamil (Ver, a calcium channel blocker) and cyclosporine A (CsA, an inhibitor of CaN) on NE-induced CFs activation. The results showed that NE induced CFs proliferation and differentiation, increased α-SMA protein expression, increased collagen I, collagen III and fibronectin production, promoted ECM expression, activated CaN and increased CaN protein expression, which were inhibited by Phen, Ver and CsA. In vivo, more collagen deposition could be observed and total collagen volume fraction (CVF) was significantly increased in NE group. Phen, Ver and CsA decreased NE-induced collagen deposition, reduced cardiac fibrosis. Thus, our results demonstrate that Ca2+/CaN is involved in NE-induced CFs proliferation and collagen synthesis. PMID:26191219

  4. Cardiac myosin light chain is phosphorylated by Ca2+/calmodulin-dependent and -independent kinase activities.

    PubMed

    Chang, Audrey N; Mahajan, Pravin; Knapp, Stefan; Barton, Hannah; Sweeney, H Lee; Kamm, Kristine E; Stull, James T

    2016-07-01

    The well-known, muscle-specific smooth muscle myosin light chain kinase (MLCK) (smMLCK) and skeletal muscle MLCK (skMLCK) are dedicated protein kinases regulated by an autoregulatory segment C terminus of the catalytic core that blocks myosin regulatory light chain (RLC) binding and phosphorylation in the absence of Ca(2+)/calmodulin (CaM). Although it is known that a more recently discovered cardiac MLCK (cMLCK) is necessary for normal RLC phosphorylation in vivo and physiological cardiac performance, information on cMLCK biochemical properties are limited. We find that a fourth uncharacterized MLCK, MLCK4, is also expressed in cardiac muscle with high catalytic domain sequence similarity with other MLCKs but lacking an autoinhibitory segment. Its crystal structure shows the catalytic domain in its active conformation with a short C-terminal "pseudoregulatory helix" that cannot inhibit catalysis as a result of missing linker regions. MLCK4 has only Ca(2+)/CaM-independent activity with comparable Vmax and Km values for different RLCs. In contrast, the Vmax value of cMLCK is orders of magnitude lower than those of the other three MLCK family members, whereas its Km (RLC and ATP) and KCaM values are similar. In contrast to smMLCK and skMLCK, which lack activity in the absence of Ca(2+)/CaM, cMLCK has constitutive activity that is stimulated by Ca(2+)/CaM. Potential contributions of autoregulatory segment to cMLCK activity were analyzed with chimeras of skMLCK and cMLCK. The constitutive, low activity of cMLCK appears to be intrinsic to its catalytic core structure rather than an autoinhibitory segment. Thus, RLC phosphorylation in cardiac muscle may be regulated by two different protein kinases with distinct biochemical regulatory properties. PMID:27325775

  5. Dictionary-Driven Ischemia Detection From Cardiac Phase-Resolved Myocardial BOLD MRI at Rest.

    PubMed

    Bevilacqua, Marco; Dharmakumar, Rohan; Tsaftaris, Sotirios A

    2016-01-01

    Cardiac Phase-resolved Blood-Oxygen-Level Dependent (CP-BOLD) MRI provides a unique opportunity to image an ongoing ischemia at rest. However, it requires post-processing to evaluate the extent of ischemia. To address this, here we propose an unsupervised ischemia detection (UID) method which relies on the inherent spatio-temporal correlation between oxygenation and wall motion to formalize a joint learning and detection problem based on dictionary decomposition. Considering input data of a single subject, it treats ischemia as an anomaly and iteratively learns dictionaries to represent only normal observations (corresponding to myocardial territories remote to ischemia). Anomaly detection is based on a modified version of One-class Support Vector Machines (OCSVM) to regulate directly the margins by incorporating the dictionary-based representation errors. A measure of ischemic extent (IE) is estimated, reflecting the relative portion of the myocardium affected by ischemia. For visualization purposes an ischemia likelihood map is created by estimating posterior probabilities from the OCSVM outputs, thus obtaining how likely the classification is correct. UID is evaluated on synthetic data and in a 2D CP-BOLD data set from a canine experimental model emulating acute coronary syndromes. Comparing early ischemic territories identified with UID against infarct territories (after several hours of ischemia), we find that IE, as measured by UID, is highly correlated (Pearson's r=0.84) with respect to infarct size. When advances in automated registration and segmentation of CP-BOLD images and full coverage 3D acquisitions become available, we hope that this method can enable pixel-level assessment of ischemia with this truly non-invasive imaging technique. PMID:26292338

  6. A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

    PubMed

    Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

    2016-03-01

    Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle. PMID:27087101

  7. MIBG scintigraphic assessment of cardiac adrenergic activity in response to altitude hypoxia

    SciTech Connect

    Richalet, J.P.; Merlet, P.; Bourguignon, M.; Le-Trong, J.L.; Keromes, A.; Rathat, C.; Jouve, B.; Hot, M.A.; Castaigne, A.; Syrota, A. )

    1990-01-01

    High altitude hypoxia induces a decrease in the cardiac chronotropic function at maximal exercise or in response to isoproterenol infusion, suggesting an alteration in the cardiac sympathetic activation. Iodine-123 metaiodobenzylguanidine (({sup 123}I)MIBG) was used to map scintigraphically the cardiac sympathetic neuronal function in six male subjects (aged 32 {plus minus} 7 yr) after an exposure to high altitude that created hypoxic conditions. Results obtained just after return to sea level (RSL) were compared with the normal values obtained after 2 or 3 mo of normoxia (N). A static image was created as the sum of the 16-EKG gated images recorded for 10 min in the anterior view of the chest at 20, 60, 120, and 240 min after injection. Regions of interest were located over the heart (H), lungs (L), and mediastinum (M) regions. There was a significant decrease in the H/M and the L/M ratios in RSL compared to N condition. Plasma norepinephrine concentration was elevated during the stay at altitude but not significantly different in RSL compared to N. In conclusion, cardiac ({sup 123}I)MIBG uptake is reduced after an exposure to altitude hypoxia, supporting the hypothesis of an hypoxia-induced reduction of adrenergic neurotransmitter reserve in the myocardium. Furthermore, the observed significant decrease in pulmonary MIBG uptake suggests an alteration of endothelial cell function after exposure to chronic hypoxia.

  8. A coarse-grained model to study calcium activation of the cardiac thin filament

    NASA Astrophysics Data System (ADS)

    Zhang, Jing; Schwartz, Steven

    2015-03-01

    Familial hypertrophic cardiomyopathy (FHC) is one of the most common heart disease caused by genetic mutations. Cardiac muscle contraction and relaxation involve regulation of crossbridge binding to the cardiac thin filament, which regulates actomyosin interactions through calcium-dependent alterations in the dynamics of cardiac troponin (cTn) and tropomyosin (Tm). An atomistic model of cTn complex interacting with Tm has been studied by our group. A more realistic model requires the inclusion of the dynamics of actin filament, which is almost 6 times larger than cTn and Tm in terms of atom numbers, and extensive sampling of the model becomes very resource-demanding. By using physics-based protein united-residue force field, we introduce a coarse-grained model to study the calcium activation of the thin filament resulting from cTn's allosteric regulation of Tm dynamics on actin. The time scale is much longer than that of all-atom molecular dynamics simulation because of the reduction of the degrees of freedom. The coarse-grained model is a good template for studying cardiac thin filament mutations that cause FHC, and reduces the cost of computational resources.

  9. Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: therapeutic perspectives

    PubMed Central

    Javadov, Sabzali; Jang, Sehwan; Agostini, Bryan

    2014-01-01

    Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling and cross-talk with other signaling networks. The extensively studied MAPKs ERK1/2, p38, JNK, and ERK5, demonstrate unique intracellular signaling mechanisms, responding to a myriad of mitogens and stressors and influencing the signaling of cardiac development, metabolism, performance, and pathogenesis. Definitive relationships between MAPK signaling and cardiac dysfunction remain elusive, despite 30 years of extensive clinical studies and basic research of various animal/cell models, severities of stress, and types of stimuli. Still, several studies have proven the importance of MAPK cross-talk with mitochondria, powerhouses of the cell that provide over 80% of ATP for normal cardiomyocyte function and play a crucial role in cell death. Although many questions remain unanswered, there exists enough evidence to consider the possibility of targeting MAPK-mitochondria interactions in the prevention and treatment of heart disease. The goal of this review is to integrate previous studies into a discussion of MAPKs and MAPK-mitochondria signaling in cardiac diseases, such as myocardial infarction (ischemia), hypertrophy and heart failure. A comprehensive understanding of relevant molecular mechanisms, as well as challenges for studies in this area, will facilitate the development of new pharmacological agents and genetic manipulations for therapy of cardiovascular diseases. PMID:24924700

  10. False alarm reduction in BSN-based cardiac monitoring using signal quality and activity type information.

    PubMed

    Tanantong, Tanatorn; Nantajeewarawat, Ekawit; Thiemjarus, Surapa

    2015-01-01

    False alarms in cardiac monitoring affect the quality of medical care, impacting on both patients and healthcare providers. In continuous cardiac monitoring using wireless Body Sensor Networks (BSNs), the quality of ECG signals can be deteriorated owing to several factors, e.g., noises, low battery power, and network transmission problems, often resulting in high false alarm rates. In addition, body movements occurring from activities of daily living (ADLs) can also create false alarms. This paper presents a two-phase framework for false arrhythmia alarm reduction in continuous cardiac monitoring, using signals from an ECG sensor and a 3D accelerometer. In the first phase, classification models constructed using machine learning algorithms are used for labeling input signals. ECG signals are labeled with heartbeat types and signal quality levels, while 3D acceleration signals are labeled with ADL types. In the second phase, a rule-based expert system is used for combining classification results in order to determine whether arrhythmia alarms should be accepted or suppressed. The proposed framework was validated on datasets acquired using BSNs and the MIT-BIH arrhythmia database. For the BSN dataset, acceleration and ECG signals were collected from 10 young and 10 elderly subjects while they were performing ADLs. The framework reduced the false alarm rate from 9.58% to 1.43% in our experimental study, showing that it can potentially assist physicians in diagnosing a vast amount of data acquired from wireless sensors and enhance the performance of continuous cardiac monitoring. PMID:25671512

  11. False Alarm Reduction in BSN-Based Cardiac Monitoring Using Signal Quality and Activity Type Information

    PubMed Central

    Tanantong, Tanatorn; Nantajeewarawat, Ekawit; Thiemjarus, Surapa

    2015-01-01

    False alarms in cardiac monitoring affect the quality of medical care, impacting on both patients and healthcare providers. In continuous cardiac monitoring using wireless Body Sensor Networks (BSNs), the quality of ECG signals can be deteriorated owing to several factors, e.g., noises, low battery power, and network transmission problems, often resulting in high false alarm rates. In addition, body movements occurring from activities of daily living (ADLs) can also create false alarms. This paper presents a two-phase framework for false arrhythmia alarm reduction in continuous cardiac monitoring, using signals from an ECG sensor and a 3D accelerometer. In the first phase, classification models constructed using machine learning algorithms are used for labeling input signals. ECG signals are labeled with heartbeat types and signal quality levels, while 3D acceleration signals are labeled with ADL types. In the second phase, a rule-based expert system is used for combining classification results in order to determine whether arrhythmia alarms should be accepted or suppressed. The proposed framework was validated on datasets acquired using BSNs and the MIT-BIH arrhythmia database. For the BSN dataset, acceleration and ECG signals were collected from 10 young and 10 elderly subjects while they were performing ADLs. The framework reduced the false alarm rate from 9.58% to 1.43% in our experimental study, showing that it can potentially assist physicians in diagnosing a vast amount of data acquired from wireless sensors and enhance the performance of continuous cardiac monitoring. PMID:25671512

  12. Evaluation of cardiac rhythm disturbances during extravehicular activity

    NASA Technical Reports Server (NTRS)

    Rossum, A. C.; Wood, M. L.; Bishop, S. L.; Deblock, H.; Charles, J. B.

    1997-01-01

    This study represents the first systematic evaluation of dysrhythmias before, during, and after spaceflight including extravehicular activity (EVA). The data, based on 7 Shuttle crew members, revealed a nonsignificant decrease in ventricular and supraventricular ectopy during EVA, suggesting that the incidence of dysrhythmias is no greater during EVA than with any other phase of a mission or preflight.

  13. Practical nonlinear method for detection of respiratory and cardiac dysfunction in human subjects

    NASA Astrophysics Data System (ADS)

    Katz, Richard A.; Lawee, Michael S.; Newman, Anthony K.; Weiss, J. Woodrow; Chandra, Shalabh; Grimm, Richard A.; Thomas, James D.

    1995-12-01

    This research applies novel nonlinear signal detection techniques in studies of human subjects with respiratory and cardiac diseases. One of the studies concerns a breathing disorder during sleep, a disease called Obstructive Sleep Apnea (OSA). In a second study we investigate a disease of the heart, Atrial Fibrillation (AF). The former study involves nonlinear processing of the time sequences of sleep apnea recordings (cardio-respirograms) collected from patients with known obstructive sleep apnea, and from a normal control. In the latter study, we apply similar nonlinear metrics to Doppler flow measurements obtained by transesophageal echocardiography (TEE). One of our metrics, the 'chaotic radius' is used for tracking the position of points in phase space relative to some reference position. A second metric, the 'differential radius' provides a measure of the separation rate of contiguous (evolving) points in phase space. A third metric, the 'chaotic frequency' gives angular position of the phase space orbit as a function of time. All are useful for identifying change of physiologic condition that is not always apparent using conventional methods.

  14. Irisin evokes bradycardia by activating cardiac-projecting neurons of nucleus ambiguus

    PubMed Central

    Brailoiu, Eugen; Deliu, Elena; Sporici, Romeo A; Cristina Brailoiu, G

    2015-01-01

    Irisin is a newly identified hormone induced in muscle and adipose tissues by physical activity. This protein and its encoding gene have been identified in the brain; in addition, the precursor for irisin, FNDC5, can cross the blood-brain barrier. The fact that irisin is secreted during exercise together with the lower resting heart rate in athletes prompted us to investigate the effect of irisin on cardiac-projecting vagal neurons of nucleus ambiguus, a key regulatory site of heart rate. In vitro experiments in cultured nucleus ambiguus neurons indicate that irisin activates these neurons, inducing an increase in cytosolic Ca2+ concentration and neuronal depolarization. In vivo microinjection of irisin into the nucleus ambiguus promotes bradycardia in conscious rats. Our study is the first to report the effects of irisin on the neurons controlling the cardiac vagal tone and to link a myokine to a cardioprotective role, by modulating central cardiovascular regulation. PMID:26038469

  15. Peroxisome Proliferator-Activated Receptor-γ Is Critical to Cardiac Fibrosis

    PubMed Central

    Liu, Huang-Jun; Liao, Hai-Han; Yang, Zheng; Tang, Qi-Zhu

    2016-01-01

    Peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily, which plays a central role in regulating lipid and glucose metabolism. However, accumulating evidence demonstrates that PPARγ agonists have potential to reduce inflammation, influence the balance of immune cells, suppress oxidative stress, and improve endothelial function, which are all involved in the cellular and molecular mechanisms of cardiac fibrosis. Thus, in this review we discuss the role of PPARγ in various cardiovascular conditions associated with cardiac fibrosis, including diabetes mellitus, hypertension, myocardial infarction, heart failure, ischemia/reperfusion injury, atrial fibrillation, and several other cardiovascular disease (CVD) conditions, and summarize the developmental status of PPARγ agonists for the clinical management of CVD. PMID:27293418

  16. A guide to modelling cardiac electrical activity in anatomically detailed ventricles.

    PubMed

    Clayton, R H; Panfilov, A V

    2008-01-01

    One of the most recent trends in cardiac electrophysiology is the development of integrative anatomically accurate models of the heart, which include description of cardiac activity from sub-cellular and cellular level to the level of the whole organ. In order to construct this type of model, a researcher needs to collect a wide range of information from books and journal articles on various aspects of biology, physiology, electrophysiology, numerical mathematics and computer programming. The aim of this methodological article is to survey recent developments in integrative modelling of electrical activity in the ventricles of the heart, and to provide a practical guide to the resources and tools that are available for work in this exciting and challenging area. PMID:17825362

  17. Cardiorespiratory Coupling: Common Rhythms in Cardiac, Sympathetic, and Respiratory Activities

    PubMed Central

    Dick, Thomas E.; Hsieh, Yee-Hsee; Dhingra, Rishi R.; Baekey, David M.; Galán, Roberto F.; Wehrwein, Erica; Morris, Kendall F.

    2014-01-01

    Cardiorespiratory coupling is an encompassing term describing more than the well-recognized influences of respiration on heart rate and blood pressure. Our data indicate that cardiorespiratory coupling reflects a reciprocal interaction between autonomic and respiratory control systems, and the cardiovascular system modulates the ventilatory pattern as well. For example, cardioventilatory coupling refers to the influence of heart beats and arterial pulse pressure on respiration and is the tendency for the next inspiration to start at a preferred latency after the last heart beat in expiration. Multiple complementary, well-described mechanisms mediate respiration’s influence on cardiovascular function, whereas mechanisms mediating the cardiovascular system’s influence on respiration may only be through the baroreceptors but are just being identified. Our review will describe a differential effect of conditioning rats with either chronic intermittent or sustained hypoxia on sympathetic nerve activity but also on ventilatory pattern variability. Both intermittent and sustained hypoxia increase sympathetic nerve activity after 2 weeks but affect sympatho-respiratory coupling differentially. Intermittent hypoxia enhances sympatho-respiratory coupling, which is associated with low variability in the ventilatory pattern. In contrast, after constant hypobaric hypoxia, 1-to-1 coupling between bursts of sympathetic and phrenic nerve activity is replaced by 2-to-3 coupling. This change in coupling pattern is associated with increased variability of the ventilatory pattern. After baro-denervating hypobaric hypoxic-conditioned rats, splanchnic sympathetic nerve activity becomes tonic (distinct bursts are absent) with decreases during phrenic nerve bursts and ventilatory pattern becomes regular. Thus, conditioning rats to either intermittent or sustained hypoxia accentuates the reciprocal nature of cardiorespiratory coupling. Finally, identifying a compelling physiologic

  18. Regulation of pyruvate dehydrogenase activity and citric acid cycle intermediates during high cardiac power generation

    PubMed Central

    Sharma, Naveen; Okere, Isidore C; Brunengraber, Daniel Z; McElfresh, Tracy A; King, Kristen L; Sterk, Joseph P; Huang, Hazel; Chandler, Margaret P; Stanley, William C

    2005-01-01

    A high rate of cardiac work increases citric acid cycle (CAC) turnover and flux through pyruvate dehydrogenase (PDH); however, the mechanisms for these effects are poorly understood. We tested the hypotheses that an increase in cardiac energy expenditure: (1) activates PDH and reduces the product/substrate ratios ([NADH]/[NAD+] and [acetyl-CoA]/[CoA-SH]); and (2) increases the content of CAC intermediates. Measurements were made in anaesthetized pigs under control conditions and during 15 min of a high cardiac workload induced by dobutamine (Dob). A third group was made hyperglycaemic (14 mm) to stimulate flux through PDH during the high work state (Dob + Glu). Glucose and fatty acid oxidation were measured with 14C-glucose and 3H-oleate. Compared with control, the high workload groups had a similar increase in myocardial oxygen consumption ( and cardiac power. Dob increased PDH activity and glucose oxidation above control, but did not reduce the [NADH]/[NAD+] and [acetyl-CoA]/[CoA-SH] ratios, and there were no differences between the Dob and Dob + Glu groups. An additional group was treated with Dob + Glu and oxfenicine (Oxf) to inhibit fatty acid oxidation: this increased [CoA-SH] and glucose oxidation compared with Dob; however, there was no further activation of PDH or decrease in the [NADH]/[NAD+] ratio. Content of the 4-carbon CAC intermediates succinate, fumarate and malate increased 3-fold with Dob, but there was no change in citrate content, and the Dob + Glu and Dob + Glu + Oxf groups were not different from Dob. In conclusion, compared with normal conditions, at high myocardial energy expenditure (1) the increase in flux through PDH is regulated by activation of the enzyme complex and continues to be partially controlled through inhibition by fatty acid oxidation, and (2) there is expansion of the CAC pool size at the level of 4-carbon intermediates that is largely independent of myocardial fatty acid oxidation. PMID:15550462

  19. Comparison of five cardiac markers in the detection of reperfusion after thrombolysis in acute myocardial infarction.

    PubMed Central

    Lavin, F.; Kane, M.; Forde, A.; Gannon, F.; Daly, K.

    1995-01-01

    OBJECTIVE--To investigate and compare the clinical usefulness of serial measurements of five cardiac marker proteins, namely creatine kinase (CK), CK-MB mass, myoglobin, troponin T, and myosin light chain 1, in the early detection of reperfusion after thrombolytic treatment. METHOD--Serial blood samples were taken from 26 patients presenting with acute myocardial infarction. Concentrations of the five markers were assayed in each sample. Thrombolytic treatment was given to the patients who were divided into those who reperfused (n = 17, group A) and those who failed to reperfuse (n = 9, group B) on the basis of clinical signs and angiography within 24 h. RESULTS--The release profiles of CK, CK-MB mass, myoglobin, and troponin T for patients in group A differed from those of patients in group B. No difference was observed in the release profile of myosin light chain 1 between the two groups. The time to peak concentration of CK, CK-MB mass, myoglobin, and troponin T occurred significantly earlier in patients of group A than in those of group B, with myoglobin peaking earlier than the other markers. An index, defined as the ratio of the concentration of each marker immediately before and 2 h after the start of thrombolytic treatment, was calculated for each marker in groups A and B. The 2 h myoglobin and troponin T indices were significantly different between groups A and B. The diagnostic efficiency of the myoglobin index, however, was best at 85%. CONCLUSIONS--These studies suggest that myoglobin has greater potential than the other markers examined in the detection of reperfusion after thrombolytic treatment. PMID:7786656

  20. Activation and modulation of cardiac poly-adenosine diphosphate ribose polymerase activity in a rat model of brain death.

    PubMed

    Brain, John G; Rostron, Anthony J; Dark, John H; Kirby, John A

    2008-05-15

    DNA damage during transplantation can activate poly-adenosine diphosphate ribose polymerase (PARP) resulting in the generation of polymers of adenosine diphosphate-ribose (PAR). Excessive linkage of PAR to nuclear proteins can induce cell death, thereby limiting the function of transplanted organs. This study uses a rat model of brain death to determine the profile of PARP activation and whether mechanisms that lead to cell death can be ameliorated by appropriate donor resuscitation. The expression of PAR-linked nuclear proteins within cardiac myocytes was greatly increased after the induction of donor brain death. Importantly, infusion of noradrenaline or vasopressin to normalize the chronic hypotension produced by brain death reduced the expression of PAR to a level below baseline. These data suggest that chronic hypotension after donor brain death has the potential to limit cardiac function through the activation of PARP; however, this early cause of graft damage can be mitigated by appropriate donor resuscitation. PMID:18475194

  1. Alterations in electrodermal activity and cardiac parasympathetic tone during hypnosis.

    PubMed

    Kekecs, Zoltán; Szekely, Anna; Varga, Katalin

    2016-02-01

    Exploring autonomic nervous system (ANS) changes during hypnosis is critical for understanding the nature and extent of the hypnotic phenomenon and for identifying the mechanisms underlying the effects of hypnosis in different medical conditions. To assess ANS changes during hypnosis, electrodermal activity and pulse rate variability (PRV) were measured in 121 young adults. Participants either received hypnotic induction (hypnosis condition) or listened to music (control condition), and both groups were exposed to test suggestions. Blocks of silence and experimental sound stimuli were presented at baseline, after induction, and after de-induction. Skin conductance level (SCL) and high frequency (HF) power of PRV measured at each phase were compared between groups. Hypnosis decreased SCL compared to the control condition; however, there were no group differences in HF power. Furthermore, hypnotic suggestibility did not moderate ANS changes in the hypnosis group. These findings indicate that hypnosis reduces tonic sympathetic nervous system activity, which might explain why hypnosis is effective in the treatment of disorders with strong sympathetic nervous system involvement, such as rheumatoid arthritis, hot flashes, hypertension, and chronic pain. Further studies with different control conditions are required to examine the specificity of the sympathetic effects of hypnosis. PMID:26488759

  2. SIRT6 suppresses isoproterenol-induced cardiac hypertrophy through activation of autophagy.

    PubMed

    Lu, Jing; Sun, Duanping; Liu, Zhiping; Li, Min; Hong, Huiqi; Liu, Cui; Gao, Si; Li, Hong; Cai, Yi; Chen, Shaorui; Li, Zhuoming; Ye, Jiantao; Liu, Peiqing

    2016-06-01

    Reduction in autophagy has been reported to contribute to the pathogenesis of cardiac hypertrophy. However, the molecular pathways leading to impaired autophagy at the presence of hypertrophic stimuli remain to be elucidated. The present study aimed to investigate the role of sirtuin 6 (SIRT6), a sirtuin family member, in regulating cardiomyocyte autophagy, and its implication in prevention of cardiac hypertrophy. Primary neonatal rat cardiomyocytes (NRCMs) or Sprague-Dawley (SD) rats were submitted to isoproterenol (ISO) treatment, and then the hypertrophic responses and changes in autophagy activity were measured. The influence of SIRT6 on autophagy was observed in cultured NRCMs with gain- and loss-of-function approaches to regulate SIRT6 expression, and further confirmed in vivo by intramyocardial delivery of an adenovirus vector encoding SIRT6 cDNA. In addition, the involvement of SIRT6-mediated autophagy in attenuation of cardiomyocyte hypertrophy induced by ISO was determined basing on genetic or pharmaceutical disruption of autophagy, and the underlying mechanism was preliminarily explored. ISO-caused cardiac hypertrophy accompanying with a significant decrease in autophagy activity. SIRT6 overexpression enhanced autophagy in NRCMs and in rat hearts, whereas knockdown of SIRT6 by RNA interference led to suppression of cardiomyocyte autophagy. Furthermore, the protective effect of SIRT6 against ISO-stimulated hypertrophy was associated with induction of autophagy. SIRT6 promoted nuclear retention of forkhead box O3 transcription factor possibly via attenuating Akt signaling, which was responsible for autophagy activation. Our findings revealed that SIRT6 positively regulates autophagy in cardiomyocytes, which may help to ameliorate ISO-induced cardiac hypertrophy. PMID:27016702

  3. Segmentation of 4D cardiac computer tomography images using active shape models

    NASA Astrophysics Data System (ADS)

    Leiner, Barba-J.; Olveres, Jimena; Escalante-Ramírez, Boris; Arámbula, Fernando; Vallejo, Enrique

    2012-06-01

    This paper describes a segmentation method for time series of 3D cardiac images based on deformable models. The goal of this work is to extend active shape models (ASM) of tree-dimensional objects to the problem of 4D (3D + time) cardiac CT image modeling. The segmentation is achieved by constructing a point distribution model (PDM) that encodes the spatio-temporal variability of a training set, i.e., the principal modes of variation of the temporal shapes are computed using some statistical parameters. An active search is used in the segmentation process where an initial approximation of the spatio-temporal shape is given and the gray level information in the neighborhood of the landmarks is analyzed. The starting shape is able to deform so as to better fit the data, but in the range allowed by the point distribution model. Several time series consisting of eleven 3D images of cardiac CT are employed for the method validation. Results are compared with manual segmentation made by an expert. The proposed application can be used for clinical evaluation of the left ventricle mechanical function. Likewise, the results can be taken as the first step of processing for optic flow estimation algorithms.

  4. Cardiac lipid content is unresponsive to a physical activity training intervention in type 2 diabetic patients, despite improved ejection fraction

    PubMed Central

    2011-01-01

    Background Increased cardiac lipid content has been associated with diabetic cardiomyopathy. We recently showed that cardiac lipid content is reduced after 12 weeks of physical activity training in healthy overweight subjects. The beneficial effect of exercise training on cardiovascular risk is well established and the decrease in cardiac lipid content with exercise training in healthy overweight subjects was accompanied by improved ejection fraction. It is yet unclear whether diabetic patients respond similarly to physical activity training and whether a lowered lipid content in the heart is necessary for improvements in cardiac function. Here, we investigated whether exercise training is able to lower cardiac lipid content and improve cardiac function in type 2 diabetic patients. Methods Eleven overweight-to-obese male patients with type 2 diabetes mellitus (age: 58.4 ± 0.9 years, BMI: 29.9 ± 0.01 kg/m2) followed a 12-week training program (combination endurance/strength training, three sessions/week). Before and after training, maximal whole body oxygen uptake (VO2max) and insulin sensitivity (by hyperinsulinemic, euglycemic clamp) was determined. Systolic function was determined under resting conditions by CINE-MRI and cardiac lipid content in the septum of the heart by Proton Magnetic Resonance Spectroscopy. Results VO2max increased (from 27.1 ± 1.5 to 30.1 ± 1.6 ml/min/kg, p = 0.001) and insulin sensitivity improved upon training (insulin stimulated glucose disposal (delta Rd of glucose) improved from 5.8 ± 1.9 to 10.3 ± 2.0 μmol/kg/min, p = 0.02. Left-ventricular ejection fraction improved after training (from 50.5 ± 2.0 to 55.6 ± 1.5%, p = 0.01) as well as cardiac index and cardiac output. Unexpectedly, cardiac lipid content in the septum remained unchanged (from 0.80 ± 0.22% to 0.95 ± 0.21%, p = 0.15). Conclusions Twelve weeks of progressive endurance/strength training was effective in improving VO2max, insulin sensitivity and cardiac function

  5. Thoracic outlet syndrome of pectoralis minor etiology mimicking cardiac symptoms on activity: a case report

    PubMed Central

    Fitzgerald, Gary

    2012-01-01

    Thoracic outlet syndrome is the result of compression or irritation of neurovascular bundles as they pass from the lower cervical spine into the arm, via the axilla. If the pectoralis minor muscle is involved the patient may present with chest pain, along with pain and paraesthesia into the arm. These symptoms are also commonly seen in patients with chest pain of a cardiac origin. In this case, a patient presents with a history of left sided chest pain with pain and paraesthesia into the left upper limb, which only occurs whilst running. The symptoms were reproduced on both digital pressure over the pectoralis minor muscle and on provocative testing for thoracic outlet syndrome. The patient’s treatment therefore focused on the pectoralis minor muscle, with a complete resolution of symptoms. This illustrates that not all cases of chest pain with associated arm symptoms that occur on physical activity are of cardiac origin. PMID:23204575

  6. Netrin-1 attenuates cardiac ischemia reperfusion injury and generates alternatively activated macrophages.

    PubMed

    Mao, Xiaogang; Xing, Hui; Mao, Aihua; Jiang, Hong; Cheng, Li; Liu, Yun; Quan, Xiaozhen; Li, Lin

    2014-04-01

    Ischemia reperfusion (IR) injury is a major issue in cardiac transplantation and inflammatory processes play a major role in myocardial IR injury. Netrin-1 is a laminin-related protein identified as a neuronal guidance cue and netrin-1 expressed outside the nervous system inhibits migration of leukocytes in vitro and in vivo and attenuates inflammation-mediated tissue injury. In our study, hearts of C57BL/6 mice were flushed and stored in cold Bretschneider solution for 8 h and then transplanted into syngeneic recipient. We found that netrin-1 decreased cardiomyocyte apoptosis and recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24 h after myocardial IR injury was reduced by netrin-1 administration. Cardiac output at 60 mmHg of afterload pressure was significantly increased in hearts with netrin-1 administration (IR + Netrin-1: 59.9 ± 5.78 ml/min; IR: 26.2 ± 4.3 ml/min; P < 0.05). Netrin-1 treatment increased expression of the alternatively activated macrophage (AAM) markers arginase-1 (Arg-1) and mannose receptor (MR) and promoted proliferator-activated receptor γ (PPARγ) expression in cardiac allograft. Furthermore, decreased TnT expression and reduced allograft infiltration of neutrophils and monocytes/macrophages by netrin-1 was abolished with addition of PPARγ antagonist. In conclusion, netrin-1 attenuates cardiac IR injury and generates AAM which contributes to the protective effect of netrin-1. PMID:24234226

  7. Detection of Telomerase Activity Using Capacitance Measurements

    NASA Astrophysics Data System (ADS)

    Kang, Bong Keun; Lee, Ri Mi; Choi, Ahmi; Jung, Hyo-Il; Yoo, Kyung-Hwa

    2007-03-01

    Telomerase activity has been found in about 85% cancer cells, while no activity observed in normal cells, so that telomerase has been proposed as a marker for cancer detection. Here, we describe electrical detection of telomerase activity using capacitance measurements. We have investigated the length dependence of capacitance on DNA solutions and found that the capacitance of DNA solutions were dependent on the DNA length. In addition, upon adding telomerase into the solution of telomeric substrate primer, the capacitance was observed to change as a function of time due to the telomeric elongation. These results suggest that this novel nanosensor may be used for rapid detection of telomerase activity.

  8. High-sensitivity cardiac troponin T is more helpful in detecting peri-operative myocardial injury and apoptosis during coronary artery bypass graft surgery

    PubMed Central

    Kocak, Emel Fatma; Altuntas, Irfan; Kocak, Cengiz; Aksoy, Ahmet; Ozdomanic, Ibrahim Fevzi; Isiklar, Ozden Ozben; Akcilar, Raziye; Unsal, Cevher; Celenk, Merve

    2015-01-01

    Summary Aim To determine whether there is a correlation between cardiac markers and peri-operative myocardial injury (PMI) and apoptosis in coronary artery bypass graft (CABG) surgery and to compare the efficacy of cardiac markers to detect PMI. Methods The study population consisted of 37 patients (24 male, 13 female, mean age 63.4 ± 8.9 years) undergoing elective CABG. Arterial and coronary sinus blood samples were collected just before aortic cross-clamping (pre-ACC) and after aortic declamping (post-ACC). Creatine kinase-MB isoenzyme (CK-MB) activity, and high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase-MB isoenzyme mass (CK-MB mass) and cardiac troponin I (cTnI) concentrations were measured in blood samples. Myocardial injury and apoptosis were examined in atrial biopsies. Results CABG caused PMI and apoptosis in all cases. Concentrations and net releases of cardiac markers significantly increased after aortic declamping (p < 0.001 for CK-MB and CK-MB mass, p < 0.01 for cTnI, p < 0.05 for hs-cTnT). A positive correlation was found between apoptotic index (r = 0.611, p < 0.001 for cTnI; r = 0.806, p < 0.001 for hs-cTnT), myocardial injury score (r = 0.544, p < 0.001 for cTnI; r = 0.719, p < 0.001 for hs-cTnT) and cTnI and hs-cTnT values in the post-ACC period. A positive correlation was found between apoptotic index (r = 0.507, p < 0.001), myocardial injury score (r = 0.416, p = 0.010) and net release of hs-cTnT. Furthermore, a positive correlation was found between aortic cross-clamp (ACC) time (r = 0.448, p = 0.007), cardiopulmonary bypass (CPB) time (r = 0.342, p = 0.047) and net release of hs-cTnT. Conclusion Although both cTnI and hs-cTnT may be specific and efficacious markers of myocardial apoptosis and injury occurring during CABG with CPB, hs-cTnT may be a more useful marker than cTnI to detect peri-operative myocardial apoptosis and injury. PMID:26212819

  9. Label-free electrical detection of cardiac biomarker with complementary metal-oxide semiconductor-compatible silicon nanowire sensor arrays.

    PubMed

    Chua, Jay Huiyi; Chee, Ru-Ern; Agarwal, Ajay; Wong, She Mein; Zhang, Guo-Jun

    2009-08-01

    Arrays of highly ordered silicon nanowire (SiNW) clusters are fabricated using complementary metal-oxide semiconductor (CMOS) field effect transistor-compatible technology, and the ultrasensitive, label-free, electrical detection of cardiac biomarker in real time using the array sensor is presented. The successful detection of human cardiac troponin-T (cTnT) has been demonstrated in an assay buffer solution of concentration down to 1 fg/mL, as well as in an undiluted human serum environment of concentration as low as 30 fg/mL. The high specificity, selectivity, and swift response time of the SiNWs to the presence of ultralow concentrations of a target protein in a biological analyte solution, even in the presence of a high total protein concentration, paves the way for the development of a medical diagnostic system for point-of-care application that is able to provide an early and accurate indication of cardiac cellular necrosis. PMID:20337397

  10. Inpatient detection of cardiac-inherited disease: the impact of improving family history taking

    PubMed Central

    Waddell-Smith, Kathryn E; Donoghue, Tom; Oates, Stephanie; Graham, Amanda; Crawford, Jackie; Stiles, Martin K; Aitken, Andrew; Skinner, Jonathan R

    2016-01-01

    Objectives ‘Idiopathic’ cardiac conditions such as dilated cardiomyopathy (DCM) and resuscitated sudden cardiac death (RSCD) may be familial. We suspected that inpatient cardiology services fail to recognise this. Our objective was to compare diagnostic value of family histories recorded by inpatient cardiology teams with a multigenerational family tree obtained by specially trained allied professionals. Methods 2 experienced cardiology nurses working in 2 tertiary adult cardiac units were trained in cardiac-inherited diseases and family history (FHx) taking, and established as regional coordinators for a National Cardiac Inherited Disease Registry. Over 6 months they sought ‘idiopathic’ cardiology inpatients with conditions with a possible familial basis, reviewed the FHx in the clinical records and pursued a minimum 3-generation family tree for syncope, young sudden death and cardiac disease (full FHx). Results 37 patients (22 males) were selected: mean age 51 years (range 15–79). Admission presentations included (idiopathic) RSCD (14), dyspnoea or heart failure (11), ventricular tachycardia (2), other (10). 3 patients had already volunteered their familial diagnosis to the admitting team. FHx was incompletely elicited in 17 (46%) and absent in 20 (54%). 29 patients (78%) provided a full FHx to the coordinator; 12 of which (41%) were strongly consistent with a diagnosis of a cardiac-inherited disease (DCM 7, hypertrophic cardiomyopathy 3, long QT 1, left ventricular non-compaction 1). Overall, a familial diagnostic rate rose from 3/37(8%) to 12/37 (32%). Conclusions Adult cardiology inpatient teams are poor at recording FHx and need to be reminded of its powerful diagnostic value. PMID:26925241

  11. A 3-D active shape model driven by fuzzy inference: application to cardiac CT and MR.

    PubMed

    van Assen, Hans C; Danilouchkine, Mikhail G; Dirksen, Martijn S; Reiber, Johan H C; Lelieveldt, Boudewijn P F

    2008-09-01

    Manual quantitative analysis of cardiac left ventricular function using Multislice CT and MR is arduous because of the large data volume. In this paper, we present a 3-D active shape model (ASM) for semiautomatic segmentation of cardiac CT and MR volumes, without the requirement of retraining the underlying statistical shape model. A fuzzy c-means based fuzzy inference system was incorporated into the model. Thus, relative gray-level differences instead of absolute gray values were used for classification of 3-D regions of interest (ROIs), removing the necessity of training different models for different modalities/acquisition protocols. The 3-D ASM was evaluated using 25 CT and 15 MR datasets. Automatically generated contours were compared to expert contours in 100 locations. For CT, 82.4% of epicardial contours and 74.1% of endocardial contours had a maximum error of 5 mm along 95% of the contour arc length. For MR, those numbers were 93.2% (epicardium) and 91.4% (endocardium). Volume regression analysis revealed good linear correlations between manual and semiautomatic volumes, r(2) >/= 0.98. This study shows that the fuzzy inference 3-D ASM is a robust promising instrument for semiautomatic cardiac left ventricle segmentation. Without retraining its statistical shape component, it is applicable to routinely acquired CT and MR studies. PMID:18779074

  12. Cardiac-specific activation of Cre expression at late fetal development

    SciTech Connect

    Opherk, Jan P.; Yampolsky, Peter; Hardt, Stefan E.; Schoels, Wolfgang; Katus, Hugo A.; Koenen, Michael . E-mail: koenen@mpimf-heidelberg.mpg.de; Zehelein, Joerg

    2007-07-27

    In a first step towards dissecting molecular mechanisms that contribute to the development of cardiac diseases, we have generated transgenic mice that express a Cre-GFP fusion protein under the transcriptional control of a 4.3 kb murine cardiac Troponin I gene (cTnI) promoter. Cre-GFP expression, similar in three transgenic lines, is described in one line. In mouse embryos, transgenic for the Cre-GFP and ROSA lacZ reporter allele, first Cre-mediated recombination appeared at 16.5 dpc selectively at the heart. Like the endogenous cTnI gene, transgenic Cre expression showed a slow rise through fetal development that increased neonatally. Bitransgenic hearts, stained at 30 days of age, showed intense signals in ventricular and atrial myocytes while no recombination occurred in other tissues. The delayed onset of Cre activity in cTnI-Cre mice could provide a useful genetic tool to evaluate the function of loxP targeted cardiac genes without interference of recombination during early heart development.

  13. Conducting polymer functionalized single-walled carbon nanotube based chemiresistive biosensor for the detection of human cardiac myoglobin

    SciTech Connect

    Puri, Nidhi; Niazi, Asad; Biradar, Ashok M.; Rajesh E-mail: adani@engr.ucr.edu; Mulchandani, Ashok E-mail: adani@engr.ucr.edu

    2014-10-13

    We report the fabrication of a single-walled carbon nanotube (SWNT) based ultrasensitive label-free chemiresistive biosensor for the detection of human cardiac biomarker, myoglobin (Ag-cMb). Poly(pyrrole-co-pyrrolepropylic acid) with pendant carboxyl groups was electrochemically deposited on electrophoretically aligned SWNT channel, as a conducting linker, for biomolecular immobilization of highly specific cardiac myoglobin antibody. The device was characterized by scanning electron microscopy, source-drain current-voltage (I-V), and charge-transfer characteristic studies. The device exhibited a linear response with a change in conductance in SWNT channel towards the target, Ag-cMb, over the concentration range of 1.0 to 1000 ng ml{sup −1} with a sensitivity of ∼118% per decade with high specificity.

  14. Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology.

    PubMed

    Thompson, John W; Wei, Jianqin; Appau, Kweku; Wang, Huilan; Yu, Hong; Spiga, Maria G; Graham, Regina M; Webster, Keith A

    2015-01-01

    Bnip3 is a hypoxia-regulated member of the Bcl-2 family of proteins that is implicated in apoptosis, programmed necrosis, autophagy and mitophagy. Mitochondria are thought to be the primary targets of Bnip3 although its activities may extend to the ER, cytoplasm, and nucleus. Bnip3 is induced in the heart by ischemia and pressure-overload, and may contribute to cardiomyopathy and heart failure. Only mitochondrial-dependent programmed death actions have been described for Bnip3 in the heart. Here we describe a novel activity of Bnip3 in cultured cardiac myocytes and transgenic mice overexpressing Bnip3 in the heart (Bnip3-TG). In cultured myocytes Bnip3 bound and activated the acetyltransferase p300, increased acetylation of histones and the transcription factor GATA4, and conferred p300 and GATA4-sensitive cellular morphological changes. In intact Bnip3-TG hearts Bnip3 also bound p300 and GATA4 and conferred enhanced GATA4 acetylation. Bnip3-TG mice underwent age-dependent ventricular dilation and heart failure that was partially prevented by p300 inhibition with curcumin. The results suggest that Bnip3 regulates cardiac gene expression and perhaps myocyte morphology by activating nuclear p300 acetyltransferase activity and hyperacetylating histones and p300-selective transcription factors. PMID:26317696

  15. Early detection and efficient therapy of cardiac angiosarcoma due to routine transesophageal echocardiography after cerebrovascular stroke

    PubMed Central

    Vogelgesang, Dirk; Dahm, Johannes B; Großmann, Holm; Hippe, Andre; Hummel, Astrid; Lotze, Christian; Vogelgesang, Silke

    2008-01-01

    Primary malignant cardiac tumors (cardiac angiosarcomas) are exceedingly rare. Since there are initially nonspecific or missing symptoms, these tumors are usually diagnosed only in an advanced, often incurable stage, after the large tumor mass elicits hemodynamic obstructive symptoms. A 59-year-old female presented with symptoms of cerebral ischemia. A computed tomography (CT) scan showed changes suggestive of stroke. Transesophageal echocardiography revealed an inhomogeneous, medium-echogenic, floating mass at the roof of the left atrium near the mouth of the right upper pulmonary vein, indicative of a thrombus. At surgery, a solitary tumor was completely enucleated. Histologically, cardiac angiosarcoma was diagnosed. The patient received adjuvant chemotherapy and was free of symptoms and recurrence of disease at 14 months follow-up. Due to the fortuitous appearance of clinical signs indicative of stroke, cardiac angiosarcoma was diagnosed and effectively treated at an early, nonmetastatic, and therefore potentially curable stage. Although cardiac angiosarcoma is a rare disease, it should be taken into consideration as a potential cause of cerebral embolic disease. PMID:19066013

  16. Detection of suspicious activity using incremental outlier detection algorithms

    NASA Astrophysics Data System (ADS)

    Pokrajac, D.; Reljin, N.; Pejcic, N.; Vance, T.; McDaniel, S.; Lazarevic, A.; Chang, H. J.; Choi, J. Y.; Miezianko, R.

    2009-08-01

    Detection of unusual trajectories of moving objects can help in identifying suspicious activity on convoy routes and thus reduce casualties caused by improvised explosive devices. In this paper, using video imagery we compare efficiency of various techniques for incremental outlier detection on detecting unusual trajectories on simulated and real-life data obtained from SENSIAC database. Incremental outlier detection algorithms that we consider in this paper include incremental Support Vector Classifier (incSVC), incremental Local Outlier Factor (incLOF) algorithm and incremental Connectivity Outlier Factor (incCOF) algorithm. Our experiments performed on ground truth trajectory data indicate that incremental LOF algorithm can provide better detection of unusual trajectories in comparison to other examined techniques.

  17. Physical activity in patients with grown-up congenital heart defects after comprehensive cardiac rehabilitation

    PubMed Central

    Haponiuk, Ireneusz; Jaworski, Radosław; Chojnicki, Maciej; Szalewska, Dominika; Leszczyńska, Katarzyna; Bakuła, Stanisław

    2014-01-01

    Introduction The group of grown-up patients with congenital heart defects (grown-up congenital heart – GUCH) complains of a number of specific medical and non-medical problems. The presented program of comprehensive cardiac rehabilitation (CCR-GUCH), dedicated to the above mentioned group, can potentially improve the physical activity of GUCH patients. Aim The aim of the study was to assess the effect of the comprehensive cardiac rehabilitation program on the physical activity of GUCH patients. Material and methods The invitation to take part in the CCR-GUCH program was addressed to a group of 57 patients (mean age: 23.7 ± 4.1 years) who had undergone the surgical correction of ventricular septal defects (VSD) or atrial septal defects (ASD) at least 12 months earlier. The patients were divided into two groups: A – patients undergoing rehabilitation, and B – patients who did not participate in the program. The patients were initially examined using functional and stress tests, and the program of comprehensive cardiac rehabilitation was started in group A. After 30 days, the patients from both groups underwent further testing using the same methods as during the initial evaluation. Results After one month of rehabilitation, the physical activity parameters of patients participating in the CCR-GUCH program (group A) were significantly better than those observed among non-participants (group B). Conclusions The introduction of the comprehensive rehabilitation program improves the physical activity and, consequently, the quality of life of GUCH patients. The CCR-GUCH program appears to be a justified supplement to holistic care in the late rehabilitation of patients after the surgical correction of congenital heart defects. PMID:26336469

  18. Controlling activation site density by low-energy far-field stimulation in cardiac tissue

    NASA Astrophysics Data System (ADS)

    Hörning, Marcel; Takagi, Seiji; Yoshikawa, Kenichi

    2012-06-01

    Tachycardia and fibrillation are potentially fatal arrhythmias associated with the formation of rotating spiral waves in the heart. Presently, the termination of these types of arrhythmia is achieved by use of antitachycardia pacing or cardioversion. However, these techniques have serious drawbacks, in that they either have limited application or produce undesirable side effects. Low-energy far-field stimulation has recently been proposed as a superior therapy. This proposed therapeutic method would exploit the phenomenon in which the application of low-energy far-field shocks induces a large number of activation sites (“virtual electrodes”) in tissue. It has been found that the formation of such sites can lead to the termination of undesired states in the heart and the restoration of normal beating. In this study we investigate a particular aspect of this method. Here we seek to determine how the activation site density depends on the applied electric field through in vitro experiments carried out on neonatal rat cardiac tissue cultures. The results indicate that the activation site density increases exponentially as a function of the intracellular conductivity and the level of cell isotropy. Additionally, we report numerical results obtained from bidomain simulations of the Beeler-Reuter model that are quantitatively consistent with our experimental results. Also, we derive an intuitive analytical framework that describes the activation site density and provides useful information for determining the ratio of longitudinal to transverse conductivity in a cardiac tissue culture. The results obtained here should be useful in the development of an actual therapeutic method based on low-energy far-field pacing. In addition, they provide a deeper understanding of the intrinsic properties of cardiac cells.

  19. Human cardiac phospholipase D activity is tightly controlled by phosphatidylinositol 4,5-bisphosphate.

    PubMed

    Kurz, Thomas; Kemken, Dorit; Mier, Kenneth; Weber, Isabel; Richardt, Gert

    2004-02-01

    Phospholipase D (PLD) plays a central role in receptor-mediated breakdown of choline phospholipids and formation of phosphatidic acid (PA), an important regulator of cardiac function. However, specific mechanisms that regulate myocardial PLD activity remain largely unknown, particularly in the human heart. We hypothesized that phosphatidylinositol 4,5-bisphosphate (PIP2), best known as substrate for phospholipase C (PLC) isozymes, plays a critical role in regulating myocardial PLD activity. We examined the effect of PIP2 on human myocardial PLD activity in vitro by utilizing a fluorescence HPLC assay. PIP2 increased 10-fold the maximal activity of a partially solubilized PLD from human atrial myocardium. PIP2-stimulated PLD activity was accompanied by a consecutive increase in diacylglycerol, indicating dephosphorylation of PA by PA phosphohydrolase. Likewise, phosphatidylinositol 3,4,5-trisphosphate, which is produced from PIP2 by phosphatidylinositol 3-kinase, increased PLD activity with about the same potency but with somewhat lower efficacy. In contrast, other phospholipids were ineffective, indicating that the action of PIP2 on PLD is highly specific. Neomycin, a high-affinity ligand of PIP2, inhibited PLD activity in human atrial myocardium, but had no effect on the activity of partially solubilized enzyme. The addition of PIP2 restored the sensitivity of solubilized PLD to neomycin inhibition, indicating that neomycin inhibits PLD activity by binding to endogenous PIP2. Our results demonstrate a critical role for PIP2 in human cardiac PLD activity and suggest that PIP2 synthesis (by phosphatidylinositol 4-phosphate 5-kinase) and hydrolysis (by PIP2-specific PLC) could be important determinants in regulating PLD signal transduction in the human heart. PMID:14871550

  20. Simultaneous detection of landmarks and key-frame in cardiac perfusion MRI using a joint spatial-temporal context model

    NASA Astrophysics Data System (ADS)

    Lu, Xiaoguang; Xue, Hui; Jolly, Marie-Pierre; Guetter, Christoph; Kellman, Peter; Hsu, Li-Yueh; Arai, Andrew; Zuehlsdorff, Sven; Littmann, Arne; Georgescu, Bogdan; Guehring, Jens

    2011-03-01

    Cardiac perfusion magnetic resonance imaging (MRI) has proven clinical significance in diagnosis of heart diseases. However, analysis of perfusion data is time-consuming, where automatic detection of anatomic landmarks and key-frames from perfusion MR sequences is helpful for anchoring structures and functional analysis of the heart, leading toward fully automated perfusion analysis. Learning-based object detection methods have demonstrated their capabilities to handle large variations of the object by exploring a local region, i.e., context. Conventional 2D approaches take into account spatial context only. Temporal signals in perfusion data present a strong cue for anchoring. We propose a joint context model to encode both spatial and temporal evidence. In addition, our spatial context is constructed not only based on the landmark of interest, but also the landmarks that are correlated in the neighboring anatomies. A discriminative model is learned through a probabilistic boosting tree. A marginal space learning strategy is applied to efficiently learn and search in a high dimensional parameter space. A fully automatic system is developed to simultaneously detect anatomic landmarks and key frames in both RV and LV from perfusion sequences. The proposed approach was evaluated on a database of 373 cardiac perfusion MRI sequences from 77 patients. Experimental results of a 4-fold cross validation show superior landmark detection accuracies of the proposed joint spatial-temporal approach to the 2D approach that is based on spatial context only. The key-frame identification results are promising.

  1. Detection of Electrographic Seizures by Critical Care Providers Using Color Density Spectral Array After Cardiac Arrest is Feasible

    PubMed Central

    Topjian, Alexis A; Fry, Michael; Jawad, Abbas F.; Herman, Susan T; Nadkarni, Vinay M.; Ichord, Rebecca; Berg, Robert A; Dlugos, Dennis J.; Abend, Nicholas S.

    2014-01-01

    Objective To determine the accuracy and reliability of electroencephalographic seizure detection by critical care providers using color density spectral array (CDSA) electroencephalography (EEG). Participants Critical care providers (attending physicians, fellow trainees and nurses.) Interventions A standardized powerpoint CDSA tutorial followed by classification of 200 CDSA images as displaying seizures or not displaying seizures. Measurements and Main Results Using conventional EEG recordings obtained from patients who underwent EEG monitoring after cardiac arrest, we created 100 CDSA images, 30% of which displayed seizures. The gold standard for seizure category was electroencephalographer determination from the full montage conventional EEG. Participants did not have access to the conventional EEG tracings. After completing a standardized CDSA tutorial, images were presented to participants in duplicate and in random order. Twenty critical care physicians (12 attendings and 8 fellows) and 19 critical care nurses classified the CDSA images as having any seizure(s) or no seizures. The 39 critical care providers had a CDSA seizure detection sensitivity of 70% [95% CI: 67%, 73%], specificity of 68% [95% CI: 67%, 70%], positive predictive value of 46%, and negative predictive value of 86%. The sensitivity of CDSA detection of status epilepticus was 72% [95% CI: 69%, 74%]. Conclusion Determining which post-cardiac arrest patients experience electrographic seizures by critical care providers is feasible after a brief training. There is moderate sensitivity for seizure and status epilepticus detection and a high negative predictive value. PMID:25651050

  2. Voice activity detection for speaker verification systems

    NASA Astrophysics Data System (ADS)

    Borowski, Filip

    2008-01-01

    Complex algorithm for speech activity detection was presented in this article. It is based on speech enhancement, features extraction and final detection algorithm. The first one was published in ETSI standard as a module of "Advanced front-end feature extraction algorithm" in distributed speech recognition system. It consists of two main parts, noise estimatiom and Wiener filtering. For the final detection modified linear prediction coefficients and spectral entropy features are extracted form denoised signal.

  3. Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy

    PubMed Central

    Wagner, Kay-Dietrich; Vukolic, Ana; Baudouy, Delphine; Michiels, Jean-François

    2016-01-01

    Peroxisome proliferator-activated receptors are nuclear receptors which function as ligand-activated transcription factors. Among them, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in the heart and thought to have cardioprotective functions due to its beneficial effects in metabolic syndrome. As we already showed that PPARβ/δ activation resulted in an enhanced cardiac angiogenesis and growth without impairment of heart function, we were interested to determine the effects of a specific activation of PPARβ/δ in the vasculature on cardiac performance under normal and in chronic ischemic heart disease conditions. We analyzed the effects of a specific PPARβ/δ overexpression in endothelial cells on the heart using an inducible conditional vascular-specific mouse model. We demonstrate that vessel-specific overexpression of PPARβ/δ induces rapid cardiac angiogenesis and growth with an increase in cardiomyocyte size. Upon myocardial infarction, vascular overexpression of PPARβ/δ, despite the enhanced cardiac vessel formation, does not protect against chronic ischemic injury. Our results suggest that the proper balance of PPARβ/δ activation in the different cardiac cell types is required to obtain beneficial effects on the outcome in chronic ischemic heart disease. PMID:27057154

  4. Detecting active comets with SDSS

    SciTech Connect

    Solontoi, Michael; Ivezic, Zeljko; West, Andrew A.; Claire, Mark; Juric, Mario; Becker, Andrew; Jones, Lynne; Hall, Patrick B.; Kent, Steve; Lupton, Robert H.; Quinn, Tom; /Washington U., Seattle, Astron. Dept. /Princeton U. Observ.

    2010-12-01

    Using a sample of serendipitously discovered active comets in the Sloan Digital Sky Survey (SDSS), we develop well-controlled selection criteria for greatly increasing the efficiency of comet identification in the SDSS catalogs. After follow-up visual inspection of images to reject remaining false positives, the total sample of SDSS comets presented here contains 19 objects, roughly one comet per 10 million other SDSS objects. The good understanding of selection effects allows a study of the population statistics, and we estimate the apparent magnitude distribution to r {approx} 18, the ecliptic latitude distribution, and the comet distribution in SDSS color space. The most surprising results are the extremely narrow range of colors for comets in our sample (e.g. root-mean-square scatter of only {approx}0.06 mag for the g-r color), and the similarity of comet colors to those of jovian Trojans. We discuss the relevance of our results for upcoming deep multi-epoch optical surveys such as the Dark Energy Survey, Pan-STARRS, and the Large Synoptic Survey Telescope (LSST), and estimate that LSST may produce a sample of about 10,000 comets over its 10-year lifetime.

  5. Mechanisms of Electrical Activation and Conduction in the Gastrointestinal System: Lessons from Cardiac Electrophysiology.

    PubMed

    Tse, Gary; Lai, Eric Tsz Him; Yeo, Jie Ming; Tse, Vivian; Wong, Sunny Hei

    2016-01-01

    The gastrointestinal (GI) tract is an electrically excitable organ system containing multiple cell types, which coordinate electrical activity propagating through this tract. Disruption in its normal electrophysiology is observed in a number of GI motility disorders. However, this is not well characterized and the field of GI electrophysiology is much less developed compared to the cardiac field. The aim of this article is to use the established knowledge of cardiac electrophysiology to shed light on the mechanisms of electrical activation and propagation along the GI tract, and how abnormalities in these processes lead to motility disorders and suggest better treatment options based on this improved understanding. In the first part of the article, the ionic contributions to the generation of GI slow wave and the cardiac action potential (AP) are reviewed. Propagation of these electrical signals can be described by the core conductor theory in both systems. However, specifically for the GI tract, the following unique properties are observed: changes in slow wave frequency along its length, periods of quiescence, synchronization in short distances and desynchronization over long distances. These are best described by a coupled oscillator theory. Other differences include the diminished role of gap junctions in mediating this conduction in the GI tract compared to the heart. The electrophysiology of conditions such as gastroesophageal reflux disease and gastroparesis, and functional problems such as irritable bowel syndrome are discussed in detail, with reference to ion channel abnormalities and potential therapeutic targets. A deeper understanding of the molecular basis and physiological mechanisms underlying GI motility disorders will enable the development of better diagnostic and therapeutic tools and the advancement of this field. PMID:27303305

  6. Mechanisms of Electrical Activation and Conduction in the Gastrointestinal System: Lessons from Cardiac Electrophysiology

    PubMed Central

    Tse, Gary; Lai, Eric Tsz Him; Yeo, Jie Ming; Tse, Vivian; Wong, Sunny Hei

    2016-01-01

    The gastrointestinal (GI) tract is an electrically excitable organ system containing multiple cell types, which coordinate electrical activity propagating through this tract. Disruption in its normal electrophysiology is observed in a number of GI motility disorders. However, this is not well characterized and the field of GI electrophysiology is much less developed compared to the cardiac field. The aim of this article is to use the established knowledge of cardiac electrophysiology to shed light on the mechanisms of electrical activation and propagation along the GI tract, and how abnormalities in these processes lead to motility disorders and suggest better treatment options based on this improved understanding. In the first part of the article, the ionic contributions to the generation of GI slow wave and the cardiac action potential (AP) are reviewed. Propagation of these electrical signals can be described by the core conductor theory in both systems. However, specifically for the GI tract, the following unique properties are observed: changes in slow wave frequency along its length, periods of quiescence, synchronization in short distances and desynchronization over long distances. These are best described by a coupled oscillator theory. Other differences include the diminished role of gap junctions in mediating this conduction in the GI tract compared to the heart. The electrophysiology of conditions such as gastroesophageal reflux disease and gastroparesis, and functional problems such as irritable bowel syndrome are discussed in detail, with reference to ion channel abnormalities and potential therapeutic targets. A deeper understanding of the molecular basis and physiological mechanisms underlying GI motility disorders will enable the development of better diagnostic and therapeutic tools and the advancement of this field. PMID:27303305

  7. Plasma cardiac natriuretic peptide determination as a screening test for the detection of patients with mild left ventricular impairment.

    PubMed Central

    Omland, T.; Aakvaag, A.; Vik-Mo, H.

    1996-01-01

    OBJECTIVE: To determine the usefulness of measuring the cardiac natriuretic peptides, atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and brain natriuretic peptide, as screening tests for identifying patients with mild left ventricular impairment. DESIGN: Cross-sectional evaluation of the diagnostic accuracy of the cardiac natriuretic peptides. SETTING: Cardiac catheterisation unit, Norwegian central hospital. PATIENTS: A consecutive series of 254 patients undergoing diagnostic left-sided cardiac catheterisation. One hundred and twenty eight of these patients had a history of previous myocardial infarction. MAIN OUTCOME MEASURES: The presence of normal and impaired left ventricular function, as evaluated by logistic regression analysis and estimation of the area under the receiver operating characteristic (ROC) curve (an index of overall diagnostic accuracy). Ventricular function was assessed by the measurement of left ventricular end diastolic pressure and angiographically determined left ventricular ejection fraction. RESULTS: Logistic regression analysis showed that plasma brain natriuretic peptide was the best predictor of increased left ventricular end diastolic pressure (> or = 15 mm Hg) (P < 0.001), decreased left ventricular ejection fraction (< or = 45%) (P < 0.001), and the combination of left ventricular ejection fraction < or = 45% and left ventricular end diastolic pressure > or = 15 mm Hg (P < 0.001). The areas under the ROC function for the detection of left ventricular dysfunction were 0.789 for brain natriuretic peptide, 0.665 for atrial natriuretic factor, and 0.610 for N-terminal pro-atrial natriuretic factor. CONCLUSIONS: Plasma brain natriuretic peptide seemed to be a better indicator of left ventricular function than plasma atrial natriuretic factor or N-terminal pro-atrial natriuretic factor. However, the overall diagnostic accuracy of circulating atrial natriuretic factor, N-terminal pro-atrial natriuretic factor, and

  8. Cardiac conduction system

    MedlinePlus Videos and Cool Tools

    ... cardiac muscle cells in the walls of the heart that send signals to the heart muscle causing it to contract. The main components ... the cardiac conduction system’s electrical activity in the heart.

  9. Role of Nongenomic Signaling Pathways Activated by Aldosterone During Cardiac Reperfusion Injury.

    PubMed

    Ashton, Anthony W; Le, Thi Y L; Gomez-Sanchez, Celso E; Morel-Kopp, Marie-Christine; McWhinney, Brett; Hudson, Amanda; Mihailidou, Anastasia S

    2015-08-01

    Aldosterone (Aldo) activates both genomic and nongenomic signaling pathways in the cardiovascular system. Activation of genomic signaling pathways contributes to the adverse cardiac actions of Aldo during reperfusion injury; however, the extent nongenomic signaling pathways contribute has been difficult to identify due to lack of a specific ligand that activates only nongenomic signaling pathways. Using a pegylated aldosterone analog, aldosterone-3-carboxymethoxylamine-TFP ester conjugated to methoxypegylated amine (Aldo-PEG), we are able for the first time to distinguish between nongenomic and genomic cardiac actions of Aldo. We confirm Aldo-PEG activates phosphorylation of ERK1/2 in rat cardiomyocyte H9c2 cells similar to Aldo and G protein-coupled receptor 30 (GPR30 or GPER) agonist G1. GPER antagonist, G36, but not mineralocorticoid receptor (MR) antagonist spironolactone, prevented ERK1/2 phosphorylation by Aldo, Aldo-PEG, and G1. The selective nongenomic actions of Aldo-PEG are confirmed, with Aldo-PEG increasing superoxide production in H9c2 cells to similar levels as Aldo but having no effect on subcellular localization of MR. Striatin serves as a scaffold for GPER and MR, with GPER antagonist G36, but not spironolactone, restoring MR-striatin complexes. Aldo-PEG had no effect on MR-dependent transcriptional activation, whereas Aldo increased transcript levels of serum-regulated kinase 1 and plasminogen activator inhibitor-1. Using our ex vivo experimental rat model of myocardial infarction, we found aggravated infarct size and apoptosis by Aldo but not Aldo-PEG. Our studies confirm that in the heart, activation of nongenomic signaling pathways alone are not sufficient to trigger the deleterious effects of aldosterone during myocardial reperfusion injury. PMID:26121234

  10. Real-time x-ray fluoroscopy-based catheter detection and tracking for cardiac electrophysiology interventions

    SciTech Connect

    Ma Yingliang; Housden, R. James; Razavi, Reza; Rhode, Kawal S.; Gogin, Nicolas; Cathier, Pascal; Gijsbers, Geert; Cooklin, Michael; O'Neill, Mark; Gill, Jaswinder; Rinaldi, C. Aldo

    2013-07-15

    Purpose: X-ray fluoroscopically guided cardiac electrophysiology (EP) procedures are commonly carried out to treat patients with arrhythmias. X-ray images have poor soft tissue contrast and, for this reason, overlay of a three-dimensional (3D) roadmap derived from preprocedural volumetric images can be used to add anatomical information. It is useful to know the position of the catheter electrodes relative to the cardiac anatomy, for example, to record ablation therapy locations during atrial fibrillation therapy. Also, the electrode positions of the coronary sinus (CS) catheter or lasso catheter can be used for road map motion correction.Methods: In this paper, the authors present a novel unified computational framework for image-based catheter detection and tracking without any user interaction. The proposed framework includes fast blob detection, shape-constrained searching and model-based detection. In addition, catheter tracking methods were designed based on the customized catheter models input from the detection method. Three real-time detection and tracking methods are derived from the computational framework to detect or track the three most common types of catheters in EP procedures: the ablation catheter, the CS catheter, and the lasso catheter. Since the proposed methods use the same blob detection method to extract key information from x-ray images, the ablation, CS, and lasso catheters can be detected and tracked simultaneously in real-time.Results: The catheter detection methods were tested on 105 different clinical fluoroscopy sequences taken from 31 clinical procedures. Two-dimensional (2D) detection errors of 0.50 {+-} 0.29, 0.92 {+-} 0.61, and 0.63 {+-} 0.45 mm as well as success rates of 99.4%, 97.2%, and 88.9% were achieved for the CS catheter, ablation catheter, and lasso catheter, respectively. With the tracking method, accuracies were increased to 0.45 {+-} 0.28, 0.64 {+-} 0.37, and 0.53 {+-} 0.38 mm and success rates increased to 100%, 99

  11. Remote detection of mental workload changes using cardiac parameters assessed with a low-cost webcam.

    PubMed

    Bousefsaf, Frédéric; Maaoui, Choubeila; Pruski, Alain

    2014-10-01

    We introduce a new framework for detecting mental workload changes using video frames obtained from a low-cost webcam. Image processing in addition to a continuous wavelet transform filtering method were developed and applied to remove major artifacts and trends on raw webcam photoplethysmographic signals. The measurements are performed on human faces. To induce stress, we have employed a computerized and interactive Stroop color word test on a set composed by twelve participants. The electrodermal activity of the participants was recorded and compared to the mental workload curve assessed by merging two parameters derived from the pulse rate variability and photoplethysmographic amplitude fluctuations, which reflect peripheral vasoconstriction changes. The results exhibit strong correlation between the two measurement techniques. This study offers further support for the applicability of mental workload detection by remote and low-cost means, providing an alternative to conventional contact techniques. PMID:25150821

  12. Cardiac Magnetic Resonance Imaging Might Complement Two-Dimensional Echocardiography in the Detection of a Reversible Nonischemic Cardiomyopathy

    PubMed Central

    Madanieh, Raef; Mathew, Shawn; Shah, Pratik; Vatti, Satya K.; Madanieh, Abed; Kosmas, Constantine E.; Vittorio, Timothy J.

    2015-01-01

    We report a case of reversible nonischemic dilated cardiomyopathy in a male in his 60s who presented with an acute heart failure syndrome. Both conventional two-dimensional echocardiography and cardiac magnetic resonance imaging (cMRI) demonstrated severe left ventricular systolic dysfunction; however, both modalities were devoid of significant valvular heart disease as well as the presence of fibrosis, infiltration, inflammation, and scar. After six months of aggressive neurohumoral modulation, there was complete reverse remodeling and normalization of left ventricular function, which highlights the role of cMRI as an adjunct to two-dimensional echocardiography in the detection of a potentially reversible nonischemic cardiomyopathy. PMID:26740746

  13. Preconcentration and detection of the phosphorylated forms of cardiac troponin I in a cascade microchip by cationic isotachophoresis.

    PubMed

    Bottenus, Danny; Hossan, Mohammad Robiul; Ouyang, Yexin; Dong, Wen-Ji; Dutta, Prashanta; Ivory, Cornelius F

    2011-11-21

    This paper describes the detection of a cardiac biomarker, cardiac troponin I (cTnI), spiked into depleted human serum using cationic isotachophoresis (ITP) in a 3.9 cm long poly(methyl methacrylate) (PMMA) microfluidic channel. The microfluidic chip incorporates a 100× cross-sectional area reduction, including a 10× depth reduction and a 10× width reduction, to increase sensitivity during ITP. The cross-sectional area reductions in combination with ITP allowed visualization of lower concentrations of fluorescently labeled cTnI. ITP was performed in both "peak mode" and "plateau mode" and the final concentrations obtained were linear with initial cTnI concentration. We were able to detect and quantify cTnI at initial concentrations as low as 46 ng mL(-1) in the presence of human serum proteins and obtain cTnI concentrations factors as high as ~ 9000. In addition, preliminary ITP experiments including both labeled cTnI and labeled protein kinase A (PKA) phosphorylated cTnI were performed to visualize ITP migration of different phosphorylated forms of cTnI. The different phosphorylated states of cTnI formed distinct ITP zones between the leading and terminating electrolytes. To our knowledge, this is the first attempt at using ITP in a cascade microchip to quantify cTnI in human serum and detect different phosphorylated forms. PMID:21935555

  14. Preconcentration and detection of the phosphorylated forms of cardiac troponin I in a cascade microchip by cationic isotachophoresis†

    PubMed Central

    Bottenus, Danny; Hossan, Mohammad Robiul; Ouyang, Yexin; Dong, Wen-Ji; Dutta, Prashanta; Ivory, Cornelius F.

    2011-01-01

    This paper describes the detection of a cardiac biomarker, cardiac troponin I (cTnI), spiked into depleted human serum using cationic isotachophoresis (ITP) in a 3.9 cm long poly(methyl methacrylate) (PMMA) microfluidic channel. The microfluidic chip incorporates a 100x cross-sectional area reduction, including a 10x depth reduction and a 10x width reduction, to increase sensitivity during ITP. The cross-sectional area reductions in combination with ITP allowedvisualization of lower concentrations of fluorescently labeled cTnI. ITP was performed in both “peak mode” and “plateau mode” and the final concentrations obtained were linear with initial cTnI concentration. We were able to detect and quantify cTnI at initial concentrations as low as 46 ng mL−1 in the presence of human serum proteins and obtain cTnI concentrations factors as high as ~ 9000. In addition, preliminary ITP experiments including both labeled cTnI and labeled protein kinase A (PKA) phosphorylated cTnI were performed to visualize ITP migration of different phosphorylated forms ofcTnI. The different phosphorylated states of cTnI formed distinct ITP zones between the leading and terminating electrolytes. To our knowledge, this is the first attempt at using ITP in a cascade microchip to quantify cTnI in human serum and detect different phosphorylated forms. PMID:21935555

  15. Xanthine oxidase, but not neutrophils, contributes to activation of cardiac sympathetic afferents during myocardial ischaemia in cats

    PubMed Central

    Tjen-A-Looi, Stephanie C; Fu, Liang-Wu; Longhurst, John C

    2002-01-01

    Activation of cardiac sympathetic afferents during myocardial ischaemia causes angina and induces important cardiovascular reflex responses. Reactive oxygen species (ROS) are important chemical stimuli of cardiac afferents during and after ischaemia. Iron-catalysed Fenton chemistry constitutes one mechanism of production of hydroxyl radicals. Another potential source of these species is xanthine oxidase-catalysed oxidation of purines. Polymorphonuclear leukocytes (PMNs) also contribute to the production of ROS in some conditions. The present study tested the hypothesis that both xanthine oxidase-catalysed oxidation of purines and neutrophils provide a source of ROS sufficient to activate cardiac afferents during ischaemia. We recorded single-unit activity of cardiac afferents innervating the ventricles recorded from the left thoracic sympathetic chain (T1-5) of anaesthetized cats to identify the afferents' responses to ischaemia. The role of xanthine oxidase in activation of these afferents was determined by infusion of oxypurinol (10 mg kg−1, i.v.), an inhibitor of xanthine oxidase. The importance of neutrophils as a potential source of ROS in the activation of cardiac afferents during ischaemia was assessed by the infusion of a polyclonal antibody (3 mg ml−1 kg−1, i.v.) raised in rabbits immunized with cat PMNs. This antibody decreased the number of circulating PMNs and, to a smaller extent, platelets. Since previous data suggest that platelets release serotonin (5-HT), which activates cardiac afferents through a serotonin receptor (subtype 3,5-HT3 receptor) mechanism, before treatment with the antibody in another group, we blocked 5-HT3 receptors on sensory nerve endings with tropisetron (300 μg kg−1, i.v.). We observed that oxypurinol significantly decreased the activity of cardiac afferents during myocardial ischaemia from 1.5 ± 0.4 to 0.8 ± 0.4 impulses s−1. Similarly, the polyclonal antibody significantly reduced the discharge frequency of

  16. Ion channel modifying agents influence the electrical activity generated by canine intrinsic cardiac neurons in situ.

    PubMed

    Thompson, G W; Horackova, M; Armour, J A

    2000-04-01

    This study was designed to establish whether agents known to modify neuronal ion channels influence the behavior of mammalian intrinsic cardiac neurons in situ and, if so, in a manner consistent with that found previously in vitro. The activity generated by right atrial neurons was recorded extracellularly in varying numbers of anesthetized dogs before and during continuous local arterial infusion of several neuronal ion channel modifying agents. Veratridine (7.5 microM), the specific modifier of Na+-selective channels, increased neuronal activity (95% above control) in 80% of dogs tested (n = 25). The membrane depolarizing agent potassium chloride (40 mM) reduced neuronal activity (43% below control) in 84% of dogs tested (n = 19). The inhibitor of voltage-sensitive K+ channels, tetraethylammonium (10 mM), decreased neuronal activity (42% below control) in 73% of dogs tested (n = 11). The nonspecific potassium channel inhibitor barium chloride (5 mM) excited neurons (47% above control) in 13 of 19 animals tested. Cadmium chloride (200 microM), which inhibits Ca2+-selective channels and Ca2+-dependent K+ channels, increased neuronal activity (65% above control) in 79% of dogs tested (n = 14). The specific L-type Ca2+ channel blocking agent nifedipine (5 microM) reduced neuronal activity (52% blow control in 72% of 11 dogs tested), as did the nonspecific inhibitor of L-type Ca2+ channels, nickel chloride (5 mM) (36% below control in 69% of 13 dogs tested). Each agent induced either excitatory or inhibitory responses, depending on the agent tested. It is concluded that specific ion channels (I(Na), I(CaL), I(Kv), and I(KCa)) that have been associated with intrinsic cardiac neurons in vitro are involved in their capacity to generate action potentials in situ. PMID:10772056

  17. Cardiac-locked bursts of muscle sympathetic nerve activity are absent in familial dysautonomia

    PubMed Central

    Macefield, Vaughan G; Norcliffe-Kaufmann, Lucy; Axelrod, Felicia B; Kaufmann, Horacio

    2013-01-01

    Familial dysautonomia (Riley–Day syndrome) is an hereditary sensory and autonomic neuropathy (HSAN type III), expressed at birth, that is associated with reduced pain and temperature sensibilities and absent baroreflexes, causing orthostatic hypotension as well as labile blood pressure that increases markedly during emotional excitement. Given the apparent absence of functional baroreceptor afferents, we tested the hypothesis that the normal cardiac-locked bursts of muscle sympathetic nerve activity (MSNA) are absent in patients with familial dysautonomia. Tungsten microelectrodes were inserted percutaneously into muscle or cutaneous fascicles of the common peroneal nerve in 12 patients with familial dysautonomia. Spontaneous bursts of MSNA were absent in all patients, but in five patients we found evidence of tonically firing sympathetic neurones, with no cardiac rhythmicity, that increased their spontaneous discharge during emotional arousal but not during a manoeuvre that unloads the baroreceptors. Conversely, skin sympathetic nerve activity (SSNA), recorded in four patients, appeared normal. We conclude that the loss of phasic bursts of MSNA and the loss of baroreflex modulation of muscle vasoconstrictor drive contributes to the poor control of blood pressure in familial dysautonomia, and that the increase in tonic firing of muscle vasoconstrictor neurones contributes to the increase in blood pressure during emotional excitement. PMID:23165765

  18. Ising model of cardiac thin filament activation with nearest-neighbor cooperative interactions

    NASA Technical Reports Server (NTRS)

    Rice, John Jeremy; Stolovitzky, Gustavo; Tu, Yuhai; de Tombe, Pieter P.; Bers, D. M. (Principal Investigator)

    2003-01-01

    We have developed a model of cardiac thin filament activation using an Ising model approach from equilibrium statistical physics. This model explicitly represents nearest-neighbor interactions between 26 troponin/tropomyosin units along a one-dimensional array that represents the cardiac thin filament. With transition rates chosen to match experimental data, the results show that the resulting force-pCa (F-pCa) relations are similar to Hill functions with asymmetries, as seen in experimental data. Specifically, Hill plots showing (log(F/(1-F)) vs. log [Ca]) reveal a steeper slope below the half activation point (Ca(50)) compared with above. Parameter variation studies show interplay of parameters that affect the apparent cooperativity and asymmetry in the F-pCa relations. The model also predicts that Ca binding is uncooperative for low [Ca], becomes steeper near Ca(50), and becomes uncooperative again at higher [Ca]. The steepness near Ca(50) mirrors the steep F-pCa as a result of thermodynamic considerations. The model also predicts that the correlation between troponin/tropomyosin units along the one-dimensional array quickly decays at high and low [Ca], but near Ca(50), high correlation occurs across the whole array. This work provides a simple model that can account for the steepness and shape of F-pCa relations that other models fail to reproduce.

  19. Perfectionism and Effort-Related Cardiac Activity: Do Perfectionists Try Harder?

    PubMed Central

    Harper, Kelly L.; Eddington, Kari M.; Silvia, Paul J.

    2016-01-01

    Do perfectionists try harder? Previous research on perfectionism and effort has used self-report items and task performance as indicators of effort. The current study investigated whether individual differences in perfectionism predicted effort-related cardiac activity during a mental effort task. Based on past research that suggests adaptive perfectionism is associated with higher effort, it was hypothesized that self-oriented perfectionism (SOP) would predict increased effort on the task. One hundred and eleven college students completed the Multidimensional Perfectionism Scale (MPS) and a self-paced parity task in which they received a small cash reward (3 cents) for each correct response. Impedance cardiography was used to assess autonomic reactivity, and regression models tested whether SOP and socially prescribed perfectionism (SPP) explained autonomic reactivity. Overall, participants showed both sympathetic (faster pre-ejection period; PEP) and parasympathetic activation (elevated high-frequency heart rate variability; HRV) during the task, reflecting higher effort and engagement. Contrary to predictions, individual differences in perfectionism did not moderate cardiac reactivity. These findings draw attention to the importance of assessing physiological components of effort and motivation directly rather than inferring them from task performance or self-reported effort. PMID:27483467

  20. Comparing the accuracy of ES-BC, EIS-GS, and ES Oxi on body composition, autonomic nervous system activity, and cardiac output to standardized assessments

    PubMed Central

    Lewis, John E; Tannenbaum, Stacey L; Gao, Jinrun; Melillo, Angelica B; Long, Evan G; Alonso, Yaima; Konefal, Janet; Woolger, Judi M; Leonard, Susanna; Singh, Prabjot K; Chen, Lawrence; Tiozzo, Eduard

    2011-01-01

    Background and purpose The Electro Sensor Complex (ESC) is software that combines three devices using bioelectrical impedance, galvanic skin response, and spectrophotometry: (1) ES-BC (Electro Sensor-Body Composition; LD Technology, Miami, FL) to assess body composition, (2) EIS-GS (Electro Interstitial Scan-Galvanic Skin; LD Technology) to predict autonomic nervous system activity, and (3) ES Oxi (Electro Sensor Oxi; LD Technology) to assess cardiac output. The objective of this study was to compare each to a standardized assessment: ES-BC to dual-energy X-ray absorptiometry (DXA), EIS-GS to heart rate variability, and ES Oxi to BioZ Dx Diagnostic System (BioZ Dx; SonoSite Inc, Bothell, WA). Patients and methods The study was conducted in two waves. Fifty subjects were assessed for body composition and autonomic nervous system activity. Fifty-one subjects were assessed for cardiac output. Results We found adequate relative and absolute agreement between ES-BC and DXA for fat mass (r = 0.97, P < 0.001) with ES-BC overestimating fat mass by 0.1 kg and for body fat percentage (r = 0.92, P < 0.001) with overestimation of fat percentage by 0.4%. For autonomic nervous system activity, we found marginal relative agreement between EIS-GS and heart rate variability by using EIS-GS as the predictor in a linear regression equation (adjusted R2 = 0.56, P = 0.03). For cardiac output, adequate relative and absolute agreement was found between ES Oxi and BioZ Dx at baseline (r = 0.60, P < 0.001), after the first exercise stage (r = 0.79, P < 0.001), and after the second exercise stage (r = 0.86, P < 0.001). Absolute agreement was found at baseline and after both bouts of exercise; ES Oxi overestimated baseline and stage 1 exercise cardiac output by 0.3 L/minute and 0.1 L/minute, respectively, but exactly estimated stage 2 exercise cardiac output. Conclusion ES-BC and ES Oxi accurately assessed body composition and cardiac output compared to standardized instruments, whereas EIS

  1. Tissue Plasminogen Activator Use in Cardiac Arrest Secondary to Fulminant Pulmonary Embolism

    PubMed Central

    Yousuf, Tariq; Brinton, Taylor; Ahmed, Khansa; Iskander, Joy; Woznicka, Daniel; Kramer, Jason; Kopiec, Adam; Chadaga, Amar R.; Ortiz, Kathia

    2016-01-01

    Background Tissue plasminogen activator (tPA) is used emergently to dissolve thrombi in the treatment of fulminant pulmonary embolism. Currently, there is a relative contraindication to tPA in the setting of traumatic or prolonged cardiopulmonary resuscitation > 10 minutes because of the risk of massive hemorrhage. Methods Our single-center, retrospective study investigated patients experiencing cardiac arrest (CA) secondary to pulmonary embolus. We compared the effectiveness of advanced cardiac life support with the administration of tPA vs. the standard of care consisting of advanced cardiac life support without thrombolysis. The primary endpoint was survival to discharge. Secondary endpoints were return of spontaneous circulation (ROSC), major bleeding, and minor bleeding. Results We analyzed 42 patients, of whom 19 received tPA during CA. Patients who received tPA were not associated with a statistically significant increase in survival to discharge (10.5% vs. 8.7%, P = 1.00) or ROSC (47.4% vs. 47.8%, P = 0.98) compared to the control group. We observed no statistically significant difference between the groups in major bleeding events (5.3% in the tPA group vs. 4.3% in the control group, P = 1.00) and minor bleeding events (10.5% in the tPA group vs. 0.0% in the control group, P = 0.11). Conclusion This study did not find a statistically significant difference in survival to discharge or in ROSC in patients treated with tPA during CA compared to patients treated with standard therapy. However, because no significant difference was found in major or minor bleeding, we suggest that the potential therapeutic benefits of this medication should not be limited by the potential for massive hemorrhage. Larger prospective studies are warranted to define the efficacy and safety profile of thrombolytic use in this population. PMID:26858790

  2. Self-reported physical activity and lung function two months after cardiac surgery – a prospective cohort study

    PubMed Central

    2014-01-01

    Background Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Methods Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health’s national survey. Formal lung function testing was performed preoperatively and two months postoperatively. Results The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). Conclusions An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results. PMID:24678691

  3. Cardiac CT for myocardial ischaemia detection and characterization—comparative analysis

    PubMed Central

    Bucher, A M; De Cecco, C N; Wang, R; Meinel, F G; Binukrishnan, S R; Spearman, J V; Vogl, T J; Ruzsics, B

    2014-01-01

    The assessment of patients presenting with symptoms of myocardial ischaemia remains one of the most common and challenging clinical scenarios faced by physicians. Current imaging modalities are capable of three-dimensional, functional and anatomical views of the heart and as such offer a unique contribution to understanding and managing the pathology involved. Evidence has accumulated that visual anatomical coronary evaluation does not adequately predict haemodynamic relevance and should be complemented by physiological evaluation, highlighting the importance of functional assessment. Technical advances in CT technology over the past decade have progressively moved cardiac CT imaging into the clinical workflow. In addition to anatomical evaluation, cardiac CT is capable of providing myocardial perfusion parameters. A variety of CT techniques can be used to assess the myocardial perfusion. The single energy first-pass CT and dual energy first-pass CT allow static assessment of myocardial blood pool. Dynamic cardiac CT imaging allows quantification of myocardial perfusion through time-resolved attenuation data. CT-based myocardial perfusion imaging (MPI) is showing promising diagnostic accuracy compared with the current reference modalities. The aim of this review is to present currently available myocardial perfusion techniques with a focus on CT imaging in light of recent clinical investigations. This article provides a comprehensive overview of currently available CT approaches of static and dynamic MPI and presents the results of corresponding clinical trials. PMID:25135617

  4. Activation of mitochondrial STAT-3 and reduced mitochondria damage during hypothermia treatment for post-cardiac arrest myocardial dysfunction.

    PubMed

    Huang, Chien-Hua; Tsai, Min-Shan; Chiang, Chih-Yen; Su, Yu-Jen; Wang, Tzung-Dau; Chang, Wei-Tien; Chen, Huei-Wen; Chen, Wen-Jone

    2015-11-01

    While therapeutic hypothermia improves the outcomes of individuals in cardiac arrest, the hemodynamic responses and mechanisms which underlie hypothermia-induced cardioprotection are not fully understood. Therefore, we investigated the mechanism by which induced hypothermia preserves cardiac function and protects against mitochondrial damage following cardiac arrest. Cardiac arrest was induced in adult male Wistar rats by asphyxiation for 8.5 min. Following resuscitation, the animals were randomly assigned to a hypothermia (32 °C) or normothermia (37 °C) group. Monitoring results showed that cardiac output at the fourth hour after resuscitation was significantly better in rats treated with hypothermia when compared to rats treated with normothermia (P < 0.01). Examinations by transmission electron microscopy showed that mitochondria in the left ventricle of rats in the hypothermia group were significantly less swollen compared to such mitochondria in the normothermia group (P < 0.001). Additionally, opening of mitochondrial permeability transition pores occurred less frequently in the hypothermic group. While complex I/III activity in the electron transport reaction was damaged after cardiac arrest and resuscitation, the degree of injury was ameliorated by hypothermia treatment (P < 0.05). The amount of STAT-3 phosphorylated at tyrosine 705 and its expression in mitochondria were significantly higher under hypothermia treatment compared to normothermia treatment. In vitro studies showed that inhibition STAT-3 activation abolished the ability of hypothermia to protect H9C2 cardiomyocytes against injury produced by simulated ischemia and reperfusion. Therapeutic hypothermia treatment can ameliorate cardiac dysfunction and help preserve both mitochondrial integrity and electron transport activity. PMID:26471891

  5. Prostacyclin Analogue Beraprost Inhibits Cardiac Fibroblast Proliferation Depending on Prostacyclin Receptor Activation through a TGF β-Smad Signal Pathway

    PubMed Central

    Yao, Wenjuan; Zhu, Hongyan; Xu, Xiaole; Meng, Guoliang; Zhang, Wei

    2014-01-01

    Previous studies showed that prostacyclin inhibited fibrosis. However, both receptors of prostacyclin, prostacyclin receptor (IP) and peroxisome proliferator-activated receptor (PPAR), are abundant in cardiac fibroblasts. Here we investigated which receptor was vital in the anti-fibrosis effect of prostacyclin. In addition, the possible mechanism involved in protective effects of prostacyclin against cardiac fibrosis was also studied. We found that beraprost, a prostacyclin analogue, inhibited angiotensin II (Ang II)-induced neonatal rat cardiac fibroblast proliferation in a concentration-dependent and time-dependent manner. Beraprost also suppressed Ang II-induced collagen I mRNA expression and protein synthesis in cardiac fibroblasts. After IP expression was knocked down by siRNA, Ang II-induced proliferation and collagen I synthesis could no longer be rescued by beraprost. However, treating cells with different specific inhibitors of PPAR subtypes prior to beraprost and Ang II stimulation, all of the above attenuating effects of beraprost were still available. Moreover, beraprost significantly blocked transforming growth factor β (TGF β) expression as well as Smad2 phosphorylation and reduced Smad-DNA binding activity. Beraprost also increased phosphorylation of cAMP response element binding protein (CREB) at Ser133 in the nucleus. Co-immunoprecipitation analysis revealed that beraprost increased CREB but decreased Smad2 binding to CREB-binding protein (CBP) in nucleus. In conclusion, beraprost inhibits cardiac fibroblast proliferation by activating IP and suppressing TGF β-Smad signal pathway. PMID:24852754

  6. Activation of AMP-activated protein kinase reduces collagen production via p38 MAPK in cardiac fibroblasts induced by coxsackievirus B3.

    PubMed

    Jiang, Shengyang; Jiang, Donglin; Zhao, Peng; He, Xinlong; Tian, Shunli; Wu, Xueming; Tao, Yijia

    2016-07-01

    Collagen deposition is the major cause of myocardial fibrosis, contributing to impaired cardiac contractile function in coxsackie virus B3 (CVB3)-infected hearts. Adenosine monophosphate-activated protein kinase (AMPK) has been considered as a cellular fuel gauge and super metabolic regulator, however, whether AMPK has an effect on collagen production in CVB3‑infected heart remains to be elucidated. In the present study, the association between AMPK activation and CVB3‑infected neonatal rat cardiac fibroblasts (NRCFs) was investigated. Collagen production was determined by the hydroxyproline content of the supernatant and by the expression of type I/IV collagen in the cell lysate. Rat hydroxyproline ELISA was used to detect hydroxyproline content in the supernatant. The expression of type I/IV collagen, and the phosphorylation of AMPKα‑Thr172 and p38 in the cell lysate were evaluated using western blotting. As expected, it was found that the hydroxyproline content in the supernatant, and the production of collagen I/IV in the cell lysate were significantly promoted at 48 h post‑CVB3‑infection. However, this effect was inhibited in a dose‑dependent manner when pretreated with 5‑aminoimidazole‑4‑carboxamide‑1‑4‑ribofuranoside (AICAR) for 2 h prior to CVB3‑infection. However, if the cells were preincubated with compound C or SB203580 for 30 min prior the treatment with AICAR, the inhibitive effects of AICAR were reversed. The results of the western blotting indicated that the phosphorylation of AMPKα‑Thr172 and p38 were significantly increased by AICAR in the NRCFs. However, only the phosphorylation of p38 mitogen‑activated protein kinase (MAPK) was inhibited by SB203580. In conclusion, AMPK activation reduced collagen production via the p38 MAPK‑dependent pathway in the cardiac fibroblasts induced by CVB3. The results of the present study may contribute to identifying an effective therapy for CVB3‑induced myocarditis and CVB3

  7. Active contraction of the cardiac ventricle and distortion of the microstructural architecture.

    PubMed

    Pezzuto, S; Ambrosi, D

    2014-12-01

    The shortening of the myocardial fibers is the microstructural engine that produces the contraction of the cardiac muscle. The complex interplay between fibers shortening and elastic macroscopic strain is functional to the ejection of blood into the pulmonary and arterial networks. Here, we address the contraction of the left ventricle in a finite elasticity framework, adopting the 'prolate ellipsoid' geometry and the invariants-based strain energy proposed by Holzapfel and Ogden, where the mechanical role of fibers and sheets is accounted for. We show that a microstructurally motivated mathematical model of active strain type reproduces the main indicators of normal cardiac function along the whole PV-loop without introduction of any further ad hoc law. The bare-bones mathematical model depends on one measurable parameter only, that is, the shortening ratio of the sarcomere units, which we assume to be nearly independent on the prestretch. Strict enforcement of incompressibility and novel treatment of boundary conditions are shown to be crucial to simulate the correct muscle torsion. PMID:25319381

  8. Dual transcriptional activator and repressor roles of TBX20 regulate adult cardiac structure and function

    PubMed Central

    Sakabe, Noboru J.; Aneas, Ivy; Shen, Tao; Shokri, Leila; Park, Soo-Young; Bulyk, Martha L.; Evans, Sylvia M.; Nobrega, Marcelo A.

    2012-01-01

    The ongoing requirement in adult heart for transcription factors with key roles in cardiac development is not well understood. We recently demonstrated that TBX20, a transcriptional regulator required for cardiac development, has key roles in the maintenance of functional and structural phenotypes in adult mouse heart. Conditional ablation of Tbx20 in adult cardiomyocytes leads to a rapid onset and progression of heart failure, with prominent conduction and contractility phenotypes that lead to death. Here we describe a more comprehensive molecular characterization of the functions of TBX20 in adult mouse heart. Coupling genome-wide chromatin immunoprecipitation and transcriptome analyses (RNA-Seq), we identified a subset of genes that change expression in Tbx20 adult cardiomyocyte-specific knockout hearts which are direct downstream targets of TBX20. This analysis revealed a dual role for TBX20 as both a transcriptional activator and a repressor, and that each of these functions regulates genes with very specialized and distinct molecular roles. We also show how TBX20 binds to its targets genome-wide in a context-dependent manner, using various cohorts of co-factors to either promote or repress distinct genetic programs within adult heart. Our integrative approach has uncovered several novel aspects of TBX20 and T-box protein function within adult heart. Sequencing data accession number (http://www.ncbi.nlm.nih.gov/geo): GSE30943. PMID:22328084

  9. Cardiac vagal activation by adrenocorticotropic hormone treatment in infants with West syndrome.

    PubMed

    Hattori, Ayako; Hayano, Junichiro; Fujimoto, Shinji; Ando, Naoki; Mizuno, Kumiko; Kamei, Michi; Kobayashi, Satoru; Ishikawa, Tatsuya; Togari, Hajime

    2007-02-01

    West syndrome (WS) is a generalized epileptic syndrome of infancy and early childhood with various etiologies, and consists of a triad of infantile spasm, arrest or regress of psychomotor development and specific electroencephalogram (EEG) pattern of hypsarrhythmia. WS had been believed to be refractory, but recent evidence supports effectiveness of adrenocorticotropic hormone (ACTH) treatment. The ACTH treatment, however, has a problem that it is often accompanied by adverse autonomic symptoms. We therefore examined heart rate variability (HRV) for assessing cardiac autonomic functions in WS and prospectively observed the changes during ACTH treatment. We studied 15 patients with WS and 9 age-matched controls during sleep (EEG stage 2). Compared with controls, the patients with WS were greater in the low-frequency component (LF) of HRV, an index reflecting sympatho-vagal interaction (p = 0.02), but were comparable for high-frequency component (HF) and LF-to-HF ratio (LF/HF), indices reflecting cardiac vagal activity and sympathetic predominance, respectively. During ACTH treatment, heart rate decreased (p < 0.01), LF and HF increased (p < 0.01), and LF/HF did not differ significantly. These results indicate that WS might be accompanied by autonomic changes and that ACTH treatment enhances parasympathetic function and causes bradycardia. PMID:17287597

  10. Interaction of ADP with skeletal and cardiac myosin and their active fragments observed by proton release.

    PubMed

    Kardami, E; De Bruin, S; Gratzer, W

    1979-07-01

    The technique of proton release measurement has been used to explore the binding of ADP to skeletal and cardiac myosins and their active fragments in a variety of conditions. It has proved possible to obtain binding profiles on intact myosin in the filamentous, undissolved form in physiological solvent conditions. Binding constants are given. At higher ionic strength (0.5 M potassium chloride) the binding profile of magnesium-ADP. is compatible with the presence of two types of site, differing from one another both in respect of affinity and the number of protons released per site. Studies with cardiac myosin reveal no such indications of heterogeneity, and are consistent with the presence of a single population of thermodynamically indistinguishable sites. In the absence of divalent cations, in solutions containing potassium ions and EDTA, ADP binds with absorption rather than liberation of protons. The pH profile of proton absorption at saturation can be fitted in terms of an ionising group with an unperturbed pK of 9.4, and at least one of lower pK(5.9). The dissociation constant (pH8 at 5 degrees C) is about 8 microM, and the affinity for uncomplexed ADP is thus only slightly weaker than that for magnesium-ADP PMID:38115

  11. Radiation Detection for Active Interrogation of HEU

    SciTech Connect

    Mihalczo, J.T.

    2004-12-09

    This report briefly describes the neutrons and gamma rays emitted by active interrogation of HEU, briefly discusses measurement methods, briefly discusses sources and detectors relevant to detection of shielded HEU in Sealand containers, and lists the measurement possibilities for the various sources. All but one of the measurement methods detect radiation emitted by induced fission in the HEU; the exception utilizes nuclear resonance fluorescence. The brief descriptions are supplemented by references. This report presents some active interrogation possibilities but the status of understanding is not advanced enough to select particular methods. Additional research is needed to evaluate these possibilities.

  12. Porous graphene oxide nanostructure as an excellent scaffold for label-free electrochemical biosensor: Detection of cardiac troponin I.

    PubMed

    Kazemi, Sayed Habib; Ghodsi, Elham; Abdollahi, Siamak; Nadri, Samad

    2016-12-01

    Herein, we report the fabrication of a novel label-free impedimetric biosensor employing porous graphene oxide (PrGO) nanostructures for the specific detection of cardiac troponin-I (cTnI) to establish the myocardial infarction (MI). This nano-immunosensor demonstrates an outstanding selectivity and high sensitivity towards the human-cTnI analyte. An excellent detection limit of 0.07ngmL(-1) and dynamic linear range of 0.1-10ngmL(-1) were calculated for anti-cTnI/PrGO/GC. Finally, this biosensor was employed to check the concentration of the MI biomarker in real clinical samples and the results are in good agreement with standard enzyme-linked fluorescence assay (ELFA) method. PMID:27612734

  13. Adiponectin is required for cardiac MEF2 activation during pressure overload induced hypertrophy.

    PubMed

    Dadson, Keith; Turdi, Subat; Hashemi, Sarah; Zhao, Jianzhong; Polidovitch, Nazar; Beca, Sanja; Backx, Peter H; McDermott, John C; Sweeney, Gary

    2015-09-01

    Cardiomyocyte (CM) hypertrophy and increased heart mass in response to pressure overload are associated with hyper-activation of the myocyte enhancer factor-2 (MEF2) family of transcriptional regulators, and concomitant initiation of the fetal gene program. Adiponectin, an adipokine that is reduced in individuals with obesity and diabetes, has been characterized both as a negative regulator or permissive factor in cardiac hypertrophy. We therefore sought to analyze temporal regulation of MEF2 activity in response to pressure overload (PO) and changes in adiponectin status. To address this we crossed a well characterized transgenic MEF2 "sensor" mouse (MEF2-lacZ) with adiponectin null mice (Ad-KO) to create compound MEF2 lacZ/Ad-KO mice. Initially, we established that transverse aortic banding induced PO in wild-type (WT) mice increased heart mass and CM hypertrophy from 1 to 4weeks following surgery, indicated by increased CM diameter and heart weight/tibia length ratio. This was associated with cardiac dysfunction determined by echocardiography. Hypertrophic changes and dysfunction were observed in Ad-KO mice 4weeks following surgery. MEF2 lacZ activity and endogenous ANF mRNA levels, used as indicators of hypertrophic gene activation, were both robustly increased in WT mice after MTAB but attenuated in the Ad-KO background. Furthermore, activation of the pro-hypertrophic molecule p38 was increased following MTAB surgery in WT mice, but not in Ad-KO animals, and treatment of primary isolated CM with recombinant adiponectin induced p38 phosphorylation in a time dependent manner. Adiponectin also increased MEF2 activation in primary cardiomyocytes, an effect attenuated by p38 MAPK inhibition. In conclusion, our data indicate that robust hypertrophic MEF2 activation in the heart in vivo requires a background of adiponectin signaling and that adiponectin signaling in primary isolated CM directly enhances MEF2 activity through activation of p38 MAPK. We conclude that

  14. Abnormal Activity Detection Using Pyroelectric Infrared Sensors

    PubMed Central

    Luo, Xiaomu; Tan, Huoyuan; Guan, Qiuju; Liu, Tong; Zhuo, Hankz Hankui; Shen, Baihua

    2016-01-01

    Healthy aging is one of the most important social issues. In this paper, we propose a method for abnormal activity detection without any manual labeling of the training samples. By leveraging the Field of View (FOV) modulation, the spatio-temporal characteristic of human activity is encoded into low-dimension data stream generated by the ceiling-mounted Pyroelectric Infrared (PIR) sensors. The similarity between normal training samples are measured based on Kullback-Leibler (KL) divergence of each pair of them. The natural clustering of normal activities is discovered through a self-tuning spectral clustering algorithm with unsupervised model selection on the eigenvectors of a modified similarity matrix. Hidden Markov Models (HMMs) are employed to model each cluster of normal activities and form feature vectors. One-Class Support Vector Machines (OSVMs) are used to profile the normal activities and detect abnormal activities. To validate the efficacy of our method, we conducted experiments in real indoor environments. The encouraging results show that our method is able to detect abnormal activities given only the normal training samples, which aims to avoid the laborious and inconsistent data labeling process. PMID:27271632

  15. Abnormal Activity Detection Using Pyroelectric Infrared Sensors.

    PubMed

    Luo, Xiaomu; Tan, Huoyuan; Guan, Qiuju; Liu, Tong; Zhuo, Hankz Hankui; Shen, Baihua

    2016-01-01

    Healthy aging is one of the most important social issues. In this paper, we propose a method for abnormal activity detection without any manual labeling of the training samples. By leveraging the Field of View (FOV) modulation, the spatio-temporal characteristic of human activity is encoded into low-dimension data stream generated by the ceiling-mounted Pyroelectric Infrared (PIR) sensors. The similarity between normal training samples are measured based on Kullback-Leibler (KL) divergence of each pair of them. The natural clustering of normal activities is discovered through a self-tuning spectral clustering algorithm with unsupervised model selection on the eigenvectors of a modified similarity matrix. Hidden Markov Models (HMMs) are employed to model each cluster of normal activities and form feature vectors. One-Class Support Vector Machines (OSVMs) are used to profile the normal activities and detect abnormal activities. To validate the efficacy of our method, we conducted experiments in real indoor environments. The encouraging results show that our method is able to detect abnormal activities given only the normal training samples, which aims to avoid the laborious and inconsistent data labeling process. PMID:27271632

  16. Transcriptional activation of muscle atrophy promotes cardiac muscle remodeling during mammalian hibernation

    PubMed Central

    Zhang, Yichi; Aguilar, Oscar A.

    2016-01-01

    during late torpor by 2.4-fold. Protein levels of MAFbx and MuRF1 increased in late torpor as well as during early arousal by as much as 2.8-fold, and MAFbx levels remained elevated during interbout arousal, whereas MuRF1 levels returned to control levels. Discussion. The present results indicate that upregulation and activation of Foxo1 and 3a, in addition to the increase in MyoG levels at late torpor, may be upregulating the expression of MAFbx and MuRF1. These findings suggest that there is activation of the ubiquitin proteasome system (UPS) as ground squirrels arouse from torpor. Therefore, the signalling pathway involving MyoG, and the E3 ligases MAFbx and MuRF1, plays a significant role in cardiac muscle remodelling during hibernation. These findings provide insights into the regulation of protein degradation and turnover in the cardiac muscle of a hibernator model. PMID:27602284

  17. Transcriptional activation of muscle atrophy promotes cardiac muscle remodeling during mammalian hibernation.

    PubMed

    Zhang, Yichi; Aguilar, Oscar A; Storey, Kenneth B

    2016-01-01

    upregulated only during late torpor by 2.4-fold. Protein levels of MAFbx and MuRF1 increased in late torpor as well as during early arousal by as much as 2.8-fold, and MAFbx levels remained elevated during interbout arousal, whereas MuRF1 levels returned to control levels. Discussion. The present results indicate that upregulation and activation of Foxo1 and 3a, in addition to the increase in MyoG levels at late torpor, may be upregulating the expression of MAFbx and MuRF1. These findings suggest that there is activation of the ubiquitin proteasome system (UPS) as ground squirrels arouse from torpor. Therefore, the signalling pathway involving MyoG, and the E3 ligases MAFbx and MuRF1, plays a significant role in cardiac muscle remodelling during hibernation. These findings provide insights into the regulation of protein degradation and turnover in the cardiac muscle of a hibernator model. PMID:27602284

  18. Parallel activation of mitochondrial oxidative metabolism with increased cardiac energy expenditure is not dependent on fatty acid oxidation in pigs

    PubMed Central

    Zhou, Lufang; Cabrera, Marco E; Huang, Hazel; Yuan, Celvie L; Monika, Duda K; Sharma, Naveen; Bian, Fang; Stanley, William C

    2007-01-01

    Steady state concentrations of ATP and ADP in vivo are similar at low and high cardiac workloads; however, the mechanisms that regulate the activation of substrate metabolism and oxidative phosphorylation that supports this stability are poorly understood. We tested the hypotheses that (1) there is parallel activation of mitochondrial and cytosolic dehydrogenases in the transition from low to high workload, which increases NADH/NAD+ ratio in both compartments, and (2) this response does not require an increase in fatty acid oxidation (FAO). Anaesthetized pigs were subjected to either sham treatment, or an abrupt increase in cardiac workload for 5 min with dobutamine infusion and aortic constriction. Myocardial oxygen consumption and FAO were increased 3- and 2-fold, respectively, but ATP and ADP concentrations did not change. NADH-generating pathways were rapidly activated in both the cytosol and mitochondria, as seen in a 40% depletion in glycogen stores, a 3.6-fold activation of pyruvate dehydrogenase, and a 50% increase in tissue NADH/NAD+. Simulations from a multicompartmental computational model of cardiac energy metabolism predicted that parallel activation of glycolysis and mitochondrial metabolism results in an increase in the NADH/NAD+ ratio in both cytosol and mitochondria. FAO was blocked by 75% in a third group of pigs, and a similar increase in and the NAHD/NAD+ ratio was observed. In conclusion, in the transition to a high cardiac workload there is rapid parallel activation of substrate oxidation that results in an increase in the NADH/NAD+ ratio. PMID:17185335

  19. Development of an automated processing method to detect still timing of cardiac motion for coronary magnetic resonance angiography

    NASA Astrophysics Data System (ADS)

    Asou, Hiroya; Ichikawa, Katsuhiro; Imada, Naoyuki; Masuda, Takanori; Satou, Tomoyasu

    2011-03-01

    Whole-heart coronary magnetic resonance angiography (WH-MRA) is useful noninvasive examination. Its signal acquisition is performed during very short still timing in each cardiac motion cycle, and therefore the adequate still timing selection is important to obtain the better image quality. However, since the current available selection method is only manual one using visual comparison of cine MRI images with different phases, the selected timings are often incorrect and their reproducibility is not sufficient. We developed an automated selection method to detect the best still timing for the WH-MRA and compared the automated method with conventional manual one. Cine MRI images were used for the analysis. In order to extract the high-speed cardiac cine image, each phase directional pixel set at each pixel position in all cine images were processed by a high-pass filtering using the Fourie transform. After this process, the cine images with low speed timing became dark, and the optimal timing could be determined by a threshold processing. We took ten volunteers' WH-MRA with the manually and automatically selected timings, and visually assessed image quality of each image on a 5-point scale (1=excellent, 2=very good, 3=good, 4=fair, 5=poor). The mean scores of the manual and automatic methods for right coronary arteries (RCA), LDA left anterior descending arteries (LAD) and LCX left circumflex arteries (LCX) were 4.2+/-0.38, 4.1+/-0.44, 3.9+/-0.52 and 4.1+/-0.42, 4.1+/-0.24, 3.2+/-0.35 respectively. The score were increased by our method in the RCA and LCX, and the LCX was significant (p<0.05). As the results, it was indicated that our automated method could determine the optimal cardiac phase more accurately than or equally to the conventional manual method.

  20. Heparin-enhanced plasma phospholipase A2 activity and prostacyclin synthesis in patients undergoing cardiac surgery.

    PubMed Central

    Nakamura, H; Kim, D K; Philbin, D M; Peterson, M B; Debros, F; Koski, G; Bonventre, J V

    1995-01-01

    Although eicosanoid production contributes to physiological and pathophysiological consequences of cardiopulmonary bypass (CPB), the mechanisms accounting for the enhanced eicosanoid production have not been defined. Plasma phospholipase A2 (PLA2) activity, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2) levels were measured at various times during cardiac surgery. Plasma PLA2 activity increased after systemic heparinization, before CPB. This was highly correlated with concurrent increases in plasma 6-keto-PGF1 alpha, TXB2 concentrations did not increase with heparin administration but did increase significantly after initiation of CPB. High plasma PLA2 activity, 6-keto-PGF1 alpha, and TXB2 concentrations were measured throughout the CPB period. Protamine, administered to neutralize the heparin, caused an acute reduction of both plasma PLA2 activity and plasma 6-keto-PGF1 alpha, but no change in plasma TXB2 concentrations. Thus the ratio of TXB2 to 6-keto-PGF1 alpha increased significantly after protamine administration. Enhanced plasma PLA2 activity was also measured in patients with lower doses of heparin used clinically for nonsurgical applications. Human plasma PLA2 was identified as group II PLA2 by its sensitivity to deoxycholate and dithiothreitol, its substrate specificity, and its elution characteristics on heparin affinity chromatography. Heparin addition to PMNs in vitro resulted in dose-dependent increases in cellular PLA2 activity and release of PLA2. The PLA2 released from the PMN had characteristics similar to those of post-heparin plasma PLA2. In conclusion, plasma PLA2 activity and 6-keto-PGF1 alpha concentrations are markedly enhanced with systemic heparinization. Part of the anticoagulant and vasodilating effects of heparin may be due to increased plasma prostacyclin (PGI2) levels. In addition the pulmonary vasoconstriction sometimes associated with protamine infusion during cardiac surgery might be due to decreased

  1. Design of Raman active nanoparticles for SERS-based detection

    NASA Astrophysics Data System (ADS)

    Garza, Javier T.; Cote, Gerard L.

    2016-03-01

    Timely detection of cardiac biomarkers is needed to diagnose acute myocardial infarction, implement the appropriate early treatment, and significantly reduce the chance of mortality. Ideally, for maximizing patient impact, a point of care device needs to be designed that is fast, sensitive, reliable, and small enough to be used in the ambulance and emergency department. Surface enhanced Raman spectroscopy (SERS) is a sensitive optical technique that can potentially be used to quantify the cardiac biomarkers of interest. In this work, silver nanoparticles were functionalized with a Raman reporter molecule and human cardiac Troponin I (cTnI) as an essential component of binding assays. Aggregated nanoparticles with the Raman reporter molecules were encapsulated in a silica shell to form SERS hotspots. Besides having a specific Raman spectra and binding affinity to cardiac Troponin I antibodies, the nanoparticles were designed to exhibit stability by using silica and polyethylene glycol (PEG) as part of the bioconjugation strategy. The specific narrow peaks from the Raman reporter molecule SERS signal allow for potential multiplexing capabilities as different Raman reporter molecules can be used in functionalized nanoparticles with different cardiac biomarkers. The SERS spectrum of the functionalized nanoparticles was measured to assess its potential to be used in an assay.

  2. Implementation of a Phase Detection Algorithm for Dynamic Cardiac Computed Tomography Analysis Based on Time Dependent Contrast Agent Distribution

    PubMed Central

    Kendziorra, Carsten; Meyer, Henning; Dewey, Marc

    2014-01-01

    This paper presents a phase detection algorithm for four-dimensional (4D) cardiac computed tomography (CT) analysis. The algorithm detects a phase, i.e. a specific three-dimensional (3D) image out of several time-distributed 3D images, with high contrast in the left ventricle and low contrast in the right ventricle. The purpose is to use the automatically detected phase in an existing algorithm that automatically aligns the images along the heart axis. Decision making is based on the contrast agent distribution over time. It was implemented in KardioPerfusion – a software framework currently being developed for 4D CT myocardial perfusion analysis. Agreement of the phase detection algorithm with two reference readers was 97% (95% CI: 82–100%). Mean duration for detection was 0.020 s (95% CI: 0.018–0.022 s), which was times less than the readers needed (s, ). Thus, this algorithm is an accurate and fast tool that can improve work flow of clinical examinations. PMID:25545863

  3. Cardiac Rehabilitation

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Cardiac Rehabilitation? Cardiac rehabilitation (rehab) is a medically supervised program ... be designed to meet your needs. The Cardiac Rehabilitation Team Cardiac rehab involves a long-term commitment ...

  4. CARDIAC SULFONYLUREA RECEPTOR SHORT FORM-BASED CHANNELS CONFER A GLIBENCLAMIDE-INSENSITIVE KATP ACTIVITY

    PubMed Central

    Pu, Jie-Lin,; Ye, Bin; Kroboth, Stacie L.; McNally, Elizabeth M.; Makielski, Jonathan C.; Shi, Nian-Qing

    2008-01-01

    The cardiac sarcolemmal ATP-sensitive potassium channel (KATP) consists of a Kir6.2 pore and a SUR2 regulatory subunit, which is an ATP-binding cassette (ABC) transporter. KATP channels have been proposed to play protective roles during ischemic preconditioning. A SUR2 mutant mouse was previously generated by disrupting the first nucleotide-binding domain (NBD1), where a glibenclamide action site was located. In the mutant ventricular myocytes, a non-conventional glibenclamide-insensitive (10 μM), ATP-sensitive current (IKATPn) was detected in 33% of single-channel recordings with an average amplitude of 12.3±5.4 pA per patch, an IC50 to ATP inhibition at 10 μM, and a mean burst duration at 20.6±1.8 ms. Newly designed SUR2-isoform or variant-specific antibodies identified novel SUR2 short forms in the sizes of 28 and 68 kDa in addition to a 150-kDa long form in the sarcolemmal membrane of wild-type (WT) heart. We hypothesized that channels constituted by these short forms that lack NBD1, confer IKATPn. The absence of the long form in the mutant corresponded to loss of the conventional glibenclamide-sensitive KATP currents (IKATP) in isolated cardiomyocytes and vascular smooth muscle cells but the SUR2 short forms remained intact. Nested exonic RT-PCR in the mutant indicated that the short forms lacked NBD1 but contained NBD2. The SUR2 short forms co-immunoprecipitated with Kir6.1 or Kir6.2 suggesting that the short forms may function as hemi-transporters reported in other eukaryotic ABC transporter subgroups. Our results indicate that different KATP compositions may co-exist in cardiac sarcolemmal membrane. PMID:18001767

  5. The antioxidant compound tert-butylhydroquinone activates Akt in myocardium, suppresses apoptosis and ameliorates pressure overload-induced cardiac dysfunction

    PubMed Central

    Zhang, Yongtao; Fang Liu, Fang; Bi, Xiaolei; Wang, Shuangxi; Wu, Xiao; Jiang, Fan

    2015-01-01

    Tert-butylhydroquinone (TBHQ) is an antioxidant compound which shows multiple cytoprotective actions. We evaluated the effects of TBHQ on pathological cardiac remodeling and dysfunction induced by chronic overload. Pressure overload was created by transverse aortic constriction (TAC) in male C57BL/6 mice. TBHQ was incorporated in the diet and administered for 4 weeks. TBHQ treatment prevented left ventricular dilatation and cardiac dysfunction induced by TAC, and decreased the prevalence of myocardial apoptosis. The beneficial effects of TBHQ were associated with an increase in Akt activation, but not related to activations of Nrf2 or AMP-activated protein kinase. TBHQ-induced Akt activation was accompanied by increased phosphorylation of Bad, glycogen synthase kinase-3β (GSK-3β) and mammalian target of rapamycin (mTOR). Mechanistically, we showed that in cultured H9c2 cells and primary cardiac myocytes, TBHQ stimulated Akt phosphorylation and suppressed oxidant-induced apoptosis; this effect was abolished by wortmannin or an Akt inhibitor. Blockade of the Akt pathway in vivo accelerated cardiac dysfunction, and abrogated the protective effects of TBHQ. TBHQ also reduced the reactive aldehyde production and protein carbonylation in stressed myocardium. We suggest that TBHQ treatment may represent a novel strategy for timely activation of the cytoprotective Akt pathway in stressed myocardium. PMID:26260024

  6. Mechanisms of caffeine activation of single calcium-release channels of sheep cardiac sarcoplasmic reticulum.

    PubMed Central

    Sitsapesan, R; Williams, A J

    1990-01-01

    1. Calcium-release channels of sheep cardiac junctional sarcoplasmic reticulum were incorporated into planar phospholipid bilayers. Single-channel current fluctuations were recorded under voltage clamp conditions. 2. Channels incorporate into the bilayer with a fixed orientation and channel open probability is regulated by the calcium concentration at the cytosolic face of the membrane. 3. Addition of caffeine (0.5-2.0 mM) to the cytosolic side of the membrane increased the open probability of the calcium-activated calcium-release channel by increasing the frequency of opening without significant alteration to the durations of open events. This effect was observed at both 0.1 and 10 microM-activating cytosolic calcium. 4. Caffeine (0.5-2.0 mM) did not activate the channel at a subactivating cytosolic calcium concentration (80 pM). 5. At subactivating calcium concentrations, channels could be activated by higher concentrations of caffeine (greater than 5.0 mM) revealing a second, calcium-independent, mechanism for channel activation. Channel openings induced by these high concentrations of caffeine at subactivating calcium concentrations displayed different kinetics from those observed with calcium as the sole activating ligand or with combinations of calcium and low concentrations of caffeine. 6. Activation of channel opening by caffeine in the presence of calcium did not affect single-channel conductance. Channel openings produced by caffeine at subactivating cytosolic calcium concentrations had identical conductance and relative permeability to those seen on calcium activation. 7. Channels activated by caffeine at both activating and subactivating calcium concentrations were characteristically modified by ryanodine, Ruthenium Red, ATP and magnesium, implying that the same channel is involved under both conditions. PMID:2167363

  7. Cardiac myocyte-specific AHR activation phenocopies TCDD-induced toxicity in zebrafish.

    PubMed

    Lanham, Kevin A; Plavicki, Jessica; Peterson, Richard E; Heideman, Warren

    2014-09-01

    Exposure of zebrafish embryos to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activates the zebrafish aryl hydrocarbon receptor 2 (AHR) to produce developmental and cardiovascular toxicity. AHR is found in the heart; however, AHR activation by TCDD is not confined to the heart and occurs throughout the organism. In order to understand the cause of cardiotoxicity, we constructed a constitutively active AHR (caAHR) based on the zebrafish AHR2 and expressed it specifically in cardiomyocytes. We show that AHR activation within the cardiomyocytes can account for the heart failure induced by TCDD. Expression of the caAHR within the heart produced cardiac malformations, loss of circulation, and pericardial edema. The heart-specific activation of AHR reproduced several other well-characterized endpoints of TCDD toxicity outside of the cardiovascular system, including defects in swim bladder and craniofacial development. This work identifies a single cellular site of TCDD action, the myocardial cell, that can account for the severe cardiovascular collapse observed following early life stage exposure to TCDD, and contributes to other forms of toxicity. PMID:25037585

  8. Cardiac Myocyte-Specific AHR Activation Phenocopies TCDD-Induced Toxicity in Zebrafish

    PubMed Central

    Lanham, Kevin A.; Plavicki, Jessica; Peterson, Richard E.; Heideman, Warren

    2014-01-01

    Exposure of zebrafish embryos to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) activates the zebrafish aryl hydrocarbon receptor 2 (AHR) to produce developmental and cardiovascular toxicity. AHR is found in the heart; however, AHR activation by TCDD is not confined to the heart and occurs throughout the organism. In order to understand the cause of cardiotoxicity, we constructed a constitutively active AHR (caAHR) based on the zebrafish AHR2 and expressed it specifically in cardiomyocytes. We show that AHR activation within the cardiomyocytes can account for the heart failure induced by TCDD. Expression of the caAHR within the heart produced cardiac malformations, loss of circulation, and pericardial edema. The heart-specific activation of AHR reproduced several other well-characterized endpoints of TCDD toxicity outside of the cardiovascular system, including defects in swim bladder and craniofacial development. This work identifies a single cellular site of TCDD action, the myocardial cell, that can account for the severe cardiovascular collapse observed following early life stage exposure to TCDD, and contributes to other forms of toxicity. PMID:25037585

  9. Effects of eating on vection-induced motion sickness, cardiac vagal tone, and gastric myoelectric activity

    NASA Technical Reports Server (NTRS)

    Uijtdehaage, S. H.; Stern, R. M.; Koch, K. L.

    1992-01-01

    This study investigated the effect of food ingestion on motion sickness severity and its physiological mechanisms. Forty-six fasted subjects were assigned either to a meal group or to a no-meal group. Electrogastrographic (EGG) indices (normal 3 cpm activity and abnormal 4-9 cpm tachyarrhythmia) and respiratory sinus arrhythmia (RSA) were measured before and after a meal and during a subsequent exposure to a rotating drum in which illusory self-motion was induced. The results indicated that food intake enhanced cardiac parasympathetic tone (RSA) and increased gastric 3 cpm activity. Postprandial effects on motion sickness severity remain equivocal due to group differences in RSA baseline levels. During drum rotation, dysrhythmic activity of the stomach (tachyarrhythmia) and vagal withdrawal were observed. Furthermore, high levels of vagal tone prior to drum rotation predicted a low incidence of motion sickness symptoms, and were associated positively with gastric 3 cpm activity and negatively with tachyarrhythmia. These data suggest that enhanced levels of parasympathetic activity can alleviate motion sickness symptoms by suppressing, in part, its dysrhythmic gastric underpinnings.

  10. Cardiac magnetic resonance detection and typical appearance of microvascular obstruction following myocardial infarction.

    PubMed

    Karatzis, Emmanouil N; Pipilis, Athanassios G; Malios, Konstantinos; Andreou, John; Roussakis, Arkadios; Tsertos, Fotios; Danias, Peter G

    2009-01-01

    We report the case of a 58-year-old man with a recent anterior myocardial infarction, for which he did not receive prompt reperfusion therapy. The patient underwent cardiac magnetic resonance (CMR) imaging, for the assessment of left ventricular function and myocardial viability, and coronary angiography, two weeks after the acute cardiac event. The CMR study demonstrated a moderately dilated left ventricle, with impaired systolic function and wall motion abnormalities in the anterior, apical and inferior left ventricular walls. The T1-weighted images obtained early after contrast administration demonstrated a dark rim in the endocardial region of the interventricular septum and apex. The delayed-enhanced images demonstrated complete absence of signal at the same rim, adjacent to a hyper-enhanced region that corresponded to the wall motion abnormalities. These findings are suggestive of microvascular obstruction in the distribution of the left anterior descending coronary artery. Microvascular obstruction has been reported to correlate positively with the size of the infarction and the left ventricular end-diastolic volume, and inversely with the left ventricular ejection fraction. Furthermore, it has been reported as an independent predictor of future major cardiovascular events. Microvascular obstruction should be routinely checked for in patients presenting in the peri-myocardial infarction period for CMR assessment of myocardial viability. PMID:19329419

  11. Inorganic polyphosphate is a potent activator of the mitochondrial permeability transition pore in cardiac myocytes

    PubMed Central

    Seidlmayer, Lea K.; Gomez-Garcia, Maria R.; Blatter, Lothar A.; Pavlov, Evgeny

    2012-01-01

    Mitochondrial dysfunction caused by excessive Ca2+ accumulation is a major contributor to cardiac cell and tissue damage during myocardial infarction and ischemia–reperfusion injury (IRI). At the molecular level, mitochondrial dysfunction is induced by Ca2+-dependent opening of the mitochondrial permeability transition pore (mPTP) in the inner mitochondrial membrane, which leads to the dissipation of mitochondrial membrane potential (ΔΨm), disruption of adenosine triphosphate production, and ultimately cell death. Although the role of Ca2+ for induction of mPTP opening is established, the exact molecular mechanism of this process is not understood. The aim of the present study was to test the hypothesis that the adverse effect of mitochondrial Ca2+ accumulation is mediated by its interaction with inorganic polyphosphate (polyP), a polymer of orthophosphates linked by phosphoanhydride bonds. We found that cardiac mitochondria contained significant amounts (280 ± 60 pmol/mg of protein) of short-chain polyP with an average length of 25 orthophosphates. To test the role of polyP for mPTP activity, we investigated kinetics of Ca2+ uptake and release, ΔΨm and Ca2+-induced mPTP opening in polyP-depleted mitochondria. polyP depletion was achieved by mitochondria-targeted expression of a polyP-hydrolyzing enzyme. Depletion of polyP in mitochondria of rabbit ventricular myocytes led to significant inhibition of mPTP opening without affecting mitochondrial Ca2+ concentration by itself. This effect was observed when mitochondrial Ca2+ uptake was stimulated by increasing cytosolic [Ca2+] in permeabilized myocytes mimicking mitochondrial Ca2+ overload observed during IRI. Our findings suggest that inorganic polyP is a previously unrecognized major activator of mPTP. We propose that the adverse effect of polyphosphate might be caused by its ability to form stable complexes with Ca2+ and directly contribute to inner mitochondrial membrane permeabilization. PMID:22547663

  12. Physical training induced resting bradycardia and its association with cardiac autonomic nervous activities.

    PubMed

    Alom, M M; Bhuiyan, N I; Hossain, M M; Hoque, M F; Rozario, R J; Nessa, W

    2011-10-01

    Regular physical exercise causes resting bradycardia. This exercise-induced resting bradycardia may be associated with exercise-induced changes in Cardiac autonomic nervous activities (CANA). Power Spectral Analysis (PSA) of Heart rate variability (HRV) is one of the most promising new techniques to quantify CANA. Regular physical exercise induced bradycardia is associated with exercise-induced adaptation in CANA. To observe the HRV parameters by frequency domain method (PSA), in male adolescent athletes in order to find out the influence of regular physical exercise on resting heart rate (HR) and CANA. The cross sectional study was carried out on 62 adolescent male athletes aged 12-18 years (group B), in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University from 1st July 2007 to 30th June 2008. For comparison 30 age, sex and socioeconomic condition matched apparently healthy sedentary subjects (group A) were also studied. The study group was selected from the BKSP (Bangladesh Krira Shikka Prothistan, Savar, Dhaka) and the control from a residential school of Dhaka city. HRV parameters were assessed by Polygraph (Polyrite D, version 2.2). For statistical analysis Independent-Samples t-test was done as applicable. Resting mean HR was significantly (p<0.001) lower in the athletes. The mean value of Total (variance), VLF, LF and HF power was significantly (p<0.001) higher in athletes than that of non-athetes. Regular physical exercise-induced resting bradycardia is associated with exercise-induced adaptation in cardiac autonomic nervous activities. PMID:22081187

  13. Meta-Analysis of Interventions to Increase Physical Activity among Cardiac Subjects

    PubMed Central

    Conn, Vicki S.; Hafdahl, Adam R.; Moore, Shirley M.; Nielsen, Paul J.; Brown, Lori M.

    2009-01-01

    Background Extensive primary research has tested interventions to increase physical activity (PA) among adults with cardiovascular disease. This meta-analysis integrates the extant research about how to increase PA in cardiac samples. Methods Extensive literature searching located published and unpublished intervention studies that measured PA outcomes. Results were coded from primary studies. Fixed-and random-effects meta-analytic procedures included moderator analyses. Results Data were synthesized across 11,877 subjects from 79 eligible research reports. The overall mean PA effect size for 2-group comparisons was 0.35 (higher mean for treatment than control), which is consistent with a difference of 1984 kilocalories/week for treatment subjects versus 1615 for control subjects. The fitness effect size for 2-group comparisons was .17. Other statistically significantly positive 2-group effect sizes were .24 for quality of life and .23 for subsequent cardiac events. Effect sizes for anthropometric measures and blood pressure did not differ significantly from 0. Exploratory moderator analyses found large effect sizes for PA among studies that had (1) an exclusive focus on PA versus diverse health behaviors, (2) more contact between interventionists and subjects, (3) supervised exercise sessions, (4) fitness testing, (5) face-to-face encounters versus mediated intervention delivery, and (6) more minutes of activity per week. Effect sizes were unrelated to funding status, dissemination vehicle, gender distribution, or attrition rate. Conclusions These findings document that interventions can be effective in increasing PA among patients with cardiovascular diseases. Primary research should compare interventions in randomized trials to confirm causal relationships. PMID:18582959

  14. The synchronous active neutron detection assay system

    SciTech Connect

    Pickrell, M.M.; Kendall, P.K.

    1994-08-01

    We have begun to develop a novel technique for active neutron assay of fissile material in spent nuclear fuel. This approach will exploit a 14-MeV neutron generator developed by Schlumberger. The technique, termed synchronous active neutron detection (SAND), follows a method used routinely in other branches of physics to detect very small signals in presence of large backgrounds. Synchronous detection instruments are widely available commercially and are termed ``lock-in`` amplifiers. We have implemented a digital lock-in amplifier in conjunction with the Schlumberger neutron generator to explore the possibility of synchronous detection with active neutrons. The Schlumberger system can operate at up to a 50% duty factor, in effect, a square wave of neutron yield. Results are preliminary but promising. The system is capable of resolving the fissile material contained in a small fraction of the fuel rods in a cold fuel assembly; it also appears resilient to background neutron interference. The interrogating neutrons appear to be non-thermal and penetrating. Work remains to fully explore relevant physics and optimize instrument design.

  15. The synchronous active neutron detection assay system

    SciTech Connect

    Pickrell, M.M.; Kendall, P.K.

    1994-09-01

    The authors have begun to develop a novel technique for active neutron assay of fissile material in spent nuclear fuel. They are using a Schlumberger neutron generator for the direct measurement of the fissile material content in spent fuel, in place of the indirect measures used at present. The technique they are investigating is termed synchronous active neutron detection (SAND). It closely follows a method that has been used routinely in other branches of physics for the detection of very small signals in the presence of large backgrounds. Synchronous detection instruments are widely available commercially and are termed ``lock-in`` amplifiers. They have implemented a digital lock-in amplifier in conjunction with the Schlumberger neutron generator to explore the possibility of synchronous detection with active neutrons. The results to data are preliminary but quite promising. The system is capable of resolving the fissile material contained in a small fraction of the fuel rods in a cold fuel assembly. It also appears to be quite resilient to background neutron interference.

  16. Ranging performance of active laser detection

    NASA Astrophysics Data System (ADS)

    Sun, Huayan; Xiong, Fei; Gu, Suolin

    2006-06-01

    Ranging performance is described for photoelectric equipment reconnaissance using an active laser detection system that is based on the 'cat's eyes' effect of optical windows. Active laser detection systems have an advantage over passive systems because they can measure target velocity and spatial coordinates. However, there are several challenging problems here because of the great distances involved, the low returned power of the uncooperative target, and the optical aberrations induced by the atmosphere. In the design of this system, the principle of detection is based on the 'cat's eyes' effect according to which the optical windows of photoelectric equipments have a strong reflect character towards incident laser beam. With 'cat's eyes' effect, the detection of uncooperative target can be translated into one of a cooperative target, so the ratio of returned laser can be increased. In this paper, the ranging performance presented here takes into account all the various elements of the system, from the laser emission, target, atmospheric propagation to the detector. The characteristics of back-reflected laser and an estimate of the laser Cross Section (LCS) from 'cat's eyes target' are investigated in theory and simulation. The Signal-to-Noise Ratio (SNR) is calculated by combining the probability of detection of the system for given electronic characteristics of the system and for a given probability of false alarms. On the basis of analysis of SNR, minimum detectable signal power, operating distance of the system and factors affecting the ranging performance is analyzed. Results indicate that system has characters of long range, and high sensitivity. It can be used to detect the aerial targets such as reconnaissance drone, navigate missile, reconnaissance satellite etc.

  17. A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase

    PubMed Central

    Fu, Zhiyao; Abou-Samra, Abdul B.; Zhang, Ren

    2015-01-01

    Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID:26687026

  18. Activation of NADPH-diaphorase-positive projections to the rostral ventrolateral medulla following cardiac mechanoreceptor stimulation in the conscious rat.

    PubMed

    Kantzides, A; Badoer, E

    2006-06-01

    Stimulation of cardiac mechanoreceptors during volume expansion elicits reflex compensatory changes in sympathetic nerve activity (SNA). The hypothalamic paraventricular nucleus (PVN) and nucleus of the tractus solitarius (NTS) are autonomic regions known to contribute to this reflex. Both of these nuclei project to the rostral ventrolateral medulla (RVLM), critical in the tonic generation of SNA. Recent reports from our laboratory show that these pathways 1) are activated following cardiac mechanoreceptor stimulation, and 2) produce nitric oxide, known to influence SNA. The aims of the present study were to determine whether 1) the activated neurons within the PVN and NTS were nitrergic and 2) these neurons projected to the RVLM. Animals were prepared, under general anesthesia, by microinjection of a retrogradely transported tracer into the pressor region of the RVLM and the placement of a balloon at the right venoatrial junction. In conscious rats, the balloon was inflated to stimulate the cardiac mechanoreceptors or was left uninflated. Balloon inflation elicited a significant increase in Fos-positive neurons in the parvocellular PVN (sevenfold) and NTS (fivefold). In the PVN, 51% of nitrergic neurons and 61% of RVLM-projecting nitrergic neurons were activated. In the NTS, these proportions were 8 and 18%, respectively. The data suggest that nitrergic neurons within the PVN and, to a lesser extent, in the NTS, some of which project to the RVLM, may contribute to the central pathways influencing SNA elicited by cardiac mechanoreceptor stimulation. PMID:16682470

  19. Active Nuclear Material Detection and Imaging

    SciTech Connect

    Daren Norman; James Jones; KevinHaskell; Peter E. Vanmier; Leon Forman

    2005-10-01

    An experimental evaluation has been conducted to assess the operational performance of a coded-aperture, thermal neutron imaging system and its detection and imaging capability for shielded nuclear material in pulsed photonuclear environments. This evaluation used an imaging system developed by Brookhaven National Laboratory. The active photonuclear environment was produced by an operationallyflexible, Idaho National Laboratory (INL) pulsed electron accelerator. The neutron environments were monitored using INL photonuclear neutron detectors. Results include experimental images, operational imaging system assessments and recommendations that would enhance nuclear material detection and imaging performance.

  20. Halogenating activities detected in Antarctic macroalgae

    SciTech Connect

    Laturnus, F.; Adams, F.C.; Gomez, I.; Mehrtens, G.

    1997-03-01

    Halogenating activities were determined in samples of 18 cultivated species of brown, red and green macroalgae from the Antarctic. Activities for the halogenating organic compounds with bromide, iodide and chloride were found. Investigated red algae (rhodophytes) showed higher brominating and iodinating activities compared to brown (phaeophytes) and green (chlorophytes) algae. The highest brominating and iodinating activities were measured in the red algae Plocamium cartilagineum (1.11 {+-} 0.01 U g{sup -1} wet algal weight and 0.18 U g{sup -1} wet algal weight, respectively) and Myriogramme mangini (3.62 {+-} 0.17 U g{sup -1} wet algal weight and 4.5 U g{sup -1} wet algal weight, respectively). Chlorinating activities were detected in the red alga Plocamium cartilagineum only (0.086 U g{sup -1} wet algal weight). 30 refs., 2 figs., 1 tab.

  1. Motor imagery muscle contraction strength influences spinal motor neuron excitability and cardiac sympathetic nerve activity

    PubMed Central

    Bunno, Yoshibumi; Suzuki, Toshiaki; Iwatsuki, Hiroyasu

    2015-01-01

    [Purpose] The aim of this study was to investigate the changes in spinal motor neuron excitability and autonomic nervous system activity during motor imagery of isometric thenar muscle activity at 10% and 50% maximal voluntary contraction (MVC). [Methods] The F-waves and low frequency/high frequency (LF/HF) ratio were recorded at rest, during motor imagery, and post-trial. For motor imagery trials, subjects were instructed to imagine thenar muscle activity at 10% and 50% MVC while holding the sensor of a pinch meter for 5 min. [Results] The F-waves and LF/HF ratio during motor imagery at 50% MVC were significantly increased compared with those at rest, whereas those during motor imagery at 10% MVC were not significantly different from those at rest. The relative values of the F/M amplitude ratio during motor imagery at 50% MVC were significantly higher than those at 10% MVC. The relative values of persistence and the LF/HF ratio during motor imagery were similar during motor imagery at the two muscle contraction strengths. [Conclusion] Motor imagery can increase the spinal motor neuron excitability and cardiac sympathetic nerve activity. Motor imagery at 50% MVC may be more effective than motor imagery at 10% MVC. PMID:26834354

  2. Echocardiographic Detection of Cardiac Dysfunction in Childhood Cancer Survivors: How Long Is Screening Required?

    PubMed Central

    Ramjaun, Aliya; AlDuhaiby, Eman; Ahmed, Sameera; Wang, Lisa; Yu, Eric; Nathan, Paul C; Hodgson, David C

    2015-01-01

    Background Childhood cancer survivors treated with anthracycline chemotherapy are at an increased risk of long-term cardiac toxicity, and guidelines recommend that exposed survivors undergo echocardiography every 1–5 years. However, it is unclear whether survivors should undergo echocardiographic screening indefinitely, or if a period of echocardiographic stability indicates that screening is no longer necessary. The objective of this study was to evaluate the outcomes of echocardiographic screening to aid in the refinement of existing guidelines. Methods We retrospectively analyzed the results of echocardiographic screening in a cohort of adult survivors of childhood cancer treated with anthracyclines and/or cardiac radiation therapy. Interval regression analysis was performed to identify predictors of single-episode or sustained abnormal echocardiograms. Results The cohort constituted 333 survivors, with median follow-up time of 15.8 years post-treatment (range: 5.0–47.9), and median age at treatment of 8 years (range: 1.5–18). Forty-nine survivors had an abnormal echocardiogram (14.7%), and 29 (8.7%) had reproducible abnormal findings. An ongoing continual increase in the incidence of sustained echocardiographic abnormality was seen among patients treated with >250 mg/m2 doxorubicin at age <5 years, reaching 43% by 20 years of therapy. In contrast, no sustained abnormal echocardiographic findings arose after 10 years of therapy in survivors treated with <250 mg/m2 at age ≥5 years. Conclusions Single-episode echocardiographic abnormalities are often not reproduced in subsequent evaluations. The duration of echocardiographic screening for childhood cancer survivors should be reassessed for patients who received lower doses of anthracycline after age 5. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc. PMID:26146944

  3. Cardiac Energy Dependence on Glucose Increases Metabolites Related to Glutathione and Activates Metabolic Genes Controlled by Mechanistic Target of Rapamycin

    PubMed Central

    Schisler, Jonathan C.; Grevengoed, Trisha J.; Pascual, Florencia; Cooper, Daniel E.; Ellis, Jessica M.; Paul, David S.; Willis, Monte S.; Patterson, Cam; Jia, Wei; Coleman, Rosalind A.

    2015-01-01

    Background Long chain acyl‐CoA synthetases (ACSL) catalyze long‐chain fatty acids (FA) conversion to acyl‐CoAs. Temporal ACSL1 inactivation in mouse hearts (Acsl1H−/−) impaired FA oxidation and dramatically increased glucose uptake, glucose oxidation, and mTOR activation, resulting in cardiac hypertrophy. We used unbiased metabolomics and gene expression analyses to elucidate the cardiac cellular response to increased glucose use in a genetic model of inactivated FA oxidation. Methods and Results Metabolomics analysis identified 60 metabolites altered in Acsl1H−/− hearts, including 6 related to glucose metabolism and 11 to cysteine and glutathione pathways. Concurrently, global cardiac transcriptional analysis revealed differential expression of 568 genes in Acsl1H−/− hearts, a subset of which we hypothesized were targets of mTOR; subsequently, we measured the transcriptional response of several genes after chronic mTOR inhibition via rapamycin treatment during the period in which cardiac hypertrophy develops. Hearts from Acsl1H−/− mice increased expression of several Hif1α‐responsive glycolytic genes regulated by mTOR; additionally, expression of Scl7a5, Gsta1/2, Gdf15, and amino acid‐responsive genes, Fgf21, Asns, Trib3, Mthfd2, were strikingly increased by mTOR activation. Conclusions The switch from FA to glucose use causes mTOR‐dependent alterations in cardiac metabolism. We identified cardiac mTOR‐regulated genes not previously identified in other cellular models, suggesting heart‐specific mTOR signaling. Increased glucose use also changed glutathione‐related pathways and compensation by mTOR. The hypertrophy, oxidative stress, and metabolic changes that occur within the heart when glucose supplants FA as a major energy source suggest that substrate switching to glucose is not entirely benign. PMID:25713290

  4. Effects of Peroxisome Proliferator-Activated Receptor-δ Agonist on Cardiac Healing after Myocardial Infarction

    PubMed Central

    Park, Jeong Rang; Ahn, Jong Hwa; Jung, Myeong Hee; Koh, Jin-Sin; Park, Yongwhi; Hwang, Seok-Jae; Jeong, Young-Hoon; Kwak, Choong Hwan; Lee, Young Soo; Seo, Han Geuk; Kim, Jin Hyun; Hwang, Jin-Yong

    2016-01-01

    Peroxisome proliferator-activated receptor-delta (PPAR-δ)-dependent signaling is associated with rapid wound healing in the skin. Here, we investigated the therapeutic effects of PPAR-δ-agonist treatment on cardiac healing in post-myocardial infarction (MI) rats. Animals were assigned to the following groups: sham-operated control group, left anterior descending coronary artery ligation (MI) group, or MI with administration of the PPAR-δ agonist GW610742 group. GW610742 (1 mg/kg) was administrated intraperitoneally after the operation and repeated every 3 days. Echocardiographic data showed no differences between the two groups in terms of cardiac function and remodeling until 4 weeks. However, the degrees of angiogenesis and fibrosis after MI were significantly higher in the GW610742-treated rats than in the untreated MI rats at 1 week following MI, which changes were not different at 2 weeks after MI. Naturally, PPAR-δ expression in infarcted myocardium was highest increased in 3 day after MI and then disappeared in 14 day after MI. GW610742 increased myofibroblast differentiation and transforming growth factor-beta 2 expression in the infarct zone at 7 days after MI. GW610742 also increased bone marrow-derived mesenchymal stem cell (MSC) recruitment in whole myocardium, and increased serum platelet-derived growth factor B, stromal-derived factor-1 alpha, and matrix metallopeptidase 9 levels at day 3 after MI. PPAR-δ agonists treatment have the temporal effect on early fibrosis of infarcted myocardium, which might not sustain the functional and structural beneficial effect. PMID:26862756

  5. Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure

    NASA Astrophysics Data System (ADS)

    Urbanek, Konrad; Torella, Daniele; Sheikh, Farooq; de Angelis, Antonella; Nurzynska, Daria; Silvestri, Furio; Beltrami, C. Alberto; Bussani, Rossana; Beltrami, Antonio P.; Quaini, Federico; Bolli, Roberto; Leri, Annarosa; Kajstura, Jan; Anversa, Piero

    2005-06-01

    In this study, we tested whether the human heart possesses a cardiac stem cell (CSC) pool that promotes regeneration after infarction. For this purpose, CSC growth and senescence were measured in 20 hearts with acute infarcts, 20 hearts with end-stage postinfarction cardiomyopathy, and 12 control hearts. CSC number increased markedly in acute and, to a lesser extent, in chronic infarcts. CSC growth correlated with the increase in telomerase-competent dividing CSCs from 1.5% in controls to 28% in acute infarcts and 14% in chronic infarcts. The CSC mitotic index increased 29-fold in acute and 14-fold in chronic infarcts. CSCs committed to the myocyte, smooth muscle, and endothelial cell lineages increased 85-fold in acute infarcts and 25-fold in chronic infarcts. However, p16INK4a-p53-positive senescent CSCs also increased and were 10%, 18%, and 40% in controls, acute infarcts, and chronic infarcts, respectively. Old CSCs had short telomeres and apoptosis involved 0.3%, 3.8%, and 9.6% of CSCs in controls, acute infarcts, and chronic infarcts, respectively. These variables reduced the number of functionally competent CSCs from 26,000/cm3 of viable myocardium in acute to 7,000/cm3 in chronic infarcts, respectively. In seven acute infarcts, foci of spontaneous myocardial regeneration that did not involve cell fusion were identified. In conclusion, the human heart possesses a CSC compartment, and CSC activation occurs in response to ischemic injury. The loss of functionally competent CSCs in chronic ischemic cardiomyopathy may underlie the progressive functional deterioration and the onset of terminal failure. cardiac progenitor cells | human heart | myocardial infarction

  6. Effects of Peroxisome Proliferator-Activated Receptor-δ Agonist on Cardiac Healing after Myocardial Infarction.

    PubMed

    Park, Jeong Rang; Ahn, Jong Hwa; Jung, Myeong Hee; Koh, Jin-Sin; Park, Yongwhi; Hwang, Seok-Jae; Jeong, Young-Hoon; Kwak, Choong Hwan; Lee, Young Soo; Seo, Han Geuk; Kim, Jin Hyun; Hwang, Jin-Yong

    2016-01-01

    Peroxisome proliferator-activated receptor-delta (PPAR-δ)-dependent signaling is associated with rapid wound healing in the skin. Here, we investigated the therapeutic effects of PPAR-δ-agonist treatment on cardiac healing in post-myocardial infarction (MI) rats. Animals were assigned to the following groups: sham-operated control group, left anterior descending coronary artery ligation (MI) group, or MI with administration of the PPAR-δ agonist GW610742 group. GW610742 (1 mg/kg) was administrated intraperitoneally after the operation and repeated every 3 days. Echocardiographic data showed no differences between the two groups in terms of cardiac function and remodeling until 4 weeks. However, the degrees of angiogenesis and fibrosis after MI were significantly higher in the GW610742-treated rats than in the untreated MI rats at 1 week following MI, which changes were not different at 2 weeks after MI. Naturally, PPAR-δ expression in infarcted myocardium was highest increased in 3 day after MI and then disappeared in 14 day after MI. GW610742 increased myofibroblast differentiation and transforming growth factor-beta 2 expression in the infarct zone at 7 days after MI. GW610742 also increased bone marrow-derived mesenchymal stem cell (MSC) recruitment in whole myocardium, and increased serum platelet-derived growth factor B, stromal-derived factor-1 alpha, and matrix metallopeptidase 9 levels at day 3 after MI. PPAR-δ agonists treatment have the temporal effect on early fibrosis of infarcted myocardium, which might not sustain the functional and structural beneficial effect. PMID:26862756

  7. Analyte detection using an active assay

    DOEpatents

    Morozov, Victor; Bailey, Charles L.; Evanskey, Melissa R.

    2010-11-02

    Analytes using an active assay may be detected by introducing an analyte solution containing a plurality of analytes to a lacquered membrane. The lacquered membrane may be a membrane having at least one surface treated with a layer of polymers. The lacquered membrane may be semi-permeable to nonanalytes. The layer of polymers may include cross-linked polymers. A plurality of probe molecules may be arrayed and immobilized on the lacquered membrane. An external force may be applied to the analyte solution to move the analytes towards the lacquered membrane. Movement may cause some or all of the analytes to bind to the lacquered membrane. In cases where probe molecules are presented, some or all of the analytes may bind to probe molecules. The direction of the external force may be reversed to remove unbound or weakly bound analytes. Bound analytes may be detected using known detection types.

  8. The Ca2+/Mg2+ Sites of Troponin C Modulate Crossbridge-Mediated Thin Filament Activation in Cardiac Myofibrils†

    PubMed Central

    Fuchs, Franklin; Grabarek, Zenon

    2011-01-01

    The Ca2+/Mg2+ sites (III and IV) located in the C-terminal domain of cardiac troponin C (cTnC) have been generally considered to play a purely structural role in keeping the cTnC bound to the thin filament. However, several lines of evidence, including the discovery of cardiomyopathy-associated mutations in the C-domain, have raised the possibility that these sites may have a more complex role in contractile regulation. To explore this possibility, the ATPase activity of rat cardiac myofibrils was assayed under conditions in which no Ca2+ was bound to the N-terminal regulatory Ca2+ -binding site (site II). Myosin-S1 was treated with N-ethylmaleimide to create strong-binding myosin heads (NEM-S1), which could activate the cardiac thin filament in the absence of Ca2+. NEM-S1 activation was assayed at pCa 8.0-6.5 and in the presence of either 1mM or 30 μM free Mg2+. ATPase activity was maximal when sites III and IV were occupied by Mg2+ and it steadily declined as Ca2+ displaced Mg2+. The data suggest that in the absence of Ca2+ at site II strong-binding myosin crossbridges cause the opening of more active sites on the thin filament if the C-domain is occupied by Mg2+ rather than Ca2+. This finding could be relevant to the contraction-relaxation kinetics of cardiac muscle. As Ca2+ dissociates from site II of cTnC during the early relaxing phase of the cardiac cycle, residual Ca2+ bound at sites III and IV might facilitate the switching off of the thin filament and the detachment of crossbridges from actin. PMID:21539814

  9. Cooperative cross-bridge activation of thin filaments contributes to the Frank-Starling mechanism in cardiac muscle.

    PubMed

    Smith, L; Tainter, C; Regnier, M; Martyn, D A

    2009-05-01

    Myosin cross-bridges play an important role in the regulation of thin-filament activation in cardiac muscle. To test the hypothesis that sarcomere length (SL) modulation of thin-filament activation by strong-binding cross-bridges underlies the Frank-Starling mechanism, we inhibited force and strong cross-bridge binding to intermediate levels with sodium vanadate (Vi). Force and stiffness varied proportionately with [Ca(2+)] and [Vi]. Increasing [Vi] (decreased force) reduced the pCa(50) of force-[Ca(2+)] relations at 2.3 and 2.0 microm SL, with little effect on slope (n(H)). When maximum force was inhibited to approximately 40%, the effects of SL on force were diminished at lower [Ca(2+)], whereas at higher [Ca(2+)] (pCa < 5.6) the relative influence of SL on force increased. In contrast, force inhibition to approximately 20% significantly reduced the sensitivity of force-[Ca(2+)] relations to changes in both SL and myofilament lattice spacing. Strong cross-bridge binding cooperatively induced changes in cardiac troponin C structure, as measured by dichroism of 5' iodoacetamido-tetramethylrhodamine-labeled cardiac troponin C. This apparent cooperativity was reduced at shorter SL. These data emphasize that SL and/or myofilament lattice spacing modulation of the cross-bridge component of cardiac thin-filament activation contributes to the Frank-Starling mechanism. PMID:19413974

  10. Hemodynamic importance of preserving the normal sequence of ventricular activation in permanent cardiac pacing.

    PubMed

    Leclercq, C; Gras, D; Le Helloco, A; Nicol, L; Mabo, P; Daubert, C

    1995-06-01

    Pacing the right ventricle in the apex profoundly modifies the sequence of activation and thus the sequence of contraction and relaxation of the left ventricle. To evaluate the relative importance of preserving normal ventricular activation sequence and optimal atrioventricular (AV) synchrony in permanent pacing, we compared the effects of three pacing modes: AAI, preserving both normal AV synchrony and normal activation sequence; DDD, with complete ventricular capture that preserves only AV synchrony; and VVI, disrupting both, at rest and during exercise. Hemodynamic and radionuclide studies were performed in 11 patients who had normal intrinsic conduction and who were implanted on a long-term basis with a DDDR pacemaker for isolated sinus node dysfunction. AAI versus DDD and VVI significantly increased cardiac output at rest (6.6 +/- 1.3 L/min vs 6 +/- 0.9 L/min vs 5 +/- 1 L/min; p < 0.01) and during exercise (13.5 +/- 2 L/min vs 12.1 +/- 2.2 L/min vs 14.4 +/- 2.1 L/min; p < 0.01). Pulmonary capillary wedge pressure was lowest with AAI (15.4 +/- 4.5 mm Hg), with an average reduction of 17% compared with DDD (19.6 +/- 5 mm Hg; p < 0.01) and of 30% compared with VVI (25.8 +/- 7 mm Hg; p < 0.01) during exercise. Identical benefits were observed for all other hemodynamic parameters: right atrial pressure, pulmonary artery pressure, left ventricular (LV) stroke work index, and systemic vascular resistances. LV ejection fraction was significantly higher in AAI than in DDD at rest (61% vs 58%, respectively; p < 0.05) and during exercise (65% vs 60%, respectively; p < 0.05). This improvement in LV systolic function resulted principally from the increase in septal ejection fraction. LV filling also was improved in AAI as demonstrated by a significant increase in peak filling rate at rest and during exercise. These data show the importance of preserving, whenever possible, not only normal AV synchrony but also normal ventricular activation sequence in permanent cardiac

  11. Cardiac Glycosides Activate the Tumor Suppressor and Viral Restriction Factor Promyelocytic Leukemia Protein (PML)

    PubMed Central

    Milutinovic, Snezana; Heynen-Genel, Susanne; Chao, Elizabeth; Dewing, Antimone; Solano, Ricardo; Milan, Loribelle; Barron, Nikki; He, Min; Diaz, Paul W.; Matsuzawa, Shu-ichi; Reed, John C.; Hassig, Christian A.

    2016-01-01

    Cardiac glycosides (CGs), inhibitors of Na+/K+-ATPase (NKA), used clinically to treat heart failure, have garnered recent attention as potential anti-cancer and anti-viral agents. A high-throughput phenotypic screen designed to identify modulators of promyelocytic leukemia protein (PML) nuclear body (NB) formation revealed the CG gitoxigenin as a potent activator of PML. We demonstrate that multiple structurally distinct CGs activate the formation of PML NBs and induce PML protein SUMOylation in an NKA-dependent fashion. CG effects on PML occur at the post-transcriptional level, mechanistically distinct from previously described PML activators and are mediated through signaling events downstream of NKA. Curiously, genomic deletion of PML in human cancer cells failed to abrogate the cytotoxic effects of CGs and other apoptotic stimuli such as ceramide and arsenic trioxide that were previously shown to function through PML in mice. These findings suggest that alternative pathways can compensate for PML loss to mediate apoptosis in response to CGs and other apoptotic stimuli. PMID:27031987

  12. Cardiac Glycosides Activate the Tumor Suppressor and Viral Restriction Factor Promyelocytic Leukemia Protein (PML).

    PubMed

    Milutinovic, Snezana; Heynen-Genel, Susanne; Chao, Elizabeth; Dewing, Antimone; Solano, Ricardo; Milan, Loribelle; Barron, Nikki; He, Min; Diaz, Paul W; Matsuzawa, Shu-ichi; Reed, John C; Hassig, Christian A

    2016-01-01

    Cardiac glycosides (CGs), inhibitors of Na+/K+-ATPase (NKA), used clinically to treat heart failure, have garnered recent attention as potential anti-cancer and anti-viral agents. A high-throughput phenotypic screen designed to identify modulators of promyelocytic leukemia protein (PML) nuclear body (NB) formation revealed the CG gitoxigenin as a potent activator of PML. We demonstrate that multiple structurally distinct CGs activate the formation of PML NBs and induce PML protein SUMOylation in an NKA-dependent fashion. CG effects on PML occur at the post-transcriptional level, mechanistically distinct from previously described PML activators and are mediated through signaling events downstream of NKA. Curiously, genomic deletion of PML in human cancer cells failed to abrogate the cytotoxic effects of CGs and other apoptotic stimuli such as ceramide and arsenic trioxide that were previously shown to function through PML in mice. These findings suggest that alternative pathways can compensate for PML loss to mediate apoptosis in response to CGs and other apoptotic stimuli. PMID:27031987

  13. PGE2 Reduces MMP-14 and Increases Plasminogen Activator Inhibitor-1 in Cardiac Fibroblasts

    PubMed Central

    Kassem, Kamal M.; Clevenger, Margarette H.; Szandzik, David L.; Peterson, Edward; Harding, Pamela

    2014-01-01

    Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the membrane type matrix metalloproteinase, MMP-14. We thus hypothesized that PGE2 regulates expression of MMP-14 and also affects fibroblast migration. Primary cultures of neonatal rat ventricular fibroblasts (NVFs) were used to test the effects of PGE2. Gene and protein expression was assessed by real time RT-PCR and Western blot, MMP activity was determined by zymography and migration of NVF was assessed by motility in a transwell system. PGE2 reduced expression of MMP-14 and these effects were antagonized by an EP4 antagonist. An EP4 agonist mimicked the effect of PGE2. PGE2 also increased mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of MMP activation. However, PGE2-stimulation of PAI-1 was mediated by the EP1/EP3 receptor and not EP4. Migration of NVF was assessed by motility in a transwell system. Treatment of NVFs with PGE2 reduced the number of cells migrating towards 10% FCS. Treatment with the EP2 agonist also reduced migration but did not affect MMP-14 expression or PAI-1. Our results suggest that PGE2 utilizes different receptors and mechanisms to ultimately decrease MMP expression and NVF migration. PMID:25263346

  14. PGE2 reduces MMP-14 and increases plasminogen activator inhibitor-1 in cardiac fibroblasts.

    PubMed

    Kassem, Kamal M; Clevenger, Margarette H; Szandzik, David L; Peterson, Edward; Harding, Pamela

    2014-10-01

    Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE2 EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the membrane type matrix metalloproteinase, MMP-14. We thus hypothesized that PGE2 regulates expression of MMP-14 and also affects fibroblast migration. Primary cultures of neonatal rat ventricular fibroblasts (NVFs) were used to test the effects of PGE2. Gene and protein expression was assessed by real time RT-PCR and Western blot, MMP activity was determined by zymography and migration of NVF was assessed by motility in a transwell system. PGE2 reduced expression of MMP-14 and these effects were antagonized by an EP4 antagonist. An EP4 agonist mimicked the effect of PGE2. PGE2 also increased mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of MMP activation. However, PGE2-stimulation of PAI-1 was mediated by the EP1/EP3 receptor and not EP4. Migration of NVF was assessed by motility in a transwell system. Treatment of NVFs with PGE2 reduced the number of cells migrating toward 10% FCS. Treatment with the EP2 agonist also reduced migration but did not affect MMP-14 expression or PAI-1. Our results suggest that PGE2 utilizes different receptors and mechanisms to ultimately decrease MMP expression and NVF migration. PMID:25263346

  15. Singular value decomposition of optically-mapped cardiac rotors and fibrillatory activity

    NASA Astrophysics Data System (ADS)

    Rabinovitch, A.; Biton, Y.; Braunstein, D.; Friedman, M.; Aviram, I.; Yandrapalli, S.; Pandit, S. V.; Berenfeld, O.

    2015-03-01

    Our progress of understanding how cellular and structural factors contribute to arrhythmia is hampered in part because of controversies as to whether a fibrillating heart is driven by a single, several, or multiple number of sources, whether they are focal or reentrant and how to localize them. Here we demonstrate how a novel usage of the neutral singular value decomposition (SVD) method enables the extraction of the governing spatial and temporal modes of excitation from a rotor and fibrillatory waves. Those modes highlight patterns and regions of organization in the midst of the otherwise seemingly random propagating excitation waves. We apply the method to experimental models of cardiac fibrillation in rabbit hearts. We show that SVD analysis is able to enhance the classification of the heart electrical patterns into regions harboring drivers in the form of fast reentrant activity and other regions of by-standing activity. This enhancement is accomplished without any prior assumptions regarding the spatial, temporal or spectral properties of those drivers. The analysis corroborates that the dominant mode has the highest activation rate and further reveals a new feature: a transfer of modes from the driving to passive regions resulting in a partial reaction of the passive region to the driving region.

  16. Singular Value Decomposition of Optically-Mapped Cardiac Rotors and Fibrillatory Activity

    PubMed Central

    Rabinovitch, A.; Biton, Y.; Braunstein, D.; Friedman, M.; Aviram, I.; Yandrapalli, S.; Pandit, S. V.; Berenfeld, O.

    2015-01-01

    Our progress of understanding how cellular and structural factors contribute to the arrhythmia is hampered in part because of controversies whether a fibrillating heart is driven by a single, several, or multiple number of sources, and whether they are focal or reentrant, and how to localize them. Here we demonstrate how a novel usage of the neutral singular value decomposition (SVD) method enables the extraction of the governing spatial and temporal modes of excitation from a rotor and fibrillatory waves. Those modes highlight patterns and regions of organization in the midst of the otherwise seemingly-randomly propagating excitation waves. We apply the method to experimental models of cardiac fibrillation in rabbit hearts. We show that the SVD analysis is able to enhance the classification of the heart electrical patterns into regions harboring drivers in the form of fast reentrant activity and other regions of by-standing activity. This enhancement is accomplished without any prior assumptions regarding the spatial, temporal or spectral properties of those drivers. The analysis corroborates that the dominant mode has the highest activation rate and further reveals a new feature: A transfer of modes from the driving to the passive regions resulting in a partial reaction of the passive region to the driving region. PMID:26668401

  17. Automated Detection of Activity Transitions for Prompting

    PubMed Central

    Feuz, Kyle D.; Cook, Diane J.; Rosasco, Cody; Robertson, Kayela; Schmitter-Edgecombe, Maureen

    2016-01-01

    Individuals with cognitive impairment can benefit from intervention strategies like recording important information in a memory notebook. However, training individuals to use the notebook on a regular basis requires a constant delivery of reminders. In this work, we design and evaluate machine learning-based methods for providing automated reminders using a digital memory notebook interface. Specifically, we identify transition periods between activities as times to issue prompts. We consider the problem of detecting activity transitions using supervised and unsupervised machine learning techniques, and find that both techniques show promising results for detecting transition periods. We test the techniques in a scripted setting with 15 individuals. Motion sensors data is recorded and annotated as participants perform a fixed set of activities. We also test the techniques in an unscripted setting with 8 individuals. Motion sensor data is recorded as participants go about their normal daily routine. In both the scripted and unscripted settings a true positive rate of greater than 80% can be achieved while maintaining a false positive rate of less than 15%. On average, this leads to transitions being detected within 1 minute of a true transition for the scripted data and within 2 minutes of a true transition on the unscripted data. PMID:27019791

  18. Asiatic acid inhibits cardiac hypertrophy by blocking interleukin-1β-activated nuclear factor-κB signaling in vitro and in vivo

    PubMed Central

    Xu, Xiaohan; Si, Linjie; Xu, Jing; Yi, Chenlong; Wang, Fang; Gu, Weijuan

    2015-01-01

    Background Activated interleukin (IL)-1β signaling pathway is closely associated with pathological cardiac hypertrophy. This study investigated whether asiatic acid (AA) could inhibit IL-1β-related hypertrophic signaling, and thus suppressing the development of cardiac hypertrophy. Methods Transverse aortic constriction (TAC) induced cardiac hypertrophy in C57BL/6 mice and cultured neonatal cardiac myocytes stimulated with IL-1β were used to evaluate the role of AA in cardiac hypertrophy. The expression of atrial natriuretic peptide (ANP) was evaluated by quantitative polymerase chain reaction (qPCR) and the nuclear factor (NF)-κB binding activity was measured by electrophoretic mobility shift assays (EMSA). Results AA pretreatment significantly attenuated the IL-1β-induced hypertrophic response of cardiomyocytes as reflected by reduction in the cardiomyocyte surface area and the inhibition of ANP mRNA expression. The protective effect of AA on IL-1β-stimulated cardiomyocytes was associated with the reduction of NF-κB binding activity. In addition, AA prevented TAC-induced cardiac hypertrophy in vivo. It was found that AA markedly reduced the excessive expression of IL-1β and ANP, and inhibited the activation of NF-κB in the hypertrophic myocardium. Conclusions Our data suggest that AA may be a novel therapeutic agent for cardiac hypertrophy. The inhibition of IL-1β-activated NF-κB signaling may be the mechanism through which AA prevents cardiac hypertrophy. PMID:26623102

  19. The Relationship between Expressive/Suppressive Hostility Behavior and Cardiac Autonomic Activations in Patients with Coronary Artery Disease

    PubMed Central

    Lin, I-Mei; Weng, Chia-Ying; Lin, Tin-Kwang; Lin, Chin-Lon

    2015-01-01

    Background Hostility is an important psychosocial risk factor in coronary artery disease (CAD). Expressive and suppressive hostility behaviors are related to cardiovascular response in healthy adults. However, the relationships of these behavioral dimensions to cardiac autonomic activations in CAD remain unclear. Method This study involved 76 patients with CAD to whom a hostility inventory was administered, who were instructed to recall a neutral event and an anger-related event. Heart rate and blood pressure were obtained for each patient as the indices of cardiovascular response; heart rate variability was transformed from electrocardiograph and as the indices of cardiac autonomic activation. Results The results showed that CAD patients with expressive hostility behavior experienced higher cardiovascular autonomic activations during the neutral and anger recall tasks, and lower parasympathetic activations during the recovery after an anger episode. On the other hand, CAD patients with suppressive hostility behavior experienced both sympathetic and parasympathetic activations during the baseline and recovery stages, as well as simultaneously activated higher parasympathetic response. Conclusions The results of this study suggested that it is appropriate to extend the cardiac autonomic activation model for expressive and suppressive hostility behaviors in patients with CAD. PMID:27122887

  20. Testing a Longitudinal Integrated Self-Efficacy and Self-Determination Theory Model for Physical Activity Post-Cardiac Rehabilitation

    PubMed Central

    Sweet, Shane N.; Fortier, Michelle S.; Strachan, Shaelyn M.; Blanchard, Chris M.; Boulay, Pierre

    2014-01-01

    Self-determination theory and self-efficacy theory are prominent theories in the physical activity literature, and studies have begun integrating their concepts. Sweet, Fortier, Strachan and Blanchard (2012) have integrated these two theories in a cross-sectional study. Therefore, this study sought to test a longitudinal integrated model to predict physical activity at the end of a 4-month cardiac rehabilitation program based on theory, research and Sweet et al.’s cross-sectional model. Participants from two cardiac rehabilitation programs (N=109) answered validated self-report questionnaires at baseline, two and four months. Data were analyzed using Amos to assess the path analysis and model fit. Prior to integration, perceived competence and self-efficacy were combined, and labeled as confidence. After controlling for 2-month physical activity and cardiac rehabilitation site, no motivational variables significantly predicted residual change in 4-month physical activity. Although confidence at two months did not predict residual change in 4-month physical activity, it had a strong positive relationship with 2-month physical activity (β=0.30, P<0.001). The overall model retained good fit indices. In conclusion, results diverged from theoretical predictions of physical activity, but self-determination and self-efficacy theory were still partially supported. Because the model had good fit, this study demonstrated that theoretical integration is feasible. PMID:26973926

  1. An incremental double-layer capacitance of a planar nano gap and its application in cardiac-troponin T detection.

    PubMed

    Hsueh, Hsiao-Ting; Lin, Chih-Ting

    2016-05-15

    Surface potential is one of the most important properties at solid-liquid interfaces. It can be modulated by the voltage applied on the electrode or by the surface properties. Hence, surface potential is a good indicator for surface modifications, such as biomolecular bindings. In this work, we proposed a planar nano-gap structure for surface-potential difference monitoring. Based on the proposed architecture, the variance of surface-potential difference can be determined by electrical double layer capacitance (EDLC) between the nano-gap electrodes. Using cyclic voltammetry method, in this work, we demonstrated a relationship between surface potential and EDLC by chemically modifying surface properties. Finally, we also showed the proposed planar nano-gap device provides the capability for cardiac-troponin T (cTnT) measurements with co-existed 10 µg/ml BSA interference. The detection dynamic range is from 100 pg/ml to 1 µg/ml. Based on experimental results and extrapolation, the detection limit is less than 100 pg/ml in diluted PBS buffer (0.01X PBS). These results demonstrated the planar nano-gap architecture having potentials on biomolecular detection through monitoring of surface-potential variation. PMID:26761619

  2. Acute Radiation Effects on Cardiac Function Detected by Strain Rate Imaging in Breast Cancer Patients

    SciTech Connect

    Erven, Katrien; Jurcut, Ruxandra; Weltens, Caroline; Giusca, Sorin; Ector, Joris; Wildiers, Hans; Van den Bogaert, Walter; Voigt, Jens-Uwe

    2011-04-01

    Purpose: To investigate the occurrence of early radiation-induced changes in regional cardiac function using strain rate imaging (SRI) by tissue Doppler echocardiography. Methods and Materials: We included 20 left-sided and 10 right-sided breast cancer patients receiving radiotherapy (RT) to the breast or chest wall. Standard echocardiography and SRI were performed before RT (baseline), immediately after RT (post-RT), and at 2 months follow-up (FUP) after RT. Regional strain (S) and strain rate (SR) values were obtained from all 18 left ventricular (LV) segments. Data were compared to the regional radiation dose. Results: A reduction in S was observed post-RT and at FUP in left-sided patients (S{sub post-RT}: -17.6 {+-} 1.5%, and S{sub FUP}: -17.4 {+-} 2.3%, vs. S{sub baseline}: -19.5 {+-} 2.1%, p < 0.001) but not in right-sided patients. Within the left-sided patient group, S and SR were significantly reduced after RT in apical LV segments (S{sub post-RT}: -15.3 {+-} 2.5%, and S{sub FUP}: -14.3 {+-} 3.7%, vs. S{sub baseline}: -19.3 {+-} 3.0%, p < 0.01; and SR{sub post-RT}: -1.06 {+-} 0.15 s {sup -1}, and SR{sub FUP}: -1.16 {+-} 0.28 s {sup -1}, vs. SR{sub baseline}: -1.29 {+-} 0.27s {sup -1}, p = 0.01), but not in mid- or basal segments. Furthermore, we observed that segments exposed to more than 3 Gy showed a significant decrease in S after RT (S{sub post-RT}: -16.1 {+-} 1.6%, and S{sub FUP}: -15.8 {+-} 3.4%, vs. S{sub baseline}: -18.9 {+-} 2.6%, p < 0.001). This could not be observed in segments receiving less than 3 Gy. Conclusions: SRI shows a dose-related regional decrease in myocardial function after RT. It might be a useful tool in the evaluation of modern RT techniques, with respect to cardiac toxicity.

  3. Object and activity detection from aerial video

    NASA Astrophysics Data System (ADS)

    Se, Stephen; Shi, Feng; Liu, Xin; Ghazel, Mohsen

    2015-05-01

    Aerial video surveillance has advanced significantly in recent years, as inexpensive high-quality video cameras and airborne platforms are becoming more readily available. Video has become an indispensable part of military operations and is now becoming increasingly valuable in the civil and paramilitary sectors. Such surveillance capabilities are useful for battlefield intelligence and reconnaissance as well as monitoring major events, border control and critical infrastructure. However, monitoring this growing flood of video data requires significant effort from increasingly large numbers of video analysts. We have developed a suite of aerial video exploitation tools that can alleviate mundane monitoring from the analysts, by detecting and alerting objects and activities that require analysts' attention. These tools can be used for both tactical applications and post-mission analytics so that the video data can be exploited more efficiently and timely. A feature-based approach and a pixel-based approach have been developed for Video Moving Target Indicator (VMTI) to detect moving objects at real-time in aerial video. Such moving objects can then be classified by a person detector algorithm which was trained with representative aerial data. We have also developed an activity detection tool that can detect activities of interests in aerial video, such as person-vehicle interaction. We have implemented a flexible framework so that new processing modules can be added easily. The Graphical User Interface (GUI) allows the user to configure the processing pipeline at run-time to evaluate different algorithms and parameters. Promising experimental results have been obtained using these tools and an evaluation has been carried out to characterize their performance.

  4. Urotensin II Promotes Vagal-Mediated Bradycardia by Activating Cardiac-Projecting Parasympathetic Neurons of Nucleus Ambiguus

    PubMed Central

    Brailoiu, G. Cristina; Deliu, Elena; Rabinowitz, Joseph E.; Tilley, Douglas G.; Koch, Walter J.; Brailoiu, Eugen

    2014-01-01

    Urotensin II (U-II) is a cyclic undecapeptide that regulates cardiovascular function at central and peripheral sites. The functional role of U-II nucleus ambiguus, a key site controlling cardiac tone, has not been established, despite the identification of U-II and its receptor at this level. We report here that U-II produces an increase in cytosolic Ca2+ concentration in retrogradely labeled cardiac vagal neurons of nucleus ambiguus via two pathways: (i) Ca2+ release from the endoplasmic reticulum via inositol 1,4,5-trisphosphate receptor; and (ii) Ca2+ influx through P/Q-type Ca2+ channels. In addition, U-II depolarizes cultured cardiac parasympathetic neurons. Microinjection of increasing concentrations of U-II into nucleus ambiguus elicits dose-dependent bradycardia in conscious rats, indicating the in vivo activation of the cholinergic pathway controlling the heart rate. Both the in vitro and in vivo effects were abolished by the urotensin receptor antagonist, urantide. Our findings suggest that, in addition, to the previously reported increase in sympathetic outflow, U-II activates cardiac vagal neurons of nucleus ambiguus, which may contribute to cardioprotection. PMID:24521102

  5. Type III Transforming Growth Factor-β Receptor Drives Cardiac Hypertrophy Through β-Arrestin2-Dependent Activation of Calmodulin-Dependent Protein Kinase II.

    PubMed

    Lou, Jie; Zhao, Dan; Zhang, Ling-Ling; Song, Shu-Ying; Li, Yan-Chao; Sun, Fei; Ding, Xiao-Qing; Yu, Chang-Jiang; Li, Yuan-Yuan; Liu, Mei-Tong; Dong, Chang-Jiang; Ji, Yong; Li, Hongliang; Chu, Wenfeng; Zhang, Zhi-Ren

    2016-09-01

    The role of type III transforming growth factor-β receptor (TβRIII) in the pathogenesis of heart diseases remains largely unclear. Here, we investigated the functional role and molecular mechanisms of TβRIII in the development of myocardial hypertrophy. Western blot and quantitative real time-polymerase chain reaction analyses revealed that the expression of TβRIII was significantly elevated in human cardiac hypertrophic samples. Consistently, TβRIII expression was substantially increased in transverse aortic constriction (TAC)- and isoproterenol-induced mouse cardiac hypertrophy in vivo and in isoproterenol-induced cardiomyocyte hypertrophy in vitro. Overexpression of TβRIII resulted in cardiomyocyte hypertrophy, whereas isoproterenol-induced cardiomyocyte hypertrophy was greatly attenuated by knockdown of TβRIII in vitro. Cardiac-specific transgenic expression of TβRIII independently led to cardiac hypertrophy in mice, which was further aggravated by isoproterenol and TAC treatment. Cardiac contractile function of the mice was not altered in TβRIII transgenic mice; however, TAC led to significantly decreased cardiac contractile function in TβRIII transgenic mice compared with control mice. Conversely, isoproterenol- and TAC-induced cardiac hypertrophy and TAC-induced cardiac contractile function impairment were partially reversed by suppression of TβRIII in vivo. Our data suggest that TβRIII mediates stress-induced cardiac hypertrophy through activation of Ca(2+)/calmodulin-dependent protein kinase II, which requires a physical interaction of β-arrestin2 with both TβRIII and calmodulin-dependent protein kinase II. Our findings indicate that stress-induced increase in TβRIII expression results in cardiac hypertrophy through β-arrestin2-dependent activation of calmodulin-dependent protein kinase II and that transforming growth factor-β and β-adrenergic receptor signaling are not involved in spontaneous cardiac hypertrophy in cardiac

  6. Possible mechanism of cardiac depressant activity of Berberis orthobotrys roots in isolated rabbit heart.

    PubMed

    Alamgeer; Akhtar, Muhammad Shoaib; Jabeen, Qaiser; Bashir, Sajid; Malik, Muhammad Nasir Hayat; Karim, Sabeha; Mushtaq, Muhammad Naveed; Rasool, Shahid; Latif, Fozia; Tabbasum, Nazia; Khan, Abdul Qayyum; Ahsan, Haseeb; Khan, Wasim; Javed, Ibrahim

    2014-01-01

    Berberis orhob, otrvs Bien. ex Aitch. (B.o.) has been reported to have antihypertensive effect in different experimental models. The aim of present study was to evaluate the possible antihypertensive mechanism. Aqueous methanolic extract of B.o. roots and its various fractions namely (ethyl acetate, n-butanol or aqueous) in different concentrations (10 ng/mL, 100 ng/mL, I pg/mL, 10 pg/mL, 100 pg/mL ) were evaluated in isolated perfused rabbit heart to assess their effect on force of contraction, HR and perfusion pressure. The crude extract of B.o. and its fractions exhibited a significant decrease in heart rate, contractility and perfusion pressure of isolated rabbit heart, however, butanolic fraction produced more prominent effect and was selected for further study. The effects of butanol fraction were not blocked by atropine (10' M) in isolated perfused heart. However, butanol fraction significantly blocked the effects of adrenaline (10' M). It is therefore conceivable that cardiac depressant activity of B.o. butanol fraction might be due to the presence of certain 3-blocking agents which might be responsible for antihypertensive effect However, further experiments are required to isolate the active compound(s) and elucidate exact mechanism of action. PMID:25272893

  7. Pitx2 promotes heart repair by activating the antioxidant response after cardiac injury.

    PubMed

    Tao, Ge; Kahr, Peter C; Morikawa, Yuka; Zhang, Min; Rahmani, Mahdis; Heallen, Todd R; Li, Lele; Sun, Zhao; Olson, Eric N; Amendt, Brad A; Martin, James F

    2016-06-01

    Myocardial infarction results in compromised myocardial function and heart failure owing to insufficient cardiomyocyte self-renewal. Unlike many vertebrates, mammalian hearts have only a transient neonatal renewal capacity. Reactivating primitive reparative ability in the mature mammalian heart requires knowledge of the mechanisms that promote early heart repair. By testing an established Hippo-deficient heart regeneration mouse model for factors that promote renewal, here we show that the expression of Pitx2 is induced in injured, Hippo-deficient ventricles. Pitx2-deficient neonatal mouse hearts failed to repair after apex resection, whereas adult mouse cardiomyocytes with Pitx2 gain-of-function efficiently regenerated after myocardial infarction. Genomic analyses indicated that Pitx2 activated genes encoding electron transport chain components and reactive oxygen species scavengers. A subset of Pitx2 target genes was cooperatively regulated with the Hippo pathway effector Yap. Furthermore, Nrf2, a regulator of the antioxidant response, directly regulated the expression and subcellular localization of Pitx2. Pitx2 mutant myocardium had increased levels of reactive oxygen species, while antioxidant supplementation suppressed the Pitx2 loss-of-function phenotype. These findings reveal a genetic pathway activated by tissue damage that is essential for cardiac repair. PMID:27251288

  8. [Features of brain oscillatory activity and cardiac defense in treatment arterial hypertensives].

    PubMed

    Aftanas, L I; Brak, I V; Gilinskaia, O M; Pavlov, S V; Reva, N V

    2014-01-01

    Stress reactivity of the motivational system of defense can be assessed with the aid the cardiac defense response (CDR) - the reaction of the cardiovascular system to unexpected aversive unconditioned stimulus. The main objective of the study was revealing putative contribution of oscillatory systems of the brain into central pathogenic mechanisms of enhanced blood pressure (BP) stress-reactivity in naive patients with arterial hypertension (AH) of the 1st-2nd degrees (n = 17) and healthy control (n = 19) subjects. Using dynamic registration "beat-by-beat" arterial pressure, and oscillatory activity related EEG (64 channels) is estimated using the event-related synchronization/desynchronization (ERD/ERS). Along with abnormally high blood pressure in patients with hypertension background set significantly lower concentrations of serotonin blood platelets and increased tonic activation of the left hemisphere, reflected in the asymmetric reduction of delta- (2-4 Hz) and theta-1 (4-6 Hz) power in the central and parietal cortex in the hemisphere CDR of the patients are characterized by hyperactivity both short- and long-latency components of blood pressure. According to the dynamic analysis of the concomitant EEG, long-latency BP components may be accounted by, among other mechanisms, weakening of the descending ("top-down") inhibitory control, hypothetically implemented with the high-frequency EEG alpha (10-12 Hz) oscillations from the medial central-parietal cortex of both hemispheres of the brain. PMID:25464727

  9. Monitoring respiration and cardiac activity using fiber Bragg grating-based sensor.

    PubMed

    Dziuda, Lukasz; Skibniewski, Franciszek Wojciech; Krej, Mariusz; Lewandowski, Jaroslaw

    2012-07-01

    This paper shows the design of a fiber-based sensor for living activities in human body and the results of a laboratory evaluation carried out on it. The authors have developed a device that allows for monitoring the vibrations of human body evoked by living activities--breathing and cardiac rhythm. The device consists of a Bragg grating inscribed into a single mode optical fiber and operating on a wavelength of around 1550 nm. The fiber Bragg grating (FBG) is mounted inside a pneumatic cushion to be placed between the backrest of the seat and the back of the monitored person. Deformations of the cushion, involving deformations of the FBG, are proportional to the vibrations of the body leaning on the cushion. Laboratory studies have shown that the sensor allows for obtaining dynamic strains on the sensing FBG in the range of 50-124 μ strain caused by breathing and approximately 8.3 μstrain induced by heartbeat, which are fully measurable by today's FBG interrogation systems. The maximum relative measurement error of the presented sensor is 12%. The sensor's simple design enables it to be easily implemented in pilot's and driver's seats for monitoring the physiological condition of pilots and drivers. PMID:22514201

  10. Are Cardiac Autonomic Nervous System Activity and Perceived Stress Related to Functional Somatic Symptoms in Adolescents? The TRAILS Study

    PubMed Central

    Janssens, Karin A. M.; Riese, Harriëtte; Van Roon, Arie M.; Hunfeld, Joke A. M.; Groot, Paul F. C.; Oldehinkel, Albertine J.; Rosmalen, Judith G. M.

    2016-01-01

    Objective Stressors have been related to medically insufficiently explained or functional somatic symptoms (FSS). However, the underlying mechanism of this association is largely unclear. In the current study, we examined whether FSS are associated with different perceived stress and cardiac autonomic nervous system (ANS) levels during a standardized stressful situation, and whether these associations are symptom-specific. Methods We examined 715 adolescents (16.1 years, 51.3% girls) from the Dutch cohort study Tracking Adolescents’ Individual Lives Sample during the Groningen Social Stress Test (GSST). FSS were assessed by the Youth Self-Report, and clustered into a cluster of overtiredness, dizziness and musculoskeletal pain and a cluster of headache and gastrointestinal symptoms. Perceived stress levels (i.e. unpleasantness and arousal) were assessed by the Self-Assessment Manikin, and cardiac ANS activity by assessing heart rate variability (HRV-HF) and pre-ejection period (PEP). Perceived stress and cardiac ANS levels before, during, and after the GSST were studied as well as cardiac ANS reactivity. Linear regression analyses were used to examine the associations. Results Perceived arousal levels during (beta = 0.09, p = 0.04) and after (beta = 0.07, p = 0.047) the GSST, and perceived unpleasantness levels before (beta = 0.07, p = 0.048) and during (beta = 0.12, p = 0.001) the GSST were related to FSS during the past couple of months. The association between perceived stress and FSS was stronger for the FSS cluster of overtiredness, dizziness and musculoskeletal pain than for the cluster of headache and gastrointestinal symptoms. Neither ANS activity levels before, during, and after the GSST, nor maximal HF-HRV and PEP reactivity were related to FSS. Conclusions This study suggests that perceived stress levels during social stress are related to FSS, whereas cardiac ANS activity and reactivity are not related to FSS. PMID:27089394

  11. Autophagic Signaling and Proteolytic Enzyme Activity in Cardiac and Skeletal Muscle of Spontaneously Hypertensive Rats following Chronic Aerobic Exercise

    PubMed Central

    McMillan, Elliott M.; Paré, Marie-France; Baechler, Brittany L.; Graham, Drew A.; Rush, James W. E.; Quadrilatero, Joe

    2015-01-01

    Hypertension is a cardiovascular disease associated with deleterious effects in skeletal and cardiac muscle. Autophagy is a degradative process essential to muscle health. Acute exercise can alter autophagic signaling. Therefore, we aimed to characterize the effects of chronic endurance exercise on autophagy in skeletal and cardiac muscle of normotensive and hypertensive rats. Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were assigned to a sedentary condition or 6 weeks of treadmill running. White gastrocnemius (WG) of hypertensive rats had higher (p<0.05) caspase-3 and proteasome activity, as well as elevated calpain activity. In addition, skeletal muscle of hypertensive animals had elevated (p<0.05) ATG7 and LC3I protein, LAMP2 mRNA, and cathepsin activity, indicative of enhanced autophagic signaling. Interestingly, chronic exercise training increased (p<0.05) Beclin-1, LC3, and p62 mRNA as well as proteasome activity, but reduced (p<0.05) Beclin-1 and ATG7 protein, as well as decreased (p<0.05) caspase-3, calpain, and cathepsin activity. Left ventricle (LV) of hypertensive rats had reduced (p<0.05) AMPKα and LC3II protein, as well as elevated (p<0.05) p-AKT, p-p70S6K, LC3I and p62 protein, which collectively suggest reduced autophagic signaling. Exercise training had little effect on autophagy-related signaling factors in LV; however, exercise training increased (p<0.05) proteasome activity but reduced (p<0.05) caspase-3 and calpain activity. Our results suggest that autophagic signaling is altered in skeletal and cardiac muscle of hypertensive animals. Regular aerobic exercise can effectively alter the proteolytic environment in both cardiac and skeletal muscle, as well as influence several autophagy-related factors in skeletal muscle of normotensive and hypertensive rats. PMID:25799101

  12. Activated macrophages as a feeder layer for growth of resident cardiac progenitor cells.

    PubMed

    Sepúlveda, Diana E; Cabeza Meckert, Patricia; Locatelli, Paola; Olea, Fernanda D; Pérez, Néstor G; Pinilla, Oscar A; Díaz, Romina G; Crottogini, Alberto; Laguens, Rubén P

    2016-08-01

    The adult heart contains a population of cardiac progenitor cells (CPCs). Growing and collecting an adequate number of CPCs demands complex culture media containing growth factors. Since activated macrophages secrete many growth factors, we investigated if activated isolated heart cells seeded on a feeder layer of activated peritoneal macrophages (PM) could result in CPCs and if these, in turn, could exert cardioprotection in rats with myocardial infarction (MI). Heart cells of inbred Wistar rats were isolated by collagenase digestion and cultured on PM obtained 72 h after intraperitoneal injection of 12 ml thioglycollate. Cells (1 × 10(6)) exhibiting CPC phenotype (immunohistochemistry) were injected in the periphery of rat MI 10 min after coronary artery occlusion. Control rats received vehicle. Three weeks later, left ventricular (LV) function (echocardiogram) was assessed, animals were euthanized and the hearts removed for histological studies. Five to six days after seeding heart cells on PM, spherical clusters composed of small bright and spherical cells expressing mostly c-Kit and Sca-1 antigens were apparent. After explant, those clusters developed cobblestone-like monolayers that expressed smooth muscle actin and sarcomeric actin and were successfully transferred for more than ten passages. When injected in the MI periphery, many of them survived at 21 days after coronary ligature, improved LV ejection fraction and decreased scar size as compared with control rats. CPC-derived cells with cardiocyte and smooth muscle phenotypes can be successfully grown on a feeder layer of activated syngeneic PM. These cells decreased scar size and improved heart function in rats with MI. PMID:25432330

  13. Peptide fragments of the dihydropyridine receptor can modulate cardiac ryanodine receptor channel activity and sarcoplasmic reticulum Ca2+ release.

    PubMed Central

    Dulhunty, Angela F; Curtis, Suzanne M; Cengia, Louise; Sakowska, Magdalena; Casarotto, Marco G

    2004-01-01

    We show that peptide fragments of the dihydropyridine receptor II-III loop alter cardiac RyR (ryanodine receptor) channel activity in a cytoplasmic Ca2+-dependent manner. The peptides were AC (Thr-793-Ala-812 of the cardiac dihydropyridine receptor), AS (Thr-671-Leu-690 of the skeletal dihydropyridine receptor), and a modified AS peptide [AS(D-R18)], with an extended helical structure. The peptides added to the cytoplasmic side of channels in lipid bilayers at > or = 10 nM activated channels when the cytoplasmic [Ca2+] was 100 nM, but either inhibited or did not affect channel activity when the cytoplasmic [Ca2+] was 10 or 100 microM. Both activation and inhibition were independent of bilayer potential. Activation by AS, but not by AC or AS(D-R18), was reduced at peptide concentrations >1 mM in a voltage-dependent manner (at +40 mV). In control experiments, channels were not activated by the scrambled AS sequence (ASS) or skeletal II-III loop peptide (NB). Resting Ca2+ release from cardiac sarcoplasmic reticulum was not altered by peptide AC, but Ca2+-induced Ca2+ release was depressed. Resting and Ca2+-induced Ca2+ release were enhanced by both the native and modified AS peptides. NMR revealed (i) that the structure of peptide AS(D-R18) is not influenced by [Ca2+] and (ii) that peptide AC adopts a helical structure, particularly in the region containing positively charged residues. This is the first report of specific functional interactions between dihydropyridine receptor A region peptides and cardiac RyR ion channels in lipid bilayers. PMID:14678014

  14. Cardiac concentric hypertrophy promoted by activated Met receptor is mitigated in vivo by inhibition of Erk1,2 signalling with Pimasertib.

    PubMed

    Sala, Valentina; Gallo, Simona; Gatti, Stefano; Medico, Enzo; Vigna, Elisa; Cantarella, Daniela; Fontani, Lara; Natale, Massimo; Cimino, James; Morello, Mara; Comoglio, Paolo Maria; Ponzetto, Antonio; Crepaldi, Tiziana

    2016-04-01

    Cardiac hypertrophy is a major risk factor for heart failure. Hence, its attenuation represents an important clinical goal. Erk1,2 signalling is pivotal in the cardiac response to stress, suggesting that its inhibition may be a good strategy to revert heart hypertrophy. In this work, we unveiled the events associated with cardiac hypertrophy by means of a transgenic model expressing activated Met receptor. c-Met proto-oncogene encodes for the tyrosine kinase receptor of Hepatocyte growth factor and is a strong inducer of Ras-Raf-Mek-Erk1,2 pathway. We showed that three weeks after the induction of activated Met, the heart presents a remarkable concentric hypertrophy, with no signs of congestive failure and preserved contractility. Cardiac enlargement is accompanied by upregulation of growth-regulating transcription factors, natriuretic peptides, cytoskeletal proteins, and Extracellular Matrix remodelling factors (Timp1 and Pai1). At a later stage, cardiac hypertrophic remodelling results into heart failure with preserved systolic function. Prevention trial by suppressing activated Met showed that cardiac hypertrophy is reversible, and progression to heart failure is prevented. Notably, treatment with Pimasertib, Mek1 inhibitor, attenuates cardiac hypertrophy and remodelling. Our results suggest that modulation of Erk1.2 signalling may constitute a new therapeutic approach for treating cardiac hypertrophies. PMID:26924269

  15. Low birth weight activates the renin–angiotensin system, but limits cardiac angiogenesis in early postnatal life

    PubMed Central

    Wang, Kimberley C W; Brooks, Doug A; Summers-Pearce, Brooke; Bobrovskaya, Larisa; Tosh, Darran N; Duffield, Jaime A; Botting, Kimberley J; Zhang, Song; Caroline McMillen, I; Morrison, Janna L

    2015-01-01

    Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin–angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life. PMID:25649246

  16. Low birth weight activates the renin-angiotensin system, but limits cardiac angiogenesis in early postnatal life.

    PubMed

    Wang, Kimberley C W; Brooks, Doug A; Summers-Pearce, Brooke; Bobrovskaya, Larisa; Tosh, Darran N; Duffield, Jaime A; Botting, Kimberley J; Zhang, Song; Caroline McMillen, I; Morrison, Janna L

    2015-02-01

    Low birth weight (LBW) is associated with increased risk of adult cardiovascular disease and this association may be partly a consequence of early programming of the renin-angiotensin system (RAS). We investigated the effects of LBW on expression of molecules in the RAS and cardiac tissue remodeling. Left ventricular samples were collected from the hearts of 21 days old lambs that were born average birth weight (ABW) and LBW. Cardiac mRNA expression was quantified using real-time RT-PCR and protein expression was quantified using Western blotting. DNA methylation and histone acetylation were assessed by combined bisulfite restriction analysis and chromatin immunoprecipitation, respectively. There were increased plasma renin activity, angiotensin I (ANGI), and ANGII concentrations in LBW compared to ABW lambs at day 20. In LBW lambs, there was increased expression of cardiac ACE2 mRNA, decreased ANGII receptor type 1 (AT1R) protein, and acetylation of histone H3K9 of the AT1R promoter but no changes in AT1R mRNA expression and AT1R promoter DNA methylation. There was no difference in the abundance of proteins involved in autophagy or fibrosis. BIRC5 and VEGF mRNA expression was increased; however, the total length of the capillaries was decreased in the hearts of LBW lambs. Activation of the circulating and local cardiac RAS in neonatal LBW lambs may be expected to increase cardiac fibrosis, autophagy, and capillary length. However, we observed only a decrease in total capillary length, suggesting a dysregulation of the RAS in the heart of LBW lambs and this may have significant implications for heart health in later life. PMID:25649246

  17. CMOS-compatible, label-free silicon-nanowire biosensors to detect cardiac troponin I for acute myocardial infarction diagnosis.

    PubMed

    Kong, Tao; Su, Ruigong; Zhang, Beibei; Zhang, Qi; Cheng, Guosheng

    2012-04-15

    A label-free biosensor for electrical detection of cardiac troponin I (cTnI), a highly sensitive and selective biomarker of acute myocardial infarction (AMI), is demonstrated using silicon nanowire (SiNW) based field-effect transistors (FETs). The FET devices were fabricated by a complementary metal oxide semiconductor (CMOS) compatible top-down approach to define the SiNW followed by tetramethylammonium hydroxide (TMAH) wet etching. Electrical characterizations of the SiNW FET revealed an ambipolar conduction characteristic with an on/off ratio of 10(5)-10(6). CTnI monoclonal antibodies were then covalently immobilized on the SiNW surfaces. By integrating with a homemade biosensor measurement system, the biosensor exhibited rapid and sensitive response to cTnI proteins. The current response showed a nature of logarithm relationship against the cTnI concentration from 46 ng/mL down to 0.092 ng/mL. Moreover, an anti-interference capability of the fabricated biosensor was also assessed. By utilizing the top-down fabrication method, this work provides an efficient way for the cTnI proteins detection with an enormous potential of mass-production, which definitely facilitate the practical applications. PMID:22386490

  18. Gender-related differences in maximum gait speed and daily physical activity in elderly hospitalized cardiac inpatients: a preliminary study.

    PubMed

    Izawa, Kazuhiro P; Watanabe, Satoshi; Hirano, Yasuyuki; Matsushima, Shinya; Suzuki, Tomohiro; Oka, Koichiro; Kida, Keisuke; Suzuki, Kengo; Osada, Naohiko; Omiya, Kazuto; Brubaker, Peter H; Shimizu, Hiroyuki; Akashi, Yoshihiro J

    2015-03-01

    Maximum gait speed and physical activity (PA) relate to mortality and morbidity, but little is known about gender-related differences in these factors in elderly hospitalized cardiac inpatients. This study aimed to determine differences in maximum gait speed and daily measured PA based on sex and the relationship between these measures in elderly cardiac inpatients.A consecutive 268 elderly Japanese cardiac inpatients (mean age, 73.3 years) were enrolled and divided by sex into female (n = 75, 28%) and male (n = 193, 72%) groups. Patient characteristics and maximum gait speed, average step count, and PA energy expenditure (PAEE) in kilocalorie per day for 2 days assessed by accelerometer were compared between groups.Gait speed correlated positively with in-hospital PA measured by average daily step count (r = 0.46, P < 0.001) and average daily PAEE (r = 0.47, P < 0.001) in all patients. After adjustment for left ventricular ejection fraction, step counts and PAEE were significantly lower in females than males (2651.35 ± 1889.92 vs 4037.33 ± 1866.81 steps, P < 0.001; 52.74 ± 51.98 vs 99.33 ± 51.40 kcal, P < 0.001), respectively.Maximum gait speed was slower and PA lower in elderly female versus male inpatients. Minimum gait speed and step count values in this study might be minimum target values for elderly male and female Japanese cardiac inpatients. PMID:25789953

  19. AMP-Activated Protein Kinase Signalling in Cancer and Cardiac Hypertrophy

    PubMed Central

    Lipovka, Yulia; Konhilas, John P

    2015-01-01

    The AMP-protein kinase (AMPK) pathway is very versatile as it regulates cellular energetic homeostasis in many different tissue types. An appreciation for the importance of AMPK signalling and regulation in cardiovascular and tumor biology is increasing. Recently, a link has been established between anti-cancer therapy and susceptibility to cardiac disease. It has been shown that some anti-cancer drugs lead to an increased risk of cardiac disease, underlined by de-regulation of AMPK signalling. This review explores the AMPK signalling axis in both cardiac and tumor metabolism. We then examine off-target AMPK inhibition by cancer drugs and how this may translate into increased risk of cardiovascular disease. Finally, we discuss the implication of deregulated AMPK signalling during different stages of cardiac hypertrophy. Better understanding of the molecular pathways behind pathological processes will lead to the development of more effective therapeutics for cancer and cardiovascular diseases. PMID:26798768

  20. Peroxisome proliferator-activated receptors in cardiac energy metabolism and cardiovascular disease.

    PubMed

    Ajith, Thekkuttuparambil Ananthanarayanan; Jayakumar, Thankamani Gopinathan

    2016-07-01

    Cardiomyocytes mainly depend on energy produced from the oxidation of fatty acids and mitochondrial oxidative phosphorylation. Shortage of energy or excessive fat accumulation can lead to cardiac disorders. High saturated fat intake and a sedentary life style have a major influence in the development of cardiovascular disease (CVD). Peroxisome proliferator-activated receptors (PPARs), one of the nuclear receptor super family members, play critical role in the metabolism of lipids by regulating their oxidation and storage. Furthermore, they are involved in glucose homeostasis as well. PPARs, mainly alpha (α) and beta/delta (β/δ), have a significant effect on the lipid metabolism and anti-inflammation in endothelial cells (ECs), vascular smooth muscle cells, and also in cardiomyocytes. Pro-inflammatory cytokines, mainly tumour necrosis factor-α, released at the site of inflammation in the sub-ECs of coronary arteries can inactivate the PPARs which can eventually lead to decreased energy production in the myocardium. Various synthetic ligands of PPAR-α and β/δ have many favourable effects in modulating the vascular diseases and heart failure. Despite the adverse effects from therapy using PPAR- gamma ligands, several laboratories are now focused on synthesizing partial activators which may combine their beneficial effects with lowering of undesirable side effects. This review discusses the role of isoforms of PPAR in the cardiomyocytes energy balance and CVD. The knowledge will help in the synthesis of ligands for their partial activation in order to render energy balance and protection from CVD. PMID:27115677

  1. Alterations in cardiac sarcolemmal Ca/sup 2 +/ pump activity during diabetes mellitus

    SciTech Connect

    Heyliger, C.E.; Prakash, A.; McNeill, J.

    1987-03-01

    Diabetes mellitus is frequently associated with a primary cardiomyopathy. The mechanisms responsible for this heart disease are not clear, but an alteration in myocardial Ca/sup 2 +/ transport is believed to be involved in its development. Even though sarcolemma plays a crucial role in cellular Ca/sup 2 +/ transport, little appears to be known about its Ca/sup 2 +/ transporting capability in the diabetic myocardium. In this regard, the authors have examined the status of the cardiac sarcolemmal Ca/sup 2 +/ pump during diabetes mellitus. Purified sarcolemmal membranes were isolated from male Wistar diabetic rat hearts 8 wk after streptozotocin injection. Ca/sup 2 +/ pump activity assessed by measuring its Ca/sup 2 +/-stimulated adenosine triphosphatase and Ca/sup 2 +/-uptake ability in the absence and presence of calmodulin was significantly depressed in the diabetic myocardium relative to controls. These results did not appear to have been influenced by the minimal sarcoplasmic reticular and mitochondrial contamination of this membrane preparation. Hence, it appears that the sarcolemmal Ca/sup 2 +/ pump is defective in the diabetic myocardium and may be involved in the altered Ca/sup 2 +/ transport of the heart during diabetes mellitus.

  2. Neural crest–derived SEMA3C activates endothelial NRP1 for cardiac outflow tract septation

    PubMed Central

    Plein, Alice; Calmont, Amélie; Fantin, Alessandro; Denti, Laura; Anderson, Naomi A.; Scambler, Peter J.; Ruhrberg, Christiana

    2015-01-01

    In mammals, the outflow tract (OFT) of the developing heart septates into the base of the pulmonary artery and aorta to guide deoxygenated right ventricular blood into the lungs and oxygenated left ventricular blood into the systemic circulation. Accordingly, defective OFT septation is a life-threatening condition that can occur in both syndromic and nonsyndromic congenital heart disease. Even though studies of genetic mouse models have previously revealed a requirement for VEGF-A, the class 3 semaphorin SEMA3C, and their shared receptor neuropilin 1 (NRP1) in OFT development, the precise mechanism by which these proteins orchestrate OFT septation is not yet understood. Here, we have analyzed a complementary set of ligand-specific and tissue-specific mouse mutants to show that neural crest–derived SEMA3C activates NRP1 in the OFT endothelium. Explant assays combined with gene-expression studies and lineage tracing further demonstrated that this signaling pathway promotes an endothelial-to-mesenchymal transition that supplies cells to the endocardial cushions and repositions cardiac neural crest cells (NCCs) within the OFT, 2 processes that are essential for septal bridge formation. These findings elucidate a mechanism by which NCCs cooperate with endothelial cells in the developing OFT to enable the postnatal separation of the pulmonary and systemic circulation. PMID:26053665

  3. Correlations between the signal complexity of cerebral and cardiac electrical activity: a multiscale entropy analysis.

    PubMed

    Lin, Pei-Feng; Lo, Men-Tzung; Tsao, Jenho; Chang, Yi-Chung; Lin, Chen; Ho, Yi-Lwun

    2014-01-01

    The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG) and a 19-channel eye-closed routine electroencephalography (EEG). Multiscale entropy (MSE) analysis was applied to three epochs (resting-awake state, photic stimulation of fast frequencies (fast-PS), and photic stimulation of slow frequencies (slow-PS)) of EEG in the 1-58 Hz frequency range, and three RR interval (RRI) time series (awake-state, sleep and that concomitant with the EEG) for each subject. The low-to-high frequency power (LF/HF) ratio of RRI was calculated to represent sympatho-vagal balance. With statistics after Bonferroni corrections, we found that: (a) the summed MSE value on coarse scales of the awake RRI (scales 11-20, RRI-MSE-coarse) were inversely correlated with the summed MSE value on coarse scales of the resting-awake EEG (scales 6-20, EEG-MSE-coarse) at Fp2, C4, T6 and T4; (b) the awake RRI-MSE-coarse was inversely correlated with the fast-PS EEG-MSE-coarse at O1, O2 and C4; (c) the sleep RRI-MSE-coarse was inversely correlated with the slow-PS EEG-MSE-coarse at Fp2; (d) the RRI-MSE-coarse and LF/HF ratio of the awake RRI were correlated positively to each other; (e) the EEG-MSE-coarse at F8 was proportional to the cognitive test score; (f) the results conform to the cholinergic hypothesis which states that cognitive impairment causes reduction in vagal cardiac modulation; (g) fast-PS significantly lowered the EEG-MSE-coarse globally. Whether these heart-brain correlations could be fully explained by the central autonomic network is unknown and needs further exploration. PMID:24498375

  4. Correlations between the Signal Complexity of Cerebral and Cardiac Electrical Activity: A Multiscale Entropy Analysis

    PubMed Central

    Lin, Pei-Feng; Lo, Men-Tzung; Tsao, Jenho; Chang, Yi-Chung; Lin, Chen; Ho, Yi-Lwun

    2014-01-01

    The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG) and a 19-channel eye-closed routine electroencephalography (EEG). Multiscale entropy (MSE) analysis was applied to three epochs (resting-awake state, photic stimulation of fast frequencies (fast-PS), and photic stimulation of slow frequencies (slow-PS)) of EEG in the 1–58 Hz frequency range, and three RR interval (RRI) time series (awake-state, sleep and that concomitant with the EEG) for each subject. The low-to-high frequency power (LF/HF) ratio of RRI was calculated to represent sympatho-vagal balance. With statistics after Bonferroni corrections, we found that: (a) the summed MSE value on coarse scales of the awake RRI (scales 11–20, RRI-MSE-coarse) were inversely correlated with the summed MSE value on coarse scales of the resting-awake EEG (scales 6–20, EEG-MSE-coarse) at Fp2, C4, T6 and T4; (b) the awake RRI-MSE-coarse was inversely correlated with the fast-PS EEG-MSE-coarse at O1, O2 and C4; (c) the sleep RRI-MSE-coarse was inversely correlated with the slow-PS EEG-MSE-coarse at Fp2; (d) the RRI-MSE-coarse and LF/HF ratio of the awake RRI were correlated positively to each other; (e) the EEG-MSE-coarse at F8 was proportional to the cognitive test score; (f) the results conform to the cholinergic hypothesis which states that cognitive impairment causes reduction in vagal cardiac modulation; (g) fast-PS significantly lowered the EEG-MSE-coarse globally. Whether these heart-brain correlations could be fully explained by the central autonomic network is unknown and needs further exploration. PMID:24498375

  5. The secretome of myocardial telocytes modulates the activity of cardiac stem cells

    PubMed Central

    Albulescu, Radu; Tanase, Cristiana; Codrici, Elena; Popescu, Daniela I; Cretoiu, Sanda M; Popescu, Laurentiu M

    2015-01-01

    Telocytes (TCs) are interstitial cells that are present in numerous organs, including the heart interstitial space and cardiac stem cell niche. TCs are completely different from fibroblasts. TCs release extracellular vesicles that may interact with cardiac stem cells (CSCs) via paracrine effects. Data on the secretory profile of TCs and the bidirectional shuttle vesicular signalling mechanism between TCs and CSCs are scarce. We aimed to characterize and understand the in vitro effect of the TC secretome on CSC fate. Therefore, we studied the protein secretory profile using supernatants from mouse cultured cardiac TCs. We also performed a comparative secretome analysis using supernatants from rat cultured cardiac TCs, a pure CSC line and TCs-CSCs in co-culture using (i) high-sensitivity on-chip electrophoresis, (ii) surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and (iii) multiplex analysis by Luminex-xMAP. We identified several highly expressed molecules in the mouse cardiac TC secretory profile: interleukin (IL)-6, VEGF, macrophage inflammatory protein 1α (MIP-1α), MIP-2 and MCP-1, which are also present in the proteome of rat cardiac TCs. In addition, rat cardiac TCs secrete a slightly greater number of cytokines, IL-2, IL-10, IL-13 and some chemokines like, GRO-KC. We found that VEGF, IL-6 and some chemokines (all stimulated by IL-6 signalling) are secreted by cardiac TCs and overexpressed in co-cultures with CSCs. The expression levels of MIP-2 and MIP-1α increased twofold and fourfold, respectively, when TCs were co-cultured with CSCs, while the expression of IL-2 did not significantly differ between TCs and CSCs in mono culture and significantly decreased (twofold) in the co-culture system. These data suggest that the TC secretome plays a modulatory role in stem cell proliferation and differentiation. PMID:26176909

  6. The secretome of myocardial telocytes modulates the activity of cardiac stem cells.

    PubMed

    Albulescu, Radu; Tanase, Cristiana; Codrici, Elena; Popescu, Daniela I; Cretoiu, Sanda M; Popescu, Laurentiu M

    2015-08-01

    Telocytes (TCs) are interstitial cells that are present in numerous organs, including the heart interstitial space and cardiac stem cell niche. TCs are completely different from fibroblasts. TCs release extracellular vesicles that may interact with cardiac stem cells (CSCs) via paracrine effects. Data on the secretory profile of TCs and the bidirectional shuttle vesicular signalling mechanism between TCs and CSCs are scarce. We aimed to characterize and understand the in vitro effect of the TC secretome on CSC fate. Therefore, we studied the protein secretory profile using supernatants from mouse cultured cardiac TCs. We also performed a comparative secretome analysis using supernatants from rat cultured cardiac TCs, a pure CSC line and TCs-CSCs in co-culture using (i) high-sensitivity on-chip electrophoresis, (ii) surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and (iii) multiplex analysis by Luminex-xMAP. We identified several highly expressed molecules in the mouse cardiac TC secretory profile: interleukin (IL)-6, VEGF, macrophage inflammatory protein 1α (MIP-1α), MIP-2 and MCP-1, which are also present in the proteome of rat cardiac TCs. In addition, rat cardiac TCs secrete a slightly greater number of cytokines, IL-2, IL-10, IL-13 and some chemokines like, GRO-KC. We found that VEGF, IL-6 and some chemokines (all stimulated by IL-6 signalling) are secreted by cardiac TCs and overexpressed in co-cultures with CSCs. The expression levels of MIP-2 and MIP-1α increased twofold and fourfold, respectively, when TCs were co-cultured with CSCs, while the expression of IL-2 did not significantly differ between TCs and CSCs in mono culture and significantly decreased (twofold) in the co-culture system. These data suggest that the TC secretome plays a modulatory role in stem cell proliferation and differentiation. PMID:26176909

  7. MicroECG: An Integrated Platform for the Cardiac Arrythmia Detection and Characterization

    NASA Astrophysics Data System (ADS)

    Nascimento, Bruno; Batista, Arnaldo; Alves, Luis Brandão; Ortigueira, Manuel; Rato, Raul

    A software tool for the analysis of the High-Resolution Electrocardiogram (HR-ECG) for Arrhythmia detection is introduced. New algorithms based on Wavelet analysis are presented and compared with the classic Simson protocol over the P and QRS segments of the Electrocardiogram (EEG). A novel procedure based on a two step wavelet analysis and synthesis is performed in order to obtain a frequency description of the P, T or QRS segments. This frequency "signature" is useful for the detection of otherwise asymptomatic Arrhythmia patients. The tool has been developed in Matlab, and deployed for a standalone C application.

  8. Cardiac Catheterization

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Cardiac Catheterization? Cardiac catheterization (KATH-eh-ter-ih-ZA-shun) is a ... disease. Doctors also can use ultrasound during cardiac catheterization to see blockages in the coronary arteries. Ultrasound ...

  9. Estrogen-related receptor gamma induces cardiac hypertrophy by activating GATA4.

    PubMed

    Kwon, Duk-Hwa; Eom, Gwang Hyeon; Kee, Hae Jin; Nam, Yoon Seok; Cho, Young Kuk; Kim, Don-Kyu; Koo, Ja Young; Kim, Hyung-Seok; Nam, Kwang-Il; Kim, Kyung Keun; Lee, In-Kyu; Park, Seung Bum; Choi, Hueng-Sik; Kook, Hyun

    2013-12-01

    Estrogen-related receptor gamma (ERRγ) is an orphan nuclear receptor that has biological roles mainly in metabolism and that controls metabolic switching in perinatal heart. In adult heart diseases, however, the functional roles of ERRγ have not yet been elucidated. In the present study, we aimed to characterize the role of ERRγ in cardiac hypertrophy. The functional roles of ERRγ in the development of cardiac hypertrophy were examined in primary cultured cardiomyocytes and in animal models. ERRγ expression was increased in hearts from human hypertrophic cardiomyopathy patients and in both cellular and animal models of cardiac hypertrophy. Transgenic overexpression in mouse heart as well as forced expression of ERRγ in cardiomyocytes induced hypertrophic phenotypes. Knock-down of ERRγ blocked agonist-induced hypertrophic phenotypes. ERRγ bound directly to the proximal ERR-responsive element in the GATA4 promoter in a sequence-specific manner and thereby induced transcription. ERRγ-induced hypertrophy was blocked by inhibition of GATA4. GSK-5182, an inverse agonist of ERRγ, completely blocked cardiac hypertrophy in cardiomyocytes. It also prevented aortic banding-induced cardiac hypertrophy and fibrosis in mouse heart. These findings demonstrate a novel ERRγ/GATA4 signal cascade in the development of cardiac hypertrophy and suggest GSK-5182 as a possible therapeutic. PMID:24083978

  10. Assessing Physical Activity as a Core Component in Cardiac Rehabilitation: A POSITION STATEMENT OF THE AMERICAN ASSOCIATION OF CARDIOVASCULAR AND PULMONARY REHABILITATION.

    PubMed

    Kaminsky, Leonard A; Brubaker, Peter H; Guazzi, Marco; Lavie, Carl J; Montoye, Alexander H K; Sanderson, Bonnie K; Savage, Patrick D

    2016-01-01

    Physical inactivity is a well-established major risk factor for cardiovascular disease. As such, physical activity counseling is 1 of the 10 core components of cardiac rehabilitation/secondary prevention programs recommended by the American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR). In addition, the ability to perform a physical activity assessment and report outcomes is 1 of the 10 core competencies of cardiac rehabilitation/secondary prevention professionals published by the AACVPR. Unfortunately, standardized procedures for physical activity assessment of cardiac rehabilitation patients have not been developed and published. Thus, the objective of this AACVPR statement is to provide an overview of physical activity assessment concepts and procedures and to provide a recommended approach for performing a standardized assessment of physical activity in all comprehensive cardiac rehabilitation programs following the core components recommendations. PMID:27307067

  11. Cardiac Myosin-binding Protein C and Troponin-I Phosphorylation Independently Modulate Myofilament Length-dependent Activation.

    PubMed

    Kumar, Mohit; Govindan, Suresh; Zhang, Mengjie; Khairallah, Ramzi J; Martin, Jody L; Sadayappan, Sakthivel; de Tombe, Pieter P

    2015-12-01

    β-Adrenergic stimulation in heart leads to increased contractility and lusitropy via activation of protein kinase A (PKA). In the cardiac sarcomere, both cardiac myosin binding protein C (cMyBP-C) and troponin-I (cTnI) are prominent myofilament targets of PKA. Treatment of permeabilized myocardium with PKA induces enhanced myofilament length-dependent activation (LDA), the cellular basis of the Frank-Starling cardiac regulatory mechanism. It is not known, however, which of these targets mediates the altered LDA and to what extent. Here, we employed two genetic mouse models in which the three PKA sites in cMyBP-C were replaced with either phospho-mimic (DDD) or phospho-null (AAA) residues. AAA- or DDD-permeabilized myocytes (n = 12-17) were exchanged (~93%) for recombinant cTnI in which the two PKA sites were mutated to either phospho-mimic (DD) or phospho-null (AA) residues. Force-[Ca(2+)] relationships were determined at two sarcomere lengths (SL = 1.9 μm and SL = 2.3 μm). Data were fit to a modified Hill equation for each individual cell preparation at each SL. LDA was indexed as ΔEC50, the difference in [Ca(2+)] required to achieve 50% force activation at the two SLs. We found that PKA-mediated phosphorylation of cMyBP-C and cTnI each independently contribute to enhance myofilament length-dependent activation properties of the cardiac sarcomere, with relative contributions of ~67 and ~33% for cMyBP-C for cTnI, respectively. We conclude that β-adrenergic stimulation enhances the Frank-Starling regulatory mechanism predominantly via cMyBP-C PKA-mediated phosphorylation. We speculate that this molecular mechanism enhances cross-bridge formation at long SL while accelerating cross-bridge detachment and relaxation at short SLs. PMID:26453301

  12. Microarray analysis of active cardiac remodeling genes in a familial hypertrophic cardiomyopathy mouse model rescued by a phospholamban knockout

    PubMed Central

    Rajan, Sudarsan; Pena, James R.; Jegga, Anil G.; Aronow, Bruce J.; Wolska, Beata M.

    2013-01-01

    Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed two mouse models that affect cardiac performance. One mouse model encodes an FHC-associated mutation in α-tropomyosin: Glu → Gly at amino acid 180, designated as Tm180. These mice display a phenotype that is characteristic of FHC, including severe cardiac hypertrophy with fibrosis and impaired physiological performance. The other model was a gene knockout of phospholamban (PLN KO), a regulator of calcium uptake in the sarcoplasmic reticulum of cardiomyocytes; these hearts exhibit hypercontractility with no pathological abnormalities. Previous work in our laboratories shows that when mice were genetically crossed between the PLN KO and Tm180, the progeny (PLN KO/Tm180) display a rescued hypertrophic phenotype with improved morphology and cardiac function. To understand the changes in gene expression that occur in these models undergoing cardiac remodeling (Tm180, PLN KO, PLN KO/Tm180, and nontransgenic control mice), we conducted microarray analyses of left ventricular tissue at 4 and 12 mo of age. Expression profiling reveals that 1,187 genes changed expression in direct response to the three genetic models. With these 1,187 genes, 11 clusters emerged showing normalization of transcript expression in the PLN KO/Tm180 hearts. In addition, 62 transcripts are highly involved in suppression of the hypertrophic phenotype. Confirmation of the microarray analysis was conducted by quantitative RT-PCR. These results provide insight into genes that alter expression during cardiac remodeling and are active during modulation of the cardiomyopathic phenotype. PMID:23800848

  13. Efficient cross-modality cardiac four-dimensional active appearance model construction

    NASA Astrophysics Data System (ADS)

    Zhang, Honghai; Abiose, Ademola K.; Buettner, Elisabeth J.; Birrer, Emily K.; Sonka, Milan; Martins, James B.; Wahle, Andreas

    2009-02-01

    The efficiency of constructing an active appearance model (AAM) is limited by establishing the independent standard via time-consuming and tedious manual tracing. It is more challenging for 3D and 4D (3D+time) datasets as the smoothness of shape and motion is essential. In this paper, a three-stage pipeline is designed for efficient cross-modality model construction. It utilizes existing AAM and active shape model (ASM) of the left ventricle (LV) for magnetic resonance (MR) datasets to build 4D AAM of the LV for real-time 3D echocardiography (RT3DE) datasets. The first AAM fitting stage uses AAM for MR to fit valid shapes onto the intensity-transformed RT3DE data that resemble low-quality MR data. The fitting is implemented in a 3D phase-by-phase fashion to prevent introducing bias due to different motion patterns related to the two modalities and patient groups. The second global-scale editing stage adjusts fitted shapes by tuning modes of ASM for MR data. The third local-scale editing stage adjusts the fitted volumes at small local regions and produces the final accurate independent standard. By visual inspection, the AAM fitting stage successfully produces results that capture the LV motion - especially its base movement - within the cardiac cycle on 29 of the 32 RT3DE datasets tested. This multi-stage approach can reduce the human effort of the manual tracing by at least 50%. With the model built for a modality A available, this approach is generalizable to constructing the model of the same organ for any other modality B.

  14. Nitric oxide formation in acutely rejecting cardiac allografts correlates with GTP cyclohydrolase I activity

    PubMed Central

    2005-01-01

    Inducible nitric oxide synthase (iNOS) is a prominent component of the complex array of mediators in acute graft rejection. While NO production is determined by iNOS expression, BH4 (tetrahydrobiopterin), a cofactor of iNOS synthesized by GTP cyclohydrolase I, has been considered critical in sustaining NO production. In the present study, we examined time-dependent changes in iNOS and GTP cyclohydrolase I in rat cardiac allografts. The increase in iNOS protein and mRNA in allografts was similar at POD4 (post-operative day 4) and POD6. However, the peak increase in intragraft NO level at POD4 was not sustained at POD6. This disparity could not be explained by any decrease in iNOS enzyme activity measured ex vivo with optimal amounts of substrate and cofactors. Lower iNOS activity could be explained by changes in total biopterin levels in allografts at POD4 that was decreased to baseline at POD6. Changes in biopterin production correlated with lower GTP cyclohydrolase I protein levels but not by any change in GTP cyclohydrolase I mRNA. Functionally, allografts displayed bradycardia and distended diastolic and systolic dimensions at POD6 but not at POD4. Likewise, histological rejection scores were increased at POD4 but with a secondary increased stage at POD6. It is hypothesized that the dissimilar amounts of NO at early and later stages of rejection is due to uncoupling of iNOS arising from disproportionate synthesis of BH4. These findings provide insight into a potential pathway regulating NO bioactivity in graft rejection. Such knowledge may potentially assist in the design of newer strategies to prevent acute graft rejection. PMID:16000090

  15. How to Calculate Renyi Entropy from Heart Rate Variability, and Why it Matters for Detecting Cardiac Autonomic Neuropathy

    PubMed Central

    Cornforth, David J.;  Tarvainen, Mika P.; Jelinek, Herbert F.

    2014-01-01

    Cardiac autonomic neuropathy (CAN) is a disease that involves nerve damage leading to an abnormal control of heart rate. An open question is to what extent this condition is detectable from heart rate variability (HRV), which provides information only on successive intervals between heart beats, yet is non-invasive and easy to obtain from a three-lead ECG recording. A variety of measures may be extracted from HRV, including time domain, frequency domain, and more complex non-linear measures. Among the latter, Renyi entropy has been proposed as a suitable measure that can be used to discriminate CAN from controls. However, all entropy methods require estimation of probabilities, and there are a number of ways in which this estimation can be made. In this work, we calculate Renyi entropy using several variations of the histogram method and a density method based on sequences of RR intervals. In all, we calculate Renyi entropy using nine methods and compare their effectiveness in separating the different classes of participants. We found that the histogram method using single RR intervals yields an entropy measure that is either incapable of discriminating CAN from controls, or that it provides little information that could not be gained from the SD of the RR intervals. In contrast, probabilities calculated using a density method based on sequences of RR intervals yield an entropy measure that provides good separation between groups of participants and provides information not available from the SD. The main contribution of this work is that different approaches to calculating probability may affect the success of detecting disease. Our results bring new clarity to the methods used to calculate the Renyi entropy in general, and in particular, to the successful detection of CAN. PMID:25250311

  16. Decline in Serum Cholinesterase Activities Predicts 2-Year Major Adverse Cardiac Events

    PubMed Central

    Arbel, Yaron; Shenhar-Tsarfaty, Shani; Waiskopf, Nir; Finkelstein, Ariel; Halkin, Amir; Revivo, Miri; Berliner, Shlomo; Herz, Itzhak; Shapira, Itzhak; Keren, Gad; Soreq, Hermona; Banai, Shmuel

    2014-01-01

    Parasympathetic activity influences long-term outcome in patients with cardiovascular disease, but the underlying mechanism(s) linking parasympathetic activity and the occurrence of major adverse cardiovascular events (MACEs) are incompletely understood. The aim of this pilot study was to evaluate the association between serum cholinesterase activities as parasympathetic biomarkers and the risk for the occurrence of MACEs. Cholinergic status was determined by measuring the cumulative capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to hydrolyze the AChE substrate acetylthiocholine. Cholinergic status was evaluated in randomly selected patients undergoing cardiac catheterization. The patients were divided into two groups of 100 patients in each group, with or without occurrence of MACEs during a follow-up period of 40 months. Cox regression models adjusted for potential clinical, metabolic and inflammatory confounders served to evaluate association with clinical outcome. We found that patients with MACE presented lower cholinergic status and AChE values at catheterization (1,127 ± 422 and 359 ± 153 nmol substrate hydrolyzed per minute per milliliter, respectively) than no-MACE patients (1,760 ± 546 and 508 ± 183 nmol substrate hydrolyzed per minute per milliliter, p < 0.001 and p < 0.001, respectively), whose levels were comparable to those of matched healthy controls (1,622 ± 303 and 504 ± 126 nmol substrate hydrolyzed per minute per milliliter, respectively). In a multivariate analysis, patients with AChE or total cholinergic status values below median showed conspicuously elevated risk for MACE (hazard ratio 1.85 [95% confidence interval [CI] 1.09–3.15, p = 0.02] and 2.21 [95% CI 1.22–4.00, p = 0.009]) compared with those above median, even after adjusting for potential confounders. We conclude that parasympathetic dysfunction expressed as reduced serum AChE and AChE activities in patients compared to healthy controls can

  17. The orally active urotensin receptor antagonist, KR36676, attenuates cellular and cardiac hypertrophy

    PubMed Central

    Oh, K S; Lee, J H; Yi, K Y; Lim, C J; Lee, S; Park, C H; Seo, H W; Lee, B H

    2015-01-01

    Background and Purpose Blockade of the actions of urotensin-II (U-II) mediated by the urotensin (UT) receptor should improve cardiac function and prevent cardiac remodelling in cardiovascular disease. Here, we have evaluated the pharmacological properties of the recently identified UT receptor antagonist, 2-(6,7-dichloro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-methyl-N-(2-(pyrrolidin-1-yl)-1-(4-(thiophen-3-yl)phenyl) ethyl)acetamide (KR36676). Experimental Approach Pharmacological properties of KR36676 were studied in a range of in vitro assays (receptor binding, calcium mobilization, stress fibre formation, cellular hypertrophy) and in vivo animal models such as cardiac hypertrophy induced by transverse aortic constriction (TAC) or myocardial infarction (MI). Key Results KR36676 displayed high binding affinity for the UT receptor (Ki: 0.7 nM), similar to that of U-II (0.4 nM), and was a potent antagonist at that receptor (IC50: 4.0 nM). U-II-induced stress fibre formation and cellular hypertrophy were significantly inhibited with low concentrations of KR36676 (≥0.01 μM). Oral administration of KR36676 (30 mg·kg−1) in a TAC model in mice attenuated cardiac hypertrophy and myocardial fibrosis. Moreover, KR36676 restored cardiac function and myocyte size in rats with MI-induced cardiac hypertrophy. Conclusions and Implications A highly potent UT receptor antagonist exerted anti-hypertrophic effects not only in infarcted rat hearts but also in pressure-overloaded mouse hearts. KR36676 could be a valuable pharmacological tool in elucidating the complicated physiological role of U-II and UT receptors in cardiac hypertrophy. PMID:25597918

  18. 5-Azacytidine Induces Cardiac Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells by Activating Extracellular Regulated Kinase

    PubMed Central

    Qian, Qian; Qian, Hui; Zhang, Xu; Zhu, Wei; Yan, Yongmin; Ye, Shengqin; Peng, Xiujuan; Li, Wei; Xu, Zhe; Sun, Lingyun

    2012-01-01

    5-Azacytidine (5-Aza) induces differentiation of mesenchymal stem cells (MSCs) into cardiomyocytes. However, the underlying mechanisms are not well understood. Our previous work showed that 5-Aza induces human bone marrow-derived MSCs to differentiate into cardiomyocytes. Here, we demonstrated that 5-Aza induced cardiac differentiation of human umbilical cord-derived MSCs (hucMSCs) and explored the potential signaling pathway. Our results showed that hucMSCs had cardiomyocyte phenotypes after 5-Aza treatment. In addition, myogenic cells differentiated from hucMSCs were positive for mRNA and protein of desmin, β-myosin heavy chain, cardiac troponin T, A-type natriuretic peptide, and Nkx2.5. Human diploid lung fibroblasts treated with 5-Aza expressed no cardiac-specific genes. 5-Aza did not induce hucMSCs to differentiate into osteoblasts. Further study revealed that 5-Aza treatment activated extracellular signal related kinases (ERK) in hucMSCs, but protein kinase C showed no response to 5-Aza administration. U0126, a specific inhibitor of ERK, could inhibit 5-Aza-induced expression of cardiac-specific genes and proteins in hucMSCs. Increased phosphorylation of signal transducers and activators of transcription 3, and up-regulation of myocyte enhancer-binding factor-2c and myogenic differentiation antigen in 5-Aza-treated hucMSCs were also suppressed by U0126. Taken together, these results suggested that sustained activation of ERK by 5-Aza contributed to the induction of the differentiation of hucMSCs into cardiomyocytes in vitro. PMID:21476855

  19. Evaluating the Interactive Web-Based Program, Activate Your Heart, for Cardiac Rehabilitation Patients: A Pilot Study

    PubMed Central

    Boyce, Sally; Houchen-Wolloff, Linzy; Sewell, Louise; Singh, Sally

    2014-01-01

    Background Conventional cardiac rehabilitation (CR) programs are traditionally based on time-constrained, structured, group-based programs, usually set in hospitals or leisure centers. Uptake for CR remains poor, despite the ongoing evidence demonstrating its benefits. Additional alternative forms of CR are needed. An Internet-based approach may offer an alternative mode of delivering CR that may improve overall uptake. Activate Your Heart (AYH) is a Web-based CR program that has been designed to support individuals with coronary heart disease (CHD). Objective The aim of this pilot study was to observe the outcome for participants following the AYH program. Methods We conducted a prospective observational trial, recruiting low-risk patients with CHD. Measures of exercise, exercise capacity, using the Incremental Shuttle Walk Test (ISWT), dietary habits, and psychosocial well-being were conducted by a CR specialist at baseline and at 8 weeks following the Web-based intervention. Results We recruited 41 participants; 33 completed the program. We documented significant improvements in the ISWT distance (mean change 49.69 meters, SD 68.8, P<.001), and Quality of Life (QOL) (mean change 0.28, SD 0.4, P<.001). Dietary habits improved with an increased proportion of patients consuming at least 5 portions of fruit and vegetables per day, (22 [71%] to 29 [94%] P=.01) and an increased proportion of patients consuming at least 2 portions of oily fish per week (14 [45%] to 21 [68%], P=.01). We did not detect changes in anxiety and depression scores or exercise behavior. Conclusions We observed important improvements in exercise capacity, QOL, and dietary habits in a group of participants following a Web-based CR program. The program may offer an alternative approach to CR. A mobile version has been developed and we need to conduct further trials to establish its value compared to supervised CR. PMID:25359204

  20. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

    The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration, a combination of these approaches could ameliorate the overall repair process to incorporate the participation of multiple cellular players. PMID:26484341

  1. Utility of cardiac troponins in patients with suspected cardiac trauma or after cardiac surgery.

    PubMed

    Adams, J E

    1997-12-01

    Detection of cardiac injury after blunt chest wall trauma or cardiac surgery is problematic. Previously available biomarkers have been hindered largely by limitations of specifity for myocardial damage. Both cardiac troponin I and T have been evaluated in these patient subgroups. While many questions remain unanswered, it appears that measurement of troponin proteins will facilitate patient care in these difficult situations. PMID:9439875

  2. A High-Performance Fluorescence Immunoassay Based on the Relaxation of Quenching, Exemplified by Detection of Cardiac Troponin I.

    PubMed

    Kim, Seung-Wan; Cho, Il-Hoon; Park, Ji-Na; Seo, Sung-Min; Paek, Se-Hwan

    2016-01-01

    The intramolecular fluorescence self-quenching phenomenon is a major drawback in developing high-performance fluorometric biosensors which use common fluorophores as signal generators. We propose two strategies involving liberation of the fluorescent molecules by means of enzymatic fragmentation of protein or dehybridization of double-stranded DNA. In the former, bovine serum albumin (BSA) was coupled with the fluorescent BODIPY dye (Red BSA), and then immobilized on a solid surface. When the insolubilized Red BSA was treated with proteinase K (10 units/mL) for 30 min, the fluorescent signal was significantly increased (3.5-fold) compared to the untreated control. In the second case, fluorophore-tagged DNA probes were linked to gold nanoparticles by hybridization with capture DNA strands densely immobilized on the surface. The quenched fluorescence signal was recovered (3.7-fold) by thermal dehybridization, which was induced with light of a specific wavelength (e.g., 530 nm) for less than 1 min. We next applied the Red BSA self-quenching relaxation technique employing enzymatic fragmentation to a high-performance immunoassay of cardiac troponin I (cTnI) in a microtiter plate format. The detection limit was 0.19 ng/mL cTnI, and the fluorescent signal was enhanced approximately 4.1-fold compared with the conventional method of direct measurement of the fluorescent signal from a non-fragmented fluorophore-labeled antibody. PMID:27171097

  3. A High-Performance Fluorescence Immunoassay Based on the Relaxation of Quenching, Exemplified by Detection of Cardiac Troponin I

    PubMed Central

    Kim, Seung-Wan; Cho, Il-Hoon; Park, Ji-Na; Seo, Sung-Min; Paek, Se-Hwan

    2016-01-01

    The intramolecular fluorescence self-quenching phenomenon is a major drawback in developing high-performance fluorometric biosensors which use common fluorophores as signal generators. We propose two strategies involving liberation of the fluorescent molecules by means of enzymatic fragmentation of protein or dehybridization of double-stranded DNA. In the former, bovine serum albumin (BSA) was coupled with the fluorescent BODIPY dye (Red BSA), and then immobilized on a solid surface. When the insolubilized Red BSA was treated with proteinase K (10 units/mL) for 30 min, the fluorescent signal was significantly increased (3.5-fold) compared to the untreated control. In the second case, fluorophore-tagged DNA probes were linked to gold nanoparticles by hybridization with capture DNA strands densely immobilized on the surface. The quenched fluorescence signal was recovered (3.7-fold) by thermal dehybridization, which was induced with light of a specific wavelength (e.g., 530 nm) for less than 1 min. We next applied the Red BSA self-quenching relaxation technique employing enzymatic fragmentation to a high-performance immunoassay of cardiac troponin I (cTnI) in a microtiter plate format. The detection limit was 0.19 ng/mL cTnI, and the fluorescent signal was enhanced approximately 4.1-fold compared with the conventional method of direct measurement of the fluorescent signal from a non-fragmented fluorophore-labeled antibody. PMID:27171097

  4. Graphene microelectrode arrays for neural activity detection.

    PubMed

    Du, Xiaowei; Wu, Lei; Cheng, Ji; Huang, Shanluo; Cai, Qi; Jin, Qinghui; Zhao, Jianlong

    2015-09-01

    We demonstrate a method to fabricate graphene microelectrode arrays (MEAs) using a simple and inexpensive method to solve the problem of opaque electrode positions in traditional MEAs, while keeping good biocompatibility. To study the interface differences between graphene-electrolyte and gold-electrolyte, graphene and gold electrodes with a large area were fabricated. According to the simulation results of electrochemical impedances, the gold-electrolyte interface can be described as a classical double-layer structure, while the graphene-electrolyte interface can be explained by a modified double-layer theory. Furthermore, using graphene MEAs, we detected the neural activities of neurons dissociated from Wistar rats (embryonic day 18). The signal-to-noise ratio of the detected signal was 10.31 ± 1.2, which is comparable to those of MEAs made with other materials. The long-term stability of the MEAs is demonstrated by comparing differences in Bode diagrams taken before and after cell culturing. PMID:25712492

  5. Design optimization of multi-pinhole micro-SPECT configurations by signal detection tasks and system performance evaluations for mouse cardiac imaging

    NASA Astrophysics Data System (ADS)

    Lee, M.-W.; Lin, W.-T.; Chen, Y.-C.

    2015-01-01

    An optimized configuration of multi-pinhole aperture can improve the spatial resolution and the sensitivity of pinhole SPECT simultaneously. In this study, an optimization strategy of the multi-pinhole configuration with a small detector is proposed for mouse cardiac imaging. A 14 mm-diameter spherical field-of-view (FOV) is used to accommodate the mouse heart. To accelerate the optimization process, the analytic models are applied to rapidly obtain the projection areas of the FOV, the sensitivities and the spatial resolutions of numerous system designs. The candidates of optimal multi-pinhole configuration are then decided by the preliminary evaluations with the analytic models. Subsequently, the pinhole SPECT systems equipped with the designed multi-pinhole apertures are modeled in GATE to generate the imaging system matrices (H matrices) for the system performance assessments. The area under the ROC curves (AUC) of the designed systems is evaluated by signal-known-exactly/background-known-statistically detection tasks with their corresponding H matrices. In addition, the spatial resolutions are estimated by the Fourier crosstalk approach, and the sensitivities are calculated with the H matrices of designed systems, respectively. Furthermore, a series of OSEM reconstruction images of synthetic phantoms, including the hot-rod phantom, mouse heart phantom and Defrise phantom, are reconstructed with the H matrices of designed systems. To quantify the sensitivity and resolution competition in the optimization process, the AUC from the detection tasks and the resolution estimated by the Fourier crosstalk are used as the figure of merits. A trade-off function of AUC and resolution is introduced to find the optimal multi-pinhole configuration. According to the examining results, a 22.5° rotated detector plus a 4-pinhole aperture with 22.5° rotation, 20% multiplexing and 1.52X magnification is the optimized multi-pinhole configuration for the micro pinhole

  6. Design optimization of multi-pinhole micro-SPECT configurations by signal detection tasks and system performance evaluations for mouse cardiac imaging.

    PubMed

    Lee, M-W; Lin, W-T; Chen, Y-C

    2015-01-21

    An optimized configuration of multi-pinhole aperture can improve the spatial resolution and the sensitivity of pinhole SPECT simultaneously. In this study, an optimization strategy of the multi-pinhole configuration with a small detector is proposed for mouse cardiac imaging. A 14 mm-diameter spherical field-of-view (FOV) is used to accommodate the mouse heart. To accelerate the optimization process, the analytic models are applied to rapidly obtain the projection areas of the FOV, the sensitivities and the spatial resolutions of numerous system designs. The candidates of optimal multi-pinhole configuration are then decided by the preliminary evaluations with the analytic models. Subsequently, the pinhole SPECT systems equipped with the designed multi-pinhole apertures are modeled in GATE to generate the imaging system matrices (H matrices) for the system performance assessments. The area under the ROC curves (AUC) of the designed systems is evaluated by signal-known-exactly/background-known-statistically detection tasks with their corresponding H matrices. In addition, the spatial resolutions are estimated by the Fourier crosstalk approach, and the sensitivities are calculated with the H matrices of designed systems, respectively. Furthermore, a series of OSEM reconstruction images of synthetic phantoms, including the hot-rod phantom, mouse heart phantom and Defrise phantom, are reconstructed with the H matrices of designed systems. To quantify the sensitivity and resolution competition in the optimization process, the AUC from the detection tasks and the resolution estimated by the Fourier crosstalk are used as the figure of merits. A trade-off function of AUC and resolution is introduced to find the optimal multi-pinhole configuration. According to the examining results, a 22.5° rotated detector plus a 4-pinhole aperture with 22.5° rotation, 20% multiplexing and 1.52X magnification is the optimized multi-pinhole configuration for the micro pinhole

  7. Complexity-Measure-Based Sequential Hypothesis Testing for Real-Time Detection of Lethal Cardiac Arrhythmias

    NASA Astrophysics Data System (ADS)

    Chen, Szi-Wen

    2006-12-01

    A novel approach that employs a complexity-based sequential hypothesis testing (SHT) technique for real-time detection of ventricular fibrillation (VF) and ventricular tachycardia (VT) is presented. A dataset consisting of a number of VF and VT electrocardiogram (ECG) recordings drawn from the MIT-BIH database was adopted for such an analysis. It was split into two smaller datasets for algorithm training and testing, respectively. Each ECG recording was measured in a 10-second interval. For each recording, a number of overlapping windowed ECG data segments were obtained by shifting a 5-second window by a step of 1 second. During the windowing process, the complexity measure (CM) value was calculated for each windowed segment and the task of pattern recognition was then sequentially performed by the SHT procedure. A preliminary test conducted using the database produced optimal overall predictive accuracy of[InlineEquation not available: see fulltext.]. The algorithm was also implemented on a commercial embedded DSP controller, permitting a hardware realization of real-time ventricular arrhythmia detection.

  8. 9 CFR 113.35 - Detection of viricidal activity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Detection of viricidal activity. 113... REQUIREMENTS Standard Procedures § 113.35 Detection of viricidal activity. The test for detection of viricidal activity provided in this section shall be conducted when such a test is prescribed in an...

  9. 9 CFR 113.35 - Detection of viricidal activity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Detection of viricidal activity. 113... REQUIREMENTS Standard Procedures § 113.35 Detection of viricidal activity. The test for detection of viricidal activity provided in this section shall be conducted when such a test is prescribed in an...

  10. 9 CFR 113.35 - Detection of viricidal activity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Detection of viricidal activity. 113... REQUIREMENTS Standard Procedures § 113.35 Detection of viricidal activity. The test for detection of viricidal activity provided in this section shall be conducted when such a test is prescribed in an...

  11. HIF-1α and PPARγ during physiological cardiac hypertrophy induced by pregnancy: Transcriptional activities and effects on target genes.

    PubMed

    Soñanez-Organis, José G; Godoy-Lugo, José A; Hernández-Palomares, Magally L E; Rodríguez-Martínez, Daniel; Rosas-Rodríguez, Jesús A; González-Ochoa, Guadalupe; Virgen-Ortiz, Adolfo; Ortiz, Rudy M

    2016-10-15

    Hypoxia inducible factor 1-α (HIF-1α) and peroxisome proliferator-activated receptor γ (PPARγ) are transcription factors that activate genes involved in cellular metabolism. Physiological cardiac hypertrophy induced by pregnancy initiates compensatory changes in metabolism. However, the contributions of HIF-1α and PPARγ to this physiological status and to its reversible, metabolic process (postpartum) in the heart are not well-defined. Therefore, the aim of the present study was to evaluate the transcriptional activities of HIF-1α and PPARγ in the left ventricle of rats before, during, and after pregnancy. Furthermore, the effects of pregnancy on target genes of glycolysis and glycerol-lipid biosynthesis, key regulatory enzymes, and metabolic intermediates were evaluated. The activities of HIF-1α and PPARγ increased 1.2- and 1.6-fold, respectively, during pregnancy, and decreased to basal levels during postpartum. Expressions of mRNA for glucose transport 1 (GLUT1), enzymes of glycolysis (HK2, PFKM, and GAPDH) and glycerol-lipid biosynthesis (GPAT and GPD1) increased 1.6- to 14-fold during pregnancy and returned to basal levels postpartum. The increase in GPD1 expression translated to an increase in its activity, but such was not the case for GAPDH suggesting that post-translational regulation of these proteins is differential during pregnancy. Glycolytic (glucose, lactate, and DHAP) and glycerol-lipid biosynthesis (G3P and FFA) intermediates increased with pregnancy and were maintained postpartum. The results demonstrate that pregnancy-induced, physiological cardiac hypertrophy activates the expression of genes involved in glycolytic and glycerol-lipid biosynthesis suggesting that the shift in cardiac metabolism is mediated by the activation of HIF-1α and PPARγ. PMID:27312951

  12. Measuring Cardiac Autonomic Nervous System (ANS) Activity in Toddlers - Resting and Developmental Challenges.

    PubMed

    Bush, Nicole R; Caron, Zoe K; Blackburn, Katherine S; Alkon, Abbey

    2016-01-01

    The autonomic nervous system (ANS) consists of two branches, the parasympathetic and sympathetic nervous systems, and controls the function of internal organs (e.g., heart rate, respiration, digestion) and responds to everyday and adverse experiences (1). ANS measures in children have been found to be related to behavior problems, emotion regulation, and health (2-7). Therefore, understanding the factors that affect ANS development during early childhood is important. Both branches of the ANS affect young children's cardiovascular responses to stimuli and have been measured noninvasively, via external monitoring equipment, using valid and reliable measures of physiological change (8-11). However, there are few studies of very young children with simultaneous measures of the parasympathetic and sympathetic nervous systems, which limits understanding of the integrated functioning of the two systems. In addition, the majority of existing studies of young children report on infants' resting ANS measures or their reactivity to commonly used mother-child interaction paradigms, and less is known about ANS reactivity to other challenging conditions. We present a study design and standardized protocol for a non-invasive and rapid assessment of cardiac autonomic control in 18 month old children. We describe methods for continuous monitoring of the parasympathetic and sympathetic branches of the ANS under resting and challenge conditions during a home or laboratory visit and provide descriptive findings from our sample of 140 ethnically diverse toddlers using validated equipment and scoring software. Results revealed that this protocol can produce a range of physiological responses to both resting and developmentally challenging conditions, as indicated by changes in heart rate and indices of parasympathetic and sympathetic activity. Individuals demonstrated variability in resting levels, responses to challenges, and challenge reactivity, which provides additional evidence

  13. Simulated 3D ultrasound LV cardiac images for active shape model training

    NASA Astrophysics Data System (ADS)

    Butakoff, Constantine; Balocco, Simone; Ordas, Sebastian; Frangi, Alejandro F.

    2007-03-01

    In this paper a study of 3D ultrasound cardiac segmentation using Active Shape Models (ASM) is presented. The proposed approach is based on a combination of a point distribution model constructed from a multitude of high resolution MRI scans and the appearance model obtained from simulated 3D ultrasound images. Usually the appearance model is learnt from a set of landmarked images. The significant level of noise, the low resolution of 3D ultrasound images (3D US) and the frequent failure to capture the complete wall of the left ventricle (LV) makes automatic or manual landmarking difficult. One possible solution is to use artificially simulated 3D US images since the generated images will match exactly the shape in question. In this way, by varying simulation parameters and generating corresponding images, it is possible to obtain a training set where the image matches the shape exactly. In this work the simulation of ultrasound images is performed by a convolutional approach. The evaluation of segmentation accuracy is performed on both simulated and in vivo images. The results obtained on 567 simulated images had an average error of 1.9 mm (1.73 +/- 0.05 mm for epicardium and 2 +/- 0.07 mm for endocardium, with 95% confidence) with voxel size being 1.1 × 1.1 × 0.7 mm. The error on 20 in vivo data was 3.5 mm (3.44 +/- 0.4 mm for epicardium and 3.73 +/- 0.4 mm for endocardium). In most images the model was able to approximate the borders of myocardium even when the latter was indistinguishable from the surrounding tissues.

  14. Stimulation of ICa by basal PKA activity is facilitated by caveolin-3 in cardiac ventricular myocytes☆

    PubMed Central

    Bryant, Simon; Kimura, Tomomi E.; Kong, Cherrie H.T.; Watson, Judy J.; Chase, Anabelle; Suleiman, M. Saadeh; James, Andrew F.; Orchard, Clive H.

    2014-01-01

    L-type Ca channels (LTCC), which play a key role in cardiac excitation–contraction coupling, are located predominantly at the transverse (t-) tubules in ventricular myocytes. Caveolae and the protein caveolin-3 (Cav-3) are also present at the t-tubules and have been implicated in localizing a number of signaling molecules, including protein kinase A (PKA) and β2-adrenoceptors. The present study investigated whether disruption of Cav-3 binding to its endogenous binding partners influenced LTCC activity. Ventricular myocytes were isolated from male Wistar rats and LTCC current (ICa) recorded using the whole-cell patch-clamp technique. Incubation of myocytes with a membrane-permeable peptide representing the scaffolding domain of Cav-3 (C3SD) reduced basal ICa amplitude in intact, but not detubulated, myocytes, and attenuated the stimulatory effects of the β2-adrenergic agonist zinterol on ICa. The PKA inhibitor H-89 also reduced basal ICa; however, the inhibitory effects of C3SD and H-89 on basal ICa amplitude were not summative. Under control conditions, myocytes stained with antibody against phosphorylated LTCC (pLTCC) displayed a striated pattern, presumably reflecting localization at the t-tubules. Both C3SD and H-89 reduced pLTCC staining at the z-lines but did not affect staining of total LTCC or Cav-3. These data are consistent with the idea that the effects of C3SD and H-89 share a common pathway, which involves PKA and is maximally inhibited by H-89, and suggest that Cav-3 plays an important role in mediating stimulation of ICa at the t-tubules via PKA-induced phosphorylation under basal conditions, and in response to β2-adrenoceptor stimulation. PMID:24412535

  15. Stress response and cardiac activity of term and preterm calves in the perinatal period.

    PubMed

    Nagel, Christina; Aurich, Jörg; Trenk, Lisa; Ille, Natascha; Drillich, Marc; Pohl, Werner; Aurich, Christine

    2016-10-01

    This study tested the hypothesis of gestational age affecting fetal cardiac activity and the stress response at birth. Heart rate (HR), heart rate variability variables, SD of the beat-to-beat interval and root mean square of successive beat-to-beat differences, and postnatal salivary cortisol concentration were studied in calves born at term (Term, n = 7, gestation length 286.3 ± 2.1 days) or after induction of parturition (Preterm, n = 7, gestation length 279.6 ± 0.2 days). Observation periods covered the last month of gestation (phase A), the last hours before birth including the first stage of labor (phase B), and the neonatal period (phase C). Fetal HR decreased in phase A (P < 0.001) and did not differ between groups. During phase B, HR increased (P < 0.05) and was higher in Preterm than in Term calves in phases B (P < 0.05) and C (P < 0.01). In Term calves, heart rate variability increased from Day 6 until birth (P < 0.05). At birth, SD of the beat-to-beat interval was higher in Term than in Preterm calves (P < 0.01). On Day 1 after birth (phase C), HR accelerations were more frequent in Term than Preterm calves (P < 0.01), whereas decelerations were more frequent in Preterm calves (P < 0.05). Cortisol concentration increased postnatally (P < 0.001) and was correlated with gestation length (r ≥ 0.68, P < 0.01). Because of a certain degree of immaturity, the ability to cope with the stress of birth may be impaired in calves born 1 week before term. PMID:27312949

  16. Various phosphodiesterase activities in different regions of the heart alter the cardiac effects of nitric oxide.

    PubMed

    Demirel-Yilmaz, Emine; Cenik, Basar; Ozcan, Gulnihal; Derici, Mehmet Kursat

    2012-09-01

    The modulation of cardiac functions by nitric oxide (NO) was established. This study examined the influences of phosphodiesterase (PDE) inhibitors on the action of NO in the different regions of the rat heart. NO donor diethylamine nonoate (DEA/NO) (0.1-100 μM) decreased functions of the right atrium. DEA/NO-induced depression of the developed tension of the right atrium was inhibited by [erythro-9-(2-hydroxy-3-nonyl)adenine] (PDE2 inhibitor), augmented by milrinone (PDE3 inhibitor), and upturned by rolipram (PDE4 inhibitor). A DEA/NO-induced decrease in the resting tension was inhibited by vinpocetine (PDE1 inhibitor) and [erythro-9-(2-hydroxy-3-nonyl)adenine] but reversed by rolipram. The decreased sinus rate by DEA/NO was prevented by vinpocetine and rolipram. DEA/NO increased cyclic guanosine monophosphate and cyclic adenosine monophosphate (cAMP) concentrations in the right atrium, and rolipram enhanced increased cAMP level. DEA/NO had no effect on the contraction of the papillary muscle. However, unchanged contraction under DEA/NO stimulation was decreased by vinpocetine, milrinone, and rolipram. DEA/NO increased cyclic guanosine monophosphate concentration but has no effect on cAMP in the papillary muscle. However, in the presence of vinpocetine and milrinone, DEA/NO reduced cAMP level. The PDE5 inhibitor sildenafil has no effect on DEA/NO actions. This study indicates that a variety of PDE activities in different regions of the rat heart shapes the action of NO on the myocardium. PMID:22653417

  17. Differentially expressed genes in embryonic cardiac tissues of mice lacking Folr1 gene activity

    PubMed Central

    Zhu, Huiping; Cabrera, Robert M; Wlodarczyk, Bogdan J; Bozinov, Daniel; Wang, Deli; Schwartz, Robert J; Finnell, Richard H

    2007-01-01

    Background Heart anomalies are the most frequently observed among all human congenital defects. As with the situation for neural tube defects (NTDs), it has been demonstrated that women who use multivitamins containing folic acid peri-conceptionally have a reduced risk for delivering offspring with conotruncal heart defects [1-3]. Cellular folate transport is mediated by a receptor or binding protein and by an anionic transporter protein system. Defective function of the Folr1 (also known as Folbp1; homologue of human FRα) gene in mice results in inadequate transport, accumulation, or metabolism of folate during cardiovascular morphogenesis. Results We have observed cardiovascular abnormalities including outflow tract and aortic arch arterial defects in genetically compromised Folr1 knockout mice. In order to investigate the molecular mechanisms underlying the failure to complete development of outflow tract and aortic arch arteries in the Folr1 knockout mouse model, we examined tissue-specific gene expression difference between Folr1 nullizygous embryos and morphologically normal heterozygous embryos during early cardiac development (14-somite stage), heart tube looping (28-somite stage), and outflow track septation (38-somite stage). Microarray analysis was performed as a primary screening, followed by investigation using quantitative real-time PCR assays. Gene ontology analysis highlighted the following ontology groups: cell migration, cell motility and localization of cells, structural constituent of cytoskeleton, cell-cell adhesion, oxidoreductase, protein folding and mRNA processing. This study provided preliminary data and suggested potential candidate genes for further description and investigation. Conclusion The results suggested that Folr1 gene ablation and abnormal folate homeostasis altered gene expression in developing heart and conotruncal tissues. These changes affected normal cytoskeleton structures, cell migration and motility as well as cellular

  18. Titin-based modulation of active tension and interfilament lattice spacing in skinned rat cardiac muscle.

    PubMed

    Fukuda, Norio; Wu, Yiming; Farman, Gerrie; Irving, Thomas C; Granzier, Henk

    2005-02-01

    The effect of titin-based passive tension on Ca2+ sensitivity of active tension and interfilament lattice spacing was studied in skinned rat ventricular trabeculae by measuring the sarcomere length (SL)-dependent change in Ca2+ sensitivity and performing small angle X-ray diffraction studies. To vary passive tension, preparations were treated with trypsin at a low concentration (0.31 mug/ml) for a short period (13 min) at 20 degrees C, that resulted in approximately 40% degradation of the I-band region of titin, with a minimal effect on A-band titin. We found that the effect of trypsin on titin-based passive tension was significantly more pronounced immediately after stretch than at steady state, 30 min after stretch (i.e., trypsin has a greater effect on viscosity than on elasticity of passive cardiac muscle). Ca2+ sensitivity was decreased by trypsin treatment at SL 2.25 microm, but not at SL 1.9 microm, resulting in marked attenuation of the SL-dependent increase in Ca2+ sensitivity. The SL-dependent change in Ca2+ sensitivity was significantly correlated with titin-based passive tension. Small-angle X-ray diffraction experiments revealed that the lattice spacing expands after trypsin treatment, especially at SL 2.25 microm, providing an inverse linear relationship between the lattice spacing and Ca2+ sensitivity. These results support the view that titin-based passive tension promotes actomyosin interaction and that the mechanism includes interfilament lattice spacing modulation. PMID:15688246

  19. Stimulation of ICa by basal PKA activity is facilitated by caveolin-3 in cardiac ventricular myocytes.

    PubMed

    Bryant, Simon; Kimura, Tomomi E; Kong, Cherrie H T; Watson, Judy J; Chase, Anabelle; Suleiman, M Saadeh; James, Andrew F; Orchard, Clive H

    2014-03-01

    L-type Ca channels (LTCC), which play a key role in cardiac excitation-contraction coupling, are located predominantly at the transverse (t-) tubules in ventricular myocytes. Caveolae and the protein caveolin-3 (Cav-3) are also present at the t-tubules and have been implicated in localizing a number of signaling molecules, including protein kinase A (PKA) and β2-adrenoceptors. The present study investigated whether disruption of Cav-3 binding to its endogenous binding partners influenced LTCC activity. Ventricular myocytes were isolated from male Wistar rats and LTCC current (ICa) recorded using the whole-cell patch-clamp technique. Incubation of myocytes with a membrane-permeable peptide representing the scaffolding domain of Cav-3 (C3SD) reduced basal ICa amplitude in intact, but not detubulated, myocytes, and attenuated the stimulatory effects of the β2-adrenergic agonist zinterol on ICa. The PKA inhibitor H-89 also reduced basal ICa; however, the inhibitory effects of C3SD and H-89 on basal ICa amplitude were not summative. Under control conditions, myocytes stained with antibody against phosphorylated LTCC (pLTCC) displayed a striated pattern, presumably reflecting localization at the t-tubules. Both C3SD and H-89 reduced pLTCC staining at the z-lines but did not affect staining of total LTCC or Cav-3. These data are consistent with the idea that the effects of C3SD and H-89 share a common pathway, which involves PKA and is maximally inhibited by H-89, and suggest that Cav-3 plays an important role in mediating stimulation of ICa at the t-tubules via PKA-induced phosphorylation under basal conditions, and in response to β2-adrenoceptor stimulation. PMID:24412535

  20. Cardiac peroxisome proliferator-activated receptor-γ expression is modulated by oxidative stress in acutely infrasound-exposed cardiomyocytes.

    PubMed

    Pei, Zhaohui; Meng, Rongsen; Zhuang, Zhiqiang; Zhao, Yiqiao; Liu, Fangpeng; Zhu, Miao-Zhang; Li, Ruiman

    2013-12-01

    The aim of the present study was to examine the effects of acute infrasound exposure on oxidative damage and investigate the underlying mechanisms in rat cardiomyocytes. Neonatal rat cardiomyocytes were cultured and exposed to infrasound for several days. In the study, the expression of CAT, GPx, SOD1, and SOD2 and their activities in rat cardiomyocytes in infrasound exposure groups were significantly decreased compared to those in the various time controls, along with significantly higher levels of O2 (-) and H2O2. Decreased cardiac cell viability was not observed in various time controls. A significant reduction in cardiac cell viability was observed in the infrasound group compared to the control, while significantly increased cardiac cell viability was observed in the infrasound exposure and rosiglitazone pretreatment group. Compared to the control, rosiglitazone significantly upregulated CAT, GPx, SOD1, and SOD2 expression and their activities in rat cardiomyocytes exposed to infrasound, while the levels of O2 (-) or H2O2 were significantly decreased. A potential link between a significant downregulation of PPAR-γ expression in rat cardiomyocytes in the infrasound group was compared to the control and infrasound-induced oxidative stress. These findings indicate that infrasound can induce oxidative damage in rat cardiomyocytes by inactivating PPAR-γ. PMID:23632742

  1. Physical Exercise Regulates p53 Activity Targeting SCO2 and Increases Mitochondrial COX Biogenesis in Cardiac Muscle with Age

    PubMed Central

    Qi, Zhengtang; He, Jie; Su, Yuhui; He, Qiang; Liu, Jingxia; Yu, Lu; Al-Attas, Omar; Hussain, Tajamul; Ding, Shuzhe; Ji, Liu; Qian, Min

    2011-01-01

    The purpose of this study was to outline the timelines of mitochondrial function, oxidative stress and cytochrome c oxidase complex (COX) biogenesis in cardiac muscle with age, and to evaluate whether and how these age-related changes were attenuated by exercise. ICR/CD-1 mice were treated with pifithrin-μ (PFTμ), sacrificed and studied at different ages; ICR/CD-1 mice at younger or older ages were randomized to endurance treadmill running and sedentary conditions. The results showed that mRNA expression of p53 and its protein levels in mitochondria increased with age in cardiac muscle, accompanied by increased mitochondrial oxidative stress, reduced expression of COX subunits and assembly proteins, and decreased expression of most markers in mitochondrial biogenesis. Most of these age-related changes including p53 activity targeting cytochrome oxidase deficient homolog 2 (SCO2), p53 translocation to mitochondria and COX biogenesis were attenuated by exercise in older mice. PFTμ, an inhibitor blocking p53 translocation to mitochondria, increased COX biogenesis in older mice, but not in young mice. Our data suggest that physical exercise attenuates age-related changes in mitochondrial COX biogenesis and p53 activity targeting SCO2 and mitochondria, and thereby induces antisenescent and protective effects in cardiac muscle. PMID:21750704

  2. Physical exercise regulates p53 activity targeting SCO2 and increases mitochondrial COX biogenesis in cardiac muscle with age.

    PubMed

    Qi, Zhengtang; He, Jie; Su, Yuhui; He, Qiang; Liu, Jingxia; Yu, Lu; Al-Attas, Omar; Hussain, Tajamul; Ding, Shuzhe; Ji, Liu; Qian, Min

    2011-01-01

    The purpose of this study was to outline the timelines of mitochondrial function, oxidative stress and cytochrome c oxidase complex (COX) biogenesis in cardiac muscle with age, and to evaluate whether and how these age-related changes were attenuated by exercise. ICR/CD-1 mice were treated with pifithrin-μ (PFTμ), sacrificed and studied at different ages; ICR/CD-1 mice at younger or older ages were randomized to endurance treadmill running and sedentary conditions. The results showed that mRNA expression of p53 and its protein levels in mitochondria increased with age in cardiac muscle, accompanied by increased mitochondrial oxidative stress, reduced expression of COX subunits and assembly proteins, and decreased expression of most markers in mitochondrial biogenesis. Most of these age-related changes including p53 activity targeting cytochrome oxidase deficient homolog 2 (SCO2), p53 translocation to mitochondria and COX biogenesis were attenuated by exercise in older mice. PFTμ, an inhibitor blocking p53 translocation to mitochondria, increased COX biogenesis in older mice, but not in young mice. Our data suggest that physical exercise attenuates age-related changes in mitochondrial COX biogenesis and p53 activity targeting SCO2 and mitochondria, and thereby induces antisenescent and protective effects in cardiac muscle. PMID:21750704

  3. Hepatocyte growth factor suppresses hypoxia/reoxygenation-induced XO activation in cardiac microvascular endothelial cells.

    PubMed

    Zhang, Yingqian; Hu, Shunying; Chen, Yundai

    2015-07-01

    Hypoxia/reoxygenation (H/R) is one of the cellular stresses in pathological conditions, such as myocardial infarction, stroke and organ transplantation. Oxidative stress caused by reactive oxygen species (ROS) is a crucial element of H/R injury in vascular endothelial cells (ECs). Xanthine oxidase (XO) has been recognized to contribute to H/R injury. Of note, xanthine oxidoreductase is synthesized as xanthine dehydrogenase (XDH) and needs to be converted to XO to become a source of superoxide. Hepatocyte growth factor (HGF) has been found to protect ECs against H/R injury. The relation, however, between HGF and XO in ECs under H/R conditions remains to be determined. Primary cultured rat cardiac microvascular endothelial cells (CMECs) were exposed to 4 h of hypoxia and followed by 1 h of reoxygenation. Generation of ROS and cytosolic Ca2+ concentration was measured by flow cytometry qualification of DCFHDA and fluo-3 AM staining cells, respectively. XDH mRNA was qualified by qRT-PCR analysis. XO activity was determined by colorimetric assay and XO protein levels were determined by Western blot. Cell apoptosis was assessed by caspase-3 activity and Annexin V/PI staining. After H/R, cellular ROS production significantly increased. Both XO activity and XO protein increased after H/R. Cellular ROS elevation was inhibited by allopurinol (a potent XO inhibitor), indicting XO accounting for the generation of ROS after H/R. In addition, XDH mRNA increased after H/R, indicating a de novo XDH synthesis, which needs to be converted to XO to become a source of superoxide. Pretreatment of HGF inhibited the elevation of XO activity and XO protein level after H/R; however, HGF has no effect on the increase of XDH mRNA. We also find an increase of the cytosolic Ca2+ in CMECs after H/R. BAPTA-AM, a cell-permeable Ca2+ chelator, prevented the increase of XO activity and XO protein levels, implicating the elevated cytosolic Ca2+ concentration involvement in XO conversion and XO

  4. The effect of obesity on electrocardiographic detection of hypertensive left ventricular hypertrophy: recalibration against cardiac magnetic resonance.

    PubMed

    Rodrigues, J C L; McIntyre, B; Dastidar, A G; Lyen, S M; Ratcliffe, L E; Burchell, A E; Hart, E C; Bucciarelli-Ducci, C; Hamilton, M C K; Paton, J F R; Nightingale, A K; Manghat, N E

    2016-03-01

    Electrocardiograph (ECG) criteria for left ventricular hypertrophy (LVH) are a widely used clinical tool. We recalibrated six ECG criteria for LVH against gold-standard cardiac magnetic resonance (CMR) and assessed the impact of obesity. One hundred and fifty consecutive tertiary hypertension clinic referrals for CMR (1.5 T) were reviewed. Patients with cardiac pathology potentially confounding hypertensive LVH were excluded (n=22). The final sample size was 128 (age: 51.0±15.2 years, 48% male). LVH was defined by CMR. From a 12-lead ECG, Sokolow-Lyon voltage and product, Cornell voltage and product, Gubner-Ungerleidger voltage and Romhilt-Estes score were evaluated, blinded to the CMR. ECG diagnostic performance was calculated. LVH by CMR was present in 37% and obesity in 51%. Obesity significantly reduced ECG sensitivity, because of significant attenuation in mean ECG values for Cornell voltage (22.2±5.7 vs 26.4±9.4 mm, P<0.05), Cornell product (2540±942 vs 3023±1185 mm • ms, P<0.05) and for Gubner-Ungerleider voltage (18.2±7.1 vs 23.3±1.2 mm, P<0.05). Obesity also significantly reduced ECG specificity, because of significantly higher prevalence of LV remodeling (no LVH but increased mass-to-volume ratio) in obese subjects without LVH (36% vs 16%, P<0.05), which correlated with higher mean ECG LVH criteria values. Obesity-specific partition values were generated at fixed 95% specificity; Cornell voltage had highest sensitivity in non-obese (56%) and Sokolow-Lyon product in obese patients (24%). Obesity significantly lowers ECG sensitivity at detecting LVH, by attenuating ECG LVH values, and lowers ECG specificity through changes associated with LV remodeling. Our obesity-specific ECG partition values could improve the diagnostic performance in obese patients with hypertension. PMID:26040440

  5. Robust algorithmic detection of the developed cardiac pathologies and emerging or transient abnormalities from short periods of RR data

    NASA Astrophysics Data System (ADS)

    Gavrishchaka, Valeriy V.; Senyukova, Olga

    2011-06-01

    Numerous research efforts and clinical testing have confirmed validity of heart rate variability (HRV) analysis as one of the cardiac diagnostics modalities. The majority of HRV analysis tools currently used in practice are based on linear indicators. Methods from nonlinear dynamics (NLD) provide more natural modeling framework for adaptive biological systems with multiple feedback loops. Compared to linear indicators, many NLD-based measures are much less sensitive to data artifacts and non-stationarity. However, majority of NLD measures require long time series for stable calculation. Similar restrictions also apply for linear indicators. Such requirements could drastically limit practical usability of HRV analysis in many applications, including express diagnostics, early indication of subtle directional changes during personalization of medical treatment, and robust detection of emerging or transient abnormalities. Recently we have illustrated that these challenges could be overcome by using classification framework based on boosting-like ensemble learning techniques that are capable of discovering robust meta-indicators from existing HRV measures and other incomplete empirical knowledge. In this paper we demonstrate universality of such meta-indicators and discuss operational details of their practical usage. Using such pathology examples as congestive heart failure (CHF) and arrhythmias, we show that classifiers trained on short RR segments (down to several minutes) could achieve reasonable classification accuracy (˜80-85% and higher). These indicators calculated from longer RR segments could be applicable for accurate diagnostics with classification accuracy approaching 100%. In addition, it is feasible to discover single "normal-abnormal" meta-classifier capable of detecting multiple abnormalities.

  6. Cadmium induced cardiac oxidative stress in rats and its attenuation by GSP through the activation of Nrf2 signaling pathway.

    PubMed

    Nazimabashir; Manoharan, Vaihundam; Miltonprabu, Selvaraj

    2015-12-01

    Cadmium (Cd) is one of the toxic heavy metals in the environment, which induces oxidative stress, dyslipidemia and membrane disturbances in heart. The present study was designed to evaluate the role of grape seed proanthocyanidins (GSP) against Cd induced oxidative stress mediated cardio-toxicity in rats. In this study, male Wistar rats were treated with Cd as cadmium chloride (CdCl2, 5 mg/ kg bw, PO) and pre-administered with GSP (100 mg/kg bw, PO) 90 min before the Cd intoxication for 4 weeks. Our results demonstrate a significant increase in the levels of cardiac troponins T and I (cTnT & I), cardiac serum markers, lipid peroxidative markers and plasma total cholesterol (TC), triglycerides (TG), phospholipids (PL) and free fatty acids (FFA). Cd induced oxidative stress decreased the levels of mitochondrial Krebs cycle enzymes as well as the respiratory chain enzyme activities and altered the levels of cardiac enzymatic and non-enzymatic antioxidants. The inflammatory (NF-kB, NO, TNF-α, IL-6), apoptotic markers (caspase 3, cytochrome C, Bax, Bcl-2), membrane bound ATPases and antioxidant Nrf2 (HO-1, keap1) markers were also measured in the control and experimental rats. All these alterations caused by Cd could be lessened by the pre-supplementation of GSP. The pre-administration of GSP significantly increased the activities of mitochondrial and respiratory chain enzymes, reduced the levels of cardio-oxidative stress markers in Cd-treated rats, which examines the stress stabilizing action of GSP. GSP also prevented the cytochrome C release, inhibited the caspase activation and maintained the ratio of Bcl-2/Bax by its free radical scavenging ability. Nrf2 expression was transiently increased while the impaired cardiac markers were restored near to their basal levels by the pre-treatment with GSP in Cd intoxicated rats. The cardioprotective nature of the GSP was further fortified by our light microscopic and ultra structural findings. Overall, our results suggest

  7. Development of the Method for Estimating Cardiac Vagal Activity in Real-Time during Body Motion and Generation of the Interactive CG

    NASA Astrophysics Data System (ADS)

    Kotani, Kiyoshi; Iida, Fumiaki; Akagawa, Tomohiro; Saitoh, Takeshi; Jimbo, Yasuhiko; Kawaguchi, Yoichiro; Takamasu, Kiyoshi

    Autonomic nervous system is important to maintain homeostasis, and respiratory sinus arrhythmia (RSA) is known as a selective index of cardiac vagal activity. In this paper, we evaluated errors in the amplitude of RSA under the condition of body motion (keyboard typing and mental arithmetic with touching panel) and proposed a method for reducing them. It was found that elastic chest band is suitable under the quiet condition, while thermistor is suitable under the condition of body motion. It was also found that Berger's interpolation method was the best for detecting instantaneous heartbeat intervals in real-time signal processing. Furthermore, we proposed a error reduction algorithm by mixing the data of thermistor and elastic chest band , and applied it for interactive CG (Computer Graphics) system that reflected the amplitude of RSA estimated in real-time.

  8. Cardiac optogenetics

    PubMed Central

    2013-01-01

    Optogenetics is an emerging technology for optical interrogation and control of biological function with high specificity and high spatiotemporal resolution. Mammalian cells and tissues can be sensitized to respond to light by a relatively simple and well-tolerated genetic modification using microbial opsins (light-gated ion channels and pumps). These can achieve fast and specific excitatory or inhibitory response, offering distinct advantages over traditional pharmacological or electrical means of perturbation. Since the first demonstrations of utility in mammalian cells (neurons) in 2005, optogenetics has spurred immense research activity and has inspired numerous applications for dissection of neural circuitry and understanding of brain function in health and disease, applications ranging from in vitro to work in behaving animals. Only recently (since 2010), the field has extended to cardiac applications with less than a dozen publications to date. In consideration of the early phase of work on cardiac optogenetics and the impact of the technique in understanding another excitable tissue, the brain, this review is largely a perspective of possibilities in the heart. It covers the basic principles of operation of light-sensitive ion channels and pumps, the available tools and ongoing efforts in optimizing them, overview of neuroscience use, as well as cardiac-specific questions of implementation and ideas for best use of this emerging technology in the heart. PMID:23457014

  9. Cardiac-induced localized thoracic motion detected by a fiber optic sensing scheme.

    PubMed

    Allsop, Thomas; Lloyd, Glynn; Bhamber, Ranjeet S; Hadzievski, Ljupco; Halliday, Michael; Webb, David J; Bennion, Ian

    2014-01-01

    The cardiovascular health of the human population is a major concern for medical clinicians, with cardiovascular diseases responsible for 48% of all deaths worldwide, according to the World Health Organization. The development of new diagnostic tools that are practicable and economical to scrutinize the cardiovascular health of humans is a major driver for clinicians. We offer a new technique to obtain seismocardiographic signals up to 54 Hz covering both ballistocardiography (below 20 Hz) and audible heart sounds (20 Hz upward), using a system based on curvature sensors formed from fiber optic long period gratings. This system can visualize the real-time three-dimensional (3-D) mechanical motion of the heart by using the data from the sensing array in conjunction with a bespoke 3-D shape reconstruction algorithm. Visualization is demonstrated by adhering three to four sensors on the outside of the thorax and in close proximity to the apex of the heart; the sensing scheme revealed a complex motion of the heart wall next to the apex region of the heart. The detection scheme is low-cost, portable, easily operated and has the potential for ambulatory applications. PMID:25393969

  10. Cardiac-induced localized thoracic motion detected by a fiber optic sensing scheme

    NASA Astrophysics Data System (ADS)

    Allsop, Thomas; Lloyd, Glynn; Bhamber, Ranjeet S.; Hadzievski, Ljupco; Halliday, Michael; Webb, David J.; Bennion, Ian

    2014-11-01

    The cardiovascular health of the human population is a major concern for medical clinicians, with cardiovascular diseases responsible for 48% of all deaths worldwide, according to the World Health Organization. The development of new diagnostic tools that are practicable and economical to scrutinize the cardiovascular health of humans is a major driver for clinicians. We offer a new technique to obtain seismocardiographic signals up to 54 Hz covering both ballistocardiography (below 20 Hz) and audible heart sounds (20 Hz upward), using a system based on curvature sensors formed from fiber optic long period gratings. This system can visualize the real-time three-dimensional (3-D) mechanical motion of the heart by using the data from the sensing array in conjunction with a bespoke 3-D shape reconstruction algorithm. Visualization is demonstrated by adhering three to four sensors on the outside of the thorax and in close proximity to the apex of the heart; the sensing scheme revealed a complex motion of the heart wall next to the apex region of the heart. The detection scheme is low-cost, portable, easily operated and has the potential for ambulatory applications.

  11. Cardiac Myosin Binding Protein-C Phosphorylation Modulates Myofilament Length-Dependent Activation.

    PubMed

    Mamidi, Ranganath; Gresham, Kenneth S; Verma, Sujeet; Stelzer, Julian E

    2016-01-01

    Cardiac myosin binding protein-C (cMyBP-C) phosphorylation is an important regulator of contractile function, however, its contributions to length-dependent changes in cross-bridge (XB) kinetics is unknown. Therefore, we performed mechanical experiments to quantify contractile function in detergent-skinned ventricular preparations isolated from wild-type (WT) hearts, and hearts expressing non-phosphorylatable cMyBP-C [Ser to Ala substitutions at residues Ser273, Ser282, and Ser302 (i.e., 3SA)], at sarcomere length (SL) 1.9 μm or 2.1μm, prior and following protein kinase A (PKA) treatment. Steady-state force generation measurements revealed a blunting in the length-dependent increase in myofilament Ca(2+)-sensitivity of force generation (pCa50) following an increase in SL in 3SA skinned myocardium compared to WT skinned myocardium. Dynamic XB behavior was assessed at submaximal Ca(2+)-activations by imposing an acute rapid stretch of 2% of initial muscle length, and measuring both the magnitudes and rates of resultant phases of force decay due to strain-induced XB detachment and delayed force rise due to recruitment of additional XBs with increased SL (i.e., stretch activation). The magnitude (P2) and rate of XB detachment (k rel) following stretch was significantly reduced in 3SA skinned myocardium compared to WT skinned myocardium at short and long SL, and prior to and following PKA treatment. Furthermore, the length-dependent acceleration of k rel due to decreased SL that was observed in WT skinned myocardium was abolished in 3SA skinned myocardium. PKA treatment accelerated the rate of XB recruitment (k df) following stretch at both SL's in WT but not in 3SA skinned myocardium. The amplitude of the enhancement in force generation above initial pre-stretch steady-state levels (P3) was not different between WT and 3SA skinned myocardium at any condition measured. However, the magnitude of the entire delayed force phase which can dip below initial pre

  12. Activation Kinetics of Skinned Cardiac Muscle by Laser Photolysis of Nitrophenyl-EGTA

    PubMed Central

    Martin, Hunter; Bell, Marcus G.; Ellis-Davies, Graham C. R.; Barsotti, Robert J.

    2004-01-01

    The kinetics of Ca2+-induced contractions of chemically skinned guinea pig trabeculae was studied using laser photolysis of NP-EGTA. The amount of free Ca2+ released was altered by varying the output from a frequency-doubled ruby laser focused on the trabeculae, while maintaining constant total [NP-EGTA] and [Ca2+]. The time courses of the rise in stiffness and tension were biexponential at 23°C, pH 7.1, and 200 mM ionic strength. At full activation (pCa < 5.0), the rates of the rapid phase of the stiffness and tension rise were 56 ± 7 s−1 (n = 7) and 48 ± 6 s−1 (n = 11) while the amplitudes were 21 ± 2 and 23 ± 3%, respectively. These rates had similar dependencies on final [Ca2+] achieved by photolysis: 43 and 50 s−1 per pCa unit, respectively, over a range of [Ca2+] producing from 15% to 90% of maximal isometric tension. At all [Ca2+], the rise in stiffness initially was faster than that of tension. The maximal rates for the slower components of the rise in stiffness and tension were 4.1 ± 0.8 and 6.2 ± 1.0 s−1. The rate of this slower phase exhibited significantly less Ca2+ sensitivity, 1 and 4 s−1 per pCa unit for stiffness and tension, respectively. These data, along with previous studies indicating that the force-generating step in the cross-bridge cycle of cardiac muscle is marginally sensitive to [Ca2+], suggest a mechanism of regulation in which Ca2+ controls the attachment step in the cross-bridge cycle via a rapid equilibrium with the thin filament activation state. Myosin kinetics sets the time course for the rise in stiffness and force generation with the biexponential nature of the mechanical responses to steps in [Ca2+] arising from a shift to slower cross-bridge kinetics as the number of strongly bound cross-bridges increases. PMID:14747333

  13. Cardiac Myosin Binding Protein-C Phosphorylation Modulates Myofilament Length-Dependent Activation

    PubMed Central

    Mamidi, Ranganath; Gresham, Kenneth S.; Verma, Sujeet; Stelzer, Julian E.

    2016-01-01

    Cardiac myosin binding protein-C (cMyBP-C) phosphorylation is an important regulator of contractile function, however, its contributions to length-dependent changes in cross-bridge (XB) kinetics is unknown. Therefore, we performed mechanical experiments to quantify contractile function in detergent-skinned ventricular preparations isolated from wild-type (WT) hearts, and hearts expressing non-phosphorylatable cMyBP-C [Ser to Ala substitutions at residues Ser273, Ser282, and Ser302 (i.e., 3SA)], at sarcomere length (SL) 1.9 μm or 2.1μm, prior and following protein kinase A (PKA) treatment. Steady-state force generation measurements revealed a blunting in the length-dependent increase in myofilament Ca2+-sensitivity of force generation (pCa50) following an increase in SL in 3SA skinned myocardium compared to WT skinned myocardium. Dynamic XB behavior was assessed at submaximal Ca2+-activations by imposing an acute rapid stretch of 2% of initial muscle length, and measuring both the magnitudes and rates of resultant phases of force decay due to strain-induced XB detachment and delayed force rise due to recruitment of additional XBs with increased SL (i.e., stretch activation). The magnitude (P2) and rate of XB detachment (krel) following stretch was significantly reduced in 3SA skinned myocardium compared to WT skinned myocardium at short and long SL, and prior to and following PKA treatment. Furthermore, the length-dependent acceleration of krel due to decreased SL that was observed in WT skinned myocardium was abolished in 3SA skinned myocardium. PKA treatment accelerated the rate of XB recruitment (kdf) following stretch at both SL's in WT but not in 3SA skinned myocardium. The amplitude of the enhancement in force generation above initial pre-stretch steady-state levels (P3) was not different between WT and 3SA skinned myocardium at any condition measured. However, the magnitude of the entire delayed force phase which can dip below initial pre-stretch steady

  14. Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules

    PubMed Central

    Nagata, Takanobu; Yasukawa, Hideo; Kyogoku, Sachiko; Oba, Toyoharu; Takahashi, Jinya; Nohara, Shoichiro; Minami, Tomoko; Mawatari, Kazutoshi; Sugi, Yusuke; Shimozono, Koutatsu; Pradervand, Sylvain; Hoshijima, Masahiko; Aoki, Hiroki; Fukumoto, Yoshihiro; Imaizumi, Tsutomu

    2015-01-01

    Myocardial ischemia reperfusion injury (IRI) adversely affects cardiac performance and the prognosis of patients with acute myocardial infarction. Although myocardial signal transducer and activator of transcription (STAT) 3 is potently cardioprotective during IRI, the inhibitory mechanism responsible for its activation is largely unknown. The present study aimed to investigate the role of the myocardial suppressor of cytokine signaling (SOCS)-3, an intrinsic negative feedback regulator of the Janus kinase (JAK)-STAT signaling pathway, in the development of myocardial IRI. Myocardial IRI was induced in mice by ligating the left anterior descending coronary artery for 1 h, followed by different reperfusion times. One hour after reperfusion, the rapid expression of JAK-STAT–activating cytokines was observed. We precisely evaluated the phosphorylation of cardioprotective signaling molecules and the expression of SOCS3 during IRI and then induced myocardial IRI in wild-type and cardiac-specific SOCS3 knockout mice (SOCS3-CKO). The activation of STAT3, AKT, and ERK1/2 rapidly peaked and promptly decreased during IRI. This decrease correlated with the induction of SOCS3 expression up to 24 h after IRI in wild-type mice. The infarct size 24 h after reperfusion was significantly reduced in SOCS3-CKO compared with wild-type mice. In SOCS3-CKO mice, STAT3, AKT, and ERK1/2 phosphorylation was sustained, myocardial apoptosis was prevented, and the expression of anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) was augmented. Cardiac-specific SOCS3 deletion led to the sustained activation of cardioprotective signaling molecules including and prevented myocardial apoptosis and injury during IRI. Our findings suggest that SOCS3 may represent a key factor that exacerbates the development of myocardial IRI. PMID:26010537

  15. Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity

    NASA Astrophysics Data System (ADS)

    Winkelmann, Donald A.; Forgacs, Eva; Miller, Matthew T.; Stock, Ann M.

    2015-08-01

    Omecamtiv Mecarbil (OM) is a small molecule allosteric effector of cardiac myosin that is in clinical trials for treatment of systolic heart failure. A detailed kinetic analysis of cardiac myosin has shown that the drug accelerates phosphate release by shifting the equilibrium of the hydrolysis step towards products, leading to a faster transition from weak to strong actin-bound states. The structure of the human β-cardiac motor domain (cMD) with OM bound reveals a single OM-binding site nestled in a narrow cleft separating two domains of the human cMD where it interacts with the key residues that couple lever arm movement to the nucleotide state. In addition, OM induces allosteric changes in three strands of the β-sheet that provides the communication link between the actin-binding interface and the nucleotide pocket. The OM-binding interactions and allosteric changes form the structural basis for the kinetic and mechanical tuning of cardiac myosin.

  16. Cardiac dysfunction and hypothalamic activation during a social crowding stressor in prairie voles.

    PubMed

    Grippo, Angela J; Sgoifo, Andrea; Mastorci, Francesca; McNeal, Neal; Trahanas, Diane M

    2010-08-25

    Negative social interactions produce several detrimental consequences in humans and non-human animals; and conversely, positive social interactions may have stress-buffering effects on both behavior and physiology. However, the mechanisms underlying specific stressor-responsiveness in the context of the social environment are not well understood. The present study investigated the integration of behavior, cardiac function, and Fos-immunoreactivity in the hypothalamic paraventricular nucleus during an acute social stressor in female, socially monogamous prairie voles exposed to previous long-term pairing (control conditions) or isolation. Animals previously exposed to social isolation displayed increased heart rate, attenuated heart rate variability, and increased incidence of cardiac arrhythmias during an acute crowding stressor versus animals previously exposed to social pairing; these cardiac alterations were not secondary to behavioral changes during the crowding stressor. Furthermore, social isolation was associated with increased c-Fos-immunoreactivity in the hypothalamic paraventricular nucleus following the crowding stressor, versus social pairing. The prairie vole provides a useful model for understanding how the social environment contributes to changes in behavior, cardiac function, and central stress-regulatory processes in humans. PMID:20347401

  17. Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity

    PubMed Central

    Winkelmann, Donald A.; Forgacs, Eva; Miller, Matthew T.; Stock, Ann M.

    2015-01-01

    Omecamtiv Mecarbil (OM) is a small molecule allosteric effector of cardiac myosin that is in clinical trials for treatment of systolic heart failure. A detailed kinetic analysis of cardiac myosin has shown that the drug accelerates phosphate release by shifting the equilibrium of the hydrolysis step towards products, leading to a faster transition from weak to strong actin-bound states. The structure of the human β-cardiac motor domain (cMD) with OM bound reveals a single OM-binding site nestled in a narrow cleft separating two domains of the human cMD where it interacts with the key residues that couple lever arm movement to the nucleotide state. In addition, OM induces allosteric changes in three strands of the β-sheet that provides the communication link between the actin-binding interface and the nucleotide pocket. The OM-binding interactions and allosteric changes form the structural basis for the kinetic and mechanical tuning of cardiac myosin. PMID:26246073

  18. Goal striving strategies and effort mobilization: When implementation intentions reduce effort-related cardiac activity during task performance.

    PubMed

    Freydefont, Laure; Gollwitzer, Peter M; Oettingen, Gabriele

    2016-09-01

    Two experiments investigate the influence of goal and implementation intentions on effort mobilization during task performance. Although numerous studies have demonstrated the beneficial effects of setting goals and making plans on performance, the effects of goals and plans on effort-related cardiac activity and especially the cardiac preejection period (PEP) during goal striving have not yet been addressed. According to the Motivational Intensity Theory, participants should increase effort mobilization proportionally to task difficulty as long as success is possible and justified. Forming goals and making plans should allow for reduced effort mobilization when participants perform an easy task. However, when the task is difficult, goals and plans should differ in their effect on effort mobilization. Participants who set goals should disengage, whereas participants who made if-then plans should stay in the field showing high effort mobilization during task performance. As expected, using an easy task in Experiment 1, we observed a lower cardiac PEP in both the implementation intention and the goal intention condition than in the control condition. In Experiment 2, we varied task difficulty and demonstrated that while participants with a mere goal intention disengaged from difficult tasks, participants with an implementation intention increased effort mobilization proportionally with task difficulty. These findings demonstrate the influence of goal striving strategies (i.e., mere goals vs. if-then plans) on effort mobilization during task performance. PMID:27374255

  19. Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity.

    PubMed

    Judenherc-Haouzi, Annick; Zhang, Xue-Qian; Sonobe, Takashi; Song, Jianliang; Rannals, Matthew D; Wang, JuFang; Tubbs, Nicole; Cheung, Joseph Y; Haouzi, Philippe

    2016-06-01

    We have previously reported that methylene blue (MB) can counteract hydrogen sulfide (H2S) intoxication-induced circulatory failure. Because of the multifarious effects of high concentrations of H2S on cardiac function, as well as the numerous properties of MB, the nature of this interaction, if any, remains uncertain. The aim of this study was to clarify 1) the effects of MB on H2S-induced cardiac toxicity and 2) whether L-type Ca(2+) channels, one of the targets of H2S, could transduce some of the counteracting effects of MB. In sedated rats, H2S infused at a rate that would be lethal within 5 min (24 μM·kg(-1)·min(-1)), produced a rapid fall in left ventricle ejection fraction, determined by echocardiography, leading to a pulseless electrical activity. Blood concentrations of gaseous H2S reached 7.09 ± 3.53 μM when cardiac contractility started to decrease. Two to three injections of MB (4 mg/kg) transiently restored cardiac contractility, blood pressure, and V̇o2, allowing the animals to stay alive until the end of H2S infusion. MB also delayed PEA by several minutes following H2S-induced coma and shock in unsedated rats. Applying a solution containing lethal levels of H2S (100 μM) on isolated mouse cardiomyocytes significantly reduced cell contractility, intracellular calcium concentration ([Ca(2+)]i) transient amplitudes, and L-type Ca(2+) currents (ICa) within 3 min of exposure. MB (20 mg/l) restored the cardiomyocyte function, ([Ca(2+)]i) transient, and ICa The present results offer a new approach for counteracting H2S toxicity and potentially other conditions associated with acute inhibition of L-type Ca(2+) channels. PMID:26962024

  20. Utility of 3-dimensional echocardiography, global longitudinal strain, and exercise stress echocardiography to detect cardiac dysfunction in breast cancer patients treated with doxorubicin-containing adjuvant therapy

    PubMed Central

    Khouri, Michel G.; Hornsby, Whitney E.; Risum, Niels; Velazquez, Eric J.; Thomas, Samantha; Lane, Amy; Scott, Jessica M.; Koelwyn, Graeme J.; Herndon, James E.; Mackey, John R.; Douglas, Pamela S.

    2015-01-01

    Conventional resting left ventricular ejection fraction (LVEF) assessments have limitations for detecting doxorubicin (DOX)-related cardiac dysfunction. Novel resting echocardiographic parameters, including 3-dimen-sional echocardiography (3DE) and global longitudinal strain (GLS), have potential for early identification of chemotherapy-related myocardial injury. Exercise “stress” is an established method to uncover impairments in cardiac function but has received limited attention in the adult oncology setting. We evaluated the utility of an integrated approach using 3DE, GLS, and exercise stress echocardiography for detecting subclinical cardiac dysfunction in early breast cancer patients treated with DOX-containing chemotherapy. Fifty-seven asymptomatic women with early breast cancer (mean 26 ± 22 months post-chemotherapy) and 20 sex-matched controls were studied. Resting left ventricular (LV) function was assessed by LVEF using 2-dimensional echocardiography (2DE) and 3DE and by GLS using 2-dimensional speckle-tracking echocardiography (2D-STE). After resting assessments, subjects completed cardiopulmonary exercise testing with stress 2DE. Resting LVEF was lower in patients than controls by 3DE (55 ± 4 vs. 59 ± 5 %; p = 0.005) but not 2DE (56 ± 4 vs. 58 ± 3 %; p = 0.169). 10 of 51 (20 %) patients had GLS greater than or equal to −17 %, which was below the calculated lower limit of normal (control mean 2SD); this patient subgroup had a mean 20 % impairment in GLS (−16.1 ± 0.9 vs. −20.1 ± 1.5 %; p < 0.001), despite similar LVEF by 2DE and 3DE compared to controls (p > 0.05). Cardiopulmonary function (VO2peak) was 20 % lower in patients than controls (p < 0.001). Exercise stress 2DE assessments of stroke volume (61 ± 11 vs. 69 ± 15 ml; p = 0.018) and cardiac index (2.3 ± 0.9 vs. 3.1 ± 0.8 1 min−1 m−2 mean increase; p = 0.003) were lower in patients than controls. Post-exercise increase in cardiac index predicted VO2peak (r = 0.429, p = 0

  1. Silent cerebral infarct after cardiac catheterization as detected by diffusion weighted Magnetic Resonance Imaging: a randomized comparison of radial and femoral arterial approaches

    PubMed Central

    Hamon, Michèle; Burzotta, Francesco; Oppenheim, Catherine; Morello, Rémy; Viader, Fausto; Hamon, Martial

    2007-01-01

    Background and objective Cerebral microembolism detected by transcranial Doppler (TCD) occurs systematically during cardiac catheterization, but its clinical relevance, remains unknown. Studies suggest that asymptomatic embolic cerebral infarction detectable by diffusion-weighted (DW) MRI might exist after percutaneous cardiac interventions with a frequency as high as 15 to 22% of cases. We have set up, for the first time, a prospective multicenter trial to assess the rate of silent cerebral infarction after cardiac catheterization and to compare the impact of the arterial access site, comparing radial and femoral access, on this phenomenon. Study design This prospective study will be performed in patients with severe aortic valve stenosis. To assess the occurrence of cerebral infarction, all patients will undergo cerebral DW-MRI and neurological assessment within 24 hours before, and 48 hours after cardiac catheterization and retrograde catheterization of the aortic valve. Randomization for the access site will be performed before coronary angiography. A subgroup will be monitored by transcranial power M-mode Doppler during cardiac catheterization to observe cerebral blood flow and track emboli. Neuropsychological tests will also be recorded in a subgroup of patients before and after the interventional procedures to assess the impact of silent brain injury on potential cognitive decline. The primary end-point of the study is a direct comparison of ischemic cerebral lesions as detected by serial cerebral DW-MRI between patients explored by radial access and patients explored by femoral access. Secondary end-points include comparison of neuropsychological test performance and number of microembolism signals observed in the two groups. Implications Using serial DW-MRI, silent cerebral infarction rate will be defined and the potential influence of vascular access site will be evaluated. Silent cerebral infarction might be a major concern during cardiac catheterization

  2. Chronic activation of the low affinity site of β1-adrenoceptors stimulates haemodynamics but exacerbates pressure-overload cardiac remodelling

    PubMed Central

    Kiriazis, Helen; Tugiono, Niquita; Xu, Qi; Gao, Xiao-Ming; Jennings, Nicole L; Ming, Ziqui; Su, Yidan; Klenowski, Paul; Summers, Roger J; Kaumann, Alberto; Molenaar, Peter; Du, Xiao-Jun

    2013-01-01

    BACKGROUND AND PURPOSE The β1-adrenoceptor has at least two binding sites, high and low affinity sites (β1H and β1L, respectively), which mediate cardiostimulation. While β1H-adrenoceptor can be blocked by all clinically used β-blockers, β1L-adrenoceptor is relatively resistant to blockade. Thus, chronic β1L-adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of β1H-adrenoceptors. Hence, it is important to determine the potential significance of β1L-adrenoceptors in vivo, particularly in pathological situations. EXPERIMENTAL APPROACH C57Bl/6 male mice were used. Chronic (4 or 8 weeks) β1L-adrenoceptor activation was achieved by treatment, via osmotic mini pumps, with (-)-CGP12177 (10 mg·kg−1·day−1). Cardiac function was assessed by echocardiography and micromanometry. KEY RESULTS (-)-CGP12177 treatment of healthy mice increased heart rate and left ventricular (LV) contractility. (-)-CGP12177 treatment of mice subjected to transverse aorta constriction (TAC), during weeks 4–8 or 4–12 after TAC, led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (-)-CGP12177 treatment of mice with TAC also exacerbated the myocardial expression of hypertrophic, fibrogenic and inflammatory genes compared to untreated TAC mice. Washout of (-)-CGP12177 revealed a more pronounced cardiac dysfunction after 12 weeks of TAC. CONCLUSIONS AND IMPLICATIONS β1L-adrenoceptor activation provides functional support to the heart, in both normal and pathological (pressure overload) situations. Sustained β1L-adrenoceptor activation in the diseased heart exacerbates LV remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure. PMID:23750586

  3. Effect of prolonged depolarizations on twitch tension and intracellular sodium activity in sheep cardiac Purkinje fibres.

    PubMed Central

    Brill, D M; Fozzard, H A; Makielski, J C; Wasserstrom, J A

    1987-01-01

    1. Twitch tension and intracellular Na+ activity (aiNa) were measured in voltage-clamped sheep cardiac Purkinje fibres. aiNa was measured using Na+-sensitive micro-electrodes filled with the liquid ion exchange resin. ETH 227. The stimulus for contraction was a constant 200 ms depolarizing pulse to 0 mV from a holding potential of -80 mV delivered at 0.25 Hz. Prolonged test pulses for 1.8 s (post-pulses) were applied at the end of the stimulus pulse. The effects of post-pulses on twitch tension and aiNa were examined. 2. Post-pulses in the range of -40 mV reduced twitch tension below control force produced without post-pulse. Progressively more positive post-pulses to levels above 0 mV profoundly increased twitch tension, with a greater than 400% rise in tension at +50 to +60 mV compared to control tension. aiNa declined at positive post-pulse potentials by more than 2 mM at +30 to +40 mV. 3. Tetrodotoxin (100 microM) did not affect the post-pulse voltage-tension or voltage-aiNa relation. Ca2+ channel modulation with nitrendipine (1 microM) similarly did not alter the post-pulse voltage-tension relation. 4. Removal of extracellular Na+ eliminated the nadir in tension at post-pulses to -40 mV and the augmentation of tension at post-pulses above 0 mV. 5. We interpret these findings as evidence of voltage-sensitive Na-Ca exchange promoting net Ca2+ influx and net Na+ efflux during positive post-pulses. The unusual shape of the post-pulse voltage-tension relation curve can be accounted for by a charged-carrier model of electrogenic Na-Ca exchange. The inverse relation between aiNa and twitch tension probably reflects the combined effects of reduced aiNa leak and changes in Na+ and Ca2+ flux via voltage-sensitive Na-Ca exchange. PMID:2443661

  4. Opposing Actions of Extracellular Signal-regulated Kinase (ERK) and Signal Transducer and Activator of Transcription 3 (STAT3) in Regulating Microtubule Stabilization during Cardiac Hypertrophy*

    PubMed Central

    Ng, Dominic C. H.; Ng, Ivan H. W.; Yeap, Yvonne Y. C.; Badrian, Bahareh; Tsoutsman, Tatiana; McMullen, Julie R.; Semsarian, Christopher; Bogoyevitch, Marie A.

    2011-01-01

    Excessive proliferation and stabilization of the microtubule (MT) array in cardiac myocytes can accompany pathological cardiac hypertrophy, but the molecular control of these changes remains poorly characterized. In this study, we examined MT stabilization in two independent murine models of heart failure and revealed increases in the levels of post-translationally modified stable MTs, which were closely associated with STAT3 activation. To explore the molecular signaling events contributing to control of the cardiac MT network, we stimulated cardiac myocytes with an α-adrenergic agonist phenylephrine (PE), and observed increased tubulin content without changes in detyrosinated (glu-tubulin) stable MTs. In contrast, the hypertrophic interleukin-6 (IL6) family cytokines increased both the glu-tubulin content and glu-MT density. When we examined a role for ERK in regulating cardiac MTs, we showed that the MEK/ERK-inhibitor U0126 increased glu-MT density in either control cardiac myocytes or following exposure to hypertrophic agents. Conversely, expression of an activated MEK1 mutant reduced glu-tubulin levels. Thus, ERK signaling antagonizes stabilization of the cardiac MT array. In contrast, inhibiting either JAK2 with AG490, or STAT3 signaling with Stattic or siRNA knockdown, blocked cytokine-stimulated increases in glu-MT density. Furthermore, the expression of a constitutively active STAT3 mutant triggered increased glu-MT density in the absence of hypertrophic stimulation. Thus, STAT3 activation contributes substantially to cytokine-stimulated glu-MT changes. Taken together, our results highlight the opposing actions of STAT3 and ERK pathways in the regulation of MT changes associated with cardiac myocyte hypertrophy. PMID:21056972

  5. Stimulation of cardiac sympathetic afferents activates glutamatergic neurons in the parabrachial nucleus: relation to neurons containing nNOS.

    PubMed

    Guo, Zhi-Ling; Moazzami, Ali R; Longhurst, John C

    2005-08-16

    Our previous studies have demonstrated that stimulation of cardiac sympathetic afferents activates neurons in the parabrachial nucleus (PBN), a region known to play a role in central integration of cardiovascular autonomic reflexes. However, phenotypes of these activated neurons have not been well identified. Glutamate, an important excitatory neurotransmitter in the brain, is involved in PBN-mediated cardiovascular responses. Recent identification of vesicular glutamate transporter 3 (VGLUT3) has provided a novel and unique marker to locate distinctive perikarya of neurons that use glutamate as a neurotransmitter. The action of glutamate in the brain is influenced by nitric oxide. Thus, using triple immunofluorescent labeling, the present study examined expression of c-Fos, an immediate early gene, in the neurons containing VGLUT3 and neuronal nitric oxide synthase (nNOS) in the PBN following stimulation of cardiac sympathetic afferents. In anesthetized cats with bilateral barodenervation and cervical vagotomy, topical application of bradykinin (BK, 1-10 microg/ml, 50 microl, n = 6) on the left ventricle was performed six times, every 20 min. Repeated administration of BK elicited consistent increases in blood pressure over a 100 min period while no changes were noted in the animals treated with the vehicle for BK (0.9% saline, n=5). Compared to control cats, c-Fos expression was increased significantly in the cell bodies containing VGLUT3 as well as both VGLUT3 and nNOS in the external lateral PBN (elPBN) in BK-treated animals (all P < 0.01). In addition, using similar triple-staining method, we noted that fibers of activated neurons containing nNOS in the elPBN co-localized with vesicular glutamate transporter 2 following BK stimulation. These data suggest that glutamatergic neurons represent a cell type in the PBN that is activated by stimulation of cardiac sympathetic afferents. Nitric oxide has the potential to influence the action of glutamatergic neurons in

  6. Cardiac lipoprotein lipase activity in the hypertrophied heart may be regulated by fatty acid flux

    PubMed Central

    Hauton, David; Caldwell, Germaine M.

    2012-01-01

    Cardiac hypertrophy is characterised by an imbalance between lipid uptake and fatty acid β-oxidation leading to an accumulation of lipids, particularly triacylglycerol (TAG). It is unclear whether uptake mechanisms such as lipoprotein lipase (LPL) can be attenuated to diminish this uptake. Rats were cold acclimated to induce cardiac hypertrophy and increase cardiac LPL. Lipid uptake and metabolism were altered by feeding a ‘Western-style’ high fat diet (WSD) or feeding oxfenicine (2 g/L) in the drinking water. Diastolic stiffness (increased volume change/unit pressure change) was induced in hypertrophied hearts for rats fed WSD (P < 0.05) or WSD + oxfenicine (P < 0.01), although absolute performance of cardiac muscle, estimated from stress–strain calculations was unchanged. Cold acclimation increased cardiac endothelial LPL (P < 0.05) but this was diminished following oxfenicine. Following WSD LPL was further decreased below WSD-fed control hearts (P < 0.05) with no further decrease by oxfenicine supplementation. A negative correlation was noted between plasma TAG and endothelial LPL (correlation coefficient = − 0.654; P < 0.001) but not cardiac TAG concentration. Transcript levels of angiopoietin-like protein-4 (ANGPTL4) were increased 6-fold by WSD (P < 0.05) and increased 15-fold following WSD + oxfenicine (P < 0.001). For CA-hearts fed WSD or WSD + oxfenicine ANGPTL4 mRNA levels were preserved at chow-fed levels. VLDLR protein levels were increased 10-fold (P < 0.01) by CA. ANGPTL4 protein levels were increased 2-fold (P < 0.05) by WSD, but restored following oxfenicine. For CA-hearts WSD increased ANGPTL4 protein levels 3-fold (P < 0.01) with WSD + oxfenicine increasing ANGPTL4 protein 4-fold (P < 0.01). These data suggest that endothelial LPL levels in the heart are altered to maintain FA flux and may exploit ANGPTL4. PMID:22226882

  7. Predictive significance of detectable cardiac troponin I measured with a contemporary-sensitive assay in a real life experience

    PubMed Central

    Bonfanti, Laura; Lippi, Giuseppe; Ciullo, Irene; Meschi, Tiziana; Ticinesi, Andrea; Aloe, Rosalia; Di Spigno, Francesco

    2016-01-01

    Background Cardiac troponin (cTn) testing has reduced the likelihood of erroneous discharge of patients with acute coronary syndrome (ACS) from the emergency department (ED), but doubts remain about optimal clinical use. This study was planned for evaluating the predictive significance of cTn values between the limit of detection of the method and the 99th percentile in ED patients evaluated for suspected ACS. Methods In this retrospective study all hospital records of patients admitted over a 6-month period to the ED and with at least one cTnI value comprised between the limit of detection (0.01 ng/mL) and the 99th percentile of the assay (0.05 ng/mL) were analyzed. Results A total of 4,749 patients with cTnI value between 0.01–0.05 ng/mL were identified among 57,879 ED visits throughout the study period. Overall, 2,189 patients (46.1%) were discharged from the ED, 2,529 (53.25%) were admitted to the hospital and 31 (0.65%) died during ED stay. A total number of 289 patients out of 2,189 who were discharged (i.e., 13.2%) had additional ED visits within 30 days. Among these, 6 were diagnosed with ACS, representing 0.27% of patients discharged [negative predictive value (NPV) 0.997; 95% CI, 0.994–0.999] and 2.1% of those with second admission (NPV 0.979; 95% CI, 0.955–0.992). Only one of the 2,529 patients admitted to the hospital (i.e., 0.04%) developed an ACS during hospital stay. Conclusions The results of our retrospective study suggest that the suitability of using a contemporary-sensitive cTnI immunoassay assay in the context of an appropriate protocol represents a safe and effective strategy for ruling in and ruling out ACS in patients presenting to the ED. PMID:27500153

  8. Fetal and maternal cardiac responses to physical activity and exercise during pregnancy.

    PubMed

    May, Linda E; Allen, John J B; Gustafson, Kathleen M

    2016-03-01

    Since the 1970s, researchers have studied the influence of exercise during pregnancy on offspring heart development. With the knowledge and current evidence of fetal programming effects, research has demonstrated that exercise is safe and beneficial for mother, fetus, and neonate. Predominantly, research has focused on maternal and fetal cardiac adaptations related to aerobic exercise during pregnancy; less is known regarding the effects of resistance or combination (aerobic and resistance) training during pregnancy. Ongoing research is focusing on fetal responses to different intensity, duration and modes of maternal exercise throughout pregnancy. This article will summarize our current state of knowledge regarding the influence of exercise intensity, duration, and modes during pregnancy on maternal and fetal cardiac responses. PMID:26805461

  9. Dipyridamole cardiac imaging

    SciTech Connect

    Iskandrian, A.S.; Heo, J.; Askenase, A.; Segal, B.L.; Auerbach, N.

    1988-02-01

    Dipyridamole cardiac imaging is a useful alternative technique to exercise stress testing in the evaluation of patients with ischemic heart disease. Intravenous dipyridamole is still in the investigational phase, while oral dipyridamole is widely available. The hemodynamic effects of dipyridamole include an increase in coronary blood flow (due to coronary vasodilation) which is in excess of the increase in myocardial oxygen consumption and cardiac output. The disparity in the increase in coronary blood flow relative to the cardiac output results in an increase in myocardial thallium activity and an increase in the myocardial/background activity ratio. The quality of the thallium images is better or similar to that of exercise thallium images. The optimal dose of intravenous dipyridamole is 0.56 mg/kg, and of the oral dose it is 300 to 400 mg, although higher doses may be necessary in some patients. Analysis of the thallium images has been to a large extent based on visual inspection of the planar images. Delayed images are helpful to establish the nature of the perfusion abnormalities (transient or fixed). The process of redistribution is based on disparate rates of washout from the normal and abnormal zones. The sensitivity and specificity of dipyridamole thallium imaging, whether intravenous or oral, have been shown in a number of studies to be quite adequate and comparable to that achieved during exercise thallium imaging. Dipyridamole two-dimensional echocardiography has also been used in the detection of coronary artery disease; transient (new or worsening of preexisting) wall motion abnormalities have been found to be a specific marker of coronary artery disease. Transmural as well as regional coronary steal phenomena have been postulated as the mechanism for dipyridamole-induced regional wall motion abnormalities. 65 references.

  10. GTPase Activating Protein (Sh3 Domain) Binding Protein 1 Regulates the Processing of MicroRNA-1 during Cardiac Hypertrophy

    PubMed Central

    He, Minzhen; Yang, Zhi; Abdellatif, Maha; Sayed, Danish

    2015-01-01

    Background MicroRNAs (miR) are small, posttranscriptional regulators, expressed as part of a longer primary transcript, following which they undergo nuclear and cytoplasmic processing by Drosha and Dicer, respectively, to form the functional mature ~20mer that gets incorporated into the silencing complex. Others and we have shown that mature miR-1 levels decrease with pressure-induced cardiac hypertrophy, however, there is little or no change in the primary transcript encompassing miR-1 stem-loop, suggesting critical regulatory step in microRNA processing. The objective of this study was to investigate the underlying mechanisms regulating miR-1 expression in cardiomyocytes. Results Here we report that GTPase–activating protein (SH3 domain) binding protein 1 (G3bp1), an endoribonuclease regulates miR-1 processing in cardiomyocytes. G3bp1 is upregulated during cardiac hypertrophy and restricts miR-1 processing by binding to its consensus sequence in the pre-miR-1-2 stem-loop. In accordance, exogenous G3bp1 is sufficient to reduce miR-1 levels, along with derepression of miR-1 targets; General transcription factor IIB (Gtf2b), cyclin dependent factor 9 (Cdk9) and eukaryotic initiation factor 4E (Eif4e). While Cdk9 and Gtf2b are essential for transcription, Eif4e is required for translation. Thus, downregulation of miR-1 is necessary for increase in these molecules. Similar to miR-1 knockdown, G3bp1 overexpression is not sufficient for development of cardiac hypertrophy. Conversely, knockdown of G3bp1 in hypertrophying cardiomyocytes inhibited downregulation of miR-1 and upregulation of its targets along with restricted hypertrophy, suggesting that G3bp1 is necessary for development of cardiac hypertrophy. These results indicate that G3bp1-mediated inhibition of miR-1 processing with growth stimulation results in decrease in mature miR-1 and, thereby, an increase of its targets, which play fundamental roles in the development of hypertrophy. Conclusion G3bp1

  11. Coordinating Electrical Activity of the Heart: Ankyrin Polypeptides in Human Cardiac Disease

    PubMed Central

    Curran, Jerry; Mohler, Peter J

    2011-01-01

    Introduction Over the past ten years, ankyrin polypeptides have emerged as critical players in cardiac excitation-contraction coupling. Once thought to solely play only a structural role, loss-of-function variants in genes encoding ankyrin polypeptides have highlighted how this protein mediates the proper subcellular localization of the various electrical components of the excitation-contraction coupling machinery. A large body of evidence has revealed how the disruption of this localization is the primary cause of various cardiomyopathies, ranging from long QT syndrome 4, to sinus node disease, to more common forms of arrhythmias. Areas Covered This review details the varied roles that ankyrin polypeptides play in excitation-contraction coupling in the heart and the development of ankyrin-specific cardiomyopathies. It will further discuss how ankyrin polypeptides may be involved in structural and electrical remodeling of the heart, post-myocardial infarct. Attention is given to how ankyrin interactions with membrane bound ion channels may regulate these channels’ response to stimuli. Special attention is given to exciting new data, which may offer the potential for unique therapies, for not only combating heart disease, but which also holds promise for wider applications to various disease states. Expert Opinion The ankyrin family of adapter proteins is emerging as an intimate player in cardiac excitation-contraction coupling. Until recently, these proteins have gone largely unappreciated for their importance in proper cardiac function. New insights into how these proteins function within the heart are offering potentially new avenues for therapies against cardiomyopathy. PMID:21457127

  12. Application of Hyperelastic-based Active Mesh Model in Cardiac Motion Recovery

    PubMed Central

    Yousefi-Banaem, Hossein; Kermani, Saeed; Daneshmehr, Alireza; Saneie, Hamid

    2016-01-01

    Considering the nonlinear hyperelastic or viscoelastic nature of soft tissues has an important effect on modeling results. In medical applications, accounting nonlinearity begets an ill posed problem, due to absence of external force. Myocardium can be considered as a hyperelastic material, and variational approaches are proposed to estimate stiffness matrix, which take into account the linear and nonlinear properties of myocardium. By displacement estimation of some points in the four-dimensional cardiac magnetic resonance imaging series, using a similarity criterion, the elementary deformations are estimated, then using the Moore–Penrose inverse matrix approach, all point deformations are obtained. Using this process, the cardiac wall motion is quantized to mechanically determine local parameters to investigate the cardiac wall functionality. This process was implemented and tested over 10 healthy and 20 patients with myocardial infarction. In all patients, the process was able to precisely determine the affected region. The proposed approach was also compared with linear one and the results demonstrated its superiority respect to the linear model. PMID:27563570

  13. Long-term abdominal adiposity activates several parameters of cardiac energy function.

    PubMed

    Mourmoura, Evangelia; Rigaudière, Jean-Paul; Couturier, Karine; Hininger, Isabelle; Laillet, Brigitte; Malpuech-Brugère, Corinne; Azarnoush, Kasra; Demaison, Luc

    2016-09-01

    Abdominal obesity increases the incidence of cardiac events but reduces mortality when one of these events occurs. The phenomenon called obesity paradox might be related to myocardial energetics. This study was aimed at determining whether long-term abdominal adiposity alters cardiac energy function. Two groups of male Wistar rats were fed a standard or a Western-type (WD) diet for 8 months. The ex vivo coronary reactivity and mechanical function as well as the mitochondrial oxidative phosphorylation (mOxPhos) and hydrogen peroxide release (mH2O2r) were determined. Abdominal adiposity was augmented by the WD. This was also the case for the coronary reactivity to acetylcholine, but the rate pressure product remained roughly stable despite a reduction of the left ventricle-developed pressure partly compensated by a slight increase in heart rate. The prolonged WD administration resulted in an improvement of mOxPhos, but the mH2O2r was exaggerated which was confirmed in the whole cell by a reduced aconitase to fumarase ratio. This did not modify the plasma oxidative stress due to an increased plasma antioxidant status. In conclusion, long-term WD administration improved the cardiac fitness and might predispose the organism to the obesity paradox. Conversely, the increased mitochondrial mH2O2r can precipitate the heart toward cardiomyopathy if the WD is maintained for a longer duration. PMID:26255304

  14. Application of Hyperelastic-based Active Mesh Model in Cardiac Motion Recovery.

    PubMed

    Yousefi-Banaem, Hossein; Kermani, Saeed; Daneshmehr, Alireza; Saneie, Hamid

    2016-01-01

    Considering the nonlinear hyperelastic or viscoelastic nature of soft tissues has an important effect on modeling results. In medical applications, accounting nonlinearity begets an ill posed problem, due to absence of external force. Myocardium can be considered as a hyperelastic material, and variational approaches are proposed to estimate stiffness matrix, which take into account the linear and nonlinear properties of myocardium. By displacement estimation of some points in the four-dimensional cardiac magnetic resonance imaging series, using a similarity criterion, the elementary deformations are estimated, then using the Moore-Penrose inverse matrix approach, all point deformations are obtained. Using this process, the cardiac wall motion is quantized to mechanically determine local parameters to investigate the cardiac wall functionality. This process was implemented and tested over 10 healthy and 20 patients with myocardial infarction. In all patients, the process was able to precisely determine the affected region. The proposed approach was also compared with linear one and the results demonstrated its superiority respect to the linear model. PMID:27563570

  15. Curvature effects on activation speed and repolarization in an ionic model of cardiac myocytes

    NASA Astrophysics Data System (ADS)

    Comtois, P.; Vinet, A.

    1999-10-01

    Reentry is a major mechanism underlying the initiation and perpetuation of many cardiac arrhythmias 12345. Stimulated ventricular myocytes give action potential characterized by a fast upstroke, a long-lasting plateau, and a late repolarization phase. The plateau phase determines the action potential duration (APD) during which the system remains refractory, a property essential to the synchronization of the heart cycle. The APD varies much with prematurity and this change has been shown to be the main determinant of the dynamics in models of paced cells and cable, and during reentry in the one-dimensional loop. Curvature has also been shown to be an important factor for propagation in experimental and theoretical cardiac extended tissue. The objective of this paper is to combine both curvature and prematurity effects in a kinematical model of propagation in cardiac tissue. First, an approximation of the ionic model is used to obtain the effects of curvature and prematurity on the speed of propagation, the APD, and the absolute refractory period. Two versions of the ionic model are studied that differ in their rate of excitability recovery. The functions are used in a kinematical model describing the propagation of period-1 solutions around an annulus.

  16. Cardiac activation heat remains inversely dependent on temperature over the range 27-37°C.

    PubMed

    Johnston, Callum M; Han, June-Chiew; Loiselle, Denis S; Nielsen, Poul M F; Taberner, Andrew J

    2016-06-01

    The relation between heat output and stress production (force per cross-sectional area) of isolated cardiac tissue is a key metric that provides insight into muscle energetic performance. The heat intercept of the relation, termed "activation heat," reflects the metabolic cost of restoring transmembrane gradients of Na(+) and K(+) following electrical excitation, and myoplasmic Ca(2+) concentration following its release from the sarcoplasmic reticulum. At subphysiological temperatures, activation heat is inversely dependent on temperature. Thus one may presume that activation heat would decrease even further at body temperature. However, this assumption is prima facie inconsistent with a study, using intact hearts, which revealed no apparent change in the combination of activation and basal metabolism between 27 and 37°C. It is thus desired to directly determine the change in activation heat between 27 and 37°C. In this study, we use our recently constructed high-thermal resolution muscle calorimeter to determine the first heat-stress relation of isolated cardiac muscle at 37°C. We compare the relation at 37°C to that at 27°C to examine whether the inverse temperature dependence of activation heat, observed under hypothermic conditions, prevails at body temperature. Our results show that activation heat was reduced (from 3.5 ± 0.3 to 2.3 ± 0.3 kJ/m(3)) at the higher temperature. This leads us to conclude that activation metabolism continues to decline as temperature is increased from hypothermia to normothermia and allows us to comment on results obtained from the intact heart by previous investigators. PMID:27016583

  17. On the theoretical limits of detecting cyclic changes in cardiac high-energy phosphates and creatine kinase reaction kinetics using in vivo ³¹P MRS.

    PubMed

    Weiss, Kilian; Bottomley, Paul A; Weiss, Robert G

    2015-06-01

    Adenosine triphosphate (ATP) is absolutely required to fuel normal cyclic contractions of the heart. The creatine kinase (CK) reaction is a major energy reserve reaction that rapidly converts creatine phosphate (PCr) to ATP during the cardiac cycle and at times of stress and ischemia, but is significantly impaired in conditions such as hypertrophy and heart failure. Because the magnitudes of possible in vivo cyclic changes in cardiac high-energy phosphates (HEPs) during the cardiac cycle are not well known from previous work, this study uses mathematical modeling to assess whether, and to what extent, cyclic variations in HEPs and in the rate of ATP synthesis through CK (CK flux) could exist in the human heart, and whether they could be measured with current in vivo (31)P MRS methods. Multi-site exchange models incorporating enzymatic rate equations were used to study the cyclic dynamics of the CK reaction, and Bloch equations were used to simulate (31)P MRS saturation transfer measurements of the CK reaction. The simulations show that short-term buffering of ATP by CK requires temporal variations over the cardiac cycle in the CK reaction velocities modeled by enzymatic rate equations. The maximum variation in HEPs in the normal human heart beating at 60 min(-1) was approximately 0.4 mM and proportional to the velocity of ATP hydrolysis. Such HEP variations are at or below the current limits of detection by in vivo (31)P MRS methods. Bloch equation simulations show that (31)P MRS saturation transfer estimates the time-averaged, pseudo-first-order forward rate constant, k(f,ap)', of the CK reaction, and that periodic short-term fluctuations in kf ' and CK flux are not likely to be detectable in human studies employing current in vivo (31)P MRS methods. PMID:25914379

  18. Variations in local calcium signaling in adjacent cardiac myocytes of the intact mouse heart detected with two-dimensional confocal microscopy

    PubMed Central

    Hammer, Karin P.; Hohendanner, Felix; Blatter, Lothar A.; Pieske, Burkert M.; Heinzel, Frank R.

    2015-01-01

    Dyssynchronous local Ca release within individual cardiac myocytes has been linked to cellular contractile dysfunction. Differences in Ca kinetics in adjacent cells may also provide a substrate for inefficient contraction and arrhythmias. In a new approach we quantify variation in local Ca transients between adjacent myocytes in the whole heart. Langendorff-perfused mouse hearts were loaded with Fluo-8 AM to detect Ca and Di-4-ANEPPS to visualize cell membranes. A spinning disc confocal microscope with a fast camera allowed us to record Ca signals within an area of 465 μm by 315 μm with an acquisition speed of 55 fps. Images from multiple transients recorded at steady state were registered to their time point in the cardiac cycle to restore averaged local Ca transients with a higher temporal resolution. Local Ca transients within and between adjacent myocytes were compared with regard to amplitude, time to peak and decay at steady state stimulation (250 ms cycle length). Image registration from multiple sequential Ca transients allowed reconstruction of high temporal resolution (2.4 ± 1.3 ms) local CaT in 2D image sets (N = 4 hearts, n = 8 regions). During steady state stimulation, spatial Ca gradients were homogeneous within cells in both directions and independent of distance between measured points. Variation in CaT amplitudes was similar across the short and the long side of neighboring cells. Variations in TAU and TTP were similar in both directions. Isoproterenol enhanced the CaT but not the overall pattern of spatial heterogeneities. Here we detected and analyzed local Ca signals in intact mouse hearts with high temporal and spatial resolution, taking into account 2D arrangement of the cells. We observed significant differences in the variation of CaT amplitude along the long and short axis of cardiac myocytes. Variations of Ca signals between neighboring cells may contribute to the substrate of cardiac remodeling. PMID:25628569

  19. FKBP12 activates the cardiac ryanodine receptor Ca2+-release channel and is antagonised by FKBP12.6.

    PubMed

    Galfré, Elena; Pitt, Samantha J; Venturi, Elisa; Sitsapesan, Mano; Zaccai, Nathan R; Tsaneva-Atanasova, Krasimira; O'Neill, Stephen; Sitsapesan, Rebecca

    2012-01-01

    Changes in FKBP12.6 binding to cardiac ryanodine receptors (RyR2) are implicated in mediating disturbances in Ca(2+)-homeostasis in heart failure but there is controversy over the functional effects of FKBP12.6 on RyR2 channel gating. We have therefore investigated the effects of FKBP12.6 and another structurally similar molecule, FKBP12, which is far more abundant in heart, on the gating of single sheep RyR2 channels incorporated into planar phospholipid bilayers and on spontaneous waves of Ca(2+)-induced Ca(2+)-release in rat isolated permeabilised cardiac cells. We demonstrate that FKBP12 is a high affinity activator of RyR2, sensitising the channel to cytosolic Ca(2+), whereas FKBP12.6 has very low efficacy, but can antagonise the effects of FKBP12. Mathematical modelling of the data shows the importance of the relative concentrations of FKBP12 and FKBP12.6 in determining RyR2 activity. Consistent with the single-channel results, physiological concentrations of FKBP12 (3 µM) increased Ca(2+)-wave frequency and decreased the SR Ca(2+)-content in cardiac cells. FKBP12.6, itself, had no effect on wave frequency but antagonised the effects of FKBP12.We provide a biophysical analysis of the mechanisms by which FK-binding proteins can regulate RyR2 single-channel gating. Our data indicate that FKBP12, in addition to FKBP12.6, may be important in regulating RyR2 function in the heart. In heart failure, it is possible that an alteration in the dual regulation of RyR2 by FKBP12 and FKBP12.6 may occur. This could contribute towards a higher RyR2 open probability, 'leaky' RyR2 channels and Ca(2+)-dependent arrhythmias. PMID:22363773

  20. A case of cerebral embolism due to cardiac myxoma presenting with multiple cerebral microaneurysms detected on first MRI scans.

    PubMed

    Sato, Takahiro; Saji, Naoki; Kobayashi, Kazuto; Shibazaki, Kensaku; Kimura, Kazumi

    2016-03-01

    A 64-year-old man developed right arm weakness and dysarthria, and was admitted to our hospital. Diffusion-weighted magnetic resonance imaging of the brain showed a high intensity area in the frontal lobe. T2*-weighted images showed multiple spotty low intensity lesions in bilateral cerebral hemispheres, mimicking cerebral microbleeds. Cerebral angiography showed multiple aneurysms in the anterior, middle, posterior cerebral arteries and cerebellar arteries. Transthoracic echocardiography revealed a floating structure in the left atrial chamber, indicating cardiac myxoma. We diagnosed cardioembolic ischemic stroke due to left atrial myxoma. Cardiac surgery for excision of a left atrial myxoma was performed on the 3rd hospital day. Multiple aneurysms should be taken into account for differential diagnosis in patients with cardiac myxoma and with atypical spotty low intensity on T2*-weighted images. PMID:26797485

  1. Scutellarin alleviates interstitial fibrosis and cardiac dysfunction of infarct rats by inhibiting TGFβ1 expression and activation of p38-MAPK and ERK1/2

    PubMed Central

    Pan, Zhenwei; Zhao, Weiming; Zhang, Xiangying; Wang, Bing; Wang, Jinghao; Sun, Xuelin; Liu, Xuantong; Feng, Shuya; Yang, Baofeng; Lu, Yanjie

    2011-01-01

    BACKGROUND AND PURPOSE Interstitial fibrosis plays a causal role in the development of heart failure after chronic myocardial infarction (MI), and anti-fibrotic therapy represents a promising strategy to mitigate this pathological process. The purpose of this study was to investigate the effect of long-term administration of scutellarin (Scu) on cardiac interstitial fibrosis of myocardial infarct rats and the underlying mechanisms. EXPERIMENTAL APPROACH Scu was administered to rats that were subjected to coronary artery ligation. Eight weeks later, its effects on cardiac fibrosis were assessed by examining cardiac function and histology. The number and collagen content of cultured cardiac fibroblasts exposed to angiotensin II (Ang II) were determined after the administration of Scu in vitro. Protein expression was detected by Western blot technique, and mRNA levels by quantitative reverse transcription-PCR. KEY RESULTS The echocardiographic and haemodynamic measurements showed that Scu improved the impaired cardiac function of infarct rats and decreased interstitial fibrosis. Scu inhibited the expression of FN1 and TGFβ1, but produced no effects on inflammatory cytokines (TNFα, IL-1β and IL-6) in the 8 week infarct hearts. Scu inhibited the proliferation and collagen production of cardiac fibroblasts (CFs) and the up-regulation of FN1 and TGFβ1 induced by Ang II. The enhanced phosphorylation of p38-MAPK and ERK1/2 in both infarct cardiac tissue and cultured CFs challenged by Ang II were suppressed by Scu. CONCLUSIONS AND IMPLICATIONS Long-term administration of Scu improved the cardiac function of MI rats by inhibiting interstitial fibrosis, and the mechanisms may involve the suppression of pro-fibrotic cytokine TGFβ1 expression and inhibition of p38 MAPK and ERK1/2 phosphorylation. PMID:20942814

  2. High glucose induces Smad activation via the transcriptional coregulator p300 and contributes to cardiac fibrosis and hypertrophy

    PubMed Central

    2014-01-01

    Background Despite advances in the treatment of heart failure, mortality remains high, particularly in individuals with diabetes. Activated transforming growth factor beta (TGF-β) contributes to the pathogenesis of the fibrotic interstitium observed in diabetic cardiomyopathy. We hypothesized that high glucose enhances the activity of the transcriptional co-activator p300, leading to the activation of TGF-β via acetylation of Smad2; and that by inhibiting p300, TGF-β activity will be reduced and heart failure prevented in a clinically relevant animal model of diabetic cardiomyopathy. Methods p300 activity was assessed in H9c2 cardiomyoblasts under normal glucose (5.6 mmol/L—NG) and high glucose (25 mmol/L—HG) conditions. 3H-proline incorporation in cardiac fibroblasts was also assessed as a marker of collagen synthesis. The role of p300 activity in modifying TGF-β activity was investigated with a known p300 inhibitor, curcumin or p300 siRNA in vitro, and the functional effects of p300 inhibition were assessed using curcumin in a hemodynamically validated model of diabetic cardiomyopathy – the diabetic TG m(Ren-2)27 rat. Results In vitro, H9c2 cells exposed to HG demonstrated increased p300 activity, Smad2 acetylation and increased TGF-β activity as assessed by Smad7 induction (all p < 0.05 c/w NG). Furthermore, HG induced 3H-proline incorporation as a marker of collagen synthesis (p < 0.05 c/w NG). p300 inhibition, using either siRNA or curcumin reduced p300 activity, Smad acetylation and TGF-β activity (all p < 0.05 c/w vehicle or scrambled siRNA). Furthermore, curcumin therapy reduced 3H-proline incorporation in HG and TGF-β stimulated fibroblasts (p < 0.05 c/w NG). To determine the functional significance of p300 inhibition, diabetic Ren-2 rats were randomized to receive curcumin or vehicle for 6 weeks. Curcumin treatment reduced cardiac hypertrophy, improved diastolic function and reduced extracellular matrix production, without

  3. Detecting eavesdropping activity in fiber optic networks

    NASA Astrophysics Data System (ADS)

    MacDonald, Gregory G.

    The secure transmission of data is critical to governments, military organizations, financial institutions, health care providers and other enterprises. The primary method of securing in-transit data is though data encryption. A number of encryption methods exist but the fundamental approach is to assume an eavesdropper has access to the encrypted message but does not have the computing capability to decrypt the message in a timely fashion. Essentially, the strength of security depends on the complexity of the encryption method and the resources available to the eavesdropper. The development of future technologies, most notably quantum computers and quantum computing, is often cited as a direct threat to traditional encryption schemes. It seems reasonable that additional effort should be placed on prohibiting the eavesdropper from coming into possession of the encrypted message in the first place. One strategy for denying possession of the encrypted message is to secure the physical layer of the communications path. Because the majority of transmitted information is over fiber-optic networks, it seems appropriate to consider ways of enhancing the integrity and security of the fiber-based physical layer. The purpose of this research is to investigate the properties of light, as they are manifested in single mode fiber, as a means of insuring the integrity and security of the physical layer of a fiber-optic based communication link. Specifically, the approach focuses on the behavior of polarization in single mode fiber, as it is shown to be especially sensitive to fiber geometry. Fiber geometry is necessarily modified during the placement of optical taps. The problem of detecting activity associated with the placement of an optical tap is herein approached as a supervised machine learning anomaly identification task. The inputs include raw polarization measurements along with additional features derived from various visualizations of the raw data (the inputs are

  4. Increased mitochondrial emission of reactive oxygen species and calpain activation are required for doxorubicin-induced cardiac and skeletal muscle myopathy

    PubMed Central

    Min, Kisuk; Kwon, Oh-Sung; Smuder, Ashley J; Wiggs, Michael P; Sollanek, Kurt J; Christou, Demetra D; Yoo, Jeung-Ki; Hwang, Moon-Hyon; Szeto, Hazel H; Kavazis, Andreas N; Powers, Scott K

    2015-01-01

    Although doxorubicin (DOX) is a highly effective anti-tumour agent used to treat a variety of cancers, DOX administration is associated with significant side effects, including myopathy of both cardiac and skeletal muscles. The mechanisms responsible for DOX-mediated myopathy remain a topic of debate. We tested the hypothesis that both increased mitochondrial reactive oxygen species (ROS) emission and activation of the cysteine protease calpain are required for DOX-induced myopathy in rat cardiac and skeletal muscle. Cause and effect was determined by administering a novel mitochondrial-targeted anti-oxidant to prevent DOX-induced increases in mitochondrial ROS emission, whereas a highly-selective pharmacological inhibitor was exploited to inhibit calpain activity. Our findings reveal that mitochondria are a major site of DOX-mediated ROS production in both cardiac and skeletal muscle fibres and the prevention of DOX-induced increases in mitochondrial ROS emission protects against fibre atrophy and contractile dysfunction in both cardiac and skeletal muscles. Furthermore, our results indicate that DOX-induced increases in mitochondrial ROS emission are required to activate calpain in heart and skeletal muscles and, importantly, calpain activation is a major contributor to DOX-induced myopathy. Taken together, these findings show that increased mitochondrial ROS production and calpain activation are significant contributors to the development of DOX-induced myopathy in both cardiac and skeletal muscle fibres. PMID:25643692

  5. The effects of chewing versus caffeine on alertness, cognitive performance and cardiac autonomic activity during sleep deprivation.

    PubMed

    Kohler, Mark; Pavy, Alan; van den Heuvel, Cameron

    2006-12-01

    Chewing has been shown to alleviate feelings of sleepiness and improve cognitive performance during the day. This study investigated the effect of chewing on alertness and cognitive performance across one night without sleep as well as the possible mediating role of cardiac autonomic activity. Fourteen adults participated in a randomized, counterbalanced protocol employing a chewing, placebo and caffeine condition. Participants completed tasks assessing psychomotor vigilance, tracking, grammatical reasoning, alertness and sleepiness each hour across the night. All participants received either placebo or caffeine (200 mg), while the chewing condition also chewed on a tasteless and odorless substance for 15 min each hour. Heart rate (HR), root mean square of the successive differences in R-R intervals on the ECG (RMSSD), and preejection period (PEP) were simultaneously recorded. Alertness and cognitive performance amongst the chewing condition did not differ or were in fact worse when compared with placebo. Similarly, measures of HR and RMSSD remained the same between these two conditions; however, PEP was reduced in the later part of the night in the chewing condition compared with a relative increase for placebo. Caffeine led to improved speed and accuracy on cognitive tasks and increased alertness when compared with chewing. Relative increases in RMSSD and reductions in HR were demonstrated following caffeine; however, no change in PEP was seen. Strong associations between cardiac parasympathetic activity and complex cognitive tasks, as well as between subjective alertness and simpler cognitive tasks, suggest a differential process mediating complex versus simple cognitive performance during sleep deprivation. PMID:17118092

  6. Comprehensive Echocardiographic Detection of Treatment-related Cardiac Dysfunction in Adult Survivors of Childhood Cancer: Results from the St. Jude Lifetime Cohort Study

    PubMed Central

    Armstrong, Gregory T.; Joshi, Vijaya M.; Ness, Kirsten K.; Marwick, Thomas H.; Zhang, Nan; Srivastava, DeoKumar; Griffin, Brian P.; Grimm, Richard A.; Thomas, James; Phelan, Dermot; Collier, Patrick; Krull, Kevin R.; Mulrooney, Daniel A.; Green, Daniel M.; Hudson, Melissa M.; Robison, Leslie L.; Plana, Juan Carlos

    2015-01-01

    Background Treatment-related cardiac death is the primary non-cancer cause of mortality in adult survivors of childhood malignancies. Early detection of cardiac dysfunction using modern echocardiographic techniques may identify a high risk subset of survivors for early intervention. Objective To determine the prevalence of cardiac dysfunction in adult survivors of childhood malignancies using state of the art echocardiographic evaluation of cardiac function including strain imaging Methods Echocardiographic assessment included three dimensional (3D) left ventricular ejection fraction (LVEF), global longitudinal and circumferential myocardial strain and diastolic function, graded per American Society of Echocardiography (ASE) guidelines on 1,820 adult (median age 31 [range 18-65] years) survivors of childhood cancer (median time from diagnosis 23 years [range10-48] years) exposed to either anthracycline chemotherapy (N=1,050), chest-directed radiotherapy (RT, N=306), or both therapies (N=464). Results Only 5.8% of survivors had an abnormal 3D LVEF (<50%). However, 32.1% of survivors with a normal 3D LVEF had evidence for cardiac dysfunction by either global longitudinal strain (28.0%), ASE graded diastolic assessment (8.7%), or both. Abnormal global longitudinal strain was associated with chest-directed RT (1-19.9 Gy, Rate Ratio (RR) 1.38, 95% Confidence Interval (CI) 1.14-1.66; 20-29.9 Gy, RR 1.65, 95% CI 1.31-2.08; >30 Gy, RR 2.39, 95% CI 1.79-3.18) and anthracycline dose >300 mg/m2 (RR 1.72, 95% CI 1.31-2.26). Survivors with metabolic syndrome were twice as likely to have abnormal global longitudinal strain (Rate Ratio [RR] 1.94, 95% CI 1.66-2.28) as well as abnormal diastolic function (RR 1.68, 95% CI 1.39-2.03), but not abnormal 3D LVEF (RR 1.07, 95% CI 0.74-1.53). Conclusions and Relevance Abnormal global longitudinal strain and abnormal diastolic function are more prevalent than reduced 3D LVEF and are associated with treatment exposure. They may identify a

  7. Cardiac Dual-source Computed Tomography for the Detection of Left Main Compression Syndrome in Patients with Pulmonary Hyper-tension

    PubMed Central

    Demerouti, Eftychia; Manginas, Athanassios; Petrou, Emmanouil; Katsilouli, Spyridoula; Karyofillis, Panagiotis; Athanassopoulos, George; Karatasakis, George; Iakovou, Ioannis; Mihas, Konstantinos; Mastorakou, Irene

    2016-01-01

    Introduction: Left Main Compression Syndrome (LMCS) represents an entity described as the extrinsic compression of the left main coronary artery (LMCA) by a dilated pulmonary artery (PA) trunk. We examined the presence of LMCS in patients with pulmonary hypertension (PH) using dual-source computed tomography (DSCT), as a non-invasive diagnostic tool. Methods: The following parameters were measured: PA trunk diameter (PAD), the distance between PAD and LMCA (LMPA) and the distance between PA and aorta (AoPA). These measurements were related with demographic, echocardiographic, hemodynamic and clinical parameters. Angiography was performed in two patients with LMCS suspected by cardiac computed tomographic angiography. Patients without PH but with angina were examined as controls, using DSCT cardiac angiography to assess the same measurements and to detect the prevalence of coronary artery disease. Results: PA diameter value over 40.00 mm has been associated with PH and LMCS. Furthermore, LMCS did not occur at a distance smaller than 0.50 mm between the PA and the LMCA, and did not correlate with the distance between the PA and the aorta or with cardiac index and NT-proBNP. Conclusion: DSCT may represent the initial testing modality in PH patients with dilated PA trunk to exclude LMCS. A periodical rule-out of this rare entity, as assessed by DSCT, in patients with a severely dilated PA seems to be mandatory for PH patients contributing to survival improvement. PMID:27499817

  8. Pulse contour analysis: Is it able to reliably detect changes in cardiac output in the haemodynamically unstable patient?

    PubMed Central

    2011-01-01

    Three pulse contour systems for monitoring cardiac output - LiDCO Plus™, PiCCO Plus™ and FloTrac™ - were compared in postcardiac surgery patients. None of the three methods demonstrated good trending ability according to concordance analysis. Pulse contour systems remain unreliable in the haemodynamically unstable patient. PMID:21349140

  9. Acrolein inhalation causes myocardial strain delay and decreased cardiac performance as detected by high-frequency echocardiography in mice

    EPA Science Inventory

    Acrolein, an unsaturated aldehyde found in air pollution, impairs Ca2+ flux and contraction in cardiomyocytes in vitro. To better define direct and delayed functional cardiac effects, we hypothesized that a single exposure to acrolein would modify myocardial strain and performanc...

  10. SU-E-T-557: Measuring Neutron Activation of Cardiac Devices Irradiated During Proton Therapy Using Indium Foils

    SciTech Connect

    Avery, S; Christodouleas, J; Delaney, K; Diffenderfer, E; Brown, K

    2014-06-01

    Purpose: Measuring Neutron Activation of Cardiac devices Irradiated during Proton Therapy using Indium Foils Methods: The foils had dimensions of 25mm x 25mm x 1mm. After being activated, the foils were placed in a Canberra Industries well chamber utilizing a NaI(Tl) scintillation detector. The resulting gamma spectrum was acquired and analyzed using Genie 2000 spectroscopy software. One activation foil was placed over the upper, left chest of RANDO where a pacemaker would be. The rest of the foils were placed over the midline of the patient at different distances, providing a spatial distribution over the phantom. Using lasers and BBs to align the patient, 200 MU square fields were delivered to various treatment sites: the brain, the pancreas, and the prostate. Each field was shot at least a day apart, giving more than enough time for activity of the foil to decay (t1=2 = 54.12 min). Results: The net counts (minus background) of the three aforementioned peaks were used for our measurements. These counts were adjusted to account for detector efficiency, relative photon yields from decay, and the natural abundance of 115-In. The average neutron flux for the closed multi-leaf collimator irradiation was measured to be 1.62 x 106 - 0.18 x 106 cm2 s-1. An order of magnitude estimate of the flux for neutrons up to 1 keV from Diffenderfer et al. gives 3 x 106 cm2 s-1 which does agree on the order of magnitude. Conclusion: Lower energy neutrons have higher interaction cross-sections and are more likely to damage pacemakers. The thermal/slow neutron component may be enough to estimate the overall risk. The true test of the applicability of activation foils is whether or not measurements are capable of predicting cardiac device malfunction. For that, additional studies are needed to provide clinical evidence one way or the other.

  11. Adiponectin Upregulates MiR-133a in Cardiac Hypertrophy through AMPK Activation and Reduced ERK1/2 Phosphorylation

    PubMed Central

    Guan, Yuqing; Wang, Lei; Wang, Shuya; Li, Yueyan; Fu, Ying; Gao, Xiaoyuan; Su, Guohai

    2016-01-01

    Adiponectin and miR-133a are key regulators in cardiac hypertrophy. However, whether APN has a potential effect on miR-133a remains unclear. In this study, we aimed to investigate whether APN could regulate miR-133a expression in Angiotensin II (Ang II) induced cardiac hypertrophy in vivo and in vitro. Lentiviral-mediated adiponectin treatment attenuated cardiac hypertrophy induced by Ang II infusion in male wistar rats as determined by reduced cell surface area and mRNA levels of atrial natriuretic peptide (ANF) and brain natriuretic peptide (BNP), also the reduced left ventricular end-diastolic posterior wall thickness (LVPWd) and end-diastolic interventricular septal thickness (IVSd). Meanwhile, APN elevated miR-133a level which was downregulated by Ang II. To further investigate the underlying molecular mechanisms, we treated neonatal rat ventricular myocytes (NRVMs) with recombinant rat APN before Ang II stimulation. Pretreating cells with recombinant APN promoted AMP-activated protein kinase (AMPK) phosphorylation and inhibited ERK activation. By using the inhibitor of AMPK or a lentiviral vector expressing AMPK short hairpin RNA (shRNA) cancelled the positive effect of APN on miR-133a. The ERK inhibitor PD98059 reversed the downregulation of miR-133a induced by Ang II. These results indicated that the AMPK activation and ERK inhibition were responsible for the positive effect of APN on miR-133a. Furthermore, adiponectin receptor 1 (AdipoR1) mRNA expression was inhibited by Ang II stimulation. The positive effects of APN on AMPK activation and miR-133a, and the inhibitory effect on ERK phosphorylation were inhibited in NRVMs transfected with lentiviral AdipoR1shRNA. In addition, APN depressed the elevated expression of connective tissue growth factor (CTGF), a direct target of miR-133a, through the AMPK pathway. Taken together, our data indicated that APN reversed miR-133a levels through AMPK activation, reduced ERK1/2 phosphorylation in cardiomyocytes

  12. Adiponectin Upregulates MiR-133a in Cardiac Hypertrophy through AMPK Activation and Reduced ERK1/2 Phosphorylation.

    PubMed

    Li, Ying; Cai, Xiaojun; Guan, Yuqing; Wang, Lei; Wang, Shuya; Li, Yueyan; Fu, Ying; Gao, Xiaoyuan; Su, Guohai

    2016-01-01

    Adiponectin and miR-133a are key regulators in cardiac hypertrophy. However, whether APN has a potential effect on miR-133a remains unclear. In this study, we aimed to investigate whether APN could regulate miR-133a expression in Angiotensin II (Ang II) induced cardiac hypertrophy in vivo and in vitro. Lentiviral-mediated adiponectin treatment attenuated cardiac hypertrophy induced by Ang II infusion in male wistar rats as determined by reduced cell surface area and mRNA levels of atrial natriuretic peptide (ANF) and brain natriuretic peptide (BNP), also the reduced left ventricular end-diastolic posterior wall thickness (LVPWd) and end-diastolic interventricular septal thickness (IVSd). Meanwhile, APN elevated miR-133a level which was downregulated by Ang II. To further investigate the underlying molecular mechanisms, we treated neonatal rat ventricular myocytes (NRVMs) with recombinant rat APN before Ang II stimulation. Pretreating cells with recombinant APN promoted AMP-activated protein kinase (AMPK) phosphorylation and inhibited ERK activation. By using the inhibitor of AMPK or a lentiviral vector expressing AMPK short hairpin RNA (shRNA) cancelled the positive effect of APN on miR-133a. The ERK inhibitor PD98059 reversed the downregulation of miR-133a induced by Ang II. These results indicated that the AMPK activation and ERK inhibition were responsible for the positive effect of APN on miR-133a. Furthermore, adiponectin receptor 1 (AdipoR1) mRNA expression was inhibited by Ang II stimulation. The positive effects of APN on AMPK activation and miR-133a, and the inhibitory effect on ERK phosphorylation were inhibited in NRVMs transfected with lentiviral AdipoR1shRNA. In addition, APN depressed the elevated expression of connective tissue growth factor (CTGF), a direct target of miR-133a, through the AMPK pathway. Taken together, our data indicated that APN reversed miR-133a levels through AMPK activation, reduced ERK1/2 phosphorylation in cardiomyocytes

  13. Atrial electrical activity detection using linear combination of 12-lead ECG signals.

    PubMed

    Perlman, Or; Katz, Amos; Weissman, Noam; Amit, Guy; Zigel, Yaniv

    2014-04-01

    ECG analysis is the method for cardiac arrhythmia diagnosis. During the diagnostic process many features should be taken into consideration, such as regularity and atrial activity. Since in some arrhythmias, the atrial electrical activity (AEA) waves are hidden in other waves, and a precise classification from surface ECG is inapplicable, a confirmation diagnosis is usually performed during an invasive procedure. In this paper, we study a "semiautomatic" method for AEA-waves detection using a linear combination of 12-lead ECG signals. This method's objective is to be applicable to a variety of arrhythmias with emphasis given to detect concealed AEA waves. It includes two variations--using maximum energy ratio and a synthetic AEA signal. In the former variation, an energy ratio-based cost function is created and maximized using the gradient ascent method. The latter variation adapted the linear combiner method, when applied on a synthetic signal, combined with surface ECG leads. A study was performed evaluating the AEA-waves detection from 63 patients (nine training, 54 validation) presenting eight arrhythmia types. Averaged sensitivity of 92.21% and averaged precision of 92.08% were achieved compared to the definite diagnosis. In conclusion, the presented method may lead to early and accurate detection of arrhythmias, which will result in a better oriented treatment. PMID:24658228

  14. The TIR/BB-loop mimetic AS-1 attenuates mechanical stress-induced cardiac fibroblast activation and paracrine secretion via modulation of large tumor suppressor kinase 1.

    PubMed

    Fan, Min; Song, Juan; He, Yijie; Shen, Xin; Li, Jiantao; Que, Linli; Zhu, Guoqing; Zhu, Quan; Cai, Xin; Ha, Tuanzhu; Chen, Qi; Xu, Yong; Li, Chuanfu; Li, Yuehua

    2016-06-01

    The TIR/BB-loop mimetic AS-1 has been reported to prevent cardiac hypertrophy by inhibiting interleukin-1 receptor (IL-1R)-mediated myeloid differentiation primary response gene 88 (MyD88)-dependent signaling. To date, it remains unknown whether and if so how AS-1 contributes to mechanical stress (MS)-induced cardiac fibroblast activation, a key process in pressure overload-induced cardiac remodeling and heart failure. Here, we show that phosphorylation and expression of large tumor suppressor kinase 1 (LATS1), a key molecule in the Hippo-Yes associated protein (YAP) signaling pathway, were down-regulated in primary neonatal rat cardiac fibroblasts (NRCFs) in response to MS and in the hearts of mice subjected to transverse aortic constriction (TAC) procedure; AS-1 treatment was able to restore LATS1 phosphorylation and expression both in vitro and in vivo. AS-1 treatment suppressed the induction of proliferation, differentiation and collagen synthesis in response to MS in NRCFs. AS-1 also ameliorated cardiomyocyte hypertrophy and apoptosis through dampening paracrine secretion of stretched cardiac fibroblasts. In mice, AS-1 treatment could protect against TAC-induced cardiac hypertrophy, myocardial fibrosis and heart failure. Of note, LATS1 depletion using siRNA completely abrogated the inhibitory effects of AS-1 on NRCFs under MS including accelerated proliferation, differentiation, enhanced ability to produce collagen and augmented paracrine secretion of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) to induce cardiomyocyte hypertrophy. Therefore, our results delineate a previously unrecognized role for LATS1 in cardiac fibroblast to mediate the beneficial effects of AS-1 in preventing pressure overload-induced cardiac remodeling and heart failure. PMID:26964796

  15. Fluorescence imaging of electrical activity in cardiac cells using an all-solid-state system.

    PubMed

    Entcheva, Emilia; Kostov, Yordan; Tchernev, Elko; Tung, Leslie

    2004-02-01

    Tracking spatial and temporal determinants of cardiac arrhythmogenesis at the cellular level presents challenges to the optical mapping techniques employed. In this paper, we describe a compact system combining two nontraditional low-cost solutions for excitation light sources and emission filters in fluorescence measurements of transmembrane potentials, Vm, or intracellular calcium, [Ca2+]i in cardiac cell networks. This is the first reported use of high-power blue and green light emitting diodes (LEDs), to excite cell monolayers stained with Vm - (di-8-ANEPPS) or [Ca2+]i - (Fluo-3) sensitive dyes. In addition, we use simple techniques for fabrication of suitable thin emission filters with uniform properties, no auto-fluorescence, high durability and good flexibility for imaging Vm or [Ca2+]i. The battery-operated LEDs and the fabricated emission filters, integrated with a fiber-optic system for contact fluorescence imaging, were used as tools to characterize conduction velocity restitution at the macro-scale. The versatility of the LEDs for illumination is further emphasized through 1) demonstration of their usage for epi-illumination recordings at the single-cell level, and 2) demonstration of their unique high-frequency light modulation ability. The LEDs showed excellent stability as excitation light sources for fluorescence measurements; acceptable signal-to-noise ratio and negligible cell photodamage and indicator dye photobleaching were observed. PMID:14765706

  16. Cardiac supporting device using artificial rubber muscle: preliminary study to active dynamic cardiomyoplasty.

    PubMed

    Saito, Yoshiaki; Suzuki, Yasuyuki; Goto, Takeshi; Daitoku, Kazuyuki; Minakawa, Masahito; Fukuda, Ikuo

    2015-12-01

    Dynamic cardiomyoplasty is a surgical treatment that utilizes the patient's skeletal muscle to support circulation. To overcome the limitations of autologous skeletal muscles in dynamic cardiomyoplasty, we studied the use of a wrapped-type cardiac supporting device using pneumatic muscles. Four straight rubber muscles (Fluidic Muscle, FESTO, Esslingen, Germany) were used and connected to pressure sensors, solenoid valves, a controller and an air compressor. The driving force was compressed air. A proportional-integral-derivative system was employed to control the device movement. An overflow-type mock circulation system was used to analyze the power and the controllability of this new device. The device worked powerfully with pumped flow against afterload of 88 mmHg, and the beating rate and contraction/dilatation time were properly controlled using simple software. Maximum pressure inside the ventricle and maximum output were 187 mmHg and 546.5 ml/min, respectively, in the setting of 50 beats per minute, a contraction/dilatation ratio of 1:2, a preload of 18 mmHg, and an afterload of 88 mmHg. By changing proportional gain, contraction speed could be modulated. This study showed the efficacy and feasibility of a pneumatic muscle for use in a cardiac supporting device. PMID:26253252

  17. Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering.

    PubMed

    Gelmi, Amy; Cieslar-Pobuda, Artur; de Muinck, Ebo; Los, Marek; Rafat, Mehrdad; Jager, Edwin W H

    2016-06-01

    The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation. PMID:27126086

  18. Robust boundary detection and tracking of left ventricles on ultrasound images using active shape model and ant colony optimization.

    PubMed

    Zhang, Yaonan; Gao, Yuan; Jiao, Jinling; Li, Xian; Li, Sai; Yang, Jun

    2014-01-01

    Information regarding the motion, strain and synchronization are important for cardiac diagnosis and therapy. Extraction of such information from ultrasound images remains an open problem till today. In this paper, a novel method is proposed to extract the boundaries of left ventricles and track these boundaries in ultrasound image sequences. The initial detection of boundaries was performed by an active shape model scheme. Subsequent refinement of the boundaries was done by using local variance information of the images. The main objective of this paper is the formulation of a new boundary tracking algorithm using ant colony optimization technique. The experiments conducted on the simulated image sequences and the real cardiac ultrasound image sequences shows a positive and promising result. PMID:25226995

  19. Cardiac Sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion.

    PubMed

    Yamamoto, Tsunehisa; Tamaki, Kayoko; Shirakawa, Kohsuke; Ito, Kentaro; Yan, Xiaoxiang; Katsumata, Yoshinori; Anzai, Atsushi; Matsuhashi, Tomohiro; Endo, Jin; Inaba, Takaaki; Tsubota, Kazuo; Sano, Motoaki; Fukuda, Keiichi; Shinmura, Ken

    2016-04-15

    Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury.Am J Physiol Heart Circ Physiol308: H894-H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specificSirt1knockout (CM-Sirt1(-/-)) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (-40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM-Sirt1(-/-)mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM-Sirt1(-/-)mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventionalC3knockout (C3(-/-)) mice treated with CR was similar to that in the ad libitum-fedC3(-/-)mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting that

  20. Co-activation of nuclear factor-κB and myocardin/serum response factor conveys the hypertrophy signal of high insulin levels in cardiac myoblasts.

    PubMed

    Madonna, Rosalinda; Geng, Yong-Jian; Bolli, Roberto; Rokosh, Gregg; Ferdinandy, Peter; Patterson, Cam; De Caterina, Raffaele

    2014-07-11

    Hyperinsulinemia contributes to cardiac hypertrophy and heart failure in patients with the metabolic syndrome and type 2 diabetes. Here, high circulating levels of tumor necrosis factor (TNF)-α may synergize with insulin in signaling inflammation and cardiac hypertrophy. We tested whether high insulin affects activation of TNF-α-induced NF-κB and myocardin/serum response factor (SRF) to convey hypertrophy signaling in cardiac myoblasts. In canine cardiac myoblasts, treatment with high insulin (10(-8) to 10(-7) m) for 0-24 h increased insulin receptor substrate (IRS)-1 phosphorylation at Ser-307, decreased protein levels of chaperone-associated ubiquitin (Ub) E3 ligase C terminus of heat shock protein 70-interacting protein (CHIP), increased SRF activity, as well as β-myosin heavy chain (MHC) and myocardin expressions. Here siRNAs to myocardin or NF-κB, as well as CHIP overexpression prevented (while siRNA-mediated CHIP disruption potentiated) high insulin-induced SR element (SRE) activation and β-MHC expression. Insulin markedly potentiated TNF-α-induced NF-κB activation. Compared with insulin alone, insulin+TNF-α increased SRF/SRE binding and β-MHC expression, which was reversed by the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) and by NF-κB silencing. In the hearts of db/db diabetic mice, in which Akt phosphorylation was decreased, p38MAPK, Akt1, and IRS-1 phosphorylation at Ser-307 were increased, together with myocardin expression as well as SRE and NF-κB activities. In response to high insulin, cardiac myoblasts increase the expression or the promyogenic transcription factors myocardin/SRF in a CHIP-dependent manner. Insulin potentiates TNF-α in inducing NF-κB and SRF/SRE activities. In hyperinsulinemic states, myocardin may act as a nuclear effector of insulin, promoting cardiac hypertrophy. PMID:24855642

  1. Cardiac myosin isoforms exhibit differential rates of MgADP release and MgATP binding detected by myocardial viscoelasticity.

    PubMed

    Wang, Yuan; Tanner, Bertrand C W; Lombardo, Andrew T; Tremble, Sarah M; Maughan, David W; Vanburen, Peter; Lewinter, Martin M; Robbins, Jeffrey; Palmer, Bradley M

    2013-01-01

    We measured myosin crossbridge detachment rate and the rates of MgADP release and MgATP binding in mouse and rat myocardial strips bearing one of the two cardiac myosin heavy chain (MyHC) isoforms. Mice and rats were fed an iodine-deficient, propylthiouracil diet resulting in ~100% expression of β-MyHC in the ventricles. Ventricles of control animals expressed ~100% α-MyHC. Chemically-skinned myocardial strips prepared from papillary muscle were subjected to sinusoidal length perturbation analysis at maximum calcium activation pCa 4.8 and 17°C. Frequency characteristics of myocardial viscoelasticity were used to calculate crossbridge detachment rate over 0.01 to 5mM [MgATP]. The rate of MgADP release, equivalent to the asymptotic value of crossbridge detachment rate at high MgATP, was highest in mouse α-MyHC (111.4±6.2s(-1)) followed by rat α-MyHC (65.0±7.3s(-1)), mouse β-MyHC (24.3±1.8s(-1)) and rat β-MyHC (15.5±0.8s(-1)). The rate of MgATP binding was highest in mouse α-MyHC (325±32 mM(-1) s(-1)) then mouse β-MyHC (152±23 mM(-1) s(-1)), rat α-MyHC (108±10 mM(-1) s(-1)) and rat β-MyHC (55±6 mM(-1) s(-1)). Because the events of MgADP release and MgATP binding occur in a post power-stroke state of the myosin crossbridge, we infer that MgATP release and MgATP binding must be regulated by isoform- and species-specific structural differences located outside the nucleotide binding pocket, which is identical in sequence for these four myosins. We postulate that differences in the stiffness profile of the entire myosin molecule, including the thick filament and the myosin-actin interface, are primarily responsible for determining the strain on the nucleotide binding pocket and the subsequent differences in the rates of nucleotide release and binding observed among the four myosins examined here. PMID:23123290

  2. Pioglitazone reverses down-regulation of cardiac PPAR{gamma} expression in Zucker diabetic fatty rats

    SciTech Connect

    Pelzer, Theo . E-mail: pelzer_t@klinik.uni-wuerzburg.de; Jazbutyte, Virginija; Arias-Loza, Paula Anahi; Segerer, Stephan; Lichtenwald, Margit; Law, Marilyn P.; Schaefers, Michael; Ertl, Georg; Neyses, Ludwig

    2005-04-08

    Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPAR{gamma} in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPAR{gamma} agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPAR{gamma}, glucose transporter-4 and {alpha}-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPAR{gamma}, glut-4, and {alpha}-MHC expression levels in diabetic ZDF rats. Cardiac [{sup 18}F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPAR{gamma} agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPAR{gamma} expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin.

  3. Post-cardiac transplant arteriopathy in piglets is associated with fragmentation of elastin and increased activity of a serine elastase.

    PubMed Central

    Oho, S.; Rabinovitch, M.

    1994-01-01

    In experimental piglets after heterotopic heart transplant, we observed an immune/inflammatory response in the coronary arteries with increased expression of interleukin-1 beta and accumulation of fibronectin and smooth muscle cells in the subendothelium (N. Clausell, S. Molossi, M. Rabinovitch, Am J Pathol 1993, 142, 1772-1786). Proteolytic enzymes including elastases regulate cytokine activity and are associated with the development of neointimal proliferation. We now report ultrastructural evidence of elastolytic activity in the donor compared to host coronary arteries judged by a fivefold increase in the breaks in the internal elastic lamina, (P < 0.01) correlating with a 10-fold increase in elastase activity per mg tissue (P < 0.01). The enzyme activity is serine elastase, i.e., inhibited by phenylmethyl sulfonyl fluoride, and elafin but not EDTA. Using a novel strategy that greatly increases the activity extractable from the tissue, we resolved the enzyme on an elastin substrate gel as a protein of approximately 23 kd. Ours is the first report and characterization of increased elastase activity associated with the development of the post-cardiac transplant coronary arteriopathy. The source may be inflammatory or smooth muscle cells, and elastase may play a pathophysiological role in neointimal proliferation by activating cytokines and growth factors and by release of chemotactic peptides. Images Figure 1 Figure 5 PMID:8030749

  4. Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11·2 microdeletion and partial DiGeorge syndrome

    PubMed Central

    Eberle, P; Berger, C; Junge, S; Dougoud, S; Büchel, E Valsangiacomo; Riegel, M; Schinzel, A; Seger, R; Güngör, T

    2009-01-01

    A subgroup of patients with 22q11·2 microdeletion and partial DiGeorge syndrome (pDGS) appears to be susceptible to non-cardiac mortality (NCM) despite sufficient overall CD4+ T cells. To detect these patients, 20 newborns with 22q11·2 microdeletion and congenital heart disease were followed prospectively for 6 years. Besides detailed clinical assessment, longitudinal monitoring of naive CD4+ and cytotoxic CD3+CD8+ T cells (CTL) was performed. To monitor thymic activity, we analysed naive platelet endothelial cell adhesion molecule-1 (CD31+) expressing CD45RA+RO−CD4+ cells containing high numbers of T cell receptor excision circle (TREC)-bearing lymphocytes and compared them with normal values of healthy children (n = 75). Comparing two age periods, low overall CD4+ and naive CD4+ T cell numbers were observed in 65%/75%, respectively, of patients in period A (< 1 year) declining to 22%/50%, respectively, of patients in period B (> 1/< 7 years). The percentage of patients with low CTLs (< P10) remained robust until school age (period A: 60%; period B: 50%). Low numbers of CTLs were associated with abnormally low naive CD45RA+RO−CD4+ T cells. A high-risk (HR) group (n = 11) and a standard-risk (SR) (n = 9) group were identified. HR patients were characterized by low numbers of both naive CD4+ and CTLs and were prone to lethal infectious and lymphoproliferative complications (NCM: four of 11; cardiac mortality: one of 11) while SR patients were not (NCM: none of nine; cardiac mortality: two of nine). Naive CD31+CD45RA+RO−CD4+, naive CD45RA+RO−CD4+ T cells as well as TRECs/106 mononuclear cells were abnormally low in HR and normal in SR patients. Longitudinal monitoring of naive CD4+ and cytotoxic T cells may help to discriminate pDGS patients at increased risk for NCM. PMID:19040613

  5. Bipart: Learning Block Structure for Activity Detection

    PubMed Central

    Mu, Yang; Lo, Henry Z.; Ding, Wei; Amaral, Kevin; Crouter, Scott E.

    2014-01-01

    Physical activity consists complex behavior, typically structured in bouts which can consist of one continuous movement (e.g. exercise) or many sporadic movements (e.g. household chores). Each bout can be represented as a block of feature vectors corresponding to the same activity type. This paper introduces a general distance metric technique to use this block representation to first predict activity type, and then uses the predicted activity to estimate energy expenditure within a novel framework. This distance metric, dubbed Bipart, learns block-level information from both training and test sets, combining both to form a projection space which materializes block-level constraints. Thus, Bipart provides a space which can improve the bout classification performance of all classifiers. We also propose an energy expenditure estimation framework which leverages activity classification in order to improve estimates. Comprehensive experiments on waist-mounted accelerometer data, comparing Bipart against many similar methods as well as other classifiers, demonstrate the superior activity recognition of Bipart, especially in low-information experimental settings. PMID:25328361

  6. TGF-β1 prevents simulated ischemia/reperfusion-induced cardiac fibroblast apoptosis by activation of both canonical and non-canonical signaling pathways.

    PubMed

    Vivar, Raúl; Humeres, Claudio; Ayala, Pedro; Olmedo, Ivonne; Catalán, Mabel; García, Lorena; Lavandero, Sergio; Díaz-Araya, Guillermo

    2013-06-01

    Ischemia/reperfusion injury is a major cause of myocardial death. In the heart, cardiac fibroblasts play a critical role in healing post myocardial infarction. TGF-β1 has shown cardioprotective effects in cardiac damage; however, if TGF-β1 can prevent cardiac fibroblast death triggered by ischemia/reperfusion is unknown. Therefore, we test this hypothesis, and whether the canonical and/or non-canonical TGF-β1 signaling pathways are involved in this protective effect. Cultured rat cardiac fibroblasts were subjected to simulated ischemia/reperfusion. Cell viability was analyzed by trypan blue exclusion and propidium iodide by flow cytometry. The processing of procaspases 8, 9 and 3 to their active forms was assessed by Western blot, whereas subG1 population was evaluated by flow cytometry. Levels of total and phosphorylated forms of ERK1/2, Akt and Smad2/3 were determined by Western blot. The role of these signaling pathways on the protective effect of TGF-β1 was studied using specific chemical inhibitors. Simulated ischemia over 8h triggers a significant cardiac fibroblast death, which increased by reperfusion, with apoptosis actively involved. These effects were only prevented by the addition of TGF-β1 during reperfusion. TGF-β1 pretreatment increased the levels of phosphorylated forms of ERK1/2, Akt and Smad2/3. The inhibition of ERK1/2, Akt and Smad3 also blocked the preventive effects of TGF-β1 on cardiac fibroblast apoptosis induced by simulated ischemia/reperfusion. Overall, our data suggest that TGF-β1 prevents cardiac fibroblast apoptosis induced by simulated ischemia-reperfusion through the canonical (Smad3) and non canonical (ERK1/2 and Akt) signaling pathways. PMID:23416528

  7. [Cardiac Rehabilitation 2015].

    PubMed

    Hoffmann, Andreas

    2015-11-25

    The goals of cardiac rehabilitation are (re-)conditioning and secondary prevention in patients with heart disease or an elevated cardiovascular risk profile. Rehabilitation is based on motivation through education, on adapted physical activity, instruction of relaxation techniques, psychological support and optimized medication. It is performed preferably in groups either in outpatient or inpatient settings. The Swiss working group on cardiac rehabilitation provides a network of institutions with regular quality auditing. Positive effects of rehabilitation programs on mortality and morbidity have been established by numerous studies. Although a majority of patients after cardiac surgery are being referred to rehabilitation, these services are notoriously underused after catheter procedures. PMID:26602848

  8. Activity Tracking for Pilot Error Detection from Flight Data

    NASA Technical Reports Server (NTRS)

    Callantine, Todd J.; Ashford, Rose (Technical Monitor)

    2002-01-01

    This report presents an application of activity tracking for pilot error detection from flight data, and describes issues surrounding such an application. It first describes the Crew Activity Tracking System (CATS), in-flight data collected from the NASA Langley Boeing 757 Airborne Research Integrated Experiment System aircraft, and a model of B757 flight crew activities. It then presents an example of CATS detecting actual in-flight crew errors.

  9. Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells

    SciTech Connect

    Nakanishi, Chiaki; Yamagishi, Masakazu; Yamahara, Kenichi; Hagino, Ikuo; Mori, Hidezo; Sawa, Yoshiki; Yagihara, Toshikatsu; Kitamura, Soichiro; Nagaya, Noritoshi

    2008-09-12

    Mesenchymal stem cells (MSC) transplantation has been proved to be promising strategy to treat the failing heart. The effect of MSC transplantation is thought to be mediated mainly in a paracrine manner. Recent reports have suggested that cardiac progenitor cells (CPC) reside in the heart. In this study, we investigated whether MSC had paracrine effects on CPC in vitro. CPC were isolated from the neonatal rat heart using an explant method. MSC were isolated from the adult rat bone marrow. MSC-derived conditioned medium promoted proliferation of CPC and inhibited apoptosis of CPC induced by hypoxia and serum starvation. Chemotaxis chamber assay demonstrated that MSC-derived conditioned medium enhanced migration of CPC. Furthermore, MSC-derived conditioned medium upregulated expression of cardiomyocyte-related genes in CPC such as {beta}-myosin heavy chain ({beta}-MHC) and atrial natriuretic peptide (ANP). In conclusion, MSC-derived conditioned medium had protective effects on CPC and enhanced their migration and differentiation.

  10. SNM detection by active muon interrogation

    SciTech Connect

    Jason, Andrew J; Miyadera, Haruo; Turchi, Peter J

    2010-01-01

    Muons are charged particles with mass between the electron and proton and can be produced indirectly through pion decay by interaction of a charged-particle beam with a target. There are several distinct features of the muon interaction with matter attractive as a probe for detection of SNM at moderate ranges. These include muon penetration of virtually any amount of material without significant nuclear interaction until stopped by ionization loss in a short distance. When stopped, high-energy penetrating x-rays (in the range of 6 MeV for uranium,) unique to isotopic composition are emitted in the capture process. The subsequent interaction with the nucleus produces additional radiation useful in assessing SNM presence. A focused muon beam can be transported through the atmosphere, at a range limited mainly by beam-size growth through scattering. A muonbeam intensity of > 10{sup 9} /second is required for efficient interrogation and, as in any other technique, dose limits are to be respected. To produce sufficient muons a high-energy (threshold {approx}140 MeV) high-intensity (<1 mA) proton or electron beam is needed implying the use of a linear accelerator to bombard a refractory target. The muon yield is fractionally small, with large angle and energy dispersion, so that efficient collection is necessary in all dimensions of phase space. To accomplish this Los Alamos has proposed a magnetic collection system followed by a unique linear accelerator that provides the requisite phase-space bunching and allows an energy sweep to successively stop muons throughout a large structure such as a sea-going vessel. A possible maritime application would entail fitting the high-gradient accelerators on a large ship with a helicopter-borne detection system. We will describe our experimental results for muon effects and particle collection along with our current design and program for a muon detection system.

  11. Pilocarpine modulates the cellular electrical properties of mammalian hearts by activating a cardiac M3 receptor and a K+ current

    PubMed Central

    Wang, Huizhen; Shi, Hong; Lu, Yanjie; Yang, Baofeng; Wang, Zhiguo

    1999-01-01

    Pilocarpine, a muscarinic acetylcholine receptor (mAChR) agonist, is widely used for treatment of xerostomia and glaucoma. It can also cause many other cellular responses by activating different subtypes of mAChRs in different tissues. However, the potential role of pilocarpine in modulating cardiac function remained unstudied.We found that pilocarpine produced concentration-dependent (0.1–10 μM) decrease in sinus rhythm and action potential duration, and hyperpolarization of membrane potential in guinea-pig hearts. The effects were nearly completely reversed by 1 μM atropine or 2 nM 4DAMP methiodide (an M3-selective antagonist).Patch-clamp recordings in dispersed myocytes from guinea-pig and canine atria revealed that pilocarpine induces a novel K+ current with delayed rectifying properties. The current was suppressed by low concentrations of M3-selective antagonists 4DAMP methiodide (2–10 nM), 4DAMP mustard (4–20 nM, an ackylating agent) and p-F-HHSiD (20–200 nM). Antagonists towards other subtypes (M1, M2 or M4) all failed to alter the current.The affinity of pilocarpine (KD) at mAChRs derived from displacement binding of [3H]-NMS in the homogenates from dog atria was 2.2 μM (65% of the total binding) and that of 4DAMP methiodide was 2.8 nM (70% of total binding), consistent with the concentration of pilocarpine needed for the current induction and for the modulation of the cardiac electrical activity and the concentration of 4DAMP to block pilocarpine effects.Our data indicate, for the first time, that pilocarpine modulates the cellular electrical properties of the hearts, likely by activating a K+ current mediated by M3 receptors. PMID:10372814

  12. Activation of endothelial nitric oxide synthase by a vanadium compound ameliorates pressure overload-induced cardiac injury in ovariectomized rats.

    PubMed

    Bhuiyan, Md Shenuarin; Shioda, Norifumi; Shibuya, Masatoshi; Iwabuchi, Yoshiharu; Fukunaga, Kohji

    2009-01-01

    We here investigated the effect of bis(1-oxy-2-pyridinethiolato) oxovanadium (IV), [VO(OPT)], against myocardial hypertrophy and cardiac functional recovery in pressure overload-induced hypertrophy in ovariectomized female rats and defined mechanisms underlying its cardioprotective action. Wistar rats subjected to bilateral ovariectomy were further treated with abdominal aortic stenosis. VO(OPT) (containing 1.25 and 2.50 mg of vanadium per kg) was administered orally once a day for 14 days starting from 2 weeks after aortic banding. Treatment with VO(OPT) significantly inhibited pressure overload-induced increase both in the heart weight:body weight ratio and the lung weight:body weight ratio. VO(OPT) also attenuated hypertrophy-induced impaired left ventricular end-diastolic pressure, left ventricular developed pressure, and left ventricular contractility (+/-dp/dt(max)). VO(OPT) treatment significantly restored pressure overload-induced impaired endothelial NO synthase activity with concomitant increased phosphorylation of endothelial NO synthase (Ser1179). Moreover, VO(OPT) treatment significantly restored pressure overload-induced reduced Akt activity, as indicated by increased phosphorylation at Ser473 and at Thr308. Treatment with VO(OPT) also secondarily inhibited calpastatin and dystrophin breakdown and decreased myosin light chain phosphorylation. Finally, VO(OPT) treatment significantly attenuated mortality after repeated isoproterenol administration in pressure overloaded-ovariectomized rats. Taken together, VO(OPT) attenuates cardiac myocytes hypertrophy in vivo in pressure overload-induced hypertrophy in ovariectomized rats and prevents the process from hypertrophy to heart failure. These effects are mediated by inhibition of calpastatin and dystrophin breakdown in addition to increased Akt and endothelial NO synthase activities. PMID:19029487

  13. Inflammatory activation following interruption of long-term cardiac resynchronization therapy.

    PubMed

    Rubaj, Andrzej; Ruciński, Piotr; Oleszczak, Krzysztof; Trojnar, Michał K; Wójcik, Maciej; Wysokiński, Andrzej; Kutarski, Andrzej

    2013-09-01

    Previous observations suggest that cardiac resynchronization therapy (CRT) may exert an anti-inflammatory effect. The objective of this study was to evaluate the effect of temporary interruption of long-term CRT on plasma concentrations of proinflammatory cytokines and brain natriuretic peptide (BNP). The study group consisted of 54 patients (32 male and 22 female, mean age 64 years) with chronic heart failure (HF) treated with CRT. BNP, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and neopterin were measured three times: after 26-28 weeks of continuous CRT (CRT-on), 48 h after its cessation (CRT-off), and 48 h after switching the CRT-on again. CRT interruption resulted in a significant worsening of left ventricular systolic function: reduction of cardiac output (CO), dP/dt, and left ventricular ejection fraction (LVEF), as well as deterioration of mitral regurgitation in the CRT responder group. A significant increase in serum concentrations of hs-CRP, neopterin, IL-6, and BNP was noted in this subpopulation. In CRT nonresponders, no significant changes were observed. In responders the changes in serum concentrations of hs-CRP, IL-6, neopterin, and BNP, following CRT interruption, significantly correlated with the respective changes in thoracic fluid content (TFC) and inversely correlated with LVEF changes. Even short (48 h) interruption of long-term CRT led to a significant increase of proinflammatory cytokines and BNP concentrations in responders. The changes in hs-CRP, IL-6, neopterin, and BNP concentrations correlated with the change in TFC-marker of pulmonary congestion and inversely correlated with the change in LVEF. PMID:23242167

  14. ADP-stimulated contraction: A predictor of thin-filament activation in cardiac disease.

    PubMed

    Sequeira, Vasco; Najafi, Aref; Wijnker, Paul J M; Dos Remedios, Cristobal G; Michels, Michelle; Kuster, Diederik W D; van der Velden, Jolanda

    2015-12-15

    Diastolic dysfunction is general to all idiopathic dilated (IDCM) and hypertrophic cardiomyopathy (HCM) patients. Relaxation deficits may result from increased actin-myosin formation during diastole due to altered tropomyosin position, which blocks myosin binding to actin in the absence of Ca(2+). We investigated whether ADP-stimulated force development (without Ca(2+)) can be used to reveal changes in actin-myosin blockade in human cardiomyopathy cardiomyocytes. Cardiac samples from HCM patients, harboring thick-filament (MYH7mut, MYBPC3mut) and thin-filament (TNNT2mut, TNNI3mut) mutations, and IDCM were compared with sarcomere mutation-negative HCM (HCMsmn) and nonfailing donors. Myofilament ADP sensitivity was higher in IDCM and HCM compared with donors, whereas it was lower for MYBPC3. Increased ADP sensitivity in IDCM, HCMsmn, and MYH7mut was caused by low phosphorylation of myofilament proteins, as it was normalized to donors by protein kinase A (PKA) treatment. Troponin exchange experiments in a TNNT2mut sample corrected the abnormal actin-myosin blockade. In MYBPC3trunc samples, ADP sensitivity highly correlated with cardiac myosin-binding protein-C (cMyBP-C) protein level. Incubation of cardiomyocytes with cMyBP-C antibody against the actin-binding N-terminal region reduced ADP sensitivity, indicative of cMyBP-C's role in actin-myosin regulation. In the presence of Ca(2+), ADP increased myofilament force development and sarcomere stiffness. Enhanced sarcomere stiffness in sarcomere mutation-positive HCM samples was irrespective of the phosphorylation background. In conclusion, ADP-stimulated contraction can be used as a tool to study how protein phosphorylation and mutant proteins alter accessibility of myosin binding on actin. In the presence of Ca(2+), pathologic [ADP] and low PKA-phosphorylation, high actin-myosin formation could contribute to the impaired myocardial relaxation observed in cardiomyopathies. PMID:26621701

  15. ADP-stimulated contraction: A predictor of thin-filament activation in cardiac disease

    PubMed Central

    Sequeira, Vasco; Najafi, Aref; Wijnker, Paul J. M.; Michels, Michelle; Kuster, Diederik W. D.; van der Velden, Jolanda

    2015-01-01

    Diastolic dysfunction is general to all idiopathic dilated (IDCM) and hypertrophic cardiomyopathy (HCM) patients. Relaxation deficits may result from increased actin–myosin formation during diastole due to altered tropomyosin position, which blocks myosin binding to actin in the absence of Ca2+. We investigated whether ADP-stimulated force development (without Ca2+) can be used to reveal changes in actin–myosin blockade in human cardiomyopathy cardiomyocytes. Cardiac samples from HCM patients, harboring thick-filament (MYH7mut, MYBPC3mut) and thin-filament (TNNT2mut, TNNI3mut) mutations, and IDCM were compared with sarcomere mutation-negative HCM (HCMsmn) and nonfailing donors. Myofilament ADP sensitivity was higher in IDCM and HCM compared with donors, whereas it was lower for MYBPC3. Increased ADP sensitivity in IDCM, HCMsmn, and MYH7mut was caused by low phosphorylation of myofilament proteins, as it was normalized to donors by protein kinase A (PKA) treatment. Troponin exchange experiments in a TNNT2mut sample corrected the abnormal actin–myosin blockade. In MYBPC3trunc samples, ADP sensitivity highly correlated with cardiac myosin-binding protein-C (cMyBP-C) protein level. Incubation of cardiomyocytes with cMyBP-C antibody against the actin-binding N-terminal region reduced ADP sensitivity, indicative of cMyBP-C’s role in actin–myosin regulation. In the presence of Ca2+, ADP increased myofilament force development and sarcomere stiffness. Enhanced sarcomere stiffness in sarcomere mutation-positive HCM samples was irrespective of the phosphorylation background. In conclusion, ADP-stimulated contraction can be used as a tool to study how protein phosphorylation and mutant proteins alter accessibility of myosin binding on actin. In the presence of Ca2+, pathologic [ADP] and low PKA-phosphorylation, high actin–myosin formation could contribute to the impaired myocardial relaxation observed in cardiomyopathies. PMID:26621701

  16. Technetium-99m stannous pyrophosphate scintigraphy in patients with calcification within the cardiac silhouette.

    PubMed Central

    Wald, R W; Sternberg, L; Huckell, V F; Staniloff, H M; Feiglin, D H; Morch, J E

    1978-01-01

    Technetium-99m stannous pyrophosphate scintiscanning was performed in 22 patients with radiographically detected calcification within the cardiac silhouette. All but one of these scintigrams showed a localised area of increased activity similar to that ordinarily seen in acute myocardial infarction. Scintiscans in 3 patients after removal of the calcified aortic valve reverted to negative. It was concluded that this technique for acute infarct detection may yield false positive results in the presence of cardiac calcification. Images PMID:207292

  17. Detection of Cochlear Amplification and Its Activation

    PubMed Central

    Dong, Wei; Olson, Elizabeth S.

    2013-01-01

    The operation of the mammalian cochlea relies on a mechanical traveling wave that is actively boosted by electromechanical forces in sensory outer hair cells (OHCs). This active cochlear amplifier produces the impressive sensitivity and frequency resolution of mammalian hearing. The cochlear amplifier has inspired scientists since its discovery in the 1970s, and is still not well understood. To explore cochlear electromechanics at the sensory cell/tissue interface, sound-evoked intracochlear pressure and extracellular voltage were measured using a recently developed dual-sensor with a microelectrode attached to a micro-pressure sensor. The resulting coincident in vivo observations of OHC electrical activity, pressure at the basilar membrane and basilar membrane displacement gave direct evidence for power amplification in the cochlea. Moreover, the results showed a phase shift of voltage relative to mechanical responses at frequencies slightly below the peak, near the onset of amplification. Based on the voltage-force relationship of isolated OHCs, the shift would give rise to effective OHC pumping forces within the traveling wave peak. Thus, the shift activates the cochlear amplifier, serving to localize and thus sharpen the frequency region of amplification. These results are the most concrete evidence for cochlear power amplification to date and support OHC somatic forces as its source. PMID:23972858

  18. elPBN neurons regulate rVLM activity through elPBN-rVLM projections during activation of cardiac sympathetic afferent nerves.

    PubMed

    Guo, Zhi-Ling; Longhurst, John C; Tjen-A-Looi, Stephanie C; Fu, Liang-Wu

    2016-08-01

    The external lateral parabrachial nucleus (elPBN) within the pons and rostral ventrolateral medulla (rVLM) contributes to central processing of excitatory cardiovascular reflexes during stimulation of cardiac sympathetic afferent nerves (CSAN). However, the importance of elPBN cardiovascular neurons in regulation of rVLM activity during CSAN activation remains unclear. We hypothesized that CSAN stimulation excites the elPBN cardiovascular neurons and, in turn, increases rVLM activity through elPBN-rVLM projections. Compared with controls, in rats subjected to microinjection of retrograde tracer into the rVLM, the numbers of elPBN neurons double-labeled with c-Fos (an immediate early gene) and the tracer were increased after CSAN stimulation (P < 0.05). The majority of these elPBN neurons contain vesicular glutamate transporter 3. In cats, epicardial bradykinin and electrical stimulation of CSAN increased the activity of elPBN cardiovascular neurons, which was attenuated (n = 6, P < 0.05) after blockade of glutamate receptors with iontophoresis of kynurenic acid (Kyn, 25 mM). In separate cats, microinjection of Kyn (1.25 nmol/50 nl) into the elPBN reduced rVLM activity evoked by both bradykinin and electrical stimulation (n = 5, P < 0.05). Excitation of the elPBN with microinjection of dl-homocysteic acid (2 nmol/50 nl) significantly increased basal and CSAN-evoked rVLM activity. However, the enhanced rVLM activity induced by dl-homocysteic acid injected into the elPBN was reversed following iontophoresis of Kyn into the rVLM (n = 7, P < 0.05). These data suggest that cardiac sympathetic afferent stimulation activates cardiovascular neurons in the elPBN and rVLM sequentially through a monosynaptic (glutamatergic) excitatory elPBN-rVLM pathway. PMID:27225950

  19. Cardiac applications of PET.

    PubMed

    Sarikaya, Ismet

    2015-10-01

    Routine use of cardiac positron emission tomography (PET) applications has been increasing but has not replaced cardiac single-photon emission computerized tomography (SPECT) studies yet. The majority of cardiac PET tracers, with the exception of fluorine-18 fluorodeoxyglucose (18F-FDG), are not widely available, as they require either an onsite cyclotron or a costly generator for their production. 18F-FDG PET imaging has high sensitivity for the detection of hibernating/viable myocardium and has replaced Tl-201 SPECT imaging in centers equipped with a PET/CT camera. PET myocardial perfusion imaging with various tracers such as Rb-82, N-13 ammonia, and O-15 H2O has higher sensitivity and specificity than myocardial perfusion SPECT for the detection of coronary artery disease (CAD). In particular, quantitative PET measurements of myocardial perfusion help identify subclinical coronary stenosis, better define the extent and severity of CAD, and detect ischemia when there is balanced reduction in myocardial perfusion due to three-vessel or main stem CAD. Fusion images of PET perfusion and CT coronary artery calcium scoring or CT coronary angiography provide additional complementary information and improve the detection of CAD. PET studies with novel 18F-labeled perfusion tracers such as 18F-flurpiridaz and 18F-FBnTP have yielded high sensitivity and specificity in the diagnosis of CAD. These tracers are still being tested in humans, and, if approved for clinical use, they will be commercially and widely available. In addition to viability studies, 18F-FDG PET can also be utilized to detect inflammation/infection in various conditions such as endocarditis, sarcoidosis, and atherosclerosis. Some recent series have obtained encouraging results for the detection of endocarditis in patients with intracardiac devices and prosthetic valves. PET tracers for cardiac neuronal imaging, such as C-11 HED, help assess the severity of heart failure and post-transplant cardiac

  20. Symmetry of cardiac function assessment

    PubMed Central

    Bai, Xu-Fang; Ma, Amy X

    2016-01-01

    Both right and left ventricles are developed from two adjacent segments of the primary heart tube. Though they are different with regard to shape and power, they mirror each other in terms of behavior. This is the first level of symmetry in cardiac function assessment. Both cardiac muscle contraction and relaxation are active. This constructs the second level of symmetry in cardiac function assessment. Combination of the two levels will help to find some hidden indexes or approaches to evaluate cardiac function. In this article, four major indexes from echocardiography were analyzed under this principal, another seventeen indexes or measurement approaches came out of the shadow, which is very helpful in the assessment of cardiac function, especially for the right cardiac function and diastolic cardiac function. PMID:27582768

  1. Symmetry of cardiac function assessment.

    PubMed

    Bai, Xu-Fang; Ma, Amy X

    2016-09-01

    Both right and left ventricles are developed from two adjacent segments of the primary heart tube. Though they are different with regard to shape and power, they mirror each other in terms of behavior. This is the first level of symmetry in cardiac function ass