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Sample records for cardiac activity detected

  1. Pulse-driven magnetoimpedance sensor detection of cardiac magnetic activity.

    PubMed

    Nakayama, Shinsuke; Sawamura, Kenta; Mohri, Kaneo; Uchiyama, Tsuyoshi

    2011-01-01

    This study sought to establish a convenient method for detecting biomagnetic activity in the heart. Electrical activity of the heart simultaneously induces a magnetic field. Detection of this magnetic activity will enable non-contact, noninvasive evaluation to be made. We improved the sensitivity of a pulse-driven magnetoimpedance (PMI) sensor, which is used as an electric compass in mobile phones and as a motion sensor of the operation handle in computer games, toward a pico-Tesla (pT) level, and measured magnetic fields on the surface of the thoracic wall in humans. The changes in magnetic field detected by this sensor synchronized with the electric activity of the electrocardiogram (ECG). The shape of the magnetic wave was largely altered by shifting the sensor position within 20 mm in parallel and/or perpendicular to the thoracic wall. The magnetic activity was maximal in the 4th intercostals near the center of the sterna. Furthermore, averaging the magnetic activity at 15 mm in the distance between the thoracic wall and the sensor demonstrated magnetic waves mimicking the P wave and QRS complex. The present study shows the application of PMI sensor in detecting cardiac magnetic activity in several healthy subjects, and suggests future applications of this technology in medicine and biology.

  2. Pulse-Driven Magnetoimpedance Sensor Detection of Cardiac Magnetic Activity

    PubMed Central

    Nakayama, Shinsuke; Sawamura, Kenta; Mohri, Kaneo; Uchiyama, Tsuyoshi

    2011-01-01

    This study sought to establish a convenient method for detecting biomagnetic activity in the heart. Electrical activity of the heart simultaneously induces a magnetic field. Detection of this magnetic activity will enable non-contact, noninvasive evaluation to be made. We improved the sensitivity of a pulse-driven magnetoimpedance (PMI) sensor, which is used as an electric compass in mobile phones and as a motion sensor of the operation handle in computer games, toward a pico-Tesla (pT) level, and measured magnetic fields on the surface of the thoracic wall in humans. The changes in magnetic field detected by this sensor synchronized with the electric activity of the electrocardiogram (ECG). The shape of the magnetic wave was largely altered by shifting the sensor position within 20 mm in parallel and/or perpendicular to the thoracic wall. The magnetic activity was maximal in the 4th intercostals near the center of the sterna. Furthermore, averaging the magnetic activity at 15 mm in the distance between the thoracic wall and the sensor demonstrated magnetic waves mimicking the P wave and QRS complex. The present study shows the application of PMI sensor in detecting cardiac magnetic activity in several healthy subjects, and suggests future applications of this technology in medicine and biology. PMID:22022453

  3. 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.

  4. Highly Sensitive Detection of Minimal Cardiac Ischemia using Positron Emission Tomography Imaging of Activated Platelets

    PubMed Central

    Ziegler, Melanie; Alt, Karen; Paterson, Brett M.; Kanellakis, Peter; Bobik, Alex; Donnelly, Paul S.; Hagemeyer, Christoph E.; Peter, Karlheinz

    2016-01-01

    A reliable method for the diagnosis of minimal cardiac ischemia would meet a strong demand for the sensitive diagnosis of coronary artery disease in cardiac stress testing and risk stratification in patients with chest pain but unremarkable ECGs and biomarkers. We hypothesized that platelets accumulate early on in ischemic myocardium and a newly developed technology of non-invasive molecular PET imaging of activated platelets can thus detect minimal degrees of myocardial ischemia. To induce different degrees of minimal cardiac ischemia, the left anterior descending artery (LAD) was ligated for 10, 20 or 60 min. Mice were injected with a newly generated scFvanti-GPIIb/IIIa-64CuMeCOSar radiotracer, composed of a single-chain antibody that only binds to activated integrin GPIIb/IIIa (αIIbβIII) and thus to activated platelets, and a sarcophagine cage MeCOSar complexing the long half-life PET tracer copper-64. A single PET/CT scan was performed. Evans Blue/TTC staining to detect necrosis as well as classical serological biomarkers like Troponin I and heart-type fatty acid-binding protein (H-FABP) were negative, whereas PET imaging of activated platelets was able to detect small degrees of ischemia. Taken together, molecular PET imaging of activated platelets represents a unique and highly sensitive method to detect minimal cardiac ischemia. PMID:27909290

  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. External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

    PubMed

    Hogan, T S

    2012-10-01

    Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient's cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless

  7. 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.

  8. TRPM4 in cardiac electrical activity.

    PubMed

    Guinamard, Romain; Bouvagnet, Patrice; Hof, Thomas; Liu, Hui; Simard, Christophe; Sallé, Laurent

    2015-10-01

    TRPM4 forms a non-selective cation channel activated by internal Ca(2+). Its functional expression was demonstrated in cardiomyocytes of several mammalian species including humans, but the channel is also present in many other tissues. The recent characterization of the TRPM4 inhibitor 9-phenanthrol, and the availability of transgenic mice have helped to clarify the role of TRPM4 in cardiac electrical activity, including diastolic depolarization from the sino-atrial node cells in mouse, rat, and rabbit, as well as action potential duration in mouse cardiomyocytes. In rat and mouse, pharmacological inhibition of TRPM4 prevents cardiac ischaemia-reperfusion injuries and decreases the occurrence of arrhythmias. Several studies have identified TRPM4 mutations in patients with inherited cardiac diseases including conduction blocks and Brugada syndrome. This review identifies TRPM4 as a significant actor in cardiac electrophysiology.

  9. Complicated Electrical Activities in Cardiac Tissue

    NASA Astrophysics Data System (ADS)

    Shiau, Yuo-Hsien; Hsueh, Ming-Pin; Hseu, Shu-Shya; Yien, Huey-Wen

    It has become widely accepted that ventricular fibrillation, the most dangerous cardiac arrhythmias, is a major cause of death in the industrialized world. Alternans and conduction block have recently been related to the progression from ventricular tachycardia to ventricular fibrillation. From the point of view in cellular electrophysiology, ventricular tachycardia is the formation of reentrant wave in cardiac tissue. And ventricular fibrillation arises from subsequent breakdown of reentrant wave into multiple drifting and meandering spiral waves. In this paper, we numerically study pulse and vortex dynamics in cardiac tissue. Our numerical results include 1:1 normal sinus rhythm, 2:1 conduction block, complete conduction block, spiral wave, and spiral breakup. All of our numerical findings can be corresponding to clinical measurements in electrocardiogram. Various electrical activities in cardiac tissue will be discussed in detail in the present manuscript.

  10. Qualitative Perfusion Cardiac Magnetic Resonance Imaging Lacks Sensitivity in Detecting Cardiac Allograft Vasculopathy

    PubMed Central

    Colvin-Adams, Monica; Petros, Salam; Raveendran, Ganesh; Missov, Emil; Medina, Eduardo; Wilson, Robert

    2011-01-01

    Background Cardiac allograft vasculopathy (CAV) is a major complication after heart transplantation, requiring frequent surveillance angiography. Though cardiac angiography is the gold standard, it is insensitive in detecting transplant vasculopathy and invasive. Perfusion MRI provides a noninvasive alternative and possibly a useful modality for studying CAV. We sought to compare the accuracy of qualitative perfusion MRI to coronary angiography in detecting CAV. Methods A retrospective analysis was performed in 68 heart transplant recipients who had simultaneous surveillance cardiac MRI and coronary angiogram and who underwent transplantation between 2000 and 2007. We compared results of qualitative MRI to those of the cardiac angiogram. Sensitivity and specificity of MR were calculated. Results Sixty-eight patients underwent both cardiac MRI and coronary angiogram. 73.5% were male; mean age was 45.37 ± 14 years. Mean duration of heart transplantation was 7.9 ± 5.2 years. The mean ejection fraction was 55% in the patients without CAV and 57.4% in those with CAV. There were 48 normal and 24 abnormal MRI studies. The overall sensitivity was 41% and specificity was 74%. Conclusions Qualitative assessment of perfusion cardiac MR has low sensitivity and moderate specificity for detecting CAV. The sensitivity of MRI was slightly improved with severity of disease.

  11. 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

  12. [A monitor of the biomechanical cardiac activity].

    PubMed

    Masloboev, Iu P; Okhritskiĭ, A A; Prilutskiĭ, D A; Selishchev, S V

    2004-01-01

    A monitor of the biomechanical cardiac activity is described, which was elaborated on the basis of the accelerometer sensor and sigma-delta ADC for the purpose of registering the ballistocardiograms and seismocardiograms. The device ensures a non-stop signal recording for as long as 8 hours with the data being preserved in an inbuilt memory. Data are fed to the computer through the USB port. An algorithm is suggested for recordings processing by using the neuron-net technologies.

  13. Infant Cardiac Activity: Developmental Changes and Relations with Attachment.

    ERIC Educational Resources Information Center

    Izard, Carroll E.; And Others

    1991-01-01

    Examined cardiac activity during the first 13 months of life. Indexes of cardiac activity changed in an orderly way with development. There were intercorrelations among the cardiac measures. Analyses indicated that measures of heart-rate variability were significantly higher in insecure children than in secure children. (BC)

  14. Cardiac autonomic nervous system activity in obesity.

    PubMed

    Liatis, Stavros; Tentolouris, Nikolaos; Katsilambros, Nikolaos

    2004-08-01

    The development of obesity is caused by a disturbance of energy balance, with energy intake exceeding energy expenditure. As the autonomic nervous system (ANS) has a role in the regulation of both these variables, it has become a major focus of investigation in the fields of obesity pathogenesis. The enhanced cardiac sympathetic drive shown in most of the studies in obese persons might be due to an increase in their levels of circulating insulin. The role of leptin needs further investigation with studies in humans. There is a blunted response of the cardiac sympathetic nervous system (SNS) activity in obese subjects after consumption of a carbohydrate-rich meal as well as after insulin administration. This might be due to insulin resistance. It is speculated that increased SNS activity in obesity may contribute to the development of hypertension in genetically susceptible individuals. It is also speculated that the increase in cardiac SNS activity under fasting conditions in obesity may be associated with high cardiovascular morbidity and mortality.

  15. Cardiac elastography: detecting pathological changes in myocardium tissues

    NASA Astrophysics Data System (ADS)

    Konofagou, Elisa E.; Harrigan, Timothy; Solomon, Scott

    2003-05-01

    Estimation of the mechanical properties of the cardiac muscle has been shown to play a crucial role in the detection of cardiovascular disease. Elastography was recently shown feasible on RF cardiac data in vivo. In this paper, the role of elastography in the detection of ischemia/infarct is explored with simulations and in vivo experiments. In finite-element simulations of a portion of the cardiac muscle containing an infarcted region, the cardiac cycle was simulated with successive compressive and tensile strains ranging between -30% and 20%. The incremental elastic modulus was also mapped uisng adaptive methods. We then demonstrated this technique utilizing envelope-detected sonographic data (Hewlett-Packard Sonos 5500) in a patient with a known myocardial infarction. In cine-loop and M-Mode elastograms from both normal and infarcted regions in simulations and experiments, the infarcted region was identifed by the up to one order of magnitude lower incremental axial displacements and strains, and higher modulus. Information on motion, deformation and mechanical property should constitute a unique tool for noninvasive cardiac diagnosis.

  16. Cardiac actomyosin ATPase activity after chronic doxorubicin treatment.

    PubMed

    Bergson, A; Inchiosa, M A

    1985-04-01

    Doxorubicin (Adriamycin), a potent antineoplastic drug, produces progressive cardiotoxicity which may lead to ultimate cardiac failure. The effects of chronic doxorubicin treatment on cardiac actomyosin ATPase were the principal focus of the present studies. This approach was based on the established correlation between cardiac contractility and contractile protein ATPase activity. Rabbits were injected intravenously with doxorubicin (4 mg/kg) at weekly intervals for 1-7 weeks. Body weight increase was attenuated in the treated animals; heart weight/body weight ratio was unchanged. Actomyosin and water contents of ventricular muscle were not different in doxorubicin-treated as compared with vehicle control animals. Cellular damage was detected histologically after one dose of doxorubicin (equivalent to a single clinical dose), and was extensive after 4-5 weeks of treatment. Animals which received 1-2 injections of doxorubicin demonstrated a 29% average increase in actomyosin ATPase activity as compared to vehicle controls; this difference was highly significant (p less than 0.001). Further treatment with doxorubicin tended to progressively decrease ATPase activity. It is suggested that the increased actomyosin ATPase activity seen with low total doses of doxorubicin may represent a compensatory mechanism for maintenance of contractility; this interpretation is supported by the clinical observation that the morphologic evidence of progressive doxorubicin toxicity is not associated with a parallel decrease in contractility, until severe cumulative toxicity has been induced.

  17. 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.

  18. Selectivity verification of cardiac troponin monoclonal antibodies for cardiac troponin detection by using conventional ELISA

    NASA Astrophysics Data System (ADS)

    Fathil, M. F. M.; Arshad, M. K. Md; Gopinath, Subash C. B.; Adzhri, R.; Ruslinda, A. R.; Hashim, U.

    2017-03-01

    This paper presents preparation and characterization of conventional enzyme-linked immunosorbent assay (ELISA) for cardiac troponin detection to determine the selectivity of the cardiac troponin monoclonal antibodies. Monoclonal antibodies, used to capture and bind the targets in this experiment, are cTnI monoclonal antibody (MAb-cTnI) and cTnT monoclonal antibody (MAb-cTnT), while both cardiac troponin I (cTnI) and T (cTnT) are used as targets. ELISA is performed inside two microtiter plates for MAb-cTnI and MAb-cTnT. For each plate, monoclonal antibodies are tested by various concentrations of cTnI and cTnT ranging from 0-6400 µg/l. The binding selectivity and level of detection between monoclonal antibodies and antigen are determined through visual observation based on the color change inside each well on the plate. ELISA reader is further used to quantitatively measured the optical density of the color changes, thus produced more accurate reading. The results from this experiment are utilized to justify the use of these monoclonal antibodies as bio-receptors for cardiac troponin detection by using field-effect transistor (FET)-based biosensors coupled with substrate-gate in the future.

  19. 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.

  20. Sensitive Detection of Cardiac Biomarkers Using a Magnetic Microbead Immunoassay.

    PubMed

    Woolley, Christine F; Hayes, Mark A

    2015-10-21

    To achieve improved sensitivity in cardiac biomarker detection, a batch incubation magnetic microbead immunoassay was developed and tested on three separate human protein targets: myoglobin, heart-type fatty acid binding protein, and cardiac troponin I. A sandwich immunoassay was performed in a simple micro-centrifuge tube allowing full dispersal of the solid capture surface during incubations. Following magnetic bead capture and wash steps, samples were analyzed in the presence of a manipulated magnetic field utilizing a modified microscope slide and fluorescent inverted microscope to collect video data files. Analysis of the video data allowed for the quantitation of myoglobin, heart-type fatty acid binding protein and cardiac troponin I to levels of 360 aM, 67 fM, and 42 fM, respectively. Compared to the previous detection limit of 50 pM for myoglobin, this offers a five-fold improvement in sensitivity. This improvement in sensitivity and incorporation of additional markers, along with the small sample volumes required, suggest the potential of this platform for incorporation as a detection method in a total sample analysis device enabling multiplexed detection for the analysis of clinical samples.

  1. 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

  2. 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.

  3. 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.

  4. Application of HTS technology to cardiac dysrhythmia detection

    SciTech Connect

    Sobel, A.L.; Avrin, W.F.

    1994-12-01

    This paper discusses the conceptual design considerations and challenges for development of a contactless, mobile, single channel biomagnetic sensor system based on High-Temperature Superconductor (HTS) Superconducting Quantum Interference Devices (SQUIDs) and employing the Three-SQUID Gradiometer (TSG) concept. Operating in magnetically unshielded environments, as are encountered in many medical scenarios, this instrument class would monitor cardiac electrical activity with minimal patient preparation and intrusiveness, and would notionally be coupled with a clinically adaptive human-system interface (HSI).

  5. New method for assessing cardiac parasympathetic activity using 24 hour electrocardiograms.

    PubMed Central

    Ewing, D J; Neilson, J M; Travis, P

    1984-01-01

    Cardiac parasympathetic activity was assessed using 24 hour electrocardiographic recordings by measuring the incidence of larger changes in successive RR intervals, which in normal subjects occur frequently but irregularly. In 25 normal subjects the mean number of times per hour in which the change in successive RR interval was greater than 50 ms was 150-250 during waking and 350-450 during sleeping. By contrast, 30 diabetics with medically denervated hearts (12 with cardiovascular reflex evidence of parasympathetic damage and 18 with additional sympathetic damage) and six cardiac transplant patients with surgically denervated hearts had extremely low counts. Additionally, of 20 diabetics with normal cardiovascular reflexes, about half had abnormally low counts, suggesting that this method is better than currently available reflex tests in detecting early cardiac parasympathetic damage. This technique provides a valid and sensitive way of monitoring cardiac parasympathetic activity over prolonged periods. PMID:6383446

  6. 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.

  7. NOD1 Activation Induces Cardiac Dysfunction and Modulates Cardiac Fibrosis and Cardiomyocyte Apoptosis

    PubMed Central

    Fernández-Velasco, María; Prieto, Patricia; Terrón, Verónica; Benito, Gemma; Flores, Juana M.; Delgado, Carmen; Zaragoza, Carlos; Lavin, Begoña; Gómez-Parrizas, Mónica; López-Collazo, Eduardo; Martín-Sanz, Paloma; Boscá, Lisardo

    2012-01-01

    The innate immune system is responsible for the initial response of an organism to potentially harmful stressors, pathogens or tissue injury, and accordingly plays an essential role in the pathogenesis of many inflammatory processes, including some cardiovascular diseases. Toll like receptors (TLR) and nucleotide-binding oligomerization domain-like receptors (NLRs) are pattern recognition receptors that play an important role in the induction of innate immune and inflammatory responses. There is a line of evidence supporting that activation of TLRs contributes to the development and progression of cardiovascular diseases but less is known regarding the role of NLRs. Here we demonstrate the presence of the NLR member NOD1 (nucleotide-binding oligomerization domain containing 1) in the murine heart. Activation of NOD1 with the specific agonist C12-iEDAP, but not with the inactive analogue iE-Lys, induces a time- and dose-dependent cardiac dysfunction that occurs concomitantly with cardiac fibrosis and apoptosis. The administration of iEDAP promotes the activation of the NF-κB and TGF-β pathways and induces apoptosis in whole hearts. At the cellular level, both native cardiomyocytes and cardiac fibroblasts expressed NOD1. The NLR activation in cardiomyocytes was associated with NF-κB activation and induction of apoptosis. NOD1 stimulation in fibroblasts was linked to NF-κB activation and to increased expression of pro-fibrotic mediators. The down-regulation of NOD1 by specific siRNAs blunted the effect of iEDAP on the pro-fibrotic TGF-β pathway and cell apoptosis. In conclusion, our report uncovers a new pro-inflammatory target that is expressed in the heart, NOD1. The specific activation of this NLR induces cardiac dysfunction and modulates cardiac fibrosis and cardiomyocyte apoptosis, pathological processes involved in several cardiac diseases such as heart failure. PMID:23028889

  8. 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.

  9. Calcineurin activity is required for cardiac remodelling in pregnancy

    PubMed Central

    Chung, Eunhee; Yeung, Fan; Leinwand, Leslie A.

    2013-01-01

    Aims Calcium fluctuations and cardiac hypertrophy occur during pregnancy, but the role of the well-studied calcium-activated phosphatase, calcineurin, has not been studied in this setting. The purpose of this study was to determine whether calcineurin signalling is required for cardiac remodelling during pregnancy in mice. Methods and results We first examined calcineurin expression in the heart of mice during pregnancy. We found both calcineurin levels and activity were significantly increased in early-pregnancy and decreased in late-pregnancy. Since progesterone levels start to rise in early-pregnancy, we investigated whether progesterone alone was sufficient to modulate calcineurin levels in vivo. After implantation of progesterone pellets in non-pregnant female mice, cardiac mass increased, whereas cardiac function was maintained. In addition, calcineurin levels increased, which is also consistent with early-pregnancy. To determine whether these effects were occurring in the cardiac myocytes, we treated neonatal rat ventricular myocytes (NRVMs) with pregnancy-associated sex hormones. We found that progesterone treatment, but not oestradiol, increased calcineurin levels. To obtain a functional read-out of increased calcineurin activity, we measured the activity of the transcription factor NFAT, a downstream target of calcineurin. Progesterone treatment significantly increased NFAT activity in NRVMs, and this was blocked by the calcineurin inhibitor cyclosporine A (CsA), showing that the progesterone-mediated increase in NFAT activity requires calcineurin activity. Importantly, CsA treatment of mice completely blocked pregnancy-induced cardiac hypertrophy. Conclusion Our results show that calcineurin is required for pregnancy-induced cardiac hypertrophy, and that calcineurin activity in early-pregnancy is due at least in part to increased progesterone. PMID:23985902

  10. Overexpression of antizyme in the hearts of transgenic mice prevents the isoprenaline-induced increase in cardiac ornithine decarboxylase activity and polyamines, but does not prevent cardiac hypertrophy.

    PubMed Central

    Mackintosh, C A; Feith, D J; Shantz, L M; Pegg, A E

    2000-01-01

    Two lines of transgenic mice were produced with constitutive expression of antizyme-1 in the heart, driven from the cardiac alpha-myosin heavy chain promoter. The use of engineered antizyme cDNA in which nucleotide 205 had been deleted eliminated the need for polyamine-mediated frameshifting, normally necessary for translation of antizyme mRNA, and thus ensured the constitutive expression of antizyme. Antizyme-1 is thought to be a major factor in regulating cellular polyamine content, acting both to inhibit ornithine decarboxylase (ODC) activity and to target it for degradation, as well as preventing polyamine uptake. The two transgenic lines had substantial, but different, levels of antizyme in the heart, as detected by Western blotting and by the ability of heart extracts to inhibit exogenous purified ODC. Despite the high levels of antizyme, endogenous ODC activity was not completely abolished, with 10-39% remaining, depending on the transgenic line. Additionally, a relatively small decrease (30-32%) in cardiac spermidine content was observed, with levels of putrescine and spermine unaffected. Interestingly, although the two lines of transgenic mice had different antizyme expression levels, they had almost identical cardiac polyamine content. When treated with a single acute dose of isoprenaline (isoproterenol), cardiac ODC activity and putrescine content were substantially increased (by 14-fold and 4.7-fold respectively) in non-transgenic littermate mice, but these increases were completely prevented in the transgenic mice from both founder lines. Prolonged exposure to isoprenaline also caused increases in cardiac ODC activity and polyamine content, as well as an increase in cardiac growth, in non-transgenic mice. Although the increases in cardiac ODC activity and polyamine content were prevented in the transgenic mice from both founder lines, the increase in cardiac growth was unaffected. These transgenic mice thus provide a valuable model system in which to

  11. Detecting cardiac events - state-of-the-art.

    PubMed

    Collinson, Paul

    2015-11-01

    Cardiac biomarker measurement currently addresses two key questions in patient management: the differential diagnosis of chest pain and the differential diagnosis of the patient with breathlessness. There are currently three major themes in the strategies for the differential diagnosis of chest pain. The first is to undertake troponin measurement in patients selected to be at lower risk, hence to have a low prior probability of disease. The second is the introduction of high-sensitivity cardiac troponin (hs cTn) assays into routine clinical use with measurement at 0 and 3 h from admission. Two other approaches that utilize the diagnostic characteristics of these assays have also been suggested. The first is to use the limit of detection or limit of blank of the assay as the diagnostic discriminant. The second approach is to use the low imprecision of the assay within the reference interval and combine a discriminant value with an absolute rate of change (delta value). The third is the use of additional biomarkers to allow early discharge from the emergency department. The concept is to measure high-sensitivity cardiac troponin plus the extra marker on admission. The role of measurement of B-type natriuretic peptide or its N-terminal prohormone, N-terminal pro-B-type natriuretic peptide, has been accepted and incorporated into guidelines for chronic heart failure for some time. More recently, guidelines for acute heart failure can also recommend a single measurement of B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide in people presenting with new suspected acute heart failure.

  12. 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.

  13. 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.

  14. 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

  15. [Study of cardiac, respiratory, and motor activity in rat fetuses].

    PubMed

    Timofeeva, O P; Vdovichenko, N D

    2009-01-01

    Development of the cardiac, respiratory, and motor activity was studied in rat fetuses with preserved placenta circulation was studied at the 16th, 18th, and 20th gestation days. The presence of three main movement types has been found: complexes of generalization activity, local movements, and jerks. In development of respiratory function, there is observed a gradual transition from individual inspirations to series of respiratory movements and then to formation of periodic respiration episodes. At the studied period, the heart rate has been found to increase. The existence of the slow-wave modulations it the heart rate with a period of 20-40 s has been revealed. Analysis of interrelations between the respiratory and motor systems has shown that in the 16-day fetuses, each respiratory movement is accompanied by extensor jerk. By the 20th days of embryonic development (E20), uncoupling of the respiratory and motor activities occurs. Comparison of the activity observed in the cardiac and somatomotor systems has shown that at E16, the cardiac rhythm fluctuations do not depend on the motor excitation jerks. In the 18-day fetuses, brief slowing down (decelerations) of the cardiac rhythm appeared during the motor activity jerks, whereas at E20, on the contrary, an increase of frequency (accelerations) of the cardiac rhythm occurred.

  16. 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.

  17. An active contour framework based on the Hermite transform for shape segmentation of cardiac MR images

    NASA Astrophysics Data System (ADS)

    Barba-J, Leiner; Escalante-Ramírez, Boris

    2016-04-01

    Early detection of cardiac affections is fundamental to address a correct treatment that allows preserving the patient's life. Since heart disease is one of the main causes of death in most countries, analysis of cardiac images is of great value for cardiac assessment. Cardiac MR has become essential for heart evaluation. In this work we present a segmentation framework for shape analysis in cardiac magnetic resonance (MR) images. The method consists of an active contour model which is guided by the spectral coefficients obtained from the Hermite transform (HT) of the data. The HT is used as model to code image features of the analyzed images. Region and boundary based energies are coded using the zero and first order coefficients. An additional shape constraint based on an elliptical function is used for controlling the active contour deformations. The proposed framework is applied to the segmentation of the endocardial and epicardial boundaries of the left ventricle using MR images with short axis view. The segmentation is sequential for both regions: the endocardium is segmented followed by the epicardium. The algorithm is evaluated with several MR images at different phases of the cardiac cycle demonstrating the effectiveness of the proposed method. Several metrics are used for performance evaluation.

  18. Mechanism of pyruvate dehydrogenase activation by increased cardiac work.

    PubMed

    Kobayashi, K; Neely, J R

    1983-06-01

    The effects of increased cardiac work, pyruvate and insulin on the state of pyruvate dehydrogenase (PDH) activation and rate of pyruvate decarboxylation was studied in the isolated perfused rat heart. At low levels of cardiac work, 61% of PDH was present in the active form when glucose was the only substrate provided. The actual rate of pyruvate decarboxylation was only 5% of the available capacity calculated from the percent of active PDH. Under this condition, the rate of pyruvate decarboxylation was restricted by the slow rate of pyruvate production from glycolysis. Increasing cardiac work accelerated glycolysis, but production of pyruvate remained rate limiting for pyruvate oxidation and only 40% of the maximal active PDH capacity was used. Addition of insulin along with glucose reduced the percent of active PDH to 16% of the total at low cardiac work. This effect of insulin was associated with increased mitochondria NADH/NAD and acetyl CoA/CoA ratios. With both glucose and insulin the calculated maximum capacity of active PDH was about the same as measured rates of pyruvate oxidation indicating that pyruvate oxidation was limited by the activation state of PDH. In this case, raising the level of cardiac work increased the active PDH to 85% and although pyruvate oxidation was accelerated, measured flux through PDH was only 73% of the maximal activity of active PDH. With pyruvate as added exogenous substrate, PDH was 82% of active at low cardiac work probably due to pyruvate inhibition of PDH kinase. In this case, the measured rate of pyruvate oxidation was 64% of the capacity of active PDH. However, increased cardiac work still caused further activation of PDH to 96% active. Thus, actual rates of pyruvate oxidation in the intact tissue were determined by (1) the supply of pyruvate in hearts receiving glucose alone, (2) by the percent of active PDH in hearts receiving both glucose and insulin at low work and (3) by end-product inhibition in hearts receiving

  19. 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.

  20. Ultrasensitive cardiac troponin I antibody based nanohybrid sensor for rapid detection of human heart attack.

    PubMed

    Bhatnagar, Deepika; Kaur, Inderpreet; Kumar, Ashok

    2017-02-01

    An ultrasensitive cardiac troponin I antibody conjugated with graphene quantum dots (GQD) and polyamidoamine (PAMAM) nanohybrid modified gold electrode based sensor was developed for the rapid detection of heart attack (myocardial infarction) in human. Screen printed gold (Au) electrode was decorated with 4-aminothiophenol for amine functionalization of the Au surface. These amino groups were further coupled with carboxyl functionalities of GQD with EDC-NHS reaction. In order to enhance the sensitivity of the sensor, PAMAM dendrimer was successively embedded on GQD through carbodiimide coupling to provide ultra-high surface area for antibody immobilization. The activated cardiac troponin I (cTnI) monoclonal antibody was immobilized on PAMAM to form nanoprobe for sensing specific heart attack marker cTnI. Various concentrations of cardiac marker, cTnI were electrochemically measured using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in human blood serum. The modifications on sensor surface were characterized by FTIR and AFM techniques. The sensor is highly specific to cTnI and showed negligible response to non-specific antigens. The sensitivity of the sensor was 109.23μAcm(-2)μg(-1) and lower limit of detection of cTnI was found 20fgmL(-1).

  1. 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

  2. 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.

  3. Small Conductance Ca2+-Activated K+ Channels and Cardiac Arrhythmias

    PubMed Central

    Zhang, Xiao-Dong; Lieu, Deborah K.; Chiamvimonvat, Nipavan

    2015-01-01

    Small conductance Ca2+-activated K+ (SK, KCa2) channels are unique in that they are gated solely by changes in intracellular Ca2+ and hence, function to integrate intracellular Ca2+ and membrane potentials on a beat-to-beat basis. Recent studies have provided evidence for the existence and functional significance of SK channels in the heart. Indeed, our knowledge of cardiac SK channels has been greatly expanded over the past decade. Interests in cardiac SK channels are further driven by recent studies suggesting the critical roles of SK channels in human atrial fibrillation, SK channel as a possible novel therapeutic target in atrial arrhythmias and up-regulation of SK channels in heart failure (HF) in animal models and human HF. However, there remain critical gaps in our knowledge. Specifically, blockade of SK channels in cardiac arrhythmias has been shown to be both anti-arrhythmic and proarrhythmic. This contemporary review will provide an overview of the literature on the role of cardiac SK channels in cardiac arrhythmias and to serve as a discussion platform for the current clinical perspectives. At the translational level, development of SK channel blockers as a new therapeutic target in the treatment of atrial fibrillation and the possible pro-arrhythmic effects merit further considerations and investigations. PMID:25956967

  4. Development of PET Imaging to Visualize Activated Macrophages Accumulated in the Transplanted iPSc-Derived Cardiac Myocytes of Allogeneic Origin for Detecting the Immune Rejection of Allogeneic Cell Transplants in Mice

    PubMed Central

    Kashiyama, Noriyuki; Miyagawa, Shigeru; Fukushima, Satsuki; Kawamura, Takuji; Kawamura, Ai; Yoshida, Shohei; Harada, Akima; Watabe, Tadashi; Kanai, Yasukazu; Toda, Koichi; Hatazawa, Jun; Sawa, Yoshiki

    2016-01-01

    Allogeneic transplantation (Tx) of induced pluripotent stem cells (iPSCs) is a promising tissue regeneration therapy. However, this inevitably induces macrophage-mediated immune response against the graft, limiting its therapeutic efficacy. Monitoring the magnitude of the immune response using imaging tools would be useful for prolonging graft survival and increasing the therapy longevity. Minimally invasive quantitative detection of activated macrophages by medical imaging technologies such as positron emission tomography (PET) imaging targets translocator protein (TSPO), which is highly expressed on mitochondrial membrane, especially in activated macrophage. N,N-diethyl-2-[4-(2-fluoroethoxy) phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (DPA-714) is known as a TSPO ligand used in clinical settings. We herein hypothesized that immune rejection of the transplanted iPSC-derived cardiomyocytes (iPSC-CMs) of allogeneic origin may be quantitated using 18F-DPA-714-PET imaging study. iPSC-CM cell-sheets of C57BL/6 mice origin were transplanted on the surface of the left ventricle (LV) of C57BL/6 mice as a syngeneic cell-transplant model (syngeneic Tx group), or Balb/c mice as an allogeneic model (allogeneic Tx group). 18F-DPA-714-PET was used to determine the uptake ratio, calculated as the maximum standardized uptake value in the anterior and septal wall of the LV. The uptake ratio was significantly higher in the allogeneic Tx group than in the syngeneic group or the sham group at days 7 and day 10 after the cell transplantation. In addition, the immunochemistry showed significant presence of CD68 and CD3-positive cells at day 7 and 10 in the transplanted graft of the allogeneic Tx group. The expression of TSPO, CD68, IL-1 beta, and MCP-1 was significantly higher in the allogeneic Tx group than in the syngeneic Tx and the sham groups at day 7. The 18F-DPA-714-PET imaging study enabled quantitative visualization of the macrophages-mediated immune rejection of

  5. 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

  6. 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.

  7. (18)F-fluoromisonidazole (FMISO) PET may have the potential to detect cardiac sarcoidosis.

    PubMed

    Manabe, Osamu; Hirata, Kenji; Shozo, Okamoto; Shiga, Tohru; Uchiyama, Yuko; Kobayashi, Kentaro; Watanabe, Shiro; Toyonaga, Takuya; Kikuchi, Hisaya; Oyama-Manabe, Noriko; Tamaki, Nagara

    2017-02-01

    (18)F-fluoromisonidazole (FMISO) is a positron emission tomography (PET) tracer that accumulates in hypoxic tissues. We here present a case of suspected cardiac sarcoidosis which was detected with increased FMISO uptake.

  8. Differential effects of defibrillation on systemic and cardiac sympathetic activity

    PubMed Central

    Bode, F; Wiegand, U; Raasch, W; Richardt, G; Potratz, J

    1998-01-01

    Objective—To assess the effect of defibrillation shocks on cardiac and circulating catecholamines.
Design—Prospective examination of myocardial catecholamine balance during dc shock by simultaneous determination of arterial and coronary sinus plasma concentrations. Internal countershocks (10-34 J) were applied in 30 patients after initiation of ventricular fibrillation for a routine implantable cardioverter defibrillator test. Another 10 patients were externally cardioverted (50-360 J) for atrial fibrillation.
Main outcome measures—Transcardiac noradrenaline, adrenaline, and lactate gradients immediately after the shock.
Results—After internal shock, arterial noradrenaline increased from a mean (SD) of 263 (128) pg/ml at baseline to 370 (148) pg/ml (p = 0.001), while coronary sinus noradrenaline fell from 448 (292) to 363 (216) pg/ml (p = 0.01), reflecting a shift from cardiac net release to net uptake. After external shock delivery, there was a similar increase in arterial noradrenaline, from 260 (112) to 459 (200) pg/ml (p = 0.03), while coronary sinus noradrenaline remained unchanged. Systemic adrenaline increased 11-fold after external shock (p = 0.01), outlasting the threefold rise following internal shock (p = 0.001). In both groups, a negative transmyocardial adrenaline gradient at baseline decreased further, indicating enhanced myocardial uptake. Cardiac lactate production occurred after ventricular fibrillation and internal shock, but not after external cardioversion, so the neurohumoral changes resulted from the defibrillation process and not from alterations in oxidative metabolism.
Conclusions—A dc shock induces marked systemic sympathoadrenal and sympathoneuronal activation, but attenuates cardiac sympathetic activity. This might promote the transient myocardial depression observed after electrical discharge to the heart.

 Keywords: defibrillation;  autonomic cardiac function;  catecholamines;  lactate

  9. Model of electrical activity in cardiac tissue under electromagnetic induction.

    PubMed

    Wu, Fuqiang; Wang, Chunni; Xu, Ying; Ma, Jun

    2016-12-01

    Complex electrical activities in cardiac tissue can set up time-varying electromagnetic field. Magnetic flux is introduced into the Fitzhugh-Nagumo model to describe the effect of electromagnetic induction, and then memristor is used to realize the feedback of magnetic flux on the membrane potential in cardiac tissue. It is found that a spiral wave can be triggered and developed by setting specific initials in the media, that is to say, the media still support the survival of standing spiral waves under electromagnetic induction. Furthermore, electromagnetic radiation is considered on this model as external stimuli, it is found that spiral waves encounter breakup and turbulent electrical activities are observed, and it can give guidance to understand the occurrence of sudden heart disorder subjected to heavily electromagnetic radiation.

  10. Photocardiography: a novel method for monitoring cardiac activity in fish.

    PubMed

    Yoshida, Masayuki; Hirano, Ruriko; Shima, Takao

    2009-05-01

    A non-invasive technique to monitor cardiac activity in small fish, such as goldfish, zebrafish, and medaka, is needed. In the present study, we developed photocardiography (PCG), a non-invasive optical method, to record cardiac activity in small fish. The method monitors changes in near-infrared light transmission through the heart using a phototransistor located outside the body. With this technique, heartbeats in fish of various sizes (14-218 mm) were stably recorded. PCG was applied to monitor the heartbeat during fear-related classical heart rate conditioning in goldfish wherein an electrical shock was used as an unconditioned stimulus. The heartbeats were continuously monitored, even when the beat coincided with the electrical shock, showing that PCG is robust even in an electrically noisy environment. This technique is particularly useful when monitoring the heartbeats of fish of small size or in the presence of ambient electrical noise, conditions in which the use of conventional electrocardiography (ECG) is difficult.

  11. Cardiac afferent activity modulates the expression of racial stereotypes

    PubMed Central

    Azevedo, Ruben T.; Garfinkel, Sarah N.; Critchley, Hugo D.; Tsakiris, Manos

    2017-01-01

    Negative racial stereotypes tend to associate Black people with threat. This often leads to the misidentification of harmless objects as weapons held by a Black individual. Yet, little is known about how bodily states impact the expression of racial stereotyping. By tapping into the phasic activation of arterial baroreceptors, known to be associated with changes in the neural processing of fearful stimuli, we show activation of race-threat stereotypes synchronized with the cardiovascular cycle. Across two established tasks, stimuli depicting Black or White individuals were presented to coincide with either the cardiac systole or diastole. Results show increased race-driven misidentification of weapons during systole, when baroreceptor afferent firing is maximal, relative to diastole. Importantly, a third study examining the positive Black-athletic stereotypical association fails to demonstrate similar modulations by cardiac cycle. We identify a body–brain interaction wherein interoceptive cues can modulate threat appraisal and racially biased behaviour in context-dependent ways. PMID:28094772

  12. A computerized system for localizing sources of cardiac activation.

    PubMed

    Salu, Y; Mehrotra, P

    1984-06-01

    A noninvasive method for locating a source of cardiac electrical activity is described. The data acquisition and its preliminary processing is done with the aid of a microcomputer, while lengthier calculations are done on a large computer. The method was tested on 18 patients, and the results indicate that it is reliable, and with further technical refinements it could be used in research and clinical settings.

  13. 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

  14. Detection of Cardiac Quiescence from B-Mode Echocardiography Using a Correlation-Based Frame-to-Frame Deviation Measure

    PubMed Central

    Mcclellan, James H.; Ravichandran, Lakshminarayan; Tridandapani, Srini

    2013-01-01

    Two novel methods for detecting cardiac quiescent phases from B-mode echocardiography using a correlation-based frame-to-frame deviation measure were developed. Accurate knowledge of cardiac quiescence is crucial to the performance of many imaging modalities, including computed tomography coronary angiography (CTCA). Synchronous electrocardiography (ECG) and echocardiography data were obtained from 10 healthy human subjects (four male, six female, 23–45 years) and the interventricular septum (IVS) was observed using the apical four-chamber echocardiographic view. The velocity of the IVS was derived from active contour tracking and verified using tissue Doppler imaging echocardiography methods. In turn, the frame-to-frame deviation methods for identifying quiescence of the IVS were verified using active contour tracking. The timing of the diastolic quiescent phase was found to exhibit both inter- and intra-subject variability, suggesting that the current method of CTCA gating based on the ECG is suboptimal and that gating based on signals derived from cardiac motion are likely more accurate in predicting quiescence for cardiac imaging. Two robust and efficient methods for identifying cardiac quiescent phases from B-mode echocardiographic data were developed and verified. The methods presented in this paper will be used to develop new CTCA gating techniques and quantify the resulting potential improvement in CTCA image quality. PMID:26609501

  15. Influence of the Cardiac Myosin Hinge Region on Contractile Activity

    NASA Astrophysics Data System (ADS)

    Margossian, Sarkis S.; Krueger, John W.; Sellers, James R.; Cuda, Giovanni; Caulfield, James B.; Norton, Paul; Slayter, Henry S.

    1991-06-01

    The participation of cardiac myosin hinge in contractility was investigated by in vitro motility and ATPase assays and by measurements of sarcomere shortening. The effect on contractile activity was analyzed using an antibody directed against a 20-amino acid peptide within the hinge region of myosin. This antibody bound specifically at the hinge at a distance of 55 nm from the S1/S2 junction, was specific to human, dog, and rat cardiac myosins, did not crossreact with gizzard or skeletal myosin, and had no effect on ATPase activity of purified S1 and myofibrils. However, it completely suppressed the movement of actin filaments in in vitro motility assays and reduced active shortening of sarcomeres of skinned cardiac myocytes by half. Suppression of motion by the antihinge antibody may reflect a mechanical constraint imposed by the antibody upon the mobility of the S2 region of myosin. The results suggest that the steps in the mechanochemical energy transduction can be separately influenced through S2.

  16. 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.

  17. Emerging Cardiac Imaging Modalities for the Early Detection of Cardiotoxicity due to Anticancer Therapies.

    PubMed

    López-Fernández, Teresa; Thavendiranathan, Paaladinesh

    2017-02-08

    The undeniable advances in the field of oncology have finally led to a decrease in overall cancer-related mortality. However, this population of long-term cancer survivors is now facing a shift toward a substantial increase in cardiovascular morbidity and mortality. Because the development of overt cardiotoxicity can be associated with poor outcomes, preclinical identification of cardiac toxicity is important. This will promote early instauration of treatments to prevent overt heart dysfunction and allow oncologists to continue cancer therapy in an uninterrupted manner. Surveillance strategies for the early detection of cardiac injury include cardiac imaging and biomarkers during treatment. In this review, we outline existing cardiac imaging modalities to detect myocardial changes in patients undergoing cancer treatment and in survivors, and their strengths and limitations.

  18. Sexual activity and cardiac risk: is depression a contributing factor?

    PubMed

    Roose, S P; Seidman, S N

    2000-07-20

    There is a well-documented association between depression, ischemic heart disease, and cardiovascular mortality. This association has a number of dimensions including: (1) depressed patients have a higher than expected rate of sudden cardiovascular death; (2) over the course of a lifetime, patients with depression develop symptomatic and fatal ischemic heart disease at a higher rate compared with a nondepressed group; and (3) depression after myocardial infarction (MI) is associated with increased cardiac mortality. Depression is also associated with sexual dysfunction, particularly erectile dysfunction. If depression is the primary illness, then erectile dysfunction can be considered a symptom of the depressive illness. However, if the erectile dysfunction is primary, men may develop a depressive syndrome in reaction to the loss of sexual function. Regardless of whether erectile dysfunction is a symptom of depression or depression is a consequence of erectile dysfunction, these conditions are frequently comorbid. Thus, the patient with ischemic heart disease who is depressed is more likely to have erectile difficulties. An attempt by this patient to engage in sexual activity is therefore more likely to be unsuccessful and, given the increase in cardiac mortality associated with depression, it may result in a serious cardiac event.

  19. Direct activation of cardiac pacemaker channels by intracellular cyclic AMP.

    PubMed

    DiFrancesco, D; Tortora, P

    1991-05-09

    Cyclic AMP acts as a second messenger in the modulation of several ion channels that are typically controlled by a phosphorylation process. In cardiac pacemaker cells, adrenaline and acetylcholine regulate the hyperpolarization-activated current (if), but in opposite ways; this current is involved in the generation and modulation of pacemaker activity. These actions are mediated by cAMP and underlie control of spontaneous rate by neurotransmitters. Whether the cAMP modulation of if is mediated by channel phosphorylation is, however, still unknown. Here we investigate the action of cAMP on if in excised patches of cardiac pacemaker cells and find that cAMP activates if by a mechanism independent of phosphorylation, involving a direct interaction with the channels at their cytoplasmic side. Cyclic AMP activates if by shifting its activation curve to more positive voltages, in agreement with whole-cell results. This is the first evidence of an ion channel whose gating is dually regulated by voltage and direct cAMP binding.

  20. Real-Time Cardiac Arrhythmia Detection Using WOLA Filterbank Analysis of EGM Signals

    NASA Astrophysics Data System (ADS)

    Sheikhzadeh, Hamid; Brennan, Robert L.; So, Simon

    2007-12-01

    Novel methods of cardiac rhythm detection are proposed that are based on time-frequency analysis by a weighted overlap-add (WOLA) oversampled filterbank. Cardiac signals are obtained from intracardiac electrograms and decomposed into the time-frequency domain and analyzed by parallel peak detectors in selected frequency subbands. The coherence (synchrony) of the subband peaks is analyzed and employed to detect an optimal peak sequence representing the beat locations. By further analysis of the synchrony of the subband beats and the periodicity and regularity of the optimal beat, various possible cardiac events (including fibrillation, flutter, and tachycardia) are detected. The Ann Arbor Electrogram Library is used to evaluate the proposed detection method in clean and in additive noise. The evaluation results show that the method never misses any episode of fibrillation or flutter in clean or in noise and is robust to far-field R-wave interference. Furthermore, all other misclassification errors were within the acceptable limits.

  1. Cardiac hypertrophy induced by active Raf depends on Yorkie-mediated transcription.

    PubMed

    Yu, Lin; Daniels, Joseph P; Wu, Huihui; Wolf, Matthew J

    2015-02-03

    Organ hypertrophy can result from enlargement of individual cells or from cell proliferation or both. Activating mutations in the serine-threonine kinase Raf cause cardiac hypertrophy and contribute to Noonan syndrome in humans. Cardiac-specific expression of activated Raf also causes hypertrophy in Drosophila melanogaster. We found that Yorkie (Yki), a transcriptional coactivator in the Hippo pathway that regulates organ size, is required for Raf-induced cardiac hypertrophy in flies. Although aberrant activation of Yki orthologs stimulates cardiac hyperplasia in mice, cardiac-specific expression of an activated mutant form of Yki in fruit flies caused cardiac hypertrophy without hyperplasia. Knockdown of Yki caused cardiac dilation without loss of cardiomyocytes and prevented Raf-induced cardiac hypertrophy. In flies, Yki-induced cardiac hypertrophy required the TEA domain-containing transcription factor Scalloped, and, in mammalian cells, expression of mouse Raf(L613V), an activated form of Raf with a Noonan syndrome mutation, increased Yki-induced Scalloped activity. Furthermore, overexpression of Tgi (a Tondu domain-containing Scalloped-binding corepressor) in the fly heart abrogated Yki- or Raf-induced cardiac hypertrophy. Thus, crosstalk between Raf and Yki occurs in the heart and can influence Raf-mediated cardiac hypertrophy.

  2. Passive and active tension in single cardiac myofibrils.

    PubMed Central

    Linke, W A; Popov, V I; Pollack, G H

    1994-01-01

    Single myofibrils were isolated from chemically skinned rabbit heart and mounted in an apparatus described previously (Fearn et al., 1993; Linke et al., 1993). We measured the passive length-tension relation and active isometric force, both normalized to cross sectional area. Myofibrillar cross sectional area was calculated based on measurements of myofibril diameter from both phase-contrast images and electron micrographs. Passive tension values up to sarcomere lengths of approximately 2.2 microns were similar to those reported in larger cardiac muscle specimens. Thus, the element responsible for most, if not all, passive force of cardiac muscle at physiological sarcomere lengths appears to reside within the myofibrils. Above 2.2 microns, passive tension continued to rise, but not as steeply as reported in multicellular preparations. Apparently, structures other than the myofibrils become increasingly important in determining the magnitude of passive tension at these stretched lengths. Knowing the myofibrillar component of passive tension allowed us to infer the stress-strain relation of titin, the polypeptide thought to support passive force in the sarcomere. The elastic modulus of titin is 3.5 x 10(6) dyn cm-2, a value similar to that reported for elastin. Maximum active isometric tension in the single myofibril at sarcomere lengths of 2.1-2.3 microns was 145 +/- 35 mN/mm2 (mean +/- SD; n = 15). This value is comparable with that measured in fixed-end contractions of larger cardiac specimens, when the amount of nonmyofibrillar space in those preparations is considered. However, it is about 4 times lower than the maximum active tension previously measured in single skeletal myofibrils under similar conditions (Bartoo et al., 1993). Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 7 PMID:7948691

  3. Measuring cardiac autonomic nervous system (ANS) activity in children.

    PubMed

    van Dijk, Aimée E; van Lien, René; van Eijsden, Manon; Gemke, Reinoud J B J; Vrijkotte, Tanja G M; de Geus, Eco J

    2013-04-29

    The autonomic nervous system (ANS) controls mainly automatic bodily functions that are engaged in homeostasis, like heart rate, digestion, respiratory rate, salivation, perspiration and renal function. The ANS has two main branches: the sympathetic nervous system, preparing the human body for action in times of danger and stress, and the parasympathetic nervous system, which regulates the resting state of the body. ANS activity can be measured invasively, for instance by radiotracer techniques or microelectrode recording from superficial nerves, or it can be measured non-invasively by using changes in an organ's response as a proxy for changes in ANS activity, for instance of the sweat glands or the heart. Invasive measurements have the highest validity but are very poorly feasible in large scale samples where non-invasive measures are the preferred approach. Autonomic effects on the heart can be reliably quantified by the recording of the electrocardiogram (ECG) in combination with the impedance cardiogram (ICG), which reflects the changes in thorax impedance in response to respiration and the ejection of blood from the ventricle into the aorta. From the respiration and ECG signals, respiratory sinus arrhythmia can be extracted as a measure of cardiac parasympathetic control. From the ECG and the left ventricular ejection signals, the preejection period can be extracted as a measure of cardiac sympathetic control. ECG and ICG recording is mostly done in laboratory settings. However, having the subjects report to a laboratory greatly reduces ecological validity, is not always doable in large scale epidemiological studies, and can be intimidating for young children. An ambulatory device for ECG and ICG simultaneously resolves these three problems. Here, we present a study design for a minimally invasive and rapid assessment of cardiac autonomic control in children, using a validated ambulatory device (1-5), the VU University Ambulatory Monitoring System (VU

  4. 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

  5. Fiber bragg grating sensor based device for simultaneous measurement of respiratory and cardiac activities.

    PubMed

    Chethana, K; Guru Prasad, A S; Omkar, S N; Asokan, S

    2017-02-01

    This paper reports a novel optical ballistocardiography technique, which is non-invasive, for the simultaneous measurement of cardiac and respiratory activities using a Fiber Bragg Grating Heart Beat Device (FBGHBD). The unique design of FBGHBD offers additional capabilities such as monitoring nascent morphology of cardiac and breathing activity, heart rate variability, heart beat rhythm, etc., which can assist in early clinical diagnosis of many conditions associated with heart and lung malfunctioning. The results obtained from the FBGHBD positioned around the pulmonic area on the chest have been evaluated against an electronic stethoscope which detects and records sound pulses originated from the cardiac activity. In order to evaluate the performance of the FBGHBD, quantitative and qualitative studies have been carried out and the results are found to be reliable and accurate, validating its potential as a standalone medical diagnostic device. The developed FBGHBD is simple in design, robust, portable, EMI proof, shock proof and non-electric in its operation which are desired features for any clinical diagnostic tool used in hospital environment.

  6. Histamine H3 activation depresses cardiac function in experimental sepsis.

    PubMed

    Li, X; Eschun, G; Bose, D; Jacobs, H; Yang, J J; Light, R B; Mink, S N

    1998-11-01

    In the heart, histamine (H3) receptors may function as inhibitory presynaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized that H3-receptor blockade might improve cardiovascular function in sepsis. In a canine model of Escherichia coli sepsis, we found that H3-receptor blockade increased cardiac output (3.6 to 5.3 l/min, P < 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left ventricular contractility compared with pretreatment values. Plasma histamine concentrations increased modestly in the H3-blocker-sepsis group compared with values obtained in a nonsepsis-time-control group. In an in vitro preparation, histamine H3 activation could be identified under conditions of septic plasma. We conclude that activation of H3 receptors may contribute to cardiovascular collapse in sepsis.

  7. Physical exercise and cardiac autonomic activity in healthy adult men.

    PubMed

    Panda, Kaninika; Krishna, Pushpa

    2014-01-01

    Physical inactivity is an important risk factor for cardiovascular mortality and morbidity. Regular exercise is known to improve health and maintain physical fitness. The heart rate response to exercise reflects autonomic control of heart and has shown to predict cardiovascular prognosis. Decreased heart rate variability (HRV) is known as a risk factor for cardiovascular mortality. The objective of this study was to study the effect of exercise on cardiac autonomic activity. Thirty two healthy adult men in the age group of 18-25 years with normal body mass index (BMI) were recruited from different physical fitness centers, who were undergoing regular exercise for past 3 months. Resting ECG was recorded for 5 minutes and analyzed for frequency analysis of HRV. HRV parameters of the subjects were compared with fifty age and BMI matched subjects who were not undergoing any exercise program. Physical activity level of all subjects was assessed by using Global Physical Activity Questionnaire. The exercising (E) subjects were found to have a lesser heart rate (73.27 ± 8.6 vs 74.41 ± 8.59) compared to non-exercising (NE) group, which was not significant. No significant difference was found in frequency domain parameters of HRV between exercising and non-exercising group with LF (47.12 ± 19.17 vs 43.55 ± 16.66), HF (41.03 ± 17.65 vs 46.03 ± 15.89) and LF/HF (1.61 ± 1.16 vs 1.22 ± 0.93) respectively. Physical activity level was significantly different between the two groups (4175 ± 1481.53 vs 1176.4?1103.83, p<0.001). This study showed 3 months of exercise did not have any effect on cardiac autonomic activity despite the difference in physical activity.

  8. 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.

  9. Active Bleeding after Cardiac Surgery: A Prospective Observational Multicenter Study

    PubMed Central

    Fellahi, Jean-Luc; Bertet, Héléna; Faucanie, Marie; Amour, Julien; Blanloeil, Yvonnick; Lanquetot, Hervé; Ouattara, Alexandre; Picot, Marie Christine

    2016-01-01

    Main Objectives To estimate the incidence of active bleeding after cardiac surgery (AB) based on a definition directly related on blood flow from chest drainage; to describe the AB characteristics and its management; to identify factors of postoperative complications. Methods AB was defined as a blood loss > 1.5 ml/kg/h for 6 consecutive hours within the first 24 hours or in case of reoperation for hemostasis during the first 12 postoperative hours. The definition was applied in a prospective longitudinal observational study involving 29 French centers; all adult patients undergoing cardiac surgery with cardiopulmonary bypass were included over a 3-month period. Perioperative data (including blood product administration) were collected. To study possible variation in clinical practice among centers, patients were classified into two groups according to the AB incidence of the center compared to the overall incidence: “Low incidence” if incidence is lower and “High incidence” if incidence is equal or greater than overall incidence. Logistic regression analysis was used to identify risk factors of postoperative complications. Results Among 4,904 patients, 129 experienced AB (2.6%), among them 52 reoperation. Postoperative bleeding loss was 1,000 [820;1,375] ml and 1,680 [1,280;2,300] ml at 6 and 24 hours respectively. Incidence of AB varied between centers (0 to 16%) but was independent of in-centre cardiac surgical experience. Comparisons between groups according to AB incidence showed differences in postoperative management. Body surface area, preoperative creatinine, emergency surgery, postoperative acidosis and red blood cell transfusion were risk factors of postoperative complication. Conclusions A blood loss > 1.5 ml/kg/h for 6 consecutive hours within the first 24 hours or early reoperation for hemostasis seems a relevant definition of AB. This definition, independent of transfusion, adjusted to body weight, may assess real time bleeding occurring

  10. Caffeine-activated large-conductance plasma membrane cation channels in cardiac myocytes: characteristics and significance.

    PubMed

    Zhang, Yu-An; Tuft, Richard A; Lifshitz, Lawrence M; Fogarty, Kevin E; Singer, Joshua J; Zou, Hui

    2007-10-01

    Caffeine-activated, large-conductance, nonselective cation channels (LCCs) have been found in the plasma membrane of isolated cardiac myocytes in several species. However, little is known about the effects of opening these channels. To examine such effects and to further understand the caffeine-activation mechanism, we carried out studies using whole-cell patch-clamp techniques with freshly isolated cardiac myocytes from rats and mice. Unlike previous studies, thapsigargin was used so that both the effect of opening LCCs and the action of caffeine were independent of Ca(2+) release from intracellular stores. These Ca(2+)-permeable LCCs were found in a majority of the cells from atria and ventricles, with a conductance of approximately 370 pS in rat atria. Caffeine and all its direct metabolic products (theophylline, theobromine, and paraxanthine) activated the channel, while isocaffeine did not. Although they share some similarities with ryanodine receptors (RyRs, the openings of which give rise to Ca(2+) sparks), LCCs also showed some different characteristics. With simultaneous Ca(2+) imaging and current recording, the localized fluorescence increase due to Ca(2+) entry through a single opening of an LCC (SCCaFT) was detected. When membrane potential, instead of current, was recorded, SCCaFT-like fluorescence transients (indicating single LCC openings) were found to accompany membrane depolarizations. To our knowledge, this is the first report directly linking membrane potential changes to a single opening of an ion channel. Moreover, these events in cardiac cells suggest a possible additional mechanism by which caffeine and theophylline contribute to the generation of cardiac arrhythmias.

  11. 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.

  12. An integrated chip for rapid, sensitive, and multiplexed detection of cardiac biomarkers from fingerprick blood.

    PubMed

    Zhang, Guo-Jun; Luo, Zhan Hong Henry; Huang, Min Joon; Ang, Jun'an Jason; Kang, Tae Goo; Ji, Hongmiao

    2011-10-15

    Cardiovascular diseases are the major cause of death among adults worldwide. Electrocardiogram (ECG) is a first test when a patient suffering from chest pain sees a doctor, however, it is lack of the required sensitivity. Standard assays to detect cardiac biomarkers, like enzyme-linked immunosorbent assay (ELISA) are sensitive, but suffer from important sample and reagent consumption in large-scale studies. Moreover they are performed in central laboratories of clinics and hospitals and take a long time, which is highly incompatible with the quick decisions needed to save a heart attack patient. Herein, we describe an integrated chip allowing rapid, sensitive, and simultaneous analysis of three cardiac biomarkers in fingerprick blood. The integrated chip is composed of a filtration chip for plasma separation from blood and a silicon nanowire (SiNW) array sensor chip for protein detection. These two chips are fabricated separately and bonded to form a single unit after alignment. The integrated chip is capable of reducing the dead volume of the sample by eliminating the tubing between the two chips. After the plasma is filtrated by the filtration chip, the SiNW sensor, spotted with three different antibodies, enabled us to detect three cardiac biomarkers, troponin T (cTnT), creatine kinase MM (CK-MM) and creatine kinase MB (CK-MB), simultaneously. The integrated chip is able to attain a low detection limit of 1 pg/ml for the three cardiac biomarkers from 2 μl blood in 45 min.

  13. Cardiac Shear Wave Velocity Detection in the Porcine Heart.

    PubMed

    Vos, Hendrik J; van Dalen, Bas M; Heinonen, Ilkka; Bosch, Johan G; Sorop, Oana; Duncker, Dirk J; van der Steen, Antonius F W; de Jong, Nico

    2017-04-01

    Cardiac muscle stiffness can potentially be estimated non-invasively with shear wave elastography. Shear waves are present on the septal wall after mitral and aortic valve closure, thus providing an opportunity to assess stiffness in early systole and early diastole. We report on the shear wave recordings of 22 minipigs with high-frame-rate echocardiography. The waves were captured with 4000 frames/s using a programmable commercial ultrasound machine. The wave pattern was extracted from the data through a local tissue velocity estimator based on one-lag autocorrelation. The wave propagation velocity was determined with a normalized Radon transform, resulting in median wave propagation velocities of 2.2 m/s after mitral valve closure and 4.2 m/s after aortic valve closure. Overall the velocities ranged between 0.8 and 6.3 m/s in a 95% confidence interval. By dispersion analysis we found that the propagation velocity only mildly increased with shear wave frequency.

  14. 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

  15. Pulseless electrical activity in cardiac arrest: electrocardiographic presentations and management considerations based on the electrocardiogram.

    PubMed

    Mehta, Chris; Brady, William

    2012-01-01

    Pulseless electrical activity (PEA), a cardiac arrest rhythm scenario with an associated poor prognosis, is defined as cardiac electrical activity without a palpable pulse. Considering both outpatient and inpatient cardiac arrest presentations, PEA as a rhythm group has been increasing over the past 10 to 20 years with a corresponding decrease in the "shockable" rhythms, such as pulseless ventricular tachycardia and ventricular fibrillation. This review focuses on electrocardiographic findings encountered in PEA cardiac arrest presentations with an emphasis on recognition of patients with a potential opportunity for successful resuscitation.

  16. Simple hand-held metal detectors are an effective means of detecting cardiac pacemakers in the deceased prior to cremation.

    PubMed

    Stone, Jason Lyle; Williams, John; Fearn, Lesley

    2010-05-01

    The hazard of undetected cardiac pacemakers exploding in crematoria is well described. This short report describes the use of an affordable hand-held metal detector to detect cardiac pacemakers. Over the course of a year, the metal detector located 100% of cardiac pacemakers in a district general hospital mortuary. A simple model using pigskin and fat is also used to demonstrate the effectiveness in vitro. Commercially purchased hand-held metal detectors should be used in all mortuaries responsible for detection and removal of cardiac pacemakers prior to cremation.

  17. Impact of myocyte strain on cardiac myofilament activation.

    PubMed

    Campbell, Kenneth S

    2011-07-01

    When cardiac myocytes are stretched by a longitudinal strain, they develop proportionally more active force at a given sub-maximal Ca(2+) concentration than they did at the shorter length. This is known as length-dependent activation. It is one of the most important contributors to the Frank-Starling relationship, a critical part of normal cardiovascular function. Despite intense research efforts, the mechanistic basis of the Frank-Starling relationship remains unclear. Potential mechanisms involving myofibrillar lattice spacing, titin-based effects, and cooperative activation have all been proposed. This review summarizes some of these mechanisms and discusses two additional potential theories that reflect the effects of localized strains that occur within and between half-sarcomeres. The main conclusion is that the Frank-Starling relationship is probably the integrated result of many interacting molecular mechanisms. Multiscale computational modeling may therefore provide the best way of determining the key processes that underlie length-dependent activation and their relative strengths.

  18. Multiplexed detection of cardiac biomarkers in serum with nanowire arrays using readout ASIC.

    PubMed

    Zhang, Guo-Jun; Chai, Kevin Tshun Chuan; Luo, Henry Zhan Hong; Huang, Joon Min; Tay, Ignatius Guang Kai; Lim, Andy Eu-Jin; Je, Minkyu

    2012-05-15

    Early detection of cardiac biomarkers for diagnosis of heart attack is the key to saving lives. Conventional method of detection like the enzyme-linked immunosorbent assay (ELISA) is time consuming and low in sensitivity. Here, we present a label-free detection system consisting of an array of silicon nanowire sensors and an interface readout application specific integrated circuit (ASIC). This system provides a rapid solution that is highly sensitive and is able to perform direct simultaneous-multiplexed detection of cardiac biomarkers in serum. Nanowire sensor arrays were demonstrated to have the required selectivity and sensitivity to perform multiplexed detection of 100 fg/ml troponin T, creatine kinase MM, and creatine kinase MB in serum. A good correlation between measurements from a probe station and the readout ASIC was obtained. Our detection system is expected to address the existing limitations in cardiac health management that are currently imposed by the conventional testing platform, and opens up possibilities in the development of a miniaturized device for point-of-care diagnostic applications.

  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. Sensory detection thresholds are modulated across the cardiac cycle: evidence that cutaneous sensibility is greatest for systolic stimulation.

    PubMed

    Edwards, L; Ring, C; McIntyre, D; Winer, J B; Martin, U

    2009-03-01

    The visceral afferent feedback hypothesis proposes that sensorimotor function is impaired by cortical inhibition associated with increased baroreceptor activation. This study is the first to examine the effects of naturally occurring variations in baroreceptor activity across the cardiac cycle on cutaneous sensory detection thresholds. In each trial, an electrocutaneous stimulus was delivered to the index finger at one of three intervals (0, 300, 600 ms) after the R-wave of the electrocardiogram. Separate interleaving up-down staircases were used to determine the 50% detection threshold for each R-wave to stimulation interval. Cutaneous sensory detection thresholds were lower for stimuli presented at R+300 ms than R+0 ms or R+600 ms. The finding that cutaneous sensibility was greater when stimulated during systole than diastole may be accounted for by a modified afferent feedback hypothesis.

  1. ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism

    PubMed Central

    Tian, Zhe; Miyata, Keishi; Kadomatsu, Tsuyoshi; Horiguchi, Haruki; Fukushima, Hiroyuki; Tohyama, Shugo; Ujihara, Yoshihiro; Okumura, Takahiro; Yamaguchi, Satoshi; Zhao, Jiabin; Endo, Motoyoshi; Morinaga, Jun; Sato, Michio; Sugizaki, Taichi; Zhu, Shunshun; Terada, Kazutoyo; Sakaguchi, Hisashi; Komohara, Yoshihiro; Takeya, Motohiro; Takeda, Naoki; Araki, Kimi; Manabe, Ichiro; Fukuda, Keiichi; Otsu, Kinya; Wada, Jun; Murohara, Toyoaki; Mohri, Satoshi; Yamashita, Jun K.; Sano, Motoaki; Oike, Yuichi

    2016-01-01

    A cardioprotective response that alters ventricular contractility or promotes cardiomyocyte enlargement occurs with increased workload in conditions such as hypertension. When that response is excessive, pathological cardiac remodelling occurs, which can progress to heart failure, a leading cause of death worldwide. Mechanisms underlying this response are not fully understood. Here, we report that expression of angiopoietin-like protein 2 (ANGPTL2) increases in pathologically-remodeled hearts of mice and humans, while decreased cardiac ANGPTL2 expression occurs in physiological cardiac remodelling induced by endurance training in mice. Mice overexpressing ANGPTL2 in heart show cardiac dysfunction caused by both inactivation of AKT and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a signalling and decreased myocardial energy metabolism. Conversely, Angptl2 knockout mice exhibit increased left ventricular contractility and upregulated AKT-SERCA2a signalling and energy metabolism. Finally, ANGPTL2-knockdown in mice subjected to pressure overload ameliorates cardiac dysfunction. Overall, these studies suggest that therapeutic ANGPTL2 suppression could antagonize development of heart failure. PMID:27677409

  2. 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.

  3. Sestrin 1 ameliorates cardiac hypertrophy via autophagy activation.

    PubMed

    Xue, Ruicong; Zeng, Junyi; Chen, Yili; Chen, Cong; Tan, Weiping; Zhao, Jingjing; Dong, Bin; Sun, Yu; Dong, Yugang; Liu, Chen

    2017-02-09

    Cardiac hypertrophy is one of the major risk factors of cardiovascular morbidity and mortality. Autophagy is acknowledged to be an important mechanism regulating cardiac hypertrophy. Sestrin 1, a downstream target gene of p53, has been proven to regulate autophagy. However, the role of Sestrin 1 in cardiac hypertrophy remains unknown. Our study showed that Sestrin 1 mRNA and protein expression declined in pressure overload cardiac hypertrophy and phenylephrine (PE)-induced cardiac hypertrophy. Knockdown of Sestrin 1 by RNAi deteriorated PE-induced cardiac hypertrophy, whereas the overexpression of Sestrin 1 by adenovirus transfection blunted hypertrophy. We discovered that knockdown of Sestrin 1 resulted in impaired autophagy while overexpression of Sestrin 1 resulted in increased autophagy without affecting lysosomal function. In addition, the antihypertrophic effect of Sestrin 1 overexpression was eliminated by autophagy blockade. Importantly, Sestrin 1 targets at the AMPK/mTORC1/autophagy pathway to inhibit cardiac hypertrophy by interaction with AMPK which is responsible for autophagy regulation. Taken together, our data indicate that Sestrin 1 regulates AMPK/mTORC1/autophagy axis to attenuate cardiac hypertrophy.

  4. Face liveness detection for face recognition based on cardiac features of skin color image

    NASA Astrophysics Data System (ADS)

    Suh, Kun Ha; Lee, Eui Chul

    2016-07-01

    With the growth of biometric technology, spoofing attacks have been emerged a threat to the security of the system. Main spoofing scenarios in the face recognition system include the printing attack, replay attack, and 3D mask attack. To prevent such attacks, techniques that evaluating liveness of the biometric data can be considered as a solution. In this paper, a novel face liveness detection method based on cardiac signal extracted from face is presented. The key point of proposed method is that the cardiac characteristic is detected in live faces but not detected in non-live faces. Experimental results showed that the proposed method can be effective way for determining printing attack or 3D mask attack.

  5. Quantitatively accurate activity measurements with a dedicated cardiac SPECT camera: Physical phantom experiments

    SciTech Connect

    Pourmoghaddas, Amir Wells, R. Glenn

    2016-01-15

    Purpose: Recently, there has been increased interest in dedicated cardiac single photon emission computed tomography (SPECT) scanners with pinhole collimation and improved detector technology due to their improved count sensitivity and resolution over traditional parallel-hole cameras. With traditional cameras, energy-based approaches are often used in the clinic for scatter compensation because they are fast and easily implemented. Some of the cardiac cameras use cadmium-zinc-telluride (CZT) detectors which can complicate the use of energy-based scatter correction (SC) due to the low-energy tail—an increased number of unscattered photons detected with reduced energy. Modified energy-based scatter correction methods can be implemented, but their level of accuracy is unclear. In this study, the authors validated by physical phantom experiments the quantitative accuracy and reproducibility of easily implemented correction techniques applied to {sup 99m}Tc myocardial imaging with a CZT-detector-based gamma camera with multiple heads, each with a single-pinhole collimator. Methods: Activity in the cardiac compartment of an Anthropomorphic Torso phantom (Data Spectrum Corporation) was measured through 15 {sup 99m}Tc-SPECT acquisitions. The ratio of activity concentrations in organ compartments resembled a clinical {sup 99m}Tc-sestamibi scan and was kept consistent across all experiments (1.2:1 heart to liver and 1.5:1 heart to lung). Two background activity levels were considered: no activity (cold) and an activity concentration 1/10th of the heart (hot). A plastic “lesion” was placed inside of the septal wall of the myocardial insert to simulate the presence of a region without tracer uptake and contrast in this lesion was calculated for all images. The true net activity in each compartment was measured with a dose calibrator (CRC-25R, Capintec, Inc.). A 10 min SPECT image was acquired using a dedicated cardiac camera with CZT detectors (Discovery NM530c, GE

  6. Smart helmet: Monitoring brain, cardiac and respiratory activity.

    PubMed

    von Rosenberg, Wilhelm; Chanwimalueang, Theerasak; Goverdovsky, Valentin; Mandic, Danilo P

    2015-01-01

    The timing of the assessment of the injuries following a road-traffic accident involving motorcyclists is absolutely crucial, particularly in the events with head trauma. Standard apparatus for monitoring cardiac activity is usually attached to the limbs or the torso, while the brain function is routinely measured with a separate unit connected to the head-mounted sensors. In stark contrast to these, we propose an integrated system which incorporates the two functionalities inside an ordinary motorcycle helmet. Multiple fabric electrodes were mounted inside the helmet at positions featuring good contact with the skin at different sections of the head. The experimental results demonstrate that the R-peaks (and therefore the heart rate) can be reliably extracted from potentials measured with electrodes on the mastoids and the lower jaw, while the electrodes on the forehead enable the observation of neural signals. We conclude that various vital sings and brain activity can be readily recorded from the inside of a helmet in a comfortable and inconspicuous way, requiring only a negligible setup effort.

  7. 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.

  8. 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

  9. 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%.

  10. Segmental origins of cardiac sympathetic nerve activity in rats.

    PubMed

    Pracejus, Natasha H; Farmer, David G S; McAllen, Robin M

    2015-01-01

    The segmental origins of cardiac sympathetic nerve activity (CSNA) were investigated in 8 urethane-anesthetized, artificially ventilated rats. The left upper thoracic sympathetic chain was exposed retropleurally after removing the heads of the second to fourth ribs. The preganglionic inputs to the chain from segments T1-T3 and the trunk distal to T3 were marked for later sectioning. CSNA was recorded conventionally, amplified, rectified and smoothed. Its mean level was quantified before and after each preganglionic input was cut, usually in rostro-caudal sequence. The level after all inputs were cut (i.e. noise and residual ECG pickup) was subtracted from previous measurements. The signal decrement from cutting each preganglionic input was then calculated as a percentage. CSNA in all rats depended on preganglionic drive from two or more segments, which were not always contiguous. Over the population, most preganglionic drive came from T3 and below, while the least came from T1. But there was striking inter-individual variation, such that the strongest drive to CSNA in any one rat could come from T1, T2, T3, or below T3. These findings provide new functional data on the segmental origins of CSNA in rats.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Exacerbated cardiac fibrosis induced by β-adrenergic activation in old mice due to decreased AMPK activity.

    PubMed

    Wang, Jingjing; Song, Yao; Li, Hao; Shen, Qiang; Shen, Jing; An, Xiangbo; Wu, Jimin; Zhang, Jianshu; Wu, Yunong; Xiao, Han; Zhang, Youyi

    2016-11-01

    Senescent hearts exhibit defective responses to β-adrenergic receptor (β-AR) over-activation upon stress, leading to more severe pathological cardiac remodelling. However, the underlying mechanisms remain unclear. Here, we investigated the role of adenosine monophosphate-activated protein kinase (AMPK) in protecting against ageing-associated cardiac remodelling in mice upon β-AR over-activation. 10-week-old (young) and 18-month-old (old) mice were subcutaneously injected with the β-AR agonist isoproterenol (ISO; 5 mg/kg). More extensive cardiac fibrosis was found in old mice upon ISO exposure than in young mice. Meanwhile, ISO treatment decreased AMPK activity and increased β-arrestin 1, but not β-arrestin 2, expression, and the effects of ISO on AMPK and β-arrestin 1 were greater in old mice than in young mice. Similarly, young AMPKα2-knockout (KO) mice showed more extensive cardiac fibrosis upon ISO exposure than that was observed in age-matched wild-type (WT) littermates. The extent of cardiac fibrosis in WT old mice was similar to that in young KO mice. Additionally, AMPK activities were decreased and β-arrestin 1 expression increased in KO mice. In contrast, the AMPK activator metformin decreased β-arrestin 1 expression and attenuated cardiac fibrosis in both young and old mice upon ISO exposure. In conclusion, more severe cardiac fibrosis is induced by ISO in old mice than in young mice. A decrease in AMPK activity, which further increases β-arrestin 1 expression, is the central mechanism underlying the ageing-related cardiac fibrosis induced by ISO. The AMPK activator metformin is a promising therapeutic agent for treating ageing-related cardiac remodelling upon β-AR over-activation.

  17. 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.

  18. 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

  19. Presentation of untreated systemic mastocytosis as recurrent, pulseless-electrical-activity cardiac arrests resistant to cardiac pacemaker.

    PubMed

    Butterfield, Joseph H; Weiler, Catherine R

    2014-01-01

    Recurrent, pulseless-electrical-activity (PEA) cardiac arrests were the novel presentation of untreated systemic mastocytosis in an 85-year-old woman who lacked cutaneous findings of mastocytosis. Despite prior implantation of a dual-chamber cardiac pacemaker 3 weeks previously for similar spells, she experienced a PEA arrest accompanied by flushing, increased urinary N-methylhistamine excretion and serum tryptase values on the day of presentation to our clinic. Bone marrow biopsy findings conducted to rule out breast cancer metastases showed 30% mast cell infiltration, aberrant expression of CD25 and a positive c-kit Asp816Val mutation. Treatment with a combination of H1 and H2 receptor blockers reduced flushing and eliminated hypotension. Maintenance medication included aspirin, cetirizine, ranitidine, montelukast, oral cromolyn sodium and an epinephrine autoinjector (as needed). At 6-month follow-up, the patient remained free of PEA arrests, flushing, or any clinical signs of mastocytosis or mast cell degranulation. PEA cardiac arrests may therefore be a presenting sign of untreated systemic mastocytosis.

  20. Heart Rate Variability for Early Detection of Cardiac Iron Deposition in Patients with Transfusion-Dependent Thalassemia

    PubMed Central

    Silvilairat, Suchaya; Charoenkwan, Pimlak; Saekho, Suwit; Tantiworawit, Adisak; Phrommintikul, Arintaya; Srichairatanakool, Somdet; Chattipakorn, Nipon

    2016-01-01

    Background Iron overload cardiomyopathy remains the major cause of death in patients with transfusion-dependent thalassemia. Cardiac T2* magnetic resonance imaging is costly yet effective in detecting cardiac iron accumulation in the heart. Heart rate variability (HRV) has been used to evaluate cardiac autonomic function and is depressed in cases of thalassemia. We evaluated whether HRV could be used as an indicator for early identification of cardiac iron deposition. Methods One hundred and one patients with transfusion-dependent thalassemia were enrolled in this study. The correlation between recorded HRV and hemoglobin, non-transferrin bound iron (NTBI), serum ferritin and cardiac T2* were evaluated. Results The median age was 18 years (range 8–59 years). The patient group with a 5-year mean serum ferritin >5,000 ng/mL included significantly more homozygous β-thalassemia and splenectomized patients, had lower hemoglobin levels, and had more cardiac iron deposit than all other groups. Anemia strongly influenced all domains of HRV. After adjusting for anemia, neither serum ferritin nor NTBI impacted the HRV. However cardiac T2* was an independent predictor of HRV, even after adjusting for anemia. For receiver operative characteristic (ROC) curve analysis of cardiac T2* ≤20 ms, only mean ferritin in the last 12 months and the average of the standard deviation of all R-R intervals for all five-minute segments in the 24-hour recording were predictors for cardiac T2* ≤20 ms, with area under the ROC curve of 0.961 (p<0.0001) and 0.701 (p = 0.05), respectively. Conclusions Hemoglobin and cardiac T2* as significant predictors for HRV indicate that anemia and cardiac iron deposition result in cardiac autonomic imbalance. The mean ferritin in the last 12 months could be useful as the best indicator for further evaluation of cardiac risk. The ability of serum ferritin to predict cardiac risk is stronger than observed in other thalassemia cohorts. HRV might be a

  1. Cardiac troponin I threonine 144: role in myofilament length dependent activation.

    PubMed

    Tachampa, Kittipong; Wang, Helen; Farman, Gerrie P; de Tombe, Pieter P

    2007-11-26

    Myofilament length-dependent activation is the main cellular mechanism responsible for the Frank-Starling law of the heart. All striated muscle display length-dependent activation properties, but it is most pronounced in cardiac muscle and least in slow skeletal muscle. Cardiac muscle expressing slow skeletal troponin (ssTn)I instead of cardiac troponin (cTn)I displays reduced myofilament length-dependent activation. The inhibitory region of troponin (Tn)I differs by a single residue, proline at position 112 in ssTnI versus threonine at position 144 in cTnI. Here we tested whether this substitution was important for myofilament length-dependent activation; using recombinant techniques, we prepared wild-type cTnI, ssTnI, and 2 mutants: cTnI(Thr>Pro) and ssTnI(Pro>Thr). Purified proteins were complexed with recombinant cardiac TnT/TnC and exchanged into skinned rat cardiac trabeculae. Force-Ca2+ relationships were determined to derive myofilament Ca2+ sensitivity (EC50) at 2 sarcomere lengths: 2.0 and 2.2 microm (n=7). Myofilament length-dependent activation was indexed as deltaEC50, the difference in EC50 between sarcomere lengths of 2.0 and 2.2 microm. Incorporation of ssTnI compared with cTnI into the cardiac sarcomere reduced deltaEC50 from 1.26+/-0.30 to 0.19+/-0.04 micromol/L. A similar reduction also could be observed when Tn contained cTnI(Thr>Pro) (deltaEC50=0.24+/-0.04 micromol/L), whereas the presence of ssTnI(Pro>Thr) increased deltaEC50 to 0.94+/-0.12 micromol/L. These results suggest that Thr144 in cardiac TnI modulates cardiac myofilament length-dependent activation.

  2. 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

  3. Detection of Cardiac Function Abnormality from MRI Images Using Normalized Wall Thickness Temporal Patterns.

    PubMed

    Wael, Mai; Ibrahim, El-Sayed H; Fahmy, Ahmed S

    2016-01-01

    Purpose. To develop a method for identifying abnormal myocardial function based on studying the normalized wall motion pattern during the cardiac cycle. Methods. The temporal pattern of the normalized myocardial wall thickness is used as a feature vector to assess the cardiac wall motion abnormality. Principal component analysis is used to reduce the feature dimensionality and the maximum likelihood method is used to differentiate between normal and abnormal features. The proposed method was applied on a dataset of 27 cases from normal subjects and patients. Results. The developed method achieved 81.5%, 85%, and 88.5% accuracy for identifying abnormal contractility in the basal, midventricular, and apical slices, respectively. Conclusions. A novel feature vector, namely, the normalized wall thickness, has been introduced for detecting myocardial regional wall motion abnormality. The proposed method provides assessment of the regional myocardial contractility for each cardiac segment and slice; therefore, it could be a valuable tool for automatic and fast determination of regional wall motion abnormality from conventional cine MRI images.

  4. 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

  5. Spatial Repolarization Heterogeneity Detected by Magnetocardiography Correlates with Cardiac Iron Overload and Adverse Cardiac Events in Beta-Thalassemia Major

    PubMed Central

    Chen, Chun-An; Lu, Meng-Yao; Peng, Shinn-Forng; Lin, Kai-Hsin; Chang, Hsiu-Hao; Yang, Yung-Li; Jou, Shiann-Tarng; Lin, Dong-Tsamn; Liu, Yen-Bin; Horng, Herng-Er; Yang, Hong-Chang; Wang, Jou-Kou; Wu, Mei-Hwan; Wu, Chau-Chung

    2014-01-01

    Background Patients with transfusion-dependent beta-thalassemia major (TM) are at risk for myocardial iron overload and cardiac complications. Spatial repolarization heterogeneity is known to be elevated in patients with certain cardiac diseases, but little is known in TM patients. The purpose of this study was to evaluate spatial repolarization heterogeneity in patients with TM, and to investigate the relationships between spatial repolarization heterogeneity, cardiac iron load, and adverse cardiac events. Methods and Results Fifty patients with TM and 55 control subjects received 64-channel magnetocardiography (MCG) to determine spatial repolarization heterogeneity, which was evaluated by a smoothness index of QTc (SI-QTc), a standard deviation of QTc (SD-QTc), and a QTc dispersion. Left ventricular function and myocardial T2* values were assessed by cardiac magnetic resonance. Patients with TM had significantly greater SI-QTc, SD-QTc, and QTc dispersion compared to the control subjects (all p values<0.001). Spatial repolarization heterogeneity was even more pronounced in patients with significant iron overload (T2*<20 ms, n = 20) compared to those with normal T2* (all p values<0.001). Loge cardiac T2* correlated with SI-QTc (r = −0.609, p<0.001), SD-QTc (r = −0.572, p<0.001), and QTc dispersion (r = −0.622, p<0.001), while all these indices had no relationship with measurements of the left ventricular geometry or function. At the time of study, 10 patients had either heart failure or arrhythmia. All 3 indices of repolarization heterogeneity were related to the presence of adverse cardiac events, with areas under the receiver operating characteristic curves (ranged between 0.79 and 0.86), similar to that of cardiac T2*. Conclusions Multichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events. PMID:24475137

  6. 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

  7. 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.

  8. 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.

  9. Label-free detection of cardiac troponin I with a photonic crystal biosensor.

    PubMed

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

    2014-08-15

    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 0.1ngmL(-1) has been achieved.

  10. EGCG inhibits CTGF expression via blocking NF-κB activation in cardiac fibroblast.

    PubMed

    Cai, Yi; Yu, Shan-Shan; Chen, Ting-Ting; Gao, Si; Geng, Biao; Yu, Yang; Ye, Jian-Tao; Liu, Pei-Qing

    2013-01-15

    Connective tissue growth factor (CTGF) has been reported to play an important role in tissue fibrosis and presents a promising therapeutic target for fibrotic diseases. In heart, inappropriate increase in level of CTGF promotes fibroblast proliferation and extracellular matrix (ECM) accumulation, thereby exacerbating cardiac hypertrophy and subsequent failure. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac fibrosis. However, the molecular mechanism by which EGCG exerts its anti-fibrotic effects has not been well investigated. In this study, we found that EGCG could significantly reduce collagen synthesis, fibronectin (FN) expression and cell proliferation in rat cardiac fibroblasts stimulated with angiotensinII (AngII). It also ameliorated cardiac fibrosis in rats submitted to abdominal aortic constriction (AAC). Moreover, EGCG attenuated the excessive expression of CTGF induced by AAC or AngII, and reduced the nuclear translocation of NF-κB p65 subunit and degradation of IκB-α. Subsequently, we demonstrated that in cardiac fibroblasts NF-κB inhibition could suppress AngII-induced CTGF expression. Taken together, these findings provide the first evidence that the effect of EGCG against cardiac fibrosis may be attributed to its inhibition on NF-κB activation and subsequent CTGF overexpression, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.

  11. 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.

  12. 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…

  13. An ontology-based annotation of cardiac implantable electronic devices to detect therapy changes in a national registry.

    PubMed

    Rosier, Arnaud; Mabo, Philippe; Chauvin, Michel; Burgun, Anita

    2015-05-01

    The patient population benefitting from cardiac implantable electronic devices (CIEDs) is increasing. This study introduces a device annotation method that supports the consistent description of the functional attributes of cardiac devices and evaluates how this method can detect device changes from a CIED registry. We designed the Cardiac Device Ontology, an ontology of CIEDs and device functions. We annotated 146 cardiac devices with this ontology and used it to detect therapy changes with respect to atrioventricular pacing, cardiac resynchronization therapy, and defibrillation capability in a French national registry of patients with implants (STIDEFIX). We then analyzed a set of 6905 device replacements from the STIDEFIX registry. Ontology-based identification of therapy changes (upgraded, downgraded, or similar) was accurate (6905 cases) and performed better than straightforward analysis of the registry codes (F-measure 1.00 versus 0.75 to 0.97). This study demonstrates the feasibility and effectiveness of ontology-based functional annotation of devices in the cardiac domain. Such annotation allowed a better description and in-depth analysis of STIDEFIX. This method was useful for the automatic detection of therapy changes and may be reused for analyzing data from other device registries.

  14. 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.

  15. 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

  16. Characterization of Cardiac-Resident Progenitor Cells Expressing High Aldehyde Dehydrogenase Activity

    PubMed Central

    Roehrich, Marc-Estienne; Spicher, Albert; Milano, Giuseppina; Vassalli, Giuseppe

    2013-01-01

    High aldehyde dehydrogenase (ALDH) activity has been associated with stem and progenitor cells in various tissues. Human cord blood and bone marrow ALDH-bright (ALDHbr) cells have displayed angiogenic activity in preclinical studies and have been shown to be safe in clinical trials in patients with ischemic cardiovascular disease. The presence of ALDHbr cells in the heart has not been evaluated so far. We have characterized ALDHbr cells isolated from mouse hearts. One percent of nonmyocytic cells from neonatal and adult hearts were ALDHbr. ALDHvery-br cells were more frequent in neonatal hearts than adult. ALDHbr cells were more frequent in atria than ventricles. Expression of ALDH1A1 isozyme transcripts was highest in ALDHvery-br cells, intermediate in ALDHbr cells, and lowest in ALDHdim cells. ALDH1A2 expression was highest in ALDHvery-br cells, intermediate in ALDHdim cells, and lowest in ALDHbr cells. ALDH1A3 and ALDH2 expression was detectable in ALDHvery-br and ALDHbr cells, unlike ALDHdim cells, albeit at lower levels compared with ALDH1A1 and ALDH1A2. Freshly isolated ALDHbr cells were enriched for cells expressing stem cell antigen-1, CD34, CD90, CD44, and CD106. ALDHbr cells, unlike ALDHdim cells, could be grown in culture for more than 40 passages. They expressed sarcomeric α-actinin and could be differentiated along multiple mesenchymal lineages. However, the proportion of ALDHbr cells declined with cell passage. In conclusion, the cardiac-derived ALDHbr population is enriched for progenitor cells that exhibit mesenchymal progenitor-like characteristics and can be expanded in culture. The regenerative potential of cardiac-derived ALDHbr cells remains to be evaluated. PMID:23484127

  17. Avoiding sports-related sudden cardiac death in children with congenital channelopathy : Recommendations for sports activities.

    PubMed

    Lang, C N; Steinfurt, J; Odening, K E

    2017-04-01

    For the past few years, children affected by an inherited channelopathy have been counseled to avoid (recreational) sports activities and all competitive sports so as to prevent exercise-induced arrhythmia and sudden cardiac death. An increased understanding of the pathophysiological mechanisms, better anti-arrhythmic strategies, and, in particular, more epidemiological data on exercise-induced arrhythmia in active athletes with channelopathies have changed the universal recommendation of "no sports," leading to revised, less strict, and more differentiated guidelines (published by the American Heart Association/American College of Cardiology in 2015). In this review, we outline the disease- and genotype-specific mechanisms of exercise-induced arrhythmia; give an overview of trigger-, symptom-, and genotype-dependent guidance in sports activities for children with long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), or short QT syndrome (SQTS); and highlight the novelties in the current guidelines compared with previous versions. While it is still recommended for patients with LQT1 and CPVT (even when asymptomatic) and all symptomatic LQTS patients (independent of genotype) to avoid any competitive and high-intensity sports, other LQTS patients successfully treated with anti-arrhythmic therapies and phenotype-negative genotype-positive patients may be allowed to perform sports at different activity levels - provided they undergo regular, sophisticated evaluations to detect any changes in arrhythmogenic risk.

  18. 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.

  19. A critical role of cardiac fibroblast-derived exosomes in activating renin angiotensin system in cardiomyocytes.

    PubMed

    Lyu, Linmao; Wang, Hui; Li, Bin; Qin, Qingyun; Qi, Lei; Nagarkatti, Mitzi; Nagarkatti, Prakash; Janicki, Joseph S; Wang, Xing Li; Cui, Taixing

    2015-12-01

    Chronic activation of the myocardial renin angiotensin system (RAS) elevates the local level of angiotensin II (Ang II) thereby inducing pathological cardiac hypertrophy, which contributes to heart failure. However, the precise underlying mechanisms have not been fully delineated. Herein we report a novel paracrine mechanism between cardiac fibroblasts (CF)s and cardiomyocytes whereby Ang II induces pathological cardiac hypertrophy. In cultured CFs, Ang II treatment enhanced exosome release via the activation of Ang II receptor types 1 (AT1R) and 2 (AT2R), whereas lipopolysaccharide, insulin, endothelin (ET)-1, transforming growth factor beta (TGFβ)1 or hydrogen peroxide did not. The CF-derived exosomes upregulated the expression of renin, angiotensinogen, AT1R, and AT2R, downregulated angiotensin-converting enzyme 2, and enhanced Ang II production in cultured cardiomyocytes. In addition, the CF exosome-induced cardiomyocyte hypertrophy was blocked by both AT1R and AT2R antagonists. Exosome inhibitors, GW4869 and dimethyl amiloride (DMA), inhibited CF-induced cardiomyocyte hypertrophy with little effect on Ang II-induced cardiomyocyte hypertrophy. Mechanistically, CF exosomes upregulated RAS in cardiomyocytes via the activation of mitogen-activated protein kinases (MAPKs) and Akt. Finally, Ang II-induced exosome release from cardiac fibroblasts and pathological cardiac hypertrophy were dramatically inhibited by GW4869 and DMA in mice. These findings demonstrate that Ang II stimulates CFs to release exosomes, which in turn increase Ang II production and its receptor expression in cardiomyocytes, thereby intensifying Ang II-induced pathological cardiac hypertrophy. Accordingly, specific targeting of Ang II-induced exosome release from CFs may serve as a novel therapeutic approach to treat cardiac pathological hypertrophy and heart failure.

  20. 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.

  1. 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

  2. Activated NHE1 is required to induce early cardiac hypertrophy in mice.

    PubMed

    Mraiche, Fatima; Oka, Tatsujiro; Gan, Xiaohong T; Karmazyn, Morris; Fliegel, Larry

    2011-06-01

    The Na+/H+ exchanger isoform 1 (NHE1) has been implicated as being causal in cardiac hypertrophy and the protein level and activity are elevated in the diseased myocardium. However, it is unclear whether mere elevation of the protein is sufficient for cardiac pathology, or whether activation of the protein is required. In this study, we examined the comparative effects of elevation of wild type and activated NHE1. Two mouse transgenic models that expressed either a wild type NHE1 protein or an activated NHE1 protein were characterized. Expression of activated NHE1 caused significant increases in heart weight to body weight, apoptosis, cross-sectional area, interstitial fibrosis and decreased cardiac performance. Expression of wild type NHE1 caused a much milder pathology. When we examined 2 or 10-week-old mouse hearts, there was neither elevation of calcineurin levels nor increased phosphorylation of ERK or p38 in either NHE1 transgenic mouse line. Expression of activated NHE1 in intact mice caused an increased sensitivity to phenylephrine-induced hypertrophy. Our results show that expression of activated NHE1 promotes cardiac hypertrophy to a much greater degree than elevated levels of wild type NHE1 alone. In addition, expression of activated NHE1 promotes greater sensitivity to neurohormonal stimulation. The results suggest that activation of NHE1 is a key component that accentuates NHE1-induced myocardial pathology.

  3. Assessment of pain during rest and during activities in the postoperative period of cardiac surgery

    PubMed Central

    de Mello, Larissa Coelho; Rosatti, Silvio Fernando Castro; Hortense, Priscilla

    2014-01-01

    Objective to assess the intensity and site of pain after Cardiac Surgery through sternotomy during rest and while performing five activities. Method descriptive study with a prospective cohort design. A total of 48 individuals participated in the study. A Multidimensional Scale for Pain Assessment was used. Results postoperative pain from cardiac surgery was moderate during rest and decreased over time. Pain was also moderate during activities performed on the 1st and 2nd postoperative days and decreased from the 3rd postoperative day, with the exception of coughing, which diminished only on the 6th postoperative day. Coughing, turning over, deep breathing and rest are presented in decreased order of intensity. The region of the sternum was the most frequently reported site of pain. Conclusion the assessment of pain in the individuals who underwent cardiac surgery during rest and during activities is extremely important to adapt management and avoid postoperative complications and delayed surgical recovery. PMID:24553714

  4. Detection of myocardial degeneration with point-of-care cardiac troponin assays and histopathology in lambs with white muscle disease.

    PubMed

    Gunes, Vehbi; Ozcan, Kadir; Citil, Mehmet; Onmaz, Ali C; Erdogan, Hidayet M

    2010-06-01

    The aim of this study was to evaluate the use of human cardiac troponin-I (cTn-I) and cardiac troponin-T (cTn-T) kits for the determination of myocardial degeneration in lambs suffering from white muscle disease (WMD). Cardiac troponin (cTn) analyses and necropsy were performed on 12 lambs with acute WMD. Only cTn analyses were tested in six healthy lambs. cTn-I and cTn-T tests were positive for all lambs with WMD, but negative in healthy lambs. Necropsy revealed that the cardiac and skeletal muscles of lambs with WMD had chalky white lesions, which appeared as necrosis and calcification in histopathology. The histopathological findings of the heart muscle and increased cTn in lambs with WMD suggested that marked myocardial degeneration may be detected by point-of-care cTn assays in lambs.

  5. 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

  6. 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.

  7. Activation of PKN mediates survival of cardiac myocytes in the heart during ischemia/reperfusion

    PubMed Central

    Takagi, Hiromitsu; Hsu, Chiao-Po; Kajimoto, Katsuya; Shao, Dan; Yang, Yanfei; Maejima, Yasuhiro; Zhai, Peiyong; Yehia, Ghassan; Yamada, Chikaomi; Zablocki, Daniela; Sadoshima, Junichi

    2011-01-01

    Rationale The function of PKN, a stress-activated protein kinase, in the heart is poorly understood. Objective We investigated the functional role of PKN during myocardial ischemia/reperfusion (I/R). Methods and Results PKN is phosphorylated at Thr774 in hearts subjected to ischemia and reperfusion. Myocardial infarction/area at risk (MI/AAR) produced by 45 min ischemia and 24 hours reperfusion was significantly smaller in transgenic mice with cardiac specific overexpression of constitutively active (CA) PKN (Tg-CAPKN) than in non-transgenic (NTg) mice (15 ± 5 vs 38 ± 5%, p<0.01). The number of TUNEL positive nuclei was significantly lower in Tg-CAPKN (0.3 ± 0.2 vs 1.0 ± 0.2%, p<0.05). Both MI/AAR (63 ± 9 vs 45 ± 8%, p<0.05) and the number of TUNEL positive cells (7.9 ± 1.0 vs 1.3 ± 0.9%, p<0.05) were greater in transgenic mice with cardiac specific overexpression of dominant negative PKN (Tg-DNPKN) than in NTg mice. Thr774 phosphorylation of PKN was also observed in response to H2O2 in cultured cardiac myocytes. Stimulation of PKN prevented, whereas inhibition of PKN aggravated cell death induced by H2O2, suggesting that the cell protective effect of PKN is cell-autonomous in cardiac myocytes. PKN induced phosphorylation of alpha B crystallin and increased cardiac proteasome activity. The infarct reducing effect in Tg-CAPKN mice was partially inhibited by epoxomicin, a proteasome inhibitor. Conclusion PKN is activated by I/R and inhibits apoptosis of cardiac myocytes, thereby protecting the heart from I/R injury. PKN mediates phosphorylation of alpha B crystallin and stimulation of proteasome activity, which in part mediates the protective effect of PKN in the heart. PMID:20595653

  8. HRVanalysis: A Free Software for Analyzing Cardiac Autonomic Activity.

    PubMed

    Pichot, Vincent; Roche, Frédéric; Celle, Sébastien; Barthélémy, Jean-Claude; Chouchou, Florian

    2016-01-01

    Since the pioneering studies of the 1960s, heart rate variability (HRV) has become an increasingly used non-invasive tool for examining cardiac autonomic functions and dysfunctions in various populations and conditions. Many calculation methods have been developed to address these issues, each with their strengths and weaknesses. Although, its interpretation may remain difficult, this technique provides, from a non-invasive approach, reliable physiological information that was previously inaccessible, in many fields including death and health prediction, training and overtraining, cardiac and respiratory rehabilitation, sleep-disordered breathing, large cohort follow-ups, children's autonomic status, anesthesia, or neurophysiological studies. In this context, we developed HRVanalysis, a software to analyse HRV, used and improved for over 20 years and, thus, designed to meet laboratory requirements. The main strength of HRVanalysis is its wide application scope. In addition to standard analysis over short and long periods of RR intervals, the software allows time-frequency analysis using wavelet transform as well as analysis of autonomic nervous system status on surrounding scored events and on preselected labeled areas. Moreover, the interface is designed for easy study of large cohorts, including batch mode signal processing to avoid running repetitive operations. Results are displayed as figures or saved in TXT files directly employable in statistical softwares. Recordings can arise from RR or EKG files of different types such as cardiofrequencemeters, holters EKG, polygraphs, and data acquisition systems. HRVanalysis can be downloaded freely from the Web page at: https://anslabtools.univ-st-etienne.fr HRVanalysis is meticulously maintained and developed for in-house laboratory use. In this article, after a brief description of the context, we present an overall view of HRV analysis and we describe the methodological approach of the different techniques provided

  9. HRVanalysis: A Free Software for Analyzing Cardiac Autonomic Activity

    PubMed Central

    Pichot, Vincent; Roche, Frédéric; Celle, Sébastien; Barthélémy, Jean-Claude; Chouchou, Florian

    2016-01-01

    Since the pioneering studies of the 1960s, heart rate variability (HRV) has become an increasingly used non-invasive tool for examining cardiac autonomic functions and dysfunctions in various populations and conditions. Many calculation methods have been developed to address these issues, each with their strengths and weaknesses. Although, its interpretation may remain difficult, this technique provides, from a non-invasive approach, reliable physiological information that was previously inaccessible, in many fields including death and health prediction, training and overtraining, cardiac and respiratory rehabilitation, sleep-disordered breathing, large cohort follow-ups, children's autonomic status, anesthesia, or neurophysiological studies. In this context, we developed HRVanalysis, a software to analyse HRV, used and improved for over 20 years and, thus, designed to meet laboratory requirements. The main strength of HRVanalysis is its wide application scope. In addition to standard analysis over short and long periods of RR intervals, the software allows time-frequency analysis using wavelet transform as well as analysis of autonomic nervous system status on surrounding scored events and on preselected labeled areas. Moreover, the interface is designed for easy study of large cohorts, including batch mode signal processing to avoid running repetitive operations. Results are displayed as figures or saved in TXT files directly employable in statistical softwares. Recordings can arise from RR or EKG files of different types such as cardiofrequencemeters, holters EKG, polygraphs, and data acquisition systems. HRVanalysis can be downloaded freely from the Web page at: https://anslabtools.univ-st-etienne.fr HRVanalysis is meticulously maintained and developed for in-house laboratory use. In this article, after a brief description of the context, we present an overall view of HRV analysis and we describe the methodological approach of the different techniques provided

  10. Acute ischemic stroke after cardiac catheterization: the protamine low-dose recombinant tissue plasminogen activator pathway.

    PubMed

    Guevara, Carlos; Quijada, Alonso; Rosas, Carolina; Bulatova, Katya; Lara, Hugo; Nieto, Elena; Morales, Marcelo

    2016-05-20

    Intravenous thrombolysis is the preferred treatment for acute ischemic stroke; however, it remains unestablished in the area of cardiac catheterization. We report three patients with acute ischemic stroke after cardiac catheterization. After reversing the anticoagulant effect of unfractionated heparin with protamine, all of the patients were successfully off-label thrombolyzed with reduced doses of intravenous recombinant tissue plasminogen activator (0.6 mg/kg). This dose was preferred to reduce the risk of symptomatic cerebral or systemic bleeding. The sequential pathway of protamine recombinant tissue plasminogen activator at reduced doses may be safer for reducing intracranial or systemic bleeding events, whereas remaining efficacious for the treatment of acute ischemic stroke after cardiac catheterization.

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

    PubMed

    Land, Sander; 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

    2015-12-08

    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.

  12. The modulation of cardiac progenitor cell function by hydrogel-dependent Notch1 activation.

    PubMed

    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

    2014-09-01

    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.

  13. 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

  14. Cardiac monitoring for detection of atrial fibrillation after TIA: A systematic review and meta-analysis.

    PubMed

    Korompoki, Eleni; Del Giudice, Angela; Hillmann, Steffi; Malzahn, Uwe; Gladstone, David J; Heuschmann, Peter; Veltkamp, Roland

    2017-01-01

    Background and purpose The detection rate of atrial fibrillation has not been studied specifically in transient ischemic attack (TIA) patients although extrapolation from ischemic stroke may be inadequate. We conducted a systematic review and meta-analysis to determine the rate of newly diagnosed atrial fibrillation using different methods of ECG monitoring in TIA. Methods A comprehensive literature search was performed following a pre-specified protocol the PRISMA statement. Prospective observational studies and randomized controlled trials were considered that included TIA patients who underwent cardiac monitoring for >12 h. Primary outcome was frequency of detection of atrial fibrillation ≥30 s. Analyses of subgroups and of duration and type of monitoring were performed. Results Seventeen studies enrolling 1163 patients were included. The pooled atrial fibrillation detection rate for all methods was 4% (95% CI: 2-7%). Yield of monitoring was higher in selected (higher age, more extensive testing for arrhythmias before enrolment, or presumed cardioembolic/cryptogenic cause) than in unselected cohorts (7% vs 3%). Pooled mean atrial fibrillation detection rates rose with duration of monitoring: 4% (24 h), 5% (24 h to 7 days) and 6% (>7 days), respectively. Yield of non-invasive was significantly lower than that of invasive monitoring (4% vs. 11%). Significant heterogeneity was observed among studies (I(2)=60.61%). Conclusion This first meta-analysis of atrial fibrillation detection in TIA patients finds a lower atrial fibrillation detection rate in TIA than reported for IS and TIA cohorts in previous meta-analyses. Prospective studies are needed to determine actual prevalence of atrial fibrillation and optimal diagnostic procedure for atrial fibrillation detection in TIA.

  15. 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.

  16. Inhibition of a signaling pathway in cardiac muscle cells by active mitogen-activated protein kinase kinase.

    PubMed Central

    Thorburn, J; Carlson, M; Mansour, S J; Chien, K R; Ahn, N G; Thorburn, A

    1995-01-01

    Signaling via the Ras pathway involves sequential activation of Ras, Raf-1, mitogen-activated protein kinase kinase (MKK), and the extracellular signal-regulated (ERK) group of mitogen-activated protein (MAP) kinases. Expression from the c-Fos, atrial natriuretic factor (ANF), and myosin light chain-2 (MLC-2) promoters during phenylephrine-induced cardiac muscle cell hypertrophy requires activation of this pathway. Furthermore, constitutively active Ras or Raf-1 can mimic the action of phenylephrine in inducing expression from these promoters. In this study, we tested whether constitutively active MKK, the molecule immediately downstream of Raf, was sufficient to induce expression. Expression of constitutively active MKK induce ERK2 kinase activity and caused expression from the c-Fos promoter, but did not significantly activate expression of reporter genes under the control of either the ANF or MLC-2 promoters. Expression of CL100, a phosphatase that inactivates ERKs, prevented expression from all of the promoters. Taken together, these data suggest that ERK activation is required for expression from the Fos, ANF, and MLC-2 promoters but MKK and ERK activation is sufficient for expression only from the Fos promoter. Constitutively active MKK synergized with phenylephrine to increase expression from a c-Fos- or an AP1-driven reporter. However, active MKK inhibited phenylephrine- and Raf-1-induced expression from the ANF and MLC-2 promoters. A DNA sequence in the MLC-2 promoter that is a target for inhibition by active MKK, but not CL100, was mapped to a previously characterized DNA element (HF1) that is responsible for cardiac specificity. Thus, activation of cardiac gene expression during phenylephrine-induced hypertrophy requires ERK activation but constitutive activation by MKK can inhibit expression by targeting a DNA element that controls the cardiac specificity of gene expression. PMID:8589450

  17. Cardiac arrest in rodents: maximal duration compatible with a recovery of neuronal activity.

    PubMed

    Charpak, S; Audinat, E

    1998-04-14

    We report here that during a permanent cardiac arrest, rodent brain tissue is "physiologically" preserved in situ in a particular quiescent state. This state is characterized by the absence of electrical activity and by a critical period of 5-6 hr during which brain tissue can be reactivated upon restoration of a simple energy (glucose/oxygen) supply. In rat brain slices prepared 1-6 hr after cardiac arrest and maintained in vitro for several hours, cells with normal morphological features, intrinsic membrane properties, and spontaneous synaptic activity were recorded from various brain regions. In addition to functional membrane channels, these neurons expressed mRNA, as revealed by single-cell reverse transcription-PCR, and could synthesize proteins de novo. Slices prepared after longer delays did not recover. In a guinea pig isolated whole-brain preparation that was cannulated and perfused with oxygenated saline 1-2 hr after cardiac arrest, cell activity and functional long-range synaptic connections could be restored although the electroencephalogram remained isoelectric. Perfusion of the isolated brain with the gamma-aminobutyric acid A receptor antagonist picrotoxin, however, could induce self-sustained temporal lobe epilepsy. Thus, in rodents, the duration of cardiac arrest compatible with a short-term recovery of neuronal activity is much longer than previously expected. The analysis of the parameters that regulate this duration may bring new insights into the prevention of postischemic damages.

  18. 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 ...

  19. 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.

  20. Vagal cardiac activity in essential hypertension: the effects of metoprolol and ramipril.

    PubMed

    Vesalainen, R K; Kantola, I M; Airaksinen, K E; Tahvanainen, K U; Kaila, T J

    1998-06-01

    Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both beta-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1-2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.

  1. Class III PI3K-mediated prolonged activation of autophagy plays a critical role in the transition of cardiac hypertrophy to heart failure.

    PubMed

    Yu, Peng; Zhang, Yangyang; Li, Chuanfu; Li, Yuehua; Jiang, Surong; Zhang, Xiaojin; Ding, Zhengnian; Tu, Fei; Wu, Jun; Gao, Xiang; Li, Liu

    2015-07-01

    Pathological cardiac hypertrophy often leads to heart failure. Activation of autophagy has been shown in pathological hypertrophic hearts. Autophagy is regulated positively by Class III phosphoinositide 3-kinase (PI3K). However, it is unknown whether Class III PI3K plays a role in the transition of cardiac hypertrophy to heart failure. To address this question, we employed a previously established cardiac hypertrophy model in heat shock protein 27 transgenic mice which shares common features with several types of human cardiomyopathy. Age-matched wild-type mice served as control. Firstly, a prolonged activation of autophagy, as reflected by autophagosome accumulation, increased LC3 conversion and decreased p62 protein levels, was detected in hypertrophic hearts from adaptive stage to maladaptive stage. Moreover, morphological abnormalities in myofilaments and mitochondria were presented in the areas accumulated with autophagosomes. Secondly, activation of Class III PI3K Vacuolar protein sorting 34 (Vps34), as demonstrated by upregulation of Vps34 expression, increased interaction of Vps34 with Beclin-1, and deceased Bcl-2 expression, was demonstrated in hypertrophic hearts from adaptive stage to maladaptive stage. Finally, administration with Wortmaninn, a widely used autophagy inhibitor by suppressing Class III PI3K activity, significantly decreased autophagy activity, improved morphologies of intracellular apartments, and most importantly, prevented progressive cardiac dysfunction in hypertrophic hearts. Collectively, we demonstrated that Class III PI3K plays a central role in the transition of cardiac hypertrophy to heart failure via a prolonged activation of autophagy in current study. Class III PI3K may serve as a potential target for the treatment and management of maladaptive cardiac hypertrophy.

  2. Expression and assembly of active human cardiac troponin in Escherichia coli.

    PubMed

    Lassalle, Michael W

    2013-02-01

    Cardiomyopathy-related mutations in human cardiac troponin subunits, including troponin C (hcTnC), troponin I (hcTnI), and troponin T (hcTnT), are well-documented. Recently, it has been recognised that human cardiac troponin (hcTn) is a sophisticated allosteric system. Therefore, the effect of drugs on this protein complex should be studied with assembled hcTn rather than a short fragment of a subunit or the subunit itself. Here, we describe the expression and assembly of active hcTn in Escherichia coli, a novel method that is rapid and simple, and produces large amounts of functional hcTn.

  3. 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

  4. Endogenous circadian rhythm in human motor activity uncoupled from circadian influences on cardiac dynamics.

    PubMed

    Ivanov, Plamen Ch; Hu, Kun; Hilton, Michael F; Shea, Steven A; Stanley, H Eugene

    2007-12-26

    The endogenous circadian pacemaker influences key physiologic functions, such as body temperature and heart rate, and is normally synchronized with the sleep/wake cycle. Epidemiological studies demonstrate a 24-h pattern in adverse cardiovascular events with a peak at approximately 10 a.m. It is unknown whether this pattern in cardiac risk is caused by a day/night pattern of behaviors, including activity level and/or influences from the internal circadian pacemaker. We recently found that a scaling index of cardiac vulnerability has an endogenous circadian peak at the circadian phase corresponding to approximately 10 a.m., which conceivably could contribute to the morning peak in cardiac risk. Here, we test whether this endogenous circadian influence on cardiac dynamics is caused by circadian-mediated changes in motor activity or whether activity and heart rate dynamics are decoupled across the circadian cycle. We analyze high-frequency recordings of motion from young healthy subjects during two complementary protocols that decouple the sleep/wake cycle from the circadian cycle while controlling scheduled behaviors. We find that static activity properties (mean and standard deviation) exhibit significant circadian rhythms with a peak at the circadian phase corresponding to 5-9 p.m. ( approximately 9 h later than the peak in the scale-invariant index of heartbeat fluctuations). In contrast, dynamic characteristics of the temporal scale-invariant organization of activity fluctuations (long-range correlations) do not exhibit a circadian rhythm. These findings suggest that endogenous circadian-mediated activity variations are not responsible for the endogenous circadian rhythm in the scale-invariant structure of heartbeat fluctuations and likely do not contribute to the increase in cardiac risk at approximately 10 a.m.

  5. Small-conductance Ca2+ -activated K+ channels and cardiac arrhythmias.

    PubMed

    Zhang, Xiao-Dong; Lieu, Deborah K; Chiamvimonvat, Nipavan

    2015-08-01

    Small-conductance Ca2+ -activated K+ (SK, KCa2) channels are unique in that they are gated solely by changes in intracellular Ca2+ and, hence, function to integrate intracellular Ca2+ and membrane potentials on a beat-to-beat basis. Recent studies have provided evidence for the existence and functional significance of SK channels in the heart. Indeed, our knowledge of cardiac SK channels has been greatly expanded over the past decade. Interests in cardiac SK channels are further driven by recent studies suggesting the critical roles of SK channels in human atrial fibrillation, the SK channel as a possible novel therapeutic target in atrial arrhythmias, and upregulation of SK channels in heart failure in animal models and in human heart failure. However, there remain critical gaps in our knowledge. Specifically, blockade of SK channels in cardiac arrhythmias has been shown to be both antiarrhythmic and proarrhythmic. This contemporary review provides an overview of the literature on the role of cardiac SK channels in cardiac arrhythmias and serves as a discussion platform for the current clinical perspectives. At the translational level, development of SK channel blockers as a new therapeutic strategy in the treatment of atrial fibrillation and the possible proarrhythmic effects merit further considerations and investigations.

  6. Pharmacological inhibition of FAAH activity in rodents: A promising pharmacological approach for psychological-cardiac comorbidity?

    PubMed

    Carnevali, Luca; Rivara, Silvia; Nalivaiko, Eugene; Thayer, Julian F; Vacondio, Federica; Mor, Marco; Sgoifo, Andrea

    2017-03-01

    Numerous studies have documented a link between psychological disorders and cardiac disease. Yet, no systematic attempts have been made to develop pharmacological approaches for mood and anxiety disorders that could also be beneficial for cardiac health. The endocannabinoid system has been implicated in the regulation of stress, emotional behavior and cardiovascular function. General preclinical findings indicate that the endocannabinoid anandamide modulates physiological and behavioral stress responses and may also protect the heart from arrhythmias. Moreover, recent experimental studies suggest that pharmacological enhancement of anandamide signaling via inhibition of its degrading enzyme fatty acid amide hydrolase (FAAH) exerts anxiolytic- and antidepressive-like effects and improves cardiac autonomic function and the electrical stability of the myocardium in rodent models that reproduce aspects of human psychological/cardiac comorbidity. Here we summarize and discuss such experimental findings, which might guide future preclinical studies towards a systematic evaluation of the therapeutic potential of pharmacological approaches that target FAAH activity for the treatment of the comorbidity between psychological disorders and cardiac disease.

  7. A polyaniline based ultrasensitive potentiometric immunosensor for cardiac troponin complex detection.

    PubMed

    Zhang, Qi; Prabhu, Alok; San, Avdar; Al-Sharab, Jafar F; Levon, Kalle

    2015-10-15

    An ultrasensitive immunosensor based on potentiometric ELISA for the detection of a cardiac biomarker, troponin I-T-C (Tn I-T-C) complex, was developed. The sensor fabrication involves typical sandwich ELISA procedures, while the final signal readout was achieved using open circuit potentiometry (OCP). Glassy carbon (GC) working electrodes were first coated with emulsion-polymerized polyaniline/dinonylnaphthalenesulfonic acid (PANI/DNNSA) and the coated surface was utilized as a transducer layer on which sandwich ELISA incubation steps were performed. An enzymatic reaction between o-phenylenediamine (OPD) and hydrogen peroxide (H2O2) was catalyzed by horseradish peroxidase (HRP) labeled on the secondary antibodies. The polymer transducer charged state was mediated through electron (e(-)) and charge transfers between the transducer and charged species generated by the same enzymatic reaction. Such a change in the polymer transducer led to potential variations against an Ag/AgCl reference electrode as a function of Tn I-T-C complex concentration during incubations. The sequence of OPD and H2O2 additions, electrochemical properties of the PANI/DNNSA layer and non-specific binding prevention were all crucial factors for the assay performance. Under optimized conditions, the assay has a low limit of detection (LOD) (< 5 pg/mL or 56 fM), a wide dynamic range (> 6 orders of magnitude), high repeatability (coefficient of variance < 8% for all concentrations higher than 5 pg/mL) and a short detection time (< 10 min).

  8. Chronic Alcohol Intoxication Is Not Accompanied by an Increase in Calpain Proteolytic Activity in Cardiac Muscle of Rats.

    PubMed

    Gritsyna, Yu V; Salmov, N N; Bobylev, A G; Fadeeva, I S; Fesenko, N I; Sadikova, D G; Kukushkin, N I; Podlubnaya, Z A; Vikhlyantsev, I M

    2017-02-01

    Enzymatic activity of Ca2+-dependent calpain proteases as well as the content and gene expression of μ-calpain (activated by micromolar calcium ion concentrations), calpastatin (inhibitor of calpains), and titin (substrate for calpains) were investigated in cardiac muscles of rats subjected to chronic alcoholization for 3 and 6 months. There was no increase in the "heart weight/body weight" parameter indicating development of heart hypertrophy in the alcoholized rats, while a decreasing trend was observed for this parameter in the rats after 6-month modeling of alcoholic cardiomyopathy, which indicated development of atrophic changes in the myocardium. Fluorometric measurements conducted using the Calpain Activity Assay Kit did not reveal any changes in total calpain activity in protein extracts of cardiac muscles of the rats alcoholized for 3 and 6 months. Western blot analysis did not show reliable changes in the contents of μ-calpain and calpastatin, and SDS-PAGE did not reveal any decrease in the titin content in the myocardium of rats after the chronic alcohol intoxication. Autolysis of μ-calpain was also not verified, which could indicate that proteolytic activity of this enzyme in myocardium of chronically alcoholized rats is not enhanced. Using Pro-Q Diamond staining, changes in phosphorylation level of titin were not detected in cardiac muscle of rats after chronic alcoholization during three and six months. A decrease in µ-calpain and calpastatin mRNA content (~1.3-fold, p ≤ 0.01 and ~1.9-fold, p ≤ 0.01, respectively) in the myocardium of rats alcoholized for 3 months and decrease in calpastatin mRNA (~1.4-fold, p ≤ 0.01) in animals alcoholized for 6 months was demonstrated using real-time PCR. These results indicate negative effect of chronic alcohol intoxication on expression of the abovementioned genes.

  9. Cardiac catheterization

    MedlinePlus

    Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization; CAD - cardiac catheterization; Coronary artery disease - cardiac catheterization; Heart valve - cardiac catheterization; Heart failure - ...

  10. Mesenchymal stem cell-loaded cardiac patch promotes epicardial activation and repair of the infarcted myocardium.

    PubMed

    Wang, Qiang-Li; Wang, Hai-Jie; Li, Zhi-Hua; Wang, Yong-Li; Wu, Xue-Ping; Tan, Yu-Zhen

    2017-02-28

    Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF-1α, Tβ4, VEGF and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF-1α, Tβ4, VEGF, SDF-1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial-derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c-kit(+) cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c-kit(+) cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.

  11. Early detection of cardiac dysfunction in the type 1 diabetic heart using speckle-tracking based strain imaging.

    PubMed

    Shepherd, Danielle L; Nichols, Cody E; Croston, Tara L; McLaughlin, Sarah L; Petrone, Ashley B; Lewis, Sara E; Thapa, Dharendra; Long, Dustin M; Dick, Gregory M; Hollander, John M

    2016-01-01

    Enhanced sensitivity in echocardiographic analyses may allow for early detection of changes in cardiac function beyond the detection limits of conventional echocardiographic analyses, particularly in a small animal model. The goal of this study was to compare conventional echocardiographic measurements and speckle-tracking based strain imaging analyses in a small animal model of type 1 diabetes mellitus. Conventional analyses revealed differences in ejection fraction, fractional shortening, cardiac output, and stroke volume in diabetic animals relative to controls at 6-weeks post-diabetic onset. In contrast, when assessing short- and long-axis speckle-tracking based strain analyses, diabetic mice showed changes in average systolic radial strain, radial strain rate, radial displacement, and radial velocity, as well as decreased circumferential and longitudinal strain rate, as early as 1-week post-diabetic onset and persisting throughout the diabetic study. Further, we performed regional analyses for the LV and found that the free wall region was affected in both the short- and long-axis when assessing radial dimension parameters. These changes began 1-week post-diabetic onset and remained throughout the progression of the disease. These findings demonstrate the use of speckle-tracking based strain as an approach to elucidate cardiac dysfunction from a global perspective, identifying left ventricular cardiac regions affected during the progression of type 1 diabetes mellitus earlier than contractile changes detected by conventional echocardiographic measurements.

  12. 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

  13. 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.

  14. Cardiac failure detection in 30 minutes: new approach based on gold nanoparticles.

    PubMed

    Namdari, Mehrdad; Negahdari, Babak; Cheraghi, Mostafa; Aiyelabegan, Hammed T; Eatmadi, Ali

    2017-03-07

    Cardiac failure occurs when heart is unable to pump sufficiently to maintain blood flow to meet the body's needs. The aim of this work is to detect highly expressed genes: follistatin-related protein 1 (FSTL1) in heart failure within 30 minutes, using gold nanoparticles. Gold nanoparticles were prepared by citrate reduction of HAuCl4 3H2O; probe sequence was designed based on the FSTL1 gene region. Preparation of gold nanoprobes (AuNPs) proceeded by treating all the containers with DEPC-treated water, followed by reduction and conjugation. Transmission electron microscopy shows that AuNPs were 10-15 nm in size. The concentration of the nanoprobes was 2.1 nM, and they bind to target. Real-time PCR shows an over-expression of FSTL1 and FSTL3 in heart failure (p < .05). Our data showed that elevated expression of the FSTL1 and FSTL3 is a marker of heart failure as detected within 30 minutes by the synthesised AuNPs; the method is accurate and fast.

  15. 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.

  16. Central command does not decrease cardiac parasympathetic efferent nerve activity during spontaneous fictive motor activity in decerebrate cats.

    PubMed

    Kadowaki, Akito; Matsukawa, Kanji; Wakasugi, Rie; Nakamoto, Tomoko; Liang, Nan

    2011-04-01

    To examine whether withdrawal of cardiac vagal efferent nerve activity (CVNA) predominantly controls the tachycardia at the start of exercise, the responses of CVNA and cardiac sympathetic efferent nerve activity (CSNA) were directly assessed during fictive motor activity that occurred spontaneously in unanesthetized, decerebrate cats. CSNA abruptly increased by 71 ± 12% at the onset of the motor activity, preceding the tachycardia response. The increase in CSNA lasted for 4-5 s and returned to the baseline, even though the motor activity was not ended. The increase of 6 ± 1 beats/min in heart rate appeared with the same time course of the increase in CSNA. In contrast, CVNA never decreased but increased throughout the motor activity, in parallel with a rise in mean arterial blood pressure (MAP). The peak increase in CVNA was 37 ± 9% at 5 s after the motor onset. The rise in MAP gradually developed to 21 ± 2 mmHg and was sustained throughout the spontaneous motor activity. Partial sinoaortic denervation (SAD) blunted the baroreflex sensitivity of the MAP-CSNA and MAP-CVNA relationship to 22-33% of the control. Although partial SAD blunted the initial increase in CSNA to 53% of the control, the increase in CSNA was sustained throughout the motor activity. In contrast, partial SAD almost abolished the increase in CVNA during the motor activity, despite the augmented elevation of 31 ± 1 mmHg in MAP. Because afferent inputs from both muscle receptors and arterial baroreceptors were absent or greatly attenuated in the partial SAD condition, only central command was operating during spontaneous fictive motor activity in decerebrate cats. Therefore, it is likely that central command causes activation of cardiac sympathetic outflow but does not produce withdrawal of cardiac parasympathetic outflow during spontaneous motor activity.

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

    PubMed Central

    Yilbas, Ayse E.; Hamilton, Alison; Wang, Yingjian; Mach, Hymn; Lacroix, Natascha; Davis, Darryl R.; Chen, Jihong; Li, Qiao

    2014-01-01

    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. PMID:24790981

  18. 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

  19. Pharmacological modulations of cardiac ultra-rapid and slowly activating delayed rectifier currents: potential antiarrhythmic approaches.

    PubMed

    Islam, Mohammed A

    2010-01-01

    Despite the emerging new insights into our understandings of the cellular mechanisms underlying cardiac arrhythmia, medical therapy for this disease remains unsatisfactory. Atrial fibrillation (AF), the most prevalent arrhythmia, is responsible for significant morbidity and mortality. On the other hand, ventricular fibrillation results in sudden cardiac deaths in many instances. Prolongation of cardiac action potential (AP) is a proven principle of antiarrhythmic therapy. Class III antiarrhythmic agents prolong AP and QT interval by blocking rapidly activating delayed rectifier current (I(Kr)). However, I(Kr) blocking drugs carry the risk of life-threatening proarrhythmia. Recently, modulation of atrial-selective ultra-rapid delayed rectifier current (I(Kur)), has emerged as a novel therapeutic approach to treat AF. A number of I(Kur) blockers are being evaluated for the treatment of AF. The inhibition of slowly activating delayed rectifier current (I(Ks)) has also been proposed as an effective and safer antiarrhythmic approach because of its distinguishing characteristics that differ in remarkable ways from other selective class III agents. Selective I(Ks) block may prolong AP duration (APD) at rapid rates without leading to proarrhythmia. This article reviews the pathophysiological roles of I(Kur) and I(Ks) in cardiac repolarization and the implications of newly developed I(Kur) and I(Ks) blocking agents as promising antiarrhythmic approaches. Several recent patents pertinent to antiarrhythmic drug development have been discussed. Further research will be required to evaluate the efficacy and safety of these agents in the clinical setting.

  20. 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.

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

    PubMed

    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 Ca(2+)-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.

  2. 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.

  3. 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

  4. Early improvement in cardiac function detected by tissue Doppler and strain imaging after melphalan-dexamethasone therapy in a 51-year old subject with severe cardiac amyloidosis.

    PubMed

    Ballo, Piercarlo; Motto, Andrea; Corsini, Francesca; Orlandini, Francesco; Mondillo, Sergio

    2008-11-12

    We report the case of a 51-year old man with symptoms of heart failure due to severe cardiac amyloidosis, in whom treatment with melphalan and dexamethasone yielded significant improvement in clinical status and both systolic and diastolic left ventricular (LV) function over a 12-week follow-up. The improvement in LV performance was detected by Tissue Doppler (TD) and strain analysis, despite no changes in standard indices such as ejection fraction and Doppler pattern of mitral inflow. Color TD-derived myocardial velocity and deformation indices also revealed a reduction in intra-ventricular early diastolic asynchrony after therapy. In addition, an improvement in intra-ventricular systolic synchrony was detected by strain rate and strain, but not by color TD velocity imaging. These findings suggest that treatment with melphalan and dexamethasone may improve symptoms of heart failure and LV performance in subjects with cardiac amyloidosis, and that TD and particularly strain imaging could represent useful techniques to monitor the effect of therapy on LV function in the follow-up of these patients.

  5. Ionizing radiation regulates cardiac Ca handling via increased ROS and activated CaMKII.

    PubMed

    Sag, Can M; Wolff, Hendrik A; Neumann, Kay; Opiela, Marie-Kristin; Zhang, Juqian; Steuer, Felicia; Sowa, Thomas; Gupta, Shamindra; Schirmer, Markus; Hünlich, Mark; Rave-Fränk, Margret; Hess, Clemens F; Anderson, Mark E; Shah, Ajay M; Christiansen, Hans; Maier, Lars S

    2013-11-01

    Ionizing radiation (IR) is an integral part of modern multimodal anti-cancer therapies. IR involves the formation of reactive oxygen species (ROS) in targeted tissues. This is associated with subsequent cardiac dysfunction when applied during chest radiotherapy. We hypothesized that IR (i.e., ROS)-dependently impaired cardiac myocytes' Ca handling might contribute to IR-dependent cardiocellular dysfunction. Isolated ventricular mouse myocytes and the mediastinal area of anaesthetized mice (that included the heart) were exposed to graded doses of irradiation (sham 4 and 20 Gy) and investigated acutely (after ~1 h) as well as chronically (after ~1 week). IR induced a dose-dependent effect on myocytes' systolic function with acutely increased, but chronically decreased Ca transient amplitudes, which was associated with an acutely unaltered but chronically decreased sarcoplasmic reticulum (SR) Ca load. Likewise, in vivo echocardiography of anaesthetized mice revealed acutely enhanced left ventricular contractility (strain analysis) that declined after 1 week. Irradiated myocytes showed persistently increased diastolic SR Ca leakage, which was acutely compensated by an increase in SR Ca reuptake. This was reversed in the chronic setting in the face of slowed relaxation kinetics. As underlying cause, acutely increased ROS levels were identified to activate Ca/calmodulin-dependent protein kinase II (CaMKII). Accordingly, CaMKII-, but not PKA-dependent phosphorylation sites of the SR Ca release channels (RyR2, at Ser-2814) and phospholamban (at Thr-17) were found to be hyperphosphorylated following IR. Conversely, ROS-scavenging as well as CaMKII-inhibition significantly attenuated CaMKII-activation, disturbed Ca handling, and subsequent cellular dysfunction upon irradiation. Targeted cardiac irradiation induces a biphasic effect on cardiac myocytes Ca handling that is associated with chronic cardiocellular dysfunction. This appears to be mediated by increased oxidative

  6. 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

  7. Influence of Physical Activity on Hypertension and Cardiac Structure and Function.

    PubMed

    Hegde, Sheila M; Solomon, Scott D

    2015-10-01

    The global burden of hypertension is rising and accounts for substantial morbidity and mortality. Lifestyle factors such as diet and physical inactivity contribute to this burden, further highlighting the need for prevention efforts to curb this public health epidemic. Regular physical activity is associated with lower blood pressure, reduced cardiovascular risk, and cardiac remodeling. While exercise and hypertension can both be associated with the development of left ventricular hypertrophy (LVH), the cardiac remodeling from hypertension is pathologic with an associated increase in myocyte hypertrophy, fibrosis, and risk of heart failure and mortality, whereas LVH in athletes is generally non-pathologic and lacks the fibrosis seen in hypertension. In hypertensive patients, physical activity has been associated with paradoxical regression or prevention of LVH, suggesting a mechanism by which exercise can benefit hypertensive patients. Further studies are needed to better understand the mechanisms underlying the benefits of physical activity in the hypertensive heart.

  8. Influence of Physical Activity on Hypertension and Cardiac Structure and Function

    PubMed Central

    Hegde, Sheila M.; Solomon, Scott D.

    2015-01-01

    The global burden of hypertension is rising and accounts for substantial morbidity and mortality. Lifestyle factors such as diet and physical inactivity contribute to this burden, further highlighting the need for prevention efforts to curb this public health epidemic. Regular physical activity is associated with lower blood pressure, reduced cardiovascular risk, and cardiac remodeling. While exercise and hypertension can both be associated with the development of left ventricular hypertrophy (LVH), the cardiac remodeling from hypertension is pathologic with an associated increase in myocyte hypertrophy, fibrosis, and risk of heart failure and mortality, whereas LVH in athletes is generally non-pathologic and lacks the fibrosis seen in hypertension. In hypertensive patients, physical activity has been associated with paradoxical regression or prevention of LVH, suggesting a mechanism by which exercise can benefit hypertensive patients. Further studies are needed to better understand the mechanisms underlying the benefits of physical activity in the hypertensive heart. PMID:26277725

  9. Individual differences in behavioral activation and cardiac vagal control influence affective startle modification.

    PubMed

    Yang, Xiao; Friedman, Bruce H

    2017-04-01

    The startle response (SR) has a close relationship with stress responses. Startle modification (SRM) has been widely used to study stress disorders (e.g., posttraumatic stress disorder). The framework of the behavioral inhibition and activation systems (BIS/BAS) has been thought to correspond with withdrawal and approach motivational processes underlying affective SRM and can influence stress reactivity. Vagally-mediated cardiac activity as indexed by heart rate variability (HRV) has been associated with SRM and regulatory processes during stress. In the present study, the influence of individual differences in the BIS/BAS and resting HRV on affective SRM were examined. Eighty-six subjects viewed affective pictures while acoustic SR stimuli were delivered. Individual differences in motivation were measured by the BIS/BAS scales. The magnitude of SR was assessed as electromyographic activity of the SR eyeblink during pictures of different valences. Resting HRV was derived from electrocardiography. In contrast to previous studies, the present results showed that startle inhibition and potentiation were related to BAS and HRV, but not to BIS. There was also an interaction of BAS and HRV, indicating that the relationship between HRV and SRM strengthened as BAS scores decreased. The present findings suggest that BAS may relate to both withdrawal and approach, and trait stress reactivity is influenced by BAS and cardiac vagal activity. In addition, BAS moderates the relationship between cardiac vagal activity and SRM. These findings have both theoretical and practical implications for the study of SRM, stress disorders, and health.

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

    PubMed Central

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

    2016-01-01

    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 Ca2+/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 Ca2+/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 Ca2+/CaM, cMLCK has constitutive activity that is stimulated by Ca2+/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

  11. Motion detection and amelioration in a dedicated cardiac solid-state CZT SPECT device.

    PubMed

    Kennedy, John A; William Strauss, H

    2017-04-01

    A solid-state cadmium zinc tellurium (CZT) dedicated multipinhole cardiac camera which acquires all views simultaneously has been introduced for myocardial SPECT acquisition. We report a method to detect and ameliorate patient motion artifacts in myocardial perfusion imaging (MPI) studies recorded with this device. To detect motion, a myocardial phantom study was recorded, and at mid-scan, the phantom was moved stepwise along each of 6 orthogonal directions, causing MPI artifacts. Using QPS software (Cedars-Sinai) and an in-house normal database, displacements giving artifactual perfusion defects (total perfusion deficit score, TPD, >5 %) were all 1.5 cm or greater (11.2 ± 1.3 % for 1.5 cm). List mode data were reframed into 10-s steps, and the norm of the changes in center of mass among the 19 projections (32 × 32 matrix, pixel size 2.46 mm) was used as a motion index. Rejection of misregistered data gave artifact-free reconstructions (TPD = 1.0 ± 0.8 %) in phantom scans and reduced blur in a rest/stress clinical study. Blur on the patient's stress scan was consistent with increased motion compared to rest (motion index of 4.4 vs. 3.0 pixels, respectively). For CZT cameras that acquire data from multiple views simultaneously, motion during MPI can cause clinically significant artifacts. Reframing acquisitions into discrete time intervals enables the detection of motion and its amelioration, improving diagnostic accuracy.

  12. Dictionary-driven Ischemia Detection from Cardiac Phase-Resolved Myocardial BOLD MRI at Rest

    PubMed Central

    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) w.r.t. 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

  13. Human Infrastructure & Human Activity Detection

    DTIC Science & Technology

    2007-07-01

    researchers are developing sensors systems that detect footfalls (or gait ) [1, 2], speech, the spectral response of human skin, etc [3]. Little work has...cone shaped field of view. • Visible imagers can capture color or grayscale video for human gait detection and object recognition. • Infrared...his/her gait produces a unique signature [13]. Indirect means of detecting personnel include the usage of acoustic, seismic, magnetic, passive

  14. PPARdelta activation normalizes cardiac substrate metabolism and reduces right ventricular hypertrophy in congestive heart failure.

    PubMed

    Jucker, Beat M; Doe, Christopher P; Schnackenberg, Christine G; Olzinski, Alan R; Maniscalco, Kristeen; Williams, Carolyn; Hu, Tom C-C; Lenhard, Stephen C; Costell, Melissa; Bernard, Roberta; Sarov-Blat, Lea; Steplewski, Klaudia; Willette, Robert N

    2007-07-01

    Previously, it was shown that selective deletion of peroxisome proliferator activated receptor delta (PPARdelta) in the heart resulted in a cardiac lipotoxicity, hypertrophy, and heart failure. The aim of the present study was to determine the effects of chronic and selective pharmacological activation of PPARdelta in a model of congestive heart failure. PPARdelta-specific agonist treatment (GW610742X at 30 and 100 mg/kg/day for 6-9 weeks) was initiated immediately postmyocardial infarction (MI) in Sprague-Dawley rats. Magnetic resonance imaging/spectroscopy was used to assess cardiac function and energetics. A 1-(13)C glucose clamp was performed to assess relative cardiac carbohydrate versus fat oxidation. Additionally, cardiac hemodynamics and reverse-transcription polymerase chain reaction gene expression analysis was performed. MI rats had significantly reduced left ventricle (LV) ejection fractions and whole heart phosphocreatine/adenosine triphosphate ratio compared with Sham animals (reduction of 43% and 14%, respectively). However, GW610742X treatment had no effect on either parameter. In contrast, the decrease in relative fat oxidation rate observed in both LV and right ventricle (RV) following MI (decrease of 58% and 54%, respectively) was normalized in a dose-dependent manner following treatment with GW610742X. These metabolic changes were associated with an increase in lipid transport/metabolism target gene expression (eg, CD36, CPT1, UCP3). Although there was no difference between groups in LV weight or infarct size measured upon necropsy, there was a dramatic reduction in RV hypertrophy and lung congestion (decrease of 22-48%, P<0.01) with treatment which was associated with a >7-fold decrease (P<0.05) in aterial natriuretic peptide gene expression in RV. Diuretic effects were not observed with GW610742X. In conclusion, chronic treatment with a selective PPARdelta agonist normalizes cardiac substrate metabolism and reduces RV hypertrophy and pulmonary

  15. Does the use of the Advanced Medical Priority Dispatch System affect cardiac arrest detection?

    PubMed Central

    Heward, A; Damiani, M; Hartley-Sharpe, C

    2004-01-01

    Methods: A two stage study was undertaken. The first, compared cases coded as "cardiac arrest" and found by the responding ambulance to be in cardiac arrest before the implementation of AMPDS. This was compared with cases triaged as "cardiac arrest" and found to be in cardiac arrest across three years after AMPDS implementation. The second stage compared AMPDS compliance, over a 32 month period against the percentage of cardiac arrest calls that were found to be cardiac arrest upon the ambulance arrival. The correlation coefficient was calculated and analysed for statistical significance. Findings: AMPDS resulted in a 200% rise in the number of patients accurately identified as suffering from cardiac arrest. A relation was identified between identification and AMPDS compliance (r2 = 0.65, p = 0.001). Discussion: The implementation of AMPDS increased accurate identification of patients in cardiac arrest. Additionally, the relation between factors identified suggests compliance with protocol is an important factor in the accurate recognition of patient conditions. PMID:14734398

  16. The Prognostic Value of Using Ultrasonography in Cardiac Resuscitation of Patients with Cardiac Arrest

    PubMed Central

    Bolvardi, Ehsan; Pouryaghobi, Seyyed Mohsen; Farzane, Roohye; Chokan, Niaz Mohamad Jafari; Ahmadi, Koorosh; Reihani, Hamidreza

    2016-01-01

    Cardiopulmonary arrest is the final result of many diseases and therefore, need for a careful implementation of cardiopulmonary resuscitation (CPR) protocols in these cases is undeniably important. The introduction of ultrasound into the emergency department has potentially allowed the addition of an extra data point in the decision about when to cease cardiopulmonary resuscitation (CPR). The aim of this study is to evaluate the ability of cardiac ultrasonography performed by emergency physicians to predict resuscitation outcome in adult cardiac arrest patients. Ultrasonographic examination of the subxiphoid cardiac area was made immediately after admission to the emergency department with pulseless cardiac arrest. Sonographic cardiac activity was defined as any detectable motion within the heart including the atria, ventricles or valves. Successful resuscitation was defined as: return of spontaneous circulation for ≥ 20 min; return of breathing; palpable pulse; measurable blood pressure. The present study includes 159 patients. The presence of sonographic cardiac activity at the beginning of resuscitation was significantly associated with a successful outcome (41/49 [83.7%] versus 15/110 [13.6%] patients without cardiac activity at the beginning of resuscitation). Ultrasonographic detection of cardiac activity may be useful in determining prognosis during cardiac arrest. Further studies are needed to elucidate the predictive value of ultrasonography in cardiac arrest patients. PMID:27829827

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. Activation of single cardiac and skeletal ryanodine receptor channels by flash photolysis of caged Ca2+.

    PubMed Central

    Györke, S; Vélez, P; Suárez-Isla, B; Fill, M

    1994-01-01

    Single ryanodine-sensitive sarcoplasmic reticulum (SR) Ca2+ release channels isolated from rabbit skeletal and canine cardiac muscle were reconstituted in planar lipid bilayers. Single channel activity was measured in simple solutions (no ATP or Mg2+) with 250 mM symmetrical Cs+ as charge carrier. A laser flash was used to photolyze caged-Ca2+ (DM-nitrophen) in a small volume directly in front of the bilayer. The free [Ca2+] in this small volume and in the bulk solution was monitored with Ca2+ electrodes. This setup allowed fast, calibrated free [Ca2+] stimuli to be applied repetitively to single SR Ca2+ release channels. A standard photolytically induced free [Ca2+] step (pCa 7-->6) was applied to both the cardiac and skeletal release channels. The rate of channel activation was determined by fitting a single exponential to ensemble currents generated from at least 50 single channel sweeps. The time constants of activation were 1.43 +/- 0.65 ms (mean +/- SD; n = 5) and 1.28 +/- 0.61 ms (n = 5) for cardiac and skeletal channels, respectively. This study presents a method for defining the fast Ca2+ regulation kinetics of single SR Ca2+ release channels and shows that the activation rate of skeletal SR Ca2+ release channels is consistent with a role for CICR in skeletal muscle excitation-contraction coupling. PMID:8075325

  2. 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.

  3. Feasibility and Accuracy of Cardiac Right-to-Left-Shunt Detection in Children by New Transpulmonary Ultrasound Dilution Method.

    PubMed

    Boehne, Martin; Baustert, Mathias; Paetzel, Verena; Boethig, Dietmar; Köditz, Harald; Dennhardt, Nils; Beerbaum, Philipp; Bertram, Harald

    2017-01-01

    Transpulmonary ultrasound dilution (TPUD) method, a novel indicator dilution (ID) technique for cardiac output measurement, detects and quantifies shunts, both in children and adults. However, its accuracy and reproducibility in cardiac right-to-left-shunt (RLS) detection have not been investigated. In a prospective observational study, we assessed the validity of TPUD algorithm for RLS detection in children with congenital heart disease (CHD) and proven RLS in comparison with controls without shunts between February 2010 and October 2011. As TPUD algorithm was unknown, we tested ID curve morphology, appearance time (AT) and central blood volume index (CBVI) as diagnostic criteria. TPUD identified RLS correctly in all 16 RLS subjects [median age (range): 18 months (1 month-15 years 6 months)] and excluded RLS in all 26 controls [74 months (8 months to 17 years 4 months)]. AT was significantly shorter in RLS (P < 0.05). Applying only AT (93.8 % sensitivity, 92.3 % specificity), RLS can be detected by shortening of ≥1.69 s of normally expected AT. RLS ID curves were subdivided into four morphological categories: (I) hump-on-upslope (n = 5); (II) double-hump (n = 3); (III) pseudonormal (n = 3); (IV) abnormal width (n = 5). No correlation was found between specific type of CHD and RLS categories. CBVI measurements were significantly smaller in RLS categories I-III than in controls (P < 0.05). TPUD appears to be a valid method for cardiac RLS detection. Shortened AT and low CBVI are reliable parameters for RLS identification. RLS categories have specific implications for cardiac output, blood volume and RLS fraction measurements. TPUD is valuable to monitor shunt direction and magnitude to optimise haemodynamic and respiratory therapy.

  4. 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.

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

    PubMed

    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

    2005-01-15

    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 (14)C-glucose and (3)H-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.

  6. Myoglobin-deficient mice activate a distinct cardiac gene expression program in response to isoproterenol-induced hypertrophy.

    PubMed

    Molojavyi, Andrei; Lindecke, Antje; Raupach, Annika; Moellendorf, Sarah; Köhrer, Karl; Gödecke, Axel

    2010-04-01

    Myoglobin knockout mice (myo-/-) adapt to the loss of myoglobin by the activation of a variety of compensatory mechanisms acting on the structural and functional level. To analyze to what extent myo-/- mice would tolerate cardiac stress we used the model of chronic isoproterenol application to induce cardiac hypertrophy in myo-/- mice and wild-type (WT) controls. After 14 days of isoproterenol infusion cardiac hypertrophy in WT and myo-/- mice reached a similar level. WT mice developed lung edema and left ventricular dilatation suggesting the development of heart failure. In contrast, myo-/- mice displayed conserved cardiac function and no signs of left ventricular dilatation. Analysis of the cardiac gene expression profiles using 40K mouse oligonucleotide arrays showed that isoproterenol affected the expression of 180 genes in WT but only 92 genes of myo-/- hearts. Only 40 of these genes were regulated in WT as well as in myo-/- hearts. In WT hearts a pronounced induction of genes of the extracellular matrix occurred suggesting a higher level of cardiac remodeling. myo-/- hearts showed altered transcription of genes involved in carbon metabolism, inhibition of apoptosis and muscular repair. Interestingly, a subset of genes that was altered in myo-/- mice already under basal conditions was differentially expressed in WT hearts under isoproterenol treatment. In summary, our data show a high capacity of myoglobin-deficient mice to adapt to catecholamine induced cardiac stress which is associated with activation of a distinct cardiac gene expression program.

  7. A New Efficient Method for Detecting Phase Singularity in Cardiac Fibrillation

    PubMed Central

    Hwang, Minki; Lim, Byounghyun; Joung, Boyoung; Pak, Hui-Nam

    2016-01-01

    Background The point of phase singularity (PS) is considered to represent a spiral wave core or a rotor in cardiac fibrillation. Computational efficiency is important for detection of PS in clinical electrophysiology. We developed a novel algorithm for highly efficient and robust detection of PS. Methods In contrast to the conventional method, which calculates PS based on the line integral of the phase around a PS point equal to ±2π (the Iyer-Gray method), the proposed algorithm (the location-centric method) looks for the phase discontinuity point at which PS actually occurs. We tested the efficiency and robustness of these two methods in a two-dimensional mathematical model of atrial fibrillation (AF), with and without remodeling of ionic currents. Results 1. There was a significant association, in terms of the Hausdorff distance (3.30 ± 0.0 mm), between the PS points measured using the Iyer-Gray and location-centric methods, with almost identical PS trajectories generated by the two methods. 2. For the condition of electrical remodeling of AF (0.3 × ICaL), the PS points calculated by the two methods were satisfactorily co-localized (with the Hausdorff distance of 1.64 ± 0.09 mm). 3. The proposed location-centric method was substantially more efficient than the Iyer-Gray method, with a 28.6-fold and 28.2-fold shorter run times for the control and remodeling scenarios, respectively. Conclusion We propose a new location-centric method for calculating PS, which is robust and more efficient compared with the conventionally used method. PMID:27907144

  8. 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

  9. 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.

  10. Automatic detection of cardiac cycle and measurement of the mitral annulus diameter in 4D TEE images

    NASA Astrophysics Data System (ADS)

    Graser, Bastian; Hien, Maximilian; Rauch, Helmut; Meinzer, Hans-Peter; Heimann, Tobias

    2012-02-01

    Mitral regurgitation is a wide spread problem. For successful surgical treatment quantification of the mitral annulus, especially its diameter, is essential. Time resolved 3D transesophageal echocardiography (TEE) is suitable for this task. Yet, manual measurement in four dimensions is extremely time consuming, which confirms the need for automatic quantification methods. The method we propose is capable of automatically detecting the cardiac cycle (systole or diastole) for each time step and measuring the mitral annulus diameter. This is done using total variation noise filtering, the graph cut segmentation algorithm and morphological operators. An evaluation took place using expert measurements on 4D TEE data of 13 patients. The cardiac cycle was detected correctly on 78% of all images and the mitral annulus diameter was measured with an average error of 3.08 mm. Its full automatic processing makes the method easy to use in the clinical workflow and it provides the surgeon with helpful information.

  11. 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.

  12. Individual-, family-, community-, and policy-level impact of a school-based cardiovascular risk detection screening program for children in underserved, rural areas: the CARDIAC Project.

    PubMed

    Cottrell, Lesley; John, Collin; Murphy, Emily; Lilly, Christa L; Ritchie, Susan K; Elliott, Eloise; Minor, Valerie; Neal, William A

    2013-01-01

    The Coronary Artery Risk Detection In Appalachian Communities (CARDIAC) Project has screened more than 80,000 children (10-12 years) for cardiovascular and diabetes risk factors over the past 15 years. Simultaneous referral and intervention efforts have also contributed to the overall program impact. In this study, we examined evidence of programmatic impact in the past decade at the individual, family, community, and policy levels from child screening outcomes, referral rates, participation in subsequent services, and policies that embed the activities of the project as a significant element. Within this period of time, fifth-grade overweight and obesity rates were maintained at a time when rates elsewhere increased. 107 children were referred for additional screening and treatment for probable familial hypercholesterolemia (FH); 82 family members were subsequently screened in family-based screening efforts. 58 grants were distributed throughout the state for community-appropriate obesity intervention. A state wellness policy embedded CARDIAC as the method of assessment and national child cholesterol screening guidelines were impacted by CARDIAC findings. The sustainability and successful impact of this school-based program within a largely underserved, rural Appalachian state are also discussed.

  13. Development of a patch type embedded cardiac function monitoring system using dual microprocessor for arrhythmia detection in heart disease patient.

    PubMed

    Jang, Yongwon; Noh, Hyung Wook; Lee, I B; Jung, Ji-Wook; Song, Yoonseon; Lee, Sooyeul; Kim, Seunghwan

    2012-01-01

    A patch type embedded cardiac function monitoring system was developed to detect arrhythmias such as PVC (Premature Ventricular Contraction), pause, ventricular fibrillation, and tachy/bradycardia. The overall system is composed of a main module including a dual processor and a Bluetooth telecommunication module. The dual microprocessor strategy minimizes power consumption and size, and guarantees the resources of embedded software programs. The developed software was verified with standard DB, and showed good performance.

  14. Diminazene aceturate enhances ACE2 activity and attenuates ischemia-induced cardiac pathophysiology

    PubMed Central

    Qi, YanFei; Zhang, Juan; Cole-Jeffrey, Colleen T; Shenoy, Vinayak; Espejo, Andrew; Hanna, Mina; Song, Chunjuan; Pepine, Carl J; Katovich, Michael J; Raizada, Mohan K

    2013-01-01

    Angiotensin-converting enzyme 2 (ACE2) plays a critical role against myocardial infarction (MI). We hypothesized that activation of intrinsic ACE2 would be protective against ischemia-induced cardiac pathophysiology. Diminazine aceturate (DIZE), a small molecule ACE2 activator has been used to evaluate this hypothesis. DIZE (15 mg/kg/day, s.c.) was injected two days prior to MI surgery and continued throughout the study-period. MI rats showed a 62% decrease in fractional shortening (FS,%) [control (Con): 51.1 ± 3.2; DIZE alone (D) : 52.1 ± 3.2; MI (M): 19.1± 3.0], a 55% decrease in contractility (dP/dtmax mmHg/s) (Con: 9480 ± 425.3; D: 9585 ± 597.4; M: 4251 ± 657.7), and a 27% increase in ventricular hypertrophy [VH, mg/mm (Con: 26.5 ± 1.5; D: 26.9 ± 1.4; M: 33.4± 1.1)]. DIZE attenuated the MI-induced decrease in FS by 89%, improved dP/dtmax by 92%, and reversed VH by 18%. MI also significantly increased ACE and angiotensin type 1 receptor levels while decreased ACE2 activity by 40% (Con: 246.2 ± 25.1; D: 254.2 ± 20.6; M: 148.9 ± 29.2, RFU/min), which was reversed by DIZE treatment. Thus, DIZE treatment decreased the infarct area, attenuated LV remodeling post-MI and restored normal balance of the cardiac renin angiotensin system. Additionally, DIZE treatment increased circulating endothelial progenitor cells, increased engraftment of cardiac progenitor cells and decreased inflammatory cells in peri-infarct cardiac regions. All of the beneficial effects associated with DIZE treatment were abolished by C-16, an ACE2 inhibitor. Collectively, DIZE and DIZE-like small molecules may represent promising new therapeutic agents for MI. PMID:23959549

  15. Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells

    PubMed Central

    Vajravelu, Bathri N.; Moktar, Afsoon; Cao, Pengxiao; Moore, Joseph B.; Bolli, Roberto

    2017-01-01

    Although transplantation of c-kit+ cardiac progenitor cells (CPCs) significantly alleviates post-myocardial infarction left ventricular dysfunction, generation of cardiomyocytes by exogenous CPCs in the recipient heart has often been limited. Inducing robust differentiation would be necessary for improving the efficacy of the regenerative cardiac cell therapy. We assessed the hypothesis that differentiation of human c-kit+ CPCs can be enhanced by priming them with cardiac transcription factors (TFs). We introduced five different TFs (Gata4, MEF2C, NKX2.5, TBX5, and BAF60C) into CPCs, either alone or in combination, and then examined the expression of marker genes associated with the major cardiac cell types using quantitative RT-PCR. When introduced individually, Gata4 and TBX5 induced a subset of myocyte markers. Moreover, Gata4 alone significantly induced smooth muscle cell and fibroblast markers. Interestingly, these gene expression changes brought by Gata4 were also accompanied by morphological changes. In contrast, MEF2C and NKX2.5 were largely ineffective in initiating cardiac gene expression in CPCs. Surprisingly, introduction of multiple TFs in different combinations mostly failed to act synergistically. Likewise, addition of BAF60C to Gata4 and/or TBX5 did not further potentiate their effects on cardiac gene expression. Based on our results, it appears that GATA4 is able to potentiate gene expression programs associated with multiple cardiovascular lineages in CPCs, suggesting that GATA4 may be effective in priming CPCs for enhanced differentiation in the setting of stem cell therapy. PMID:28355297

  16. Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells.

    PubMed

    Al-Maqtari, Tareq; Hong, Kyung U; Vajravelu, Bathri N; Moktar, Afsoon; Cao, Pengxiao; Moore, Joseph B; Bolli, Roberto

    2017-01-01

    Although transplantation of c-kit+ cardiac progenitor cells (CPCs) significantly alleviates post-myocardial infarction left ventricular dysfunction, generation of cardiomyocytes by exogenous CPCs in the recipient heart has often been limited. Inducing robust differentiation would be necessary for improving the efficacy of the regenerative cardiac cell therapy. We assessed the hypothesis that differentiation of human c-kit+ CPCs can be enhanced by priming them with cardiac transcription factors (TFs). We introduced five different TFs (Gata4, MEF2C, NKX2.5, TBX5, and BAF60C) into CPCs, either alone or in combination, and then examined the expression of marker genes associated with the major cardiac cell types using quantitative RT-PCR. When introduced individually, Gata4 and TBX5 induced a subset of myocyte markers. Moreover, Gata4 alone significantly induced smooth muscle cell and fibroblast markers. Interestingly, these gene expression changes brought by Gata4 were also accompanied by morphological changes. In contrast, MEF2C and NKX2.5 were largely ineffective in initiating cardiac gene expression in CPCs. Surprisingly, introduction of multiple TFs in different combinations mostly failed to act synergistically. Likewise, addition of BAF60C to Gata4 and/or TBX5 did not further potentiate their effects on cardiac gene expression. Based on our results, it appears that GATA4 is able to potentiate gene expression programs associated with multiple cardiovascular lineages in CPCs, suggesting that GATA4 may be effective in priming CPCs for enhanced differentiation in the setting of stem cell therapy.

  17. Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction

    PubMed Central

    Tang, Juan; Shen, Yujun; Chen, Guilin; Wan, Qiangyou; Wang, Kai; Zhang, Jian; Qin, Jing; Liu, Guizhu; Zuo, Shengkai; Tao, Bo; Yu, Yu; Wang, Junwen; Lazarus, Michael; Yu, Ying

    2017-01-01

    Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6Clow and Ly6Chigh) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E2 is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6Clow Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signalling and subsequently inhibits Ly6Clow Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE2/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6Clow Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI. PMID:28256515

  18. Modeling of Cardiac Muscle Thin Films: Pre-stretch, Passive and Active Behavior

    PubMed Central

    Shim, Jongmin; Grosberg, Anna; Nawroth, Janna C.; Parker, Kevin Kit; Bertoldi, Katia

    2012-01-01

    Recent progress in tissue engineering has made it possible to build contractile bio-hybrid materials that undergo conformational changes by growing a layer of cardiac muscle on elastic polymeric membranes. Further development of such muscular thin films for building actuators and powering devices requires exploring several design parameters, which include the alignment of the cardiac myocytes and the thickness/Young’s modulus of elastomeric film. To more efficiently explore these design parameters, we propose a 3-D phenomenological constitutive model, which accounts for both the passive deformation including pre-stretch and the active behavior of the cardiomyocytes. The proposed 3-D constitutive model is implemented within a finite element framework, and can be used to improve the current design of bio-hybrid thin films and help developing bio-hybrid constructs capable of complex conformational changes. PMID:22236531

  19. Kruppel-like factor 4 protein regulates isoproterenol-induced cardiac hypertrophy by modulating myocardin expression and activity.

    PubMed

    Yoshida, Tadashi; Yamashita, Maho; Horimai, Chihiro; Hayashi, Matsuhiko

    2014-09-19

    Kruppel-like factor 4 (KLF4) plays an important role in vascular diseases, including atherosclerosis and vascular injury. Although KLF4 is expressed in the heart in addition to vascular cells, the role of KLF4 in cardiac disease has not been fully determined. The goals of this study were to investigate the role of KLF4 in cardiac hypertrophy and to determine the underlying mechanisms. Cardiomyocyte-specific Klf4 knockout (CM Klf4 KO) mice were generated by the Cre/LoxP technique. Cardiac hypertrophy was induced by chronic infusion of the β-adrenoreceptor agonist isoproterenol (ISO). Results showed that ISO-induced cardiac hypertrophy was enhanced in CM Klf4 KO mice compared with control mice. Accelerated cardiac hypertrophy in CM Klf4 KO mice was accompanied by the augmented cellular enlargement of cardiomyocytes as well as the exaggerated expression of fetal cardiac genes, including atrial natriuretic factor (Nppa). Additionally, induction of myocardin, a transcriptional cofactor regulating fetal cardiac genes, was enhanced in CM Klf4 KO mice. Interestingly, KLF4 regulated Nppa expression by modulating the expression and activity of myocardin, providing a mechanical basis for accelerated cardiac hypertrophy in CM Klf4 KO mice. Moreover, we showed that KLF4 mediated the antihypertrophic effect of trichostatin A, a histone deacetylase inhibitor, because ISO-induced cardiac hypertrophy in CM Klf4 KO mice was attenuated by olmesartan, an angiotensin II type 1 antagonist, but not by trichostatin A. These results provide novel evidence that KLF4 is a regulator of cardiac hypertrophy by modulating the expression and the activity of myocardin.

  20. Effects of Intracerebroventricularly (ICV) Injected Ghrelin on Cardiac Inducible Nitric Oxide Synthase Activity/Expression in Obese Rats.

    PubMed

    Sudar Milovanovic, E; Jovanovic, A; Misirkic-Marjanovic, M; Vucicevic, Lj; Janjetovic, K; Isenovic, E R

    2015-11-01

    The aim of this study was to examine the effects of ghrelin on regulation of cardiac inducible nitric oxide synthase (iNOS) activity/expression in high fat (HF), obese rats.For this study, male Wistar rats fed with HF diet (30% fat) for 4 weeks were injected every 24 h for 5 days intracerebroventricularly (ICV) with ghrelin (0.3 nmol/5 µl) or with an equal volume of phosphate buffered saline (PBS). Control rats were ICV injected with an equal volume of PBS. Glucose, insulin and nitric oxide (NO) concentrations were measured in serum, while arginase activity and citrulline concentrations were measured in heart lysate. Protein iNOS and regulatory subunit of nuclear factor-κB (NFκB-p65), phosphorylation of enzymes protein kinase B (Akt) at Ser(473), and extracellular signal-regulated kinases 1/2 (ERK1/2) at Tyr(202)/Tyr(204) were determined in heart lysate by Western blot. For gene expression of iNOS qRT-PCR was used.Results show significantly (p<0.01) higher serum NO production in ghrelin treated HF rats compared with HF rats. Ghrelin significantly reduced citrulline concentration (p<0.05) and arginase activity (p<0.01) in HF rats. In ghrelin treated HF rats, gene and protein expression of iNOS and NFκB-p65 levels were significantly (p<0.05) increased compared with HF rats. Increased phosphorylation of Akt (p<0.01) and decreased (p<0.05) ERK1/2 phosphorylation were detected in HF ghrelin treated rats compared with HF rats hearts.Results from this study indicate that exogenous ghrelin induces expression and activity of cardiac iNOS via Akt phosphorylation followed by NFκB activation in HF rats.

  1. In vitro activation of rat cardiac glucocorticoid antagonist- versus agonist-receptor complexes.

    PubMed

    Schmidt, T J; Diehl, E E

    1988-06-30

    The synthetic antiglucocorticoid RU 38486 interacts with cardiac cytoplasmic glucocorticoid receptors and competes for in vitro binding with the potent agonist triamcinolone acetonide. In addition to binding to receptors with high affinity, RU 38486 also facilitates the in vitro conformational change in the receptor which is a consequence of the physiologically relevant activation step during which the receptor is converted from a non DNA- to a DNA-binding form. This ability of RU 38486 to promote receptor activation is reflected by both the appropriate shift in the elution profile of [3H]RU 38486-receptor complexes from DEAE-cellulose as well as by an increased binding of these complexes to DNA-cellulose. Although less effective than triamcinolone acetonide, RU 38486 promotes in vitro receptor activation under a variety of experimental conditions, including incubation of labeled cardiac cytosols at 25 degrees C for 30 min or at 15 degrees C for 30 min in the presence of 5 mM pyridoxal 5'-phosphate. Once thermally activated, the cardiac [3H]triamcinolone acetonide and [3H]RU 38486-receptor complexes bind to nonspecific DNA-cellulose with the same relative affinities, as evidenced by the fact that 50% of both activated complexes are eluted at approx. 215-250 mM NaCl. Thus, this pure antiglucocorticoid does promote, at least to some extent, many of the crucial in vitro events including high-affinity binding, activation, and DNA binding which have been shown to be required to elicit a physiological response in vivo.

  2. Caveolae-specific activation loop between CaMKII and L-type Ca(2+) channel aggravates cardiac hypertrophy in α1-adrenergic stimulation.

    PubMed

    Tonegawa, Kota; Otsuka, Wataru; Kumagai, Shohei; Matsunami, Sachi; Hayamizu, Nao; Tanaka, Shota; Moriwaki, Kazumasa; Obana, Masanori; Maeda, Makiko; Asahi, Michio; Kiyonari, Hiroshi; Fujio, Yasushi; Nakayama, Hiroyuki

    2017-03-01

    Activation of CaMKII induces a myriad of biological processes and plays dominant roles in cardiac hypertrophy. Caveolar microdomain contains many calcium/calmodulin-dependent kinase II (CaMKII) targets, including L-type Ca(2+) channel (LTCC) complex, and serves as a signaling platform. The location of CaMKII activation is thought to be critical; however, the roles of CaMKII in caveolae are still elusive due to lack of methodology for the assessment of caveolae-specific activation. Our aim was to develop a novel tool for the specific analysis of CaMKII activation in caveolae and to determine the functional role of caveolar CaMKII in cardiac hypertrophy. To assess the caveolae-specific activation of CaMKII, we generated a fusion protein composed of phospholamban and caveolin-3 (cPLN-Cav3) and GFP fusion protein with caveolin-binding domain fused to CaMKII inhibitory peptide (CBD-GFP-AIP), which inhibits CaMKII activation specifically in caveolae. Caveolae-specific activation of CaMKII was detected using phosphospecific antibody for PLN (Thr(17)). Furthermore, adenoviral overexpression of LTCC β2a-subunit (β2a) in NRCMs showed its constitutive phosphorylation by CaMKII, which induces hypertrophy, and that both phosphorylation and hypertrophy are abolished by CBD-GFP-AIP expression, indicating that β2a phosphorylation occurs specifically in caveolae. Finally, β2a phosphorylation was observed after phenylephrine stimulation in β2a-overexpressing mice, and attenuation of cardiac hypertrophy after chronic phenylephrine stimulation was observed in nonphosphorylated mutant of β2a-overexpressing mice. We developed novel tools for the evaluation and inhibition of caveolae-specific activation of CaMKII. We demonstrated that phosphorylated β2a dominantly localizes to caveolae and induces cardiac hypertrophy after α1-adrenergic stimulation in mice.NEW & NOTEWORTHY While signaling in caveolae is thought to be important in cardiac hypertrophy, direct evidence is missing

  3. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury.

    PubMed

    Kawaguchi, Masanori; Takahashi, Masafumi; Hata, Takeki; Kashima, Yuichiro; Usui, Fumitake; Morimoto, Hajime; Izawa, Atsushi; Takahashi, Yasuko; Masumoto, Junya; Koyama, Jun; Hongo, Minoru; Noda, Tetsuo; Nakayama, Jun; Sagara, Junji; Taniguchi, Shun'ichiro; Ikeda, Uichi

    2011-02-15

    Background- Inflammation plays a key role in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury; however, the mechanism by which myocardial I/R induces inflammation remains unclear. Recent evidence indicates that a sterile inflammatory response triggered by tissue damage is mediated through a multiple-protein complex called the inflammasome. Therefore, we hypothesized that the inflammasome is an initial sensor for danger signal(s) in myocardial I/R injury. Methods and Results- We demonstrate that inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, is crucially involved in the initial inflammatory response after myocardial I/R injury. We found that inflammasomes are formed by I/R and that its subsequent activation of inflammasomes leads to interleukin-1β production, resulting in inflammatory responses such as inflammatory cell infiltration and cytokine expression in the heart. In mice deficient for apoptosis-associated speck-like adaptor protein and caspase-1, these inflammatory responses and subsequent injuries, including infarct development and myocardial fibrosis and dysfunction, were markedly diminished. Bone marrow transplantation experiments with apoptosis-associated speck-like adaptor protein-deficient mice revealed that inflammasome activation in bone marrow cells and myocardial resident cells such as cardiomyocytes or cardiac fibroblasts plays an important role in myocardial I/R injury. In vitro experiments revealed that hypoxia/reoxygenation stimulated inflammasome activation in cardiac fibroblasts, but not in cardiomyocytes, and that hypoxia/reoxygenation-induced activation was mediated through reactive oxygen species production and potassium efflux. Conclusions- Our results demonstrate the molecular basis for the initial inflammatory response after I/R and suggest that the inflammasome is a potential novel therapeutic target for preventing myocardial I/R injury.

  4. Dexamethasone-induced cardiac deterioration is associated with both calcium handling abnormalities and calcineurin signaling pathway activation.

    PubMed

    de Salvi Guimarães, Fabiana; de Moraes, Wilson Max Almeida Monteiro; Bozi, Luis Henrique Marchesi; Souza, Pâmela R; Antonio, Ednei Luiz; Bocalini, Danilo Sales; Tucci, Paulo José Ferreira; Ribeiro, Daniel Araki; Brum, Patricia Chakur; Medeiros, Alessandra

    2017-01-01

    Dexamethasone is a potent and widely used anti-inflammatory and immunosuppressive drug. However, recent evidences suggest that dexamethasone cause pathologic cardiac remodeling, which later impairs cardiac function. The mechanism behind the cardiotoxic effect of dexamethasone is elusive. The present study aimed to verify if dexamethasone-induced cardiotoxicity would be associated with changes in the cardiac net balance of calcium handling protein and calcineurin signaling pathway activation. Wistar rats (~400 g) were treated with dexamethasone (35 µg/g) in drinking water for 15 days. After dexamethasone treatment, we analyzed cardiac function, cardiomyocyte diameter, cardiac fibrosis, and the expression of proteins involved in calcium handling and calcineurin signaling pathway. Dexamethasone-treated rats showed several cardiovascular abnormalities, including elevated blood pressure, diastolic dysfunction, cardiac fibrosis, and cardiomyocyte apoptosis. Regarding the expression of proteins involved in calcium handling, dexamethasone increased phosphorylation of phospholamban at threonine 17, reduced protein levels of Na(+)/Ca(2+) exchanger, and had no effect on protein expression of Serca2a. Protein levels of NFAT and GATA-4 were increased in both cytoplasmic and nuclear faction. In addition, dexamethasone increased nuclear protein levels of calcineurin. Altogether our findings suggest that dexamethasone causes pathologic cardiac remodeling and diastolic dysfunction, which is associated with impaired calcium handling and calcineurin signaling pathway activation.

  5. Suppression of NLRP3 Inflammasome Activation Ameliorates Chronic Kidney Disease-Induced Cardiac Fibrosis and Diastolic Dysfunction

    PubMed Central

    Bugyei-Twum, Antoinette; Abadeh, Armin; Thai, Kerri; Zhang, Yanling; Mitchell, Melissa; Kabir, Golam; Connelly, Kim A.

    2016-01-01

    Cardiac fibrosis is a common finding in patients with chronic kidney disease. Here, we investigate the cardio-renal effects of theracurmin, a novel formulation of the polyphenolic compound curcumin, in a rat model of chronic kidney disease. Briefly, Sprague-Dawley rats were randomized to undergo sham or subtotal nephrectomy (SNx) surgery. At 3 weeks post surgery, SNx animals were further randomized to received theracurmin via once daily oral gavage or vehicle for 5 consecutive weeks. At 8 weeks post surgery, cardiac function was assessed via echocardiography and pressure volume loop analysis, followed by LV and renal tissue collection for analysis. SNx animals developed key hallmarks of renal injury including hypertension, proteinuria, elevated blood urea nitrogen, and glomerulosclerosis. Renal injury in SNx animals was also associated with significant diastolic dysfunction, macrophage infiltration, and cardiac NLRP3 inflammasome activation. Treatment of SNx animals with theracurmin improved structural and functional manifestations of cardiac injury associated with renal failure and also attenuated cardiac NLRP3 inflammasome activation and mature IL-1β release. Taken together, our findings suggest a significant role for the NLRP3 inflammasome in renal injury-induced cardiac dysfunction and presents inflammasome attenuation as a unique strategy to prevent adverse cardiac remodeling in the setting of chronic kidney disease. PMID:28000751

  6. Detection of Active Topology Probing Deception

    DTIC Science & Technology

    2015-09-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS DETECTION OF ACTIVE TOPOLOGY PROBING DECEPTION by Weiyou Nicholas Phua September 2015 Thesis...SUBTITLE DETECTION OF ACTIVE TOPOLOGY PROBING DECEPTION 5. FUNDING NUMBERS H98230221650 6. AUTHOR(S) Weiyou Nicholas Phua 7. PERFORMING ORGANIZATION NAME(S...intents, being able to infer the topology of a network is crucial to both operators and adversaries alike. Tracer- oute is a common active probing

  7. Metformin inhibits aldosterone-induced cardiac fibroblast activation, migration and proliferation in vitro, and reverses aldosterone+salt-induced cardiac fibrosis in vivo.

    PubMed

    Mummidi, Srinivas; Das, Nitin A; Carpenter, Andrea J; Kandikattu, Hemanthkumar; Krenz, Maike; Siebenlist, Ulrich; Valente, Anthony J; Chandrasekar, Bysani

    2016-09-01

    The overall goals of this study were to investigate whether metformin exerts anti-fibrotic effects in aldosterone (Aldo)+salt-treated wild type mouse hearts, and determine the underlying molecular mechanisms in isolated adult cardiac fibroblasts (CF). In vitro, Aldo induced CF activation, migration, and proliferation, and these effects were inhibited by metformin. Further, Aldo induced PPM1A (Protein Phosphatase Magnesium Dependent 1A) activation and inhibited AMPK phosphorylation. At a pharmacologically relevant concentration, metformin restored AMPK activation, and inhibited Aldo-induced Nox4/H2O2-dependent TRAF3IP2 induction, pro-inflammatory cytokine expression, and CF migration and proliferation. Further, metformin potentiated the inhibitory effects of spironolactone, a mineralocorticoid receptor antagonist, on Aldo-induced collagen expression, and CF migration and proliferation. These results were recapitulated in vivo, where metformin reversed Aldo+salt-induced oxidative stress, suppression of AMPK activation, TRAF3IP2 induction, pro-inflammatory cytokine expression, and cardiac fibrosis, without significantly modulating systolic blood pressure. These in vitro and in vivo data indicate that metformin has the potential to reduce adverse cardiac remodeling in hypertensive heart disease.

  8. Severe hypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoadrenal activation.

    PubMed

    Reno, Candace M; Daphna-Iken, Dorit; Chen, Y Stefanie; VanderWeele, Jennifer; Jethi, Krishan; Fisher, Simon J

    2013-10-01

    For people with insulin-treated diabetes, severe hypoglycemia can be lethal, though potential mechanisms involved are poorly understood. To investigate how severe hypoglycemia can be fatal, hyperinsulinemic, severe hypoglycemic (10-15 mg/dL) clamps were performed in Sprague-Dawley rats with simultaneous electrocardiogram monitoring. With goals of reducing hypoglycemia-induced mortality, the hypotheses tested were that: 1) antecedent glycemic control impacts mortality associated with severe hypoglycemia; 2) with limitation of hypokalemia, potassium supplementation could limit hypoglycemia-associated deaths; 3) with prevention of central neuroglycopenia, brain glucose infusion could prevent hypoglycemia-associated arrhythmias and deaths; and 4) with limitation of sympathoadrenal activation, adrenergic blockers could prevent hypoglycemia-induced arrhythmic deaths. Severe hypoglycemia-induced mortality was noted to be worsened by diabetes, but recurrent antecedent hypoglycemia markedly improved the ability to survive an episode of severe hypoglycemia. Potassium supplementation tended to reduce mortality. Severe hypoglycemia caused numerous cardiac arrhythmias including premature ventricular contractions, tachycardia, and high-degree heart block. Intracerebroventricular glucose infusion reduced severe hypoglycemia-induced arrhythmias and overall mortality. β-Adrenergic blockade markedly reduced cardiac arrhythmias and completely abrogated deaths due to severe hypoglycemia. Under conditions studied, sudden deaths caused by insulin-induced severe hypoglycemia were mediated by lethal cardiac arrhythmias triggered by brain neuroglycopenia and the marked sympathoadrenal response.

  9. 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.

  10. Large-deflection statics analysis of active cardiac catheters through co-rotational modelling.

    PubMed

    Peng Qi; Chen Qiu; Mehndiratta, Aadarsh; I-Ming Chen; Haoyong Yu

    2016-08-01

    This paper presents a co-rotational concept for large-deflection formulation of cardiac catheters. Using this approach, the catheter is first discretized with a number of equal length beam elements and nodes, and the rigid body motions of an individual beam element are separated from its deformations. Therefore, it is adequate for modelling arbitrarily large deflections of a catheter with linear elastic analysis at the local element level. A novel design of active cardiac catheter of 9 Fr in diameter at the beginning of the paper is proposed, which is based on the contra-rotating double helix patterns and is improved from the previous prototypes. The modelling section is followed by MATLAB simulations of various deflections when the catheter is exerted different types of loads. This proves the feasibility of the presented modelling approach. To the best knowledge of the authors, it is the first to utilize this methodology for large-deflection static analysis of the catheter, which will enable more accurate control of robot-assisted cardiac catheterization procedures. Future work would include further experimental validations.

  11. 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.

  12. Neurally released pituitary adenylate cyclase-activating polypeptide enhances guinea pig intrinsic cardiac neurone excitability.

    PubMed

    Tompkins, John D; Ardell, Jeffrey L; Hoover, Donald B; Parsons, Rodney L

    2007-07-01

    Intracellular recordings were made in vitro from guinea-pig cardiac ganglia to determine whether endogenous neuropeptides such as pituitary adenylate cyclase-activating polypeptide (PACAP) or substance P released during tetanic neural stimulation modulate cardiac neurone excitability and/or contribute to slow excitatory postsynaptic potentials (sEPSPs). When nicotinic and muscarinic receptors were blocked by hexamethonium and atropine, 20 Hz stimulation for 10 s initiated a sEPSP in all innervated neurones. In 40% of the cells, excitability was enhanced after termination of the sEPSP. This suggested that non-cholinergic receptor-mediated mechanisms contributed to the sEPSP and modulated neuronal excitability. Exogenous PACAP and substance P initiated a slow depolarization in the neurones whereas neuronal excitability was only increased by PACAP. When ganglia were treated with the PAC1 antagonist PACAP6-38 (500 nM), the sEPSP evoked by 20 Hz stimulation was reduced by approximately 50% and an enhanced excitability occurred in only 10% of the cells. These observations suggested that PACAP released from preganglionic nerve terminals during tetanic stimulation enhanced neuronal excitability and evoked sEPSPs. After addition of 1 nM PACAP to the bath, 7 of 9 neurones exhibited a tonic firing pattern whereas in untreated preparations, the neurons had a phasic firing pattern. PACAP6-38 (500 nM) diminished the increase in excitability caused by 1 nM PACAP so that only 4 of 13 neurones exhibited a tonic firing pattern and the other 9 cells retained a phasic firing pattern. These findings indicate that PACAP can be released by tetanic neural stimulation in vitro and increase the excitability of intrinsic cardiac neurones. We hypothesize that in vivo PACAP released during preganglionic firing may modulate neurotransmission within the intrinsic cardiac ganglia.

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

    PubMed

    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.

  14. 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.

  15. Molluscicidal activity of cardiac glycosides from Nerium indicum against Pomacea canaliculata and its implications for the mechanisms of toxicity.

    PubMed

    Dai, Lingpeng; Wang, Wanxian; Dong, Xinjiao; Hu, Renyong; Nan, Xuyang

    2011-09-01

    Cardiac glycosides from fresh leaves of Nerium indicum were evaluated for its molluscicidal activity against Pomacea canaliculata (golden apple snail: GAS) under laboratory conditions. The results showed that LC(50) value of cardiac glycosides against GAS was time dependent and the LC(50) value at 96 h was as low as 3.71 mg/L, which was comparable with that of metaldehyde at 72 h (3.88 mg/L). These results indicate that cardiac glycosides could be an effective molluscicide against GAS. The toxicological mechanism of cardiac glucosides on GAS was also evaluated through changes of selected biochemical parameters, including cholinesterase (ChE) and esterase (EST) activities, glycogen and protein contents in hepatopancreas tissues of GAS. Exposure to sublethal concentrations of cardiac glycosides, GAS showed lower activities of EST isozyme in the later stages of the exposure period as well as drastically decreased glycogen content, although total protein content was not affected at the end of 24 and 48 h followed by a significant depletion at the end of 72 and 96 h. The initial increase followed by a decline of ChE activity was also observed during the experiment. These results suggest that cardiac glycosides seriously impair normal physiological metabolism, resulting in fatal alterations in major biochemical constituents of hepatopancreas tissues of P. canaliculata.

  16. Is recombinant activated factor VII effective in the treatment of excessive bleeding after paediatric cardiac surgery?

    PubMed Central

    Okonta, Kelechi E.; Edwin, Frank; Falase, Bode

    2012-01-01

    A best evidence topic in paediatric cardiac surgery was written according to a structured protocol. The question addressed was whether recombinant activated factor VII was effective for the treatment of excessive bleeding after paediatric cardiac surgery. Altogether 150 papers were found using the reported search; 13 papers were identified that provided the best evidence to answer the question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these studies were tabulated. A total of 311 children experienced excessive bleeding following cardiac surgery that was refractory to the conventional methods of achieving haemostasis. One hundred and ninety-two patients received the rFVIIa while 116 were in control arm from five studies. The primary end-point was on chest tube drainage, the plasma prothrombin time, the activated partial thromboplastin time after the administration of rFVIIa and the secondary end-point was reduction of blood products transfusion. Thrombosis was a complication in 8 patients (4.2%); three deaths (1.6%) but not attributable to thromboembolic events following the use of rFVIIa. Most of the studies failed to clearly state the doses but the extracted doses ranged between 30 and 180 µg/kg/dose, the interval between doses ranged between 15 and 120 min with a maximum of four doses. However, most of the patients had 180 µg/kg/dose with interval between dose of 2 h and maximum of two doses with dosage moderated with respect to weight, prior coagulopathy and responsiveness. There were two randomized studies with good sample size. One showed no significant differences in the secondary end points between the two arms and noted no adverse complications. However, the rFVIIa was used prophylactically. The other observed that there were no increase in thromboembolic events rather rFVIIa was effective in decreasing excessive bleeding that may complicate cardiac surgery in children

  17. Ultrasensitive nanostructure sensor arrays on flexible substrates for multiplexed and simultaneous electrochemical detection of a panel of cardiac biomarkers.

    PubMed

    Radha Shanmugam, Nandhinee; Muthukumar, Sriram; Chaudhry, Shajee; Anguiano, Jonathan; Prasad, Shalini

    2017-03-15

    Multiplexed detection of protein biomarkers offers new opportunities for early diagnosis and efficient treatment of complex diseases. Cardiovascular diseases (CVDs) has the highest mortality risk in USA and Europe with 15-20 million cases being reported annually. Cardiac Troponins (T and I) are well established protein biomarkers associated with heart muscle damage and point-of-care monitoring of both these two biomarkers has significant benefits on patient care. A flexible disposable electrochemical biosensor device comprising of vertically oriented zinc oxide (ZnO) nanostructures was developed for rapid and simultaneous screening of cardiac Troponin-I (cTnI) and cardiac-Troponin-T (cTnT) in a point-of-care sensor format. The biosensors were designed by selective hydrothermal growth of ZnO nanostructures onto the working electrodes of polyimide printed circuit board platforms, resulting in the generation of high density nanostructure ZnO arrays based electrodes. The size, density and surface terminations of the nanostructures were leveraged towards achieving surface confinement of the target cTnT and cTnI molecules on to the electrode surface. Multiplexing and simultaneous detection was achieved through sensor platform design comprising of arrays of Troponin functionalized ZnO nanostructure electrodes. The sensitivity and specificity of the biosensor was characterized using two types of electrochemical techniques; electrochemical impedance spectroscopy (EIS) and Mott-Schottky analysis on the same sensor platform to demonstrate multi-configurable modes. Limit of detection of 1pg/mL in human serum was achieved for both cTnI and cTnT. Cross reactivity analysis showed the selectivity of detecting cTnT and cTnI in human serum with wide dynamic range.

  18. 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

  19. Early detection of cardiac ischemia using a conductometric pCO(2) sensor: real-time drift correction and parameterization.

    PubMed

    Tronstad, Christian; Pischke, Soeren E; Holhjem, Lars; Tønnessen, Tor Inge; Martinsen, Orjan G; Grimnes, Sverre

    2010-09-01

    For detection of cardiac ischemia based on regional pCO(2) measurement, sensor drift becomes a problem when monitoring over several hours. A real-time drift correction algorithm was developed based on utilization of the time-derivative to distinguish between physiological responses and the drift, customized by measurements from a myocardial infarction porcine model (6 pigs, 23 sensors). IscAlert conductometric pCO(2) sensors were placed in the myocardial regions supplied by the left anterior descending coronary artery (LAD) and the left circumflex artery (LCX) while the LAD artery was fully occluded for 1, 3, 5 and 15 min leading to ischemia in the LAD-dependent region. The measured pCO(2), the drift-corrected pCO(2) (DeltapCO(2)) and its time-derivative (TDpCO(2)) were compared with respect to detection ability. Baseline stability in the DeltapCO(2) led to earlier, more accurate detection. The TDpCO(2) featured the earliest sensitivity, but with a lower specificity. Combining DeltapCO(2) and TDpCO(2) enables increased accuracy. Suggestions are given for the utilization of the parameters for an automated early warning and alarming system. In conclusion, early detection of cardiac ischemia is feasible using the conductometric pCO(2) sensor together with parameterization methods.

  20. Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.

    PubMed

    Nishio, Y; Kashiwagi, A; Taki, H; Shinozaki, K; Maeno, Y; Kojima, H; Maegawa, H; Haneda, M; Hidaka, H; Yasuda, H; Horiike, K; Kikkawa, R

    1998-08-01

    Gene regulation in the cardiovascular tissues of diabetic subjects has been reported to be altered. To examine abnormal activities in transcription factors as a possible cause of this altered gene regulation, we studied the activity of two redox-sensitive transcription factors--nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1)--and the change in the mRNA content of heme oxygenase-1, which is regulated by these transcription factors in the cardiac tissues of rats with streptozotocin-induced diabetes. Increased activity of NF-kappaB and AP-1 but not nuclear transcription-activating factor, as determined by an electrophoretic mobility shift assay, was found in the hearts of 4-week diabetic rats. Glycemic control by a subcutaneous injection of insulin prevented these diabetes-induced changes in transcription factor activity. In accordance with these changes, the mRNA content of heme oxygenase-1 was increased fourfold in 4-week diabetic rats and threefold in 24-week diabetic rats as compared with control rats (P < 0.01 and P < 0.05, respectively). Insulin treatment also consistently prevented changes in the mRNA content of heme oxygenase-1. The oral administration of an antioxidant, probucol, to these diabetic rats partially prevented the elevation of the activity of both NF-kappaB and AP-1, and normalized the mRNA content of heme oxygenase-1 without producing any change in the plasma glucose concentration. These results suggest that elevated oxidative stress is involved in the activation of the transcription factors NF-kappaB and AP-1 in the cardiac tissues of diabetic rats, and that these abnormal activities of transcription factors could be associated with the altered gene regulation observed in the cardiovascular tissues of diabetic rats.

  1. ZYZ-168 alleviates cardiac fibrosis after myocardial infarction through inhibition of ERK1/2-dependent ROCK1 activation

    PubMed Central

    Luo, Shanshan; Hieu, Tran Ba; Ma, Fenfen; Yu, Ying; Cao, Zhonglian; Wang, Minjun; Wu, Weijun; Mao, Yicheng; Rose, Peter; Law, Betty Yuen-Kwan; Zhu, Yi Zhun

    2017-01-01

    Selective treatments for myocardial infarction (MI) induced cardiac fibrosis are lacking. In this study, we focus on the therapeutic potential of a synthetic cardio-protective agent named ZYZ-168 towards MI-induced cardiac fibrosis and try to reveal the underlying mechanism. ZYZ-168 was administered to rats with coronary artery ligation over a period of six weeks. Ecocardiography and Masson staining showed that ZYZ-168 substantially improved cardiac function and reduced interstitial fibrosis. The expression of α–smooth muscle actin (α-SMA) and Collagen I were reduced as was the activity of matrix metalloproteinase 9 (MMP-9). These were related with decreased phosphorylation of ERK1/2 and expression of Rho-associated coiled-coil containing protein kinase 1 (ROCK1). In cardiac fibroblasts stimulated with TGF-β1, phenotypic switches of cardiac fibroblasts to myofibroblasts were observed. Inhibition of ERK1/2 phosphorylation or knockdown of ROCK1 expectedly reduced TGF-β1 induced fibrotic responses. ZYZ-168 appeared to inhibit the fibrotic responses in a concentration dependent manner, in part via a decrease in ROCK 1 expression through inhibition of the phosphorylation status of ERK1/2. For inhibition of ERK1/2 phosphorylation with a specific inhibitor reduced the activation of ROCK1. Considering its anti-apoptosis activity in MI, ZYZ-168 may be a potential drug candidate for treatment of MI-induced cardiac fibrosis. PMID:28266583

  2. Cardiac metastasis from renal cell carcinoma successfully treated with pazopanib: impact of TKIs' antiangiogenic activity.

    PubMed

    Schinzari, Giovanni; Monterisi, Santa; Signorelli, Diego; Cona, Silvia; Cassano, Alessandra; Danza, Francesco; Barone, Carlo

    2014-01-01

    Cardiac metastasis from renal cell carcinoma, especially without neoplastic thrombosis of the vena cava, is extremely rare. The prognosis of patients with metastatic renal cell carcinoma has been radically influenced by the introduction of tyrosine kinase inhibitors, but very few reports in the literature have described their activity in heart metastasis. We report the case of a woman with a left ventricle metastasis from kidney cancer without renal vein involvement, who was treated with pazopanib. The patient achieved a prolonged partial response, with clear signs of metastasis devascularization and a favorable toxicity profile.

  3. Zymographic detection of cinnamic acid decarboxylase activity.

    PubMed

    Prim, Núria; Pastor, F I Javier; Diaz, Pilar

    2002-11-01

    The manuscript includes a concise description of a new, fast and simple method for detection of cinnamic acid decarboxylase activity. The method is based on a color shift caused a by pH change and may be an excellent procedure for large screenings of samples from natural sources, as it involves no complex sample processing or purification. The method developed can be used in preliminary approaches to biotransformation processes involving detection of hydroxycinnamic acid decarboxylase activity.

  4. Activation of Cardiac Fibroblast Growth Factor Receptor 4 Causes Left Ventricular Hypertrophy

    PubMed Central

    Grabner, Alexander; Amaral, Ansel P.; Schramm, Karla; Singh, Saurav; Sloan, Alexis; Yanucil, Christopher; Li, Jihe; Shehadeh, Lina A.; Hare, Joshua M.; David, Valentin; Martin, Aline; Fornoni, Alessia; Marco, Giovana Seno Di; Kentrup, Dominik; Reuter, Stefan; Mayer, Anna B.; Pavenstädt, Hermann; Stypmann, Jörg; Kuhn, Christian; Hille, Susanne; Frey, Norbert; Leifheit-Nestler, Maren; Richter, Beatrice; Haffner, Dieter; Abraham, Reimar; Bange, Johannes; Sperl, Bianca; Ullrich, Axel; Brand, Marcus; Wolf, Myles; Faul, Christian

    2015-01-01

    Summary Chronic kidney disease (CKD) is a worldwide public health threat that increases risk of death due to cardiovascular complications, including left ventricular hypertrophy (LVH). Novel therapeutic targets are needed to design treatments to alleviate the cardiovascular burden of CKD. Previously, we demonstrated that circulating concentrations of fibroblast growth factor (FGF) 23 rise progressively in CKD and induce LVH through an unknown FGF receptor (FGFR)-dependent mechanism. Here, we report that FGF23 exclusively activates FGFR4 on cardiac myocytes to stimulate phospholipase Cγ/calcineurin/nuclear factor of activated T cells signaling. A specific FGFR4 blocking antibody inhibits FGF23-induced hypertrophy of isolated cardiac myocytes and attenuates LVH in rats with CKD. Mice lacking FGFR4 do not develop LVH in response to elevated FGF23, whereas knock-in mice carrying an FGFR4 gain-of-function mutation spontaneously develop LVH. Thus, FGF23 promotes LVH by activating FGFR4, thereby establishing FGFR4 as a pharmacological target for reducing cardiovascular risk in CKD. PMID:26437603

  5. Vagal tone regulates cardiac shunts during activity and at low temperatures in the South American rattlesnake, Crotalus durissus.

    PubMed

    Filogonio, Renato; Wang, Tobias; Taylor, Edwin W; Abe, Augusto S; Leite, Cléo A C

    2016-12-01

    The undivided ventricle of non-crocodilian reptiles allows for intracardiac admixture of oxygen-poor and oxygen-rich blood returning via the atria from the systemic circuit and the lungs. The distribution of blood flow between the systemic and pulmonary circuits may vary, based on differences between systemic and pulmonary vascular conductances. The South American rattlesnake, Crotalus durissus, has a single pulmonary artery, innervated by the left vagus. Activity in this nerve controls pulmonary conductance so that left vagotomy abolishes this control. Experimental left vagotomy to abolish cardiac shunting had no effect on long-term survival and failed to identify a functional role in determining metabolic rate, growth or resistance to food deprivation. Accordingly, the present investigation sought to evaluate the extent to which cardiac shunt patterns are actively controlled during changes in body temperature and activity levels. We compared hemodynamic parameters between intact and left-vagotomized rattlesnakes held at different temperatures and subjected to enforced physical activity. Increased temperature and enforced activity raised heart rate, cardiac output, pulmonary and systemic blood flow in both groups, but net cardiac shunt was reversed in the vagotomized group at lower temperatures. We conclude that vagal control of pulmonary conductance is an active mechanism regulating cardiac shunts in C. durissus.

  6. Architecture design of the multi-functional wavelet-based ECG microprocessor for realtime detection of abnormal cardiac events.

    PubMed

    Cheng, Li-Fang; Chen, Tung-Chien; Chen, Liang-Gee

    2012-01-01

    Most of the abnormal cardiac events such as myocardial ischemia, acute myocardial infarction (AMI) and fatal arrhythmia can be diagnosed through continuous electrocardiogram (ECG) analysis. According to recent clinical research, early detection and alarming of such cardiac events can reduce the time delay to the hospital, and the clinical outcomes of these individuals can be greatly improved. Therefore, it would be helpful if there is a long-term ECG monitoring system with the ability to identify abnormal cardiac events and provide realtime warning for the users. The combination of the wireless body area sensor network (BASN) and the on-sensor ECG processor is a possible solution for this application. In this paper, we aim to design and implement a digital signal processor that is suitable for continuous ECG monitoring and alarming based on the continuous wavelet transform (CWT) through the proposed architectures--using both programmable RISC processor and application specific integrated circuits (ASIC) for performance optimization. According to the implementation results, the power consumption of the proposed processor integrated with an ASIC for CWT computation is only 79.4 mW. Compared with the single-RISC processor, about 91.6% of the power reduction is achieved.

  7. 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.

  8. Contributions of Ca2+-Independent Thin Filament Activation to Cardiac Muscle Function

    PubMed Central

    Aboelkassem, Yasser; Bonilla, Jordan A.; McCabe, Kimberly J.; Campbell, Stuart G.

    2015-01-01

    Although Ca2+ is the principal regulator of contraction in striated muscle, in vitro evidence suggests that some actin-myosin interaction is still possible even in its absence. Whether this Ca2+-independent activation (CIA) occurs under physiological conditions remains unclear, as does its potential impact on the function of intact cardiac muscle. The purpose of this study was to investigate CIA using computational analysis. We added a structurally motivated representation of this phenomenon to an existing myofilament model, which allowed predictions of CIA-dependent muscle behavior. We found that a certain amount of CIA was essential for the model to reproduce reported effects of nonfunctional troponin C on myofilament force generation. Consequently, those data enabled estimation of ΔGCIA, the energy barrier for activating a thin filament regulatory unit in the absence of Ca2+. Using this estimate of ΔGCIA as a point of reference (∼7 kJ mol−1), we examined its impact on various aspects of muscle function through additional simulations. CIA decreased the Hill coefficient of steady-state force while increasing myofilament Ca2+ sensitivity. At the same time, CIA had minimal effect on the rate of force redevelopment after slack/restretch. Simulations of twitch tension show that the presence of CIA increases peak tension while profoundly delaying relaxation. We tested the model’s ability to represent perturbations to the Ca2+ regulatory mechanism by analyzing twitch records measured in transgenic mice expressing a cardiac troponin I mutation (R145G). The effects of the mutation on twitch dynamics were fully reproduced by a single parameter change, namely lowering ΔGCIA by 2.3 kJ mol−1 relative to its wild-type value. Our analyses suggest that CIA is present in cardiac muscle under normal conditions and that its modulation by gene mutations or other factors can alter both systolic and diastolic function. PMID:26588569

  9. 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.

  10. 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

  11. Activation of ATP-sensitive K+ channels by epoxyeicosatrienoic acids in rat cardiac ventricular myocytes

    PubMed Central

    Lu, Tong; Hoshi, Toshinori; Weintraub, Neal L; Spector, Arthur A; Lee, Hon-Chi

    2001-01-01

    We examined the effects of epoxyeicosatrienoic acids (EETs), which are cytochrome P450 metabolites of arachidonic acid (AA), on the activities of the ATP-sensitive K+ (KATP) channels of rat cardiac myocytes, using the inside-out patch-clamp technique. In the presence of 100 μm cytoplasmic ATP, the KATP channel open probability (Po) was increased by 240 ± 60% with 0.1 μm 11,12-EET and by 400 ± 54% with 5 μm 11,12-EET (n = 5 –10, P < 0.05 vs. control), whereas neither 5 μm AA nor 5 μm 11,12-dihydroxyeicosatrienoic acid (DHET), which is the epoxide hydrolysis product of 11,12-EET, had any effect on Po. The half-maximal activating concentration (EC50) was 18.9 ± 2.6 nm for 11,12-EET (n = 5) and 19.1 ± 4.8 nm for 8,9-EET (n = 5), P = n.s. vs. 11,12-EET). Furthermore, 11,12-EET failed to alter the inhibition of KATP channels by glyburide. Application of 11,12-EET markedly decreased the channel sensitivity to cytoplasmic ATP. The half-maximal inhibitory concentration of ATP (IC50) was increased from 21.2 ± 2.0 μm at baseline to 240 ± 60 μm with 0.1 μm 11,12-EET (n = 5, P < 0.05 vs. control) and to 780 ± 30 μm with 5 μm 11,12-EET (n = 11, P < 0.05vs. control). Increasing the ATP concentration increased the number of kinetically distinguishable closed states, promoting prolonged closure durations. 11,12-EET antagonized the effects of ATP on the kinetics of the KATP channels in a dose and voltage-dependent manner. 11,12-EET (1 μm) reduced the apparent association rate constant of ATP to the channel by 135-fold. Application of 5 μm 11,12-EET resulted in hyperpolarization of the resting membrane potential in isolated cardiac myocytes, which could be blocked by glyburide. These results suggest that EETs are potent activators of the cardiac KATP channels, modulating channel behaviour by reducing the channel sensitivity to ATP. Thus, EETs could be important endogenous regulators of cardiac electrical excitability. PMID:11744757

  12. 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

  13. Undetected cardiac lesions cause unexpected sudden cardiac death during occasional sport activity. A report of 80 cases.

    PubMed

    Tabib, A; Miras, A; Taniere, P; Loire, R

    1999-06-01

    The retrospective analysis of 1500 forensic autopsies after sudden cardiac death showed that 80 (77 men, three women) had died following sport, for which they had been inadequately trained. The chosen sport (both dynamic and static), and the cardiac pathology discovered during autopsy make it possible to divide the population into two groups. Group 1 were those under 30 years of age (27 cases) engaged in jogging, gymnastics, rugby, tennis and boxing who suffered from hypertrophic cardiomyopathy (29.6%), arrhythmogenic right ventricular cardiomyopathy (25.9%), non-atherosclerotic (14. 8%), aortic stenosis (7.4%), atrial septal defect (3.7%), stenosing coronary atherosclerosis (3.7%), and structural abnormalities of the His bundle (3.7%). Group 2 were those over 30 years of age (53 cases), engaged in swimming, cycling, jogging and football. The cardiac lesions responsible were stenosing atherosclerotic coronary disease (49%), non-atherosclerotic coronary disease (1.8%), hypertrophic cardiomyopathy (20%), obstructive cardiomyopathy (4.8%), structural abnormalities of the His bundle (7.4%), myocardic bruise scar (4%), and arrhythmogenic right ventricular cardiomyopathy (3. 7%). In both groups, dilated cardiomyopathy occurred with identical frequency (11%).Conclusions The lesions discovered are the same as those identified in professional athletes, when the body tries to avoid mortal rhythmic decompensation in the case of an over-loading volume and tension during an ill-adapted effort. Forensic autopsy should establish these anomalies because the transmissible genetic characteristics of some of them could underline the need for check-ups in other members of the family.

  14. 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.

  15. Myocyte-Derived Hsp90 Modulates Collagen Upregulation via Biphasic Activation of STAT-3 in Fibroblasts during Cardiac Hypertrophy.

    PubMed

    Datta, Ritwik; Bansal, Trisha; Rana, Santanu; Datta, Kaberi; Datta Chaudhuri, Ratul; Chawla-Sarkar, Mamta; Sarkar, Sagartirtha

    2017-03-15

    Signal transducer and activator of transcription 3 (STAT-3)-mediated signaling in relation to upregulated collagen expression in fibroblasts during cardiac hypertrophy is well defined. Our recent findings have identified heat shock protein 90 (Hsp90) to be a critical modulator of fibrotic signaling in cardiac fibroblasts in this disease milieu. The present study was therefore intended to analyze the role of Hsp90 in the STAT-3-mediated collagen upregulation process. Our data revealed a significant difference between in vivo and in vitro results, pointing to a possible involvement of myocyte-fibroblast cross talk in this process. Cardiomyocyte-targeted knockdown of Hsp90 in rats (Rattus norvegicus) in which the renal artery was ligated showed downregulated collagen synthesis. Furthermore, the results obtained with cardiac fibroblasts conditioned with Hsp90-inhibited hypertrophied myocyte supernatant pointed toward cardiomyocytes' role in the regulation of collagen expression in fibroblasts during hypertrophy. Our study also revealed a novel signaling mechanism where myocyte-derived Hsp90 orchestrates not only p65-mediated interleukin-6 (IL-6) synthesis but also its release in exosomal vesicles. Such myocyte-derived exosomes and myocyte-secreted IL-6 are responsible in unison for the biphasic activation of STAT-3 signaling in cardiac fibroblasts that culminates in excess collagen synthesis, leading to severely compromised cardiac function during cardiac hypertrophy.

  16. Cardiac glycoside activities link Na(+)/K(+) ATPase ion-transport to breast cancer cell migration via correlative SAR.

    PubMed

    Magpusao, Anniefer N; Omolloh, George; Johnson, Joshua; Gascón, José; Peczuh, Mark W; Fenteany, Gabriel

    2015-02-20

    The cardiac glycosides ouabain and digitoxin, established Na(+)/K(+) ATPase inhibitors, were found to inhibit MDA-MB-231 breast cancer cell migration through an unbiased chemical genetics screen for cell motility. The Na(+)/K(+) ATPase acts both as an ion-transporter and as a receptor for cardiac glycosides. To delineate which function is related to breast cancer cell migration, structure-activity relationship (SAR) profiles of cardiac glycosides were established at the cellular (cell migration inhibition), molecular (Na(+)/K(+) ATPase inhibition), and atomic (computational docking) levels. The SAR of cardiac glycosides and their analogs revealed a similar profile, a decrease in potency when the parent cardiac glycoside structure was modified, for each activity investigated. Since assays were done at the cellular, molecular, and atomic levels, correlation of SAR profiles across these multiple assays established links between cellular activity and specific protein-small molecule interactions. The observed antimigratory effects in breast cancer cells are directly related to the inhibition of Na(+)/K(+) transport. Specifically, the orientation of cardiac glycosides at the putative cation permeation path formed by transmembrane helices αM1-M6 correlates with the Na(+) pump activity and cell migration. Other Na(+)/K(+) ATPase inhibitors that are structurally distinct from cardiac glycosides also exhibit antimigratory activity, corroborating the conclusion that the antiport function of Na(+)/K(+) ATPase and not the receptor function is important for supporting the motility of MDA-MB-231 breast cancer cells. Correlative SAR can establish new relationships between specific biochemical functions and higher-level cellular processes, particularly for proteins with multiple functions and small molecules with unknown or various modes of action.

  17. 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

  18. 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.

  19. Noise-induced ectopic activity in a simple cardiac cell model

    NASA Astrophysics Data System (ADS)

    Hastings, Harold

    2005-03-01

    Ectopic activity in the form of premature ventricular contractions (PVCs) is relatively common in the normal heart. Although PVCs are normally harmless, sometimes but rarely PVCs can generate spiral waves of activation through interaction with other waves of activation, potentially progressing to ventricular tachycardia, followed by ventricular fibrillation and sudden cardiac death. Clusters of PVCs have been found to be significantly more dangerous than isolated PVCs. We model PVC generation by applying triggers (noise) to the generic FitzHugh-Nagumo model as substrate, and study the effects the noise level and excitability. We find: exponential waiting time behavior at fixed parameter levels; no evidence of clustering at fixed parameter levels; and a sharp increase in PVCs as excitability approaches the auto-oscillatory threshold or noise increases beyond a similar threshold. This produces sharp increases in theoretical rates of PVC-induced fibrillation, consistent with results of A Gelzer et al. in animal models. Partially supported by the NSF and NIH.

  20. Age-related decline in cardiac autonomic function is not attenuated with increased physical activity

    PubMed Central

    Njemanze, Hugo; Warren, Charlotte; Eggett, Christopher; MacGowan, Guy A.; Bates, Matthew G D; Siervo, Mario; Ivkovic, Srdjan; Trenell, Michael I.; Jakovljevic, Djordje G.

    2016-01-01

    Age and physical inactivity are important risk factors for cardiovascular mortality. Heart rate response to exercise (HRRE) and heart rate recovery (HRR), measures of cardiac autonomic function, are strong predictors of mortality. The present study defined the effect of age and physical activity on HRRE and HRR. Healthy women (N=72) grouped according to age (young, 20-30 years; middle, 40-50 years; and older, 65-81 years) and daily physical activity (low active <7500, high active >12,500 steps/day) performed a maximal cardiopulmonary exercise test. The HRRE was defined as an increase in heart rate from rest to 1, 3 and 5 minutes of exercise and at 1/3 of total exercise time, and HRR as the difference in heart rate between peak exercise and 1, 2, and 3 minutes later. Age was associated with a significant decline in HRRE at 1 min and 1/3 of exercise time (r= − 0.27, p=0.04, and r=−0.39, p=0.02) and HRR at 2 min and 3 min (r=−0.35, p=0.01, and r=−0.31, p=0.02). There was no significant difference in HRRE and HRR between high and low-active middle-age and older women (p>0.05). Increased level of habitual physical activity level appears to have a limited effect on age-related decline in cardiac autonomic function in women. PMID:27705949

  1. 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.

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

    PubMed

    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.

  3. 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

  4. 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

  5. Rate-dependent activation failure in isolated cardiac cells and tissue due to Na+ channel block

    PubMed Central

    Spindler, Anthony J.; Paterson, David; Noble, Denis

    2015-01-01

    While it is well established that class-I antiarrhythmics block cardiac sodium channels, the mechanism of action of therapeutic levels of these drugs is not well understood. Using a combination of mathematical modeling and in vitro experiments, we studied the failure of activation of action potentials in single ventricular cells and in tissue caused by Na+ channel block. Our computations of block and unblock of sodium channels by a theoretical class-Ib antiarrhythmic agent predict differences in the concentrations required to cause activation failure in single cells as opposed to multicellular preparations. We tested and confirmed these in silico predictions with in vitro experiments on isolated guinea-pig ventricular cells and papillary muscles stimulated at various rates (2–6.67 Hz) and exposed to various concentrations (5 × 10−6 to 500 × 10−6 mol/l) of lidocaine. The most salient result was that whereas large doses (5 × 10−4 mol/l or higher) of lidocaine were required to inhibit action potentials temporarily in single cells, much lower doses (5 × 10−6 mol/l), i.e., therapeutic levels, were sufficient to have the same effect in papillary muscles: a hundredfold difference. Our experimental results and mathematical analysis indicate that the syncytial nature of cardiac tissue explains the effects of clinically relevant doses of Na+ channel blockers. PMID:26342072

  6. Cross bridge-dependent activation of contraction in cardiac myofibrils at low pH.

    PubMed

    Swartz, D R; Zhang, D; Yancey, K W

    1999-05-01

    Striated muscle contracts in the absence of calcium at low concentrations of MgATP ([MgATP]), and this has been termed rigor activation because rigor cross bridges attach and activate adjacent actin sites. This process is well characterized in skeletal muscle but not in cardiac muscle. Rigor cross bridges are also thought to increase calcium binding to troponin C and play a synergistic role in activation. We tested the hypothesis that cross bridge-dependent activation results in an increase in contractile activity at normal and low pH values. Myofibrillar ATPase activity was measured as a function of pCa and [MgATP] at pH 7.0, and the data showed that, at pCa values of >/=5.5, there was a biphasic relationship between activity and [MgATP]. Peak activity occurred at 10-50 microM MgATP, and [MgATP] for peak activity was lower with increased pCa. The ATPase activity of rat cardiac myofibrils as a function of [MgATP] at a pCa of 9.0 was measured at several pH levels (pH 5.4-7.0). The ATPase activity as a function of [MgATP] was biphasic with a maximum at 8-10 microM MgATP. Lower pH did not result in a substantial decrease in myofibrillar ATPase activity even at pH 5.4. The extent of shortening, as measured by Z-line spacing, was greatest at 8 microM MgATP and less at both lower and higher [MgATP], and this response was observed at all pH levels. These studies suggest that the peak ATPase activity associated with low [MgATP] was coupled to sarcomere shortening. These results support the hypothesis that cross bridge-dependent activation of contraction may be responsible for contracture in the ischemic heart.

  7. [Changes in electrocardiogram and cardiac phase during various stages in foreign manned spaceflight activities and the analysis of their possible mechanisms].

    PubMed

    Wang, D S; Ren, W; Xiang, Q L; Sun, L; Liu, Z X; Su, S N

    2000-12-01

    Electrocardiography (ECG) is still the only method for continuous medical observation during various stages of foreign manned spaceflight activities, and it also serves as an important item for medical monitoring in the project for manned spaceflight activities in our country. With electrocardiography, pulse or heart rate (one of the four life signs) and cardiac function can continuously be observed. Cardiac phase relative to ECG is a main index reflecting cardiac function. Understanding of the results of ECG and cardiac phase and their mechanisms during various stages of foreign manned spaceflight activities will be helpful in establishing emergency measures in the course of manned spaceflight activities in our country.

  8. Detection of First and Second Cardiac Sounds Based on Time Frequency Analysis

    DTIC Science & Technology

    2001-10-25

    derived from the closing/opening of heart valves [3][4][6]. It will be shown that the proposed method results in a very precise timing of PCG signals...important cardiac sounds, S1 and S2, are generated by sudden distention of the valves leaflets or by acceleration of blood mass in the moment of...aortic insufficiency (AI), aortic stenoses (AS) and mitral insufficiency (MI). From the 19 volunteers, 756 cycles were used to evaluate the performance of

  9. Cardiac sympathetic activity in chronic heart failure: cardiac (123)I-mIBG scintigraphy to improve patient selection for ICD implantation.

    PubMed

    Verschure, D O; van Eck-Smit, B L F; Somsen, G A; Knol, R J J; Verberne, H J

    2016-12-01

    Heart failure is a life-threatening disease with a growing incidence in the Netherlands. This growing incidence is related to increased life expectancy, improvement of survival after myocardial infarction and better treatment options for heart failure. As a consequence, the costs related to heart failure care will increase. Despite huge improvements in treatment, the prognosis remains unfavourable with high one-year mortality rates. The introduction of implantable devices such as implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) has improved the overall survival of patients with chronic heart failure. However, after ICD implantation for primary prevention in heart failure a high percentage of patients never have appropriate ICD discharges. In addition 25-50 % of CRT patients have no therapeutic effect. Moreover, both ICDs and CRTs are associated with malfunction and complications (e. g. inappropriate shocks, infection). Last but not least is the relatively high cost of these devices. Therefore, it is essential, not only from a clinical but also from a socioeconomic point of view, to optimise the current selection criteria for ICD and CRT. This review focusses on the role of cardiac sympathetic hyperactivity in optimising ICD selection criteria. Cardiac sympathetic hyperactivity is related to fatal arrhythmias and can be non-invasively assessed with (123)I-meta-iodobenzylguanide ((123)I-mIBG) scintigraphy. We conclude that cardiac sympathetic activity assessed with (123)I-mIBG scintigraphy is a promising tool to better identify patients who will benefit from ICD implantation.

  10. 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

  11. Orthotropic active strain models for the numerical simulation of cardiac biomechanics.

    PubMed

    Rossi, Simone; Ruiz-Baier, Ricardo; Pavarino, Luca F; Quarteroni, Alfio

    2012-01-01

    A model for the active deformation of cardiac tissue considering orthotropic constitutive laws is introduced and studied. In particular, the passive mechanical properties of the myocardium are described by the Holzapfel-Ogden relation, whereas the activation model is based on the concept of active strain. There, an incompatible intermediate configuration is considered, which entails a multiplicative decomposition between active and passive deformation gradients. The underlying Euler-Lagrange equations for minimizing the total energy are written in terms of these deformation factors, where the active part is assumed to depend, at the cell level, on the electrodynamics and on the specific orientation of the cardiomyocytes. The active strain formulation is compared with the classical active stress model from both numerical and modeling perspectives. The well-posedness of the linear system derived from a generic Newton iteration of the original problem is analyzed, and different mechanical activation functions are considered. Taylor-Hood and MINI finite elements are used in the discretization of the overall mechanical problem. The results of several numerical experiments show that the proposed formulation is mathematically consistent and is able to represent the main features of the phenomenon, while allowing savings in computational costs.

  12. Model of an inductive sensor of cardiac activity attached to patient

    NASA Astrophysics Data System (ADS)

    Vedru, Jüri; Gordon, Rauno

    2010-04-01

    An electric circuit model describing an inductive sensor of cardiac mechanical activity in its working condition has been developed. The sensor comprises a single-turn coil which is fed by 7.7 MHz constant current and induces probing eddy currents in the body. The inductor is considered to be attached to the thoracic surface of a normal human male, in front of the heart. A simple axial-symmetric model of the thorax, formed of tightly packed circular current tubes, has been used to calculate the resistances, self-inductances and mutual inductances within the human body. Then the inductor and the eddy currents in the body were reduced to a system of two inductively coupled coils; estimates of the parameters and frequency response of the system have been found; the active and reactive contributions of the human body to the resulting impedance of the inductor were calculated.

  13. Unsupervised Cardiac Image Segmentation via Multiswarm Active Contours with a Shape Prior

    PubMed Central

    Cruz-Aceves, I.; Avina-Cervantes, J. G.; Lopez-Hernandez, J. M.; Garcia-Hernandez, M. G.; Ibarra-Manzano, M. A.

    2013-01-01

    This paper presents a new unsupervised image segmentation method based on particle swarm optimization and scaled active contours with shape prior. The proposed method uses particle swarm optimization over a polar coordinate system to perform the segmentation task, increasing the searching capability on medical images with respect to different interactive segmentation techniques. This method is used to segment the human heart and ventricular areas from datasets of computed tomography and magnetic resonance images, where the shape prior is acquired by cardiologists, and it is utilized as the initial active contour. Moreover, to assess the performance of the cardiac medical image segmentations obtained by the proposed method and by the interactive techniques regarding the regions delineated by experts, a set of validation metrics has been adopted. The experimental results are promising and suggest that the proposed method is capable of segmenting human heart and ventricular areas accurately, which can significantly help cardiologists in clinical decision support. PMID:24198850

  14. A generalized activating function for predicting virtual electrodes in cardiac tissue.

    PubMed Central

    Sobie, E A; Susil, R C; Tung, L

    1997-01-01

    To fully understand the mechanisms of defibrillation, it is critical to know how a given electrical stimulus causes membrane polarizations in cardiac tissue. We have extended the concept of the activating function, originally used to describe neuronal stimulation, to derive a new expression that identifies the sources that drive changes in transmembrane potential. Source terms, or virtual electrodes, consist of either second derivatives of extracellular potential weighted by intracellular conductivity or extracellular potential gradients weighted by derivatives of intracellular conductivity. The full response of passive tissue can be considered, in simple cases, to be a convolution of this "generalized activating function" with the impulse response of the tissue. Computer simulations of a two-dimensional sheet of passive myocardium under steady-state conditions demonstrate that this source term is useful for estimating the effects of applied electrical stimuli. The generalized activating function predicts oppositely polarized regions of tissue when unequally anisotropic tissue is point stimulated and a monopolar response when a point stimulus is applied to isotropic tissue. In the bulk of the myocardium, this new expression is helpful for understanding mechanisms by which virtual electrodes can be produced, such as the hypothetical "sawtooth" pattern of polarization, as well as polarization owing to regions of depressed conductivity, missing cells or clefts, changes in fiber diameter, or fiber curvature. In comparing solutions obtained with an assumed extracellular potential distribution to those with fully coupled intra- and extracellular domains, we find that the former provides a reliable estimate of the total solution. Thus the generalized activating function that we have derived provides a useful way of understanding virtual electrode effects in cardiac tissue. Images FIGURE 2 FIGURE 4 FIGURE 5 FIGURE 6 PMID:9284308

  15. Effect of muscle metaboreflex activation on spontaneous cardiac baroreflex sensitivity during exercise in humans.

    PubMed

    Hartwich, Doreen; Dear, William E; Waterfall, Jessica L; Fisher, James P

    2011-12-15

    We sought to determine whether the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) is a potential mechanism for the decrease in spontaneous cardiac baroreflex sensitivity (cBRS) during exercise in humans. In protocol 1, 15 male subjects (22 ± 1 years) performed steady-state leg cycling at low (26 ± 4 W) and moderate workloads (105 ± 7 W), under free-flow conditions and with partial flow restriction (bilateral thigh cuff inflation at 100 mmHg) to evoke muscle metaboreflex activation during exercise. In protocol 2, rhythmic handgrip exercise at 35% maximum voluntary contraction was performed with progressive upper arm cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded metaboreflex activation. Both protocols were followed by post-exercise ischaemia (PEI) to isolate the muscle metaboreflex. Leg cycling-induced increases in HR and mean BP were augmented by partial flow restriction (P < 0.05 vs. free flow), while HR and mean BP both remained elevated during PEI (P < 0.05 vs. rest). Leg cycling evoked an intensity-dependent decrease in cBRS (16 ± 2, 7 ± 1 and 2 ± 0.2 ms mmHg(-1) at rest, low and moderate workloads, respectively; P < 0.05), which was further reduced with partial flow restriction (by -2.6 ± 0.8 and -0.4 ± 0.1 ms mmHg(-1) at low and moderate workloads). cBRS remained suppressed during PEI following leg cycling with partial flow restriction (4 ± 1 ms mmHg(-1); P < 0.05 vs. rest). cBRS was unchanged during handgrip under free-flow conditions, handgrip with partial flow restriction and PEI following handgrip (P > 0.05 vs. rest). These data indicate that the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) decreases cardiac baroreflex responsiveness during leg cycling exercise in humans.

  16. Sympathetic network drive during water deprivation does not increase respiratory or cardiac rhythmic sympathetic nerve activity.

    PubMed

    Holbein, Walter W; Toney, Glenn M

    2013-06-15

    Effects of water deprivation on rhythmic bursting of sympathetic nerve activity (SNA) were investigated in anesthetized, bilaterally vagotomized, euhydrated (control) and 48-h water-deprived (WD) rats (n = 8/group). Control and WD rats had similar baseline values of mean arterial pressure, heart rate, end-tidal CO2, and central respiratory drive. Although integrated splanchnic SNA (sSNA) was greater in WD rats than controls (P < 0.01), analysis of respiratory rhythmic bursting of sSNA revealed that inspiratory rhythmic burst amplitude was actually smaller (P < 0.005) in WD rats (+68 ± 6%) than controls (+208 ± 20%), and amplitudes of the early expiratory (postinspiratory) trough and late expiratory burst of sSNA were not different between groups. Further analysis revealed that water deprivation had no effect on either the amplitude or periodicity of the cardiac rhythmic oscillation of sSNA. Collectively, these data indicate that the increase of sSNA produced by water deprivation is not attributable to either increased respiratory or cardiac rhythmic burst discharge. Thus the sympathetic network response to acute water deprivation appears to differ from that of chronic sympathoexcitation in neurogenic forms of arterial hypertension, where increased respiratory rhythmic bursting of SNA and baroreflex adaptations have been reported.

  17. Electrocardiograhic findings resulting in inappropriate cardiac catheterization laboratory activation for ST-segment elevation myocardial infarction

    PubMed Central

    Shamim, Shariq; McCrary, Justin; Wayne, Lori; Gratton, Matthew

    2014-01-01

    Background Prompt reperfusion has been shown to improve outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) with a goal of culprit vessel patency in <90 minutes. This requires a coordinated approach between the emergency medical services (EMS), emergency department (ED) and interventional cardiology. The urgency of this process can contribute to inappropriate cardiac catheterization laboratory (CCL) activations. Objectives One of the major determinants of inappropriate activations has been misinterpretation of the electrocardiogram (ECG) in the patient with acute chest pain. Methods We report the ECG findings for all CCL activations over an 18-month period after the inception of a STEMI program at our institution. Results There were a total of 139 activations with 77 having a STEMI diagnosis confirmed and 62 activations where there was no STEMI. The inappropriate activations resulted from a combination of atypical symptoms and misinterpretation of the ECG (45% due to anterior ST-segment elevation) on patient presentation. The electrocardiographic abnormalities were particularly problematic in African-Americans with left ventricular hypertrophy. Conclusions In this single-center, prospective observational study, nearly half of the inappropriate STEMI activations were due to the misinterpretation of anterior ST-segment elevation and this finding was commonly seen in African-Americans with left ventricular hypertrophy. PMID:25009790

  18. 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.

  19. Catching broken hearts: pre-clinical detection of doxorubicin and trastuzumab mediated cardiac dysfunction in the breast cancer setting.

    PubMed

    Saeed, Mahwash F; Premecz, Sheena; Goyal, Vineet; Singal, Pawan K; Jassal, Davinder S

    2014-07-01

    Although breast cancer is one of the leading causes of death in women worldwide, there is an overall improvement in the survival of this patient population. This is likely due to a combination of early detection through screening and awareness, improved targeted biological therapy, and an overall improvement in disease management. Despite the beneficial effects of the 2 anti-cancer drugs doxorubicin (DOX) and trastuzumab (TRZ) in women with breast cancer, development of cardiotoxicity is a major concern. The occurrence of left ventricular systolic dysfunction is unacceptably high in nearly 1 in 4 women treated with DOX+TRZ in the breast cancer setting. In this review, we explore the use of non-invasive cardiac imaging for the early detection of chemotherapy-mediated cardiotoxicity in women with breast cancer, in the hope of preventing end-stage heart disease in this cancer population.

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

    PubMed Central

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

    1977-01-01

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

  1. Speckle-tracking strain echocardiography for detecting cardiac dyssynchrony in a canine model of dyssynchrony and heart failure.

    PubMed

    Arita, Takeshi; Sorescu, George P; Schuler, Brian T; Schmarkey, Laura S; Merlino, John D; Vinten-Johansen, Jakob; Leon, Angel R; Martin, Randolph P; Sorescu, Dan

    2007-07-01

    Multiple echocardiographic criteria have been proposed to diagnose mechanical dyssynchrony in patients with heart failure without being validated against a model of cardiac dyssynchrony with heart failure. This study examines which of these methods can detect dyssynchrony in a canine model. Adult mongrel dogs underwent His-bundle ablation and right-ventricular pacing for 4 wk at either 110 bpm to induce dyssynchrony without heart failure (D group, n = 12) or 170 bpm to induce dyssynchrony with heart failure (DHF group, n = 9). To induce heart failure with narrow QRS, atria were paced at 190 bpm for 4 wk (HF group, n = 8). Tissue Doppler imaging (TDI) and two-dimensional echocardiography were performed at baseline and at end of study. Standard deviation of time to peak systolic velocity (color-coded TDI), time to peak S wave on pulse-wave TDI, time to peak radial and circumferential strain by speckle-tracking analysis (E(rr) and E(cc), respectively), and septal-to-posterior wall motion delay on M mode were obtained. In D group, only E(rr) and E(cc) were increased by dyssynchrony. In contrast, all the echocardiographic parameters of dyssynchrony appeared significantly augmented in the DHF group. Receiver-operator curve analysis showed good sensitivity of E(rr) (90%) and E(cc) (100%) to detected dyssynchrony without heart failure and excellent sensitivity and specificity of E(rr) and E(cc) to detect dyssynchrony with heart failure. Radial strain by speckle tracking is more accurate than TDI velocity to detect cardiac dyssynchrony in a canine model of dyssynchrony with or without heart failure.

  2. Abnormal Activity Detection Using Pyroelectric Infrared Sensors.

    PubMed

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

    2016-06-03

    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.

  3. 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

  4. 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

  5. The effects of carbonated water upon gastric and cardiac activities and fullness in healthy young women.

    PubMed

    Wakisaka, Shiori; Nagai, Hajime; Mura, Emi; Matsumoto, Takehiro; Moritani, Toshio; Nagai, Narumi

    2012-01-01

    Although previous reports suggested that carbonated water drinking was effective against gastrointestinal symptoms, there is little information about the effects of carbonated water on gastric and appetite sensation. We therefore investigated the effect of carbonated water on short-term fullness with respect to gastric and cardiac responses in 19 healthy young women. Each subject was tested on three separate days at approximately 9 a.m. after an overnight fast. Gastric motility, evaluated by electrogastrography (EGG) and heart rate (HR), was measured for 20 min in the fasting state and 40 min after ingestion of water. Preloads consisted of an equivalent amount (250 mL) of water (W) or carbonated water (CW) and no drinking (blank). Fullness scores were measured using visual analog scales. To determine gastric motility, we assessed the component of bradygastria (1-2 cycles/min [cpm]), normogastria (2-4 cpm), tachygastria (4-9 cpm), and dominant frequency of the EGG power spectrum. After ingestion of CW, significant increases in fullness scores were observed compared with W. All postprandial EGG powers were significantly greater than preprandial, but no group difference was found. However, a dominant frequency tended to shift toward a lower band after ingestion of W. A significantly higher HR was found following consumption of CW as opposed to W. Multiple regression analysis revealed that increased HR was a significant variable contributing to the variances in fullness after ingestion of CW at 40 min. Our data suggest that CW may induce a short-term, but significant, satiating effect through enhanced postprandial gastric and cardiac activities due possibly to the increased sympathetic activity and/or withdrawal of parasympathetic activity.

  6. Vagal nerve stimulation activates vagal afferent fibers that reduce cardiac efferent parasympathetic effects

    PubMed Central

    Yamakawa, Kentaro; Rajendran, Pradeep S.; Takamiya, Tatsuo; Yagishita, Daigo; So, Eileen L.; Mahajan, Aman; Shivkumar, Kalyanam

    2015-01-01

    Vagal nerve stimulation (VNS) has been shown to have antiarrhythmic effects, but many of these benefits were demonstrated in the setting of vagal nerve decentralization. The purpose of this study was to evaluate the role of afferent fiber activation during VNS on efferent control of cardiac hemodynamic and electrophysiological parameters. In 37 pigs a 56-electrode sock was placed over the ventricles to record local activation recovery intervals (ARIs), a surrogate of action potential duration. In 12 of 37 animals atropine was given systemically. Right and left VNS were performed under six conditions: both vagal trunks intact (n = 25), ipsilateral right (n = 11), ipsilateral left (n = 14), contralateral right (n = 7), contralateral left (n = 10), and bilateral (n = 25) vagal nerve transection (VNTx). Unilateral VNTx significantly affected heart rate, PR interval, Tau, and global ARIs. Right VNS after ipsilateral VNTx had augmented effects on hemodynamic parameters and increase in ARI, while subsequent bilateral VNTx did not significantly modify this effect (%change in ARI in intact condition 2.2 ± 0.9% vs. ipsilateral VNTx 5.3 ± 1.7% and bilateral VNTx 5.3 ± 0.8%, P < 0.05). Left VNS after left VNTx tended to increase its effects on hemodynamics and ARI response (P = 0.07), but only after bilateral VNTx did these changes reach significance (intact 1.1 ± 0.5% vs. ipsilateral VNTx 3.6 ± 0.7% and bilateral VNTx 6.6 ± 1.6%, P < 0.05 vs. intact). Contralateral VNTx did not modify VNS response. The effect of atropine on ventricular ARI was similar to bilateral VNTx. We found that VNS activates afferent fibers in the ipsilateral vagal nerve, which reflexively inhibit cardiac parasympathetic efferent electrophysiological and hemodynamic effects. PMID:26371172

  7. Potential Effects of Heliogeophysical Activity on the Dynamics of Sudden Cardiac Death at Earth Middle Latitudes

    NASA Astrophysics Data System (ADS)

    Dimitrova, S.; Babayev, E.; Mustafa, F.

    2017-01-01

    Limited studies exist on comparing the possible effects of heliogeophysical activity (solar and geomagnetic) on the dynamics of sudden cardiac death (SCD) as a function of latitude on Earth. In this work we continue our earlier studies concerning the changing space environment and SCD dynamics at middle latitudes. The study covered 25 to 80-year old males and females, and used medical data provided by all emergency and first medical aid stations in the Grand Baku Area, Azerbaijan. Data coverage includedthe second peak of Solar Cycle 23 and its descending activity years followed by its long-lasting minimum. Gradation of geomagnetic activity into six levels was introduced to study the effect of space weather on SCD. The ANalysis Of VAriance (ANOVA) test was applied to study the significance of the geomagnetic activity effect, estimated by different geomagnetic indices, on SCD dynamics. Variations inthe number of SCDs occurring on days preceding and following the development of geomagnetic storms were also studied. Results revealed that the SCD number was largest on days of very low geomagnetic activity and on days proceeding and following geomagnetic storms with different intensities. Vulnerability for males was found to be higher around days of major and severe geomagnetic storms. Females, on the other hand, were more threatened around days of lower intensity storms. It is concluded that heliogeophysical activity could be considered as one of the regulating external/environmental factors in human homeostasis.

  8. HeartSaver: a mobile cardiac monitoring system for auto-detection of atrial fibrillation, myocardial infarction, and atrio-ventricular block.

    PubMed

    Sankari, Ziad; Adeli, Hojjat

    2011-04-01

    A mobile medical device, dubbed HeartSaver, is developed for real-time monitoring of a patient's electrocardiogram (ECG) and automatic detection of several cardiac pathologies, including atrial fibrillation, myocardial infarction and atrio-ventricular block. HeartSaver is based on adroit integration of four different modern technologies: electronics, wireless communication, computer, and information technologies in the service of medicine. The physical device consists of four modules: sensor and ECG processing unit, a microcontroller, a link between the microcontroller and the cell phone, and mobile software associated with the system. HeartSaver includes automated cardiac pathology detection algorithms. These algorithms are simple enough to be implemented on a low-cost, limited-power microcontroller but powerful enough to detect the relevant cardiac pathologies. When an abnormality is detected, the microcontroller sends a signal to a cell phone. This operation triggers an application software on the cell phone that sends a text message transmitting information about patient's physiological condition and location promptly to a physician or a guardian. HeartSaver can be used by millions of cardiac patients with the potential to transform the cardiac diagnosis, care, and treatment and save thousands of lives.

  9. Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis

    PubMed Central

    Adlan, Ahmed M.; Paton, Julian F. R.; Lip, Gregory Y. H.; Kitas, George D.

    2016-01-01

    Key points Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of cardiovascular mortality.Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity heighten cardiovascular risk, althogh whether such autonomic dysfunction is present in RA is not known.In the present study, we observed an increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in patients with RA compared to matched controls.Pain was positively correlated with sympathetic nerve activity and negatively correlated with cardiac baroreflex sensitivity.The pattern of autonomic dysfunction that we describe may help to explain the increased cardiovascular risk in RA, and raises the possibility that optimizing pain management may resolve autonomic dysfunction in RA. Abstract Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesized that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age‐ and sex‐matched RA‐normotensive (n = 13), RA‐hypertensive patients (RA‐HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C‐reactive protein (hs‐CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA‐HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts min–1) compared to NC (22 ± 9 bursts min–1; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), whereas cardiac BRS (cBRS) was

  10. Cathepsin‐L Ameliorates Cardiac Hypertrophy Through Activation of the Autophagy–Lysosomal Dependent Protein Processing Pathways

    PubMed Central

    Sun, Mei; Ouzounian, Maral; de Couto, Geoffrey; Chen, Manyin; Yan, Ran; Fukuoka, Masahiro; Li, Guohua; Moon, Mark; Liu, Youan; Gramolini, Anthony; Wells, George J.; Liu, Peter P.

    2013-01-01

    Background Autophagy is critical in the maintenance of cellular protein quality control, the final step of which involves the fusion of autophagosomes with lysosomes. Cathepsin‐L (CTSL) is a key member of the lysosomal protease family that is expressed in the murine and human heart, and it may play an important role in protein turnover. We hypothesized that CTSL is important in regulating protein processing in the heart, particularly under pathological stress. Methods and Results Phenylephrine‐induced cardiac hypertrophy in vitro was more pronounced in CTSL‐deficient neonatal cardiomyocytes than in in controls. This was accompanied by a significant accumulation of autophagosomes, increased levels of ubiquitin‐conjugated protein, as well as impaired protein degradation and decreased cell viability. These effects were partially rescued with CTSL1 replacement via adeno‐associated virus–mediated gene transfer. In the in vivo murine model of aortic banding (AB), a deficiency in CTSL markedly exacerbated cardiac hypertrophy, worsened cardiac function, and increased mortality. Ctsl−/− AB mice demonstrated significantly decreased lysosomal activity and increased sarcomere‐associated protein aggregation. Homeostasis of the endoplasmic reticulum was also altered by CTSL deficiency, with increases in Bip and GRP94 proteins, accompanied by increased ubiquitin–proteasome system activity and higher levels of ubiquitinated proteins in response to AB. These changes ultimately led to a decrease in cellular ATP production, enhanced oxidative stress, and increased cellular apoptosis. Conclusions Lysosomal CTSL attenuates cardiac hypertrophy and preserves cardiac function through facilitation of autophagy and proteasomal protein processing. PMID:23608608

  11. Approximate active fault detection and control

    NASA Astrophysics Data System (ADS)

    Škach, Jan; Punčochář, Ivo; Šimandl, Miroslav

    2014-12-01

    This paper deals with approximate active fault detection and control for nonlinear discrete-time stochastic systems over an infinite time horizon. Multiple model framework is used to represent fault-free and finitely many faulty models. An imperfect state information problem is reformulated using a hyper-state and dynamic programming is applied to solve the problem numerically. The proposed active fault detector and controller is illustrated in a numerical example of an air handling unit.

  12. 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.

  13. Cardiac-Activity Measures for Assessing Airport Ramp-Tower Controller's Workload

    NASA Technical Reports Server (NTRS)

    Hayashi, Miwa; Dulchinos, Victoria

    2016-01-01

    Heart rate (HR) and heart rate variability (HRV) potentially offer objective, continuous, and non-intrusive measures of human-operators mental workload. Such measurement capability is attractive for workload assessment in complex laboratory simulations or safety-critical field testing. The present study compares mean HR and HRV data with self-reported subjective workload ratings collected during a high-fidelity human-in-the-loop simulation of airport ramp traffic control operations, which involve complex cognitive and coordination tasks. Mean HR was found to be weakly sensitive to the workload ratings, while HRV was not sensitive or even contradictory to the assumptions. Until more knowledge on stress response mechanisms of the autonomic nervous system is obtained, it is recommended that these cardiac-activity measures be used with other workload assessment tools, such as subjective measures.

  14. [Studies on cardiac ingredients of plants. X. Preparation of nitrates of tetrahydroproscillaridin and their pharmacological activities].

    PubMed

    Tanase, T; Murakami, N; Nagatsu, A; Nagai, S; Sakakibara, J; Ando, H; Hotta, Y; Takeya, K; Asano, M

    1992-11-01

    To reduce the vascular contracting effect of the hydrogenated cardiac glycosides, 20-(R)- and 20-(S)-tetrahydroproscillaridins (THPs, 1a, 1b), and to extend the concentration-dependent range, mono- and dinitrates of THPs were prepared. The pharmacological activities of the nitrates of THP were evaluated by use of isolated guinea-pig papillary muscle preparations and Na+,K(+)-adenosine triphosphatase preparations from dog kidney. Furthermore, the effect for smooth muscle was examined using the helical strips isolated from 13-week-old spontaneously hypertensive rat. The positive inotropic effects of mononitrates (11a, 11b, 2a, 2b, 8a, and 8b) were more potent than those of THPs. Nitration of the sugar moiety in THPs resulted in a vascular relaxing effect unobserved in the case of THPs.

  15. Cardiac-Activity Measures for Assessing Airport Ramp-Tower Controller's Workload

    NASA Technical Reports Server (NTRS)

    Hayashi, Miwa; Dulchinos, Victoria L.

    2016-01-01

    Heart rate (HR) and heart rate variability (HRV) potentially offer objective, continuous, and non-intrusive measures of human-operator's mental workload. Such measurement capability is attractive for workload assessment in complex laboratory simulations or safety-critical field testing. The present study compares mean HR and HRV data with self-reported subjective workload ratings collected during a high-fidelity human-in-the-loop simulation of airport ramp traffic control operations, which involve complex cognitive and coordination tasks. Mean HR was found to be weakly sensitive to the workload ratings, while HRV was not sensitive or even contradictory to the assumptions. Until more knowledge on stress response mechanisms of the autonomic nervous system is obtained, it is recommended that these cardiac-activity measures be used with other workload assessment tools, such as subjective measures.

  16. 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.

  17. Detection of cardiac hypertrophy in the fetus by approximation of the current dipole using magnetocardiography.

    PubMed

    Horigome, H; Shiono, J; Shigemitsu, S; Asaka, M; Matsui, A; Kandori, A; Miyashita, T; Tsukada, K

    2001-08-01

    To determine the developmental changes in the myocardial current during fetal life, and to evaluate the clinical usefulness of magnetocardiography for prenatal diagnosis of cardiac hypertrophy or enlargement, we approximated the magnitude of the one-current dipole of the fetal heart using fetal magnetocardiography (fMCG). A total of 95 fetuses with gestational age of 20-40 wk were included in this study. fMCG was recorded with a nine-channel superconducting quantum interference device system in a magnetically shielded room. The magnitude of the dipole (Q) was calculated using an equation based on the fMCG amplitude obtained on the maternal abdomen and the distance between the maternal surface and fetal heart measured ultrasonographically. In uncomplicated pregnancies, the Q value correlated significantly with gestational age, reflecting an increase in the amount of myocardial current, i.e. myocardial mass. Moreover, the Q values in fetuses with cardiomegaly caused by various cardiovascular abnormalities tended to be higher than the normal values. Although there are some limitations of the methodology based on the half-space model, and fetal orientation may influence the magnitude of the dipole, making it smaller, fMCG recorded with a multichannel superconducting quantum interference device system is a clinically useful tool for noninvasive, prenatal, and electrical evaluation of fetal cardiac hypertrophy.

  18. Stochastic initiation and termination of calcium-mediated triggered activity in cardiac myocytes

    PubMed Central

    Song, Zhen; Qu, Zhilin; Karma, Alain

    2017-01-01

    Cardiac myocytes normally initiate action potentials in response to a current stimulus that depolarizes the membrane above an excitation threshold. Aberrant excitation can also occur due to spontaneous calcium (Ca2+) release (SCR) from intracellular stores after the end of a preceding action potential. SCR drives the Na+/Ca2+ exchange current inducing a “delayed afterdepolarization” that can in turn trigger an action potential if the excitation threshold is reached. This “triggered activity” is known to cause arrhythmias, but how it is initiated and terminated is not understood. Using computer simulations of a ventricular myocyte model, we show that initiation and termination are inherently random events. We determine the probability of those events from statistical measurements of the number of beats before initiation and before termination, respectively, which follow geometric distributions. Moreover, we elucidate the origin of randomness by a statistical analysis of SCR events, which do not follow a Poisson process observed in other eukaryotic cells. Due to synchronization of Ca2+ releases during the action potential upstroke, waiting times of SCR events after the upstroke are narrowly distributed, whereas SCR amplitudes follow a broad normal distribution with a width determined by fluctuations in the number of independent Ca2+ wave foci. This distribution enables us to compute the probabilities of initiation and termination of bursts of triggered activity that are maintained by a positive feedback between the action potential upstroke and SCR. Our results establish a theoretical framework for interpreting complex and varied manifestations of triggered activity relevant to cardiac arrhythmias. PMID:28049836

  19. Effects of vigorous late-night exercise on sleep quality and cardiac autonomic activity.

    PubMed

    Myllymäki, Tero; Kyröläinen, Heikki; Savolainen, Katri; Hokka, Laura; Jakonen, Riikka; Juuti, Tanja; Martinmäki, Kaisu; Kaartinen, Jukka; Kinnunen, Marja-Liisa; Rusko, Heikki

    2011-03-01

    Sleep is the most important period for recovery from daily load. Regular physical activity enhances overall sleep quality, but the effects of acute exercise on sleep are not well defined. In sleep hygiene recommendations, intensive exercising is not suggested within the last 3 h before bed time, but this recommendation has not been adequately tested experimentally. Therefore, the effects of vigorous late-night exercise on sleep were examined by measuring polysomnographic, actigraphic and subjective sleep quality, as well as cardiac autonomic activity. Eleven (seven men, four women) physically fit young adults (VO(2max) 54±8 mL·kg(-1)·min(-1) , age 26±3 years) were monitored in a sleep laboratory twice in a counterbalanced order: (1) after vigorous late-night exercise; and (2) after a control day without exercise. The incremental cycle ergometer exercise until voluntary exhaustion started at 21:00±00:28 hours, lasted for 35±3 min, and ended 2:13±00:19 hours before bed time. The proportion of non-rapid eye movement sleep was greater after the exercise day than the control day (P<0.01), while no differences were seen in actigraphic or subjective sleep quality. During the whole sleep, no differences were found in heart rate (HR) variability, whereas HR was higher after the exercise day than the control day (54±7 versus 51±7, P<0.01), and especially during the first three sleeping hours. The results indicate that vigorous late-night exercise does not disturb sleep quality. However, it may have effects on cardiac autonomic control of heart during the first sleeping hours.

  20. Cardiac M2 muscarinic cholinoceptor activation by human chagasic autoantibodies: association with bradycardia

    PubMed Central

    Goin, J; Borda, E; Auger, S; Storino, R; Sterin-Borda, L

    1999-01-01

    OBJECTIVE—To assess whether exposure of cardiac muscarinic acetylcholine receptors (mAChR) to activating chagasic antimyocardial immunoglobulins results in bradycardia and other dysautonomic symptoms associated with the regulation of heart rate.
METHODS—Trypanosoma cruzi infected patients with bradycardia and other abnormalities in tests of the autonomic nervous system were studied and compared with normal subjects. Antipeptide antibodies in serum were demonstrated by an enzyme linked immunosorbent assay using a synthetic 24-mer-peptide corresponding antigenically to the second extracellular loop of the human heart M2 mAChR. The functional effect of affinity purified antipeptide IgG from chagasic patients on spontaneous beating frequency and cAMP production of isolated normal rat atria was studied.
RESULTS—There was a strong association between the finding of antipeptide antibodies in chagasic patients and the presence of basal bradycardia and an altered Valsalva manoeuvre (basal bradycardia: χ2 = 37.5, p < 0.00001; Valsalva manoeuvre: χ2 = 70.0, p < 0.00001). The antipeptide autoantibodies also showed agonist activity, decreasing the rate of contraction and cAMP production. The effects on rat atria resembled the effects of the authentic agonist and those of the total polyclonal chagasic IgG, being selectively blunted by atropine and AF-DX 116, and neutralised by the synthetic peptide corresponding in amino acid sequence to the second extracellular loop of the human M2 mAChR.
CONCLUSIONS—There is an association between circulating antipeptide autoantibodies in chagasic patients and the presence of bradycardia and other dysautonomic symptoms. Thus these autoantibodies are a marker of autoimmune cardiac autonomic dysfunction. The results support the hypothesis that autoimmune mechanisms play a role in the pathogenesis of chagasic cardioneuromyopathy.


Keywords: heart rate; bradycardia; autoantibodies; chagasic cardiomyopathy PMID

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

    PubMed

    Seidlmayer, Lea K; Gomez-Garcia, Maria R; Blatter, Lothar A; Pavlov, Evgeny; Dedkova, Elena N

    2012-05-01

    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.

  2. 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.

  3. Resveratrol activates endogenous cardiac stem cells and improves myocardial regeneration following acute myocardial infarction

    PubMed Central

    Ling, Lin; Gu, Shaohua; Cheng, Yan

    2017-01-01

    Stem cell antigen-1-positive (Sca-1+) cardiac stem cells (CSCs) therapy for myocardial regeneration following acute myocardial infarction (AMI) is limited by insufficient cell viability and a high rate of apoptosis, due to the poor regional microenvironment. Resveratrol, which is a compound extracted from red wine, has been reported to protect myocardial tissue post-AMI by increasing the expression of angiogenic and chemotactic factors. The present study aimed to investigate the effects of resveratrol on Sca-1+ CSCs, and to optimize Sca-1+ CSCs therapy for myocardial regeneration post-AMI. C57/BL6 mice (age, 6 weeks) were divided into two groups, which received intragastric administration of PBS or 2.5 mg/kg.d resveratrol. The endogenous expression of Sca-1+ CSCs in the heart was assessed on day 7. Furthermore, C57/BL6 mice underwent left anterior descending coronary artery ligation for the construction of an AMI model, and received an injection of 1×106 CSCs into the peri-ischemic area (n=8/group). Mice received intragastric administration of PBS or resveratrol (2.5 mg/kg.d) for 4 weeks after cell transplantation. Echocardiography was used to evaluate cardiac function 4 weeks after cell transplantation. Capillary density and cardiomyocyte apoptosis in the peri-ischemic myocardium were assessed by cluster of differentiation 31 immunofluorescent staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, respectively. Western blot analysis was conducted to detect the protein expression levels of vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF)-1α in the myocardium. Treatment with resveratrol increased the number of endogenous Sca-1+ CSCs in heart tissue after 7 days (PBS vs. Res, 1.85±0.41/field vs. 3.14±0.26/field, P<0.05). Furthermore, intragastric administration of resveratrol significantly increased left ventricle (LV) function 4 weeks after AMI, as determined by an increase in LV fractional

  4. [Deoxyribonuclease activity detection in Clostridium chauvoei strains].

    PubMed

    Carloni, G H; Bentancor, L D; De Torres, R A

    2005-01-01

    Beta toxin of C. chauvoei has desoxiribonuclease (DNase) activity which is regarded as one of its virulence factors. The production of DNase was detected in strains isolated from bovines, using as controls C. chauvoei ATCC 10092, and C. perfringens Type A and C. septicum, both laboratory isolates. The enzyme activity was made evident on a DNA substrate observing the macroscopic degradation. A simple methodology was developed using a commercial medium for DNase test, with the incorporation of sterile horse serum. Each strain was streaked on the surface of the medium, incubated in anaerobic atmosphere at 37 degrees C for 48 hours. The plates were revealed with HCI 1 N. The appearance of a clear and transparent zone around and under the microbial growing was considered a positive reaction. Enzyme activity was detected in 10 of 12 strains and also in the controls. The serum addition to the commercial basal medium allows the optimum development of the microorganism showing the enzymatic digestion zone.

  5. Cardiac arrest with pulseless electrical activity associated with methylphenidate in an adolescent with a normal baseline echocardiogram.

    PubMed

    Daly, Michael W; Custer, Geoffrey; McLeay, Peter D

    2008-11-01

    Recent concerns of adverse cardiac events associated with drugs used to treat attention-deficit-hyperactivity disorder (ADHD) have prompted debate over whether these drugs are truly safe. We describe a 17-year-old boy with a normal baseline echocardiogram who had been taking methylphenidate for ADHD for 18 months and experienced cardiac arrest. Emergency personnel attempted to resuscitate him, performing defibrillation twice for ventricular fibrillation, with subsequent pulseless electrical activity. The patient was immediately taken to the hospital where he received continued resuscitation, intravenous boluses of cardiac drugs, and additional defibrillation. A persistent pulsatile rhythm returned about 2 minutes after arrival. Overall, the patient was pulseless for 22 minutes. Emergency cardiac catheterization revealed wall motion abnormalities without coronary lesions. He was mechanically ventilated and was transferred to the intensive care unit, where he remained comatose. Neurologic studies performed the next day revealed diffuse encephalopathy due to anoxic brain injury. An echocardiogram on day 3 showed slightly improved left ventricular systolic function, which improved further by day 15. As the patient did not regain purposeful movement, he was discharged to a rehabilitation facility on day 33. The patient's methylphenidate therapy had been started at an appropriate dose of 18 mg/day and titrated over a period of 3 months up to 36 mg/day, which he continued until the event. The drug had been discontinued on admission, was not restarted, and for the next 2 years, the patient experienced no further cardiac events, although his severe mental deficiencies persisted. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 6) between the patient's adverse cardiac event and methylphenidate. To our knowledge, this is the first case report of a patient with documentation of a normal baseline echocardiogram who

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

    PubMed

    Bunno, Yoshibumi; Suzuki, Toshiaki; Iwatsuki, Hiroyasu

    2015-12-01

    [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.

  7. Nebivolol Ameliorates Cardiac NLRP3 Inflammasome Activation in a Juvenile-Adolescent Animal Model of Diet-Induced Obesity.

    PubMed

    Xie, Qihai; Wei, Tong; Huang, Chenglin; Liu, Penghao; Sun, Mengwei; Shen, Weili; Gao, Pingjin

    2016-09-30

    NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d). Treatment with nebivolol prevented HFD-induced obesity associated excess cardiac lipid accumulation as well as myocardial mitochondrial dysfunction. Nebivolol attenuated pro-inflammatory cytokines secretion and NLRP3 inflammasome activation in myocardium of obese rats. In parallel, nebivolol treatment of obese animals increased cardiac β3-AR expression, reversing the reduction of endothelial nitric oxide synthase (eNOS). In vitro, nebivolol treatment of palmitate-incubated H9C2 cells suppressed autophagy, restored mitochondrial biogenesis, leading to decreased mitochondrial reactive oxygen species (mtROS) generation, and suppressed NLRP3 inflammasome activation. Meanwhile the presence of shRNA against β3-AR or against eNOS deteriorated the protective effects of nebivolol. These data suggest the beneficial effect of nebivolol on myocardial lipotoxicity contributing to inhibiting NLRP3 inflammasome activation possibly via improved mitochondrial dysfunction.

  8. Nebivolol Ameliorates Cardiac NLRP3 Inflammasome Activation in a Juvenile-Adolescent Animal Model of Diet-Induced Obesity

    PubMed Central

    Xie, Qihai; Wei, Tong; Huang, Chenglin; Liu, Penghao; Sun, Mengwei; Shen, Weili; Gao, Pingjin

    2016-01-01

    NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d). Treatment with nebivolol prevented HFD-induced obesity associated excess cardiac lipid accumulation as well as myocardial mitochondrial dysfunction. Nebivolol attenuated pro-inflammatory cytokines secretion and NLRP3 inflammasome activation in myocardium of obese rats. In parallel, nebivolol treatment of obese animals increased cardiac β3-AR expression, reversing the reduction of endothelial nitric oxide synthase (eNOS). In vitro, nebivolol treatment of palmitate-incubated H9C2 cells suppressed autophagy, restored mitochondrial biogenesis, leading to decreased mitochondrial reactive oxygen species (mtROS) generation, and suppressed NLRP3 inflammasome activation. Meanwhile the presence of shRNA against β3-AR or against eNOS deteriorated the protective effects of nebivolol. These data suggest the beneficial effect of nebivolol on myocardial lipotoxicity contributing to inhibiting NLRP3 inflammasome activation possibly via improved mitochondrial dysfunction. PMID:27686325

  9. Physical activity levels during phase IV cardiac rehabilitation in a group of male myocardial infarction patients

    PubMed Central

    Woolf-May, K; Bird, S; MacIntyre, P

    2005-01-01

    Objective: To determine physical activity levels during phase IV cardiac rehabilitation in 31 male myocardial infarction patients (median age 62, range 53–77 years). Methods: Patients recorded daily physical activity over 16 weeks in a diary. Diaries were analysed for total general physical activity (TGPA), leisure time physical activity (LTPA), and "active for life" exercise classes (AFL). Pre- and post-observation period (OP) subjects underwent a 10 m shuttle walking test (SWT) to determine changes in aerobic fitness. Rate of perceived exertion (RPE) determined exercise intensity. Estimated gross energy expenditure (EEE) was determined by a regression equation between RPE and Vo2 (l min–1) during SWT. A total of 97% of subjects were on lipid lowering medication. Results: There were no correlations between Vo2 (l min–1) and body mass, therefore kcal min–1 indicated activity intensity. There were no significant changes in physical activity patterns or in aerobic fitness. Estimated total LTPA (median 1376, range 128–3380 kcal week–1) was less than that recommended to improve aerobic fitness and/or slow progression of coronary artery disease. Sixteen subjects attended a median of 29 (range 1–46) AFL during LTPA; one way ANOVA showed these subjects worked at greater EEE (AFL, n = 16, 6.6 (standard deviation 1.4) v no-AFL, n = 15, 5.1 (1.8) EEE kcal min–1, p = 0.017). Conclusion: Physical activity was stable, but patients' EEE appeared insufficient to improve aerobic fitness or slow progression of coronary artery disease. It was suggested that the promotion of LTPA and the availability of AFL classes should be reconsidered. PMID:15728680

  10. 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.

  11. Surface plasmon resonance biosensor with high anti-fouling ability for the detection of cardiac marker troponin T.

    PubMed

    Liu, Jen Tsai; Chen, Ching Jung; Ikoma, Toshiyuki; Yoshioka, Tomohiko; Cross, Jeffrey S; Chang, Shwu-Jen; Tsai, Jang-Zern; Tanaka, Junzo

    2011-10-03

    Designing a surface recognition layer with high anti-fouling ability, high affinity, and high specificity is an important issue to produce high sensitivity biosensing transducers. In this study, a self-assembled monolayer (SAM) consisting of a homogeneous mixture of oligo(ethylene glycol) (OEG)-terminated alkanethiolate and mercaptohexadecanoic acid (MHDA) on Au was employed for immobilizing troponin T antibody and applied in detecting cardiac troponin T by using surface plasmon resonance (SPR). The mixed SAM showed no phase segregation and exhibited human serum albumin resistance, particularly with an antibody-immobilized surface. X-ray photoemission spectra revealed that the chemical composition ratio of OEG to the mixed SAM was 69% and the OEG packing density was 82%. The specific binding of troponin T on the designed surface indicated a good linear correlation (R=0.991, P<0.0009) at concentrations lower than 50 μgmL(-1) with the limit of detection of 100 ngmL(-1) using a SPR measuring instrument. It is concluded that the mixed SAM functions as designed since it has high detection capability, high accuracy and reproducibility, as well as shows strong potential to be applied in rapid clinical diagnosis for label-free detection within 2 min.

  12. 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

  13. Ventricular Tachycardia in Fabry Disease Detected in a 50-Year-Old Woman during 14-Day Continuous Cardiac Monitoring

    PubMed Central

    Silva-Gburek, Jaime; Rochford, Laura; Hopkin, Robert

    2016-01-01

    Fabry disease is an X-linked lysosomal storage disorder. Female carriers were long thought to be asymptomatic; however, research has revealed the opposite. Cardiac conditions are the chief causes of death in women with Fabry disease. Although ventricular tachycardia has been reported in male patients with Fabry disease, it is not thought to be a frequent finding in females. We describe the case of a 50-year-old woman in whom we used 14-day continuous electrocardiographic monitoring to identify nonsustained ventricular tachycardia, after electrocardiograms and 24-hour Holter monitoring failed to detect the arrhythmia. A permanent implantable cardioverter-defibrillator relieved the patient's symptoms. We discuss why this case supports the need for more extensive electrophysiologic evaluation in women who have Fabry disease. PMID:28100976

  14. HDAC3-dependent Reversible Lysine Acetylation of Cardiac Myosin Heavy Chain Isoforms Modulates Their Enzymatic and Motor Activity*

    PubMed Central

    Samant, Sadhana A.; Courson, David S.; Sundaresan, Nagalingam R.; Pillai, Vinodkumar B.; Tan, Minjia; Zhao, Yingming; Shroff, Sanjeev G.; Rock, Ronald S.; Gupta, Mahesh P.

    2011-01-01

    Reversible lysine acetylation is a widespread post-translational modification controlling the activity of proteins in different subcellular compartments. We previously demonstrated that a class II histone deacetylase (HDAC), HDAC4, and a histone acetyltransferase, PCAF, associate with cardiac sarcomeres, and a class I and II HDAC inhibitor, trichostatin A, enhances contractile activity of myofilaments. In this study, we show that a class I HDAC, HDAC3, is also present at cardiac sarcomeres. By immunohistochemical and electron microscopic analyses, we found that HDAC3 was localized to the A band of sarcomeres and was capable of deacetylating myosin heavy chain (MHC) isoforms. The motor domains of both cardiac α- and β-MHC isoforms were found to be reversibly acetylated. Biomechanical studies revealed that lysine acetylation significantly decreased the Km for the actin-activated ATPase activity of both α- and β-MHC isoforms. By an in vitro motility assay, we found that lysine acetylation increased the actin sliding velocity of α-myosin by 20% and β-myosin by 36%, compared to their respective non-acetylated isoforms. Moreover, myosin acetylation was found to be sensitive to cardiac stress. During induction of hypertrophy, myosin isoform acetylation increased progressively with duration of stress stimuli, independent of isoform shift, suggesting that lysine acetylation of myosin could be an early response of myofilaments to increase contractile performance of the heart. These studies provide the first evidence for localization of HDAC3 at myofilaments and uncover a novel mechanism modulating the motor activity of cardiac MHC isoforms. PMID:21177250

  15. HDAC3-dependent reversible lysine acetylation of cardiac myosin heavy chain isoforms modulates their enzymatic and motor activity.

    PubMed

    Samant, Sadhana A; Courson, David S; Sundaresan, Nagalingam R; Pillai, Vinodkumar B; Tan, Minjia; Zhao, Yingming; Shroff, Sanjeev G; Rock, Ronald S; Gupta, Mahesh P

    2011-02-18

    Reversible lysine acetylation is a widespread post-translational modification controlling the activity of proteins in different subcellular compartments. We previously demonstrated that a class II histone deacetylase (HDAC), HDAC4, and a histone acetyltransferase, PCAF, associate with cardiac sarcomeres, and a class I and II HDAC inhibitor, trichostatin A, enhances contractile activity of myofilaments. In this study, we show that a class I HDAC, HDAC3, is also present at cardiac sarcomeres. By immunohistochemical and electron microscopic analyses, we found that HDAC3 was localized to the A band of sarcomeres and was capable of deacetylating myosin heavy chain (MHC) isoforms. The motor domains of both cardiac α- and β-MHC isoforms were found to be reversibly acetylated. Biomechanical studies revealed that lysine acetylation significantly decreased the K(m) for the actin-activated ATPase activity of both α- and β-MHC isoforms. By an in vitro motility assay, we found that lysine acetylation increased the actin sliding velocity of α-myosin by 20% and β-myosin by 36%, compared to their respective non-acetylated isoforms. Moreover, myosin acetylation was found to be sensitive to cardiac stress. During induction of hypertrophy, myosin isoform acetylation increased progressively with duration of stress stimuli, independent of isoform shift, suggesting that lysine acetylation of myosin could be an early response of myofilaments to increase contractile performance of the heart. These studies provide the first evidence for localization of HDAC3 at myofilaments and uncover a novel mechanism modulating the motor activity of cardiac MHC isoforms.

  16. 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

  17. 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

  18. 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.

  19. 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

    2009-05-06

    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.

  20. Cooperative Cross-Bridge Activation of Thin Filaments Contributes to the Frank-Starling Mechanism in Cardiac Muscle

    PubMed Central

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

    2009-01-01

    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 [Ca2+] and [Vi]. Increasing [Vi] (decreased force) reduced the pCa50 of force-[Ca2+] relations at 2.3 and 2.0 μm SL, with little effect on slope (nH). When maximum force was inhibited to ∼40%, the effects of SL on force were diminished at lower [Ca2+], whereas at higher [Ca2+] (pCa < 5.6) the relative influence of SL on force increased. In contrast, force inhibition to ∼20% significantly reduced the sensitivity of force-[Ca2+] 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

  1. A new method for FMRI activation detection

    NASA Astrophysics Data System (ADS)

    Wei, Jianing; Talavage, Thomas M.; Pollak, Ilya

    2009-02-01

    The objective of fMRI data analysis is to detect the region of the brain that gets activated in response to a specific stimulus presented to the subject. We develop a new algorithm for activation detection in event-related fMRI data. We utilize a forward model for fMRI data acquisition which explicitly incorporates physiological noise, scanner noise and the spatial blurring introduced by the scanner. After slice-by-slice image restoration procedure that independently restores each data slice corresponding to each time index, we estimate the parameters of the hemodynamic response function (HRF) model for each pixel of the restored data. In order to enforce spatial regularity in our estimates, we model the prior distribution of the HRF parameters as a generalized Gaussian Markov random field (GGMRF) model. We develop an algorithm to compute the maximum a posteriori (MAP) estimates of the parameters. We then threshold the amplitude parameters to obtain the final activation map. We illustrate our algorithm by comparing it with the widely used general linear model (GLM) method. In synthetic data experiments, under the same probability of false alarm, the probability of correct detection for our method is up to 15% higher than GLM. In real data experiments, through anatomical analysis and benchmark testing using block paradigm results, we demonstrate that our algorithm produces fewer false alarms than GLM.

  2. Daily sesame oil supplementation attenuates local renin-angiotensin system via inhibiting MAPK activation and oxidative stress in cardiac hypertrophy.

    PubMed

    Liu, Chuan-Teng; Liu, Ming-Yie

    2017-04-01

    The renin-angiotensin system (RAS) is involved in the development of left ventricular hypertrophy (LVH) by which increases cardiac morbidity and mortality. Activation of mitogen-activated protein kinases (MAPKs) and oxidative stress are important in RAS-mediated cardiac hypertrophy. Sesame oil, a potent antioxidant, attenuates hypertension-dependent LVH. We examined the protective role of sesame oil on RAS-mediated MAPK activation and oxidative stress in rats. We induced LVH using a hypertensive model by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/ml/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was gavaged (0.5 or 1 ml/kg/day for 7 days) after 4 weeks of DOCA/salt treatment. Cardiac histopathology, RAS parameters, expression of MAPKs, reactive oxygen species and lipid peroxidation were assessed 24 h after the last dose of sesame oil. Sesame oil significantly decreased the size of cardiomyocytes and the levels of cardiac renin, angiotensin-converting enzyme and angiotensin II. In addition, sesame oil down-regulated the expression of angiotensin type 1 receptor, JNK and p38 MAPK and apoptosis signal regulating kinase 1, c-Fos and c-Jun in rats receiving DOCA/salt. Furthermore, the induction of nicotinamide adenine dinucleotide phosphate oxidase, superoxide anion and hydroxyl radical and lipid peroxidation by DOCA/salt were inhibited by sesame oil. Sesame oil modulates cardiac RAS to ameliorate LVH by inhibiting MAPK activation and lowering oxidative stress.

  3. 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

  4. Multiplex detection of B-type natriuretic peptide, cardiac troponin I and C-reactive protein with photonic suspension array.

    PubMed

    Lu, Wenbin; Fu, Cong; Chen, Yong; Lu, Jun; Yao, Yuyu; Shen, Chengxing; Gu, Zhongze

    2012-01-01

    A novel photonic suspension array has been developed for multiplex immunoassay. The carriers of this array were silica colloidal crystal beads (SCCBs). The codes of these carriers have characteristic reflection peaks originating from their structural periodicity; therefore they do not suffer from fading, bleaching, quenching or chemical instability. In addition, the fluorescence background of SCCBs is negligible because no fluorescence materials or dyes are involved. With a sandwich method, the proposed suspension array was used for simultaneous multiplex detection of heart failure (HF) and coronary heart disease (CAD) biomarkers in one test tube. The results showed that the three biomarkers: cardiac troponin I (cTnI), C-reactive protein (CRP) and B-type natriuretic peptide (BNP) could be assayed in the ranges of 0.1-500 ng/ml, 1-500 mg/L and 0.02-50 ng/ml with detection limits of 0.01 ng/ml, 0.36 mg/L and 0.004 ng/ml at 3σ, respectively. There were no significant differences between the photonic suspension array and traditional parallel single-analyte test. This novel method demonstrated acceptable accuracy, high detection sensitivity and reproducibility and excellent storage stability. This technique provides a new strategy for low cost, automated, and simultaneous multiplex immunoassays of bio-markers.

  5. A label-free electrochemical immunosensor for the detection of cardiac marker using graphene quantum dots (GQDs).

    PubMed

    Tuteja, Satish K; Chen, Rui; Kukkar, Manil; Song, Chung Kil; Mutreja, Ruchi; Singh, Suman; Paul, Ashok K; Lee, Haiwon; Kim, Ki-Hyun; Deep, Akash; Suri, C Raman

    2016-12-15

    A label-free immunosensor based on electrochemical impedance spectroscopy has been developed for the sensitive detection of a cardiac biomarker myoglobin (cMyo). Hydrothermally synthesized graphene quantum dots (GQDs) have been used as an immobilized template on screen printed electrodes for the construction of an impedimetric sensor platform. The GQDs-modified electrode was conjugated with highly specific anti-myoglobin antibodies to develop the desired immunosensor. The values of charge transfer resistance (Rct) were monitored as a function of varying antigen concentration. The Rct value of the immunosensor showed a linear increase (from 0.20 to 0.31kΩ) in the range of 0.01-100ng/mL cMyo. The specific detection of cMyo was also made in the presence of other competing proteins. The limit of detection for the proposed immunosensor was estimated as 0.01ng/mL which is comparable to the standard ELISA techniques.

  6. 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.

  7. Spontaneous baroreflex control of cardiac output during dynamic exercise, muscle metaboreflex activation, and heart failure.

    PubMed

    Ichinose, Masashi; Sala-Mercado, Javier A; O'Leary, Donal S; Hammond, Robert L; Coutsos, Matthew; Ichinose, Tomoko; Pallante, Marco; Iellamo, Ferdinando

    2008-03-01

    We have previously shown that spontaneous baroreflex-induced changes in heart rate (HR) do not always translate into changes in cardiac output (CO) at rest. We have also shown that heart failure (HF) decreases this linkage between changes in HR and CO. Whether dynamic exercise and muscle metaboreflex activation (via imposed reductions in hindlimb blood flow) further alter this translation in normal and HF conditions is unknown. We examined these questions using conscious, chronically instrumented dogs before and after pacing-induced HF during mild and moderate dynamic exercise with and without muscle metaboreflex activation. We measured left ventricular systolic pressure (LVSP), CO, and HR and analyzed the spontaneous HR-LVSP and CO-LVSP relationships. In normal animals, mild exercise significantly decreased HR-LVSP (-3.08 +/- 0.5 vs. -5.14 +/- 0.6 beats.min(-1).mmHg(-1); P < 0.05) and CO-LVSP (-134.74 +/- 24.5 vs. -208.6 +/- 22.2 ml.min(-1).mmHg(-1); P < 0.05). Moderate exercise further decreased both and, in addition, significantly reduced HR-CO translation (25.9 +/- 2.8% vs. 52.3 +/- 4.2%; P < 0.05). Muscle metaboreflex activation at both workloads decreased HR-LVSP, whereas it had no significant effect on CO-LVSP and the HR-CO translation. HF significantly decreased HR-LVSP, CO-LVSP, and the HR-CO translation in all situations. We conclude that spontaneous baroreflex HR responses do not always cause changes in CO during exercise. Moreover, muscle metaboreflex activation during mild and moderate dynamic exercise reduces this coupling. In addition, in HF the HR-CO translation also significantly decreases during both workloads and decreases even further with muscle metaboreflex activation.

  8. A Novel Cardioprotective Agent in Cardiac Transplantation: Metformin Activation of AMP-Activated Protein Kinase Decreases Acute Ischemia-Reperfusion Injury and Chronic Rejection

    PubMed Central

    Chin, Jocelyn T.; Troke, Joshua J.; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P.; Robbins, Robert C.; Fischbein, Michael P.

    2011-01-01

    The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury. PMID:22180679

  9. A novel cardioprotective agent in cardiac transplantation: metformin activation of AMP-activated protein kinase decreases acute ischemia-reperfusion injury and chronic rejection.

    PubMed

    Chin, Jocelyn T; Troke, Joshua J; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P; Robbins, Robert C; Fischbein, Michael P

    2011-12-01

    The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury.

  10. 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.

  11. Early-Onset Hypertrophic Cardiomyopathy Mutations Significantly Increase the Velocity, Force, and Actin-Activated ATPase Activity of Human β-Cardiac Myosin.

    PubMed

    Adhikari, Arjun S; Kooiker, Kristina B; Sarkar, Saswata S; Liu, Chao; Bernstein, Daniel; Spudich, James A; Ruppel, Kathleen M

    2016-12-13

    Hypertrophic cardiomyopathy (HCM) is a heritable cardiovascular disorder that affects 1 in 500 people. A significant percentage of HCM is attributed to mutations in β-cardiac myosin, the motor protein that powers ventricular contraction. This study reports how two early-onset HCM mutations, D239N and H251N, affect the molecular biomechanics of human β-cardiac myosin. We observed significant increases (20%-90%) in actin gliding velocity, intrinsic force, and ATPase activity in comparison to wild-type myosin. Moreover, for H251N, we found significantly lower binding affinity between the S1 and S2 domains of myosin, suggesting that this mutation may further increase hyper-contractility by releasing active motors. Unlike previous HCM mutations studied at the molecular level using human β-cardiac myosin, early-onset HCM mutations lead to significantly larger changes in the fundamental biomechanical parameters and show clear hyper-contractility.

  12. Heart Rate Changes in Response to Mechanical Pressure Stimulation of Skeletal Muscles Are Mediated by Cardiac Sympathetic Nerve Activity.

    PubMed

    Watanabe, Nobuhiro; Hotta, Harumi

    2016-01-01

    Stimulation of mechanoreceptors in skeletal muscles such as contraction and stretch elicits reflexive autonomic nervous system changes which impact cardiovascular control. There are pressure-sensitive mechanoreceptors in skeletal muscles. Mechanical pressure stimulation of skeletal muscles can induce reflex changes in heart rate (HR) and blood pressure, although the neural mechanisms underlying this effect are unclear. We examined the contribution of cardiac autonomic nerves to HR responses induced by mechanical pressure stimulation (30 s, ~10 N/cm(2)) of calf muscles in isoflurane-anesthetized rats. Animals were artificially ventilated and kept warm using a heating pad and lamp, and respiration and core body temperature were maintained within physiological ranges. Mechanical stimulation was applied using a stimulation probe 6 mm in diameter with a flat surface. Cardiac sympathetic and vagus nerves were blocked to test the contribution of the autonomic nerves. For sympathetic nerve block, bilateral stellate ganglia, and cervical sympathetic nerves were surgically sectioned, and for vagus nerve block, the nerve was bilaterally severed. In addition, mass discharges of cardiac sympathetic efferent nerve were electrophysiologically recorded. Mechanical stimulation increased or decreased HR in autonomic nerve-intact rats (range: -56 to +10 bpm), and the responses were negatively correlated with pre-stimulus HR (r = -0.65, p = 0.001). Stimulation-induced HR responses were markedly attenuated by blocking the cardiac sympathetic nerve (range: -9 to +3 bpm, p < 0.0001) but not the vagus nerve (range: -75 to +30 bpm, p = 0.17). In the experiments with cardiac sympathetic efferent nerve activity recordings, mechanical stimulation increased, or decreased the frequency of sympathetic nerve activity in parallel with HR (r = 0.77, p = 0.0004). Furthermore, the changes in sympathetic nerve activity were negatively correlated with its tonic level (r = -0.62, p = 0.0066). These

  13. Heart Rate Changes in Response to Mechanical Pressure Stimulation of Skeletal Muscles Are Mediated by Cardiac Sympathetic Nerve Activity

    PubMed Central

    Watanabe, Nobuhiro; Hotta, Harumi

    2017-01-01

    Stimulation of mechanoreceptors in skeletal muscles such as contraction and stretch elicits reflexive autonomic nervous system changes which impact cardiovascular control. There are pressure-sensitive mechanoreceptors in skeletal muscles. Mechanical pressure stimulation of skeletal muscles can induce reflex changes in heart rate (HR) and blood pressure, although the neural mechanisms underlying this effect are unclear. We examined the contribution of cardiac autonomic nerves to HR responses induced by mechanical pressure stimulation (30 s, ~10 N/cm2) of calf muscles in isoflurane-anesthetized rats. Animals were artificially ventilated and kept warm using a heating pad and lamp, and respiration and core body temperature were maintained within physiological ranges. Mechanical stimulation was applied using a stimulation probe 6 mm in diameter with a flat surface. Cardiac sympathetic and vagus nerves were blocked to test the contribution of the autonomic nerves. For sympathetic nerve block, bilateral stellate ganglia, and cervical sympathetic nerves were surgically sectioned, and for vagus nerve block, the nerve was bilaterally severed. In addition, mass discharges of cardiac sympathetic efferent nerve were electrophysiologically recorded. Mechanical stimulation increased or decreased HR in autonomic nerve-intact rats (range: −56 to +10 bpm), and the responses were negatively correlated with pre-stimulus HR (r = −0.65, p = 0.001). Stimulation-induced HR responses were markedly attenuated by blocking the cardiac sympathetic nerve (range: −9 to +3 bpm, p < 0.0001) but not the vagus nerve (range: −75 to +30 bpm, p = 0.17). In the experiments with cardiac sympathetic efferent nerve activity recordings, mechanical stimulation increased, or decreased the frequency of sympathetic nerve activity in parallel with HR (r = 0.77, p = 0.0004). Furthermore, the changes in sympathetic nerve activity were negatively correlated with its tonic level (r = −0.62, p = 0

  14. 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

  15. Autophagic signaling and proteolytic enzyme activity in cardiac and skeletal muscle of spontaneously hypertensive rats following chronic aerobic exercise.

    PubMed

    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.

  16. Detection of complement activation by counterimmunoelectrophoresis (CIE).

    PubMed

    Arroyave, C M; Tan, E M

    1976-01-01

    Counterimmunoelectrophoresis (CIE) was used as a method of detecting activation of the third component of the complement system (C3). Highly purified C3, normal human serum (NHS), EDTA-treated plasma and serum activated with aggregated human immunoglobulin (agg-IgG) or inulin were used as sources of C3 and/or C3 split products. Activation of the alternative pathway of complement was assayed in the presence of EGTA (10 mM) and MgCl2 (0.3 mM), conditions which block activation of the classical pathway. When purified native C3, fresh NHS and fresh EDTA-plasma were tested in CIE against either antisera to whole C3 or to C3 split products, only one precipitin line was found, which was identified as native C3. However, when serum activated with agg-IgG or inulin were tested against the same reagents, two precipitin lines were seen. The first, with more cathodal mobility was identical to that of native C3. The second line had a more anodal mobility, was distinctly separated from the first and contained C3c and C3d as shown immunochemically with specific antisera. Native C3 and split products of C3 were identified by this CIE method in patients showing evidence of activated complement by having subnormal total complement (CH50) levels. When C3 split products were identified, the C3c-C3d precipitin line could always be distinguished from native C3 by its different electrophoretic mobility, even when C3 concentrations in serum varied from 0.25 mg/ml to 1.5 mg/ml. The sensitivity of CIE was compared to that of CH50 by asssaying at different time intervals after agg-IgG was added to fresh NHS. C3c-C3d split products were detected by CIE before any fall in CH50 and at all times when a significant decrease in CH50 was present. This study shows that the CIE technique is a highly sensitive, specific and rapid method for detecting activation of the complement system via classical or alternative pathways in human disease.

  17. 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

  18. Detection of mutagenic activity in automobile exhaust.

    PubMed

    Ohnishi, Y; Kachi, K; Sato, K; Tahara, I; Takeyoshi, H; Tokiwa, H

    1980-03-01

    Using the Ames Salmonella-microsome system, we detected mutagenic activity in the exhaust from two kinds of 4-cycle gasoline engines of unregulated and regulated cars, and from diesel engines, as well as in the particulates from air collected in tunnels. The mutagenicity of particulates from a car equipped with a catalyst (regulated car), as compared with that from an unregulated car, was reduced very much (down to 500 from 4500 revertants/plate/m3 in tester strain TA98). However, the mutagenicity of the ether-soluble acid and neutral fractions from the condensed water of emissions from a regulated car was still high (down to 2880 from 10 900 revertants/plate/m3 in tester strain TA100). The mutagenic activity of emission exhaust from old diesel car engines was very high; the particulates showed 9140 and 19 600 revertants/plate/m3 from strain TA98 incubated with an activating rat-liver S9 fraction. A small diesel engine of the type used for the generation of electric power or in farm machinery also produced exhaust with highly mutagenic particulates. The mutagenic activity of a methanol extract of particulate air pollutants collected in a highway tunnel showed 39 revertants/plate/m3 toward strain TA98 and 87 toward strain TA100. The ether-soluble neutral fraction yielded 86 revertants/plate/m3 from strain TA98 and 100 from strain TA100. This fraction also contained carcinogenic compounds, including benzo[a]pyrene, benzo[e]pyrene, benz[a]anthracene, benzo[ghi]perylene and chrysene. Very high mutagenic activity was detected, especially in the particulate air pollutants collected at night, in another tunnel on a superhighway: 60-88 revertants/plate/m3 from strain TA100 for the sample collected by day, but 121-238, by night. Night traffic includes many more diesel-powered vehicles compared with gasoline-powered automobiles.

  19. Evaluation of a modified lateral flow immunoassay for detection of high-sensitivity cardiac troponin I and myoglobin.

    PubMed

    Zhu, Jimin; Zou, Nengli; Mao, Hongju; Wang, Ping; Zhu, Danian; Ji, Huoyan; Cong, Hui; Sun, Changjiang; Wang, Huimin; Zhang, Feng; Qian, Juying; Jin, Qinghui; Zhao, Jianlong

    2013-04-15

    We prospectively evaluated the use of lateral flow immunoassay (LFIA) test modified with nanoparticles for combined detection of high-sensitivity cardiac troponin I (hs-cTnI) and myoglobin with the aim of excluding acute myocardial infarction (AMI). Specimens from 173 patients with symptoms suggestive of AMI were collected to measure hs-cTnI and myoglobin using an electrochemiluminescence immunoassay (ECLI) and the LFIA test modified with nanoparticles, and a comparison was performed between the modified method and a commercial LFIA test for detection of the two proteins. The accuracy of the modified LFIA test was also evaluated. Consistent agreement was observed in the quantitative comparison of 173 clinical samples using the modified LFIA and ECLI, and the modified method was more sensitive than the commercial LFIA test. The accuracy of the modified LFIA was <12% for both hs-cTnI and myoglobin. Thus, the new approach has great potential to improve LFIAs test, demonstrating its usefulness for simple screening applications and for sensitivity and quantitative immunoassays for diagnosis ofAMI.

  20. Increased detection of human cardiac troponin I by a decrease of nonspecific adsorption in diluted self-assembled monolayers

    NASA Astrophysics Data System (ADS)

    Ren, Jun; Ding, Xiuqing; Greer, John J.; Shankar, Karthik

    2012-04-01

    In this paper, we tested the hypothesis that there is an increased sensitivity for detecting and measuring disease biomarkers (such as human cardiac troponin I, cTnI) by a decrease of nonspecific adsorption in diluted self-assembled monolayers (SAMs) on planar sputtered gold films. Combining grazing angle Fourier-transform infrared spectroscopy (FT-IR) and antibody-antigen-antibody (sandwich) fluorescence-based immunoassay, we examined the relationship of sensitivity, specificity of detection of cTnI and the level of nonspecific protein adsorption in the following SAMs: pure MHA (16-mercaptohexadecanoic acid, 1 mM, with head COO-, x = 1.0), a mixed SAM comprising MHA (0.1 mM) and UDT (1-undecane thiol, 0.9 mM, with hydrophobic head CH3, x = 0.1UDT), and a mixed SAM comprising MHA (0.1 mM) and MUD (11-mercapto-1-undecanol, 0.9 mM, with hydrophilic head OH, x = 0.1MUD). Our data revealed that nonspecific binding to SAMs is favored in the following order: CH3 > COO- > OH, consistent with previous studies. Compared with pure SAMs, diluting MHA SAMs with MUD increases the sensitivity of cTnI, whereas diluted MHA SAMs with UDT has the same sensitivity of detection of cTnI, suggesting it is the nature of the second diluting thiol that plays an important role on the amount of adsorbed protein on the surface. We obtained a 10-fold increase in the limit of detection of cTnI to 10 ng/ml using x = 0.1MUD due to a decrease of nonspecific binding. Further, specific binding between the antigen cTnI and its antibody is unaltered on pure and diluted SAMs.

  1. Statins suppress glucose-induced plasminogen activator inhibitor-1 expression by regulating RhoA and nuclear factor-κB activities in cardiac microvascular endothelial cells.

    PubMed

    Ni, Xiao-Qing; Zhu, Jian-Hua; Yao, Ning-Hua; Qian, Juan; Yang, Xiang-Jun

    2013-01-01

    The aim of this study was to investigate the possible proinflammatory signaling pathways involved in statin inhibition of glucose-induced plasminogen activator inhibitor-1 (PAI-1) expression in cardiac microvascular endothelial cells (CMECs). Primary rat CMECs were grown in the presence of 5.7 or 23 mmol/L glucose. PAI-1 mRNA and protein expression levels were measured by realtime polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay, respectively. A pull-down assay was performed to determine RhoA activity. IκBα protein expression was measured by Western blotting, nuclear factor (NF)-κB activation was detected by electrophoretic mobility shift assay and its transcription activity was determined by a dual luciferase reporter gene assay. PAI-1 mRNA and protein expression levels were both increased with high glucose concentrations, but they were significantly suppressed by simvastatin and atorvastatin treatment (P < 0.01) and the effects were reversed by mevalonate (100 μmol/L) and geranylgeranyl pyrophosphate (10 μmol/L) but not farnesyl pyrophosphate (10 μmol/L). Such effects were similar to those of a RhoA inhibitor, C3 exoenzyme (5 μg/mL), inhibitors of RhoA kinase (ROCK), Y-27632 (10 μmol/L) and hydroxyfasudil (10 μmol/L) and an NF-κB inhibitor, BAY 11-7082 (5 μmol/L). High glucose-induced RhoA and NF-κB activations in CMECs were both significantly inhibited by statins (P < 0.01). Simvastatin and atorvastatin equally suppress high glucose-induced PAI-1 expression. These effects of statins may occur partly by regulating the RhoA/ROCK-NF-κB pathway. The multifunctional roles of statins may be particularly beneficial for patients with metabolic syndrome.

  2. Notch Inhibition Enhances Cardiac Reprogramming by Increasing MEF2C Transcriptional Activity.

    PubMed

    Abad, Maria; Hashimoto, Hisayuki; Zhou, Huanyu; Morales, Maria Gabriela; Chen, Beibei; Bassel-Duby, Rhonda; Olson, Eric N

    2017-03-14

    Conversion of fibroblasts into functional cardiomyocytes represents a potential means of restoring cardiac function after myocardial infarction, but so far this process remains inefficient and little is known about its molecular mechanisms. Here we show that DAPT, a classical Notch inhibitor, enhances the conversion of mouse fibroblasts into induced cardiac-like myocytes by the transcription factors GATA4, HAND2, MEF2C, and TBX5. DAPT cooperates with AKT kinase to further augment this process, resulting in up to 70% conversion efficiency. Moreover, DAPT promotes the acquisition of specific cardiomyocyte features, substantially increasing calcium flux, sarcomere structure, and the number of spontaneously beating cells. Transcriptome analysis shows that DAPT induces genetic programs related to muscle development, differentiation, and excitation-contraction coupling. Mechanistically, DAPT increases binding of the transcription factor MEF2C to the promoter regions of cardiac structural genes. These findings provide mechanistic insights into the reprogramming process and may have important implications for cardiac regeneration therapies.

  3. The Electrical Activity of Canine Cardiac Purkinje Fibers in Sodium-Free, Calcium-Rich Solutions

    PubMed Central

    Aronson, Ronald S.; Cranefield, Paul F.

    1973-01-01

    Propagated action potentials can be obtained in canine cardiac Purkinje fibers exposed to Na-free solutions containing no inorganic cation other than Ca and K. Essentially similar action potentials are obtained if Na is replaced by tetraethylammonium (TEA), tetramethylammonium (TMA), or choline. In a solution containing 128 mM TEA and 16.2 mM Ca the characteristics of these electrical responses were: maximum diastolic potential, -59 ± 3.3 mV; overshoot, 20 ± 6.8 mV; maximum upstroke velocity, 3.7 ± 2.3 V/s; conduction velocity, 0.1 m/s; and action potential duration, 360 ± 45 ms. The magnitude of the overshoot varied with log Cao with a slope of about 30 mV/10-fold concentration change. The upstroke velocity was an approximately linear function of Cao. The active response was greatly diminished or abolished by Mn and D-600 but was unaffected by tetrodotoxin. These Ca-dependent responses appeared in a region of transmembrane potential (about -50 mV) at which the rapid Na-dependent upstroke is abolished even when Na is present. PMID:4708407

  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 selective activation of the cardiac sarcolemmal sodium-calcium exchanger by plasmalogenic phosphatidic acid produced by phospholipase D.

    PubMed

    Hale, C C; Ebeling, E G; Hsu, F F; Ford, D A

    1998-01-30

    Since plasmalogens are the predominant phospholipid of cardiac sarcolemma, the activation of the sodium-calcium exchanger by either plasmenylethanolamine or plasmalogenic phosphatidic acid generated by phospholipase D was explored. Sodium-calcium exchange activity was 7-fold greater in proteoliposomes comprised of plasmenylethanolamine compared to proteoliposomes comprised of only plasmenylcholine. Phospholipase D treatment of proteoliposomes resulted in 1 mol % conversion of plasmenylcholine or phosphatidylcholine to their respective phosphatidic acid molecular species with a concomitant 8-fold or 2-fold activation of sodium-calcium exchange activity, respectfully. Thus, phospholipase D-mediated hydrolysis of plasmalogens to phosphatidic acid may be an important mechanism for the regulation of the sodium-calcium exchanger.

  6. 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.

  7. Redox modification of sodium-calcium exchange activity in cardiac sarcolemmal vesicles.

    PubMed

    Reeves, J P; Bailey, C A; Hale, C C

    1986-04-15

    Na-Ca exchange activity in bovine cardiac sarcolemmal vesicles was stimulated up to 10-fold by preincubating the vesicles with 1 microM FeSO4 plus 1 mM dithiothreitol (DTT) in a NaCl medium. The increase in activity was not reversed upon removing the Fe and DTT. Stimulation of exchange activity under these conditions was completely blocked by 0.1 mM EDTA or o-phenanthroline; this suggests that the production of reduced oxygen species (H2O2, O2-.,.OH) during Fecatalyzed DTT oxidation might be involved in stimulating exchange activity. In agreement with this hypothesis, the increase in exchange activity in the presence of Fe-DTT was inhibited 80% by anaerobiosis and 60% by catalase. H2O2 (0.1 mM) potentiated the stimulation of Na-Ca exchange by Fe-DTT under both aerobic and anaerobic conditions; H2O2 also produced an increase in activity in the presence of either FeSO4 (1 microM) or DTT (1 mM), but it had no effect on activity by itself. Superoxide dismutase did not block the effects of Fe-DTT on exchange activity; however, the generation of O2-. by xanthine oxidase in the presence of an oxidizable substrate stimulated activity more than 2-fold. Hydroxyl radical scavenging agents (mannitol, sodium formate, sodium benzoate) did not attenuate the stimulation of activity observed with Fe-H2O2. Exchange activity was also stimulated by the simultaneous presence of glutathione (GSH; 1-2 mM) and glutathione disulfide (GSSG; 1-2 mM). Neither GSH nor GSSG was effective by itself and either 0.1 mM EDTA or o-phenanthroline blocked the effects on transport activity of the combination of GSH + GSSG. Treatment of the GSH and GSSG solutions with Chelex ion-exchange resin to remove contaminating transition metal ions reduced (by 40%) the degree of stimulation observed with GSH + GSSG. Full stimulating activity was restored to the Chelex-treated GSH and GSSG solutions by the addition of 1 microM Fe2+; Cu2+ was less effective than Fe2+ whereas Co2+ and Mn2+ were without effect. In the

  8. [Effect of change in activity level of catecholaminergic systems on motor, respiratory, and cardiac activities in rat embryos].

    PubMed

    Timofeeva, O P; Vdovichenko, N D; Kuznetsov, S V

    2012-01-01

    Parameters of motor, respiratory and cardiac activities were studied in rat embryos (E17-20) after changes in activity level of catecholaminergic systems. To produce conditions for excessive level of catecholamines, the animal were administered individually with preparation of L-DOPA at doses of 25, 50 and 100 mg/kg. Also studied was action of L-DOPA after blockade of D1-(antagonist - SCH-23390, 0.1 mg/kg), D2-(antagonist - sulpiride, 50 mg/kg) dopaminic, and beta2-(antagonist - propranolol, 1 mg/kg) adrenergic receptors. It was found out in E17-18 that the DOPA administration regardless of dose, while in E19-20 dose-dependently produces continuous generalized activity. Between E18 and E19, ontogenetically new is the appearance in 92 % of embryos of stereotypical head movements (circular movements, lateral and dorso-ventral flexions) following in the nearsecond rhythm. Injection of DOPA to rat embryos increased 2-6 times the number of respiratory movements by the gasping type in E17-20 and decreased the amount of episodes of continuous rhythmical respiration in E19-20. No significant heart rate changes were observed after introduction of DOPA to E17-20. There was noted a tendency for a weak acceleration of the heart rate. The changes in activities of the motor and respiratory systems due to a rise of catecholamine level are not connected with activation of the dopamine system, as they are not reduced by blockade of dopamine receptors.

  9. Cardiac Mitochondrial Respiratory Dysfunction and Tissue Damage in Chronic Hyperglycemia Correlate with Reduced Aldehyde Dehydrogenase-2 Activity

    PubMed Central

    Deshpande, Mandar; Thandavarayan, Rajarajan A.; Xu, Jiang; Yang, Xiao-Ping; Palaniyandi, Suresh S.

    2016-01-01

    Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial isozyme of the heart involved in the metabolism of toxic aldehydes produced from oxidative stress. We hypothesized that hyperglycemia-mediated decrease in ALDH2 activity may impair mitochondrial respiration and ultimately result in cardiac damage. A single dose (65 mg/kg; i.p.) streptozotocin injection to rats resulted in hyperglycemia with blood glucose levels of 443 ± 9 mg/dl versus 121 ± 7 mg/dl in control animals, p<0.0001, N = 7–11. After 6 months of diabetes mellitus (DM) induction, the rats were sacrificed after recording the functionality of their hearts. Increase in the cardiomyocyte cross sectional area (446 ± 32 μm2 Vs 221 ± 10 μm2; p<0.0001) indicated cardiac hypertrophy in DM rats. Both diastolic and systolic dysfunctions were observed with DM rats compared to controls. Most importantly, myocardial ALDH2 activity and levels were reduced, and immunostaining for 4HNE protein adducts was increased in DM hearts compared to controls. The mitochondrial oxygen consumption rate (OCR), an index of mitochondrial respiration, was decreased in mitochondria isolated from DM hearts compared to controls (p<0.0001). Furthermore, the rate of mitochondrial respiration and the increase in carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-induced maximal respiration were also decreased with chronic hyperglycemia. Chronic hyperglycemia reduced mitochondrial OXPHOS proteins. Reduced ALDH2 activity was correlated with mitochondrial dysfunction, pathological remodeling and cardiac dysfunction, respectively. Our results suggest that chronic hyperglycemia reduces ALDH2 activity, leading to mitochondrial respiratory dysfunction and consequently cardiac damage and dysfunction. PMID:27736868

  10. Cardiac Myosin-binding Protein C and Troponin-I Phosphorylation Independently Modulate Myofilament Length-dependent Activation*

    PubMed Central

    Kumar, Mohit; Govindan, Suresh; Zhang, Mengjie; Khairallah, Ramzi J.; Martin, Jody L.; Sadayappan, Sakthivel; de Tombe, Pieter P.

    2015-01-01

    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-[Ca2+] 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 [Ca2+] 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

  11. Characterization of two Bunodosoma granulifera toxins active on cardiac sodium channels

    PubMed Central

    Goudet, Cyril; Ferrer, Tania; Galàn, Loipa; Artiles, Adriana; Batista, Cesar F V; Possani, Lourival D; Alvarez, Julio; Aneiros, Abel; Tytgat, Jan

    2001-01-01

    Two sodium channel toxins, BgII and BgIII, have been isolated and purified from the sea anemone Bunodosoma granulifera. Combining different techniques, we have investigated the electrophysiological properties of these toxins. We examined the effect of BgII and BgIII on rat ventricular strips. These toxins prolong action potentials with EC50 values of 60 and 660 nM and modify the resting potentials. The effect on Na+ currents in rat cardiomyocytes was studied using the patch-clamp technique. BgII and BgIII slow the rapid inactivation process and increase the current density with EC50 values of 58 and 78 nM, respectively. On the cloned hH1 cardiac Na+ channel expressed in Xenopus laevis oocytes, BgII and BgIII slow the inactivation process of Na+ currents (respective EC50 values of 0.38 and 7.8 μM), shift the steady-state activation and inactivation parameters to more positive potentials and the reversal potential to more negative potentials. The amino acid sequences of these toxins are almost identical except for an asparagine at position 16 in BgII which is replaced by an aspartic acid in BgIII. In all experiments, BgII was more potent than BgIII suggesting that this conservative residue is important for the toxicity of sea anemone toxins. We conclude that BgII and BgIII, generally known as neurotoxins, are also cardiotoxic and combine the classical effects of sea anemone Na+ channels toxins (slowing of inactivation kinetics, shift of steady-state activation and inactivation parameters) with a striking decrease on the ionic selectivity of Na+ channels. PMID:11704639

  12. 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.

  13. 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

  14. How to Calculate Renyi Entropy from Heart Rate Variability, and Why it Matters for Detecting Cardiac Autonomic Neuropathy.

    PubMed

    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.

  15. Efficient and robust ventricular tachycardia and fibrillation detection method for wearable cardiac health monitoring devices.

    PubMed

    Prabhakararao, Eedara; Manikandan, M Sabarimalai

    2016-09-01

    In this Letter, the authors propose an efficient and robust method for automatically determining the VT and VF events in the electrocardiogram (ECG) signal. The proposed method consists of: (i) discrete cosine transform (DCT)-based noise suppression; (ii) addition of bipolar sequence of amplitudes with alternating polarity; (iii) zero-crossing rate (ZCR) estimation-based VTVF detection; and (iv) peak-to-peak interval (PPI) feature based VT/VF discrimination. The proposed method is evaluated using 18,000 episodes of different ECG arrhythmias taken from 6 PhysioNet databases. The method achieves an average sensitivity (Se) of 99.61%, specificity (Sp) of 99.96%, and overall accuracy (OA) of 99.92% in detecting VTVF and non-VTVF episodes by using a ZCR feature. Results show that the method achieves a Se of 100%, Sp of 99.70% and OA of 99.85% for discriminating VT from VF episodes using PPI features extracted from the processed signal. The robustness of the method is tested using different kinds of ECG beats and various types of noises including the baseline wanders, powerline interference and muscle artefacts. Results demonstrate that the proposed method with the ZCR, PPI features can achieve significantly better detection rates as compared with the existing methods.

  16. Cardiac tissue-restricted deletion of plakoglobin results in progressive cardiomyopathy and activation of {beta}-catenin signaling.

    PubMed

    Li, Jifen; Swope, David; Raess, Natalia; Cheng, Lan; Muller, Eliane J; Radice, Glenn L

    2011-03-01

    Mutations in the plakoglobin (JUP) gene have been identified in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. However, the mechanisms underlying plakoglobin dysfunction involved in the pathogenesis of ARVC remain poorly understood. Plakoglobin is a component of both desmosomes and adherens junctions located at the intercalated disc (ICD) of cardiomyocytes, where it functions to link cadherins to the cytoskeleton. In addition, plakoglobin functions as a signaling protein via its ability to modulate the Wnt/β-catenin signaling pathway. To investigate the role of plakoglobin in ARVC, we generated an inducible cardiorestricted knockout (CKO) of the plakoglobin gene in mice. Plakoglobin CKO mice exhibited progressive loss of cardiac myocytes, extensive inflammatory infiltration, fibrous tissue replacement, and cardiac dysfunction similar to those of ARVC patients. Desmosomal proteins from the ICD were decreased, consistent with altered desmosome ultrastructure in plakoglobin CKO hearts. Despite gap junction remodeling, plakoglobin CKO hearts were refractory to induced arrhythmias. Ablation of plakoglobin caused increase β-catenin stabilization associated with activated AKT and inhibition of glycogen synthase kinase 3β. Finally, β-catenin/TCF transcriptional activity may contribute to the cardiac hypertrophy response in plakoglobin CKO mice. This novel model of ARVC demonstrates for the first time how plakoglobin affects β-catenin activity in the heart and its implications for disease pathogenesis.

  17. Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation.

    PubMed

    Corrà, Ugo; Piepoli, Massimo F; Carré, François; Heuschmann, Peter; Hoffmann, Uwe; Verschuren, Monique; Halcox, Julian; Giannuzzi, Pantaleo; Saner, Hugo; Wood, David; Piepoli, Massimo F; Corrà, Ugo; Benzer, Werner; Bjarnason-Wehrens, Birna; Dendale, Paul; Gaita, Dan; McGee, Hannah; Mendes, Miguel; Niebauer, Josef; Zwisler, Ann-Dorthe Olsen; Schmid, Jean-Paul

    2010-08-01

    Cardiac patients after an acute event and/or with chronic heart disease deserve special attention to restore their quality of life and to maintain or improve functional capacity. They require counselling to avoid recurrence through a combination of adherence to a medication plan and adoption of a healthy lifestyle. These secondary prevention targets are included in the overall goal of cardiac rehabilitation (CR). Cardiac rehabilitation can be viewed as the clinical application of preventive care by means of a professional multi-disciplinary integrated approach for comprehensive risk reduction and global long-term care of cardiac patients. The CR approach is delivered in tandem with a flexible follow-up strategy and easy access to a specialized team. To promote implementation of cardiac prevention and rehabilitation, the CR Section of the EACPR (European Association of Cardiovascular Prevention and Rehabilitation) has recently completed a Position Paper, entitled 'Secondary prevention through cardiac rehabilitation: A condition-oriented approach'. Components of multidisciplinary CR for seven clinical presentations have been addressed. Components include patient assessment, physical activity counselling, exercise training, diet/nutritional counselling, weight control management, lipid management, blood pressure monitoring, smoking cessation, and psychosocial management. Cardiac rehabilitation services are by definition multi-factorial and comprehensive, with physical activity counselling and exercise training as central components in all rehabilitation and preventive interventions. Many of the risk factor improvements occurring in CR can be mediated through exercise training programmes. This call-for-action paper presents the key components of a CR programme: physical activity counselling and exercise training. It summarizes current evidence-based best practice for the wide range of patient presentations of interest to the general cardiology community.

  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. Decoupled active contour (DAC) for boundary detection.

    PubMed

    Mishra, Akshaya Kumar; Fieguth, Paul W; Clausi, David A

    2011-02-01

    The accurate detection of object boundaries via active contours is an ongoing research topic in computer vision. Most active contours converge toward some desired contour by minimizing a sum of internal (prior) and external (image measurement) energy terms. Such an approach is elegant, but suffers from a slow convergence rate and frequently misconverges in the presence of noise or complex contours. To address these limitations, a decoupled active contour (DAC) is developed which applies the two energy terms separately. Essentially, the DAC consists of a measurement update step, employing a Hidden Markov Model (HMM) and Viterbi search, and then a separate prior step, which modifies the updated curve based on the relative strengths of the measurement uncertainty and the nonstationary prior. By separating the measurement and prior steps, the algorithm is less likely to misconverge; furthermore, the use of a Viterbi optimizer allows the method to converge far more rapidly than energy-based iterative solvers. The results clearly demonstrate that the proposed approach is robust to noise, can capture regions of very high curvature, and exhibits limited dependence on contour initialization or parameter settings. Compared to five other published methods and across many image sets, the DAC is found to be faster with better or comparable segmentation accuracy.

  20. Hypoxia augments the calcium-activated chloride current carried by anoctamin-1 in cardiac vascular endothelial cells of neonatal mice

    PubMed Central

    Wu, Ming-Ming; Lou, Jie; Song, Bin-Lin; Gong, Yuan-Feng; Li, Yan-Chao; Yu, Chang-Jiang; Wang, Qiu-Shi; Ma, Tian-Xing; Ma, Ke; Hartzell, H Criss; Duan, Dayue Darrel; Zhao, Dan; Zhang, Zhi-Ren

    2014-01-01

    BACKGROUND AND PURPOSE The molecular identity of calcium-activated chloride channels (CaCCs) in vascular endothelial cells remains unknown. This study sought to identify whether anoctamin-1 (Ano1, also known as TMEM16A) functions as a CaCC and whether hypoxia alters the biophysical properties of Ano1 in mouse cardiac vascular endothelial cells (CVECs). EXPERIMENTAL APPROACH Western blot, quantitative real-time PCR, confocal imaging analysis and patch-clamp analysis combined with pharmacological approaches were used to determine whether Ano1 was expressed and functioned as CaCC in CVECs. KEY RESULTS Ano1 was expressed in CVECs. The biophysical properties of the current generated in the CVECs, including the Ca2+ and voltage dependence, outward rectification, anion selectivity and the pharmacological profile, are similar to those described for CaCCs. The density of ICl(Ca) detected in CVECs was significantly inhibited by T16Ainh-A01, an Ano1 inhibitor, and a pore-targeting, specific anti-Ano1 antibody, and was markedly decreased in Ano1 gene knockdown CVECs. The density of ICl(Ca) was significantly potentiated in CVECs exposed to hypoxia, and this hypoxia-induced increase in the density of ICl(Ca) was inhibited by T16Ainh-A01 or anti-Ano1 antibody. Hypoxia also increased the current density of ICl(Ca) in Ano1 gene knockdown CVECs. CONCLUSIONS AND IMPLICATIONS Ano1 formed CaCC in CVECs of neonatal mice. Hypoxia enhances Ano1-mediated ICl(Ca) density via increasing its expression, altering the ratio of its splicing variants, sensitivity to membrane voltage and to Ca2+. Ano1 may play a role in the pathophysiological processes during ischaemia in heart, and therefore, Ano1 might be a potential therapeutic target to prevent ischaemic damage. PMID:24758567

  1. 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

    2016-05-10

    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.

  2. 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

  3. 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.

  4. An Interactive Computer Session to Initiate Physical Activity in Sedentary Cardiac Patients: Randomized Controlled Trial

    PubMed Central

    Smith-Ray, Renae L; Dzewaltowski, David A; Glasgow, Russell E; Lee, Rebecca E; Thomas, Deborah SK; Xu, Stanley; Estabrooks, Paul A

    2015-01-01

    Background Physical activity (PA) improves many facets of health. Despite this, the majority of American adults are insufficiently active. Adults who visit a physician complaining of chest pain and related cardiovascular symptoms are often referred for further testing. However, when this testing does not reveal an underlying disease or pathology, patients typically receive no additional standard care services. A PA intervention delivered within the clinic setting may be an effective strategy for improving the health of this population at a time when they may be motivated to take preventive action. Objective Our aim was to determine the effectiveness of a tailored, computer-based, interactive personal action planning session to initiate PA among a group of sedentary cardiac patients following exercise treadmill testing (ETT). Methods This study was part of a larger 2x2 randomized controlled trial to determine the impact of environmental and social-cognitive intervention approaches on the initiation and maintenance of weekly PA for patients post ETT. Participants who were referred to an ETT center but had a negative-test (ie, stress tests results indicated no apparent cardiac issues) were randomized to one of four treatment arms: (1) increased environmental accessibility to PA resources via the provision of a free voucher to a fitness facility in close proximity to their home or workplace (ENV), (2) a tailored social cognitive intervention (SC) using a “5 As”-based (ask, advise, assess, assist, and arrange) personal action planning tool, (3) combined intervention of both ENV and SC approaches (COMBO), or (4) a matched contact nutrition control (CON). Each intervention was delivered using a computer-based interactive session. A general linear model for repeated measures was conducted with change in PA behavior from baseline to 1-month post interactive computer session as the primary outcome. Results Sedentary participants (n=452; 34.7% participation rate) without

  5. Global cardiac alterations detected by speckle-tracking echocardiography in Fabry disease: left ventricular, right ventricular, and left atrial dysfunction are common and linked to worse symptomatic status.

    PubMed

    Morris, Daniel A; Blaschke, Daniela; Canaan-Kühl, Sima; Krebs, Alice; Knobloch, Gesine; Walter, Thula C; Haverkamp, Wilhelm

    2015-02-01

    The aim of this study was to test the hypothesis that in patients with Fabry disease, 2D speckle-tracking echocardiography (2DSTE) could detect functional myocardial alterations such as left ventricular (LV), right ventricular (RV), and left atrial (LA) dysfunction, even when conventional cardiac measurements are normal. In addition, we hypothesized that these global cardiac alterations could be linked to worse symptomatic status in these patients. Fifty patients with Fabry disease and a control group of 118 healthy subjects of similar age and gender were included. The myocardial function and structural changes of the LV, RV, and LA were analyzed by 2DSTE and cardiac magnetic resonance imaging. Patients with Fabry disease had significantly lower functional myocardial values of the LV, RV, and LA than healthy subjects (LV, RV, and LA strain -18.1 ± 4.0, -21.4 ± 4.9, and 29.7 ± 9.9 % vs. -21.6 ± 2.2, -25.2 ± 4.0, and 44.8 ± 11.1 %, respectively, P < 0.001) and elevated rates of LV, RV, and LA myocardial dysfunction (24, 20, and 26 %, respectively), even when conventional cardiac measurements such as LVEF, TAPSE, and LAVI were normal. LV septal wall thickness ≥15 mm, RV free wall thickness ≥7 mm, and LV longitudinal dysfunction were the principal factors linked to reduced LV, RV, and LA strain, respectively. In addition, but to a lesser extent, LV and RV fibrosis were linked to reduced LV and RV strain. Patients with reduced LV, RV, and LA strain had worse functional class (dyspnea-NYHA classification) than those with normal cardiac function. In conclusion, in patients with Fabry disease, 2DSTE analyses detect LV, RV, and LA functional myocardial alterations, even when conventional cardiac measurements are normal. These functional myocardial alterations are common and significantly associated with worse symptomatic status in Fabry patients. Therefore, these findings provide important evidence to introduce global myocardial analyses using 2DSTE in the early

  6. Single-molecule detection with active transport

    NASA Astrophysics Data System (ADS)

    Ball, David Allan

    A glass capillary is used near the focal region of a custom-built confocal microscope to investigate the use of active transport for single-molecule detection in solution, with both one and two-photon laser excitation. The capillary tip has a diameter of several microns and is carefully aligned nearby to the sub-micron laser beam waist, collinear to the optical axis, so that a negative pressure-difference causes molecules to be drawn into the capillary, along the laser beam axis. The flow of solution, which is characterized by fluorescence correlation spectroscopy (FCS), can increase the single-molecule detection rate for slowly diffusing proteins by over a factor of 100, while the mean rate of photons during each burst is similar to that for random diffusional transport. Also, the flow is along the longest axis of the ellipsoidally-shaped confocal volume, which results in more collected photons per molecule than that for transverse flow at the same speed. When transport is dominated by flow, FCS can no longer distinguish molecules with differing translational diffusion, and hence a fluorescence fluctuation spectroscopy method based on differences in fluorescence brightness is investigated as a means for assaying different solution components, for applications in pharmaceutical drug discovery. Multi-channel fluctuation spectroscopy techniques can also be used for assays with the flow system and hence this dissertation also reports the characterization of a prototype 4-channel single-photon detector with a two-wavelength polarization-resolved optical set-up.

  7. 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.

  8. 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.

  9. Measuring Cardiac Autonomic Nervous System (ANS) Activity in Toddlers - Resting and Developmental Challenges

    PubMed Central

    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 that

  10. Detection of leukocyte filtration and potential selective migration during use of cardiopulmonary bypass in cardiac surgery by flow cytometry

    NASA Astrophysics Data System (ADS)

    Hambsch, Joerg; Schlykow, Veronika; Bocsi, Jozsef; Schneider, Peter; Pipek, Michal; Tarnok, Attila

    1999-06-01

    Cardiac surgery with cardiopulmonary bypass (CPB) can induce severe post-operative immune responses. During CPB loss of activated lymphocytes from the peripheral blood (PBL) was observed. We investigated if PBL get lost by binding to the CPB or by migration into the peripheral tissue and if the cells adhere selectively to different filter types. PBL were collected before, during and after surgery of pediatric patients and from the filters of the CPB by washing. Immunophenotype was determined by four color flow cytometry (FCM). In addition, PBL adhesion to CPB was analyzed in vitro. During surgery, B-cell counts decreased by greater than 50% due to the loss of CD69+ cells. The fraction of CD25+ and CD54+ T-lymphocytes decreased by 70%, that of CD69+ natural killer cells by 40%. In vivo in the CPB the proportion of CD69+ cells increased by up to 50%. These findings were supported by in vitro filtration studies. In contrast, the proportion of T-lymphocytes CD25+ or CD54+ were lower in the CPB. CD69+ cells adhere selectively to CPB filters. Loss of activated CD25+ or CD54+ T-lymphocytes could be due to their selective migration into the peripheral tissue. This FCM technique could be applied to test various filter types used in CPB in order to test their biocompatibility.

  11. 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

  12. Inhibition of microglial activation contributes to propofol-induced protection against post-cardiac arrest brain injury in rats.

    PubMed

    Wang, Wei; Lu, Rui; Feng, Da-Yun; Liang, Li-Rong; Liu, Bing; Zhang, Hui

    2015-09-01

    It has been suggested that propofol can modulate microglial activity and hence may have potential roles against neuroinflammation following brain ischemic insult. However, whether and how propofol can inhibit post-cardiac arrest brain injury via inhibition of microglia activation remains unclear. A rat model of asphyxia cardiac arrest (CA) was created followed by cardiopulmonary resuscitation. CA induced marked microglial activation in the hippocampal CA1 region, revealed by increased OX42 and P2 class of purinoceptor 7 (P2X7R) expression, as well as p38 MAPK phosphorylation. Morris water maze showed that learning and memory deficits following CA could be inhibited or alleviated by pre-treatment with the microglial inhibitor minocycline or propofol. Microglial activation was significantly suppressed likely via the P2X7R/p-p38 pathway by propofol. Moreover, hippocampal neuronal injuries after CA were remarkably attenuated by propofol. In vitro experiment showed that propofol pre-treatment inhibited ATP-induced microglial activation and release of tumor necrosis factor-α and interleukin-1β. In addition, propofol protected neurons from injury when co-culturing with ATP-treated microglia. Our data suggest that propofol pre-treatment inhibits CA-induced microglial activation and neuronal injury in the hippocampus and ultimately improves cognitive function. We proposed a possible mechanism of propofol-mediated brain protection after cardiac arrest (CA). CA induces P2X7R upregulation and p38 phosphorylation in microglia, which induces release of TNF-α and IL-1β and consequent neuronal injury. Propofol could inhibit microglial activation and alleviate neuronal damage. Our results suggest propofol-induced anti-inflammatory treatment as a plausible strategy for therapeutic intervention in post-CA brain injury.

  13. Fatty acid augmentation of the cardiac slowly activating delayed rectifier current (IKs) is conferred by hminK.

    PubMed

    Doolan, Gavin K; Panchal, Rekha G; Fonnes, Eva L; Clarke, Alison L; Williams, David A; Petrou, Steven

    2002-10-01

    The mechanism by which dietary fatty acids confer protection against cardiac arrhythmias and sudden cardiac death is not resolved. Here, we study the effects of several known cardio-protective and arrhythmogenic fatty acids on the slowly activating delayed rectifier potassium current (IKs), which is responsible for the repolarization phase of the cardiac action potential. cRNAs encoding either or both of the two subunits, KvLQT1 and hminK, that together produce IKs, were injected into Xenopus oocytes, and the effects of various fatty acids were determined. Docosahexaenoic acid (DHA) significantly augmented IKs as did the short-chained fully saturated lauric acid, and to a lesser extent the cis-unsaturated oleic acid. Eicosapentaenoic acid (EPA) was without significant effect on current magnitude, although it reduced the rate of activation. These results suggest that not all "antiarrhythmic" fatty acids target the same channel. To examine the role of hminK in this response, KvLQT1 was expressed alone. In this case, DHA, lauric acid, and oleic acid did not augment current, suggesting that hminK confers fatty acid sensitivity to IKs.

  14. Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity

    PubMed Central

    Ryu, Yuhee; Jin, Li; Kee, Hae Jin; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Lin, Ming Quan; Jeong, Myung Ho

    2016-01-01

    Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway. PMID:27703224

  15. 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.

  16. Using Lorenz plot and Cardiac Sympathetic Index of heart rate variability for detecting seizures for patients with epilepsy.

    PubMed

    Jeppesen, Jesper; Beniczky, Sandor; Johansen, Peter; Sidenius, Per; Fuglsang-Frederiksen, Anders

    2014-01-01

    Tachycardia is often seen during epileptic seizures, but it also occurs during physical exercise. In order to assess whether focal epileptic seizures can be detected by short term moving window Heart Rate Variability (HRV) analysis, we modified the geometric HRV method, Lorenz plot, to consist of only 30, 50 or 100 R-R intervals per analyzed window. From each window we calculated the longitudinal (L) and transverse (T) variability of Lorenz plot to retrieve the Cardiac Sympathetic Index (CSI) as (L/T) and "Modified CSI" (described in methods), and compared the maximum during the patient's epileptic seizures with that during the patient's own exercise and non-seizure sessions as control. All five analyzed patients had complex partial seizures (CPS) originating in the temporal lobe (11 seizures) during their 1-5 days long term video-EEG monitoring. All CPS with electroencephalographic correlation were selected for the HRV analysis. The CSI and Modified CSI were correspondently calculated after each heart beat depicting the prior 30, 50 and 100 R-R intervals at the time. CSI (30, 50 and 100) and Modified CSI (100) showed a higher maximum peak during seizures than exercise/non-seizure (121-296%) for 4 of the 5 patients within 4 seconds before till 60 seconds after seizure onset time even though exercise maximum HR exceeded that of the seizures. The results indicate a detectable, sudden and inordinate shift towards sympathetic overdrive in the sympathovagal balance of the autonomic nervous system just around seizure-onset for certain patients. This new modified moving window Lorenz plot method seems promising way of constructing a portable ECG-based epilepsy alarm for certain patients with epilepsy who needs aid during seizure.

  17. The influence of reduced insulin sensitivity via short-term reductions in physical activity on cardiac baroreflex sensitivity during acute hyperglycemia.

    PubMed

    Holwerda, S W; Reynolds, L J; Restaino, R M; Credeur, D P; Leidy, H J; Thyfault, J P; Fadel, P J

    2015-12-15

    Reduced insulin sensitivity and impaired glycemic control are among the consequences of physical inactivity and have been associated with reduced cardiac baroreflex sensitivity (BRS). However, the effect of reduced insulin sensitivity and acute hyperglycemia following glucose consumption on cardiac BRS in young, healthy subjects has not been well characterized. We hypothesized that a reduction in insulin sensitivity via reductions in physical activity would reduce cardiac BRS at rest and following an oral glucose tolerance test (OGTT). Nine recreationally active men (23 ± 1 yr; >10,000 steps/day) underwent 5 days of reduced daily physical activity (RA5) by refraining from planned exercise and reducing daily steps (<5,000 steps/day). Spontaneous cardiac BRS (sequence technique) was compared at rest and for 120 min following an OGTT at baseline and after RA5. A substudy (n = 8) was also performed to independently investigate the influence of elevated insulin alone on cardiac BRS using a 120-min hyperinsulinemic-euglycemic clamp. Insulin sensitivity (Matsuda index) was significantly reduced following RA5 (BL 9.2 ± 1.3 vs. RA5 6.4 ± 1.1, P < 0.001). Resting cardiac BRS was unaffected by RA5 and significantly reduced during the OGTT similarly at baseline and RA5 (baseline 0 min, 28 ± 4 vs. 120 min, 18 ± 4; RA5 0 min, 28 ± 4 vs. 120 min, 21 ± 3 ms/mmHg). Spontaneous cardiac BRS was also reduced during the hyperinsulinemic-euglycemic clamp (P < 0.05). Collectively, these data demonstrate that acute elevations in plasma glucose and insulin can impair spontaneous cardiac BRS in young, healthy subjects, and that reductions in cardiac BRS following acute hyperglycemia are unaffected by reduced insulin sensitivity via short-term reductions in physical activity.

  18. Enhanced Ca2+ binding of cardiac troponin reduces sarcomere length dependence of contractile activation independently of strong crossbridges.

    PubMed

    Korte, F Steven; Feest, Erik R; Razumova, Maria V; Tu, An-Yue; Regnier, Michael

    2012-10-01

    Calcium sensitivity of the force-pCa relationship depends strongly on sarcomere length (SL) in cardiac muscle and is considered to be the cellular basis of the Frank-Starling law of the heart. SL dependence may involve changes in myofilament lattice spacing and/or myosin crossbridge orientation to increase probability of binding to actin at longer SLs. We used the L48Q cardiac troponin C (cTnC) variant, which has enhanced Ca(2+) binding affinity, to test the hypotheses that the intrinsic properties of cTnC are important in determining 1) thin filament binding site availability and responsiveness to crossbridge activation and 2) SL dependence of force in cardiac muscle. Trabeculae containing L48Q cTnC-cTn lost SL dependence of the Ca(2+) sensitivity of force. This occurred despite maintaining the typical SL-dependent changes in maximal force (F(max)). Osmotic compression of preparations at SL 2.0 μm with 3% dextran increased F(max) but not pCa(50) in L48Q cTnC-cTn exchanged trabeculae, whereas wild-type (WT)-cTnC-cTn exchanged trabeculae exhibited increases in both F(max) and pCa(50). Furthermore, crossbridge inhibition with 2,3-butanedione monoxime at SL 2.3 μm decreased F(max) and pCa(50) in WT cTnC-cTn trabeculae to levels measured at SL 2.0 μm, whereas only F(max) was decreased with L48Q cTnC-cTn. Overall, these results suggest that L48Q cTnC confers reduced crossbridge dependence of thin filament activation in cardiac muscle and that changes in the Ca(2+) sensitivity of force in response to changes in SL are at least partially dependent on properties of thin filament troponin.

  19. 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

    2015-12-05

    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

  20. An immunological model for detecting bot activities

    NASA Astrophysics Data System (ADS)

    Karim, Md E.; Phoha, Vir V.; Sultan, Md A.

    2009-05-01

    We develop a hierarchical immunological model to detect bot activities in a computer network. In the proposed model antibody (detector)-antigen (foreign object) reactions are defined using negative selection based approach and negative systems-properties are defined by various temporal as well as non-temporal systems features. Theory of sequential hypothesis testing has been used in the literature for identifying spatial-temporal correlations among malicious remote hosts and among the bots within a botnet. We use it for combining multiple immunocomputing based decisions too. Negative selection based approach defines a self and helps identifying non-selves. We define non-selves with respect to various systems characteristics and then use different combinations of non-selves to design bot detectors. Each detector operates at the client sites of the network under surveillance. A match with any of the detectors suggests presence of a bot. Preliminary results suggest that the proposed model based solutions can improve the identification of bot activities.

  1. 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

  2. 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.

  3. A comparative study of graph-based, eikonal, and monodomain simulations for the estimation of cardiac activation times.

    PubMed

    Wallman, Mikael; Smith, Nicolas P; Rodriguez, Blanca

    2012-06-01

    The bidomain and monodomain equations are well established as the standard set of equations for the simulation of cardiac electrophysiological behavior. However, the computational cost of detailed bidomain/monodomain simulations limits their applicability in scenarios where a large number of simulations needs to be performed (e.g., parameter estimation). In this study, we present a graph-based method, which relies on point-to-point path finding to estimate activation times for single points in cardiac tissue with minimal computational costs. To validate our approach, activation times are compared to monodomain simulation results for an anatomically based rabbit ventricular model, incorporating realistic fiber orientation and conduction heterogeneities. Differences in activation times between the graph-based method and monodomain results are less than 10% of the total activation time, and computational performance is orders of magnitude faster with the proposed method when calculating activation times at single points. These results suggest that the graph-based method is well suited for estimating activation times when the need for fast performance justifies a limited loss of accuracy.

  4. 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

  5. Clinical Cosmobiology - Sudden Cardiac Death and Daily / Monthly Geomagnetic, Cosmic Ray and Solar Activity - the Baku Study (2003-2005)

    NASA Astrophysics Data System (ADS)

    Stoupel, E.; Babayev, E. S.; Mustafa, F. R.; Abramson, E.; Israelevich, P.; Sulkes, J.

    2006-12-01

    Part of results of collaborative studies for revealing an influence of the periodical changes of solar, geomagnetic and cosmic ray activities on the sudden cardiac death (SCD) mortality is described in this paper. The data covering daily and monthly temporal distribution of SCD (788 patients in 36 months in 2003-2005), taken from all of emergency and first medical aid stations of grand Baku area, were analyzed and compared with certain cosmophysical parameters. It was obtained that SCD is higher on the highest and lowest daily levels of geomagnetic activity. Days with SCD are accompanied by higher cosmic ray (neutron) activity. The monthly number of SCD was inversely related to solar and geomagnetic activities while was positively linked with cosmic ray activity level. It was concluded that cosmic ray activity could be considered as one of regulating external/environmental factors in human homeostasis.

  6. Tripartite Motif 8 Contributes to Pathological Cardiac Hypertrophy Through Enhancing Transforming Growth Factor β-Activated Kinase 1-Dependent Signaling Pathways.

    PubMed

    Chen, Lijuan; Huang, Jia; Ji, Yan-Xiao; Mei, Fanghua; Wang, Pi-Xiao; Deng, Ke-Qiong; Jiang, Xi; Ma, Genshan; Li, Hongliang

    2017-02-01

    Tripartite motif (TRIM) 8 functions as an E3 ubiquitin ligase, interacting with and ubiquitinating diverse substrates, and is implicated in various pathological processes. However, the function of TRIM8 in the heart remains largely uncharacterized. This study aims to explore the role of TRIM8 in the development of pathological cardiac hypertrophy. Mice and isolated neonatal rat cardiomyocytes overexpressing or lacking TRIM8 were examined in several experiments. The effect of aortic banding-induced cardiac hypertrophy was analyzed by echocardiographic, pathological and molecular analyses. Our results indicated that the TRIM8 overexpression in hearts exacerbated the cardiac hypertrophy triggered by aortic banding. In contrast, the development of pathological cardiac hypertrophy was profoundly blocked in TRIM8-deficient hearts. Mechanistically, our study suggests that TRIM8 may elicit cardiodetrimental effects by promoting the activation of transforming growth factor β-activated kinase 1 (TAK1)-p38/JNK signaling pathways. Similar results were observed in cultured neonatal rat cardiomyocytes treated with angiotensin II. The rescue experiments using the TAK1-specific inhibitor 5z-7-ox confirmed the requirement of TAK1 activation in TRIM8-mediated pathological cardiac hypertrophy. Furthermore, TRIM8 contributed to TAK1 activation by binding to and promoting TAK1 ubiquitination. In conclusion, our study demonstrates that TRIM8 plays a deleterious role in pressure overload-induced cardiac hypertrophy by accelerating the activation of TAK1-dependent signaling pathways.

  7. Cardiac catheterization - discharge

    MedlinePlus

    Catheterization - cardiac - discharge; Heart catheterization - discharge: Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization discharge; CAD - cardiac catheterization discharge; Coronary artery disease - cardiac catheterization ...

  8. Discovery of a small molecule activator of the human ether-a-go-go-related gene (HERG) cardiac K+ channel.

    PubMed

    Kang, Jiesheng; Chen, Xiao-Liang; Wang, Hongge; Ji, Junzhi; Cheng, Hsien; Incardona, Josephine; Reynolds, William; Viviani, Fabrice; Tabart, Michel; Rampe, David

    2005-03-01

    Many drugs inhibit the human ether-a-go-go-related gene (HERG) cardiac K+ channel. This leads to action potential prolongation on the cellular level, a prolongation of the QT interval on the electrocardiogram, and sometimes cardiac arrhythmia. To date, no activators of this channel have been reported. Here, we describe the in vitro electrophysiological effects of (3R,4R)-4-[3-(6-methoxyquinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluoro-phenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid (RPR260243), a novel activator of HERG. Using patch-clamp electrophysiology, we found that RPR260243 dramatically slowed current deactivation when applied to cells stably expressing HERG. The effects of RPR260243 on HERG channel deactivation were temperature- and voltage-dependent and occurred over the concentration range of 1 to 30 microM. RPR260243-modified HERG currents were inhibited by dofetilide (IC50 = 58 nM). RPR260243 had little effect on HERG current amplitude and no significant effects on steady-state activation parameters or on channel inactivation processes. RPR260243 displayed no activator-like effects on other voltage-dependent ion channels, including the closely related erg3 K+ channel. RPR260243 enhanced the delayed rectifier current in guinea pig myocytes but, when administered alone, had little effect on action potential parameters in these cells. However, RPR260243 completely reversed the action potential-prolonging effects of dofetilide in this preparation. Using the Langendorff heart method, we found that 5 microM RPR260243 increased T-wave amplitude, prolonged the PR interval, and shortened the QT interval. We believe RPR260243 represents the first known HERG channel activator and that the drug works primarily by inhibiting channel closure, leading to a persistent HERG channel current upon repolarization. Compounds like RPR260243 will be useful for studying the physiological role of HERG and may one day find use in treating cardiac disease.

  9. 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

  10. Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity.

    PubMed

    Winkelmann, Donald A; Forgacs, Eva; Miller, Matthew T; Stock, Ann M

    2015-08-06

    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.

  11. 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.

  12. Influence of aging on the activity of mice Sca-1+CD31− cardiac stem cells

    PubMed Central

    Pu, Shiming; Qin, Liu; Li, Yun; Zhou, Zuping

    2017-01-01

    Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31− subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done. Proliferation and cell cycle were measured by flow cytometry assay, then used microarray to dissect variability from younger and older mice. Although the number of CSCs was higher in older mice, the advanced age significantly reduced the differentiation ability into cardiac cell lineages and the proliferation ability. Transcriptional changes in Sca-1+CD31− subgroups of CSCs during aging are related to Vitamin B6 metabolism, circadian rhythm, Tyrosine metabolism, Complement and coagulation cascades. Taking together these results indicate that Cardiac resident stem/progenitor cells have significant differences in their proliferative, pluripotency and gene profiles and those differences are age depending. PMID:27980224

  13. Nitric oxide synthase in cardiac sarcoplasmic reticulum.

    PubMed

    Xu, K Y; Huso, D L; Dawson, T M; Bredt, D S; Becker, L C

    1999-01-19

    NO. is a free radical that modulates heart function and metabolism. We report that a neuronal-type NO synthase (NOS) is located on cardiac sarcoplasmic reticulum (SR) membrane vesicles and that endogenous NO. produced by SR-associated NOS inhibits SR Ca2+ uptake. Ca2+-dependent biochemical conversion of L-arginine to L-citrulline was observed from isolated rabbit cardiac SR vesicles in the presence of NOS substrates and cofactors. Endogenous NO. was generated from the vesicles and detected by electron paramagnetic resonance spin-trapping measurements. Immunoelectron microscopy demonstrated labeling of cardiac SR vesicles by using anti-neuronal NOS (nNOS), but not anti-endothelial NOS (eNOS) or anti-inducible NOS (iNOS) antibodies, whereas skeletal muscle SR vesicles had no nNOS immunoreactivity. The nNOS immunoreactivity also displayed a pattern consistent with SR localization in confocal micrographs of sections of human myocardium. Western blotting demonstrated that cardiac SR NOS is larger than brain NOS (160 vs. 155 kDa). No immunodetection was observed in cardiac SR vesicles from nNOS knockout mice or with an anti-nNOS mu antibody, suggesting the possibility of a new nNOS-type isoform. 45Ca uptake by cardiac SR vesicles, catalyzed by Ca2+-ATPase, was inhibited by NO. produced endogenously from cardiac SR NOS, and 7-nitroindazole, a selective nNOS inhibitor, completely prevented this inhibition. These results suggest that a cardiac muscle nNOS isoform is located on SR of cardiac myocytes, where it may respond to intracellular Ca2+ concentration and modulate SR Ca2+ ion active transport in the heart.

  14. Nitric oxide synthase in cardiac sarcoplasmic reticulum

    PubMed Central

    Xu, Kai Y.; Huso, David L.; Dawson, Ted M.; Bredt, David S.; Becker, Lewis C.

    1999-01-01

    NO⋅ is a free radical that modulates heart function and metabolism. We report that a neuronal-type NO synthase (NOS) is located on cardiac sarcoplasmic reticulum (SR) membrane vesicles and that endogenous NO⋅ produced by SR-associated NOS inhibits SR Ca2+ uptake. Ca2+-dependent biochemical conversion of l-arginine to l-citrulline was observed from isolated rabbit cardiac SR vesicles in the presence of NOS substrates and cofactors. Endogenous NO⋅ was generated from the vesicles and detected by electron paramagnetic resonance spin-trapping measurements. Immunoelectron microscopy demonstrated labeling of cardiac SR vesicles by using anti-neuronal NOS (nNOS), but not anti-endothelial NOS (eNOS) or anti-inducible NOS (iNOS) antibodies, whereas skeletal muscle SR vesicles had no nNOS immunoreactivity. The nNOS immunoreactivity also displayed a pattern consistent with SR localization in confocal micrographs of sections of human myocardium. Western blotting demonstrated that cardiac SR NOS is larger than brain NOS (160 vs. 155 kDa). No immunodetection was observed in cardiac SR vesicles from nNOS knockout mice or with an anti-nNOSμ antibody, suggesting the possibility of a new nNOS-type isoform. 45Ca uptake by cardiac SR vesicles, catalyzed by Ca2+-ATPase, was inhibited by NO⋅ produced endogenously from cardiac SR NOS, and 7-nitroindazole, a selective nNOS inhibitor, completely prevented this inhibition. These results suggest that a cardiac muscle nNOS isoform is located on SR of cardiac myocytes, where it may respond to intracellular Ca2+ concentration and modulate SR Ca2+ ion active transport in the heart. PMID:9892689

  15. 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.

  16. Multiple mechanisms of spiral wave breakup in a model of cardiac electrical activity

    NASA Astrophysics Data System (ADS)

    Fenton, Flavio H.; Cherry, Elizabeth M.; Hastings, Harold M.; Evans, Steven J.

    2002-09-01

    It has become widely accepted that the most dangerous cardiac arrhythmias are due to reentrant waves, i.e., electrical wave(s) that recirculate repeatedly throughout the tissue at a higher frequency than the waves produced by the heart's natural pacemaker (sinoatrial node). However, the complicated structure of cardiac tissue, as well as the complex ionic currents in the cell, have made it extremely difficult to pinpoint the detailed dynamics of these life-threatening reentrant arrhythmias. A simplified ionic model of the cardiac action potential (AP), which can be fitted to a wide variety of experimentally and numerically obtained mesoscopic characteristics of cardiac tissue such as AP shape and restitution of AP duration and conduction velocity, is used to explain many different mechanisms of spiral wave breakup which in principle can occur in cardiac tissue. Some, but not all, of these mechanisms have been observed before using other models; therefore, the purpose of this paper is to demonstrate them using just one framework model and to explain the different parameter regimes or physiological properties necessary for each mechanism (such as high or low excitability, corresponding to normal or ischemic tissue, spiral tip trajectory types, and tissue structures such as rotational anisotropy and periodic boundary conditions). Each mechanism is compared with data from other ionic models or experiments to illustrate that they are not model-specific phenomena. Movies showing all the breakup mechanisms are available at http://arrhythmia.hofstra.edu/breakup and at ftp://ftp.aip.org/epaps/chaos/E-CHAOEH-12-039203/ INDEX.html. The fact that many different breakup mechanisms exist has important implications for antiarrhythmic drug design and for comparisons of fibrillation experiments using different species, electromechanical uncoupling drugs, and initiation protocols.

  17. [Cardiac, respiratory, and motor activity in norm and after activation of catecholaminergic systems in newborn rat pups].

    PubMed

    Kuznetsov, S V; Dmitrieva, L E; Sizonov, V A

    2012-01-01

    Study of parameters of the cardiac, respiratory, and motor activity (MA) was carried out on newborn rat pups for the first day after birth (P0) and at the 14th day of postnatal development (P14) after change of the level of activity of catecholaminergic systems. The animals were administered with L-DOPA (25-100 mg/kg) and the indirect adrenomimetic isoamine (3 and 10 mg/kg). Additionally there were studied effects of L-DOPA and isoamine after blockade of D1 and D2 dopamine receptors (antagonists SCH-23390 and sulpiride). The L-DOPA administration produced a dose-dependent MA enhancement with its possible transition into the uninterrupted activity. In P0 the release of monoamines was accompanied by development of weak bradycardia. There was noted a tendency for acceleration of respiration at administration of the low dose both of L-DOPA and of isoamine and for its retardation at high doses. In P14 the L-DOPA administration was accompanied by retardation of the heart rate (HR) by 8 % and by acceleration of respiratory rate by 26%. The isoamine administration produced an insignificant decrease of HR and an increase of respiratory rate (RR) by 8% at the low dose and by 21% at the high dose of the agent. At the blockade of D1 receptors, RR remained close to the background values, while at the blockade of D2 - decreased insignificantly. Blockade of D1 and D2 receptors did not cause significant HR changes. Analysis of the HR variability has shown that both after L-DOPA administration and at blockade of dopamine receptors no unidirectional reaction was observed: in 80 % of rat pups the portion of nerve mechanisms of HR regulation increased, while in the rest--of sympathetic and humoral factors at a decrease of parasympathetic effects. In all rat pups the isoamine administration was accompanied by a shift of the specter power into the higher frequency area; in 60% of animals there were enhanced sympathetic influences. In P14 in rat pups after administration both of L

  18. 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.

  19. Gender-related Differences in Maximum Gait Speed and Daily Physical Activity in Elderly Hospitalized Cardiac Inpatients

    PubMed Central

    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.

    2015-01-01

    Abstract 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

  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

    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; Jones, Lee W

    2014-02-01

    Conventional resting left ventricular ejection fraction (LVEF) assessments have limitations for detecting doxorubicin (DOX)-related cardiac dysfunction. Novel resting echocardiographic parameters, including 3-dimensional 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 l 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. 9 CFR 113.35 - Detection of viricidal activity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Detection of viricidal activity. 113.35 Section 113.35 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... REQUIREMENTS Standard Procedures § 113.35 Detection of viricidal activity. The test for detection of...

  2. Dynamic response of cardiac autonomic nervous system activity to habitual exercise during gradual variation of breathing frequency.

    PubMed

    Nakamura, H

    2015-01-01

    The purpose of this study is to measure cardiac autonomic nervous system activity during breathing control with gradual alteration of the frequency between habitual exercise and sedentary young male subjects. In this study, to evaluate CANS activity, Tone-Entropy analysis, which is based on statistical property of acceleration between consecutive R-R intervals, was used. Sixteen healthy young male subjects (21.6+/-1.4yrs) were participated in these experiments and their R-R interval sequences were recorded. The controlled breathing trials let the subjects synchronize their breathing frequency ranging 3 to 30 breathing per minute. After that, breathing frequency was gradually and reversely decreased from 30 to 3 breathing per minute. Before and after the breathing controlled trials, 5 minute voluntary breathing trials were performed. Our results showed that total CANS activities of HE group were activated more than those of SE group in the entire sections and also that, as compared with HE group, maximum of average HR in SE group was appeared at 30 breathing per minute and it is recognized that the statistically significant difference between HE and SE group was shown. In conclusion, our results suggest that efficiency of cardiac function on habitual exercise in breathing control may be quantitatively and graphically evaluated with HR and Tone-Entropy analysis without any physical stimulation.

  3. Distinct association between the antagonistic jaw muscle activity levels and cardiac activity during chewing and NREM sleep in the freely moving guinea pigs.

    PubMed

    Kato, Takafumi; Masuda, Yuji; Miyano, Keiji; Higashiyama, Makoto; Yano, Hiroyuki; Haque, Tahsinul; Sato, Fumihiko; Yoshida, Atsushi

    2015-04-10

    The aim of this study was to investigate the changes of the association between cardiac activity and the electromyographic (EMG) level of the antagonistic jaw muscles during chewing and NREM sleep in guinea pigs after systemic clonidine injections. Ten animals were prepared for chronic experiments to monitor sleep, cardiac activity and EMG activity of jaw-closing masseter (MAS) and jaw-opening anterior belly of digastric (ADG) muscles. The recordings were made for ten hours with the injections of saline or clonidine (10 μg/kg, i.p.). Integrated EMG activity of the two muscles and mean heart rate (mHR) were calculated for every 10-s epoch. During the two hours after clonidine injection, the duration of REM sleep and mHR were significantly reduced. During chewing, the high EMG activity level of the two muscles and the activity ratio between the two muscles were not modified although mHR was decreased. During NREM sleep, after clonidine injection, the low EMG activity level at baseline was further decreased by 20-30% in parallel to a decrease of mHR although the heterogeneity of the activity ratio remained unaltered. The results suggest that the maintenance of the activity level for the antagonistic jaw muscles are regulated by the distinct physiological mechanisms reflecting the behavioral states during conscious chewing and unconscious NREM sleep.

  4. Roles of the NH2-terminal domains of cardiac ryanodine receptor in Ca2+ release activation and termination.

    PubMed

    Liu, Yingjie; Sun, Bo; Xiao, Zhichao; Wang, Ruiwu; Guo, Wenting; Zhang, Joe Z; Mi, Tao; Wang, Yundi; Jones, Peter P; Van Petegem, Filip; Chen, S R Wayne

    2015-03-20

    The NH2-terminal region (residues 1-543) of the cardiac ryanodine receptor (RyR2) harbors a large number of mutations associated with cardiac arrhythmias and cardiomyopathies. Functional studies have revealed that the NH2-terminal region is involved in the activation and termination of Ca(2+) release. The three-dimensional structure of the NH2-terminal region has recently been solved. It is composed of three domains (A, B, and C). However, the roles of these individual domains in Ca(2+) release activation and termination are largely unknown. To understand the functional significance of each of these NH2-terminal domains, we systematically deleted these domains and assessed their impact on caffeine- or Ca(2+)-induced Ca(2+) release and store overload-induced Ca(2+) release (SOICR) in HEK293 cells. We found that all deletion mutants were capable of forming caffeine- and ryanodine-sensitive functional channels, indicating that the NH2-terminal region is not essential for channel gating. Ca(2+) release measurements revealed that deleting domain A markedly reduced the threshold for SOICR termination but had no effect on caffeine or Ca(2+) activation or the threshold for SOICR activation, whereas deleting domain B substantially enhanced caffeine and Ca(2+) activation and lowered the threshold for SOICR activation and termination. Conversely, deleting domain C suppressed caffeine activation, abolished Ca(2+) activation and SOICR, and diminished protein expression. These results suggest that domain A is involved in channel termination, domain B is involved in channel suppression, and domain C is critical for channel activation and expression. Our data shed new insights into the structure-function relationship of the NH2-terminal domains of RyR2 and the action of NH2-terminal disease mutations.

  5. A Phased-Array Stimulator System for Studying Planar and Curved Cardiac Activation Wave Fronts

    PubMed Central

    Abbas, Rashida A.; Lin, Shien Fong; Mashburn, David; Xu, Junkai; Wikswo, John P.

    2009-01-01

    Wave front propagation in cardiac tissue is affected greatly by the geometry of the wave front. We describe a computer-controlled stimulator system that creates reproducible wave fronts of a predetermined shape and orientation for the investigation of the effects of wave front geometry. We conducted demonstration experiments on isolated perfused rabbit hearts, which were stained with the voltage-sensitive dye, di-4-ANEPPS. The wave fronts were imaged using a laser and a CCD camera. The stimulator and imaging systems have been used to characterize the relationship between wave front velocity and fiber orientation. This approach has potential applications in investigating curvature effects, testing numerical models of cardiac tissue, and creating complex wave fronts using one-, twoor three-dimensional electrode arrays. PMID:18232365

  6. Turbulent electrical activity at sharp-edged inexcitable obstacles in a model for human cardiac tissue.

    PubMed

    Majumder, Rupamanjari; Pandit, Rahul; Panfilov, A V

    2014-10-01

    Wave propagation around various geometric expansions, structures, and obstacles in cardiac tissue may result in the formation of unidirectional block of wave propagation and the onset of reentrant arrhythmias in the heart. Therefore, we investigated the conditions under which reentrant spiral waves can be generated by high-frequency stimulation at sharp-edged obstacles in the ten Tusscher-Noble-Noble-Panfilov (TNNP) ionic model for human cardiac tissue. We show that, in a large range of parameters that account for the conductance of major inward and outward ionic currents of the model [fast inward Na(+) current (INa), L-type slow inward Ca(2+) current (ICaL), slow delayed-rectifier current (IKs), rapid delayed-rectifier current (IKr), inward rectifier K(+) current (IK1)], the critical period necessary for spiral formation is close to the period of a spiral wave rotating in the same tissue. We also show that there is a minimal size of the obstacle for which formation of spirals is possible; this size is ∼2.5 cm and decreases with a decrease in the excitability of cardiac tissue. We show that other factors, such as the obstacle thickness and direction of wave propagation in relation to the obstacle, are of secondary importance and affect the conditions for spiral wave initiation only slightly. We also perform studies for obstacle shapes derived from experimental measurements of infarction scars and show that the formation of spiral waves there is facilitated by tissue remodeling around it. Overall, we demonstrate that the formation of reentrant sources around inexcitable obstacles is a potential mechanism for the onset of cardiac arrhythmias in the presence of a fast heart rate.

  7. The Solar Activity Effect on the Rate of Complications in Cardiac Surgery

    NASA Astrophysics Data System (ADS)

    Sheyner, Olga; Matusova, Elena; Fridman, Vladimir

    2010-05-01

    The essential effect of powerful solar flares on a rate of post voperation bleedings and tachyarrhythmias is revealed. The latter complication rate is found to increase in 1.5 times during the first 5-7- days after solar proton events and reach the maximum in the 2-4 days. The analysis of a flareless periods does not show such correlation. Thus, geoeffective solar flares are shown to be the additional risk factor for cardiac surgery.

  8. 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

  9. 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

  10. 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.

  11. Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes

    PubMed Central

    Lu, Fang-Min; Deisl, Christine; Hilgemann, Donald W

    2016-01-01

    Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes. DOI: http://dx.doi.org/10.7554/eLife.19267.001 PMID:27627745

  12. SK4 Ca2+ activated K+ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells.

    PubMed

    Weisbrod, David; Peretz, Asher; Ziskind, Anna; Menaker, Nataly; Oz, Shimrit; Barad, Lili; Eliyahu, Sivan; Itskovitz-Eldor, Joseph; Dascal, Nathan; Khananshvili, Daniel; Binah, Ofer; Attali, Bernard

    2013-04-30

    Proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. Two main mechanisms have been proposed: (i) the "voltage-clock," where the hyperpolarization-activated funny current If causes diastolic depolarization that triggers action potential cycling; and (ii) the "Ca(2+) clock," where cyclical release of Ca(2+) from Ca(2+) stores depolarizes the membrane during diastole via activation of the Na(+)-Ca(2+) exchanger. Nonetheless, these mechanisms remain controversial. Here, we used human embryonic stem cell-derived cardiomyocytes (hESC-CMs) to study their autonomous beating mechanisms. Combined current- and voltage-clamp recordings from the same cell showed the so-called "voltage and Ca(2+) clock" pacemaker mechanisms to operate in a mutually exclusive fashion in different cell populations, but also to coexist in other cells. Blocking the "voltage or Ca(2+) clock" produced a similar depolarization of the maximal diastolic potential (MDP) that culminated by cessation of action potentials, suggesting that they converge to a common pacemaker component. Using patch-clamp recording, real-time PCR, Western blotting, and immunocytochemistry, we identified a previously unrecognized Ca(2+)-activated intermediate K(+) conductance (IK(Ca), KCa3.1, or SK4) in young and old stage-derived hESC-CMs. IK(Ca) inhibition produced MDP depolarization and pacemaker suppression. By shaping the MDP driving force and exquisitely balancing inward currents during diastolic depolarization, IK(Ca) appears to play a crucial role in human embryonic cardiac automaticity.

  13. Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production.

    PubMed

    Shmist, Yelena A; Goncharov, Igor; Eichler, Maor; Shneyvays, Vladimir; Isaac, Ahuva; Vogel, Zvi; Shainberg, Asher

    2006-02-01

    Delta-9-tetrahydrocannabinol (THC), the major active component of marijuana, has a beneficial effect on the cardiovascular system during stress conditions, but the defence mechanism is still unclear. The present study was designed to investigate the central (CB1) and the peripheral (CB2) cannabinoid receptor expression in neonatal cardiomyoctes and possible function in the cardioprotection of THC from hypoxia. Pre-treatment of cardiomyocytes that were grown in vitro with 0.1 - 10 microM THC for 24 h prevented hypoxia-induced lactate dehydrogenase (LDH) leakage and preserved the morphological distribution of alpha-sarcomeric actin. The antagonist for the CB2 (10 microM), but not CB1 receptor antagonist (10 microM) abolished the protective effect of THC. In agreement with these results using RT-PCR, it was shown that neonatal cardiac cells express CB2, but not CB1 receptors. Involvement of NO in the signal transduction pathway activated by THC through CB2 was examined. It was found that THC induces nitric oxide (NO) production by induction of NO synthase (iNOS) via CB2 receptors. L-NAME (NOS inhibitor, 100 microM) prevented the cardioprotection provided by THC. Taken together, our findings suggest that THC protects cardiac cells against hypoxia via CB2 receptor activation by induction of NO production. An NO mechanism occurs also in the classical pre-conditioning process; therefore, THC probably pre-trains the cardiomyocytes to hypoxic conditions.

  14. 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

  15. 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.

  16. Wheat Germ Agglutinin Staining as a Suitable Method for Detection and Quantification of Fibrosis in Cardiac Tissue after Myocardial Infarction

    PubMed Central

    Emde, B.; Heinen, A.; Gödecke, A.; Bottermann, K.

    2014-01-01

    The quantification of fibrotic tissue is an important task in the analysis of cardiac remodeling. The use of established fibrosis staining techniques is limited on frozen cardiac tissue sections due to a reduced color contrast compared to paraffin embedded sections. We therefore used FITC-labeled wheat germ agglutinin (WGA), which marks fibrotic tissue in comparable quality as the established picrosirius red (SR) staining, for the staining of post myocardial infarction scar tissue. The fibrosis amount was quantified in a histogram-based approach using the non-commercial image processing program ImageJ. Our results clearly demonstrate that WGA-FITC is a suitable marker for cardiac fibrosis in frozen tissue sections. In combination with the histogram-based analysis, this new quantification approach is i) easy and fast to perform; ii) suitable for raw frozen tissue sections; and iii) allows the use of additional antibodies in co-immunostaining. PMID:25578975

  17. Pulse pressure monitoring through non-contact cardiac motion detection using 2.45 GHz microwave Doppler radar.

    PubMed

    Singh, Aditya; Lubecke, Victor; Boric-Lubecke, Olga

    2011-01-01

    The use of a Continuous Wave (CW) quadrature Doppler radar is proposed here for continuous non-invasive Pulse Pressure monitoring. A correspondence between the variation in systemic pulse and variation in the displacement of the chest due to heart is demonstrated, establishing feasibility for the approach. Arctangent demodulation technique was used to process baseband data from radar measurements on two test subjects, in order to determine the absolute cardiac motion. An Omron digital Blood pressure cuff was used to measure the systolic and diastolic blood pressures from which the pulse pressure was calculated. Correlation between pulse pressure and cardiac motion was observed through changes induced due to different postures of the body.

  18. Comparison of three point-of-care testing devices to detect hemostatic changes in adult elective cardiac surgery: a prospective observational study

    PubMed Central

    2014-01-01

    Background Bleeding complications in cardiac surgery may lead to increased morbidity and mortality. Traditional blood coagulation tests are not always suitable to detect rapid changes in the patient's coagulation status. Point-of-care instruments such as the TEG (thromboelastograph) and RoTEM (thromboelastometer) have been shown to be useful as a guide for the clinician in the choice of blood products and they may lead to a reduction in the need for blood transfusion, contributing to better patient blood management. Methods The purpose of this study was to evaluate the ability of the TEG, RoTEM and Sonoclot instruments to detect changes in hemostasis in elective cardiac surgery with cardiopulmonary bypass and to investigate possible correlations between variables from these three instruments and routine hematological coagulation tests. Blood samples from thirty-five adult patients were drawn before and after surgery and analyzed in TEG, RoTEM, Sonoclot and routine coagulation tests. Data were compared using repeated measures analysis of variance and Pearson's test for linear correlation. Results We found significant changes for all TEG variables after surgery, for three of the RoTEM variables, and for one variable from the Sonoclot. There were significant correlations postoperatively between plasma fibrinogen levels and variables from the three instruments. Conclusions TEG and RoTEM may be used to detect changes in hemostasis following cardiac surgery with CPB. Sonoclot seems to be less suitable to detect such changes. Variables from the three instruments correlated with plasma fibrinogen and could be used to monitor treatment with fibrinogen concentrate. PMID:25276093

  19. Increased mitochondrial emission of reactive oxygen species and calpain activation are required for doxorubicin-induced cardiac and skeletal muscle myopathy.

    PubMed

    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

    2015-04-15

    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.

  20. 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

  1. Membrane phospholipid fatty acid composition regulates cardiac SERCA activity in a hibernator, the Syrian hamster (Mesocricetus auratus).

    PubMed

    Giroud, Sylvain; Frare, Carla; Strijkstra, Arjen; Boerema, Ate; Arnold, Walter; Ruf, Thomas

    2013-01-01

    Polyunsaturated fatty acids (PUFA) have strong effects on hibernation and daily torpor. Increased dietary uptake of PUFA of the n-6 class, particularly of Linoleic acid (LA, C18:2 n-6) lengthens torpor bout duration and enables animals to reach lower body temperatures (T(b)) and metabolic rates. As previously hypothesized, this well-known influence of PUFA may be mediated via effects of the membrane fatty acid composition on sarcoplasmic reticulum (SR) Ca(2+-)ATPase 2a (SERCA) in the heart of hibernators. We tested the hypotheses that high proportions of n-6 PUFA in general, or specifically high proportions of LA (C18:2 n-6) in SR phospholipids (PL) should be associated with increased cardiac SERCA activity, and should allow animals to reach lower minimum T(b) in torpor. We measured activity of SERCA from hearts of hibernating and non-hibernating Syrian hamsters (Mesocricetus auratus) in vitro at 35 °C. Further, we determined the PL fatty acid composition of the SR membrane of these hearts. We found that SERCA activity strongly increased as the proportion of LA in SR PL increased but was negatively affected by the content of Docosahexaenoic acid (DHA; C22:6 n-3). SR PL from hibernating hamsters were characterized by high proportions of LA and low proportions of DHA. As a result, SERCA activity was significantly higher during entrance into torpor and in torpor compared to inter-bout arousal. Also, animals with increased SERCA activity reached lower T(b) during torpor. Interestingly, a subgroup of hamsters which never entered torpor but remained euthermic throughout winter displayed a phenotype similar to animals in summer. This was characterized by lower proportions of LA and increased proportions of DHA in SR membranes, which is apparently incompatible with torpor. We conclude that the PUFA composition of SR membranes affects cardiac function via modulating SERCA activity, and hence determines the minimum T(b) tolerated by hibernators.

  2. 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.

  3. Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII

    PubMed Central

    Velez Rueda, J. Omar; Mattiazzi, Alicia

    2012-01-01

    The objective of this study was to establish whether 1) hyperactivity of renin-angiotensin-aldosterone system (RAAS) produces apoptosis in early stages of cardiac disease; and 2) Ca2+-calmodulin-dependent protein kinase II (CaMKII) is involved in these apoptotic events. Two models of hypertrophy were used at an early stage of cardiac disease: spontaneously hypertensive rats (SHR) and isoproterenol-treated rats (Iso-rats). At 4 mo, SHR showed blood pressure, aldosterone serum levels, used as RAAS activity index, and left ventricular mass index, used as hypertrophy index, above control values by 84.2 ± 2.6 mmHg, 211.2 ± 25.8%, and 8.6 ± 1.1 mg/mm, respectively. There was also an increase in apoptotis (Bax-to-Bcl-2 ratio and terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling positive cells) associated with an enhancement of CaMKII activity with respect to age-matched controls (phosphorylated-CaMKII, 98.7 ± 14.1 above control). Similar results were observed in 4-mo-old Iso-rats. Cardiac function studied by echocardiography remained unaltered in all groups. Enalapril treatment significantly prevented hypertrophy, apoptosis, and CaMKII activity. Moreover, intracellular Ca2+ handling in isolated myocytes was similar between SHR, Iso-rats, and their aged-matched controls. However, SHR and Iso-rats showed a significant increase in superoxide anion generation (lucigenin) and lipid peroxidation (thiobarbituric acid reactive substance). In transgenic mice with targeted cardiomyocyte expression of a CaMKII inhibitory peptide (AC3-I) or a scrambled control peptide (AC3-C), Iso treatment increased thiobarbituric acid reactive substance in both strains, whereas it increased CaMKII activity and apoptosis only in AC3-C mice. Endogenous increases in RAAS activity induce ROS and CaMKII-dependent apoptosis in vivo. CaMKII activation could not be associated with intracellular Ca2+ increments and was directly related to the increase in oxidative stress. PMID

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  8. Exercise Stress Echocardiography with Tissue Doppler Imaging (TDI) Detects Early Systolic Dysfunction in Beta-Thalassemia Major Patients without Cardiac Iron Overload

    PubMed Central

    Barbero, Umberto; Destefanis, Paola; Pozzi, Roberto; Longo, Filomena; Piga, Antonio

    2012-01-01

    Objectives To evaluate left and right myocardial performance at rest and after maximal exercise by conventional and Tissue Doppler Imaging (TDI) echocardiography. Background Iron Overload Cardiomyopathy (IOC) is the main cause of death in thalassemia major (TM) patients but conventional Echocardiography fails to predict early cardiac dysfunction. As TDI is able to demonstrate regional myocardial dysfunction and stress test may reveal abnormalities which are not evident at rest, we wondered if echocardiographic parameters may reveal abnormalities when applied first at rest and then after a physical effort. Methods We enrolled 46 consecutive beta-TM patients and 39 control subjects without evidence of cardiac disease; two echocardiograms, at baseline and at the end of maximal exercise on supine bicycle ergometer, were done. All TM patients had a liver iron assessment by SQUID (Superconducting Quantum Interference Device) and a cardiac iron one by MRI (T2*) evaluation. Results 38 TM patients had no evidence of cardiac iron overload. Whereas TM patients did not shown diastolic dysfunction and all of them presented a good global response to exercise, TDI detected a reduced increase of the S’ waves of left ventricle basal segment during exercise. This finding seems to have some weak but interesting relations with iron overload markers. Pulmonary artery systolic pressure (PAPs) values were greater than in control subjects both at rest and after exercise Conclusions in our study, exercise stress TDI-echocardiography was able to demonstrate subtle systolic abnormalities that were missed by Conventional Echocardiography. Further studies are required to determine the meaning and the clinical impact of these results. PMID:22811786

  9. Associations between attention, affect and cardiac activity in a single yoga session for female cancer survivors: an enactive neurophenomenology-based approach.

    PubMed

    Mackenzie, Michael J; Carlson, Linda E; Paskevich, David M; Ekkekakis, Panteleimon; Wurz, Amanda J; Wytsma, Kathryn; Krenz, Katie A; McAuley, Edward; Culos-Reed, S Nicole

    2014-07-01

    Yoga practice is reported to lead to improvements in quality of life, psychological functioning, and symptom indices in cancer survivors. Importantly, meditative states experienced within yoga practice are correlated to neurophysiological systems that moderate both focus of attention and affective valence. The current study used a mixed methods approach based in neurophenomenology to investigate associations between attention, affect, and cardiac activity during a single yoga session for female cancer survivors. Yoga practice was associated with a linear increase in associative attention and positive affective valence, while shifts in cardiac activity were related to the intensity of each yoga sequence. Changes in attention and affect were predicted by concurrently assessed cardiac activity. Awareness of breathing, physical movement, and increased relaxation were reported by participants as potential mechanisms for yoga's salutary effects. While yoga practice shares commonalities with exercise and relaxation training, yoga may serve primarily as a promising meditative attention-affect regulation training methodology.

  10. Active noncontact tonometer for glaucoma detection

    NASA Astrophysics Data System (ADS)

    Han, Yanmei; Bryanston-Cross, Peter J.; Lee, Wing K. A.; Hero, Mark

    2002-09-01

    Glaucoma is an increasingly common cause of visual impairment, and in some cases causes blindness. The approach to develop a low cost and non-contact tonometer for the detection of glaucoma, to replace the Goldmann tonometer used worldwide, is presented in this paper. The new tonometer exploits the vibration property of the cornea - the resonance frequency of the cornea rises with increasing intra-ocular pressure (IOP). An audio frequency signal is used to vibrate the cornea of the eye, the vibration of the cornea is measured using a fibre optic lever probe, and then the IOP can be calculated from the detected resonance frequency of the cornea. The initial PC-version experiment system of the new tonometer has been demonstrated and preliminary testing has been performed, showing a suitable sensitivity in detecting the resonance frequency against the IOP using both the simulated-eye model and the pig's eye. The initial system has been improved to be suitable for greater than 15mm detecting distance, and the measurement of vibrations of human cornea in-vivo has been carried out. Work is now focusing on increasing the sensitivity of the fibre probe, and reducing the measuring time to less than 1 second.

  11. Effects of cardiac Myosin binding protein-C on actin motility are explained with a drag-activation-competition model.

    PubMed

    Walcott, Sam; Docken, Steffen; Harris, Samantha P

    2015-01-06

    Although mutations in cardiac myosin binding protein-C (cMyBP-C) cause heart disease, its role in muscle contraction is not well understood. A mechanism remains elusive partly because the protein can have multiple effects, such as dual biphasic activation and inhibition observed in actin motility assays. Here we develop a mathematical model for the interaction of cMyBP-C with the contractile proteins actin and myosin and the regulatory protein tropomyosin. We use this model to show that a drag-activation-competition mechanism accurately describes actin motility measurements, while models lacking either drag or competition do not. These results suggest that complex effects can arise simply from cMyBP-C binding to actin.

  12. Effects of Cardiac Myosin Binding Protein-C on Actin Motility Are Explained with a Drag-Activation-Competition Model

    PubMed Central

    Walcott, Sam; Docken, Steffen; Harris, Samantha P.

    2015-01-01

    Although mutations in cardiac myosin binding protein-C (cMyBP-C) cause heart disease, its role in muscle contraction is not well understood. A mechanism remains elusive partly because the protein can have multiple effects, such as dual biphasic activation and inhibition observed in actin motility assays. Here we develop a mathematical model for the interaction of cMyBP-C with the contractile proteins actin and myosin and the regulatory protein tropomyosin. We use this model to show that a drag-activation-competition mechanism accurately describes actin motility measurements, while models lacking either drag or competition do not. These results suggest that complex effects can arise simply from cMyBP-C binding to actin. PMID:25564844

  13. 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 Physiol 308: H894-H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (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 conventional C3 knockout (C3(-/-)) mice treated with CR was similar to that in the ad libitum-fed C3(-/-)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

  14. Co-Activation of Nuclear Factor-κB and Myocardin/Serum Response Factor Conveys the Hypertrophy Signal of High Insulin Levels in Cardiac Myoblasts*

    PubMed Central

    Madonna, Rosalinda; Geng, Yong-Jian; Bolli, Roberto; Rokosh, Gregg; Ferdinandy, Peter; Patterson, Cam; De Caterina, Raffaele

    2014-01-01

    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

  15. PKCepsilon activation augments cardiac mitochondrial respiratory post-anoxic reserve--a putative mechanism in PKCepsilon cardioprotection.

    PubMed

    McCarthy, Joy; McLeod, Christopher J; Minners, Jan; Essop, M Faadiel; Ping, Peipei; Sack, Michael N

    2005-04-01

    Modest cardiac-overexpression of constitutively active PKCepsilon (aPKCepsilon) in transgenic mice evokes cardioprotection against ischemia. As aPKCepsilon interacts with mitochondrial respiratory-chain proteins we hypothesized that aPKCepsilon modulates respiration to induce cardioprotection. Using isolated cardiac mitochondria wild-type and aPKCepsilon mice display similar basal mitochondrial respiration, rate of ATP synthesis and adenosine nucleotide translocase (ANT) functional content. Conversely, the aPKCepsilon mitochondria exhibit modest hyperpolarization of their inner mitochondrial membrane potential (DeltaPsi(m)) compared to wild-type mitochondrial by flow cytometry. To assess whether this hyperpolarization engenders resilience to simulated ischemia, anoxia-reoxygenation experiments were performed. Mitochondria were exposed to 45 min anoxia followed by reoxygenation. At reoxygenation, aPKCepsilon mitochondria recovered ADP-dependent respiration to 44 +/- 3% of baseline compared to 28 +/- 2% in WT controls (P = 0.03) in parallel with enhanced ATP synthesis. This preservation in oxidative phosphorylation is coupled to greater ANT functional content [42% > concentration of atractyloside for inhibition in the aPKCepsilon mitochondria vs. WT control (P < 0.0001)], retention of mitochondrial cytochrome c and conservation of DeltaPsi(m). These data demonstrate that mitochondria from PKCepsilon activated mice are intrinsically resilient to anoxia-reoxygenation compared to WT controls. This resilience is in part due to enhanced recovery of oxidative phosphorylation coupled to maintained ANT activity. As maintenance of ATP is a prerequisite for cellular viability we conclude that PKCepsilon activation augmented mitochondrial respiratory capacity in response to anoxia-reoxygenation may contribute to the PKCepsilon cardioprotective program.

  16. Evaluation of Pulsed Power Architectures for Active Detection

    DTIC Science & Technology

    2013-06-01

    strongest responses of the fissile material, prompt and delayed neutrons and delayed gammas . Based on a notional detection scenario, the...EVALUATION OF PULSED POWER ARCHITECTURES FOR ACTIVE DETECTION* I.D. Smith, P.A. Corcoran, R. Altes, D. Morton, R. Stevens and B. Whitney L-3...Abstract: Intense pulsed active detection (IPAD, [1]; also see presentations at this conference by B.V. Weber, et al., D.P Murphy et al

  17. Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank–Starling response

    PubMed Central

    Scotcher, Jenna; Prysyazhna, Oleksandra; Boguslavskyi, Andrii; Kistamas, Kornel; Hadgraft, Natasha; Martin, Eva D.; Worthington, Jenny; Rudyk, Olena; Rodriguez Cutillas, Pedro; Cuello, Friederike; Shattock, Michael J.; Marber, Michael S.; Conte, Maria R.; Greenstein, Adam; Greensmith, David J.; Venetucci, Luigi; Timms, John F.; Eaton, Philip

    2016-01-01

    The Frank–Starling mechanism allows the amount of blood entering the heart from the veins to be precisely matched with the amount pumped out to the arterial circulation. As the heart fills with blood during diastole, the myocardium is stretched and oxidants are produced. Here we show that protein kinase G Iα (PKGIα) is oxidant-activated during stretch and this form of the kinase selectively phosphorylates cardiac phospholamban Ser16—a site important for diastolic relaxation. We find that hearts of Cys42Ser PKGIα knock-in (KI) mice, which are resistant to PKGIα oxidation, have diastolic dysfunction and a diminished ability to couple ventricular filling with cardiac output on a beat-to-beat basis. Intracellular calcium dynamics of ventricular myocytes isolated from KI hearts are altered in a manner consistent with impaired relaxation and contractile function. We conclude that oxidation of PKGIα during myocardial stretch is crucial for diastolic relaxation and fine-tunes the Frank–Starling response. PMID:27782102

  18. Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response.

    PubMed

    Scotcher, Jenna; Prysyazhna, Oleksandra; Boguslavskyi, Andrii; Kistamas, Kornel; Hadgraft, Natasha; Martin, Eva D; Worthington, Jenny; Rudyk, Olena; Rodriguez Cutillas, Pedro; Cuello, Friederike; Shattock, Michael J; Marber, Michael S; Conte, Maria R; Greenstein, Adam; Greensmith, David J; Venetucci, Luigi; Timms, John F; Eaton, Philip

    2016-10-26

    The Frank-Starling mechanism allows the amount of blood entering the heart from the veins to be precisely matched with the amount pumped out to the arterial circulation. As the heart fills with blood during diastole, the myocardium is stretched and oxidants are produced. Here we show that protein kinase G Iα (PKGIα) is oxidant-activated during stretch and this form of the kinase selectively phosphorylates cardiac phospholamban Ser16-a site important for diastolic relaxation. We find that hearts of Cys42Ser PKGIα knock-in (KI) mice, which are resistant to PKGIα oxidation, have diastolic dysfunction and a diminished ability to couple ventricular filling with cardiac output on a beat-to-beat basis. Intracellular calcium dynamics of ventricular myocytes isolated from KI hearts are altered in a manner consistent with impaired relaxation and contractile function. We conclude that oxidation of PKGIα during myocardial stretch is crucial for diastolic relaxation and fine-tunes the Frank-Starling response.

  19. Identifying Model Inaccuracies and Solution Uncertainties in Non-Invasive Activation-Based Imaging of Cardiac Excitation using Convex Relaxation

    PubMed Central

    Erem, Burak; van Dam, Peter M.; Brooks, Dana H.

    2014-01-01

    Noninvasive imaging of cardiac electrical function has begun to move towards clinical adoption. Here we consider one common formulation of the problem, in which the goal is to estimate the spatial distribution of electrical activation times during a cardiac cycle. We address the challenge of understanding the robustness and uncertainty of solutions to this formulation. This formulation poses a non-convex, non-linear least squares optimization problem. We show that it can be relaxed to be convex, at the cost of some degree of physiological realism of the solution set, and that this relaxation can be used as a framework to study model inaccuracy and solution uncertainty. We present two examples, one using data from a healthy human subject and the other synthesized with the ECGSIM software package. In the first case, we consider uncertainty in the initial guess and regularization parameter. In the second case, we mimic the presence of an ischemic zone in the heart in a way which violates a model assumption. We show that the convex relaxation allows understanding of spatial distribution of parameter sensitivity in the first case, and identification of model violation in the second. PMID:24710159

  20. Persistent low thymic activity and non-cardiac mortality in children with chromosome 22q11.2 microdeletion and partial DiGeorge syndrome.

    PubMed

    Eberle, P; Berger, C; Junge, S; Dougoud, S; Büchel, E Valsangiacomo; Riegel, M; Schinzel, A; Seger, R; Güngör, T

    2009-02-01

    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 (T(REC))-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 T(RECs)/10(6) 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.

  1. 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.

  2. TNF, acting through inducibly expressed TNFR2, drives activation and cell cycle entry of c-Kit+ cardiac stem cells in ischemic heart disease.

    PubMed

    Al-Lamki, Rafia S; Lu, Wanhua; Wang, Jun; Yang, Jun; Sargeant, Timothy J; Wells, Richard; Suo, Chenqu; Wright, Penny; Goddard, Martin; Huang, Qunhua; Lebastchi, Amir H; Tellides, George; Huang, Yingqun; Min, Wang; Pober, Jordan S; Bradley, John R

    2013-09-01

    TNF, signaling through TNFR2, has been implicated in tissue repair, a process that in the heart may be mediated by activated resident cardiac stem cells (CSCs). The objective of our study is to determine whether ligation of TNFR2 can induce activation of resident CSCs in the setting of ischemic cardiac injury. We show that in human cardiac tissue affected by ischemia heart disease (IHD), TNFR2 is expressed on intrinsic CSCs, identified as c-kit(+)/CD45(-)/VEGFR2(-) interstitial round cells, which are activated as determined by entry to cell cycle and expression of Lin-28. Wild-type mouse heart organ cultures subjected to hypoxic conditions both increase cardiac TNF expression and show induced TNFR2 and Lin-28 expression in c-kit(+) CSCs that have entered cell cycle. These CSC responses are enhanced by exogenous TNF. TNFR2(-/-) mouse heart organ cultures subjected to hypoxia increase cardiac TNF but fail to induce CSC activation. Similarly, c-kit(+) CSCs isolated from mouse hearts exposed to hypoxia or TNF show induction of Lin-28, TNFR2, cell cycle entry, and cardiogenic marker, α-sarcomeric actin (α-SA), responses more pronounced by hypoxia in combination with TNF. Knockdown of Lin-28 by siRNA results in reduced levels of TNFR2 expression, cell cycle entry, and diminished expression of α-SA. We conclude that hypoxia-induced c-kit(+) CSC activation is mediated by TNF/TNFR2/Lin-28 signaling. These observations suggest that TNFR2 signaling in resident c-kit(+) CSCs induces cardiac repair, findings which provide further understanding of the unanticipated harmful effects of TNF blockade in human IHD.

  3. 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.

  4. 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.

  5. Activity of Cecropia lyratiloba extract on contractility of cardiac and smooth muscles in Wistar rats.

    PubMed

    Ramos Almeida, Roberta; Montani Raimundo, Juliana; Rodrigues Oliveira, Rodrigo; Coelho Kaplan, Maria Auxiliadora; Gattass, Cerli Rocah; Sudo, Roberto Takashi; Zapata-Sudo, Gisele

    2006-01-01

    1. Brazilian forests show high diversity of medicinal plants and several are used in folk medicine for the treatment of hypertension and asthma. The aim of the present study was to investigate the effects of a methanol extract (ME) of Cecropia lyratiloba and its flavonoid fraction (FF) on the contractility of cardiac, vascular and tracheal smooth muscles. 2. Twitches of rat papillary muscles were obtained with electrical stimulation and were recorded before and after exposure to increasing concentrations of ME and FF. 3. Cardiac depression was induced by FF. At 500 microg/mL FF, the amplitude of twitches was reduced to 56.7 +/- 5.1% of control values (P < 0.05). 4. The contractile response to a single concentration of adrenaline (10 micromol/L) was measured before and after exposure to ME and FF in rat aorta rings with intact endothelium. Both ME and FF inhibited adrenaline-induced contractions of the aorta in a concentration-dependent manner. Adrenaline-induced contractions were reduced to 46.4 +/- 9.9 and 34.2 +/- 6.9% (P < 0.05) of control in the presence of 500 microg/mL ME and FF, respectively. 5. The flavonoids isolated from FF, namely isoorientin and a mixture of orientin and isovitexin, were also tested in the aorta. These flavonoid do not seem to be responsible for the vasorelaxant effects of ME and FF. 6. No changes were observed in acetylcholine-precontracted trachea when exposed to ME or FF. 7. Endothelium-dependent vasodilation induced by FF is likely to be mediated by the release of nitric oxide because vascular relaxation was abolished in the presence of N(omega)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. 8. In conclusion, vascular relaxation induced by ME and FF could explain the traditional use of the extract of C. lyratiloba for treatment of arterial hypertension.

  6. SK4 Ca2+ activated K+ channel is a critical player in cardiac pacemaker derived from human embryonic stem cells

    PubMed Central

    Weisbrod, David; Peretz, Asher; Ziskind, Anna; Menaker, Nataly; Oz, Shimrit; Barad, Lili; Eliyahu, Sivan; Itskovitz-Eldor, Joseph; Dascal, Nathan; Khananshvili, Daniel; Binah, Ofer; Attali, Bernard

    2013-01-01

    Proper expression and function of the cardiac pacemaker is a critical feature of heart physiology. Two main mechanisms have been proposed: (i) the “voltage-clock,” where the hyperpolarization-activated funny current If causes diastolic depolarization that triggers action potential cycling; and (ii) the “Ca2+ clock,” where cyclical release of Ca2+ from Ca2+ stores depolarizes the membrane during diastole via activation of the Na+–Ca2+ exchanger. Nonetheless, these mechanisms remain controversial. Here, we used human embryonic stem cell-derived cardiomyocytes (hESC-CMs) to study their autonomous beating mechanisms. Combined current- and voltage-clamp recordings from the same cell showed the so-called “voltage and Ca2+ clock” pacemaker mechanisms to operate in a mutually exclusive fashion in different cell populations, but also to coexist in other cells. Blocking the “voltage or Ca2+ clock” produced a similar depolarization of the maximal diastolic potential (MDP) that culminated by cessation of action potentials, suggesting that they converge to a common pacemaker component. Using patch-clamp recording, real-time PCR, Western blotting, and immunocytochemistry, we identified a previously unrecognized Ca2+-activated intermediate K+ conductance (IKCa, KCa3.1, or SK4) in young and old stage-derived hESC-CMs. IKCa inhibition produced MDP depolarization and pacemaker suppression. By shaping the MDP driving force and exquisitely balancing inward currents during diastolic depolarization, IKCa appears to play a crucial role in human embryonic cardiac automaticity. PMID:23589888

  7. 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.

  8. Detection of cochlear amplification and its activation.

    PubMed

    Dong, Wei; Olson, Elizabeth S

    2013-08-20

    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.

  9. 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

  10. In Situ Time-Resolved FRET Reveals Effects of Sarcomere Length on Cardiac Thin-Filament Activation

    PubMed Central

    Li, King-Lun; Rieck, Daniel; Solaro, R. John; Dong, Wenji

    2014-01-01

    During cardiac thin-filament activation, the N-domain of cardiac troponin C (N-cTnC) binds to Ca2+ and interacts with the actomyosin inhibitory troponin I (cTnI). The interaction between N-cTnC and cTnI stabilizes the Ca2+-induced opening of N-cTnC and is presumed to also destabilize cTnI–actin interactions that work together with steric effects of tropomyosin to inhibit force generation. Recently, our in situ steady-state FRET measurements based on N-cTnC opening suggested that at long sarcomere length, strongly bound cross-bridges indirectly stabilize this Ca2+-sensitizing N-cTnC–cTnI interaction through structural effects on tropomyosin and cTnI. However, the method previously used was unable to determine whether N-cTnC opening depends on sarcomere length. In this study, we used time-resolved FRET to monitor the effects of cross-bridge state and sarcomere length on the Ca2+-dependent conformational behavior of N-cTnC in skinned cardiac muscle fibers. FRET donor (AEDANS) and acceptor (DDPM)-labeled double-cysteine mutant cTnC(T13C/N51C)AEDANS-DDPM was incorporated into skinned muscle fibers to monitor N-cTnC opening. To study the structural effects of sarcomere length on N-cTnC, we monitored N-cTnC opening at relaxing and saturating levels of Ca2+ and 1.80 and 2.2-μm sarcomere length. Mg2+-ADP and orthovanadate were used to examine the structural effects of noncycling strong-binding and weak-binding cross-bridges, respectively. We found that the stabilizing effect of strongly bound cross-bridges on N-cTnC opening (which we interpret as transmitted through related changes in cTnI and tropomyosin) become diminished by decreases in sarcomere length. Additionally, orthovanadate blunted the effect of sarcomere length on N-cTnC conformational behavior such that weak-binding cross-bridges had no effect on N-cTnC opening at any tested [Ca2+] or sarcomere length. Based on our findings, we conclude that the observed sarcomere length-dependent positive feedback

  11. In situ time-resolved FRET reveals effects of sarcomere length on cardiac thin-filament activation.

    PubMed

    Li, King-Lun; Rieck, Daniel; Solaro, R John; Dong, Wenji

    2014-08-05

    During cardiac thin-filament activation, the N-domain of cardiac troponin C (N-cTnC) binds to Ca(2+) and interacts with the actomyosin inhibitory troponin I (cTnI). The interaction between N-cTnC and cTnI stabilizes the Ca(2+)-induced opening of N-cTnC and is presumed to also destabilize cTnI-actin interactions that work together with steric effects of tropomyosin to inhibit force generation. Recently, our in situ steady-state FRET measurements based on N-cTnC opening suggested that at long sarcomere length, strongly bound cross-bridges indirectly stabilize this Ca(2+)-sensitizing N-cTnC-cTnI interaction through structural effects on tropomyosin and cTnI. However, the method previously used was unable to determine whether N-cTnC opening depends on sarcomere length. In this study, we used time-resolved FRET to monitor the effects of cross-bridge state and sarcomere length on the Ca(2+)-dependent conformational behavior of N-cTnC in skinned cardiac muscle fibers. FRET donor (AEDANS) and acceptor (DDPM)-labeled double-cysteine mutant cTnC(T13C/N51C)AEDANS-DDPM was incorporated into skinned muscle fibers to monitor N-cTnC opening. To study the structural effects of sarcomere length on N-cTnC, we monitored N-cTnC opening at relaxing and saturating levels of Ca(2+) and 1.80 and 2.2-μm sarcomere length. Mg(2+)-ADP and orthovanadate were used to examine the structural effects of noncycling strong-binding and weak-binding cross-bridges, respectively. We found that the stabilizing effect of strongly bound cross-bridges on N-cTnC opening (which we interpret as transmitted through related changes in cTnI and tropomyosin) become diminished by decreases in sarcomere length. Additionally, orthovanadate blunted the effect of sarcomere length on N-cTnC conformational behavior such that weak-binding cross-bridges had no effect on N-cTnC opening at any tested [Ca(2+)] or sarcomere length. Based on our findings, we conclude that the observed sarcomere length-dependent positive

  12. AOP-1 interacts with cardiac-specific protein kinase TNNI3K and down-regulates its kinase activity.

    PubMed

    Feng, Yan; Liu, Dong-Qing; Wang, Zhen; Liu, Zhao; Cao, Hui-Qing; Wang, Lai-Yuan; Shi, Na; Meng, Xian-Min

    2007-11-01

    In the present study, a yeast two-hybrid screening system was used to identify the interaction partners of cardiac troponin I-interacting kinase (TNNI3K) that might serve as regulators or targets, and thus in turn to gain some insights on the roles of TNNI3K. After screening the adult heart cDNA library with a bait construct encoding the ANK motif of TNNI3K, antioxidant protein 1 (AOP-1) was isolated. The interaction between TNNI3K and AOP-1 was confirmed by the in vitro binding assay and coexpression experiments in vivo. The colocalization of TNNI3K and AOP-1 was clarified by confocal immunofluorescence. Moreover, coexpression of AOP-1 inhibited TNNI3K kinase activity in the in vitro kinase assay.

  13. Cardiac Sarcoidosis.

    PubMed

    Birnie, David; Ha, Andrew C T; Gula, Lorne J; Chakrabarti, Santabhanu; Beanlands, Rob S B; Nery, Pablo

    2015-12-01

    Studies suggest clinically manifest cardiac involvement occurs in 5% of patients with pulmonary/systemic sarcoidosis. The principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. Data indicate that an 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic (clinically silent) cardiac involvement. An international guideline for the diagnosis and management of CS recommends that patients be screened for cardiac involvement. Most studies suggest a benign prognosis for patients with clinically silent CS. Immunosuppression therapy is advocated for clinically manifest CS. Device therapy, with implantable cardioverter defibrillators, is recommended for some patients.

  14. 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

  15. Lower arm electromyography (EMG) activity detection using local binary patterns.

    PubMed

    McCool, Paul; Chatlani, Navin; Petropoulakis, Lykourgos; Soraghan, John J; Menon, Radhika; Lakany, Heba

    2014-09-01

    This paper presents a new electromyography activity detection technique in which 1-D local binary pattern histograms are used to distinguish between periods of activity and inactivity in myoelectric signals. The algorithm is tested on forearm surface myoelectric signals occurring due to hand gestures. The novel features of the presented method are that: 1) activity detection is performed across multiple channels using few parameters and without the need for majority vote mechanisms, 2) there are no per-channel thresholds to be tuned, which makes the process of activity detection easier and simpler to implement and less prone to errors, 3) it is not necessary to measure the properties of the signal during a quiescent period before using the algorithm. The algorithm is compared to other offline single- and double-threshold activity detection methods and, for the data sets tested, it is shown to have a better overall performance with greater tolerance to the noise in the real data set used.

  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. Optimal Placement of Accelerometers for the Detection of Everyday Activities

    PubMed Central

    Cleland, Ian; Kikhia, Basel; Nugent, Chris; Boytsov, Andrey; Hallberg, Josef; Synnes, Kåre; McClean, Sally; Finlay, Dewar

    2013-01-01

    This article describes an investigation to determine the optimal placement of accelerometers for the purpose of detecting a range of everyday activities. The paper investigates the effect of combining data from accelerometers placed at various bodily locations on the accuracy of activity detection. Eight healthy males participated within the study. Data were collected from six wireless tri-axial accelerometers placed at the chest, wrist, lower back, hip, thigh and foot. Activities included walking, running on a motorized treadmill, sitting, lying, standing and walking up and down stairs. The Support Vector Machine provided the most accurate detection of activities of all the machine learning algorithms investigated. Although data from all locations provided similar levels of accuracy, the hip was the best single location to record data for activity detection using a Support Vector Machine, providing small but significantly better accuracy than the other investigated locations. Increasing the number of sensing locations from one to two or more statistically increased the accuracy of classification. There was no significant difference in accuracy when using two or more sensors. It was noted, however, that the difference in activity detection using single or multiple accelerometers may be more pronounced when trying to detect finer grain activities. Future work shall therefore investigate the effects of accelerometer placement on a larger range of these activities. PMID:23867744

  18. Influence of increased adrenergic activity and magnesium depletion on cardiac rhythm in alcohol withdrawal.

    PubMed Central

    Denison, H; Jern, S; Jagenburg, R; Wendestam, C; Wallerstedt, S

    1994-01-01

    OBJECTIVE--To investigate the prevalence of arrhythmias in alcoholic men during detoxification and its relation to neuroendocrine activation and electrolyte disturbances. DESIGN--Consecutive case-control study. SETTING--Primary and secondary care, detoxification ward. PATIENTS AND CONTROLS--19 otherwise healthy alcoholic men (DSM-III-R) with withdrawal symptoms necessitating detoxification in hospital. 19 age matched, healthy non-alcoholic men as controls for Holter recordings. INTERVENTIONS--Treatment with chlomethiazole; additional treatment with carbamazepine in patients with previous seizures. MAIN OUTCOME MEASURES--Computer based analyses of mean heart rate and arrhythmias from 24 hour Holter recordings, 24 hour urinary excretion of adrenaline and noradrenaline, magnesium retention measured by means of intravenous loading test, and serum concentrations of electrolytes. RESULTS--The 24 hour mean heart rate was higher in the alcoholic men (97.4 beats/minute, 95% confidence interval (CI) 91.2 to 103.6) than in the controls (69.6 beats/minute, 95% CI 65.4 to 73.8, P < 0.001). However, there was no difference in diurnal heart rate variation. The prevalence of premature supraventricular depolarisations was lower in the alcoholic men (P < 0.05). Neither atrial fibrillation nor malignant ventricular arrhythmias occurred. The sinus tachycardia in the alcoholic men correlated with the concomitant urinary excretion of catecholamines (P < 0.05). The mean serum magnesium concentration was 0.78 mmol/l (95% CI 0.73 to 0.83) in the alcoholic men and 0.83 mmol/l (95% CI 0.81 to 0.85) in a reference population of 55 men aged 40. Magnesium depletion (defined as magnesium retention > 30%) was detected in 10 alcoholic men (53%). Three alcoholic men had serum potassium concentrations < or = 3.3 mmol/l on admission. CONCLUSION--Increased adrenergic activity, magnesium depletion, and hypokalaemia are often seen after heavy drinking, but in alcoholic men without clinical heart disease

  19. Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals.

    PubMed

    Matsukawa, Kanji

    2012-01-01

    Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

  20. Inter-individual variability and modeling of electrical activity: a possible new approach to explore cardiac safety?

    PubMed Central

    Le Guennec, Jean-Yves; Thireau, Jérôme; Ouillé, Aude; Roussel, Julien; Roy, Jérôme; Richard, Serge; Richard, Sylvain; Martel, Eric; Champéroux, Pascal

    2016-01-01

    Safety pharmacology aims to predict rare side effects of new drugs. We explored whether rare pro-arrhythmic effects could be linked to the variability of the effects of these drugs on ion currents and whether taking into consideration this variability in computational models could help to better detect and predict cardiac side effects. For this purpose, we evaluated how intra- and inter-individual variability influences the effect of hERG inhibition on both the action potential duration and the occurrence of arrhythmias. Using two computer simulation models of human action potentials (endocardial and Purkinje cells), we analyzed the contribution of two biological parameters on the pro-arrhythmic effects of several hERG channel blockers: (i) spermine concentration, which varies with metabolic status, and (ii) L-type calcium conductance, which varies due to single nucleotide polymorphisms or mutations. By varying these parameters, we were able to induce arrhythmias in 1 out of 16 simulations although conventional modeling methods to detect pro-arrhythmic molecules failed. On the basis of our results, taking into consideration only 2 parameters subjected to intra- and inter-individual variability, we propose that in silico computer modeling may help to better define the risks of new drug candidates at early stages of pre-clinical development. PMID:27901061

  1. Almanac 2013: cardiac arrhythmias and pacing.

    PubMed

    Liew, Reginald

    2013-10-01

    Important advances have been made in the past few years in the fields of clinical cardiac electrophysiology and pacing. Researchers and clinicians have a greater understanding of the pathophysiological mechanisms underlying atrial fibrillation (AF), which has transpired into improved methods of detection, risk stratification, and treatments. The introduction of novel oral anticoagulants has provided clinicians with alternative options in managing patients with AF at moderate to high thromboembolic risk and further data has been emerging on the use of catheter ablation for the treatment of symptomatic AF. Another area of intense research in the field of cardiac arrhythmias and pacing is in the use of cardiac resynchronisation therapy (CRT) for the treatment of patients with heart failure. Following the publication of major landmark randomised controlled trials reporting that CRT confers a survival advantage in patients with severe heart failure and improves symptoms, many subsequent studies have been performed to further refine the selection of patients for CRT and determine the clinical characteristics associated with a favourable response. The field of sudden cardiac death and implantable cardioverter defibrillators also continues to be actively researched, with important new epidemiological and clinical data emerging on improved methods for patient selection, risk stratification, and management. This review covers the major recent advances in these areas related to cardiac arrhythmias and pacing.

  2. Activity and Life After Survival of a Cardiac Arrest (ALASCA) and the effectiveness of an early intervention service: design of a randomised controlled trial

    PubMed Central

    Moulaert, Véronique RMP; Verbunt, Jeanine A; van Heugten, Caroline M; Bakx, Wilbert GM; Gorgels, Anton PM; Bekkers, Sebastiaan CAM; de Krom, Marc CFTM; Wade, Derick T

    2007-01-01

    Background Cardiac arrest survivors may experience hypoxic brain injury that results in cognitive impairments which frequently remain unrecognised. This may lead to limitations in daily activities and participation in society, a decreased quality of life for the patient, and a high strain for the caregiver. Publications about interventions directed at improving quality of life after survival of a cardiac arrest are scarce. Therefore, evidence about effective rehabilitation programmes for cardiac arrest survivors is urgently needed. This paper presents the design of the ALASCA (Activity and Life After Survival of a Cardiac Arrest) trial, a randomised, controlled clinical trial to evaluate the effects of a new early intervention service for survivors of a cardiac arrest and their caregivers. Methods/design The study population comprises all people who survive two weeks after a cardiac arrest and are admitted to one of the participating hospitals in the Southern part of the Netherlands. In a two-group randomised, controlled clinical trial, half of the participants will receive an early intervention service. The early intervention service consists of several consultations with a specialised nurse for the patient and their caregiver during the first three months after the cardiac arrest. The intervention is directed at screening for cognitive problems, provision of informational, emotional and practical support, and stimulating self-management. If necessary, referral to specialised care can take place. Persons in the control group will receive the care as usual. The primary outcome measures are the extent of participation in society and quality of life of the patient one year after a cardiac arrest. Secondary outcome measures are the level of cognitive, emotional and cardiovascular impairment and daily functioning of the patient, as well as the strain for and quality of life of the caregiver. Participants and their caregivers will be followed for twelve months after the

  3. Dependent component analysis for the magnetogastrographic detection of human electrical response activity.

    PubMed

    Estombelo-Montesco, C A; de Araujo, D B; Silva Filho, A C R; Moraes, E R; Barros, A K; Wakai, R T; Baffa, O

    2007-09-01

    The detection of the basic electric rhythm (BER), composed of a 3 cycles min(-1) oscillation, can be performed using SQUID magnetometers. However, the electric response activity (ERA), which is generated when the stomach is performing a mechanical activity, was detected mainly by invasive electrical measurements and only recently was one report published describing its detection by magnetic measurements. This study was performed with the aim of detecting the ERA noninvasively after a meal. MGG recordings were made with a 74-channel first-order gradiometer (Magnes II, biomagnetic technologies) housed in a shielded room. Seven nonsymptomatic volunteers were measured in the study. Initially a 10 min recording was performed with the subject in the fasted state. A 250 kcal meal was given to the subject without moving out of the magnetometers and two epochs of 10 min each were acquired. The signals were processed to remove cardiac interference by an algorithm based on a variation of independent component analysis (ICA), then autoregressive and wavelet analysis was performed. Preliminary results have shown that there is an increase in the signal power at higher frequencies around (0.6 Hz-1.3 Hz) usually associated with the basic electric rhythm. The center of the frequency band and its width varied from subject to subject, demonstrating the importance of pre-prandial acquisition as a control. Another interesting finding was an increase in power after about 5 min of meal ingestion. This period roughly agrees with the lag phase of gastric emptying, measured by scintigraphy and other techniques. We confirm that MGG can detect the electric response activity in normal volunteers. Further improvements in signal processing and standardization of signal acquisition are necessary to ascertain its possible use in clinical situations.

  4. Dependence of deoxycorticosterone/salt hypertension in the rat on the activity of adrenergic cardiac nerves.

    PubMed

    Bell, C; McLachlan, E M

    1979-08-01

    1. Chronic hypertension was induced in Wistar rats with intact kidneys by subcutaneous implantation of 50 mg of deoxycorticosterone acetate (DOCA) in wax and addition of sodium chloride (9 g/l) to the drinking water. 2. The development of DOCA/salt hypertension, as monitored by tail-cuff plethysmography, was prevented by: (a) destruction of the peripheral adrenergic nerves with neonatal administration of guanethidine (80 mg/kg subcutaneously for the first 14 days postnatally); (b) bilateral stellate ganglionectomy; (c) oral administration of the beta-adrenoreceptor antagonists propranolol or atenolol (1 mg day-1 kg-1) during the period of DOCA/salt treatment. 3. The dose of DOCA used was sufficient to inhibit the atrial Uptake2 pathway completely: this process appears to participate in termination of action of neurally released noradrenaline in the heart. 4. It is suggested that this model of DOCA/salt hypertension is due to adrenergic enhancement of cardiac output in the presence of an increased sodium load. The enhancement may be partly due to deficient myocardial inactivation of noradrenaline.

  5. Central command does not suppress baroreflex control of cardiac sympathetic nerve activity at the onset of spontaneous motor activity in the decerebrate cat.

    PubMed

    Matsukawa, Kanji; Ishii, Kei; Asahara, Ryota; Idesako, Mitsuhiro

    2016-10-01

    Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in animals. We have examined whether baroreflex control of cardiac sympathetic nerve activity (CSNA) and/or cardiovagal baroreflex sensitivity are altered at the onset of spontaneously occurring motor behavior, which was monitored with tibial nerve activity in paralyzed, decerebrate cats. CSNA exhibited a peak increase (126 ± 17%) immediately after exercise onset, followed by increases in HR and mean arterial pressure (MAP). With development of the pressor response, CSNA and HR decreased near baseline, although spontaneous motor activity was not terminated. Atropine methyl nitrate (0.1-0.2 mg/kg iv) with little central influence delayed the initial increase in HR but did not alter the response magnitudes of HR and CSNA, while atropine augmented the pressor response. The baroreflex-induced decreases in CSNA and HR elicited by brief occlusion of the abdominal aorta were challenged at the onset of spontaneous motor activity. Spontaneous motor activity blunted the baroreflex reduction in HR by aortic occlusion but did not alter the baroreflex inhibition of CSNA. Similarly, atropine abolished the baroreflex reduction in HR but did not influence the baroreflex inhibition of CSNA. Thus it is likely that central command increases CSNA and decreases cardiac vagal outflow at the onset of spontaneous motor activity while preserving baroreflex control of CSNA. Accordingly, central command must attenuate cardiovagal baroreflex sensitivity against an excess rise in MAP as estimated from the effect of muscarinic blockade.

  6. Cardiac Cytochrome c Oxidase Activity and Contents of Submits 1 and 4 are Altered in Offspring by Low Prenatal Intake by Rat Dams

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been reported previously that the offspring of rat dams consuming low dietary copper (Cu) during pregnancy and lactation experience a deficiency in cardiac cytochrome c oxidase (CCO) characterized by reduced catalytic activity and mitochondrial- and nuclear-subunit content after postnatal day...

  7. Cardiac cytochrome C oxidase activity and contents of subunits 1 and 4 are altered in offspring by low prenatal copper intake by rat dams.

    PubMed

    Johnson, W Thomas; Anderson, Cindy M

    2008-07-01

    It has been reported previously that the offspring of rat dams consuming low dietary copper (Cu) during pregnancy and lactation experience a deficiency in cardiac cytochrome c oxidase (CCO) characterized by reduced catalytic activity and mitochondrial and nuclear subunit content after postnatal d 10. The present study was undertaken to determine whether the cardiac CCO deficiency was caused directly by low postnatal Cu intake or whether it was a prenatal effect of low Cu intake by the dams that became manifest postnatally. Dams were fed either a Cu-adequate diet (6 mg Cu/kg) or Cu-deficient diet (1 mg Cu/kg) beginning 3 wk before conception and throughout gestation and lactation. One day following parturition, several litters from Cu-adequate dams were cross fostered to Cu-deficient dams and several litters from Cu-deficient dams were cross fostered to Cu-adequate dams. Litters that remained with their birth dams served as controls. CCO activity, the content of the mitochondrial-encoded CCO subunit 1 (COX1), and the content of the nuclear-encoded subunit COX4 in cardiac mitochondria were reduced in the 21-d-old offspring of Cu-deficient dams. COX1 content was normal in the 21-d-old cross-fostered offspring of Cu-deficient dams, but CCO activity and COX4 were reduced. Cross fostering the offspring of Cu-adequate dams to Cu-deficient dams did not significantly affect CCO activity, COX1 content, or COX4 content in cardiac mitochondria of 21-d-old offspring. These data indicate that low prenatal Cu intake by dams was the determinant of CCO activity in cardiac mitochondria of the 21-d-old offspring and may have led to the assembly of a less-than-fully active holoenzyme.

  8. Rapid Automated Treatment Planning Process to Select Breast Cancer Patients for Active Breathing Control to Achieve Cardiac Dose Reduction

    SciTech Connect

    Wang Wei; Purdie, Thomas G.; Rahman, Mohammad; Marshall, Andrea; Liu Feifei; Fyles, Anthony

    2012-01-01

    Purpose: To evaluate a rapid automated treatment planning process for the selection of patients with left-sided breast cancer for a moderate deep inspiration breath-hold (mDIBH) technique using active breathing control (ABC); and to determine the dose reduction to the left anterior descending coronary artery (LAD) and the heart using mDIBH. Method and Materials: Treatment plans were generated using an automated method for patients undergoing left-sided breast radiotherapy (n = 53) with two-field tangential intensity-modulated radiotherapy. All patients with unfavorable cardiac anatomy, defined as having >10 cm{sup 3} of the heart receiving 50% of the prescribed dose (V{sub 50}) on the free-breathing automated treatment plan, underwent repeat scanning on a protocol using a mDIBH technique and ABC. The doses to the LAD and heart were compared between the free-breathing and mDIBH plans. Results: The automated planning process required approximately 9 min to generate a breast intensity-modulated radiotherapy plan. Using the dose-volume criteria, 20 of the 53 patients were selected for ABC. Significant differences were found between the free-breathing and mDIBH plans for the heart V{sub 50} (29.9 vs. 3.7 cm{sup 3}), mean heart dose (317 vs. 132 cGy), mean LAD dose (2,047 vs. 594 cGy), and maximal dose to 0.2 cm{sup 3} of the LAD (4,155 vs. 1,507 cGy, all p <.001). Of the 17 patients who had a breath-hold threshold of {>=}0.8 L, 14 achieved a {>=}90% reduction in the heart V{sub 50} using the mDIBH technique. The 3 patients who had had a breath-hold threshold <0.8 L achieved a lower, but still significant, reduction in the heart V{sub 50}. Conclusions: A rapid automated treatment planning process can be used to select patients who will benefit most from mDIBH. For selected patients with unfavorable cardiac anatomy, the mDIBH technique using ABC can significantly reduce the dose to the LAD and heart, potentially reducing the cardiac risks.

  9. Small Molecule AKAP-Protein Kinase A (PKA) Interaction Disruptors That Activate PKA Interfere with Compartmentalized cAMP Signaling in Cardiac Myocytes*

    PubMed Central

    Christian, Frank; Szaszák, Márta; Friedl, Sabine; Drewianka, Stephan; Lorenz, Dorothea; Goncalves, Andrey; Furkert, Jens; Vargas, Carolyn; Schmieder, Peter; Götz, Frank; Zühlke, Kerstin; Moutty, Marie; Göttert, Hendrikje; Joshi, Mangesh; Reif, Bernd; Haase, Hannelore; Morano, Ingo; Grossmann, Solveig; Klukovits, Anna; Verli, Judit; Gáspár, Róbert; Noack, Claudia; Bergmann, Martin; Kass, Robert; Hampel, Kornelia; Kashin, Dmitry; Genieser, Hans-Gottfried; Herberg, Friedrich W.; Willoughby, Debbie; Cooper, Dermot M. F.; Baillie, George S.; Houslay, Miles D.; von Kries, Jens Peter; Zimmermann, Bastian; Rosenthal, Walter; Klussmann, Enno

    2011-01-01

    A-kinase anchoring proteins (AKAPs) tether protein kinase A (PKA) and other signaling proteins to defined intracellular sites, thereby establishing compartmentalized cAMP signaling. AKAP-PKA interactions play key roles in various cellular processes, including the regulation of cardiac myocyte contractility. We discovered small molecules, 3,3′-diamino-4,4′-dihydroxydiphenylmethane (FMP-API-1) and its derivatives, which inhibit AKAP-PKA interactions in vitro and in cultured cardiac myocytes. The molecules bind to an allosteric site of regulatory subunits of PKA identifying a hitherto unrecognized region that controls AKAP-PKA interactions. FMP-API-1 a