Science.gov

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. A prospective, multicenter study of cardiac-based seizure detection to activate vagus nerve stimulation.

    PubMed

    Boon, Paul; Vonck, Kristl; van Rijckevorsel, Kenou; El Tahry, Riem; Elger, Christian E; Mullatti, Nandini; Schulze-Bonhage, Andreas; Wagner, Louis; Diehl, Beate; Hamer, Hajo; Reuber, Markus; Kostov, Hrisimir; Legros, Benjamin; Noachtar, Soheyl; Weber, Yvonne G; Coenen, Volker A; Rooijakkers, Herbert; Schijns, Olaf E M G; Selway, Richard; Van Roost, Dirk; Eggleston, Katherine S; Van Grunderbeek, Wim; Jayewardene, Amara K; McGuire, Ryan M

    2015-11-01

    This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623). Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS. Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials. The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. 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

  7. Automatic basal slice detection for cardiac analysis

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  8. [Muscarinic modulation of cardiac activity].

    PubMed

    Sauviat, M P

    1999-01-01

    The goal of the present review is to report information concerning cardiac innervation or more precisely to approach the modulation of cardiac electrical and mechanical activity by parasympathetic innervation. Acetylcholine (ACh) release by nerve endings from the vagus nerve hyperpolarizes the membrane, shortens action potential (AP) duration and has a negative inotropic effect on cardiac muscle. Toxins are usefull tools in the study of membrane signals. The Caribbean ciguatoxin (C-CTX-1) has a muscarinic effect on frog atrial fibres. The toxin evokes the release of ACh from motoneuron nerve terminals innervating this tissue which allows us to propose a model, similar to the one of the neuromuscular junction (nmj), to describe the events occurring during the triggering and release of ACh. Trachynilysin (TLY) is a proteic toxin which causes an influx of Ca2+ into the cells and releases ACh from nmj synaptic vesicles. TLY has a muscarinic effect on atrial fibres which is explicated in the release of neurotransmitter from the nerve endings generated by the TLY-induced Ca2+ influx. It is known that ACh release from nmj is known to be due to exocytosis of synaptic vesicles via the activation of a proteic complex blocked by botulinum toxins. One of these proteins SNAP-25 is the target of type A botulinum toxin (BoNT/A). The study of hearts isolated from BoNT/A poisoned frogs show that atrial AP is lengthened and reveals the presence of SNAP-25 in nerve endings of this tissue. Moreover, the electrical activity of ventricular muscle is markedly altered; in BoNT/A treated frog, an important outward current activated by internal Ca2+ develops. ACh released from nerve terminals binds to a G protein coupled membrane receptor and activates a K+ channel and other effectors. Five subtypes of muscarinic receptors have been cloned from different tissue (M1, M2, M3, M4) subtypes have been identified in cardiac tissues throughout many species. These receptors coupled with different G

  9. Remote continuous cardiac arrhythmias detection and monitoring.

    PubMed

    Zhou, Haiying; Hou, Kun Mean; Ponsonnaille, Jean; Gineste, Laurent; Coudon, Julien; de Sousa, Gil; de Vaulx, Christophe; Li, Jian-Jin; Chainais, Pierre; Aufrère, Romuald; Amamra, Abdelaziz; Chanet, Jean-Pierre

    2004-01-01

    The current techniques used to diagnose cardiac arrhythmias such as Holter, Rtest and telemetry systems are partially efficient because they are limited either in time or in space. In this paper, a platform dedicated to the real-time remote continuous cardiac arrhythmias detection and monitoring is proposed. Such a platform allows to improve the accuracy and the efficiency of the diagnostic of ventricular tachycardia among the high-risk patients and enables the implantation of ICD to prevent sudden death. The new method allows the patient to lead a normal life while being remotely monitored in real-time by an ambulatory wireless ECG sensor. When a cardiac arrhythmia is detected a message including a sequence of ECG signals and the patient's images (indoors only) is sent to a remote surveillance server. According to the gravity of the symptom, the cardiologist can intervene in real time or later. The system has been evaluated on some ten patients with regard to heartbeat and cardiac rhythm disturbance. The real-time results are similar to those offered by HP telemetry systems.

  10. 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

  11. 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.

  12. Cardiac phase detection in intravascular ultrasound images

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

  13. Noninvasive ambulatory measurement system of cardiac activity.

    PubMed

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  15. 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.

  16. 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.

  17. Cardiac computed tomographic angiography for detection of cardiac sources of embolism in stroke patients.

    PubMed

    Hur, Jin; Kim, Young Jin; Lee, Hye-Jeong; Ha, Jong-Won; Heo, Ji Hoe; Choi, Eui-Young; Shim, Chi-Young; Kim, Tae Hoon; Nam, Ji Eun; Choe, Kyu Ok; Choi, Byoung Wook

    2009-06-01

    We assessed the diagnostic performance of 2-phase 64-slice cardiac computed tomographic angiography (CCTA) for the detection of a cardiac source of embolism in stroke patients using transesophageal echocardiography (TEE) as the reference standard. We selected 137 patients who had experienced a recent episode of stroke and had undergone both 2-phase 64-slice CCTA and TEE within a period of 5 days. A potential cardiac source of embolism detected at both CCTA and TEE was recorded, and echocardiographic findings were categorized into high- and medium-risk sources based on the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Of 137 patients, 100 abnormal findings in 91 patients were found on TEE, and 46 patients had no abnormal finding on TEE. The overall sensitivity, specificity, positive predictive value, and negative predictive value of the 64-slice CCTA for detecting cardiac sources of embolism were 89% (95% CI, 82%, 95%), 100% (95% CI, 90%, 100%), 100% (95% CI, 95%, 100%), and 81% (95% CI, 70%, 92%), respectively. TEE detected a total of 47 high-risk sources of embolism, whereas CT detected 44 lesions. For medium-risk sources of cardiac embolic stroke, TEE detected a total of 53 abnormal findings, whereas CT detected 44 abnormal findings. Of 53 lesions, there were 8 false-negative results on CT (5 patent foramen ovale and 3 atrial septal aneurysm). Two-phase 64-slice CCTA is a noninvasive and useful modality for detecting high-risk cardiac sources of embolism in stroke patients.

  18. 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.

  19. Detection of cardiac variability in the isolated rat heart.

    PubMed

    Schumacher, Autumn M; Zbilut, Joseph P; Webber, Charles L; Schwertz, Dorie W; Piano, Mariann R

    2006-07-01

    Cardiac variability can be assessed from two perspectives: beat-to-beat performance and continuous performance during the cardiac cycle. Linear analysis techniques assess cardiac variability by measuring the physical attributes of a signal, whereas nonlinear techniques evaluate signal dynamics. This study sought to determine if recurrence quantification analysis (RQA), a nonlinear technique, could detect pharmacologically induced autonomic changes in the continuous left ventricular pressure (LVP) and electrographic (EC) signals from an isolated rat heart-a model that theoretically contains no inherent variability. LVP and EC signal data were acquired simultaneously during Langendorff perfusion of isolated rat hearts before and after the addition of acetylcholine (n = 11), norepinephrine (n = 12), or no drug (n = 12). Two-minute segments of the continuous LVP and EC signal data were analyzed by RQA. Findings showed that%recurrence,%determinism, entropy, maxline, and trend from the continuous LVP signal significantly increased in the presence of both acetylcholine and norepinephrine, although systolic LVP significantly increased only with norepinephrine. In the continuous EC signal, the RQA trend variable significantly increased in the presence of norepinephrine. These results suggest that when either the sympathetic or parasympathetic division of the autonomic nervous system overwhelms the other, the dynamics underlying cardiac variability become stationary. This study also shows that information concerning inherent variability in the isolated rat heart can be gained via RQA of the continuous cardiac signal. Although speculative, RQA may be a tool for detecting alterations in cardiac variability and evaluating signal dynamics as a nonlinear indicator of cardiac pathology.

  20. The iDigoxin Assay is More Sensitive than LOCI Digoxin Assay for Rapid Detection of Convallatoxin, the Active Cardiac Glycoside of Lily of The Valley.

    PubMed

    Everett, Jamie M; Kojima, Yumi A; Davis, Barbara; Wahed, Amer; Dasgupta, Amitava

    2015-01-01

    Lily of the valley is a poisonous plant due to the presence of the cardiac glycoside convallatoxin. We compared two immunoassays (LOCI digoxin assay and iDigoxin assay) for rapid detection of convallatoxin if present in human serum. Aliquots of a drug free serum pool and a digoxin serum pool were supplemented with microliter amounts of lily of the valley extract or nanogram to microgram quantities of convallatoxin, followed by measurement of apparent digoxin concentrations using the LOCI and iDigxoin assays. Apparent digoxin concentrations were observed when aliquots of a drug free serum pool were supplemented with convallatoxin or lily of the valley extract using both assays but apparent digoxin concentrations were significantly higher using the iDigoxin assay. In addition, the interference of convallatoxin in serum digoxin measurement was also significantly higher using iDigxoin assay compared to the LOCI digoxin assay. The iDigxoin assay is more sensitive in detecting convallatoxin in human serum. © 2015 by the Association of Clinical Scientists, Inc.

  1. 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

  2. [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.

  3. 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.

  4. 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)

  5. 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.

  6. How active are young cardiac device patients? Objective assessment of activity in children with cardiac devices.

    PubMed

    de la Uz, Caridad M; Burch, Ashley E; Gunderson, Bruce; Koehler, Jodi; Sears, Samuel F

    2017-09-12

    The daily activity of pediatric patients with implantable cardiac devices provides behavioral evidence of functional outcomes. Modern devices provide continuous accelerometer data that is sensitive to movement, but normative values have not been published for pediatric activity rates. This study provides the first normative accelerometer data on activity rates in a large sample of pediatric cardiac device patients. Patients were between 3 and 18 years old, (N = 1,905) and implanted with a cardiac device from a single device company, and enrolled in remote monitoring. The median age at implant was 14 years (IQR = 12-16); 61.3% were male. Data for 4 weeks was extracted from a company database at 53 weeks post-implant and an average of daily activity was calculated. Daily average activity for all patients was 5.4 hours (SD = 2.0). In a multivariate analysis, increased level of activity was associated with: being male, having a pacemaker vs implantable cardioverter defibrillator, epicardial device location, rate response turned off, having experienced a shock, and younger age. These results provide the first baseline data of physical activity in children with implanted cardiac devices and provide a clinical guide to physical activity assessment in this population. Further, our data suggest physical activity in children with implantable cardiac devices may differ based on demographic variables, device type, device location, indication for implantation, and history of ICD shock. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Quantification of cardiac autonomic nervous activities in ambulatory dogs by eliminating cardiac electric activities using cubic smoothing spline.

    PubMed

    Lee, Seung Min; Choi, Eue Keun; Chung, Gih Sung; Oh, Seil; Park, Kwang Suk

    2012-02-01

    With the development of an implantable radio transmitter system, direct measurement of cardiac autonomic nervous activities (CANAs) became possible for ambulatory animals for a couple of months. However, measured CANAs include not only CANA but also cardiac electric activity (CEA) that can affect the quantification of CANAs. In this study, we propose a novel CEA removal method using moving standard deviation and cubic smoothing spline. This method consisted of two steps of detecting CEA segments and eliminating CEAs in detected segments. Using implanted devices, we recorded stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA) and superior left ganglionated plexi nerve activity (SLGPNA) directly from four ambulatory dogs. The CEA-removal performance of the proposed method was evaluated and compared with commonly used high-pass filtration (HPF) for various heart rates and CANA amplitudes. Results tested with simulated CEA and simulated true CANA revealed stable and excellent performance of the suggested method compared to the HPF method. The averaged relative error percentages of the proposed method were less than 0.67%, 0.65% and 1.76% for SGNA, VNA and SLGPNA, respectively.

  12. 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.

  13. DJ-1 activates autophagy in the repression of cardiac hypertrophy.

    PubMed

    Xue, Ruicong; Jiang, Jingzhou; Dong, Bin; Tan, Weiping; Sun, Yu; Zhao, Jingjing; Chen, Yili; Dong, Yugang; Liu, Chen

    2017-09-21

    Cardiac hypertrophy is the risk factor of heart failure when the heart is confronted with pressure overload or neurohumoral stimuli. Autophagy, a conserved degradative pathway, is one of the important mechanisms involved in the regulation of cardiac hypertrophy. DJ-1 is a traditional anti-oxidative protein and emerging evidence suggested that DJ-1 might modulate autophagy. However, the regulation of autophagy by DJ-1 in the process of cardiac hypertrophy remains unknown. In our study, we firstly discovered that the expression of DJ-1declined in the process of pressure overload cardiac hypertrophy, and its alteration was parallel with the impairment of autophagy. Furthermore, we proved that DJ-1 knockout mice exhibited a more hypertrophied phenotype than wildtype mice in cardiac hypertrophy which indicated that DJ-1 is responsible for the repression of cardiac hypertrophy. Furthermore, DJ-1 knockout significantly exacerbated pulmonary edema due to cardiac hypertrophy. In the process of cardiac hypertrophy, DJ-1 knockout significantly impaired autophagy activation and enhanced mTORC1 and mTORC2 phosphorylation were found. Similarly, our in vitro study proved that DJ-1 overexpression ameliorated phenylephrine (PE)-induced cardiac hypertrophy and promoted autophagy activation. Taken together, DJ-1 might repress both pressure overload and PE-induced cardiac hypertrophy via the activation of autophagy. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2016-01-01

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

  15. 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.

  16. 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

  17. 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.

  18. 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).

  19. [Changes of mitogen-activated protein kinase activity in cardiac tissues, Ang II and cardiac hypertrophy in spontaneously hypertensive rats].

    PubMed

    He, K L; Zheng, Q F; Mu, S C; Li, T C; Pang, Y Z; Tang, C S

    1998-10-01

    Mitogen-activated protein kinases (MAPKs) are thought to be critical components in signal transduction pathways in regulation of cell growth and differentiation. The purpose of the present investigation is to study possible involvement of MAPKs in the progress of cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and effects of age on Angiotensin II (Ang II), MAPK activity and cardiac hypertrophy. The animals were divided into three groups: 4 months old WKY rats (n = 8), 4 month old SHRs (n = 8) and 15 month old SHRs (n = 6). Ratio of heart to body weight was measured. Ang II was determined by RIA. MAPK activity in cardiac tissue was assayed by the "in-gel" myelin basic protein phosphorylation. The results show that in comparison with 4 month old WKY rats, Ang II in plasma and cardiac tissues were elevated (216.4%, P < 0.01; 101.2%, P < 0.01) in 4 months old SHRs, while the MAPK activity was increased 107.0% (P < 0.01) with a parallel cardiac hypertrophy (P < 0.01). In comparison with 4 month old SHRs, Ang II and MAPK activity in cardiac tissue of the 15 months old SHRs were decreased (31.3%, P < 0.01; 29.7%, P < 0.05) but the cardiac hypertrophy increased by 38.5% (P < 0.01). MAPK may be involved in the progress of cardiac hypetrophy in SHR and the increased MAPK activity may be partly induced by Ang II.

  20. Automatic detection of cardiac waves on fetal magnetocardiographic signals.

    PubMed

    Comani, S; Mantini, D; Alleva, G; Di Luzio, S; Romani, G L

    2005-08-01

    Fetal magnetocardiography (fMCG) provides fetal cardiac traces useful for the prenatal monitoring of fetal heart function. In this paper, we describe an analytical model (ACWD) for the automatic detection of cardiac waves boundaries that works on fetal signals reconstructed from fMCG by means of independent component analysis. ACWD was validated for 45 healthy and 4 arrhythmic fetuses ranging from 22 to 37 weeks; ACWD outcomes were compared with the estimates of three independent investigators. Descriptive statistics were used to assess correspondence between the outcomes of the automatic and manual approaches. The parametric two-tailed Pearson correlation test (alpha=0.01) was employed to quantify, by means of the coefficients of determination, the amount of common variation between the sequences of intervals quantified automatically and manually. ACWD performances on short and long rhythm strips were investigated. ACWD demonstrated to be a robust tool providing dependable estimates of cardiac intervals and their variability during the third gestational trimester also in case of fetal arrhythmias. SNR and stability of fetal traces were the factors limiting ACWD performances. ACWD computation time, which was approximately 1:600 with respect to the manual procedure, was comparable with the time required for fCTI estimation on averaged beats.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  3. 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.

  4. Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.

    PubMed

    Hinze, Florian; Dieterich, Christoph; Radke, Michael H; Granzier, Henk; Gotthardt, Michael

    2016-12-01

    Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no treatment. Both collagen and the giant sarcomeric protein titin determine diastolic function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as a therapeutic target. We adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain cardiac filling in diastole but also ameliorates cardiac atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced RBM20 activity partially normalized gene expression related to muscle development and fatty acid metabolism. The adaptation of cardiac growth was related to hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into hypertrophy signals. We provide a novel link between cardiac isoform expression and trophic signaling via FHLs and suggest cardiac splicing as a therapeutic target in diastolic dysfunction. Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction.

  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. Theoretical considerations for mapping activation in human cardiac fibrillation

    PubMed Central

    Rappel, Wouter-Jan; Narayan, Sanjiv M.

    2013-01-01

    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. PMID:23822478

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Straightforward and robust QRS detection algorithm for wearable cardiac monitor.

    PubMed

    Manikandan, M Sabarimalai; Ramkumar, Barathram

    2014-01-01

    This Letter presents a fairly straightforward and robust QRS detector for wearable cardiac monitoring applications. The first stage of the QRS detector contains a powerful ℓ1-sparsity filter with overcomplete hybrid dictionaries for emphasising the QRS complexes and suppressing the baseline drifts, powerline interference and large P/T waves. The second stage is a simple peak-finding logic based on the Gaussian derivative filter for automatically finding locations of R-peaks in the ECG signal. Experiments on the standard MIT-BIH arrythmia database show that the method achieves an average sensitivity of 99.91% and positive predictivity of 99.92%. Unlike existing methods, the proposed method improves detection performance under small-QRS, wide-QRS complexes and noisy conditions without using the searchback algorithms.

  14. Straightforward and robust QRS detection algorithm for wearable cardiac monitor

    PubMed Central

    Ramkumar, Barathram

    2014-01-01

    This Letter presents a fairly straightforward and robust QRS detector for wearable cardiac monitoring applications. The first stage of the QRS detector contains a powerful ℓ1-sparsity filter with overcomplete hybrid dictionaries for emphasising the QRS complexes and suppressing the baseline drifts, powerline interference and large P/T waves. The second stage is a simple peak-finding logic based on the Gaussian derivative filter for automatically finding locations of R-peaks in the ECG signal. Experiments on the standard MIT-BIH arrythmia database show that the method achieves an average sensitivity of 99.91% and positive predictivity of 99.92%. Unlike existing methods, the proposed method improves detection performance under small-QRS, wide-QRS complexes and noisy conditions without using the searchback algorithms. PMID:26609375

  15. 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.

  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. 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

  18. [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.

  19. Comparative evaluation of (18)F-FLT and (18)F-FDG for detecting cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis.

    PubMed

    Norikane, Takashi; Yamamoto, Yuka; Maeda, Yukito; Noma, Takahisa; Dobashi, Hiroaki; Nishiyama, Yoshihiro

    2017-08-29

    (18)F-FDG PET has been used in sarcoidosis for diagnosis and determination of the extent of the disease. However, assessing inflammatory lesions in cardiac sarcoidosis using (18)F-FDG can be challenging because it accumulates physiologically in normal myocardium. Another radiotracer, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), has been investigated as a promising PET tracer for evaluating tumor proliferative activity. In contrast to (18)F-FDG, (18)F-FLT uptake in the normal myocardium is low. The purpose of this retrospective study was to compare the uptake of (18)F-FLT and (18)F-FDG in the evaluation of cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis. Data for 20 patients with newly diagnosed sarcoidosis were examined. (18)F-FLT and (18)F-FDG PET/CT studies had been performed at 1 h after each radiotracer injection. The patients had fasted for at least 18 h before (18)F-FDG PET/CT but were given no special dietary instructions regarding the period before (18)F-FLT PET/CT. Uptake of (18)F-FLT and (18)F-FDG was examined visually and semiquantitatively using maximal standardized uptake value (SUVmax). Two patients had cardiac sarcoidosis, 7 had extra-cardiac thoracic sarcoidosis, and 11 had both cardiac and extra-cardiac thoracic sarcoidosis. On visual analysis for diagnosis of cardiac sarcoidosis, 4/20 (18)F-FDG scans were rated as inconclusive because the (18)F-FDG pattern was diffuse, whereas no FLT scans were rated as inconclusive. The sensitivity of (18)F-FDG PET/CT for detection of cardiac sarcoidosis was 85%; specificity, 100%; and accuracy, 90%. The corresponding values for (18)F-FLT PET/CT were 92, 100, and 95%, respectively. Using semiquantitative analysis of cardiac sarcoidosis, the mean (18)F-FDG SUVmax was significantly higher than the mean (18)F-FLT SUVmax (P < 0.005). Both (18)F-FDG and (18)F-FLT PET/CT studies detected all 24 extra-cardiac lesions. Using semiquantitative analysis of extra-cardiac

  20. 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.

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

    PubMed

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

    2004-01-01

    Cardiac arrest is the most widely recognised prehospital event that early intervention can directly affect. Chance of survival from this event decreases every minute that passes without treatment. To deliver a rapid ambulance response to these patients the early detection of cardiac arrest by control room staff is crucial. To achieve this, the London Ambulance Service (LAS) uses the Advanced Medical Priority Dispatch System. What impact has AMPDS had on identifying patients in cardiac arrest? Does compliance with AMPDS protocol influence the identification of patients in cardiac arrest? 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. 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 (r(2) = 0.65, p = 0.001). 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.

  2. 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

  3. 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). Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Measure of synchrony in the activity of intrinsic cardiac neurons.

    PubMed

    Longpré, Jean-Philippe; Salavatian, Siamak; Beaumont, Eric; Armour, J Andrew; Ardell, Jeffrey L; Jacquemet, Vincent

    2014-04-01

    Recent multielectrode array recordings in ganglionated plexi of canine atria have opened the way to the study of population dynamics of intrinsic cardiac neurons. These data provide critical insights into the role of local processing that these ganglia play in the regulation of cardiac function. Low firing rates, marked non-stationarity, interplay with the cardiovascular and pulmonary systems and artifacts generated by myocardial activity create new constraints not present in brain recordings for which almost all neuronal analysis techniques have been developed. We adapted and extended the jitter-based synchrony index (SI) to (1) provide a robust and computationally efficient tool for assessing the level and statistical significance of SI between cardiac neurons, (2) estimate the bias on SI resulting from neuronal activity possibly hidden in myocardial artifacts, (3) quantify the synchrony or anti-synchrony between neuronal activity and the phase in the cardiac and respiratory cycles. The method was validated on firing time series from a total of 98 individual neurons identified in 8 dog experiments. SI ranged from -0.14 to 0.66, with 23 pairs of neurons with SI > 0.1. The estimated bias due to artifacts was typically <1%. Strongly cardiovascular- and pulmonary-related neurons (SI > 0.5) were found. Results support the use of jitter-based SI in the context of intrinsic cardiac neurons.

  5. Measure of synchrony in the activity of intrinsic cardiac neurons

    PubMed Central

    Longpré, Jean-Philippe; Salavatian, Siamak; Beaumont, Eric; Armour, J. Andrew; Ardell, Jeffrey L.; Jacquemet, Vincent

    2014-01-01

    Recent multielectrode array recordings in ganglionated plexi of canine atria have opened the way to the study of population dynamics of intrinsic cardiac neurons. These data provide critical insights into the role of local processing that these ganglia play in the regulation of cardiac function. Low firing rates, marked non-stationarity, interplay with the cardiovascular and pulmonary systems and artifacts generated by myocardial activity create new constraints not present in brain recordings for which almost all neuronal analysis techniques have been developed. We adapted and extended the jitter-based synchrony index (SI) to (1) provide a robust and computationally-efficient tool for assessing the level and statistical significance of SI between cardiac neurons, (2) estimate the bias on SI resulting from neuronal activity possibly hidden in myocardial artifacts, (3) quantify the synchrony or anti-synchrony between neuronal activity and the phase in the cardiac and respiratory cycles. The method was validated on firing time series from a total of 98 individual neurons identified in 8 dog experiments. SI ranged from −0.14 to 0.66, with 23 pairs of neurons with SI>0.1. The estimated bias due to artifacts was typically < 1%. Strongly cardiovascular- and pulmonary-related neurons (SI>0.5) were found. Results support the use of jitter-based synchrony index in the context of intrinsic cardiac neurons. PMID:24621585

  6. 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.

  7. 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

  8. Peroxisome proliferator-activated receptor beta stimulation induces rapid cardiac growth and angiogenesis via direct activation of calcineurin.

    PubMed

    Wagner, Nicole; Jehl-Piétri, Chantal; Lopez, Pascal; Murdaca, Joseph; Giordano, Christian; Schwartz, Chantal; Gounon, Pierre; Hatem, Stéphane N; Grimaldi, Paul; Wagner, Kay-Dietrich

    2009-07-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors. PPARbeta agonists were suggested as potential drugs for the treatment of metabolic syndrome, but effects of PPARbeta activation on cardiac growth and vascularization are unknown. Thus, we investigated the consequences of pharmacological PPARbeta activation on the heart and the underlying molecular mechanisms. Male C57/Bl6 mice were injected with the specific PPARbeta agonists GW0742 or GW501516, or vehicle. Cardiomyocyte size and vascularisation were determined at different time points. Expression differences were investigated by quantitative reverse transcriptase-polymerase chain reaction and western blotting. In addition, the effects of PPARbeta stimulation were compared with hearts of mice undergoing long-term voluntary exercise or pharmacological PPARalpha activation. Five hours after GW0742 injection, we detected an enhanced angiogenesis compared with vehicle-injected controls. After 24 h, the heart-to-body weight ratios were higher in mice injected with either GW0742 or GW501516 vs. controls. The increased heart size was due to cardiomyocyte enlargement. No signs of pathological cardiac hypertrophy (i.e. apoptosis, fibrosis, or deteriorated cardiac function) could be detected. The effects are mediated via calcineurin A (CnA) activation as: (i) CnA was upregulated, (ii) GW0742 administration or co-transfection of PPARbeta significantly stimulated the activity of the CnA promoter, (iii) PPARbeta protein bound directly to the CnA promoter, (iv) the CnA target genes NFATc3, Hif-1alpha, and Cdk 9 were upregulated in response to PPARbeta stimulation, and (v) the inhibition of CnA activity by cyclosporine A abolished the hypertrophic and angiogenic responses to PPARbeta stimulation. Our data suggest PPARbeta pharmacological activation as a novel approach to increase cardiac vascularization and cardiac muscle mass.

  9. 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

  10. 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

  11. 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

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

    SciTech Connect

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

    2006-02-10

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

  13. (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.

  14. Echocardiography integrated ACLS protocol versus conventional cardiopulmonary resuscitation in patients with pulseless electrical activity cardiac arrest.

    PubMed

    Chardoli, Mojtaba; Heidari, Farhad; Rabiee, Helaleh; Sharif-Alhoseini, Mahdi; Shokoohi, Hamid; Rahimi-Movaghar, Vafa

    2012-01-01

    To examine the utility of bedside echocardiography in detecting the reversible causes of pulseless electrical activity (PEA) cardiac arrest and predicting the resuscitation outcomes. In this prospective interventional study, patients presenting with PEA cardiac arrest were randomized into two groups. In Group A, ultrasound trained emergency physicians performed echocardiography evaluating cardiac activity, right ventricle dilation, left ventricle function, pericardial effusion/tamponade and IVC size along with the advanced cardiac life support (ACLS) protocol. Patients in Group B solely underwent ACLS protocol without applying echocardiography. The presence or absence of mechanical ventricular activity (MVA) and evidences of PEA reversible causes were recorded. The return of spontaneous circulation (ROSC) and death were evaluated in both groups. One hundred patients with the mean age of (58+/-6.1) years were enrolled in this study. Fifty patients (Group A) had echocardiography detected in parallel with cardiopulmonary resuscitation (CPR). Among them, 7 patients (14%) had pericardial effusion, 11 (22%) had hypovolemia, and 39 (78%) were revealed the presence of MVA. In the pseudo PEA subgroup (presence of MVA), 43% had ROSC (positive predictive value) and in the true PEA subgroup with cardiac standstill (absence of MVA), there was no recorded ROSC (negative predictive value). Among patients in Group B, no reversible etiology was detected. There was no significant difference in resuscitation results between Groups A and B observed (P equal to 0.52). Bedside echocardiography can identify some reversible causes of PEA. However, there are no significant changes in survival outcome between the echo group and those with traditional CPR.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. Phase singularities in cardiac electrical activity

    NASA Astrophysics Data System (ADS)

    Uzelac, Ilija; Sidorov, Veniamin; Wikswo, John

    2010-03-01

    theory of topological spaces has its analogy in biological systems, one of which is the heart. The heart is an excitable medium that can be represented as a set of excitable elements (cardiomyocytes) that behave similarly to hourglasses. Excitable element needs external stimuli to be excited and after finite time goes back to its initial state, so its natural topological space is a ring. Topological space set (phases) can be simple set as ``rest,'' ``excited,'' ``refractory,'' ``relatively refractory'', but it can be as continuous as a set of angles on a 2π circle. In topological spaces topological charge is defined by: [ W=12πldθ (l) ] where l is the integration path and dθ is the change in phase. Non zero topological charge is called phase singularity of mapping. Practical application of topological charge analysis is a powerful method to quantify electrical dynamics during ventricular fibrillation (VF). Particularly by means of phase singularity detection it is possible to track wave breaks which relate to anatomical and electrophysiological heterogeneities.

  20. 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.

  1. 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

  2. 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.

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

    PubMed

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

    2016-12-23

    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.

  4. 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.

  5. Cardiac ACE2/angiotensin 1-7/Mas receptor axis is activated in thyroid hormone-induced cardiac hypertrophy.

    PubMed

    Diniz, Gabriela P; Senger, Nathalia; Carneiro-Ramos, Marcela S; Santos, Robson A S; Barreto-Chaves, Maria Luiza M

    2016-08-01

    Thyroid hormone (TH) promotes marked effects on the cardiovascular system, including the development of cardiac hypertrophy. Some studies have demonstrated that the renin-angiotensin system (RAS) is a key mediator of the cardiac growth in response to elevated TH levels. Although some of the main RAS components are changed in cardiac tissue on hyperthyroid state, the potential modulation of the counter regulatory components of the RAS, such as angiotensin-converting enzyme type 2 (ACE2), angiotensin 1-7 (Ang 1-7) levels and Mas receptor induced by hyperthyroidism is unknown. The aim of this study was to investigate the effect of hyperthyroidism on cardiac Ang 1-7, ACE2 and Mas receptor levels. Hyperthyroidism was induced in Wistar rats by daily intraperitoneal injections of T4 for 14 days. Although plasma Ang 1-7 levels were unchanged by hyperthyroidism, cardiac Ang 1-7 levels were increased in TH-induced cardiac hypertrophy. ACE2 enzymatic activity was significantly increased in hearts from hyperthyroid animals, which may be contributing to the higher Ang 1-7 levels observed in the T4 group. Furthermore, elevated cardiac levels of Ang 1-7 levels were accompanied by increased Mas receptor protein levels. The counter-regulatory components of the RAS are activated in hyperthyroidism and may be contributing to modulate the cardiac hypertrophy in response to TH. © The Author(s), 2015.

  6. 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.

  7. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 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.

  9. Human Infrastructure & Human Activity Detection

    DTIC Science & Technology

    2007-07-01

    packages. etc. Accelerometers can also detect vibrations in pipes that are produced by the flow of water. • RF detectors can detect any RF activity...such as the use of cell phones. • Magnetic (B-field) sensors can be used to detect ferromagnetic materials carried by people, e.g., keys, firearms...electric charge on personnel. Together with magnetic sensors, they can also detect electrical activity in the vicinity such as the usage of computer

  10. 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.

  11. Developmental heterogeneity of cardiac fibroblasts does not predict pathological proliferation and activation.

    PubMed

    Ali, Shah R; Ranjbarvaziri, Sara; Talkhabi, Mahmood; Zhao, Peng; Subat, Ali; Hojjat, Armin; Kamran, Paniz; Müller, Antonia M S; Volz, Katharina S; Tang, Zhaoyi; Red-Horse, Kristy; Ardehali, Reza

    2014-09-12

    Fibrosis is mediated partly by extracellular matrix-depositing fibroblasts in the heart. Although these mesenchymal cells are reported to have multiple embryonic origins, the functional consequence of this heterogeneity is unknown. We sought to validate a panel of surface markers to prospectively identify cardiac fibroblasts. We elucidated the developmental origins of cardiac fibroblasts and characterized their corresponding phenotypes. We also determined proliferation rates of each developmental subset of fibroblasts after pressure overload injury. We showed that Thy1(+)CD45(-)CD31(-)CD11b(-)Ter119(-) cells constitute the majority of cardiac fibroblasts. We characterized these cells using flow cytometry, epifluorescence and confocal microscopy, and transcriptional profiling (using reverse transcription polymerase chain reaction and RNA-seq). We used lineage tracing, transplantation studies, and parabiosis to show that most adult cardiac fibroblasts derive from the epicardium, a minority arises from endothelial cells, and a small fraction from Pax3-expressing cells. We did not detect generation of cardiac fibroblasts by bone marrow or circulating cells. Interestingly, proliferation rates of fibroblast subsets on injury were identical, and the relative abundance of each lineage remained the same after injury. The anatomic distribution of fibroblast lineages also remained unchanged after pressure overload. Furthermore, RNA-seq analysis demonstrated that Tie2-derived and Tbx18-derived fibroblasts within each operation group exhibit similar gene expression profiles. The cellular expansion of cardiac fibroblasts after transaortic constriction surgery was not restricted to any single developmental subset. The parallel proliferation and activation of a heterogeneous population of fibroblasts on pressure overload could suggest that common signaling mechanisms stimulate their pathological response. © 2014 American Heart Association, Inc.

  12. Severely impaired cardiac autonomic nervous activity after the Fontan operation.

    PubMed

    Ohuchi, H; Hasegawa, S; Yasuda, K; Yamada, O; Ono, Y; Echigo, S

    2001-09-25

    Elevated neurohumoral activity and an abnormal cardiopulmonary response to exercise are well-established characteristics in patients after the Fontan operation. However, there have been few studies addressing cardiac autonomic nervous activity (CANA) in these patients. We evaluated CANA in 63 post-Fontan patients and 44 controls. Cardiac parasympathetic nervous activity (PSNA) was estimated by heart rate (HR) changes after cholinergic blockade, HR variability, and arterial baroreflex sensitivity. Cardiac sympathetic nervous activity was estimated by the heart to mediastinum [(123)I]metaiodobenzylguanidine activity ratio (H/M) and the HR increase (DeltaHR) after isoproterenol infusion (beta). DeltaHR and peak oxygen uptake (VO(2)) were measured by exercise test. There was no difference in beta between the Fontan group and controls. PSNA and H/M were markedly lower than in controls (P<0.001). PSNA and beta were related to DeltaHR (P<0.05); however, peak VO(2) was not correlated with DeltaHR. Neither PSNA nor H/M was associated with clinical features, including hemodynamics, type of repair, number of surgical procedures, age at Fontan operation, or follow-up period, and administration of an angiotensin-converting enzyme inhibitor did not improve the impaired CANA in these patients. After the Fontan procedure, postsynaptic beta-sensitivity is maintained and is important in DeltaHR during exercise as is PSNA, although DeltaHR does not determine exercise capacity. The lack of a relationship between CANA and clinical features implies that, in addition to surgical damage, the Fontan circulation per se may impair CANA. Angiotensin-converting enzyme inhibitor administration does not change this abnormality.

  13. A novel software program for detection of potential air emboli during cardiac surgery.

    PubMed

    Secretain, Frank; Pollard, Andrew; Uddin, Mesbah; Ball, Christopher G; Hamilton, Andrew; Tanzola, Robert C; Thorpe, Joelle B; Milne, Brian

    2015-01-12

    Risks associated with air emboli introduced during cardiac surgery have been highlighted by reports of postoperative neuropsychological dysfunction, myocardial dysfunction, and mortality. Presently, there are no standard effective methods for quantifying potential emboli in the bloodstream during cardiac surgery. Our objective was to develop software that can automatically detect and quantify air bubbles within the ascending aorta and/or cardiac chambers during cardiac surgery in real time. We created a software algorithm ("Detection of Emboli using Transesophageal Echocardiography for Counting, Total volume, and Size estimation", or DETECTS™) to identify and measure potential emboli present during cardiac surgery using two-dimensional ultrasound. An in vitro experiment was used to validate the accuracy of DETECTS™ at identifying and measuring air emboli. An experimental rig was built to correlate the ultrasound images to high definition camera images of air bubbles created in water by an automatic bubbler system. There was a correlation between true bubble size and the size reported by DETECTS™ in our in vitro experiment (r = 0.76). We also tested DETECTS™ using TEE images obtained during cardiac surgery, and provide visualization of the software interface. While monitoring the heart during cardiac surgery using existing ultrasound technology and DETECTS™, the operative team can obtain real-time data on the number and volume of potential air emboli. This system will potentially allow de-airing techniques to be evaluated and improved upon. This could lead to reduced air in the cardiac chambers after cardiopulmonary bypass, possibly reducing the risk of neurological dysfunction following cardiac surgery.

  14. 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.

  15. 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.

  16. 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

  17. 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. Copyright © 2015, American Association for the Advancement of Science.

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

    PubMed Central

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

    2015-01-01

    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 RafL613V, 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. PMID:25650441

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Activation of the Homeostatic Intracellular Repair Response during Cardiac Surgery

    PubMed Central

    Jahania, Salik M.; Sengstock, David; Vaitkevicius, Peter; Andres, Allen; Ito, Bruce R.; Gottlieb, Roberta A.; Mentzer, Robert M.

    2013-01-01

    Introduction The homeostatic intracellular repair response (HIR2) is an endogenous beneficial pathway that eliminates damaged mitochondria and dysfunctional proteins in response to stress. The underlying mechanism is adaptive autophagy. The purpose of this study was to determine whether the HIR2 response is activated in the heart in patients undergoing cardiac surgery and to assess whether it is associated with the duration of ischemic arrest and predicted surgical outcome. Methods Autophagy was assessed in 19 patients undergoing coronary artery bypass or valve surgery requiring cardiopulmonary bypass (CPB). Biopsies of the right atrial appendage obtained before initiation of CPB and after weaning from CPB were analyzed for autophagy by immunoblotting for LC3, Beclin-1, Atg5-12, and p62. Changes in p62, a marker of autophagic flux, were correlated with duration of ischemia and with the mortality/morbidity risk scores obtained from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (v2.73). Results Heart surgery was associated with a robust increase in autophagic flux indicated by depletion of LC3-I, LC3-II, Beclin-1, and Atg5-12; the magnitude of change for each of these factors correlated significantly with changes in the flux marker p62. Moreover, changes in p62 correlated directly with cross clamp time and inversely with the mortality/morbidity risk scores. Conclusion These findings are consistent with preclinical studies indicating that HIR2 is cardioprotective, and reveal that it is activated in patients in response to myocardial ischemic stress. Strategies designed to amplify HIR2 during conditions of cardiac stress may have therapeutic utility and represent an entirely new approach to myocardial protection in patients undergoing heart surgery. PMID:23415552

  4. 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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. 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.

  6. 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.

  7. An active strain electromechanical model for cardiac tissue.

    PubMed

    Nobile, F; Quarteroni, A; Ruiz-Baier, R

    2012-01-01

    We propose a finite element approximation of a system of partial differential equations describing the coupling between the propagation of electrical potential and large deformations of the cardiac tissue. The underlying mathematical model is based on the active strain assumption, in which it is assumed that there is a multiplicative decomposition of the deformation tensor into a passive and active part holds, the latter carrying the information of the electrical potential propagation and anisotropy of the cardiac tissue into the equations of either incompressible or compressible nonlinear elasticity, governing the mechanical response of the biological material. In addition, by changing from a Eulerian to a Lagrangian configuration, the bidomain or monodomain equations modeling the evolution of the electrical propagation exhibit a nonlinear diffusion term. Piecewise quadratic finite elements are employed to approximate the displacements field, whereas for pressure, electrical potentials and ionic variables are approximated by piecewise linear elements. Various numerical tests performed with a parallel finite element code illustrate that the proposed model can capture some important features of the electromechanical coupling and show that our numerical scheme is efficient and accurate.

  8. Acute physical activity effects on cardiac gene expression.

    PubMed

    Simonsen, Michelle L; Alessio, Helaine M; White, Peter; Newsom, David L; Hagerman, Ann E

    2010-11-01

    Regular bouts of physical activity may cause changes in gene expression that accumulate over time and ultimately affect phenotypes, such as body weight, blood lipid profile and tumour development. Furthermore, acute activity may affect gene expression and phenotypes differently depending on whether the individual is regularly inactive or active. One-month-old male Sprague-Dawley rats (n = 72) were equally divided into SED (standard laboratory cage, n = 24), PA (large activity box, n = 24) and EX groups (exercise wheel inside standard cage, n = 24). At 3 months of age, half the animals from each group were killed at rest and the other half following 30 min of physical activity. The RNA was extracted from cardiac tissue, and microarray analysis was performed on 27,000 genes. Select gene results were validated using quantitative PCR. No gene expression differences occurred when comparing all 3-month-old groups at rest. A relatively small percentage of genes (1.9%) were differentially expressed (P < 0.05) following acute swimming activity in all groups, but only 37 unique and identifiable genes reached or exceeded twofold differences in expression. The genes Atf3, Fos, Apold1 and Pxdn were expressed differently among SED, PA and EX following acute activity, with a clear separation of the magnitude in gene expression with SED > PA > EX. Differences in gene expression levels in young physically inactive and active animals following acute activity have different regulatory roles in gene networks that affect health-related phenotypes.

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

    PubMed Central

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

    2015-01-01

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

  10. 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

  11. Human CD55 Expression Blocks Hyperacute Rejection and Restricts Complement Activation in Gal Knockout Cardiac Xenografts

    PubMed Central

    McGregor, Christopher G.A.; Ricci, Davide; Miyagi, Naoto; Stalboerger, Paul G.; Du, Zeji; Oehler, Elise A.; Tazelaar, Henry D.; Byrne, Guerard W.

    2012-01-01

    Background Transgenic expression of human complement regulatory proteins (hCRPs) reduces the frequency of hyperacute rejection (HAR) in Gal-positive cardiac xenotransplantation. In this study we examine the impact of human CD55 (hCD55) expression on a Gal knock-out (GTKO) background using pig-to-primate heterotopic cardiac xenotransplantation. Methods Cardiac xenotransplantation was performed with GTKO (Group 1; n=6) and GTKO.hCD55 (Group 2; n=5) donor pigs using similar immunosuppression. Cardiac biopsies were obtained 30 minutes after organ reperfusion. Rejection was characterized by histology and immunohistology. Intragraft gene expression, serum non-Gal antibody and antibody recovered from rejected hearts were analyzed. Results HAR of a GTKO heart was observed. Remaining grafts developed delayed xenograft rejection. Median survival was 21 and 28 days for Groups 1 and 2 respectively. Vascular antibody deposition was uniformly detected 30 minutes after organ reperfusion and at explant. A higher frequency of vascular C5b deposition was seen in GTKO organs at explant. Serum non-Gal antibody, antibody recovered from the graft and intragraft gene expression were similar between the groups. Conclusion HAR of GTKO hearts without hCD55 may occur. Expression of hCD55 appeared to restrict local complement activation, but did not improve graft survival. Chronic vascular antibody deposition with evidence of protracted endothelial cell activation was seen. These observations suggest that non-Gal antibody-induced chronic endothelial cell activation coupled to possible haemostatic incompatibilities may be the primary stimulus for DXR of GTKO hearts. To avoid possible HAR, future clinical studies should employ donors expressing hCRPs in the GTKO background. PMID:22391577

  12. 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.

  13. 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

  14. 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. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. MicroRNA-22 increases senescence and activates cardiac fibroblasts in the aging heart.

    PubMed

    Jazbutyte, Virginija; Fiedler, Jan; Kneitz, Susanne; Galuppo, Paolo; Just, Annette; Holzmann, Angelika; Bauersachs, Johann; Thum, Thomas

    2013-06-01

    MicroRNAs (miRs) are small non- coding RNA molecules controlling a plethora of biological processes such as development, cellular survival and senescence. We here determined miRs differentially regulated during cardiac postnatal development and aging. Cardiac function, morphology and miR expression profiles were determined in neonatal, 4 weeks, 6 months and 19 months old normotensive male healthy C57/Bl6N mice. MiR-22 was most prominently upregulated during cardiac aging. Cardiac expression of its bioinformatically predicted target mimecan (osteoglycin, OGN) was gradually decreased with advanced age. Luciferase reporter assays validated mimecan as a bona fide miR-22 target. Both, miR-22 and its target mimecan were co- expressed in cardiac fibroblasts and smooth muscle cells. Functionally, miR-22 overexpression induced cellular senescence and promoted migratory activity of cardiac fibroblasts. Small interference RNA-mediated silencing of mimecan in cardiac fibroblasts mimicked the miR-22-mediated effects. Rescue experiments revealed that the effects of miR-22 on cardiac fibroblasts were only partially mediated by mimecan. In conclusion, miR-22 upregulation in the aging heart contributed at least partly to accelerated cardiac fibroblast senescence and increased migratory activity. Our results suggest an involvement of miR-22 in age-associated cardiac changes, such as cardiac fibrosis.

  16. 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.

  17. 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.

  18. Sudden Cardiac Arrest During Sports Activity in Middle Age

    PubMed Central

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

    2015-01-01

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

  19. Sudden cardiac arrest during sports activity in middle age.

    PubMed

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

    2015-04-21

    Sports-associated sudden cardiac arrests (SCAs) occur mostly during middle age. We sought to determine the burden, characteristics, and outcomes of SCA during sports among middle-aged residents of a large US community. Patients with SCA who were 35 to 65 years of age were identified in a large, prospective, population-based study (2002-2013), with systematic and comprehensive assessment of their lifetime medical history. Of the 1247 SCA cases, 63 (5%) occurred during sports activities at a mean age of 51.1±8.8 years, yielding an incidence of 21.7 (95% confidence interval, 8.1-35.4) per 1 million per year. The incidence varied significantly by sex, with a higher incidence among men (relative risk, 18.68; 95% confidence interval, 2.50-139.56) for sports SCAs compared with all other SCAs (relative risk 2.58; 95% confidence interval, 2.12-3.13). Sports SCA was also more likely to be a witnessed event (87% versus 53%; P<0.001) with cardiopulmonary resuscitation (44% versus 25%; P=0.001) and ventricular fibrillation (84% versus 51%; P<0.0001). Survival to hospital discharge was higher for sports-associated SCA (23.2% versus 13.6%; P=0.04). Sports SCA cases presented with known preexisting cardiac disease in 16% and ≥1 cardiovascular risk factors in 56%, and overall, 36% of cases had typical cardiovascular symptoms during the week preceding the SCA. Sports-associated SCA in middle age represents a relatively small proportion of the overall SCA burden, reinforcing the idea of the high-benefit, low-risk nature of sports activity. Especially in light of current population aging trends, our findings emphasize that targeted education could maximize both safety and acceptance of sports activity in the older athlete. © 2015 American Heart Association, Inc.

  20. Cardiac magnetic field mapping quantified by Kullback-Leibler entropy detects patients with coronary artery disease.

    PubMed

    Gapelyuk, A; Schirdewan, A; Fischer, R; Wessel, N

    2010-10-01

    Cardiac magnetic field mapping (CMFM) is a noninvasive method to determine cardiac electrical activity. We analysed the utility of CMFM for the detection of patients with coronary artery disease (CAD) without subjecting them to stress. We studied 59 healthy control subjects and 101 patients with CAD without previous myocardial infarction (MI). The heart's magnetic field was recorded over the anterior chest wall using a multichannel magnetic measurement system with axial second-order gradiometers. The evaluation of CMFM was based on comparison of the 'ideal' group mean maps of young healthy subjects and maps of examined individuals. Three measures of similarity were considered: Kullback-Leibler (KL) entropy, normalized residual magnetic field strength and deviations in the magnetic field map orientation. The mean values of these parameters during the depolarization and repolarization were used for further classification with the help of logistic regression. The feature set based on the KL-entropy demonstrated the best classification results (sensitivity/specificity of 85/80%), followed by the residual feature (85/75%) and the magnetic field orientation feature (80/73%) sets. The forward stepwise technique was applied to select the best set of features from the combined feature set. Two parameters were selected, namely the KL-entropy for the repolarization period and the residual parameter for the depolarization period. The classification based on these parameters demonstrated a sensitivity of 88% and a specificity of 88% for the distinction of CAD patients from the control subjects. The area under the receiver operator curve was 94%. Hence, we suggest that CMFM evaluation based on KL-entropy is a promising technique to identify patients with CAD.

  1. 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.

  2. 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.

  3. 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.

  4. Detection of acute myocardial ischemic injury by gender using a novel cardiac electrical biomarker.

    PubMed

    Schreck, David M; Fishberg, Robert D

    2015-03-01

    The objective of this study us to stratify by gender a new cardiac electrical biomarker (CEB) diagnostic accuracy for detection of acute myocardial ischemic injury (AMII). This is a noninferiority retrospective, case-control, blinded study of 310 archived measured electrocardiograms (ECGs) acquired from 218 men and 92 women. The CEB is constructed from the derived ECG (dECG) synthesized from 3 leads. Electrocardiograms were included if acquired less than or equal to 1 day from patient presentation. Electrocardiograms were interpreted by 2 blinded physicians and adjudicated by consensus. Standard ST analyses and computerized ECG interpretations were active controls. Electrocardiograms were excluded for noise and baseline wander, age younger than 18 years, and ectopic beats in the 10-second ECG acquisition. Diagnostic accuracy measures of sensitivity, specificity, positive and negative predictive values, and likelihood ratios were stratified by gender. Measured vs derived ECG correlations were quantitatively compared using Pearson correlation and qualitatively by percent agreement methodology. The CEB sensitivities for AMII detection in men and women were 93.9% and 90.5%, respectively, and CEB specificities were 90.7% and 95.2%, respectively, and were superior to active controls. Derived and measured ECGs showed high correlation for both men and women with r = 0.857 and r = 0.893, respectively. Reference standard intra-agreement analysis for measured ECGs and dECGs with AMII was 99.4%. The CEB demonstrates high diagnostic accuracy for detection of AMII in men and women. The ECG can be derived with accuracy from 3 leads. This technology is an efficient real-time method of identifying patients with AMII who are being monitored in acute care settings. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed

    Rubin, M B

    2016-08-01

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

  6. Practical tips and tricks for assessing prosthetic valves and detecting paravalvular regurgitation using cardiac CT.

    PubMed

    O'Neill, Ailbhe C; Martos, Ramon; Murtagh, Gillian; Ryan, Edmund Ronan; McCreery, Charles; Keane, David; Quinn, Martin; Dodd, Jonathan D

    2014-01-01

    Paravalvular leaks are an uncommon but serious complication of prosthetic valves. Transthoracic echocardiography is used in the assessment of prosthetic valves but can be limited by acoustic shadowing from the prosthesis and poor acoustic windowing. Small case series have previously shown cardiac CT to have promising results in detecting paravalvular leaks. We assessed 32 valves in our institution on cardiac CT using echocardiography results as standard and developed methods for improved evaluation of prosthetic valves. These include optimizing prescan drug therapy for heart rate control, optimum window and center adjustments, and carefully selected image planes to best demonstrate the valve ring and valve annulus. Recognition of surgical material is also important to recognize. In this review, we provide a detailed description of these techniques with imaging examples of prosthetic valve evaluation using cardiac CT. Copyright © 2014 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  7. 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.

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

    PubMed Central

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

    2014-01-01

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

  9. Differential and conditional activation of PKC-isoforms dictates cardiac adaptation during physiological to pathological hypertrophy.

    PubMed

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

    2014-01-01

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

  10. Automated fetal cardiac valve movement detection for modified myocardial performance index calculation.

    PubMed

    Wang, Jingjing; Henry, Amanda; Welsh, Alec W; Redmond, Stephen J

    2014-01-01

    The Modified Myocardial Performance Index (Mod-MPI) is becoming an important index in fetal cardiac function evaluation. However, the current method for Mod-MPI calculation can be time-consuming and demonstrates poor inter-operator repeatability. This paper presents an automated method for detecting the opening and closing events of fetal cardiac valves with the aim of automating the Mod-MPI calculation. Fifty-four Doppler ultrasound images, showing blood inflow and outflow for the left ventricle, are analyzed to attempt to automatically detect the timings of a total of 905 opening and closing events for both aortic and mitral valves. Timings are found according to the morphological characteristics of waveforms as well as intensity information of images. The proposed method can detect the four valve movement events with high sensitivity (95.60-98.64%) and precision (96.85-100.00%). Results are verified by comparison with manual annotation of same images from an expert.

  11. 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.

  12. 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.

  13. 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.

  14. Reconstruction of the electrical activity of cardiac Purkinje fibres.

    PubMed Central

    McAllister, R E; Noble, D; Tsien, R W

    1975-01-01

    1. The electrical activity of Cardiac Purkinje fibres was reconstructed using a mathematical model of the membrane current. The individual components of ionic curent were described by equations which wee based as closely as possible on previous experiments using the voltage clamp technique. 2. Membrane action potentials and pace-maker activity were calculated and compared with time course of underlying changes in two functionally distinct outeard currents, iX1 and iK2. 3. The repolarization of the theoretical action potential is triggered by the onset of iX1, which becomes activated over the plateau range of potentials. iK2 also activates during the plateau but does not play a controlling role in the repolarization. Hwever, iK2 does govern the slow pace-maker depolarization through its subsequent deactivation at negative potentials. 4. The individual phases of the calculated action potential and their 'experimental' modifications were compared with published records. The upstroke is generated by a Hodgkin-Huxley type sodium conductance (gNa), and rises with a maximum rate of 478 V/sec, somewhat less than experimentally observed values ( up to 800 V/sec). The discrepancy is discussed in relation to experimental attempts at measuring gNa. 5. The ole of the transient outward chloride current (called igr) was studied in calculations of the rapid phase of repolarization and 'notch' configuration... PMID:1185607

  15. 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

  16. 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

  17. 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%.

  18. 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.

  19. 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

  20. 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.

  1. Basis for the preferential activation of cardiac sympathetic nerve activity in heart failure

    PubMed Central

    Ramchandra, Rohit; Hood, Sally G.; Denton, Derek A.; Woods, Robin L.; McKinley, Michael J.; McAllen, Robin M.; May, Clive N.

    2009-01-01

    In heart failure (HF), sympathetic nerve activity is increased. Measurements in HF patients of cardiac norepinephrine spillover, reflecting cardiac sympathetic nerve activity (CSNA), indicate that it is increased earlier and to a greater extent than sympathetic activity to other organs. This has important consequences because it worsens prognosis, provoking arrhythmias and sudden death. To elucidate the mechanisms responsible for the activation of CSNA in HF, we made simultaneous direct neural recordings of CSNA and renal SNA (RSNA) in two groups of conscious sheep: normal animals and animals in HF induced by chronic, rapid ventricular pacing. In normal animals, the level of activity, measured as burst incidence (bursts of pulse related activity/100 heart beats), was significantly lower for CSNA (30 ± 5%) than for RSNA (94 ± 2%). Furthermore, the resting level of CSNA, relative to its maximum achieved while baroreceptors were unloaded by reducing arterial pressure, was set at a much lower percentage than RSNA. In HF, burst incidence of CSNA increased from 30 to 91%, whereas burst incidence of RSNA remained unaltered at 95%. The sensitivity of the control of both CSNA and RSNA by the arterial baroreflex remained unchanged in HF. These data show that, in the normal state, the resting level of CSNA is set at a lower level than RSNA, but in HF, the resting levels of SNA to both organs are close to their maxima. This finding provides an explanation for the preferential increase in cardiac norepinephrine spillover observed in HF. PMID:19136635

  2. 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.

  3. 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.

  4. Noninvasive detection of cardiac amyloidosis using delayed enhanced MDCT: a pilot study.

    PubMed

    Deux, Jean-François; Mihalache, Cristian-Ionut; Legou, François; Damy, Thibaud; Mayer, Julie; Rappeneau, Stéphane; Planté-Bordeneuve, Violaine; Luciani, Alain; Kobeiter, Hicham; Rahmouni, Alain

    2015-08-01

    To evaluate myocardial enhancement of patients with cardiac amyloidosis (CA) using computed tomography (CT). Thirteen patients with CA and 11 control patients were examined with first-pass and delayed CT acquisition. A qualitative and quantitative analysis of images was performed. Myocardial attenuation, myocardial signal-to-noise ratio (SNRmyoc), blood pool SNR (SNRblood), contrast-to-noise ratio between blood pool and myocardium (CNRblood-myoc) and relative attenuation index (RAI) defined as variation of myocardial attenuation between delayed and first-pass acquisitions were calculated. Two false negative cases (15 %) and three false positive cases (27 %) were detected on qualitative analysis. SNRmyoc of patients with CA was significantly (p < 0.05) lower on first-pass (4.08 ± 1.9) and higher on delayed acquisition (7.10 ± 2.7) than control patients (6.1 ± 2.2 and 5.03 ± 1.8, respectively). Myocardial attenuation was higher in CA (121 ± 39 HU) than control patients (81 ± 17 HU) on delayed acquisition. CNRblood-myoc was significantly (p < 0.05) lower in CA (1.51 ± 0.7) than control patients (2.85 ± 1.2) on delayed acquisition. The RAI was significantly (p < 0.05) higher in CA (0.12 ± 0.25) than in control patients (-0.56 ± 0.21). Dual phase MDCT can detect abnormal myocardial enhancement in patients with CA. • CT can detect abnormal first-pass and delayed enhancement in cardiac amyloidosis. • Measurement of relative myocardial enhancement between acquisitions helps to detect cardiac amyloidosis. • CT may provide useful data to diagnose cardiac amyloidosis.

  5. 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. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. 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.

  7. Ion Fluxes in Giant Excised Cardiac Membrane Patches Detected and Quantified with Ion-selective Microelectrodes

    PubMed Central

    Kang, Tong Mook; Markin, Vladislav S.; Hilgemann, Donald W.

    2003-01-01

    We have used ion-selective electrodes (ISEs) to quantify ion fluxes across giant membrane patches by measuring and simulating ion gradients on both membrane sides. Experimental conditions are selected with low concentrations of the ions detected on the membrane side being monitored. For detection from the cytoplasmic (bath) side, the patch pipette is oscillated laterally in front of an ISE. For detection on the extracellular (pipette) side, ISEs are fabricated from flexible quartz capillary tubing (tip diameters, 2–3 microns), and an ISE is positioned carefully within the patch pipette with the tip at a controlled distance from the mouth of the patch pipette. Transport activity is then manipulated by solution changes on the cytoplasmic side. Ion fluxes can be quantified by simulating the ion gradients with appropriate diffusion models. For extracellular (intrapatch pipette) recordings, ion diffusion coefficients can be determined from the time courses of concentration changes. The sensitivity and utility of the methods are demonstrated with cardiac membrane patches by measuring (a) potassium fluxes via ion channels, valinomycin, and Na/K pumps; (b) calcium fluxes mediated by Na/Ca exchangers; (c) sodium fluxes mediated by gramicidin and Na/K pumps; and (d) proton fluxes mediated by an unknown electrogenic mechanism. The potassium flux-to-current ratio for the Na/K pump is approximately twice that determined for potassium channels and valinomycin, as expected for a 3Na/2K pump stoichiometery (i.e., 2K/charge moved). For valinomycin-mediated potassium currents and gramicidin-mediated sodium currents, the ion fluxes calculated from diffusion models are typically 10–15% smaller than expected from the membrane currents. As presently implemented, the ISE methods allow reliable detection of calcium and proton fluxes equivalent to monovalent cation currents <1 pA in magnitude, and they allow detection of sodium and potassium fluxes equivalent to <5 pA currents. The

  8. Speckle-Tracking Echocardiography to Detect Cardiac Toxicity in Children Who Received Anthracyclines During Pregnancy.

    PubMed

    Avilès, Agustin; Nambo, Marìa-Jesus; Huerta-Guzmàn, Judith; Neri, Natividad; Cleto, Sergio

    2016-01-01

    Cardiac toxicities remain a possible risk to fetuses that received anthracyclines during pregnancy. The introduction of new echocardiographic techniques will improve the detection of early cardiac damage. Thus, we began a observational study using speckle-tracking echocardiography (STE) in children who had received anthracyclines during pregnancy, including the first trimester. From 2009 to 2013, we performed STE on patients > 5 years old, whose mothers had received anthracyclines during pregnancy. Siblings or cousins of equivalent age and gender were used as the control group. A total of 90 children fulfilled the entry criteria. Our results with STE were normal in all echocardiography parameters and did not show any differences when compared with the findings from the control group. We consider that the use of anthracyclines during pregnancy does not produce cardiac damage in newborns and can be safely administered, because no cardiac toxicity was evident in these children and it is of benefit to the mother. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. 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.

  10. 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.

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

    PubMed Central

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

    2015-01-01

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

  12. 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.

  13. Development and evaluation of a new fully automatic motion detection and correction technique in cardiac SPECT imaging.

    PubMed

    Bai, Chuanyong; Maddahi, Jamshid; Kindem, Joel; Conwell, Richard; Gurley, Michael; Old, Rex

    2009-01-01

    In cardiac SPECT perfusion imaging, motion correction of the data is critical to the minimization of motion introduced artifacts in the reconstructed images. Software-based (data-driven) motion correction techniques are the most convenient and economical approaches to fulfill this purpose. However, the accuracy is significantly affected by how the data complexities, such as activity overlap, non-uniform tissue attenuation, and noise are handled. We developed STASYS, a new, fully automatic technique, for motion detection and correction in cardiac SPECT. We evaluated the performance of STASYS by comparing its effectiveness of motion correcting patient studies with the current industry standard software (Cedars-Sinai MoCo) through blind readings by two readers independently. For 204 patient studies from multiple clinical sites, the first reader identified (1) 69 studies with medium to large axial motion, of which STASYS perfectly or significantly corrected 86.9% and MoCo 72.5%; and (2) 20 studies with medium to large lateral motion, of which STASYS perfectly or significantly corrected 80.0% and MoCo 60.0%. The second reader identified (1) 84 studies with medium to large axial motion, of which STASYS perfectly or significantly corrected 82.2% and MoCo 76.2%; and (2) 34 studies with medium to large lateral motion, of which STASYS perfectly or significantly corrected 58.9% and MoCo 50.0%. We developed a fully automatic software-based motion correction technique, STASYS, for cardiac SPECT. Clinical studies showed that STASYS was effective and corrected a larger percent of cardiac SPECT studies than the current industrial standard software.

  14. Colorectal patients and cardiac arrhythmias detected on the surgical high dependency unit.

    PubMed Central

    Batra, G. S.; Molyneux, J.; Scott, N. A.

    2001-01-01

    INTRODUCTION: Surgical high dependency unit (SHDU) care is becoming an integral feature of colorectal surgical practice. Routine ECG monitoring is a feature of surgical care in this setting. The aim of this study was to determine the incidence and outcome of cardiac arrhythmias detected in an SHDU population of colorectal patients. PATIENTS AND METHODS: 226 patients over a 12 month period were admitted to a 6-bedded SHDU under the care of 3 colorectal surgeons. A total of 29 patients (13%) had significant arrhythmias on ECG monitoring (median age 74 years, range 35-88 years). Pre-existing ischaemic heart disease was present in 9 patients--colorectal cancer and inflammatory bowel disease accounted for the underlying problem in the majority of these patients. RESULTS: Equal numbers of supraventricular and ventricular arrhythmias were detected--atrial fibrillation being the most commonly detected abnormality. Therapeutic intervention (electrolyte correction and anti-arrhythmic agents) was required in 23 patients. One patient required DC shock for ventricular fibrillation. Seven patients were transferred to the heart care unit or intensive care unit to manage their cardiac problems. Two patients died as a result of their cardiac problem, 27 were discharged home alive--3 on long-term anti-arrhythmic therapy. CONCLUSIONS: The postoperative environment of colorectal patients has been radically altered by the introduction of the SHDU. If colorectal surgeons are to remain central to the postoperative care of their patients, all surgical staff will require training in the recognition and protocol prevention and management of cardiac arrhythmias. Certification of colorectal surgeons in advanced life support is more relevant to colorectal surgery than certification in trauma care. Images Figure 1 PMID:11432135

  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. Emergence of Orai3 activity during cardiac hypertrophy

    PubMed Central

    Saliba, Youakim; Keck, Mathilde; Marchand, Alexandre; Atassi, Fabrice; Ouillé, Aude; Cazorla, Olivier; Trebak, Mohamed; Pavoine, Catherine; Lacampagne, Alain; Hulot, Jean-Sébastien; Farès, Nassim; Fauconnier, Jérémy; Lompré, Anne-Marie

    2015-01-01

    Aims Stromal interaction molecule 1 (STIM1) has been shown to control a calcium (Ca2+) influx pathway that emerges during the hypertrophic remodelling of cardiomyocytes. Our aim was to determine the interaction of Orai1 and Orai3 with STIM1 and their role in the constitutive store-independent and the store-operated, STIM1-dependent, Ca2+ influx in cardiomyocytes. Methods and results We characterized the expression profile of Orai proteins and their interaction with STIM1 in both normal and hypertrophied adult rat ventricular cardiomyocytes. Orai1 and 3 protein levels were unaltered during the hypertrophic process and both proteins co-immunoprecipitated with STIM1. The level of STIM1 and Orai1 were significantly greater in the macromolecular complex precipitated by the Orai3 antibody in hypertrophied cardiomyocytes. We then used a non-viral method to deliver Cy3-tagged siRNAs in vivo to adult ventricular cardiomyocytes and silence Orai channel candidates. Cardiomyocytes were subsequently isolated then the voltage-independent, i.e. store-independent and store-operated Ca2+ entries were measured on Fura-2 AM loaded Cy3-labelled and control isolated cardiomyocytes. The whole cell patch-clamp technique was used to measure Orai-mediated currents. Specific Orai1 and Orai3 knockdown established Orai3, but not Orai1, as the critical partner of STIM1 carrying these voltage-independent Ca2+ entries in the adult hypertrophied cardiomyocytes. Orai3 also drove an arachidonic acid-activated inward current. Conclusion Cardiac Orai3 is the essential partner of STIM1 and drives voltage-independent Ca2+ entries in adult cardiomyocytes. Arachidonic acid-activated currents, which are supported by Orai3, are present in adult cardiomyocytes and increased during hypertrophy. PMID:25213556

  17. 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.

  18. Both central command and exercise pressor reflex activate cardiac sympathetic nerve activity in decerebrate cats

    PubMed Central

    Tsuchimochi, Hirotsugu; Hayes, Shawn G.; McCord, Jennifer L.; Kaufman, Marc P.

    2009-01-01

    Both static and dynamic exercise are known to increase cardiac pump function as well as arterial blood pressure. Feedforward control by central command and feedback control by the exercise pressor reflex are thought to be the neural mechanisms causing these effects during exercise. It remains unknown as to how each mechanism activates cardiac sympathetic nerve activity (CSNA) during exercise, especially at its onset. Thus we examined the response of CSNA to stimulation of the mesencephalic locomotor region (MLR, i.e., central command) and to static muscle contraction of the triceps surae muscles or stretch of the calcaneal tendon in decerebrate cats. We found that MLR stimulation immediately increased CSNA, which was followed by a gradual increase in heart rate, mean arterial pressure, and ventral root activity in a stimulus intensity-dependent manner. The latency of the increase in CSNA from the onset of MLR stimulation ranged from 67 to 387 ms. Both static contraction and tendon stretch also rapidly increased CSNA. Their latency from the development of tension in response to ventral root stimulation ranged from 78 to 670 ms. These findings suggest that both central command and the muscle mechanoreflex play a role in controlling cardiac sympathetic outflow at the onset of exercise. PMID:19234088

  19. 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.

  20. Spatial repolarization heterogeneity detected by magnetocardiography correlates with cardiac iron overload and adverse cardiac events in beta-thalassemia major.

    PubMed

    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

    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. 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*. Multichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events.

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

    PubMed

    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

    2015-04-21

    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.

  2. 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

  3. 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.

  4. 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.

  5. 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

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

    PubMed

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

    2016-01-01

    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. 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. 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. 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 stronger predictor of cardiac iron in study

  7. Resveratrol, an activator of SIRT1, upregulates AMPK and improves cardiac function in heart failure.

    PubMed

    Gu, X S; Wang, Z B; Ye, Z; Lei, J P; Li, L; Su, D F; Zheng, X

    2014-01-21

    Reduced AMP-activated protein kinase (AMPK) expression has been shown to play a significant role in the cardiac dysfunction in heart failure. This study was designed to examine the effect of resveratrol, a potent activator of silent information regulator (SIRT1), on cardiac function and AMPK expression in heart failure. Adult male rat left anterior descending arteries were ligated, and they were fed with either a regular diet or a diet enriched with resveratrol. Heart failure was produced by myocardial infarction, and was associated with markedly increased AMPK and SIRT1 protein levels. Resveratrol treatment had a tremendous beneficial effect, both in terms of improving AMPK expression and on cardiac function. Decreased cardiac function and AMPK expression were also found in SIRT1 knockout (+/-) mice. In cultured cardiomyocytes, resveratrol increased AMPK and SIRT1 expressions, and overexpression of SIRT1 was found to be sufficient to activate AMPK in H9c2 cells. In contrast, pretreatment of cardiomyocytes with an SIRT1 antagonist, nicotinamide, blocked these beneficial effects of resveratrol. Therefore, the protective effects of resveratrol were found to be dependent on its ability to activate SIRT1 and improve AMPK expression. These results demonstrated that in heart failure, the enzymatic activity of cardiac SIRT1 is increased, which contributes to increased expression of AMPK, and resveratrol enhances the expression of AMPK and improves cardiac function through the activation of SIRT1.

  8. 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.

  9. Cardiac valve replacement in patients with active infective endocarditis.

    PubMed

    Wilson, W R; Geraci, J E

    1983-12-01

    Since the introduction of effective antimicrobial therapy, the leading cause of death in patients with infective endocarditis is no longer sepsis but, rather, congestive heart failure. The mortality is higher in patients with severe heart failure due to infective endocarditis who are treated with medical therapy only than in those who additionally undergo cardiac valve replacement. The mortality is also higher in patients with severe heart failure due to aortic infective endocarditis (40 to 93%) than in those with heart failure due to mitral infective endocarditis (17 to 66%). In patients with and in those without infective endocarditis, surgical intervention can be carried out with comparable mortality not only for aortic valve replacement (9 vs 8.4%) but also overall for valve replacement (10 vs 12%). In patients with class IV heart failure, overall mortality of valve replacement was higher (17%) than in patients with class II (8%) or class III heart failure (7%) and, similarly, comparable with that of matched groups of patients without infective endocarditis. In patients with class IV disability, the mortality of valve replacement was higher in those with active infective endocarditis (19%) than in those with inactive infective endocarditis, possibly due to a higher incidence of sudden onset of severe aortic regurgitation and myocardial abscess. No patient with valve replacement for inactive infective endocarditis developed prosthetic valve endocarditis; a single case of prosthetic valve endocarditis occurred in a patient with active infective endocarditis. In general, early surgical intervention is preferable to procrastination in the management of patients with progressive or severe heart failure due to infective endocarditis. Although, in at least 70% of patients, blood cultures may be rendered sterile within one week of initiation of appropriate antimicrobial therapy, patients with infective endocarditis due to staphylococci, multiply-resistant gram

  10. Detectability of perfusion defect in five-dimensional gated-dynamic cardiac SPECT images.

    PubMed

    Niu, Xiaofeng; Yang, Yongyi; King, Michael A; Wernick, Miles N

    2010-09-01

    In previous work, the authors developed and demonstrated the concept of an image reconstruction procedure aimed to unify gated and dynamic nuclear cardiac imaging, which the authors have termed five-dimensional (5D) SPECT. Gated imaging permits the clinician to evaluate wall motion and, through the use of stress and rest scans, allows perfusion defects to be observed. Dynamic imaging depicts kinetics in the myocardium, which can be used to evaluate perfusion, but traditional dynamic images are motionless and do not depict wall motion. In this article, the authors investigate the degree to which perfusion defects can be detected from the dynamic information conveyed by 5D images, a problem that is particularly challenging in the absence of multiple fast camera rotations. The authors first demonstrate the usefulness of dynamic reconstructed images for perfusion detection by using linear discriminant analyses (Fisher linear discriminant analysis and principal component analysis) and a numerical channelized Hotelling observer. The authors then derive three types of discriminant metrics for characterizing the temporal kinetic information in reconstructed dynamic images for differentiating perfusion defects from normal cardiac perfusion, which are the Fisher linear discriminant map, temporal derivative map, and kinetic parametric images. Results are based on the NURBS-based cardiac-torso phantom with simulation of Tc99m-teboroxime as the imaging agent. The derived metric maps and quantitative contrast-to-noise ratio results demonstrate that the reconstructed dynamic images could yield higher detectability of the perfusion defect than conventional gated reconstruction while providing wall motion information simultaneously. The proposed metrics can be used to produce new types of visualizations, showing wall motion and perfusion information, that may potentially be useful for clinical evaluation. Since 5D imaging permits wall motion and kinetics to be observed

  11. Compatibility of Radiofrequency Surgical Sponge Detection Technology with Cardiac Implantable Electronic Devices and Temporary Pacemakers.

    PubMed

    Salcedo, Jonathan D; Pretorius, Victor G; Hsu, Jonathan C; Lalani, Gautam G; Schricker, Amir A; Hebsur, Shrinivas M; McGARRY, Thomas J; Hunter, Jessica A; Lewis, Kathryn E; Krummen, David E; Feld, Gregory K; Birgersdotter-Green, Ulrika

    2016-11-01

    Radiofrequency (RF) technology has improved detection of retained surgical sponges with a reported 100% sensitivity and specificity. However, the potential for interactions of the RF signals emitted by the detection system with cardiac implantable electronic devices (CIEDs) or temporary pacemakers may limit its use in those patients with these devices. This study investigated whether RF detection technology causes interference or clinically significant changes in the programmed settings of implanted pacemakers and defibrillators or temporary epicardial pacemakers. Fifty patients who were scheduled either for CIED removal or placement of a temporary epicardial pacemaker (at the time of open heart surgery) were recruited for this study. Device settings and measurements from separate interrogations before and after scanning with the RF detection system were compared. For the temporary pacemakers, we observed for any changes in hemodynamics or signs of pacing interference. Twenty (40%) pacemakers, 20 (40%) implantable cardioverter defibrillators, and 10 (20%) temporary pacemakers were analyzed in this study. During scanning, no signal interference was detected in any permanent device, and there were no significant changes in programmed settings after scanning with the RF detection system. However, pacing inhibition was detected with temporary pacing systems when programmed to a synchronous mode (DDD). RF detection technology can be safely used to scan for retained surgical sponges in patients with permanent CIEDs and temporary pacemakers set to asynchronous mode. © 2016 Wiley Periodicals, Inc.

  12. Cardiac biomarkers for detection of myocardial infarction: perspectives from past to present.

    PubMed

    Rosalki, Sidney B; Roberts, Robert; Katus, Hugo A; Giannitsis, Evangelos; Ladenson, Jack H; Apple, Fred S

    2004-11-01

    With great pleasure and anticipation in recognition of Clinical Chemistry's 50th anniversary, I have been able to arm-twist four talented scientists to document their impressive marks on the science of diagnostics in the field of cardiac biomarkers and detection of myocardial infarction. Their exciting discoveries and applications have dramatically influenced the fields of laboratory medicine and cardiology and have greatly influenced the care and management of thousands of patients suffering from coronary artery disease leading to acute myocardial infarction. As a matter of historical record, I owe a great deal of thanks to each one of the coauthors of this special report because each one has personally influenced my scientific career. I met Dr. Rosalki, during my postdoctoral training, at a national AACC meeting, where he kindly answered my numerous queries regarding creatine kinase enzymology and muscle physiology. Dr. Roberts, while serving as Director of the Coronary Care Unit at Washington University in St. Louis, generously allowed this fledgling fellow into his laboratory and shared many of his clinical and experimental findings with me. Dr. Katus, whom I first met at a scientific meeting sponsored by Boehringer Mannheim in 1986 in Bavaria, where I first became fascinated with cardiac troponin T, has remained a friend and colleague. Lastly, Dr. Ladenson, who as mentor, scientific colleague, and close friend remains ultimately responsible for both my professional growth as a clinical chemist (he was my postdoctoral fellowship advisor) and for stimulating and encouraging my goals and aspirations in the field of cardiac biomarkers. With the descriptions of the ground-breaking science described below, I am extremely excited and optimistic that the future of cardiac biomarkers is secure and open to new discoveries by the Rosalkis, Robertses, Katuses, and Ladensons of the future.

  13. Graphene-gated biochip for the detection of cardiac marker Troponin I.

    PubMed

    Tuteja, Satish K; Priyanka; Bhalla, Vijayender; Deep, Akash; Paul, A K; Suri, C Raman

    2014-01-27

    We report lithium ion intercalation mediated efficient exfoliation of graphite to form monolithic graphene sheets which have subsequently been investigated for the development of highly sensitive label-free electrochemical detection platform for cardiac biomarker, Troponin I (cTnI). The spectroscopic and morphological analysis demonstrated the formation of defect free graphene sheets which were successfully employed to fabricate an inter-digited microdevice in a drain-source configuration on a silicon biochip. The graphene gated biochip functionalized with anti-cTnI antibodies used in label free detection of cTnI which exhibited an excellent sensitivity in the picogram range (~1 pg mL(-1)) for cTnI without the use of any enzymatic amplification that promises its potential applicability for bio-molecular detection in clinical diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. 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.

  15. 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.

  16. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. 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.

  18. Cardiac hyporesponsiveness in severe sepsis is associated with nitric oxide-dependent activation of G protein receptor kinase.

    PubMed

    Dal-Secco, Daniela; DalBó, Silvia; Lautherbach, Natalia E S; Gava, Fábio N; Celes, Mara R N; Benedet, Patricia O; Souza, Adriana H; Akinaga, Juliana; Lima, Vanessa; Silva, Katiussia P; Kiguti, Luiz Ricardo A; Rossi, Marcos A; Kettelhut, Isis C; Pupo, André S; Cunha, Fernando Q; Assreuy, Jamil

    2017-07-01

    G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP). Heart function was assessed by isolated and perfused heart, echocardiography, and β-adrenergic receptor binding. GRK2 was determined by immunofluorescence and Western blot analysis in the heart and isolated cardiac myocytes. Sepsis increased NOS2 expression in the heart, increased plasma nitrite + nitrate levels, and reduced isoproterenol-induced isolated ventricle contraction, whole heart tension development, and β-adrenergic receptor density. Treatment with 1400W or with GRK2 inhibitor prevented CLP-induced cardiac hyporesponsiveness 12 and 24 h after CLP. Increased labeling of total and phosphorylated GRK2 was detected in hearts after CLP. With treatment of 1400W or in hearts taken from septic NOS2 knockout mice, the activation of GRK2 was reduced. 1400W or GRK2 inhibitor reduced mortality, improved echocardiographic cardiac parameters, and prevented organ damage. Therefore, during sepsis, NOS2-derived NO increases GRK2, which leads to a reduction in β-adrenergic receptor density, contributing to the heart dysfunction. Isolated cardiac myocyte data indicate that NO acts through the soluble guanylyl cyclase/cGMP/PKG pathway. GRK2 inhibition may be a potential therapeutic target in sepsis-induced cardiac dysfunction.NEW & NOTEWORTHY The main novelty presented here is to show that septic shock induces cardiac hyporesponsiveness to isoproterenol by a mechanism dependent on nitric oxide and mediated by G protein-coupled receptor kinase isoform 2. Therefore

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation.

    PubMed

    Fujiu, Katsuhito; Shibata, Munehiko; Nakayama, Yukiteru; Ogata, Fusa; Matsumoto, Sahohime; Noshita, Koji; Iwami, Shingo; Nakae, Susumu; Komuro, Issei; Nagai, Ryozo; Manabe, Ichiro

    2017-05-01

    Heart failure is a complex clinical syndrome characterized by insufficient cardiac function. In addition to abnormalities intrinsic to the heart, dysfunction of other organs and dysregulation of systemic factors greatly affect the development and consequences of heart failure. Here we show that the heart and kidneys function cooperatively in generating an adaptive response to cardiac pressure overload. In mice subjected to pressure overload in the heart, sympathetic nerve activation led to activation of renal collecting-duct (CD) epithelial cells. Cell-cell interactions among activated CD cells, tissue macrophages and endothelial cells within the kidney led to secretion of the cytokine CSF2, which in turn stimulated cardiac-resident Ly6C(lo) macrophages, which are essential for the myocardial adaptive response to pressure overload. The renal response to cardiac pressure overload was disrupted by renal sympathetic denervation, adrenergic β2-receptor blockade or CD-cell-specific deficiency of the transcription factor KLF5. Moreover, we identified amphiregulin as an essential cardioprotective mediator produced by cardiac Ly6C(lo) macrophages. Our results demonstrate a dynamic interplay between the heart, brain and kidneys that is necessary for adaptation to cardiac stress, and they highlight the homeostatic functions of tissue macrophages and the sympathetic nervous system.

  6. 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…

  7. 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…

  8. Adiponectin protects against angiotensin II-induced cardiac fibrosis through activation of PPAR-alpha.

    PubMed

    Fujita, Koichi; Maeda, Norikazu; Sonoda, Mina; Ohashi, Koji; Hibuse, Toshiyuki; Nishizawa, Hitoshi; Nishida, Makoto; Hiuge, Aki; Kurata, Akifumi; Kihara, Shinji; Shimomura, Iichiro; Funahashi, Tohru

    2008-05-01

    Adiponectin is recognized as an antidiabetic, antiatherosclerotic, and anti-inflammatory protein derived from adipocytes. However, the role of adiponectin in cardiac fibrosis remains uncertain. We herein explore the effects of adiponectin on cardiac fibrosis induced by angiotensin II (Ang II). Wild-type (WT), adiponectin knockout (Adipo-KO), and PPAR-alpha knockout (PPAR-alpha-KO) mice were infused with Ang II at 1.2 mg/kg/d. Severe cardiac fibrosis and left ventricular dysfunction were observed in Ang II-infused Adipo-KO mice compared to WT mice. Adenovirus-mediated adiponectin treatment improved the above phenotypes and the dysregulation of reactive oxygen species (ROS)-related mRNAs in Adipo-KO mice, whereas such amelioration was not observed in PPAR-alpha-KO mice despite adiponectin accumulation in heart tissue. In cultured cardiac fibroblasts, adiponectin improved the reduction of AMP-activated protein kinase (AMPK) activity and elevation of extracellular signal-regulated kinase 1/2 (ERK1/2) activity induced by Ang II. Adiponectin significantly enhanced PPAR-alpha activity, whereas the adiponectin-dependent PPAR-alpha activation was diminished by Compound C, an inhibitor of AMPK. The present study suggests that adiponectin protects against Ang II-induced cardiac fibrosis possibly through AMPK-dependent PPAR-alpha activation.

  9. 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.

  10. The transcutaneous oxygen challenge test: a noninvasive method for detecting low cardiac output in septic patients.

    PubMed

    He, Huai-Wu; Liu, Da-Wei; Long, Yun; Wang, Xiao-Ting; Chai, Wen-Zhao; Zhou, Xiang

    2012-02-01

    The transcutaneous partial pressure of oxygen (PtcO₂) index has been used to detect low-flow state in circulatory failure, but the value of the transcutaneous oxygen challenge test (OCT) to estimate low cardiac output has not been thoroughly evaluated. The prospective observational study examined 62 septic patients requiring PiCCO-Plus for cardiac output monitoring. Simultaneous basal blood gases from the arterial, central venous catheters were obtained. Cardiac indices were measured by the transpulmonary thermodilution technique at the same time, then the 10-min inspired 1.0 fractional inspired oxygen concentration (FIO₂) defined as the OCT was performed. Transcutaneous partial pressure of oxygen was measured continuously by using a noninvasive transcutaneous monitor throughout the test. The values for arterial pressure of oxygen (PaO₂) were examined on inspired of 1.0 FIO₂. We calculated the PtcO₂ index = (baseline PtcO₂/baseline PaO₂), 10-min OCT (10 OCT) = (PtcO₂ after 10 min on inspired 1.0 O₂) - (baseline PtcO₂), and the oxygen challenge index = (10 OCT) / (PaO₂ on inspired 1.0 O₂ - baseline PaO₂). Patients were divided into two groups: a normal cardiac index (CI) group with CI of greater than 3 L/min per m (n = 41) and a low CI group with CI of 3 L/min per m or less (n = 21). The 10 OCT and the oxygen challenge index predicted a low CI (≤ 3 L/min per m) with an accuracy that was similar to central venous oxygen saturation, which was significantly better than the PtcO₂ index. For a 10 OCT value of 53 mmHg, sensitivity was 0.83; specificity, 0.86; a positive predictive value, 0.92; and a negative predictive value, 0.72 for detecting CI of 3 L/min per m or less. We propose that the OCT substituted for the PtcO₂ index as an accurate alternative method of PtcO₂ for revealing low CI in septic patients.

  11. 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

  12. Cardiac function as related to adrenergic activity in hypertensive left ventricular hypertrophy.

    PubMed

    Agabiti-Rosei, E; Muiesan, M L; Romanelli, G; Castellano, M; Beschi, M; Alicandri, C; Muiesan, G

    1987-06-01

    Studies in experimental animals and in hypertensive patients have shown that changes in cardiac anatomy and function are not just a simple consequence of the increased pressure load. The activity of the sympathetic nervous system is one of the factors that may influence cardiac performance and also, possibly, the cardiac anatomy of hypertensive patients. Animal studies have strongly suggested a possible role of adrenergic factors in the development of left ventricular hypertrophy. In man, plasma catecholamines are usually higher in hypertensive patients with left ventricular hypertrophy, and a correlation between left ventricular mass and plasma noradrenaline has also been observed. The decrease of cardiac performance after acute beta blockade has been found to be directly related to basal plasma noradrenaline concentration. An impaired response to beta-adrenergic stimulation has been reported in hypertensive animals and has been confirmed in hypertensive patients with left ventricular hypertrophy.

  13. 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.

  14. 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

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

    Thompson, Jeremy; Hu, Ying; Lesnefsky, Edward J.

    2015-01-01

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

  17. 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.

  18. 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

  19. 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.

  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. 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.

  2. 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

  3. Differential effect of oestrogen on post-exercise cardiac muscle myeloperoxidase and calpain activities in female rats.

    PubMed

    Tiidus, P M; Zajchowski, S; Enns, D; Holden, D; Bombardier, E; Belcastro, A N

    2002-02-01

    The effects of oestrogen administration on 1 h post-exercise cardiac muscle myeloperoxidase (MPO) and calpain activities were determined in female rats. Rats were ovariectomized and implanted for 2 weeks with either oestrogen (25 mg 17-oestradiol) or placebo pellets or left with ovaries intact. Rats were then run for 1 h at 21 m min-1, 12% grade, killed 1 h post-exercise and cardiac muscle and blood samples were removed. Control animals from each group were killed without prior exercise. Serum oestrogen levels in the order of the highest to lowest were; ovariectomized oestrogen replaced rats > intact ovaries rats > ovariectomized placebo rats. Oestrogen induced significant (P < 0.05) elevations in cardiac MPO activity at rest and at 1 h post-exercise in ovariectomized rats. No significant elevations in cardiac MPO activity were evident in placebo ovariectomized or normal ovary rats at rest or post-exercise. Cardiac calpain activities were similar in all unexercised groups. Ovariectomized placebo and intact ovary rats had significantly (P < 0.05) elevated cardiac calpain activities 1 h post-exercise while calpain activity was not significantly elevated in hearts from ovariectomized oestrogen rats. These results demonstrate that oestrogen supplementation in ovariectomized rats induces elevations in cardiac muscle MPO activities at rest and at 1 h post-exercise. This is opposite to the effect of oestrogen in post-exercise skeletal muscle and implies a greater neutrophil infiltration into cardiac muscle caused by oestrogen. This effect cannot be explained by changes in 1 h post-exercise cardiac muscle calpain activity, the elevation of which was suppressed by oestrogen administration. Oestrogen influences cardiac calpain activity similarly to its effect in skeletal muscle. Thus, oestrogen administration to ovariectomized rats induces elevations in cardiac MPO activity while suppressing cardiac calpain activity.

  4. Cardiac imaging to detect coronary artery disease in athletes aged 35 years and older. A scoping review.

    PubMed

    Braber, Thijs L; Reitsma, Johannes B; Mosterd, Arend; Willemink, Martin J; Prakken, Niek H J; Halle, Martin; Sharma, Sanjay; Velthuis, Birgitta K

    2017-08-23

    Sudden cardiac death (SCD) is a devastating event in athletes. Screening efforts that were first directed at athletes younger than 35 years, are now focusing on the rapidly growing group of older sportspersons. Athletes aged ≥35 years have a 10-fold increased risk of exercise-related cardiac arrest, mostly due to coronary artery disease (CAD). Although cardiac imaging is pivotal in identifying CAD, the role of imaging modalities in screening asymptomatic older sportspersons remains unclear. We performed a scoping review to identify the role of cardiac imaging to detect CAD in older sportspersons and to identify gaps in the existing literature. We searched Medline, Embase and the Cochrane library for studies reporting data on cardiac imaging of CAD in sportspersons ≥35 years. The systematic search yielded 1737 articles and 14 were included in this scoping review. Imaging modalities included 2 echocardiography, 1 unenhanced Computed Tomography (CT) for coronary artery calcium scoring (CACS), 3 CACS and contrast-enhanced CT angiography (CCTA), 2 CACS and Cardiac Magnetic Resonance (CMR), 1 CCTA with CMR and echocardiography, 2 CCTA, 2 CMR, and 1 myocardial perfusion imaging article. The low number of relevant articles and the selection bias introduced by studying specific groups, like veteran marathon runners, indicate the need for future research. Cardiac CT (CACS and CCTA) probably has the highest potential for pre-participation screening, with high diagnostic value to detect CAD and low radiation dose. However, currently there is insufficient evidence for incorporating routine cardiac imaging in the pre-participation screening of asymptomatic sportspersons over 35 years. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. 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.

  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. 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

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

    PubMed

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

    2014-01-01

    to assess the intensity and site of pain after Cardiac Surgery through sternotomy during rest and while performing five activities. descriptive study with a prospective cohort design. A total of 48 individuals participated in the study. A Multidimensional Scale for Pain Assessment was used. 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. 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.

  9. Association between patient activity and long-term cardiac death in patients with implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators.

    PubMed

    Zhao, Shuang; Chen, Keping; Su, Yangang; Hua, Wei; Chen, Silin; Liang, Zhaoguang; Xu, Wei; Dai, Yan; Liu, Zhimin; Fan, Xiaohan; Hou, Cuihong; Zhang, Shu

    2017-05-01

    Background Patient activity (PA) has been demonstrated to predict all-cause mortality. However, the association between PA and cardiac death is unclear. Aims The aims of this study were to determine whether PA can predict cardiac death and what is the cut-off of PA to discriminate cardiac death, as well as the mechanism underlying the relationship between PA and survival in patients with home monitoring. Methods This study retrospectively analysed clinical and implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator device data in 845 patients. Data regarding PA and PP variability during the first 30-60 days of home monitoring were collected, and mean values were calculated. The primary endpoint was cardiac death, and the secondary endpoint was all-cause mortality. Results The mean PA percentage was 11 ± 5.8%. Based on receiver operating characteristic curve analysis, we determined that a PA cut-off value of 7.84% (113 min) can predict cardiac death. During a mean follow-up period of 31.1 ± 12.9 months (ranging from three to 60 months), PA ≤ 7.84% was associated with increased risks of cardiac death in an unadjusted analysis; after adjusting in a multivariate Cox model, the relationship remained significant between PA≤7.84% and cardiac death (hazard ratio = 3.644, 95% confidence interval = 2.424-5.477, p < 0.001). Moreover, a significant correlation was observed between PA and PP variability ( r = 0.601, p < 0.001). Conclusions A baseline PA ≤ 7.84% was associated with a higher risk of cardiac death in patients who have survived more than three months after implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator implantation. PA had a sizable effect on heart rate variability, reflecting autonomic function.

  10. 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.

  11. The utility of cardiac stress testing for detection of cardiovascular disease in breast cancer survivors: a systematic review.

    PubMed

    Kirkham, Amy A; Virani, Sean A; Campbell, Kristin L

    2015-01-01

    Heart function tests performed with myocardial stress, or "cardiac stress tests", may be beneficial for detection of cardiovascular disease. Women who have been diagnosed with breast cancer are more likely to develop cardiovascular diseases than the general population, in part due to the direct toxic effects of cancer treatment on the cardiovascular system. The aim of this review was to determine the utility of cardiac stress tests for the detection of cardiovascular disease after cardiotoxic breast cancer treatment. Systematic review. Medline and Embase were searched for studies utilizing heart function tests in breast cancer survivors. Studies utilizing a cardiac stress test and a heart function test performed at rest were included to determine whether stress provided added benefit to identifying cardiac abnormalities that were undetected at rest within each study. Fourteen studies were identified. Overall, there was a benefit to utilizing stress tests over tests at rest in identifying evidence of cardiovascular disease in five studies, a possible benefit in five studies, and no benefit in four studies. The most common type of stress test was myocardial perfusion imaging, where reversible perfusion defects were detected under stress in individuals who had no defects at rest, in five of seven studies of long-term follow-up. Two studies demonstrated the benefit of stress echocardiography over resting echocardiography for detecting left ventricular dysfunction in anthracycline-treated breast cancer survivors. There was no benefit of stress cardiac magnetic resonance imaging in one study. Two studies showed a potential benefit of stress electrocardiography, whereas three others did not. The use of cardiac stress with myocardial perfusion imaging and echocardiography may provide added benefit to tests performed at rest for detection of cardiovascular disease in breast cancer survivors, and merits further research.

  12. The utility of cardiac stress testing for detection of cardiovascular disease in breast cancer survivors: a systematic review

    PubMed Central

    Kirkham, Amy A; Virani, Sean A; Campbell, Kristin L

    2015-01-01

    Background Heart function tests performed with myocardial stress, or “cardiac stress tests”, may be beneficial for detection of cardiovascular disease. Women who have been diagnosed with breast cancer are more likely to develop cardiovascular diseases than the general population, in part due to the direct toxic effects of cancer treatment on the cardiovascular system. The aim of this review was to determine the utility of cardiac stress tests for the detection of cardiovascular disease after cardiotoxic breast cancer treatment. Design Systematic review. Methods Medline and Embase were searched for studies utilizing heart function tests in breast cancer survivors. Studies utilizing a cardiac stress test and a heart function test performed at rest were included to determine whether stress provided added benefit to identifying cardiac abnormalities that were undetected at rest within each study. Results Fourteen studies were identified. Overall, there was a benefit to utilizing stress tests over tests at rest in identifying evidence of cardiovascular disease in five studies, a possible benefit in five studies, and no benefit in four studies. The most common type of stress test was myocardial perfusion imaging, where reversible perfusion defects were detected under stress in individuals who had no defects at rest, in five of seven studies of long-term follow-up. Two studies demonstrated the benefit of stress echocardiography over resting echocardiography for detecting left ventricular dysfunction in anthracycline-treated breast cancer survivors. There was no benefit of stress cardiac magnetic resonance imaging in one study. Two studies showed a potential benefit of stress electrocardiography, whereas three others did not. Conclusion The use of cardiac stress with myocardial perfusion imaging and echocardiography may provide added benefit to tests performed at rest for detection of cardiovascular disease in breast cancer survivors, and merits further research. PMID

  13. Pulmonary and cardiac sequelae of subarachnoid haemorrhage: time for active management?

    PubMed

    Macmillan, C S A; Grant, I S; Andrews, P J D

    2002-08-01

    Cardiac injury and pulmonary oedema occurring after acute neurological injury have been recognised for more than a century. Catecholamines, released in massive quantities due to hypothalamic stress from subarachnoid haemorrhage (SAH), result in specific myocardial lesions and hydrostatic pressure injury to the pulmonary capillaries causing neurogenic pulmonary oedema (NPO). The acute, reversible cardiac injury ranges from hypokinesis with a normal cardiac index, to low output cardiac failure. Some patients exhibit both catastrophic cardiac failure and NPO, while others exhibit signs of either one or other, or have subclinical evidence of the same. Hypoxia and hypotension are two of the most important insults which influence outcome after acute brain injury. However, despite this, little attention has hitherto been devoted to prevention and reversal of these potentially catastrophic medical complications which occur in patients with SAH. It is not clear which patients with SAH will develop important cardiac and respiratory complications. An active approach to investigation and organ support could provide a window of opportunity to intervene before significant hypoxia and hypotension develop, potentially reducing adverse consequences for the long-term neurological status of the patient. Indeed, there is an argument for all SAH patients to have echocardiography and continuous monitoring of respiratory rate, pulse oximetry, blood pressure and electrocardiogram. In the event of cardio-respiratory compromise developing i.e. cardiogenic shock and/or NPO, full investigation, attentive monitoring and appropriate intervention are required immediately to optimise cardiorespiratory function and allow subsequent definitive management of the SAH.

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

    PubMed

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

    Diabetes mellitus is a prominent risk factor for cardiovascular diseases. Diabetic cardiomyopathy is an important complication of the heart independent of hypertension and coronary artery disease and is accompanied by cardiac hypertrophy. Cardiac hypertrophy easily leads to heart failure, which is a leading cause of morbidity and mortality. Glucagon-like peptide 1 (GLP-1) is an incretin hormone, which has various beneficial roles in the cardiovascular system, and exendin-4 is a highly potent glucagon-like peptide 1 receptor agonist. However, the role of GLP-1 in cardiac hypertrophy remains unknown. Our study revealed that exendin-4 treatment ameliorated phenylephrine (PE)-induced cardiac hypertrophy, which presented as decreased cardiac hypertrophic markers (ANP, BNP, and β-MHC) and cell surface area. This condition was significantly reversed upon treatment with the GLP-1 receptor antagonist exendin9-39. We also discovered that Erk1/2 and AMPK signaling pathways were involved in this process. Furthermore, our data demonstrate that the AMPK inhibitor compound C inhibited the anti-hypertrophic effect of exendin-4, which is associated with the mTOR/p70S6K/4-EBP1 signaling pathway. Finally, exendin-4 enhanced the anti-hypertrophic effect of rapamycin. In summary, our study disclosed that exedin-4 inhibits cardiac hypertrophy by upregulating GLP-1 receptor expression and activating the AMPK/mTOR signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

  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. 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

  17. 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

  18. 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

  19. Equivalent Moving Dipole Localization of Cardiac Ectopic Activity in a Swine Model during Pacing

    PubMed Central

    Lai, Dakun; Liu, Chenguang; Eggen, Michael D.; Iaizzo, Paul. A.; He, Bin

    2010-01-01

    Localization of the initial site of cardiac ectopic activity has direct clinical benefits for treating focal cardiac arrhythmias. The aim of the present study is to experimentally evaluate the performance of the equivalent moving dipole technique on non-invasively localizing the origin of the cardiac ectopic activity from body surface potential maps (BSPMs) in a well-controlled experimental setting. The cardiac ectopic activities were induced in 4 well-controlled intact pigs by either single-site pacing or dual-site pacing within the ventricles. In each pacing study, the initiation sites (ISs) of cardiac ectopic activity were localized by estimating the locations of a single moving dipole (SMD) or two moving dipoles (TMDs) from the measured BSPMs, and compared with the precise pacing sites (PSs). For the single-site pacing, the averaged SMD localization error was 18.6 ± 3.8 mm over 16 sites, while the averaged distance between the TMD locations and the two corresponding pacing sites was slightly larger (24.9 ± 6.2 mm over 5 pairs of sites), both occurring at the onset of the QRS complex (10–25 ms following the pacing spike). The obtained SMD trajectories originated near the stimulus site and then traversed across the heart during the ventricular depolarization. The present experimental results show that the initial location of the moving dipole can provide the approximate site of origin of a cardiac ectopic activity in vivo, and that the migration of the dipole can portray the passage of an ectopic beat across the heart. PMID:20515710

  20. Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-β/Smad3 pathway.

    PubMed

    Chen, Tongshuai; Li, Jingyuan; Liu, Junni; Li, Na; Wang, Shujian; Liu, Hui; Zeng, Mei; Zhang, Yun; Bu, Peili

    2015-03-01

    Sirtuins [sirtuin (SIRT)1-SIRT7] mediate the longevity-promoting effects of calorie restriction in yeast, worms, flies, and mice. Additionally, SIRT3 is the only SIRT analog whose increased expression has been shown to be associated with longevity in humans. The polyphenol resveratrol (RSV) is the first compound discovered able to mimic calorie restriction by stimulating SIRTs. In the present study, we report that RSV activated SIRT3 in cardiac fibroblasts both in vivo and in vitro. Moreover, in wild-type mice, RSV prevented cardiac hypertrophy in response to hypertrophic stimuli. However, this protective effect was not observed in SIRT3 knockout mice. Additionally, the activation of SIRT3 by RSV ameliorated collagen deposition and improved cardiac function. In isolated cardiac fibroblasts, pretreatment with RSV suppressed fibroblast-to-myoblast transformation by inhibiting the transforming growth factor-β/Smad3 pathway. Therefore, these data indicate that the activation of SIRT3 by RSV could ameliorate cardiac fibrosis and improve cardiac function via the transforming growth factor-β/Smad3 pathway. Copyright © 2015 the American Physiological Society.

  1. 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.

  2. 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).

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

    PubMed

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

    2016-03-15

    We have demonstrated highly sensitive and label-free detection of cardiac troponin I (cTnI), a biomarker for diagnosis of acute myocardial infarction, using silicon nanowire field-effect transistors. A honeycomb-like structure is utilized for nanowire configuration to offer improved electrical performance and increased sensing area. The fabricated devices show n-type behavior with a relatively high ON-OFF current ratio, small sub-threshold swing and low gate leakage current. Monoclonal antibodies for cTnI were covalently immobilized on the nanowire surface and the attachment of antibodies is clearly visualized by atomic force microscope. The sensitivity with various concentrations of buffer solution was also investigated in order to determine the optimal buffer condition. The devices exhibit highest sensitivity under buffer solutions with low ion concentration. In addition, the detection limit of the sensor is as low as ~5 pg/mL, the lowest reported in the literature to date and nearly an order of magnitude smaller than the suggested threshold limit. The fabricated devices demonstrate a good selectivity for detecting cTnI. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. 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.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Motivational counselling for physical activity in patients with coronary artery disease not participating in cardiac rehabilitation.

    PubMed

    Reid, Robert D; Morrin, Louise I; Higginson, Lyall A J; Wielgosz, Andreas; Blanchard, Chris; Beaton, Louise J; Nelson, Chantal; McDonnell, Lisa; Oldridge, Neil; Wells, George A; Pipe, Andrew L

    2012-04-01

    Many patients with coronary artery disease (CAD) fail to attend cardiac rehabilitation following acute coronary events because they lack motivation to exercise. Theory-based approaches to promote physical activity among non-participants in cardiac rehabilitation are required. A randomized trial comparing physical activity levels at baseline, 6, and 12 months between a motivational counselling (MC) intervention group and a usual care (UC) control group. One hundred and forty-one participants hospitalized with acute coronary syndromes not planning to attend cardiac rehabilitation were recruited at a single centre and randomized to either MC (n = 69) or UC (n = 72). The MC intervention, designed from an ecological perspective, included one face-to-face contact and eight telephone contacts with a trained physiotherapist over a 52-week period. The UC group received written information about starting a walking programme and brief physical activity advice from their attending cardiologist. Physical activity was measured by: 7-day physical activity recall interview; self-report questionnaire; and pedometer at baseline, 6, and 12 months after randomization. Latent growth curve analyses, which combined all three outcome measures into a single latent construct, showed that physical activity increased more over time in the MC versus the UC group (µ(add) = 0.69, p < 0.05). Patients with CAD not participating in cardiac rehabilitation receiving a theory-based motivational counselling intervention were more physically active at follow-up than those receiving usual care. This intervention may extend the reach of cardiac rehabilitation by increasing physical activity in those disinclined to participate in structured programmes.

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

    PubMed

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

    2016-04-04

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

  10. Peroxisome proliferator-activated receptor-alpha and receptor-gamma activators prevent cardiac fibrosis in mineralocorticoid-dependent hypertension.

    PubMed

    Iglarz, Marc; Touyz, Rhian M; Viel, Emilie C; Paradis, Pierre; Amiri, Farhad; Diep, Quy N; Schiffrin, Ernesto L

    2003-10-01

    Peroxisome proliferator-activated receptor (PPAR) activation may prevent cardiac hypertrophy and inhibit production of endothelin-1 (ET-1), a hypertrophic agent. The aim of this in vivo study was to investigate the effects of PPAR activators on cardiac remodeling in DOCA-salt rats, a model overexpressing ET-1. Unilaterally nephrectomized 16-week-old Sprague-Dawley rats (Uni-Nx) were randomly divided into 4 groups: control rats, DOCA-salt, DOCA-salt+rosiglitazone (PPAR-gamma activator, 5 mg/kg per day), and DOCA-salt+fenofibrate (PPAR-alpha activator, 100 mg/kg per day). After 3 weeks of treatment, mean arterial blood pressure was significantly increased in DOCA-salt by 36 mm Hg. Mean arterial blood pressure was normalized by coadministration of rosiglitazone but not by fenofibrate. Both PPAR activators prevented cardiac fibrosis and abrogated the increase in prepro-ET-1 mRNA content in the left ventricle of DOCA-salt rats. Coadministration of rosiglitazone or fenofibrate failed to prevent thickening of left ventricle (LV) walls as measured by echocardiography and the increase in atrial natriuretic peptide mRNA levels. However, rosiglitazone and fenofibrate prevented the decrease in LV internal diameter and thus concentric remodeling of the LV found in DOCA-salt rats. Taken together, these data indicate a modulatory role of PPAR activators on cardiac remodeling in mineralocorticoid-induced hypertension, in part associated with decreased ET-1 production.

  11. 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

  12. Exploration of flexible phenylpropylurea scaffold as novel cardiac myosin activators for the treatment of systolic heart failure.

    PubMed

    Manickam, Manoj; Jalani, Hitesh B; Pillaiyar, Thanigaimalai; Sharma, Niti; Boggu, Pulla Reddy; Venkateswararao, Eeda; Lee, You-Jung; Jeon, Eun-Seok; Jung, Sang-Hun

    2017-07-07

    A series of flexible urea derivatives have been synthesized and demonstrated as selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3-phenylpropyl)urea (1, cardiac myosin ATPase activation at 10 μM = 51.1%; FS = 18.90; EF = 12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase activation = 53.3%; FS = 30.04; EF = 18.27) showed significant activity in vitro and in vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1-(3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin ATPase activation = 81.4%; FS = 20.50; EF = 13.10), and morpholine moiety viz., 1-(2-morpholinoethyl)-3-(3-phenylpropyl)urea (21, cardiac myosin ATPase activation = 44.0%; FS = 24.79; EF = 15.65), proved to be efficient to activate the cardiac myosin. The potent compounds 1, 9, 14 and 21 were found to be selective for cardiac myosin over skeletal and smooth myosins. Thus, these urea derivatives are potent scaffold to develop as a newer cardiac myosin activator for the treatment of systolic heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. 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. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  14. 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.

  15. 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.

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

    EPA Science Inventory

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

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

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

  17. 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 ...

  18. Modulation of adverse cardiac remodeling by STARS, a mediator of MEF2 signaling and SRF activity.

    PubMed

    Kuwahara, Koichiro; Teg Pipes, Gordon C; McAnally, John; Richardson, James A; Hill, Joseph A; Bassel-Duby, Rhonda; Olson, Eric N

    2007-05-01

    Cytoskeletal proteins have been implicated in the pathogenesis of cardiomyopathy, but how the cytoskeleton influences the transcriptional alterations associated with adverse cardiac remodeling remains unclear. Striated muscle activator of Rho signaling (STARS) is a muscle-specific actin-binding protein localized to the Z disc that activates serum response factor-dependent (SRF-dependent) transcription by inducing nuclear translocation of the myocardin-related SRF coactivators MRTF-A and -B. We show that STARS expression is upregulated in mouse models of cardiac hypertrophy and in failing human hearts. A conserved region of the STARS promoter containing an essential binding site for myocyte enhancer factor-2 (MEF2), a stress-responsive transcriptional activator, mediates cardiac expression of STARS, which in turn activates SRF target genes. Forced overexpression of STARS in the heart sensitizes the heart to pressure overload and calcineurin signaling, resulting in exaggerated deterioration in cardiac function in response to these hypertrophic stimuli. These findings suggest that STARS modulates the responsiveness of the heart to stress signaling by functioning as a cytoskeletal intermediary between MEF2 and SRF.

  19. 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.

  20. 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.

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

    PubMed

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

    2012-01-01

    The perception of internal bodily signals (interoception) plays a relevant role for emotion processing and feelings. This study investigated changes of interoceptive awareness and cardiac autonomic activity induced by short-term food deprivation and its relationship to hunger and affective experience. 20 healthy women were exposed to 24h of food deprivation in a controlled setting. Interoceptive awareness was assessed by using a heartbeat tracking task. Felt hunger, cardiac autonomic activity, mood and subjective appraisal of interoceptive sensations were assessed before and after fasting. Results show that short-term fasting intensifies interoceptive awareness, not restricted to food cues, via changes of autonomic cardiac and/or cardiodynamic activity. The increase of interoceptive awareness was positively related to felt hunger. Additionally, the results demonstrate the role of cardiac vagal activity as a potential index of emotion related self-regulation, for hunger, mood and the affective appraisal of interoceptive signals during acute fasting. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. 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.

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

    SciTech Connect

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

    1995-12-31

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

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

    PubMed Central

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

    2007-01-01

    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 ≈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 ≈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. (≈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 ≈10 a.m. PMID:18093917

  6. 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.

  7. 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

  8. Proteasome activation during cardiac hypertrophy by the chaperone H11 Kinase/Hsp22.

    PubMed

    Hedhli, Nadia; Wang, Li; Wang, Qian; Rashed, Eman; Tian, Yimin; Sui, Xiangzhen; Madura, Kiran; Depre, Christophe

    2008-02-01

    The regulation of protein degradation by the proteasome during cardiac hypertrophy remains largely unknown. Also, the proteasome translocates to the nuclear periphery in response to cellular stress in yeast, which remains unexplored in mammals. The purpose of this study was to determine the quantitative and qualitative adaptation of the proteasome during stable cardiac hypertrophy. We measured proteasome activity, expression and sub-cellular distribution in a model of chronic cardiac hypertrophy induced by the stress-response chaperone H11 Kinase/Hsp22 (Hsp22). Over-expression of Hsp22 in a transgenic (TG) mouse leads to a 30% increase in myocyte cross-sectional area compared to wild-type (WT) mice (P < 0.01). Characterization of the proteasome in hearts from TG mice vs. WT revealed an increased expression of both 19S and 20S subunits (P < 0.05), a doubling in 20S catalytic activity (P < 0.01), a redistribution of both subunits from the cytosol to the nuclear periphery, and a four-fold increase in nuclear-associated 20S catalytic activity (P < 0.001). The perinuclear proteasome co-localized and interacted with Hsp22. Inhibition of proteasome activity by epoxomicin reduced hypertrophy in TG by 50% (P < 0.05). Adeno-mediated over-expression of Hsp22 in isolated cardiac myocytes increased both cell growth and proteasome activity, and both were prevented upon inhibition of the proteasome. Similarly, stimulation of cardiac cell growth by pro-hypertrophic stimuli increased Hsp22 expression and proteasome activity, and proteasome inhibition in that setting prevented hypertrophy. Proteasome inhibitors also prevented the increase in rate of protein synthesis observed after over-expression of Hsp22 or upon addition of pro-hypertrophic stimuli. Hsp22-mediated cardiac hypertrophy promotes an increased expression and activity, and a subcellular redistribution of the proteasome. Inhibition of the proteasome reverses cardiac hypertrophy upon Hsp22 over-expression or upon

  9. Cardiac dysfunction and hypothalamic activation during a social crowding stressor in prairie voles

    PubMed Central

    Grippo, Angela J.; Sgoifo, Andrea; Mastorci, Francesca; McNeal, Neal; Trahanas, Diane M.

    2010-01-01

    Cardiac dysfunction and hypothalamic activation during a social crowding stressor in prairie voles. – Negative social interactions produce several detrimental consequences in humans and non-human animals; and conversely, positive social interactions may have stress-buffering effects on both behavior and physiology. However, the mechanisms underlying specific stressor-responsiveness in the context of the social environment are not well understood. The present study investigated the integration of behavior, cardiac function, and Fos-immunoreactivity in the hypothalamic paraventricular nucleus during an acute social stressor in female, socially monogamous prairie voles exposed to previous long-term pairing (control conditions) or isolation. Animals previously exposed to social isolation displayed increased heart rate, attenuated heart rate variability, and increased incidence of cardiac arrhythmias during an acute crowding stressor versus animals previously exposed to social pairing; these cardiac alterations were not secondary to behavioral changes during the crowding stressor. Furthermore, social isolation was associated with increased c-Fos-immunoreactivity in the hypothalamic paraventricular nucleus following the crowding stressor, versus social pairing. The prairie vole provides a useful model for understanding how the social environment contributes to changes in behavior, cardiac function, and central stress-regulatory processes in humans. PMID:20347401

  10. 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.

  11. 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.

  12. Motion estimation and segmentation in CT cardiac images using the Hermite transform and active shape models

    NASA Astrophysics Data System (ADS)

    Escalante-Ramírez, Boris; Moya-Albor, Ernesto; Barba-J, Leiner; Arambula Cosio, Fernando; Vallejo, Enrique

    2013-09-01

    Considering the importance of studying the movement of certain cardiac structures such as left ventricle and myocardial wall for better medical diagnosis, we propose a method for motion estimation and image segmentation in sequential Computed Tomography images. Two main tasks are tackled. The first one consists of a method to estimate the heart's motion based on a bio-inspired image representation model. Our proposal for optical flow estimation incorporates image structure information extracted from the steered Hermite transform coefficients that is later used as local motion constraints in a differential estimation approach. The second task deals with cardiac structure segmentation in time series of cardiac images based on deformable models. The goal is to extend active shape models (ASM) of 2D objects to the problem of 3D (2D + time) cardiac CT image modeling. The segmentation is achieved by constructing a point distribution model (PDM) that encodes the spatio-temporal variability of a training set. Combination of both motion estimation and image segmentation allows isolating motion in cardiac structures of medical interest such as ventricle walls.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Murine cardiac images obtained with focusing pinhole SPECT are barely influenced by extra-cardiac activity

    NASA Astrophysics Data System (ADS)

    Branderhorst, Woutjan; van der Have, Frans; Vastenhouw, Brendan; Viergever, Max A.; Beekman, Freek J.

    2012-02-01

    Ultra-high-resolution SPECT images can be obtained with focused multipinhole collimators. Here we investigate the influence of unwanted high tracer uptake outside the scan volume on reconstructed tracer distributions inside the scan volume, for 99mTc-tetrofosmin myocardial perfusion scanning in mice. Simulated projections of a digital mouse phantom (MOBY) in a focusing multipinhole SPECT system (U-SPECT-II, MILabs, The Netherlands) were generated. With this system differently sized user-defined scan volumes can be selected, by translating the animal in 3D through the focusing collimators. Scan volume selections were set to (i) a minimal volume containing just the heart, acquired without translating the animal during scanning, (ii) a slightly larger scan volume as is typically applied for the heart, requiring only small XYZ translations during scanning, (iii) same as (ii), but extended further transaxially, and (iv) same as (ii), but extended transaxially to cover the full thorax width (gold standard). Despite an overall negative bias that is significant for the minimal scan volume, all selected volumes resulted in visually similar images. Quantitative differences in the reconstructed myocardium between gold standard and the results from the smaller scan volume selections were small; the 17 standardized myocardial segments of a bull's eye plot, normalized to the myocardial mean of the gold standard, deviated on average 6.0%, 2.5% and 1.9% for respectively the minimal, the typical and the extended scan volume, while maximum absolute deviations were respectively 18.6%, 9.0% and 5.2%. Averaged over ten low-count noisy simulations, the mean absolute deviations were respectively 7.9%, 3.2% and 1.9%. In low-count noisy simulations, the mean and maximum absolute deviations for the minimal scan volume could be reduced to respectively 4.2% and 12.5% by performing a short survey scan of the exterior activity and focusing the remaining scan time at the organ of interest. We

  18. 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.

  19. Garlic activates SIRT-3 to prevent cardiac oxidative stress and mitochondrial dysfunction in diabetes.

    PubMed

    Sultana, Md Razia; Bagul, Pankaj K; Katare, Parameshwar B; Anwar Mohammed, Soheb; Padiya, Raju; Banerjee, Sanjay K

    2016-11-01

    Cardiac complications are major contributor in the mortality of diabetic people. Mitochondrial dysfunctioning is a crucial contributor for the cardiac complications in diabetes, and SIRT-3 remains the major mitochondrial deacetylase. We hypothesized whether garlic has any role on SIRT-3 to prevent mitochondrial dysfunction in diabetic heart. Rats with developed hyperglycemia after STZ injection were divided into two groups; diabetic (Dia) and diabetic+garlic (Dia+Garl). Garlic was administered at a dose of 250mg/kg/day, orally for four weeks. An additional group was maintained to evaluate the effect of raw garlic administration on control rat heart. We have observed altered functioning of cardiac mitochondrial enzymes involved in metabolic pathways, and increased levels of cardiac ROS with decreased activity of catalase and SOD in diabetic rats. Cardiac mRNA expression of TFAM, PGC-1α, and CO1 was also altered in diabetes. In addition, reduced levels of electron transport chain complexes that observed in Dia group were normalized with garlic administration. This indicates the presence of increased oxidative stress with mitochondrial dysfunctioning in diabetic heart. We have observed reduced activity of SIRT3 and increased acetylation of MnSOD. Silencing SIRT-3 in cells also revealed the same. However, administration of garlic improved the SIRT-3 and MnSOD activity, by deacetylating MnSOD. Increased SOD activity was correlated with reduced levels of ROS in garlic-administered rat hearts. Collectively, our results provide an insight into garlic's protection to T1DM heart through activation of SIRT3-MnSOD pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Detection of Telomerase Activity Using Capacitance Measurements

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

  1. Cancer-induced cardiac cachexia: Pathogenesis and impact of physical activity (Review).

    PubMed

    Belloum, Yassine; Rannou-Bekono, Françoise; Favier, François B

    2017-05-01

    Cachexia is a wasting syndrome observed in many patients suffering from several chronic diseases including cancer. In addition to the progressive loss of skeletal muscle mass, cancer cachexia results in cardiac function impairment. During the severe stage of the disease, patients as well as animals bearing cancer cells display cardiac atrophy. Cardiac energy metabolism is also impeded with disruption of mitochondrial homeostasis and reduced oxidative capacity, although the available data remain equivocal. The release of inflammatory cytokines by tumor is a key mechanism in the initiation of heart failure. Oxidative stress, which results from the combination of chemotherapy, inadequate antioxidant consumption and chronic inflammation, will further foster heart failure. Protein catabolism is due to the concomitant activation of proteolytic systems and inhibition of protein synthesis, both processes being triggered by the deactivation of the Akt/mammalian target of rapamycin pathway. The reduction in oxidative capacity involves AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1α dysregulation. The nuclear factor-κB transcription factor plays a prominent role in the coordination of these alterations. Physical exercise appears as an interesting non-pharmaceutical way to counteract cancer cachexia-induced-heart failure. Indeed, aerobic training has anti-inflammatory effects, increases anti-oxidant defenses, prevents atrophy and promotes oxidative metabolism. The present review points out the importance of better understanding the concurrent structural and metabolic changes within the myocardium during cancer and the protective effects of exercise against cardiac cachexia.

  2. Rapid Changes in Cardiac Myofilament Function following the Acute Activation of Estrogen Receptor-Alpha

    PubMed Central

    Kulpa, Justyna; Chinnappareddy, Nirmala; Pyle, W. Glen

    2012-01-01

    Estrogens have well-recognized and complex cardiovascular effects, including altering myocardial contractility through changes in myofilament function. The presence of multiple estrogen receptor (ER) isoforms in the heart may explain some discrepant findings about the cardiac effects of estrogens. Most studies examining the impact of estrogens on the heart have focused on chronic changes in estrogen levels, and have not investigated rapid, non-genomic pathways. The first objective of this study was to determine how acute activation of ERα impacts cardiac myofilaments. Nongenomic myocardial estrogen signaling is associated with the activation of a variety of signaling pathways. p38 MAPK has been implicated in acute ER signaling in the heart, and is known to affect myofilament function. Thus, the second objective of this study was to determine if acute ERα activation mediates its myofilament effects through p38 MAPK recruitment. Hearts from female C57Bl/6 mice were perfused with the ERα agonist PPT and myofilaments isolated. Activation of ERα depressed actomyosin MgATPase activity and decreased myofilament calcium sensitivity. Inhibition of p38 MAPK attenuated the myofilament effects of ERα activation. ERα stimulation did not affect global myofilament protein phosphorylation, but troponin I phosphorylation at the putative PKA phosphorylation sites was decreased. Changes in myofilament activation did not translate into alterations in whole heart function. The present study provides evidence supporting rapid, non-genomic changes in cardiac myofilament function following acute ERα stimulation mediated by the p38 MAPK pathway. PMID:22859967

  3. [Effectiveness of activated factor VII in postoperative bleeding after cardiac surgery with extracorporeal membrane oxygenation].

    PubMed

    López-Herce Cid, J; Arriola Pereda, G; Zunzunegui Martínez, J L; Brandstrup Azuero, K B

    2005-05-01

    A 4-year-old girl suffered severe postoperative chest tube drainage bleeding after cardiac transplant surgery requiring extracorporeal membrane oxygenation. Transfusions of platelets and fresh frozen plasma failed to decrease the bleeding. At 2.5 hours a dose of 180 mcg/kg of recombinant activated Factor VII was administered. The hemorrhage decreased from 45 ml/kg/h in the first 2.5 hours to 17 ml/kg/h in the next 2.5 hours. The same dose of recombinant activated Factor VII was administered and the hemorrhage suddenly decreased to 1.5 ml/kg/h in the next 2.5 hours, with subsequent disappearance. No adverse events related to activated Factor VII were observed. Recombinant activated Factor VII may be useful in some cases of severe postoperative bleeding in children after cardiac surgery. Randomized controlled studies are needed to confirm its safety and efficacy, and to evaluate the most suitable dose.

  4. 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.

  5. [PPARα attenuates palmitate-induced endoplasmic reticulum stress in human cardiac cells by enhancing AMPK activity].

    PubMed

    Palomer, Xavier; Capdevila-Busquets, Eva; Garreta, Gerard; Davidson, Mercy M; Vázquez-Carrera, Manuel

    2014-01-01

    Endoplasmic reticulum (ER) stress has been linked to several cardiovascular diseases, such as atherosclerosis, heart failure and cardiac hypertrophy. ER stress impairs insulin signalling, thus contributing to the development of insulin resistance and diabetes. Since several studies have reported that PPARα may inhibit ER stress, the main aim of this study consisted in investigating whether activation of this nuclear receptor is able to prevent lipid-induced ER stress in cardiac cells, as well as studying the mechanisms involved. A cardiomyocyte cell line of human origin, AC16, was treated with palmitate in the presence or absence of several AMPK and PPARα pharmacological agonists and antagonists. For the in vivo studies, wild-type male mice were fed a standard diet, or a high-fat diet (HFD), for two months. At the end of the experiments, several ER stress markers were assessed in cardiac cells or in the mice hearts, using real-time RT-PCR and Western-blot analyses. The results demonstrate that both palmitate and the HFD induced ER stress in cardiac cells, since they upregulated the expression (ATF3, BiP/GRP78 and CHOP), splicing (sXBP1), and phosphorylation (IRE-1α and eIF2α) of several ER stress markers. Interestingly, treatment with the PPARα agonist Wy-14,643 prevented an increase in the majority of these ER stress markers in human cardiac cells by means of AMPK activation. These data indicate that PPARα activation by Wy-14,643 might be useful to prevent the harmful effects of ER stress and associated cardiovascular diseases in obese patients, and even during diabetic cardiomyopathy, by enhancing AMPK activity. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  6. 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.

  7. 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.

  8. 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

  9. Detection of Left Ventricular Thrombus by Cardiac Magnetic Resonance in Embolic Stroke of Undetermined Source.

    PubMed

    Takasugi, Junji; Yamagami, Hiroshi; Noguchi, Teruo; Morita, Yoshiaki; Tanaka, Tomotaka; Okuno, Yoshinori; Yasuda, Satoshi; Toyoda, Kazunori; Gon, Yasufumi; Todo, Kenichi; Sakaguchi, Manabu; Nagatsuka, Kazuyuki

    2017-09-01

    We aimed to use contrast-enhanced cardiac magnetic resonance (CE-CMR) imaging to elucidate the prevalence of left ventricular (LV) thrombus in patients suspected of embolic stroke of undetermined source (ESUS) with previous myocardial infarction or LV dysfunction (LV ejection fraction [LVEF] <50%). We prospectively investigated 797 consecutive patients who presented to our hospital with acute ischemic stroke between 2014 and 2015. Patients with myocardial infarction or LVEF<50% underwent CE-CMR imaging. ESUS was diagnosed according to proposal criteria based on transthoracic echocardiography findings. The prevalence of ESUS was 22% (178 of 797) on initial diagnosis. Among 60 patients with myocardial infarction or LVEF<50%, the stroke subtypes were as follows: small artery disease, 17% (10 of 60); large artery atherosclerosis, 5% (3 of 60); cardioembolic stroke, 49% (29 of 60); ESUS, 23% (14 of 60); and undetermined causes other than ESUS, 6% (4 of 60). Of 60 patients examined via CE-CMR, LV thrombus was confirmed in 12 patients, whereas only 1 had been detected on transthoracic echocardiography (P=0.04). Importantly, 29% (4 of 14) of patients with ESUS had LV thrombus. A prediction model based on CE-CMR findings showed higher performance in LV thrombus detection, permitting a net improvement of 0.46 (95% confidence interval, 0.08-0.82; P=0.016) in cardioembolic stroke reclassification. Compared with patients without LV thrombus, those with LV thrombus had lower LVEF (median: 26% versus 40%; P=0.003). Notably, 42% (5 of 12) of patients with LV thrombus had LVEF≥30%. When ESUS-suspected patients have myocardial infarction or LV dysfunction, CE-CMR may help improve detection of cardioembolic stroke and provide relevant information for anticoagulation therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02251665. © 2017 American Heart Association, Inc.

  10. Multiview active appearance models for simultaneous segmentation of cardiac 2- and 4-chamber long-axis magnetic resonance images.

    PubMed

    Uzümcü, Mehmet; van der Geest, Rob J; Sonka, Milan; Lamb, Hildo J; Reiber, Johan H C; Lelieveldt, Boudewijn P F

    2005-04-01

    Long-axis cardiac magnetic resonance (MR) views enable a rapid, online evaluation of cardiac function from only 2 views. In this article, we aimed to evaluate a model-based method for the simultaneous detection of 2- and 4-chamber endocardial and epicardial contours in end-diastolic and end-systolic phases of MR images. We introduce multiview Active Appearance Models for the automated segmentation of long-axis cardiac MR images of the left ventricle. Two modes of initialization were used to test the accuracy of the model with minimal user interaction and the best-obtainable accuracy with this model. The segmentation was initialized by annotating 2 points in the base and one in the apex. We tested the method's performance by comparing the point-to-curve errors, ejection fractions, and biplane area-length volumes calculated with the automatically detected contours to those calculated from contours that were annotated manually by experts. Leave-one-out experiments were performed with 2- and 4-chamber long axis MR images of 59 subjects in end-diastolic and end-systolic phases. When initializing in all 4 frames, 97% of the segmentations were successful, and the standard deviation in the volume-errors with respect to the average manually identified volume was 9.0% for the end-diastolic volumes and 15% for the end-systolic volumes. When the method was initialized in the end-systolic frames only, 92% of the segmentations were successful, and the standard deviation in the errors in the volumes with respect to the average manually identified volume was 13.3% for the end-diastolic volumes and 16.7% for the end-systolic volumes. Bland-Altman plots showed that the errors were distributed randomly around 0, and by using a paired t test comparing manual and computer-determined volumes, we were able to detect that the volume differences were not significant. Simultaneous detection of the endocardial and epicardial contours in 2- and 4-chamber views and end-diastolic and end

  11. 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.

  12. Effects of endoscopic thoracic sympathectomy for primary hyperhidrosis on cardiac autonomic nervous activity.

    PubMed

    Cruz, Jorge; Sousa, João; Oliveira, Antonio G; Silva-Carvalho, Luis

    2009-03-01

    Endoscopic thoracic sympathectomy is performed to treat primary hyperhidrosis. The second and third sympathetic thoracic ganglia excised also innervate the heart. Some studies have shown decreased heart rate but have not been conclusive regarding other cardiac effects of sympathectomy. We studied the cardiac autonomic effects of endoscopic thoracic sympathectomy in a group of patients with primary hyperhidrosis. Heart rate variability is a simple, noninvasive electrocardiographic marker reflecting the activity and balance of the sympathetic and vagal components of the autonomous nervous system. We performed a prospective study in 38 patients with primary hyperhidrosis with 24-hour Holter recordings obtained before endoscopic thoracic sympathectomy and 6 months later. We found statistically significant differences (P < .05) in both time and frequency domains. Parameters that evaluate global cardiac autonomic activity (total power, SD of normal R-R intervals, SD of average normal R-R intervals) and vagal activity (rhythm corresponding to percentage of normal R-R intervals with cycle greater than 50 ms relative to previous interval, square root of mean squared differences of successive normal R-R intervals, high-frequency power, high-frequency power in normalized units) were statistically significantly increased after sympathectomy. Low-frequency power in normalized units, reflecting sympathetic activity, was statistically significantly decreased after sympathectomy. Low-/high-frequency power ratio also showed a significant decrease, indicating relative decrease in sympathetic activity and increase in vagal activity. These results provide, for the first time to our knowledge, clear evidence of increased vagal and global cardiac autonomic activity and decreased sympathetic activity after endoscopic thoracic sympathectomy.

  13. Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation.

    PubMed

    Anker, S D; Coats, A J

    1999-03-01

    Chronic heart failure (CHF) is a complex syndrome affecting many body systems. Body wasting (ie, cardiac cachexia) is a serious complication of CHF long known but little investigated. Although no specific diagnostic criteria have been established, we have suggested that cardiac cachexia be defined on the basis of the presence of documented nonintentional and nonedematous weight loss > 7.5% of the premorbid normal weight, occurring over a time period of > 6 months. Using this definition, 16% of an unselected CHF outpatient population was found to be cachectic. The cachectic state is predictive of impaired prognosis independently of age, functional disease classification, left ventricular ejection fraction, and peak oxygen consumption. The mortality in the cachectic cohort is 50% at 18 months. Analyzing body composition in detail, it has been found that patients with cardiac cachexia suffer from a general loss of fat tissue (ie, energy reserves), lean tissue (ie, skeletal muscle), and bone tissue (ie, osteoporosis). Cachectic CHF patients are weaker and fatigue earlier, which is due to both reduced skeletal muscle mass and impaired muscle quality. The pathophysiologic alterations leading to cardiac cachexia remain unclear, but initial cross-sectional studies have suggested that humoral neuroendocrine and immunologic abnormalities are linked, independently of established heart failure severity markers, to the presence of body wasting. Comparing the features of cachectic and noncachectic CHF patients with those of healthy control subjects, it is mainly the cachectic CHF patients who show raised plasma levels of epinephrine, norepinephrine, and cortisol; the highest plasma renin activity and aldosterone plasma concentrations; and the lowest plasma sodium level. Several studies have shown that cardiac cachexia is linked to raised plasma levels of tumor necrosis factor-ac. The degree of body wasting is strongly correlated with neurohormonal and immune abnormalities. The

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

    PubMed

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

    2012-03-01

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

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

    PubMed Central

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

    2015-01-01

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

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  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. Detection of benign cardiac fibroma on thallium-201 imaging in an adult

    SciTech Connect

    Helmer, S.; Abghari, R.; Stone, A.J.; Lee, C.C.

    1987-05-01

    A rare case of benign cardiac fibroma causing a focal defect on Tl-201 imaging in an adult patient is presented. The abnormalities on the Tl-201 scan are correlated with other studies performed on the same patient. The usefulness of the Tl-201 myocardial perfusion scan as an early, noninvasive test in cardiac workup is stressed.

  4. 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

  5. Resveratrol induces nuclear factor-κB activity in human cardiac cells.

    PubMed

    Palomer, Xavier; Capdevila-Busquets, Eva; Alvarez-Guardia, David; Barroso, Emma; Pallàs, Mercè; Camins, Antoni; Davidson, Mercy M; Planavila, Ana; Villarroya, Francesc; Vázquez-Carrera, Manuel

    2013-09-10

    Resveratrol is a grape polyphenol that prevents cardiac hypertrophy and protects the heart from ischemic injury, metabolic dysregulation, and inflammatory processes in several murine models. The aim of this study was to investigate the effects of resveratrol on the inflammatory processes in human cardiac AC16 cells in order to gain a better understanding of its cardioprotective mechanisms in the human heart. Resveratrol induced the DNA-binding activity of the pro-inflammatory transcription factor NF-κB in AC16 cells, and exacerbated the increase caused by tumor necrosis factor-α (TNF-α). In accordance with this, resveratrol increased the expression of the pro-inflammatory genes ICAM-1 (intercellular adhesion molecule-1) and TNF-α. In contrast, resveratrol decreased the expression of pro-inflammatory genes IL-6 (interleukin-6) and MCP-1 (monocyte chemoattractant protein-1). Likewise, resveratrol also induced inflammation in rat neonatal cardiomyocytes, and in the heart of mice fed a standard chow diet supplemented with resveratrol (1g/kg diet) for four months. Western-blot analyses revealed that NF-κB p65 subunit levels were upregulated in an IκB-dependent manner in the nuclei of resveratrol-treated human cardiac cells. Finally, resveratrol activated the signal transducer and activator of transcription 3 (STAT3) signaling and induced the expression of its anti-apoptotic downstream effector Bcl-xL, both involved in the cardioprotective survival activating factor enhancement (SAFE) pathway. Resveratrol enhanced NF-κB activity in human and murine cardiac cells, in a process that coincided with the activation of STAT3 and anti-apoptotic downstream effectors. Therefore, activation of the SAFE pathway by resveratrol might be involved in the cardioprotective effects of this compound. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. 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.

  7. Automatic detection of measurement points for non-contact vibrometer-based diagnosis of cardiac arrhythmias

    NASA Astrophysics Data System (ADS)

    Metzler, Jürgen; Kroschel, Kristian; Willersinn, Dieter

    2017-03-01

    Monitoring of the heart rhythm is the cornerstone of the diagnosis of cardiac arrhythmias. It is done by means of electrocardiography which relies on electrodes attached to the skin of the patient. We present a new system approach based on the so-called vibrocardiogram that allows an automatic non-contact registration of the heart rhythm. Because of the contactless principle, the technique offers potential application advantages in medical fields like emergency medicine (burn patient) or premature baby care where adhesive electrodes are not easily applicable. A laser-based, mobile, contactless vibrometer for on-site diagnostics that works with the principle of laser Doppler vibrometry allows the acquisition of vital functions in form of a vibrocardiogram. Preliminary clinical studies at the Klinikum Karlsruhe have shown that the region around the carotid artery and the chest region are appropriate therefore. However, the challenge is to find a suitable measurement point in these parts of the body that differs from person to person due to e. g. physiological properties of the skin. Therefore, we propose a new Microsoft Kinect-based approach. When a suitable measurement area on the appropriate parts of the body are detected by processing the Kinect data, the vibrometer is automatically aligned on an initial location within this area. Then, vibrocardiograms on different locations within this area are successively acquired until a sufficient measuring quality is achieved. This optimal location is found by exploiting the autocorrelation function.

  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. 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

  10. Activation of catalase by apelin prevents oxidative stress-linked cardiac hypertrophy.

    PubMed

    Foussal, Camille; Lairez, Olivier; Calise, Denis; Pathak, Atul; Guilbeau-Frugier, Celine; Valet, Philippe; Parini, Angelo; Kunduzova, Oksana

    2010-06-03

    Adipose tissue secretes a variety of bioactive factors, which can regulate cardiomyocyte hypertrophy via reactive oxygen species (ROS). In the present study we investigated whether apelin affects ROS-dependent cardiac hypertrophy. In cardiomyocytes apelin inhibited the hypertrophic response to 5-HT and oxidative stress induced by 5-HT- or H(2)O(2) in a dose-dependent manner. These effects were concomitant to the increase in mRNA expression and activity of catalase. Chronic treatment of mice with apelin attenuated pressure-overload-induced left ventricular hypertrophy. The prevention of hypertrophy by apelin was associated with increased myocardial catalase activity and decreased plasma lipid hydroperoxide, as an index of oxidative stress. These results show that apelin behaves as a catalase activator and prevents cardiac ROS-dependent hypertrophy. Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    2015-10-01

    Measurements of cardiac conduction velocity provide valuable functional and structural insight into the initiation and perpetuation of cardiac arrhythmias, in both a clinical and laboratory context. The interpretation of activation wavefronts and their propagation can identify mechanistic properties of a broad range of electrophysiological pathologies. However, the sparsity, distribution and uncertainty of recorded data make accurate conduction velocity calculation difficult. A wide range of mathematical approaches have been proposed for addressing this challenge, often targeted towards specific data modalities, species or recording environments. Many of these algorithms require identification of activation times from electrogram recordings which themselves may have complex morphology or low signal-to-noise ratio. This paper surveys algorithms designed for identifying local activation times and computing conduction direction and speed. Their suitability for use in different recording contexts and applications is assessed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. 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.

  13. 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

  14. 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.

  15. Cardiac catheterization

    MedlinePlus

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

  16. 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.

  17. Using cardiovascular imaging modalities to determine cardiac disorders before starting sports activities.

    PubMed

    Ceylan, Özgür; Meşe, Timur; Gürsu, Alper Hazım

    2017-03-01

    We re-examined children who had previously been declared eligible to participate in competitive sports activities for cardiac disorders, using cardiac investigation protocol. Total of 250 children (224 males [89.6%], and 26 females [10.4%]) between the ages of 8 and 17 years who had just started or were already engaged in sports activities were included in the study. Participants had detailed physical examination evaluated by a pediatric cardiologist. Those with findings suggesting cardiac disorder in their history and/or physical examinations, and/or 12-channel electrocardiography (ECG) were examined with echocardiography (ECHO), 24-hour Holter monitoring, and exercise test. Mean duration of participation in sports activities was 13 months. Among all, 10.4% of the children had abnormalities on ECG. ECHO demonstrated cardiomyopathy in 1, mitral valve prolapse in 2, tricuspid insufficiency in 2, and mitral insufficiency in 1 participant. Holter monitoring revealed non-sustained ventricular tachycardia attacks in 1, and supraventricular tachycardia in another child. Three were ultimately disqualified from partaking in competitive sports. Sports and medical communities must work together to establish study protocols to prevent sudden death related to sports and to make these activities safer for athletes. Pediatric cardiology consultation for young athletes before they start sports activities is needed.

  18. Physical activity in relation to cardiac risk markers in secondary prevention of coronary artery disease.

    PubMed

    Bäck, Maria; Cider, Asa; Gillström, John; Herlitz, Johan

    2013-09-20

    The relationship between physical activity and cardiac risk markers in secondary prevention for patients with coronary artery disease (CAD) is uncertain. The aims of the study were therefore to examine the level of physical activity in patients with CAD, and to investigate the association between physical activity and cardiac risk markers. In total, 332 patients, mean age, 65 ± 9.1 years, diagnosed with CAD at a university hospital were included in the study 6 months after their cardiac event. Physical activity was measured with a pedometer (steps/day) and two questionnaires. Investigation of cardiac risk markers included serum lipids, oral glucose-tolerance test, twenty-four hour blood pressure and heart rate monitoring, smoking, body-mass index (BMI), waist-hip ratio, and muscle endurance. The study had a cross-sectional design. The patients performed a median of 7,027 steps/day. After adjustment for confounders, statistically significant correlations between steps/day and risk markers were found with regard to; high-density lipoprotein cholesterol (HDL-C) (r=0.19, p<0.001), muscle endurance measures (r ranging from 0.19 to 0.25, p=0.001 or less) triglycerides (r=-0.19, p<0.001), glucose-tolerance (r=-0.23, p<0.001), BMI (r=-0.21, p<0.001), 24-h heart rate recording during night (r=-0.17, p=0.004), and average 24-h heart rate (r=-0.13, p=0.02). A relatively high level of physical activity was found among patients with CAD. There was a weak, but significant, association between pedometer steps/day and HDL-C, muscle endurance, triglycerides, glucose-tolerance, BMI and 24-h heart rate, indicating potential positive effects of physical activity on these parameters. However, before clinical implications can be formed, more confirmatory data are needed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. 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

  20. 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

  1. 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

  2. Evaluation of cardiac rhythm disturbances during extravehicular activity.

    PubMed

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

    1997-04-15

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

  3. 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

  4. Exercise-induced physiological hypertrophy initiates activation of cardiac progenitor cells.

    PubMed

    Xiao, Junjie; Xu, Tianzhao; Li, Jin; Lv, Dongcao; Chen, Ping; Zhou, Qiulian; Xu, Jiahong

    2014-01-01

    Physiological hypertrophy is featured by the hypertrophy of pre-existing cardiomyocytes and the formation of new cardiomyocytes. C-kit positive cardiac progenitor cells increased their numbers in exercise-induced physiological hypertrophy. However, the participation of Sca-1 positive cells in the physiological adaptation of the heart to exercise training is unclear. Physiological hypertrophy was induced by swimming and the mRNA levels of GATA binding protein 4 (GATA4), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), endogenous hepatocyte growth factor (HGF), and insulin like growth factor-1 (IGF-1) from the whole heart were determined by real-time polymerase chain reactions (RT-PCRs) analysis. Immunofluorescent staining was used to compare the number of C-kit and Sca-1 positive cardiac progenitor cells. In addition, mRNA levels of C-kit and Sca-1 in left ventricle (LV), right ventricle (RV), and outflow tract (OFT) were determined in mice swimming for 7, 14, and 21 days by RT-PCRs. The ratio of heart weight (HW) to body weight and HW to tibia length and the mRNA level of GATA4 were increased while mRNA levels of ANP and BNP remained unchanged. C-kit and Sca-1 positive cardiac progenitor cells were activated by swimming training. An increased endogenous production of HGF and IGF was observed at least at the mRNA level. Swimming induced a significant up-regulation of C-kit in LV of mice swimming for 1, 2 and 3 weeks and in RV of mice swimming for 3 weeks. Sca-1 positive cardiac progenitor cells were increased in LV and OFT in mice swimming for 3 weeks. This study presents that swimming-induced physiological hypertrophy initiates activation of cardiac progenitor cells.

  5. 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.

  6. 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.

  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. 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.

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

    PubMed Central

    Javadov, Sabzali; Jang, Sehwan; Agostini, Bryan

    2014-01-01

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

  10. Transient receptor potential vanilloid 2 function regulates cardiac hypertrophy via stretch-induced activation.

    PubMed

    Koch, Sheryl E; Mann, Adrien; Jones, Shannon; Robbins, Nathan; Alkhattabi, Abdullah; Worley, Mariah C; Gao, Xu; Lasko-Roiniotis, Valerie M; Karani, Rajiv; Fulford, Logan; Jiang, Min; Nieman, Michelle; Lorenz, John N; Rubinstein, Jack

    2017-03-01

    Hypertension (increased afterload) results in cardiomyocyte hypertrophy leading to left ventricular hypertrophy and subsequently, heart failure with preserved ejection fraction. This study was performed to test the hypothesis that transient receptor potential vanilloid 2 subtype (TRPV2) function regulates hypertrophy under increased afterload conditions. We used functional (pore specific) TRPV2 knockout mice to evaluate the effects of increased afterload-induced stretch on cardiac size and function via transverse aortic constriction (TAC) as well as hypertrophic stimuli including adrenergic and angiotensin stimulation via subcutaneous pumps. Wild-type animals served as control for all experiments. Expression and localization of TRPV2 was investigated in wild-type cardiac samples. Changes in cardiac function were measured in vivo via echocardiography and invasive catheterization. Molecular changes, including protein and real-time PCR markers of hypertrophy, were measured in addition to myocyte size. TRPV2 is significantly upregulated in wild-type mice after TAC, though not in response to beta-adrenergic or angiotensin stimulation. TAC-induced stretch stimulus caused an upregulation of TRPV2 in the sarcolemmal membrane. The absence of functional TRPV2 resulted in significantly reduced left ventricular hypertrophy after TAC, though not in response to beta-adrenergic or angiotensin stimulation. The decreased development of hypertrophy was not associated with significant deterioration of cardiac function. We conclude that TRPV2 function, as a stretch-activated channel, regulates the development of cardiomyocyte hypertrophy in response to increased afterload.

  11. 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.

  12. 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

  13. Deletion of peroxisome proliferator-activated receptor-alpha induces an alteration of cardiac functions.

    PubMed

    Loichot, Cécile; Jesel, Laurence; Tesse, Angela; Tabernero, Antonia; Schoonjans, Kristina; Roul, Gérard; Carpusca, Irina; Auwerx, Johan; Andriantsitohaina, Ramaroson

    2006-07-01

    The peroxisome proliferator-activated receptor-alpha (PPARalpha) plays a major role in the control of cardiac energy metabolism. The role of PPARalpha on cardiac functions was evaluated by using PPARalpha knockout (PPARalpha -/-) mice. Hemodynamic parameters by sphygmomanometric measurements show that deletion of PPARalpha did not affect systolic blood pressure and heart rate. Echocardiographic measurements demonstrated reduced systolic performance as shown by the decrease of left ventricular fractional shortening in PPARalpha -/- mice. Telemetric electrocardiography revealed neither atrio- nor intraventricular conduction defects in PPARalpha -/- mice. Also, heart rate, P-wave duration and amplitude, and QT interval were not affected. However, the amplitude of T wave from PPARalpha -/- mice was lower compared with wild-type (PPARalpha +/+) mice. When the myocardial function was measured by ex vivo Langendorff's heart preparation, basal and beta-adrenergic agonist-induced developed forces were significantly reduced in PPARalpha-null mice. In addition, Western blot analysis shows that the protein expression of beta1-adrenergic receptor is reduced in hearts from PPARalpha -/- mice. Histological analysis showed that hearts from PPARalpha -/- but not PPARalpha +/+ mice displayed myocardial fibrosis. These results suggest that PPARalpha-null mice have an alteration of cardiac contractile performance under basal and under stimulation of beta1-adrenergic receptors. These effects are associated with myocardial fibrosis. The data shed light on the role of PPARalpha in maintaining cardiac functions.

  14. Resveratrol Inhibits Cardiac Hypertrophy via AMP-activated Protein Kinase and Akt*

    PubMed Central

    Chan, Anita Y. M.; Dolinsky, Vernon W.; Soltys, Carrie-Lynn M.; Viollet, Benoit; Baksh, Shairaz; Light, Peter E.; Dyck, Jason R. B.

    2008-01-01

    Whereas studies involving animal models of cardiovascular disease demonstrated that resveratrol is able to inhibit hypertrophic growth, the mechanisms involved have not been elucidated. Because studies in cells other than cardiomyocytes revealed that AMP-activated protein kinase (AMPK) and Akt are affected by resveratrol, we hypothesized that resveratrol prevents cardiac myocyte hypertrophy via these two kinase systems. Herein, we demonstrate that resveratrol reduces phenylephrine-induced protein synthesis and cell growth in rat cardiac myocytes via alterations of intracellular pathways involved in controlling protein synthesis (p70S6 kinase and eukaryotic elongation factor-2). Additionally, we demonstrate that resveratrol negatively regulates the calcineurin-nuclear factor of activated T cells pathway thus modifying a critical component of the transcriptional mechanism involved in pathological cardiac hypertrophy. Our data also indicate that these effects of resveratrol are mediated via AMPK activation and Akt inhibition, and in the case of AMPK, is dependent on the presence of the AMPK kinase, LKB1. Taken together, our data suggest that resveratrol exerts anti-hypertrophic effects by activating AMPK via LKB1 and inhibiting Akt, thus suppressing protein synthesis and gene transcription. PMID:18562309

  15. Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt.

    PubMed

    Chan, Anita Y M; Dolinsky, Vernon W; Soltys, Carrie-Lynn M; Viollet, Benoit; Baksh, Shairaz; Light, Peter E; Dyck, Jason R B

    2008-08-29

    Whereas studies involving animal models of cardiovascular disease demonstrated that resveratrol is able to inhibit hypertrophic growth, the mechanisms involved have not been elucidated. Because studies in cells other than cardiomyocytes revealed that AMP-activated protein kinase (AMPK) and Akt are affected by resveratrol, we hypothesized that resveratrol prevents cardiac myocyte hypertrophy via these two kinase systems. Herein, we demonstrate that resveratrol reduces phenylephrine-induced protein synthesis and cell growth in rat cardiac myocytes via alterations of intracellular pathways involved in controlling protein synthesis (p70S6 kinase and eukaryotic elongation factor-2). Additionally, we demonstrate that resveratrol negatively regulates the calcineurin-nuclear factor of activated T cells pathway thus modifying a critical component of the transcriptional mechanism involved in pathological cardiac hypertrophy. Our data also indicate that these effects of resveratrol are mediated via AMPK activation and Akt inhibition, and in the case of AMPK, is dependent on the presence of the AMPK kinase, LKB1. Taken together, our data suggest that resveratrol exerts anti-hypertrophic effects by activating AMPK via LKB1 and inhibiting Akt, thus suppressing protein synthesis and gene transcription.

  16. 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

  17. 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.

  18. 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.

  19. Protein kinase C epsilon activation delays neuronal depolarization during cardiac arrest in the euthermic arctic ground squirrel

    PubMed Central

    Dave, Kunjan R.; DeFazio, R. Anthony; Raval, Ami P.; Dashkin, Oleksandr; Saul, Isabel; Iceman, Kimberly E.; Perez-Pinzon, Miguel A.; Drew, Kelly L.

    2009-01-01

    During the pre-hibernation season, arctic ground squirrels (AGS) can tolerate 8 minutes of asphyxial cardiac arrest (CA) without detectable brain pathology. Better understanding of the mechanisms regulating innate ischemia tolerance in AGS has the potential to facilitate the development of novel, prophylactic agents to induce ischemic tolerance in patients at risk of stroke or cardiac arrest. We hypothesized that neuroprotection in AGS involves robust maintenance of ion homeostasis similar to anoxia-tolerant turtles. Ion homeostasis was assessed by monitoring ischemic depolarization (ID) in cerebral cortex during CA in vivo and during oxygen glucose deprivation in vitro in acutely prepared hippocampal slices. In both models, the onset of ID was significantly delayed in AGS compared to rats. The epsilon protein kinase C (εPKC) is a key mediator of neuroprotection and inhibits both Na+/K+-ATPase and voltage-gated sodium channels, primary mediators of the collapse of ion homeostasis during ischemia. The selective peptide inhibitor of εPKC (εV1–2) shortened the time to ID in brain slices from AGS but not in rats despite evidence that εV1–2 decreased activation of εPKC in brain slices from both rats and AGS. These results support the hypothesis that εPKC activation delays the collapse of ion homeostasis during ischemia in AGS. PMID:19493168

  20. 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.

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

    PubMed Central

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

    2016-01-01

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

  2. Peroxisome proliferator-activated receptors modulate cardiac dysfunction in diabetic cardiomyopathy.

    PubMed

    Lee, T-I; Kao, Y-H; Chen, Y-C; Huang, J-H; Hsiao, F-C; Chen, Y-J

    2013-06-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). Chronic inflammation and derangement of myocardial energy and lipid homeostasis are common features of DM. The transcription factors of peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily, which are important in regulating energy and lipid homeostasis. There are three PPAR isoforms, α, γ, and δ, and their roles have been increasingly recognized to be important in CVD. These three isoforms are expressed in the heart and play pivotal roles in myocardial lipid metabolism, as well as glucose and energy homeostasis, and contribute to extra metabolic roles with effects on inflammation and oxidative stress. Moreover, regulation of PPARs may have significant effects on cardiac electrical activity and arrhythmogenesis. This review describes the roles of PPARs and their agonists in DM cardiomyopathy, inflammation, and cardiac electrophysiology. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Neuropeptide F peptides act through unique signaling pathways to affect cardiac activity

    PubMed Central

    Setzu, M.; Biolchini, M.; Lilliu, A.; Manca, M.; Muroni, P.; Poddighe, S.; Bass, C.; Angioy, A.M.; Nichols, R.

    2012-01-01

    Elucidating how neuropeptides affect physiology may result in delineating peptidergic mechanisms and identifying antagonists for application in basic and translational science. Human neuropeptide Y (NPY) regulates cardiac activity; frequently invertebrates contain orthologs of vertebrate peptides. We report invertebrate NPY-like neuropeptide F (NPF) arrested the signal frequency of the slow phase of the cardiac cycle (EC50 = 1 pM); however, signal frequency of the fast phase was affected only minimally. Neuropeptide F decreased the duration of the slow phase by ~70% (EC50 = 0.6 pM), but increased the duration of the fast phase by ~57% (EC50 = 10 nM). Short NPF-1 (sNPF-1) decreased the signal frequency of the slow phase by ~70% (EC50 = 9 nM); yet, signal frequency of the fast phase was unaffected. Short NPF-1 decreased the duration of the slow phase ~55% (EC50 ~ 50 nM), but increased the duration of the fast phase ~20% without dose dependency. Neuropeptide F and sNPF-1 increased isoelectric period duration. This novel report demonstrated NPY-like peptides are cardioactive but functionally unique. These data contribute to understanding how invertebrate orthologs affect cardiovascular activity. Dipteran fast and slow phases may be generated from separate pacemakers in the abdominal heart and in the anterior thoracocephalic aorta, respectively. Thus, our research suggests NPF and sNPF-1 act through different mechanisms to regulate cardiac activity. Invertebrate NPY-like peptides act in olfaction and feeding yet mechanisms which are associated with their cardioactive effects remain unknown; our work may provide evidence linking their roles in sensory response and cardiac activity. PMID:22289500

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

    PubMed Central

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

    2005-01-01

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

  10. [Contra-indications to sports activities in cardiac patients].

    PubMed

    Rivière, A; Denolin, H

    1984-04-01

    The cardiologist is faced with the problem of eliminating a subject with heart disease from a sports competition and of prescribing beneficial physical activity to patients with heart disease. The difficulty in the prescription (or contra-indication) is due to the need for an individual assessment of each case. Several general rules can be proposed for cases of heart disease with a high risk of mortality or with a poor haemodynamic status. In most cases, the beneficial or detrimental effect can not be predicted. In this review, the authors present various approaches, based on data from the literature, for different types of heart disease and for different sports. They conclude that each case requires a thorough investigation in order to reduce the number of victims of the sports stadium.

  11. Sexually dimorphic adaptation of cardiac function: roles of epoxyeicosatrienoic acid and peroxisome proliferator-activated receptors.

    PubMed

    Qin, Jun; Le, Yicong; Froogh, Ghezal; Kandhi, Sharath; Jiang, Houli; Luo, Meng; Sun, Dong; Huang, An

    2016-06-01

    Epoxyeicosatrienoic acids (EETs) are cardioprotective mediators metabolized by soluble epoxide hydrolase (sEH) to form corresponding diols (DHETs). As a sex-susceptible target, sEH is involved in the sexually dimorphic regulation of cardiovascular function. Thus, we hypothesized that the female sex favors EET-mediated potentiation of cardiac function via downregulation of sEH expression, followed by upregulation of peroxisome proliferator-activated receptors (PPARs). Hearts were isolated from male (M) and female (F) wild-type (WT) and sEH-KO mice, and perfused with constant flow at different preloads. Basal coronary flow required to maintain the perfusion pressure at 100 mmHg was significantly greater in females than males, and sEH-KO than WT mice. All hearts displayed a dose-dependent decrease in coronary resistance and increase in cardiac contractility, represented as developed tension in response to increases in preload. These responses were also significantly greater in females than males, and sEH-KO than WT 14,15-EEZE abolished the sex-induced (F vs. M) and transgenic model-dependent (KO vs. WT) differences in the cardiac contractility, confirming an EET-driven response. Compared with M-WT controls, F-WT hearts expressed downregulation of sEH, associated with increased EETs and reduced DHETs, a pattern comparable to that observed in sEH-KO hearts. Coincidentally, F-WT and sEH-KO hearts exhibited increased PPARα expression, but comparable expression of eNOS, PPARβ, and EET synthases. In conclusion, female-specific downregulation of sEH initiates an EET-dependent adaptation of cardiac function, characterized by increased coronary flow via reduction in vascular resistance, and promotion of cardiac contractility, a response that could be further intensified by PPARα. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  12. 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.

  13. Inflammatory activation: cardiac, renal, and cardio-renal interactions in patients with the cardiorenal syndrome

    PubMed Central

    Ganda, Anjali; Lin, Jeffrey; Onat, Duygu; Harxhi, Ante; Iyasere, Julia E.; Uriel, Nir; Cotter, Gad

    2013-01-01

    Although inflammation is a physiologic response designed to protect us from infection, when unchecked and ongoing it may cause substantial harm. Both chronic heart failure (CHF) and chronic kidney disease (CKD) are known to cause elaboration of several pro-inflammatory mediators that can be detected at high concentrations in the tissues and blood stream. The biologic sources driving this chronic inflammatory state in CHF and CKD are not fully established. Traditional sources of inflammation include the heart and the kidneys which produce a wide range of proinflammatory cytokines in response to neurohormones and sympathetic activation. However, growing evidence suggests that non-traditional biomechanical mechanisms such as venous and tissue congestion due to volume overload are also important as they stimulate endotoxin absorption from the bowel and peripheral synthesis and release of proinflammatory mediators. Both during the chronic phase and, more rapidly, during acute exacerbations of CHF and CKD, inflammation and congestion appear to amplify each other resulting in a downward spiral of worsening cardiac, vascular, and renal functions that may negatively impact patients’ outcome. Anti-inflammatory treatment strategies aimed at attenuating end organ damage and improving clinical prognosis in the cardiorenal syndrome have been disappointing to date. A new therapeutic paradigm may be needed, which involves different anti-inflammatory strategies for individual etiologies and stages of CHF and CKD. It may also include specific (short-term) anti-inflammatory treatments that counteract inflammation during the unsettled phases of clinical decompensation. Finally, it will require greater focus on volume overload as an increasingly significant source of systemic inflammation in the cardiorenal syndrome. PMID:21688186

  14. Joint influence of transmural heterogeneities and wall deformation on cardiac bioelectrical activity: A simulation study.

    PubMed

    Colli Franzone, P; Pavarino, L F; Scacchi, S

    2016-10-01

    The aim of this work is to investigate, by means of numerical simulations, the influence of myocardial deformation due to muscle contraction and relaxation on the cardiac repolarization process in presence of transmural intrinsic action potential duration (APD) heterogeneities. The three-dimensional electromechanical model considered consists of the following four coupled components: the quasi-static transversely isotropic finite elasticity equations for the deformation of the cardiac tissue; the active tension model for the intracellular calcium dynamics and cross-bridge binding; the anisotropic Bidomain model for the electrical current flow through the deforming cardiac tissue; the membrane model of ventricular myocytes, including stretch-activated channels. The numerical simulations are based on our finite element parallel solver, which employs Multilevel Additive Schwarz preconditioners for the solution of the discretized Bidomain equations and Newton-Krylov methods for the solution of the discretized non-linear finite elasticity equations. Our findings show that: (i) the presence of intrinsic transmural cellular APD heterogeneities is not fully masked by electrotonic current flow or by the presence of the mechanical deformation; (ii) despite the presence of transmural APD heterogeneities, the recovery process follows the activation sequence and there is no significant transmural repolarization gradient; (iii) with or without transmural APD heterogeneities, epicardial electrograms always display the same wave shape and discordance between the polarity of QRS complex and T-wave; (iv) the main effects of the mechanical deformation are an increase of the dispersion of repolarization time and APD, when computed over the total cardiac domain and over the endo- and epicardial surfaces, while there is a slight decrease along the transmural direction. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. 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

  16. Extracellular signal-regulated kinase activation during cardiac hypertrophy reduces sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) transcription

    PubMed Central

    Huang, Haiyan; Joseph, Leroy C.; Gurin, Michael I.; Thorp, Edward B.; Morrow, John P.

    2014-01-01

    Pathologic cardiac hypertrophy can lead to heart failure, but the mechanisms involved are poorly understood. SERCA2 is critical for normal cardiac calcium handling and function and SERCA2 mRNA and protein levels are reduced by cardiac hypertrophy. We hypothesized that Extracellular Signal-regulated Kinase (ERK) 1/2 activation during hypertrophy reduced SERCA2 transcription. Using a neonatal rat ventricular myocyte model of hypertrophy, we found that pharmacologic inhibitors of ERK activation preserve SERCA2 mRNA levels during hypertrophy. ERK activation is sufficient to reduce SERCA2 mRNA. We determined that ERK represses SERCA2 transcription via nuclear factor-kappaB (NFkB), and activation of NFkB is sufficient to reduce SERCA2 mRNA in cardiomyocytes. This work establishes novel connections between ERK, NFkB, and SERCA2 repression during cardiac hypertrophy. This mechanism may have implications for the progression of hypertrophy to heart failure. PMID:25008120

  17. Parasympathetic cardiac activity is associated with cardiorespiratory fitness in overweight and obese adolescents.

    PubMed

    da Silva, Danilo Fernandes; Bianchini, Josiane Aparecida Alves; Antonini, Vanessa Drieli Seron; Hermoso, Danielle Aparecida Munhos; Lopera, Carlos Andres; Pagan, Bruno Guilherme Morais; McNeil, Jessica; Nardo Junior, Nelson

    2014-04-01

    The aim of this study was to investigate the association between cardiac parasympathetic activity and cardiorespiratory fitness, insulin, and hemodynamic profile in overweight and obese adolescent girls and boys (aged 12-16 years). Data were taken from the Multidisciplinary Obesity Treatment Program. Only post-intervention measurements are presented herein. Body composition, cardiorespiratory fitness, blood pressure, and metabolic profile (insulin and glucose profile) of adolescents were assessed. Cardiac parasympathetic activity was determined by resting heart rate variability, which was analyzed using a heart rate monitor. Greater parasympathetic cardiac activity was associated with higher levels of cardiorespiratory fitness in both girls and boys (0.375 ≤ r ≤ 0.900), while the sympathetic-vagal balance was negatively related to maximal oxygen uptake (VO2max) in girls (r = 0.478). An association between lower parasympathetic activity and insulin resistance was noted in girls (mean of R-R intervals [RRmean] and homeostasis model assessment insulin-resistance index [HOMA-IR]: r = -0.678), while greater systolic blood pressure (SBP) and lower parasympathetic activity were associated in both sexes (RRmean and SBP: r = -0.526; high frequency [HF (nu)] and SBP: r = -0.754). In conclusion, autonomic nervous system activity was associated with cardiorespiratory fitness, insulin resistance, and SBP in overweight and obese adolescents. The identification of these potential relationships assists with the establishment of future long-term exercise interventions that evaluate the improvements in parasympathetic nervous system activity, in addition to metabolic profile and cardiorespiratory fitness in overweight and obese adolescents.

  18. 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

  19. 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.

  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. 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

  2. Neonatal cardiac MRI using prolonged balanced SSFP imaging at 3T with active frequency stabilization.

    PubMed

    Price, Anthony N; Malik, Shaihan J; Broadhouse, Kathryn M; Finnemore, Anna E; Durighel, Giuliana; Cox, David J; Edwards, A David; Groves, Alan M; Hajnal, Joseph V

    2013-09-01

    Cardiac MRI in neonates holds promise as a tool that can provide detailed functional information in this vulnerable group. However, their small size, rapid heart rate, and inability to breath-hold, pose particular challenges that require prolonged high-contrast and high-SNR methods. Balanced-steady state free precession (SSFP) offers high SNR efficiency and excellent contrast, but is vulnerable to off-resonance effects that cause banding artifacts. This is particularly problematic in the blood-pool, where off-resonance flow artifacts severely degrade image quality. In this article, we explore active frequency stabilization, combined with image-based shimming, to achieve prolonged SSFP imaging free of banding artifacts. The method was tested using 2D multislice SSFP cine acquisitions on 18 preterm infants, and the functional measures derived were validated against phase-contrast flow assessment. Significant drifts in the resonant frequency (165 ± 23Hz) were observed during 10-min SSFP examinations. However, full short-axis stacks free of banding artifacts were achieved in 16 subjects with stabilization; the cardiac output obtained revealed a mean difference of 9.0 ± 8.5% compared to phase-contrast flow measurements. Active frequency stabilization has enabled the use of prolonged SSFP acquisitions for neonatal cardiac imaging at 3T. The findings presented could have broader implications for other applications using prolong SSFP acquisitions. Copyright © 2012 Wiley Periodicals, Inc.

  3. Caffeine restores myocardial cytochrome oxidase activity and improves cardiac function during sepsis.

    PubMed

    Verma, Richa; Huang, Zhishan; Deutschman, Clifford S; Levy, Richard J

    2009-04-01

    Impaired mitochondrial function is a potential cause of sepsis-associated myocardial depression. Cytochrome oxidase (CcOX), the terminal oxidase of the electron transport chain, is inhibited in the septic heart. Caffeine increases CcOX activity by increasing cyclic adenosine monophosphate and protein kinase A activity. We hypothesized that caffeine will restore myocardial CcOX activity, increase cardiac function, and improve survival during sepsis. Prospective randomized controlled study. University hospital-based laboratory. One hundred twenty Sprague-Dawley male rats. Sprague-Dawley male rats underwent cecal ligation and puncture (CLP) or sham operation. At 24 and 48 hours, rats underwent intraperitoneal injection of either caffeine (7.5 mg/kg, the equivalent of 1-1.5 cups of coffee) or equal volume of saline. One hour following the 48-hour injection, steady-state CcOX kinetic activity was measured in isolated mitochondria and normalized to citrate synthase activity. Cardiac function was assessed using an isolated rat heart preparation and survival was tracked to 96 hours. CLP significantly decreased myocardial CcOX activity, oxygen consumption, left ventricular pressure, and pressure developed during isovolumic contraction (+dP/dt) and relaxation (-dP/dt). Caffeine restored CcOX activity and increased left ventricular pressure and +/-dP/dt toward sham values following CLP. Survival significantly improved following CLP in caffeine-injected animals compared with saline injection. Caffeine may be a novel therapy to treat sepsis-associated myocardial depression.

  4. 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

  5. Recombinant activated factor VII for life-threatening pulmonary hemorrhage after pediatric cardiac surgery.

    PubMed

    Leibovitch, Leah; Kenet, Gili; Mazor, Kineret; Matok, Ilan; Vardi, Amir; Barzilay, Zohar; Paret, Gideon

    2003-10-01

    To report intractable life-threatening pulmonary hemorrhage after cardiac surgery in an infant who was treated successfully with recombinant activated factor VII (rFVIIa). Descriptive case report. An 18-bed pediatric intensive care unit at a tertiary-care children's hospital. A 10-wk-old child with acute life-threatening pulmonary hemorrhage after cardiac surgery. General supportive intensive care. Care included mechanical ventilatory support, inotropic support, and concurrent treatment with blood products (packed cells, platelet concentrates, and plasma-derived products), as well as aprotinin and desmopressin to improve hemostasis. The addition of rFVIIa resulted in complete resolution of the hemorrhage. rFVIIa should be considered as a possible novel therapeutic approach to be used as rescue therapy for patients presenting with massive life-threatening hemorrhage progressing into hemorrhagic shock. Further controlled trials to elucidate the safety of this treatment are warranted.

  6. Modeling of cardiac muscle thin films: pre-stretch, passive and active behavior.

    PubMed

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

    2012-03-15

    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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin.

    PubMed

    Qiu, Mingning; Ke, Longzhi; Zhang, Sai; Zeng, Xin; Fang, Zesong; Liu, Jianjun

    2017-08-01

    Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species. We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production. JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

  8. Kruppel-like Factor 4 Protein Regulates Isoproterenol-induced Cardiac Hypertrophy by Modulating Myocardin Expression and Activity*

    PubMed Central

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

    2014-01-01

    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. PMID:25100730

  9. Blockage of angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation.

    PubMed

    Carneiro-Ramos, M S; Diniz, G P; Nadu, A P; Almeida, J; Vieira, R L P; Santos, R A S; Barreto-Chaves, M L M

    2010-05-01

    Although most of effects of Angiotensin II (Ang II) related to cardiac remodelling can be attributed to type 1 Ang II receptor (AT(1)R), the type 2 receptor (AT(2)R) has been shown to be involved in the development of some cardiac hypertrophy models. In the present study, we investigated whether the thyroid hormone (TH) action leading to cardiac hypertrophy is also mediated by increased Ang II levels or by change on AT(1)R and AT(2)R expression, which could contribute to this effect. In addition, we also evaluated the possible contribution of AT(2)R in the activation of Akt and in the development of TH-induced cardiac hypertrophy. To address these questions, Wistar rats were treated with thyroxine (T(4), 0.1 mg/kg BW/day, i.p.), with or without AT(2)R blocker (PD123319), for 14 days. Cardiac hypertrophy was identified based on heart/body weight ratio and confirmed by analysis of atrial natriuretic factor mRNA expression. Cardiomyocyte cultures were used to exclude the influence of TH-related hemodynamic effects. Our results demonstrate that the cardiac Ang II levels were significantly increased (80%, P < 0.001) as well as the AT(2)R expression (50%, P < 0.05) in TH-induced cardiac hypertrophy. The critical involvement of AT(2)R to the development of this cardiac hypertrophy in vivo was evidenced after administration of AT(2) blocker, which was able to prevent in 40% (P < 0.01) the cardiac mass gain and the Akt activation induced by TH. The role of AT(2)R to the TH-induced cardiomyocyte hypertrophy was also confirmed after using PD123319 in the in vitro studies. These findings improve understanding of the cardiac hypertrophy observed in hyperthyroidism and provide new insights into the generation of future therapeutic strategies.

  10. 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.

  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. 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

  13. 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.

  14. Abnormal Activity Detection Using Pyroelectric Infrared Sensors

    PubMed Central

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

    2016-01-01

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

  15. 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.

  16. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Changes in plasma dopamine-beta-hydroxylase activity during the perioperative period of cardiac surgery: an index of sympathetic nerve activity.

    PubMed

    Yoshizumi, M; Katoh, I; Egawa, Y; Kitagawa, T; Miki, O; Masuda, Y; Ohuchi, T; Oka, M

    1993-01-01

    To evaluate the usefulness of plasma dopamine-beta-hydroxylase (DBH) activity as an index of sympathetic nerve activity during cardiac operations, we examined the serial changes in plasma DBH activity, in relation to the plasma noradrenaline (NA) level and hemodynamic parameters, in patients who underwent cardiac surgery. The plasma DBH activity decreased significantly after cardiopulmonary bypass, and remained low during dopamine (DA) infusion until 72 h after the operation. However, recovery of the hemodynamic parameters, being the mean arterial pressure, heart rate and cardiac index, was seen as early as 1-3 h postoperatively. It was therefore assumed that the plasma DBH activity takes a long time to recover after an operation. The time-course changes in the plasma NA level were quite different from the changes in DBH activity, with an apparent negative correlation being observed between them. Thus, there is a possibility that exogenously administered DA, as well as increased plasma NA, might inhibit DBH activity during cardiac surgery. Moreover, since catecholamines are often administered upon completion of cardiac surgery, measurement of the plasma catecholamine level would be inappropriate for evaluating real sympathetic nerve activity. From the results of this study, it is surmised that measurement of the plasma DBH activity could be useful for estimating the intrinsic sympathetic nerve activity of patients who have undergone cardiac surgery.

  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. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Prediction of myocardial infarction by assessing regional cardiac wall in CMR images through active mesh modeling.

    PubMed

    Yousefi-Banaem, Hossein; Kermani, Saeed; Asiaei, Sasan; Sanei, Hamid

    2017-01-01

    Myocardial infarction is a leading cause of morbidity and mortality. In this study, using Cine MRI images, the infarct region was precisely determined by examining the local migration path length of critical points on myocardium borders and the fractional thickening effects. First, MRI Cine images of Epi/Endocardium were processed in 3D for all slices, and then incorporated in all frames to build a dynamic model. Epi/Endocardium images were segmented using Heiberg algorithm, and then by a robust restricted block matching algorithm, the sparse points were tracked. Finally, by fitting a 3D active mesh model to the sparse point displacements, a dense motion field was obtained, and some useful local parameters of left ventricle in patients with myocardial infarction were estimated. The local parameters are path length, fractional thickening, and strain. Using this process, the cardiac wall motion was quantized to determine the region and extent of infarct lesion. The process was implemented, and the results were examined and modified against the cardiac perfusion scan. Data were acquired from 10 healthy individuals and 20 patients with the myocardial infarction. The findings also reveal that the infarct region can be determined by locating less than 20% in the wall thickening. In all the patients, the process was able to precisely determine the affected region. The cardiac wall kinesis in damaged regions was properly evaluated by normalized path length and presented in standard bull's-eye format. The above approach is promising and can be extended in prognosis of acute heart infraction by prediction of prone to the wall kinesis regions in the patients close to MI by examining the local indexes of the myocardium in the cardiac MRI images. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. 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.

  8. 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.

  9. 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.

  10. ATP released from cardiac fibroblasts via connexin hemichannels activates profibrotic P2Y2 receptors

    PubMed Central

    Lu, David; Soleymani, Sahar; Madakshire, Rohit; Insel, Paul A.

    2012-01-01

    Cardiac fibroblasts (CFs) play an essential role in remodeling of the cardiac extracellular matrix. Extracellular nucleotide signaling may provoke a profibrotic response in CFs. We tested the hypothesis that physical perturbations release ATP from CFs and that ATP participates in profibrotic signaling. ATP release was abolished by the channel inhibitor carbenoxolone and inhibited by knockdown of either connexin (Cx)43 or Cx45 (47 and 35%, respectively), implying that hypotonic stimulation induces ATP release via Cx43 and Cx45 hemichannels, although pannexin 1 may also play a role. ATP released by hypotonic stimulation rapidly (<10 min) increased phosphorylated ERK by 5-8 fold, an effect largely eliminated by P2Y2 receptor knockdown or ATP hydrolysis with apyrase. ATP stimulation of P2Y2 receptors increased α-smooth muscle actin (α-SMA) production, and in an ERK-dependent manner, ATP increased collagen accumulation by 60% and mRNA expression of profibrotic markers: plasminogen activator inhibitor-1 and monocyte chemotactic protein-1 by 4.5- and 4.0-fold, respectively. Apyrase treatment substantially reduced the basal profibrotic phenotype, decreasing collagen and α-SMA content and increasing matrix metalloproteinase expression. Thus, ATP release activates P2Y2 receptors to mediate profibrotic responses in CFs, implying that nucleotide release under both basal and activated states is likely an important mechanism for fibroblast homeostasis.—Lu, D., Soleymani, S., Madakshire, R., Insel, P. A. ATP released from cardiac fibroblasts via connexin hemichannels activates profibrotic P2Y2 receptors. PMID:22415310

  11. 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.

  12. Cascading Crater Detection with Active Learning

    NASA Astrophysics Data System (ADS)

    Miller, W. I.; Stepinski, T. F.; Mu, Y.; Ding, W.

    2011-03-01

    Our strategy for automatic crater detection consists of employing a cascading AdaBoost classifier for identification of craters in images, and using the SOM as an active learning tool to minimize the number of image examples that need to be labeled by an analyst.

  13. 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

  14. 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.

  15. Detection, characterisation, and quantification of carnosine and other histidyl derivatives in cardiac and skeletal muscle.

    PubMed

    O'Dowd, J J; Robins, D J; Miller, D J

    1988-11-17

    Isocratic reverse phase analytical high performance liquid chromatography (HPLC) has been used to examine naturally occurring imidazoles of cardiac and skeletal muscles. Elution of muscle extracts with a phosphate buffer mobile phase from columns packed with hypersil ODS (5 micron) resulted in good separation of the skeletal muscle imidazole-containing dipeptides carnosine and anserine. Measured concentrations corresponded to published values. N-Acetyl forms that were not commercially available were prepared from their parent compounds and their identities verified by NMR-spectroscopy. Examination of frog cardiac muscle confirmed the presence of N-acetylhistidine and also indicated the presence of its 1-methyl derivative. Extracts of mammalian cardiac muscle were examined by HPLC which indicated the presence of low concentrations of carnosine but substantial amounts of N-acetyl forms of histidine, 1-methylhistidine, carnosine and anserine. Fractions corresponding to the numerous peaks were examined using staining systems specific for certain chemical features and compared to results obtained for commercial or synthetic standards. Results of these tests supported the chromatographic data. The total concentrations in cardiac muscle of these imidazole-containing substances (approx. 10 mM) is sufficient to alter significantly the sensitivity of their contractile apparatus to calcium ions.

  16. Cardiac V1 and V3 myosins differ in their hydrolytic and mechanical activities in vitro.

    PubMed

    VanBuren, P; Harris, D E; Alpert, N R; Warshaw, D M

    1995-08-01

    The two mammalian cardiac myosin heavy chain isoforms, alpha and beta, have 93% amino acid homology, but hearts expressing these myosins exhibit marked differences in their mechanical activities. To further understand the function of these cardiac myosins as molecular motors, we compared the ability of these myosins to hydrolyze ATP and to both translocate actin filaments and generate force in an in vitro motility assay. V1 myosin has twice the actin-activated ATPase activity and three times the actin filament sliding velocity when compared with V3 myosin. In contrast, the force-generating ability of these myosins is quite different when the total force produced by a small population of myosin molecules (> 50) is examined. V1 myosin produces only one half the average cross-bridge force of V3 myosin. With discrete areas of primary structural heterogeneity known to exist between alpha and beta heavy chains, the differences we report in the hydrolytic and mechanical activities of the motors are explored in the context of potential structural and kinetic differences between the V1 and V3 myosins.

  17. Improved discretisation and linearisation of active tension in strongly coupled cardiac electro-mechanics simulations

    PubMed Central

    Sundnes, J.; Wall, S.; Osnes, H.; Thorvaldsen, T.; McCulloch, A.D.

    2013-01-01

    Mathematical models of cardiac electro-mechanics typically consist of three tightly coupled parts: systems of ordinary differential equations describing electro-chemical reactions and cross-bridge dynamics in the muscle cells, a system of partial differential equations modelling the propagation of the electrical activation through the tissue and a nonlinear elasticity problem describing the mechanical deformations of the heart muscle. The complexity of the mathematical model motivates numerical methods based on operator splitting, but simple explicit splitting schemes have been shown to give severe stability problems for realistic models of cardiac electro-mechanical coupling. The stability may be improved by adopting semi-implicit schemes, but these give rise to challenges in updating and linearising the active tension. In this paper we present an operator splitting framework for strongly coupled electro-mechanical simulations and discuss alternative strategies for updating and linearising the active stress component. Numerical experiments demonstrate considerable performance increases from an update method based on a generalised Rush–Larsen scheme and a consistent linearisation of active stress based on the first elasticity tensor. PMID:22800534

  18. Improved discretisation and linearisation of active tension in strongly coupled cardiac electro-mechanics simulations.

    PubMed

    Sundnes, J; Wall, S; Osnes, H; Thorvaldsen, T; McCulloch, A D

    2014-01-01

    Mathematical models of cardiac electro-mechanics typically consist of three tightly coupled parts: systems of ordinary differential equations describing electro-chemical reactions and cross-bridge dynamics in the muscle cells, a system of partial differential equations modelling the propagation of the electrical activation through the tissue and a nonlinear elasticity problem describing the mechanical deformations of the heart muscle. The complexity of the mathematical model motivates numerical methods based on operator splitting, but simple explicit splitting schemes have been shown to give severe stability problems for realistic models of cardiac electro-mechanical coupling. The stability may be improved by adopting semi-implicit schemes, but these give rise to challenges in updating and linearising the active tension. In this paper we present an operator splitting framework for strongly coupled electro-mechanical simulations and discuss alternative strategies for updating and linearising the active stress component. Numerical experiments demonstrate considerable performance increases from an update method based on a generalised Rush-Larsen scheme and a consistent linearisation of active stress based on the first elasticity tensor.

  19. 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.

  20. 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

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

    PubMed

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

    2013-07-01

    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. 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. 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%, 99.2%, and 96.5% for the CS, ablation

  2. 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.

  3. [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.

  4. 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

  5. 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.

  6. Targeting Mll1 H3K4 methyltransferase activity to guide cardiac lineage specific reprogramming of fibroblasts.

    PubMed

    Liu, Liu; Lei, Ienglam; Karatas, Hacer; Li, Yangbing; Wang, Li; Gnatovskiy, Leonid; Dou, Yali; Wang, Shaomeng; Qian, Li; Wang, Zhong

    2016-01-01

    Generation of induced cardiomyocytes (iCMs) directly from fibroblasts offers a great opportunity for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation is the low conversion rate. To address this issue, we attempted to identify small molecules that could potentiate the reprogramming ability towards cardiac fate by removing inhibitory roadblocks. Using mouse embryonic fibroblasts as the starting cell source, we first screened 47 cardiac development related epigenetic and transcription factors, and identified an unexpected role of H3K4 methyltransferase Mll1 and related factor Men1 in inhibiting iCM reprogramming. We then applied small molecules (MM408 and MI503) of Mll1 pathway inhibitors and observed an improved efficiency in converting embryonic fibroblasts and cardiac fibroblasts into functional cardiomyocyte-like cells. We further observed that these inhibitors directly suppressed the expression of Mll1 target gene Ebf1 involved in adipocyte differentiation. Consequently, Mll1 inhibition significantly decreased the formation of adipocytes during iCM induction. Therefore, Mll1 inhibitors likely increased iCM efficiency by suppressing alternative lineage gene expression. Our studies show that targeting Mll1 dependent H3K4 methyltransferase activity provides specificity in the process of cardiac reprogramming. These findings shed new light on the molecular mechanisms underlying cardiac conversion of fibroblasts and provide novel targets and small molecules to improve iCM reprogramming for clinical applications.

  7. The synchronous active neutron detection assay system

    SciTech Connect

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

    1994-08-01

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

  8. 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.

  9. Ranging performance of active laser detection

    NASA Astrophysics Data System (ADS)

    Sun, Huayan; Xiong, Fei; Gu, Suolin

    2006-06-01

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

  10. 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

  11. 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.

  12. ATP released from cardiac fibroblasts via connexin hemichannels activates profibrotic P2Y2 receptors.

    PubMed

    Lu, David; Soleymani, Sahar; Madakshire, Rohit; Insel, Paul A

    2012-06-01

    Cardiac fibroblasts (CFs) play an essential role in remodeling of the cardiac extracellular matrix. Extracellular nucleotide signaling may provoke a profibrotic response in CFs. We tested the hypothesis that physical perturbations release ATP from CFs and that ATP participates in profibrotic signaling. ATP release was abolished by the channel inhibitor carbenoxolone and inhibited by knockdown of either connexin (Cx)43 or Cx45 (47 and 35%, respectively), implying that hypotonic stimulation induces ATP release via Cx43 and Cx45 hemichannels, although pannexin 1 may also play a role. ATP released by hypotonic stimulation rapidly (<10 min) increased phosphorylated ERK by 5-8 fold, an effect largely eliminated by P2Y(2) receptor knockdown or ATP hydrolysis with apyrase. ATP stimulation of P2Y(2) receptors increased α-smooth muscle actin (α-SMA) production, and in an ERK-dependent manner, ATP increased collagen accumulation by 60% and mRNA expression of profibrotic markers: plasminogen activator inhibitor-1 and monocyte chemotactic protein-1 by 4.5- and 4.0-fold, respectively. Apyrase treatment substantially reduced the basal profibrotic phenotype, decreasing collagen and α-SMA content and increasing matrix metalloproteinase expression. Thus, ATP release activates P2Y(2) receptors to mediate profibrotic responses in CFs, implying that nucleotide release under both basal and activated states is likely an important mechanism for fibroblast homeostasis.

  13. Tanshinone-induced ERs suppresses IGFII activation to alleviate Ang II-mediated cardiac hypertrophy.

    PubMed

    Chen, Ya-Fang; Lee, Nien-Hung; Pai, Pei-Ying; Chung, Li-Chin; Shen, Chia-Yao; Rajendran, Peramaiyan; Chen, Yu-Feng; Chen, Ray-Jade; Padma Viswanadha, Vijaya; Kuo, Wei-Wen; Huang, Chih-Yang

    2017-10-01

    Cardiomyopathy involves changes in myocardial ultrastructure and cardiac hypertrophy. Angiotensin II (AngII) has previously been shown to stimulate the expression of IGF-2 and IGF-2R in H9c2 cardiomyoblasts and increase of blood pressure, and cardiac hypertrophy. Estrogen receptors (ERs) exert protective effects, such as anti-hypertrophy in cadiomyocytes. Tanshinone IIA (TSN), a main active ingredient from a Chinese medical herb, Salvia miltiorrhiza Bunge (Danshen), was shown to protect cardiomyocytes hypertrophy by different stress signals. We aimed to investigate whether TSN protected H9c2 cardiomyocytes from AngII-induced activation of IGF-2R pathway and hypertrophy by mediating through ERs. AngII resulted in H9c2 cardiomyoblast hypertrophy and increased inflammatory molecular markers. These were down-regulated by TSN via estrogen receptors. AngII resulted in elevation in MAPKs, IGF-2R and hypertrophic protein markers. These, again, were reduced by addition of the phytoestrogen with activation of ERs. Finally, AngII induced phosphorylation of heat shock factor-1 (HSF1) and decreased sirtuin-1 (SIRT1). In addition, AngII also caused an increase in distribution of IGF-2R molecules on cell membrane. In contrast, TSN reduced HSF1 phosphorylation and cell surface IGF-2R while elevating SIRT1 via ERs. TSN was capable of attenuating AngII-induced IGF-2R pathway and hypertrophy through ERs in H9c2 cardiomyoblast cells.

  14. 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

  15. Cardiac cachexia.

    PubMed

    Anker, Stefan D; Steinborn, Wolfram; Strassburg, Sabine

    2004-01-01

    Chronic heart failure (CHF) remains an important and increasing public health care problem. It is a complex syndrome affecting many body systems. Body wasting (i.e., cardiac cachexia) has long been recognised as a serious complication of CHF. Cardiac cachexia is associated with poor prognosis, independently of functional disease severity, age, and measures of exercise capacity and cardiac function. Patients with cardiac cachexia suffer from a general loss of fat tissue, lean tissue, and bone tissue. Cachectic CHF patients are weaker and fatigue earlier, which is due to both reduced skeletal muscle mass and impaired muscle quality. The pathophysiologic alterations leading to cardiac cachexia remain unclear, but there is increasing evidence that metabolic, neurohormonal and immune abnormalities may play an important role. Cachectic CHF patients show raised plasma levels of epinephrine, norepinephrine, and cortisol, and they show high plasma renin activity and increased plasma aldosterone level. Several studies have also shown that cardiac cachexia is linked to raised plasma levels of tumour necrosis factor alpha and other inflammatory cytokines. The degree of body wasting is strongly correlated with neurohormonal and immune abnormalities. The available evidence suggests that cardiac cachexia is a multifactorial neuroendocrine and metabolic disorder with a poor prognosis. A complex imbalance of different body systems may cause the development of body wasting.

  16. Cardiac proteasome activity in muscle ring finger-1 null mice at rest and following synthetic glucocorticoid treatment

    PubMed Central

    Hwee, Darren T.; Gomes, Aldrin V.

    2011-01-01

    Muscle ring finger-1 (MuRF1) is a muscle-specific E3 ubiquitin ligase that has been implicated in the regulation of cardiac mass through its control of the ubiquitin proteasome system. While it has been suggested that MuRF1 is required for cardiac atrophy, a resting cardiac phenotype has not been reported in mice with a null deletion [knockout (KO)] of MuRF1. Here, we report that MuRF1 KO mice have significantly larger hearts than age-matched wild-type (WT) littermates at ≥6 mo of age and that loss of cardiac mass can occur in the absence of MuRF1. The objective of this study was to determine whether changes in proteasome activity were responsible for the cardiac phenotypes observed in MuRF1 KO mice. Cardiac function, architecture, and proteasome activity were analyzed at rest and following 28 days of dexamethasone (Dex) treatment in 6-mo-old WT and MuRF1 KO mice. Echocardiography demonstrated normal cardiac function in the enlarged hearts in MURF1 KO mice. At rest, heart mass and cardiomyocyte diameter were significantly greater in MuRF1 KO than in WT mice. The increase in cardiac size in MuRF1 KO mice was related to a decrease in proteasome activity and an increase in Akt signaling relative to WT mice. Dex treatment induced a significant loss of cardiac mass in MuRF1 KO, but not WT, mice. Furthermore, Dex treatment resulted in an increase in proteasome activity in KO, but a decrease in WT, mice. In contrast, Akt/mammalian target of rapamycin signaling decreased in MuRF1 KO mice and increased in WT mice in response to Dex treatment. These findings demonstrate that MuRF1 plays an important role in regulating cardiac size through alterations in protein turnover and that MuRF1 is not required to induce cardiac atrophy. PMID:21828340

  17. Cardiac proteasome activity in muscle ring finger-1 null mice at rest and following synthetic glucocorticoid treatment.

    PubMed

    Hwee, Darren T; Gomes, Aldrin V; Bodine, Sue C

    2011-11-01

    Muscle ring finger-1 (MuRF1) is a muscle-specific E3 ubiquitin ligase that has been implicated in the regulation of cardiac mass through its control of the ubiquitin proteasome system. While it has been suggested that MuRF1 is required for cardiac atrophy, a resting cardiac phenotype has not been reported in mice with a null deletion [knockout (KO)] of MuRF1. Here, we report that MuRF1 KO mice have significantly larger hearts than age-matched wild-type (WT) littermates at ≥ 6 mo of age and that loss of cardiac mass can occur in the absence of MuRF1. The objective of this study was to determine whether changes in proteasome activity were responsible for the cardiac phenotypes observed in MuRF1 KO mice. Cardiac function, architecture, and proteasome activity were analyzed at rest and following 28 days of dexamethasone (Dex) treatment in 6-mo-old WT and MuRF1 KO mice. Echocardiography demonstrated normal cardiac function in the enlarged hearts in MURF1 KO mice. At rest, heart mass and cardiomyocyte diameter were significantly greater in MuRF1 KO than in WT mice. The increase in cardiac size in MuRF1 KO mice was related to a decrease in proteasome activity and an increase in Akt signaling relative to WT mice. Dex treatment induced a significant loss of cardiac mass in MuRF1 KO, but not WT, mice. Furthermore, Dex treatment resulted in an increase in proteasome activity in KO, but a decrease in WT, mice. In contrast, Akt/mammalian target of rapamycin signaling decreased in MuRF1 KO mice and increased in WT mice in response to Dex treatment. These findings demonstrate that MuRF1 plays an important role in regulating cardiac size through alterations in protein turnover and that MuRF1 is not required to induce cardiac atrophy.

  18. Long-term detection of atrial fibrillation with insertable cardiac monitors in a real-world cryptogenic stroke population.

    PubMed

    Ziegler, Paul D; Rogers, John D; Ferreira, Scott W; Nichols, Allan J; Richards, Mark; Koehler, Jodi L; Sarkar, Shantanu

    2017-10-01

    The long-term incidence of atrial fibrillation (AF) in cryptogenic stroke (CS) patients has been explored in carefully controlled clinical trials but real-world data are limited. We investigated the two-year incidence of AF in real-world clinical practice among a large cohort of patients with an insertable cardiac monitor (ICM) placed for AF detection following CS. Patients in the de-identified Medtronic Discovery™ Link database who received an ICM (Reveal LINQ™) for the purpose of AF detection following CS were included and monitored for up to 2years. All detected AF episodes (≥2min) were adjudicated. We quantified the AF detection rate using Kaplan-Meier survival estimates, analyzed the median time to initial detection of AF, and simulated the ability of various intermittent monitoring strategies to detect AF. A total of 1247 patients (65.3±13.0years, 53% male) were included and followed for 579±222days. AF episodes (n=4183) were detected in 238 patients, resulting in an AF detection rate of 21.5% at 2years. The median time to AF detection was 112 [IQR 35-293] days. Intermittent monitoring for AF detection was inferior to continuous ICM monitoring with sensitivities ranging from 2.9% (annual 24-hour Holter) to 29.9% (quarterly 7-day Holters), p<0.001. AF episodes were detected via continuous monitoring with ICMs in approximately 1 of every 5 CS patients within 2years of follow-up. The vast majority of patients with AF would not have been detected with conventional external ambulatory monitors. ICMs should therefore be considered in the evaluation of CS patients. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  1. 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.

  2. 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

  3. 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

  4. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction.

    PubMed

    Sharma, Umesh C; Pokharel, Saraswati; van Brakel, Thomas J; van Berlo, Jop H; Cleutjens, Jack P M; Schroen, Blanche; André, Sabine; Crijns, Harry J G M; Gabius, Hans-J; Maessen, Jos; Pinto, Yigal M

    2004-11-09

    Inflammatory mechanisms have been proposed to be important in heart failure (HF), and cytokines have been implicated to add to the progression of HF. However, it is unclear whether such mechanisms are already activated when hypertrophied hearts still appear well-compensated and whether such early mechanisms contribute to the development of HF. In a comprehensive microarray study, galectin-3 emerged as the most robustly overexpressed gene in failing versus functionally compensated hearts from homozygous transgenic TGRmRen2-27 (Ren-2) rats. Myocardial biopsies obtained at an early stage of hypertrophy before apparent HF showed that expression of galectin-3 was increased specifically in the rats that later rapidly developed HF. Galectin-3 colocalized with activated myocardial macrophages. We found galectin-3-binding sites in rat cardiac fibroblasts and the extracellular matrix. Recombinant galectin-3 induced cardiac fibroblast proliferation, collagen production, and cyclin D1 expression. A 4-week continuous infusion of low-dose galectin-3 into the pericardial sac of healthy Sprague-Dawley rats led to left ventricular dysfunction, with a 3-fold differential increase of collagen I over collagen III. Myocardial galectin-3 expression was increased in aortic stenosis patients with depressed ejection fraction. This study shows that an early increase in galectin-3 expression identifies failure-prone hypertrophied hearts. Galectin-3, a macrophage-derived mediator, induces cardiac fibroblast proliferation, collagen deposition, and ventricular dysfunction. This implies that HF therapy aimed at inflammatory responses may need to be targeted at the early stages of HF and probably needs to antagonize multiple inflammatory mediators, including galectin-3.

  5. beta-Adrenergic activation reveals impaired cardiac calcium handling at early stage of diabetes.

    PubMed

    op den Buijs, Jorn; Miklós, Zsuzsanna; van Riel, Natal A W; Prestia, Christina M; Szenczi, Orsolya; Tóth, András; Van der Vusse, Ger J; Szabó, Csaba; Ligeti, László; Ivanics, Tamás

    2005-01-21

    Cardiac function is known to be impaired in diabetes. Alterations in intracellular calcium handling have been suggested to play a pivotal role. This study aimed to test the hypothesis that beta-adrenergic activation can reveal the functional derangements of intracellular calcium handling of the 4-week diabetic heart. Langendorff perfused hearts of 4-week streptozotocin-induced diabetic rats were subjected to the beta-adrenoceptor agonist isoproterenol. Cyclic changes in [Ca(2+)](i) levels were measured throughout the cardiac cycle using Indo-1 fluorescent dye. Based on the computational analysis of the [Ca(2+)](i) transient the kinetic parameters of the sarcoplasmic reticulum Ca(2+)-ATPase and the ryanodine receptor were determined by minimizing the squared error between the simulated and the experimentally obtained [Ca(2+)](i) transient. Under unchallenged conditions, hemodynamic parameters were comparable between control and diabetic hearts. Isoproterenol administration stimulated hemodynamic function to a greater extent in control than in diabetic hearts, which was exemplified by more pronounced increases in rate of pressure development and decline. Under unchallenged conditions, [Ca(2+)](i) amplitude and rate of rise and decline of [Ca(2+)](i) as measured throughout the cardiac cycle were comparable between diabetic and control hearts. Differences became apparent under beta-adrenoceptor stimulation. Upon beta-activation the rate-pressure product showed a blunted response, which was accompanied by a diminished rise in [Ca(2+)](i) amplitude in diabetic hearts. Computational analysis revealed a reduced function of the sarcoplasmic reticulum Ca(2+)-ATPase and Ca(2+)-release channel in response to beta-adrenoceptor challenge. Alterations in Ca(2+)(i) handling may play a causative role in depressed hemodynamic performance of the challenged heart at an early stage of diabetes.

  6. Older Adults' Music Listening Preferences to Support Physical Activity Following Cardiac Rehabilitation.

    PubMed

    Clark, Imogen N; Baker, Felicity A; Taylor, Nicholas F

    2016-01-01

    Music listening during exercise is thought to increase physiological arousal and enhance subjective experience, and may support physical activity participation among older adults with cardiac disease. However, little is known about how music preferences, or perceptions of music during exercise, inform clinical practice with this population. Identify predominant musical characteristics of preferred music selected by older adults, and explore participants' music listening experiences during walking-based exercise following cardiac rehabilitation. Twenty-seven participants aged 60 years and older (21 men, 6 women; mean age = 67.3 years) selected music to support walking over a 6-month intervention period, and participated in post-intervention interviews. In this two-phase study, we first identified predominant characteristics of participant-selected music using the Structural Model of Music Analysis. Second, we used inductive thematic analysis to explore participant experiences. Predominant characteristics of participant-selected music included duple meter, consistent rhythm, major key, rounded melodic shape, legato articulation, predictable harmonies, variable volume, and episodes of tension with delayed resolution. There was no predominant tempo, with music selections ranging from slow through to medium and fast. Four themes emerged from thematic analysis of participant interviews: psycho-emotional responses, physical responses, influence on exercise behavior, and negative experiences. Findings are consistent with theory and research explaining influences from music listening on physiological arousal and subjective experience during exercise. Additionally, for older adults with cardiac disease, a holistic approach to music selection considering general well-being and adjustment issues, rather than just exercise performance, may improve long-term lifestyle changes and compliance with physical activity guidelines. © the American Music Therapy Association 2016. All

  7. 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.

  8. 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

  9. Analyte detection using an active assay

    DOEpatents

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

    2010-11-02

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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Elevated myocardial Na+/H+ exchanger isoform 1 activity elicits gene expression that leads to cardiac hypertrophy

    PubMed Central

    Xue, Jin; Mraiche, Fatima; Zhou, Dan; Karmazyn, Morris; Oka, Tatsujiro; Fliegel, Larry

    2010-01-01

    In myocardial disease, elevated expression and activity of Na+/H+ exchanger isoform 1 (NHE1) are detrimental. To better understand the involvement of NHE1, transgenic mice with elevated heart-specific NHE1 expression were studied. N-line mice expressed wild-type NHE1, and K-line mice expressed activated NHE1. Cardiac morphology, interstitial fibrosis, and cardiac function were examined by histological staining and echocardiography. Differences in gene expression between the N-line or K-line and nontransgenic littermates were probed with genechip analysis. We found that NHE1 K-line (but not N-line) hearts developed hypertrophy, including elevated heart weight-to-body weight ratio and increased cross-sectional area of the cardiomyocytes, interstitial fibrosis, as well as depressed cardiac function. N-line hearts had modest changes in gene expression (50 upregulations and 99 downregulations, P < 0.05), whereas K-line hearts had a very strong transcriptional response (640 upregulations and 677 downregulations, P < 0.05). In addition, the magnitude of expression alterations was much higher in K-line than N-line mice. The most significant changes in gene expression were involved in cardiac hypertrophy, cardiac necrosis/cell death, and cardiac infarction. Secreted phosphoprotein 1 and its signaling pathways were upregulated while peroxisome proliferator-activated receptor γ signaling was downregulated in K-line mice. Our study shows that expression of activated NHE1 elicits specific pathways of gene activation in the myocardium that lead to cardiac hypertrophy, cell death, and infarction. PMID:20460605

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Automated Detection of Activity Transitions for Prompting

    PubMed Central

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

    2016-01-01

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

  1. Automated Detection of Activity Transitions for Prompting.

    PubMed

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

    2015-10-01

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

  2. 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.

  3. Simultaneous recordings of intrinsic cardiac nerve activity and skin sympathetic nerve activity from human patients during the postoperative period.

    PubMed

    Shen, Mark J; Coffey, Arthur C; Straka, Susan; Adams, David E; Wagner, David B; Kovacs, Richard J; Clark, Michael; Shen, Changyu; Chen, Lan S; Everett, Thomas H; Lin, Shien-Fong; Chen, Peng-Sheng

    2017-06-23

    Intrinsic cardiac nerve activity (ICNA) and skin nerve activity (SKNA) are both associated with cardiac arrhythmias in dogs. The purpose of this study was to test the hypothesis that ICNA and SKNA correlate with postoperative cardiac arrhythmias in humans. Eleven patients (mean age 60 ± 13 years; 4 women) were enrolled in this study. Electrical signals were simultaneously recorded from electrocardiogram (ECG) patch electrodes on the chest wall and from 2 temporary pacing wires placed during open heart surgery on the left atrial epicardial fat pad. The signals were filtered to display SKNA and ICNA. Premature atrial contractions (PACs) and premature ventricular contractions were determined manually. The SKNA and ICNA of the first 300 minutes of each patient were calculated minute by minute to determine baseline average amplitudes of nerve activities and to determine their correlation with ar