Genome-wide computational analysis reveals cardiomyocyte-specific transcriptional Cis-regulatory motifs that enable efficient cardiac gene therapy.

PubMed

Rincon, Melvin Y; Sarcar, Shilpita; Danso-Abeam, Dina; Keyaerts, Marleen; Matrai, Janka; Samara-Kuko, Ermira; Acosta-Sanchez, Abel; Athanasopoulos, Takis; Dickson, George; Lahoutte, Tony; De Bleser, Pieter; VandenDriessche, Thierry; Chuah, Marinee K

2015-01-01

Gene therapy is a promising emerging therapeutic modality for the treatment of cardiovascular diseases and hereditary diseases that afflict the heart. Hence, there is a need to develop robust cardiac-specific expression modules that allow for stable expression of the gene of interest in cardiomyocytes. We therefore explored a new approach based on a genome-wide bioinformatics strategy that revealed novel cardiac-specific cis-acting regulatory modules (CS-CRMs). These transcriptional modules contained evolutionary-conserved clusters of putative transcription factor binding sites that correspond to a "molecular signature" associated with robust gene expression in the heart. We then validated these CS-CRMs in vivo using an adeno-associated viral vector serotype 9 that drives a reporter gene from a quintessential cardiac-specific α-myosin heavy chain promoter. Most de novo designed CS-CRMs resulted in a >10-fold increase in cardiac gene expression. The most robust CRMs enhanced cardiac-specific transcription 70- to 100-fold. Expression was sustained and restricted to cardiomyocytes. We then combined the most potent CS-CRM4 with a synthetic heart and muscle-specific promoter (SPc5-12) and obtained a significant 20-fold increase in cardiac gene expression compared to the cytomegalovirus promoter. This study underscores the potential of rational vector design to improve the robustness of cardiac gene therapy.

Microwave influence on the isolated heart function. 2: Combined effect of radiation and some drugs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pakhomov, A.G.; Dubovick, B.V.; Degtyariov, I.G.

1995-09-01

The combined effects of microwave radiation and some drugs were studied in an isolated frog auricle preparation. The experiments established that exposure to pulse-modulated 915 Mhz microwaves for up to 40 min had no effect on either the rate or the amplitude of spontaneous auricle twitches, unless the average absorbed power was high enough to produce preparation heating. Treatment of the preparation with saline containing (0.6--3.0) 10{sup {minus}5} M of propranolol or (0.5--1.5) 10{sup {minus}7} M of atropine altered neither its pacemaker nor its contractile functions; these drugs also had no effect when they were combined with nonthermal microwave irradiation.more » Caffeine (1 mM) strongly increased the average heart power, which was calculated as the product of twitch rate ad amplitude. The caffeine effect appeared to be significantly augmented (by about 15%, P<0.02) under exposure to burst-type pulsed microwaves (pulse width, 1.5 msec; pause, 2.5 msec; 8 pulses/burst, 16 bursts/s; average SAR, 8--10 W/kg). By itself, this modulation was not effective; the heating of the preparation and saline during exposure was approximately 0.1 C, which could not account for the detected changes. The experimental results demonstrate that caffeine treatment increases the microwave sensitivity of the frog auricle preparation and reveals primarily subthreshold, nonthermal microwave effect.« less

Applying the technique of volume-modulated arc radiotherapy to upper esophageal carcinoma.

PubMed

Ma, Pan; Wang, Xiaozhen; Xu, Yingjie; Dai, Jianrong; Wang, Luhua

2014-05-08

This study aims to evaluate the possibility of using the technique of volume-modulated arc therapy (VMAT) to combine the advantages of simplified intensity-modulated radiation therapy (sIMRT) with that of regular intensity-modulated radiation therapy (IMRT) in upper esophageal cancer. Ten patients with upper esophageal carcinoma were randomly chosen in this retrospective study. sIMRT, IMRT, and VMAT plans were generated to deliver 60 Gy in 30 fractions to the planning target volume (PTV). For each patient, with the same clinical requirements (target dose prescription, and dose/dose-volume constraints to organs at risk (OARs)), three plans were designed for sIMRT (five equispaced coplanar beams), IMRT (seven equispaced coplanar beams), and VMAT (two complete arcs). Comparisons were performed for dosimetric parameters of PTV and of OARs (lungs, spinal cord PRV, heart and normal tissue (NT)). All the plans were delivered to a phantom to evaluate the treatment time. The Wilcoxon matched-pairs, signed-rank test was used for intragroup comparison. For all patients, compared to sIMRT plans, VMAT plans statistically provide: a) significant improvement in HI and CI for PTV; b) significant decrease in delivery time, lung V20, MLD, heart V30 and spinal cord PRV D1cc; c) significant increase in NT V5; and d) no significant reduction in lung V5, V10, and heart MD. For all patients, compared to IMRT plans, VMAT plans statistically provide: a) significant improvement in CI for PTV; b) significant decrease in delivery time, lung V20, MLD, NT and spinal cord PRV D1cc; c) significant increase in NT V5; and d) no significant reduction in HI for PTV, lung V5, V10, heart V30 and heart MD. For patients with upper esophageal carcinoma, using VMAT significantly reduces the delivery time and the dose to the lungs compared with IMRT, and consequently saves as much treatment time as sIMRT. Considering those significant advantages, compared to sIMRT and IMRT, VMAT is the first choice of radiotherapy techniques for upper esophageal carcinoma.

Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling.

PubMed

Kumari, Neema; Gaur, Himanshu; Bhargava, Anamika

2018-02-01

Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculated. Copyright © 2017 Elsevier Inc. All rights reserved.

A Multidisciplinary Self-Directed Learning Module Improves Knowledge of a Quality Improvement Instrument: The HEART Pathway.

PubMed

Hartman, Nicholas D; Harper, Erin N; Leppert, Lauren M; Browning, Brittany M; Askew, Kim; Manthey, David E; Mahler, Simon A

We created and tested an educational intervention to support implementation of an institution wide QI project (the HEART Pathway) designed to improve care for patients with acute chest pain. Although online learning modules have been shown effective in imparting knowledge regarding QI projects, it is unknown whether these modules are effective across specialties and healthcare professions. Participants, including nurses, advanced practice clinicians, house staff and attending physicians (N = 486), were enrolled into an online, self-directed learning course exploring the key concepts of the HEART Pathway. The module was completed by 97% of enrollees (469/486) and 90% passed on the first attempt (422/469). Out of 469 learners, 323 completed the pretest, learning module and posttest in the correct order. Mean test scores across learners improved significantly from 74% to 89% from the pretest to the posttest. Following the intervention, the HEART Pathway was used for 88% of patients presenting to our institution with acute chest pain. Our data demonstrate that this online, self-directed learning module can improve knowledge of the HEART Pathway across specialties-paving the way for more efficient and informed care for acute chest pain patients.

VERY LOW FREQUENCY 16 HZ AMPLITUDE MODULATED ELECTROMAGNETIC RADIATION INCREASES CALCIUM EFFLUX FROM THE FROG HEART

EPA Science Inventory

The effects of continuous and amplitude-modulated radiofrequency electromagnetic waves on calcium efflux from 45Ca preloaded frog hearts were examined. rog hearts, electrically stimulated at their natural beating frequency, were exposed for 30 min to 240 MHz radiowaves in a Crawf...

Post-exercise heart-rate recovery correlates to resting heart-rate variability in healthy men.

PubMed

Molina, Guilherme Eckhardt; Fontana, Keila Elizabeth; Porto, Luiz Guilherme Grossi; Junqueira, Luiz Fernando

2016-12-01

The relationship between post-exercise heart-rate recovery (HRR) and resting cardiac autonomic modulation is an incompletely explored issue. To correlate HRR with resting supine and orthostatic autonomic status. HRR at the 1st, 3th, and 5th min following maximal treadmill exercise were correlated with 5-min time-domain (CV, pNN50 and rMSSD) and frequency-domain (TP, LF, HF, LFn, HFn, and LF/HF ratio) indices of heart-rate variability (HRV) in both supine and standing positions in 31 healthy physically active non-athletes men. Statistical analysis employed non-parametric tests with two-tailed p value set at 5 %. Absolute HRR and Δ %HRR at each post-exercise time did not correlated with HRV in supine position, as well as at 1st min in standing position. At the 3rd min and 5th min, these measures negatively correlated with pNN50, rMSSD, TP, and HF indices, and only in the 5th min, they showed negative correlation with HFn and positive correlation with LF, LFn, and LF/HF ratio in the standing position. Coefficient of HRR (CHRR) at the 1st min negatively correlated with pNN50 and rMSSD and at 3rd and 5th min showed positive correlation with LFn and LF/HF ratio in supine position. With HRV indices in standing position CHRR from the 1st to 5th min showed the same respective negative and positive correlations as the other measures. HRR from the 1st to 5th min post-exercise negatively correlated with parasympathetic modulation in resting orthostatic, but showed no correlation in supine position. At the 3rd and 5th min, a positive correlation with combined sympathetic-parasympathetic modulation in both positions was observed.

Brain correlates of autonomic modulation: combining heart rate variability with fMRI.

PubMed

Napadow, Vitaly; Dhond, Rupali; Conti, Giulia; Makris, Nikos; Brown, Emery N; Barbieri, Riccardo

2008-08-01

The central autonomic network (CAN) has been described in animal models but has been difficult to elucidate in humans. Potential confounds include physiological noise artifacts affecting brainstem neuroimaging data, and difficulty in deriving non-invasive continuous assessments of autonomic modulation. We have developed and implemented a new method which relates cardiac-gated fMRI timeseries with continuous-time heart rate variability (HRV) to estimate central autonomic processing. As many autonomic structures of interest are in brain regions strongly affected by cardiogenic pulsatility, we chose to cardiac-gate our fMRI acquisition to increase sensitivity. Cardiac-gating introduces T1-variability, which was corrected by transforming fMRI data to a fixed TR using a previously published method [Guimaraes, A.R., Melcher, J.R., et al., 1998. Imaging subcortical auditory activity in humans. Hum. Brain Mapp. 6(1), 33-41]. The electrocardiogram was analyzed with a novel point process adaptive-filter algorithm for computation of the high-frequency (HF) index, reflecting the time-varying dynamics of efferent cardiovagal modulation. Central command of cardiovagal outflow was inferred by using the resample HF timeseries as a regressor to the fMRI data. A grip task was used to perturb the autonomic nervous system. Our combined HRV-fMRI approach demonstrated HF correlation with fMRI activity in the hypothalamus, cerebellum, parabrachial nucleus/locus ceruleus, periaqueductal gray, amygdala, hippocampus, thalamus, and dorsomedial/dorsolateral prefrontal, posterior insular, and middle temporal cortices. While some regions consistent with central cardiovagal control in animal models gave corroborative evidence for our methodology, other mostly higher cortical or limbic-related brain regions may be unique to humans. Our approach should be optimized and applied to study the human brain correlates of autonomic modulation for various stimuli in both physiological and pathological states.

Predominance of Intrinsic Mechanism of Resting Heart Rate Control and Preserved Baroreflex Sensitivity in Professional Cyclists after Competitive Training.

PubMed

Azevedo, Luciene Ferreira; Perlingeiro, Patricia; Hachul, Denise Tessariol; Gomes-Santos, Igor Lucas; Tsutsui, Jeane Mike; Negrao, Carlos Eduardo; De Matos, Luciana D N J

2016-01-01

Different season trainings may influence autonomic and non-autonomic cardiac control of heart rate and provokes specific adaptations on heart's structure in athletes. We investigated the influence of transition training (TT) and competitive training (CT) on resting heart rate, its mechanisms of control, spontaneous baroreflex sensitivity (BRS) and relationships between heart rate mechanisms and cardiac structure in professional cyclists (N = 10). Heart rate (ECG) and arterial blood pressure (Pulse Tonometry) were recorded continuously. Autonomic blockade was performed (atropine-0.04 mg.kg-1; esmolol-500 μg.kg-1 = 0.5 mg). Vagal effect, intrinsic heart rate, parasympathetic (n) and sympathetic (m) modulations, autonomic influence, autonomic balance and BRS were calculated. Plasma norepinephrine (high-pressure liquid chromatography) and cardiac structure (echocardiography) were evaluated. Resting heart rate was similar in TT and CT. However, vagal effect, intrinsic heart rate, autonomic influence and parasympathetic modulation (higher n value) decreased in CT (P≤0.05). Sympathetic modulation was similar in both trainings. The autonomic balance increased in CT but still showed parasympathetic predominance. Cardiac diameter, septum and posterior wall thickness and left ventricular mass also increased in CT (P<0.05) as well as diastolic function. We observed an inverse correlation between left ventricular diastolic diameter, septum and posterior wall thickness and left ventricular mass with intrinsic heart rate. Blood pressure and BRS were similar in both trainings. Intrinsic heart rate mechanism is predominant over vagal effect during CT, despite similar resting heart rate. Preserved blood pressure levels and BRS during CT are probably due to similar sympathetic modulation in both trainings.

A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs

NASA Astrophysics Data System (ADS)

Javed, Faizan; Venkatachalam, P. A.; H, Ahmad Fadzil M.

2006-04-01

In this paper a Signal Processing Module (SPM) for the computer-aided analysis of heart sounds has been developed. The module reveals important information of cardiovascular disorders and can assist general physician to come up with more accurate and reliable diagnosis at early stages. It can overcome the deficiency of expert doctors in rural as well as urban clinics and hospitals. The module has five main blocks: Data Acquisition & Pre-processing, Segmentation, Feature Extraction, Murmur Detection and Murmur Classification. The heart sounds are first acquired using an electronic stethoscope which has the capability of transferring these signals to the near by workstation using wireless media. Then the signals are segmented into individual cycles as well as individual components using the spectral analysis of heart without using any reference signal like ECG. Then the features are extracted from the individual components using Spectrogram and are used as an input to a MLP (Multiple Layer Perceptron) Neural Network that is trained to detect the presence of heart murmurs. Once the murmur is detected they are classified into seven classes depending on their timing within the cardiac cycle using Smoothed Pseudo Wigner-Ville distribution. The module has been tested with real heart sounds from 40 patients and has proved to be quite efficient and robust while dealing with a large variety of pathological conditions.

Cardiovascular effects of black tea and nicotine alone or in combination against experimental induced heart injury.

PubMed

Joukar, Siyavash; Bashiri, Hamideh; Dabiri, Shahriar; Ghotbi, Payam; Sarveazad, Arash; Divsalar, Kouros; Joukar, Farzin; Abbaszadeh, Mahsa

2012-06-01

The present study was designed to elucidate the outcome of subchronic co-administration of black tea and nicotine on cardiovascular performance and whether these substances could modulate the isoproterenol-induced cardiac injury. Animal groups were control, black tea, nicotine and black tea plus nicotine. Test groups received nicotine (2 mg/kg s.c.) and black tea brewed (p.o.) each alone and in combination for 4 weeks. On the 28th day, myocardial damage was induced by isoproterenol (50 mg/kg i.p.), and blood samples were taken. On day 29, after hemodynamic parameters recording, hearts were removed for histopathological evaluation. Tea or nicotine consumption had no significant effects on hemodynamic indices of animals without heart damage. When the cardiac injury was induced, tea consumption maintained the maximum dp/dt, and nicotine significantly decreased the pressure-rate product. Moreover, severity of heart lesions was lower in the presence of nicotine or black tea. Concomitant use of these materials did not show extra effects on mentioned parameters more than the effect of each of them alone. The results suggest that subchronic administration of black tea or nicotine for a period of 4 weeks may have a mild cardioprotective effect, while concomitant use of these materials cannot intensify this beneficial effect.

Model for heart failure education.

PubMed

Baldonado, Analiza; Dutra, Danette; Abriam-Yago, Katherine

2014-01-01

Heart failure (HF) is the heart's inability to meet the body's need for blood and oxygen. According to the American Heart Association 2013 update, approximately 5.1 million people are diagnosed with HF in the United States in 2006. Heart failure is the most common diagnosis for hospitalization. In the United States, the HF direct and indirect costs are estimated to be US $39.2 billion in 2010. To address this issue, nursing educators designed innovative teaching frameworks on HF management both in academia and in clinical settings. The model was based on 2 resources: the American Association of Heart Failure Nurses (2012) national nursing certification and the award-winning Pierce County Responsive Care Coordination Program. The HF educational program is divided into 4 modules. The initial modules offer foundational levels of Bloom's Taxonomy then progress to incorporate higher-levels of learning when modules 3 and 4 are reached. The applicability of the key components within each module allows formatting to enhance learning in all areas of nursing, from the emergency department to intensive care units to the medical-surgical step-down units. Also applicable would be to provide specific aspects of the modules to nurses who care for HF patients in skilled nursing facility, rehabilitation centers, and in the home-health care setting.

Voluntary control of breathing does not alter vagal modulation of heart rate

NASA Technical Reports Server (NTRS)

Patwardhan, A. R.; Evans, J. M.; Bruce, E. N.; Eckberg, D. L.; Knapp, C. F.

1995-01-01

Variations in respiratory pattern influence the heart rate spectrum. It has been suggested, hence, that metronomic respiration should be used to correctly assess vagal modulation of heart rate by using spectral analysis. On the other hand, breathing to a metronome has been reported to increase heart rate spectral power in the high- or respiratory frequency region; this finding has led to the suggestion that metronomic respiration enhances vagal tone or alters vagal modulation of heart rate. To investigate whether metronomic breathing complicates the interpretation of heart rate spectra by altering vagal modulation, we recorded the electrocardiogram and respiration from eight volunteers during three breathing trials of 10 min each: 1) spontaneous breathing (mean rate of 14.4 breaths/min); 2) breathing to a metronome at the rate of 15, 18, and 21 breaths/min for 2, 6, and 2 min, respectively; and 3) breathing to a metronome at the rate of 18 breaths/min for 10 min. Data were also collected from eight volunteers who breathed spontaneously for 20 min and breathed metronomically at each subject's mean spontaneous breathing frequency for 20 min. Results from the three 10-min breathing trials showed that heart rate power in the respiratory frequency region was smaller during metronomic breathing than during spontaneous breathing. This decrease could be explained fully by the higher breathing frequencies used during trials 2 and 3 of metronomic breathing. When the subjects breathed metronomically at each subject's mean breathing frequency, the heart rate powers during metronomic breathing were similar to those during spontaneous breathing. Our results suggest that vagal modulation of heart rate is not altered and vagal tone is not enhanced during metronomic breathing.

Evidence for a possible role for nitric oxide in the modulation of heart activity in Achatina fulica and Helix aspersa.

PubMed

White, A R; Curtis, S A; Walker, R J

2004-02-01

The effects of nitric oxide (NO) donors, S-nitroso-N-acetylpenicillamine, S-nitroso-l-glutathione, sodium nitroprusside and sodium nitrite were investigated on the activity of the isolated hearts of Achatina fulica and Helix aspersa. NO donors inhibited heart activity in a concentration-dependent manner. The only exception was sodium nitroprusside, which excited H. aspersa heart. The inhibitory effects of these NO donors were reduced by the NO scavenger, methylene blue, the guanylyl cyclase inhibitor, 1H-(1,2,4) Oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), and potentiated by 8-Br-cGMP and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Acetylcholine also inhibited the heart activity, and this inhibition was reduced by methylene blue and ODQ. Positive NADPH-diaphorase staining was located in the outer pericardial layer of the heart of A. fulica. The present results provide evidence that NO may modulate the activity of gastropod hearts, and this modulation may modify the inhibitory action of acetylcholine on heart activity.

Cardiac autonomic modulation impairments in advanced breast cancer patients.

PubMed

Arab, Claudia; Vanderlei, Luiz Carlos Marques; da Silva Paiva, Laércio; Fulghum, Kyle Levi; Fristachi, Carlos Elias; Nazario, Afonso Celso Pinto; Elias, Simone; Gebrim, Luiz Henrique; Ferreira Filho, Celso; Gidron, Yori; Ferreira, Celso

2018-05-02

To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.

Breathing frequency-independent effect of Tai Chi Chuan on autonomic modulation.

PubMed

Lu, Wan-An; Kuo, Cheng-Deng

2014-04-01

This study investigates the breathing frequency (BF)-independent effect of Tai Chi Chuan (TCC) on autonomic nervous modulation in TCC practitioners. Twenty-five TCC practitioners and 25 sedentary normal controls were recruited. The stationary heart rate variability (HRV) measures of TCC practitioners and controls were compared. The same HRV measures in TCC practitioners and among the controls, TCC practitioners before TCC and TCC practitioners 30 min after TCC were compared. In TCC practitioners, the BF, normalized high-frequency power (nHFP), and normalized very low-frequency power were significantly increased, while the normalized low-frequency power (nLFP) was significantly decreased 30 min after TCC. The BF correlated significantly and negatively with heart rate (HR), nHFP and nLFP, and correlated significantly and positively with mean RR interval (MnRR) before TCC in TCC practitioners. A slower BF is associated with a higher HR, a greater vagal modulation, and a greater combined sympatho-vagal modulation before TCC. To remove the effect of BF on HRV measures, new indices such as HR*BF, nHFP*BF, nLFP*BF, and MnRR/BF were introduced for comparison among the controls, TCC practitioners before TCC, and TCC practitioners 30 min after TCC. Thirty minutes after TCC, the MnRR/BF of TCC practitioner was smaller whereas HR*BF and nHFP*BF were greater than those before TCC. The BF-independent effects of TCC on the autonomic nervous modulation of TCC practitioners are an increase in vagal modulation and HR, and a decrease in mean RR interval. The mechanism underlying the parallel increase in HR and vagal modulation in TCC practitioners is not understood yet at present.

The Influence of Motor Impairment on Autonomic Heart Rate Modulation among Children with Cerebral Palsy

ERIC Educational Resources Information Center

Zamuner, Antonio Roberto; Cunha, Andrea Baraldi; da Silva, Ester; Negri, Ana Paola; Tudella, Eloisa; Moreno, Marlene Aparecida

2011-01-01

The study of heart rate variability is an important tool for a noninvasive evaluation of the neurocardiac integrity. The present study aims to evaluate the autonomic heart rate modulation in supine and standing positions in 12 children diagnosed with cerebral palsy and 16 children with typical motor development (control group), as well as to…

Differentiation and characterization of rhesus monkey atrial and ventricular cardiomyocytes from induced pluripotent stem cells.

PubMed

Zhang, Xiaoqian; Cao, Henghua; Bai, Shuyun; Huo, Weibang; Ma, Yue

2017-04-01

The combination of non-human primate animals and their induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) provides not only transplantation models for cell-based therapy of heart diseases, but also opportunities for heart-related drug research on both cellular and animal levels. However, the subtypes and electrophysiology properties of non-human primate iPSC-CMs hadn't been detailed characterized. In this study, we generated rhesus monkey induced pluripotent stem cells (riPSCs), and efficiently differentiated them into ventricular or atrial cardiomyocytes by modulating retinoic acid (RA) pathways. Our results revealed that the electrophysiological characteristics and response to canonical drugs of riPSC-CMs were similar with those of human pluripotent stem cell derived CMs. Therefore, rhesus monkeys and their iPSC-CMs provide a powerful and practicable system for heart related biomedical research. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Heart Rate and Blood Pressure Variability under Moon, Mars and Zero Gravity Conditions During Parabolic Flights

NASA Astrophysics Data System (ADS)

Aerts, Wouter; Joosen, Pieter; Widjaja, Devy; Varon, Carolina; Vandeput, Steven; Van Huffel, Sabine; Aubert, Andre E.

2013-02-01

Gravity changes during partial-G parabolic flights (0g -0.16g - 0.38g) lead to changes in modulation of the autonomic nervous system (ANS), studied via the heart rate variability (HRV) and blood pressure variability (BPV). HRV and BPV were assessed via classical time and frequency domain measures. Mean systolic and diastolic blood pressure show both increasing trends towards higher gravity levels. The parasympathetic and sympathetic modulation show both an increasing trend with decreasing gravity, although the modulation is sympathetic predominant during reduced gravity. For the mean heart rate, a non-monotonic relation was found, which can be explained by the increased influence of stress on the heart rate. This study shows that there is a relation between changes in gravity and modulations in the ANS. With this in mind, countermeasures can be developed to reduce postflight orthostatic intolerance.

Cardiac Exposure in the Dynamic Conformal Arc Therapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer

PubMed Central

Ming, Xin; Feng, Yuanming; Liu, Huan; Zhang, Ying; Zhou, Li; Deng, Jun

2015-01-01

Purpose To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT), intensity-modulated radiotherapy (IMRT), or volumetric modulated arc therapy (VMAT) at our institution in the past seven years. Methods and Materials A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated. Results The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2%) with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance. Conclusions Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin’s disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy. PMID:26630566

Searching for synergistic calcium antagonists and novel therapeutic regimens for coronary heart disease therapy from a Traditional Chinese Medicine, Suxiao Jiuxin Pill.

PubMed

Lei, Wei; Ni, Jianan; Xia, Xueting; Jiang, Min; Bai, Gang

2018-06-08

Coronary heart disease is a vital cause of morbidity and mortality worldwide, and calcium channel blockers (CCBs) are important drugs that can be used to treat cardiovascular diseases. Suxiao Jiuxin Pill (SX), a traditional Chinese medicine, is widely used as an emergency drug for coronary heart disease therapy. However, understanding its potential mechanism in intracellular calcium concentration ([Ca 2+ ] i ) modulation remains a challenge. To identify the active pharmacological ingredients (APIs) and reveal a novel combination therapy for ameliorating cardiovascular diseases, the ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) combined with a dual-luciferase reporter [Ca 2+ ] i assay system was applied. Ligustrazine, ferulic acid, senkyunolide I, senkyunolide A and ligustilide were identified as potential calcium antagonists in SX, and the combination of ligustrazine and senkyunolide A showed synergetic calcium antagonistic activity. Additionally, the synergetic mechanism was further investigated by live-imaging analysis with the Ca 2+ indicator fluo-4/AM by monitoring fluorescence changes. Our results indicated that ligustrazine can block voltage-operated Ca 2+ channels (VDCCs) effectively and senkyunolide A can exert an inhibition effect mostly on ryanodine receptors (RYRs) and partly on VDCCs. Finally, an arterial ring assay showed that the combination of ligustrazine and senkyunolide A exerted a better vasodilatation function than using any components alone. In this study, we first revealed that a pair of natural APIs in combination acting on VDCCs and RYRs was more effective on vasodilatation by regulating [Ca 2+ ] i . Copyright © 2018. Published by Elsevier B.V.

Optimization of combined electron and photon beams for breast cancer

NASA Astrophysics Data System (ADS)

Xiong, W.; Li, J.; Chen, L.; Price, R. A.; Freedman, G.; Ding, M.; Qin, L.; Yang, J.; Ma, C.-M.

2004-05-01

Recently, intensity-modulated radiation therapy and modulated electron radiotherapy have gathered a growing interest for the treatment of breast and head and neck tumours. In this work, we carried out a study to combine electron and photon beams to achieve differential dose distributions for multiple target volumes simultaneously. A Monte Carlo based treatment planning system was investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We compared breast treatment plans generated using this home-grown optimization and dose calculation software for different treatment techniques. Five different planning techniques have been developed for this study based on a standard photon beam whole breast treatment and an electron beam tumour bed cone down. Technique 1 includes two 6 MV tangential wedged photon beams followed by an anterior boost electron field. Technique 2 includes two 6 MV tangential intensity-modulated photon beams and the same boost electron field. Technique 3 optimizes two intensity-modulated photon beams based on a boost electron field. Technique 4 optimizes two intensity-modulated photon beams and the weight of the boost electron field. Technique 5 combines two intensity-modulated photon beams with an intensity-modulated electron field. Our results show that technique 2 can reduce hot spots both in the breast and the tumour bed compared to technique 1 (dose inhomogeneity is reduced from 34% to 28% for the target). Techniques 3, 4 and 5 can deliver a more homogeneous dose distribution to the target (with dose inhomogeneities for the target of 22%, 20% and 9%, respectively). In many cases techniques 3, 4 and 5 can reduce the dose to the lung and heart. It is concluded that combined photon and electron beam therapy may be advantageous for treating breast cancer compared to conventional treatment techniques using tangential wedged photon beams followed by a boost electron field.

The effects of oxytocin and atosiban on the modulation of heart rate in pregnant women.

PubMed

Weissman, Amir; Tobia, Rana Swed; Burke, Yechiel Z; Maxymovski, Olga; Drugan, Arie

2017-02-01

To evaluate autonomic modulation of heart rate in pregnant women treated with oxytocin to induce labor and with atosiban (an oxytocin antagonist) to arrest preterm labor. A prospective study with two cohorts: 14 pregnant women treated with atosiban for premature uterine contractions, and 28 women undergoing induction of labor with oxytocin. Computerized analyses of the electrocardiogram were performed with spectral and nonlinear dynamic analyses. Atosiban did not alter any of the variables associated with heart rate variability, whereas oxytocin showed a dose-dependent decrease in heart rate (p < 0.05) and a significant increase in all spectral variables studied (p < 0.01). Atosiban has no adverse effects on the cardiovascular system or the modulation of heart rate. Oxytocin, on the other hand, can cause a dose-dependent bradycardic effect and an increase in the spectral power, thus should be used with caution in certain pregnant women.

Modeling of Diffusion Based Correlations Between Heart Rate Modulations and Respiration Pattern

DTIC Science & Technology

2001-10-25

1 of 4 MODELING OF DIFFUSION BASED CORRELATIONS BETWEEN HEART RATE MODULATIONS AND RESPIRATION PATTERN R.Langer,(1) Y.Smorzik,(2) S.Akselrod,(1...generations of the bronchial tree. The second stage describes the oxygen diffusion process from the pulmonary gas in the alveoli into the pulmonary...patterns (FRC, TV, rate). Keywords – Modeling, Diffusion , Heart Rate fluctuations I. INTRODUCTION Under a whole-body management perception, the

Cell Type-Specific Chromatin Signatures Underline Regulatory DNA Elements in Human Induced Pluripotent Stem Cells and Somatic Cells.

PubMed

Zhao, Ming-Tao; Shao, Ning-Yi; Hu, Shijun; Ma, Ning; Srinivasan, Rajini; Jahanbani, Fereshteh; Lee, Jaecheol; Zhang, Sophia L; Snyder, Michael P; Wu, Joseph C

2017-11-10

Regulatory DNA elements in the human genome play important roles in determining the transcriptional abundance and spatiotemporal gene expression during embryonic heart development and somatic cell reprogramming. It is not well known how chromatin marks in regulatory DNA elements are modulated to establish cell type-specific gene expression in the human heart. We aimed to decipher the cell type-specific epigenetic signatures in regulatory DNA elements and how they modulate heart-specific gene expression. We profiled genome-wide transcriptional activity and a variety of epigenetic marks in the regulatory DNA elements using massive RNA-seq (n=12) and ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing; n=84) in human endothelial cells (CD31 + CD144 + ), cardiac progenitor cells (Sca-1 + ), fibroblasts (DDR2 + ), and their respective induced pluripotent stem cells. We uncovered 2 classes of regulatory DNA elements: class I was identified with ubiquitous enhancer (H3K4me1) and promoter (H3K4me3) marks in all cell types, whereas class II was enriched with H3K4me1 and H3K4me3 in a cell type-specific manner. Both class I and class II regulatory elements exhibited stimulatory roles in nearby gene expression in a given cell type. However, class I promoters displayed more dominant regulatory effects on transcriptional abundance regardless of distal enhancers. Transcription factor network analysis indicated that human induced pluripotent stem cells and somatic cells from the heart selected their preferential regulatory elements to maintain cell type-specific gene expression. In addition, we validated the function of these enhancer elements in transgenic mouse embryos and human cells and identified a few enhancers that could possibly regulate the cardiac-specific gene expression. Given that a large number of genetic variants associated with human diseases are located in regulatory DNA elements, our study provides valuable resources for deciphering the epigenetic modulation of regulatory DNA elements that fine-tune spatiotemporal gene expression in human cardiac development and diseases. © 2017 American Heart Association, Inc.

Muscle wasting and sarcopenia in heart failure and beyond: update 2017.

PubMed

Springer, Jochen; Springer, Joshua-I; Anker, Stefan D

2017-11-01

Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF-1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Globally conditioned Granger causality in brain–brain and brain–heart interactions: a combined heart rate variability/ultra-high-field (7 T) functional magnetic resonance imaging study

PubMed Central

Passamonti, Luca; Wald, Lawrence L.; Barbieri, Riccardo

2016-01-01

The causal, directed interactions between brain regions at rest (brain–brain networks) and between resting-state brain activity and autonomic nervous system (ANS) outflow (brain–heart links) have not been completely elucidated. We collected 7 T resting-state functional magnetic resonance imaging (fMRI) data with simultaneous respiration and heartbeat recordings in nine healthy volunteers to investigate (i) the causal interactions between cortical and subcortical brain regions at rest and (ii) the causal interactions between resting-state brain activity and the ANS as quantified through a probabilistic, point-process-based heartbeat model which generates dynamical estimates for sympathetic and parasympathetic activity as well as sympathovagal balance. Given the high amount of information shared between brain-derived signals, we compared the results of traditional bivariate Granger causality (GC) with a globally conditioned approach which evaluated the additional influence of each brain region on the causal target while factoring out effects concomitantly mediated by other brain regions. The bivariate approach resulted in a large number of possibly spurious causal brain–brain links, while, using the globally conditioned approach, we demonstrated the existence of significant selective causal links between cortical/subcortical brain regions and sympathetic and parasympathetic modulation as well as sympathovagal balance. In particular, we demonstrated a causal role of the amygdala, hypothalamus, brainstem and, among others, medial, middle and superior frontal gyri, superior temporal pole, paracentral lobule and cerebellar regions in modulating the so-called central autonomic network (CAN). In summary, we show that, provided proper conditioning is employed to eliminate spurious causalities, ultra-high-field functional imaging coupled with physiological signal acquisition and GC analysis is able to quantify directed brain–brain and brain–heart interactions reflecting central modulation of ANS outflow. PMID:27044985

Baroreflex modulation of muscle sympathetic nerve activity during cold pressor test in humans

NASA Technical Reports Server (NTRS)

Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

2002-01-01

The purpose of this project was to test the hypothesis that baroreceptor modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered during the cold pressor test. Ten subjects were exposed to a cold pressor test by immersing a hand in ice water for 3 min while arterial blood pressure, heart rate, and MSNA were recorded. During the second and third minute of the cold pressor test, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.005) during the cold pressor test (-244.9 +/- 26.3 units x beat(-1) x mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1) x mmHg(-1)), whereas no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that baroreceptors remain capable of modulating MSNA and heart rate during a cold pressor test; however, the sensitivity of baroreflex modulation of MSNA is elevated without altering the sensitivity of baroreflex control of heart rate.

FlyNap (Triethylamine) Increases the Heart Rate of Mosquitoes and Eliminates the Cardioacceleratory Effect of the Neuropeptide CCAP

PubMed Central

Chen, Weihan; Hillyer, Julián F.

2013-01-01

FlyNap (triethylamine) is commonly used to anesthetize Drosophila melanogaster fruit flies. The purpose of this study was to determine whether triethylamine is a suitable anesthetic agent for research into circulatory physiology and immune competence in the mosquito, Anopheles gambiae (Diptera: Culicidae). Recovery experiments showed that mosquitoes awaken from traditional cold anesthesia in less than 7 minutes, but that recovery from FlyNap anesthesia does not begin for several hours. Relative to cold anesthesia, moderate exposures to FlyNap induce an increase in the heart rate, a decrease in the percentage of the time the heart contracts in the anterograde direction, and a decrease in the frequency of heartbeat directional reversals. Experiments employing various combinations of cold and FlyNap anesthesia then showed that cold exposure does not affect basal heart physiology, and that the differences seen between the cold and the FlyNap groups are due to a FlyNap-induced alteration of heart physiology. Furthermore, exposure to FlyNap eliminated the cardioacceleratory effect of crustacean cardioactive peptide (CCAP), and reduced a mosquito’s ability to survive a bacterial infection. Together, these data show that FlyNap is not a suitable substitute to cold anesthesia in experiments assessing mosquito heart function or immune competence. Moreover, these data also illustrate the intricate biology of the insect heart. Specifically, they confirm that the neurohormone CCAP modulates heart rhythms and that it serves as an anterograde pacemaker. PMID:23875027

Muscle wasting and sarcopenia in heart failure and beyond: update 2017

PubMed Central

Springer, Joshua‐I.; Anker, Stefan D.

2017-01-01

Abstract Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF‐1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one. PMID:29154428

Heart rate recovery and variability following combined aerobic and resistance exercise training in adults with and without Down syndrome.

PubMed

Mendonca, Goncalo V; Pereira, Fernando D; Fernhall, Bo

2013-01-01

Persons with Down syndrome (DS) are at high risk for cardiovascular morbidity and mortality, and there is compelling evidence of autonomic dysfunction in these individuals. The main purpose of this study was to determine whether a combined aerobic and resistance exercise intervention produces similar results in cardiac autonomic function between adults with and without DS. Twenty-five participants (13 DS; 12 non-DS), aged 27-50 years, were included. Aerobic training was performed 3 days/week for 30 min at 65-85% of peak oxygen uptake (VO(2peak)). Resistance training was prescribed for 2 days/week and consisted of two rotations in a circuit of 9 exercises at 12-repetition-maximum. There was a significant improvement in the VO(2peak) and muscle strength of participants with and without DS after training. Heart rate recovery improved at 1 min post-exercise, but only in participants with DS. Both groups of participants exhibited a similar increase in normalized high frequency power and of decrease in normalized low frequency power after training. Therefore, 12 weeks of exercise training enhanced the heart rate recovery in adults with DS, but not in those without DS. Contrasting, the intervention elicited similar gains between groups for cardiovagal modulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aznar, Marianne C., E-mail: marianne.camille.aznar@regionh.dk; Faculty of Sciences, Niels Bohr Institute, and Faculty of Health Sciences, University of Copenhagen, Copenhagen; Maraldo, Maja V.

Purpose: Hodgkin lymphoma (HL) survivors have an increased risk of cardiovascular disease (CD), lung cancer, and breast cancer. We investigated the risk for the development of CD and secondary lung, breast, and thyroid cancer after radiation therapy (RT) delivered with deep inspiration breath-hold (DIBH) compared with free-breathing (FB) using 3-dimensional conformal RT (3DCRT) and intensity modulated RT (IMRT). The aim of this study was to determine which treatment modality best reduced the combined risk of life-threatening late effects in patients with mediastinal HL. Methods and Materials: Twenty-two patients with early-stage mediastinal HL were eligible for the study. Treatment plans weremore » calculated with both 3DCRT and IMRT on both DIBH and FB planning computed tomographic scans. We reported the estimated dose to the heart, lung, female breasts, and thyroid and calculated the estimated life years lost attributable to CD and to lung, breast, and thyroid cancer. Results: DIBH lowered the estimated dose to heart and lung regardless of delivery technique (P<.001). There was no significant difference between IMRT-FB and 3DCRT-DIBH in mean heart dose, heart V20Gy, and lung V20Gy. The mean breast dose was increased with IMRT regardless of breathing technique. Life years lost was lowest with DIBH and highest with FB. Conclusions: In this cohort, 3DCRT-DIBH resulted in lower estimated doses and lower lifetime excess risks than did IMRT-FB. Combining IMRT and DIBH could be beneficial for a subgroup of patients.« less

Modulation of heart rate and heart rate variability by n-3 long chain polyunsaturated fatty acids: Speculation on mechanism(s).

PubMed

Drewery, Merritt L; Spedale, Steven B; Lammi-Keefe, Carol J

2017-09-01

Heart rate (HR) and heart rate variability (HRV) are valuable markers of health. Although the underlying mechanism(s) are controversial, it is well documented that n-3 long chain polyunsaturated fatty acid (LCPUFA) intake improves HR and HRV in various populations. Autonomic modulation and/or alterations in cardiac electrophysiology are commonly cited as potential mechanisms responsible for these effects. This article reviews existing evidence for each and explores a separate mechanism which has not received much attention but has scientific merit. Based on presented evidence, it is proposed that n-3 LCPUFAs affect HR and HRV directly by autonomic modulation and indirectly by altering circulating factors, both dependently and independently of the autonomic nervous system. The evidence for changes in cardiac electrophysiology as the mechanism by which n-3 LCPUFAs affect HR and HRV needs strengthening. Copyright © 2017 Elsevier Ltd. All rights reserved.

The recursive combination filter approach of pre-processing for the estimation of standard deviation of RR series.

PubMed

Mishra, Alok; Swati, D

2015-09-01

Variation in the interval between the R-R peaks of the electrocardiogram represents the modulation of the cardiac oscillations by the autonomic nervous system. This variation is contaminated by anomalous signals called ectopic beats, artefacts or noise which mask the true behaviour of heart rate variability. In this paper, we have proposed a combination filter of recursive impulse rejection filter and recursive 20% filter, with recursive application and preference of replacement over removal of abnormal beats to improve the pre-processing of the inter-beat intervals. We have tested this novel recursive combinational method with median method replacement to estimate the standard deviation of normal to normal (SDNN) beat intervals of congestive heart failure (CHF) and normal sinus rhythm subjects. This work discusses the improvement in pre-processing over single use of impulse rejection filter and removal of abnormal beats for heart rate variability for the estimation of SDNN and Poncaré plot descriptors (SD1, SD2, and SD1/SD2) in detail. We have found the 22 ms value of SDNN and 36 ms value of SD2 descriptor of Poincaré plot as clinical indicators in discriminating the normal cases from CHF cases. The pre-processing is also useful in calculation of Lyapunov exponent which is a nonlinear index as Lyapunov exponents calculated after proposed pre-processing modified in a way that it start following the notion of less complex behaviour of diseased states.

Health Activities Project (HAP): Heart Fitness and Action Module.

ERIC Educational Resources Information Center

Buller, Dave; And Others

Contained within this Health Activities Project (HAP) learning packet are activities for children in grades 5-8. Design of the activities centers around the idea that students can control their own health and safety. Within the Heart Fitness and Action Module are teacher and student folios describing five activities which involve students in…

Hippocampal-Brainstem Connectivity Associated with Vagal Modulation after an Intense Exercise Intervention in Healthy Men

PubMed Central

Bär, Karl-Jürgen; Herbsleb, Marco; Schumann, Andy; de la Cruz, Feliberto; Gabriel, Holger W.; Wagner, Gerd

2016-01-01

Regular physical exercise leads to increased vagal modulation of the cardiovascular system. A combination of peripheral and central processes has been proposed to underlie this adaptation. However, specific changes in the central autonomic network have not been described in human in more detail. We hypothesized that the anterior hippocampus known to be influenced by regular physical activity might be involved in the development of increased vagal modulation after a 6 weeks high intensity intervention in young healthy men (exercise group: n = 17, control group: n = 17). In addition to the determination of physical capacity before and after the intervention, we used resting state functional magnetic resonance imaging and simultaneous heart rate variability assessment. We detected a significant increase of the power output at the anaerobic threshold of 11.4% (p < 0.001), the maximum power output Pmax of 11.2% (p < 0.001), and VO2max adjusted for body weight of 4.7% (p < 0.001) in the exercise group (EG). Comparing baseline (T0) and post-exercise (T1) values of parasympathetic modulation of the exercise group, we observed a trend for a decrease in heart rate (p < 0.06) and a significant increase of vagal modulation as indicated by RMSSD (p < 0.026) during resting state. In the whole brain analysis, we found that the connectivity pattern of the right anterior hippocampus (aHC) was specifically altered to the ventromedial anterior cortex, the dorsal striatum and to the dorsal vagal complex (DVC) in the brainstem. Moreover, we observed a highly significant negative correlation between increased RMSSD after exercise and decreased functional connectivity from the right aHC to DVC (r = −0.69, p = 0.003). This indicates that increased vagal modulation was associated with functional connectivity between aHC and the DVC. In conclusion, our findings suggest that exercise associated changes in anterior hippocampal function might be involved in increased vagal modulation. PMID:27092046

eNOS gene haplotype is indirectly associated with the recovery of cardiovascular autonomic modulation from exercise.

PubMed

Silva, Bruno M; Barbosa, Thales C; Neves, Fabricia J; Sales, Allan K; Rocha, Natalia G; Medeiros, Renata F; Pereira, Felipe S; Garcia, Vinicius P; Cardoso, Fabiane T; Nobrega, Antonio C L

2014-12-01

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene decrease expression and activation of eNOS in vitro, which is associated with lower post-exercise increase in vasodilator reactivity in vivo. However, it is unknown whether such polymorphisms are associated with other eNOS-related phenotypes during recovery from exercise. Therefore, we investigated the impact of an eNOS haplotype containing polymorphic alleles at loci -786 and 894 on the recovery of cardiovascular autonomic function from exercise. Sedentary, non-obese, healthy subjects were enrolled [n = 107, age 32 ± 1 years (mean ± SEM)]. Resting autonomic modulation (heart rate variability, systolic blood pressure variability, and spontaneous baroreflex sensitivity) and vascular reactivity (forearm hyperemic response post-ischemia) were assessed at baseline, 10, 60, and 120 min after a maximal cardiopulmonary exercise test. Besides, autonomic function was assessed by heart rate recovery (HRR) immediately after peak exercise. Haplotype analysis showed that vagal modulation (i.e., HF n.u.) was significantly higher, combined sympathetic and vagal modulation (i.e., LF/HF) was significantly lower and total blood pressure variability was significantly lower post-exercise in a haplotype containing polymorphic alleles (H2) compared to a haplotype with wild type alleles (H1). HRR was similar between groups. Corroborating previous evidence, H2 had significantly lower post-exercise increase in vasodilator reactivity than H1. In conclusion, a haplotype containing polymorphic alleles at loci -786 and 894 had enhanced recovery of autonomic modulation from exercise, along with unchanged HRR, and attenuated vasodilator reactivity. Then, these results suggest an autonomic compensatory response of a direct deleterious effect of eNOS polymorphisms on the vascular function. Copyright © 2014 Elsevier B.V. All rights reserved.

[Management of chronic heart failure - a systematic review of guidelines in the context of the DMP revision].

PubMed

Kötter, Thomas; Bartel, Carmen; Schramm, Susanne; Lange, Petra; Höfer, Eva; Hänsel, Michaela; Waffenschmidt, Siw; Waldt, Susanne Ein; Hoffmann-Eßer, Wiebke; Rüther, Alric; Lühmann, Dagmar; Scherer, Martin

2013-01-01

Disease Management Programmes (DMPs) are structured treatment programmes for chronic diseases. The DMP requirements are primarily derived from evidence-based guidelines. DMPs are regularly revised to ensure that they reflect current best practice and medical knowledge. The aim of this study was to assess the need for updating the German DMP module on heart failure by comparing it to relevant guidelines and identifying recommendations that should be revised. We systematically searched for clinical guidelines on heart failure published in German, English or French, and extracted relevant guideline recommendations. All included guidelines were assessed for methodological quality. To identify revision needs in the DMP, we performed a synoptic analysis of the extracted guideline recommendations and DMP requirements. 27 guidelines were included. The extracted recommendations covered all aspects of the management of heart failure. The comparison of guideline recommendations with DMP requirements showed that, overall, guideline recommendations were more detailed than DMP requirements, and that the guidelines covered topics not included in the DMP module. The DMP module is largely consistent with current guidelines on heart failure. We did not identify any need for significant revision of the DMP requirements. However, some specific recommendations of the DMP module could benefit from revision. Copyright © 2013. Published by Elsevier GmbH.

Observation Platform for Dynamic Biomedical and Biotechnology Experiments Using the International Space Station (ISS) Light Microscopy Module (LMM)

NASA Technical Reports Server (NTRS)

Kurk, Michael A. (Andy)

2015-01-01

Techshot, Inc., has developed an observation platform for the LMM on the ISS that will enable biomedical and biotechnology experiments. The LMM Dynamic Stage consists of an electronics module and the first two of a planned suite of experiment modules. Specimens and reagent solutions can be injected into a small, hollow microscope slide-the heart of the innovation-via a combination of small reservoirs, pumps, and valves. A life science experiment module allows investigators to load up to two different fluids for on-orbit, real-time image cytometry. Fluids can be changed to initiate a process, fix biological samples, or retrieve suspended cells. A colloid science experiment module conducts microparticle and nanoparticle tests for investigation of colloid self-assembly phenomena. This module includes a hollow glass slide and heating elements for the creation of a thermal gradient from one end of the slide to the other. The electronics module supports both experiment modules and contains a unique illuminator/condenser for bright and dark field and phase contrast illumination, power supplies for two piezoelectric pumps, and controller boards for pumps and valves. This observation platform safely contains internal fluids and will greatly accelerate the research and development (R&D) cycle of numerous experiments, products, and services aboard the ISS.

Xinyinqin: a computer-based heart sound simulator.

PubMed

Zhan, X X; Pei, J H; Xiao, Y H

1995-01-01

"Xinyinqin" is the Chinese phoneticized name of the Heart Sound Simulator (HSS). The "qin" in "Xinyinqin" is the Chinese name of a category of musical instruments, which means that the operation of HSS is very convenient--like playing an electric piano with the keys. HSS is connected to the GAME I/O of an Apple microcomputer. The generation of sound is controlled by a program. Xinyinqin is used as a teaching aid of Diagnostics. It has been applied in teaching for three years. In this demonstration we will introduce the following functions of HSS: 1) The main program has two modules. The first one is the heart auscultation training module. HSS can output a heart sound selected by the student. Another program module is used to test the student's learning condition. The computer can randomly simulate a certain heart sound and ask the student to name it. The computer gives the student's answer an assessment: "correct" or "incorrect." When the answer is incorrect, the computer will output that heart sound again for the student to listen to; this process is repeated until she correctly identifies it. 2) The program is convenient to use and easy to control. By pressing the S key, it is able to output a slow heart rate until the student can clearly identify the rhythm. The heart rate, like the actual rate of a patient, can then be restored by hitting any key. By pressing the SPACE BAR, the heart sound output can be stopped to allow the teacher to explain something to the student. The teacher can resume playing the heart sound again by hitting any key; she can also change the content of the training by hitting RETURN key. In the future, we plan to simulate more heart sounds and incorporate relevant graphs.

Perinatal hypothyroidism modulates antioxidant defence status in the developing rat liver and heart.

PubMed

Zhang, Hongmei; Dong, Yan; Su, Qing

2017-02-01

In the present study, we investigated oxidative stress parameters and antioxidant defence status in perinatal hypothyroid rat liver and heart. We found that the proteincarbonyl content did not differ significantly between the three groups both in the pup liver and in the heart. The OH˙ level was significantly decreased in the hypothyroid heart but not in the liver compared with controls. A slight but not significant decrease in SOD activity was observed in both perinatal hypothyroid liver and heart. A significantly increased activity of CAT was observed in the liver but not in the heart of hypothyroid pups. The GPx activity was considerably increased compared with controls in the perinatal hypothyroid heart and was unaltered in the liver of hypothyroid pups. We also found that vitamin E levels in the liver decreased significantly in hypothyroidism and were unaltered in the heart of perinatal hypothyroid rats. The GSH content was elevated significantly in both hypothyroid liver and heart. The total antioxidant capacity was higher in the liver of the hypothyroid group but not in the hypothyroid heart. Thyroxine replacement could not repair the above changes to normal. In conclusion, perinatal hypothyroidism modulates the oxidative stress status of the perinatal liver and heart.

Online educational tools developed by Heart improve the knowledge and skills of hospital doctors in cardiology

PubMed Central

Walsh, Kieran; Rafiq, Isma; Hall, Roger

2007-01-01

We conducted this study to find out if online learning packages in cardiology enabled users to increase their knowledge and skills. We also looked at how acceptable users found these packages. The journal Heart in association with BMJ Learning produced a series of modules on common cardiology problems. The modules involved a pre‐test, a number of interactive cases and a post‐test. A total of 1786 users completed these modules. Doing the modules enabled users to improve their score from the pre‐test to the post‐test by a significant amount (p<0.001). Feedback to the modules was very positive. PMID:17621623

Health Instruction Packages: Consumer--Your Heart and Blood Pressure.

ERIC Educational Resources Information Center

Woods, James W.; And Others

Text, illustrations, and exercises are utilized in this set of learning modules to instruct the general public in the prevention and treatment of heart disease. The first module, by James W. Woods, presents a medical definition of high blood pressure, reviews its causes and effects, and discusses its treatment. A script to a slide version of this…

Blockade of hyperpolarizing currents produces a dose-dependent effect on heart rate.

PubMed

Ziyatdinova, N I; Giniatullin, R A; Svyatova, N V; Zefirov, T L

2001-03-01

Intravenous injection of ZD 7288, a new specific hyperpolarizing current blocker, dose-dependently reduces heart rate in adult rats. The autonomic nervous system modulates changes in heart rate caused by hyperpolarizing currents.

Synergistic Cardioprotective Effects of Combined Chromium Picolinate and Atorvastatin Treatment in Triton X-100-Induced Hyperlipidemia in Rats: Impact on Some Biochemical Markers.

PubMed

Shafik, Noha M; Baalash, Amal; Ebeid, Abla M

2017-12-01

Hyperlipidemia is one of the major risk factors for atherosclerosis and ischemic heart disease. Chromium (Cr) mineral is playing a crucial role in glucose and lipid homeostasis. The aim of this study was to evaluate the protective effects of combined chromium picolinate (CrPic) and atorvastatin treatment against hyperlipidemia-induced cardiac injury. Seventy-five male albino rats were divided into five groups (15 rats each). Hyperlipidemia was induced by intraperitoneal injection of a single dose of Triton X-100 (300 mg/kg body weight (b.w) (group ІІ). Treatment of hyperlipidemic rats was induced by daily administration of CrPic at a dose of 200 μg/kg b.w/day (group ІІІ), atorvastatin at a dose of 10 mg/kg/day (group IV), and combined treatment with both (group V) by gavage for 7 days. At the end of experiment, serum and heart tissues were obtained. Hyperlipidemia was confirmed by histopathology of heart tissues, marked serum dyslipidemia, increased atherogenic indices, and values of ischemia-modified albumin. In addition to increased values of proprotein convertase subtilisin/kexin type 9, activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme and high relative expression levels of pentraxin-3 were observed. However, paraoxonase-1 activity was markedly decreased in the hyperlipidemic group. Significant improvement in all assessed parameters was observed in the rat group treated with both CrPic and atorvastatin. It can be concluded that combined CrPic and atorvastatin treatments had synergistic cardioprotective effects against hyperlipidemia which may be through modulating atherosclerosis as well as cardiac and aortic damage and/or activation of anti-inflammatory and anti-oxidant pathways, thus reversing endothelial dysfunction.

Spaceflight-induced cardiovascular changes and recovery during NASA's Functional Task Test

NASA Astrophysics Data System (ADS)

Arzeno, Natalia M.; Stenger, Michael B.; Bloomberg, Jacob J.; Platts, Steven H.

2013-11-01

Microgravity-induced physiologic changes could impair a crewmember's performance upon return to a gravity environment. The Functional Task Test aims to correlate these physiologic alterations with changes in performance during mission-critical tasks. In this study, we evaluated spaceflight-induced cardiovascular changes during 11 functional tasks in 7 Shuttle astronauts before spaceflight, on landing day, and 1, 6, and 30 days after landing. Mean heart rate was examined during each task and autonomic activity was approximated by heart rate variability during the Recovery from Fall/Stand Test, a 2-min prone rest followed by a 3-min stand. Heart rate was increased on landing day during all of the tasks, and remained elevated 6 days after landing during 6 of the 11 tasks. Parasympathetic modulation was diminished and sympathovagal balance was increased on landing day. Additionally, during the stand test 6 days after landing, parasympathetic modulation remained suppressed and heart rate remained elevated compared to preflight levels. Heart rate and autonomic activity were not different from preflight levels 30 days after landing. We detected changes in heart rate and autonomic activity during a 3-min stand and a variety of functional tasks, where cardiovascular deconditioning was still evident 6 days after returning from short-duration spaceflight. The delayed recovery times for heart rate and parasympathetic modulation indicate the necessity of assessing functional performance after long-duration spaceflight to ensure crew health and safety.

Characteristics of cardio-Cerebrovascular modulation in patients with generalized anxiety disorder: an observational study.

PubMed

Guo, Zhen-Ni; Feng, Liangshu; Yan, Xiuli; Yang, Le; Huang, Shuo; Xing, Yingqi; Yang, Yi

2017-07-18

Generalized anxiety disorder (GAD) has been shown in previous studies to display abnormal cerebral blood flow velocity (CBFV); however, the characteristics of cardio-cerebrovascular modulation are unknown. We aimed to analyze cardio-cerebrovascular modulation using parameters from a supine-to-standing test. There are 2 parts to this study; in Part 1, 125 participants with Hamilton Anxiety scale scores ≥14 were enrolled, and 33 age- and sex-matched medically and psychiatrically healthy volunteers were recruited as control participants. Patients were divided by score into mild, moderate, and severe anxiety groups. The cardio-cerebrovascular modulation using the parameters of dynamic changes of CBFV and heart rate in response to an orthostatic challenge were investigated. In Part 2, we followed up the severe GAD patients for 6 months and repeated the supine-to-standing test, and severe GAD patients were divided into recovery and non-recovery groups. In part 1, the GAD group displayed more marked CBFV and heart rate changes than the healthy group, but there was no difference in the CBFV and heart rate changes from the supine to upright position in mild, moderate, and severe anxiety groups. In part 2, The recovery group demonstrated significant improvement in changes in the CBFV and heart rate values from the supine to the upright position after treatment compared with before treatment. In the non-recovery group, the CBFV and heart rate changes were significantly higher than the healthy group regardless of treatment. Cardio-cerebrovascular modulation is compromised in patients with GAD, however, this impairment can be restored to normal after the disappearance of anxiety.

The human heart and the circulatory system as an interesting interdisciplinary topic in lessons of physics and biology

NASA Astrophysics Data System (ADS)

Volná, M.; Látal, F.; Kubínek, R.; Richterek, L.

2014-01-01

Many topics which are closely related can be found in the national curriculum of the Czech Republic for physics and biology. One of them is the heart and the circulatory system in the human body. This topic was examined cross curriculum, a teaching module was created and the topic was chosen for our research. The task was to determine if the students of bachelor study are aware of connections between physics and biology within this topic and whether we can help them effectively to describe the corresponding physics phenomena in the human body connected, for example, with a heart attack or with the measurement of blood pressure. In this paper, the heart and the circulatory system are presented as suitable topics for an interdisciplinary teaching module which includes both theoretical and experimental parts. The module was evaluated by a group of first-year undergraduate students of physics at the Faculty of Science, Palacký University. The acquired knowledge was compared with another control group through a test. The highest efficiency of the module was evaluated on the basis of questions that covered the calculation problems.

Short-term variability in QT interval and ventricular arrhythmias induced by dofetilide are dependent on high-frequency autonomic oscillations

PubMed Central

Champeroux, P; Thireau, J; Judé, S; Laigot-Barbé, C; Maurin, A; Sola, M L; Fowler, J S L; Richard, S; Le Guennec, J Y

2015-01-01

Background and Purpose The present study was undertaken to investigate an effect of dofetilide, a potent arrhythmic blocker of the voltage-gated K+ channel, hERG, on cardiac autonomic control. Combined with effects on ardiomyocytes, these properties could influence its arrhythmic potency. Experimental Approach The short-term variability of beat-to-beat QT interval (STVQT), induced by dofetilide is a strong surrogate of Torsades de pointes liability. Involvement of autonomic modulation in STVQT was investigated in healthy cynomolgus monkeys and beagle dogs by power spectral analysis under conditions of autonomic blockade with hexamethonium. Key Results Increase in STVQT induced by dofetilide in monkeys and dogs was closely associated with an enhancement of endogenous heart rate and QT interval high-frequency (HF) oscillations. These effects were fully suppressed under conditions of autonomic blockade with hexamethonium. Ventricular arrhythmias, including Torsades de pointes in monkeys, were prevented in both species when HF oscillations were suppressed by autonomic blockade. Similar enhancements of heart rate HF oscillations were found in dogs with other hERG blockers described as causing Torsades de pointes in humans. Conclusions and Implications These results demonstrate for the first time that beat-to-beat ventricular repolarization variability and ventricular arrhythmias induced by dofetilide are dependent on endogenous HF autonomic oscillations in heart rate. When combined with evidence of hERG-blocking properties, enhancement of endogenous HF oscillations in heart rate could constitute an earlier and more sensitive biomarker than STVQT for Torsades de pointes liability, applicable to preclinical regulatory studies conducted in healthy animals. PMID:25625756

Short-term variability in QT interval and ventricular arrhythmias induced by dofetilide are dependent on high-frequency autonomic oscillations.

PubMed

Champeroux, P; Thireau, J; Judé, S; Laigot-Barbé, C; Maurin, A; Sola, M L; Fowler, J S L; Richard, S; Le Guennec, J Y

2015-06-01

The present study was undertaken to investigate an effect of dofetilide, a potent arrhythmic blocker of the voltage-gated K(+) channel, hERG, on cardiac autonomic control. Combined with effects on ardiomyocytes, these properties could influence its arrhythmic potency. The short-term variability of beat-to-beat QT interval (STVQT ), induced by dofetilide is a strong surrogate of Torsades de pointes liability. Involvement of autonomic modulation in STVQT was investigated in healthy cynomolgus monkeys and beagle dogs by power spectral analysis under conditions of autonomic blockade with hexamethonium. Increase in STVQT induced by dofetilide in monkeys and dogs was closely associated with an enhancement of endogenous heart rate and QT interval high-frequency (HF) oscillations. These effects were fully suppressed under conditions of autonomic blockade with hexamethonium. Ventricular arrhythmias, including Torsades de pointes in monkeys, were prevented in both species when HF oscillations were suppressed by autonomic blockade. Similar enhancements of heart rate HF oscillations were found in dogs with other hERG blockers described as causing Torsades de pointes in humans. These results demonstrate for the first time that beat-to-beat ventricular repolarization variability and ventricular arrhythmias induced by dofetilide are dependent on endogenous HF autonomic oscillations in heart rate. When combined with evidence of hERG-blocking properties, enhancement of endogenous HF oscillations in heart rate could constitute an earlier and more sensitive biomarker than STVQT for Torsades de pointes liability, applicable to preclinical regulatory studies conducted in healthy animals. © 2015 The British Pharmacological Society.

Reproducible deep-inspiration breath-hold irradiation with forward intensity-modulated radiotherapy for left-sided breast cancer significantly reduces cardiac radiation exposure compared to inverse intensity-modulated radiotherapy.

PubMed

Bolukbasi, Yasemin; Saglam, Yucel; Selek, Ugur; Topkan, Erkan; Kataria, Anglina; Unal, Zeynep; Alpan, Vildan

2014-01-01

To investigate the objective utility of our clinical routine of reproducible deep-inspiration breath-hold irradiation for left-sided breast cancer patients on reducing cardiac exposure. Free-breathing and reproducible deep-inspiration breath-hold scans were evaluated for our 10 consecutive left-sided breast cancer patients treated with reproducible deep-inspiration breath-hold. The study was based on the adjuvant dose of 50 Gy in 25 fractions of 2 Gy/fraction. Both inverse and forward intensity-modulated radiotherapy plans were generated for each computed tomography dataset. Reproducible deep-inspiration breath-hold plans with forward intensity-modulated radiotherapy significantly spared the heart and left anterior descending artery compared to generated free-breathing plans based on mean doses - free-breathing vs reproducible deep-inspiration breath-hold, left ventricle (296.1 vs 94.5 cGy, P = 0.005), right ventricle (158.3 vs 59.2 cGy, P = 0.005), left anterior descending artery (171.1 vs 78.1 cGy, P = 0.005), and whole heart (173.9 vs 66 cGy, P = 0.005), heart V20 (2.2% vs 0%, P = 0.007) and heart V10 (4.2% vs 0.3%, P = 0.007) - whereas they revealed no additional burden on the ipsilateral lung. Reproducible deep-inspiration breath-hold and free-breathing plans with inverse intensity-modulated radiotherapy provided similar organ at risk sparing by reducing the mean doses to the left ventricle, left anterior descending artery, heart, V10-V20 of the heart and right ventricle. However, forward intensity-modulated radiotherapy showed significant reduction in doses to the left ventricle, left anterior descending artery, heart, right ventricle, and contralateral breast (mean dose, 248.9 to 12.3 cGy, P = 0.005). The mean doses for free-breathing vs reproducible deep-inspiration breath-hold of the proximal left anterior descending artery were 1.78 vs 1.08 Gy and of the distal left anterior descending artery were 8.11 vs 3.89 Gy, whereas mean distances to the 50 Gy isodose line of the proximal left anterior descending artery were 6.6 vs 3.3 cm and of the distal left anterior descending artery were 7.4 vs 4.1 cm, with forward intensity-modulated radiotherapy. Overall reduction in mean doses to proximal and distal left anterior descending artery with deep-inspiration breath-hold irradiation was 39% (P = 0.02) and 52% (P = 0.002), respectively. We found a significant reduction of radiation exposure to the contralateral breast, left and right ventricles, as well as of proximal and especially distal left anterior descending artery with the deep-inspiration breath-hold technique with forward intensity-modulated radiotherapy planning.

Oxytocin receptor gene polymorphism modulates the effects of social support on heart rate variability

PubMed Central

Kanthak, Magdalena K.; Chen, Frances S.; Kumsta, Robert; Hill, LaBarron K.; Thayer, Julian F.; Heinrichs, Markus

2017-01-01

A large body of empirical research has demonstrated stress-buffering effects of social support. However, recent studies suggest that genetic variation of the oxytocin system (specifically, a common single nucleotide polymorphism, rs53576, of the oxytocin receptor gene) modulates the efficacy of social support. The timing and neurobiological basis of this genetic modulation were investigated using a standardized, laboratory-based psychological stress procedure (Trier Social Stress Test for Groups, TSST-G). To index potential stress buffering effects of social support mediated by the oxytocin system, heart rate variability (HRV) was obtained before and during the TSST-G from 40 healthy participants. Results indicate that social support is associated with higher HRV only in G allele carriers. Specifically, social support increased heart rate variability during direct social interaction and only in individuals with at least one copy of the G allele of rs53576. These findings support the idea that the stress-attenuating effects of social support are modulated by genetic variation of the oxytocin system. PMID:26903384

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

PubMed

Inoue, Tatsuya; Widder, Joachim; van Dijk, Lisanne V; Takegawa, Hideki; Koizumi, Masahiko; Takashina, Masaaki; Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru; Saito, Anneyuko I; Sasai, Keisuke; Van't Veld, Aart A; Langendijk, Johannes A; Korevaar, Erik W

2016-11-01

To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

A model of mechanical interactions between heart and lungs.

PubMed

Fontecave Jallon, Julie; Abdulhay, Enas; Calabrese, Pascale; Baconnier, Pierre; Gumery, Pierre-Yves

2009-12-13

To study the mechanical interactions between heart, lungs and thorax, we propose a mathematical model combining a ventilatory neuromuscular model and a model of the cardiovascular system, as described by Smith et al. (Smith, Chase, Nokes, Shaw & Wake 2004 Med. Eng. Phys.26, 131-139. (doi:10.1016/j.medengphy.2003.10.001)). The respiratory model has been adapted from Thibault et al. (Thibault, Heyer, Benchetrit & Baconnier 2002 Acta Biotheor. 50, 269-279. (doi:10.1023/A:1022616701863)); using a Liénard oscillator, it allows the activity of the respiratory centres, the respiratory muscles and rib cage internal mechanics to be simulated. The minimal haemodynamic system model of Smith includes the heart, as well as the pulmonary and systemic circulation systems. These two modules interact mechanically by means of the pleural pressure, calculated in the mechanical respiratory system, and the intrathoracic blood volume, calculated in the cardiovascular model. The simulation by the proposed model provides results, first, close to experimental data, second, in agreement with the literature results and, finally, highlighting the presence of mechanical cardiorespiratory interactions.

Exercise science: research to sustain and enhance performance

NASA Astrophysics Data System (ADS)

Wingo, Jonathan E.

2013-05-01

Cardiovascular adjustments accompanying exercise in high ambient temperatures are likely responsible for diminished aerobic capacity and performance in such conditions. These adjustments include a phenomenon known as cardiovascular drift in which heart rate rises and stroke volume declines progressively over time during constant-rate exercise. A variety of factors modulate the magnitude of cardiovascular drift, e.g., elevated core and skin temperatures, dehydration, and exercise intensity. Regardless of the mode of manipulation, decreases in stroke volume associated with cardiovascular drift result in directionally and proportionally similar decreases in maximal aerobic capacity. Maximal aerobic capacity is determined by maximal heart rate, maximal tissue oxygen extraction, and maximal stroke volume. Because maximal heart rate and maximal tissue oxygen extraction are unaffected during exercise in the heat, decreased stroke volume associated with cardiovascular drift likely persists during maximal efforts and explains the decrease in maximal aerobic capacity. Decreased maximal aerobic capacity results in a greater perceptual and physiological strain accompanying any given level of work. Therefore, sustaining and enhancing performance involves sophisticated monitoring of physiological strain combined with development of countermeasures that mitigate the magnitude of deleterious phenomena like cardiovascular drift.

Hearts and minds: Coordination of neurocognitive and cardiovascular regulation in children and adolescents.

PubMed

Chapman, H A; Woltering, S; Lamm, C; Lewis, M D

2010-05-01

Emotional reactions involve changes in both cognitive and bodily processes. Therefore, effective emotion regulation may also involve modulation of responses in both of these systems. The present study investigated the relationship between regulation of cognition and regulation of the heart in children and adolescents, using a go/nogo task in combination with the induction of negative emotions. Behavioral, temperamental and event-related brain potential (ERP) indicators of inhibitory cognitive control were collected, as was a measure of parasympathetic control of the heart (respiratory sinus arrhythmia, RSA). Independently of age, RSA was correlated with nogo N2 magnitudes during the emotion-induction procedure. RSA during the task was also correlated with N2 latencies and with behavioral accuracy before, during and after the emotion induction. Resting RSA was correlated with individual differences in the capacity for effortful cognitive control, as measured by questionnaire. These results suggest that emotional responses in seemingly distinct neurophysiological systems may be regulated in an integrated fashion throughout the developmental span tested. Copyright 2010 Elsevier B.V. All rights reserved.

A dual-input nonlinear system analysis of autonomic modulation of heart rate

NASA Technical Reports Server (NTRS)

Chon, K. H.; Mullen, T. J.; Cohen, R. J.

1996-01-01

Linear analyses of fluctuations in heart rate and other hemodynamic variables have been used to elucidate cardiovascular regulatory mechanisms. The role of nonlinear contributions to fluctuations in hemodynamic variables has not been fully explored. This paper presents a nonlinear system analysis of the effect of fluctuations in instantaneous lung volume (ILV) and arterial blood pressure (ABP) on heart rate (HR) fluctuations. To successfully employ a nonlinear analysis based on the Laguerre expansion technique (LET), we introduce an efficient procedure for broadening the spectral content of the ILV and ABP inputs to the model by adding white noise. Results from computer simulations demonstrate the effectiveness of broadening the spectral band of input signals to obtain consistent and stable kernel estimates with the use of the LET. Without broadening the band of the ILV and ABP inputs, the LET did not provide stable kernel estimates. Moreover, we extend the LET to the case of multiple inputs in order to accommodate the analysis of the combined effect of ILV and ABP effect on heart rate. Analyzes of data based on the second-order Volterra-Wiener model reveal an important contribution of the second-order kernels to the description of the effect of lung volume and arterial blood pressure on heart rate. Furthermore, physiological effects of the autonomic blocking agents propranolol and atropine on changes in the first- and second-order kernels are also discussed.

Selected phenolic compounds in cultivated plants: ecologic functions, health implications, and modulation by pesticides.

PubMed Central

Daniel, O; Meier, M S; Schlatter, J; Frischknecht, P

1999-01-01

Phenolic compounds are widely distributed in the plant kingdom. Plant tissues may contain up to several grams per kilogram. External stimuli such as microbial infections, ultraviolet radiation, and chemical stressors induce their synthesis. The phenolic compounds resveratrol, flavonoids, and furanocoumarins have many ecologic functions and affect human health. Ecologic functions include defense against microbial pathogens and herbivorous animals. Phenolic compounds may have both beneficial and toxic effects on human health. Effects on low-density lipoproteins and aggregation of platelets are beneficial because they reduce the risk of coronary heart disease. Mutagenic, cancerogenic, and phototoxic effects are risk factors of human health. The synthesis of phenolic compounds in plants can be modulated by the application of herbicides and, to a lesser extent, insecticides and fungicides. The effects on ecosystem functioning and human health are complex and cannot be predicted with great certainty. The consequences of the combined natural and pesticide-induced modulating effects for ecologic functions and human health should be further evaluated. PMID:10229712

[Combined heart-kidney transplantation in Mexic].

PubMed

Careaga-Reyna, Guillermo; Zetina-Tun, Hugo Jesús; Lezama-Urtecho, Carlos Alberto; Hernández-Domínguez, José Mariano; Santos-Caballero, Marlene

In our country, heart and kidney transplantation is a novel option for treatment of combined terminal heart and kidney failure. This program began in 2012 for selected patients with documented terminal heart failure and structural kidney damage with renal failure. Description of cases: Between January 1, 2012 and April 30, 2016, we made 92 orthotopic heart transplantations. In five of these cases the heart transplantation was combined with kidney transplantation. There were three male and two female patients with a mean age 25.6 ± 5.2 years (range, 17-29). The patients improved their renal function and the heart transplantation was successful with an improved quality of life. One patient died from abdominal sepsis. The other patients are doing well. The combined heart-kidney transplantation is a safe and efficient procedure for patients with structural kidney and heart damage as a cause of terminal failure.

Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling.

PubMed

Li, Y Y; McTiernan, C F; Feldman, A M

2000-05-01

Myocardial fibrosis due to maladaptive extracellular matrix remodeling contributes to dysfunction of the failing heart. Further elucidation of the mechanism by which myocardial fibrosis and dilatation can be prevented or even reversed remains of great interest as a potential means to limit myocardial remodeling and dysfunction. Matrix metalloproteinases (MMPs) are the driving force behind extracellular matrix degradation during remodeling and are increased in the failing human heart. MMPs are regulated by a variety of growth factors, cytokines, and matrix fragments such as matrikines. In the present report, we discuss the regulation of MMPs, the role of MMPs in the development of cardiac fibrosis, and the modulation of MMP activity using gene transfer and knockout technologies. We also present recent findings from our laboratory on the regulation of the extracellular MMP inducer (EMMPRIN), MMPs, and transforming growth factor-beta(1) in the failing human heart before and after left ventricular assist device support, as well as the possibility of preventing ventricular fibrosis using different anti-MMP strategies. Several studies suggest that such modulation of MMP activity can alter ventricular remodeling, myocardial dysfunction, and the progression of heart failure. It is therefore suggested that the interplay of MMPs and their regulators is important in the development of the heart failure phenotype, and myocardial fibrosis in heart failure may be modified by modulating MMP activity.

[Renin-angiotensin-aldosterone system (RAAS) and its pharmacologic modulation].

PubMed

Giestas, Anabela; Palma, Isabel; Ramos, Maria Helena

2010-01-01

The renin-angiotensin-aldosterone system (RAAS) is a neuroendocrine complex system that regulates the modulation of salt and water homeostasis, and regulation of blood pressure. Through its multiple interactions it protects the endothelium, heart, brain and kidney. In addition, the RAAS regulates the vascular response to injury and inflammation. Chronic activation/dysregulation of the RAAS leads to hypertension and perpetuates a cascade of proinflammatory, prothrombotic and atherogenic effects associated with endorgan damage (heart, brain, kidney, endothelium). Consequently, the RAAS is an important therapeutic target in these situations. This article presents an overview of physiology, pathophysiology and pharmacologic modulation of the RAAS.

Neural network for photoplethysmographic respiratory rate monitoring

NASA Astrophysics Data System (ADS)

Johansson, Anders

2001-10-01

The photoplethysmographic signal (PPG) includes respiratory components seen as frequency modulation of the heart rate (respiratory sinus arrhythmia, RSA), amplitude modulation of the cardiac pulse, and respiratory induced intensity variations (RIIV) in the PPG baseline. The aim of this study was to evaluate the accuracy of these components in determining respiratory rate, and to combine the components in a neural network for improved accuracy. The primary goal is to design a PPG ventilation monitoring system. PPG signals were recorded from 15 healthy subjects. From these signals, the systolic waveform, diastolic waveform, respiratory sinus arrhythmia, pulse amplitude and RIIV were extracted. By using simple algorithms, the rates of false positive and false negative detection of breaths were calculated for each of the five components in a separate analysis. Furthermore, a simple neural network (NN) was tried out in a combined pattern recognition approach. In the separate analysis, the error rates (sum of false positives and false negatives) ranged from 9.7% (pulse amplitude) to 14.5% (systolic waveform). The corresponding value of the NN analysis was 9.5-9.6%.

Low heart rate variability in unemployed men: The possible mediating effects of life satisfaction.

PubMed

Jandackova, V K; Jackowska, M

2015-01-01

Unemployment has consistently been associated with increased risk of cardiovascular disease and premature mortality, and impaired autonomic modulation of the heart might be one mechanism partly explaining this. This study examined whether the possible effect of unemployment on cardiac autonomic modulation is in part mediated by lower psychological well-being. The sample comprised of 15 job-seeking men aged 30-49 years matched with 15 employed men on age, type of job, smoking habits, alcohol intake, frequency of physical activity, and body mass index. Heart rate variability (HRV) during a modified orthostatic test was the measure of cardiac autonomic modulation, and life satisfaction was the measure of psychological well-being. Unemployed men had significantly lower overall HRV (p = .040) than controls. This association was partially mediated through lower general life satisfaction, and in particular, by low financial satisfaction, independently of demographic and/or behavioral factors that influence HRV. These findings suggest that seeking a job is a potential stressor that may reduce overall HRV and contribute towards disturbance of cardiac autonomic modulation in men. Financial difficulties could be one mechanism through which the effects of unemployment are translated into impaired autonomic modulation.

The marine mammal dive response is exercise modulated to maximize aerobic dive duration.

PubMed

Davis, Randall W; Williams, Terrie M

2012-08-01

When aquatically adapted mammals and birds swim submerged, they exhibit a dive response in which breathing ceases, heart rate slows, and blood flow to peripheral tissues and organs is reduced. The most intense dive response occurs during forced submersion which conserves blood oxygen for the brain and heart, thereby preventing asphyxiation. In free-diving animals, the dive response is less profound, and energy metabolism remains aerobic. However, even this relatively moderate bradycardia seems diametrically opposed to the normal cardiovascular response (i.e., tachycardia and peripheral vasodilation) during physical exertion. As a result, there has been a long-standing paradox regarding how aquatic mammals and birds exercise while submerged. We hypothesized based on cardiovascular modeling that heart rate must increase to ensure adequate oxygen delivery to active muscles. Here, we show that heart rate (HR) does indeed increase with flipper or fluke stroke frequency (SF) during voluntary, aerobic dives in Weddell seals (HR = 1.48SF - 8.87) and bottlenose dolphins (HR = 0.99SF + 2.46), respectively, two marine mammal species with different evolutionary lineages. These results support our hypothesis that marine mammals maintain aerobic muscle metabolism while swimming submerged by combining elements of both dive and exercise responses, with one or the other predominating depending on the level of exertion.

Weighted gene co‑expression network analysis in identification of key genes and networks for ischemic‑reperfusion remodeling myocardium.

PubMed

Guo, Nan; Zhang, Nan; Yan, Liqiu; Lian, Zheng; Wang, Jiawang; Lv, Fengfeng; Wang, Yunfei; Cao, Xufen

2018-06-14

Acute myocardial infarction induces ventricular remodeling, which is implicated in dilated heart and heart failure. The pathogenical mechanism of myocardium remodeling remains to be elucidated. The aim of the present study was to identify key genes and networks for myocardium remodeling following ischemia‑reperfusion (IR). First, the mRNA expression data from the National Center for Biotechnology Information database were downloaded to identify differences in mRNA expression of the IR heart at days 2 and 7. Then, weighted gene co‑expression network analysis, hierarchical clustering, protein‑protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to identify key genes and networks for the heart remodeling process following IR. A total of 3,321 differentially expressed genes were identified during the heart remodeling process. A total of 6 modules were identified through gene co‑expression network analysis. GO and KEGG analysis results suggested that each module represented a different biological function and was associated with different pathways. Finally, hub genes of each module were identified by PPI network construction. The present study revealed that heart remodeling following IR is a complicated process, involving extracellular matrix organization, neural development, apoptosis and energy metabolism. The dysregulated genes, including SRC proto‑oncogene, non‑receptor tyrosine kinase, discs large MAGUK scaffold protein 1, ATP citrate lyase, RAN, member RAS oncogene family, tumor protein p53, and polo like kinase 2, may be essential for heart remodeling following IR and may be used as potential targets for the inhibition of heart remodeling following acute myocardial infarction.

Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

PubMed

Carnevali, Luca; Trombini, Mimosa; Graiani, Gallia; Madeddu, Denise; Quaini, Federico; Landgraf, Rainer; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

2014-04-10

In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Proton therapy for locally advanced breast cancer: A systematic review of the literature.

PubMed

Kammerer, Emmanuel; Guevelou, Jennifer Le; Chaikh, Abdulhamid; Danhier, Serge; Geffrelot, Julien; Levy, Christelle; Saloux, Eric; Habrand, Jean-Louis; Thariat, Juliette

2018-02-01

Radiation therapy plays a major role in the management of adjuvant breast cancer with nodal involvement, with an iatrogenic increase of cardio-vascular risk. Photon therapy, even with intensity modulation, has the downsides of high mean heart dose and heterogeneous target coverage, particularly in the case of internal mammary irradiation. This systematic review of the literature aims to evaluate proton therapy in locally advanced breast cancer. PubMed was searched for original full-text articles with the following search terms: «Proton Therapy» and «Breast Cancer». On-going trials were collected using the words "Breast Cancer" and "Protons". 13 articles met the criteria: 6 with passive proton therapy (Double Scattering), 5 with Pencil Beam Scanning (PBS) and 2 with a combination of both. Proton therapy offered a better target coverage than photons, even compared with intensity modulation radiation therapy (including static or rotational IMRT or tomotherapy). With proton therapy, volumes receiving 95% of the dose were around 98%, with low volumes receiving 105% of the dose. Proton therapy often decreased mean heart dose by a factor of 2 or 3, i.e. 1 Gy with proton therapy versus 3 Gy with conventional 3D, and 6 Gy for IMRT. Lungs were better spared with proton therapy than with photon therapy. Cutaneous toxicity observed with double scattering is improved with PBS. Proton therapy reduces mean heart dose in breast cancer irradiation, probably reducing late cardio-vascular toxicity. Large clinical studies will likely confirm a clinical benefit of proton therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Generating pulsatility by pump speed modulation with continuous-flow total artificial heart in awake calves.

PubMed

Fukamachi, Kiyotaka; Karimov, Jamshid H; Sunagawa, Gengo; Horvath, David J; Byram, Nicole; Kuban, Barry D; Dessoffy, Raymond; Sale, Shiva; Golding, Leonard A R; Moazami, Nader

2017-12-01

The purpose of this study was to evaluate the effects of sinusoidal pump speed modulation of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) on hemodynamics and pump flow in an awake chronic calf model. The sinusoidal pump speed modulations, performed on the day of elective sacrifice, were set at ±15 and ± 25% of mean pump speed at 80 bpm in four awake calves with a CFTAH. The systemic and pulmonary arterial pulse pressures increased to 12.0 and 12.3 mmHg (±15% modulation) and to 15.9 and 15.7 mmHg (±25% modulation), respectively. The pulsatility index and surplus hemodynamic energy significantly increased, respectively, to 1.05 and 1346 ergs/cm at ±15% speed modulation and to 1.51 and 3381 ergs/cm at ±25% speed modulation. This study showed that it is feasible to generate pressure pulsatility with pump speed modulation; the platform is suitable for evaluating the physiologic impact of pulsatility and allows determination of the best speed modulations in terms of magnitude, frequency, and profiles.

In Vivo Bio-distribution and Efficient Tumor Targeting of Gelatin/Silica Nanoparticles for Gene Delivery

NASA Astrophysics Data System (ADS)

Zhao, Xueqin; Wang, Jun; Tao, SiJie; Ye, Ting; Kong, Xiangdong; Ren, Lei

2016-04-01

The non-viral gene delivery system is an attractive alternative to cancer therapy. The clinical success of non-viral gene delivery is hampered by transfection efficiency and tumor targeting, which can be individually overcome by addition of functional modules such as cell penetration or targeting. Here, we first engineered the multifunctional gelatin/silica (GS) nanovectors with separately controllable modules, including tumor-targeting aptamer AGRO100, membrane-destabilizing peptide HA2, and polyethylene glycol (PEG), and then studied their bio-distribution and in vivo transfection efficiencies by contrast resonance imaging (CRI). The results suggest that the sizes and zeta potentials of multifunctional gelatin/silica nanovectors were 203-217 nm and 2-8 mV, respectively. Functional GS-PEG nanoparticles mainly accumulated in the liver and tumor, with the lowest uptake by the heart and brain. Moreover, the synergistic effects of tumor-targeting aptamer AGRO100 and fusogenic peptide HA2 promoted the efficient cellular internalization in the tumor site. More importantly, the combined use of AGRO100 and PEG enhanced tumor gene expression specificity and effectively reduced toxicity in reticuloendothelial system (RES) organs after intravenous injection. Additionally, low accumulation of GS-PEG was observed in the heart tissues with high gene expression levels, which could provide opportunities for non-invasive gene therapy.

Understanding the physiology of mindfulness: aortic hemodynamics and heart rate variability.

PubMed

May, Ross W; Bamber, Mandy; Seibert, Gregory S; Sanchez-Gonzalez, Marcos A; Leonard, Joseph T; Salsbury, Rebecca A; Fincham, Frank D

2016-01-01

Data were collected to examine autonomic and hemodynamic cardiovascular modulation underlying mindfulness from two independent samples. An initial sample (N = 185) underwent laboratory assessments of central aortic blood pressure and myocardial functioning to investigated the association between mindfulness and cardiac functioning. Controlling for religiosity, mindfulness demonstrated a strong negative relationship with myocardial oxygen consumption and left ventricular work but not heart rate or blood pressure. A second sample (N = 124) underwent a brief (15 min) mindfulness inducing intervention to examine the influence of mindfulness on cardiovascular autonomic modulation via blood pressure variability and heart rate variability. The intervention had a strong positive effect on cardiovascular modulation by decreasing cardiac sympathovagal tone, vasomotor tone, vascular resistance and ventricular workload. This research establishes a link between mindfulness and cardiovascular functioning via correlational and experimental methodologies in samples of mostly female undergraduates. Future directions for research are outlined.

'BeAWARE': supporting non-clinical staff within general practice to promptly identify patients presenting with warning signs of heart attack or stroke.

PubMed

Poulter, Christopher; Stewart, Michelle; Fitzpatrick, Cliona; Keech, Wendy; Stavreski, Bill; Grenfell, Robert

2014-06-01

General practice requires systems to deal with patients presenting with urgent needs. BeAWARE was developed to support non-clinical staff to promptly identify patients with symptoms of heart attack or stroke. Data were collected from May 2012 to December 2012 on participants completing the BeAWARE learning module, including pre- and post-assessments on knowledge, confidence and intended action. From May 2012 to December 2012, 1865 participants completed the module. There were significant increases in recall of heart attack and stroke symptoms among non-clinical participants, including chest tightness (23.4-48.7%, P DISCUSSION: BeAWARE fulfils a practice gap in patient safety by improving non-clinical staff's knowledge, confidence and intended action in response to patients presenting with heart attack or stroke warning signs.

Design and analysis of a field modulated magnetic screw for artificial heart

NASA Astrophysics Data System (ADS)

Ling, Zhijian; Ji, Jinghua; Wang, Fangqun; Bian, Fangfang

2017-05-01

This paper proposes a new electromechanical energy conversion system, called Field Modulated Magnetic Screw (FMMS) as a high force density linear actuator for artificial heart. This device is based on the concept of magnetic screw and linear magnetic gear. The proposed FMMS consists of three parts with the outer and inner carrying the radially magnetized helically permanent-magnet (PM), and the intermediate having a set of helically ferromagnetic pole pieces, which modulate the magnetic fields produced by the PMs. The configuration of the newly designed FMMS is presented and its electromagnetic performances are analyzed by using the finite-element analysis, verifying the advantages of the proposed structure.

The multi-mode modulator: A versatile fluidic device for two-dimensional gas chromatography.

PubMed

Seeley, John V; Schimmel, Nicolaas E; Seeley, Stacy K

2018-02-09

A fluidic device called the multi-mode modulator (MMM) has been developed for use as a comprehensive two-dimensional gas chromatography (GC x GC) modulator. The MMM can be employed in a wide range of capacities including as a traditional heart-cutting device, a low duty cycle GC x GC modulator, and a full transfer GC x GC modulator. The MMM is capable of producing narrow component pulses (widths <50ms) while operating at flows compatible with high resolution chromatography. The sample path of modulated components is confined to the interior of a joining capillary. The joining capillary dimensions and the position of the columns within the joining capillary can be optimized for the selected modulation mode. Furthermore, the joining capillary can be replaced easily and inexpensively if it becomes fouled due to sample matrix components or column bleed. The principles of operation of the MMM are described and its efficacy is demonstrated as a heart-cutting device and as a GC x GC modulator. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of space flight on cardiovascular autonomic control

NASA Astrophysics Data System (ADS)

Beckers, F.; Verheyden, B.; Morukov, B.; Aubert, Ae

Introduction: Space flight alters the distribution of blood in the human body, leading to altered cardiovascular neurohumoral regulation with a blunted carotid-cardiac baroreflex. These changes contribute to the occurrence of orthostatic intolerance after space flight. Heart rate variability (HRV) and blood pressure variability (BPV) provide non-invasive means to study the autonomic modulation of the heart. Low frequency (LF) oscillations provide information about sympathetic modulation and baroreflex, while high frequency (HF) modulation is an index of vagal heart rate modulation. Methods: ECG and continuous blood pressure were measured for at least 10 minutes in supine, sitting and standing position 45 days and 10 days (L-45, L-10) before launch; and at 1, 2, 4, 9, 15, 19 and 25 days after return to earth (R+x). In space, ECG and continuous blood pressure were measured at day 5 (FD5) and day 8 (FD8). These measurements were performed in 3. HRV and BPV indices were calculated in time and frequency domain. Results: Measurements in supine position and sitting position did not show as high differences as the measurements in standing position. During space flight heart rate was significantly lower compared to the pre- and post-flight measurements in standing position (RR-values: L-45: 837± 42 ms; FD5: 1004± 40 ms; FD8: 1038± 53 ms; R+1: 587± 21 ms; p<0.05). This was accompanied by a significant increase in the proportion of HF power during space flight and a decrease in LF power. Immediately after space flight both LF and HF modulation of heart rate were extremely depressed compared to the pre-flight conditions (p<0.005). A gradual recovery towards baseline conditions of both indices was observed up to 25 days after return from space (LF: L-45: 3297± 462 ms2; FD5: 1251± 332 ms2; FD8: 1322± 462 ms2; R+1: 547± 188 ms2; R+4: 1958± 709 ms2; R+9: 1220± 148 ms2; R+15: 1704± 497 ms2; R+25: 2644± 573 ms2). However, even 25 days after return, values were below baseline condition. Mean systolic blood pressure did not differ significantly before during and after space flight. In space both LF and HF were decreased compared the standing measurements pre- and post-flight. No evolution was present in BPV after return to Earth. Conclusion: During space flight autonomic modulation is characterised by a vagal predominance. Immediately after return to Earth overall autonomic modulation is extremely depressed. Vasomotor autonomic control is restored rather quickly after space flight, while the restoration of autonomic modulation of heart rate is very slow.

Combined heart-kidney transplantation after total artificial heart insertion.

PubMed

Ruzza, A; Czer, L S C; Ihnken, K A; Sasevich, M; Trento, A; Ramzy, D; Esmailian, F; Moriguchi, J; Kobashigawa, J; Arabia, F

2015-01-01

We present the first single-center report of 2 consecutive cases of combined heart and kidney transplantation after insertion of a total artificial heart (TAH). Both patients had advanced heart failure and developed dialysis-dependent renal failure after implantation of the TAH. The 2 patients underwent successful heart and kidney transplantation, with restoration of normal heart and kidney function. On the basis of this limited experience, we consider TAH a safe and feasible option for bridging carefully selected patients with heart and kidney failure to combined heart and kidney transplantation. Recent FDA approval of the Freedom driver may allow outpatient management at substantial cost savings. The TAH, by virtue of its capability of providing pulsatile flow at 6 to 10 L/min, may be the mechanical circulatory support device most likely to recover patients with marginal renal function and advanced heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.

Dosimetric comparison between modulated arc therapy and static intensity modulated radiotherapy in thoracic esophageal cancer: a single institutional experience.

PubMed

Choi, Kyu Hye; Kim, Jina; Lee, Sea-Won; Kang, Young-Nam; Jang, HongSeok

2018-03-01

The objective of this study was to compare dosimetric characteristics of three-dimensional conformal radiotherapy (3D-CRT) and two types of intensity-modulated radiotherapy (IMRT) which are step-and-shoot intensity modulated radiotherapy (s-IMRT) and modulated arc therapy (mARC) for thoracic esophageal cancer and analyze whether IMRT could reduce organ-at-risk (OAR) dose. We performed 3D-CRT, s-IMRT, and mARC planning for ten patients with thoracic esophageal cancer. The dose-volume histogram for each plan was extracted and the mean dose and clinically significant parameters were analyzed. Analysis of target coverage showed that the conformity index (CI) and conformation number (CN) in mARC were superior to the other two plans (CI, p = 0.050; CN, p = 0.042). For the comparison of OAR, lung V 5 was lowest in s-IMRT, followed by 3D-CRT, and mARC (p = 0.033). s-IMRT and mARC had lower values than 3D-CRT for heart V 30 (p = 0.039), V 40 (p = 0.040), and V 50 (p = 0.032). Effective conservation of the lung and heart in thoracic esophageal cancer could be expected when using s-IMRT. The mARC was lower in lung V 10 , V 20 , and V 30 than in 3D-CRT, but could not be proven superior in lung V 5 . In conclusion, low-dose exposure to the lung and heart were expected to be lower in s-IMRT, reducing complications such as radiation pneumonitis or heart-related toxicities.

HYPNOTIZABILITY AND PAIN MODULATION: A Body-Mind Perspective.

PubMed

Varanini, Maurizio; Balocchi, Rita; Carli, Giancarlo; Paoletti, Giulia; Santarcangelo, Enrica L

2018-01-01

The study investigated whether the cardiac activity and cognitive-emotional traits sustained by the behavioral inhibition/activation system (BIS/BAS) may contribute to hypnotizability-related pain modulation. Nociceptive stimulation (cold-pressor test) was administered to healthy participants with high (highs) and low (lows) hypnotizability in the presence and absence of suggestions for analgesia. Results showed that heart rate increased abruptly at the beginning of nociceptive stimulation in all participants. Then, only in highs heart rate decreased for the entire duration of hand immersion. During stimulation with suggestions of analgesia, pain threshold negatively correlated with heart rate. BIS/BAS activity partially accounted for the observed hypnotizability-related differences in the relation between cardiac interoception and pain experience.

In vitro performance testing of a pediatric oxygenator with an integrated pulsatile pump.

PubMed

Borchardt, Ralf; Schlanstein, Peter; Mager, Ilona; Arens, Jutta; Schmitz-Rode, Thomas; Steinseifer, Ulrich

2012-01-01

For different lung and heart diseases (e.g., acute respiratory distress syndrome, congenital heart failure, and cardiomyopathy) extracorporeal membrane oxygenation is a well-established therapy, particularly in the field of neonatal and pediatric medicine. To reduce the priming volume of the extracorporeal circuit, different components can be combined. In this study, an oval-shaped oxygenator (called ExMeTrA) with integrated pulsatile pump was tested in vitro using porcine blood. A feasibility study regarding the performance of collapsing and expanding silicone tubes within an oxygenator fiber bundle as a pulsatile pump was previously completed with successful results. The findings of this study improve upon the previous feasibility results, particularly in terms of gas exchange and filling volume. Five modules were manufactured in sizes of 20 ± 2.2 ml (priming volume) with fiber surface areas of 0.24 ± 0.027 m(2) and an analytically calculated volume pumping capacity of 692 ± 75 ml/min. The modules were made of polymethylpentene fibers with dense outer layer to permit long-term applications. The gas exchange rates at a gas/blood flow ratio of 2:1 were between 64 and 72.7 ml(O)(2)/l(blood) and between 62.5 and 81.5 ml/l(blood), depending on the blood flow. The individual module's pumping capacity ranged from 200-500 ml/min thus providing room for further improvements. In order to enhance the pumping capacity while maintaining sufficient gas exchange rates future optimization, adjustments will be made to the inlet and outlet geometries.

First successful combined heart and kidney transplant in Iran: a case report.

PubMed

Ahmadi, Zargham-Hossein; Mirhosseini, Seyed Mohsen; Fakhri, Mohammad; Mozaffary, Amirhossein; Lotfaliany, Mojtaba; Nejatollahi, Seyed Mohammad Reza; Marashi, Seyed-Ali; Behzadnia, Neda; Sharif-Kashani, Babak

2013-08-01

Combined heart and kidney transplant has become an accepted therapy for patients with coexisting heart and kidney failure. This method, compared with single-organ transplant, has a better outcome. Here, we report the first successful combined heart and kidney transplant in Iran. The patient was a 36-year-old man with end-stage renal disease owing to IgA nephropathy, admitted to Masih Daneshvari Hospital in Tehran, Iran for progressive dyspnea and chest pain. In-patient evaluations revealed cardiomyopathy leading to end-stage heart failure. Owing to concurrent heart and kidney end-stage diseases, combined cardiorenal transplant was done. Eight months after his transplant, routine follow-ups have not shown any signs of acute rejection. He is now New York Heart Association functional class I. Both cardiac and renal functions are within normal ranges. Good outcome during follow-up for this case justifies simultaneous heart plus kidney transplants as an alternate treatment for patients with advanced disease of both organs.

Mechanism and novel therapeutic approaches to wasting in chronic disease.

PubMed

Ebner, Nicole; Springer, Jochen; Kalantar-Zadeh, Kamyar; Lainscak, Mitja; Doehner, Wolfram; Anker, Stefan D; von Haehling, Stephan

2013-07-01

Cachexia is a multifactorial syndrome defined by continuous loss of skeletal muscle mass - with or without loss of fat mass - which cannot be fully reversed by conventional nutritional support and which may lead to progressive functional impairment and increased death risk. Its pathophysiology is characterized by negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. Muscle wasting is encountered in virtually all chronic disease states in particular during advanced stages of the respective illness. Several pre-clinical and clinical studies are ongoing to ameliorate this clinical problem. The mechanisms of muscle wasting and cachexia in chronic diseases such as cancer, chronic heart failure, chronic obstructive pulmonary disease and chronic kidney disease are described. We discuss therapeutic targets and such potential modulators as appetite stimulants, selective androgen receptor modulators, amino acids and naturally occurring peptide hormones. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Chinese version of the Pediatric Quality of Life Inventory™ (PedsQL™) Family Impact Module: cross-cultural adaptation and psychometric evaluation.

PubMed

Chen, Ruoqing; Hao, Yuantao; Feng, Lifen; Zhang, Yingfen; Huang, Zhuoyan

2011-03-23

A pediatric chronic health condition not only influences a child's life, but also has impacts on parent health-related quality of life (HRQOL) and family functioning. To provide care and social support to these families, a psychometrically well-developed instrument for measuring these impacts is of great importance. The present study is aimed to evaluate the psychometric properties of the Chinese version of the PedsQL™ Family Impact Module. The cross-cultural adaptation of the PedsQL™ Family Impact Module was performed following the PedsQL™ Measurement Model Translation Methodology. The Chinese version of the PedsQL™ Family Impact Module was administered to 136 parents of children with asthma and 264 parents of children with heart disease from four Triple A hospitals. The psychometric properties such as feasibility, internal consistency reliability, item-subscale correlations and construct validity were evaluated. The percentage of missing item responses was less than 0.1% for both asthma and heart disease sample groups. The Chinese version of the PedsQL™ Family Impact Module showed ceiling effects but had acceptable reliability (Cronbach's Alpha Coefficients were higher than 0.7 in all the subscales except "Daily Activities" in the asthma sample group). There were higher correlation coefficients between items and their hypothesized subscales than those with other subscales. The asthma sample group reported higher parent HRQOL and family functioning than the heart disease sample group. In the heart disease sample group, parents of outpatients reported higher parent HRQOL and family functioning than parents of inpatients. Confirmatory factor analysis showed that the instrument had marginally acceptable construct validity with some Goodness-of-Fit indices not reaching the standard indicating acceptable model fit. The Chinese version of the PedsQL™ Family Impact Module has adequate psychometric properties and could be used to assess the impacts of pediatric asthma or pediatric heart disease on parent HRQOL and family functioning in China. This instrument should be field tested on parents of children with other chronic medical conditions in other areas. Construct validity tested by confirmatory factor analysis and test-retest reliability should be further assessed.

Using a whole-body 31P birdcage transmit coil and 16-element receive array for human cardiac metabolic imaging at 7T

PubMed Central

Dragonu, Iulius; Almujayyaz, Salam; Batzakis, Alex; Young, Liam A. J.; Purvis, Lucian A. B.; Clarke, William T.; Wichmann, Tobias; Lanz, Titus; Neubauer, Stefan; Robson, Matthew D.; Klomp, Dennis W. J.; Rodgers, Christopher T.

2017-01-01

Purpose Cardiac phosphorus magnetic resonance spectroscopy (31P-MRS) provides unique insight into the mechanisms of heart failure. Yet, clinical applications have been hindered by the restricted sensitivity of the surface radiofrequency-coils normally used. These permit the analysis of spectra only from the interventricular septum, or large volumes of myocardium, which may not be meaningful in focal disease. Löring et al. recently presented a prototype whole-body (52 cm diameter) transmit/receive birdcage coil for 31P at 7T. We now present a new, easily-removable, whole-body 31P transmit radiofrequency-coil built into a patient-bed extension combined with a 16-element receive array for cardiac 31P-MRS. Materials and methods A fully-removable (55 cm diameter) birdcage transmit coil was combined with a 16-element receive array on a Magnetom 7T scanner (Siemens, Germany). Electro-magnetic field simulations and phantom tests of the setup were performed. In vivo maps of B1+, metabolite signals, and saturation-band efficiency were acquired across the torsos of eight volunteers. Results The combined (volume-transmit, local receive array) setup increased signal-to-noise ratio 2.6-fold 10 cm below the array (depth of the interventricular septum) compared to using the birdcage coil in transceiver mode. The simulated coefficient of variation for B1+ of the whole-body coil across the heart was 46.7% (surface coil 129.0%); and the in vivo measured value was 38.4%. Metabolite images of 2,3-diphosphoglycerate clearly resolved the ventricular blood pools, and muscle tissue was visible in phosphocreatine (PCr) maps. Amplitude-modulated saturation bands achieved 71±4% suppression of phosphocreatine PCr in chest-wall muscles. Subjects reported they were comfortable. Conclusion This easy-to-assemble, volume-transmit, local receive array coil combination significantly improves the homogeneity and field-of-view for metabolic imaging of the human heart at 7T. PMID:29073228

FGF2 modulates cardiac remodeling in an isoform- and sex-specific manner

PubMed Central

Nusayr, Eyad; Sadideen, Doraid Tarek; Doetschman, Tom

2013-01-01

Pathological cardiac hypertrophy and cardiac fibrosis are remodeling events that result in mechanical stiffness and pathophysiological changes in the myocardium. Both humans and animal models display a sexual dimorphism where females are more protected from pathological remodeling. Fibroblast growth factor 2 (FGF2) mediates cardiac hypertrophy, cardiac fibrosis, and protection against cardiac injury, and is made in high molecular weight and low molecular weight isoforms (Hi FGF2 and Lo FGF2, respectively). Although some light has been shed on isoform-specific functions in cardiac pathophysiology, their roles in pathologic cardiac remodeling have yet to be determined. We tested the hypothesis that Lo FGF2 and Hi FGF2 modulate pathological cardiac remodeling in an isoform-specific manner. Young adult male and female mice between 8 and 12 weeks of age of mixed background that were deficient in either Hi FGF2 or Lo FGF2 (Hi KO or Lo KO, respectively) were subjected to daily injections of isoproterenol (Iso) for 4 days after which their hearts were compared to wild-type cohorts. Post-Iso treatment, female Lo KO hearts do not exhibit significant differences in their hypertrophic and fibrotic response, whereas female Hi KO hearts present with a blunted hypertrophic response. In male animals, Lo KO hearts present with an exacerbated fibrotic response and increased α-smooth muscle actin protein expression, whereas Hi KO hearts present with a blunted fibrotic response and increased atrial natriuretic factor protein expression Thus, in female hearts Hi FGF2 mediates cardiac hypertrophy, whereas in male hearts Lo FGF2 and Hi FGF2 display an antithetical role in cardiac fibrosis where Lo FGF2 is protective while Hi FGF2 is damaging. In conclusion, cardiac remodeling following catecholamine overactivation is modulated by FGF2 in isoform- and sex-specific manners. PMID:24244869

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits.

PubMed

Li, Yun-Wei; Li, Yan-Ming; Hon, Yan; Wan, Qi-Lin; He, Rui-Li; Wang, Zhi-Zhong; Zhao, Cui-Hua

2017-03-01

Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N 5 -(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.

AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits

PubMed Central

Li, Yun-Wei; Hon, Yan; Wan, Qi-Lin; He, Rui-Li; Wang, Zhi-Zhong; Zhao, Cui-Hua

2017-01-01

Background and Objectives Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats. Materials and Methods HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts. Results Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N5-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS). Conclusion Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC. PMID:28382073

Live dynamic analysis of mouse embryonic cardiogenesis with functional optical coherence tomography

NASA Astrophysics Data System (ADS)

Lopez, Andrew L.; Wang, Shang; Larina, Irina V.

2018-02-01

Hemodynamic load, contractile forces, and tissue elasticity are regulators of cardiac development and contribute to the mechanical homeostasis of the developing vertebrate heart. Congenital heart disease (CHD) is a prevalent condition in the United States that affects 8 in 1000 live births[1], and has been linked to disrupted cardiac biomechanics[2-4]. Therefore, it is important to understand how these forces integrate and regulate vertebrate cardiac development to inform clinical strategies to treat CHD early on by reintroducing proper mechanical load or modulating downstream factors that rely on mechanical signalling. Toward investigation of biomechanical regulation of mammalian cardiovascular dynamics and development, our methodology combines live mouse embryo culture protocols, state-of-the-art structural and functional Optical Coherence Tomography (OCT), second harmonic generation (SHG) microscopy, and computational analysis. Using these approaches, we assess functional aspects of the developing heart and characterize how they coincide with a determinant of tissue stiffness and main constituent of the extracellular matrix (ECM)—type I collagen. This work is bringing us closer to understanding how cardiac biomechanics change temporally and spatially during normal development, and how it regulates ECM to maintain mechanical homeostasis for proper function.

Genetic modulation of plasma NPY stress response is suppressed in substance abuse: association with clinical outcomes.

PubMed

Xu, Ke; Hong, Kwangik Adam; Zhou, Zhifeng; Hauger, Richard L; Goldman, David; Sinha, Rajita

2012-04-01

Neuropeptide Y (NPY) is involved in stress regulation. Genetic variations predict plasma NPY and neural correlates of emotion and stress. We examined whether the functional NPY haplotype modulates stress-induced NPY and anxiety responses, and if plasma NPY stress responses are associated with substance dependence outcomes. Thirty-seven treatment-engaged, abstinent substance dependent (SD) patients and 28 healthy controls (HCs) characterized on NPY diplotypes (HH: high expression; HLLL: intermediate/low expression) were exposed to stress, alcohol/drug cues and neutral relaxing cues, using individualized guided imagery, in a 3-session laboratory experiment. Plasma NPY, heart rate and anxiety were assessed. Patients were prospectively followed for 90-days post-treatment to assess relapse outcomes. HH individuals showed significantly lower stress-induced NPY with greater heart rate and anxiety ratings, while the HLLL group showed the reverse pattern of NPY, anxiety and heart rate responses. This differential genetic modulation of NPY stress response was suppressed in the SD group, who showed no stress-related increases in NPY and higher heart rate and greater anxiety, regardless of diplotype. Lower NPY predicted subsequent higher number of days and greater amounts of post-treatment drug use. These preliminary findings are the first to document chronic drug abuse influences on NPY diplotype expression where NPY diplotype modulation of stress-related plasma NPY, heart rate and anxiety responses was absent in the substance abuse sample. The finding that lower stress-related NPY is predictive of greater relapse severity provides support for therapeutic development of neuropeptide Y targets in the treatment of substance use disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

SU-E-T-62: Cardiac Toxicity in Dynamic Conformal Arc Therapy, Intensity-Modulated Radiation Therapy and Volumetric Modulated Arc Therapy of Lung Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ming, X; Zhang, Y; Yale University, New Haven, CT, US

2014-06-01

Purpose: The cardiac toxicity for lung cancer patients, each treated with dynamic conformal arc therapy (DAT), intensity-modulated radiation therapy (IMRT), or volumetric modulated arc therapy (VMAT) is investigated. Methods: 120 lung patients were selected for this study: 25 treated with DAT, 50 with IMRT and 45 with VMAT. For comparison, all plans were generated in the same treatment planning system, normalized such that the 100% isodose lines encompassed 95% of planning target volume. The plan quality was evaluated in terms of homogeneity index (HI) and 95% conformity index (%95 CI) for target dose coverage and mean dose, maximum dose, V{submore » 30} Gy as well as V{sub 5} Gy for cardiac toxicity analysis. Results: When all the plans were analyzed, the VMAT plans offered the best target coverage with 95% CI = 0.992 and HI = 1.23. The DAT plans provided the best heart sparing with mean heart dose = 2.3Gy and maximum dose = 11.6Gy, as compared to 5.7 Gy and 31.1 Gy by IMRT as well as 4.6 Gy and 30.9 Gy by VMAT. The mean V30Gy and V5Gy of the heart in the DAT plans were up to 11.7% lower in comparison to the IMRT and VMAT plans. When the tumor volume was considered, the VMAT plans spared up to 70.9% more doses to the heart when the equivalent diameter of the tumor was larger than 4cm. Yet the maximum dose to the heart was reduced the most in the DAT plans with up to 139.8% less than that of the other two plans. Conclusion: Overall, the VMAT plans achieved the best target coverage among the three treatment modalities, and would spare the heart the most for the larger tumors. The DAT plans appeared advantageous in delivering the least maximum dose to the heart as compared to the IMRT and VMAT plans.« less

Algorithm for the classification of multi-modulating signals on the electrocardiogram.

PubMed

Mita, Mitsuo

2007-03-01

This article discusses the algorithm to measure electrocardiogram (ECG) and respiration simultaneously and to have the diagnostic potentiality for sleep apnoea from ECG recordings. The algorithm is composed by the combination with the three particular scale transform of a(j)(t), u(j)(t), o(j)(a(j)) and the statistical Fourier transform (SFT). Time and magnitude scale transforms of a(j)(t), u(j)(t) change the source into the periodic signal and tau(j) = o(j)(a(j)) confines its harmonics into a few instantaneous components at tau(j) being a common instant on two scales between t and tau(j). As a result, the multi-modulating source is decomposed by the SFT and is reconstructed into ECG, respiration and the other signals by inverse transform. The algorithm is expected to get the partial ventilation and the heart rate variability from scale transforms among a(j)(t), a(j+1)(t) and u(j+1)(t) joining with each modulation. The algorithm has a high potentiality of the clinical checkup for the diagnosis of sleep apnoea from ECG recordings.

Modulation of RAAS-natriuretic peptides in the treatment of HF: Old guys and newcomers.

PubMed

Mollace, Vincenzo; Gliozzi, Micaela; Capuano, Annalisa; Rossi, Francesco

2017-01-01

The use of renin-angiotensin-aldosterone system (RAAS) inhibitors in the treatment of chronic heart failure (HF) and arterial hypertension is recommended by the European Society of Cardiology Guidelines on the basis of consolidated evidence supporting their efficacy in the development of such a disease. However, the high incidence of re-hospitalization and mortality in patients undergoing chronic HF, leads to the need for the development of novel RAAS inhibitors possessing a better pharmacokinetic/pharmacodynamics profile in approaching hemodynamic imbalance and myocardial dysfunction associated with the development of chronic HF. Here we summarize some of the recent advances in the area of RAAS-modulators, including novel renin inhibitors, mineralcorticoid receptor antagonists and novel AT1 and AT2-receptor modulators. In addition, the pharmacology of a new class of compounds which display both AT1-receptor blocking properties combined with inhibition of neprilysin, the vasopeptidase enzyme degradating natriuretic peptide (ARNi), will be reviewed, alongside with their impact in the pathophysiology of chronic HF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Playing with Cardiac “Redox Switches”: The “HNO Way” to Modulate Cardiac Function

PubMed Central

Tocchetti, Carlo G.; Stanley, Brian A.; Murray, Christopher I.; Sivakumaran, Vidhya; Donzelli, Sonia; Mancardi, Daniele; Pagliaro, Pasquale; Gao, Wei Dong; van Eyk, Jennifer; Kass, David A.; Wink, David A.

2011-01-01

Abstract The nitric oxide (NO•) sibling, nitroxyl or nitrosyl hydride (HNO), is emerging as a molecule whose pharmacological properties include providing functional support to failing hearts. HNO also preconditions myocardial tissue, protecting it against ischemia-reperfusion injury while exerting vascular antiproliferative actions. In this review, HNO's peculiar cardiovascular assets are discussed in light of its unique chemistry that distinguish HNO from NO• as well as from reactive oxygen and nitrogen species such as the hydroxyl radical and peroxynitrite. Included here is a discussion of the possible routes of HNO formation in the myocardium and its chemical targets in the heart. HNO has been shown to have positive inotropic/lusitropic effects under normal and congestive heart failure conditions in animal models. The mechanistic intricacies of the beneficial cardiac effects of HNO are examined in cellular models. In contrast to β-receptor/cyclic adenosine monophosphate/protein kinase A-dependent enhancers of myocardial performance, HNO uses its “thiophylic” nature as a vehicle to interact with redox switches such as cysteines, which are located in key components of the cardiac electromechanical machinery ruling myocardial function. Here, we will briefly review new features of HNO's cardiovascular effects that when combined with its positive inotropic/lusitropic action may render HNO donors an attractive addition to the current therapeutic armamentarium for treating patients with acutely decompensated congestive heart failure. Antioxid. Redox Signal. 14, 1687–1698. PMID:21235349

Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis.

PubMed

Huang, Zhan-Peng; Kataoka, Masaharu; Chen, Jinghai; Wu, Gengze; Ding, Jian; Nie, Mao; Lin, Zhiqiang; Liu, Jianming; Hu, Xiaoyun; Ma, Lixin; Zhou, Bin; Wakimoto, Hiroko; Zeng, Chunyu; Kyselovic, Jan; Deng, Zhong-Liang; Seidman, Christine E; Seidman, J G; Pu, William T; Wang, Da-Zhi

2015-11-02

Cardiomyopathy is a common human disorder that is characterized by contractile dysfunction and cardiac remodeling. Genetic mutations and altered expression of genes encoding many signaling molecules and contractile proteins are associated with cardiomyopathy; however, how cardiomyocytes sense pathophysiological stresses in order to then modulate cardiac remodeling remains poorly understood. Here, we have described a regulator in the heart that harmonizes the progression of cardiac hypertrophy and dilation. We determined that expression of the myocyte-enriched protein cardiac ISL1-interacting protein (CIP, also known as MLIP) is reduced in patients with dilated cardiomyopathy. As CIP is highly conserved between human and mouse, we evaluated the effects of CIP deficiency on cardiac remodeling in mice. Deletion of the CIP-encoding gene accelerated progress from hypertrophy to heart failure in several cardiomyopathy models. Conversely, transgenic and AAV-mediated CIP overexpression prevented pathologic remodeling and preserved cardiac function. CIP deficiency combined with lamin A/C deletion resulted in severe dilated cardiomyopathy and cardiac dysfunction in the absence of stress. Transcriptome analyses of CIP-deficient hearts revealed that the p53- and FOXO1-mediated gene networks related to homeostasis are disturbed upon pressure overload stress. Moreover, FOXO1 overexpression suppressed stress-induced cardiomyocyte hypertrophy in CIP-deficient cardiomyocytes. Our studies identify CIP as a key regulator of cardiomyopathy that has potential as a therapeutic target to attenuate heart failure progression.

Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis

PubMed Central

Huang, Zhan-Peng; Kataoka, Masaharu; Chen, Jinghai; Wu, Gengze; Ding, Jian; Nie, Mao; Lin, Zhiqiang; Liu, Jianming; Hu, Xiaoyun; Ma, Lixin; Zhou, Bin; Wakimoto, Hiroko; Zeng, Chunyu; Kyselovic, Jan; Deng, Zhong-Liang; Seidman, Christine E.; Seidman, J.G.; Pu, William T.; Wang, Da-Zhi

2015-01-01

Cardiomyopathy is a common human disorder that is characterized by contractile dysfunction and cardiac remodeling. Genetic mutations and altered expression of genes encoding many signaling molecules and contractile proteins are associated with cardiomyopathy; however, how cardiomyocytes sense pathophysiological stresses in order to then modulate cardiac remodeling remains poorly understood. Here, we have described a regulator in the heart that harmonizes the progression of cardiac hypertrophy and dilation. We determined that expression of the myocyte-enriched protein cardiac ISL1-interacting protein (CIP, also known as MLIP) is reduced in patients with dilated cardiomyopathy. As CIP is highly conserved between human and mouse, we evaluated the effects of CIP deficiency on cardiac remodeling in mice. Deletion of the CIP-encoding gene accelerated progress from hypertrophy to heart failure in several cardiomyopathy models. Conversely, transgenic and AAV-mediated CIP overexpression prevented pathologic remodeling and preserved cardiac function. CIP deficiency combined with lamin A/C deletion resulted in severe dilated cardiomyopathy and cardiac dysfunction in the absence of stress. Transcriptome analyses of CIP-deficient hearts revealed that the p53- and FOXO1-mediated gene networks related to homeostasis are disturbed upon pressure overload stress. Moreover, FOXO1 overexpression suppressed stress-induced cardiomyocyte hypertrophy in CIP-deficient cardiomyocytes. Our studies identify CIP as a key regulator of cardiomyopathy that has potential as a therapeutic target to attenuate heart failure progression. PMID:26436652

The effects of the modulation of NMDA receptors by homocysteine thiolactone and dizocilpine on cardiodynamics and oxidative stress in isolated rat heart.

PubMed

Srejovic, Ivan; Jakovljevic, Vladimir; Zivkovic, Vladimir; Barudzic, Nevena; Radovanovic, Ana; Stanojlovic, Olivera; Djuric, Dragan M

2015-03-01

In light of the limited data concerning the role of N-methyl-D-aspartate (NMDA) receptors in cardiac function, the aim of the present study was to determine the role of NMDA receptors in cardiac function, as well as the possible role played by the oxidative stress induced by the overstimulation of NMDA receptors in isolated rat heart. The hearts of male, Wistar albino rats (n = 24, 12 in each experimental group, BM 180-200 g) were retrogradely perfused at a constant perfusion pressure (70 cm H₂O₂), using the Langendorff technique, and cardiodynamic parameters were determined during the subsequent administration of DL-homocysteine thiolactone (DL-Hcy TLHC) alone, the combination of DL-Hcy TLHC and dizocilpine (MK-801), and MK-801 alone. In the second experimental group, the order of the administration of each of the substances was reversed. The oxidative stress biomarkers, including thiobarbituric acid reactive substances (TBARS), NO(2)(-), O(2)(-) and H₂O₂, were each determined spectrophotometrically. DL-Hcy TLHC and MK-801 depressed cardiac function. DL-Hcy TLHC decreased oxidative stress, a finding that contrasted with the results of the experiments in which MK-801 was administered first. The findings of this study were suggestive of the likely role played by NMDA receptors in the regulation of cardiac function and coronary circulation in isolated rat heart.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Tatsuya; Widder, Joachim; Dijk, Lisanne V. van

2016-11-01

Purpose: To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Methods and Materials: Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2.more » The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D{sub 2} − D{sub 98}, where D{sub 2} and D{sub 98} are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. Results: The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. Conclusions: In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters.« less

Hydroxytyrosol and its complex forms (secoiridoids) modulate aorta and heart proteome in healthy rats: Potential cardio-protective effects.

PubMed

Catalán, Úrsula; Rubió, Laura; López de Las Hazas, Maria-Carmen; Herrero, Pol; Nadal, Pedro; Canela, Núria; Pedret, Anna; Motilva, Maria-José; Solà, Rosa

2016-10-01

Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in both free and complex forms (secoiridoids; SEC). Proteomics of cardiovascular tissues such as aorta or heart represents a promising tool to uncover the mechanisms of action of phenolic compounds in healthy animals. Twelve female Wistar rats were separated into three groups: a standard diet and two diets supplemented in phenolic compounds (HT and SEC) adjusted to 5 mg/kg/day during 21 days. Proteomic analyses of aorta and heart tissues were performed by nano-LC and MS. Ingenuity Pathway Analysis was used to generate interaction networks. HT or SEC modulated aorta and heart proteome compared to the standard diet. The top-scored networks were related to Cardiovascular System. HT and SEC downregulated proteins related to proliferation and migration of endothelial cells and occlusion of blood vessels in aorta and proteins related to heart failure in heart tissue. SEC showed higher fold change values compared to HT, attributed to higher concentration of HT detected in heart tissue. Changes at proteomic level in cardiovascular tissues may partially account for the underlying mechanisms of VOO phenols cardiovascular protection being the SEC effects higher than free HT. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Model for the heart beat-to-beat time series during meditation

NASA Astrophysics Data System (ADS)

Capurro, A.; Diambra, L.; Malta, C. P.

2003-09-01

We present a model for the respiratory modulation of the heart beat-to-beat interval series. The model consists of a pacemaker, that simulates the membrane potential of the sinoatrial node, modulated by a periodic input signal plus correlated noise that simulates the respiratory input. The model was used to assess the waveshape of the respiratory signals needed to reproduce in the phase space the trajectory of experimental heart beat-to-beat interval data. The data sets were recorded during meditation practices of the Chi and Kundalini Yoga techniques. Our study indicates that in the first case the respiratory signal has the shape of a smoothed square wave, and in the second case it has the shape of a smoothed triangular wave.

Interrelationship between 3,5,3´-triiodothyronine and the circadian clock in the rodent heart.

PubMed

Peliciari-Garcia, Rodrigo Antonio; Prévide, Rafael Maso; Nunes, Maria Tereza; Young, Martin Elliot

2016-01-01

Triiodothyronine (T3) is an important modulator of cardiac metabolism and function, often through modulation of gene expression. The cardiomyocyte circadian clock is a transcriptionally based molecular mechanism capable of regulating cardiac processes, in part by modulating responsiveness of the heart to extra-cardiac stimuli/stresses in a time-of-day (TOD)-dependent manner. Although TOD-dependent oscillations in circulating levels of T3 (and its intermediates) have been established, oscillations in T3 sensitivity in the heart is unknown. To investigate the latter possibility, euthyroid male Wistar rats were treated with vehicle or T3 at distinct times of the day, after which induction of known T3 target genes were assessed in the heart (4-h later). The expression of mRNA was assessed by real-time quantitative polymerase chain reaction (qPCR). Here, we report greater T3 induction of transcript levels at the end of the dark phase. Surprisingly, use of cardiomyocyte-specific clock mutant (CCM) mice revealed that TOD-dependent oscillations in T3 sensitivity were independent of this cell autonomous mechanism. Investigation of genes encoding for proteins that affect T3 sensitivity revealed that Dio1, Dio2 and Thrb1 exhibited TOD-dependent variations in the heart, while Thra1 and Thra2 did not. Of these, Dio1 and Thrb1 were increased in the heart at the end of the dark phase. Interestingly, we observed that T3 acutely altered the expression of core clock components (e.g. Bmal1) in the rat heart. To investigate this further, rats were injected with a single dose of T3, after which expression of clock genes was interrogated at 3-h intervals over the subsequent 24-h period. These studies revealed robust effects of T3 on oscillations of both core clock components and clock-controlled genes. In summary, the current study exposed TOD-dependent sensitivity to T3 in the heart and its effects in the circadian clock genes expression.

Nuclear Engineering Computer Modules, Thermal-Hydraulics, TH-2: Liquid Metal Fast Breeder Reactors.

ERIC Educational Resources Information Center

Reihman, Thomas C.

This learning module is concerned with the temperature field, the heat transfer rates, and the coolant pressure drop in typical liquid metal fast breeder reactor (LMFBR) fuel assemblies. As in all of the modules of this series, emphasis is placed on developing the theory and demonstrating the use with a simplified model. The heart of the module is…

Nuclear Engineering Computer Modules, Thermal-Hydraulics, TH-1: Pressurized Water Reactors.

ERIC Educational Resources Information Center

Reihman, Thomas C.

This learning module is concerned with the temperature field, the heat transfer rates, and the coolant pressure drop in typical pressurized water reactor (PWR) fuel assemblies. As in all of the modules of this series, emphasis is placed on developing the theory and demonstrating its use with a simplified model. The heart of the module is the PWR…

SpeedyTime_3_Treadmill_2

NASA Image and Video Library

2017-07-31

When you live in a place where your heart doesn’t even have to work against the pull of gravity, you need help with exercise: the astronauts on the International Space Station have a suite of exercise equipment at their disposal, including a treadmill. In this “SpeedyTime” segment Expedition 52 flight engineer Jack Fischer runs through the workout they get on the Combined Operational Load Bearing External Resistance Treadmill (COLBERT) in the station’s Tranquility module. HD Link: https://archive.org/details/jsc2017m000676_SpeedyTime_3_Treadmill_2 _______________________________________ FOLLOW THE SPACE STATION! Twitter: https://twitter.com/Space_Station Facebook: https://www.facebook.com/ISS Instagram: https://instagram.com/iss/

Simultaneous measurement and modulation of multiple physiological parameters in the isolated heart using optical techniques

PubMed Central

Lee, Peter; Yan, Ping; Ewart, Paul; Kohl, Peter

2012-01-01

Whole-heart multi-parametric optical mapping has provided valuable insight into the interplay of electro-physiological parameters, and this technology will continue to thrive as dyes are improved and technical solutions for imaging become simpler and cheaper. Here, we show the advantage of using improved 2nd-generation voltage dyes, provide a simple solution to panoramic multi-parametric mapping, and illustrate the application of flash photolysis of caged compounds for studies in the whole heart. For proof of principle, we used the isolated rat whole-heart model. After characterising the blue and green isosbestic points of di-4-ANBDQBS and di-4-ANBDQPQ, respectively, two voltage and calcium mapping systems are described. With two newly custom-made multi-band optical filters, (1) di-4-ANBDQBS and fluo-4 and (2) di-4-ANBDQPQ and rhod-2 mapping are demonstrated. Furthermore, we demonstrate three-parameter mapping using di-4-ANBDQPQ, rhod-2 and NADH. Using off-the-shelf optics and the di-4-ANBDQPQ and rhod-2 combination, we demonstrate panoramic multi-parametric mapping, affording a 360° spatiotemporal record of activity. Finally, local optical perturbation of calcium dynamics in the whole heart is demonstrated using the caged compound, o-nitrophenyl ethylene glycol tetraacetic acid (NP-EGTA), with an ultraviolet light-emitting diode (LED). Calcium maps (heart loaded with di-4-ANBDQPQ and rhod-2) demonstrate successful NP-EGTA loading and local flash photolysis. All imaging systems were built using only a single camera. In conclusion, using novel 2nd-generation voltage dyes, we developed scalable techniques for multi-parametric optical mapping of the whole heart from one point of view and panoramically. In addition to these parameter imaging approaches, we show that it is possible to use caged compounds and ultraviolet LEDs to locally perturb electrophysiological parameters in the whole heart. PMID:22886365

Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

PubMed Central

Gomez, Juan F.; Cardona, Karen; Martinez, Laura; Saiz, Javier; Trenor, Beatriz

2014-01-01

Background Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure. Objective In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations. Methods The electrical activity of human transmural ventricular tissue (5 cm×5 cm) was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW) for reentry was evaluated following cross-field stimulation. Results No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components. Conclusion Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity. PMID:25054335

Sensor fusion using a hybrid median filter for artifact removal in intraoperative heart rate monitoring.

PubMed

Yang, Ping; Dumont, Guy A; Ansermino, J Mark

2009-04-01

Intraoperative heart rate is routinely measured independently from the ECG monitor, pulse oximeter, and the invasive blood pressure monitor if available. The presence of artifacts, in one or more of theses signals, especially sustained artifacts, represents a critical challenge for physiological monitoring. When temporal filters are used to suppress sustained artifacts, unwanted delays or signal distortion are often introduced. The aim of this study was to remove artifacts and derive accurate estimates for the heart rate signal by using measurement redundancy. Heart rate measurements from multiple sensors and previous estimates that fall in a short moving window were treated as samples of the same heart rate. A hybrid median filter was used to align these samples into one ordinal series and to select the median as the fused estimate. This method can successfully remove artifacts that are sustained for shorter than half the length of the filter window, or artifacts that are sustained for a longer duration but presented in no more than half of the sensors. The method was tested on both simulated and clinical cases. The performance of the hybrid median filter in the simulated study was compared with that of a two-step estimation process, comprising a threshold-controlled artifact-removal module and a Kalman filter. The estimation accuracy of the hybrid median filter is better than that of the Kalman filter in the presence of artifacts. The hybrid median filter combines the structural and temporal information from two or more sensors and generates a robust estimate of heart rate without requiring strict assumptions about the signal's characteristics. This method is intuitive, computationally simple, and the performance can be easily adjusted. These considerable benefits make this method highly suitable for clinical use.

[Combined gunshot injuries of the heart and lungs].

PubMed

Škorpil, J; Vodička, J; Kohut, M; Žídková, A; Havelka, J

2014-11-01

The authors present a case report of a 38-year-old man who suffered combined gunshot injuries of the heart and lungs from a small caliber gun. The gunshot resulted in combined injuries of a penetrating wound of the left lung, the right heart chambers and the right lung which were successfully managed despite a delay in surgery of several hours by pledget sutures of the heart wounds, wedge resection of the lingula and right lower lung lobectomy performed via a clamshell thoracotomy.

Angiotensin receptor-neprilysin inhibitors: clinical potential in heart failure and beyond

PubMed Central

Singh, Jagdeep SS; Lang, Chim C

2015-01-01

Heart failure remains a major concern across the globe as life expectancies and delivery of health care continue to improve. There has been a dearth of new developments in heart failure therapies in the last decade until last year, with the release of the results from the PARADIGM-HF Trial heralding the arrival of a promising new class of drug, ie, the angiotensin receptor-neprilysin inhibitor. In this review, we discuss the evolution of our incremental understanding of the neurohormonal mechanisms involved in the pathophysiology of heart failure, which has led to our success in modulating its various pathways. We start by examining the renin-angiotensin-aldosterone system, followed by the challenges of modulating the natriuretic peptide system. We then delve deeper into the pharmacology and mechanisms by which angiotensin receptor-neprilysin inhibitors achieve their significant cardiovascular benefits. Finally, we also consider the potential application of this new class of drug in other areas, such as heart failure with preserved ejection fraction, hypertension, patients with renal impairment, and following myocardial infarction. PMID:26082640

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor.

PubMed

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

2015-11-15

Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1-30 μg/kg) decreased resting heart rate; at high doses (150-300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03-0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias. Copyright © 2015 the American Physiological Society.

Leptin decreases heart rate associated with increased ventricular repolarization via its receptor

PubMed Central

Lin, Yen-Chang; Huang, Jianying; Hileman, Stan; Martin, Karen H.; Hull, Robert; Davis, Mary

2015-01-01

Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1–30 μg/kg) decreased resting heart rate; at high doses (150–300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03–0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias. PMID:26408544

Introducing a novel mechanism to control heart rate in the ancestral Pacific hagfish.

PubMed

Wilson, Christopher M; Roa, Jinae N; Cox, Georgina K; Tresguerres, Martin; Farrell, Anthony P

2016-10-15

Although neural modulation of heart rate is well established among chordate animals, the Pacific hagfish (Eptatretus stoutii) lacks any cardiac innervation, yet it can increase its heart rate from the steady, depressed heart rate seen in prolonged anoxia to almost double its normal normoxic heart rate, an almost fourfold overall change during the 1-h recovery from anoxia. The present study sought mechanistic explanations for these regulatory changes in heart rate. We provide evidence for a bicarbonate-activated, soluble adenylyl cyclase (sAC)-dependent mechanism to control heart rate, a mechanism never previously implicated in chordate cardiac control. © 2016. Published by The Company of Biologists Ltd.

Lipid modifying action of atorvastatin in comparison to combination of atorvastatin and nicotinic acid in patients with ischaemic heart disease.

PubMed

Santanu, Guha; Suhrita, Paul; Mookerjee, Soura; Tania, Kundu; Mita, Saha; Pramit, Ghosh; Sharmila, Guha; Miraj, Mandal; Debdutta, Majumder

2011-01-01

The current study is a prospective, randomized controlled study with two parallel treatment groups done to assess the tolerability and efficacy of a combination of atorvastatin (10 mg) and extended release nicotinic acid (1G) in comparison to atorvastatin (20 mg) alone in modulating the lipid profile in patients of Ischemic Heart Disease in our population. Patients were randomly allocated into two equal groups (n = 216) as per selection criteria. Group A received Atorvastatin 20 mg while Group B received combination of Atorvastatin -10 mg and extended release nicotinic acid (1G), both once daily at bed time, for a period of 24 weeks. Final end-of-study assessment and evaluation of tolerability and efficacy was done after 24 weeks. Comparison between the groups was performed with paired t-test. A p value < 0.05 was considered to be statistically significant. There was significant reduction in cholesterol, LDL & triglycerides in both the groups. Mean values of cholesterol and LDL were comparable in both groups where as there was increased reduction of triglycerides in Group B. Mean value of HDL cholesterol significantly increased only in group B thus the total cholesterol: HDL ratio was decreased more favorably. SGPT level was not significantly altered in either of the groups. In the Indian perspective, where HDL is low and the LDL values are not very high, a combination of low dose atorvastatin with nicotinic acid may influence the lipid profile more favorably and reduce the cholesterol/HDL ratio in comparison to atorvastatin alone and is also fairly well tolerated.

Motion-compensated detection of heart rate based on the time registration adaptive filter

NASA Astrophysics Data System (ADS)

Yang, Lei; Zhou, Jinsong; Jing, Juanjuan; Li, Yacan; Wei, Lidong; Feng, Lei; He, Xiaoying; Bu, Meixia; Fu, Xilu

2018-01-01

A non-contact heart rate detection method based on the dual-wavelength technique is proposed and demonstrated experimentally. The heart rate is obtained based on the PhotoPlethysmoGraphy (PPG). Each detection module uses the reflection detection probe which is composed of the LED and the photodiode. It is a well-known fact that the differences in the circuits of two detection modules result in different responses of two modules for motion artifacts. It will cause a time delay between the two signals. This poses a great challenge to compensate the motion artifacts during measurements. In order to solve this problem, we have firstly used the time registration and translated the signals to ensure that the two signals are consistent in time domain. Then the adaptive filter is used to compensate the motion artifacts. Moreover, the data obtained by using this non-contact detection system is compared with those of the conventional finger blood volume pulse (BVP) sensor by simultaneously measuring the heart rate of the subject. During the experiment, the left hand remains stationary and is detected by a conventional finger BVP sensor. Meanwhile, the moving palm of right hand is detected by the proposed system. The data obtained from the proposed non-contact system are consistent and comparable with that of the BVP sensor. This method can effectively suppress the interference caused by the two circuit differences and successfully compensate the motion artifacts. This technology can be used in medical and daily heart rate measurement.

The Tropomyosin Binding Region of Cardiac Troponin T Modulates Crossbridge Recruitment Dynamics in Rat Cardiac Muscle Fibers

PubMed Central

Gollapudi, Sampath K.; Gallon, Clare E.; Chandra, Murali

2013-01-01

The cardiac muscle comprises dynamically interacting components that use allosteric/cooperative mechanisms to yield unique heart-specific properties. An essential protein in this allosteric/cooperative mechanism is cardiac muscle troponin T (cTnT), the central region (CR) and the T2 region of which differ significantly from those of fast skeletal muscle troponin T (fsTnT). To understand the biological significance of such sequence heterogeneity, we replaced the T1 or T2 domain of rat cTnT (RcT1 or RcT2) with its counterpart from rat fsTnT (RfsT1or RfsT2) to generate RfsT1-RcT2 and RcT1-RfsT2 recombinant proteins. In addition to contractile function measurements, dynamic features of RfsT1-RcT2 and RcT1-RfsT2 reconstituted rat cardiac muscle fibers were captured by fitting the recruitment-distortion model to force response of small amplitude (0.5%) muscle length changes. RfsT1-RcT2 fibers showed a ~40% decrease in tension and ~44% decrease in ATPase activity, but RcT1-RfsT2 fibers were unaffected. The magnitude of length-mediated increase in crossbridge recruitment (E0) decreased by ~33% and the speed of crossbridge recruitment (b) increased by ~100% in RfsT1-RcT2 fibers. Our data suggest the following: (1) the CR of cTnT modulates crossbridge recruitment dynamics; (2) the N-terminal end region of cTnT has a synergistic effect on the ability of CR to modulate crossbridge recruitment dynamics; (3) the T2 region is important for tuning the Ca2+ regulation of cardiac thin filaments. The combined effects of CR-Tm interactions and the modulating effect of the N-terminal end of cTnT on CR-Tm interactions may lead to the emergence of a unique property that tunes contractile dynamics to heart rates. PMID:23357173

Impact of Diabetes Type 1 in Children on Autonomic Modulation at Rest and in Response to the Active Orthostatic Test

PubMed Central

Giacon, Thais Roque; Vanderlei, Franciele Marques; Christofaro, Diego Giulliano Destro; Vanderlei, Luiz Carlos Marques

2016-01-01

Introduction Cardiovascular autonomic neuropathy is one of the most common complications of diabetes mellitus type 1 (DM1), of which one of the first subclinical manifestations is changes in heart rate variability (HRV). Thus, analysis of HRV associated with the autonomic active orthostatic test is important in this population. Objectives To analyze the autonomic modulation responses induced by the implementation of the active orthostatic test, in children with DM1, and study the autonomic modulation by means of HRV indices. Method Data of 35 children were analyzed, of both sexes, aged between 7 and 15 years, who were divided into two groups: Diabetic (n = 16) and Control (n = 19). The following variables were collected initially: weight, height, body fat percentage, heart rate, blood pressure and casual blood glucose. Subsequently, for analysis of autonomic modulation, the beat-to-beat heart rate was captured by a heart rate monitor in the supine position for 30 minutes and after 10 minutes standing during performance of the active orthostatic test. HRV indices were calculated in the time and frequency domains. For data analysis, covariance analysis was used to compare groups and ANOVA for repeated measures to compare the effects of the active orthostatic test. These data were adjusted for age, sex, ethnicity, body fat percentage and casual blood glucose, with a 5% significance level. Results The results suggested that diabetic children at rest present a decrease in SDNN (50.4 vs. 75.2), rMSSD (38.7 vs 57.6) and LF [ms2] (693.6 vs 1874.6). During the active orthostatic test the children in both groups demonstrated a reduction in SDNN, RMSSD and LF [ms2] compared to the resting position, and this response was less pronounced in the diabetic group. Conclusion We conclude that regardless of age, sex, ethnicity, body fat percentage and casual blood glucose, performing the active orthostatic test promoted increased sympathetic modulation and reduced parasympathetic modulation in both groups, and this response was less pronounced in diabetic children, who presented reduced overall variability and parasympathetic modulation. PMID:27788152

Impact of Diabetes Type 1 in Children on Autonomic Modulation at Rest and in Response to the Active Orthostatic Test.

PubMed

Giacon, Thais Roque; Vanderlei, Franciele Marques; Christofaro, Diego Giulliano Destro; Vanderlei, Luiz Carlos Marques

2016-01-01

Cardiovascular autonomic neuropathy is one of the most common complications of diabetes mellitus type 1 (DM1), of which one of the first subclinical manifestations is changes in heart rate variability (HRV). Thus, analysis of HRV associated with the autonomic active orthostatic test is important in this population. To analyze the autonomic modulation responses induced by the implementation of the active orthostatic test, in children with DM1, and study the autonomic modulation by means of HRV indices. Data of 35 children were analyzed, of both sexes, aged between 7 and 15 years, who were divided into two groups: Diabetic (n = 16) and Control (n = 19). The following variables were collected initially: weight, height, body fat percentage, heart rate, blood pressure and casual blood glucose. Subsequently, for analysis of autonomic modulation, the beat-to-beat heart rate was captured by a heart rate monitor in the supine position for 30 minutes and after 10 minutes standing during performance of the active orthostatic test. HRV indices were calculated in the time and frequency domains. For data analysis, covariance analysis was used to compare groups and ANOVA for repeated measures to compare the effects of the active orthostatic test. These data were adjusted for age, sex, ethnicity, body fat percentage and casual blood glucose, with a 5% significance level. The results suggested that diabetic children at rest present a decrease in SDNN (50.4 vs. 75.2), rMSSD (38.7 vs 57.6) and LF [ms2] (693.6 vs 1874.6). During the active orthostatic test the children in both groups demonstrated a reduction in SDNN, RMSSD and LF [ms2] compared to the resting position, and this response was less pronounced in the diabetic group. We conclude that regardless of age, sex, ethnicity, body fat percentage and casual blood glucose, performing the active orthostatic test promoted increased sympathetic modulation and reduced parasympathetic modulation in both groups, and this response was less pronounced in diabetic children, who presented reduced overall variability and parasympathetic modulation.

BIOMEDICAL - MEDICAL (ECHOCARDIOGRAPH) - JSC

NASA Image and Video Library

1987-03-12

S87-28936 (March 1987) --- The Spacelab Life Sciences-1 (SLS-1) echocardiograph, installed in a science module rack, displays the image of a human heart. One of the objectives on SLS-1 is the investigation of the effects of microgravity on heart size and function.

[Design of Oxygen Saturation, Heart Rate, Respiration Rate Detection System Based on Smartphone of Android Operating System].

PubMed

Zhu, Mingshan; Zeng, Bixin

2015-03-01

In this paper, we designed an oxygen saturation, heart rate, respiration rate monitoring system based on smartphone of android operating system, physiological signal acquired by MSP430 microcontroller and transmitted by Bluetooth module.

Software development for the analysis of heartbeat sounds with LabVIEW in diagnosis of cardiovascular disease.

PubMed

Topal, Taner; Polat, Hüseyin; Güler, Inan

2008-10-01

In this paper, a time-frequency spectral analysis software (Heart Sound Analyzer) for the computer-aided analysis of cardiac sounds has been developed with LabVIEW. Software modules reveal important information for cardiovascular disorders, it can also assist to general physicians to come up with more accurate and reliable diagnosis at early stages. Heart sound analyzer (HSA) software can overcome the deficiency of expert doctors and help them in rural as well as urban clinics and hospitals. HSA has two main blocks: data acquisition and preprocessing, time-frequency spectral analyses. The heart sounds are first acquired using a modified stethoscope which has an electret microphone in it. Then, the signals are analysed using the time-frequency/scale spectral analysis techniques such as STFT, Wigner-Ville distribution and wavelet transforms. HSA modules have been tested with real heart sounds from 35 volunteers and proved to be quite efficient and robust while dealing with a large variety of pathological conditions.

The chromatin-binding protein Smyd1 restricts adult mammalian heart growth

PubMed Central

Kimball, Todd; Rasmussen, Tara L.; Rosa-Garrido, Manuel; Chen, Haodong; Tran, Tam; Miller, Mickey R.; Gray, Ricardo; Jiang, Shanxi; Ren, Shuxun; Wang, Yibin; Tucker, Haley O.; Vondriska, Thomas M.

2016-01-01

All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle-specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. PMID:27663768

The chromatin-binding protein Smyd1 restricts adult mammalian heart growth.

PubMed

Franklin, Sarah; Kimball, Todd; Rasmussen, Tara L; Rosa-Garrido, Manuel; Chen, Haodong; Tran, Tam; Miller, Mickey R; Gray, Ricardo; Jiang, Shanxi; Ren, Shuxun; Wang, Yibin; Tucker, Haley O; Vondriska, Thomas M

2016-11-01

All terminally differentiated organs face two challenges, maintaining their cellular identity and restricting organ size. The molecular mechanisms responsible for these decisions are of critical importance to organismal development, and perturbations in their normal balance can lead to disease. A hallmark of heart failure, a condition affecting millions of people worldwide, is hypertrophic growth of cardiomyocytes. The various forms of heart failure in human and animal models share conserved transcriptome remodeling events that lead to expression of genes normally silenced in the healthy adult heart. However, the chromatin remodeling events that maintain cell and organ size are incompletely understood; insights into these mechanisms could provide new targets for heart failure therapy. Using a quantitative proteomics approach to identify muscle-specific chromatin regulators in a mouse model of hypertrophy and heart failure, we identified upregulation of the histone methyltransferase Smyd1 during disease. Inducible loss-of-function studies in vivo demonstrate that Smyd1 is responsible for restricting growth in the adult heart, with its absence leading to cellular hypertrophy, organ remodeling, and fulminate heart failure. Molecular studies reveal Smyd1 to be a muscle-specific regulator of gene expression and indicate that Smyd1 modulates expression of gene isoforms whose expression is associated with cardiac pathology. Importantly, activation of Smyd1 can prevent pathological cell growth. These findings have basic implications for our understanding of cardiac pathologies and open new avenues to the treatment of cardiac hypertrophy and failure by modulating Smyd1. Copyright © 2016 the American Physiological Society.

The E3 ubiquitin ligase Nedd4/Nedd4L is directly regulated by microRNA 1

PubMed Central

Heidersbach, Amy; Kathiriya, Irfan S.; Garay, Bayardo I.; Ivey, Kathryn N.

2017-01-01

miR-1 is a small noncoding RNA molecule that modulates gene expression in heart and skeletal muscle. Loss of Drosophila miR-1 produces defects in somatic muscle and embryonic heart development, which have been partly attributed to miR-1 directly targeting Delta to decrease Notch signaling. Here, we show that overexpression of miR-1 in the fly wing can paradoxically increase Notch activity independently of its effects on Delta. Analyses of potential miR-1 targets revealed that miR-1 directly regulates the 3′UTR of the E3 ubiquitin ligase Nedd4. Analysis of embryonic and adult fly heart revealed that the Nedd4 protein regulates heart development in Drosophila. Larval fly hearts overexpressing miR-1 have profound defects in actin filament organization that are partially rescued by concurrent overexpression of Nedd4. These results indicate that miR-1 and Nedd4 act together in the formation and actin-dependent patterning of the fly heart. Importantly, we have found that the biochemical and genetic relationship between miR-1 and the mammalian ortholog Nedd4-like (Nedd4l) is evolutionarily conserved in the mammalian heart, potentially indicating a role for Nedd4L in mammalian postnatal maturation. Thus, miR-1-mediated regulation of Nedd4/Nedd4L expression may serve to broadly modulate the trafficking or degradation of Nedd4/Nedd4L substrates in the heart. PMID:28246214

The canonical way to make a heart: β-catenin and plakoglobin in heart development and remodeling.

PubMed

Piven, Oksana O; Winata, Cecilia L

2017-12-01

The main mediator of the canonical Wnt pathway, β-catenin, is a major effector of embryonic development, postnatal tissue homeostasis, and adult tissue regeneration. The requirement for β-catenin in cardiogenesis and embryogenesis has been well established. However, many questions regarding the molecular mechanisms by which β-catenin and canonical Wnt signaling regulate these developmental processes remain unanswered. An interesting question that emerged from our studies concerns how β-catenin signaling is modulated through interaction with other factors. Recent experimental data implicate new players in canonical Wnt signaling, particularly those which modulate β-catenin function in many its biological processes, including cardiogenesis. One of the interesting candidates is plakoglobin, a little-studied member of the catenin family which shares several mechanistic and functional features with its close relative, β-catenin. Here we have focused on the function of β-catenin in cardiogenesis. We also summarize findings on plakoglobin signaling function and discuss possible interplays between β-catenin and plakoglobin in the regulation of embryonic heart development. Impact statement Heart development, function, and remodeling are complex processes orchestrated by multiple signaling networks. This review examines our current knowledge of the role of canonical Wnt signaling in cardiogenesis and heart remodeling, focusing primarily on the mechanistic action of its effector β-catenin. We summarize the generally accepted understanding of the field based on experimental in vitro and in vivo data, and address unresolved questions in the field, specifically relating to the role of canonical Wnt signaling in heart maturation and regeneration. What are the modulators of canonical Wnt, and particularly what are the potential roles of plakoglobin, a close relative of β-catenin, in regulating Wnt signaling?Answers to these questions will enhance our understanding of the mechanism by which the canonical Wnt signaling regulates development of the heart and its regeneration after damage.

Mutual information and phase dependencies: measures of reduced nonlinear cardiorespiratory interactions after myocardial infarction.

PubMed

Hoyer, Dirk; Leder, Uwe; Hoyer, Heike; Pompe, Bernd; Sommer, Michael; Zwiener, Ulrich

2002-01-01

The heart rate variability (HRV) is related to several mechanisms of the complex autonomic functioning such as respiratory heart rate modulation and phase dependencies between heart beat cycles and breathing cycles. The underlying processes are basically nonlinear. In order to understand and quantitatively assess those physiological interactions an adequate coupling analysis is necessary. We hypothesized that nonlinear measures of HRV and cardiorespiratory interdependencies are superior to the standard HRV measures in classifying patients after acute myocardial infarction. We introduced mutual information measures which provide access to nonlinear interdependencies as counterpart to the classically linear correlation analysis. The nonlinear statistical autodependencies of HRV were quantified by auto mutual information, the respiratory heart rate modulation by cardiorespiratory cross mutual information, respectively. The phase interdependencies between heart beat cycles and breathing cycles were assessed basing on the histograms of the frequency ratios of the instantaneous heart beat and respiratory cycles. Furthermore, the relative duration of phase synchronized intervals was acquired. We investigated 39 patients after acute myocardial infarction versus 24 controls. The discrimination of these groups was improved by cardiorespiratory cross mutual information measures and phase interdependencies measures in comparison to the linear standard HRV measures. This result was statistically confirmed by means of logistic regression models of particular variable subsets and their receiver operating characteristics.

QRS peak detection for heart rate monitoring on Android smartphone

NASA Astrophysics Data System (ADS)

Pambudi Utomo, Trio; Nuryani, Nuryani; Darmanto

2017-11-01

In this study, Android smartphone is used for heart rate monitoring and displaying electrocardiogram (ECG) graph. Heart rate determination is based on QRS peak detection. Two methods are studied to detect the QRS complex peak; they are Peak Threshold and Peak Filter. The acquisition of ECG data is utilized by AD8232 module from Analog Devices, three electrodes, and Microcontroller Arduino UNO R3. To record the ECG data from a patient, three electrodes are attached to particular body’s surface of a patient. Patient’s heart activity which is recorded by AD8232 module is decoded by Arduino UNO R3 into analog data. Then, the analog data is converted into a voltage value (mV) and is processed to get the QRS complex peak. Heart rate value is calculated by Microcontroller Arduino UNO R3 uses the QRS complex peak. Voltage, heart rate, and the QRS complex peak are sent to Android smartphone by Bluetooth HC-05. ECG data is displayed as the graph by Android smartphone. To evaluate the performance of QRS complex peak detection method, three parameters are used; they are positive predictive, accuracy and sensitivity. Positive predictive, accuracy, and sensitivity of Peak Threshold method is 92.39%, 70.30%, 74.62% and for Peak Filter method are 98.38%, 82.47%, 83.61%, respectively.

Heparan Sulfate Biosynthesis Enzyme, Ext1, Contributes to Outflow Tract Development of Mouse Heart via Modulation of FGF Signaling.

PubMed

Zhang, Rui; Cao, Peijuan; Yang, Zhongzhou; Wang, Zhenzhen; Wu, Jiu-Lin; Chen, Yan; Pan, Yi

2015-01-01

Glycosaminoglycans are important regulators of multiple signaling pathways. As a major constituent of the heart extracellular matrix, glycosaminoglycans are implicated in cardiac morphogenesis through interactions with different signaling morphogens. Ext1 is a glycosyltransferase responsible for heparan sulfate synthesis. Here, we evaluate the function of Ext1 in heart development by analyzing Ext1 hypomorphic mutant and conditional knockout mice. Outflow tract alignment is sensitive to the dosage of Ext1. Deletion of Ext1 in the mesoderm induces a cardiac phenotype similar to that of a mutant with conditional deletion of UDP-glucose dehydrogenase, a key enzyme responsible for synthesis of all glycosaminoglycans. The outflow tract defect in conditional Ext1 knockout(Ext1f/f:Mesp1Cre) mice is attributable to the reduced contribution of second heart field and neural crest cells. Ext1 deletion leads to downregulation of FGF signaling in the pharyngeal mesoderm. Exogenous FGF8 ameliorates the defects in the outflow tract and pharyngeal explants. In addition, Ext1 expression in second heart field and neural crest cells is required for outflow tract remodeling. Our results collectively indicate that Ext1 is crucial for outflow tract formation in distinct progenitor cells, and heparan sulfate modulates FGF signaling during early heart development.

Awareness of heart attack symptoms among US adults in 2007, and changes in awareness from 2001 to 2007.

PubMed

Fang, Jing; Gillespie, Cathleen; Keenan, Nora L; Greenlund, Kurt J

2011-05-01

Timely access to emergency care, prompt receipt of advanced treatment and survival from heart attack is dependent on both the early recognition of heart attack symptoms, by both victims and bystanders, and by immediately calling the emergency services. The objective of this study is to measure the awareness of heart attack symptoms and the emergency response among US adults. We analyzed data from the Behavioral Risk Factor Surveillance System's module on heart attack and stroke, which was conducted in 17 states/territories in 2001 and 12 states/territories in 2007. The module included five questions related to heart attack symptoms, one decoy question and one question regarding the first action to take if someone is having a heart attack. Age-adjusted prevalence of awareness was estimated, and odds ratios were calculated. Differences between 2001 and 2007 were assessed for five states that used the module in both years. In 2007, among 76,864 adults, awareness of individual heart attack symptoms ranged from 49% (pain in jaw, neck or back) to 92% (chest pain). Although 97% of adults recognized at least one symptom, only 10.7% recognized all five symptoms, knew that 'sudden trouble seeing in one or both eyes' was not a symptom of heart attack and recognized the need to call the emergency services. This estimate varied significantly by age, sex, race/ethnicity and level of education. The estimate was significantly higher for women (12.2%) than men (7.7%), White (11.6%) than Black (5.7%) or Hispanic people (4.5%), those with a higher level of education (13.5%) than lower educational level (4.5%) and for those with coronary heart disease (16.2%) than without the disease (9.5%). Comparison of awareness between 2001 (the referent) and 2007, in five states, revealed that awareness of all symptoms and calling the emergency services, were 9.7 and 10.3% for 2001 and 2007, respectively (p < 0.01). Compared to 2001, the odds ratio of awareness in 2007 was 1.08 (95% CI: 0.99-1.19) after controlling for socioeconomic and clinical characteristics. Awareness of all heart attack symptoms among adults in 12 states was low and little improvement was observed between 2001 and 2007. Accordingly, both clinicians and public health officials should seek ways in order to increase public awareness of the symptoms of heart attack. Special efforts should be focused on men, Black and Hispanic people and those with only modest levels of education.

Effects of moderate and heavy endurance exercise on nocturnal HRV.

PubMed

Hynynen, E; Vesterinen, V; Rusko, H; Nummela, A

2010-06-01

This study examined the effects of endurance exercise on nocturnal autonomic modulation. Nocturnal R-R intervals were collected after a rest day, after a moderate endurance exercise and after a marathon run in ten healthy, physically active men. Heart rate variability (HRV) was analyzed as a continuous four-hour period starting 30 min after going to bed for sleep. In relation to average nocturnal heart rate after rest day, increases to 109+/-6% and 130+/-11% of baseline were found after moderate endurance exercise and marathon, respectively. Standard deviation of R-R intervals decreased to 90+/-9% and 64+/-10%, root-mean-square of differences between adjacent R-R intervals to 87+/-10% and 55+/-16%, and high frequency power to 77+/-19% and 34+/-19% of baseline after moderate endurance exercise and marathon, respectively. Also nocturnal low frequency power decreased to 56+/-26% of baseline after the marathon. Changes in nocturnal heart rate and HRV suggest prolonged dose-response effects on autonomic modulation after exercises, which may give useful information on the extent of exercise-induced nocturnal autonomic modulation and disturbance to the homeostasis.

Integromics network meta-analysis on cardiac aging offers robust multi-layer modular signatures and reveals micronome synergism.

PubMed

Dimitrakopoulou, Konstantina; Vrahatis, Aristidis G; Bezerianos, Anastasios

2015-03-04

The avalanche of integromics and panomics approaches shifted the deciphering of aging mechanisms from single molecular entities to communities of them. In this orientation, we explore the cardiac aging mechanisms - risk factor for multiple cardiovascular diseases - by capturing the micronome synergism and detecting longevity signatures in the form of communities (modules). For this, we developed a meta-analysis scheme that integrates transcriptome expression data from multiple cardiac-specific independent studies in mouse and human along with proteome and micronome interaction data in the form of multiple independent weighted networks. Modularization of each weighted network produced modules, which in turn were further analyzed so as to define consensus modules across datasets that change substantially during lifespan. Also, we established a metric that determines - from the modular perspective - the synergism of microRNA-microRNA interactions as defined by significantly functionally associated targets. The meta-analysis provided 40 consensus integromics modules across mouse datasets and revealed microRNA relations with substantial collective action during aging. Three modules were reproducible, based on homology, when mapped against human-derived modules. The respective homologs mainly represent NADH dehydrogenases, ATP synthases, cytochrome oxidases, Ras GTPases and ribosomal proteins. Among various observations, we corroborate to the involvement of miR-34a (included in consensus modules) as proposed recently; yet we report that has no synergistic effect. Moving forward, we determined its age-related neighborhood in which HCN3, a known heart pacemaker channel, was included. Also, miR-125a-5p/-351, miR-200c/-429, miR-106b/-17, miR-363/-92b, miR-181b/-181d, miR-19a/-19b, let-7d/-7f, miR-18a/-18b, miR-128/-27b and miR-106a/-291a-3p pairs exhibited significant synergy and their association to aging and/or cardiovascular diseases is supported in many cases by a disease database and previous studies. On the contrary, we suggest that miR-22 has not substantial impact on heart longevity as proposed recently. We revised several proteins and microRNAs recently implicated in cardiac aging and proposed for the first time modules as signatures. The integromics meta-analysis approach can serve as an efficient subvening signature tool for more-oriented better-designed experiments. It can also promote the combinational multi-target microRNA therapy of age-related cardiovascular diseases along the continuum from prevention to detection, diagnosis, treatment and outcome.

The Role of PDH Inhibition in the Development of Hypertrophy in the Hyperthyroid Rat Heart: A Combined MRI and Hyperpolarized MRS Study

PubMed Central

Atherton, Helen J.; Dodd, Michael S.; Heather, Lisa C.; Schroeder, Marie A.; Griffin, Julian L.; Radda, George K.; Clarke, Kieran; Tyler, Damian J.

2015-01-01

Background Hyperthyroidism increases heart rate, contractility and cardiac output, as well as metabolic rate. It is also accompanied by alterations in the regulation of cardiac substrate utilisation. Specifically, hyperthyroidism increases the ex vivo activity of pyruvate dehydrogenase kinase (PDK), thereby inhibiting glucose oxidation via pyruvate dehydrogenase (PDH). Cardiac hypertrophy is another effect of hyperthyroidism, with an increase in the abundance of mitochondria. Although the hypertrophy is initially beneficial, it can eventually lead to heart failure. The aim of this study was to use hyperpolarized magnetic resonance spectroscopy (MRS) to investigate the rate and regulation of in vivo pyruvate dehydrogenase (PDH) flux in the hyperthyroid heart, and to establish whether modulation of flux through PDH would alter cardiac hypertrophy. Methods & Results Hyperthyroidism was induced in 18 male Wistar rats with 7 daily intraperitoneal injections of freshly prepared triiodothyronine (T3; 0.2 mg/kg/day). In vivo PDH flux, assessed using hyperpolarized MRS, was reduced by 59% in hyperthyroid animals (0.0022 ± 0.0002 s−1 vs 0.0055 ± 0.0005 s−1, P = 0.0003) and this reduction was completely reversed by both acute and chronic delivery of the PDK inhibitor, dichloroacetic acid (DCA). Hyperpolarized [2-13C]pyruvate was also used to evaluate Krebs cycle metabolism and demonstrated a unique marker of anaplerosis, the level of which was significantly increased in the hyperthyroid heart. Cine MRI showed that chronic DCA treatment significantly reduced the hypertrophy observed in hyperthyroid animals (100 ± 20 mg vs 200 ± 30 mg; P = 0.04) despite no change to the increase observed in cardiac output. Conclusions This work has demonstrated that inhibition of glucose oxidation in the hyperthyroid heart in vivo is PDK mediated. Relieving this inhibition can increase the metabolic flexibility of the hyperthyroid heart and reduce the level of hypertrophy that develops whilst maintaining the increased cardiac output required to meet the higher systemic metabolic demand. PMID:21606392

The effects of heart rate control in chronic heart failure with reduced ejection fraction.

PubMed

Grande, Dario; Iacoviello, Massimo; Aspromonte, Nadia

2018-07-01

Elevated heart rate has been associated with worse prognosis both in the general population and in patients with heart failure. Heart rate is finely modulated by neurohormonal signals and it reflects the balance between the sympathetic and the parasympathetic limbs of the autonomic nervous system. For this reason, elevated heart rate in heart failure has been considered an epiphenomenon of the sympathetic hyperactivation during heart failure. However, experimental and clinical evidence suggests that high heart rate could have a direct pathogenetic role. Consequently, heart rate might act as a pathophysiological mediator of heart failure as well as a marker of adverse outcome. This hypothesis has been supported by the observation that the positive effect of beta-blockade could be linked to the degree of heart rate reduction. In addition, the selective heart rate control with ivabradine has recently been demonstrated to be beneficial in patients with heart failure and left ventricular systolic dysfunction. The objective of this review is to examine the pathophysiological implications of elevated heart rate in chronic heart failure and explore the mechanisms underlying the effects of pharmacological heart rate control.

Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart.

PubMed

Martins-Marques, Tania; Anjo, Sandra Isabel; Pereira, Paulo; Manadas, Bruno; Girão, Henrique

2015-11-01

The coordinated and synchronized cardiac muscle contraction relies on an efficient gap junction-mediated intercellular communication (GJIC) between cardiomyocytes, which involves the rapid anisotropic impulse propagation through connexin (Cx)-containing channels, namely of Cx43, the most abundant Cx in the heart. Expectedly, disturbing mechanisms that affect channel activity, localization and turnover of Cx43 have been implicated in several cardiomyopathies, such as myocardial ischemia. Besides gap junction-mediated intercellular communication, Cx43 has been associated with channel-independent functions, including modulation of cell adhesion, differentiation, proliferation and gene transcription. It has been suggested that the role played by Cx43 is dictated by the nature of the proteins that interact with Cx43. Therefore, the characterization of the Cx43-interacting network and its dynamics is vital to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication, but also to unveil novel and unanticipated biological functions of Cx43. In the present report, we applied a quantitative SWATH-MS approach to characterize the Cx43 interactome in rat hearts subjected to ischemia and ischemia-reperfusion. Our results demonstrate that, in the heart, Cx43 interacts with proteins related with various biological processes such as metabolism, signaling and trafficking. The interaction of Cx43 with proteins involved in gene transcription strengthens the emerging concept that Cx43 has a role in gene expression regulation. Importantly, our data shows that the interactome of Cx43 (Connexome) is differentially modulated in diseased hearts. Overall, the characterization of Cx43-interacting network may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions. Data are available via ProteomeXchange with identifier PXD002331. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Activation of PPAR-α in the early stage of heart failure maintained myocardial function and energetics in pressure-overload heart failure.

PubMed

Kaimoto, Satoshi; Hoshino, Atsushi; Ariyoshi, Makoto; Okawa, Yoshifumi; Tateishi, Shuhei; Ono, Kazunori; Uchihashi, Motoki; Fukai, Kuniyoshi; Iwai-Kanai, Eri; Matoba, Satoaki

2017-02-01

Failing heart loses its metabolic flexibility, relying increasingly on glucose as its preferential substrate and decreasing fatty acid oxidation (FAO). Peroxisome proliferator-activated receptor α (PPAR-α) is a key regulator of this substrate shift. However, its role during heart failure is complex and remains unclear. Recent studies reported that heart failure develops in the heart of myosin heavy chain-PPAR-α transgenic mice in a manner similar to that of diabetic cardiomyopathy, whereas cardiac dysfunction is enhanced in PPAR-α knockout mice in response to chronic pressure overload. We created a pressure-overload heart failure model in mice through transverse aortic constriction (TAC) and activated PPAR-α during heart failure using an inducible transgenic model. After 8 wk of TAC, left ventricular (LV) function had decreased with the reduction of PPAR-α expression in wild-type mice. We examined the effect of PPAR-α induction during heart failure using the Tet-Off system. Eight weeks after the TAC operation, LV construction was preserved significantly by PPAR-α induction with an increase in PPAR-α-targeted genes related to fatty acid metabolism. The increase of expression of fibrosis-related genes was significantly attenuated by PPAR-α induction. Metabolic rates measured by isolated heart perfusions showed a reduction in FAO and glucose oxidation in TAC hearts, but the rate of FAO preserved significantly owing to the induction of PPAR-α. Myocardial high-energy phosphates were significantly preserved by PPAR-α induction. These results suggest that PPAR-α activation during pressure-overloaded heart failure improved myocardial function and energetics. Thus activating PPAR-α and modulation of FAO could be a promising therapeutic strategy for heart failure. NEW & NOTEWORTHY The present study demonstrates the role of PPAR-α activation in the early stage of heart failure using an inducible transgenic mouse model. Induction of PPAR-α preserved heart function, and myocardial energetics. Activating PPAR-α and modulation of fatty acid oxidation could be a promising therapeutic strategy for heart failure. Copyright © 2017 the American Physiological Society.

[Feasibility of sonography in the diagnosis of congenital heart diseases in dogs].

PubMed

Schneider, M; Schneider, I; Neu, H

1998-05-01

In ultrasound examination of the heart it is useful to combine the following techniques: echocardiography (in 2D and M-mode) gives information about morphology and motion of the heart. By using Doppler echocardiography (black and white or preferably colour) it is possible to evaluate bloodstreams and with contrast echocardiography shunts in the heart can be demonstrated. In our study (1994-1996) the following congenital heart defects were the most common in dogs: subaortic stenosis (SAS, 41%), pulmonic stenosis (PS, 19%), patent ductus arteriosus (PDA, 11%) and the combination of subaortic stenosis with pulmonic stenosis (11%). Echocardiography allows the morphologic evaluation of the primary defect in detail, for example the differentiation between aortic valve stenosis and subaortic stenosis. However the exact identification of the patent ductus arterious and of the morphology in pulmonic stenosis can remain difficult, especially in patients showing dyspnoe. In heart sonography quantitative measurements are available to graduate the defects, but guidelines for these measurements are not yet defined. The demonstration of secondary and combined defects, which are important for therapy is easily possible with heart ultrasound examination. Secondary insufficiencies are often seen at the mitral valve because of primary subaortic stenosis or patent ductus arteriosus and at the tricuspid valve because of pulmonic stenosis. For differentiation of combined heart defects (SAS with PS; SAS with PDA; PS with atrium septum defect) heart ultrasound is extremely valuable.

Case Report: First Reported Combined Heart-Liver Transplant in a Patient With a Congenital Solitary Kidney.

PubMed

Hanna, R M; Kamgar, M; Hasnain, H; Khorsan, R; Nsair, A; Kaldas, F; Baas, A; Bunnapradist, S; Wilson, J M

2018-04-01

We report a case of successful combined heart liver transplant in a patient with a congenital solitary kidney. The patient had normal renal function before combined heart-liver transplantation and developed acute kidney injury requiring slow continuous dialysis and subsequent intermittent dialysis for almost 8 weeks post transplantation. Her renal function recovered and she remains off dialysis now 7 months post transplantation. She only currently has mild chronic renal insufficiency. We believe this is the first reported case of successful heart liver transplant in a patient with a congenital solitary kidney. Published by Elsevier Inc.

Transport stress induces weight loss and heart injury in chicks: disruption of ionic homeostasis via modulating ion transporting ATPases

PubMed Central

Xia, Jun; Li, Xue-Nan; Ge, Jing; Zhang, Cong; Li, Jin-Long

2017-01-01

Transportation is inevitable in the poultry industry, and it can induce stress to chicks in varying degrees, such as mild discomfort, sometimes even death. However, the research about the effects of transport stress on the weight loss and heart injury of chicks is lacking. To elucidate the underlying mechanism of transport stress-induced effects, chicks were transported for 2h, 4h and 8h. The creatinine kinase (CK) activities, the ionic contents, the ATPases activities and the transcription of the ATPase associated subunits in chick heart were detected. The results showed that transport stress increased the weight loss and the CK activity, disturbed the ionic (K+, Ca2+, Mg2+) homeostasis and inhibited the ATPase (Na+-K+-ATPase, Ca2+-ATPase, Mg2+-ATPase and Ca2+-Mg2+-ATPase) activities, increased the ATP content and downregulated the gene expression levels of the ATPase associated subunits in heart. In conclusion, transport stress disturbed the ionic homeostasis via modulating ion transporting ATPases and the transcriptions of the associated subunits, and ultimately induced weight loss and heart injury in chicks. PMID:28445983

Case studies on the effect of exercise and hot water submersion on intracardiac temperature and the performance of a pacemaker which varies pacing rate based on temperature.

PubMed

Fearnot, N E; Kitoh, O; Fujita, T; Okamura, H; Smith, H J; Calderini, M

1989-05-01

The effectiveness of using blood temperature change as an indicator to automatically vary heart rate physiologically was evaluated in 3 patients implanted with Model Sensor Kelvin 500 (Cook Pacemaker Corporation, Leechburg, PA, USA) pacemakers. Each patient performed two block-randomized treadmill exercise tests: one while programmed for temperature-based, rate-modulated pacing and the other while programmed without rate modulation. In 1 pacemaker patient and 4 volunteers, heart rates were recorded during exposure to a hot water bath. Blood temperature measured at 10 sec intervals and pacing rate measured at 1 min intervals were telemetered to a diagnostic programmer and data collector for storage and transfer to a computer. Observation comments and ECG-derived heart rates were manually recorded. The temperature-based pacemaker was shown to respond promptly not only to physical exertion but also to emotionally caused stress and submersion in a hot bath. These events cause increased heart rate in the normal heart. Using a suitable algorithm to process the measurement of blood temperature, it was possible to produce appropriate pacing rates in paced patients.

[Sacubitril/valsartan, a new and effective treatment for heart failure with reduced ejection fraction].

PubMed

Senni, Michele; Trimarco, Bruno; Emdin, Michele; De Biase, Luciano

2017-01-01

Despite significant therapeutic advances, patients with chronic heart failure and reduced ejection fraction (HFrEF) remain at high risk for heart failure progression and death. The PARADIGM-HF study, the largest outcome trial in HFrEF, has shown improved cardiovascular outcomes with sacubitril/valsartan (Entresto®, Novartis), previously known as LCZ696, compared with angiotensin-converting enzyme (ACE) inhibitor therapy, possibly leading us to a new era for heart failure treatment. Sacubitril/valsartan represents a first-in-class drug acting through inhibition of angiotensin receptor and neprilysin, thus modulating the renin-angiotensin-aldosterone system and vasoactive substances such as natriuretic peptides. This approach can be considered a "paradigm shift" from neurohumoral inhibition to neurohumoral modulation. Based on the PARADIGM-HF results, the European Society of Cardiology and the American Heart Association/American College of Cardiology guidelines proposed a substitution of ACE-inhibitor/angiotensin receptor blocker therapy rather than an "add-on" strategy in HFrEF. Sacubitril/valsartan can be considered a milestone in cardiovascular therapy, like aspirin, statins, beta-blockers. Of course there are many questions that arise spontaneously from this trial, three recognized experts can help us to answer them.

Kvβ1.1 (AKR6A8) senses pyridine nucleotide changes in the mouse heart and modulates cardiac electrical activity.

PubMed

Tur, Jared; Chapalamadugu, Kalyan C; Katnik, Christopher; Cuevas, Javier; Bhatnagar, Aruni; Tipparaju, Srinivas M

2017-03-01

The present study investigates the physiological role of Kvβ1 subunit for sensing pyridine nucleotide (NADH/NAD+) changes in the heart. We used Kvβ1.1 knockout (KO) or wild-type (WT) mice and established that Kvβ1.1 preferentially binds with Kv4.2 and senses the pyridine nucleotide changes in the heart. The cellular action potential duration (APD) obtained from WT cardiomyocytes showed longer APDs with lactate perfusion, which increases intracellular NADH levels, while the APDs remained unaltered in the Kvβ1.1 KO. Ex vivo monophasic action potentials showed a similar response, in which the APDs were prolonged in WT mouse hearts with lactate perfusion; however, the Kvβ1.1 KO mouse hearts did not show APD changes upon lactate perfusion. COS-7 cells coexpressing Kv4.2 and Kvβ1.1 were used for whole cell patch-clamp recordings to evaluate changes caused by NADH (lactate). These data reveal that Kvβ1.1 is required in the mediated inactivation of Kv4.2 currents, when NADH (lactate) levels are increased. In vivo, isoproterenol infusion led to increased NADH in the heart along with QTc prolongation in wild-type mice; regardless of the approach, our data show that Kvβ1.1 recognizes NADH changes and modulates Kv4.2 currents affecting AP and QTc durations. Overall, this study uses multiple levels of investigation, including the heterologous overexpression system, cardiomyocyte, ex vivo, and ECG, and clearly depicts that Kvβ1.1 is an obligatory sensor of NADH/NAD changes in vivo, with a physiological role in the heart. NEW & NOTEWORTHY Cardiac electrical activity is mediated by ion channels, and Kv4.2 plays a significant role, along with its binding partner, the Kvβ1.1 subunit. In the present study, we identify Kvβ1.1 as a sensor of pyridine nucleotide changes and as a modulator of Kv4.2 gating, action potential duration, and ECG in the mouse heart. Copyright © 2017 the American Physiological Society.

Dosimetric comparison to the heart and cardiac substructure in a large cohort of esophageal cancer patients treated with proton beam therapy or Intensity-modulated radiation therapy.

PubMed

Shiraishi, Yutaka; Xu, Cai; Yang, Jinzhong; Komaki, Ritsuko; Lin, Steven H

2017-10-01

To compare heart and cardiac substructure radiation exposure using intensity-modulated radiotherapy (IMRT) vs. proton beam therapy (PBT) for patients with mid- to distal esophageal cancer who received chemoradiation therapy. We identified 727 esophageal cancer patients who received IMRT (n=477) or PBT (n=250) from March 2004 to December 2015. All patients were treated to 50.4Gy with IMRT or to 50.4 cobalt Gray equivalents with PBT. IMRT and PBT dose-volume histograms (DVHs) of the whole heart, atria, ventricles, and four coronary arteries were compared. For PBT patients, passive scattering proton therapy (PSPT; n=237) and intensity-modulated proton therapy (IMPT; n=13) DVHs were compared. Compared with IMRT, PBT resulted in significantly lower mean heart dose (MHD) and heart V5, V10, V20, V30, and V40as well as lower radiation exposure to the four chambers and four coronary arteries. Compared with PSPT, IMPT resulted in significantly lower heart V20, V30, and V40 but not MHD or heart V5 or V10. IMPT also resulted in significantly lower radiation doses to the left atrium, right atrium, left main coronary artery, and left circumflex artery, but not the left ventricle, right ventricle, left anterior descending artery, or right coronary artery. Factors associated with lower MHD included PBT (P<0.001), smaller planning target volume (PTV; P<0.001), and gastroesophageal junction (GEJ) tumor (P<0.001). Among PBT patients, factors associated with lower MHD included IMPT (P=0.038), beam arrangement other than AP/PA (P<0.001), smaller PTV (P<0.001), and GEJ tumor (P<0.001). In patients with mid- to distal esophageal cancer, PBT results in significantly lower radiation exposure to the whole heart and cardiac substructures than IMRT. Long-term studies are necessary to determine how this cardiac sparing effect impacts the development of coronary artery disease and other cardiac complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Interrelationship between 3,5,3′-triiodothyronine and the circadian clock in the rodent heart

PubMed Central

Peliciari-Garcia, Rodrigo Antonio; Prévide, Rafael Maso; Nunes, Maria Tereza; Young, Martin Elliot

2017-01-01

Triiodothyronine (T3) is an important modulator of cardiac metabolism and function, often through modulation of gene expression. The cardiomyocyte circadian clock is a transcriptionally-based molecular mechanism capable of regulating cardiac processes, in part by modulating responsiveness of the heart to extra-cardiac stimuli/stresses in a time-of-day- (TOD) dependent manner. Although TOD-dependent oscillations in circulating levels of T3 (and its intermediates) have been established, whether oscillations in T3 sensitivity in the heart occur is unknown. To investigate the latter possibility, euthyroid male Wistar rats were treated with vehicle or T3 at distinct times of the day, after which induction of known T3 target genes were assessed in the heart (4-h later). The expression of mRNA was assessed by Real-Time qPCR. Here, we report greater T3 induction of transcript levels at the end of the dark phase. Surprisingly, use of cardiomyocyte-specific clock mutant (CCM) mice revealed that TOD-dependent oscillations in T3 sensitivity were independent of this cell autonomous mechanism. Investigation of genes encoding for proteins that affect T3 sensitivity revealed that Dio1, Dio2, and Thrb1 exhibited TOD-dependent variations in the heart, while Thra1 and Thra2 did not. Of these, Dio1 and Thrb1 were increased in the heart at the end of the dark phase. Interestingly, we observed that T3 acutely altered the expression of core clock components (e.g., Bmal1) in the rat heart. To investigate this further, rats were injected with a single dose of T3, after which expression of clock genes were interrogated at 3-h intervals over the subsequent 24h-period. These studies revealed robust effects of T3 on oscillations of both core clock components and clock-controlled genes. In summary, the current study exposed time-of-day-dependent rhythms in cardiac T3 sensitivity, and that T3 alters the circadian clock in the heart. PMID:27661292

Pulse transducer with artifact signal attenuator. [heart rate sensors

NASA Technical Reports Server (NTRS)

Cash, W. H., Jr.; Polhemus, J. T. (Inventor)

1980-01-01

An artifact signal attenuator for a pulse rate sensor is described. The circuit for attenuating background noise signals is connected with a pulse rate transducer which has a light source and a detector for light reflected from blood vessels of a living body. The heart signal provided consists of a modulated dc signal voltage indicative of pulse rate. The artifact signal resulting from light reflected from the skin of the body comprises both a constant dc signal voltage and a modulated dc signal voltage. The amplitude of the artifact signal is greater and the frequency less than that of the heart signal. The signal attenuator circuit includes an operational amplifier for canceling the artifact signal from the output signal of the transducer and has the capability of meeting packaging requirements for wrist-watch-size packages.

Spatially distributed fiber sensor with dual processed outputs

NASA Astrophysics Data System (ADS)

Xu, X.; Spillman, William B., Jr.; Claus, Richard O.; Meissner, K. E.; Chen, K.

2005-05-01

Given the rapid aging of the world"s population, improvements in technology for automation of patient care and documentation are badly needed. We have previously demonstrated a 'smart bed' that can non-intrusively monitor a patient in bed and determine a patient's respiration, heart rate and movement without intrusive or restrictive medical measurements. This is an application of spatially distributed integrating fiber optic sensors. The basic concept is that any patient movement that also moves an optical fiber within a specified area will produce a change in the optical signal. Two modal modulation approaches were considered, a statistical mode (STM) sensor and a high order mode excitation (HOME) sensor. The present design includes an STM sensor combined with a HOME sensor, using both modal modulation approaches. A special lens system allows only the high order modes of the optical fiber to be excited and coupled into the sensor. For handling output from the dual STM-HOME sensor, computer processing methods are discussed that offer comprehensive perturbation analysis for more reliable patient monitoring.

A 3D virtual reality simulator for training of minimally invasive surgery.

PubMed

Mi, Shao-Hua; Hou, Zeng-Gunag; Yang, Fan; Xie, Xiao-Liang; Bian, Gui-Bin

2014-01-01

For the last decade, remarkable progress has been made in the field of cardiovascular disease treatment. However, these complex medical procedures require a combination of rich experience and technical skills. In this paper, a 3D virtual reality simulator for core skills training in minimally invasive surgery is presented. The system can generate realistic 3D vascular models segmented from patient datasets, including a beating heart, and provide a real-time computation of force and force feedback module for surgical simulation. Instruments, such as a catheter or guide wire, are represented by a multi-body mass-spring model. In addition, a realistic user interface with multiple windows and real-time 3D views are developed. Moreover, the simulator is also provided with a human-machine interaction module that gives doctors the sense of touch during the surgery training, enables them to control the motion of a virtual catheter/guide wire inside a complex vascular model. Experimental results show that the simulator is suitable for minimally invasive surgery training.

Medications Used in the Treatment of Ischemic Heart Disease.

ERIC Educational Resources Information Center

Plummer, Nancy; Michael, Nancy, Ed.

This module on medications used in the treatment of ischemic heart disease is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first.…

Possible Mechanism for Modulating Cardiovascular System During Running in Humans

DTIC Science & Technology

2001-10-25

odulated by rhythmic muscle contractions during running. It cillates when step rate and heart rate are not synchronised but abilises when they are... synchronised . A maximum cardiac output n be achieved by synchronising step rate with heart rate at an timal phase delay. eywords – Cardiovascular model...trained athletes. Researches from [3][4][5] suggest at synchronization between the heart rate and the step rate uring running may favor an athlete with

Automated process control for plasma etching

NASA Astrophysics Data System (ADS)

McGeown, Margaret; Arshak, Khalil I.; Murphy, Eamonn

1992-06-01

This paper discusses the development and implementation of a rule-based system which assists in providing automated process control for plasma etching. The heart of the system is to establish a correspondence between a particular data pattern -- sensor or data signals -- and one or more modes of failure, i.e., a data-driven monitoring approach. The objective of this rule based system, PLETCHSY, is to create a program combining statistical process control (SPC) and fault diagnosis to help control a manufacturing process which varies over time. This can be achieved by building a process control system (PCS) with the following characteristics. A facility to monitor the performance of the process by obtaining and analyzing the data relating to the appropriate process variables. Process sensor/status signals are input into an SPC module. If trends are present, the SPC module outputs the last seven control points, a pattern which is represented by either regression or scoring. The pattern is passed to the rule-based module. When the rule-based system recognizes a pattern, it starts the diagnostic process using the pattern. If the process is considered to be going out of control, advice is provided about actions which should be taken to bring the process back into control.

Combat Surgery: Medical Decision Trees for Treatment of Naval Combat Casualties

DTIC Science & Technology

1991-02-01

inferior vena cava ? NO Is there a hole or tear of left atrium and/or pulmonary veins? NO l ** HEART INJURY ASSESSMENT MODULE T027 2...from holes in either superior or inferior vena cava ? YES NO See Pericardial Vena Cava Injury Module See Bleeding Into Pericardium Module T018...MODULE T018 1/1 Is blood coming from area of superior vena cava ? YES NO See Superior Vena Cava Wound

Glutaredoxin-2 is required to control oxidative phosphorylation in cardiac muscle by mediating deglutathionylation reactions.

PubMed

Mailloux, Ryan J; Xuan, Jian Ying; McBride, Skye; Maharsy, Wael; Thorn, Stephanie; Holterman, Chet E; Kennedy, Christopher R J; Rippstein, Peter; deKemp, Robert; da Silva, Jean; Nemer, Mona; Lou, Marjorie; Harper, Mary-Ellen

2014-05-23

Glutaredoxin-2 (Grx2) modulates the activity of several mitochondrial proteins in cardiac tissue by catalyzing deglutathionylation reactions. However, it remains uncertain whether Grx2 is required to control mitochondrial ATP output in heart. Here, we report that Grx2 plays a vital role modulating mitochondrial energetics and heart physiology by mediating the deglutathionylation of mitochondrial proteins. Deletion of Grx2 (Grx2(-/-)) decreased ATP production by complex I-linked substrates to half that in wild type (WT) mitochondria. Decreased respiration was associated with increased complex I glutathionylation diminishing its activity. Tissue glucose uptake was concomitantly increased. Mitochondrial ATP output and complex I activity could be recovered by restoring the redox environment to that favoring the deglutathionylated states of proteins. Grx2(-/-) hearts also developed left ventricular hypertrophy and fibrosis, and mice became hypertensive. Mitochondrial energetics from Grx2 heterozygotes (Grx2(+/-)) were also dysfunctional, and hearts were hypertrophic. Intriguingly, Grx2(+/-) mice were far less hypertensive than Grx2(-/-) mice. Thus, Grx2 plays a vital role in modulating mitochondrial metabolism in cardiac muscle, and Grx2 deficiency leads to pathology. As mitochondrial ATP production was restored by the addition of reductants, these findings may be relevant to novel redox-related therapies in cardiac disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Combining neuroendocrine inhibitors in heart failure: reflections on safety and efficacy.

PubMed

Jneid, Hani; Moukarbel, George V; Dawson, Bart; Hajjar, Roger J; Francis, Gary S

2007-12-01

Neuroendocrine activation in heart failure has become the major target of pharmacotherapy for this growing epidemic. Agents targeting the renin-angiotensin-aldosterone and sympathetic nervous systems have shown cardiovascular and survival benefits in clinical trials. Beta-blockers and angiotensin-converting enzyme (ACE) inhibitors remain the mainstream initial therapy. The benefits of aldosterone antagonists have been demonstrated in advanced heart failure (spironolactone) and after myocardial infarction complicated by left ventricular dysfunction and heart failure (eplerenone). Emerging clinical evidence demonstrated that angiotensin receptor blockers may be a reasonable alternative to ACE inhibitors in patients with heart failure (candesartan) and following myocardial infarction complicated by heart failure or left ventricular dysfunction (valsartan). Angiotensin receptor blockers (candesartan) also provided incremental benefits when added to ACE inhibitors in chronic heart failure. Thus, combining neuroendocrine inhibitors in heart failure appears both biologically plausible and evidence-based. However, this approach raised concerns about side effects, such as hypotension, renal insufficiency, hyperkalemia, and others. Close follow-up and implementation of evidence-based medicine (ie, using agents and doses proven beneficial in clinical trials) should therefore be undertaken when combining neuroendocrine inhibitors.

Comparison of the effect of valsartan and lisinopril on autonomic nervous system activity in chronic heart failure.

PubMed

De Tommasi, Elisabetta; Iacoviello, Massimo; Romito, Roberta; Ceconi, Claudio; Guida, Pietro; Massari, Francesco; Francolini, Gloria; Bertocchi, Federico; Ferrari, Roberto; Rizzon, Paolo; Pitzalis, Maria Vittoria

2003-11-01

In chronic heart failure (CHF), the derangement of autonomic nervous system activity has a deep impact on the progression of the disease. It has been demonstrated that modulation of the renin-angiotensin aldosterone system (RAAS) increases autonomic control of heart rate and reduces adrenergic activity. We sought to evaluate, in CHF, the different effects of an ACE inhibitor (lisinopril) and of an AT1 receptor antagonist (valsartan) on heart rate variability, baroreflex sensitivity and norepinephrine plasma levels. Ninety patients (61 +/- 10 years, 2.3 +/- 0.5, New York Heart Association class) with CHF and left ventricular ejection fraction <40% were randomly assigned in a double-blind fashion to receive lisinopril (uptitrated to 20 mg/d) or valsartan (uptitrated to 160 mg/d) therapy for 16 weeks. Heart rate variability (evaluated by measuring standard deviation of normal R-R intervals on 24-hour ECG recordings), spontaneous baroreflex sensitivity and aldosterone and norepinephrine plasma levels were assessed before and after drug therapy. There were no significant differences between valsartan and lisinopril in their effects on left ventricular function, arterial pressure, aldosterone plasma levels and autonomic control of heart rate. Both lisinopril and valsartan significantly reduced plasma norepinephrine levels, but the reduction induced by valsartan was significantly greater than that observed for lisinopril (27% vs 6%, P <.05). This study shows a comparable effect of ACE inhibition (lisinopril) and of AT1 receptor antagonism (valsartan) on cardiac vagal control of heart rate, whereas valsartan has shown a more effective modulation of sympathetic activity measured by plasma norepinephrine levels.

Acute Effects of Different Types of Resistance Training on Cardiac Autonomic Modulation in COPD.

PubMed

Vanderlei, Franciele M; Zandonadi, Fernando; de Lima, Fabiano Franciso; Silva, Bruna S A; Freire, Ana Paula C F; Ramos, Dionei; Ramos, Ercy Mara C

2018-05-22

An exercise modality that has been gaining significant importance in the rehabilitation of subjects with COPD is resistance training. When considering that patients with COPD present alterations in autonomic cardiac modulation caused by the disease itself, it is necessary to investigate the behavior of the autonomic nervous system in relation to this type of exercise. Thus, the objective of this study was to compare the acute effects of resistance training with elastic tubes, elastic bands, and conventional weightlifitng on the behavior of cardiac autonomic modulation in post-exercise recovery in subjects with COPD. Thirty-four subjects with COPD performed an single session of resistance training divided according to the therapeutic resource used: elastic tubes ( n = 10), elastic bands ( n = 11), and conventional bodybuilding ( n = 13). For analysis of cardiac autonomic modulation, the heart rate was obtained beat to beat at rest and immediately after the end of the session for 60 min in a seated position. Heart rate variability indices were obtained in the time and frequency domains. The 3 therapeutic resource types used in the single session of resistance training promoted changes in heart rate variability linear indices in the time and frequency domains; however, post-exercise recovery time was similar for all protocols performed. After single resistance training the elastic tubes group presented a minimum alteration in the post-exercise recovery of cardiac autonomic modulation in the subjects with COPD; however, at 5 min after exercising, the subjects with COPD had already recovered. Therefore, if the purpose of the training is to restore autonomic cardiac modulation, the use of elastic tubes is suggested, when considering their low cost and versatility. Copyright © 2018 by Daedalus Enterprises.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tobler, Matt; Watson, Gordon; Leavitt, Dennis

Radiotherapy plays a key role in the definitive or adjuvant management of patients with mesothelioma of the pleural surface. Many patients are referred for radiation with intact lung following biopsy or subtotal pleurectomy. Delivery of efficacious doses of radiation to the pleural lining while avoiding lung parenchyma toxicity has been a difficult technical challenge. Using opposed photon fields produce doses in lung that result in moderate-to-severe pulmonary toxicity in 100% of patients treated. Combined photon-electron beam treatment, at total doses of 4250 cGy to the pleural surface, results in two-thirds of the lung volume receiving over 2100 cGy. We havemore » developed a technique using intensity-modulated photon arc therapy (IMRT) that significantly improves the dose distribution to the pleural surface with concomitant decrease in dose to lung parenchyma compared to traditional techniques. IMRT treatment of the pleural lining consists of segments of photon arcs that can be intensity modulated with varying beam weights and multileaf positions to produce a more uniform distribution to the pleural surface, while at the same time reducing the overall dose to the lung itself. Computed tomography (CT) simulation is critical for precise identification of target volumes as well as critical normal structures (lung and heart). Rotational arc trajectories and individual leaf positions and weightings are then defined for each CT plane within the patient. This paper will describe the proposed rotational IMRT technique and, using simulated isodose distributions, show the improved potential for sparing of dose to the critical structures of the lung, heart, and spinal cord.« less

Impact of task-related changes in heart rate on estimation of hemodynamic response and model fit.

PubMed

Hillenbrand, Sarah F; Ivry, Richard B; Schlerf, John E

2016-05-15

The blood oxygen level dependent (BOLD) signal, as measured using functional magnetic resonance imaging (fMRI), is widely used as a proxy for changes in neural activity in the brain. Physiological variables such as heart rate (HR) and respiratory variation (RV) affect the BOLD signal in a way that may interfere with the estimation and detection of true task-related neural activity. This interference is of particular concern when these variables themselves show task-related modulations. We first establish that a simple movement task reliably induces a change in HR but not RV. In group data, the effect of HR on the BOLD response was larger and more widespread throughout the brain than were the effects of RV or phase regressors. The inclusion of HR regressors, but not RV or phase regressors, had a small but reliable effect on the estimated hemodynamic response function (HRF) in M1 and the cerebellum. We next asked whether the inclusion of a nested set of physiological regressors combining phase, RV, and HR significantly improved the model fit in individual participants' data sets. There was a significant improvement from HR correction in M1 for the greatest number of participants, followed by RV and phase correction. These improvements were more modest in the cerebellum. These results indicate that accounting for task-related modulation of physiological variables can improve the detection and estimation of true neural effects of interest. Copyright © 2016 Elsevier Inc. All rights reserved.

Transgenic expression of Bcl-2 modulates energy metabolism, prevents cytosolic acidification during ischemia, and reduces ischemia/reperfusion injury.

PubMed

Imahashi, Kenichi; Schneider, Michael D; Steenbergen, Charles; Murphy, Elizabeth

2004-10-01

The antiapoptotic protein Bcl-2 is targeted to the mitochondria, but it is uncertain whether Bcl-2 affects only myocyte survival after ischemia, or whether it also affects metabolic functions of mitochondria during ischemia. Hearts from mice overexpressing human Bcl-2 and from their wild-type littermates (WT) were subjected to 24 minutes of global ischemia followed by reperfusion. During ischemia, the decrease in pH(i) and the initial rate of decline in ATP were significantly reduced in Bcl-2 hearts compared with WT hearts (P<0.05). The reduced acidification during ischemia was dependent on the activity of mitochondrial F1F0-ATPase. In the presence of oligomycin (Oligo), an F1F0-ATPase inhibitor, the decrease in pH(i) was attenuated in WT hearts, but in Bcl-2 hearts, Oligo had no additional effect on pH(i) during ischemia. Likewise, addition of Oligo to WT hearts slowed the rate of decline in ATP during ischemia to a level similar to that observed in Bcl-2 hearts, but addition of Oligo had no significant effect on the rate of decline in ATP in Bcl-2 hearts during ischemia. These data are consistent with Bcl-2-mediated inhibition of consumption of glycolytic ATP. Furthermore, mitochondria from Bcl-2 hearts have a reduced rate of consumption of ATP on uncoupler addition. This could be accomplished by limiting ATP entry into the mitochondria through the voltage-dependent anion channel, and/or the adenine nucleotide transporter, or by direct inhibition of the F1F0-ATPase. Immunoprecipitation showed greater interaction between Bcl-2 and voltage-dependent anion channel during ischemia. These data indicate that Bcl-2 modulation of metabolism contributes to cardioprotection.

Disbalance of calcium regulation-related genes in broiler hearts induced by selenium deficiency.

PubMed

Zhang, Ziwei; Liu, Man; Guan, Zhenqiong; Yang, Jie; Liu, Zhonghua; Xu, Shiwen

2017-06-01

Dietary selenium (Se) deficiency may influence the calcium (Ca) homeostasis in broilers. Our objective was to investigate the effects of Se deficiency on Ca regulation-related genes in broiler hearts. In the present study, 1-day-old broilers were fed either a commercial diet (as control group) with 0.15 mg/kg Se or a Se-deficient diet (as L group) with 0.033 mg/kg Se for 35 days. We examined the mRNA expression levels of 15 Ca regulation-related genes (ITPR 1, ITPR 2, ITPR3, RyR2, RyR3, SERCA1s, SLC8A1, PMCA1, CACNA1S, TRPC1, TRPC3, stromal interacting molecule 1, ORAI1, calmodulin (CaLM) and calreticulin (CRT) in broiler hearts. Then, Kyoto Encyclopedia of Genes and Genomes analysis, protein-protein interactions (PPI) analysis and correlation analysis were performed to analyse the relationships between these genes. The results showed that the mRNA expression levels of ITPR 1, ITPR 2, RyR2, RyR3, SERCA1s, SLC8A1, PMCA1, CACNA1S, CaLM and CRT were generally decreased by Se deficiency, while mRNA expression levels of TRPC1, TRPC3, stromal interacting molecule 1, ORAI1 and ITPR3 were increased by Se deficiency. Kyoto Encyclopedia of Genes and Genomes and PPI analysis showed that these Ca regulation-related genes are involved in the Ca signalling pathway and a total of 15 PPIs with a combined score of >0.4 were obtained. In conclusion, the results demonstrated that Se deficiency might cause heart injury via modulating the Ca-related pathway genes, and then induce Ca 2+ overload in the heart of broilers.

The phylogeny and ontogeny of autonomic control of the heart and cardiorespiratory interactions in vertebrates.

PubMed

Taylor, Edwin W; Leite, Cleo A C; Sartori, Marina R; Wang, Tobias; Abe, Augusto S; Crossley, Dane A

2014-03-01

Heart rate in vertebrates is controlled by activity in the autonomic nervous system. In spontaneously active or experimentally prepared animals, inhibitory parasympathetic control is predominant and is responsible for instantaneous changes in heart rate, such as occur at the first air breath following a period of apnoea in discontinuous breathers like inactive reptiles or species that surface to air breathe after a period of submersion. Parasympathetic control, exerted via fast-conducting, myelinated efferent fibres in the vagus nerve, is also responsible for beat-to-beat changes in heart rate such as the high frequency components observed in spectral analysis of heart rate variability. These include respiratory modulation of the heartbeat that can generate cardiorespiratory synchrony in fish and respiratory sinus arrhythmia in mammals. Both may increase the effectiveness of respiratory gas exchange. Although the central interactions generating respiratory modulation of the heartbeat seem to be highly conserved through vertebrate phylogeny, they are different in kind and location, and in most species are as yet little understood. The heart in vertebrate embryos possesses both muscarinic cholinergic and β-adrenergic receptors very early in development. Adrenergic control by circulating catecholamines seems important throughout development. However, innervation of the cardiac receptors is delayed and first evidence of a functional cholinergic tonus on the heart, exerted via the vagus nerve, is often seen shortly before or immediately after hatching or birth, suggesting that it may be coordinated with the onset of central respiratory rhythmicity and subsequent breathing.

Early life environment and social determinants of cardiac health in children with congenital heart disease.

PubMed

Wong, Peter; Denburg, Avram; Dave, Malini; Levin, Leo; Morinis, Julia Orkin; Suleman, Shazeen; Wong, Jonathan; Ford-Jones, Elizabeth; Moore, Aideen M

2018-04-01

Congenital heart disease is a significant cause of infant mortality. Epidemiology and social context play a crucial role in conditioning disease burden and modulating outcomes, while diagnosis and treatment remain resource intensive. This review will address the role of social demographics, environmental exposure, epigenetics and nutrition in the aetiology of congenital heart disease. We then discuss the determinant effect of social factors on the provision and outcomes of care for congenital heart disease and implications for practice. It is our hope that enhanced knowledge of the intersection of social determinants of health and congenital heart disease will facilitate effective preventative strategies at the individual and population levels to optimize heart health outcomes across the life course.

Looking inside the heart: a see-through view of the vascular tree

PubMed Central

Nehrhoff, Imke; Ripoll, Jorge; Samaniego, Rafael; Desco, Manuel; Gómez-Gaviro, Maria Victoria

2017-01-01

The ability to acquire 3D images of the heart and its vasculature at cellular resolution facilitates a more detailed study of many heart diseases. Here, we describe a novel technique to image in 3D the heart vasculature by combining the CUBIC clearing protocol combined with in vivo administration of fluorescent-labeled lectin. The use of these techniques in combination with Selective Plane Illumination Microscopy (SPIM) made it possible to obtain high resolution 3D images of the cardiac vascular tree. This methodological approach may enhance the visualization of 3D images of the cardiac vasculature remodeling associated with coronary disease. PMID:28663930

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

PubMed Central

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-01-01

Within the framework of ‘Network Physiology’, we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain–heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain–heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems. PMID:27044991

Erbin is a negative modulator of cardiac hypertrophy

PubMed Central

Rachmin, Inbal; Tshori, Sagi; Smith, Yoav; Oppenheim, Amit; Marchetto, Sylvie; Kay, Gillian; Foo, Roger S.-Y.; Dagan, Noa; Golomb, Eliahu; Gilon, Dan; Borg, Jean-Paul; Razin, Ehud

2014-01-01

ErbB2 interacting protein (Erbin) is a widely expressed protein and participates in inhibition of several intracellular signaling pathways. Its mRNA has been found to be present in relatively high levels in the heart. However, its physiological role in the heart has not been explored. In the present work, we elucidated the role of Erbin in cardiac hypertrophy. Cardiac hypertrophy was induced in mice either by isoproterenol administration or by aortic constriction. The level of Erbin was significantly decreased in both models. Erbin−/− mice rapidly develop decompensated cardiac hypertrophy, and following severe pressure overload all Erbin−/− mice died from heart failure. Down-regulation of Erbin expression was also observed in biopsies derived from human failing hearts. It is known that Erbin inhibits Ras-mediated activation of the extracellular signal-regulated kinase (ERK) by binding to Soc-2 suppressor of clear homolog (Shoc2). Our data clearly show that ERK phosphorylation is enhanced in the heart tissues of Erbin−/− mice. Furthermore, we clearly demonstrate here that Erbin associates with Shoc2 in both whole hearts and in cardiomyocytes, and that in the absence of Erbin, Raf is phosphorylated and binds Shoc2, resulting in ERK phosphorylation. In conclusion, Erbin is an inhibitor of pathological cardiac hypertrophy, and this inhibition is mediated, at least in part, by modulating ERK signaling. PMID:24711380

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

NASA Astrophysics Data System (ADS)

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-05-01

Within the framework of `Network Physiology', we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain-heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain-heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems.

Use of New Imaging CARTO® Segmentation Module Software to Facilitate Ablation of Ventricular Arrhythmias.

PubMed

Tovia-Brodie, Oholi; Belhassen, Bernard; Glick, Aharon; Shmilovich, Haim; Aviram, Galit; Rosso, Raphael; Michowitz, Yoav

2017-02-01

A new imaging software (CARTO® Segmentation Module, Biosense Webster) allows preprocedural 3-D reconstruction of all heart chambers based on cardiac CT. We describe our initial experience with the new module during ablation of ventricular arrhythmias. Eighteen consecutive patients with idiopathic ventricular arrhythmias or ischemic ventricular tachycardia (VT) were studied. In the latter group, a combined endocardial and epicardial ablation was performed. Of the 14 patients with idiopathic arrhythmias, 12 were ablated in the outflow tract (OT), 1 in the midseptal left ventricle, and 1 at the left posterior fascicular area; acute successful ablation was achieved in 11 (78.6%) patients. The procedure was discontinued due to close proximity of the arrhythmia origin to the coronary arteries (CA) in 2 patients. Acute successful uncomplicated ablation was achieved in all 4 patients with ischemic VT. During ablation in the coronary cusps commissures, the CARTO® Segmentation Module accurately defined the cusps anatomy. The precise anatomic location provided by the module assisted in successfully ablating when information from activation mapping was not optimal, by ablating at the opposite side of the cusps. In addition, by demonstrating the precise location of the CA, it allowed safe ablation of arrhythmias that originated in close proximity to the CA both in the OT area and the epicardium, eliminating the need for repeat angiography. The CARTO® Segmentation Module is useful for accurate definition of the exact anatomic location of ventricular arrhythmias and for safely ablating them especially in close proximity to the CA. © 2016 Wiley Periodicals, Inc.

Device therapy in heart failure with reduced ejection fraction-cardiac resynchronization therapy and more.

PubMed

Duncker, D; Veltmann, C

2018-05-09

In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology. However, the vast majority of heart failure patients show a narrow QRS complex or a non-LBBB morphology. These patients are not candidates for CRT and alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) may be considered. BAT modulates vegetative dysregulation in heart failure. CCM improves contractility, functional capacity, and symptoms. Although a broad data set is available for BAT and CCM, mortality data are still lacking for both methods. This article provides an overview of the device-based therapeutic options for patients with HFrEF.

[Design of a Front-end Device of Heart Rate Variability Analysis System Based on Photoplethysmography].

PubMed

Shi, Lei; Sun, Peng; Pang, Yu; Luo, Zhiyong; Wang, Wei; Wang, Yanxiang

2016-02-01

Heart rate variability (HRV) is the difference between the successive changes in the heartbeat cycle, and it is produced in the autonomic nervous system modulation of the sinus node of the heart. The HRV is a valuable indicator in predicting the sudden cardiac death and arrhythmic events. Traditional analysis of HRV is based on a multielectrocardiogram (ECG), but the ECG signal acquisition is complex, so we have designed an HRV analysis system based on photoplethysmography (PPG). PPG signal is collected by a microcontroller from human's finger, and it is sent to the terminal via USB-Serial module. The terminal software not only collects the data and plot waveforms, but also stores the data for future HRV analysis. The system is small in size, low in power consumption, and easy for operation. It is suitable for daily care no matter whether it is used at home or in a hospital.

The impact of cardiac perception on emotion experience and cognitive performance under mental stress.

PubMed

Kindermann, Nicole K; Werner, Natalie S

2014-12-01

Mental stress evokes several physiological responses such as the acceleration of heart rate, increase of electrodermal activity and the release of adrenaline. Moreover, physiological stress responses interact with emotional and behavioral stress responses. In the present study we provide evidence that viscero-sensory feedback from the heart (cardiac perception) is an important factor modulating emotional and cognitive stress responses. In our study, we compared participants with high versus low cardiac perception using a computerized mental stress task, in which they had to respond to rapidly presented visual and acoustic stimuli. Additionally, we assessed physiological responses (heart rate, skin conductance). Participants high in cardiac perception reported more negative emotions and showed worse task performance under the stressor than participants low in cardiac perception. These results were not moderated by physiological responses. We conclude that cardiac perception modulates stress responses by intensifying negative emotions and by impairing cognitive performance.

Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC.

PubMed

Lile, Joshua A; Kelly, Thomas H; Hays, Lon R

2014-10-01

Our previous research suggested the involvement of γ-aminobutyric acid (GABA), in particular the GABAB receptor subtype, in the interoceptive effects of Δ(9)-tetrahydrocannabinol (Δ(9)-THC). The aim of the present study was to determine the potential involvement of the GABAA receptor subtype by assessing the separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ(9)-THC using pharmacologically selective drug-discrimination procedures. Ten cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received diazepam (5 and 10mg), Δ(9)-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Δ(9)-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug) and elevated heart rate. Diazepam alone impaired performance on psychomotor performance tasks and increased ratings on a limited number of self-report questionnaire items (e.g., Any Effect, Sedated), but did not substitute for the Δ(9)-THC discriminative stimulus or alter the Δ(9)-THC discrimination dose-response function. Similarly, diazepam had limited impact on the other behavioral effects of Δ(9)-THC. These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of Δ(9)-THC, and by extension cannabis, in humans. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Nuclear Engineering Computer Modules, Thermal-Hydraulics, TH-3: High Temperature Gas Cooled Reactor Thermal-Hydraulics.

ERIC Educational Resources Information Center

Reihman, Thomas C.

This learning module is concerned with the temperature field, the heat transfer rates, and the coolant pressure drop in typical high temperature gas-cooled reactor (HTGR) fuel assemblies. As in all of the modules of this series, emphasis is placed on developing the theory and demonstrating its use with a simplified model. The heart of the module…

Cardiovascular microRNAs: as modulators and diagnostic biomarkers of diabetic heart disease

PubMed Central

2014-01-01

Diabetic heart disease (DHD) is the leading cause of morbidity and mortality among the people with diabetes, with approximately 80% of the deaths in diabetics are due to cardiovascular complications. Importantly, heart disease in the diabetics develop at a much earlier stage, although remaining asymptomatic till the later stage of the disease, thereby restricting its early detection and active therapeutic management. Thus, a better understanding of the modulators involved in the pathophysiology of DHD is necessary for the early diagnosis and development of novel therapeutic implications for diabetes-associated cardiovascular complications. microRNAs (miRs) have recently been evolved as key players in the various cardiovascular events through the regulation of cardiac gene expression. Besides their credible involvement in controlling the cellular processes, they are also released in to the circulation in disease states where they serve as potential diagnostic biomarkers for cardiovascular disease. However, their potential role in DHD as modulators as well as diagnostic biomarkers is largely unexplored. In this review, we describe the putative mechanisms of the selected cardiovascular miRs in relation to cardiovascular diseases and discuss their possible involvement in the pathophysiology and early diagnosis of DHD. PMID:24528626

Early in vivo experience with the pediatric continuous-flow total artificial heart.

PubMed

Karimov, Jamshid H; Horvath, David J; Byram, Nicole; Sunagawa, Gengo; Kuban, Barry D; Gao, Shengqiang; Dessoffy, Raymond; Fukamachi, Kiyotaka

2018-03-30

Heart transplantation in infants and children is an accepted therapy for end-stage heart failure, but donor organ availability is low and always uncertain. Mechanical circulatory support is another standard option, but there is a lack of intracorporeal devices due to size and functional range. The purpose of this study was to evaluate the in vivo performance of our initial prototype of a pediatric continuous-flow total artificial heart (P-CFTAH), comprising a dual pump with one motor and one rotating assembly, supported by a hydrodynamic bearing. In acute studies, the P-CFTAH was implanted in 4 lambs (average weight: 28.7 ± 2.3 kg) via a median sternotomy under cardiopulmonary bypass. Pulmonary and systemic pump performance parameters were recorded. The experiments showed good anatomical fit and easy implantation, with an average aortic cross-clamp time of 98 ± 18 minutes. Baseline hemodynamics were stable in all 4 animals (pump speed: 3.4 ± 0.2 krpm; pump flow: 2.1 ± 0.9 liters/min; power: 3.0 ± 0.8 W; arterial pressure: 68 ± 10 mm Hg; left and right atrial pressures: 6 ± 1 mm Hg, for both). Any differences between left and right atrial pressures were maintained within the intended limit of ±5 mm Hg over a wide range of ratios of systemic-to-pulmonary vascular resistance (0.7 to 12), with and without pump-speed modulation. Pump-speed modulation was successfully performed to create arterial pulsation. This initial P-CFTAH prototype met the proposed requirements for self-regulation, performance, and pulse modulation. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Combinatorial screening of 3D biomaterial properties that promote myofibrogenesis for mesenchymal stromal cell-based heart valve tissue engineering.

PubMed

Usprech, Jenna; Romero, David A; Amon, Cristina H; Simmons, Craig A

2017-08-01

The physical and chemical properties of a biomaterial integrate with soluble cues in the cell microenvironment to direct cell fate and function. Predictable biomaterial-based control of integrated cell responses has been investigated with two-dimensional (2D) screening platforms, but integrated responses in 3D have largely not been explored systematically. To address this need, we developed a screening platform using polyethylene glycol norbornene (PEG-NB) as a model biomaterial with which the polymer wt% (to control elastic modulus) and adhesion peptide types (RGD, DGEA, YIGSR) and densities could be controlled independently and combinatorially in arrays of 3D hydrogels. We applied this platform and regression modeling to identify combinations of biomaterial and soluble biochemical (TGF-β1) factors that best promoted myofibrogenesis of human mesenchymal stromal cells (hMSCs) in order to inform our understanding of regenerative processes for heart valve tissue engineering. In contrast to 2D culture, our screens revealed that soft hydrogels (low PEG-NB wt%) best promoted spread myofibroblastic cells that expressed high levels of α-smooth muscle actin (α-SMA) and collagen type I. High concentrations of RGD enhanced α-SMA expression in the presence of TGF-β1 and cell spreading regardless of whether TGF-β1 was in the culture medium. Strikingly, combinations of peptides that maximized collagen expression depended on the presence or absence of TGF-β1, indicating that biomaterial properties can modulate MSC response to soluble signals. This combination of a 3D biomaterial array screening platform with statistical modeling is broadly applicable to systematically identify combinations of biomaterial and microenvironmental conditions that optimally guide cell responses. We present a novel screening platform and methodology to model and identify how combinations of biomaterial and microenvironmental conditions guide cell phenotypes in 3D. Our approach to systematically identify complex relationships between microenvironmental cues and cell responses enables greater predictive power over cell fate in conditions with interacting material design factors. We demonstrate that this approach not only predicts that mesenchymal stromal cell (MSC) myofibrogenesis is promoted by soft, porous 3D biomaterials, but also generated new insights which demonstrate how biomaterial properties can differentially modulate MSC response to soluble signals. An additional benefit of the process includes utilizing both parametric and non parametric analyses which can demonstrate dominant significant trends as well as subtle interactions between biochemical and biomaterial cues. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The independent and combined effects of respiratory events and cortical arousals on the autonomic nervous system across sleep stages.

PubMed

Liang, Jiuxing; Zhang, Xiangmin; He, Xiaomin; Ling, Li; Zeng, Chunyao; Luo, Yuxi

2018-05-10

During sleep, respiratory events readily modulate the autonomic nervous system (ANS). Whether such modulation is caused by the respiratory event itself or the cortical arousal that follows and whether these influences differ across sleep stages are not clear. Thus, we aimed to study the independent and combined effects of respiratory events and cortical arousals on the ANS across sleep stages. We recruited 22 male patients with sleep apnea-hypopnea syndrome (SAHS) and analyzed the differences in the indices of heart rate variability among normal respiration (NR), pathological respiratory events without cortical arousals (PR), cortical arousals without respiratory events (CA), and the coexistence of PR and CA (PR&CA), by sleep stage. Compared with NR, four indices of variation of the beat-to-beat interval demonstrated consistent results in all sleep stages generally: PR&CA showed the biggest difference, followed by PR and followed by CA, which exhibited the least difference. Thus, the respiratory event itself affects ANS modulation, but the cortical arousal that follows generally enhances this effect. For low-frequency power and low-frequency/high-frequency power ratio (LF/HF), PR&CA had the greatest impact. For mean beat-to-beat interval and high-frequency power (HFP), the influence of PR, CA, and PR&CA depended on sleep depth. However, PR&CA had a different influence on HFP in N2 stage vs. REM stage. Sleep stage also has an effect on this neuromodulatory mechanism. These findings may help clarify the relationship between SAHS and cardiovascular disease.

The in vivo regulation of heart rate in the murine sinoatrial node by stimulatory and inhibitory heterotrimeric G proteins

PubMed Central

Sebastian, Sonia; Ang, Richard; Abramowitz, Joel; Weinstein, Lee S.; Chen, Min; Ludwig, Andreas; Birnbaumer, Lutz

2013-01-01

Reciprocal physiological modulation of heart rate is controlled by the sympathetic and parasympathetic systems acting on the sinoatrial (SA) node. However, there is little direct in vivo work examining the role of stimulatory and inhibitory G protein signaling in the SA node. Thus, we designed a study to examine the role of the stimulatory (Gαs) and inhibitory G protein (Gαi2) in in vivo heart rate regulation in the SA node in the mouse. We studied mice with conditional deletion of Gαs and Gαi2 in the conduction system using cre-loxP technology. We crossed mice in which cre recombinase expression was driven by a tamoxifen-inducible conduction system-specific construct with “Gαs floxed” and “Gαi2 floxed” mice. We studied the heart rate responses of adult mice compared with littermate controls by using radiotelemetry before and after administration of tamoxifen. The mice with conditional deletion of Gαs and Gαi2 had a loss of diurnal variation and were bradycardic or tachycardic, respectively, in the daytime. In mice with conditional deletion of Gαs, there was a selective loss of low-frequency power, while with deletion of Gαi2, there was a loss of high-frequency power in power spectral analysis of heart rate variability. There was no evidence of pathological arrhythmia. Pharmacological modulation of heart rate by isoprenaline was impaired in the Gαs mice, but a muscarinic agonist was still able to slow the heart rate in Gαi2 mice. We conclude that Gαs- and Gαi2-mediated signaling in the sinoatrial node is important in the reciprocal regulation of heart rate through the autonomic nervous system. PMID:23697798

The in vivo regulation of heart rate in the murine sinoatrial node by stimulatory and inhibitory heterotrimeric G proteins.

PubMed

Sebastian, Sonia; Ang, Richard; Abramowitz, Joel; Weinstein, Lee S; Chen, Min; Ludwig, Andreas; Birnbaumer, Lutz; Tinker, Andrew

2013-08-15

Reciprocal physiological modulation of heart rate is controlled by the sympathetic and parasympathetic systems acting on the sinoatrial (SA) node. However, there is little direct in vivo work examining the role of stimulatory and inhibitory G protein signaling in the SA node. Thus, we designed a study to examine the role of the stimulatory (Gαs) and inhibitory G protein (Gαi2) in in vivo heart rate regulation in the SA node in the mouse. We studied mice with conditional deletion of Gαs and Gαi2 in the conduction system using cre-loxP technology. We crossed mice in which cre recombinase expression was driven by a tamoxifen-inducible conduction system-specific construct with "Gαs floxed" and "Gαi2 floxed" mice. We studied the heart rate responses of adult mice compared with littermate controls by using radiotelemetry before and after administration of tamoxifen. The mice with conditional deletion of Gαs and Gαi2 had a loss of diurnal variation and were bradycardic or tachycardic, respectively, in the daytime. In mice with conditional deletion of Gαs, there was a selective loss of low-frequency power, while with deletion of Gαi2, there was a loss of high-frequency power in power spectral analysis of heart rate variability. There was no evidence of pathological arrhythmia. Pharmacological modulation of heart rate by isoprenaline was impaired in the Gαs mice, but a muscarinic agonist was still able to slow the heart rate in Gαi2 mice. We conclude that Gαs- and Gαi2-mediated signaling in the sinoatrial node is important in the reciprocal regulation of heart rate through the autonomic nervous system.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

PubMed

Woodford, Katrina; Panettieri, Vanessa; Ruben, Jeremy D; Senthi, Sashendra

2016-05-01

Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

MODULATION OF HYPOXIC PULMONARY VASOCONSTRICTION BY ERYTHROCYTIC NITRIC OXIDE

EPA Science Inventory

Abstract
American Heart Association 2001

Modulation of Hypoxic Pulmonary Vasoconstriction by Erythrocytic NO
McMahon TJ1, Gow AJ1, Huang YCT4, Stamler JS1,2,3
Departments of Medicine1 and Biochemistry2, and Howard Hughes Medical Institute3,
Duke University Med...

Intravenous Milrinone in Treatment of Advanced Congestive Heart Failure

PubMed Central

Zewail, Aly M.; Nawar, Mohammad; Vrtovec, Bojan; Eastwood, Cathy; Kar, Biswajit; Delgado, Reynolds M.

2003-01-01

Phosphodiesterase inhibitors such as milrinone can relieve symptoms and improve hemodynamics in patients with advanced congestive heart failure. We retrospectively evaluated the hemodynamic and clinical outcomes of long-term combination therapy with intravenous milrinone and oral β-blockers in 65 patients with severe congestive heart failure (New York Heart Association class IV function and ejection fraction <25%) refractory to oral medical therapy. Fifty-one patients successfully began β-blocker therapy while on intravenous milrinone. Oral medical therapy was maximized when possible. The mean duration of milrinone treatment in this combination-treatment group was 269 days (range, 14–1,026 days). Functional class improved from IV to II–III with milrinone therapy. Twenty-four such patients tolerated β-blocker up-titration and were successfully weaned from milrinone. Sixteen patients (31%) died while receiving combination therapy; one died of sudden cardiac death (on treatment day 116); the other 15 died of progressive heart failure or other complications. Hospital admissions during the previous 6 months and admissions within 6 months after milrinone initiation stayed the same. Meanwhile, the total number of hospital days decreased from 450 to 380 (a 15.6% reduction), and the mean length of stay decreased by 1.4 days (a 14.7% reduction). We conclude that 1) milrinone plus β-blocker combination therapy is an effective treatment for heart failure even with β-blocker up-titration, 2) weaning from milrinone may be possible once medications are maximized, 3) patients' functional status improves on the combination regimen, and 4) treatment-related sudden death is relatively infrequent during the combination regimen. (Tex Heart Inst J 2003;30:109–13) PMID:12809251

Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis.

PubMed

Natriuretic Peptides Studies Collaboration; Willeit, Peter; Kaptoge, Stephen; Welsh, Paul; Butterworth, Adam; Chowdhury, Rajiv; Spackman, Sarah; Pennells, Lisa; Gao, Pei; Burgess, Stephen; Freitag, Daniel; Sweeting, Michael; Wood, Angela; Cook, Nancy; Judd, Suzanne; Trompet, Stella; Nambi, Vijay; Olsen, Michael; Everett, Brendan; Kee, Frank; Ärnlöv, Johan; Salomaa, Veikko; Levy, Daniel; Kauhanen, Jussi; Laukkanen, Jari; Kavousi, Maryam; Ninomiya, Toshiharu; Casas, Juan-Pablo; Daniels, Lori; Lind, Lars; Kistorp, Caroline; Rosenberg, Jens; Mueller, Thomas; Rubattu, Speranza; Panagiotakos, Demosthenes; Franco, Oscar; de Lemos, James; Luchner, Andreas; Kizer, Jorge; Kiechl, Stefan; Salonen, Jukka; Goya Wannamethee, S; de Boer, Rudolf; Nordestgaard, Børge; Andersson, Jonas; Jørgensen, Torben; Melander, Olle; Ballantyne, Christie; DeFilippi, Christopher; Ridker, Paul; Cushman, Mary; Rosamond, Wayne; Thompson, Simon; Gudnason, Vilmundur; Sattar, Naveed; Danesh, John; Di Angelantonio, Emanuele

2016-10-01

Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention. British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Can fish oil supplementation and physical training improve oxidative metabolism in aged rat hearts?

PubMed

da Silva Pedroza, Anderson Apolonio; Lopes, Andréia; Mendes da Silva, Rosângela F; Braz, Glauber Ruda; Nascimento, Luciana P; Ferreira, Diorginis Soares; dos Santos, Ângela Amâncio; Batista-de-Oliveira-Hornsby, Manuella; Lagranha, Claudia J

2015-09-15

It is well known that in the aging process a variety of physiological functions such as cardiac physiology and energy metabolism decline. Imbalance in production and elimination of reactive oxygen species (ROS) may induce oxidative stress. Research shows that oxidative stress is an important factor in the aging process. Studies suggest that ɷ-3 polyunsaturated fatty acids (PUFAs) and moderate physical exercise modulate the ROS system. Therefore, the present study aimed to investigate whether ɷ-3 present in fish oil supplementation coupled with moderate physical training could improve antioxidant and metabolic enzymes in the hearts of adult and aged rats and, if these effects could be associated to glycemia, plasma lipid profile or murinometric parameters. Adult (weighing 315.1±9.3g) and aged rats (weighing 444.5±11.8g) exercised and receive fish oil supplementation for 4weeks. Then they were used to evaluate murinometric parameters, fasting glucose and lipid profile. After this, their hearts were collected to measure the levels of malondialdehyde (MDA), antioxidant enzyme activity (superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase-GPx) and oxidative metabolism marker (citrate synthase-CS activity). Fish oil supplementation increases HDL concentration and activity of CAT and CS. Moreover, physical training coupled with fish oil supplementation induces additional effects on SOD, GPx and CS activity mainly in aged rats. Our data suggest that combined treatment in aged rat hearts improves the antioxidant capacities and metabolic enzyme that can prevent the deleterious effects of aging. Copyright © 2015. Published by Elsevier Inc.

Novel application of multi dynamic trend analysis as a sensitive tool for detecting the effects of aging and congestive heart failure on heart rate variability

NASA Astrophysics Data System (ADS)

Lin, Yu-Cheng; Lin, Yu-Hsuan; Lo, Men-Tzung; Peng, Chung-Kang; Huang, Norden E.; Yang, Cheryl C. H.; Kuo, Terry B. J.

2016-02-01

The complex fluctuations in heart rate variability (HRV) reflect cardiac autonomic modulation and are an indicator of congestive heart failure (CHF). This paper proposes a novel nonlinear approach to HRV investigation, the multi dynamic trend analysis (MDTA) method, based on the empirical mode decomposition algorithm of the Hilbert-Huang transform combined with a variable-sized sliding-window method. Electrocardiographic signal data obtained from the PhysioNet database were used. These data were from subjects with CHF (mean age = 59.4 ± 8.4), an age-matched elderly healthy control group (59.3 ± 10.6), and a healthy young group (30.3 ± 4.8); the HRVs of these subjects were processed using the MDTA method, time domain analysis, and frequency domain analysis. Among all HRV parameters, the MDTA absolute value slope (MDTS) and MDTA deviation (MDTD) exhibited the greatest area under the curve (AUC) of the receiver operating characteristics in distinguishing between the CHF group and the healthy controls (AUC = 1.000) and between the healthy elderly subject group and the young subject group (AUC = 0.834 ± 0.067 for MDTS; 0.837 ± 0.066 for MDTD). The CHF subjects presented with lower MDTA indices than those of the healthy elderly subject group. Furthermore, the healthy elderly subjects exhibited lower MDTA indices than those of the young controls. The MDTA method can adaptively and automatically identify the intrinsic fluctuation on variable temporal and spatial scales when investigating complex fluctuations in the cardiac autonomic regulation effects of aging and CHF.

Heart Rate Complexity in Response to Upright Tilt in Persons with Down Syndrome

ERIC Educational Resources Information Center

Agiovlasitis, Stamatis; Baynard, Tracy; Pitetti, Kenneth H.; Fernhall, Bo

2011-01-01

People with Down syndrome (DS) show altered autonomic response to sympatho-excitation. Cardiac autonomic modulation may be examined with heart rate (HR) complexity which is associated uniquely with cardiovascular risk. This study examined whether the response of HR complexity to passive upright tilt differs between persons with and without DS and…

Regulation of signal transduction by reactive oxygen species in the cardiovascular system.

PubMed

Brown, David I; Griendling, Kathy K

2015-01-30

Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species (ROS) in normal physiological signaling has been elucidated. Signaling pathways modulated by ROS are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here, we review the current literature on ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases, including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy, and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis, and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress. © 2015 American Heart Association, Inc.

Modulation of tissue repair by regeneration enhancer elements.

PubMed

Kang, Junsu; Hu, Jianxin; Karra, Ravi; Dickson, Amy L; Tornini, Valerie A; Nachtrab, Gregory; Gemberling, Matthew; Goldman, Joseph A; Black, Brian L; Poss, Kenneth D

2016-04-14

How tissue regeneration programs are triggered by injury has received limited research attention. Here we investigate the existence of enhancer regulatory elements that are activated in regenerating tissue. Transcriptomic analyses reveal that leptin b (lepb) is highly induced in regenerating hearts and fins of zebrafish. Epigenetic profiling identified a short DNA sequence element upstream and distal to lepb that acquires open chromatin marks during regeneration and enables injury-dependent expression from minimal promoters. This element could activate expression in injured neonatal mouse tissues and was divisible into tissue-specific modules sufficient for expression in regenerating zebrafish fins or hearts. Simple enhancer-effector transgenes employing lepb-linked sequences upstream of pro- or anti-regenerative factors controlled the efficacy of regeneration in zebrafish. Our findings provide evidence for 'tissue regeneration enhancer elements' (TREEs) that trigger gene expression in injury sites and can be engineered to modulate the regenerative potential of vertebrate organs.

A novel approach in extracorporeal circulation: individual, integrated, and interactive heart-lung assist (I3-Assist).

PubMed

Wagner, Georg; Schlanstein, Peter; Fiehe, Sandra; Kaufmann, Tim; Kopp, Rüdger; Bensberg, Ralf; Schmitz-Rode, Thomas; Steinseifer, Ulrich; Arens, Jutta

2014-04-01

Extracorporeal life support (ECLS) is a well-established technique for the treatment of different cardiac and pulmonary diseases, e.g., congenital heart disease and acute respiratory distress syndrome. Additionally, severely ill patients who cannot be weaned from the heart-lung machine directly after surgery have to be put on ECLS for further therapy. Although both systems include identical components, a seamless transition is not possible yet. The adaption of the circuit to the patients' size and demand is limited owing to the components available. The project I³-Assist aims at a novel concept for extracorporeal circulation. To better match the patient's therapeutic demand of support, an individual number of one-size oxygenators and heat exchangers will be combined. A seamless transition between cardiopulmonary bypass and ECLS will be possible as well as the exchange of components during therapy to enhance circuit maintenance throughout long-term support. Until today, a novel oxygenator and heat exchanger along with a simplified manufacturing protocol have been established. The first layouts of the unit to allow the spill- and bubble-free connection and disconnection of modules as well as improved cannulas and a rotational pump are investigated using computational fluid dynamics. Tests were performed according to current guidelines in vitro and in vivo. The test results show the feasibility and potential of the concept.

[Cardiac cachexia].

PubMed

Miján, Alberto; Martín, Elvira; de Mateo, Beatriz

2006-05-01

Chronic heart failure (CHF), especially affecting the right heart, frequently leads to malnutrition. If the latter is severe and is combined to other factors, it may lead to cardiac cachexia. This one is associated to increased mortality and lower survival of patients suffering from it. The causes of cardiac cachexia are diverse, generally associated to maintenance of a negative energy balance, with increasing evidence of its multifactorial origin. Neurohumoral, inflammatory, immunological, and metabolic factors, among others, are superimposed in the patient with CHF, leading to involvement and deterioration of several organs and systems, since this condition affects both lean (or active cellular) mass and adipose and bone tissue osteoporosis. Among all, the most pronounced deterioration may be seen at skeletal muscle tissue, at both structural and functional levels, the heart not being spared. As for treatment, it should be based on available scientific evidence. Assessment of nutritional status of any patient with CHF is a must, with the requirement of nutritional intervention in case of malnutrition. In this situation, especially if accompanied by cardiac cachexia, it is required to modify energy intake and oral diet quality, and to consider the indication of specific complementary or alternative artificial nutrition. Besides, the causal relationship of the beneficial role of moderate physical exertion is increasing, as well as modulation of metabolic and inflammatory impairments observed in cardiac cachexia with several drugs, leading to a favorable functional and structural response in CHF patients.

N-acetylcysteine prevents ketamine-induced adverse effects on development, heart rate and monoaminergic neurons in zebrafish.

PubMed

Robinson, Bonnie; Dumas, Melanie; Gu, Qiang; Kanungo, Jyotshna

2018-06-08

N-acetylcysteine, a precursor molecule of glutathione, is an antioxidant. Ketamine, a pediatric anesthetic, has been implicated in cardiotoxicity and neurotoxicity including modulation of monoaminergic systems in mammals and zebrafish. Here, we show that N-acetylcysteine prevents ketamine's adverse effects on development and monoaminergic neurons in zebrafish embryos. The effects of ketamine and N-acetylcysteine alone or in combination were measured on the heart rate, body length, brain serotonergic neurons and tyrosine hydroxylase-immunoreactive (TH-IR) neurons. In the absence of N-acetylcysteine, a concentration of ketamine that produces an internal embryo exposure level comparable to human anesthetic plasma concentrations significantly reduced heart rate and body length and those effects were prevented by N-acetylcysteine co-treatment. Ketamine also reduced the areas occupied by serotonergic neurons in the brain, whereas N-acetylcysteine co-exposure counteracted this effect. TH-IR neurons in the embryo brain and TH-IR cells in the trunk were significantly reduced with ketamine treatment, but not in the presence of N-acetylcysteine. In our continued search for compounds that can prevent ketamine toxicity, this study using specific endpoints of developmental toxicity, cardiotoxicity and neurotoxicity, demonstrates protective effects of N-acetylcysteine against ketamine's adverse effects. This is the first study that shows the protective effects of N-acetylcysteine on ketamine-induced developmental defects of monoaminergic neurons as observed in a whole organism. Published by Elsevier B.V.

Cryo-Vacuum Testing of JWST's Integrated Telescope & Scientific Instrument Suite (OTIS)

NASA Astrophysics Data System (ADS)

Kimble, Randy; Apollo, Peter; Feinberg, Lee; Glazer, Stuart; Hanley, Jeffrey; Keski-Kuha, Ritva; Kirk, Jeffrey; Knight, J. Scott; Lambros, Scott; Lander, Juli; McGuffey, Douglas; Mehalick, Kimberly; Ohl, Raymond; Ousley, Wes; Reis, Carl; Reynolds, Paul; Begoña Vila, Maria; Waldman, Mark; Whitman, Tony

2018-01-01

A year ago we reported on the planning for a major test in the James Webb Space Telescope (JWST) program: cryo-vacuum testing of the combination of the Optical Telescope Element (OTE) and the Integrated Science Instrument Module (ISIM). The cryo-vacuum testing of that scientific heart of the JWST observatory, known as OTIS (= OTE + ISIM), has now been completed in historic chamber A at NASA’s Johnson Space Center. From July through October 2017, the flight payload was cooled to its operating temperatures, put through a comprehensive suite of optical, thermal, and operational tests, and then safely warmed back to room temperature. We report here on the execution and top-level results from this milestone event in the JWST program.

Comparison of heart and coronary artery doses associated with intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for distal esophageal cancer.

PubMed

Kole, Thomas P; Aghayere, Osarhieme; Kwah, Jason; Yorke, Ellen D; Goodman, Karyn A

2012-08-01

To compare heart and coronary artery radiation exposure using intensity-modulated radiotherapy (IMRT) vs. four-field three-dimensional conformal radiotherapy (3D-CRT) treatment plans for patients with distal esophageal cancer undergoing chemoradiation. Nineteen patients with distal esophageal cancers treated with IMRT from March 2007 to May 2008 were identified. All patients were treated to 50.4 Gy with five-field IMRT plans. Theoretical 3D-CRT plans with four-field beam arrangements were generated. Dose-volume histograms of the planning target volume, heart, right coronary artery, left coronary artery, and other critical normal tissues were compared between the IMRT and 3D-CRT plans, and selected parameters were statistically evaluated using the Wilcoxon rank-sum test. Intensity-modulated radiotherapy treatment planning showed significant reduction (p < 0.05) in heart dose over 3D-CRT as assessed by average mean dose (22.9 vs. 28.2 Gy) and V30 (24.8% vs. 61.0%). There was also significant sparing of the right coronary artery (average mean dose, 23.8 Gy vs. 35.5 Gy), whereas the left coronary artery showed no significant improvement (mean dose, 11.2 Gy vs. 9.2 Gy), p = 0.11. There was no significant difference in percentage of total lung volume receiving at least 10, 15, or 20 Gy or in the mean lung dose between the planning methods. There were also no significant differences observed for the kidneys, liver, stomach, or spinal cord. Intensity-modulated radiotherapy achieved a significant improvement in target conformity as measured by the conformality index (ratio of total volume receiving 95% of prescription dose to planning target volume receiving 95% of prescription dose), with the mean conformality index reduced from 1.56 to 1.30 using IMRT. Treatment of patients with distal esophageal cancer using IMRT significantly decreases the exposure of the heart and right coronary artery when compared with 3D-CRT. Long-term studies are necessary to determine how this will impact on development of coronary artery disease and other cardiac complications. Copyright © 2012 Elsevier Inc. All rights reserved.

miRNAs as therapeutic targets in ischemic heart disease.

PubMed

Frost, Robert J A; van Rooij, Eva

2010-06-01

Ischemic heart disease is a form of congestive heart failure that is caused by insufficient blood supply to the heart, resulting in a loss of viable tissue. In response to the injury, the non-ischemic myocardium displays signs of secondary remodeling, like interstitial fibrosis and hypertrophy of cardiac myocytes. This remodeling process further deteriorates pump function and increases susceptibility to arrhythmias. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression in a sequence-dependent manner. Recently, several groups identified miRNAs as crucial gene regulators in response to myocardial infarction (MI) and during post-MI remodeling. In this review, we discuss how modulation of these miRNAs represents a promising new therapeutic strategy to improve the clinical outcome in ischemic heart disease.

Autophagy-Inflammasome Interplay in Heart Failure: A Systematic Review on Basics, Pathways, and Therapeutic Perspectives.

PubMed

Chiu, Bonnie; Jantuan, Eugeniu; Shen, Fan; Chiu, Brian; Sergi, Consolato

2017-05-01

Aging of the population contributes to the increasing prevalence of heart failure. Autophagy is an evolutionarily conserved process aiming to degrade both long-lived proteins and damaged or excessive cyto-organelles via the lysosomal-mediated pathway. Although autophagy is involved in the normal homeostasis of cardiovascular cells, upregulation of autophagy and its abnormal modulation by inflammation may lead to cardiovascular functional decline and heart failure. Despite major improvements in the prevention, diagnosis, and treatment of cardiovascular diseases, heart failure remains one of the major diagnostic and therapeutic challenges. Here, we review the cardiovascular autophagy and its interplay with inflammation which may lead to heart failure exploring some potential treatment options. © 2017 by the Association of Clinical Scientists, Inc.

Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy.

PubMed

Giugliano, Francesca M; Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

2016-04-26

Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three-dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity-modulated radiotherapy appears to be the appropriate treatment in heart-transplanted oncologic patients.

[Combined G-banded karyotyping and multiplex ligation-dependent probe amplification for the detection of chromosomal abnormalities in fetuses with congenital heart defects].

PubMed

Liu, Yang; Xie, Jiansheng; Geng, Qian; Xu, Zhiyong; Wu, Weiqin; Luo, Fuwei; Li, Suli; Wang, Qin; Chen, Wubin; Tan, Hongxi; Zhang, Hu

2017-02-10

To assess the value of G-banded karyotyping in combination with multiplex ligation-dependent probe amplification (MLPA) as a tool for the detection of chromosomal abnormalities in fetuses with congenital heart defects. The combined method was used to analyze 104 fetuses with heart malformations identified by ultrasonography. Abnormal findings were confirmed with chromosomal microarray analysis (CMA). Nineteen (18%) fetuses were found to harbor chromosomal aberrations by G-banded karyotyping and MLPA. For 93 cases, CMA has detected abnormalities in 14 cases including 10 pathogenic copy number variations (CNVs) and 4 CNVs of uncertain significance (VOUS). MLPA was able to detect all of the pathogenic CNVs and 1 VOUS CNV. Combined use of G-banded karyotyping and MLPA is a rapid, low-cost and effective method to detect chromosomal abnormalities in fetuses with various heart malformations.

Combined exposure of Japanese quails to cyanotoxins, Newcastle virus and lead: oxidative stress responses.

PubMed

Paskova, Veronika; Veronika, Paskova; Paskerova, Hana; Hana, Paskerova; Pikula, Jiri; Jiri, Pikula; Bandouchova, Hana; Hana, Bandouchova; Sedlackova, Jana; Jana, Sedlackova; Hilscherova, Klara; Klara, Hilscherova

2011-10-01

Wild birds are continually exposed to many anthropogenic and natural stressors in their habitats. Over the last decades, mass mortalities of wild birds constitute a serious problem and may possibly have more causations such as natural toxins including cyanotoxins, parasitic diseases, industrial chemicals and other anthropogenic contaminants. This study brings new knowledge on the effects of controlled exposure to multiple stressors in birds. The aim was to test the hypothesis that influence of cyanobacterial biomass, lead and antigenic load may combine to enhance the effects on birds, including modulation of antioxidative and detoxification responses. Eight treatment groups of model species Japanese quail (Coturnix coturnix japonica) were exposed to various combinations of these stressors. The parameters of detoxification and oxidative stress were studied in liver and heart after 30 days of exposure. The antioxidative enzymatic defense in birds seems to be activated quite efficiently, which was documented by the elevated levels and activities of antioxidative and detoxification compounds and by the low incidence of damage to lipid membranes. The greatest modulations of glutathione level and activities of glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and lipid peroxidation were shown mostly in the groups with combined multiple exposures. The results indicate that the antioxidative system plays an important role in the protective response of the tissues to applied stressors and that its greater induction helps to protect the birds from more serious damage. Most significant changes of these "defense" parameters in case of multiple stressors suggest activation of this universal mechanism in situation with complex exposure and its crucial role in protection of the bird health in the environment. Copyright © 2011 Elsevier Inc. All rights reserved.

Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats

PubMed Central

Rocha, Juraci Aparecida; Ribeiro, Susan Pereira; França, Cristiane Miranda; Coelho, Otávio; Alves, Gisele; Kallás, Esper Georges; Irigoyen, Maria Cláudia

2016-01-01

We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg−1·day−1) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups—denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups—were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3+ cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4+CD25+FOXP3+), and a less extreme decrease in conventional T cells (CD25+FOXP3−) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats. PMID:26791829

Increase in cholinergic modulation with pyridostigmine induces anti-inflammatory cell recruitment soon after acute myocardial infarction in rats.

PubMed

Rocha, Juraci Aparecida; Ribeiro, Susan Pereira; França, Cristiane Miranda; Coelho, Otávio; Alves, Gisele; Lacchini, Silvia; Kallás, Esper Georges; Irigoyen, Maria Cláudia; Consolim-Colombo, Fernanda M

2016-04-15

We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4+, CD8+, FOXP3+) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg(-1)·day(-1)) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groups-denominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3(+)cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4(+)CD25(+)FOXP3(+)), and a less extreme decrease in conventional T cells (CD25(+)FOXP3(-)) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats. Copyright © 2016 the American Physiological Society.

Microwave effects on isolated chick embryo hearts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caddemi, A.; Tamburello, C.C.; Zanforlin, L.

1986-01-01

This study was designed to examine the effects of microwaves on the electric activity of hearts as a means of elucidating interactive mechanisms of nonionizing radiation with cardiac tissue. Experiments were performed on isolated hearts of 9-12-day-old chick embryos placed in small petri dishes. Oxygenated isotonic Ringer's solution at 37 degrees C permitted heart survival. Samples were irradiated at 2.45 GHz with a power density of 3 mW/cm2. The heart signal was detected with a glass micropipet inserted into the sinoatrial node and examined by means of a Berg-Fourier analyzer. Pulsed microwaves caused the locking of the heartbeat to themore » modulation frequency, whereas continuous wave irradiation might have induced slight bradycardia. Pulsed fields induced stimulation or regularization of the heartbeat in arrhythmia, fibrillation, or arrest of the heart.« less

Simultaneous exposure to concentrated ambient particles and acrolein causes cardiac effects mediated by parasympathetic modulation in mice

EPA Science Inventory

This study shows that exposure to CAPs and acrolein causes an increase in HRV that is mediated by the parasympathetic nervous system. Numerous studies show that short-term air pollution exposure modulates heart rate variability (HRV), which is an indicator of autonomic influence...

PORTRAIT - APOLLO 7

NASA Image and Video Library

1968-02-13

S68-21590 (September 1968) --- This is a portrait of the Apollo-Saturn 7 crew members. They are, left to right, astronauts Walter M. Schirra Jr., commander; Walter Cunningham, lunar module pilot; and Donn F. Eisele, command module pilot. EDITOR'S NOTE: Since this photograph was made astronaut Eisele died Dec. 2, 1987 in Tokyo, Japan, of a heart attack.

Arousal Modulation in Females with Fragile X or Turner Syndrome

ERIC Educational Resources Information Center

Roberts, Jane; Mazzocco, Michele M. M.; Murphy, Melissa M.; Hoehn-Saric, Rudolf

2008-01-01

The present study was carried out to examine physiological arousal modulation (heart activity and skin conductance), across baseline and cognitive tasks, in females with fragile X or Turner syndrome and a comparison group of females with neither syndrome. Relative to the comparison group, for whom a greater increase in skin conductance was…

OC19 - Measuring feasibility, reliability and validity of the Greek version of PedsQL cardiac module.

PubMed

Drakouli, Maria; Petsios, Konstantinos; Matziou, Vasiliki

2016-05-09

Theme: Cardiology Introduction: Measuring quality of life (QoL) in children and adolescents with congenital heart disease (CHD) is of great clinical importance. The aim of the study was: (a) to adapt the PedsQL Cardiac Module for children aged two to 18 years with CHD in a sample of the Greek population; (b) to determine its reliability and validity. Forward and backward translation methodology was used. Parents and children completed the instrument during: (a) hospitalization and (b) visits in the paediatric cardiology outpatient department. Cross-informant variance between children and parents was thoroughly assessed. Missing item responses did not exceed 5%. All internal consistency reliability coefficients for the inventory exceeded the minimum standards for group comparisons, over 0.75. Hypothesized correlations between cardiac module and core scales were statistically significant, (p<0.05). Agreement between children and parents was relatively high. Pilot study results will be additionally presented. The findings support the feasibility, reliability and validity of the Greek translation of the PedsQL Cardiac Module in children with congenital heart defect (CHD).

Role of the autonomic nervous system in the control of heart rate and blood pressure in the defence reaction in conscious dogs.

PubMed

Federici, A; Rizzo, A; Cevese, A

1985-04-01

The present study was performed on conscious, chronically instrumented dogs, which underwent selective blockade of sympathetic adrenergic and vagal outflows. Excitements were performed on these animals in normal states (N), after chronic treatment with guanethidine, for sympathetic blockade (SB), after cold vagal blockade (VB), and after combined sympathetic and vagal blockade (SB + VB). Heart rate and arterial blood pressure were monitored in all the experiments, while a group of dogs was also tested with an electromagnetic flowmeter on the superior mesenteric artery. The role of the sympathetic and parasympathetic controls in the defence reaction was assumed from comparison of experiments performed in the presence or in the absence of each (or both) autonomic component(s). In the SB + VB condition, excitement was followed by sudden hypotension, without changes in heart rate. In VB experiments, a brief and transient hypotension appeared, followed by gradually developed hypertension, while heart rate progressively rose in about 5 s; there was no sudden increase in mesenteric vascular resistance, which contrasted with the very marked reaction in N experiments. Under vagal control alone (SB), the stimulus elicited prompt tachycardia and hypertension, followed by a period of moderately reduced blood pressure. We conclude that, while the defence reaction leads to a sudden fall of arterial blood pressure, in the absence of compensatory mechanisms, both branches of the autonomic nervous system play a protective role against hypotension. In addition, the modulation of the vagal outflow, leading to sudden changes in the heart performance, seems to be responsible for the initiation of the overall haemodynamic adjustments following excitements. The possibility that withdrawal of the parasympathetic outflow to the heart may raise arterial blood pressure was verified in a special experiment in which artificial vagal stimulation in a conscious (vagal blocked) dog, was turned off for brief periods, before and after guanethidine. This led to changes in blood pressure and heart rate very similar to those seen at the onset of the defence reaction, both in N and SB conditions.

Role of pyruvate dehydrogenase inhibition in the development of hypertrophy in the hyperthyroid rat heart: a combined magnetic resonance imaging and hyperpolarized magnetic resonance spectroscopy study.

PubMed

Atherton, Helen J; Dodd, Michael S; Heather, Lisa C; Schroeder, Marie A; Griffin, Julian L; Radda, George K; Clarke, Kieran; Tyler, Damian J

2011-06-07

Hyperthyroidism increases heart rate, contractility, cardiac output, and metabolic rate. It is also accompanied by alterations in the regulation of cardiac substrate use. Specifically, hyperthyroidism increases the ex vivo activity of pyruvate dehydrogenase kinase, thereby inhibiting glucose oxidation via pyruvate dehydrogenase. Cardiac hypertrophy is another effect of hyperthyroidism, with an increase in the abundance of mitochondria. Although the hypertrophy is initially beneficial, it can eventually lead to heart failure. The aim of this study was to use hyperpolarized magnetic resonance spectroscopy to investigate the rate and regulation of in vivo pyruvate dehydrogenase flux in the hyperthyroid heart and to establish whether modulation of flux through pyruvate dehydrogenase would alter cardiac hypertrophy. Hyperthyroidism was induced in 18 male Wistar rats with 7 daily intraperitoneal injections of freshly prepared triiodothyronine (0.2 mg x kg(-1) x d(-1)). In vivo pyruvate dehydrogenase flux, assessed with hyperpolarized magnetic resonance spectroscopy, was reduced by 59% in hyperthyroid animals (0.0022 ± 0.0002 versus 0.0055 ± 0.0005 second(-1); P=0.0003), and this reduction was completely reversed by both short- and long-term delivery of dichloroacetic acid, a pyruvate dehydrogenase kinase inhibitor. Hyperpolarized [2-(13)C]pyruvate was also used to evaluate Krebs cycle metabolism and demonstrated a unique marker of anaplerosis, the level of which was significantly increased in the hyperthyroid heart. Cine magnetic resonance imaging showed that long-term dichloroacetic acid treatment significantly reduced the hypertrophy observed in hyperthyroid animals (100 ± 20 versus 200 ± 30 mg; P=0.04) despite no change in the increase observed in cardiac output. This work has demonstrated that inhibition of glucose oxidation in the hyperthyroid heart in vivo is mediated by pyruvate dehydrogenase kinase. Relieving this inhibition can increase the metabolic flexibility of the hyperthyroid heart and reduce the level of hypertrophy that develops while maintaining the increased cardiac output required to meet the higher systemic metabolic demand.

Cardiac Metabolism in Heart Failure - Implications beyond ATP production

PubMed Central

Doenst, Torsten; Nguyen, T. Dung; Abel, E. Dale

2013-01-01

The heart has a high rate of ATP production and turnover which is required to maintain its continuous mechanical work. Perturbations in ATP generating processes may therefore affect contractile function directly. Characterizing cardiac metabolism in heart failure revealed several metabolic alterations termed metabolic remodeling, ranging from changes in substrate utilization to mitochondrial dysfunction, ultimately resulting in ATP deficiency and impaired contractility. However, ATP depletion is not the only relevant consequence of metabolic remodeling during heart failure. By providing cellular building blocks and signaling molecules, metabolic pathways control essential processes such as cell growth and regeneration. Thus, alterations in cardiac metabolism may also affect the progression to heart failure by mechanisms beyond ATP supply. Our aim is therefore to highlight that metabolic remodeling in heart failure not only results in impaired cardiac energetics, but also induces other processes implicated in the development of heart failure such as structural remodeling and oxidative stress. Accordingly, modulating cardiac metabolism in heart failure may have significant therapeutic relevance that goes beyond the energetic aspect. PMID:23989714

Fatty acids identified in the Burmese python promote beneficial cardiac growth.

PubMed

Riquelme, Cecilia A; Magida, Jason A; Harrison, Brooke C; Wall, Christopher E; Marr, Thomas G; Secor, Stephen M; Leinwand, Leslie A

2011-10-28

Burmese pythons display a marked increase in heart mass after a large meal. We investigated the molecular mechanisms of this physiological heart growth with the goal of applying this knowledge to the mammalian heart. We found that heart growth in pythons is characterized by myocyte hypertrophy in the absence of cell proliferation and by activation of physiological signal transduction pathways. Despite high levels of circulating lipids, the postprandial python heart does not accumulate triglycerides or fatty acids. Instead, there is robust activation of pathways of fatty acid transport and oxidation combined with increased expression and activity of superoxide dismutase, a cardioprotective enzyme. We also identified a combination of fatty acids in python plasma that promotes physiological heart growth when injected into either pythons or mice.

Anesthetic management during the first combined heart-liver transplant performed in Korea: a case report.

PubMed

Park, Hyejin; Park, Jungchan; Lee, Jonghwan; Kim, Gaabsoo

2017-10-01

Herein, we describe the anesthetic management during the first combined heart-liver transplant (CHLT) performed in Korea. Though CHLT is a rare procedure, accumulating evidence suggests that it is a feasible option for patients with coexisting heart and liver failure. A 45-year-old female patient presented with severe cardiac dysfunction requiring extracorporeal membrane oxygenation (ECMO) support and secondary congestive hepatopathy. The patient underwent consecutive heart and liver transplantation using extracorporeal circulatory devices-heart transplant with cardiopulmonary bypass, and liver transplant with peripheral ECMO. In this case report, we focus on the specific anesthetic considerations for CHLT pertaining to the challenges associated with dual pathophysiology.

Effects of Posteroanterior Thoracic Mobilization on Heart Rate Variability and Pain in Women with Fibromyalgia

PubMed Central

Reis, Michel Silva; Durigan, João Luiz Quagliotti; Arena, Ross; Rossi, Bruno Rafael Orsini; Mendes, Renata Gonçalves; Borghi-Silva, Audrey

2014-01-01

Fibromyalgia (FM) has been associated with cardiac autonomic abnormalities and pain. Heart rate variability (HRV) is reduced in FM with autonomic tone dominated by sympathetic activity. The purpose of this study was to evaluate the effects of one session of a posteroanterior glide technique on both autonomic modulation and pain in woman with FM. This was a controlled trial with immediate followup; twenty premenopausal women were allocated into 2 groups: (i) women diagnosed with FM (n = 10) and (ii) healthy women (n = 10). Both groups received one session of Maitland mobilization grade III posteroanterior central pressure glide, at 2 Hz for 60 s at each vertebral segment. Autonomic modulation was assessed by HRV and pain by a numeric pain scale before and after the intervention. For HRV analyses, heart rate and RR intervals were recorded for 10 minutes. FM subjects demonstrated reduced HRV compared to controls. Although the mobilization technique did not significantly reduce pain, it was able to improve HRV quantified by an increase in rMSSD and SD1 indices, reflecting an improved autonomic profile through increased vagal activity. In conclusion, women with FM presented with impaired cardiac autonomic modulation. One session of Maitland spine mobilization was able to acutely improve HRV. PMID:24991436

Power consumption of rotary blood pumps: pulsatile versus constant-speed mode.

PubMed

Pirbodaghi, Tohid; Cotter, Chris; Bourque, Kevin

2014-12-01

We investigated the power consumption of a HeartMate III rotary blood pump based on in vitro experiments performed in a cardiovascular simulator. To create artificial-pulse mode, we modulated the pump speed by decreasing the mean speed by 2000 rpm for 200 ms and then increasing speed by 4000 rpm (mean speeds plus 2000 rpm) for another 200 ms, creating a square waveform shape. The HeartMate III was connected to a cardiovascular simulator consisting of a hydraulic pump system to simulate left ventricle pumping action, arterial and venous compliance chambers, and an adjustable valve for peripheral resistance to facilitate the desired aortic pressure. The simulator operated based on Suga's elastance model to mimic the Starling response of the heart, thereby reproducing physiological blood flow and pressure conditions. We measured the instantaneous total electrical current and voltage of the pump to evaluate its power consumption. The aim was to answer these fundamental questions: (i) How does pump speed modulation affect pump power consumption? (ii) How does the power consumption vary in relation to external pulsatile flow? The results indicate that speed modulation and external pulsatile flow both moderately increase the power consumption. Increasing the pump speed reduces the impact of external pulsatile flow. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Relationship between cardiac autonomic function and cognitive function in Alzheimer's disease.

PubMed

Nonogaki, Zen; Umegaki, Hiroyuki; Makino, Taeko; Suzuki, Yusuke; Kuzuya, Masafumi

2017-01-01

Alzheimer's disease (AD) affects many central nervous structures and neurotransmitter systems. These changes affect not only cognitive function, but also cardiac autonomic function. However, the functional relationship between cardiac autonomic function and cognition in AD has not yet been investigated. The objective of the present study was to evaluate the association between cardiac autonomic function measured by heart rate variability and cognitive function in AD. A total of 78 AD patients were recruited for this study. Cardiac autonomic function was evaluated using heart rate variability analysis. Multiple linear regression analysis was used to model the association between heart rate variability and cognitive function (global cognitive function, memory, executive function and processing speed), after adjustment for covariates. Global cognitive function was negatively associated with sympathetic modulation (low-to-high frequency power ratio). Memory performance was positively associated with parasympathetic modulation (high frequency power) and negatively associated with sympathetic modulation (low-to-high frequency power ratio). These associations were independent of age, sex, educational years, diabetes, hypertension and cholinesterase inhibitor use. Cognitive function, especially in the areas of memory, is associated with cardiac autonomic function in AD. Specifically, lower cognitive performance was found to be associated with significantly higher cardiac sympathetic and lower parasympathetic function in AD. Geriatr Gerontol Int 2017; 17: 92-98. © 2015 Japan Geriatrics Society.

Cardiac ryanodine receptor phosphorylation by CaM Kinase II: keeping the balance right.

PubMed

Currie, Susan

2009-06-01

Phosphorylation of the cardiac ryanodine receptor (RyR2) is a key mechanism regulating sarcoplasmic reticulum (SR) Ca2+ release. Differences in opinion have arisen over the importance assigned to specific phosphorylation sites on RyR2, over the kinase (s) suggested to directly phosphorylate RyR2 and surrounding the possibility that altered phosphorylation of RyR2 is associated with contractile dysfunction observed in heart failure. Ca2+/calmodulin dependent protein kinase II (CaMKII) can phosphorylate RyR2 and modulate its activity. This phosphorylation positively modulates cardiac inotropic function but in extreme situations such as heart failure, elevated CaMKII activity can adversely increase Ca2+ release from the SR and lead to arrhythmogenesis. Although other kinases can phosphorylate RyR2, most notably cAMP-dependent protein kinase (PKA), evidence for a key role of CaMKII in mediating RyR2-dependent Ca2+ release is emerging. Future challenges include (i) fully identifying mechanisms of CaMKII interaction with the RyR2 complex and (ii) given the ubiquitous expression of CaMKII, developing selective strategies to modulate RyR2-targeted CaMKII activity and allow improved understanding of its role in normal and diseased heart.

Electrophysiological and structural determinants of electrotonic modulation of repolarization by the activation sequence

PubMed Central

Walton, Richard D.; Benson, Alan P.; Hardy, Matthew E. L.; White, Ed; Bernus, Olivier

2013-01-01

Spatial dispersion of repolarization is known to play an important role in arrhythmogenesis. Electrotonic modulation of repolarization by the activation sequence has been observed in some species and tissue preparations, but to varying extents. Our study sought to determine the mechanisms underlying species- and tissue-dependent electrotonic modulation of repolarization in ventricles. Epi-fluorescence optical imaging of whole rat hearts and pig left ventricular wedges were used to assess epicardial spatial activation and repolarization characteristics. Experiments were supported by computer simulations using realistic geometries. Tight coupling between activation times (AT) and action potential duration (APD) were observed in rat experiments but not in pig. Linear correlation analysis found slopes of −1.03 ± 0.59 and −0.26 ± 0.13 for rat and pig, respectively (p < 0.0001). In rat, maximal dispersion of APD was 11.0 ± 3.1 ms but dispersion of repolarization time (RT) was relatively homogeneous (8.2 ± 2.7, p < 0.0001). However, in pig no such difference was observed between the dispersion of APD and RT (17.8 ± 6.1 vs. 17.7 ± 6.5, respectively). Localized elevations of APD (12.9 ± 8.3%) were identified at ventricular insertion sites of rat hearts both in experiments and simulations. Tissue geometry and action potential (AP) morphology contributed significantly to determining influence of electrotonic modulation. Simulations of a rat AP in a pig geometry decreased the slope of AT and APD relationships by 70.6% whereas slopes were increased by 75.0% when implementing a pig AP in a rat geometry. A modified pig AP, shortened to match the rat APD, showed little coupling between AT and APD with greatly reduced slope compared to the rat AP. Electrotonic modulation of repolarization by the activation sequence is especially pronounced in small hearts with murine-like APs. Tissue architecture and AP morphology play an important role in electrotonic modulation of repolarization. PMID:24115934

Heart Rate Monitor for Portable MP3 Player.

PubMed

Kim, Jaywoo; Lee, Mi-Hee; Lee, Hyoung-Ki; Choi, Kiwan; Bang, Seokwon; Kim, Sangryong

2005-01-01

This paper presents a photoplethysmography sensor based on a heart rate monitor for a portable MP3 player. Two major design issues are addressed: one is to acquire the sensor signal with a proper amplitude despite a wide range of variation and the other is to handle the noise contaminated signal which is caused by a motion artifact. A benchmarking test with a professional medical photoplethysmography sensor shows that our device performs very well in calculating heart rate even though our photoplethysmography sensor module was designed to be cost effective.

Roselle Polyphenols Exert Potent Negative Inotropic Effects via Modulation of Intracellular Calcium Regulatory Channels in Isolated Rat Heart.

PubMed

Lim, Yi-Cheng; Budin, Siti Balkis; Othman, Faizah; Latip, Jalifah; Zainalabidin, Satirah

2017-07-01

Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt max , suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca 2+ channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.

Novel approaches to determine contractile function of the isolated adult zebrafish ventricular cardiac myocyte.

PubMed

Dvornikov, Alexey V; Dewan, Sukriti; Alekhina, Olga V; Pickett, F Bryan; de Tombe, Pieter P

2014-05-01

The zebrafish (Danio rerio) has been used extensively in cardiovascular biology, but mainly in the study of heart development. The relative ease of its genetic manipulation may indicate the suitability of this species as a cost-effective model system for the study of cardiac contractile biology. However, whether the zebrafish heart is an appropriate model system for investigations pertaining to mammalian cardiac contractile structure-function relationships remains to be resolved. Myocytes were isolated from adult zebrafish hearts by enzymatic digestion, attached to carbon rods, and twitch force and intracellular Ca(2+) were measured. We observed the modulation of twitch force, but not of intracellular Ca(2+), by both extracellular [Ca(2+)] and sarcomere length. In permeabilized cells/myofibrils, we found robust myofilament length-dependent activation. Moreover, modulation of myofilament activation-relaxation and force redevelopment kinetics by varied Ca(2+) activation levels resembled that found previously in mammalian myofilaments. We conclude that the zebrafish is a valid model system for the study of cardiac contractile structure-function relationships.

Model for the respiratory modulation of the heart beat-to-beat time interval series

NASA Astrophysics Data System (ADS)

Capurro, Alberto; Diambra, Luis; Malta, C. P.

2005-09-01

In this study we present a model for the respiratory modulation of the heart beat-to-beat interval series. The model consists of a set of differential equations used to simulate the membrane potential of a single rabbit sinoatrial node cell, excited with a periodic input signal with added correlated noise. This signal, which simulates the input from the autonomous nervous system to the sinoatrial node, was included in the pacemaker equations as a modulation of the iNaK current pump and the potassium current iK. We focus at modeling the heart beat-to-beat time interval series from normal subjects during meditation of the Kundalini Yoga and Chi techniques. The analysis of the experimental data indicates that while the embedding of pre-meditation and control cases have a roughly circular shape, it acquires a polygonal shape during meditation, triangular for the Kundalini Yoga data and quadrangular in the case of Chi data. The model was used to assess the waveshape of the respiratory signals needed to reproduce the trajectory of the experimental data in the phase space. The embedding of the Chi data could be reproduced using a periodic signal obtained by smoothing a square wave. In the case of Kundalini Yoga data, the embedding was reproduced with a periodic signal obtained by smoothing a triangular wave having a rising branch of longer duration than the decreasing branch. Our study provides an estimation of the respiratory signal using only the heart beat-to-beat time interval series.

Electrical stimulation of acupuncture points and blood pressure responses to postural changes: a pilot study.

PubMed

Jones, Alice Y M; Kwan, Y L; Leung, Nathan T F; Yu, Rachel P W; Wu, Cindy M Y; Warburton, Darren E R

2011-05-01

Application of transcutaneous electrical stimulation over acupuncture points (Acu-TENS) facilitates heart rate recovery after exercise and restores hemodynamic stability after open heart surgery. The role of Acu-TENS on cardiovascular parameters in response to postural changes has not been reported. To investigate (1) the effect of Acu-TENS on blood pressure responses to -10º head-down postural change and (2) whether such effects were associated with modulation by the autonomic nervous system. Sixteen healthy volunteers, mean age 22.8 (SD, 3.1) years, were subjected to a -10º head-down tilt from the supine position on 3 separate occasions and received in random order the following 3 intervention protocols for 40 minutes before the postural change: Acu-TENS (over bilateral acupuncture points, PC6), sham-TENS (TENS applied to the skin over the patellae), and control (no electrical output from the TENS device applied at PC6). Mean arterial pressure, large artery elasticity index, cardiac output, and heart rate were recorded and compared at different stimulation protocols in the supine and -10º head-down tilt positions. Spectral analysis of heart rate variability was used to determine any modulation by the autonomic nervous system. Change in large artery elasticity index was observed only in the Acu-TENS group (P < .05) and mean arterial pressure appeared most stable during Acu-TENS. Autonomic nervous system modulation was not apparent with spectral analysis, irrespective of intervention. Sympathetic activity predominated in all positions. Acu-TENS seems to reduce blood pressure changes with -10º head-down tilt with concomitant changes in arterial vessel tone.

Combining module based on coherent polarization beam combining.

PubMed

Yang, Yan; Geng, Chao; Li, Feng; Li, Xinyang

2017-03-01

A multiaperture receiver with a phased array is an effective approach to overcome the effect of the random optical disturbance in coherent free-space laser communications, in which one of the key technologies is how to efficiently combine the multiple laser beams received by the phased array antenna. A combining module based on coherent polarization beam combining (CPBC), which can combine multiple laser beams to one laser beam with high combining efficiency and output a linearly polarized beam, is proposed in this paper. The principle of the combining module is introduced, the coherent polarization combining efficiency of CPBC is analyzed, and the performance of the combining module is evaluated. Moreover, the feasibility and the expansibility of the proposed combining module are validated in experiments of CPBC based on active phase-locking.

Heart rate variability measure in breast cancer patients and survivors: A systematic review.

PubMed

Arab, Claudia; Dias, Daniel Penteado Martins; Barbosa, Renata Thaís de Almeida; Carvalho, Tatiana Dias de; Valenti, Vitor Engrácia; Crocetta, Tânia Brusque; Ferreira, Marcelo; Abreu, Luiz Carlos de; Ferreira, Celso

2016-06-01

In the current study, we aimed to review literature findings showing the clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in breast cancer (BC) patients and survivors. We conducted a systematic review according to The PRISMA Statement in Medline, Scopus and Web of Science (_-2015) databases. The search was limited to articles in English language, published in peer-reviewed journals, and with adult age samples only (e.g., women, patients, or survivors, diagnosed with BC in any stage). We included observational studies and randomized trials. Detailed heart rate variability analysis (instruments, data collection protocol, and analysis methods) was required. Search terms included autonomic nervous system, heart rate variability, sympathetic and parasympathetic nervous system, autonomic dysfunction, vagal nervous and breast neoplasms, breast cancer and breast tumor. Twelve studies were included in this review. The clinical importance of cardiac autonomic modulation assessed by heart rate variability analysis in BC patients and survivors is demonstrated by association with effects of BC surgery, and treatments, and the adverse effects of surgery and treatments on survivors (e.g., cardiotoxicity, fatigue, and stress). The strength of evidence of included studies is low: small samples size and heterogeneity, presence of confounders, and observational studies design. The heart rate variability analysis could be used as a complementary non-invasive tool for the early diagnosis and better prognosis of autonomic dysfunction, and survival in BC patients. There are many potential clinical applications of heart rate variability analysis in BC patients, and the employment of such approaches could lead to lower impairment of autonomic function in this individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

SU-E-T-605: RapidArc Combined with DIBH Technique for Thoracic Esophageal Carcinoma: The Potential Value of Target Immobilization and Reduced Lung Density in Dose Escalation.

PubMed

Yin, Y; Liu, T; Zhai, D

2012-06-01

To compare the dosimetric benefits of Rapidarc (RA) combined with deep inspiration breath-hold (DIBH) with those of other standard techniques, including free breathing (FB) during fixed-field intensity modulated radiation therapy (IMRT) and dual arc RA, in the treatment of patients with thoracic esophageal carcinoma (EC). Ten patients with EC underwent computed tomography (CT) scans under 2 respiration conditions: free-breathing (FB) and DIBH. These scans were used to generate 3-dimensional conformal treatment plans. For breath-hold scans, the patients were brought to reproducible respiration levels using active breathing control (ABC) maneuvers. Planning target volumes (PTVs) for FB plans included a 0.5 cm margin for setup plus a 1 cm margin equal to the extent of tumor motion for respiration. PTVs for DIBH plans included a 0.5 cm margin for setup error and a 0.5 cm margin for residual uncertainty in tumor position. Using a dose level of 60 Gy to the PTV, three treatment plans were generated: IMRT-FB, RA-FB and RA-ABC, and the target and normal tissue volumes were compared, as were the dosimetry parameters. On average, the DIBH technique resulted in increased lung volumes compared with FB techniques. There was no significant differences in gross tumor volume between the two breathing states (p > 0.05); but PTV and heart volume were larger for FB than for DIBH (p < 0.05). The overall CI and HI for the RA-ABC plan was slightly inferior to those of the IMRT- FB and RA-FB plans (p < 0.05 each). With DIBH, the heart was partly out of the beam portals and the average mean heart dose was reduced. Compared with conventional FB, RA combined with DIBH significantly reduced cardiac and pulmonary doses without compromising the target coverage and may reduce treatment toxicity, enabling dose escalation in future prospective studies of patients with EC. © 2012 American Association of Physicists in Medicine.

Cross-band broadcasting

DOEpatents

Bynum, Leo; Gramann, Mark R.; Bacon, Larry D.

2015-06-23

A radio communications device has a modulator that modulates each of a number of different carrier signals with the same message. A combiner combines the modulated carrier signals into a single combined output signal. A radio transmitter receives the single combined output signal and in response simultaneously transmits the modulated carrier signals over the air. Other embodiments are also described.

Time-lapse imaging of human heart motion with switched array UWB radar.

PubMed

Brovoll, Sverre; Berger, Tor; Paichard, Yoann; Aardal, Øyvind; Lande, Tor Sverre; Hamran, Svein-Erik

2014-10-01

Radar systems for detection of human heartbeats have mostly been single-channel systems with limited spatial resolution. In this paper, a radar system for ultra-wideband (UWB) imaging of the human heart is presented. To make the radar waves penetrate the human tissue the antenna is placed very close to the body. The antenna is an array with eight elements, and an antenna switch system connects the radar to the individual elements in sequence to form an image. Successive images are used to build up time-lapse movies of the beating heart. Measurements on a human test subject are presented and the heart motion is estimated at different locations inside the body. The movies show rhythmic motion consistent with the beating heart, and the location and shape of the reflections correspond well with the expected response form the heart wall. The spatial dependent heart motion is compared to ECG recordings, and it is confirmed that heartbeat modulations are seen in the radar data. This work shows that radar imaging of the human heart may provide valuable information on the mechanical movement of the heart.

[EFFICIENCY OF COMBINATION OF ROFLUMILAST AND QUERCETIN FOR CORRECTION OXYGEN- INDEPENDENT MECHANISMS AND PHAGOCYTIC ACTIVITY OF MACROPHAGE CELLS OF PATIENTS WITH ACUTE EXACERBATION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHEN COMBINED WITH CORONARY HEART DISEASE].

PubMed

Gerych, P; Yatsyshyn, R

2015-01-01

Studied oxygen independent reaction and phagocytic activity of macrophage cells of patients with chronic obstructive pulmonary disease (COPD) II-III stage when combined with coronary heart disease (CHD). The increasing oxygen independent reactions monocytes and neutrophils and a decrease of the parameters that characterize the functional state of phagocytic cells, indicating a decrease in the functional capacity of macrophage phagocytic system (MPS) in patients with acute exacerbation of COPD, which runs as its own or in combination with stable coronary heart disease angina I-II. FC. Severity immunodeficiency state in terms of cellular component of nonspecific immunity in patients with acute exacerbation of COPD II-III stage in conjunction with the accompanying CHD increases with the progression of heart failure. Inclusion of basic therapy of COPD exacerbation and standard treatment of coronary artery disease and drug combinations Roflumilastand quercetin causes normalization of phagocytic indices MFS, indicating improved immune status and improves myocardial perfusion in terms of daily ECG monitoring.

The Heart of Matter: A Nuclear Chemistry Module. Teacher's Guide.

ERIC Educational Resources Information Center

Viola, Vic; Hearle, Robert

This teacher's guide is designed to provide science teachers with the necessary guidance and suggestions for teaching nuclear chemistry. In this book, the fundamental concepts of nuclear science and the applications of nuclear energy are discussed. The material in this book can be integrated with the other modules in a sequence that helps students…

Measures of Autonomic Nervous System Regulation

DTIC Science & Technology

2011-04-01

and most often used measures of ANS activation encompass non-invasive tools, which measure cardiac, skin conductance, respiratory , and vascular...regulation, osmotic balance, metabolism, digestion, excretion, and cardiac and respiratory activity. The ANS consists of the sympathetic and...modulate heart rate, as a function of the respiratory cycles. Generally, these two systems should be seen as permanently modulating vital functions to

Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension.

PubMed

Namba, Masashi; Kim, Shokei; Zhan, Yumei; Nakao, Takafumi; Iwao, Hiroshi

2002-05-01

The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure.

Aging reduces complexity of heart rate variability assessed by conditional entropy and symbolic analysis.

PubMed

Takahashi, Anielle C M; Porta, Alberto; Melo, Ruth C; Quitério, Robison J; da Silva, Ester; Borghi-Silva, Audrey; Tobaldini, Eleonora; Montano, Nicola; Catai, Aparecida M

2012-06-01

Increasing age is associated with a reduction in overall heart rate variability as well as changes in complexity of physiologic dynamics. The aim of this study was to verify if the alterations in autonomic modulation of heart rate caused by the aging process could be detected by Shannon entropy (SE), conditional entropy (CE) and symbolic analysis (SA). Complexity analysis was carried out in 44 healthy subjects divided into two groups: old (n = 23, 63 ± 3 years) and young group (n = 21, 23 ± 2). It was analyzed SE, CE [complexity index (CI) and normalized CI (NCI)] and SA (0V, 1V, 2LV and 2ULV patterns) during short heart period series (200 cardiac beats) derived from ECG recordings during 15 min of rest in a supine position. The sequences characterized by three heart periods with no significant variations (0V), and that with two significant unlike variations (2ULV) reflect changes in sympathetic and vagal modulation, respectively. The unpaired t test (or Mann-Whitney rank sum test when appropriate) was used in the statistical analysis. In the aging process, the distributions of patterns (SE) remain similar to young subjects. However, the regularity is significantly different; the patterns are more repetitive in the old group (a decrease of CI and NCI). The amounts of pattern types are different: 0V is increased and 2LV and 2ULV are reduced in the old group. These differences indicate marked change of autonomic regulation. The CE and SA are feasible techniques to detect alteration in autonomic control of heart rate in the old group.

Hibiscus and lemon verbena polyphenols modulate appetite-related biomarkers in overweight subjects: a randomized controlled trial.

PubMed

Boix-Castejón, Marina; Herranz-López, María; Pérez Gago, Alberto; Olivares-Vicente, Mariló; Caturla, Nuria; Roche, Enrique; Micol, Vicente

2018-06-04

Plant-derived polyphenols have shown potential to alleviate obesity-related pathologies by a multi-targeted mechanism in animal models and human intervention studies. A dietary supplement based on a combination of Lippia citriodora (LC) and Hibiscus sabdariffa (HS) polyphenolic extracts was assayed in a double blind and placebo-controlled intervention study with 54 overweight subjects. Blood pressure, body weight, height, triceps, biceps and abdominal skinfold thickness, and arm and abdominal circumferences were taken at the baseline, 30 and 60 days of the intervention period. The validated Visual Analogue Scale used to record hunger and satiety-related sensations was passed at the beginning and at 15, 30, 45 and 60 days of the intervention. Subjective health status was assessed through the validated SF-36 questionnaire at the beginning and end of the study. Finally, plasma from fasting blood samples was obtained at the beginning, 30 and 60 days of the study. The results showed an improvement of anthropometric measurements, decreased blood pressure and heart rate and a more positive perception in the overall health status. We also observed that plant polyphenols increased anorexigenic hormones (glucagon-like peptide-1) and decreased orexigenic hormones (ghrelin). Based on previous evidence we postulate that AMP-activated protein kinase may have a role in such effects through its capability to modulate energy homeostasis, total daily energy expenditure and lipid management. Although further research may be required, we propose that this polyphenolic combination may be used for weight management by increasing long-term weight loss maintenance through the modulation of appetite biomarkers. This may help to avoid the undesired weight regain typical of calorie restriction diets.

Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure.

PubMed

Ichige, Marcelo H A; Santos, Carla R; Jordão, Camila P; Ceroni, Alexandre; Negrão, Carlos E; Michelini, Lisete C

2016-11-01

Heart Failure (HF) is accompanied by reduced ventricular function, activation of compensatory neurohormonal mechanisms and marked autonomic dysfunction characterized by exaggerated sympathoexcitation and reduced parasympathetic activity. With 6 weeks of exercise training, HF-related loss of choline acetyltransferase (ChAT)-positive vagal preganglionic neurones is avoided, restoring the parasympathetic tonus to the heart, and the immunoreactivity of dopamine β-hydroxylase-positive premotor neurones that drive sympathetic outflow to the heart is reduced. Training-induced correction of autonomic dysfunction occurs even with the persistence of abnormal ventricular function. Strong positive correlation between improved parasympathetic tonus to the heart and increased ChAT immunoreactivity in vagal preganglionic neurones after training indicates this is a crucial mechanism to restore autonomic function in heart failure. Exercise training is an efficient tool to attenuate sympathoexcitation, a hallmark of heart failure (HF). Although sympathetic modulation in HF is widely studied, information regarding parasympathetic control is lacking. We examined the combined effects of sympathetic and vagal tonus to the heart in sedentary (Sed) and exercise trained (ET) HF rats and the contribution of respective premotor and preganglionic neurones. Wistar rats submitted to coronary artery ligation or sham surgery were assigned to training or sedentary protocols for 6 weeks. After haemodynamic, autonomic tonus (atropine and atenolol i.v.) and ventricular function determinations, brains were collected for immunoreactivity assays (choline acetyltransferase, ChATir; dopamine β-hydroxylase, DBHir) and neuronal counting in the dorsal motor nucleus of vagus (DMV), nucleus ambiguus (NA) and rostroventrolateral medulla (RVLM). HF-Sed vs. SHAM-Sed exhibited decreased exercise capacity, reduced ejection fraction, increased left ventricle end diastolic pressure, smaller positive and negative dP/dt, decreased intrinsic heart rate (IHR), lower parasympathetic and higher sympathetic tonus, reduced preganglionic vagal neurones and ChATir in the DMV/NA, and increased RVLM DBHir. Training increased treadmill performance, normalized autonomic tonus and IHR, restored the number of DMV and NA neurones and corrected ChATir without affecting ventricular function. There were strong positive correlations between parasympathetic tonus and ChATir in NA and DMV. RVLM DBHir was also normalized by training, but there was no change in neurone number and no correlation with sympathetic tonus. Training-induced preservation of preganglionic vagal neurones is crucial to normalize parasympathetic activity and restore autonomic balance to the heart even in the persistence of cardiac dysfunction. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Structural basis for modulation and agonist specificity of HCN pacemaker channels.

PubMed

Zagotta, William N; Olivier, Nelson B; Black, Kevin D; Young, Edgar C; Olson, Rich; Gouaux, Eric

2003-09-11

The family of hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels are crucial for a range of electrical signalling, including cardiac and neuronal pacemaker activity, setting resting membrane electrical properties and dendritic integration. These nonselective cation channels, underlying the I(f), I(h) and I(q) currents of heart and nerve cells, are activated by membrane hyperpolarization and modulated by the binding of cyclic nucleotides such as cAMP and cGMP. The cAMP-mediated enhancement of channel activity is largely responsible for the increase in heart rate caused by beta-adrenergic agonists. Here we have investigated the mechanism underlying this modulation by studying a carboxy-terminal fragment of HCN2 containing the cyclic nucleotide-binding domain (CNBD) and the C-linker region that connects the CNBD to the pore. X-ray crystallographic structures of this C-terminal fragment bound to cAMP or cGMP, together with equilibrium sedimentation analysis, identify a tetramerization domain and the mechanism for cyclic nucleotide specificity, and suggest a model for ligand-dependent channel modulation. On the basis of amino acid sequence similarity to HCN channels, the cyclic nucleotide-gated, and eag- and KAT1-related families of channels are probably related to HCN channels in structure and mechanism.

Utility of the Seattle Heart Failure Model in patients with advanced heart failure.

PubMed

Kalogeropoulos, Andreas P; Georgiopoulou, Vasiliki V; Giamouzis, Grigorios; Smith, Andrew L; Agha, Syed A; Waheed, Sana; Laskar, Sonjoy; Puskas, John; Dunbar, Sandra; Vega, David; Levy, Wayne C; Butler, Javed

2009-01-27

The aim of this study was to validate the Seattle Heart Failure Model (SHFM) in patients with advanced heart failure (HF). The SHFM was developed primarily from clinical trial databases and extrapolated the benefit of interventions from published data. We evaluated the discrimination and calibration of SHFM in 445 advanced HF patients (age 52 +/- 12 years, 68.5% male, 52.4% white, ejection fraction 18 +/- 8%) referred for cardiac transplantation. The primary end point was death (n = 92), urgent transplantation (n = 14), or left ventricular assist device (LVAD) implantation (n = 3); a secondary analysis was performed on mortality alone. Patients were receiving optimal therapy (angiotensin-II modulation 92.8%, beta-blockers 91.5%, aldosterone antagonists 46.3%), and 71.0% had an implantable device (defibrillator 30.4%, biventricular pacemaker 3.4%, combined 37.3%). During a median follow-up of 21 months, 109 patients (24.5%) had an event. Although discrimination was adequate (c-statistic >0.7), the SHFM overall underestimated absolute risk (observed vs. predicted event rate: 11.0% vs. 9.2%, 21.0% vs. 16.6%, and 27.9% vs. 22.8% at 1, 2, and 3 years, respectively). Risk underprediction was more prominent in patients with an implantable device. The SHFM had different calibration properties in white versus black patients, leading to net underestimation of absolute risk in blacks. Race-specific recalibration improved the accuracy of predictions. When analysis was restricted to mortality, the SHFM exhibited better performance. In patients with advanced HF, the SHFM offers adequate discrimination, but absolute risk is underestimated, especially in blacks and in patients with devices. This is more prominent when including transplantation and LVAD implantation as an end point.

Effects of Respiratory Training on Heart Rate Variability and Baroreflex Sensitivity in Individuals With Chronic Spinal Cord Injury.

PubMed

Legg Ditterline, Bonnie E; Aslan, Sevda C; Randall, David C; Harkema, Susan J; Castillo, Camilo; Ovechkin, Alexander V

2018-03-01

To evaluate the effects of pressure threshold respiratory training (RT) on heart rate variability and baroreflex sensitivity in persons with chronic spinal cord injury (SCI). Before-after intervention case-controlled clinical study. SCI research center and outpatient rehabilitation unit. Participants (N=44) consisted of persons with chronic SCI ranging from C2 to T11 who participated in RT (n=24), and untrained control subjects with chronic SCI ranging from C2 to T9 (n=20). A total of 21±2 RT sessions performed 5 days a week during a 4-week period using a combination of pressure threshold inspiratory and expiratory devices. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1 ), and beat-to-beat arterial blood pressure and heart rate changes during the 5-second-long maximum expiratory pressure maneuver (5s MEP) and the sit-up orthostatic stress test, acquired before and after the RT program. In contrast to the untrained controls, individuals in the RT group experienced significantly increased FVC and FEV 1 (both P<.01) in association with improved quality of sleep, cough, and speech. Sympathetically (phase II) and parasympathetically (phase IV) mediated baroreflex sensitivity both significantly (P<.05) increased during the 5s MEP. During the orthostatic stress test, improved autonomic control over heart rate was associated with significantly increased sympathetic and parasympathetic modulation (low- and high-frequency change: P<.01 and P<.05, respectively). Inspiratory-expiratory pressure threshold RT is a promising technique to positively affect both respiratory and cardiovascular dysregulation observed in persons with chronic SCI. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Is autonomic modulation different between European and Chinese astronauts?

PubMed

Liu, Jiexin; Li, Yongzhi; Verheyden, Bart; Chen, Shanguang; Chen, Zhanghuang; Gai, Yuqing; Liu, Jianzhong; Gao, Jianyi; Xie, Qiong; Yuan, Ming; Li, Qin; Li, Li; Aubert, André E

2015-01-01

The objective was to investigate autonomic control in groups of European and Chinese astronauts and to identify similarities and differences. Beat-to-beat heart rate and finger blood pressure, brachial blood pressure, and respiratory frequency were measured from 10 astronauts (five European taking part in three different space missions and five Chinese astronauts taking part in two different space missions). Data recording was performed in the supine and standing positions at least 10 days before launch, and 1, 3, and 10 days after return. Cross-correlation analysis of heart rate and systolic pressure was used to assess cardiac baroreflex modulation. A fixed breathing protocol was performed to measure respiratory sinus arrhythmia and low-frequency power of systolic blood pressure variability. Although baseline cardiovascular parameters before spaceflight were similar in all astronauts in the supine position, a significant increase in sympathetic activity and a decrease in vagal modulation occurred in the European astronauts when standing; spaceflight resulted in a remarkable vagal decrease in European astronauts only. Similar baseline supine and standing values for heart rate, mean arterial pressure, and respiratory frequency were shown in both groups. Standing autonomic control was based on a balance of higher vagal and sympathetic modulation in European astronauts. Post-spaceflight orthostatic tachycardia was observed in all European astronauts, whereas post-spaceflight orthostatic tachycardia was significantly reduced in Chinese astronauts. The basis for orthostatic intolerance is not apparent; however, many possibilities can be considered and need to be further investigated, such as genetic diversities between races, astronaut selection, training, and nutrition, etc.

Is Autonomic Modulation Different between European and Chinese Astronauts?

PubMed Central

Liu, Jiexin; Li, Yongzhi; Verheyden, Bart; Chen, Shanguang; Chen, Zhanghuang; Gai, Yuqing; Liu, Jianzhong; Gao, Jianyi; Xie, Qiong; Yuan, Ming; Li, Qin; Li, Li; Aubert, André E.

2015-01-01

Purpose The objective was to investigate autonomic control in groups of European and Chinese astronauts and to identify similarities and differences. Methods Beat-to-beat heart rate and finger blood pressure, brachial blood pressure, and respiratory frequency were measured from 10 astronauts (five European taking part in three different space missions and five Chinese astronauts taking part in two different space missions). Data recording was performed in the supine and standing positions at least 10 days before launch, and 1, 3, and 10 days after return. Cross-correlation analysis of heart rate and systolic pressure was used to assess cardiac baroreflex modulation. A fixed breathing protocol was performed to measure respiratory sinus arrhythmia and low-frequency power of systolic blood pressure variability. Results Although baseline cardiovascular parameters before spaceflight were similar in all astronauts in the supine position, a significant increase in sympathetic activity and a decrease in vagal modulation occurred in the European astronauts when standing; spaceflight resulted in a remarkable vagal decrease in European astronauts only. Similar baseline supine and standing values for heart rate, mean arterial pressure, and respiratory frequency were shown in both groups. Standing autonomic control was based on a balance of higher vagal and sympathetic modulation in European astronauts. Conclusion Post-spaceflight orthostatic tachycardia was observed in all European astronauts, whereas post-spaceflight orthostatic tachycardia was significantly reduced in Chinese astronauts. The basis for orthostatic intolerance is not apparent; however, many possibilities can be considered and need to be further investigated, such as genetic diversities between races, astronaut selection, training, and nutrition, etc. PMID:25799561

Physical therapy for airway clearance improves cardiac autonomic modulation in children with acute bronchiolitis

PubMed Central

Jacinto, Cynthia P.; Gastaldi, Ada C.; Aguiar, Daniela Y.; Maida, Karina D.; Souza, Hugo C. D.

2013-01-01

Background The effects of physical therapy on heart rate variability (HRV), especially in children, are still inconclusive. Objective We investigated the effects of conventional physical therapy (CPT) for airway clearance and nasotracheal suction on the HRV of pediatric patients with acute bronchiolitis. Method 24 children were divided into two groups: control group (CG, n=12) without respiratory diseases and acute bronchiolitis group (BG, n=12). The heart rate was recorded in the BG at four different moments: basal recording (30 minutes), 5 minutes after the CPT (10 minutes), 5 minutes after nasotracheal suction (10 minutes), and 40 minutes after nasotracheal suction (30 minutes). The CG was subjected to the same protocol, except for nasotracheal suction. To assess the HRV, we used spectrum analysis, which decomposes the heart rate oscillations into frequency bands: low frequency (LF=0.04-0.15Hz), which corresponds mainly to sympathetic modulation; and high frequency (HF=0.15-1.2Hz), corresponding to vagal modulation. Results Under baseline conditions, the BG showed higher values in LF oscillations, lower values in HF oscillations, and increased LF/HF ratio when compared to the CG. After CPT, the values for HRV in the BG were similar to those observed in the CG during basal recording. Five minutes after nasotracheal suction, the BG showed a decrease in LF and HF oscillations; however, after 40 minutes, the values were similar to those observed after application of CPT. Conclusions The CPT and nasotracheal suction, both used for airway clearance, promote improvement in autonomic modulation of HRV in children with acute bronchiolitis. PMID:24271093

Distinguishing Health Benefits of Eicosapentaenoic and Docosahexaenoic Acids

PubMed Central

Russell, Fraser D.; Bürgin-Maunder, Corinna S.

2012-01-01

Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) are recommended for management of patients with wide-ranging chronic diseases, including coronary heart disease, rheumatoid arthritis, dementia, and depression. Increased consumption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is recommended by many health authorities to prevent (up to 0.5 g/day) or treat chronic disease (1.0 g/day for coronary heart disease; 1.2–4 g/day for elevated triglyceride levels). Recommendations for dietary intake of LC n-3 PUFAs are often provided for α-linolenic acid, and for the combination of EPA and DHA. However, many studies have also reported differential effects of EPA, DHA and their metabolites in the clinic and at the laboratory bench. The aim of this article is to review studies that have identified divergent responses to EPA and DHA, and to explore reasons for these differences. In particular, we review potential contributing factors such as differential membrane incorporation, modulation of gene expression, activation of signaling pathways and metabolite formation. We suggest that there may be future opportunity to refine recommendations for intake of individual LC n-3 PUFAs. PMID:23203276

Development of an Arbitrary Waveform Membrane Stretcher for Dynamic Cell Culture

PubMed Central

Lau, Jason J.; Wang, Raymond M.; Black, Lauren D.

2014-01-01

In this paper, a novel cell stretcher design that mimics the real-time stretch of the heart wall is introduced. By culturing cells under stretched conditions that mimics the mechanical aspects of the native cardiac environment, better understanding on the role of biomechanical signaling on cell development can be achieved. The device utilizes a moving magnet linear actuator controlled through pulse-width modulated power combined with an automated closed loop feedback system for accurate generation of a designated mechanical stretch profile. The system’s capability to stretch a cell culture membrane and accuracy of the designated frequency and waveform production for cyclic stretching were evaluated. Temperature and degradation assessments as well as a scalable design demonstrated the system’s cell culture application for long term, in vitro studies. PMID:24473700

Accurate positioning of long, flexible ARM's (Articulated Robotic Manipulator)

NASA Technical Reports Server (NTRS)

Malachowski, Michael J.

1988-01-01

An articulated robotic manipulator (ARM) system is being designed for space applications. Work being done on a concept utilizing an infinitely stiff laser beam for position reference is summarized. The laser beam is projected along the segments of the ARM, and the position is sensed by the beam rider modules (BRM) mounted on the distal ends of the segments. The BRM concept is the heart of the system. It utilizes a combination of lateral displacements and rotational and distance measurement sensors. These determine the relative position of the two ends of the segments with respect to each other in six degrees of freedom. The BRM measurement devices contain microprocessor controlled data acquisition and active positioning components. An indirect adaptive controller is used to accurately control the position of the ARM.

The Vascular Marker Soluble Fms-like Tyrosine Kinase 1 is Associated with Disease Severity and Adverse Outcomes in Chronic Heart Failure

PubMed Central

Ky, Bonnie; French, Benjamin; Ruparel, Kosha; Sweitzer, Nancy K.; Fang, James C.; Levy, Wayne C.; Sawyer, Douglas B.; Cappola, Thomas P.

2011-01-01

Objectives We sought to evaluate placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) as clinical biomarkers in chronic heart failure (HF). Background Vascular remodeling is a crucial compensatory mechanism in chronic HF. The angiogenic ligand PlGF and its target receptor fms-like tyrosine kinase 1 (Flt-1) modulate vascular growth and function, but their relevance in human HF is undefined. Methods We measured plasma PlGF and sFlt-1 in 1,403 patients from the Penn Heart Failure Study, a multi-center cohort of chronic systolic HF. Subjects were followed for death, cardiac transplantation, or ventricular assist device placement over a median follow-up of 2 years. Results sFlt-1 was independently associated with measures of HF severity, including NYHA Class (p<0.01) and BNP (p<0.01). Patients in the 4th quartile of sFlt-1 (>379pg/ml) had a 6.17-fold increased risk of adverse outcomes (p<0.01). This association was robust, even after adjustment for the Seattle Failure Model (HR 2.54, 95%CI 1.76–2.27, p<0.01) and clinical confounders including heart failure etiology (HR 1.67, 95%CI 1.06–2.63, p=0.03). Combined assessment of sFlt-1 and BNP exhibited high predictive accuracy at 1-year (AUC 0.791, 95%CI 0.752–0.831), that was greater than either marker alone (p<0.01 and p=0.03, respectively). In contrast, PlGF was not an independent marker of disease severity or outcomes. Conclusions Our findings support a role for sFlt-1 in the biology of human heart failure. With additional study, circulating sFlt-1 may emerge as a clinically useful biomarker to assess the influence of vascular remodeling on clinical outcomes. PMID:21757116

[Endothelial dysfunction as a marker of vascular aging syndrome on the background of hypertension, coronary heart disease, gout and obesity].

PubMed

Vatseba, M O

2013-09-01

Under observation were 40 hypertensive patients with coronary heart disease, gout and obesity I and II degree. Patients with hypertension in combination with coronary heart disease, gout and obesity, syndrome of early vascular aging is shown by increased stiffness of arteries, increased peak systolic flow velocity, pulse blood presure, the thickness of the intima-media complex, higher level endotelinemia and reduced endothelial vasodilation. Obtained evidence that losartan in complex combination with basic therapy and metamaks in complex combination with basic therapy positively affect the elastic properties of blood vessels and slow the progression of early vascular aging syndrome.

The effect of resistance training on clinical outcomes in heart failure: A systematic review and meta-analysis.

PubMed

Jewiss, D; Ostman, C; Smart, N A

2016-10-15

To quantify the change in effect sizes, for selected clinical outcome measures, in people with heart failure, from resistance exercise, either in isolation, or in combination with aerobic training. Most exercise training data in heart failure, relates to aerobic exercise, we sought to provide current evidence for the benefits of resistance training in this population. We conducted a MEDLINE search (1985 to May 1, 2016), for exercise based rehabilitation trials in heart failure, using search terms 'resistance training, combined training, left ventricular dysfunction, peak VO2, cardio-myopathy and systolic heart dysfunction'. The 27 included studies provided a total of 2321 participants, 1172 in an intervention and 1149 in either sedentary controls or aerobic exercise only groups, producing over 31,263 patient-hours of training. Mortality, hospitalization, resting blood pressure and Left ventricular fraction were all unchanged with resistance or combined aerobic and resistance training. Peak VO2 was improved in combined exercise vs. control MD of 1.43ml·kg(-1)·min(-1) (95% CI 0.63, 2.23, p=0.0004; and in resistance vs. control MD 3.99ml·kg(-1)·min(-1) (95% CI 1.47, 6.51, p=0.002). Quality of Life (MLwHFQ) was improved in combined vs. control MD -8.31 (95% CI -14.3, -2.33, p=0.006). Six-minute walk distance was improved combined exercise vs. control, MD 13.49m (95% CI 1.13, 25.84, p=0.03); and resistance vs. control MD 41.77m (95% CI 21.90, 61.64, p<0.0001): SMD 1.25 (95%CI 0.53, 1.98, p=0.0007). Resistance only or combined training improves peak VO2, quality of life and walking performance in heart failure patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A-kinase anchoring proteins that regulate cardiac remodeling.

PubMed

Carnegie, Graeme K; Burmeister, Brian T

2011-11-01

In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation-contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multiprotein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function.

A-Kinase Anchoring Proteins That Regulate Cardiac Remodeling

PubMed Central

Carnegie, Graeme K.; Burmeister, Brian T.

2012-01-01

In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation–contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multi-protein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function. PMID:22075671

[The effect of combined treatment with the use of magnetotherapy on the systemic hemodynamics of patients with ischemic heart disease and spinal osteochondrosis].

PubMed

Dudchenko, M A; Vesel'skiĭ, I Sh; Shtompel', V Iu

1992-05-01

The authors examined 66 patients with ischemic heart disease and concomitant cervico-thoracic osteochondrosis and 22 patients without osteochondrosis. Differences were revealed in values of the systemic hemodynamics with prevalence of the hypokinetic type in patients with combined pathology. Inclusion of magnetotherapy in the treatment complex of patients with ischemic heart disease and osteochondrosis favours clinical improvement, normalization of indices of central and regional blood circulation.

Hyperthyroidism is characterized by both increased sympathetic and decreased vagal modulation of heart rate: evidence from spectral analysis of heart rate variability.

PubMed

Chen, Jin-Long; Chiu, Hung-Wen; Tseng, Yin-Jiun; Chu, Woei-Chyn

2006-06-01

The clinical manifestations of hyperthyroidism resemble those of the hyperadrenergic state. This study was designed to evaluate the impact of hyperthyroidism on the autonomic nervous system (ANS) and to investigate the relationship between serum thyroid hormone concentrations and parameters of spectral heart rate variability (HRV) analysis in hyperthyroidism. Thirty-two hyperthyroid Graves' disease patients (mean age 31 years) and 32 sex-, age-, and body mass index (BMI)-matched normal control subjects were recruited to receive one-channel electrocardiogram (ECG) recording. The cardiac autonomic nervous function was evaluated by the spectral analysis of HRV, which indicates the autonomic modulation of the sinus node. The correlation coefficients between serum thyroid hormone concentrations and parameters of the spectral HRV analysis were also computed. The hyperthyroid patients revealed significant differences (P < 0.001) compared with the controls in the following HRV parameters: a decrease in total power (TP), very low frequency power (VLF), low frequency power (LF), high frequency power (HF), and HF in normalized units (HF%); and an increase in LF in normalized units (LF%) and in the ratio of LF to HF (LF/HF). After correction of hyperthyroidism in 28 patients, all of the above parameters were restored to levels comparable to those of the controls. In addition, serum thyroid hormone concentrations showed significant correlations with spectral HRV parameters. Hyperthyroidism is in a sympathovagal imbalanced state, characterized by both increased sympathetic and decreased vagal modulation of the heart rate. These autonomic dysfunctions can be detected simultaneously by spectral analysis of HRV, and the spectral HRV parameters could reflect the disease severity in hyperthyroid patients.

Acute rosiglitazone treatment is cardioprotective against ischemia-reperfusion injury by modulating AMPK, Akt, and JNK signaling in nondiabetic mice.

PubMed

Morrison, Alex; Yan, Xiaoyan; Tong, Chao; Li, Ji

2011-09-01

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been demonstrated to possess cardioprotective properties during ischemia-reperfusion. However, this notion remains controversial as recent evidence has suggested an increased risk in cardiac events associated with long-term use of RGZ in patients with type 2 diabetes. In this study, we tested the hypothesis that acute RGZ treatment is beneficial during I/R by modulating cardioprotective signaling pathways in a nondiabetic mouse model. RGZ (1 μg/g) was injected intravenously via the tail vein 5 min before reperfusion. Myocardial infarction was significantly reduced in mice treated with RGZ compared with vehicle controls (8.7% ± 1.1% vs. 20.2% ± 2.5%, P < 0.05). Moreover, isolated hearts were subjected to 20 min of global, no-flow ischemia in an ex vivo heart perfusion system. Postischemic recovery was significantly improved with RGZ treatment administered at the onset of reperfusion compared with vehicle (P < 0.001). Immunoblot analysis data revealed that the levels of both phospho-AMP-activated protein kinase (Thr(172)) and phospho-Akt (Ser(473)) were significantly upregulated when RGZ was administered 5 min before reperfusion compared with vehicle. On the other hand, inflammatory signaling [phospho-JNK (Thr(183)/Tyr(185))] was significantly downregulated as a result of RGZ treatment compared with vehicle (P < 0.05). Intriguingly, pretreatment with the selective PPAR-γ inhibitor GW-9662 (1 μg/g iv) 10 min before reperfusion significantly attenuated these beneficial effects of RGZ on the ischemic heart. Taken together, acute treatment with RGZ can reduce ischemic injury in a nondiabetic mouse heart via modulation of AMP-activated protein kinase, Akt, and JNK signaling pathways, which is dependent on PPAR-γ activation.

Dosimetric comparison of normal structures associated with accelerated partial breast irradiation and whole breast irradiation delivered by intensity modulated radiotherapy for early breast cancer after breast conserving surgery.

PubMed

Wu, S; He, Z; Guo, J; Li, F; Lin, Q; Guan, X

2014-01-01

To assess the heart and lung dosimetry results associated with accelerated partial breast irradiation intensity-modulated radiotherapy (APBI-IMRT) and whole breast field-in-field intensity-modulated radiotherapy (WBI-FIF-IMRT). A total of 29 patients with early-stage breast cancer after lumpectomy were included in this study. APBI-IMRT and WBI-FIF-IMRT plans were generated for each patient. The dosimetric parameters of ipsilateral lung and heart in both plans were then compared with and without radiobiological correction. With and without radiobiological correction, the volume of ipsilateral lung showed a substantially lower radiation exposure in APBI-IMRT with moderate to high doses (P < 0.05) but non-significant increases in volume of ipsilateral lung in 2.5 Gy than WBI-FIF-IMRT (P > 0.905).There was no significant difference in volume of ipsilateral lung receiving 1, 2.5, and 5 Gy between APBI-IMRT and WBI (P > 0.05) in patients with medial tumor location, although APBI-IMRT exposed more lung to 2.5 and 5 Gy. APBI-IMRT significantly decreases the volume of heart receiving low to high doses in left-sided breast cancer (P < 0.05). APBI-IMRT can significantly spare the volume of heart and ipsilateral lung receiving moderate and high dose. Non-significant increases in volume of the ipsilateral lung exposed to low doses of radiation were observed for APBI-IMRT in comparison to WBI-FIF-IMRT, particularly in patients with medial tumor location. With the increasing interest in APBI-IMRT, our data may help clinicians individualize patient treatment decisions.

Combined effects of family history of CVD and heart rate on ischemic stroke incidence among Inner Mongolians in China.

PubMed

Zhou, Yipeng; Tian, Yunfan; Zhong, Chongke; Batu, Buren; Xu, Tian; Li, Hongmei; Zhang, Mingzhi; Wang, Aili; Zhang, Yonghong

2016-05-01

This study aimed to evaluate the combined effects of family history of cardiovascular diseases (FHCVD) and heart rate on ischemic stroke incidence among Inner Mongolians in China. A prospective cohort study was conducted among 2589 participants aged 20 years and older from Inner Mongolia, China. The participants were divided into four groups according to status of FHCVD and heart rate and followed up from June 2002 to July 2012. Cox proportional hazards models were used to evaluate the combined effects of FHCVD and heart rate on the incidence of ischemic stroke. A total of 76 ischemic stroke occurred during the follow-up period. The observed ischemic stroke cases tended to be older and male, and had higher prevalence of smoking, drinking, hypertension and FHCVD as well as higher systolic and diastolic blood pressures at baseline compared with those who did not experience ischemic stroke. Age- and gender-adjusted hazard ratio (95% confidence interval) of ischemic stroke in the participants with both FHCVD and heart rate ≥ 80 were 2.89 (1.51-5.53), compared with those without FHCVD and heart rate < 80. After multiple adjustment, the association between ischemic stroke risk and both FHCVD and heart rate ≥ 80 remained statistically significant (hazard ratio, 2.47; 95% confidence interval: 1.22-5.01). Our main finding that participants with both FHCVD and faster heart rate have the highest risk of ischemic stroke suggests that faster heart rate may increase the risk of ischemic stroke among people with FHCVD.

Combined Angiotensin Receptor Antagonism and Neprilysin Inhibition

PubMed Central

Hubers, Scott A.; Brown, Nancy J.

2016-01-01

Heart failure affects approximately 5.7 million people in the United States alone. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists have improved mortality in patients with heart failure and reduced ejection fraction, but mortality remains high. In July 2015, the FDA approved the first of a new class of drugs for the treatment of heart failure; valsartan/sacubitril (formerly known as LCZ696 and currently marketed by Novartis as Entresto) combines the angiotensin receptor blocker valsartan and the neprilysin inhibitor prodrug sacubitril in a 1:1 ratio in a sodium supramolecular complex. Sacubitril is converted by esterases to LBQ657, which inhibits neprilysin, the enzyme responsible for the degradation of the natriuretic peptides and many other vasoactive peptides. Thus, this combined angiotensin receptor antagonist and neprilysin inhibitor addresses two of the pathophysiologic mechanisms of heart failure - activation of the renin-angiotensin-aldosterone system and decreased sensitivity to natriuretic peptides. In the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial, valsartan/sacubitril significantly reduced mortality and hospitalization for heart failure, as well as blood pressure, compared to enalapril in patients with heart failure, reduced ejection fraction, and an elevated circulating level of brain natriuretic peptide or N-terminal pro-brain natriuretic peptide. Ongoing clinical trials are evaluating the role of valsartan/sacubitril in the treatment of heart failure with preserved ejection fraction and hypertension. We review here the mechanisms of action of valsartan/sacubitril, the pharmacologic properties of the drug, and its efficacy and safety in the treatment of heart failure and hypertension. PMID:26976916

Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment

PubMed Central

Hasan, Al Shaimaa; Luo, Lan; Yan, Chen; Zhang, Tian-Xia; Urata, Yoshishige; Goto, Shinji; Mangoura, Safwat A.; Abdel-Raheem, Mahmoud H.; Zhang, Shouhua; Li, Tao-Sheng

2016-01-01

Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages), but decreased the expression of CD86 (a marker for M1 macrophages) 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair. PMID:27764217

MURC, a Muscle-Restricted Coiled-Coil Protein That Modulates the Rho/ROCK Pathway, Induces Cardiac Dysfunction and Conduction Disturbance▿

PubMed Central

Ogata, Takehiro; Ueyama, Tomomi; Isodono, Koji; Tagawa, Masashi; Takehara, Naofumi; Kawashima, Tsuneaki; Harada, Koichiro; Takahashi, Tomosaburo; Shioi, Tetsuo; Matsubara, Hiroaki; Oh, Hidemasa

2008-01-01

We identified a novel muscle-restricted putative coiled-coil protein, MURC, which is evolutionarily conserved from frog to human. MURC was localized to the cytoplasm with accumulation in the Z-line of the sarcomere in the murine adult heart. MURC mRNA expression in the heart increased during the developmental process from the embryonic stage to adulthood. In response to pressure overload, MURC mRNA expression increased in the hypertrophied heart. Using the yeast two-hybrid system, we identified the serum deprivation response (SDPR) protein, a phosphatidylserine-binding protein, as a MURC-binding protein. MURC induced activation of the RhoA/ROCK pathway, which modulated serum response factor-mediated atrial natriuretic peptide (ANP) expression and myofibrillar organization. SDPR augmented MURC-induced transactivation of the ANP promoter in cardiomyocytes, and RNA interference of SDPR attenuated the action of MURC on the ANP promoter. Transgenic mice expressing cardiac-specific MURC (Tg-MURC) exhibited cardiac contractile dysfunction and atrioventricular (AV) conduction disturbances with atrial chamber enlargement, reduced thickness of the ventricular wall, and interstitial fibrosis. Spontaneous episodes of atrial fibrillation and AV block were observed in Tg-MURC mice. These findings indicate that MURC modulates RhoA signaling and that MURC plays an important role in the development of cardiac dysfunction and conduction disturbance with increased vulnerability to atrial arrhythmias. PMID:18332105

MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK pathway, induces cardiac dysfunction and conduction disturbance.

PubMed

Ogata, Takehiro; Ueyama, Tomomi; Isodono, Koji; Tagawa, Masashi; Takehara, Naofumi; Kawashima, Tsuneaki; Harada, Koichiro; Takahashi, Tomosaburo; Shioi, Tetsuo; Matsubara, Hiroaki; Oh, Hidemasa

2008-05-01

We identified a novel muscle-restricted putative coiled-coil protein, MURC, which is evolutionarily conserved from frog to human. MURC was localized to the cytoplasm with accumulation in the Z-line of the sarcomere in the murine adult heart. MURC mRNA expression in the heart increased during the developmental process from the embryonic stage to adulthood. In response to pressure overload, MURC mRNA expression increased in the hypertrophied heart. Using the yeast two-hybrid system, we identified the serum deprivation response (SDPR) protein, a phosphatidylserine-binding protein, as a MURC-binding protein. MURC induced activation of the RhoA/ROCK pathway, which modulated serum response factor-mediated atrial natriuretic peptide (ANP) expression and myofibrillar organization. SDPR augmented MURC-induced transactivation of the ANP promoter in cardiomyocytes, and RNA interference of SDPR attenuated the action of MURC on the ANP promoter. Transgenic mice expressing cardiac-specific MURC (Tg-MURC) exhibited cardiac contractile dysfunction and atrioventricular (AV) conduction disturbances with atrial chamber enlargement, reduced thickness of the ventricular wall, and interstitial fibrosis. Spontaneous episodes of atrial fibrillation and AV block were observed in Tg-MURC mice. These findings indicate that MURC modulates RhoA signaling and that MURC plays an important role in the development of cardiac dysfunction and conduction disturbance with increased vulnerability to atrial arrhythmias.

Poly(A) tail length regulates PABPC1 expression to tune translation in the heart.

PubMed

Chorghade, Sandip; Seimetz, Joseph; Emmons, Russell; Yang, Jing; Bresson, Stefan M; Lisio, Michael De; Parise, Gianni; Conrad, Nicholas K; Kalsotra, Auinash

2017-06-27

The rate of protein synthesis in the adult heart is one of the lowest in mammalian tissues, but it increases substantially in response to stress and hypertrophic stimuli through largely obscure mechanisms. Here, we demonstrate that regulated expression of cytosolic poly(A)-binding protein 1 (PABPC1) modulates protein synthetic capacity of the mammalian heart. We uncover a poly(A) tail-based regulatory mechanism that dynamically controls PABPC1 protein synthesis in cardiomyocytes and thereby titrates cellular translation in response to developmental and hypertrophic cues. Our findings identify PABPC1 as a direct regulator of cardiac hypertrophy and define a new paradigm of gene regulation in the heart, where controlled changes in poly(A) tail length influence mRNA translation.

Mechanical Circulatory Support for Advanced Heart Failure: Are We about to Witness a New "Gold Standard"?

PubMed

Capoccia, Massimo

2016-12-12

The impact of left ventricular assist devices (LVADs) for the treatment of advanced heart failure has played a significant role as a bridge to transplant and more recently as a long-term solution for non-eligible candidates. Continuous flow left ventricular assist devices (CF-LVADs), based on axial and centrifugal design, are currently the most popular devices in view of their smaller size, increased reliability and higher durability compared to pulsatile flow left ventricular assist devices (PF-LVADs). The trend towards their use is increasing. Therefore, it has become mandatory to understand the physics and the mathematics behind their mode of operation for appropriate device selection and simulation set up. For this purpose, this review covers some of these aspects. Although very successful and technologically advanced, they have been associated with complications such as pump thrombosis, haemolysis, aortic regurgitation, gastro-intestinal bleeding and arterio-venous malformations. There is perception that the reduced arterial pulsatility may be responsible for these complications. A flow modulation control approach is currently being investigated in order to generate pulsatility in rotary blood pumps. Thrombus formation remains the most feared complication that can affect clinical outcome. The development of a preoperative strategy aimed at the reduction of complications and patient-device suitability may be appropriate. Patient-specific modelling based on 3D reconstruction from CT-scan combined with computational fluid dynamic studies is an attractive solution in order to identify potential areas of stagnation or challenging anatomy that could be addressed to achieve the desired outcome. The HeartMate II (axial) and the HeartWare HVAD (centrifugal) rotary blood pumps have been now used worldwide with proven outcome. The HeartMate III (centrifugal) is now emerging as the new promising device with encouraging preliminary results. There are now enough pumps on the market: it is time to focus on the complications in order to achieve the full potential and selling-point of this type of technology for the treatment of the increasing heart failure patient population.

Frequency ranges of heart rate variability related to autonomic nerve activity in the mouse.

PubMed

Tsai, Meng-Li; Chen, Chien-Chang; Yeh, Chang-Jyi; Chou, Li-Ming; Cheng, Chiung-Hsiang

2012-01-01

Mice have gained more and more attention in recent years and been widely used in transgenic experiments. Although the number of researches on the heart rate variability (HRV) of mice has been gradually increasing, a consensus on the frequency ranges of autonomic modulation has not been established. Therefore, the main purpose of this study was to find a HRV "prototype" for conscious mice in the state of being motionless and breathing regularly (called "genuinely resting"), and to determine the frequency ranges corresponding to the autonomic modulation. Further, whether these frequencies will change when the mice move freely was studied to evaluate the feasibility of the HRV spectrum as an index of the autonomic modulation of mice. The recording sites were specially arranged to simultaneously obtain the electrocardiography and electromyography data to be provided for the use of HRV analysis and motion monitoring, respectively. The states of being motionless and breathing regularly as judged from the electromyography results were selected as a genuine resting state of a conscious mouse. The frequencies related to autonomic modulation of HRV were determined by comparing the spectrum changes before and after blockades of the autonomic tone by different pharmaceutical agents in both the genuine resting state and freely moving states. Our results showed that the HRV of mice is not suitable for indexing sympathetic modulation; however, it is possible to use the spectral power in the frequency range between 0.1 and 1 Hz as an index of parasympathetic modulation.

Modulation of Hypercholesterolemia-Induced Oxidative/Nitrative Stress in the Heart

PubMed Central

Sárközy, Márta; Pipicz, Márton; Dux, László; Csont, Tamás

2016-01-01

Hypercholesterolemia is a frequent metabolic disorder associated with increased risk for cardiovascular morbidity and mortality. In addition to its well-known proatherogenic effect, hypercholesterolemia may exert direct effects on the myocardium resulting in contractile dysfunction, aggravated ischemia/reperfusion injury, and diminished stress adaptation. Both preclinical and clinical studies suggested that elevated oxidative and/or nitrative stress plays a key role in cardiac complications induced by hypercholesterolemia. Therefore, modulation of hypercholesterolemia-induced myocardial oxidative/nitrative stress is a feasible approach to prevent or treat deleterious cardiac consequences. In this review, we discuss the effects of various pharmaceuticals, nutraceuticals, some novel potential pharmacological approaches, and physical exercise on hypercholesterolemia-induced oxidative/nitrative stress and subsequent cardiac dysfunction as well as impaired ischemic stress adaptation of the heart in hypercholesterolemia. PMID:26788247

The potential of ultrasound in cardiac pacing and rhythm modulation.

PubMed

Kohut, Andrew R; Vecchio, Christopher; Adam, Dan; Lewin, Peter A

2016-09-01

This review examines the potential for ultrasound to induce or otherwise influence cardiac pacing and rhythm modulation. Of particular interest is the possibility of developing new, truly non-invasive, nonpharmacological, acute and chronic, ultrasound-based arrhythmia treatments. Such approaches would not depend upon implanted or indwelling devices of any kind and would use ultrasound at diagnostic exposure levels (so as not to harm the heart or surrounding tissues). It is known that ultrasound can cause cardiomyocyte depolarization and a variety of underlying mechanisms have been proposed. Expert commentary: Questions still remain regarding the effect of exposure parameters and work will also be necessary to identify the optimal target regions within the heart if ultrasound energy is to be used to induce safe and reliable pacing in a clinical setting.

The evaluation of clinical therapy effects of oral western medicine combined with magnetic pulse acupoint stimulation in treating elderly patients with coronary heart disease.

PubMed

Fu, Xin; Guo, Li; Jiang, Zheng-Ming; Xu, Ai-Guo

2015-01-01

Treat the patients suffered from coronary heart disease with oral western medicine, combining with magnetic pulse acupoint stimulation, and observe the therapeutic effects of such combination therapy method. 56 old people with coronary heart disease are randomly divided into a treatment group and a control group. Both groups of patients are treated by the routine drugs, in addition, the patients of the treatment group are treated by magnetic pulse therapy additionally. Compare clinical symptoms, blood lipid and blood rheological indexes of the patients in the two groups when they are selected and after 30 days' treatment. after 30 days' treatment, it is found that clinical symptoms, blood lipid and blood rheological indexes of the patients in the treatment group are significantly improved compared with those when they are selected and those of the control group (P<0.05). patients with coronary heart disease, treated by pulsed magnetic therapy and the conventional drug intervention, had relieved synptom, improve blood lipid and heart blood supply function.

The evaluation of clinical therapy effects of oral western medicine combined with magnetic pulse acupoint stimulation in treating elderly patients with coronary heart disease

PubMed Central

Fu, Xin; Guo, Li; Jiang, Zheng-Ming; Xu, Ai-Guo

2015-01-01

Objective: Treat the patients suffered from coronary heart disease with oral western medicine, combining with magnetic pulse acupoint stimulation, and observe the therapeutic effects of such combination therapy method. Methods: 56 old people with coronary heart disease are randomly divided into a treatment group and a control group. Both groups of patients are treated by the routine drugs, in addition, the patients of the treatment group are treated by magnetic pulse therapy additionally. Compare clinical symptoms, blood lipid and blood rheological indexes of the patients in the two groups when they are selected and after 30 days’ treatment. Results: after 30 days’ treatment, it is found that clinical symptoms, blood lipid and blood rheological indexes of the patients in the treatment group are significantly improved compared with those when they are selected and those of the control group (P<0.05). Conclusion: patients with coronary heart disease, treated by pulsed magnetic therapy and the conventional drug intervention, had relieved synptom, improve blood lipid and heart blood supply function. PMID:26309664

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts.

PubMed

Stracina, Tibor; Slaninova, Iva; Polanska, Hana; Axmanova, Martina; Olejnickova, Veronika; Konecny, Petr; Masarik, Michal; Krizanova, Olga; Novakova, Marie

2015-07-01

Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

A pilot investigation of the effect of extremely low frequency pulsed electromagnetic fields on humans' heart rate variability.

PubMed

Baldi, Emilio; Baldi, Claudio; Lithgow, Brian J

2007-01-01

The question whether pulsed electromagnetic field (PEMF) can affect the heart rhythm is still controversial. This study investigates the effects on the cardiocirculatory system of ELF-PEMFs. It is a follow-up to an investigation made of the possible therapeutic effect ELF-PEMFs, using a commercially available magneto therapeutic unit, had on soft tissue injury repair in humans. Modulation of heart rate (HR) or heart rate variability (HRV) can be detected from changes in periodicity of the R-R interval and/or from changes in the numbers of heart-beat/min (bpm), however, R-R interval analysis gives only a quantitative insight into HRV. A qualitative understanding of HRV can be obtained considering the power spectral density (PSD) of the R-R intervals Fourier transform. In this study PSD is the investigative tool used, more specifically the low frequency (LF) PSD and high frequency (HF) PSD ratio (LF/HF) which is an indicator of sympatho-vagal balance. To obtain the PSD value, variations of the R-R time intervals were evaluated from a continuously recorded ECG. The results show a HR variation in all the subjects when they are exposed to the same ELF-PEMF. This variation can be detected by observing the change in the sympatho-vagal equilibrium, which is an indicator of modulation of heart activity. Variation of the LF/HF PSD ratio mainly occurs at transition times from exposure to nonexposure, or vice versa. Also of interest are the results obtained during the exposure of one subject to a range of different ELF-PEMFs. This pilot study suggests that a full investigation into the effect of ELF-PEMFs on the cardiovascular system is justified.

Radiation dose to patients and image quality evaluation from coronary 256-slice computed tomographic angiography

NASA Astrophysics Data System (ADS)

Chen, Liang-Kuang; Wu, Tung-Hsin; Yang, Ching-Ching; Tsai, Chia-Jung; Lee, Jason J. S.

2010-07-01

The aim of this study is to assess radiation dose and the corresponding image quality from suggested CT protocols which depends on different mean heart rate and high heart rate variability by using 256-slice CT. Fifty consecutive patients referred for a cardiac CT examination were included in this study. All coronary computed tomographic angiography (CCTA) examinations were performed on a 256-slice CT scanner with one of five different protocols: retrospective ECG-gating (RGH) with full dose exposure in all R-R intervals (protocol A), RGH of 30-80% pulsing window with tube current modulation (B), RGH of 78±5% pulsing window with tube current modulation (C), prospective ECG-triggering (PGT) of 78% R-R interval with 5% padding window (D) and PGT of 78% R-R interval without padding window (E). Radiation dose parameters and image quality scoring were determined and compared. In this study, no significant differences were found in comparison on image quality of the five different protocols. Protocol A obtained the highest radiation dose comparing with those of protocols B, C, D and E by a factor of 1.6, 2.4, 2.5 and 4.3, respectively ( p<0.001), which were ranged between 2.7 and 11.8 mSv. The PGT could significantly reduce radiation dose delivered to patients, as compared to the RGH. However, the use of PGT has limitations and is only good in assessing cases with lower mean heart rate and stable heart rate variability. With higher mean heart rate and high heart rate variability circumstances, the RGH within 30-80% of R-R interval pulsing window is suggested as a feasible technique for assessing diagnostic performance.

Combination of RNA interference and virus receptor trap exerts additive antiviral activity in coxsackievirus B3-induced myocarditis in mice.

PubMed

Stein, Elisabeth A; Pinkert, Sandra; Becher, Peter Moritz; Geisler, Anja; Zeichhardt, Heinz; Klopfleisch, Robert; Poller, Wolfgang; Tschöpe, Carsten; Lassner, Dirk; Fechner, Henry; Kurreck, Jens

2015-02-15

Coxsackievirus B3 (CVB3) is a major heart pathogen against which no therapy exists to date. The potential of a combination treatment consisting of a proteinaceous virus receptor trap and an RNA interference-based component to prevent CVB3-induced myocarditis was investigated. A soluble variant of the extracellular domain of the coxsackievirus-adenovirus receptor (sCAR-Fc) was expressed from an adenoviral vector and 2 short hairpin RNAs (shRdRp2.4) directed against CVB3 were delivered by an adeno-associated virus (AAV) vector. Cell culture experiments revealed additive antiviral activity of the combined application. In a CVB3-induced mouse myocarditis model, both components applied individually significantly reduced inflammation and viral load in the heart. The combination exerted an additive antiviral effect and reduced heart pathology. Hemodynamic measurement revealed that infection with CVB3 resulted in impaired heart function, as illustrated by a drastically reduced cardiac output and impaired contractility and relaxation. Treatment with either sCAR-Fc or shRdRp2.4 significantly improved these parameters. Importantly, the combination of both components led to a further significant improvement of heart function. Combination of sCAR-Fc and shRdRp2.4 exerted additive effects and was significantly more effective than either of the single treatments in inhibiting CVB3-induced myocarditis and preventing cardiac dysfunction. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Chronic condition combinations and health care expenditures and out-of-pocket spending burden among adults, Medical Expenditure Panel Survey, 2009 and 2011.

PubMed

Meraya, Abdulkarim M; Raval, Amit D; Sambamoorthi, Usha

2015-01-29

Little is known about how combinations of chronic conditions in adults affect total health care expenditures. Our objective was to estimate the annual average total expenditures and out-of-pocket spending burden among US adults by combinations of conditions. We conducted a cross-sectional study using 2009 and 2011 data from the Medical Expenditure Panel Survey. The sample consisted of 9,296 adults aged 21 years or older with at least 2 of the following 4 highly prevalent chronic conditions: arthritis, diabetes mellitus, heart disease, and hypertension. Unadjusted and adjusted regression techniques were used to examine the association between chronic condition combinations and log-transformed total expenditures. Logistic regressions were used to analyze the relationship between chronic condition combinations and high out-of-pocket spending burden. Among adults with chronic conditions, adults with all 4 conditions had the highest average total expenditures ($20,016), whereas adults with diabetes/hypertension had the lowest annual total expenditures ($7,116). In adjusted models, adults with diabetes/hypertension and hypertension/arthritis had lower health care expenditures than adults with diabetes/heart disease (P < .001). In adjusted models, adults with all 4 conditions had higher expenditures compared with those with diabetes and heart disease. However, the difference was only marginally significant (P = .04). Among adults with arthritis, diabetes, heart disease, and hypertension, total health care expenditures differed by type of chronic condition combinations. For individuals with multiple chronic conditions, such as heart disease and diabetes, new models of care management are needed to reduce the cost burden on the payers.

February Is American Heart Month | Poster

Cancer.gov

By Camille Rees, Guest Writer February is American Heart Month, and Feb. 7 was designated “National Wear Red Day” by the American Heart Association. The American Heart Association has sponsored the “Go Red for Women” campaign for 10 years. The message: heart disease is the number one killer of women. Did you know that more women die of heart disease than men?  In fact, it is more deadly than all forms of cancer combined. Over the years, the red dress has become the symbol of the fight against heart disease in women.

Effects of late administration of pentoxifylline and tocotrienols in an image-guided rat model of localized heart irradiation.

PubMed

Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil; Corry, Peter M; Moros, Eduardo G; Singh, Awantika; Compadre, Cesar M; Hauer-Jensen, Martin; Boerma, Marjan

2013-01-01

Radiation-induced heart disease (RIHD) is a long-term side effect of radiotherapy of intrathoracic, chest wall and breast tumors when radiation fields encompass all or part of the heart. Previous studies have shown that pentoxifylline (PTX) in combination with α-tocopherol reduced manifestations of RIHD in rat models of local heart irradiation. The relative contribution of PTX and α-tocopherol to these beneficial effects are not known. This study examined the effects of PTX alone or in combination with tocotrienols, forms of vitamin E with potential potent radiation mitigation properties. Rats received localized X-irradiation of the heart with an image-guided irradiation technique. At 3 months after irradiation rats received oral treatment with vehicle, PTX, or PTX in combination with a tocotrienol-enriched formulation. At 6 months after irradiation, PTX-treated rats showed arrhythmia in 5 out of 14 animals. PTX alone or in combination with tocotrienols did not alter cardiac radiation fibrosis, left ventricular protein expression of the endothelial markers von Willebrand factor and neuregulin-1, or phosphorylation of the signal mediators Akt, Erk1/2, or PKCα. On the other hand, tocotrienols reduced cardiac numbers of mast cells and macrophages, but enhanced the expression of tissue factor. While this new rat model of localized heart irradiation does not support the use of PTX alone, the effects of tocotrienols on chronic manifestations of RIHD deserve further investigation.

Effects of Late Administration of Pentoxifylline and Tocotrienols in an Image-Guided Rat Model of Localized Heart Irradiation

PubMed Central

Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil; Corry, Peter M.; Moros, Eduardo G.; Singh, Awantika; Compadre, Cesar M.; Hauer-Jensen, Martin; Boerma, Marjan

2013-01-01

Radiation-induced heart disease (RIHD) is a long-term side effect of radiotherapy of intrathoracic, chest wall and breast tumors when radiation fields encompass all or part of the heart. Previous studies have shown that pentoxifylline (PTX) in combination with α-tocopherol reduced manifestations of RIHD in rat models of local heart irradiation. The relative contribution of PTX and α-tocopherol to these beneficial effects are not known. This study examined the effects of PTX alone or in combination with tocotrienols, forms of vitamin E with potential potent radiation mitigation properties. Rats received localized X-irradiation of the heart with an image-guided irradiation technique. At 3 months after irradiation rats received oral treatment with vehicle, PTX, or PTX in combination with a tocotrienol-enriched formulation. At 6 months after irradiation, PTX-treated rats showed arrhythmia in 5 out of 14 animals. PTX alone or in combination with tocotrienols did not alter cardiac radiation fibrosis, left ventricular protein expression of the endothelial markers von Willebrand factor and neuregulin-1, or phosphorylation of the signal mediators Akt, Erk1/2, or PKCα. On the other hand, tocotrienols reduced cardiac numbers of mast cells and macrophages, but enhanced the expression of tissue factor. While this new rat model of localized heart irradiation does not support the use of PTX alone, the effects of tocotrienols on chronic manifestations of RIHD deserve further investigation. PMID:23894340

Essential Hypertension: Cardiovascular Response to Breath Hold Combined with Exercise.

PubMed

Hoffmann, U; Urban, P; Koschate, J; Drescher, U; Pfister, R; Michels, G

2015-07-01

Essential hypertension (EH) is a widespread disease and might be prevalent in apnea divers and master athletes. Little is known about the influence of EH and the antihypertensive drugs (AHD) on cardiovascular reactions to combined breath hold (BH) and exercise. In this pilot study, healthy divers (HCON) were compared with treated hypertensive divers with regard to heart rate (HR) and mean blood-pressure (MAP) responses to BH, exercise and the combination of both. Ten subjects with EH and ten healthy divers were tested. 3 different 20 s stimuli were applied: BH combined with 30 W or 150 W and 150 W without BH. The time-charts during the stress intervals and during recovery were compared. Subjects treated with an angiotensin-converting enzyme (ACE) inhibitor showed higher changes for MAP values if breath hold was performed. HR responses were obviously changed if a β-blocker was part of the medication. One subject showed extreme MAP responses to all stimuli and conspicuous HR if BH was involved. The modulation of HR-/MAP-response in EH subjects depends on the mechanisms of antihypertensive agents. The combination of an ACE inhibitor and a β-blocker may give the best protection. It is recommended to include short apnea tests in the fitness-to-dive examination to individually predict potential endangerment. © Georg Thieme Verlag KG Stuttgart · New York.

Simultaneous fNIRS and thermal infrared imaging during cognitive task reveal autonomic correlates of prefrontal cortex activity

NASA Astrophysics Data System (ADS)

Pinti, Paola; Cardone, Daniela; Merla, Arcangelo

2015-12-01

Functional Near Infrared-Spectroscopy (fNIRS) represents a powerful tool to non-invasively study task-evoked brain activity. fNIRS assessment of cortical activity may suffer for contamination by physiological noises of different origin (e.g. heart beat, respiration, blood pressure, skin blood flow), both task-evoked and spontaneous. Spontaneous changes occur at different time scales and, even if they are not directly elicited by tasks, their amplitude may result task-modulated. In this study, concentration changes of hemoglobin were recorded over the prefrontal cortex while simultaneously recording the facial temperature variations of the participants through functional infrared thermal (fIR) imaging. fIR imaging provides touch-less estimation of the thermal expression of peripheral autonomic. Wavelet analysis revealed task-modulation of the very low frequency (VLF) components of both fNIRS and fIR signals and strong coherence between them. Our results indicate that subjective cognitive and autonomic activities are intimately linked and that the VLF component of the fNIRS signal is affected by the autonomic activity elicited by the cognitive task. Moreover, we showed that task-modulated changes in vascular tone occur both at a superficial and at larger depth in the brain. Combined use of fNIRS and fIR imaging can effectively quantify the impact of VLF autonomic activity on the fNIRS signals.

Arterial Stiffness and Autonomic Modulation After Free-Weight Resistance Exercises in Resistance Trained Individuals.

PubMed

Kingsley, J Derek; Mayo, Xián; Tai, Yu Lun; Fennell, Curtis

2016-12-01

Kingsley, JD, Mayo, X, Tai, YL, and Fennell, C. Arterial stiffness and autonomic modulation after free-weight resistance exercises in resistance trained individuals. J Strength Cond Res 30(12): 3373-3380, 2016-We investigated the effects of an acute bout of free-weight, whole-body resistance exercise consisting of the squat, bench press, and deadlift on arterial stiffness and cardiac autonomic modulation in 16 (aged 23 ± 3 years; mean ± SD) resistance-trained individuals. Arterial stiffness, autonomic modulation, and baroreflex sensitivity (BRS) were assessed at rest and after 3 sets of 10 repetitions at 75% 1-repetition maximum on each exercise with 2 minutes of rest between sets and exercises. Arterial stiffness was analyzed using carotid-femoral pulse wave velocity (cf-PWV). Linear heart rate variability (log transformed [ln] absolute and normalized units [nu] of low-frequency [LF] and high-frequency [HF] power) and nonlinear heart rate complexity (Sample Entropy [SampEn], Lempel-Ziv Entropy [LZEn]) were measured to determine autonomic modulation. BRS was measured by the sequence method. A 2 × 2 repeated measures analysis of variance (ANOVA) was used to analyze time (rest, recovery) across condition (acute resistance exercise, control). There were significant increases in cf-PWV (p = 0.05), heart rate (p = 0.0001), normalized LF (LFnu; p = 0.001), and the LF/HF ratio (p = 0.0001). Interactions were also noted for ln HF (p = 0.006), HFnu (p = 0.0001), SampEn (p = 0.001), LZEn (p = 0.005), and BRS (p = 0.0001) such that they significantly decreased during recovery from the resistance exercise compared with rest and the control. There was no effect on ln total power, or ln LF. These data suggest that a bout of resistance exercise using free-weights increases arterial stiffness and reduces vagal activity and BRS in comparison with a control session. Vagal tone may not be fully recovered up to 30 minutes after a resistance exercise bout.

Comparing treatment plan in all locations of esophageal cancer: volumetric modulated arc therapy versus intensity-modulated radiotherapy.

PubMed

Lin, Jang-Chun; Tsai, Jo-Ting; Chang, Chih-Chieh; Jen, Yee-Min; Li, Ming-Hsien; Liu, Wei-Hsiu

2015-05-01

The aim of this study was to compare treatment plans of volumetric modulated arc therapy (VMAT) with intensity-modulated radiotherapy (IMRT) for all esophageal cancer (EC) tumor locations.This retrospective study from July 2009 to June 2014 included 20 patients with EC who received definitive concurrent chemoradiotherapy with radiation doses >50.4 Gy. Version 9.2 of Pinnacle with SmartArc was used for treatment planning. Dosimetric quality was evaluated based on doses to several organs at risk, including the spinal cord, heart, and lung, over the same coverage of gross tumor volume.In upper thoracic EC, the IMRT treatment plan had a lower lung mean dose (P = 0.0126) and lung V5 (P = 0.0037) compared with VMAT; both techniques had similar coverage of the planning target volumes (PTVs) (P = 0.3575). In middle thoracic EC, a lower lung mean dose (P = 0.0010) and V5 (P = 0.0145), but higher lung V20 (P = 0.0034), spinal cord Dmax (P = 0.0262), and heart mean dose (P = 0.0054), were observed for IMRT compared with VMAT; IMRT provided better PTV coverage. Patients with lower thoracic ECs had a lower lung mean dose (P = 0.0469) and V5 (P = 0.0039), but higher spinal cord Dmax (P = 0.0301) and heart mean dose (P = 0.0020), with IMRT compared with VMAT. PTV coverage was similar (P = 0.0858) for the 2 techniques.IMRT provided a lower mean dose and lung V5 in upper thoracic EC compared with VMAT, but exhibited different advantages and disadvantages in patients with middle or lower thoracic ECs. Thus, choosing different techniques for different EC locations is warranted.

Free energy landscape remodeling of the cardiac pacemaker channel explains the molecular basis of familial sinus bradycardia

PubMed Central

Boulton, Stephen; Akimoto, Madoka; Akbarizadeh, Sam; Melacini, Giuseppe

2017-01-01

The hyperpolarization-activated and cyclic nucleotide-modulated ion channel (HCN) drives the pacemaker activity in the heart, and its malfunction can result in heart disorders. One such disorder, familial sinus bradycardia, is caused by the S672R mutation in HCN, whose electrophysiological phenotypes include a negative shift in the channel activation voltage and an accelerated HCN deactivation. The outcomes of these changes are abnormally low resting heart rates. However, the molecular mechanism underlying these electrophysiological changes is currently not fully understood. Crystallographic investigations indicate that the S672R mutation causes limited changes in the structure of the HCN intracellular gating tetramer, but its effects on protein dynamics are unknown. Here, we utilize comparative S672R versus WT NMR analyses to show that the S672R mutation results in extensive perturbations of the dynamics in both apo- and holo-forms of the HCN4 isoform, reflecting how S672R remodels the free energy landscape for the modulation of HCN4 by cAMP, i.e. the primary cyclic nucleotide modulator of HCN channels. We show that the S672R mutation results in a constitutive shift of the dynamic auto-inhibitory equilibrium toward inactive states of HCN4 and broadens the free-energy well of the apo-form, enhancing the millisecond to microsecond dynamics of the holo-form at sites critical for gating cAMP binding. These S672R-induced variations in dynamics provide a molecular basis for the electrophysiological phenotypes of this mutation and demonstrate that the pathogenic effects of the S672R mutation can be rationalized primarily in terms of modulations of protein dynamics. PMID:28174302

SU-E-P-51: Dosimetric Comparison to Organs at Risk Sparing Using Volumetric-Modulated Arc Therapy Versus Intensity-Modulated Radiotherapy in Postoperative Radiotherapy of Left-Sided Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiao, L; Deng, G; Xie, J

2015-06-15

Purpose: To compare the dosimetric characteristics of volumetric-modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for left-sided breast cancer patients with modified radical mastectomy. Methods: Twenty-four left-sided breast cancer patients treated with modified radical mastectomy were selected in this study. The planning target volume (PTV) was generated by using 7-mm uniform expansion of the clinical target volume (CTV) in all direction except the skin surface. The organs at risk (OARs) included heart, left lung, right lung, and right breast. Dose volume histograms (DVHs) were utilized to evaluate the dose distribution in PTV and OARs. Results: Bothmore » VMAT and IMRT plans met the requirement of PTV coverage. VMAT was superior to IMRT in terms of conformity, with a statistically significant difference (p=0.024). Mean doses, V5 and V10 of heart and both lungs in VMAT plans were significantly decreased compared to IMRT plans (P<0.05), but in terms of heart volume irradiated by high doses (V30 and V45), no significant differences were observed (P>0.05). For right breast, VMAT showed the reduction of V5 in comparison with IMRT (P<0.05). Additionally, the mean number of monitor units (MU) and treatment time in VMAT (357.21, 3.62 min) were significantly less than those in IMRT (1132.85, 8.74 min). Conclusion: VMAT showed similar PTV coverage and significant advantage in OARs sparing compared with IMRT, especially in terms of decreased volumes irradiated by low doses, while significantly reducing the treatment time and MU number.« less

Biological effects of combined resveratrol and vitamin D3 on ovarian tissue.

PubMed

Uberti, Francesca; Morsanuto, Vera; Aprile, Silvio; Ghirlanda, Sabrina; Stoppa, Ian; Cochis, Andrea; Grosa, Giorgio; Rimondini, Lia; Molinari, Claudio

2017-09-15

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural antioxidant polyphenol able to exert a wide range of biological effect on several tissues. Despite its important beneficial properties, it has a low water solubility, which limits its therapeutic applications in humans. Resveratrol also acts as a phytoestrogen that modulates estrogen receptor (ER)-mediated transcription. In addition, it has been shown that ovarian tissues benefit greatly from vitamin D3, which exerts its beneficial effects through VDR receptors. The aim was to evaluate the cooperative effects of resveratrol combined with vitamin D3 on ovarian cells and tissues and some other organs as well. Moreover, the modulation of specific intracellular pathways involving ER and VDR receptors has been studied. The experiments were performed both in vitro and in vivo, to analyze cell viability, radical oxygen species production, signal transductions through Western Blot, and resveratrol quantification by HPLC. Cell viability, radical oxygen species production, and intracellular pathways have been studied on CHO-K1 cells. Also, the relative mechanism activated following oral intake in female Wistar rats as animal model was investigated, evaluating bioavailability, biodistribution and signal transduction in heart, kidney, liver and ovarian tissues. Both in in vitro and in vivo experiments, resveratrol exerts more evident effects when administered in combination with vitD in ovarian cells, showing a common biphasic cooperative effect: The role of vitamin D3 in maintaining and supporting the biological activity of resveratrol has been clearly observed. Moreover, resveratrol plus vitamin D3 blood concentrations showed a biphasic absorption rate. Such results could be used as a fundamental data for the development of new therapies for gynecological conditions, such as hot-flashes.

Heart rate variability and aerobic fitness.

PubMed

De Meersman, R E

1993-03-01

Heart rate variability, a noninvasive marker of parasympathetic activity, diminishes with aging and is augmented after exercise training. Whether habitual exercise over time can attenuate this loss is unknown. This cross-sectional investigation compared 72 male runners, aged 15 to 83 to 72 age- and weight-matched sedentary control subjects for the amplitude of their heart rate variability. Heart rate variability was assessed during rest while subjects were breathing at a rate of 6 breaths per minute and at an augmented tidal volume (tidal volume = 30% of vital capacity). Fitness levels were assessed with on-line, open-circuit spirometry while subjects were performing an incremental stress test. Overall results between the two groups showed that the physically active group had significantly higher fitness levels (p < 0.001), which were associated with significantly higher levels of heart rate variability, when compared with their sedentary counterparts (p < 0.001). These findings provide suggestive evidence for habitual aerobic exercise as a beneficial modulator of heart rate variability in an aging population.

Analysis of the dynamic co-expression network of heart regeneration in the zebrafish

PubMed Central

Rodius, Sophie; Androsova, Ganna; Götz, Lou; Liechti, Robin; Crespo, Isaac; Merz, Susanne; Nazarov, Petr V.; de Klein, Niek; Jeanty, Céline; González-Rosa, Juan M.; Muller, Arnaud; Bernardin, Francois; Niclou, Simone P.; Vallar, Laurent; Mercader, Nadia; Ibberson, Mark; Xenarios, Ioannis; Azuaje, Francisco

2016-01-01

The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration. PMID:27241320

Analysis of the dynamic co-expression network of heart regeneration in the zebrafish

NASA Astrophysics Data System (ADS)

Rodius, Sophie; Androsova, Ganna; Götz, Lou; Liechti, Robin; Crespo, Isaac; Merz, Susanne; Nazarov, Petr V.; de Klein, Niek; Jeanty, Céline; González-Rosa, Juan M.; Muller, Arnaud; Bernardin, Francois; Niclou, Simone P.; Vallar, Laurent; Mercader, Nadia; Ibberson, Mark; Xenarios, Ioannis; Azuaje, Francisco

2016-05-01

The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration.

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

42 CFR 482.70 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... geographic area specified by CMS. Heart-Lung transplant center means a transplant center that is located in a hospital with an existing Medicare-approved heart transplant center and an existing Medicare-approved lung center that performs combined heart-lung transplants. Intestine transplant center means a Medicare...

Combining aspirin with angiotensin converting enzyme inhibitors in heart failure: how safe is it?

PubMed

Mehta, H; Mahajan, A; Bansal, N; Vaidya, S; Pathak, L

1998-11-01

The above discussion on the interaction of aspirin and ACE inhibitors seems to suggest that aspirin in high doses may have adverse interaction with ACE inhibitors in patients with heart failure but the data obtained is not sufficient or conclusive to recommended omission of aspirin in patients with heart failure. This raises a query in the mind of the physician whether to use a combination or not? The role of aspirin in the early period after myocardial infarction is well established so is the role of ACE inhibitors. Hence in patients with myocardial infarction and preserved left ventricular function it would not be wrong to administer combination of ACE inhibitors and aspirin. Albeit at a lower dose. In patients with large myocardial infarction or heart failure, warfarin may be an option but still needs to be documented in large trials. As suggested long term use of aspirin after infarction is still ambiguous and may be harmful in patients with heart failure with its anticedent side effects. But long term benefits of ACE inhibitors in heart failure are well documented. Hence if a choice has to be made whether to discontinue either of the two drugs it would be preferable to stop the aspirin. To answer the issue of use of aspirin in patients with heart failure it would be essential to conduct a double blind randomized trial comparing known anti-thrombotic treatment, aspirin and anti-coagulants on mortality in patients with heart failure, especially caused by coronary artery disease. Such a trial is underway at the present and till the results are available it should be left to clinical judgement of the physician whether to administer aspirin in patients with heart failure after weighing the benefits versus risk.

Protecting Juno Electronics from Radiation

NASA Image and Video Library

2010-07-12

Technicians installed the special radiation vault for NASA Juno spacecraft on the propulsion module. The radiation vault has titanium walls to protect the spacecraft electronic brain and heart from Jupiter harsh radiation environment.

CCN2 plays a key role in extracellular matrix gene expression in severe hypertrophic cardiomyopathy and heart failure.

PubMed

Tsoutsman, Tatiana; Wang, Xiaoyu; Garchow, Kendra; Riser, Bruce; Twigg, Stephen; Semsarian, Christopher

2013-09-01

Hypertrophic cardiomyopathy (HCM) is the most common inherited primary myocardial disorder. HCM is characterized by interstitial fibrosis and excessive accumulation of extracellular matrix (ECM) proteins. Fibrosis in HCM has been associated with impaired cardiac function and heart failure, and has been considered a key substrate for ventricular arrhythmias and sudden death. The molecular triggers underpinning ECM production are not well established. We have previously developed a double-mutant mouse model of HCM that recapitulates the phenotype seen in humans with multiple mutations, including earlier onset of the disease, progression to a dilated phenotype, severe heart failure and premature mortality. The present study investigated the expression of ECM-encoding genes in severe HCM and heart failure. Significant upregulation of structural Fn1, regulatory Mmp14, Timp1, Serpin3A, SerpinE1, SerpineE2, Tgfβ1, and Tgfβ2; and matricellular Ccn2, Postn, Spp1, Thbs1, Thbs4, and Tnc was evident from the early, pre-phenotype stage. Non-myocytes expressed ECM genes at higher levels than cardiomyocytes in normal and diseased hearts. Synchronous increase of secreted CCN2 and TIMP1 plasma levels and decrease of MMP3 levels were observed in end-stage disease. CCN2 protein expression was increased from early disease in double-mutant hearts and played an important role in ECM responses. It was a powerful modulator of ECM regulatory (Timp1 and SerpinE1) and matricellular protein-encoding (Spp1, Thbs1, Thbs4 and Tnc) gene expression in cardiomyocytes when added exogenously in vitro. Modulation of CCN2 (CTGF, connective tissue growth factor) and associated early ECM changes may represent a new therapeutic target in the treatment and prevention of heart failure in HCM. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sacubitril and valsartan fixed combination to reduce heart failure events in post-acute myocardial infarction patients.

PubMed

Zaid Iskandar, M; Lang, C C

2017-10-01

Heart failure is a term used to define a constellation of symptoms and signs that are commonly attributed to the inability of the heart to produce a cardiac output that meets the demands of the body. It remains a deadly disease, affecting between 1-2% of the population, and is more common in the elderly, with around 6-10% of patients over 65 suffering from the condition. Sacubitril/valsartan (LCZ-696) is a combined neprilysin inhibitor and angiotensin AT1 receptor blocker approved in recent years for the treatment of chronic heart failure with reduced ejection fraction. In an area where there have been limited pharmacological advances in the last 10 years, this drug was a game changer and a much welcomed addition to contemporary heart failure therapy. It is currently being studied in patients with heart failure with preserved ejection fraction and for the reduction of heart failure events post-acute myocardial infarction. Results from the ongoing PARADISE-MI study are awaited by the global cardiology community with great interest. Copyright 2017 Clarivate Analytics.

adwTools Developed: New Bulk Alloy and Surface Analysis Software for the Alloy Design Workbench

NASA Technical Reports Server (NTRS)

Bozzolo, Guillermo; Morse, Jeffrey A.; Noebe, Ronald D.; Abel, Phillip B.

2004-01-01

A suite of atomistic modeling software, called the Alloy Design Workbench, has been developed by the Computational Materials Group at the NASA Glenn Research Center and the Ohio Aerospace Institute (OAI). The main goal of this software is to guide and augment experimental materials research and development efforts by creating powerful, yet intuitive, software that combines a graphical user interface with an operating code suitable for real-time atomistic simulations of multicomponent alloy systems. Targeted for experimentalists, the interface is straightforward and requires minimum knowledge of the underlying theory, allowing researchers to focus on the scientific aspects of the work. The centerpiece of the Alloy Design Workbench suite is the adwTools module, which concentrates on the atomistic analysis of surfaces and bulk alloys containing an arbitrary number of elements. An additional module, adwParams, handles ab initio input for the parameterization used in adwTools. Future modules planned for the suite include adwSeg, which will provide numerical predictions for segregation profiles to alloy surfaces and interfaces, and adwReport, which will serve as a window into the database, providing public access to the parameterization data and a repository where users can submit their own findings from the rest of the suite. The entire suite is designed to run on desktop-scale computers. The adwTools module incorporates a custom OAI/Glenn-developed Fortran code based on the BFS (Bozzolo- Ferrante-Smith) method for alloys, ref. 1). The heart of the suite, this code is used to calculate the energetics of different compositions and configurations of atoms.

The impact of multiple blood donations on the risk of cardiovascular diseases: Insight of lipid profile.

PubMed

Bani-Ahmad, M A; Khabour, O F; Gharibeh, M Y; Alshlool, K N

2017-11-01

The reduction in blood viscosity and iron store were proposed to be connected to the reduction in the risk of cardiovascular disease (CVD) among multiple blood donors. Herein, we evaluated the modulation of serum lipids levels in accordance with donation events. Furthermore, atherogenic impacts on the risk of CVD were investigated. A total of 100 voluntarily male donors were included in the study. Fifty donors were multiple time donors (MTD) and 50 were single time donors (STD). Levels of serum lipids were determined and atherogenic indices including TG/HDL and CHO/HDL ratios were calculated. QRISK2 parameters were determined to evaluate the 10-years risk of developing CVD. Among MTD, there were significantly higher serum levels of triglycerides (TG) and very low-density lipoproteins (VLDL) combined with significantly lower HDL level. These modulations were significantly correlated to the extent of donation. Both CHO/HDL and TG/HDL ratios were also significantly higher among MTD. However, only TG/HDL ratio was strongly correlated to the donation extent even when controlled for age, BMI and smoking status. Despite the significant difference in QRISK2 parameters between study groups, none of these parameters was correlated to the extent of donation when controlling for age, BMI and smoking status. We demonstrate that multiple blood donation is associated with an unfavorable modulation of serum levels of lipids that is influenced by donation extent. This modulation is not associated with an increased risk of CVD but may weakly contribute in a higher risk for coronary heart disease (CHD). Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cross-correlation of heartbeat and respiration rhythms

NASA Astrophysics Data System (ADS)

Capurro, A.; Malta, C. P.; Diambra, L.; Contreras, P.; Migliaro, E. R.

2005-10-01

The cross-correlation function between respiration and heart beat interval series shows that during metronomized breathing the heart beat follows the respiration more closely than during spontaneous breathing. We reproduced the heart beat interval modulations during metronomized breathing using a biophysical model of the sinoatrial node excited by an input signal formed by the recorded respiration. In the case of spontaneous breathing, a good agreement with the experimental data was obtained only by using an input signal formed by the sum of the recorded respiration and a realization of correlated noise. Metronomized breathing refers to the situation where a subject breathes following the rhythm of a metronome.

Effect of antihypertensive drug therapy on short-term heart rate variability in newly diagnosed essential hypertension.

PubMed

Pavithran, Purushothaman; Prakash, E Sankaranarayanan; Dutta, Tarun K; Madanmohan, Trakroo

2010-02-01

1. Abnormalities of cardiac autonomic regulation are a potential mechanism for morbidity despite blood pressure (BP) lowering in hypertension. Analysis of short-term (5 min) heart rate variability (HRV) provides a non-invasive probe of autonomic regulation of sino-atrial (SA) node automaticity. 2. We hypothesized that antihypertensive drug therapy would be associated with an increase in 5 min overall HRV, along with a decrease in blood pressure (BP), at 8 weeks follow up in subjects with newly diagnosed, never-treated essential hypertension. 3. One hundred and fifty patients (84 men and 66 women; mean (+/-SD) age 48 +/- 10 years) with newly diagnosed essential hypertension were divided to five groups of 30 patients each to receive one of the following antihypertensive drugs (or drug combinations): 5 mg/day amlodipine; 50 mg/day atenolol; 5 mg/day enalapril; 25 mg/day hydrochlorothiazide; or a combination of 5 mg/day amlodipine and 50 mg/day atenolol. 4. The only significant change in HRV indices was an increase in total variability of RR intervals and an increase in high-frequency (HF) RR interval spectral power in the amlodipine + atenolol-treated group (P < 0.05). 5. The results indicate that there is a dissociation between changes in short-term HRV and mean RR interval and BP lowering in patients with newly diagnosed hypertension. 6. We interpret the increase in HF RR interval spectral power in the amlodipine + atenolol-treated group as being due to an increase in vagal modulation of RR intervals and/or diminution in sympathetic restraint of respiratory sinus arrhythmia.

LCZ696 (Valsartan/Sacubitril)--A Possible New Treatment for Hypertension and Heart Failure.

PubMed

Andersen, Mathilde Borring; Simonsen, Ulf; Wehland, Markus; Pietsch, Jessica; Grimm, Daniela

2016-01-01

The aim of this MiniReview was to introduce the newly invented dual-acting drug valsartan/sacubitril (LCZ696), which combines an angiotensin receptor blocker (valsartan) with sacubitril, a specific inhibitor of the neutral endopeptidase (NEP) that degrades vasoactive peptides, including natriuretic peptides ANP and BNP, but also glucagon, enkephalins and bradykinin, among others. The MiniReview presents the data of four available trials NCT01193101, NCT00549770, NCT00887588 and NCT01035255 and provides the current knowledge about LCZ696 effects in patients with hypertension and heart failure. Presently, patients suffering from hypertension and heart failure are treated with ACE inhibitors or angiotensin receptor antagonists often in combination with other drugs. These current medications lead to a reduction in blood pressure in hypertensive patients and a decreased mortality and morbidity in patients with heart failure with reduced ejection fraction, but not in patients with heart failure with preserved ejection fraction. LCZ696 had been tested to utilize the beneficial properties of natriuretic peptides in combination with angiotensin receptor antagonism. It induces even greater blood pressure reductions and decreased mortality and morbidity in patients with heart failure with reduced ejection fraction, while patients with heart failure with preserved ejection fraction show lowered blood pressure and decreased NT-pro-BNP levels. Although long-term studies remain to be performed, these initial data suggest that there is a potential clinical benefit of LCZ696 in the treatment of hypertension and heart failure. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

SU-F-T-85: Energy Modulated Electron Postmastectomy Unreconstructed (PU) Chest Wall (CW) Irradiation Technique to Achieve Heart Sparing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, L; Ballangrud, A; Mechalakos, J

Purpose: For left-sided PU patients requiring CW and nodal irradiation, sometimes partial wide tangents (PWT) are not feasible due to abnormal chest wall contour or heart position close to the anterior chest wall or unusual wide excision scar. We developed an energy modulated electron chest wall irradiation technique that will achieve heart sparing. Methods: Ten left-sided PU patients were selected for this dosimetry study. If PWT were used, the amount of the ipsilateral lung would be ranged 3.4 to 4.4 cm, and the amount of heart would be ranged 1.3 to 3.8 cm. We used electron paired fields that matchedmore » on the skin to achieve dose conformity to the chest wall. The enface electron fields were designed at extended SSD from a single isocenter and gantry angle with different energy beams using different cutout. Lower energy was used in the central chest wall part and higher energy was used in the periphery of the chest wall. Bolus was used for the electron fields to ensure adequate skin dose coverage. The electron fields were matched to the photon supra-clavicle field in the superior region. Daily field junctions were used to feather the match lines between all the fields. Target volumes and normal tissues were drawn according to institutional protocols. Prescription dose was 2Gy per fraction for a total 50Gy. Dose calculations were done with Eclipse EMC-11031 for Electron and AAA-11031 for photons. Results: Six patients were planned using 6/9MeV, three using 9/12MeV and one 6/12MeV. Target volumes achieved adequate coverage. For heart, V30Gy, V20Gy and Mean Dose were 0.6%±0.6%, 2.7%±1.7%, and 3.0Gy±0.8Gy respectively. For ipsilateral lung, V50Gy, V20Gy, V10Gy and V5Gy were 0.9%±1.1%, 34.3%±5.1%, 51.6%±6.3% and 64.1%±7.5% respectively. Conclusion: For left-sided PU patients with unusual anatomy, energy modulated electron CW irradiation technique can achieve heart sparing with acceptable lung dose.« less

Inspecting Juno Radiation Vault

NASA Image and Video Library

2010-07-12

A technician inspects the special radiation vault being installed atop the propulsion module of NASA Juno spacecraft; the vault has titanium walls to protect the spacecraft electronic brain and heart from Jupiter harsh radiation environment.

A Calmodulin C-Lobe Ca2+-Dependent Switch Governs Kv7 Channel Function.

PubMed

Chang, Aram; Abderemane-Ali, Fayal; Hura, Greg L; Rossen, Nathan D; Gate, Rachel E; Minor, Daniel L

2018-02-21

Kv7 (KCNQ) voltage-gated potassium channels control excitability in the brain, heart, and ear. Calmodulin (CaM) is crucial for Kv7 function, but how this calcium sensor affects activity has remained unclear. Here, we present X-ray crystallographic analysis of CaM:Kv7.4 and CaM:Kv7.5 AB domain complexes that reveal an Apo/CaM clamp conformation and calcium binding preferences. These structures, combined with small-angle X-ray scattering, biochemical, and functional studies, establish a regulatory mechanism for Kv7 CaM modulation based on a common architecture in which a CaM C-lobe calcium-dependent switch releases a shared Apo/CaM clamp conformation. This C-lobe switch inhibits voltage-dependent activation of Kv7.4 and Kv7.5 but facilitates Kv7.1, demonstrating that mechanism is shared by Kv7 isoforms despite the different directions of CaM modulation. Our findings provide a unified framework for understanding how CaM controls different Kv7 isoforms and highlight the role of membrane proximal domains for controlling voltage-gated channel function. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy.

PubMed

Sivaguru, Mayandi; Fried, Glenn; Sivaguru, Barghav S; Sivaguru, Vignesh A; Lu, Xiaochen; Choi, Kyung Hwa; Saif, M Taher A; Lin, Brian; Sadayappan, Sakthivel

2015-11-01

The ability to image the entire adult mouse heart at high resolution in 3-D would provide enormous advantages in the study of heart disease. However, a technique for imaging nuclear/cellular detail as well as the overall structure of the entire heart in 3-D with minimal effort is lacking. To solve this problem, we modified the benzyl alcohol:benzyl benzoate (BABB) clearing technique by labeling mouse hearts with periodic acid Schiff (PAS) stain. We then imaged the hearts with a combination of two-photon fluorescence microscopy and automated tile-scan imaging/stitching. Utilizing the differential spectral properties of PAS, we could identify muscle and nuclear compartments in the heart. We were also able to visualize the differences between a 3-month-old normal mouse heart and a mouse heart that had undergone heart failure due to the expression of cardiac myosin binding protein-C (cMyBP-C) gene mutation (t/t). Using 2-D and 3-D morphometric analysis, we found that the t/t heart had anomalous ventricular shape, volume, and wall thickness, as well as a disrupted sarcomere pattern. We further validated our approach using decellularized hearts that had been cultured with 3T3 fibroblasts, which were tracked using a nuclear label. We were able to detect the 3T3 cells inside the decellularized intact heart tissue, achieving nuclear/cellular resolution in 3-D. The combination of labeling, clearing, and two-photon microscopy together with tiling eliminates laborious and time-consuming physical sectioning, alignment, and 3-D reconstruction.

Chronic Condition Combinations and Health Care Expenditures and Out-of-Pocket Spending Burden Among Adults, Medical Expenditure Panel Survey, 2009 and 2011

PubMed Central

Raval, Amit D.; Sambamoorthi, Usha

2015-01-01

Introduction Little is known about how combinations of chronic conditions in adults affect total health care expenditures. Our objective was to estimate the annual average total expenditures and out-of-pocket spending burden among US adults by combinations of conditions. Methods We conducted a cross-sectional study using 2009 and 2011 data from the Medical Expenditure Panel Survey. The sample consisted of 9,296 adults aged 21 years or older with at least 2 of the following 4 highly prevalent chronic conditions: arthritis, diabetes mellitus, heart disease, and hypertension. Unadjusted and adjusted regression techniques were used to examine the association between chronic condition combinations and log-transformed total expenditures. Logistic regressions were used to analyze the relationship between chronic condition combinations and high out-of-pocket spending burden. Results Among adults with chronic conditions, adults with all 4 conditions had the highest average total expenditures ($20,016), whereas adults with diabetes/hypertension had the lowest annual total expenditures ($7,116). In adjusted models, adults with diabetes/hypertension and hypertension/arthritis had lower health care expenditures than adults with diabetes/heart disease (P < .001). In adjusted models, adults with all 4 conditions had higher expenditures compared with those with diabetes and heart disease. However, the difference was only marginally significant (P = .04). Conclusion Among adults with arthritis, diabetes, heart disease, and hypertension, total health care expenditures differed by type of chronic condition combinations. For individuals with multiple chronic conditions, such as heart disease and diabetes, new models of care management are needed to reduce the cost burden on the payers. PMID:25633487

Control system for an artificial heart

NASA Technical Reports Server (NTRS)

Gebben, V. D.; Webb, J. A., Jr.

1970-01-01

Inexpensive industrial pneumatic components are combined to produce control system to drive sac-type heart-assistance blood pump with controlled pulsatile pressure that makes pump rate of flow sensitive to venous /atrial/ pressure, while stroke is centered about set operating point and pump is synchronized with natural heart.

Mechanisms of Autonomic Dysfunction Associated with Extreme Exertional Heat Stroke and Potential Efficacy of Novel Pharmacological Treatments

DTIC Science & Technology

2014-12-01

cardiovascular diseases. At higher doses, these medications have been prescribed to treat high blood pressure in humans and both may have relevance as...HR, and Tc. § Low frequency (LF) systolic blood pressure variability as an index of sympathetic modulation of vascular tone. § LF and high ... blood pressure variability (LFSYS), LF heart rate variability (LFHR), and high frequency heart rate variability (HFHR) in placebo-, clonidine-, and

Modifications to the Patient Rule-Induction Method that utilize non-additive combinations of genetic and environmental effects to define partitions that predict ischemic heart disease.

PubMed

Dyson, Greg; Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne; Sing, Charles F

2009-05-01

This article extends the Patient Rule-Induction Method (PRIM) for modeling cumulative incidence of disease developed by Dyson et al. (Genet Epidemiol 31:515-527) to include the simultaneous consideration of non-additive combinations of predictor variables, a significance test of each combination, an adjustment for multiple testing and a confidence interval for the estimate of the cumulative incidence of disease in each partition. We employ the partitioning algorithm component of the Combinatorial Partitioning Method to construct combinations of predictors, permutation testing to assess the significance of each combination, theoretical arguments for incorporating a multiple testing adjustment and bootstrap resampling to produce the confidence intervals. An illustration of this revised PRIM utilizing a sample of 2,258 European male participants from the Copenhagen City Heart Study is presented that assesses the utility of genetic variants in predicting the presence of ischemic heart disease beyond the established risk factors.

Modifications to the Patient Rule-Induction Method that utilize non-additive combinations of genetic and environmental effects to define partitions that predict ischemic heart disease

PubMed Central

Dyson, Greg; Frikke-Schmidt, Ruth; Nordestgaard, Børge G.; Tybjærg-Hansen, Anne; Sing, Charles F.

2009-01-01

This paper extends the Patient Rule-Induction Method (PRIM) for modeling cumulative incidence of disease developed by Dyson et al. (2007) to include the simultaneous consideration of non-additive combinations of predictor variables, a significance test of each combination, an adjustment for multiple testing and a confidence interval for the estimate of the cumulative incidence of disease in each partition. We employ the partitioning algorithm component of the Combinatorial Partitioning Method (CPM) to construct combinations of predictors, permutation testing to assess the significance of each combination, theoretical arguments for incorporating a multiple testing adjustment and bootstrap resampling to produce the confidence intervals. An illustration of this revised PRIM utilizing a sample of 2258 European male participants from the Copenhagen City Heart Study is presented that assesses the utility of genetic variants in predicting the presence of ischemic heart disease beyond the established risk factors. PMID:19025787

Influence of Heart Rate in Non-linear HRV Indices as a Sampling Rate Effect Evaluated on Supine and Standing.

PubMed

Bolea, Juan; Pueyo, Esther; Orini, Michele; Bailón, Raquel

2016-01-01

The purpose of this study is to characterize and attenuate the influence of mean heart rate (HR) on nonlinear heart rate variability (HRV) indices (correlation dimension, sample, and approximate entropy) as a consequence of being the HR the intrinsic sampling rate of HRV signal. This influence can notably alter nonlinear HRV indices and lead to biased information regarding autonomic nervous system (ANS) modulation. First, a simulation study was carried out to characterize the dependence of nonlinear HRV indices on HR assuming similar ANS modulation. Second, two HR-correction approaches were proposed: one based on regression formulas and another one based on interpolating RR time series. Finally, standard and HR-corrected HRV indices were studied in a body position change database. The simulation study showed the HR-dependence of non-linear indices as a sampling rate effect, as well as the ability of the proposed HR-corrections to attenuate mean HR influence. Analysis in a body position changes database shows that correlation dimension was reduced around 21% in median values in standing with respect to supine position ( p < 0.05), concomitant with a 28% increase in mean HR ( p < 0.05). After HR-correction, correlation dimension decreased around 18% in standing with respect to supine position, being the decrease still significant. Sample and approximate entropy showed similar trends. HR-corrected nonlinear HRV indices could represent an improvement in their applicability as markers of ANS modulation when mean HR changes.

Effects of temperature on the nitric oxide-dependent modulation of the Frank-Starling mechanism: the fish heart as a case study.

PubMed

Amelio, D; Garofalo, F; Capria, C; Tota, B; Imbrogno, S

2013-02-01

The Frank-Starling law is a fundamental property of the vertebrate myocardium which allows, when the end-diastolic volume increases, that the consequent stretch of the myocardial fibers generates a more forceful contraction. It has been shown that in the eel (Anguilla anguilla) heart, nitric oxide (NO) exerts a direct myocardial relaxant effect, increasing the sensitivity of the Frank-Starling response (Garofalo et al., 2009). With the use of isolated working heart preparations, this study investigated the relationship between NO modulation of Frank-Starling response and temperature challenges in the eel. The results showed that while, in long-term acclimated fish (spring animals perfused at 20 °C and winter animals perfused at 10 °C) the inhibition of NO production by L-N5 (1-iminoethyl)ornithine (L-NIO) significantly reduced the Frank-Starling response, under thermal shock conditions (spring animals perfused at 10 or 15 °C and winter animals perfused at 15 or 20 °C) L-NIO treatment resulted without effect. Western blotting analysis revealed a decrease of peNOS and pAkt expressions in samples subjected to thermal shock. Moreover, an increase in Hsp90 protein levels was observed under heat thermal stress. Together, these data suggest that the NO synthase/NO-dependent modulation of the Frank-Starling mechanism in fish is sensitive to thermal stress. Copyright © 2012 Elsevier Inc. All rights reserved.

Sequential modulation of cardiac autonomic control induced by cardiopulmonary and arterial baroreflex mechanisms

NASA Technical Reports Server (NTRS)

Furlan, R.; Jacob, G.; Palazzolo, L.; Rimoldi, A.; Diedrich, A.; Harris, P. A.; Porta, A.; Malliani, A.; Mosqueda-Garcia, R.; Robertson, D.

2001-01-01

BACKGROUND: Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate. METHODS AND RESULTS: Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to -40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (alpha(LF)) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at -10, R-R interval at -20, SAP at -40, and the indexes alpha(LF) and baroreceptor sensitivity at -30 and -20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at -20 mm Hg. The normalized low-frequency component of R-R variability (LF(R-R)) progressively increased and was significantly higher than in the control condition at -15 mm Hg. CONCLUSIONS: Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LF(R-R), which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control.

Video to Text (V2T) in Wide Area Motion Imagery

DTIC Science & Technology

2015-09-01

microtext) or a document (e.g., using Sphinx or Apache NLP ) as an automated approach [102]. Previous work in natural language full-text searching...language processing ( NLP ) based module. The heart of the structured text processing module includes the following seven key word banks...Features Tracker MHT Multiple Hypothesis Tracking MIL Multiple Instance Learning NLP Natural Language Processing OAB Online AdaBoost OF Optic Flow

Animal product consumption and mortality because of all causes combined, coronary heart disease, stroke, diabetes, and cancer in Seventh-day Adventists.

PubMed

Snowdon, D A

1988-09-01

This report reviews, contrasts, and illustrates previously published findings from a cohort of 27,529 California Seventh-day Adventist adults who completed questionnaires in 1960 and were followed for mortality between 1960 and 1980. Within this population, meat consumption was positively associated with mortality because of all causes of death combined (in males), coronary heart disease (in males and females), and diabetes (in males). Egg consumption was positively associated with mortality because of all causes combined (in females), coronary heart disease (in females), and cancers of the colon (in males and females combined) and ovary. Milk consumption was positively associated with only prostate cancer mortality, and cheese consumption did not have a clear relationship with any cause of death. The consumption of meat, eggs, milk, and cheese did not have negative associations with any of the causes of death investigated.

Selection of reference genes for gene expression studies in heart failure for left and right ventricles.

PubMed

Li, Mengmeng; Rao, Man; Chen, Kai; Zhou, Jianye; Song, Jiangping

2017-07-15

Real-time quantitative reverse transcriptase-PCR (qRT-PCR) is a feasible tool for determining gene expression profiles, but the accuracy and reliability of the results depends on the stable expression of selected housekeeping genes in different samples. By far, researches on stable housekeeping genes in human heart failure samples are rare. Moreover the effect of heart failure on the expression of housekeeping genes in right and left ventricles is yet to be studied. Therefore we aim to provide stable housekeeping genes for both ventricles in heart failure and normal heart samples. In this study, we selected seven commonly used housekeeping genes as candidates. By using the qRT-PCR, the expression levels of ACTB, RAB7A, GAPDH, REEP5, RPL5, PSMB4 and VCP in eight heart failure and four normal heart samples were assessed. The stability of candidate housekeeping genes was evaluated by geNorm and Normfinder softwares. GAPDH showed the least variation in all heart samples. Results also indicated the difference of gene expression existed in heart failure left and right ventricles. GAPDH had the highest expression stability in both heart failure and normal heart samples. We also propose using different sets of housekeeping genes for left and right ventricles respectively. The combination of RPL5, GAPDH and PSMB4 is suitable for the right ventricle and the combination of GAPDH, REEP5 and RAB7A is suitable for the left ventricle. Copyright © 2017 Elsevier B.V. All rights reserved.

SU-F-T-87: Comparison of Advanced Radiotherapy Techniques for Post- Mastectomy Breast Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heins, D; Zhang, R; Hogstrom, K

2016-06-15

Purpose: To determine if bolus electron conformal therapy (Bolus-ECT) combined with intensity modulated x-ray therapy (IMXT) and flattening filter free volumetric modulated arc therapy (FFF-VMAT (6x and 10x)) can maintain equal or better dose coverage than standard volumetric modulated arc therapy (Std-VMAT) while reducing doses to organs at risk (OARs). Methods: Bolus-ECT with IMXT, FFF-VMAT, and Std-VMAT treatment plans were produced for ten post-mastectomy radiotherapy (PMRT) patients previously treated at our clinic. The treatment plans were created on commercially available treatment planning system (TPS) and all completed treatment plans were reviewed and approved by a radiation oncologist. The plans weremore » evaluated based on planning target volume (PTV) coverage, tumor control probability (TCP), dose homogeneity index (DHI), conformity index (CI), and dose to organs at risk (OAR). Results: All techniques produced clinically acceptable PMRT plans. Overall, Bolus-ECT with IMXT exhibited higher maximum dose compared to all VMAT techniques. Bolus-ECT with IMXT and FFF-VMAT10x had slightly improved TCP over FFF-VMAT6x and Std-VMAT. However, all VMAT techniques showed improved CI and DHI over Bolus-ECT with IMXT. All techniques showed very similar mean lung dose. Bolus-ECT with IMXT exhibited a reduced mean heart dose over Std-VMAT. Both FFF-VMAT techniques had higher mean heart dose compared to Std-VMAT. In addition, Bolus-ECT with IMXT was able to reduce mean dose to the contralateral breast compared to Std-VMAT and both FFF-VMAT techniques had comparable but slightly reduced dose compared to Std-VMAT. Conclusion: This work has shown that Bolus-ECT with IMXT produces clinically acceptable plans while reducing OAR doses. Both FFF-VMAT techniques are comparable to Std-VMAT with slight improvements. Even though all VMAT techniques produce more homogenous and conformal dose distributions, Bolus-ECT with IMXT is a viable option for treating post-mastectomy patients possibly leading to reduced risks of normal tissue complications.« less

Foot reflexology can increase vagal modulation, decrease sympathetic modulation, and lower blood pressure in healthy subjects and patients with coronary artery disease.

PubMed

Lu, Wan-An; Chen, Gau-Yang; Kuo, Cheng-Deng

2011-01-01

Complementary and alternative medicine (CAM) has long been used by people to postpone the aging process and to reverse disease progression. Reflexology is a CAM method that involves massage to reflex areas in the feet and hands. This study investigated the effect of foot reflexology (FR) on the autonomic nervous modulation in patients with coronary artery disease (CAD) by using heart rate variability analysis. Seventeen people with angiographically patent coronary arteries and 20 patients with CAD scheduled for coronary artery bypass graft surgery were recruited as the control and CAD groups, respectively. The normalized high-frequency power (nHFP) was used as the index of vagal modulation and the normalized very low-frequency power (nVLFP) as the index of vagal withdrawal and renin-angiotensin modulation. In both control and CAD groups, the nHFP was increased significantly whereas the nVLFP was decreased significantly 30 and 60 minutes after FR, as compared with those before FR. The systolic, diastolic, mean arterial, and pulse pressures were significantly decreased after FR in both groups of participants. In the CAD group, the percentage change in heart rate 30 and 60 minutes after FR was smaller than that in the control, and the percentage change in nVLFP 60 minutes after FR was smaller than that in the control. In conclusion, a higher vagal modulation, lower sympathetic modulation, and lower blood pressure can be observed following 60 minutes of FR in both controls and CAD patients. The magnitude of change in the autonomic nervous modulation in CAD patients was slightly smaller than that in the controls. FR may be used as an efficient adjunct to the therapeutic regimen to increase the vagal modulation and decrease blood pressure in both healthy people and CAD patients.

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling

PubMed Central

Dick, Thomas E.; Molkov, Yaroslav I.; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J.; Doyle, John; Scheff, Jeremy D.; Calvano, Steve E.; Androulakis, Ioannis P.; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma. PMID:22783197

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling.

PubMed

Dick, Thomas E; Molkov, Yaroslav I; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J; Doyle, John; Scheff, Jeremy D; Calvano, Steve E; Androulakis, Ioannis P; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma.

Caloric restriction: powerful protection for the aging heart and vasculature.

PubMed

Weiss, Edward P; Fontana, Luigi

2011-10-01

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Research has shown that the majority of the cardiometabolic alterations associated with an increased risk of CVD (e.g., insulin resistance/type 2 diabetes, abdominal obesity, dyslipidemia, hypertension, and inflammation) can be prevented, and even reversed, with the implementation of healthier diets and regular exercise. Data from animal and human studies indicate that more drastic interventions, i.e., calorie restriction with adequate nutrition (CR), may have additional beneficial effects on several metabolic and molecular factors that are modulating cardiovascular aging itself (e.g., cardiac and arterial stiffness and heart rate variability). The purpose of this article is to review the current knowledge on the effects of CR on the aging of the cardiovascular system and CVD risk in rodents, monkeys, and humans. Taken together, research shows that CR has numerous beneficial effects on the aging cardiovascular system, some of which are likely related to reductions in inflammation and oxidative stress. In the vasculature, CR appears to protect against endothelial dysfunction and arterial stiffness and attenuates atherogenesis by improving several cardiometabolic risk factors. In the heart, CR attenuates age-related changes in the myocardium (i.e., CR protects against fibrosis, reduces cardiomyocyte apoptosis, prevents myosin isoform shifts, etc.) and preserves or improves left ventricular diastolic function. These effects, in combination with other benefits of CR, such as protection against obesity, diabetes, hypertension, and cancer, suggest that CR may have a major beneficial effect on health span, life span, and quality of life in humans.

Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology.

PubMed

Eschenhagen, Thomas; Force, Thomas; Ewer, Michael S; de Keulenaer, Gilles W; Suter, Thomas M; Anker, Stefan D; Avkiran, Metin; de Azambuja, Evandro; Balligand, Jean-Luc; Brutsaert, Dirk L; Condorelli, Gianluigi; Hansen, Arne; Heymans, Stephane; Hill, Joseph A; Hirsch, Emilio; Hilfiker-Kleiner, Denise; Janssens, Stefan; de Jong, Steven; Neubauer, Gitte; Pieske, Burkert; Ponikowski, Piotr; Pirmohamed, Munir; Rauchhaus, Mathias; Sawyer, Douglas; Sugden, Peter H; Wojta, Johann; Zannad, Faiez; Shah, Ajay M

2011-01-01

The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.

Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy

PubMed Central

2013-01-01

Background In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. Results We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Conclusions Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities. PMID:23937664

Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy.

PubMed

Benz, Peter M; Merkel, Carla J; Offner, Kristin; Abeßer, Marco; Ullrich, Melanie; Fischer, Tobias; Bayer, Barbara; Wagner, Helga; Gambaryan, Stepan; Ursitti, Jeanine A; Adham, Ibrahim M; Linke, Wolfgang A; Feller, Stephan M; Fleming, Ingrid; Renné, Thomas; Frantz, Stefan; Unger, Andreas; Schuh, Kai

2013-08-12

In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.

Beam combining and SBS suppression in white noise and pseudo-random modulated amplifiers

NASA Astrophysics Data System (ADS)

Anderson, Brian; Flores, Angel; Holten, Roger; Ehrenreich, Thomas; Dajani, Iyad

2015-03-01

White noise phase modulation (WNS) and pseudo-random binary sequence phase modulation (PRBS) are effective techniques for mitigation of nonlinear effects such as stimulated Brillouin scattering (SBS); thereby paving the way for higher power narrow linewidth fiber amplifiers. However, detailed studies comparing both coherent beam combination and the SBS suppression of these phase modulation schemes have not been reported. In this study an active fiber cutback experiment is performed comparing the enhancement factor of a PRBS and WNS broadened seed as a function of linewidth and fiber length. Furthermore, two WNS and PRBS modulated fiber lasers are coherently combined to measure and compare the fringe visibility and coherence length as a function of optical path length difference. Notably, the discrete frequency comb of PRBS modulation provides a beam combining re-coherence effect where the lasers periodically come back into phase. Significantly, this may reduce path length matching complexity in coherently combined fiber laser systems.

Predicting depressed patients with suicidal ideation from ECG recordings.

PubMed

Khandoker, A H; Luthra, V; Abouallaban, Y; Saha, S; Ahmed, K I; Mostafa, R; Chowdhury, N; Jelinek, H F

2017-05-01

Globally suicidal behavior is the third most common cause of death among patients with major depressive disorder (MDD). This study presents multi-lag tone-entropy (T-E) analysis of heart rate variability (HRV) as a screening tool for identifying MDD patients with suicidal ideation. Sixty-one ECG recordings (10 min) were acquired and analyzed from control subjects (29 CONT), 16 MDD subjects with (MDDSI+) and 16 without suicidal ideation (MDDSI-). After ECG preprocessing, tone and entropy values were calculated for multiple lags (m: 1-10). The MDDSI+ group was found to have a higher mean tone value compared to that of the MDDSI- group for lags 1-8, whereas the mean entropy value was lower in MDDSI+ than that in CONT group at all lags (1-10). Leave-one-out cross-validation tests, using a classification and regression tree (CART), obtained 94.83 % accuracy in predicting MDDSI+ subjects by using a combination of tone and entropy values at all lags and including demographic factors (age, BMI and waist circumference) compared to results with time and frequency domain HRV analysis. The results of this pilot study demonstrate the usefulness of multi-lag T-E analysis in identifying MDD patients with suicidal ideation and highlight the change in autonomic nervous system modulation of the heart rate associated with depression and suicidal ideation.

Effects of high flavanol dark chocolate on cardiovascular function and platelet aggregation.

PubMed

Rull, Gurvinder; Mohd-Zain, Zetty N; Shiel, Julian; Lundberg, Martina H; Collier, David J; Johnston, Atholl; Warner, Timothy D; Corder, Roger

2015-08-01

Regular consumption of chocolate and cocoa products has been linked to reduced cardiovascular mortality. This study compared the effects of high flavanol dark chocolate (HFDC; 1064mg flavanols/day for 6weeks) and low flavanol dark chocolate (LFDC; 88mg flavanols/day for 6weeks) on blood pressure, heart rate, vascular function and platelet aggregation in men with pre-hypertension or mild hypertension. Vascular function was assessed by pulse wave analysis using radial artery applanation tonometry in combination with inhaled salbutamol (0.4mg) to assess changes due to endothelium-dependent vasodilatation. HFDC did not significantly reduce blood pressure compared to baseline or LFDC. Heart rate was increased by LFDC compared to baseline, but not by HFDC. Vascular responses to salbutamol tended to be greater after HFDC. Platelet aggregation induced by collagen or the thromboxane analogue U46619 was unchanged after LFDC or HFDC, whereas both chocolates reduced responses to ADP and the thrombin receptor activator peptide, SFLLRNamide (TRAP6), relative to baseline. Pre-incubation of platelets with theobromine also attenuated platelet aggregation induced by ADP or TRAP6. We conclude that consumption of HFDC confers modest improvements in cardiovascular function. Platelet aggregation is modulated by a flavanol-independent mechanism that is likely due to theobromine. Copyright © 2015 Elsevier Inc. All rights reserved.

Biomechanics of the Chick Embryonic Heart Outflow Tract at HH18 Using 4D Optical Coherence Tomography Imaging and Computational Modeling

PubMed Central

Liu, Aiping; Yin, Xin; Shi, Liang; Li, Peng; Thornburg, Kent L.; Wang, Ruikang; Rugonyi, Sandra

2012-01-01

During developmental stages, biomechanical stimuli on cardiac cells modulate genetic programs, and deviations from normal stimuli can lead to cardiac defects. Therefore, it is important to characterize normal cardiac biomechanical stimuli during early developmental stages. Using the chicken embryo model of cardiac development, we focused on characterizing biomechanical stimuli on the Hamburger–Hamilton (HH) 18 chick cardiac outflow tract (OFT), the distal portion of the heart from which a large portion of defects observed in humans originate. To characterize biomechanical stimuli in the OFT, we used a combination of in vivo optical coherence tomography (OCT) imaging, physiological measurements and computational fluid dynamics (CFD) modeling. We found that, at HH18, the proximal portion of the OFT wall undergoes larger circumferential strains than its distal portion, while the distal portion of the OFT wall undergoes larger wall stresses. Maximal wall shear stresses were generally found on the surface of endocardial cushions, which are protrusions of extracellular matrix onto the OFT lumen that later during development give rise to cardiac septa and valves. The non-uniform spatial and temporal distributions of stresses and strains in the OFT walls provide biomechanical cues to cardiac cells that likely aid in the extensive differential growth and remodeling patterns observed during normal development. PMID:22844414

Cardiovascular disease and type 2 diabetes in evolutionary perspective: A critical role for helminths?

PubMed Central

Gurven, Michael D.; Trumble, Benjamin C.; Stieglitz, Jonathan; Blackwell, Aaron D.; Michalik, David E.; Finch, Caleb E.; Kaplan, Hillard S.

2016-01-01

Heart disease and type 2 diabetes are commonly believed to be rare among contemporary subsistence-level human populations, and by extension prehistoric populations. Although some caveats remain, evidence shows these diseases to be unusual among well-studied hunter-gatherers and other subsistence populations with minimal access to healthcare. Here we expand on a relatively new proposal for why these and other populations may not show major signs of these diseases. Chronic infections, especially helminths, may offer protection against heart disease and diabetes through direct and indirect pathways. As part of a strategy to insure their own survival and reproduction, helminths exert multiple cardio-protective effects on their host through their effects on immune function and blood lipid metabolism. Helminths consume blood lipids and glucose, alter lipid metabolism, and modulate immune function towards Th-2 polarization—which combined can lower blood cholesterol, reduce obesity, increase insulin sensitivity, decrease atheroma progression, and reduce likelihood of atherosclerotic plaque rupture. Traditional cardiometabolic risk factors, coupled with the mismatch between our evolved immune systems and modern, hygienic environments may interact in complex ways. In this review, we survey existing studies in the non-human animal and human literature, highlight unresolved questions and suggest future directions to explore the role of helminths in the etiology of cardio-metabolic disease. PMID:27666719

Cascade and parallel combination (CPC) of adaptive filters for estimating heart rate during intensive physical exercise from photoplethysmographic signal

PubMed Central

Islam, Mohammad Tariqul; Tanvir Ahmed, Sk.; Zabir, Ishmam; Shahnaz, Celia

2018-01-01

Photoplethysmographic (PPG) signal is getting popularity for monitoring heart rate in wearable devices because of simplicity of construction and low cost of the sensor. The task becomes very difficult due to the presence of various motion artefacts. In this study, an algorithm based on cascade and parallel combination (CPC) of adaptive filters is proposed in order to reduce the effect of motion artefacts. First, preliminary noise reduction is performed by averaging two channel PPG signals. Next in order to reduce the effect of motion artefacts, a cascaded filter structure consisting of three cascaded adaptive filter blocks is developed where three-channel accelerometer signals are used as references to motion artefacts. To further reduce the affect of noise, a scheme based on convex combination of two such cascaded adaptive noise cancelers is introduced, where two widely used adaptive filters namely recursive least squares and least mean squares filters are employed. Heart rates are estimated from the noise reduced PPG signal in spectral domain. Finally, an efficient heart rate tracking algorithm is designed based on the nature of the heart rate variability. The performance of the proposed CPC method is tested on a widely used public database. It is found that the proposed method offers very low estimation error and a smooth heart rate tracking with simple algorithmic approach. PMID:29515812

Prognostic capacity of a clinically indicated exercise test for cardiovascular mortality is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans.

PubMed

Minkkinen, Mikko; Nieminen, Tuomo; Verrier, Richard L; Leino, Johanna; Lehtimäki, Terho; Viik, Jari; Lehtinen, Rami; Nikus, Kjell; Kööbi, Tiit; Turjanmaa, Väinö; Kähönen, Mika

2015-09-01

Exercise capacity, heart rate recovery and T-wave alternans are independent predictors of cardiovascular mortality. We tested whether these parameters contain supplementary prognostic information. A total of 3609 consecutive patients (2157 men) referred for a routine, clinically indicated bicycle exercise test were enrolled in the Finnish Cardiovascular Study (FINCAVAS). Exercise capacity was measured in metabolic equivalents, heart rate recovery as the decrease in heart rate from maximum to one minute post-exercise, and T-wave alternans by time-domain Modified Moving Average method. During 57-month median follow-up (interquartile range 35-78 months), 96 patients died of cardiovascular causes (primary endpoint) and 233 from any cause. All three parameters were independent predictors of cardiovascular mortality when analysed as continuous variables. Adding metabolic equivalents (p < 0.001), heart rate recovery (p = 0.002) or T-wave alternans (p = 0.01) to the linear model improved its predictive power for cardiovascular mortality. The combination of low exercise capacity (<6 metabolic equivalents), reduced heart rate recovery (≤12 beats/min) and elevated T-wave alternans (≥60 μV) yielded the highest hazard ratio for cardiovascular mortality of 16.5 (95% confidence interval 4.0-67.7, p < 0.001). Harrell's C index was 0.719 (confidence interval 0.665-0.772) for cardiovascular mortality with previously defined cutpoints (<8 units for metabolic equivalents, ≤18 beats/min for heart rate recovery and ≥60 μV for T-wave alternans). The prognostic capacity of the clinical exercise test is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans. © The European Society of Cardiology 2014.

76 FR 38180 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... lookback module, and a pretest of colorectal cancer screening questions. The asthma supplement will collect... high risk for heart disease and stroke. Finally, a small pretest in hospital-based ASLs and...

Combined short-arm centrifuge and aerobic exercise training improves cardiovascular function and physical working capacity in humans.

PubMed

Yang, Chang-Bin; Zhang, Shu; Zhang, Yu; Wang, Bing; Yao, Yong-Jie; Wang, Yong-Chun; Wu, Yan-Hong; Liang, Wen-Bin; Sun, Xi-Qing

2010-12-01

Musculoskeletal and cardiovascular deconditioning occurring in long-term spaceflight gives rise to the needs to develop new strategies to counteract these adverse effects. Short-arm centrifuge combined with ergometer has been proposed as a strategy to counteract adverse effects of microgravity. This study sought to investigate whether the combination of short-arm centrifuge and aerobic exercise training have advantages over short-arm centrifuge or aerobic exercise training alone. One week training was conducted by 24 healthy men. They were randomly divided into 3 groups: (1) short-arm centrifuge training, (2) aerobic exercise training, 40 W, and (3) combined short-arm centrifuge and aerobic exercise training. Before and after training, the cardiac pump function represented by stroke volume, cardiac output, left ventricular ejection time, and total peripheral resistance was evaluated. Variability of heart rate and systolic blood pressure were determined by spectral analysis. Physical working capacity was surveyed by near maximal physical working capacity test. The 1-week combined short-arm centrifuge and aerobic exercise training remarkably ameliorated the cardiac pump function and enhanced vasomotor sympathetic nerve modulation and improved physical working capacity by 10.9% (P<.05, n=8). In contrast, neither the short-arm centrifuge nor the aerobic exercise group showed improvements in these functions. These results demonstrate that combined short-arm centrifuge and aerobic exercise training has advantages over short-arm centrifuge or aerobic exercise training alone in influencing several physiologically important cardiovascular functions in humans. The combination of short-arm centrifuge and aerobic exercise offers a promising countermeasure to microgravity.

Preattentive processing of heart cues and the perception of heart symptoms in congenital heart disease.

PubMed

Karsdorp, Petra A; Kindt, Merel; Everaerd, Walter; Mulder, Barbara J M

2007-08-01

The present study was aimed at clarifying whether preattentive processing of heart cues results in biased perception of heart sensations in patients with congenital heart disease (ConHD) who are also highly trait anxious. Twenty-six patients with ConHD and 22 healthy participants categorized heart-related (heart rate) or neutral sensations (constant vibration) as either heart or neutral. Both sensations were evoked using a bass speaker that was attached on the chest of the participant. Before each physical sensation, a subliminal heart-related or neutral prime was presented. Biased perception of heart-sensations would become evident by a delayed categorization of the heart-related sensations. In line with the prediction, a combination of high trait anxiety and ConHD resulted in slower responses after a heart-related sensation that was preceded by a subliminal heart cue. Preattentive processing of harmless heart cues may easily elicit overperception of heart symptoms in highly trait anxious patients with ConHD.

Renin-angiotensin-aldosterone system (RAAS) pharmacogenomics: implications in heart failure management.

PubMed

Beitelshees, Amber L; Zineh, Issam

2010-05-01

Blockade of the renin-angiotensin-aldosterone system (RAAS) with ACE inhibitors has been a cornerstone of heart failure therapy for over 15 years. More recently, further blockade of RAAS with aldosterone antagonists and angiotensin receptor blockers (ARBs) has been studied. While these therapies have certainly improved outcomes in the treatment of heart failure, morbidity and mortality remain extremely high. Furthermore, polypharmacy and complex regimens of seven medications on average is the norm for management of heart failure. This results in increased costs, patient burden, and uncertainty as to the best course of therapy. The ability to personalize patients' therapeutic regimens using pharmacogenomics has the potential of providing more effective and efficient use of RAAS-modulating medications. This review highlights the implications of major RAAS pharmacogenetic studies, while outlining future directions for translation to practice.

The role of 17-beta estradiol in ischemic preconditioning protection of the heart.

PubMed

Babiker, Fawzi A; Hoteit, Lamia J; Joseph, Shaji; Mustafa, Abu Salim; Juggi, Jasbir S

2012-09-01

The protective effects of 17-beta estradiol (E2) on cardiac tissue during ischemia/reperfusion (I/R) injury have not yet been fully elucidated. To assess the protective effects of short- and long-term E2 treatments on cardiac tissue exposed to I/R, and to assess the effects of these treatments in combination with ischemic preconditioning (IPC) on cardiac protection from I/R injury. SPRAGUE DAWLEY RATS WERE ASSIGNED TO THE FOLLOWING TREATMENT PROTOCOLS: control (no preconditioning); IPC (isolated hearts were subjected to two cycles of 5 min global ischemia followed by 10 min of reperfusion); E2 preconditioning (E2PC; isolated hearts were subjected to E2 pharmacological perfusion for 15 min); short-term in vivo E2 pretreatment for 3 h; long-term in vivo E2 pretreatment or withdrawal (ovariectomy followed by a six-week treatment with E2 or a placebo); combined IPC and E2PC; combined IPC and short- or long-term E2 pretreatments or withdrawal. All hearts were isolated and stabilized for at least 30 min before being subjected to 40 min of global ischemia followed by 30 min of reperfusion; left ventricular function and vascular hemodynamics were then assessed. IPC, E2PC and short-term E2 pretreatment led to the recovery of left ventricle function and vascular hemodynamics. Long-term E2 and placebo treatments did not result in any protection compared with untreated controls. The combination of E2PC or short-term E2 treatments with IPC did not block the IPC protection or result in any additional protection to the heart. Long-term E2 treatment blocked IPC protection; however, placebo treatment did not. Short-term treatment with E2 protected the heart against I/R injury through a pathway involving the regulation of tumour necrosis factor-alpha. The combination of short-term E2 treatment with IPC did not provide additional protection to the heart. Short-term E2 treatment may be a suitable alternative for classical estrogen replacement therapy.

Plasma pro-brain natriuretic peptide and electrocardiographic changes in combination improve risk prediction in persons without known heart disease.

PubMed

Jørgensen, Peter G; Jensen, Jan S; Appleyard, Merete; Jensen, Gorm B; Mogelvang, Rasmus

2015-12-15

Though the electrocardiogram(ECG) and plasma pro-brain-natriuretic-peptide (pro-BNP) are widely used markers of subclinical cardiac injury and can be used to predict future cardiovascular disease(CVD), they could merely be markers of the same underlying pathology. We aimed to determine if ECG changes and pro-BNP are independent predictors of CVD and if the combination improves risk prediction in persons without known heart disease. Pro-BNP and ECG were obtained on 5454 persons without known heart disease from the 4th round of the Copenhagen City Heart Study, a prospective cohort study. Median follow-up was 10.4 years. High pro-BNP was defined as above 90th percentile of age and sex adjusted levels. The end-points were all-cause mortality and the combination of admission with ischemic heart disease, heart failure or CVD death. ECG changes were present in 907 persons and were associated with high levels of pro-BNP. In a fully adjusted model both high pro-BNP and ECG changes remained significant predictors: all-cause mortality(high pro-BNP, no ECG changes: HR: 1.43(1.12-1.82);P=0.005, low pro-BNP, ECG changes: HR: 1.22(1.05-1.42);P=0.009, and both high pro-BNP and ECG changes: HR: 1.99(1.54-2.59);P<0.001), CVD event(high pro-BNP, no ECG changes: HR: 1.94(1.45-2.58);P<0.001, low pro-BNP, ECG changes: HR: 1.55(1.29-1.87);P<0.001, and both high pro-BNP and ECG changes: HR: 3.86(2.94-5.08);P<0.001). Adding the combination of pro-BNP and ECG changes to a fully adjusted model correctly reclassified 33.9%(26.5-41.3);P<0.001 on the continuous net reclassification scale for all-cause mortality and 49.7%(41.1-58.4);P<0.001 for CVD event. Combining ECG changes and pro-BNP improves risk prediction in persons without known heart disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reduced lung dose during radiotherapy for thoracic esophageal carcinoma: VMAT combined with active breathing control for moderate DIBH.

PubMed

Gong, Guanzhong; Wang, Ruozheng; Guo, Yujie; Zhai, Deyin; Liu, Tonghai; Lu, Jie; Chen, Jinhu; Liu, Chengxin; Yin, Yong

2013-12-20

Lung radiation injury is a critical complication of radiotherapy (RT) for thoracic esophageal carcinoma (EC). Therefore, the goal of this study was to investigate the feasibility and dosimetric effects of reducing the lung tissue irradiation dose during RT for thoracic EC by applying volumetric modulated arc radiotherapy (VMAT) combined with active breathing control (ABC) for moderate deep inspiration breath-hold (mDIBH). Fifteen patients with thoracic EC were randomly selected to undergo two series of computed tomography (CT) simulation scans with ABC used to achieve mDIBH (representing 80% of peak DIBH value) versus free breathing (FB). Gross tumor volumes were contoured on different CT images, and planning target volumes (PTVs) were obtained using different margins. For PTV-FB, intensity-modulated radiotherapy (IMRT) was designed with seven fields, and VMAT included two whole arcs. For PTV-DIBH, VMAT with three 135° arcs was applied, and the corresponding plans were named: IMRT-FB, VMAT-FB, and VMAT-DIBH, respectively. Dosimetric differences between the different plans were compared. The heart volumes decreased by 19.85%, while total lung volume increased by 52.54% in mDIBH, compared to FB (p < 0.05). The mean conformality index values and homogeneity index values for VMAT-DIBH (0.86, 1.07) were slightly worse than those for IMRT-FB (0.90, 1.05) and VMAT-FB (0.90, 1.06) (p > 0.05). Furthermore, compared to IMRT-FB and VMAT-FB, VMAT-DIBH reduced the mean total lung dose by 18.64% and 17.84%, respectively (p < 0.05); moreover, the V5, V10, V20, and V30 values for IMRT-FB and VMAT-FB were reduced by 10.84% and 10.65% (p > 0.05), 12.5% and 20% (p < 0.05), 30.77% and 33.33% (p < 0.05), and 50.33% and 49.15% (p < 0.05), respectively. However, the heart dose-volume indices were similar between VMAT-DIBH and VMAT-FB which were lower than IMRT-FB without being statistically significant (p > 0.05). The monitor units and treatment time of VMAT-DIBH were also the lowest (p < 0.05). VMAT combined with ABC to achieve mDIBH is a feasible approach for RT of thoracic EC. Furthermore, this method has the potential to effectively reduce lung dose in a shorter treatment time and with better targeting accuracy.

The 'aerobic/resistance/inspiratory muscle training hypothesis in heart failure'.

PubMed

Laoutaris, Ioannis D

2018-01-01

Evidence from large multicentre exercise intervention trials in heart failure patients, investigating both moderate continuous aerobic training and high intensity interval training, indicates that the 'crème de la crème' exercise programme for this population remains to be found. The 'aerobic/resistance/inspiratory (ARIS) muscle training hypothesis in heart failure' is introduced, suggesting that combined ARIS muscle training may result in maximal exercise pathophysiological and functional benefits in heart failure patients. The hypothesis is based on the decoding of the 'skeletal muscle hypothesis in heart failure' and on revision of experimental evidence to date showing that exercise and functional intolerance in heart failure patients are associated not only with reduced muscle endurance, indication for aerobic training (AT), but also with reduced muscle strength and decreased inspiratory muscle function contributing to weakness, dyspnoea, fatigue and low aerobic capacity, forming the grounds for the addition of both resistance training (RT) and inspiratory muscle training (IMT) to AT. The hypothesis will be tested by comparing all potential exercise combinations, ARIS, AT/RT, AT/IMT, AT, evaluating both functional and cardiac indices in a large sample of heart failure patients of New York Heart Association class II-III and left ventricular ejection fraction ≤35% ad hoc by the multicentre randomized clinical trial, Aerobic Resistance, InSpiratory Training OutcomeS in Heart Failure (ARISTOS-HF trial).

Effect of pedal rate and power output on rating of perceived exertion during cycle ergometry exercise.

PubMed

Hamer, Mark; Boutcher, Yati N; Boutcher, Stephen H

2005-12-01

This study examined differentiated rating of perceived exertion (RPE), heart rate, and heart-rate variability during light cycle ergometry exercise at two different pedal rates. 30 healthy men (22.6 +/- 0.9 yr.) were recruited from a student population and completed a continuous 20-min. cycle ergometry exercise protocol, consisting of a 4-min. warm-up (60 rev./min., 30 Watts), followed by four bouts of 4 min. at different combinations of pedal rate (40 or 80 rev./min.) and power output (40 or 80 Watts). The order of the four combinations was counterbalanced across participants. Heart rate was measured using a polar heart-rate monitor, and parasympathetic balance was assessed through time series analysis of heart-rate variability. Measures were compared using a 2 (pedal rate) x 2 (power output) repeated-measures analysis of variance. RPE was significantly greater (p<.05) at 80 versus 40 rev./min. at 40 W. For both power outputs heart rate was significantly increased, and the high frequency component of heart-rate variability was significantly reduced at 80 compared with 40 rev./min. These findings indicate the RPE was greater at higher than at lower pedalling rates for a light absolute power output which contrasts with previous findings based on use of higher power output. Also, pedal rate had a significant effect on heart rate and heart-rate variability at constant power output.

The endothelin pathway: a protective or detrimental target of bardoxolone methyl on cardiac function in patients with advanced chronic kidney disease?

PubMed

Camer, Danielle; Huang, Xu-Feng

2014-01-01

Bardoxolone methyl has been reported to cause detrimental cardiovascular events in the terminated BEACON Phase III human clinical trial via modulation of the renal endothelin pathway. However, the effects of bardoxolone methyl administration on the endothelin pathway in the heart are unknown. Our purpose in this perspective is to highlight the distinctive opposing roles of the renal and heart endothelin pathway in cardiac function. Furthermore, we address the need for further investigation in order to determine if bardoxolone methyl has a protective role in cardiac function through the suppression of the endothelin pathway in the heart. © 2014 S. Karger AG, Basel.

Iron status and its association with coronary heart disease: systematic review and meta-analysis of prospective studies.

PubMed

Das De, Sudeep; Krishna, Sreedhar; Jethwa, Ankeet

2015-02-01

Observations in the past have hypothesized an association between body iron status and coronary heart disease (CHD). Epidemiological studies to date have however been inconclusive without the existence of strongly positive or strongly negative associations between iron status and coronary heart disease. To investigate the association between iron status and coronary heart disease. A systematic review was performed using the databases PubMed and Cochrane Library. Search terms included iron, ferritin, transferrin, total iron binding capacity, coronary heart disease and angina. Only prospective studies investigating the association of body iron status and coronary heart disease were included. All participants were free from coronary heart disease at baseline. There were no language or geographic restrictions imposed on the search strategy. Independent extraction of articles by 2 authors using predefined data fields. All pooled analyses were based on random-effects models. A total of 17 studies were identified for analysis, involving a total of 9236 cases of coronary heart disease and 156,427 participants. Several studies reported more than 1 marker of iron status. For serum ferritin, comparison of individuals in the top third versus the bottom third of baseline measurements yielded a combined risk ratio of 1.03 (95%CI, 0.87-1.23) for CHD/MI. For transferrin saturation, the combined risk ratio for CHD/MI was 0.82 (95% CI, 0.75-0.89) for individuals in the top third versus the bottom third of baseline measurements. Comparison of individuals in top and bottom thirds of baseline measurements yielded non-significant risk ratios of studies involving total iron-binding capacity (combined risk ratio, 0.99; 95% CI 0.86-1.13) and serum iron (combined risk ratio, 0.87; 95% CI 0.73-1.04). For serum iron, the combined risk ratio for CHD/MI after excluding the study by Morrisson et al. [1] was 0.80 (95% CI, 0.73-0.87). The results suggest that there is a negative association of transferrin levels and coronary heart disease with high transferrin saturations being associated with a lower risk of CHD/MI. There was also a negative association of serum iron and CHD/MI after one study [1] was excluded. There is no significant association between the other markers of iron status and CHD. It is however difficult to infer causality from these findings due to limitations in terms of reverse causality bias and residual confounding. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Aldosterone Promotes Cardiac Endothelial Cell Proliferation In Vivo

PubMed Central

Gravez, Basile; Tarjus, Antoine; Pelloux, Véronique; Ouvrard‐Pascaud, Antoine; Delcayre, Claude; Samuel, Janelise; Clément, Karine; Farman, Nicolette; Jaisser, Fréderic; Messaoudi, Smail

2015-01-01

Background Experimentally, aldosterone in association with NaCl induces cardiac fibrosis, oxidative stress, and inflammation through mineralocorticoid receptor activation; however, the biological processes regulated by aldosterone alone in the heart remain to be identified. Methods and Results Mice were treated for 7 days with aldosterone, and then cardiac transcriptome was analyzed. Aldosterone regulated 60 transcripts (51 upregulated and 9 downregulated) in the heart (fold change ≥1.5, false discovery rate <0.01). To identify the biological processes modulated by aldosterone, a gene ontology analysis was performed. The majority of aldosterone‐regulated genes were involved in cell division. The cardiac Ki‐67 index (an index of proliferation) of aldosterone‐treated mice was higher than that of nontreated mice, confirming microarray predictions. Costaining of Ki‐67 with vinculin, CD68, α‐smooth muscle actin, CD31, or caveolin 1 revealed that the cycling cells were essentially endothelial cells. Aldosterone‐induced mineralocorticoid receptor–dependent proliferation was confirmed ex vivo in human endothelial cells. Moreover, pharmacological‐specific blockade of mineralocorticoid receptor by eplerenone inhibited endothelial cell proliferation in a preclinical model of heart failure (transverse aortic constriction). Conclusions Aldosterone modulates cardiac gene expression and induces the proliferation of cardiac endothelial cells in vivo. PMID:25564371

The heart as an extravascular target of endothelin-1 in ...

EPA Pesticide Factsheets

Exposure to particulate matter air pollution has been causally linked to cardiovascular disease in humans. Several broad and overlapping hypotheses describing the biological mechanisms by which particulate matter exposure leads to cardiovascular disease and cardiac dysfunction have been explored, though linkage with specific factors or genes remains limited. Given evidence pointing to autocrine/paracrine signaling systems as modulators of cardiac dysfunction, the present review highlights the emerging role of endothelins as mediators of cardiac dysfunction following particulate matter exposure. Endothelin-1 is a small multifunctional protein expressed in the pulmonary and cardiovascular system, known for its ability to constrict blood vessels. Although endothelin-1 can also directly and indirectly (via secondary signaling events) modulate cardiac contractility, heart rate, and rhythm, research on the role of endothelins in the context of air pollution has tended to focus on the vascular effects. The plausibility of endothelin as a mechanism underlying particulate matter-induced cardiac dysfunction is further supported by the therapeutic utility of certain endothelin receptor antagonists. Extravascular effects of endothelin on the heart could better explain one mechanism by which particulate matter exposure may lead to cardiac dysfunction. We propose and support the novel hypothesis that autocrine/paracrine signaling systems, such as endothelins, mediate cardiac

Modulation of cardiac fibrosis by Krüppel-like factor 6 through transcriptional control of thrombospondin 4 in cardiomyocytes

PubMed Central

Sawaki, Daigo; Hou, Lianguo; Tomida, Shota; Sun, Junqing; Zhan, Hong; Aizawa, Kenichi; Son, Bo-Kyung; Kariya, Taro; Takimoto, Eiki; Otsu, Kinya; Conway, Simon J.; Manabe, Ichiro; Komuro, Issei; Friedman, Scott L.; Nagai, Ryozo; Suzuki, Toru

2015-01-01

Aims Krüppel-like factors (KLFs) are a family of transcription factors which play important roles in the heart under pathological and developmental conditions. We previously identified and cloned Klf6 whose homozygous mutation in mice results in embryonic lethality suggesting a role in cardiovascular development. Effects of KLF6 on pathological regulation of the heart were investigated in the present study. Methods and results Mice heterozygous for Klf6 resulted in significantly diminished levels of cardiac fibrosis in response to angiotensin II infusion. Intriguingly, a similar phenotype was seen in cardiomyocyte-specific Klf6 knockout mice, but not in cardiac fibroblast-specific knockout mice. Microarray analysis revealed increased levels of the extracellular matrix factor, thrombospondin 4 (TSP4), in the Klf6-ablated heart. Mechanistically, KLF6 directly suppressed Tsp4 expression levels, and cardiac TSP4 regulated the activation of cardiac fibroblasts to regulate cardiac fibrosis. Conclusion Our present studies on the cardiac function of KLF6 show a new mechanism whereby cardiomyocytes regulate cardiac fibrosis through transcriptional control of the extracellular matrix factor, TSP4, which, in turn, modulates activation of cardiac fibroblasts. PMID:25987545

Radome Positioner for the RFSS (Radio Frequency Simulation System).

DTIC Science & Technology

1978-02-27

its associated circuits contained on the Motorola M68MM01A-I micro- module (See Drawing 64). This board contains the 6800 microprocessor. Ik bytes of...D 00 1~ 0 41 + C.) ) -44 208 g. Small encoder diameter achieved by using integrated circuit modules . h. Stainless steel case. U...to the 30 integrated circuits which actually comprise the heart of the-microcomputer. This dramatic reduction in parts count re- sults in a similar

Is the normal heart rate ``chaotic'' due to respiration?

NASA Astrophysics Data System (ADS)

Wessel, Niels; Riedl, Maik; Kurths, Jürgen

2009-06-01

The incidence of cardiovascular diseases increases with the growth of the human population and an aging society, leading to very high expenses in the public health system. Therefore, it is challenging to develop sophisticated methods in order to improve medical diagnostics. The question whether the normal heart rate is chaotic or not is an attempt to elucidate the underlying mechanisms of cardiovascular dynamics and therefore a highly controversial topical challenge. In this contribution we demonstrate that linear and nonlinear parameters allow us to separate completely the data sets of the three groups provided for this controversial topic in nonlinear dynamics. The question whether these time series are chaotic or not cannot be answered satisfactorily without investigating the underlying mechanisms leading to them. We give an example of the dominant influence of respiration on heart beat dynamics, which shows that observed fluctuations can be mostly explained by respiratory modulations of heart rate and blood pressure (coefficient of determination: 96%). Therefore, we recommend reformulating the following initial question: "Is the normal heart rate chaotic?" We rather ask the following: "Is the normal heart rate `chaotic' due to respiration?"

Detection of the valvular split within the second heart sound using the reassigned smoothed pseudo Wigner–Ville distribution

PubMed Central

2013-01-01

Background In this paper, we developed a novel algorithm to detect the valvular split between the aortic and pulmonary components in the second heart sound which is a valuable medical information. Methods The algorithm is based on the Reassigned smoothed pseudo Wigner–Ville distribution which is a modified time–frequency distribution of the Wigner–Ville distribution. A preprocessing amplitude recovery procedure is carried out on the analysed heart sound to improve the readability of the time–frequency representation. The simulated S2 heart sounds were generated by an overlapping frequency modulated chirp–based model at different valvular split durations. Results Simulated and real heart sounds are processed to highlight the performance of the proposed approach. The algorithm is also validated on real heart sounds of the LGB–IRCM (Laboratoire de Génie biomédical–Institut de recherches cliniques de Montréal) cardiac valve database. The A2–P2 valvular split is accurately detected by processing the obtained RSPWVD representations for both simulated and real data. PMID:23631738

Chaos in the heart: the interaction between body and mind

NASA Astrophysics Data System (ADS)

Redington, Dana

1993-11-01

A number of factors influence the chaotic dynamics of heart function. Genetics, age, sex, disease, the environment, experience, and of course the mind, play roles in influencing cardiovascular dynamics. The mind is of particular interest because it is an emergent phenomenon of the body admittedly seated and co-occurrent in the brain. The brain serves as the body's controller, and commands the heart through complex multipathway feedback loops. Structures deep within the brain, the hypothalamus and other centers in the brainstem, modulate heart function, partially as a result of afferent input from the body but also a result of higher mental processes. What can chaos in the body, i.e., the nonlinear dynamics of the heart, tell of the mind? This paper presents a brief overview of the spectral structure of heart rate activity followed by a summary of experimental results based on phase space analysis of data from semi-structured interviews. This paper then describes preliminary quantification of cardiovascular dynamics during different stressor conditions in an effort to apply more quantitative methods to clinical data.

Combined non-adaptive light and smell stimuli lowered blood pressure, reduced heart rate and reduced negative affect.

PubMed

Dong, Shan; Jacob, Tim J C

2016-03-15

Bright light therapy has been shown to have a positive impact on seasonal affective disorder (SAD), depression and anxiety. Smell has also has been shown to have effects on mood, stress, anxiety and depression. The objective of this study was to investigate the effect of the combination of light and smell in a non-adaptive cycle. Human subjects were given smell (lemon, lavender or peppermint) and light stimuli in a triangular wave (60scycle) for 15min. Blood pressure and heart rate were monitored before and after each session for 5 consecutive days and a Profile of Mood States (POMS) test was administered before and after the sensory stimulation on days 1, 3 and 5. The light-smell stimulus lowered blood pressure, both systolic and diastolic, and reduced heart rate for all odours compared to control. Of the two sensory stimuli, the odour stimulus contributed most to this effect. The different aromas in the light-smell combinations could be distinguished by their different effects on the mood factors with lemon inducing the greatest mood changes in Dejection-Depression, Anger-Hostility, Tension-Anxiety. In conclusion, combined light and smell stimulation was effective in lowering blood pressure, reducing heart rate and improving mood. The combination was more effective than either smell or light stimuli alone, suggesting that a light-smell combination would be a more robust and efficacious alternative treatment for depression, anxiety and stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Multiple morbidity combinations impact on medical expenditures among older adults.

PubMed

Chi, Mei-ju; Lee, Cheng-yi; Wu, Shwu-chong

2011-01-01

This study aims to explore the medical needs of patients who have different combinations of multiple chronic diseases in order to improve care strategy for chronic patients. This study was based on a national probability proportional to size (PPS) sampling to older adults over 50 years old. We collaborated the files of the 2000-2001 health insurance claims and selected 8 types of common chronic diseases among seniors, for the discussion of multiple combinations of chronic diseases, including hypertension, diabetes, heart disease, stroke, dementia, cancer, arthritis and chronic obstructive pulmonary disease. Among the NHI users, there are 50.6% of the cases suffering from at least one chronic disease, 27.3% suffering from two types of chronic diseases and above. From possible combinations of eight common chronic diseases, it is found hypertension has the highest prevalence rate (7.5%); arthritis ranks the next (6.2%); the combination of hypertension and heart disease ranks the third (3.4%). In the 22 types of major chronic disease clusters, the average total medical expense for people who have five or more chronic diseases ranks the highest, USD 4465; the combination of hypertension, diabetes, heart disease, and arthritis ranks the next, USD 2703; the combination of hypertension, diabetes, and heart disease ranks the third, USD 2550; cancer only ranks the fourth, USD 2487. Our study may provide statistical data concerning co-morbidity among older adults and their medical needs. Through our analysis, the major population that exhausts the medical resources may be discovered. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Split Tolerance in a Murine Model of Heterotopic En Bloc Chest Wall Transplantation

PubMed Central

Oh, Byoungchol; Furtmüller, Georg J.; Malek, Veronika; Fryer, Madeline L.; Brayton, Cory; Walczak, Piotr; Janowski, Miroslaw

2017-01-01

Background: Congenital and acquired chest wall deformities represent a significant challenge to functional reconstruction and may impact feasibility of heart transplantation for patients with end-stage organ failure. In the recent past, the concept of replacing like-with-like tissue by using vascularized composite allografts (VCA) has been enthusiastically employed for reconstruction of complex tissue defects. Methods: In this study, we introduce a novel murine model for en bloc chest wall, heart, and thymus transplantation and thereby the use of complex tissue allografts for reconstruction of both chest wall defects and also end-stage organ failure. Additionally, this model allows us to study the features of combined vascularized bone marrow (VBM), thymus, and heart transplantation on allograft survival and function. Heterotopic chest wall, thymus, and heart transplants were performed in untreated syngeneic and allogeneic combinations and in allogeneic combinations treated with costimulation blockade (CTLA4-Ig and MR-1). Results: Indefinite (ie, 150 d, N = 3) graft survival was observed in syngeneic controls. In untreated recipients of allogeneic grafts, the skin component was rejected after 10 (±1) days, whereas rejection of the heart occurred after 13 (± 1) days (N = 3). Costimulation blockade treatment prolonged survival of the heart and chest wall component (130 d, N = 3) as well as the VBM niche as evidenced by donor-specific chimerism (average: 2.35 ± 1.44%), whereas interestingly, the skin component was rejected after 13 (±1) days. Conclusion: Thus, this novel microsurgical model of VCA combined with solid organ transplantation is technically feasible and results in split tolerance when treated with costimulatory blockade. PMID:29632774

Heart Rate Sensor for Freshwater Mussels

NASA Astrophysics Data System (ADS)

Just, C. L.; Vial, D. P.; Kruger, A.; Niemeier, J. J.; Lee, H. W.; Schroer, H. W.

2014-12-01

Researchers have long been interested the cardiac activity of mollusks. First, it is important as a basic measure of the animal's metabolism. Further, activities such as feeding and burrowing affect heart rate, as do environmental factors such as water salinity, water temperature, exposure, and predation. We have developed a small, noninvasive sensor for measuring freshwater mussel heart rate. Its working principle is as follows. An infrared (IR) light-emitting diode is placed in contact with the mussel shell. Some of the IR penetrates through the shell, reflects off internal organs, and traverses back. A photodetector detects this IR, and electronics condition the signal. The heartbeat of the animal modulates the IR, allowing one to measure the heart rate. The technique is widely-used in finger heart-rate monitors in humans. The sensors do not have to be positioned above the heart and several locations on the mussel shell work well. The sensor is small (8 mm × 10 mm) and consumes less than 1 mA, and has a simple one-wire interface that allows for easy integration into data acquisition hardware. We present heart rate measurements for the common pocketbook (lampsilis cardium) freshwater mussel.

Vagal Nerve Stimulation Evoked Heart Rate Changes and Protection from Cardiac Remodeling.

PubMed

Agarwal, Rahul; Mokelke, Eric; Ruble, Stephen B; Stolen, Craig M

2016-02-01

This study investigated whether vagal nerve stimulation (VNS) leads to improvements in ischemic heart failure via heart rate modulation. At 7 ± 1 days post left anterior descending artery (LAD) ligation, 63 rats with myocardial infarctions (MI) were implanted with ECG transmitters and VNS devices (MI + VNS, N = 44) or just ECG transmitters (MI, N = 17). VNS stimulation was active from 14 ± 1 days to 8 ± 1 weeks post MI. The average left ventricular (LV) end diastolic volumes at 8 ± 1 weeks were MI = 672.40 μl and MI + VNS = 519.35 μl, p = 0.03. The average heart weights, normalized to body weight (± std) at 14 ± 1 weeks were MI = 3.2 ± 0.6 g*kg(-1) and MI + VNS = 2.9 ± 0.3 g*kg(-1), p = 0.03. The degree of cardiac remodeling was correlated with the magnitude of acute VNS-evoked heart rate (HR) changes. Further research is required to determine if the acute heart rate response to VNS activation is useful as a heart failure biomarker or as a tool for VNS therapy characterization.

G protein-coupled estrogen receptor regulates embryonic heart rate in zebrafish

PubMed Central

Romano, Shannon N.; Edwards, Hailey E.; Ryan, Kevin J.

2017-01-01

Estrogens act by binding to estrogen receptors alpha and beta (ERα, ERβ), ligand-dependent transcription factors that play crucial roles in sex differentiation, tumor growth and cardiovascular physiology. Estrogens also activate the G protein-coupled estrogen receptor (GPER), however the function of GPER in vivo is less well understood. Here we find that GPER is required for normal heart rate in zebrafish embryos. Acute exposure to estrogens increased heart rate in wildtype and in ERα and ERβ mutant embryos but not in GPER mutants. GPER mutant embryos exhibited reduced basal heart rate, while heart rate was normal in ERα and ERβ mutants. We detected gper transcript in discrete regions of the brain and pituitary but not in the heart, suggesting that GPER acts centrally to regulate heart rate. In the pituitary, we observed gper expression in cells that regulate levels of thyroid hormone triiodothyronine (T3), a hormone known to increase heart rate. Compared to wild type, GPER mutants had reduced levels of T3 and estrogens, suggesting pituitary abnormalities. Exposure to exogenous T3, but not estradiol, rescued the reduced heart rate phenotype in gper mutant embryos, demonstrating that T3 acts downstream of GPER to regulate heart rate. Using genetic and mass spectrometry approaches, we find that GPER regulates maternal estrogen levels, which are required for normal embryonic heart rate. Our results demonstrate that estradiol plays a previously unappreciated role in the acute modulation of heart rate during zebrafish embryonic development and suggest that GPER regulates embryonic heart rate by altering maternal estrogen levels and embryonic T3 levels. PMID:29065151

G protein-coupled estrogen receptor regulates embryonic heart rate in zebrafish.

PubMed

Romano, Shannon N; Edwards, Hailey E; Souder, Jaclyn Paige; Ryan, Kevin J; Cui, Xiangqin; Gorelick, Daniel A

2017-10-01

Estrogens act by binding to estrogen receptors alpha and beta (ERα, ERβ), ligand-dependent transcription factors that play crucial roles in sex differentiation, tumor growth and cardiovascular physiology. Estrogens also activate the G protein-coupled estrogen receptor (GPER), however the function of GPER in vivo is less well understood. Here we find that GPER is required for normal heart rate in zebrafish embryos. Acute exposure to estrogens increased heart rate in wildtype and in ERα and ERβ mutant embryos but not in GPER mutants. GPER mutant embryos exhibited reduced basal heart rate, while heart rate was normal in ERα and ERβ mutants. We detected gper transcript in discrete regions of the brain and pituitary but not in the heart, suggesting that GPER acts centrally to regulate heart rate. In the pituitary, we observed gper expression in cells that regulate levels of thyroid hormone triiodothyronine (T3), a hormone known to increase heart rate. Compared to wild type, GPER mutants had reduced levels of T3 and estrogens, suggesting pituitary abnormalities. Exposure to exogenous T3, but not estradiol, rescued the reduced heart rate phenotype in gper mutant embryos, demonstrating that T3 acts downstream of GPER to regulate heart rate. Using genetic and mass spectrometry approaches, we find that GPER regulates maternal estrogen levels, which are required for normal embryonic heart rate. Our results demonstrate that estradiol plays a previously unappreciated role in the acute modulation of heart rate during zebrafish embryonic development and suggest that GPER regulates embryonic heart rate by altering maternal estrogen levels and embryonic T3 levels.

Spectro-temporal modulation masking patterns reveal frequency selectivity.

PubMed

Oetjen, Arne; Verhey, Jesko L

2015-02-01

The present study investigated the possibility that the human auditory system demonstrates frequency selectivity to spectro-temporal amplitude modulations. Threshold modulation depth for detecting sinusoidal spectro-temporal modulations was measured using a generalized masked threshold pattern paradigm with narrowband masker modulations. Four target spectro-temporal modulations were examined, differing in their temporal and spectral modulation frequencies: a temporal modulation of -8, 8, or 16 Hz combined with a spectral modulation of 1 cycle/octave and a temporal modulation of 4 Hz combined with a spectral modulation of 0.5 cycles/octave. The temporal center frequencies of the masker modulation ranged from 0.25 to 4 times the target temporal modulation. The spectral masker-modulation center-frequencies were 0, 0.5, 1, 1.5, and 2 times the target spectral modulation. For all target modulations, the pattern of average thresholds for the eight normal-hearing listeners was consistent with the hypothesis of a spectro-temporal modulation filter. Such a pattern of modulation-frequency sensitivity was predicted on the basis of psychoacoustical data for purely temporal amplitude modulations and purely spectral amplitude modulations. An analysis of separability indicates that, for the present data set, selectivity in the spectro-temporal modulation domain can be described by a combination of a purely spectral and a purely temporal modulation filter function.

RGS6, but not RGS4, is the dominant regulator of G protein signaling (RGS) modulator of the parasympathetic regulation of mouse heart rate.

PubMed

Wydeven, Nicole; Posokhova, Ekaterina; Xia, Zhilian; Martemyanov, Kirill A; Wickman, Kevin

2014-01-24

Parasympathetic activity decreases heart rate (HR) by inhibiting pacemaker cells in the sinoatrial node (SAN). Dysregulation of parasympathetic influence has been linked to sinus node dysfunction and arrhythmia. RGS (regulator of G protein signaling) proteins are negative modulators of the parasympathetic regulation of HR and the prototypical M2 muscarinic receptor (M2R)-dependent signaling pathway in the SAN that involves the muscarinic-gated atrial K(+) channel IKACh. Both RGS4 and RGS6-Gβ5 have been implicated in these processes. Here, we used Rgs4(-/-), Rgs6(-/-), and Rgs4(-/-):Rgs6(-/-) mice to compare the relative influence of RGS4 and RGS6 on parasympathetic regulation of HR and M2R-IKACh-dependent signaling in the SAN. In retrogradely perfused hearts, ablation of RGS6, but not RGS4, correlated with decreased resting HR, increased heart rate variability, and enhanced sensitivity to the negative chronotropic effects of the muscarinic agonist carbachol. Similarly, loss of RGS6, but not RGS4, correlated with enhanced sensitivity of the M2R-IKACh signaling pathway in SAN cells to carbachol and a significant slowing of M2R-IKACh deactivation rate. Surprisingly, concurrent genetic ablation of RGS4 partially rescued some deficits observed in Rgs6(-/-) mice. These findings, together with those from an acute pharmacologic approach in SAN cells from Rgs6(-/-) and Gβ5(-/-) mice, suggest that the partial rescue of phenotypes in Rgs4(-/-):Rgs6(-/-) mice is attributable to another R7 RGS protein whose influence on M2R-IKACh signaling is masked by RGS4. Thus, RGS6-Gβ5, but not RGS4, is the primary RGS modulator of parasympathetic HR regulation and SAN M2R-IKACh signaling in mice.

Rad-deletion Phenocopies Tonic Sympathetic Stimulation of the Heart.

PubMed

Levitan, Bryana M; Manning, Janet R; Withers, Catherine N; Smith, Jeffrey D; Shaw, Robin M; Andres, Douglas A; Sorrell, Vincent L; Satin, Jonathan

2016-12-01

Sympathetic stimulation modulates L-type calcium channel (LTCC) gating to contribute to increased systolic heart function. Rad is a monomeric G-protein that interacts with LTCC. Genetic deletion of Rad (Rad -/- ) renders LTCC in a sympathomimetic state. The study goal was to use a clinically inspired pharmacological stress echocardiography test, including analysis of global strain, to determine whether Rad -/- confers tonic positive inotropic heart function. Sarcomere dynamics and strain showed partial parallel isoproterenol (ISO) responsiveness for wild-type (WT) and for Rad -/- . Rad -/- basal inotropy was elevated compared to WT but was less responsiveness to ISO. Rad protein levels were lower in human patients with end-stage non-ischemic heart failure. These results show that Rad reduction provides a stable inotropic response rooted in sarcomere level function. Thus, reduced Rad levels in heart failure patients may be a compensatory response to need for increased output in the setting of HF. Rad deletion suggests a future therapeutic direction for inotropic support.

Accumulation of 5-oxoproline in myocardial dysfunction and the protective effects of OPLAH.

PubMed

van der Pol, Atze; Gil, Andres; Silljé, Herman H W; Tromp, Jasper; Ovchinnikova, Ekaterina S; Vreeswijk-Baudoin, Inge; Hoes, Martijn; Domian, Ibrahim J; van de Sluis, Bart; van Deursen, Jan M; Voors, Adriaan A; van Veldhuisen, Dirk J; van Gilst, Wiek H; Berezikov, Eugene; van der Harst, Pim; de Boer, Rudolf A; Bischoff, Rainer; van der Meer, Peter

2017-11-08

In response to heart failure (HF), the heart reacts by repressing adult genes and expressing fetal genes, thereby returning to a more fetal-like gene profile. To identify genes involved in this process, we carried out transcriptional analysis on murine hearts at different stages of development and on hearts from adult mice with HF. Our screen identified Oplah , encoding for 5-oxoprolinase, a member of the γ-glutamyl cycle that functions by scavenging 5-oxoproline. OPLAH depletion occurred as a result of cardiac injury, leading to elevated 5-oxoproline and oxidative stress, whereas OPLAH overexpression improved cardiac function after ischemic injury. In HF patients, we observed elevated plasma 5-oxoproline, which was associated with a worse clinical outcome. Understanding and modulating fetal-like genes in the failing heart may lead to potential diagnostic, prognostic, and therapeutic options in HF. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Does respiratory sinus arrhythmia occur in fishes?

PubMed Central

Campbell, Hamish A; Taylor, Edwin W; Egginton, Stuart

2005-01-01

The hypothesis that respiratory modulation of heart rate variability (HRV) or respiratory sinus arrhythmia (RSA) is restricted to mammals was tested on four Antarctic and four sub-Antarctic species of fish, that shared close genotypic or ecotypic similarities but, due to their different environmental temperatures, faced vastly different selection pressures related to oxygen supply. The intrinsic heart rate (fH) for all the fish species studied was ∼25% greater than respiration rate (fV), but vagal activity successively delayed heart beats, producing a resting fH that was synchronized with fV in a progressive manner. Power spectral statistics showed that these episodes of relative bradycardia occurred in a cyclical manner every 2–4 heart beats in temperate species but at >4 heart beats in Antarctic species, indicating a more relaxed selection pressure for cardio-respiratory coupling. This evidence that vagally mediated control of fH operates around the ventilatory cycle in fish demonstrates that influences similar to those controlling RSA in mammals operate in non-mammalian vertebrates. PMID:17148239

Rad-deletion Phenocopies Tonic Sympathetic Stimulation of the Heart

PubMed Central

Levitan, Bryana M.; Manning, Janet R.; Withers, Catherine N.; Smith, Jeffrey D.; Shaw, Robin M.; Andres, Douglas A.; Sorrell, Vincent L.

2016-01-01

Sympathetic stimulation modulates L-type calcium channel (LTCC) gating to contribute to increased systolic heart function. Rad is a monomeric G-protein that interacts with LTCC. Genetic deletion of Rad (Rad−/−) renders LTCC in a sympathomimetic state. The study goal was to use a clinically inspired pharmacological stress echocardiography test, including analysis of global strain, to determine whether Rad−/− confers tonic positive inotropic heart function. Sarcomere dynamics and strain showed partial parallel isoproterenol (ISO) responsiveness for wild-type (WT) and for Rad−/−. Rad−/− basal inotropy was elevated compared to WT but was less responsiveness to ISO. Rad protein levels were lower in human patients with end-stage non-ischemic heart failure. These results show that Rad reduction provides a stable inotropic response rooted in sarcomere level function. Thus, reduced Rad levels in heart failure patients may be a compensatory response to need for increased output in the setting of HF. Rad deletion suggests a future therapeutic direction for inotropic support. PMID:27798760

Reduced capacity of cardiac efferent sympathetic neurons to release noradrenaline and modify cardiac function in tachycardia-induced canine heart failure.

PubMed

Cardinal, R; Nadeau, R; Laurent, C; Boudreau, G; Armour, J A

1996-09-01

To investigate the capacity of efferent sympathetic neurons to modulate the failing heart, stellate ganglion stimulation was performed in dogs with biventricular heart failure induced by rapid ventricular pacing (240 beats/min) for 4-6 weeks. Less noradrenaline was released from cardiac myoneural junctions into coronary sinus blood in response to left stellate ganglion stimulation in anesthetized failing heart preparations (582 pg/mL, lower and upper 95% confidence intervals of 288 and 1174 pg/mL, n = 19) compared with healthy heart preparations (6391 pg/mL, 95% confidence intervals of 4180 and 9770 pg/mL, n = 14; p < 0.001). There was substantial adrenaline extraction by failing hearts (49 +/- 6%), although it was slightly lower than in healthy heart preparations (65 +/- 9%, p = 0.055). In contrast with healthy heart preparations, no net release of adrenaline occurred during stellate ganglion stimulation in any of the failing heart preparations, and ventricular tissue levels of adrenaline fell below the sensitivity limit of the HPLC technique. In failing heart preparations, maximal electrical stimulation of right or left stellate ganglia resulted in minimal augmentation of left ventricular intramyocardial (17%) and chamber (12%) systolic pressures. These indices were augmented by 145 and 97%, respectively, following exogenous noradrenaline administration. Thus, the cardiac efferent sympathetic neurons' reduced capacity to release noradrenaline and modify cardiac function can contribute to reduction of sympathetic support to the failing heart.

Optimizing fluid management in patients with acute decompensated heart failure (ADHF): the emerging role of combined measurement of body hydration status and brain natriuretic peptide (BNP) levels.

PubMed

Valle, Roberto; Aspromonte, Nadia; Milani, Loredano; Peacock, Frank W; Maisel, Alan S; Santini, Massimo; Ronco, Claudio

2011-11-01

The study tests the hypothesis that in patients admitted with acutely decompensated heart failure (ADHF), achievement of adequate body hydration status with intensive medical therapy, modulated by combined bioelectrical vectorial impedance analysis (BIVA) and B-type natriuretic peptide (BNP) measurement, may contribute to optimize the timing of patient's discharge and to improve clinical outcomes. Three hundred patients admitted for ADHF underwent serial BIVA and BNP measurement. Therapy was titrated to reach a BNP value of <250 pg/ml, whenever possible. Patients were categorized as early responders (rapid BNP fall below 250 pg/ml); late responders (slow BNP fall below 250 pg/ml, after aggressive therapy); and non-responders (BNP persistently >250 pg/ml). Worsening of renal function (WRF) was evaluated during hospitalization. Death and rehospitalization were monitored with a 6-month follow-up. BNP value on discharge of ≤250 pg/ml led to a 25% event rate within 6 months (Group A: 17.4%; Group B: 21%, Chi2; n.s.), whereas a value >250 pg/ml (Group C) was associated with a far higher percentage (37%). At discharge, body hydration was 73.8 ± 3.2% in the total population and 73.2 ± 2.1, 73.5 ± 2.8, 74.1 ± 3.6% in the three groups, respectively. WRF was observed in 22.3% of the total. WRF occurred in 22% in Group A, 32% in Group B, and 20% in Group C (P = n.s.). Our study confirms the hypothesis that combined BNP/BIVA sequential measurements help to achieve adequate fluid balance status in patients with ADHF and can be used to drive a "tailored therapy," allowing clinicians to identify high-risk patients and possibly to reduce the incidence of complications secondary to fluid management strategies.

Positive effect of combined exercise training in a model of metabolic syndrome and menopause: autonomic, inflammatory, and oxidative stress evaluations.

PubMed

Conti, Filipe Fernandes; Brito, Janaina de Oliveira; Bernardes, Nathalia; Dias, Danielle da Silva; Malfitano, Christiane; Morris, Mariana; Llesuy, Susana Francisca; Irigoyen, Maria-Cláudia; De Angelis, Kátia

2015-12-15

It is now well established that after menopause cardiometabolic disorders become more common. Recently, resistance exercise has been recommended as a complement to aerobic (combined training, CT) for the treatment of cardiometabolic diseases. The aim of this study was to evaluate the effects of CT in hypertensive ovariectomized rats undergoing fructose overload in blood pressure variability (BPV), inflammation, and oxidative stress parameters. Female rats were divided into the following groups (n = 8/group): sedentary normotensive Wistar rats (C), and sedentary (FHO) or trained (FHOT) ovariectomized spontaneously hypertensive rats undergoing and fructose overload. CT was performed on a treadmill and ladder adapted to rats in alternate days (8 wk; 40-60% maximal capacity). Arterial pressure (AP) was directly measured. Oxidative stress and inflammation were measured on cardiac and renal tissues. The association of risk factors (hypertension + ovariectomy + fructose) promoted increase in insulin resistance, mean AP (FHO: 174 ± 4 vs. C: 108 ± 1 mmHg), heart rate (FHO: 403 ± 12 vs. C: 352 ± 11 beats/min), BPV, cardiac inflammation (tumor necrosis factor-α-FHO: 65.8 ± 9.9 vs. C: 23.3 ± 4.3 pg/mg protein), and oxidative stress cardiac and renal tissues. However, CT was able to reduce mean AP (FHOT: 158 ± 4 mmHg), heart rate (FHOT: 303 ± 5 beats/min), insulin resistance, and sympathetic modulation. Moreover, the trained rats presented increased nitric oxide bioavailability, reduced tumor necrosis factor-α (FHOT: 33.1 ± 4.9 pg/mg protein), increased IL-10 in cardiac tissue and reduced lipoperoxidation, and increased antioxidant defenses in cardiac and renal tissues. In conclusion, the association of risk factors promoted an additional impairment in metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters and combined exercise training was able to attenuate these dysfunctions. Copyright © 2015 the American Physiological Society.

A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with systolic heart failure: rationale, design, and baseline patient characteristics.

PubMed

Abraham, William T; Burkhoff, Daniel; Nademanee, Koonlawee; Carson, Peter; Bourge, Robert; Ellenbogen, Kenneth A; Parides, Michael; Kadish, Alan

2008-10-01

Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the cardiac absolute refractory period that enhance the strength of cardiac muscular contraction. Prior research in experimental and human heart failure has shown that CCM signals normalize phosphorylation of key proteins and expression of genes coding for proteins involved in regulation of calcium cycling and contraction. The results of prior clinical studies of CCM have supported its safety and efficacy. A large-scale clinical study, the FIX-HF-5 study, is currently underway to test the safety and efficacy of this treatment. In this article, we provide an overview of the system used to deliver CCM signals, the implant procedure, and the details and rationale of the FIX-HF-5 study design. Baseline characteristics for patients randomized in this trial are also presented.

A long-range and long-life telemetry data-acquisition system for heart rate and multiple body temperatures from free-ranging animals

NASA Technical Reports Server (NTRS)

Lund, G. F.; Westbrook, R. M.; Fryer, T. B.; Miranda, R. F.

1979-01-01

The system includes an implantable transmitter, external receiver-retransmitter collar, and a microprocessor-controlled demodulator. The size of the implant is suitable for animals with body weights of a few kilograms or more; further size reduction of the implant is possible. The ECG is sensed by electrodes designed for internal telemetry and to reduce movement artifacts. The R-wave characteristics are then specifically selected to trigger a short radio frequency pulse. Temperatures are sensed at desired locations by thermistors and then, based on a heartbeat counter, transmitted intermittently via pulse interval modulation. This modulation scheme includes first and last calibration intervals for a reference by ratios with the temperature intervals to achieve good accuracy even over long periods. Pulse duration and pulse sequencing are used to discriminate between heart rate and temperature pulses as well as RF interference.

Gender differences in cardiac autonomic modulation during medical internship.

PubMed

Lin, Yu-Hsuan; Chen, Ching-Yen; Lin, Sheng-Hsuan; Liu, Chun-Hao; Weng, Wei-Hung; Kuo, Terry B J; Yang, Cheryl C H

2013-06-01

Medical internship is known to be a time of high stress and long working hours, which increases the risk of depression and cardiovascular disease. Gender differences in medical interns' cardiovascular risk have not been reported previously. Thirty-eight medical interns (29 males) were repeatedly tested for depressive symptoms using the Hospital Anxiety and Depression Scale and 5-min spectral analysis of heart rate variability (HRV) at 3-month intervals during their internship. Among the male interns, the variance of the heart rate decreased at 6, 9, 12 months, and a reduced high frequency, which suggests reduced cardiac parasympathetic modulation, was found at 9 and 12 months into their internship. Increased depressive symptoms were also identified at 12 months in the male group. No significant differences in depression or any of the HRV indices were identified among the female interns during their internship. Copyright © 2013 Society for Psychophysiological Research.

Effect of low-dose scopolamine on autonomic control of the heart

NASA Technical Reports Server (NTRS)

Raeder, E. A.; Stys, A.; Cohen, R. J.

1997-01-01

Background: In low doses, scopolamine paradoxically enhances parasympathetic outflow to the heart. The mechanisms which mediate this action are not fully understood. Moreover, there are conflicting data regarding the potential role of sympathetic activity. This study in 17 healthy individuals was designed to characterize the influence of low dose transdermal scopolamine on the gain of the baroreflex and respiratory heart rate reflex and to determine the role of sympathetic activity. Methods: The effect of scopolamine was analyzed in the time and frequency domain by computing heart rate variability indices. The gains of the respiratory heart rate reflex and the baroreflex were estimated simultaneously by means of a cardiovascular system identification approach using an optimized autoregressive moving average algorithm. Measurements were repeated in the upright posture to assess the influence of enhanced sympathetic activity. In six subjects ambulatory ECGs were recorded to determine whether there are diurnal variations of the effect of scopolamine. Results: Scopolamine enhances vagal modulation of heart rate through both the respiratory-heart rate reflex and the baroreflex, as the gains of both were augmented by the drug in the supine and in the upright postures. Conclusions: Scopolamine increases parasympathetic cardiac control by augmenting the gain of the respiratory-heart rate and baroreflex. This action is not attenuated in the upright posture when sympathetic tone is increased.

Interaction of small G protein signaling modulator 3 with connexin 43 contributes to myocardial infarction in rat hearts.

PubMed

Lee, Chang Youn; Choi, Jung-Won; Shin, Sunhye; Lee, Jiyun; Seo, Hyang-Hee; Lim, Soyeon; Lee, Seahyoung; Joo, Hyun-Chul; Kim, Sang Woo; Hwang, Ki-Chul

2017-09-16

Connexin 43 (Cx43), a ubiquitous connexin expressed in the heart and skin, is associated with a variety of hereditary conditions. Therefore, the characterization of Cx43-interacting proteins and their dynamics is important to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication but also to identify novel and unanticipated biological functions of Cx43. In the present study, we observed potential targets of Cx43 to determine new molecular functions in cardio-protection. MALDI-TOF mass spectrometry analysis of Cx43 co-immunoprecipitated proteins showed that Cx43 interacts with several proteins related to metabolism. In GeneMANIA network analysis, SGSM3, which has not been previously associated with Cx43, was highly correlated with Cx43 in heart functions, and high levels of SGSM3 appeared to induce the turnover of Cx43 through lysosomal degradation in myocardial infarcted rat hearts. Moreover, we confirmed that lysosomal degradation of Cx43 is dependent upon the interaction between SGSM3 and Cx43 in H9c2 cardiomyocytes. The functional importance of the interaction between SGSM3 and Cx43 was confirmed by results showing that Cx43 expression was enhanced by SGSM3 siRNA knockdown in H9c2 cells. In summary, the results of this study elucidate the molecular mechanisms in which Cx43 with SGSM3 is degraded in myocardial infarcted rat hearts, which may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

A brief review and clinical application of heart rate variability biofeedback in sports, exercise, and rehabilitation medicine.

PubMed

Prinsloo, Gabriell E; Rauch, H G Laurie; Derman, Wayne E

2014-05-01

An important component of the effective management of chronic noncommunicable disease is the assessment and management of psychosocial stress. The measurement and modulation of heart rate variability (HRV) may be valuable in this regard. To describe the measurement and physiological control of HRV; to describe the impact of psychosocial stress on cardiovascular disease, metabolic syndrome, and chronic respiratory disease, and the relationship between these diseases and changes in HRV; and to describe the influence of biofeedback and exercise on HRV and the use of HRV biofeedback in the management of chronic disease. The PubMed, Medline, and Embase databases were searched (up to August 2013). Additional articles were obtained from the reference lists of relevant articles and reviews. Articles were individually selected for further review based on the quality and focus of the study, and the population studied. Heart rate variability is reduced in stress and in many chronic diseases, and may even predict the development and prognosis of some diseases. Heart rate variability can be increased with both exercise and biofeedback. Although the research on the effect of exercise is conflicting, there is evidence that aerobic training may increase HRV and cardiac vagal tone both in healthy individuals and in patients with disease. Heart rate variability biofeedback is also an effective method of increasing HRV and cardiac vagal tone, and has been shown to decrease stress and reduce the morbidity and mortality of disease. The assessment and management of psychosocial stress is a challenging but important component of effective comprehensive lifestyle interventions for the management of noncommunicable disease. It is, therefore, important for the sports and exercise physician to have an understanding of the therapeutic use of HRV modulation, both in the reduction of stress and in the management of chronic disease.

Respiratory sinus arrhythmia is a limited measure of cardiac parasympathetic control in man.

PubMed Central

Kollai, M; Mizsei, G

1990-01-01

1. Respiratory modulation of cardiac parasympathetic activity and the relationship between respiratory sinus arrhythmia and parasympathetic control has been studied in twenty-nine conscious, healthy young adult subjects. 2. Changes in heart period in propranolol-treated subjects were taken as the measure of changes in cardiac parasympathetic activity; respiratory sinus arrhythmia was quantified as the difference between maximum and minimum heart periods in a given respiratory cycle; cardiac parasympathetic control was defined as the change in heart period after administration of a full dose of atropine. 3. During normal quiet breathing the inspiratory level of cardiac parasympathetic activity was not reduced to zero. The expiratory level was influenced by excitatory inputs whose activation was related to respiratory cycle length. 4. Slow breathing was associated with augmented sinus arrhythmia, but in different individuals the influence on minimum and maximum heart periods varied so that mean heart period was increased in some subjects but decreased in others. This occurred both in control conditions and after administration of a full dose of propranolol. 5. During normal breathing the correlation across subjects between respiratory sinus arrhythmia and parasympathetic control, although significant, was not close (r = 0.61). The relationship was not affected by beta-adrenergic blockade (r = 0.63). The strength of the correlation improved when multiple regression of respiratory sinus arrhythmia was performed on three variables: parasympathetic control, respiratory cycle length and tidal volume (R = 0.93). 6. It is concluded that in conscious human subjects the respiratory modulation of cardiac parasympathetic activity is different from that observed in the anaesthetized dog, and that variations in the amplitude of respiratory sinus arrhythmia do not necessarily reflect proportional changes in cardiac parasympathetic control. PMID:2391653

Metabolic support for the heart: complementary therapy for heart failure?

PubMed

Heggermont, Ward A; Papageorgiou, Anna-Pia; Heymans, Stephane; van Bilsen, Marc

2016-12-01

The failing heart has an increased metabolic demand and at the same time suffers from impaired energy efficiency, which is a detrimental combination. Therefore, therapies targeting the energy-deprived failing heart and rewiring cardiac metabolism are of great potential, but are lacking in daily clinical practice. Metabolic impairment in heart failure patients has been well characterized for patients with reduced ejection fraction, and is coming of age in patients with 'preserved' ejection fraction. Targeting cardiomyocyte metabolism in heart failure could complement current heart failure treatments that do improve cardiovascular haemodynamics, but not the energetic status of the heart. In this review, we discuss the hallmarks of normal cardiac metabolism, typical metabolic disturbances in heart failure, and past and present therapeutic targets that impact on cardiac metabolism. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

A Pulse Rate Detection Method for Mouse Application Based on Multi-PPG Sensors

PubMed Central

Chen, Wei-Hao

2017-01-01

Heart rate is an important physiological parameter for healthcare. Among measurement methods, photoplethysmography (PPG) is an easy and convenient method for pulse rate detection. However, as the PPG signal faces the challenge of motion artifacts and is constrained by the position chosen, the purpose of this paper is to implement a comfortable and easy-to-use multi-PPG sensor module combined with a stable and accurate real-time pulse rate detection method on a computer mouse. A weighted average method for multi-PPG sensors is used to adjust the weight of each signal channel in order to raise the accuracy and stability of the detected signal, therefore reducing the disturbance of noise under the environment of moving effectively and efficiently. According to the experiment results, the proposed method can increase the usability and probability of PPG signal detection on palms. PMID:28708112

PPAR delta: a dagger in the heart of the metabolic syndrome.

PubMed

Barish, Grant D; Narkar, Vihang A; Evans, Ronald M

2006-03-01

Obesity is a growing threat to global health by virtue of its association with insulin resistance, glucose intolerance, hypertension, and dyslipidemia, collectively known as the metabolic syndrome or syndrome X. The nuclear receptors PPARalpha and PPARgamma are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively, and drugs that modulate these receptors are currently in clinical use. More recent work on the less-described PPAR isotype PPARdelta has uncovered a dual benefit for both hypertriglyceridemia and insulin resistance, highlighting the broad potential of PPARdelta in the treatment of metabolic disease. PPARdelta enhances fatty acid catabolism and energy uncoupling in adipose tissue and muscle, and it suppresses macrophage-derived inflammation. Its combined activities in these and other tissues make it a multifaceted therapeutic target for the metabolic syndrome with the potential to control weight gain, enhance physical endurance, improve insulin sensitivity, and ameliorate atherosclerosis.

Introducing a modular activity monitoring system.

PubMed

Reiss, Attila; Stricker, Didier

2011-01-01

In this paper, the idea of a modular activity monitoring system is introduced. By using different combinations of the system's three modules, different functionality becomes available: 1) a coarse intensity estimation of physical activities 2) different features based on HR-data and 3) the recognition of basic activities and postures. 3D-accelerometers--placed on lower arm, chest and foot--and a heart rate monitor were used as sensors. A dataset with 8 subjects and 14 different activities was recorded to evaluate the performance of the system. The overall performance on the intensity estimation task, relying on the chest-worn accelerometer and the HR-monitor, was 94.37%. The overall performance on the activity recognition task, using all three accelerometer placements and the HR-monitor, was 90.65%. This paper also gives an analysis of the importance of different accelerometer placements and the importance of a HR-monitor for both tasks.

Redox signaling in cardiovascular health and disease

PubMed Central

Madamanchi, Nageswara R.; Runge, Marschall S.

2013-01-01

Spatiotemporal regulation of the activity of a vast array of intracellular proteins and signaling pathways by reactive oxygen species (ROS) governs normal cardiovascular function. However, data from experimental and animal studies strongly support that dysregulated redox signaling, resulting from hyper-activation of various cellular oxidases or mitochondrial dysfunction, is integral to the pathogenesis and progression of cardiovascular disease (CVD). In this review, we address how redox signaling modulates the protein function, the various sources of increased oxidative stress in CVD, and the labyrinth of redox-sensitive molecular mechanisms involved in the development of atherosclerosis, hypertension, cardiac hypertrophy and heart failure, and ischemia–reperfusion injury. Advances in redox biology and pharmacology for inhibiting ROS production in specific cell types and subcellular organelles combined with the development of nanotechnology-based new in vivo imaging systems and targeted drug delivery mechanisms may enable fine-tuning of redox signaling for the treatment and prevention of CVD. PMID:23583330

Cardiac CRFR1 Expression Is Elevated in Human Heart Failure and Modulated by Genetic Variation and Alternative Splicing

PubMed Central

Lewis, Kathy A.; Perrin, Marilyn H.; Sweet, Wendy E.; Moravec, Christine S.; Tang, W. H. Wilson; Huising, Mark O.; Troughton, Richard W.; Cameron, Vicky A.

2016-01-01

Corticotropin-releasing factor (CRF) and the CRF-related peptides, urocortin (Ucn)-1, Ucn2, and Ucn3 signal through receptors CRFR1 and CRFR2 to restore homeostasis in response to stress. The Ucns exert potent cardioprotective effects and may have clinical utility in heart failure. To explore the activity of this system in the heart, we measured the levels of myocardial gene expression of the CRF/Ucn family of ligands/receptors and investigated genetic variation and alternative splicing of CRFR1 in 110 heart failure patients and 108 heart donors. Using quantitative real-time PCR, we detected CRFR1, CRFR2, CRF, Ucn1, Ucn2, and Ucn3 in all samples. CRFR2α was the most abundant receptor and Ucn3 the most abundant ligand, both in patients and donors. Compared with donors, cardiac expression of CRFR1, CRF, and Ucn3 was higher (P < .001) and CRFR2α lower (P = .012) in patients. In patients and donors, genetic variation within CRFR1, represented by the chromosome 17q21.31 inversion polymorphism, was associated with markedly higher CRFR1 expression (P < .001), making CRFR1 and CRFR2α expression almost equivalent in some patients. A novel, truncated splice variant of CRFR1, designated CRFR1j, was identified and shown to exert a dominant-negative effect on CRFR1 signaling in vitro. The novel variant was expressed in a greater proportion of patients (60%) than donors (3%, P < .001). In summary, cardiac expression of CRFR1, CRF, and Ucn3 genes is elevated in heart failure and may contribute to the activation of the CRF/Ucn system in these patients. A common variant within the CRFR1 gene and a novel CRFR1 splice variant may modulate CRFR1 expression and signaling. PMID:27754786

Impaired nitric oxide modulation of myocardial oxygen consumption in genetically cardiomyopathic hamsters.

PubMed

Loke, K E; Messina, E J; Mital, S; Hintze, T H

2000-12-01

We investigated the role of kinin and nitric oxide (NO) in the modulation of cardiac O(2)consumption in Syrian hamsters with overt heart failure (HF) and age-matched normal hamsters. Using echocardiography, the hamsters with heart failure had reduced ejection fraction [31(+/-8) v 76(+/-5)%] and LV dilation [4.9(+/-0. 2) v 5.7(+/-0.3) mm, both P<0.05 from normal]. O(2)consumption in the left ventricular free wall was measured using a Clark-type O(2)electrode in an air-tight chamber, containing Krebs solution buffered with Hepes (37 degrees C, pH 7.4). Concentration response curves to bradykinin (BK), ramiprilat (RAM), amlodipine (AMLO) and the NO donor, S -nitroso- N -acetyl-penicillamine (SNAP) were performed. Basal myocardial O(2)consumption was lower in the HF group compared to normal [316(+/-21) v 404(+/-36) nmol O(2)/min/g, respectively, P<0.05]. In the hearts from normal hamsters BK (10(-4)mol/l), RAM (10(-4)mol/l), and AMLO (10(-5)mol/l) all significantly reduced myocardial O(2)consumption by 42(+/-6)%, 29(+/-7)% and 27(+/-5)% respectively. This reduction was attenuated in the presence of N -nitro- l -arginine methyl ester (l -NAME) [BK: 3.3(+/-1.5)%, RAM: 3.3(+/-1.2)%, AMLO: 2.3(+/-1.2)%, P<0.05]. Interestingly in the hearts from HF group, BK, RAM and AMLO caused a significantly smaller reduction in myocardial O(2)consumption [10(+/-2)%, 2.5(+/-1.3)%, 6.3(+/-2.3)%, P<0.05]. In contrast, the NO donor SNAP reduced myocardial O(2)consumption in both groups and all those responses were not affected by l -NAME. These data indicate that endogenous NO production through the kinin-dependent mechanism is impaired at end-stage heart failure. The loss of kinin and NO control of mitochondrial respiration may contribute to the pathogenesis of heart failure. Copyright 2000 Academic Press.

The Role of Auxiliary Subunits for the Functional Diversity of Voltage-Gated Calcium Channels

PubMed Central

Campiglio, Marta; Flucher, Bernhard E

2015-01-01

Voltage-gated calcium channels (VGCCs) represent the sole mechanism to convert membrane depolarization into cellular functions like secretion, contraction, or gene regulation. VGCCs consist of a pore-forming α1 subunit and several auxiliary channel subunits. These subunits come in multiple isoforms and splice-variants giving rise to a stunning molecular diversity of possible subunit combinations. It is generally believed that specific auxiliary subunits differentially regulate the channels and thereby contribute to the great functional diversity of VGCCs. If auxiliary subunits can associate and dissociate from pre-existing channel complexes, this would allow dynamic regulation of channel properties. However, most auxiliary subunits modulate current properties very similarly, and proof that any cellular calcium channel function is indeed modulated by the physiological exchange of auxiliary subunits is still lacking. In this review we summarize available information supporting a differential modulation of calcium channel functions by exchange of auxiliary subunits, as well as experimental evidence in support of alternative functions of the auxiliary subunits. At the heart of the discussion is the concept that, in their native environment, VGCCs function in the context of macromolecular signaling complexes and that the auxiliary subunits help to orchestrate the diverse protein–protein interactions found in these calcium channel signalosomes. Thus, in addition to a putative differential modulation of current properties, differential subcellular targeting properties and differential protein–protein interactions of the auxiliary subunits may explain the need for their vast molecular diversity. J. Cell. Physiol. 999: 00–00, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. J. Cell. Physiol. 230: 2019–2031, 2015. © 2015 Wiley Periodicals, Inc. PMID:25820299

Adding HRV biofeedback to psychotherapy increases heart rate variability and improves the treatment of major depressive disorder.

PubMed

Caldwell, Yoko Tsui; Steffen, Patrick R

2018-01-05

Heart rate variability (HRV) is a significant marker of health outcomes with decreased HRV predicting increased disease risk. HRV is decreased in major depressive disorder (MDD) but existing treatments for depression do not return heart rate variability to normal levels even with successful treatment of depression. Heart rate variability biofeedback (HRVB) increases heart rate variability but no studies to date have examined whether combining HRVB with psychotherapy improves outcome in MDD treatment. The present study used a randomized controlled design to compare the effects of HRVB combined with psychotherapy on MDD relative to a psychotherapy treatment as usual group and to a non-depressed control group. The HRVB+psychotherapy group showed a larger increase in HRV and a larger decrease in depressive symptoms relative to the other groups over a six-week period, whereas the psychotherapy group only did not improve HRV. Results support the supplementation of psychotherapy with HRVB in the treatment of MDD. Copyright © 2018 Elsevier B.V. All rights reserved.

The plasminogen activator system modulates sympathetic nerve function.

PubMed

Schaefer, Ulrich; Machida, Takuji; Vorlova, Sandra; Strickland, Sidney; Levi, Roberto

2006-09-04

Sympathetic neurons synthesize and release tissue plasminogen activator (t-PA). We investigated whether t-PA modulates sympathetic activity. t-PA inhibition markedly reduced contraction of the guinea pig vas deferens to electrical field stimulation (EFS) and norepinephrine (NE) exocytosis from cardiac synaptosomes. Recombinant t-PA (rt-PA) induced exocytotic and carrier-mediated NE release from cardiac synaptosomes and cultured neuroblastoma cells; this was a plasmin-independent effect but was potentiated by a fibrinogen cleavage product. Notably, hearts from t-PA-null mice released much less NE upon EFS than their wild-type (WT) controls (i.e., a 76.5% decrease; P<0.01), whereas hearts from plasminogen activator inhibitor-1 (PAI-1)-null mice released much more NE (i.e., a 275% increase; P<0.05). Furthermore, vasa deferentia from t-PA-null mice were hyporesponsive to EFS (P<0.0001) but were normalized by the addition of rt-PA. In contrast, vasa from PAI-1-null mice were much more responsive (P<0.05). Coronary NE overflow from hearts subjected to ischemia/reperfusion was much smaller in t-PA-null than in WT control mice (P<0.01). Furthermore, reperfusion arrhythmias were significantly reduced (P<0.05) in t-PA-null hearts. Thus, t-PA enhances NE release from sympathetic nerves and contributes to cardiac arrhythmias in ischemia/reperfusion. Because the risk of arrhythmias and sudden cardiac death is increased in hyperadrenergic conditions, targeting the NE-releasing effect of t-PA may have valuable therapeutic potential.

[Virtual educational proposal in cardiopulmonary resuscitation for the neonate care].

PubMed

Gonçalves, Gilciane Ribeiro; Peres, Heloisa Helena Ciqueto; Rodrigues, Rita de Cássia; Tronchin, Daisy Maria Rizatto; Pereira, Irene Mari

2010-06-01

The purpose of this study was to develop an educational proposal using virtual multimedia resources, to innovate, stimulate and diversify areas of communication and interaction, facilitating nurses' autonomous and reflexive process of teaching and learning. This is an applied research, following the cyclical and interactive phases of designing, planning, developing and implementing. The educational proposal was developed on the TelEduc platform, using specific tools for content organization and communication between students and administrator. The teaching modules were on the following themes: Module 1--Fundamentals of the heart anatomy and physiology in newborns; Module 2--Risk factors for the occurrence of cardiorespiratory arrest in newborns; Module 3--Planning nursing care; Module 4--Medications used in cardiopulmonary arrests in newborns; and Module 5--Cardiorespiratory arrest care in newborns. This study may contribute to innovating teaching in nursing from a virtual educational proposal on the important issue of newborn cardiopulmonary resuscitation care.

Broad modulation of tissue responses (immune activation) by celacade may favorably influence pathologic processes associated with heart failure progression.

PubMed

Torre-Amione, Guillermo; Sestier, François; Radovancevic, Branislav; Young, James

2005-06-06

Immune activation and inflammation contribute to the progression of chronic heart failure (CHF), but therapeutic approaches directed against these processes have been largely unsuccessful. This clinical study evaluated a novel, nonpharmacologic immune modulation therapy, shown experimentally to reduce inflammatory and increase anti-inflammatory cytokines. A total of 75 patients with New York Heart Association (NYHA) functional class III or IV CHF were randomized to receive either Celacade (immune modulation therapy) or placebo (n = 38 and n = 37, respectively) in a double-blind trial for 6 months, during which standard therapy for CHF was maintained. Patients were evaluated using the 6-minute walk test, changes in NYHA class, cardiac function, and quality-of-life assessments, and were observed for the occurrence of death and hospitalization. There was no between-treatment difference in the 6-minute walk test results, but 15 Celacade-treated patients (compared with 9 placebo-treated patients) improved NYHA classification by > or = 1 class (p = 0.140). Kaplan-Meier survival analysis showed that Celacade significantly reduced the risk of death (p = 0.022) and hospitalization (p = 0.008). Analysis of a clinical composite score demonstrated a significant between-group difference (p = 0.006). There was no difference in left ventricular ejection fraction between groups, but there was a trend toward improved quality of life favoring the Celacade-treated group (p = 0.110). These preliminary findings are consistent with the hypothesis that immune activation is important in the pathogenesis of CHF, and they establish the basis for a phase 3 trial to define the benefit of Celacade in CHF.

Autonomic cardiovascular modulation in masters and young cyclists following high-intensity interval training.

PubMed

Borges, Nattai R; Reaburn, Peter R; Doering, Thomas M; Argus, Christos K; Driller, Matthew W

2017-04-01

This study aimed at examining the autonomic cardiovascular modulation in well-trained masters and young cyclists following high-intensity interval training (HIT). Nine masters (age 55.6 ± 5.0 years) and eight young cyclists (age 25.9 ± 3.0 years) completed a HIT protocol of 6 x 30 sec at 175% of peak power output, with 4.5-min' rest between efforts. Immediately following HIT, heart rate and R-R intervals were monitored for 30-min during passive supine recovery. Autonomic modulation was examined by i) heart rate recovery in the first 60-sec of recovery (HRR 60 ); ii) the time constant of the 30-min heart rate recovery curve (HRRτ); iii) the time course of the root mean square for successive 30-sec R-R interval (RMSSD 30 ); and iv) time and frequency domain analyses of subsequent 5-min R-R interval segments. No significant between-group differences were observed for HRR 60 (P = 0.096) or HRR τ (P = 0.617). However, a significant interaction effect was found for RMSSD 30 (P = 0.021), with the master cyclists showing higher RMSSD 30 values following HIT. Similar results were observed in the time and frequency domain analyses with significant interaction effects found for the natural logarithm of the RMSSD (P = 0.008), normalised low-frequency power (P = 0.016) and natural logarithm of high-frequency power (P = 0.012). Following high-intensity interval training, master cyclists demonstrated greater post-exercise parasympathetic reactivation compared to young cyclists, indicating that physical training at older ages has significant effects on autonomic function.

Viscosity-adjusted estimation of pressure head and pump flow with quasi-pulsatile modulation of rotary blood pump for a total artificial heart.

PubMed

Yurimoto, Terumi; Hara, Shintaro; Isoyama, Takashi; Saito, Itsuro; Ono, Toshiya; Abe, Yusuke

2016-09-01

Estimation of pressure and flow has been an important subject for developing implantable artificial hearts. To realize real-time viscosity-adjusted estimation of pressure head and pump flow for a total artificial heart, we propose the table estimation method with quasi-pulsatile modulation of rotary blood pump in which systolic high flow and diastolic low flow phased are generated. The table estimation method utilizes three kinds of tables: viscosity, pressure and flow tables. Viscosity is estimated from the characteristic that differential value in motor speed between systolic and diastolic phases varies depending on viscosity. Potential of this estimation method was investigated using mock circulation system. Glycerin solution diluted with salty water was used to adjust viscosity of fluid. In verification of this method using continuous flow data, fairly good estimation could be possible when differential pulse width modulation (PWM) value of the motor between systolic and diastolic phases was high. In estimation under quasi-pulsatile condition, inertia correction was provided and fairly good estimation was possible when the differential PWM value was high, which was not different from the verification results using continuous flow data. In the experiment of real-time estimation applying moving average method to the estimated viscosity, fair estimation could be possible when the differential PWM value was high, showing that real-time viscosity-adjusted estimation of pressure head and pump flow would be possible with this novel estimation method when the differential PWM value would be set high.

Interval training based on ventilatory anaerobic threshold increases cardiac vagal modulation and decreases high-sensitivity c-reative protein: randomized clinical trial in coronary artery disease.

PubMed

Tamburus, Nayara Y; Paula, Roberta F L; Kunz, Vandeni C; César, Marcelo C; Moreno, Marlene A; da Silva, Ester

2015-01-01

Autonomic dysfunction and inflammatory activity are involved in the development and progression of coronary artery disease (CAD), and exercise training has been shown to confer a cardiovascular benefit. To evaluate the effects that interval training (IT) based on ventilatory anaerobic threshold (VAT) has on heart rate variability (HRV) and high-sensitivity C-reactive protein (hs-CRP) levels, as well as the relationship between both levels, in patients with CAD and/or cardiovascular risk factors (RF). Forty-two men (aged 57.88±6.20 years) were divided into two training groups, CAD-T (n= 12) and RF-T (n= 10), and two control groups, CAD-C (n= 10) and RF-C (n=10). Heart rate and RR intervals in the supine position, cardiopulmonary exercise tests, and hs-CRP levels were measured before and after IT. HRV was analyzed by spectral and symbolic analysis. The CAD-T and RF-T underwent a 16-week IT program of three weekly sessions at training intensities based on the VAT. In the RF-T, cardiac sympathetic modulation index and hs-CRP decreased (p<0.02), while cardiac parasympathetic modulation index increased (p<0.02). In the CAD-T, cardiac parasympathetic modulation index increased, while hs-CRP, systolic, and diastolic blood pressures decreased (p<0.02). Both control groups showed increase in hs-CRP parameters (p<0.02). There was a strong and significant association between parasympathetic and sympathetic modulations with hs-CRP. The IT program based on the VAT promoted a decrease in hs-CRP associated with improvement in cardiac autonomic modulation.

21 CFR 884.2740 - Perinatal monitoring system and accessories.

Code of Federal Regulations, 2012 CFR

2012-04-01

... monitoring system is a device used to show graphically the relationship between maternal labor and the fetal heart rate by means of combining and coordinating uterine contraction and fetal heart monitors with...

21 CFR 884.2740 - Perinatal monitoring system and accessories.

Code of Federal Regulations, 2013 CFR

2013-04-01

... monitoring system is a device used to show graphically the relationship between maternal labor and the fetal heart rate by means of combining and coordinating uterine contraction and fetal heart monitors with...

21 CFR 884.2740 - Perinatal monitoring system and accessories.

Code of Federal Regulations, 2014 CFR

2014-04-01

... monitoring system is a device used to show graphically the relationship between maternal labor and the fetal heart rate by means of combining and coordinating uterine contraction and fetal heart monitors with...

21 CFR 884.2740 - Perinatal monitoring system and accessories.

Code of Federal Regulations, 2011 CFR

2011-04-01

... monitoring system is a device used to show graphically the relationship between maternal labor and the fetal heart rate by means of combining and coordinating uterine contraction and fetal heart monitors with...

21 CFR 884.2740 - Perinatal monitoring system and accessories.

Code of Federal Regulations, 2010 CFR

2010-04-01

... monitoring system is a device used to show graphically the relationship between maternal labor and the fetal heart rate by means of combining and coordinating uterine contraction and fetal heart monitors with...

Genetics Home Reference: critical congenital heart disease

MedlinePlus

... into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination ... defects classified as CCHD include coarctation of the aorta , double-outlet right ventricle, D-transposition of the ...

Drug insight: If inhibitors as specific heart-rate-reducing agents.

PubMed

Borer, Jeffrey S

2004-12-01

Heart rate is determined primarily by spontaneously repeating net inward current carried by sodium ions and potassium ions through hyperpolarization-activated cyclic-nucleotide-gated channels. Within the heart, these channels are found most abundantly in sinoatrial cardiomyocytes. The channels open in response to membrane hyperpolarization, modulated by local cAMP concentrations. They permit activation of the I(f) current, which can be blocked specifically by molecules characterized by linked benzazepinone and benzocyclobutane rings, and which are devoid of effects on cardiac conduction, inotropy or peripheral vascular tone. The resulting heart-rate reduction has been effective in angina prevention in clinical trials involving 4,000 patients, using the prototype I(f) inhibitor, ivabradine. No serious adverse events have been attributed to the treatment; the most prominent side-effect is dose-related, always reversible and often transient visual symptoms that seldom result in voluntary drug discontinuation.

The Role of Exercise in Cardiac Aging: From Physiology to Molecular Mechanisms.

PubMed

Roh, Jason; Rhee, James; Chaudhari, Vinita; Rosenzweig, Anthony

2016-01-22

Aging induces structural and functional changes in the heart that are associated with increased risk of cardiovascular disease and impaired functional capacity in the elderly. Exercise is a diagnostic and therapeutic tool, with the potential to provide insights into clinical diagnosis and prognosis, as well as the molecular mechanisms by which aging influences cardiac physiology and function. In this review, we first provide an overview of how aging impacts the cardiac response to exercise, and the implications this has for functional capacity in older adults. We then review the underlying molecular mechanisms by which cardiac aging contributes to exercise intolerance, and conversely how exercise training can potentially modulate aging phenotypes in the heart. Finally, we highlight the potential use of these exercise models to complement models of disease in efforts to uncover new therapeutic targets to prevent or treat heart disease in the aging population. © 2016 American Heart Association, Inc.

Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus - Mechanisms, Management, and Clinical Considerations.

PubMed

Low Wang, Cecilia C; Hess, Connie N; Hiatt, William R; Goldfine, Allison B

2016-06-14

Cardiovascular disease remains the principal cause of death and disability among patients with diabetes mellitus. Diabetes mellitus exacerbates mechanisms underlying atherosclerosis and heart failure. Unfortunately, these mechanisms are not adequately modulated by therapeutic strategies focusing solely on optimal glycemic control with currently available drugs or approaches. In the setting of multifactorial risk reduction with statins and other lipid-lowering agents, antihypertensive therapies, and antihyperglycemic treatment strategies, cardiovascular complication rates are falling, yet remain higher for patients with diabetes mellitus than for those without. This review considers the mechanisms, history, controversies, new pharmacological agents, and recent evidence for current guidelines for cardiovascular management in the patient with diabetes mellitus to support evidence-based care in the patient with diabetes mellitus and heart disease outside of the acute care setting. © 2016 American Heart Association, Inc.

ICV Echo Ultrasound Scan

NASA Image and Video Library

2012-12-31

View of Integrated Cardiovascular (ICV) Echo Ultrasound Scan,in the Columbus module. ICV aims to quantify the extent,time course and clinical significance of cardiac atrophy (decrease in the size of the heart muscle) in space. Photo was taken during Expedition 34.

Single-Cell Sequencing of the Healthy and Diseased Heart Reveals Ckap4 as a New Modulator of Fibroblasts Activation.

PubMed

Gladka, Monika M; Molenaar, Bas; de Ruiter, Hesther; van der Elst, Stefan; Tsui, Hoyee; Versteeg, Danielle; Lacraz, Grègory P A; Huibers, Manon M H; van Oudenaarden, Alexander; van Rooij, Eva

2018-01-31

Background -Genome-wide transcriptome analysis has greatly advanced our understanding of the regulatory networks underlying basic cardiac biology and mechanisms driving disease. However, so far, the resolution of studying gene expression patterns in the adult heart has been limited to the level of extracts from whole tissues. The use of tissue homogenates inherently causes the loss of any information on cellular origin or cell type-specific changes in gene expression. Recent developments in RNA amplification strategies provide a unique opportunity to use small amounts of input RNA for genome-wide sequencing of single cells. Methods -Here, we present a method to obtain high quality RNA from digested cardiac tissue from adult mice for automated single-cell sequencing of both the healthy and diseased heart. Results -After optimization, we were able to perform single-cell sequencing on adult cardiac tissue under both homeostatic conditions and after ischemic injury. Clustering analysis based on differential gene expression unveiled known and novel markers of all main cardiac cell types. Based on differential gene expression we were also able to identify multiple subpopulations within a certain cell type. Furthermore, applying single-cell sequencing on both the healthy and the injured heart indicated the presence of disease-specific cell subpopulations. As such, we identified cytoskeleton associated protein 4 ( Ckap4 ) as a novel marker for activated fibroblasts that positively correlates with known myofibroblast markers in both mouse and human cardiac tissue. Ckap4 inhibition in activated fibroblasts treated with TGFβ triggered a greater increase in the expression of genes related to activated fibroblasts compared to control, suggesting a role of Ckap4 in modulating fibroblast activation in the injured heart. Conclusions -Single-cell sequencing on both the healthy and diseased adult heart allows us to study transcriptomic differences between cardiac cells, as well as cell type-specific changes in gene expression during cardiac disease. This new approach provides a wealth of novel insights into molecular changes that underlie the cellular processes relevant for cardiac biology and pathophysiology. Applying this technology could lead to the discovery of new therapeutic targets relevant for heart disease.

Cardiac Autonomic Dysfunction in Offspring of Hypertensive Parents During Exercise.

PubMed

Almeida, Leonardo Barbosa de; Peçanha, Tiago; Mira, Pedro Augusto de Carvalho; Souza, Livia Victorino de; da Silva, Lílian Pinto; Martinez, Daniel Godoy; Freitas, Isabelle Magalhães Guedes; Laterza, Mateus Camaroti

2017-12-01

Offspring of hypertensive parents present autonomic dysfunction at rest and during physiological maneuvers. However, the cardiac autonomic modulation during exercise remains unknown. This study tested whether the cardiac autonomic modulation would be reduced in offspring of hypertensive parents during exercise. Fourteen offspring of hypertensive and 14 offspring of normotensive individuals were evaluated. The groups were matched by age (24.5±1.0 vs. 26.6±1.5 years; p=0.25) and BMI (22.8±0.6 vs. 24.2±1.0 kg/m 2 ; p=0.30). Blood pressure and heart rate were assessed simultaneously during 3 min at baseline followed by 3-min isometric handgrip at 30% of maximal voluntary contraction. Cardiac autonomic modulation was evaluated using heart rate variability. Primary variables were subjected to two-way ANOVA (group vs. time). P value<0.05 was considered statistically significant. Blood pressure and heart rate were similar between groups during exercise protocol. In contrast, offspring of hypertensive subjects showed a reduction of SDNN (Basal=34.8±3.5 vs. 45.2±3.7 ms; Exercise=30.8±3.3 vs. 41.5±3.9 ms; p group=0.01), RMSSD (Basal=37.1±3.7 vs. 52.0±6.0 ms; Exercise=28.6±3.4 vs. 41.9±5.3 ms; p group=0.02) and pNN50 (Basal=15.7±4.0 vs. 29.5±5.5%; Exercise=7.7±2.4 vs. 18.0±4.3%; p group=0.03) during the exercise protocol in comparison with offspring of normotensive parents. We concluded that normotensive offspring of hypertensive parents exhibit impaired cardiac autonomic modulation during exercise. © Georg Thieme Verlag KG Stuttgart · New York.

Living nano-micro fibrous woven fabric/hydrogel composite scaffolds for heart valve engineering.

PubMed

Wu, Shaohua; Duan, Bin; Qin, Xiaohong; Butcher, Jonathan T

2017-03-15

Regeneration and repair of injured or diseased heart valves remains a clinical challenge. Tissue engineering provides a promising treatment approach to facilitate living heart valve repair and regeneration. Three-dimensional (3D) biomimetic scaffolds that possess heterogeneous and anisotropic features that approximate those of native heart valve tissue are beneficial to the successful in vitro development of tissue engineered heart valves (TEHV). Here we report the development and characterization of a novel composite scaffold consisting of nano- and micro-scale fibrous woven fabrics and 3D hydrogels by using textile techniques combined with bioactive hydrogel formation. Embedded nano-micro fibrous scaffolds within hydrogel enhanced mechanical strength and physical structural anisotropy of the composite scaffold (similar to native aortic valve leaflets) and also reduced its compaction. We determined that the composite scaffolds supported the growth of human aortic valve interstitial cells (HAVIC), balanced the remodeling of heart valve ECM against shrinkage, and maintained better physiological fibroblastic phenotype in both normal and diseased HAVIC over single materials. These fabricated composite scaffolds enable the engineering of a living heart valve graft with improved anisotropic structure and tissue biomechanics important for maintaining valve cell phenotypes. Heart valve-related disease is an important clinical problem, with over 300,000 surgical repairs performed annually. Tissue engineering offers a promising strategy for heart valve repair and regeneration. In this study, we developed and tissue engineered living nano-micro fibrous woven fabric/hydrogel composite scaffolds by using textile technique combined with bioactive hydrogel formation. The novelty of our technique is that the composite scaffolds can mimic physical structure anisotropy and the mechanical strength of natural aortic valve leaflet. Moreover, the composite scaffolds prevented the matrix shrinkage, which is major problem that causes the failure of TEHV, and better maintained physiological fibroblastic phenotype in both normal and diseased HAVIC. This work marks the first report of a combination composite scaffold using 3D hydrogel enhanced by nano-micro fibrous woven fabric, and represents a promising tissue engineering strategy to treat heart valve injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans

NASA Technical Reports Server (NTRS)

Cui, J.; Wilson, T. E.; Shibasaki, M.; Hodges, N. A.; Crandall, C. G.

2001-01-01

To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.001) during posthandgrip muscle ischemia (-201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (-142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.

Dosimetric aspects of breast radiotherapy with three-dimensional and intensity-modulated radiotherapy helical tomotherapy planning modules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadav, Poonam; Service of Radiation Therapy, University of Wisconsin Aspirus Cancer Center, Wisconsin Rapids, WI; Yan, Yue, E-mail: yyan5@mdanderson.org

In this work, we investigated the dosimetric differences between the intensity-modulated radiotherapy (IMRT) plans and the three-dimensional (3D) helical plans based on the TomoTherapy system. A total of 15 patients with supine setup were randomly selected from the data base. For patients with lumpectomy planning target volume (PTV), regional lymph nodes were also included as part of the target. For dose sparing, the significant differences between the helical IMRT and helical 3D were only found in the heart and contralateral breast. For the dose to the heart, helical IMRT reduced the maximum point dose by 6.98 Gy compared to themore » helical 3D plan (p = 0.01). For contralateral breast, the helical IMRT plans significantly reduced the maximum point dose by 5.6 Gy compared to the helical 3D plan. However, compared to the helical 3D plan, the helical IMRT plan increased the volume for lower dose (13.08% increase in V{sub 5} {sub Gy}, p = 0.01). In general, there are no significant differences in dose sparing between helical IMRT and helical 3D plans.« less

A System for Heart Sounds Classification

PubMed Central

Redlarski, Grzegorz; Gradolewski, Dawid; Palkowski, Aleksander

2014-01-01

The future of quick and efficient disease diagnosis lays in the development of reliable non-invasive methods. As for the cardiac diseases – one of the major causes of death around the globe – a concept of an electronic stethoscope equipped with an automatic heart tone identification system appears to be the best solution. Thanks to the advancement in technology, the quality of phonocardiography signals is no longer an issue. However, appropriate algorithms for auto-diagnosis systems of heart diseases that could be capable of distinguishing most of known pathological states have not been yet developed. The main issue is non-stationary character of phonocardiography signals as well as a wide range of distinguishable pathological heart sounds. In this paper a new heart sound classification technique, which might find use in medical diagnostic systems, is presented. It is shown that by combining Linear Predictive Coding coefficients, used for future extraction, with a classifier built upon combining Support Vector Machine and Modified Cuckoo Search algorithm, an improvement in performance of the diagnostic system, in terms of accuracy, complexity and range of distinguishable heart sounds, can be made. The developed system achieved accuracy above 93% for all considered cases including simultaneous identification of twelve different heart sound classes. The respective system is compared with four different major classification methods, proving its reliability. PMID:25393113

Neurohumoral and mechanical factors in the modulation of left ventricular mass

NASA Technical Reports Server (NTRS)

Franklin, Eleanor I.; Hawthorne, Edward W.

1987-01-01

The goals for the research were to define, describe, and study those neuroendocrine and mechanical mechanisms that may play a role in the initiation and maintenance of an increase in, or cause regression of, the mass of the left ventricle. Dynamic changes in heart mass have been observed to occur in man and animals: (1) enlargement of the heart is frequently encountered in patients with hypertensive disease, and (2) decrease in heart mass has been reported for men exposed to prolonged space flight. The basic physiologic processes which may explain how these changes occur, and the effects of gain or loss of myocardial mass on cardiac performance were considered significant questions to be answered for the benefit of the National Aeronautics and Space Administration.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

PubMed

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas ( e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang ). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

PubMed Central

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas (e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses. PMID:29403392

Binocular Combination of Second-Order Stimuli

PubMed Central

Zhou, Jiawei; Liu, Rong; Zhou, Yifeng; Hess, Robert F.

2014-01-01

Phase information is a fundamental aspect of visual stimuli. However, the nature of the binocular combination of stimuli defined by modulations in contrast, so-called second-order stimuli, is presently not clear. To address this issue, we measured binocular combination for first- (luminance modulated) and second-order (contrast modulated) stimuli using a binocular phase combination paradigm in seven normal adults. We found that the binocular perceived phase of second-order gratings depends on the interocular signal ratio as has been previously shown for their first order counterparts; the interocular signal ratios when the two eyes were balanced was close to 1 in both first- and second-order phase combinations. However, second-order combination is more linear than previously found for first-order combination. Furthermore, binocular combination of second-order stimuli was similar regardless of whether the carriers in the two eyes were correlated, anti-correlated, or uncorrelated. This suggests that, in normal adults, the binocular phase combination of second-order stimuli occurs after the monocular extracting of the second-order modulations. The sensory balance associated with this second-order combination can be obtained from binocular phase combination measurements. PMID:24404180

Quality of life following paediatric heart transplant: are age and activity level factors?

PubMed

Parent, John J; Sterrett, Lauren; Caldwell, Randall; Darragh, Robert; Schamberger, Marcus; Murphy, Debbie; Ebenroth, Eric

2015-03-01

We evaluated whether quality of life correlates to age and activity in children following heart transplantation. In addition, quality of life in children following heart transplantation was compared with previously reported values in children with congenital heart disease. Quality of life remains an important aspect of therapy. The Pediatric Quality of Life Inventory Generic Core Scales and Cardiac Module were administered to 14 children who had previously undergone heart transplantation. Patients wore a pedometer for 7 days to assess daily activity. The age at assessment was 13.1±1.9 years. The patients were 7.1±5.7 years post heart transplantation. There was a negative correlation between age at first heart transplantation and emotional (r=-0.64; p<0.05) and school function (r=-0.57; p<0.05). A negative correlation between patient's age at assessment and perceived physical appearance existed (r=-0.53; p<0.05). Daily steps negatively correlated with cognitive (r=-0.58; p<0.05), physical (r=-0.63; p<0.05), emotional (r=-0.62; p<0.05), and school function (r=-0.66; p<0.01). Heart transplantation patients reported better scores for treatment and symptoms (p<0.05) but lower physical health scores (p<0.01) than those with moderate congenital heart disease. Paediatric heart transplantation patients reported overall similar quality of life as patients with moderate congenital heart disease. Children receiving heart transplants at an older age may require additional emotional and educational support. Heart transplantation patients with higher activity levels may be more aware of their physical, emotional, and cognitive limitations, and thus score lower on these quality of life indicators.

Anterior Myocardial Territory May Replace the Heart as Organ at Risk in Intensity-Modulated Radiotherapy for Left-Sided Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan Wenyong; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan; Liu Dong

Purpose: We investigated whether the heart could be replaced by the anterior myocardial territory (AMT) as the organ at risk (OAR) in intensity-modulated radiotherapy (IMRT) of the breast for patients with left-sided breast cancer. Methods and Materials: Twenty-three patients with left-sided breast cancer who received postoperative radiation after breast-conserving surgery were studied. For each patient, we generated five IMRT plans including heart (H), left ventricle (LV), AMT, LV+AMT, and H+LV as the primary OARs, respectively, except both lungs and right breast, which corresponded to IMRT(H), IMRT(LV), IMRT(AMT), IMRT(LV+AMT), and IMRT(H+LV). For the planning target volumes and OARs, the parameters ofmore » dose-volume histograms were compared. Results: The homogeneity index, conformity index, and coverage index were not compromised significantly in IMRT(AMT), IMRT(LV) and IMRT(LV+ AMT), respectively, when compared with IMRT(H). The mean dose to the heart, LV, and AMT decreased 5.3-21.5% (p < 0.05), 19.9-29.5% (p < 0.05), and 13.3-24.5% (p < 0.05), respectively. Similarly, the low (e.g., V5%), middle (e.g., V20%), and high (e.g., V30%) dose-volume of the heart, LV, and AMT decreased with different levels. The mean dose and V10% of the right lung increased by 9.2% (p < 0.05) and 27.6% (p < 0.05), respectively, in IMRT(LV), and the mean dose and V5% of the right breast decreased significantly in IMRT(AMT) and IMRT(LV+AMT). IMRT(AMT) was the preferred plan and was then compared with IMRT(H+LV); the majority of dose-volume histogram parameters of OARs including the heart, LV, AMT, both lungs, and the right breast were not statistically different. However, the low dose-volume of LV increased and the middle dose-volume decreased significantly (p < 0.05) in IMRT(AMT). Also, those of the right lung (V10%, V15%) and right breast (V5%, V10%) decreased significantly (p < 0.05). Conclusions: The AMT may replace the heart as the OAR in left-sided breast IMRT after breast-conserving surgery to decrease the radiation dose to the heart.« less

[Combined surgical intervention treatments for lung cancer and coronary heart disease patients].

PubMed

Ma, Xuchen; Zhang, Zhitai; Hu, Yansheng; Song, Feiqiang; Zhang, Shaoyan; Ou, Songlei

2012-10-01

The number of patients with both lung cancer and coronary heart disease has increased for the last ten years. The aim of this study is to analyze the outcome of the combined treatment of radical surgery and off-pump coronary artery bypass grafting (OPCABG) for patients with both lung cancer and coronary heart disease. The clinical data of 18 patients (16 males and 2 females, mean age of 66.11 years) with both lung cancer and coronary heart disease who went through combined surgical interventions between 2003 and 2012 were summarized and analyzed. The lung cancer in these patients was predominantly at stages I and II (TNM). All patients' cardio-pulmonary function was favorable. All the patients survived the operation, without any recorded death and new myocardial infarction occurrence during the perioperative period. Squamous carcinoma and adenocarcinoma were found in 10 and 8 patients, respectively. Pathological lung cancer stage was Ia in 2 cases, Ib in 8 cases, IIa in 3 cases, II b in 3 cases, and IIIa in 2 cases. The most frequently observed complications were cardiac arrhythmias, atelectasis, and pulmonary infections. The mean values of operating room time, postoperative drainage, drainage tube time, and blood transfusion were significantly different between video-assisted thoracoscopic surgery (VATS) groups and thoractomy groups. No significant differences in survival rate were found (P=0.187). The combined method of OPCABG and pulmonary resection is a safe and effective treatment for patients with both lung cancer and coronary heart disease. VATS lobectomy is beneficial for lung cancer patients because it reduces lesions.

Long-term organ protection by doxazosin and/or quinapril as antihypertensive therapy.

PubMed

Gallego-Delgado, Julio; Lazaro, Alberto; Gomez-Garre, Dulcenombre; Osende, Julio I; Gonzalez-Rubio, Maria L; Herraiz, Marta; Manzarbeitia, Félix; Fortes, José; Fernandez-Cruz, Arturo; Egido, Jesús

2006-01-01

Even with optimal blood pressure control, organ protection may also depend on the selected therapeutic regime. Angiotensin-converting enzyme inhibitors have been shown to provide excellent organ protection in hypertension, and may show dose-dependent protective effects. Adrenergic alpha blockers have been associated with an increased rate of heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and Vasodilator-Heart Failure Trial (V-HeFT). This has been related to a proapoptotic effect of this drug in cardiomyocytes. Our purpose is to compare the heart and renal protection of a high quinapril dose, with a combined low quinapril dose plus doxazosin, in an animal model of chronic hypertension. Uninephrectomized spontaneously hypertensive 12-week-old rats were treated for 36 weeks with either quinapril or a combination of doxazosin plus a low quinapril dose. Tight blood pressure control was achieved with both treatments. Renal and cardiac protection was assessed by different parameters, and cardiac apoptosis was evaluated by active caspase-3, apoptotic protein and heat shock protein levels. Untreated hypertensive and normotensive rats were included as controls. Both treatments showed significant heart and renal protection compared with untreated animals. Both therapeutic regimes showed similar protection in renal and cardiac pathology, coronary media fibrosis, myocardial apoptosis and cardiac index. Proteinuria and left ventricular hypertrophy regression were significantly lower in the quinapril group compared with the combined treatment group. Blood pressure control with a high quinapril dose provided higher organ protection than a combined therapy with a lower quinapril dose. This effect was not due to a deleterious effect of doxazosin.

Is depressed myocyte contractility centrally involved in heart failure?

PubMed

Houser, Steven R; Margulies, Kenneth B

2003-03-07

This review examines the evidence for and against the hypothesis that abnormalities in cardiac contractility initiate the heart failure syndrome and drive its progression. There is substantial evidence that the contractility of failing human hearts is depressed and that abnormalities of basal Ca2+ regulation and adrenergic regulation of Ca2+ signaling are responsible. The cellular and molecular defects that cause depressed myocyte contractility are not well established but seem to culminate in abnormal sarcoplasmic reticulum uptake, storage, and release. There are also strong links between Ca2+ regulation, Ca2+ signaling pathways, hypertrophy, and heart failure that need to be more clearly delineated. There is not substantial direct evidence for a causative role for depressed contractility in the initiation and progression of human heart failure, and some studies show that heart failure can occur without depressed myocyte contractility. Stronger support for a causal role for depressed contractility in the initiation of heart failure comes from animal studies where maintaining or improving contractility can prevent heart failure. Recent clinical studies in humans also support the idea that beneficial heart failure treatments, such as beta-adrenergic antagonists, involve improved contractility. Current or previously used heart failure treatments that increase contractility, primarily by increasing cAMP, have generally increased mortality. Novel heart failure therapies that increase or maintain contractility or adrenergic signaling by selectively modulating specific molecules have produced promising results in animal experiments. How to reliably implement these potentially beneficial inotropic therapies in humans without introducing negative side effects is the major unanswered question in this field.

Heart rate and respiratory rhythm dynamics on ascent to high altitude.

PubMed Central

Lipsitz, L. A.; Hashimoto, F.; Lubowsky, L. P.; Mietus, J.; Moody, G. B.; Appenzeller, O.; Goldberger, A. L.

1995-01-01

OBJECTIVE--To investigate the alterations in autonomic control of heart rate at high altitude and to test the hypothesis that hypoxaemic stress during exposure to high altitude induces non-linear, periodic heart rate oscillations, similar to those seen in heart failure and the sleep apnoea syndrome. SUBJECTS--11 healthy subjects aged 24-64. MAIN OUTCOME MEASURES--24 hour ambulatory electrocardiogram records obtained at baseline (1524 m) and at 4700 m. Simultaneous heart rate and respiratory dynamics during 2.5 hours of sleep by fast Fourier transform analysis of beat to beat heart rate and of an electrocardiographically derived respiration signal. RESULTS--All subjects had resting hypoxaemia at high altitude, with an average oxyhaemoglobin saturation of 81% (5%). There was no significant change in mean heart rate, but low frequency (0.01-0.05 Hz) spectral power was increased (P < 0.01) at high altitude. Time series analysis showed a complex range of non-linear sinus rhythm dynamics. Striking low frequency (0.04-0.06 Hz) heart rate oscillations were observed during sleep in eight subjects at high altitude. Analysis of the electrocardiographically derived respiration signal indicated that these heart rate oscillations correlated with low frequency respiratory oscillations. CONCLUSIONS--These data suggest (a) that increased low frequency power during high altitude exposure is not simply attributable to increased sympathetic modulation of heart rate, but relates to distinctive cardiopulmonary oscillations at approximately 0.05 Hz and (b) that the emergence of periodic heart rate oscillations at high altitude is consistent with an unstable cardiopulmonary control system that may develop on acute exposure to hypoxaemic stress. PMID:7488453

Heart rate and respiratory rhythm dynamics on ascent to high altitude

NASA Technical Reports Server (NTRS)

Lipsitz, L. A.; Hashimoto, F.; Lubowsky, L. P.; Mietus, J.; Moody, G. B.; Appenzeller, O.; Goldberger, A. L.

1995-01-01

OBJECTIVE--To investigate the alterations in autonomic control of heart rate at high altitude and to test the hypothesis that hypoxaemic stress during exposure to high altitude induces non-linear, periodic heart rate oscillations, similar to those seen in heart failure and the sleep apnoea syndrome. SUBJECTS--11 healthy subjects aged 24-64. MAIN OUTCOME MEASURES--24 hour ambulatory electrocardiogram records obtained at baseline (1524 m) and at 4700 m. Simultaneous heart rate and respiratory dynamics during 2.5 hours of sleep by fast Fourier transform analysis of beat to beat heart rate and of an electrocardiographically derived respiration signal. RESULTS--All subjects had resting hypoxaemia at high altitude, with an average oxyhaemoglobin saturation of 81% (5%). There was no significant change in mean heart rate, but low frequency (0.01-0.05 Hz) spectral power was increased (P < 0.01) at high altitude. Time series analysis showed a complex range of non-linear sinus rhythm dynamics. Striking low frequency (0.04-0.06 Hz) heart rate oscillations were observed during sleep in eight subjects at high altitude. Analysis of the electrocardiographically derived respiration signal indicated that these heart rate oscillations correlated with low frequency respiratory oscillations. CONCLUSIONS--These data suggest (a) that increased low frequency power during high altitude exposure is not simply attributable to increased sympathetic modulation of heart rate, but relates to distinctive cardiopulmonary oscillations at approximately 0.05 Hz and (b) that the emergence of periodic heart rate oscillations at high altitude is consistent with an unstable cardiopulmonary control system that may develop on acute exposure to hypoxaemic stress.

A Health Education Program for Parents and Children Who Exhibit High Risk Factors of Coronary Heart Disease.

ERIC Educational Resources Information Center

Hopp, Joyce W.; And Others

This study demonstrated the feasibility of joint parent-child education to change the behaviors known to be associated with increased risk of coronary heart disease. Earlier studies have shown that parents who are at increased risk of coronary heart disease can be identified by studying certain factors in the children. Utilizing a combined risk…

Reiter works with Heart Rate and Blood Pressure measuring devices in the SM during Expedition 13

NASA Image and Video Library

2006-07-01

ISS013-E-54170 (July 2006) --- European Space Agency (ESA) astronaut Thomas Reiter, Expedition 13 flight engineer, looks over a procedures checklist in the Zvezda Service Module of the International Space Station.

A New MRI-Based Model of Heart Function with Coupled Hemodynamics and Application to Normal and Diseased Canine Left Ventricles

PubMed Central

Choi, Young Joon; Constantino, Jason; Vedula, Vijay; Trayanova, Natalia; Mittal, Rajat

2015-01-01

A methodology for the simulation of heart function that combines an MRI-based model of cardiac electromechanics (CE) with a Navier–Stokes-based hemodynamics model is presented. The CE model consists of two coupled components that simulate the electrical and the mechanical functions of the heart. Accurate representations of ventricular geometry and fiber orientations are constructed from the structural magnetic resonance and the diffusion tensor MR images, respectively. The deformation of the ventricle obtained from the electromechanical model serves as input to the hemodynamics model in this one-way coupled approach via imposed kinematic wall velocity boundary conditions and at the same time, governs the blood flow into and out of the ventricular volume. The time-dependent endocardial surfaces are registered using a diffeomorphic mapping algorithm, while the intraventricular blood flow patterns are simulated using a sharp-interface immersed boundary method-based flow solver. The utility of the combined heart-function model is demonstrated by comparing the hemodynamic characteristics of a normal canine heart beating in sinus rhythm against that of the dyssynchronously beating failing heart. We also discuss the potential of coupled CE and hemodynamics models for various clinical applications. PMID:26442254

MPI as high temporal resolution imaging technique for in vivo bolus tracking of Ferucarbotran in mouse model

NASA Astrophysics Data System (ADS)

Jung, C.; Salamon, J.; Hofmann, M.; Kaul, M. G.; Adam, G.; Ittrich, H.; Knopp, T.

2016-03-01

Purpose: The goal of this study was to achieve a real time 3D visualisation of the murine cardiovascular system by intravenously injected superparamagnetic nanoparticles using Magnetic particle imaging (MPI). Material and Methods: MPI scans of FVB mice were performed using a 3D imaging sequence (1T/m gradient strength, 10mT drive-field strength). A dynamic scan with a temporal resolution of 21.5ms per 3D volume acquisition was performed. 50μl ferucarbotran (Resovist®, Bayer Healthcare AG) were injected into the tail vein after baseline MPI measurements. As MPI delivers no anatomic information, MRI scans at a 7T ClinScan (Bruker) were performed using a T2-weighted 2D TSE sequence. The reconstruction of the MPI data was performed on the MPI console (ParaVision 6.0/MPI, Bruker). Image fusion was done using additional image processing software (Imalytics, Philips). The dynamic information was extracted using custom software developed in the Julia programming environment. Results: The combined MRI-MPI measurements were carried out successfully. MPI data clearly demonstrated the passage of the SPIO tracer through the inferior vena cava, the heart and finally the liver. By co-registration with MRI the anatomical regions were identified. Due to the volume frame rate of about 46 volumes per second a signal modulation with the frequency of the heart beat was detectable and a heart beat of 520 beats per minute (bpm) has been assumed. Moreover, the blood flow velocity of approximately 5cm/s in the vena cava has been estimated. Conclusions: The high temporal resolution of MPI allows real-time imaging and bolus tracking of intravenous injected nanoparticles and offers a real time tool to assess blood flow velocity.

Electrophysiological correlates of word recognition memory process in patients with ischemic left ventricular dysfunction.

PubMed

Giovannelli, Fabio; Simoni, David; Gavazzi, Gioele; Giganti, Fiorenza; Olivotto, Iacopo; Cincotta, Massimo; Pratesi, Alessandra; Baldasseroni, Samuele; Viggiano, Maria Pia

2016-09-01

The relationship between left ventricular ejection fraction (LVEF) and cognitive performance in patients with coronary artery disease without overt heart failure is still under debate. In this study we combine behavioral measures and event-related potentials (ERPs) to verify whether electrophysiological correlates of recognition memory (old/new effect) are modulated differently as a function of LVEF. Twenty-three male patients (12 without [LVEF>55%] and 11 with [LVEF<40%] left ventricular dysfunction), and a Mini Mental State Examination score >25 were enrolled. ERPs were recorded while participants performed an old/new visual word recognition task. A late positive ERP component between 350 and 550ms was differentially modulated in the two groups: a clear old/new effect (enhanced mean amplitude for old respect to new items) was observed in patients without LVEF dysfunction; whereas patients with overt LVEF dysfunction did not show such effect. In contrast, no significant differences emerged for behavioral performance and neuropsychological evaluations. These data suggest that ERPs may reveal functional brain abnormalities that are not observed at behavioral level. Detecting sub-clinical measures of cognitive decline may contribute to set appropriate treatments and to monitor asymptomatic or mildly symptomatic patients with LVEF dysfunction. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Optimization of pharmacotherapy in chronic heart failure: is heart rate adequately addressed?

PubMed

Franke, Jennifer; Wolter, Jan Sebastian; Meme, Lillian; Keppler, Jeannette; Tschierschke, Ramon; Katus, Hugo A; Zugck, Christian

2013-01-01

The aim of the study is to evaluate the use of beta-blockers in chronic heart failure (CHF) and the extent of heart rate reduction achieved in clinical practice and to determine differences in outcome of patients who fulfilled select inclusion criteria of the SHIFT study according to resting heart rate modulated by beta-blocker therapy. We evaluated an all-comer population of our dedicated CHF outpatient clinic between 2006 and 2010. For inclusion, individually optimized doses of guideline-recommended pharmacotherapy including beta-blockers had to be maintained for at least 3 months and routine follow-up performed at our outpatient CHF-clinic thereafter. Treatment dosages of beta-blockers, and demographic and clinical profiles including resting heart rate were assessed. The outcome of patients who fulfilled select inclusion criteria of the SHIFT study (left-ventricular ejection fraction (LVEF) ≤35 %, sinus rhythm, NYHA II-IV) and were followed-up for at least 1 year was stratified according to resting heart rates: ≥75 versus <75 bpm and ≥70 versus <70 bpm. The composite primary endpoint was defined as all-cause death or hospital admission for worsening heart failure during 12-month follow-up. In total, 3,181 patients were assessed in regard to treatment dosages of beta-blockers, and demographic and clinical profiles including resting heart rate. Of the overall studied population, 443 patients fulfilled all inclusion criteria and entered outcome analysis. Median observation time of survivors was 27.5 months with 1,039.7 observation-years in total. Up-titration to at least half the evidence-based target dose of beta-blockers was achieved in 69 % and full up-titration in 29 % of these patients. Patients with increased heart rates were younger, more often male, exhibited a higher NYHA functional class and lower LVEF. The primary endpoint occurred in 21 % of patients in the ≥70 bpm group versus 9 % of patients in the group with heart rates <70 bpm (p <0.01). Likewise, comparing the groups ≥75 and <75 bpm, the primary endpoint was significantly increased in the group of patients with heart rates ≥75 bpm 27 vs. 12.2 %; p < 0.01). 5-year event-free survival was significantly lower among patients with heart rates ≥70 bpm as compared to those with <70 bpm (log-rank test p < 0.05) and among patients in the ≥75 bpm group versus <75 bpm group (log-rank test p < 0.01). In conclusion, in clinical practice, 53 % of CHF patients have inadequate heart rate control (heart rates ≥75 bpm) despite concomitant beta-blocker therapy. In this non-randomized cohort, adequate heart rate control under individually optimized beta-blocker therapy was associated with improved mid- and long-term clinical outcome up to 5 years. As further up titration of beta-blockers is not achievable in many patients, the administration of a selective heart rate lowering agent, such as ivabradine adjuvant to beta-blockers may pose an opportunity to further modulate outcome.

Effects of Vibration and G-Loading on Heart Rate, Breathing Rate, and Response Time

NASA Technical Reports Server (NTRS)

Godinez, Angelica; Ayzenberg, Ruthie; Liston, Dorian B.; Stone, Leland S.

2013-01-01

Aerospace and applied environments commonly expose pilots and astronauts to G-loading and vibration, alone and in combination, with well-known sensorimotor (Cohen, 1970) and performance consequences (Adelstein et al., 2008). Physiological variables such as heart rate (HR) and breathing rate (BR) have been shown to increase with G-loading (Yajima et al., 1994) and vibration (e.g. Guignard, 1965, 1985) alone. To examine the effects of G-loading and vibration, alone and in combination, we measured heart rate and breathing rate under aerospace-relevant conditions (G-loads of 1 Gx and 3.8 Gx; vibration of 0.5 gx at 8, 12, and 16 Hz).

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.

[Doses to organs at risk in conformational radiotherapy and stereotaxic irradiation: The heart].

PubMed

Vandendorpe, B; Servagi Vernat, S; Ramiandrisoa, F; Bazire, L; Kirova, Y M

2017-10-01

Radiation therapy of breast cancer, Hodgkin lymphoma, lung cancer and others thoracic irradiations induce an ionizing radiation dose to the heart. Irradiation of the heart, associated with patient cardiovascular risk and cancer treatment-induced cardiotoxicity, increase cardiovascular mortality. The long survival after breast or Hodgkin lymphoma irradiation requires watching carefully late treatment toxicity. The over-risk of cardiac events is related to the dose received by the heart and the irradiated cardiac volume. The limitation of cardiac irradiation should be a priority in the planning of thoracic irradiations. Practices have to be modified, using modern techniques to approach of the primary objective of radiotherapy which is to optimize the dose to the target volume, sparing healthy tissues, in this case the heart. We have reviewed the literature on cardiac toxicity induced by conformational tridimensional radiation therapy, intensity-modulated radiation therapy or stereotactic body radiation therapy, in order to evaluate the possibilities to limit cardiotoxicity. Finally, we summarise the recommendations on dose constraints to the heart and coronary arteries. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Realization of pure frequency modulation of DFB laser via combined optical and electrical tuning.

PubMed

Tian, Chao; Chen, I-Chun Anderson; Park, Seong-Wook; Martini, Rainer

2013-04-08

In this paper we present a novel approach to convert AM signal into FM signal in semiconductor lasers via off resonance optical pumping and report on experimental results obtained with a commercial DFB laser. Aside of demonstrating discrete and fast frequency modulation, we achieve pure frequency modulation through combination with electrical modulation suppressing the associated amplitude modulation, which is detrimental to application such as spectroscopy and communication.

Valsartan and Sacubitril

MedlinePlus

Entresto® (as a combination product containing Sacubitril, Valsartan) ... The combination of valsartan and sacubitril is usually used in combination with other medications to lower the risk of death and hospitalization with certain types of heart ...

Selective estrogen receptor modulators and risk for coronary heart disease.

PubMed

Cano, A; Hermenegildo, C; Oviedo, P; Tarín, J J

2007-04-01

Coronary heart disease (CHD) is the leading cause of death in women in most countries. Atherosclerosis is the main biological process determining CHD. Clinical data support the notion that CHD is sensitive to estrogens, but debate exists concerning the effects of the hormone on atherosclerosis and its complications. Selective estrogen receptor modulators (SERMs) are compounds capable of binding the estrogen receptor to induce a functional profile distinct from estrogens. The possibility that SERMs may shift the estrogenic balance on cardiovascular risk towards a more beneficial profile has generated interest in recent years. There is considerable information on the effects of SERMs on distinct areas that are crucial in atherogenesis. The complexity derived from the diversity of variables affecting their mechanism of action plus the differences between compounds make it difficult to delineate one uniform trend for SERMs. The present picture, nonetheless, is one where SERMs seem less powerful than estrogens in atherosclerosis protection, but more gentle with advanced forms of the disease. The recent publication of the Raloxifene Use for The Heart (RUTH) study has confirmed a neutral effect for raloxifene. Prothrombotic states may favor occlusive thrombi at sites occupied by atheromatous plaques. Platelet activation has received attention as an important determinant of arterial thrombogenesis. Although still sparse, available evidence globally suggests neutral or beneficial effects for SERMs.

The effect of a single session of short duration biofeedback-induced deep breathing on measures of heart rate variability during laboratory-induced cognitive stress: a pilot study.

PubMed

Prinsloo, Gabriell E; Derman, Wayne E; Lambert, Michael I; Laurie Rauch, H G

2013-06-01

This study examines the acute effect of heart rate variability (HRV) biofeedback on HRV measures during and immediately after biofeedback and during the following laboratory-induced stress. Eighteen healthy males exposed to work-related stress were randomised into an HRV biofeedback group (BIO) or a comparative group (COM). Subjects completed a modified Stroop task before (Stroop 1) and after (Stroop 2) the intervention. Both groups had similar physiological responses to stress in Stroop 1. In Stroop 2, the COM group responded similarly to the way they did to Stroop 1: respiratory frequency (RF) and heart rate (HR) increased, RMSSD and high frequency (HF) power decreased or had a tendency to decrease, while low frequency (LF) power showed no change. The BIO group responded differently in Stroop 2: while RF increased and LF power decreased, HR, RMSSD and HF power showed no change. In the BIO group, RMSSD was higher in Stroop 2 compared to Stroop 1. In conclusion, HRV biofeedback induced a short term carry-over effect during both the following rest period and laboratory-induced stress suggesting maintained HF vagal modulation in the BIO group after the intervention, and maintained LF vagal modulation in the COM group.

Cardiovascular autonomic adaptation in lunar and martian gravity during parabolic flight.

PubMed

Widjaja, Devy; Vandeput, Steven; Van Huffel, Sabine; Aubert, André E

2015-06-01

Weightlessness has a well-known effect on the autonomic control of the cardiovascular system. With future missions to Mars in mind, it is important to know what the effect of partial gravity is on the human body. We aim to study the autonomic response of the cardiovascular system to partial gravity levels, as present on the Moon and on Mars, during parabolic flight. ECG and blood pressure were continuously recorded during parabolic flight. A temporal analysis of blood pressure and heart rate to changing gravity was conducted to study the dynamic response. In addition, cardiovascular autonomic control was quantified by means of heart rate (HR) and blood pressure (BP) variability measures. Zero and lunar gravity presented a biphasic cardiovascular response, while a triphasic response was noted during martian gravity. Heart rate and blood pressure are positively correlated with gravity, while the general variability of HR and BP, as well as vagal indices showed negative correlations with increasing gravity. However, the increase in vagal modulation during weightlessness is not in proportion when compared to the increase during partial gravity. Correlations were found between the gravity level and modulations in the autonomic nervous system during parabolic flight. Nevertheless, with future Mars missions in mind, more studies are needed to use these findings to develop appropriate countermeasures.

Baroreflex modulation of sympathetic nerve activity to muscle in heat-stressed humans

NASA Technical Reports Server (NTRS)

Cui, Jian; Wilson, Thad E.; Crandall, Craig G.

2002-01-01

To identify whether whole body heating alters arterial baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA and beat-by-beat arterial blood pressure were recorded in seven healthy subjects during acute hypotensive and hypertensive stimuli in both normothermic and heat stress conditions. Whole body heating significantly increased sublingual temperature (P < 0.01), MSNA (P < 0.01), heart rate (P < 0.01), and skin blood flow (P < 0.001), whereas mean arterial blood pressure did not change significantly (P > 0.05). During both normothermic and heat stress conditions, MSNA increased and then decreased significantly when blood pressure was lowered and then raised via intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure during heat stress (-128.3 +/- 13.9 U x beats(-1) x mmHg(-1)) was similar (P = 0.31) with normothermia (-140.6 +/- 21.1 U x beats(-1) x mmHg(-1)). Moreover, no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that arterial baroreflex modulation of MSNA and heart rate are not altered by whole body heating, with the exception of an upward shift of these baroreflex curves to accommodate changes in these variables that occur with whole body heating.

History of Music Therapy and Its Contemporary Applications in Cardiovascular Diseases.

PubMed

Montinari, Maria Rosa; Giardina, Simona; Minelli, Pierluca; Minelli, Sergio

2018-02-01

Contrary to what is commonly believed, music therapy is an old cure, the use of which is lost in the mists of time. Music always has been perceived to have particular healing powers, and the entire history of civilization contains aspects that link music to physical and mental healing. It seems that the adoption of music for therapeutic purposes harks back to a distant past, probably since the Paleolithic period: it was believed that listening to music could affect the behavior of human beings. In later centuries, the concept of "musical organ-tropism" was born and developed, because according to the type of music, one may affect the cardiovascular, respiratory, and neuroendocrine systems. Studies have shown that music can powerfully evoke and modulate emotions and moods, along with changes in heart activity, blood pressure, and breathing. Indeed, the following findings arise from the literature: heart and respiratory rates are higher in response to exciting music than in the case of tranquilizing music. In addition, music produces activity changes in brain structures (amygdala, hypothalamus, insular and orbitofrontal cortex) known to modulate heart function. This article provides a careful overview of music therapy history from prehistory to the present and a review of the latest applications of music therapy in cardiovascular diseases.

Regulator of G Protein Signaling 6 Protects the Heart from Ischemic Injury

PubMed Central

Chakravarti, Bandana; Mabe, Nathaniel W.; Seeley, Sarah L.; Bui, Albert D.; Yang, Jianqi; Watts, Stephanie W.; Neubig, Richard R.; Fisher, Rory A.

2017-01-01

Gαi-coupled receptors play important roles in protecting the heart from ischemic injury. Regulator of G protein signaling (RGS) proteins suppress Gαi signaling by accelerating the GTPase activity of Gαi subunits. However, the roles of individual RGS proteins in modulating ischemic injury are unknown. In this study, we investigated the effect of RGS6 deletion on myocardial sensitivity to ischemic injury. Hearts from RGS6 knockout (RGS6−/−) and RGS6 wild-type (RGS6+/+) mice were subjected to 30 minutes of ischemia and 2 hours of reperfusion on a Langendorff heart apparatus. Infarcts in RGS6−/− hearts were significantly larger than infarcts in RGS6+/+ hearts. RGS6−/− hearts also exhibited increased phosphorylation of β2-adrenergic receptors and G protein–coupled receptor kinase 2 (GRK2). Mitochondrial GRK2 as well as caspase-3 cleavage were increased significantly in RGS6−/− hearts compared with RGS6+/+ hearts after ischemia. Chronic propranolol treatment of mice prevented the observed increases in ischemic injury and the GRK2 phosphorylation observed in RGS6−/− hearts. Our findings suggest that loss of RGS6 predisposes the ventricle to prodeath signaling through a β2AR-GRK2–dependent signaling mechanism, and they provide evidence for a protective role of RGS6 in the ischemic heart. Individuals expressing genetic polymorphisms that suppress the activity of RGS6 may be at increased risk of cardiac ischemic injury. Furthermore, the development of agents that increase RGS6 expression or activity might provide a novel strategy for the treatment of ischemic heart disease. PMID:28035008

Combined effect of whole-body vibration and ambient lighting on human discomfort, heart rate, and reaction time.

PubMed

Monazzam, Mohammad Reza; Shoja, Esmaeil; Zakerian, Seyed Abolfazl; Foroushani, Abbas Rahimi; Shoja, Mohsen; Gharaee, Masoumeh; Asgari, Amin

2018-07-01

This study aimed to investigate the effect of whole-body vibration and ambient lighting, as well as their combined effect on human discomfort, heart rate, and reaction time in laboratory conditions. 44 men were recruited with an average age of 25.4 ± 1.9 years. Each participant was subjected to 12 experimental steps, each step lasting five minutes for four different vibration accelerations in X, Y, and Z axes at a fixed frequency; three different lighting intensities of 50, 500, and 1000 lx were also considered. At each step, a visual computerized reaction test was taken from subjects and their heart rate recorded by pulse oximeter. In addition, the discomfort rate of subjects was measured using Borg scale. Increasing vibration acceleration significantly increased the discomfort rate and heart beat but not the reaction time. Lack of lighting caused more discomfort in the subjects, but there was no significant correlation between lighting intensity with heart rate and reaction time. The results also showed that the combined effect of vibration and lighting had no significant effect on any of the discomfort, heart rate, and reaction time variables. Whole-body vibration is an important factor in the development of human subjective and physiological reactions compared to lighting. Therefore, consideration of the level of vibration to which an individual is exposed in workplaces subject to vibration plays an important role in reducing the level of human discomfort, but its interaction with ambient lighting does not have a significant effect on human subjective and physiological responses.

To ventricular assist devices or not: When is implantation of a ventricular assist device appropriate in advanced ambulatory heart failure?

PubMed Central

Cerier, Emily; Lampert, Brent C; Kilic, Arman; McDavid, Asia; Deo, Salil V; Kilic, Ahmet

2016-01-01

Advanced heart failure has been traditionally treated via either heart transplantation, continuous inotropes, consideration for hospice and more recently via left ventricular assist devices (LVAD). Heart transplantation has been limited by organ availability and the futility of other options has thrust LVAD therapy into the mainstream of therapy for end stage heart failure. Improvements in technology and survival combined with improvements in the quality of life have made LVADs a viable option for many patients suffering from heart failure. The question of when to implant these devices in those patients with advanced, yet still ambulatory heart failure remains a controversial topic. We discuss the current state of LVAD therapy and the risk vs benefit of these devices in the treatment of heart failure. PMID:28070237

The Impact of Worsening Heart Failure in the United States

PubMed Central

Cooper, Lauren B.; DeVore, Adam D.; Felker, G. Michael

2015-01-01

Synopsis In-hospital worsening heart failure represents a clinical scenario in which a patient hospitalized for treatment of acute heart failure experiences a worsening of their condition while in the hospital, requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and post-discharge outcomes. In-hospital worsening heart failure is increasingly being used as an endpoint, or as part of a combined endpoint, in many clinical trials in acute heart failure. This endpoint has advantages over other endpoints commonly used in acute and chronic heart failure trials, such as dyspnea relief and mortality or rehospitalization. Despite the extensive study of this condition, no treatment strategies have been approved for the prevention of this condition. However, several prediction models have been developed to identify worsening heart failure. Continued study in this area is warranted. PMID:26462100

Forkhead box transcription factors in embryonic heart development and congenital heart disease.

PubMed

Zhu, Hong

2016-01-01

Embryonic heart development is a very complicated process regulated precisely by a network composed of many genes and signaling pathways in time and space. Forkhead box (Fox, FOX) proteins are a family of transcription factors characterized by the presence of an evolutionary conserved "forkhead"or "winged-helix" DNA-binding domain and able to organize temporal and spatial gene expression during development. They are involved in a wide variety of cellular processes, such as cell cycle progression, proliferation, differentiation, migration, metabolism and DNA damage response. An abundance of studies in model organisms and systems has established that Foxa2, Foxc1/c2, Foxh1 and Foxm1, Foxos and Foxps are important components of the signaling pathways that instruct cardiogenesis and embryonic heart development, playing paramount roles in heart development. The previous studies also have demonstrated that mutations in some of the forkhead box genes and the aberrant expression of forkhead box gene are heavily implicated in the congenital heart disease (CHD) of humans. This review primarily focuses on the current understanding of heart development regulated by forkhead box transcription factors and molecular genetic mechanisms by which forkhead box factors modulate heart development during embryogenesis and organogenesis. This review also summarizes human CHD related mutations in forkhead box genes as well as the abnormal expression of forkhead box gene, and discusses additional possible regulatory mechanisms of the forkhead box genes during embryonic heart development that warrant further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Practical Applications for Single Pill Combinations in the Cardiovascular Continuum

PubMed Central

Iellamo, Ferdinando; Werdan, Karl; Narkiewicz, Krzysztof; Rosano, Giuseppe

2017-01-01

Despite the availability of new drugs and devices, the treatment of cardiovascular disease remains suboptimal. Single-pill combination therapy offers a number of potential advantages. It can combine different classes of drugs to increase efficacy while mitigating the risks of treatment-related adverse events, reduce pill burden, lower medical cost, and improve patient adherence. Furthermore, in hypertension, single pill combinations include standard to lower doses of each drug than would be necessary to achieve goals with monotherapy, which may explain their better tolerability compared with higher dose monotherapy. Combination therapy is now established in the treatment of hypertension. In ischaemic heart disease, the concept of a preventative polypill has been studied, but its benefits have not been established conclusively. However, the combination of ivabradine and beta-blockers has proven efficacy in patients with stable angina pectoris. This combination has also demonstrated benefits in patients with chronic heart failure. PMID:28785474

Idiosyncratic heart rate response in men during sexual arousal.

PubMed

Rowland, David L; Crawford, Sara B

2011-05-01

Heart rate, sensitive to sympathetic activation, is known to change during sexual arousal and therefore may be a useful tool for investigating psychosomatic differences between sexually functional and dysfunctional men. However, heart rate during arousal also tends to be highly variable across individual men, making its predictability based on group patterns relatively poor. We wanted to determine whether individual men show idiosyncratic heart rate patterns during sexual arousal, that is, whether they exhibit consistent patterns across similar (though not identical) stimulus situations. Agreement between heart rates under the two conditions, visual sexual stimulation (VSS) and VSS + vibrotactile (VIB), was assessed using the concordance correlation coefficient (CCC).   Thirty-eight men, 25 of whom were diagnosed with premature ejaculation (PE), were monitored for penile response and heart rate under two similar (though not identical) conditions: a 9-minute erotic video (VSS), then a 9-minute erotic video combined with vibrotactile penile stimulation (VSS + VIB). CCC for men with PE was 0.65; for the sexually functional comparison group, CCC was 0.82. For both groups combined, CCC was 0.71. For all groupings, the CCC was relatively high, indicating agreement in heart rate from one session to the next within individual men. Despite high intersubject variation in heart rate patterns, individual men show signature heart rates across similar sexual stimulus sessions. Such stereotypy helps explain previous inconsistent findings and may also serve as a marker for the effectiveness of treatments designed to improve ejaculatory control in men with PE. © 2011 International Society for Sexual Medicine.

Neuroendocrine and cardiovascular parameters during simulation of stress-induced rise in circulating oxytocin in the rat.

PubMed

Ondrejcakova, M; Bakos, J; Garafova, A; Kovacs, L; Kvetnansky, R; Jezova, D

2010-07-01

Physiological functions of oxytocin released during stress are not well understood. We have (1) investigated the release of oxytocin during chronic stress using two long-term stress models and (2) simulated stress-induced oxytocin secretion by chronic treatment with oxytocin via osmotic minipumps. Plasma oxytocin levels were significantly elevated in rats subjected to acute immobilization stress for 120 min, to repeated immobilization for 7 days and to combined chronic cold stress exposure for 28 days with 7 days immobilization. To simulate elevation of oxytocin during chronic stress, rats were implanted with osmotic minipumps subcutaneously and treated with oxytocin (3.6 microg/100 g body weight/day) or vehicle for 2 weeks. Chronic subcutaneous oxytocin infusion led to an increase in plasma oxytocin, adrenocorticotropic hormone, corticosterone, adrenal weights and heart/body weight ratio. Oxytocin treatment had no effect on the incorporation of 5-bromo-2-deoxyuridine into DNA in the heart ventricle. Mean arterial pressure response to intravenous phenylephrine was reduced in oxytocin-treated animals. Decrease in adrenal tyrosin hydroxylase mRNA following oxytocin treatment was not statistically significant. Oxytocin treatment failed to modify food intake and slightly increased water consumption. These data provide evidence on increased concentrations of oxytocin during chronic stress. It is possible that the role of oxytocin released during stress is in modulating hypothalamic-pituitary-adrenocortical axis and selected sympathetic functions.

Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving

PubMed Central

Shiels, H. A.; Galli, G. L. J.; Block, B. A.

2015-01-01

Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation–contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 28°C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca2+ transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation–contraction coupling across an acute 20°C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range. PMID:25540278

Power modulates over-reliance on false cardiac arousal when judging target attractiveness: the powerful are more centered on their own false arousal than the powerless.

PubMed

Jouffre, Stéphane

2015-01-01

Individuals attempting to label their emotions look for a plausible source of their physiological arousal. Co-occurrence of plausible sources can lead to the misattribution of real (or bogus) physiological arousal, resulting in physically attractive individuals being perceived as more attractive than they actually are. In two experiments, female participants heard bogus heart rate feedback while viewing photos of attractive male models. Compared with low-power and control participants, high-power participants rated reinforced photos (increased heart rate) more attractive than non-reinforced photos (stable heart rate) to a greater extent when they heard their own bogus heart rate feedback (Experiments 1 and 2) and to a lesser extent when they heard a recording of another participant's heart rate (Experiment 2). These findings, which suggest that power increases the tendency to misattribute one's physiological arousal to physically attractive individuals, are discussed with reference to theories linking power and social perception. © 2014 by the Society for Personality and Social Psychology, Inc.

Oxidative Stress and Heart Failure in Altered Thyroid States

PubMed Central

Mishra, Pallavi; Samanta, Luna

2012-01-01

Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that hyperthyroidism induces a hyperdynamic cardiovascular state, which is associated with a faster heart rate, enhanced left ventricular systolic and diastolic function whereas hypothyroidism is characterized by the opposite changes. Hyperthyroidism and hypothyroidism represent opposite clinical conditions, albeit not mirror images. Recent experimental and clinical studies have suggested the involvement of ROS tissue damage under altered thyroid status. Altered-thyroid state-linked changes in heart modify their susceptibility to oxidants and the extent of the oxidative damage they suffer following oxidative challenge. Chronic increase in the cellular levels of ROS can lead to a catastrophic cycle of DNA damage, mitochondrial dysfunction, further ROS generation and cellular injury. Thus, these cellular events might play an important role in the development and progression of myocardial remodeling and heart failure in altered thyroid states (hypo- and hyper-thyroidism). The present review aims at elucidating the various signaling pathways mediated via ROS and their modulation under altered thyroid state and the possibility of antioxidant therapy. PMID:22649319

Activity in the human brain predicting differential heart rate responses to emotional facial expressions.

PubMed

Critchley, Hugo D; Rotshtein, Pia; Nagai, Yoko; O'Doherty, John; Mathias, Christopher J; Dolan, Raymond J

2005-02-01

The James-Lange theory of emotion proposes that automatically generated bodily reactions not only color subjective emotional experience of stimuli, but also necessitate a mechanism by which these bodily reactions are differentially generated to reflect stimulus quality. To examine this putative mechanism, we simultaneously measured brain activity and heart rate to identify regions where neural activity predicted the magnitude of heart rate responses to emotional facial expressions. Using a forewarned reaction time task, we showed that orienting heart rate acceleration to emotional face stimuli was modulated as a function of the emotion depicted. The magnitude of evoked heart rate increase, both across the stimulus set and within each emotion category, was predicted by level of activity within a matrix of interconnected brain regions, including amygdala, insula, anterior cingulate, and brainstem. We suggest that these regions provide a substrate for translating visual perception of emotional facial expression into differential cardiac responses and thereby represent an interface for selective generation of visceral reactions that contribute to the embodied component of emotional reaction.

Assessment of the Noise Immune Stethoscope in a Clinical Environment

DTIC Science & Technology

2014-03-01

compared to using a traditional stethoscope . Anecdotal feedback from the clinicians indicated that sounds from the heart and related cardiothoracic...same technology as widely available fetal heart rate monitors for the consumer market. Comparable to other devices that combine acoustic and Doppler...understand Doppler” Congestive heart failure “able to hear crackles” Aortic stenosis “similar to traditional stethoscope , able to hear flows across

Immunogenicity of a combined schedule of 7-valent pneumococcal conjugate vaccine followed by a 23-valent polysaccharide vaccine in adult recipients of heart or lung transplants.

PubMed

Gattringer, R; Winkler, H; Roedler, S; Jaksch, P; Herkner, H; Burgmann, H

2011-10-01

A combined schedule of 7-valent pneumococcal conjugate vaccine (PCV7) followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) was evaluated retrospectively in 26 adult recipients of heart or lung transplants. PCV7 was immunogenic in these patients but there appeared to be no benefit from the additional PPV23 dose. © 2011 John Wiley & Sons A/S.

Multi-aperture all-fiber active coherent beam combining for free-space optical communication receivers.

PubMed

Yang, Yan; Geng, Chao; Li, Feng; Huang, Guan; Li, Xinyang

2017-10-30

Multi-aperture receiver with optical combining architecture is an effective approach to overcome the turbulent atmosphere effect on the performance of the free-space optical (FSO) communications, in which how to combine the multiple laser beams received by the sub-apertures efficiently is one of the key technologies. In this paper, we focus on the combining module based on fiber couplers, and propose the all-fiber coherent beam combining (CBC) with two architectures by using active phase locking. To validate the feasibility of the proposed combining module, corresponding experiments and simulations on the CBC of four laser beams are carried out. The experimental results show that the phase differences among the input beams can be compensated and the combining efficiency can be stably promoted by active phase locking in CBC with both of the two architectures. The simulation results show that the combining efficiency fluctuates when turbulent atmosphere is considered, and the effectiveness of the combining module decreases as the turbulence increases. We believe that the combining module proposed in this paper has great potential, and the results can provide significant advices for researchers when building such a multi-aperture receiver with optical combining architecture for FSO commutation systems.

Driver-receiver combined optical transceiver modules for bidirectional optical interconnection

NASA Astrophysics Data System (ADS)

Park, Hyo-Hoon; Kang, Sae-Kyoung; Kim, Do-Won; Nga, Nguyen T. H.; Hwang, Sung-Hwan; Lee, Tae-Woo

2008-02-01

We review a bidirectional optical link scheme for memory-interface applications. A driver-receiver combined optical transceiver (TRx) modules was demonstrated on an optical printed-circuit board (OPCB) platform. To select the bidirectional electric input/output signals, a driver-receiver combined TRx IC with a switching function was designed in 0.18-μm CMOS technology. The TRx IC was integrated with VCSEL/PD chips for optical link in the TRx module. The optical TRx module was assembled on a fiber-embedded OPCB, employing a 90°-bent fiber connector for 90° deflection of light beams between the TRx module and the OPCB. The TRx module and the 90° connector were passively assembled on the OPCB, using ferrule-type guide pins/ holes. Employing these constituent components, the bidirectional optical link between a pair of TRx modules has been successfully demonstrated up to 1.25 Gb/s on the OPCB.

Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK/STAT pathway

PubMed Central

Al-rasheed, Nouf M; Al-Oteibi, Maha M; Al-Manee, Reem Z; Al-shareef, Sarah A; Al-Rasheed, Nawal M; Hasan, Iman H; Mohamad, Raeesa A; Mahmoud, Ayman M

2015-01-01

Simvastatin (SIM) is a lipid-soluble inhibitor of hydroxy-3-methylglutaryl coenzyme A reductase with multiple reported therapeutic benefits. The present study was designed to investigate the effect of pretreatment with SIM on isoproterenol (ISO)-induced cardiac hypertrophy in rats. Twenty-four male albino Wistar rats weighing 180–200 g were divided into four groups. Groups I and III received normal saline while groups II and IV received SIM (10 mg/kg body weight) for 30 days per gavage. In the last 7 days, rats of groups III and IV were administered ISO (5 mg/kg) intraperitoneally to induce cardiac hypertrophy. Administration of ISO induced an increase in heart-to-body weight (HW/BW) ratio, an increase in serum interleukin-6, and elevated systolic and diastolic blood pressure. Serum levels of lipids, cardiovascular risk indices, and cardiac troponin I and creatine phosphokinase-MB showed significant increase in ISO-induced hypertrophic rats. Histopathological examination of heart tissue revealed focal areas of subendocardium degeneration, mononuclear cellular infiltrations, fibrous tissue deposition, and increased thickness of the myocardium of left ventricle. In addition, ISO-administered rats exhibited significant upregulation of cardiac Janus kinase, phosphorylated signal transducer and activator of transcription, and nuclear factor-kappa B. Pretreatment with SIM significantly prevented ISO-induced cardiac hypertrophy, alleviated the altered biochemical parameters, and improved the heart architecture. In conclusion, our study provides evidence that SIM prevented the development of cardiac hypertrophy via modulation of the Janus kinase/signal transducer and activator of transcription-signaling pathway in the heart of ISO-administered animals. PMID:26150695

Modulation of gene expression in heart and liver of hibernating black bears (Ursus americanus)

PubMed Central

2011-01-01

Background Hibernation is an adaptive strategy to survive in highly seasonal or unpredictable environments. The molecular and genetic basis of hibernation physiology in mammals has only recently been studied using large scale genomic approaches. We analyzed gene expression in the American black bear, Ursus americanus, using a custom 12,800 cDNA probe microarray to detect differences in expression that occur in heart and liver during winter hibernation in comparison to summer active animals. Results We identified 245 genes in heart and 319 genes in liver that were differentially expressed between winter and summer. The expression of 24 genes was significantly elevated during hibernation in both heart and liver. These genes are mostly involved in lipid catabolism and protein biosynthesis and include RNA binding protein motif 3 (Rbm3), which enhances protein synthesis at mildly hypothermic temperatures. Elevated expression of protein biosynthesis genes suggests induction of translation that may be related to adaptive mechanisms reducing cardiac and muscle atrophies over extended periods of low metabolism and immobility during hibernation in bears. Coordinated reduction of transcription of genes involved in amino acid catabolism suggests redirection of amino acids from catabolic pathways to protein biosynthesis. We identify common for black bears and small mammalian hibernators transcriptional changes in the liver that include induction of genes responsible for fatty acid β oxidation and carbohydrate synthesis and depression of genes involved in lipid biosynthesis, carbohydrate catabolism, cellular respiration and detoxification pathways. Conclusions Our findings show that modulation of gene expression during winter hibernation represents molecular mechanism of adaptation to extreme environments. PMID:21453527

Comparative Analysis of mRNA Isoform Expression in Cardiac Hypertrophy and Development Reveals Multiple Post-Transcriptional Regulatory Modules

PubMed Central

Park, Ji Yeon; Li, Wencheng; Zheng, Dinghai; Zhai, Peiyong; Zhao, Yun; Matsuda, Takahisa; Vatner, Stephen F.; Sadoshima, Junichi; Tian, Bin

2011-01-01

Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the “fetal gene program”. Here, using a genome-wide approach we systematically defined genes and pathways regulated in short- and long-term cardiac hypertrophy conditions using mice with transverse aortic constriction (TAC), and compared them with those regulated at different stages of embryonic and postnatal development. In addition, exon-level analysis revealed widespread mRNA isoform changes during cardiac hypertrophy resulting from alternative usage of terminal or internal exons, some of which are also developmentally regulated and may be attributable to decreased expression of Fox-1 protein in cardiac hypertrophy. Genes with functions in certain pathways, such as cell adhesion and cell morphology, are more likely to be regulated by alternative splicing. Moreover, we found 3′UTRs of mRNAs were generally shortened through alternative cleavage and polyadenylation in hypertrophy, and microRNA target genes were generally de-repressed, suggesting coordinated mechanisms to increase mRNA stability and protein production during hypertrophy. Taken together, our results comprehensively delineated gene and mRNA isoform regulation events in cardiac hypertrophy and revealed their relations to those in development, and suggested that modulation of mRNA isoform expression plays an importance role in heart remodeling under pressure overload. PMID:21799842

Simvastatin prevents isoproterenol-induced cardiac hypertrophy through modulation of the JAK/STAT pathway.

PubMed

Al-Rasheed, Nouf M; Al-Oteibi, Maha M; Al-Manee, Reem Z; Al-Shareef, Sarah A; Al-Rasheed, Nawal M; Hasan, Iman H; Mohamad, Raeesa A; Mahmoud, Ayman M

2015-01-01

Simvastatin (SIM) is a lipid-soluble inhibitor of hydroxy-3-methylglutaryl coenzyme A reductase with multiple reported therapeutic benefits. The present study was designed to investigate the effect of pretreatment with SIM on isoproterenol (ISO)-induced cardiac hypertrophy in rats. Twenty-four male albino Wistar rats weighing 180-200 g were divided into four groups. Groups I and III received normal saline while groups II and IV received SIM (10 mg/kg body weight) for 30 days per gavage. In the last 7 days, rats of groups III and IV were administered ISO (5 mg/kg) intraperitoneally to induce cardiac hypertrophy. Administration of ISO induced an increase in heart-to-body weight (HW/BW) ratio, an increase in serum interleukin-6, and elevated systolic and diastolic blood pressure. Serum levels of lipids, cardiovascular risk indices, and cardiac troponin I and creatine phosphokinase-MB showed significant increase in ISO-induced hypertrophic rats. Histopathological examination of heart tissue revealed focal areas of subendocardium degeneration, mononuclear cellular infiltrations, fibrous tissue deposition, and increased thickness of the myocardium of left ventricle. In addition, ISO-administered rats exhibited significant upregulation of cardiac Janus kinase, phosphorylated signal transducer and activator of transcription, and nuclear factor-kappa B. Pretreatment with SIM significantly prevented ISO-induced cardiac hypertrophy, alleviated the altered biochemical parameters, and improved the heart architecture. In conclusion, our study provides evidence that SIM prevented the development of cardiac hypertrophy via modulation of the Janus kinase/signal transducer and activator of transcription-signaling pathway in the heart of ISO-administered animals.

Behavioral neurocardiac training in hypertension: a randomized, controlled trial.

PubMed

Nolan, Robert P; Floras, John S; Harvey, Paula J; Kamath, Markad V; Picton, Peter E; Chessex, Caroline; Hiscock, Natalie; Powell, Jonathan; Catt, Michael; Hendrickx, Hilde; Talbot, Duncan; Chen, Maggie H

2010-04-01

It is not established whether behavioral interventions add benefit to pharmacological therapy for hypertension. We hypothesized that behavioral neurocardiac training (BNT) with heart rate variability biofeedback would reduce blood pressure further by modifying vagal heart rate modulation during reactivity and recovery from standardized cognitive tasks ("mental stress"). This randomized, controlled trial enrolled 65 patients with uncomplicated hypertension to BNT or active control (autogenic relaxation), with six 1-hour sessions over 2 months with home practice. Outcomes were analyzed with linear mixed models that adjusted for antihypertensive drugs. BNT reduced daytime and 24-hour systolic blood pressures (-2.4+/-0.9 mm Hg, P=0.009, and -2.1+/-0.9 mm Hg, P=0.03, respectively) and pulse pressures (-1.7+/-0.6 mm Hg, P=0.004, and -1.4+/-0.6 mm Hg, P=0.02, respectively). No effect was observed for controls (P>0.10 for all indices). BNT also increased RR-high-frequency power (0.15 to 0.40 Hz; P=0.01) and RR interval (P<0.001) during cognitive tasks. Among controls, high-frequency power was unchanged (P=0.29), and RR interval decreased (P=0.03). Neither intervention altered spontaneous baroreflex sensitivity (P>0.10). In contrast to relaxation therapy, BNT with heart rate variability biofeedback modestly lowers ambulatory blood pressure during wakefulness, and it augments tonic vagal heart rate modulation. It is unknown whether efficacy of this treatment can be improved with biofeedback of baroreflex gain. BNT, alone or as an adjunct to drug therapy, may represent a promising new intervention for hypertension.

Cardioprotective effects of baicalein on heart failure via modulation of Ca(2+) handling proteins in vivo and in vitro.

PubMed

Zhao, Fali; Fu, Lu; Yang, Wei; Dong, Yuhui; Yang, Jing; Sun, Shoubin; Hou, Yuling

2016-01-15

Baicalein is a widely used Chinese herbal medicine extracted from Labiatae plants Scutellaria baicalensis Georgi's dry root, which has multiple pharmacological activities. However, the precise mechanism of baicalein against myocardial remodeling remains poorly understood. The aim of our study was to investigate the underlying mechanism of baicalein treatment in rats model of heart failure (HF) and rat myocardial cells (H9C2). HF model was established by abdominal aorta constriction in rats and incubation with 50μM isoproterenol for 48h in H9C2 cells. Various molecular biological experiments were performed to assess the effects of baicalein on cardiac function, myocardial remodeling, apoptosis and Ca(2+) handling proteins. In the present study, first we found that baicalein alleviated HF in vivo. Additionally, treatment with baicalein inhibited the myocardial fibrosis, restrained the expression and activity of MMP2 and MMP9, and suppressed apoptosis in heart tissue. Moreover, baicalein could inhibit the cardiac myocyte hypertrophy and apoptosis induced by isoproterenol in vitro. Finally we found that baicalein could modulate the expressions and activities of Ca(2+) handling proteins, including downregulation of phosphorylation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and expression of Na(+)/Ca(2+)-exchangers (NCX1), upregulation of sarcoplasmic reticulum Ca(2+) ATPase 2 (SERCA2) and ryanodine receptor 2 (RYR2). Baicalein also restrained the decreased SERCA activity induced by aortic banding. Our studies suggested that baicalein alleviated myocardial remodeling and improved cardiac function via modulation of Ca(2+) handling proteins, which may be a potential phytochemical flavonoid for therapeutics of HF. Copyright © 2015 Elsevier Inc. All rights reserved.

Physiological roles of taurine in heart and muscle

PubMed Central

2010-01-01

Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals. PMID:20804594

Physiological roles of taurine in heart and muscle.

PubMed

Schaffer, Stephen W; Jong, Chian Ju; Ramila, K C; Azuma, Junichi

2010-08-24

Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals.

Hydroalcoholic extract from Nerium oleander L. (Apocynaceae) elicits arrhythmogenic activity.

PubMed

Botelho, Ana Flávia Machado; Santos-Miranda, Artur; Joca, Humberto Cavalcante; Mattoso, Cláudio Roberto Scabelo; de Oliveira, Maira Souza; Pierezan, Felipe; Cruz, Jader Santos; Soto-Blanco, Benito; Melo, Marília Martins

2017-07-12

Nerium oleander L. (OLE) has been used medicinally and is reported to possess a wide range of pharmacological activities. OLE effects are caused by different cardiac glycosides (CG), primarily oleandrin, found within the plant. CG can potentially impair sodium-potassium ATPase (NKA) pump activity and cause positive inotropic effects on the heart. The aim of this study was to investigate the potential arrhythmogenic effects of hydroalcoholic extracts from N. oleander (OLE). OLE hydroalcoholic extracts were obtained from N. oleander leaves and analyzed by HPLC. In vivo experiments with guinea pigs consisted if oral administration of water, 150mg/kg and 300mg/kg OLE extract. Clinical signs and ECG analysis were evaluated. Sample tissues from the heart were processed for histopathological and ultra-structural analysis. Autonomic effects were assessed through pharmacological blockade and ECG monitoring. In vitro experiments were conducted with isolated ventricular myocytes from adult mice. The effects of OLE extract on cardiac excitability, Na + /K + pump current and global Ca 2+ transients were evaluated. Our results demonstrated that OLE hydroalcoholic extract elicited severe cardiac arrhythmias that can lead to death with minimal tissue damage. In vitro experiments suggest that OLE causes electromechanical disturbances in the heart due to inhibition of Na + /K + pump, mitochondrial swelling, and modulation of the sarco(endo)plasmic Ca 2+ ATPase without interfering with the autonomic nervous system. Thus, arrhythmias and electrical conduction disturbances promoted by OLE are mainly associated with impaired cardiomyocyte dysfunction, rather than anatomical tissue remodeling and/or autonomic modulation. Our data revealed the potential cardiotoxicity and positive inotropic effect of OLE and its important role in modulation of electrophysiology in cardiomyocytes. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

User Experience May be Producing Greater Heart Rate Variability than Motor Imagery Related Control Tasks during the User-System Adaptation in Brain-Computer Interfaces

PubMed Central

Alonso-Valerdi, Luz M.; Gutiérrez-Begovich, David A.; Argüello-García, Janet; Sepulveda, Francisco; Ramírez-Mendoza, Ricardo A.

2016-01-01

Brain-computer interface (BCI) is technology that is developing fast, but it remains inaccurate, unreliable and slow due to the difficulty to obtain precise information from the brain. Consequently, the involvement of other biosignals to decode the user control tasks has risen in importance. A traditional way to operate a BCI system is via motor imagery (MI) tasks. As imaginary movements activate similar cortical structures and vegetative mechanisms as a voluntary movement does, heart rate variability (HRV) has been proposed as a parameter to improve the detection of MI related control tasks. However, HR is very susceptible to body needs and environmental demands, and as BCI systems require high levels of attention, perceptual processing and mental workload, it is important to assess the practical effectiveness of HRV. The present study aimed to determine if brain and heart electrical signals (HRV) are modulated by MI activity used to control a BCI system, or if HRV is modulated by the user perceptions and responses that result from the operation of a BCI system (i.e., user experience). For this purpose, a database of 11 participants who were exposed to eight different situations was used. The sensory-cognitive load (intake and rejection tasks) was controlled in those situations. Two electrophysiological signals were utilized: electroencephalography and electrocardiography. From those biosignals, event-related (de-)synchronization maps and event-related HR changes were respectively estimated. The maps and the HR changes were cross-correlated in order to verify if both biosignals were modulated due to MI activity. The results suggest that HR varies according to the experience undergone by the user in a BCI working environment, and not because of the MI activity used to operate the system. PMID:27458384

Autonomic modulation of arterial pressure and heart rate variability in hypertensive diabetic rats.

PubMed

Farah, Vera de Moura Azevedo; De Angelis, Kátia; Joaquim, Luis Fernando; Candido, Georgia O; Bernardes, Nathalia; Fazan, Rubens; Schaan, Beatriz D'Agord; Irigoyen, Maria-Claudia

2007-08-01

The aim of the present study was to evaluate the autonomic modulation of the cardiovascular system in streptozotocin (STZ)-induced diabetic spontaneously hypertensive rats (SHR), evaluating baroreflex sensitivity and arterial pressure and heart rate variability. Male SHR were divided in control (SHR) and diabetic (SHR+DM, 5 days after STZ) groups. Arterial pressure (AP) and baroreflex sensitivity (evaluated by tachycardic and bradycardic responses to changes in AP) were monitored. Autoregressive spectral estimation was performed for systolic AP (SAP) and pulse interval (PI) with oscillatory components quantified as low (LF:0.2-0.6Hz) and high (HF:0.6-3.0Hz) frequency ranges. Mean AP and heart rate in SHR+DM (131+/-3 mmHg and 276+/-6 bpm) were lower than in SHR (160+/-7 mmHg and 330+/-8 bpm). Baroreflex bradycardia was lower in SHR+DM as compared to SHR (0.55+/-0.1 vs. 0.97+/-0.1 bpm/mmHg). Overall SAP variability in the time domain (standard deviation of beat-by-beat time series of SAP) was lower in SHR+DM (3.1+/-0.2 mmHg) than in SHR (5.7+/-0.6 mmHg). The standard deviation of the PI was similar between groups. Diabetes reduced the LF of SAP (3.3+/-0.8 vs. 28.7+/-7.6 mmHg2 in SHR), while HF of SAP were unchanged. The power of oscillatory components of PI did not differ between groups. These results show that the association of hypertension and diabetes causes an impairment of the peripheral cardiovascular sympathetic modulation that could be, at least in part, responsible for the reduction in AP levels. Moreover, this study demonstrates that diabetes might actually impair the reduced buffer function of the baroreceptors while reducing blood pressure.

Absence of arterial baroreflex modulation of skin sympathetic activity and sweat rate during whole-body heating in humans

NASA Technical Reports Server (NTRS)

Wilson, T. E.; Cui, J.; Crandall, C. G.

2001-01-01

1. Prior findings suggest that baroreflexes are capable of modulating skin blood flow, but the effects of baroreceptor loading/unloading on sweating are less clear. Therefore, this project tested the hypothesis that pharmacologically induced alterations in arterial blood pressure in heated humans would lead to baroreflex-mediated changes in both skin sympathetic nerve activity (SSNA) and sweat rate. 2. In seven subjects mean arterial blood pressure was lowered (approximately 8 mmHg) and then raised (approximately 13 mmHg) by bolus injections of sodium nitroprusside and phenylephrine, respectively. Moreover, in a separate protocol, arterial blood pressure was reduced via steady-state administration of sodium nitroprusside. In both normothermia and heat-stress conditions the following responses were monitored: sublingual and mean skin temperatures, heart rate, beat-by-beat blood pressure, skin blood flow (laser-Doppler flowmetry), local sweat rate and SSNA (microneurography from peroneal nerve). 3. Whole-body heating increased skin and sublingual temperatures, heart rate, cutaneous blood flow, sweat rate and SSNA, but did not change arterial blood pressure. Heart rate was significantly elevated (from 74 +/- 3 to 92 +/- 4 beats x min(-1); P < 0.001) during bolus sodium nitroprusside-induced reductions in blood pressure, and significantly reduced (from 92 +/- 4 to 68 +/- 4 beats x min(-1); P < 0.001) during bolus phenylephrine-induced elevations in blood pressure, thereby demonstrating normal baroreflex function in these subjects. 4. Neither SSNA nor sweat rate was altered by rapid (bolus infusion) or sustained (steady-state infusion) changes in blood pressure regardless of the thermal condition. 5. These data suggest that SSNA and sweat rate are not modulated by arterial baroreflexes in normothermic or moderately heated individuals.

Is Heart Disease or Cancer the Leading Cause of Death in United States Women?

PubMed

Pathak, Elizabeth B

This paper compares the mortality burden of heart disease versus cancer among women by age, race, and ethnicity. U.S. death and population data for the years 2000 through 2013 were used to calculate heart disease and cancer death rates. Detailed analyses focused on age (15-19 years old to ≥100 years old) and race and ethnicity (Whites, Blacks, Hispanics, Asians and Pacific Islanders (A/PIs), and American Indians and Alaska Natives (AI/ANs)). Among women aged 15 years and older, there were 289,467 heart disease deaths and 276,716 cancer deaths in 2013. The majority of heart disease deaths (51.6%) occurred among women 85 years or older, compared with 18.9% of female cancer deaths. The age-adjusted death rates (per 100,000 population) were 171 (95% confidence interval [CI], 170-171) for heart disease versus 177 (95% CI, 176-178) for cancer. For all racial and ethnic groups, cancer mortality was significantly higher than heart disease mortality among women younger than 80 years of age. For all ages combined, cancer deaths exceeded heart disease deaths among Hispanics, A/PIs, and AI/ANs. Black non-Hispanic women were the only racial/ethnic group who had a higher age-adjusted death rate for heart disease than for cancer: 224 (95% CI, 222-226) versus 207 (95% CI, 205-209). Heart disease remains the leading cause of death among all women combined in the United States by a narrow margin. However, cancer predominantly kills middle-aged and young women, whereas heart disease predominantly kills the very old. New research on the overreporting of heart disease on death certificates for elderly women is needed. National summary statistics obscure the fact that cancer is already the overall leading cause of death for Hispanic women, Asian and Pacific Islander women, and American Indian and Alaska Native women. Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Effects of Combination of Ezetimibe and Rosuvastatin on Coronary Artery Plaque in Patients with Coronary Heart Disease.

PubMed

Wang, Xiaofang; Zhao, Xiaoyan; Li, Ling; Yao, Haimu; Jiang, Yan; Zhang, Jinying

2016-05-01

In approximately 80% of cardiovascular disease-related deaths, patients suffer from coronary atherosclerotic heart disease. Ezetimibe is the first intestinal cholesterol absorption inhibitor. Its combination with statins for treating coronary atherosclerotic heart disease has attracted attention worldwide. The study group comprised 106 patients with coronary atherosclerotic heart disease and hyperlipidaemia. Each was randomly assigned to one of two groups: (1) Ezetimibe (10mg, once a night) plus rosuvastatin (10mg, once a night) (n=55) or (2) Rosuvastatin alone (10mg, once a night) (n=51). The primary endpoint was new or recurrent myocardial infarction, unstable angina pectoris, cardiac death, and stroke. Blood lipid, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) levels were measured before treatment and at one, six and 12 months after treatment. Coronary plaque size and compositional changes were determined using intravascular ultrasonography. The combination of ezetimibe plus rosuvastatin decreased total cholesterol, low-density lipoprotein cholesterol, hsCRP, IL-6, and MMP-9 levels at six and 12 months after treatment. Statistical significance was detected between two groups. At 12 months, the plaque burden, plaque cross-sectional area, and percentage of necrotic plaque composition were significantly lower in the combination group than in rosuvastatin alone group (P<0.05). And compared with rosuvastatin alone group, the primary endpoint decreased more effectively in combination group. The combination of ezetimibe and rosuvastatin apparently diminishes lipid levels and plaque burden and improves plaque stability, which may be associated with the potent inhibitory effects of ezetimibe and rosuvastatin on inflammatory cytokines. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013.

PubMed

Taylor, Carolyn W; Wang, Zhe; Macaulay, Elizabeth; Jagsi, Reshma; Duane, Frances; Darby, Sarah C

2015-11-15

Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this "mean heart dose." In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28 countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of in vitro cytochrome P450 modulators to detect induction by prototype inducers in the mallard duckling (Anas platyrhynchos

USGS Publications Warehouse

Renauld, A.E.; Melancon, M.J.; Sordillo, L.M.

1999-01-01

Seven modulators of mammalian monooxygenase activity were screened for their ability to selectively stimulate or inhibit in vitro monooxygenase activities of hepatic microsomes from mallard ducklings treated with phenobarbital, β-naphthoflavone, 3,3′,4,4′,5-pentachlorobiphenyl or vehicle. Microsomes were assayed fluorometrically for four monooxygenases: benzyloxy-, ethoxy-, methoxy-, and pentoxyresorufin-O-dealkylase, in combination with each of the seven modulators. Four combinations: α-naphthoflavone and 2-methylbenzimidazole with benzyloxyresorufin, and Proadifen with methoxy- and ethoxyresorufin, respectively, were evaluated further. β-Naphthoflavone-treated groups were clearly distinguished from the corn oil vehicle control group by all of the assays and by the effects of the modulators in three of the four assay/modulator combinations. Enzyme activities of the phenobarbital and saline groups were statistically similar (P≥0.05) when assayed without modulator added, but each assay/modulator combination distinguished between these groups. The PCB-treated group was distinguished from the corn oil vehicle control group only for BROD activity, with or without the presence of modulator. Graphing of per cent modulation of BROD activity versus initial BROD activity provided the clearest distinction between all of the study groups. Identification of these selective in vitro modulators may improve detection and measurement of low level cytochrome P450 induction in avian species. Also, both the monooxygenase activities induced and the impacts of the modulators indicated differences between mammalian and avian cytochromes P450.

Model-specific selection of molecular targets for heart failure gene therapy

PubMed Central

Katz, Michael G.; Fargnoli, Anthony S.; Tomasulo, Catherine E.; Pritchette, Louella A.; Bridges, Charles R.

2013-01-01

Heart failure (HF) is a complex multifaceted problem of abnormal ventricular function and structure. In recent years, new information has been accumulated allowing for a more detailed understanding of the cellular and molecular alterations that are the underpinnings of diverse causes of HF, including myocardial ischemia, pressure-overload, volume-overload or intrinsic cardiomyopathy. Modern pharmacological approaches to treat HF have had a significant impact on the course of the disease, although they do not reverse the underlying pathological state of the heart. Therefore gene-based therapy holds a great potential as a targeted treatment for cardiovascular diseases. Here, we survey the relative therapeutic efficacy of genetic modulation of β-adrenergic receptor signaling, Ca2+ handling proteins and angiogenesis in the most common extrinsic models of HF. PMID:21954055

The heart as a self-regulating system: integration of homeodynamic mechanisms.

PubMed

Kresh, J Y; Armour, J A

1997-04-01

In the past the study of mechanical and electrical properties of the heart has been disjointed with minimal overlap and unification. The fact remains that these features are tightly coupled and central to the functioning heart. The maintenance of adequate cardiac output relies upon the highly integrated autoregulatory mechanisms and modulation of cardiac myocyte function. Regional ventricular mechanics and energetics are dependent upon muscle fiber stress-strain rate, the passive properties of myocardial collagen matrix, adequate vascular perfusion, transcapillary transport and electrical activation pattern. Intramural hydraulic "loading" is regulated by coronary arterial and venous dynamics. All of these components are under the constant influence of intrinsic cardiac and extracardiac autonomic neurons, as well as circulating hormones. A brief overview of the putative regulation of these various components is presented in this paper.

[Effects of long-term Tai Ji Quan exercise on automatic nervous modulation in the elderly].

PubMed

Guo, Feng

2015-03-01

To examine the effects of long-term Tai Ji Quan (Chinnese Traditional Exercise) on automatic nervous modulation in the elders. The 18 subjects from Tai Ji Quan exercise class in Liaoning University of Retired Veteran Cadres were assigned into long-term Tai Ji Quan exercise group including 10 subjects and novice group including 8 subjects. Electrocardiography, respiratory and blood pressure data were collected on the following time points: at rest before Tai Ji Qhuan exercise and 30 min or 60 min after Tai Ji Quan exercise. The subjects at rest state in the long-term Tai Ji Quan exercise group showed higher than the subjects in the novice group in resperitory rate (RR), standard deviations of normal to normal intervals (SDNN), total power (TP), low frequency power (LFP), high frequency power (HFP), normalized high frequency power (nHFP), but lower in LFP/HFP, systolic and diastolic blood pressure, and heart rate. At rest state the respiratory rate of subjects in long-term Tai Ji Quan exercise group was significantly lower than the novices. After Tai Ji Quan exercise, TP, nHFP, LFP/HFP, heart rate and systolic pressure showed significantly changes, and the change level of Tai Ji Quan on these indices was larger in Tai Ji Quan exercise group than that in the novice group. Long-term Tai Ji Quan exercise can improve vagal modulations, and tend to reduce the sympathetic modulations.

Widespread cardiovascular autonomic dysfunction in primary amyloidosis: does spontaneous hyperventilation have a compensatory role against postural hypotension?

PubMed Central

Bernardi, L; Passino, C; Porta, C; Anesi, E; Palladini, G; Merlini, G

2002-01-01

Objective: To investigate the possible causes of abnormal blood pressure control in light chain related (primary, AL) amyloidosis. Design: Cardiovascular, autonomic, and respiratory response to passive tilting were investigated in 51 patients with primary amyloidosis (mean (SEM) age 56 (2) years) and in 20 age matched controls. Spontaneous fluctuations in RR interval, respiration, end tidal carbon dioxide, blood pressure, and skin microcirculation were recorded during supine rest and with tilting. The values were subjected to spectral analysis to assess baroreflex sensitivity and the autonomic modulation of cardiac and vascular responses. Setting: Tertiary referral centre. Results: Autonomic modulation of the heart and blood pressure was nearly absent in the patients with amyloidosis: thus baroreflex sensitivity and the low frequency (0.1 Hz) fluctuations in all cardiovascular signals were severely reduced (p < 0.01 or more), as were respiratory fluctuations in the RR interval, and no change was observed upon tilting. Despite reduced autonomic modulation, blood pressure remained relatively stable in the amyloid group from supine to tilting. End tidal carbon dioxide was reduced in the amyloid patients (p < 0.001) indicating persistent hyperventilation; the breathing rate correlated inversely with the fall in blood pressure on tilting (p < 0.05). Conclusions: In primary amyloidosis, pronounced abnormalities in arterial baroreflexes and cardiovascular autonomic modulation to the heart and the vessels may be partly compensated for by hyperventilation at a slow breathing rate. PMID:12433892

Influence of skin type and wavelength on light wave reflectance.

PubMed

Fallow, Bennett A; Tarumi, Takashi; Tanaka, Hirofumi

2013-06-01

A new application of photoplethysmography (PPG) has emerged recently to provide the possibility of heart rate monitoring without a telemetric chest strap. The aim of this study was to determine if a new device could detect pulsation over a broad range of skin types, and what light wavelength would be most suitable for detecting the signals. A light emitting diode-based PPG system was used to detect changes in pulsatile blood flow on 23 apparently healthy individuals (11 male and 12 female, 20-59 years old) of varying skin types classified according to a questionnaire in combination with digital photographs with a skin type chart. Four different light wavelengths (470, 520, 630, and 880 nm) were tested. Normalized modulation level is calculated as the AC/DC component ratio and represents the change in flow over the underlying constant state of flow or perfusion. In the resting condition, green light wavelength (520 nm) displayed greater modulation (p < 0.001) than all the other wavelengths analyzed regardless of skin types. Type V (dark brown) skin type was significantly lower in modulation than all other skin types. In the exercise condition, both blue (470 nm) and green (520 nm) light wavelengths displayed greater signal-to-noise ratios than red (630 nm) or infrared (880 nm) light wavelengths (p < 0.001). We concluded that a PPG-based device can detect pulsation across all skin types and that a greater resolution was obtained using a green light wavelength at rest and a green or blue light wavelength during exercise.

Initial in vitro testing of a paediatric continuous-flow total artificial heart.

PubMed

Fukamachi, Kiyotaka; Karimov, Jamshid H; Horvath, David J; Sunagawa, Gengo; Byram, Nicole A; Kuban, Barry D; Moazami, Nader

2018-06-01

Mechanical circulatory support has become standard therapy for adult patients with end-stage heart failure; however, in paediatric patients with congenital heart disease, the options for chronic mechanical circulatory support are limited to paracorporeal devices or off-label use of devices intended for implantation in adults. Congenital heart disease and cardiomyopathy often involve both the left and right ventricles; in such cases, heart transplantation, a biventricular assist device or a total artificial heart is needed to adequately sustain both pulmonary and systemic circulations. We aimed to evaluate the in vitro performance of the initial prototype of our paediatric continuous-flow total artificial heart. The paediatric continuous-flow total artificial heart pump was downsized from the adult continuous-flow total artificial heart configuration by a scale factor of 0.70 (1/3 of total volume) to enable implantation in infants. System performance of this prototype was evaluated using the continuous-flow total artificial heart mock loop set to mimic paediatric circulation. We generated maps of pump performance and atrial pressure differences over a wide range of systemic vascular resistance/pulmonary vascular resistance and pump speeds. Performance data indicated left pump flow range of 0.4-4.7 l/min at 100 mmHg delta pressure. The left/right atrial pressure difference was maintained within ±5 mmHg with systemic vascular resistance/pulmonary vascular resistance ratios between 1.4 and 35, with/without pump speed modulation, verifying expected passive self-regulation of atrial pressure balance. The paediatric continuous-flow total artificial heart prototype met design requirements for self-regulation and performance; in vivo pump performance studies are ongoing.

Psychophysiological effects of an iTBS modulated virtual reality challenge including participants with spider phobia.

PubMed

Notzon, S; Deppermann, S; Fallgatter, A; Diemer, J; Kroczek, A; Domschke, K; Zwanzger, P; Ehlis, A-C

2015-12-01

Preliminary evidence suggests beneficial effects of transcranial magnetic stimulation (TMS) on anxiety. The objective of this study was to investigate the effects of intermittent theta burst stimulation (iTBS) as a form of TMS on acute anxiety provoked by a virtual reality (VR) scenario. Participants with spider phobia (n=41) and healthy controls (n=42) were exposed to a spider scenario in VR after one session of iTBS over the prefrontal cortex or sham treatment. Participants with spider phobia reacted with more anxiety compared to healthy controls. Their heart rate and skin conductance increased compared to baseline. Contrary to expectations, iTBS did not influence these reactions, but modulated heart rate variability (HRV). Sympathetic influence on HRV showed an increase in the active iTBS group only. This study does not support the idea of beneficial effects of a single session of iTBS on anxiety, although other protocols or repeated sessions might be effective. Copyright © 2015 Elsevier B.V. All rights reserved.

Buenos hábitos alimenticios para una buena salud : evaluation of a nutrition education program to improve heart health and brain health in Latinas.

PubMed

Otilingam, Poorni G; Gatz, Margaret; Tello, Elizabeth; Escobar, Antonio Jose; Goldstein, Aviva; Torres, Mina; Varma, Rohit

2015-02-01

The goal of this research was to evaluate nutrition education targeting Latinas, a group at particular risk of obesity and diabetes, which predict to later life cardiovascular disease and dementia. Culturally tailored, theory-based nutrition education was provided to Mexican origin Latinas aged 48 to 84. The randomized design compared participants in workshops incorporating the connection between dietary fat and brain health, participants in workshops focusing only on dietary fat and heart health, a waitlist control group, and a posttest only control group. Among those assigned to either intervention, there was statistically significant gain in health literacy, knowledge about dietary fat, and behaviors to reduce dietary fat compared with waitlist control. There was no difference in outcomes between those given the module about diet and brain health and those not provided that module. A program to encourage dietary fat modification in Latinas proved feasible and modestly effective. © The Author(s) 2014.

Inflammatory cytokine response and reduced heart rate variability in newborns with hypoxic-ischemic encephalopathy.

PubMed

Al-Shargabi, T; Govindan, R B; Dave, R; Metzler, M; Wang, Y; du Plessis, A; Massaro, A N

2017-06-01

To determine whether systemic inflammation-modulating cytokine expression is related to heart rate variability (HRV) in newborns with hypoxic-ischemic encephalopathy (HIE). The data from 30 newborns with HIE were analyzed. Cytokine levels (IL-2, IL-4, IL-6, IL-8, IL-10, IL-13, IL-1β, TNF-α, IFN-λ) were measured either at 24 h of cooling (n=5), 72 h of cooling (n=4) or at both timepoints (n=21). The following HRV metrics were quantified in the time domain: alpha_S, alpha_L, root mean square (RMS) at short time scales (RMS_S), RMS at long time scales (RMS_L), while low-frequency power (LF) and high-frequency power (HF) were quantified in the frequency domain. The relationships between HRV metrics and cytokines were evaluated using mixed-models. IL-6, IL-8, IL-10, and IL-13 levels were inversely related to selected HRV metrics. Inflammation-modulating cytokines may be important mediators in the autonomic dysfunction observed in newborns with HIE.

Domain-domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel.

PubMed

Zaydman, Mark A; Kasimova, Marina A; McFarland, Kelli; Beller, Zachary; Hou, Panpan; Kinser, Holly E; Liang, Hongwu; Zhang, Guohui; Shi, Jingyi; Tarek, Mounir; Cui, Jianmin

2014-12-23

Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (Barhanin et al., 1996; Sanguinetti et al., 1996), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (Wrobel et al., 2012; Sun et al., 2012; Abbott, 2014). These changes are essential for the physiological role of IKs (Silva and Rudy, 2005); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore.

Domain–domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel

PubMed Central

Zaydman, Mark A; Kasimova, Marina A; McFarland, Kelli; Beller, Zachary; Hou, Panpan; Kinser, Holly E; Liang, Hongwu; Zhang, Guohui; Shi, Jingyi; Tarek, Mounir; Cui, Jianmin

2014-01-01

Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (Barhanin et al., 1996; Sanguinetti et al., 1996), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (Wrobel et al., 2012; Sun et al., 2012; Abbott, 2014). These changes are essential for the physiological role of IKs (Silva and Rudy, 2005); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore. DOI: http://dx.doi.org/10.7554/eLife.03606.001 PMID:25535795

Buenos Hábitos Alimenticios para Una Buena Salud: Evaluation of a Nutrition Education Program to Improve Heart Health and Brain Health in Latinas

PubMed Central

Otilingam, Poorni G.; Gatz, Margaret; Tello, Elizabeth; Escobar, Antonio Jose; Goldstein, Aviva; Torres, Mina; Varma, Rohit

2015-01-01

Objectives The goal of this research was to evaluate nutrition education targeting Latinas, a group at particular risk of obesity and diabetes, which predict to later life cardiovascular disease and dementia. Methods Culturally tailored, theory-based nutrition education was provided to Mexican origin Latinas aged 48 to 84. The randomized design compared participants in workshops incorporating the connection between dietary fat and brain health, participants in workshops focusing only on dietary fat and heart health, a waitlist control group, and a posttest only control group. Results Among those assigned to either intervention, there was statistically significant gain in health literacy, knowledge about dietary fat, and behaviors to reduce dietary fat compared to waitlist control. There was no difference in outcomes between those given the module about diet and brain health and those not provided that module. Discussion A program to encourage dietary fat modification in Latinas proved feasible and modestly effective. PMID:25231884

Electrical 2π phase control of infrared light in a 350-nm footprint using graphene plasmons

NASA Astrophysics Data System (ADS)

Woessner, Achim; Gao, Yuanda; Torre, Iacopo; Lundeberg, Mark B.; Tan, Cheng; Watanabe, Kenji; Taniguchi, Takashi; Hillenbrand, Rainer; Hone, James; Polini, Marco; Koppens, Frank H. L.

2017-07-01

Modulating the amplitude and phase of light is at the heart of many applications such as wavefront shaping, transformation optics, phased arrays, modulators and sensors. Performing this task with high efficiency and small footprint is a formidable challenge. Metasurfaces and plasmonics are promising, but metals exhibit weak electro-optic effects. Two-dimensional materials, such as graphene, have shown great performance as modulators with small drive voltages. Here, we show a graphene plasmonic phase modulator that is capable of tuning the phase between 0 and 2π in situ. The device length of 350 nm is more than 30 times shorter than the 10.6 μm free-space wavelength. The modulation is achieved by spatially controlling the plasmon phase velocity in a device where the spatial carrier density profile is tunable. We provide a scattering theory for plasmons propagating through spatial density profiles. This work constitutes a first step towards two-dimensional transformation optics for ultracompact modulators and biosensing.

Measuring health-related quality of life in Hungarian children with heart disease: psychometric properties of the Hungarian version of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and the Cardiac Module.

PubMed

Berkes, Andrea; Pataki, István; Kiss, Mariann; Kemény, Csilla; Kardos, László; Varni, James W; Mogyorósy, Gábor

2010-01-28

The aim of the study was to investigate the psychometric properties of the Hungarian version of the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales and Cardiac Module. The PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Cardiac Module was administered to 254 caregivers of children (aged 2-18 years) and to 195 children (aged 5-18 years) at a pediatric cardiology outpatient unit. A postal survey on a demographically group-matched sample of the general population with 525 caregivers of children (aged 2-18 years) and 373 children (aged 5-18 years) was conducted with the PedsQL 4.0 Generic Core Scale. Responses were described, compared over subgroups of subjects, and were used to assess practical utility, distributional coverage, construct validity, internal consistency, and inter-reporter agreement of the instrument. The moderate scale-level mean percentage of missing item responses (range 1.8-2.3%) supported the feasibility of the Generic Core Scales for general Hungarian children. Minimal to moderate ceiling effects and no floor effects were found on the Generic Core Scales. We observed stronger ceiling than floor effects in the Cardiac Module. Most of the scales showed satisfactory reliability with Cronbach's alpha estimates exceeding 0.70. Generally, moderate to good agreement was found between self- and parent proxy-reports in the patient and in the comparison group (intraclass correlation coefficient range 0.52-0.77), but remarkably low agreement in the perceived physical appearance subscale in the age group 5-7 years (0.18) and for the treatment II scale (problems on taking heart medicine) scale of the Cardiac Module in children aged 8-12 years (0.39). Assessing the construct validity of the questionnaires, statistically significant difference was found between the patient group and the comparison group only in the Physical Functioning Scale scores (p = 0.003) of the child self-report component, and in Physical (p = 0.022), Emotional, (p = 0.017), Psychosocial Summary (p = 0.019) scores and in the total HRQoL (health-related quality of life) scale score (p = 0.034) for parent proxy-report. The findings generally support the feasibility, reliability and validity of the Hungarian translation of the PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Cardiac Module in Hungarian children with heart disease.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kole, Thomas P.; Aghayere, Osarhieme; Kwah, Jason

Purpose: To compare heart and coronary artery radiation exposure using intensity-modulated radiotherapy (IMRT) vs. four-field three-dimensional conformal radiotherapy (3D-CRT) treatment plans for patients with distal esophageal cancer undergoing chemoradiation. Methods and Materials: Nineteen patients with distal esophageal cancers treated with IMRT from March 2007 to May 2008 were identified. All patients were treated to 50.4 Gy with five-field IMRT plans. Theoretical 3D-CRT plans with four-field beam arrangements were generated. Dose-volume histograms of the planning target volume, heart, right coronary artery, left coronary artery, and other critical normal tissues were compared between the IMRT and 3D-CRT plans, and selected parameters weremore » statistically evaluated using the Wilcoxon rank-sum test. Results: Intensity-modulated radiotherapy treatment planning showed significant reduction (p < 0.05) in heart dose over 3D-CRT as assessed by average mean dose (22.9 vs. 28.2 Gy) and V30 (24.8% vs. 61.0%). There was also significant sparing of the right coronary artery (average mean dose, 23.8 Gy vs. 35.5 Gy), whereas the left coronary artery showed no significant improvement (mean dose, 11.2 Gy vs. 9.2 Gy), p = 0.11. There was no significant difference in percentage of total lung volume receiving at least 10, 15, or 20 Gy or in the mean lung dose between the planning methods. There were also no significant differences observed for the kidneys, liver, stomach, or spinal cord. Intensity-modulated radiotherapy achieved a significant improvement in target conformity as measured by the conformality index (ratio of total volume receiving 95% of prescription dose to planning target volume receiving 95% of prescription dose), with the mean conformality index reduced from 1.56 to 1.30 using IMRT. Conclusions: Treatment of patients with distal esophageal cancer using IMRT significantly decreases the exposure of the heart and right coronary artery when compared with 3D-CRT. Long-term studies are necessary to determine how this will impact on development of coronary artery disease and other cardiac complications.« less

Do mobile phones pose a potential risk to autonomic modulation of the heart?

PubMed

Barutcu, Irfan; Esen, Ali Metin; Kaya, Dayimi; Turkmen, Muhsin; Karakaya, Osman; Saglam, Mustafa; Melek, Mehmet; Çelik, Ataç; Kilit, Celal; Onrat, Ersel; Kirma, Cevat

2011-11-01

It has long been speculated that mobile phones may interact with the cardiac devices and thereby cardiovascular system may be a potential target for the electromagnetic fields emitted by the mobile phones. Therefore, the present study was designed to test possible effects of radiofrequency waves emitted by digital mobile phones on cardiac autonomic modulation by short-time heart rate variability (HRV) analysis. A total of 20 healthy young subjects were included to the study. All participants were rested in supine position at least for 15 minutes on a comfortable bed, and then time and frequency domain HRV parameters were recorded at baseline in supine position for 5 minutes. After completion of baseline records, by using a mobile GSM (Global System for Mobile Communication) phone, HRV parameters were recorded at turned off mode, at turned on mode, and at calling mode over 5 minutes periods for each stage. Neither time nor frequency domain HRV parameters altered significantly during off mode compare to their baseline values. Also, neither time nor frequency domain HRV parameters altered significantly during turned on and calling mode compared to their baseline values. Short-time exposure to electromagnetic fields emitted by mobile phone does not affect cardiac autonomic modulation in healthy subjects.

Functional food addressing heart health: do we have to target the gut microbiota?

PubMed

Ryan, Paul M; Ross, Reynolds Paul; Fitzgerald, Gerald F; Caplice, Noel M; Stanton, Catherine

2015-11-01

Health promoting functional food ingredients for cardiovascular health are generally aimed at modulating lipid metabolism in consumers. However, significant advances have furthered our understanding of the mechanisms involved in development, progression, and treatment of cardiovascular disease. In parallel, a central role of the gut microbiota, both in accelerating and attenuating cardiovascular disease, has emerged. Modulation of the gut microbiota, by use of prebiotics and probiotics, has recently shown promise in cardiovascular disease prevention. Certain prebiotics can promote a short chain fatty acid profile that alters hormone secretion and attenuates cholesterol synthesis, whereas bile salt hydrolase and exopolysaccharide-producing probiotics have been shown to actively correct hypercholesterolemia. Furthermore, specific microbial genera have been identified as potential cardiovascular disease risk factors. This effect is attributed to the ability of certain members of the gut microbiota to convert dietary quaternary amines to trimethylamine, the primary substrate of the putatively atherosclerosis-promoting compound trimethylamine-N-oxide. In this respect, current research is indicating trimethylamine-depleting Achaea - termed Archeabiotics as a potential novel dietary strategy for promoting heart health. The microbiota offers a modifiable target, which has the potential to progress or prevent cardiovascular disease development. Whereas host-targeted interventions remain the standard, current research implicates microbiota-mediated therapies as an effective means of modulating cardiovascular health.

Wearable Sensing of In-Ear Pressure for Heart Rate Monitoring with a Piezoelectric Sensor

PubMed Central

Park, Jang-Ho; Jang, Dae-Geun; Park, Jung Wook; Youm, Se-Kyoung

2015-01-01

In this study, we developed a novel heart rate (HR) monitoring approach in which we measure the pressure variance of the surface of the ear canal. A scissor-shaped apparatus equipped with a piezoelectric film sensor and a hardware circuit module was designed for high wearability and to obtain stable measurement. In the proposed device, the film sensor converts in-ear pulse waves (EPW) into electrical current, and the circuit module enhances the EPW and suppresses noise. A real-time algorithm embedded in the circuit module performs morphological conversions to make the EPW more distinct and knowledge-based rules are used to detect EPW peaks. In a clinical experiment conducted using a reference electrocardiogram (ECG) device, EPW and ECG were concurrently recorded from 58 healthy subjects. The EPW intervals between successive peaks and their corresponding ECG intervals were then compared to each other. Promising results were obtained from the samples, specifically, a sensitivity of 97.25%, positive predictive value of 97.17%, and mean absolute difference of 0.62. Thus, highly accurate HR was obtained from in-ear pressure variance. Consequently, we believe that our proposed approach could be used to monitor vital signs and also utilized in diverse applications in the near future. PMID:26389912

Signal recognition and parameter estimation of BPSK-LFM combined modulation

NASA Astrophysics Data System (ADS)

Long, Chao; Zhang, Lin; Liu, Yu

2015-07-01

Intra-pulse analysis plays an important role in electronic warfare. Intra-pulse feature abstraction focuses on primary parameters such as instantaneous frequency, modulation, and symbol rate. In this paper, automatic modulation recognition and feature extraction for combined BPSK-LFM modulation signals based on decision theoretic approach is studied. The simulation results show good recognition effect and high estimation precision, and the system is easy to be realized.

Coronary Artery Formation Is Driven by Localized Expression of R-spondin3.

PubMed

Da Silva, Fabio; Rocha, Ana Sofia; Motamedi, Fariba Jian; Massa, Filippo; Basboga, Cem; Morrison, Harris; Wagner, Kay Dietrich; Schedl, Andreas

2017-08-22

Coronary arteries are essential to support the heart with oxygen, and coronary heart disease is one of the leading causes of death worldwide. The coronary arteries form at highly stereotyped locations and are derived from the primitive vascular plexus of the heart. How coronary arteries are remodeled and the signaling molecules that govern this process are poorly understood. Here, we have identified the Wnt-signaling modulator Rspo3 as a crucial regulator of coronary artery formation in the developing heart. Rspo3 is specifically expressed around the coronary stems at critical time points in their development. Temporal ablation of Rspo3 at E11.5 leads to decreased β-catenin signaling and a reduction in arterial-specific proliferation. As a result, the coronary stems are defective and the arterial tree does not form properly. These results identify a mechanism through which localized expression of RSPO3 induces proliferation of the coronary arteries at their stems and permits their formation. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Targeting G protein-coupled receptor kinases (GRKs) in Heart Failure

PubMed Central

Brinks, Henriette; Koch, Walter J

2010-01-01

In the human body, over 1000 different G protein-coupled receptors (GPCRs) mediate a broad spectrum of extracellular signals at the plasma membrane, transmitting vital physiological features such as pain, sight, smell, inflammation, heart rate and contractility of muscle cells. Signaling through these receptors is primarily controlled and regulated by a group of kinases, the GPCR kinases (GRKs), of which only seven are known and thus, interference with these common downstream GPCR regulators suggests a powerful therapeutic strategy. Molecular modulation of the kinases that are ubiquitously expressed in the heart has proven GRK2, and also GRK5, to be promising targets for prevention and reversal of one of the most severe pathologies in man, chronic heart failure (HF). In this article we will focus on the structural aspects of these GRKs important for their physiological and pathological regulation as well as well known and novel therapeutic approaches that target these GRKs in order to overcome the development of cardiac injury and progression of HF. PMID:21218155

Resetting the epigenome for heart regeneration.

PubMed

Quaife-Ryan, Gregory A; Sim, Choon Boon; Porrello, Enzo R; Hudson, James E

2016-10-01

In contrast to adults, recent evidence suggests that neonatal mice are able to regenerate following cardiac injury. This regenerative capacity is reliant on robust induction of cardiomyocyte proliferation, which is required for faithful regeneration of the heart following injury. However, cardiac regenerative potential is lost as cardiomyocytes mature and permanently withdraw from the cell cycle shortly after birth. Recently, a handful of factors responsible for the regenerative disparity between the adult and neonatal heart have been identified, but the proliferative response of adult cardiomyocytes following modulation of these factors rarely reaches neonatal levels. The inefficient re-induction of proliferation in adult cardiomyocytes may be due to the epigenetic landscape, which drastically changes during cardiac development and maturation. In this review, we provide an overview of the role of epigenetic modifiers in developmental processes related to cardiac regeneration. We propose an epigenetic framework for heart regeneration whereby adult cardiomyocyte identity requires resetting to a neonatal-like state to facilitate cell cycle re-entry and regeneration following cardiac injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Variability of heart rhythm in dynamic study of the psychovegetative relationship in neurogenic syncope].

PubMed

Musaeva, Z A; Khaspekova, N B; Veĭn, A M

2001-01-01

Physiological changes accompanying syncopes of neural origin (SNO) in patients with psychovegetative syndrome are still insufficiently studied. The data concerning the role of the autonomic nervous system are discrepant. Heart rate variability was analyzed in 68 patients with SNO in a supine position and during the active 20-min orthostatic test taking into account the heart rate components of very low frequency (VLF, an index of cerebral sympathetic activity) and high frequency (HF, a marker of vagal modulation). Steady growth of the VLF and progressive decrease in the LF within 15-20 min of the orthostasis were observed in all the patients (n = 33), who fainted after this period. The predominance of the VLF in the heart rate power spectra was correlated with a high level of anxiety. It is suggested that this fact indicates the stable cerebral sympathetic activation resulting in a baroreceptor dysfunction, i.e., a failure of vasomotor regulation in patients with SNO.

Implication of microRNAs in the development and potential treatment of radiation-induced heart disease.

PubMed

Kura, Branislav; Babal, Pavel; Slezak, Jan

2017-10-01

Radiotherapy is the most commonly used methodology to treat oncological disease, one of the most widespread causes of death worldwide. Oncological patients cured by radiotherapy applied to the mediastinal area have been shown to suffer from cardiovascular disease. The increase in the prevalence of radiation-induced heart disease has emphasized the need to seek new therapeutic targets to mitigate the negative impact of radiation on the heart. In this regard, microRNAs (miRNAs) have received considerable interest. miRNAs regulate post-transcriptional gene expression by their ability to target various mRNA sequences because of their imperfect pairing with mRNAs. It has been recognized that miRNAs modulate a diverse spectrum of cardiac functions with developmental, pathophysiological, and clinical implications. This makes them promising potential targets for diagnosis and treatment. This review summarizes the recent findings about the possible involvement of miRNAs in radiation-induced heart disease and their potential use as diagnostic or treatment targets in this respect.

BIOPHYSICAL CHARACTERISATION OF THE UNDER-APPRECIATED AND IMPORTANT RELATIONSHIP BETWEEN HEART RATE VARIABILITY AND HEART RATE

PubMed Central

Monfredi, Oliver; Lyashkov, Alexey E; Johnsen, Anne-Berit; Inada, Shin; Schneider, Heiko; Wang, Ruoxi; Nirmalan, Mahesh; Wisloff, Ulrik; Maltsev, Victor A; Lakatta, Edward G; Zhang, Henggui; Boyett, Mark R

2014-01-01

Heart rate variability (beat-to-beat changes in the RR interval) has attracted considerable attention over the last 30+ years (PubMed currently lists >17,000 publications). Clinically, a decrease in heart rate variability is correlated to higher morbidity and mortality in diverse conditions, from heart disease to foetal distress. It is usually attributed to fluctuation in cardiac autonomic nerve activity. We calculated heart rate variability parameters from a variety of cardiac preparations (including humans, living animals, Langendorff-perfused heart and single sinoatrial nodal cell) in diverse species, combining this with data from previously published papers. We show that regardless of conditions, there is a universal exponential decay-like relationship between heart rate variability and heart rate. Using two biophysical models, we develop a theory for this, and confirm that heart rate variability is primarily dependent on heart rate and cannot be used in any simple way to assess autonomic nerve activity to the heart. We suggest that the correlation between a change in heart rate variability and altered morbidity and mortality is substantially attributable to the concurrent change in heart rate. This calls for re-evaluation of the findings from many papers that have not adjusted properly or at all for heart rate differences when comparing heart rate variability in multiple circumstances. PMID:25225208

Exercise-Induced Changes in Glucose Metabolism Promote Physiological Cardiac Growth

PubMed Central

Gibb, Andrew A.; Epstein, Paul N.; Uchida, Shizuka; Zheng, Yuting; McNally, Lindsey A.; Obal, Detlef; Katragadda, Kartik; Trainor, Patrick; Conklin, Daniel J.; Brittian, Kenneth R.; Tseng, Michael T.; Wang, Jianxun; Jones, Steven P.; Bhatnagar, Aruni

2017-01-01

Background: Exercise promotes metabolic remodeling in the heart, which is associated with physiological cardiac growth; however, it is not known whether or how physical activity–induced changes in cardiac metabolism cause myocardial remodeling. In this study, we tested whether exercise-mediated changes in cardiomyocyte glucose metabolism are important for physiological cardiac growth. Methods: We used radiometric, immunologic, metabolomic, and biochemical assays to measure changes in myocardial glucose metabolism in mice subjected to acute and chronic treadmill exercise. To assess the relevance of changes in glycolytic activity, we determined how cardiac-specific expression of mutant forms of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase affect cardiac structure, function, metabolism, and gene programs relevant to cardiac remodeling. Metabolomic and transcriptomic screenings were used to identify metabolic pathways and gene sets regulated by glycolytic activity in the heart. Results: Exercise acutely decreased glucose utilization via glycolysis by modulating circulating substrates and reducing phosphofructokinase activity; however, in the recovered state following exercise adaptation, there was an increase in myocardial phosphofructokinase activity and glycolysis. In mice, cardiac-specific expression of a kinase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase transgene (GlycoLo mice) lowered glycolytic rate and regulated the expression of genes known to promote cardiac growth. Hearts of GlycoLo mice had larger myocytes, enhanced cardiac function, and higher capillary-to-myocyte ratios. Expression of phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in the heart (GlycoHi mice) increased glucose utilization and promoted a more pathological form of hypertrophy devoid of transcriptional activation of the physiological cardiac growth program. Modulation of phosphofructokinase activity was sufficient to regulate the glucose–fatty acid cycle in the heart; however, metabolic inflexibility caused by invariantly low or high phosphofructokinase activity caused modest mitochondrial damage. Transcriptomic analyses showed that glycolysis regulates the expression of key genes involved in cardiac metabolism and remodeling. Conclusions: Exercise-induced decreases in glycolytic activity stimulate physiological cardiac remodeling, and metabolic flexibility is important for maintaining mitochondrial health in the heart. PMID:28860122

Insulin receptor substrate signaling controls cardiac energy metabolism and heart failure.

PubMed

Guo, Cathy A; Guo, Shaodong

2017-06-01

The heart is an insulin-dependent and energy-consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth and survival. Heart failure is highly associated with insulin resistance, and heart failure patients suffer from the cardiac energy deficiency and structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics and impairing cardiac contractility. Recent studies demonstrated that insulin receptor substrates 1 and 2 (IRS-1,-2) are major mediators of both insulin and insulin-like growth factor-1 (IGF-1) signaling responsible for myocardial energetics, structure, function and organismal survival. Importantly, the insulin receptor substrates (IRS) play an important role in the activation of the phosphatidylinositide-3-dependent kinase (PI-3K) that controls Akt and Foxo1 signaling cascade, regulating the mitochondrial function, cardiac energy metabolism and the renin-angiotensin system. Dysregulation of this branch in signaling cascades by insulin resistance in the heart through the endocrine system promotes heart failure, providing a novel mechanism for diabetic cardiomyopathy. Therefore, targeting this branch of IRS→PI-3K→Foxo1 signaling cascade and associated pathways may provide a fundamental strategy for the therapeutic and nutritional development in control of metabolic and cardiovascular diseases. In this review, we focus on insulin signaling and resistance in the heart and the role energetics play in cardiac metabolism, structure and function. © 2017 Society for Endocrinology.

The antiarrhythmic effect of vagal stimulation after acute coronary occlusion: Role of the heart rate.

PubMed

Manati, Waheed; Pineau, Julien; Doñate Puertas, Rosa; Morel, Elodie; Quadiri, Timour; Bui-Xuan, Bernard; Chevalier, Philippe

2018-01-03

Strong evidence suggests a causal link between autonomic disturbances and ventricular arrhythmias. However, the mechanisms underlying the antiarrhythmic effect of vagal stimulation are poorly understood. The vagal antiarrhythmic effect might be modulated by a decrease in heart rate. the proximal anterior interventricular artery was occluded in 16 pigs by clamping under general anaesthesia. Group 1: heart rates remained spontaneous (n = 6; 12 occlusions); Group 2: heart rates were fixed at 190 beats per minute (bpm) with atrial electrical stimulation (n = 10; 20 occlusions). Each pig received two occlusions, 30 min apart, one without and one with vagal stimulation (10 Hz, 2 ms, 5-20 mA). The antiarrhythmic effect of vagal activation was defined as the time to the appearance of ventricular fibrillation (VF) after occlusion. In Group 1, vagal stimulation triggered a significant decrease in basal heart rate (132 ± 4 vs. 110 ± 17 bpm, p < 0.05), and delayed the time to VF after coronary occlusion (1102 ± 85 vs. 925 ± 41 s, p < 0.05). In Group 2, vagal stimulation did not modify the time to VF (103 ± 39 vs. 91 ± 20 s). Analyses revealed that heart rate and the time to VF were positively linearly related. Maintaining a constant heart rate with atrial electrical stimulation in pigs prevented vagal stimulation from modifying the time to VF after acute coronary occlusion.

Protein kinase-dependent oxidative regulation of the cardiac Na+–K+ pump: evidence from in vivo and in vitro modulation of cell signalling

PubMed Central

Galougahi, Keyvan Karimi; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A S; Hamilton, Elisha J; Rasmussen, Helge H; Figtree, Gemma A

2013-01-01

The widely reported stimulation of the cardiac Na+–K+ pump by protein kinase A (PKA) should oppose other effects of PKA to increase contractility of the normal heart. It should also reduce harmful raised myocyte Na+ levels in heart failure, yet blockade of the β1 adrenergic receptor (AR), coupled to PKA signalling, is beneficial. We treated rabbits with the β1 AR antagonist metoprolol to modulate PKA activity and studied cardiac myocytes ex vivo. Metoprolol increased electrogenic pump current (Ip) in voltage clamped myocytes and reduced glutathionylation of the β1 pump subunit, an oxidative modification causally related to pump inhibition. Activation of adenylyl cyclase with forskolin to enhance cAMP synthesis or inclusion of the catalytic subunit of PKA in patch pipette solutions abolished the increase in Ip in voltage clamped myocytes induced by treatment with metoprolol, supporting cAMP/PKA-mediated pump inhibition. Metoprolol reduced myocardial PKA and protein kinase C (PKC) activities, reduced coimmunoprecipitation of cytosolic p47phox and membranous p22phox NADPH oxidase subunits and reduced myocardial O2•−-sensitive dihydroethidium fluorescence. Treatment also enhanced coimmunoprecipitation of the β1 pump subunit with glutaredoxin 1 that catalyses de-glutathionylation. Since angiotensin II induces PKC-dependent activation of NADPH oxidase, we examined the effects of angiotensin-converting enzyme inhibition with captopril. This treatment had no effect on PKA activity but reduced the activity of PKC, reduced β1 subunit glutathionylation and increased Ip. The PKA-induced Na+–K+ pump inhibition we report should act with other mechanisms that enhance contractility of the normal heart but accentuate the harmful effects of raised cytosolic Na+ in the failing heart. This scheme is consistent with the efficacy of β1 AR blockade in the treatment of heart failure. PMID:23587884

Nutritional leucine supplementation attenuates cardiac failure in tumour-bearing cachectic animals.

PubMed

Toneto, Aline Tatiane; Ferreira Ramos, Luiz Alberto; Salomão, Emilianne Miguel; Tomasin, Rebeka; Aereas, Miguel Arcanjo; Gomes-Marcondes, Maria Cristina Cintra

2016-12-01

The condition known as cachexia presents in most patients with malignant tumours, leading to a poor quality of life and premature death. Although the cancer-cachexia state primarily affects skeletal muscle, possible damage in the cardiac muscle remains to be better characterized and elucidated. Leucine, which is a branched chain amino acid, is very useful for preserving lean body mass. Thus, this amino acid has been studied as a coadjuvant therapy in cachectic cancer patients, but whether this treatment attenuates the effects of cachexia and improves cardiac function remains poorly understood. Therefore, using an experimental cancer-cachexia model, we evaluated whether leucine supplementation ameliorates cachexia in the heart. Male Wistar rats were fed either a leucine-rich or a normoprotein diet and implanted or not with subcutaneous Walker-256 carcinoma. During the cachectic stage (approximately 21 days after tumour implantation), when the tumour mass was greater than 10% of body weight, the rats were subjected to an electrocardiogram analysis to evaluate the heart rate, QT-c, and T wave amplitude. The myocardial tissues were assayed for proteolytic enzymes (chymotrypsin, alkaline phosphatase, cathepsin, and calpain), cardiomyopathy biomarkers (myeloperoxidase, tissue inhibitor of metalloproteinases, and total plasminogen activator inhibitor 1), and caspase-8, -9, -3, and -7 activity. Both groups of tumour-bearing rats, especially the untreated group, had electrocardiography alterations that were suggestive of ischemia, dilated cardiomyopathy, and sudden death risk. Additionally, the rats in the untreated tumour-bearing group but not their leucine-supplemented littermates exhibited remarkable increases in chymotrypsin activity and all three heart failure biomarkers analysed, including an increase in caspase-3 and -7 activity. Our data suggest that a leucine-rich diet could modulate heart damage, cardiomyocyte proteolysis, and apoptosis driven by cancer-cachexia. Further studies must be conducted to elucidate leucine's mechanisms of action, which potentially includes the modulation of the heart's inflammatory process.

4D CT-based Treatment Planning for Intensity-Modulated Radiation Therapy and Proton Therapy for Distal Esophagus Cancer

PubMed Central

Zhang, Xiaodong; Zhao, Kuai-Le; Guerrero, Thomas M.; McGuire, Sean E.; Yaremko, Brian; Komaki, Ritsuko; Cox, James D.; Hui, Zhouguang; Li, Yupeng; Newhauser, Wayne D.; Mohan, Radhe; Liao, Zhongxing

2008-01-01

Purpose To compare three-dimensional (3D) and 4D computed tomography (CT)– based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. Materials and Methods IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Results Compared with IMRT, median lung volumes exposed to 5,10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%,5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%,8.4%,5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index CI=1.99) and greater irradiation of the heart (heart-V40=41.8%) compared with the IMRT plan(CI=1.55, heart-V40=35.7%) or the three-beam proton plan (CI=1.46, heart-V40=27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas-filling. Conclusions Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses. PMID:18722278

Mesenchymal Stromal Cells Modulate Monocytes Trafficking in Coxsackievirus B3‐Induced Myocarditis

PubMed Central

Miteva, Kapka; Pappritz, Kathleen; El‐Shafeey, Muhammad; Dong, Fengquan; Ringe, Jochen; Tschöpe, Carsten

2017-01-01

Abstract Mesenchymal stromal cell (MSC) application in Coxsackievirus B3 (CVB3)‐induced myocarditis reduces myocardial inflammation and fibrosis, exerts prominent extra‐cardiac immunomodulation, and improves heart function. Although the abovementioned findings demonstrate the benefit of MSC application, the mechanism of the MSC immunomodulatory effects leading to a final cardioprotective outcome in viral myocarditis remains poorly understood. Monocytes are known to be a trigger of myocardial tissue inflammation. The present study aims at investigating the direct effect of MSC on the mobilization and trafficking of monocytes to the heart in CVB3‐induced myocarditis. One day post CVB3 infection, C57BL/6 mice were intravenously injected with 1 x 106 MSC and sacrificed 6 days later for molecular biology and flow cytometry analysis. MSC application reduced the severity of myocarditis, and heart and blood pro‐inflammatory Ly6Chigh and Ly6Cmiddle monocytes, while those were retained in the spleen. Anti‐inflammatory Ly6Clow monocytes increased in the blood, heart, and spleen of MSC‐treated CVB3 mice. CVB3 infection induced splenic myelopoiesis, while MSC application slightly diminished the spleen myelopoietic activity in CVB3 mice. Left ventricular (LV) mRNA expression of the chemokines monocyte chemotactic protein‐1 (MCP)−1, MCP‐3, CCL5, the adhesion molecules intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, the pro‐inflammatory cytokines interleukin‐6, interleukin‐12, tumor necrosis factor‐α, the pro‐fibrotic transforming growth factorβ1, and circulating MCP‐1 and MCP‐3 levels decreased in CVB3 MSC mice, while LV stromal cell‐derived factor‐1α RNA expression and systemic levels of fractalkine were increased in CVB3 MSC mice. MSC application in CVB3‐induced myocarditis modulates monocytes trafficking to the heart and could be a promising strategy for the resolution of cardiac inflammation and prevention of the disease progression. Stem Cells Translational Medicine 2017;6:1249–1261 PMID:28186704

Four-dimensional computed tomography-based treatment planning for intensity-modulated radiation therapy and proton therapy for distal esophageal cancer.

PubMed

Zhang, Xiaodong; Zhao, Kuai-le; Guerrero, Thomas M; McGuire, Sean E; Yaremko, Brian; Komaki, Ritsuko; Cox, James D; Hui, Zhouguang; Li, Yupeng; Newhauser, Wayne D; Mohan, Radhe; Liao, Zhongxing

2008-09-01

To compare three-dimensional (3D) and four-dimensional (4D) computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. The IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Compared with IMRT, median lung volumes exposed to 5, 10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%, 5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%, 5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index [CI], 1.99) and greater irradiation of the heart (heart-V40, 41.8%) compared with the IMRT plan(CI, 1.55, heart-V40, 35.7%) or the three-beam proton plan (CI, 1.46, heart-V40, 27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas filling. Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses.