Science.gov

Sample records for cardiac function index

  1. Relationship of radionuclide indexes of cardiac function during interventions: volume loading, afterload stress, exercise, and pacing

    SciTech Connect

    Slutsky, R.A.

    1983-04-01

    We compared three radionuclide index of cardiac function: 1) the ejection fraction (EF), 2) the mean ejection rate (ER), and 3) the mean velocity of circumferential fiber shortening (MVCF) during volume loading, phenylephrine hydrochloride stress, exercise, and atrial pacing. All behaved in a similar (linear) fashion, allowing appropriate hemodynamic conclusions to be drawn using either index. During atrial pacing, the ejection fraction declined when velocity indexes increased, suggesting that the ejection fraction may not be a suitable index to characterize alterations in inotropic state during rapid alterations in heart rate, particular in the absence of angina pectoris. This may result from the reductions in cardiac volume for the duration of pacing, where the velocity index is preserved. In most circumstances excluding atrial pacing, ejection fraction during interventions is an adequate index of the change of myocardial contractile state. Overall, radionuclide angiography is an excellent technique to characterize acute hemodynamic interventions, with ejection fraction, in general, the simplest and most reliable of cardiac indexes during stress interventions.

  2. Exercise capacity in the Bidirectional Glenn Physiology: coupling cardiac index, ventricular function and oxygen extraction ratio

    PubMed Central

    Vallecilla, Carolina; Khiabani, Reza H.; Trusty, Phillip; Sandoval, Néstor; Fogel, Mark; Briceño, Juan Carlos; Yoganathan, Ajit P.

    2015-01-01

    In Bi-directional Glenn (BDG) physiology, the superior systemic circulation and pulmonary circulation are in series. Consequently, only blood from the superior vena cava is oxygenated in the lungs. Oxygenated blood then travels to the ventricle where it is mixed with blood returning from the lower body. Therefore, incremental changes in oxygen extraction ratio (OER) could compromise exercise tolerance. In this study, the effect of exercise on the hemodynamic and ventricular performance of BDG physiology was investigated using clinical patient data as inputs for a lumped parameter model coupled with oxygenation equations. Changes in cardiac index, Qp/Qs, systemic pressure, oxygen extraction ratio and ventricular/vascular coupling ratio were calculated for three different exercise levels. The patient cohort (n=29) was sub-grouped by age and pulmonary vascular resistance (PVR) at rest. It was observed that the changes in exercise tolerance are significant in both comparisons, but most significant when sub-grouped by PVR at rest. Results showed that patients over 2 years old with high PVR are above or close to the upper tolerable limit of OER (0.32) at baseline. Patients with high PVR at rest had very poor exercise tolerance while patients with low PVR at rest could tolerate low exercise conditions. In general, ventricular function of SV patients is too poor to increase CI and fulfill exercise requirements. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different exercise levels according to patient specific data. PMID:25913242

  3. Exercise capacity in the Bidirectional Glenn physiology: Coupling cardiac index, ventricular function and oxygen extraction ratio.

    PubMed

    Vallecilla, Carolina; Khiabani, Reza H; Trusty, Phillip; Sandoval, Néstor; Fogel, Mark; Briceño, Juan Carlos; Yoganathan, Ajit P

    2015-07-16

    In Bi-directional Glenn (BDG) physiology, the superior systemic circulation and pulmonary circulation are in series. Consequently, only blood from the superior vena cava is oxygenated in the lungs. Oxygenated blood then travels to the ventricle where it is mixed with blood returning from the lower body. Therefore, incremental changes in oxygen extraction ratio (OER) could compromise exercise tolerance. In this study, the effect of exercise on the hemodynamic and ventricular performance of BDG physiology was investigated using clinical patient data as inputs for a lumped parameter model coupled with oxygenation equations. Changes in cardiac index, Qp/Qs, systemic pressure, oxygen extraction ratio and ventricular/vascular coupling ratio were calculated for three different exercise levels. The patient cohort (n=29) was sub-grouped by age and pulmonary vascular resistance (PVR) at rest. It was observed that the changes in exercise tolerance are significant in both comparisons, but most significant when sub-grouped by PVR at rest. Results showed that patients over 2 years old with high PVR are above or close to the upper tolerable limit of OER (0.32) at baseline. Patients with high PVR at rest had very poor exercise tolerance while patients with low PVR at rest could tolerate low exercise conditions. In general, ventricular function of SV patients is too poor to increase CI and fulfill exercise requirements. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different exercise levels according to patient specific data.

  4. Symmetry of cardiac function assessment

    PubMed Central

    Bai, Xu-Fang; Ma, Amy X

    2016-01-01

    Both right and left ventricles are developed from two adjacent segments of the primary heart tube. Though they are different with regard to shape and power, they mirror each other in terms of behavior. This is the first level of symmetry in cardiac function assessment. Both cardiac muscle contraction and relaxation are active. This constructs the second level of symmetry in cardiac function assessment. Combination of the two levels will help to find some hidden indexes or approaches to evaluate cardiac function. In this article, four major indexes from echocardiography were analyzed under this principal, another seventeen indexes or measurement approaches came out of the shadow, which is very helpful in the assessment of cardiac function, especially for the right cardiac function and diastolic cardiac function. PMID:27582768

  5. The assessment of cardiac functions by tissue Doppler-derived myocardial performance index in patients with Behcet's disease.

    PubMed

    Tavil, Yusuf; Ozturk, Mehmet Akif; Sen, Nihat; Kaya, Mehmet Gungor; Hizal, Fatma; Poyraz, Fatih; Turfan, Murat; Onder, Meltem; Gurer, Mehmet Ali; Cengel, Atiye

    2008-03-01

    Vascular involvement is one of the major characteristics of Behcet's disease (BD). However, there are controversial findings regarding cardiac involvement in BD. Although early reports demonstrated that there is diastolic dysfunction in BD, conflicting results were found in the following trials. Hence, a new method for more objectively estimating the cardiac functions is needed. For this aim, we used high-usefulness tissue Doppler echocardiography for detailed analysis of cardiac changes in BD patients because this method was superior to other conventional echocardiographic techniques. The study population included 42 patients with BD (19 men, 23 women; mean age, 35 +/- 10 years, mean disease duration, 2.7 +/- 1.6 years) and 30 healthy subjects (14 men, 16 women; mean age, 38 +/- 7 years). Cardiac functions were determined using echocardiography, comprising standard two-dimensional and conventional Doppler and tissue Doppler imaging (TDI). Peak systolic myocardial velocity at mitral annulus, early diastolic mitral annular velocity (Em), late diastolic mitral annular velocity (Am), Em/Am, and myocardial performance index (MPI) were calculated by TDI. The conventional echocardiographic parameters and tissue Doppler measurements were similar between the groups. Tissue Doppler derived mitral relaxation time was longer (75 +/- 13 vs 63 +/- 16 msn, p = 0.021) in patients with BD. There was statistically significant difference between the two groups regarding left ventricular MPI (0.458 +/- 0.072 vs 0.416 +/- 0.068%, p = 0.016), which were calculated from tissue Doppler systolic time intervals. There was also significant correlation between the disease duration and MPI (r = 0.38, p = 0.017). We have demonstrated that tissue Doppler-derived myocardial left ventricular relaxation time and MPI were impaired in BD patients, although systolic and diastolic function parameters were comparable in the patients and controls.

  6. Optimal vortex formation as an index of cardiac health.

    PubMed

    Gharib, Morteza; Rambod, Edmond; Kheradvar, Arash; Sahn, David J; Dabiri, John O

    2006-04-18

    Heart disease remains a leading cause of death worldwide. Previous research has indicated that the dynamics of the cardiac left ventricle (LV) during diastolic filling may play a critical role in dictating overall cardiac health. Hence, numerous studies have aimed to predict and evaluate global cardiac health based on quantitative parameters describing LV function. However, the inherent complexity of LV diastole, in its electrical, muscular, and hemodynamic processes, has prevented the development of tools to accurately predict and diagnose heart failure at early stages, when corrective measures are most effective. In this work, it is demonstrated that major aspects of cardiac function are reflected uniquely and sensitively in the optimization of vortex formation in the blood flow during early diastole, as measured by a dimensionless numerical index. This index of optimal vortex formation correlates well with existing measures of cardiac health such as the LV ejection fraction. However, unlike existing measures, this previously undescribed index does not require patient-specific information to determine numerical index values corresponding to normal function. A study of normal and pathological cardiac health in human subjects demonstrates the ability of this global index to distinguish disease states by a straightforward analysis of noninvasive LV measurements.

  7. Biomechanics of Cardiac Function

    PubMed Central

    Voorhees, Andrew P.; Han, Hai-Chao

    2015-01-01

    The heart pumps blood to maintain circulation and ensure the delivery of oxygenated blood to all the organs of the body. Mechanics play a critical role in governing and regulating heart function under both normal and pathological conditions. Biological processes and mechanical stress are coupled together in regulating myocyte function and extracellular matrix structure thus controlling heart function. Here we offer a brief introduction to the biomechanics of left ventricular function and then summarize recent progress in the study of the effects of mechanical stress on ventricular wall remodeling and cardiac function as well as the effects of wall mechanical properties on cardiac function in normal and dysfunctional hearts. Various mechanical models to determine wall stress and cardiac function in normal and diseased hearts with both systolic and diastolic dysfunction are discussed. The results of these studies have enhanced our understanding of the biomechanical mechanism in the development and remodeling of normal and dysfunctional hearts. Biomechanics provide a tool to understand the mechanism of left ventricular remodeling in diastolic and systolic dysfunction and guidance in designing and developing new treatments. PMID:26426462

  8. CUQI: cardiac ultrasound video quality index

    PubMed Central

    Razaak, Manzoor; Martini, Maria G.

    2016-01-01

    Abstract. Medical images and videos are now increasingly part of modern telecommunication applications, including telemedicinal applications, favored by advancements in video compression and communication technologies. Medical video quality evaluation is essential for modern applications since compression and transmission processes often compromise the video quality. Several state-of-the-art video quality metrics used for quality evaluation assess the perceptual quality of the video. For a medical video, assessing quality in terms of “diagnostic” value rather than “perceptual” quality is more important. We present a diagnostic-quality–oriented video quality metric for quality evaluation of cardiac ultrasound videos. Cardiac ultrasound videos are characterized by rapid repetitive cardiac motions and distinct structural information characteristics that are explored by the proposed metric. Cardiac ultrasound video quality index, the proposed metric, is a full reference metric and uses the motion and edge information of the cardiac ultrasound video to evaluate the video quality. The metric was evaluated for its performance in approximating the quality of cardiac ultrasound videos by testing its correlation with the subjective scores of medical experts. The results of our tests showed that the metric has high correlation with medical expert opinions and in several cases outperforms the state-of-the-art video quality metrics considered in our tests. PMID:27014715

  9. GPCR signaling and cardiac function.

    PubMed

    Capote, Leany A; Mendez Perez, Roberto; Lymperopoulos, Anastasios

    2015-09-15

    G protein-coupled receptors (GPCRs), such as β-adrenergic and angiotensin II receptors, located in the membranes of all three major cardiac cell types, i.e. myocytes, fibroblasts and endothelial cells, play crucial roles in regulating cardiac function and morphology. Their importance in cardiac physiology and disease is reflected by the fact that, collectively, they represent the direct targets of over a third of the currently approved cardiovascular drugs used in clinical practice. Over the past few decades, advances in elucidation of their structure, function and the signaling pathways they elicit, specifically in the heart, have led to identification of an increasing number of new molecular targets for heart disease therapy. Here, we review these signaling modalities employed by GPCRs known to be expressed in the cardiac myocyte membranes and to directly modulate cardiac contractility. We also highlight drugs and drug classes that directly target these GPCRs to modulate cardiac function, as well as molecules involved in cardiac GPCR signaling that have the potential of becoming novel drug targets for modulation of cardiac function in the future.

  10. Motor current waveforms as an index for evaluation of native cardiac function during left ventricular support with a centrifugal blood pump.

    PubMed

    Kikugawa, D

    2001-09-01

    Control of ventricular assist devices (VADs) for native heart preservation should be attempted, and it could be one strategy for dealing with the shortage of donors in the future. In the application of a nonpulsatile blood pump for ventricular assistance from its apex to the aorta, the bypass flow and hence motor current of the pumps change in response to the ventricular pressure change. Utilizing these intrinsic characteristics of the continuous flow pumps, this study investigated whether or not motor current could be used as an index for continuous monitoring of native cardiac function. In Study 1, a centrifugal blood pump (CFP) VAD was installed between the apex and descending aorta of a mock circulatory loop. In this model, a baseline with a preload of 10 mm Hg, afterload of 40 mm Hg, and left ventricular (LV) systolic pressure of 40 mm Hg was used. The pump rpm were fixed at 1,300, 1,500, and 1,700, and LV systolic pressure was increased up to 140 mm Hg by a step of 20 mm Hg while observing the changes in LV pressure, motor current, pump flow, and aortic pressure. In Study 2, in vivo experiments were performed using 5 sheep. A left heart bypass model was created using a centrifugal pump from the ventricular apex to the descending aorta. The LV pressure was varied through administration of dopamine while observing the changes in LV pressure, pump flow, motor current, and aortic pressure at 1,500 and 1,700 rpm. An excellent correlation was observed both in vitro and in vivo studies in the relationship between motor current and LV pressure. In Study 1, the correlation coefficients were 0.77, 0.92, and 0.99 for 1,300, 1,500, and 1,700 rpm, respectively. In Study 2, they were 0.90 (Animal 1), 0.82 (Animal 2), 0.89 (Animal 3), 0.93 (Animal 4), and 0.70 (Animal 5) respectively for 1,500 rpm, and 0.94 (Animal 2), 0.85 (Animal 3), 0.94 (Animal 4), and 0.89 (Animal 5) respectively, for 1,700 rpm. The relationship between motor current and pump flow and LV pressure

  11. Return of Viable Cardiac Function After Sonographic Cardiac Standstill in Pediatric Cardiac Arrest.

    PubMed

    Steffen, Katherine; Thompson, W Reid; Pustavoitau, Aliaksei; Su, Erik

    2017-01-01

    Sonographic cardiac standstill during adult cardiac arrest is associated with failure to get return to spontaneous circulation. This report documents 3 children whose cardiac function returned after standstill with extracorporeal membranous oxygenation. Sonographic cardiac standstill may not predict cardiac death in children.

  12. Normal cardiac function in mice with supraphysiological cardiac creatine levels.

    PubMed

    Santacruz, Lucia; Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A; Jacobs, Danny O

    2014-02-01

    Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies.

  13. Context indexing of digital cardiac ultrasound records in PACS

    NASA Astrophysics Data System (ADS)

    Lobodzinski, S. Suave; Meszaros, Georg N.

    1998-07-01

    Recent wide adoption of the DICOM 3.0 standard by ultrasound equipment vendors created a need for practical clinical implementations of cardiac imaging study visualization, management and archiving, DICOM 3.0 defines only a logical and physical format for exchanging image data (still images, video, patient and study demographics). All DICOM compliant imaging studies must presently be archived on a 650 Mb recordable compact disk. This is a severe limitation for ultrasound applications where studies of 3 to 10 minutes long are a common practice. In addition, DICOM digital echocardiography objects require physiological signal indexing, content segmentation and characterization. Since DICOM 3.0 is an interchange standard only, it does not define how to database composite video objects. The goal of this research was therefore to address the issues of efficient storage, retrieval and management of DICOM compliant cardiac video studies in a distributed PACS environment. Our Web based implementation has the advantage of accommodating both DICOM defined entity-relation modules (equipment data, patient data, video format, etc.) in standard relational database tables and digital indexed video with its attributes in an object relational database. Object relational data model facilitates content indexing of full motion cardiac imaging studies through bi-directional hyperlink generation that tie searchable video attributes and related objects to individual video frames in the temporal domain. Benefits realized from use of bi-directionally hyperlinked data models in an object relational database include: (1) real time video indexing during image acquisition, (2) random access and frame accurate instant playback of previously recorded full motion imaging data, and (3) time savings from faster and more accurate access to data through multiple navigation mechanisms such as multidimensional queries on an index, queries on a hyperlink attribute, free search and browsing.

  14. Mathematical Models of Cardiac Pacemaking Function

    NASA Astrophysics Data System (ADS)

    Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

    2013-10-01

    Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

  15. Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure.

    PubMed

    Ishikawa, Kiyotake; Fish, Kenneth M; Tilemann, Lisa; Rapti, Kleopatra; Aguero, Jaume; Santos-Gallego, Carlos G; Lee, Ahyoung; Karakikes, Ioannis; Xie, Chaoqin; Akar, Fadi G; Shimada, Yuichi J; Gwathmey, Judith K; Asokan, Aravind; McPhee, Scott; Samulski, Jade; Samulski, Richard Jude; Sigg, Daniel C; Weber, Thomas; Kranias, Evangelia G; Hajjar, Roger J

    2014-12-01

    Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 10(13) vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 10(12) vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure-volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.

  16. Comparison and relation of indirect and direct dynamic indexes of cardiac pumping capacity in chronic heart failure.

    PubMed

    Williams, Simon G; Tzeng, Bing-H; Barker, Diane; Tan, Lip-Bun

    2005-10-15

    Cardiac power output (CPO), the product of cardiac output (CO) and mean arterial pressure (MAP), is a direct measure of cardiac pumping capability and is strongly indicative of prognosis and exercise ability in patients with chronic heart failure (CHF). However, it is not as easily measured as indirect indicators of cardiac function, such as peak oxygen consumption (VO(2)) or peak "circulatory power" (CircP), the product of VO(2) and MAP. The relation between direct and indirect indexes of cardiac pumping capacity was evaluated in 219 ambulatory patients with CHF. CircP was found to have a direct and consistent relation with CPO, overall (R = 0.93, p <0.0001) and at peak exercise (R = 0.84, p < 0.0001). The results suggest CircP to be an adequate measure of cardiac pumping capacity when the more directly measured CPO is not available.

  17. Ultrasound assessment of fetal cardiac function

    PubMed Central

    Crispi, Fàtima; Valenzuela‐Alcaraz, Brenda; Cruz‐Lemini, Monica

    2015-01-01

    Abstract Introduction: Fetal heart evaluation with US is feasible and reproducible, although challenging due to the smallness of the heart, the high heart rate and limited access to the fetus. However, some cardiac parameters have already shown a strong correlation with outcomes and may soon be incorporated into clinical practice. Materials and Methods: Cardiac function assessment has proven utility in the differential diagnosis of cardiomyopathies or prediction of perinatal mortality in congenital heart disease. In addition, some cardiac parameters with high sensitivity such as MPI or annular peak velocities have shown promising results in monitoring and predicting outcome in intrauterine growth restriction or congenital diaphragmatic hernia. Conclusion: Cardiac function can be adequately evaluated in most fetuses when appropriate expertise, equipment and time are available. Fetal cardiac function assessment is a promising tool that may soon be incorporated into clinical practice to diagnose, monitor or predict outcome in some fetal conditions. Thus, more research is warranted to further define specific protocols for each fetal condition that may affect cardiac function. PMID:28191192

  18. The effect of age on the relationship between cardiac and vascular function.

    PubMed

    Houghton, David; Jones, Thomas W; Cassidy, Sophie; Siervo, Mario; MacGowan, Guy A; Trenell, Michael I; Jakovljevic, Djordje G

    2016-01-01

    Age-related changes in cardiac and vascular function are associated with increased risk of cardiovascular mortality and morbidity. The aim of the present study was to define the effect of age on the relationship between cardiac and vascular function. Haemodynamic and gas exchange measurements were performed at rest and peak exercise in healthy individuals. Augmentation index was measured at rest. Cardiac power output, a measure of overall cardiac function, was calculated as the product of cardiac output and mean arterial blood pressure. Augmentation index was significantly higher in older than younger participants (27.7 ± 10.1 vs. 2.5 ± 10.1%, P<0.01). Older people demonstrated significantly higher stroke volume and mean arterial blood pressure (P<0.05), but lower heart rate (145 ± 13 vs. 172 ± 10 beats/min, P<0.01) and peak oxygen consumption (22.5 ± 5.2 vs. 41.2 ± 8.4 ml/kg/min, P<0.01). There was a significant negative relationship between augmentation index and peak exercise cardiac power output (r=-0.73, P=0.02) and cardiac output (r=-0.69, P=0.03) in older participants. Older people maintain maximal cardiac function due to increased stroke volume. Vascular function is a strong predictor of overall cardiac function in older but in not younger people.

  19. Functions of Autophagy in Pathological Cardiac Hypertrophy

    PubMed Central

    Li, Zhenhua; Wang, Jian; Yang, Xiao

    2015-01-01

    Pathological cardiac hypertrophy is the response of heart to various biomechanical and physiopathological stimuli, such as aging, myocardial ischemia and hypertension. However, a long-term exposure to the stress makes heart progress to heart failure. Autophagy is a dynamic self-degradative process necessary for the maintenance of cellular homeostasis. Accumulating evidence has revealed a tight link between cardiomyocyte autophagy and cardiac hypertrophy. Sophisticatedly regulated autophagy protects heart from various physiological and pathological stimuli by degradating and recycling of protein aggregates, lipid drops, or organelles. Here we review the recent progresses concerning the functions of autophagy in cardiac hypertrophy induced by various hypertrophic stimuli. Moreover, the therapeutic strategies targeting autophagy for cardiac hypertrophy will also be discussed. PMID:25999790

  20. Cardiac function in long-term survivors of childhood lymphoma.

    PubMed

    Friedberg, Mark K; Solt, Ido; Weyl-Ben-Arush, Myriam; Braver, Yulia; Lorber, Avraham

    2011-01-20

    Objectives. We studied long-term effects of therapy for childhood lymphoma on cardiac function. Design and patients. We prospectively evaluated 45 survivors of childhood lymphoma, using clinical parameters, electrocardiography and echocardiography. Further comparisons were made between lymphoma subgroups and between males and females. Results. Mean age at diagnosis was 9.1 years. Mean followup duration was 10.9 years. The NYHA functional class was I in 43 patients and II in 2 patients. A prolonged QTc interval (>0.44 msec) was found in 8 patients. Left ventricular (LV) systolic function and compliance were normal (LV shortening fraction 40 ± 5.6%; cardiac index 2.84 ± 1.13 L/min/m(2); E/A wave ratio 2.5 ± 1.3; mean ± S.D.), LV mass was normal (97 ± 40 grams/m(2), mean ± S.D.). Mitral regurgitation was observed in 7/45 patients (16%). Asymptomatic pericardial effusions were found in 3/45 (7%) patients. Conclusions. Long-term follow-up shows that most parameters of cardiac function are normal in survivors of childhood lymphoma. This is likely due to relatively low doses of anthracyclines in modern protocol modalities. Abnormalities in mitral valve flow, QTc prolongation and in a small proportion of survivors, and functional capacity necessitate long-term cardiac follow-up of these patients.

  1. Regulation of cardiac function during a cold pressor test in athletes and untrained subjects.

    PubMed

    Ifuku, Hirotoshi; Moriyama, Kayo; Arai, Kuniko; Shiraishi-Hichiwa, Yumiko

    2007-09-01

    By using (dP/dt)/P of carotid artery pulse, a non-invasive index of cardiac contractility, we examined the regulatory mechanism of cardiac function during a cold pressor test in athletes and untrained subjects. Twenty-four healthy subjects (9 athletes, 8 untrained subjects, and 7 hyperreactors of 4 athletes and 3 untrained subjects with a rise of 15 mmHg or greater in systolic and/or diastolic blood pressure) underwent the cold pressor test according to Hines and Brown (Am Heart J 11:1-9, 1936): immersion of the right hand in 4 degrees C water for 1 min. Although mean blood pressure increased during the cold stress in all the groups, cardiac function differed. In athletes, heart rate and cardiac contractility caused cardiac output to increase while total peripheral resistance (TPR) did not change. In untrained subjects, however, heart rate and cardiac contractility tended to decrease cardiac output and thus TPR increased. In hyperreactors, heart rate and cardiac contractility increased during cold stress, and also TPR increased. After the end of the test, heart rate and cardiac contractility decreased only in untrained group. The findings that during a cold pressor test heart rate and cardiac contractility are enhanced in athletes but depressed in untrained subjects indicate that the state of physical training influences cardiac sympathetic neural reactivity to cold stress, except for hyperreactors.

  2. Cardiac Structure and Function in Cushing's Syndrome: A Cardiac Magnetic Resonance Imaging Study

    PubMed Central

    Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

    2014-01-01

    Background: Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. Objectives: The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Methods: Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2–12 mo) after the treatment of hypercortisolism. Results: Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Conclusion: Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism. PMID:25093618

  3. Human sinus arrhythmia as an index of vagal cardiac outflow

    NASA Technical Reports Server (NTRS)

    Eckberg, D. L.

    1983-01-01

    The human central vagal mechanisms were investigated by measuring the intervals between heartbeats during controlled breathing (at breathing intervals of 2.5-10 s and nominal tidal volumes of 1000 and 1500 ml) in six young men and women. It was found that as the breathing interval increased, the longest heart periods became longer, the shortest heart periods became shorter, and the peak-valley P-P intervals increased asymptotically. Peak-valley intervals also increased in proportion to tidal volume, although this influence was small. The phase angles between heart period changes and respiration were found to vary as linear functions of breathing interval. Heart period shortening began in inspiration at short breathing intervals and in expiration at long breathing intervals, while heart period lengthening began in early expiration at all breathing intervals studied. It is concluded that a close relationship exists between variations of respiratory depth and interval and the quantity, periodicity, and timing of vagal cardiac outflow in conscious humans. The results indicate that at usual breathing rates, phasic respiration-related changes of vagal motoneuron activity begin in expiration, progress slowly, and are incompletely expressed at fast breathing ratges.

  4. The effect of age on the relationship between cardiac and vascular function

    PubMed Central

    Houghton, David; Jones, Thomas W.; Cassidy, Sophie; Siervo, Mario; MacGowan, Guy A.; Trenell, Michael I.; Jakovljevic, Djordje G.

    2016-01-01

    Age-related changes in cardiac and vascular function are associated with increased risk of cardiovascular mortality and morbidity. The aim of the present study was to define the effect of age on the relationship between cardiac and vascular function. Haemodynamic and gas exchange measurements were performed at rest and peak exercise in healthy individuals. Augmentation index was measured at rest. Cardiac power output, a measure of overall cardiac function, was calculated as the product of cardiac output and mean arterial blood pressure. Augmentation index was significantly higher in older than younger participants (27.7 ± 10.1 vs. 2.5 ± 10.1%, P < 0.01). Older people demonstrated significantly higher stroke volume and mean arterial blood pressure (P < 0.05), but lower heart rate (145 ± 13 vs. 172 ± 10 beats/min, P < 0.01) and peak oxygen consumption (22.5 ± 5.2 vs. 41.2 ± 8.4 ml/kg/min, P < 0.01). There was a significant negative relationship between augmentation index and peak exercise cardiac power output (r = −0.73, P = 0.02) and cardiac output (r = −0.69, P = 0.03) in older participants. Older people maintain maximal cardiac function due to increased stroke volume. Vascular function is a strong predictor of overall cardiac function in older but in not younger people. PMID:26590322

  5. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    PubMed Central

    Gotzhein, Frauke; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk

    2017-01-01

    Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice. PMID:28352641

  6. Prognostic significance of early cardiac index measurements in severely burned patients.

    PubMed

    Bernard, F; Gueugniaud, P Y; Bertin-Maghit, M; Bouchard, C; Vilasco, B; Petit, P

    1994-12-01

    Invasive monitoring during early resuscitation was performed. To compare the heamodynamic results of severely burned patients, the results of 38 patients hospitalized between 1988 and 1991 in the burn centre of Lyon were retrospectively reviewed. Survivors and non-Survivors' data were compared. No difference existed between the two groups in age, unit burn score, fluid requirement and dose of dobutamine. Survivors had a significantly higher cardiac index, O2 delivery and systolic blood pressure index than non-survivors. It is suggested that the ability to sustain a high cardiac index in response to the burn injury plays a role in the outcome of the patients. There is an indication that dobutamine could have a beneficial effect in this way. Further studies are needed to confirm the benefit of the maintenance of high cardiac index levels by the pressors.

  7. Altered cardiac autonomic nervous function in depression

    PubMed Central

    2013-01-01

    Background Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship; however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia. Methods Individuals (n = 53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score ≥20 and a Zung Self-Rating Depression Scale score > 53 were compared to 53 healthy individuals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals > 50 ms different from preceding interval (pNN50). Pearson’s correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)). Results The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group (P<.05). The mean value of the LF in the depression group was higher than the in control group (P<.05). Furthermore the ratio of LF/HF was higher among the depression group than the control group (P<.05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group (P<.05), particularly

  8. Effect of prolonged space flight on cardiac function and dimensions

    NASA Technical Reports Server (NTRS)

    Henry, W. L.; Epstein, S. E.; Griffith, J. M.; Goldstein, R. E.; Redwood, D. R.

    1977-01-01

    By taking advantage of the capabilities of echocardiography to measure noninvasively left ventricular volume, stroke volume, and ejection fraction, and of the fact that the astronauts were routinely subjected to lower body negative pressure (whereby cardiac filling is progressively decreased), it was possible to construct classic ventricular function curves noninvasively, thereby obviating the difficulties encountered in comparing cardiac function at different end-diastolic volumes preflight and postflight. In this manner, the effect of an 84-day period of weightlessness on cardiac structure and function was evaluated in the Skylab 4 astronauts.

  9. Nuclear cardiac ejection fraction and cardiac index in abdominal aortic surgery

    SciTech Connect

    Fiser, W.P.; Thompson, B.W.; Thompson, A.R.; Eason, C.; Read, R.C.

    1983-11-01

    Since atherosclerotic heart disease results in more than half of the perioperative deaths that follow abdominal aortic surgery, a prospective protocol was designed for preoperative evaluation and intraoperative hemodynamic monitoring. Twenty men who were prepared to undergo elective operation for aortoiliac occlusive disease (12 patients) and abdominal aortic aneurysm (eight patients) were evaluated with a cardiac scan and right heart catheterization. The night prior to operation, each patient received volume loading with crystalloid based upon ventricular performance curves. At the time of the operation, all patients were anesthetized with narcotics and nitrous oxide, and hemodynamic parameters were recorded throughout the operation. Aortic crossclamping resulted in a marked depression in CI in all patients. CI remained depressed after unclamping in the majority of patients. There were two perioperative deaths, both from myocardial infarction or failure. Both patients had ejection fractions less than 30% and initial CIs less than 2 L/M2, while the survivors' mean ejection fraction was 63% +/- 1 and their mean CI was 3.2 L/M2 +/- 0.6. The authors conclude that preoperative evaluation of ejection fraction can select those patients at a high risk of cardiac death from abdominal aortic operation. These patients should receive intensive preoperative monitoring with enhancement of ventricular performance.

  10. Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function

    PubMed Central

    Lakhal-Littleton, Samira; Wolna, Magda; Carr, Carolyn A.; Miller, Jack J. J.; Christian, Helen C.; Ball, Vicky; Santos, Ana; Diaz, Rebeca; Biggs, Daniel; Stillion, Richard; Holdship, Philip; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A.

    2015-01-01

    Iron is essential to the cell. Both iron deficiency and overload impinge negatively on cardiac health. Thus, effective iron homeostasis is important for cardiac function. Ferroportin (FPN), the only known mammalian iron-exporting protein, plays an essential role in iron homeostasis at the systemic level. It increases systemic iron availability by releasing iron from the cells of the duodenum, spleen, and liver, the sites of iron absorption, recycling, and storage respectively. However, FPN is also found in tissues with no known role in systemic iron handling, such as the heart, where its function remains unknown. To explore this function, we generated mice with a cardiomyocyte-specific deletion of Fpn. We show that these animals have severely impaired cardiac function, with a median survival of 22 wk, despite otherwise unaltered systemic iron status. We then compared their phenotype with that of ubiquitous hepcidin knockouts, a recognized model of the iron-loading disease hemochromatosis. The phenotype of the hepcidin knockouts was far milder, with normal survival up to 12 mo, despite far greater iron loading in the hearts. Histological examination demonstrated that, although cardiac iron accumulates within the cardiomyocytes of Fpn knockouts, it accumulates predominantly in other cell types in the hepcidin knockouts. We conclude, first, that cardiomyocyte FPN is essential for intracellular iron homeostasis and, second, that the site of deposition of iron within the heart determines the severity with which it affects cardiac function. Both findings have significant implications for the assessment and treatment of cardiac complications of iron dysregulation. PMID:25713362

  11. External validation of the Revised Cardiac Risk Index and update of its renal variable to predict 30-day risk of major cardiac complications after non-cardiac surgery: rationale and plan for analyses of the VISION study

    PubMed Central

    Walsh, Michael; Devereaux, P J; MacNeil, S Danielle; Lam, Ngan N; Hildebrand, Ainslie M; Acedillo, Rey R; Mrkobrada, Marko; Chow, Clara K; Lee, Vincent W; Thabane, Lehana; Garg, Amit X

    2017-01-01

    Introduction The Revised Cardiac Risk Index (RCRI) is a popular classification system to estimate patients' risk of postoperative cardiac complications based on preoperative risk factors. Renal impairment, defined as serum creatinine >2.0 mg/dL (177 µmol/L), is a component of the RCRI. The estimated glomerular filtration rate has become accepted as a more accurate indicator of renal function. We will externally validate the RCRI in a modern cohort of patients undergoing non-cardiac surgery and update its renal component. Methods and analysis The Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) study is an international prospective cohort study. In this prespecified secondary analysis of VISION, we will test the risk estimation performance of the RCRI in ∼34 000 participants who underwent elective non-cardiac surgery between 2007 and 2013 from 29 hospitals in 15 countries. Using data from the first 20 000 eligible participants (the derivation set), we will derive an optimal threshold for dichotomising preoperative renal function quantified using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) glomerular filtration rate estimating equation in a manner that preserves the original structure of the RCRI. We will also develop a continuous risk estimating equation integrating age and CKD-Epi with existing RCRI risk factors. In the remaining (approximately) 14 000 participants, we will compare the risk estimation for cardiac complications of the original RCRI to this modified version. Cardiac complications will include 30-day non-fatal myocardial infarction, non-fatal cardiac arrest and death due to cardiac causes. We have examined an early sample to estimate the number of events and the distribution of predictors and missing data, but have not seen the validation data at the time of writing. Ethics and dissemination The research ethics board at each site approved the VISION protocol prior to recruitment. We will

  12. Cardiac Autonomic Function in Patients With Ankylosing Spondylitis

    PubMed Central

    Wei, Cheng-Yu; Kung, Woon-Man; Chou, Yi-Sheng; Wang, Yao-Chin; Tai, Hsu-Chih; Wei, James Cheng-Chung

    2016-01-01

    Abstract Ankylosing spondylitis (AS) is a chronic inflammatory disease involing spine and enthesis. The primary aim of this study is to investigate the autonomic nervous system (ANS) function and the association between ANS and the functional status or disease activity in AS. The study included 42 AS patients, all fulfilling the modified New York criteria. All the patients are totally symptom free for ANS involvement and had normal neurological findings. These AS patients and 230 healthy volunteers receive analysis of 5 minutes heart rate variability (HRV) in lying posture. In addition, disease activity and functional status of these AS patients are assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Score (BAS-G). Both groups were age and sex-matched. Although the HRV analysis indicates that the peaks of total power (TP, 0–0.5 Hz) and high-frequency power (HF, 0.15–0.40 Hz) are similar in both groups, the activities of low-frequency power (LF, 0.04–0.15 Hz), LF in normalized units (LF%), and the ratio of LF to HF (LF/HF) in AS patients are obviously lower than healthy controls. The erythrocyte sedimentation rate and C-reactive protein revealed negative relationship with HF. The AS patients without peripheral joint disease have higher LF, TP, variance, LF%, and HF than the patients with peripheral joint disease. The AS patients without uvetis have higher HF than the patients with uvetis. The total scores of BASDI, BASFI, and BAS-G do not show any association to HRV parameters. AS patients have significantly abnormal cardiac autonomic regulation. This is closely related with some inflammatory activities. Reduced autonomic function may be one of the factors of high cardiovascular risk in AS patients. PMID:27227940

  13. Operation Everest II: Preservation of Cardiac Function at Extreme Altitude,

    DTIC Science & Technology

    1986-10-01

    environmental control. The exercise intensity was measured in terms of both physical work and oxygen uptake. Oxygen uptakes at submaximal work loads were...at high altitude could depress cardiac function and decrease exercise capacity. If so, impaired cardiac function should occur with the extreme...chronic hypoxemia of the 40-day simulated climb of Mt. Everest (8840m, PB 240 mmHg, PIO 2 43 mmHg). In the five subjects having resting and exercise

  14. Low Cardiac Index is Associated with Incident Dementia and Alzheimer’s Disease: The Framingham Heart Study

    PubMed Central

    Jefferson, Angela L.; Beiser, Alexa S.; Himali, Jayandra J.; Seshadri, Sudha; O’Donnell, Christopher J.; Manning, Warren J.; Wolf, Philip A.; Au, Rhoda; Benjamin, Emelia J.

    2015-01-01

    Background Cross-sectional epidemiological and clinical research suggest lower cardiac index is associated with abnormal brain aging, including smaller brain volumes, increased white matter hyperintensities, and worse cognitive performances. Lower systemic blood flow may have implications for dementia among older adults. Methods & Results 1039 Framingham Offspring Cohort participants free from clinical stroke, transient ischemic attack, or dementia formed our sample (69±6 years; 53% women). Multivariable-adjusted proportional hazard models adjusting for Framingham Stroke Risk Profile score (age, sex, systolic blood pressure, anti-hypertensive medication, diabetes, cigarette smoking, cardiovascular disease [CVD] history, atrial fibrillation), education, and apolipoprotein E4 status related cardiac MRI-assessed cardiac index (cardiac output/body surface area) to incident all-cause dementia and Alzheimer’s disease (AD). Over the median 7.7 year follow-up period, 32 participants developed dementia, including 26 cases of AD. Each one standard deviation unit decrease in cardiac index increased the relative risk of both dementia (HR=1.66; 95% confidence intervals [CI], 1.11–2.47; p=0.013) and AD (HR=1.65; 95% CI, 1.07–2.54; p=0.022). Compared to normal cardiac index, individuals with clinically low cardiac index had a higher relative risk of dementia (HR=2.07; 95% CI, 1.02–4.19; p=0.044). If participants with clinically prevalent CVD and atrial fibrillation were excluded (n=184), individuals with clinically low cardiac index had a higher relative risk of both dementia (HR=2.92; 95% CI, 1.34–6.36; p=0.007) and AD (HR=2.87; 95% CI, 1.21–6.80; p=0.016) compared to individuals with normal cardiac index. Conclusions Lower cardiac index is associated with an increased risk for the development of dementia and AD. PMID:25700178

  15. Assessment of cardiac parameters in evaluation of cardiac functions in patients with thalassemia major.

    PubMed

    Oztarhan, Kazim; Delibas, Yavuz; Salcioglu, Zafer; Kaya, Guldemet; Bakari, Suleyman; Bornaun, Helen; Aydogan, Gonul

    2012-04-01

    The aim of the study was to evaluate cardiac function and early cardiac dysfunction of patients followed as thalassemia major. In this study, the authors compared 100 patients, diagnosed as thalassemia major with mean age 11.84 ± 4.35, with 60 healthy control subjects at the same age between 2008 and 2011. Early diagnosis of iron overload that may occur after repeated transfusions is important in this patient group. To detect early iron accumulation, the authors compared ferritin with the echo findings, the 24-hour Holter, and cardiac magnetic resonance imaging (MRI) T2* values in the patients of same age and sex, treated with chelators, without heart failure, nonsplenectomized, and do not differ in the presence of hepatitis C. Ferritin levels, left ventricular systolic functions (ejection fraction [EF], shortening fraction [SF]), left ventricular measurements, left ventricular diastolic functions, T2* image on cardiac magnetic resonance, heart rate variables in 24 hours, and Holter rhythm were evaluated to show the early failure of cardiac functions. In this study the authors confirmed that iron-related cardiac toxicity damages electrical activity earlier than myocardial contractility. Left ventricular diastolic diameter (LVDd), left ventricular mass (LVM), and LV systolic diameter (LVDs) levels were significantly higher in the patient group with ectopia. Patients with ectopia are the ones in whom LVM and LVDd are increased. In thalassemia major patients with ectopia, LF/HF ratio was markedly increased, QTc dispersion was clearly found higher in patients with ectopia rather than nonectopic patients. The standard deviation all normal RR interval series (SDNN) was found clearly lower in thalassemia major group with ectopia than control group because it is assumed that increase in cardiac sympathetic neuronal activity is related to exposure to chronic diastolic and systolic failure.

  16. Cardiac systolic regional function and synchrony in endurance trained and untrained females

    PubMed Central

    Hedman, Kristofer; Tamás, Éva; Bjarnegård, Niclas; Brudin, Lars; Nylander, Eva

    2015-01-01

    Background Most studies on cardiac function in athletes describe overall heart function in predominately male participants. We aimed to compare segmental, regional and overall myocardial function and synchrony in female endurance athletes (ATH) and in age-matched sedentary females (CON). Methods In 46 ATH and 48 CON, echocardiography was used to measure peak longitudinal systolic strain and myocardial velocities in 12 left ventricular (LV) and 2 right ventricular (RV) segments. Regional and overall systolic function were calculated together with four indices of dyssynchrony. Results There were no differences in regional or overall LV systolic function between groups, or in any of the four dyssynchrony indices. Peak systolic velocity (s′) was higher in the RV of ATH than in CON (9.7±1.5 vs 8.7±1.5 cm/s, p=0.004), but not after indexing by cardiac length (p=0.331). Strain was similar in ATH and CON in 8 of 12 LV myocardial segments. In septum and anteroseptum, basal and mid-ventricular s′ was 6–7% and 17–19% higher in ATH than in CON (p<0.05), respectively, while s′ was 12% higher in CON in the basal LV lateral wall (p=0.013). After indexing by cardiac length, s′ was only higher in ATH in the mid-ventricular septum (p=0.041). Conclusions We found differences between trained and untrained females in segmental systolic myocardial function, but not in global measures of systolic function, including cardiac synchrony. These findings give new insights into cardiac adaptation to endurance training and could also be of use for sports cardiologists evaluating female athletes. PMID:27900120

  17. EANM/ESC guidelines for radionuclide imaging of cardiac function.

    PubMed

    Hesse, B; Lindhardt, T B; Acampa, W; Anagnostopoulos, C; Ballinger, J; Bax, J J; Edenbrandt, L; Flotats, A; Germano, G; Stopar, T Gmeiner; Franken, P; Kelion, A; Kjaer, A; Le Guludec, D; Ljungberg, M; Maenhout, A F; Marcassa, C; Marving, J; McKiddie, F; Schaefer, W M; Stegger, L; Underwood, R

    2008-04-01

    Radionuclide imaging of cardiac function represents a number of well-validated techniques for accurate determination of right (RV) and left ventricular (LV) ejection fraction (EF) and LV volumes. These first European guidelines give recommendations for how and when to use first-pass and equilibrium radionuclide ventriculography, gated myocardial perfusion scintigraphy, gated PET, and studies with non-imaging devices for the evaluation of cardiac function. The items covered are presented in 11 sections: clinical indications, radiopharmaceuticals and dosimetry, study acquisition, RV EF, LV EF, LV volumes, LV regional function, LV diastolic function, reports and image display and reference values from the literature of RVEF, LVEF and LV volumes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "prevailing or general consensus". The guidelines are designed to assist in the practice of referral to, performance, interpretation and reporting of nuclear cardiology studies for the evaluation of cardiac performance.

  18. Adaptive responses of cardiac function to fetal postural change as gestational age increases

    PubMed Central

    Kim, Woo Jin; Choi, Hye Jin; Yang, Sun Young; Koo, Boo Hae; Ahn, Ki Hoon; Hong, Soon Cheol; Oh, Min-Jeong; Kim, Hai-Joong

    2016-01-01

    Objective The cardiovascular system maintains homeostasis through a series of adaptive responses to physiological requirements. However, little is known about the adaptation of fetal cardiac function to gravity, according to gestational age. In the present study, we aimed to evaluate the adaptive responses of cardiac function to postural changes, using Tei index measurements. Methods Fetal echocardiography and Doppler examination were performed on 114 women with vertex singleton pregnancies at 19 to 40 weeks' gestation. Participants were placed in an upright seated position, and the Tei index for fetal left ventricular cardiac function was measured. The women were then moved into a supine position and the Tei index was re-measured. Results The mean Tei index when measured in an upright seated position was significantly lower than that measured in a supine positioning for all fetuses (0.528±0.103 vs. 0.555±0.106, P=0.014, respectively). This difference was also noted in fetuses with a gestational age of 28–40 weeks (0.539±0.107 vs. 0.574±0.102, P=0.011, respectively). However, there was no difference in the Tei index between an upright seated and a supine position among fetuses with a gestational age of <28 weeks (0.505±0.091 vs. 0.516±0.103, P=0.571, respectively). Conclusion Postural changes from an upright seated to a supine position result in an increased Tei index after a gestational age of 28 weeks. This appears to reflect maturation in the adaptive responses of the fetal cardiovascular system to postural changes. PMID:27896244

  19. Mammalian enabled (Mena) is a critical regulator of cardiac function.

    PubMed

    Aguilar, Frédérick; Belmonte, Stephen L; Ram, Rashmi; Noujaim, Sami F; Dunaevsky, Olga; Protack, Tricia L; Jalife, Jose; Todd Massey, H; Gertler, Frank B; Blaxall, Burns C

    2011-05-01

    Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

  20. Control of cardiac function and venous return in thyrotoxic calves.

    PubMed

    Gay, R; Lee, R W; Appleton, C; Olajos, M; Martin, G V; Morkin, E; Goldman, S

    1987-03-01

    The mechanisms responsible for maintenance of the high-output state associated with thyrotoxicosis have been investigated by measurement of cardiac-function curves and venous compliance during ganglionic blockade with trimethaphan. Thirteen calves were injected daily with L-thyroxine (200 micrograms/kg) for 12-14 days. Thyroxine treatment increased heart rate (70%), left ventricular systolic pressure (22%), cardiac output (120%), left ventricular maximum rate of pressure development (dP/dt) (56%), and total blood volume (18%) and decreased systemic vascular resistance (39%). These hemodynamic changes persisted during ganglionic blockade or autonomic blockade with atropine and propranolol. Cardiac-function curves in conscious thyrotoxic calves were displaced upward and to the left. Mean circulatory filling pressure (MCFP), measured during anesthesia, was increased from 8 +/- 1 to 12 +/- 1 mmHg. During autonomic and ganglionic blockade MCFP remained elevated after treatment with thyroxine. Venous compliance decreased from 2.1 +/- 0.2 to 1.3 +/- 0.1 ml X mmHg-1 X kg-1 after thyroxine. Unstressed vascular volume was increased from 52.3 +/- 1.1 to 67.1 +/- 0.9 ml/kg. Thus the elevated cardiac output and new cardiac-function curve in thyrotoxicosis are associated with a combination of increased inotropic state, increased blood volume, and decreased venous compliance. These effects are not the result of autonomic influences and may represent direct actions of thyroid hormone on the heart and peripheral venous circulation.

  1. Impairment of cardiac function and energetics in experimental renal failure.

    PubMed Central

    Raine, A E; Seymour, A M; Roberts, A F; Radda, G K; Ledingham, J G

    1993-01-01

    Cardiac function and energetics in experimental renal failure in the rat (5/6 nephrectomy) have been investigated by means of an isolated perfused working heart preparation and an isometric Langendorff preparation using 31P nuclear magnetic resonance (31P NMR). 4 wk after nephrectomy cardiac output of isolated hearts perfused with Krebs-Henseleit buffer was significantly lower (P < 0.0001) at all levels of preload and afterload in the renal failure groups than in the pair-fed sham operated control group. In control hearts, cardiac output increased with increases in perfusate calcium from 0.73 to 5.61 mmol/liter whereas uremic hearts failed in high calcium perfusate. Collection of 31P NMR spectra from hearts of renal failure and control animals during 30 min normoxic Langendorff perfusion showed that basal phosphocreatine was reduced by 32% to 4.7 mumol/g wet wt (P < 0.01) and the phosphocreatine to ATP ratio was reduced by 32% (P < 0.01) in uremic hearts. During low flow ischemia, there was a substantial decrease in phosphocreatine in the uremic hearts and an accompanying marked increase in release of inosine into the coronary effluent (14.9 vs 6.1 microM, P < 0.01). We conclude that cardiac function is impaired in experimental renal failure, in association with abnormal cardiac energetics and increased susceptibility to ischemic damage. Disordered myocardial calcium utilization may contribute to these derangements. PMID:8254048

  2. EPAC expression and function in cardiac fibroblasts and myofibroblasts

    SciTech Connect

    Olmedo, Ivonne; Muñoz, Claudia; Guzmán, Nancy; Catalán, Mabel; Vivar, Raúl; Ayala, Pedro; Humeres, Claudio; Aránguiz, Pablo; García, Lorena; Velarde, Victoria; Díaz-Araya, Guillermo

    2013-10-15

    In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF were treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in cardiac

  3. Overexpressing Superoxide Dismutase 2 Induces a Supernormal Cardiac Function by Enhancing Redox-dependent Mitochondrial Function and Metabolic Dilation*

    PubMed Central

    Kang, Patrick T.; Chen, Chwen-Lih; Ohanyan, Vahagn; Luther, Daniel J.; Meszaros, J. Gary; Chilian, William M.; Chen, Yeong-Renn

    2015-01-01

    During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate × MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, “spilled” over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function. PMID:26374996

  4. Overexpressing superoxide dismutase 2 induces a supernormal cardiac function by enhancing redox-dependent mitochondrial function and metabolic dilation.

    PubMed

    Kang, Patrick T; Chen, Chwen-Lih; Ohanyan, Vahagn; Luther, Daniel J; Meszaros, J Gary; Chilian, William M; Chen, Yeong-Renn

    2015-11-01

    During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate×MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, "spilled" over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function.

  5. Cardiac nuclear receptors: architects of mitochondrial structure and function.

    PubMed

    Vega, Rick B; Kelly, Daniel P

    2017-04-03

    The adult heart is uniquely designed and equipped to provide a continuous supply of energy in the form of ATP to support persistent contractile function. This high-capacity energy transduction system is the result of a remarkable surge in mitochondrial biogenesis and maturation during the fetal-to-adult transition in cardiac development. Substantial evidence indicates that nuclear receptor signaling is integral to dynamic changes in the cardiac mitochondrial phenotype in response to developmental cues, in response to diverse postnatal physiologic conditions, and in disease states such as heart failure. A subset of cardiac-enriched nuclear receptors serve to match mitochondrial fuel preferences and capacity for ATP production with changing energy demands of the heart. In this Review, we describe the role of specific nuclear receptors and their coregulators in the dynamic control of mitochondrial biogenesis and energy metabolism in the normal and diseased heart.

  6. Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction.

    PubMed

    Efraim, Yael; Sarig, Hadar; Cohen Anavy, Noa; Sarig, Udi; de Berardinis, Elio; Chaw, Su-Yin; Krishnamoorthi, Muthukumar; Kalifa, Jérôme; Bogireddi, Hanumakumar; Duc, Thang Vu; Kofidis, Theodoros; Baruch, Limor; Boey, Freddy Y C; Venkatraman, Subbu S; Machluf, Marcelle

    2017-03-01

    Injectable scaffolds for cardiac tissue regeneration are a promising therapeutic approach for progressive heart failure following myocardial infarction (MI). Their major advantage lies in their delivery modality that is considered minimally invasive due to their direct injection into the myocardium. Biomaterials comprising such scaffolds should mimic the cardiac tissue in terms of composition, structure, mechanical support, and most importantly, bioactivity. Nonetheless, natural biomaterial-based gels may suffer from limited mechanical strength, which often fail to provide the long-term support required by the heart for contraction and relaxation. Here we present newly-developed injectable scaffolds, which are based on solubilized decellularized porcine cardiac extracellular matrix (pcECM) cross-linked with genipin alone or engineered with different amounts of chitosan to better control the gel's mechanical properties while still leveraging the ECM biological activity. We demonstrate that these new biohybrid materials are naturally remodeled by mesenchymal stem cells, while supporting high viabilities and affecting cell morphology and organization. They exhibit neither in vitro nor in vivo immunogenicity. Most importantly, their application in treating acute and long term chronic MI in rat models clearly demonstrates the significant therapeutic potential of these gels in the long-term (12weeks post MI). The pcECM-based gels enable not only preservation, but also improvement in cardiac function eight weeks post treatment, as measured using echocardiography as well as hemodynamics. Infiltration of progenitor cells into the gels highlights the possible biological remodeling properties of the ECM-based platform.

  7. Renal Doppler Resistive Index as a Marker of Oxygen Supply and Demand Mismatch in Postoperative Cardiac Surgery Patients

    PubMed Central

    Corradi, Francesco; Brusasco, Claudia; Paparo, Francesco; Manca, Tullio; Santori, Gregorio; Benassi, Filippo; Molardi, Alberto; Gallingani, Alan; Ramelli, Andrea; Gherli, Tiziano; Vezzani, Antonella

    2015-01-01

    Background and Objective. Renal Doppler resistive index (RDRI) is a noninvasive index considered to reflect renal vascular perfusion. The aim of this study was to identify the independent hemodynamic determinants of RDRI in mechanically ventilated patients after cardiac surgery. Methods. RDRI was determined in 61 patients by color and pulse Doppler ultrasonography of the interlobar renal arteries. Intermittent thermodilution cardiac output measurements were obtained and blood samples taken from the tip of pulmonary artery catheter to measure hemodynamics and mixed venous oxygen saturation (SvO2). Results. By univariate analysis, RDRI was significantly correlated with SvO2, oxygen extraction ratio, left ventricular stroke work index, and cardiac index, but not heart rate, central venous pressure, mean artery pressure, pulmonary capillary wedge pressure, systemic vascular resistance index, oxygen delivery index, oxygen consumption index, arterial lactate concentration, and age. However, by multivariate analysis RDRI was significantly correlated with SvO2 only. Conclusions. The present data suggests that, in mechanically ventilated patients after cardiac surgery, RDRI increases proportionally to the decrease in SvO2, thus reflecting an early vascular response to tissue hypoxia. PMID:26605339

  8. The relationship between positive end expiratory pressure and cardiac index in patients with acute respiratory distress syndrome

    PubMed Central

    Fares, Wassim H; Carson, Shannon S

    2013-01-01

    Purpose To evaluate the association between positive end-expiratory pressure (PEEP) and cardiac index in patients with acute respiratory distress syndrome (ARDS). Methods This is a secondary cross-sectional analysis of the FACTT multi-center randomized controlled trial enrolling adult patients within 48 hours of ARDS onset. Patients randomized to the pulmonary artery catheter arm, who had PEEP and cardiac index measurements performed within a short period of each other during the first 3 days of the FACTT study enrollment were included in this study. Since FACTT had a 2×2 factorial design, half of the patients were in a ‘liberal fluids’ study arm, and the other half were in a ‘conservative fluids’ study arm. Results The final study population (833 measurements or observations, in 367 patients) was comparable to the original overall FACTT study population. The mean PEEP level used was 8.2 ± 3.4 cm H2O, and the mean cardiac index was 4.2 ± 1.2 liters/minute/m2. There was no association between PEEP and cardiac index in patients with ARDS, even when adjusted for APACHE score, age, fluid study arm in FACTT, and sepsis. Conclusion In patients with ARDS who are managed with liberal or conservative fluid management protocols, PEEP is not associated with lower cardiac index. PMID:23993772

  9. Longitudinal changes of cardiac structure and function in CKD (CASCADE study).

    PubMed

    Cai, Qi-Zhe; Lu, Xiu-Zhang; Lu, Ye; Wang, Angela Yee-Moon

    2014-07-01

    Little is known regarding the natural longitudinal changes in cardiac structure and function in CKD. We hypothesized that baseline CKD stage is associated with progressive worsening in cardiac structure and function. We conducted a prospective longitudinal study, recruiting 300 patients with stages 3-5 CKD from a major regional tertiary center and university teaching hospital in Hong Kong. Baseline CKD stages were studied in relation to natural longitudinal changes in echocardiographic and tissue Doppler imaging-derived parameters. Over 1 year, the prevalence of left ventricular (LV) hypertrophy increased from 40.3% to 48.9%, median left atrial volume index increased 4.8 (interquartile range [IQR], 2.1, 7.7) ml/m(2) (P<0.001), peak systolic mitral annular velocity decreased 0.5 (IQR, -1.5, 0.5) cm/s (P<0.001), early diastolic mitral annular velocity decreased 0.5 (IQR, -1.5, 0.5) cm/s (P<0.001), and eGFR declined 2.0 (IQR, -5.0, 0.0) ml/min per 1.73 m(2). CKD stages 4 and 5 were associated with more baseline abnormalities in cardiac structure and function and predicted greater longitudinal progression in LV mass index (odds ratio [OR], 3.02; 95% confidence interval [95% CI], 1.39 to 6.58), volume index (OR, 2.58; 95% CI, 1.18 to 5.62), and left atrial volume index (OR, 2.61; 95% CI, 1.20 to 5.69) and worse diastolic dysfunction grade (OR, 3.17; 95% CI, 1.16 to 8.69) compared with stage 3a in the fully adjusted analysis. In conclusion, more advanced CKD at baseline may be associated with larger longitudinal increases in LV mass and volume and greater deterioration in diastolic function.

  10. Propofol Induction's Effect on Cardiac Function

    ClinicalTrials.gov

    2015-03-31

    This Study Was Focused to Evaluate Feasibility of Doppler Tissue Monitoring During the Induction Anesthesia,; and Evaluate Routine Propofol Induction's Effect on Myocardial Tissue Motion, Using Non-invasive Doppler Tissue and 2D Speckle Tracking Imaging.; This is the First Study, to Our Knowledge, Which Has Evaluated the Possible Impact of Propofol Induction on LV Function.

  11. Cardiac Autonomic Functions in Obese Children

    PubMed Central

    Taşçılar, Mehmet Emre; Yokuşoğlu, Mehmet; Boyraz, Mehmet; Baysan, Oben; Köz, Cem; Dündaröz, Ruşen

    2011-01-01

    Objective: The autonomic nervous system is assumed to have a role in the pathophysiology of obesity. In this study, we evaluated the autonomic system by measuring heart rate variability (HRV) in obese children. Methods: Thirty-two obese and 30 healthy children (mean ages: 11.6±2.0 years and 11.0±2.9 years, respectively) were enrolled in the study. Obesity was defined as a body mass index higher than 97th percentile for age- and gender-specific reference values. All participants were free of any disease and none of them was receiving any medication. Twenty-four-hour ambulatory electrocardiographic recordings were obtained and the time-domain and frequency-domain indices of HRV were analyzed. The study group was evaluated with respect to insulin resistance by HOMA-IR values. Results: A significant decrease in calculated HRV variables was observed in obese children as compared to controls. The HRV alteration was found in both time-domain and frequency-domain parameters. The subgroup analysis of the study group revealed a significant decrease in all investigated HRV parameters in the insulin-resistant obese children compared to the non-insulin-resistant obese ones. Conclusions: Our results indicate that HRV is decreased in obese children, which implies parasympathetic withdrawal and sympathetic predominance. A marked decrease in HRV was observed in insulin-resistant obese children compared to their non-insulin-resistant counterparts. We propose that autonomic imbalance pertaining especially to insulin resistance may be involved in the pathogenesis of obesity in pediatric patients Conflict of interest:None declared. PMID:21750633

  12. Skeletal and cardiac muscle pericytes: Functions and therapeutic potential.

    PubMed

    Murray, Iain R; Baily, James E; Chen, William C W; Dar, Ayelet; Gonzalez, Zaniah N; Jensen, Andrew R; Petrigliano, Frank A; Deb, Arjun; Henderson, Neil C

    2017-03-01

    Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease.

  13. Impaired regulation of cardiac function in sepsis, SIRS, and MODS.

    PubMed

    Werdan, Karl; Schmidt, Hendrik; Ebelt, Henning; Zorn-Pauly, Klaus; Koidl, Bernd; Hoke, Robert Sebastian; Heinroth, Konstantin; Müller-Werdan, Ursula

    2009-04-01

    In sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction syndrome (MODS), a severe prognostically relevant cardiac autonomic dysfunction exists, as manifested by a strong attenuation of sympathetically and vagally mediated heart rate variability (HRV). The mechanisms underlying this attenuation are not limited to the nervous system. They also include alterations of the cardiac pacemaker cells on a cellular level. As shown in human atrial cardiomyocytes, endotoxin interacts with cardiac hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, which mediate the pacemaker current If and play an important role in transmitting sympathetic and vagal signals on heart rate and HRV. Moreover, endotoxin sensitizes cardiac HCN channels to sympathetic signals. These findings identify endotoxin as a pertinent modulator of the autonomic nervous regulation of heart function. In MODS, the vagal pathway of the autonomic nervous system is particularly compromised, leading to an attenuation of the cholinergic antiinflammatory reflex. An amelioration of the blunted vagal activity appears to be a promising novel therapeutic target to achieve a suppression of the inflammatory state and thereby an improvement of prognosis in MODS patients. Preliminary data revealed therapeutic benefits (increased survival rates and improvements of the depressed vagal activity) of the administration of statins, beta-blockers, and angiotensin-converting enzyme inhibitors in patients with MODS.

  14. Early treatment with hepatocyte growth factor improves cardiac function in experimental heart failure induced by myocardial infarction.

    PubMed

    Jin, Hongkui; Yang, Renhui; Li, Wei; Ogasawara, Annie K; Schwall, Ralph; Eberhard, David A; Zheng, Zhong; Kahn, David; Paoni, Nicholas F

    2003-02-01

    Plasma levels of hepatocyte growth factor (HGF) are increased within hours of cardiac ischemia/reperfusion in rats, and HGF has been shown to be cardioprotective toward acute ischemic injury. Myocardial levels of HGF mRNA and protein are increased for several days after myocardial infarction (MI), however, indicating a possible additional protective effect of HGF toward the progression of MI to heart failure. The purpose of this study was to determine whether HGF administration during the time course of endogenous cardiac HGF induction would lead to long-term improvement in cardiac function in rats with MI. MI was induced by 2-h occlusion of the left coronary artery, followed by reperfusion. HGF was given by intravenous infusion at 0.45 mg/kg/day for 6 days beginning on the day after surgery. Cardiac function and hemodynamic parameters were measured by using indwelling catheters and perivascular flow probes in conscious animals 8 weeks post-MI. Myocardial infarcts were approximately 30% of the left ventricle, and there was no difference in infarct size between the vehicle-treated and HGF-treated groups. Compared with untreated sham-operated rats, vehicle-treated MI animals had significantly lower cardiac index and stroke volume index and higher systemic vascular resistance, indicating heart failure developed. Treatment with HGF caused a significant increase in cardiac index and stroke volume index and a reduction in systemic vascular resistance in rats with MI, restoring these parameters close to those observed in sham-operated control animals. These results provide direct evidence that HGF may be of benefit to cardiovascular function in ischemic cardiomyopathy.

  15. Liver Function Tests Following Open Cardiac Surgery

    PubMed Central

    Sabzi, Feridoun; Faraji, Reza

    2015-01-01

    Introduction: The cardiopulmonary bypass may have multiple systemic effects on the body organs as liver. This prospective study was planned to explore further the incidence and significance of this change. Methods: Two hundred patients with coronary artery bypass grafting (CABG), were randomly selected for the study. Total and indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase were measured preoperatively and at 24, 48 and 72 hours, following coronary artery bypass grafting. Postoperative value of the liver function tests with respect to hypothermia or hypotension were compared by one way analysis of variance for repeated measure and compared with t test. Patient’s characteristics with bilirubin value (≤1.5 mg or >1.5 mg) were compared with t test. Results: A significant increase of total bilirubin, aspartate aminotransferase, and alkaline phosphatase were noted in the third postoperative day. Significant relation was seen between hypotension and alkaline phosphatase, and aspartate aminotransferase change but hypothermia had not affected alanine aminotransferase, total bilirubin and indirect bilirubin change. Pump time, alanine aminotransferase in third postoperative day and direct bilirubin in first and second day of postoperative period had significant relation with pre and post-operative bilirubin change. Conclusion: Transient but not permanent alterations of hepatic enzymes after coronary artery bypass grafting presumably attributed to the decreased hepatic flow, hypoxia, or pump-induced inflammation. PMID:26191391

  16. Functional and hemodynamic cardiac determinants of exercise capacity in patients with systolic heart failure.

    PubMed

    Hummel, Yoran M; Bugatti, Silvia; Damman, Kevin; Willemsen, Suzan; Hartog, Jasper W L; Metra, Marco; Sipkens, Johannes S; van Veldhuisen, Dirk J; Voors, Adriaan A

    2012-11-01

    Decreased exercise capacity is the main symptom in patients with heart failure (HF). We assessed the association among noninvasively determined maximal cardiac output at exercise, systolic and diastolic cardiac functions at rest, and peak oxygen uptake (pVo(2)) exercise capacity in patients with congestive HF. We studied 102 patients 62 ± 11 years of age with New York Heart Association class II to IV stable HF and left ventricular (LV) ejection fraction <45%. All patients underwent echocardiography and a treadmill cardiopulmonary exercise test for evaluation of pVo(2) corrected for fat-free mass. During the cardiopulmonary exercise test, cardiac output was estimated noninvasively and continuously using Nexfin HD. Fat-free mass-corrected pVo(2) was associated in an univariate linear regression analysis with peak exercise cardiac index (CI) (beta 0.511, p <0.001), LV end-diastolic pressure estimates (peak early diastolic filling velocity/early diastolic tissue velocity [E/e'], beta -0.363, p = 0.001), and right ventricular function (tricuspid annular plane systolic excursion, beta 0.393, p <0.001). In multivariate analysis peak exercise CI (beta 0.380, p = 0.001), but not cardiac output or LV ejection fraction at rest, was an independent predictor of pVo(2). Other independent predictors of pVo(2) were E/e' (beta -0.276, p = 0.009) and tricuspid annular plane systolic excursion (beta 0.392, p <0.001), also when adjusted for age and gender. In conclusion, peak CI is an independent predictor of fat-free mass-corrected pVo(2) in patients with systolic HF. Of all echocardiographic parameters at rest, right ventricular function and E/e' were independently and significantly associated with pVo(2), whereas LV ejection fraction at rest was not.

  17. Relationship between indexed epicardial fat volume and coronary plaque volume assessed by cardiac multidetector CT

    PubMed Central

    You, Seulgi; Sun, Joo Sung; Park, Seon Young; Baek, Yoolim; Kang, Doo Kyoung

    2016-01-01

    Abstract We explored whether baseline indexed epicardial fat volume (EFVi) and serial changes in EFVi were associated with increase in coronary plaque volume as assessed by multidetector computed tomography. We retrospectively reviewed 87 patients with coronary artery plaque, identified during either baseline or follow-up cardiac computed tomography (CT) examinations. Each plaque volume was measured in volumetric units using a semiautomatic software tool. EFVi was quantified by calculating the total volume of epicardial tissue of CT density −190 to −30 HU, indexed to the body surface area. Clinical cardiovascular risk factors were extracted by medical record review at the time of the cardiac CT examinations. The relationship between EFVi and coronary plaque volume was explored by regression analysis. Although the EFVi did not change significantly from baseline to the time of the follow-up CT (65.7 ± 21.8 vs 66.0 ± 21.8 cm3/m3, P = 0.620), the plaque volumes were increased significantly on the follow-up CT scans. The annual change in EFVi was not accompanied by a parallel change in coronary plaque volume (P = 0.096–0.500). On univariate analysis, smoking, hypercholesterolemia, 10-year coronary heart disease risk, obesity, and baseline EFVi predicted rapid increases in lipid-rich and fibrous plaque volumes. On multivariate analysis, baseline EFVi (odds ratio = 1.029, P = 0.016) was an independent predictor of a rapid increase in lipid-rich plaque volume. EFVi was shown to be an independent predictor of a rapid increase in lipid-rich plaque volume. However, changes in EFVi were not associated with parallel changes in coronary plaque volume. PMID:27399137

  18. Motion corrected LV quantification based on 3D modelling for improved functional assessment in cardiac MRI

    NASA Astrophysics Data System (ADS)

    Liew, Y. M.; McLaughlin, R. A.; Chan, B. T.; Aziz, Y. F. Abdul; Chee, K. H.; Ung, N. M.; Tan, L. K.; Lai, K. W.; Ng, S.; Lim, E.

    2015-04-01

    Cine MRI is a clinical reference standard for the quantitative assessment of cardiac function, but reproducibility is confounded by motion artefacts. We explore the feasibility of a motion corrected 3D left ventricle (LV) quantification method, incorporating multislice image registration into the 3D model reconstruction, to improve reproducibility of 3D LV functional quantification. Multi-breath-hold short-axis and radial long-axis images were acquired from 10 patients and 10 healthy subjects. The proposed framework reduced misalignment between slices to subpixel accuracy (2.88 to 1.21 mm), and improved interstudy reproducibility for 5 important clinical functional measures, i.e. end-diastolic volume, end-systolic volume, ejection fraction, myocardial mass and 3D-sphericity index, as reflected in a reduction in the sample size required to detect statistically significant cardiac changes: a reduction of 21-66%. Our investigation on the optimum registration parameters, including both cardiac time frames and number of long-axis (LA) slices, suggested that a single time frame is adequate for motion correction whereas integrating more LA slices can improve registration and model reconstruction accuracy for improved functional quantification especially on datasets with severe motion artefacts.

  19. Teaching cardiac autonomic function dynamics employing the Valsalva (Valsalva-Weber) maneuver.

    PubMed

    Junqueira, Luiz Fernando

    2008-03-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated, and some guidelines are established for simple application of the maneuver in a teaching or research laboratory setting. These include the hemodynamic and cardiac autonomic mechanisms involved, technical aspects such as the intensity and duration of the expiratory straining, frequency of maneuver sessions, training and posture of the individuals tested, different time- and grade change-dependent indexes of heart interval variation, and clinical application of the maneuver.

  20. Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.

    PubMed

    Wyrwoll, Caitlin S; Noble, June; Thomson, Adrian; Tesic, Dijana; Miller, Mark R; Rog-Zielinska, Eva A; Moran, Carmel M; Seckl, Jonathan R; Chapman, Karen E; Holmes, Megan C

    2016-05-31

    Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction.

  1. Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess

    PubMed Central

    Wyrwoll, Caitlin S.; Noble, June; Thomson, Adrian; Tesic, Dijana; Miller, Mark R.; Rog-Zielinska, Eva A.; Moran, Carmel M.; Seckl, Jonathan R.; Chapman, Karen E.; Holmes, Megan C.

    2016-01-01

    Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2−/− mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2+/+, Hsd11b2+/−, and Hsd11b2−/− littermates from heterozygous (Hsd11b+/−) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2−/− fetuses did not undergo the normal gestational increase seen in Hsd11b2+/+ littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2−/− fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2−/− fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2−/− fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction. PMID:27185937

  2. On the mechanics of cardiac function of Drosophila embryo.

    PubMed

    Wu, Mingming; Sato, Thomas N

    2008-01-01

    The heart is a vital organ that provides essential circulation throughout the body. Malfunction of cardiac pumping, thus, leads to serious and most of the times, to fatal diseases. Mechanics of cardiac pumping is a complex process, and many experimental and theoretical approaches have been undertaken to understand this process. We have taken advantage of the simplicity of the embryonic heart of an invertebrate, Drosophila melanogaster, to understand the fundamental mechanics of the beating heart. We applied a live imaging technique to the beating embryonic heart combined with analytical imaging tools to study the dynamic mechanics of the pumping. Furthermore, we have identified one mutant line that exhibits aberrant pumping mechanics. The Drosophila embryonic heart consists of only 104 cardiac cells forming a simple straight tube that can be easily accessed for real-time imaging. Therefore, combined with the wealth of available genetic tools, the embryonic Drosophila heart may serve as a powerful model system for studies of human heart diseases, such as arrhythmia and congenital heart diseases. We, furthermore, believe our mechanistic data provides important information that is useful for our further understanding of the design of biological structure and function and for engineering the pumps for medical uses.

  3. Effects of Allicin on Hypertension and Cardiac Function in Chronic Kidney Disease.

    PubMed

    García-Trejo, Ehécatl M A; Arellano-Buendía, Abraham S; Argüello-García, Raúl; Loredo-Mendoza, María L; García-Arroyo, Fernando E; Arellano-Mendoza, Mónica G; Castillo-Hernández, María C; Guevara-Balcázar, Gustavo; Tapia, Edilia; Sánchez-Lozada, Laura G; Osorio-Alonso, Horacio

    2016-01-01

    This work was performed to study the effect of allicin on hypertension and cardiac function in a rat model of CKD. The groups were control, CKD (5/6 nephrectomy), and CKD-allicin treated (CKDA) (40 mg/kg day/p.o.). Blood pressure was monitored (weekly/6 weeks). The cardiac function, vascular response to angiotensin II, oxidative stress, and heart morphometric parameters were determined. The CKD group showed hypertension and proteinuria. The coronary perfusion and left ventricular pressures were decreased in CKD group. In contrast, the vascular response to angiotensin II and expression of angiotensin II type 1 receptor (AT1R) were increased. These data were associated with the increment in morphometric parameters (weight of heart and left ventricle, heart/BW and left ventricular mass index, and wall thickness). Concurrently, the oxidative stress was increased and correlated inversely with the expression of Nrf2, Keap1, and antioxidant enzymes Nrf2-regulated. Allicin treatment attenuated hypertension and improved the renal and the cardiac dysfunctions; furthermore, it decreased the vascular reactivity to angiotensin II, AT1R overexpression, and preserved morphometric parameters. Allicin also downregulated Keap1 and increased Nrf2 expression, upregulated the antioxidant enzymes, and reduced oxidative stress. In conclusion, allicin showed an antihypertensive, nephroprotective, cardioprotective, and antioxidant effects, likely through downregulation of AT1R and Keap1 expression.

  4. Effects of Allicin on Hypertension and Cardiac Function in Chronic Kidney Disease

    PubMed Central

    Guevara-Balcázar, Gustavo; Sánchez-Lozada, Laura G.

    2016-01-01

    This work was performed to study the effect of allicin on hypertension and cardiac function in a rat model of CKD. The groups were control, CKD (5/6 nephrectomy), and CKD-allicin treated (CKDA) (40 mg/kg day/p.o.). Blood pressure was monitored (weekly/6 weeks). The cardiac function, vascular response to angiotensin II, oxidative stress, and heart morphometric parameters were determined. The CKD group showed hypertension and proteinuria. The coronary perfusion and left ventricular pressures were decreased in CKD group. In contrast, the vascular response to angiotensin II and expression of angiotensin II type 1 receptor (AT1R) were increased. These data were associated with the increment in morphometric parameters (weight of heart and left ventricle, heart/BW and left ventricular mass index, and wall thickness). Concurrently, the oxidative stress was increased and correlated inversely with the expression of Nrf2, Keap1, and antioxidant enzymes Nrf2-regulated. Allicin treatment attenuated hypertension and improved the renal and the cardiac dysfunctions; furthermore, it decreased the vascular reactivity to angiotensin II, AT1R overexpression, and preserved morphometric parameters. Allicin also downregulated Keap1 and increased Nrf2 expression, upregulated the antioxidant enzymes, and reduced oxidative stress. In conclusion, allicin showed an antihypertensive, nephroprotective, cardioprotective, and antioxidant effects, likely through downregulation of AT1R and Keap1 expression. PMID:27990229

  5. Novel MRI-derived quantitative biomarker for cardiac function applied to classifying ischemic cardiomyopathy within a Bayesian rule learning framework

    NASA Astrophysics Data System (ADS)

    Menon, Prahlad G.; Morris, Lailonny; Staines, Mara; Lima, Joao; Lee, Daniel C.; Gopalakrishnan, Vanathi

    2014-03-01

    Characterization of regional left ventricular (LV) function may have application in prognosticating timely response and informing choice therapy in patients with ischemic cardiomyopathy. The purpose of this study is to characterize LV function through a systematic analysis of 4D (3D + time) endocardial motion over the cardiac cycle in an effort to define objective, clinically useful metrics of pathological remodeling and declining cardiac performance, using standard cardiac MRI data for two distinct patient cohorts accessed from CardiacAtlas.org: a) MESA - a cohort of asymptomatic patients; and b) DETERMINE - a cohort of symptomatic patients with a history of ischemic heart disease (IHD) or myocardial infarction. The LV endocardium was segmented and a signed phase-to-phase Hausdorff distance (HD) was computed at 3D uniformly spaced points tracked on segmented endocardial surface contours, over the cardiac cycle. An LV-averaged index of phase-to-phase endocardial displacement (P2PD) time-histories was computed at each tracked point, using the HD computed between consecutive cardiac phases. Average and standard deviation in P2PD over the cardiac cycle was used to prepare characteristic curves for the asymptomatic and IHD cohort. A novel biomarker of RMS error between mean patient-specific characteristic P2PD over the cardiac cycle for each individual patient and the cumulative P2PD characteristic of a cohort of asymptomatic patients was established as the RMS-P2PD marker. The novel RMS-P2PD marker was tested as a cardiac function based feature for automatic patient classification using a Bayesian Rule Learning (BRL) framework. The RMS-P2PD biomarker indices were significantly different for the symptomatic patient and asymptomatic control cohorts (p<0.001). BRL accurately classified 83.8% of patients correctly from the patient and control populations, with leave-one-out cross validation, using standard indices of LV ejection fraction (LV-EF) and LV end-systolic volume

  6. Isosmotic media prevent edema in amphibian larvae without cardiac function.

    PubMed

    Smith, S C

    2000-03-01

    The absence of cardiac and circulatory function causes severe edema in amphibian embryos. Analyzing the roles of embryonic and larval circulation in respiration may thus be confounded by the increased diffusion distance and decreased surface area/volume ratio caused by edema. Similarly, detailed morphological analyses of embryos/larvae with defective circulatory or renal function is difficult or impossible due to the gross morphological anomalies engendered by edematous swelling. To circumvent these problems, two media have been developed which are isosmotic with the plasma of a common experimental amphibian species (Ambystoma mexicanun). These media are remarkably effective in preventing fluid accumulation in embryos and larvae lacking heart function and, when used in slightly lower concentrations, cause no apparent harm to embryos and larvae with normal circulation for periods up to 3 weeks. These media should prove useful for a variety of studies on the developmental physiology of the circulatory system and possibly also when examining the development of renal function and ionoregulation.

  7. Calculation of electron wave functions and refractive index of Ne

    NASA Astrophysics Data System (ADS)

    Zhu, Min; Liu, Wei; Zhang, Tao

    2008-10-01

    The radial wave functions of inner electron shell and outer electron shell of a Ne atom were obtained by the approximate analytical method and tested by calculating the ground state energy of the Ne atom. The equivalent volume of electron cloud and the refractive index of Ne were calculated. The calculated refractive index agrees well with the experimental result. Relationship between the refractive index and the wave function of Ne was discovered.

  8. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    NASA Astrophysics Data System (ADS)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  9. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    PubMed Central

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-01-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

  10. Carnitine levels and cardiac functions in children with solid malignancies receiving doxorubicin therapy

    PubMed Central

    Khositseth, Anant; Jirasakpisarn, Suwadee; Pakakasama, Samart; Choubtuym, Lulin; Wattanasirichaigoon, Duangrurdee

    2011-01-01

    Aim: Previous studies demonstrated l-carnitine decreasing doxorubicin-induced cardiotoxicity. Our objectives were to study carnitine levels and cardiac functions in children treated with doxorubicin and the effect of short-term l-carnitine supplements. Materials and Methods: Serial carnitine levels and cardiac functions were obtained in children with newly diagnosed solid malignancies before doxorubicin, after cumulative doses of ≥150 mg/m2 and ≥300 mg/m2, respectively. Oral l-carnitine 100 mg/kg/day for 3 days were given to the children treated with doxorubicin at cumulative doses of ≥150 mg/m2 and ≥300 mg/m2. Carnitine levels and cardiac functions were also obtained in those children before and after short-term oral l-carnitine at each cumulative dose of doxorubicin. Results: Five children (3 females), median age of 9.1 years (range 1.5–13 years) with newly diagnosed solid malignancies were enrolled in the study. Free carnitine (FC) tended to decrease while acyl-carnitine (AC) increased making AC/FC ratio increased after cumulative dose of ≥150 and ≥300 mg/m2 but the statistics was not significant. Left ventricular (LV) systolic function was not significantly changed. Interestingly, LV global function (LV myocardial performance index) was significantly increased after 150 mg/m2 (median 0.39, 0.27–0.51) and 300 mg/2 (median 0.46, 0.27–0.50) when compared to baseline (median 0.28, 0.14–0.48) (P=0.05). Carnitine levels and cardiac functions were not significantly changed after oral l-carnitine supplement at cumulative dose of ≥150 mg/m2 (n=6) and ≥300 mg/m2 (n=9). Conclusions: Carnitine levels tended to decrease after doxorubicin treatment. LV global dysfunction was documented early after doxorubicin. However, short-term l-carnitine supplement did not improve cardiac function. PMID:21731215

  11. Effect of prolonged space flight on cardiac function and dimensions

    NASA Technical Reports Server (NTRS)

    Henry, W. L.; Epstein, S. E.; Griffith, J. M.; Goldstein, R. E.; Redwood, D. R.

    1974-01-01

    Echocardiographic studies were performed preflight 5 days before launch and on recovery day and 1, 2, 4, 11, 31 and 68 days postflight. From these echocardiograms measurements were made. From these primary measurements, left ventricular end-diastolic volume, end-systolic volume, stroke volume, and mass were derived using the accepted assumptions. Findings in the Scientist Pilot and Pilot resemble those seen in trained distance runners. Wall thickness measurements were normal in all three crewmembers preflight. Postflight basal studies were unchanged in the Commander on recovery day through 68 days postflight in both the Scientist Pilot and Pilot, however, the left ventricular end-diastolic volume, stroke volume, and mass were decreased slightly. Left ventricular function curves were constructed for the Commander and Pilot by plotting stroke volume versus end-diastolic volume. In both astronauts, preflight and postflight data fell on the same straight line demonstrating that no deterioration in cardiac function had occurred. These data indicate that the cardiovascular system adapts well to prolonged weightlessness and suggest that alterations in cardiac dimensions and function are unlikely to limit man's future in space.

  12. Decreased Bioenergetic Health Index in monocytes isolated from the pericardial fluid and blood of post-operative cardiac surgery patients.

    PubMed

    Kramer, Philip A; Chacko, Balu K; George, David J; Zhi, Degui; Wei, Chih-Cheng; Dell'Italia, Louis J; Melby, Spencer J; George, James F; Darley-Usmar, Victor M

    2015-07-01

    Monitoring the bioenergetics of leucocytes is now emerging as an important approach in translational research to detect mitochondrial dysfunction in blood or other patient samples. Using the mitochondrial stress test, which involves the sequential addition of mitochondrial inhibitors to adherent leucocytes, we have calculated a single value, the Bioenergetic Health Index (BHI), which represents the mitochondrial function in cells isolated from patients. In the present report, we assess the BHI of monocytes isolated from the post-operative blood and post-operative pericardial fluid (PO-PCF) from patients undergoing cardiac surgery. Analysis of the bioenergetics of monocytes isolated from patients' PO-PCF revealed a profound decrease in mitochondrial function compared with monocytes isolated from their blood or from healthy controls. Further, patient blood monocytes showed no significant difference in the individual energetic parameters from the mitochondrial stress test but, when integrated into the BHI evaluation, there was a significant decrease in BHI compared with healthy control monocytes. These data support the utility of BHI measurements in integrating the individual parameters from the mitochondrial stress test into a single value. Supporting our previous finding that the PO-PCF is pro-oxidant, we found that exposure of rat cardiomyocytes to PO-PCF caused a significant loss of mitochondrial membrane potential and increased reactive oxygen species (ROS). These findings support the hypothesis that integrated measures of bioenergetic health could have prognostic and diagnostic value in translational bioenergetics.

  13. Gate-based decomposition of index generation functions

    NASA Astrophysics Data System (ADS)

    Łuba, Tadeusz; Borowik, Grzegorz; Jankowski, Cezary

    2016-09-01

    Index Generation Functions may be useful in distribution of IP addresses, virus scanning, or undesired data detection. Traditional approach leads to universal cells based decomposition. In this paper an original method is proposed. The proposed multilevel logic synthesis method based on functional decomposition uses gates instead of cells. Furthermore, it preserves advantages of functional decomposition and is well suited for ROM-based synthesis of Index Generation Functions.

  14. The effect of childhood obesity on cardiac functions.

    PubMed

    Üner, Abdurrahman; Doğan, Murat; Epcacan, Zerrin; Epçaçan, Serdar

    2014-03-01

    Obesity is a metabolic disorder defined as excessive accumulation of body fat, which is made up of genetic, environmental, and hormonal factors and has various social, psychological, and medical complications. Childhood obesity is a major indicator of adult obesity. The aim of this study is to evaluate the cardiac functions via electrocardiography (ECG), echocardiography (ECHO), and treadmill test in childhood obesity. A patient group consisting of 30 obese children and a control group consisting of 30 non-obese children were included in the study. The age range was between 8 and 17 years. Anthropometric measurements, physical examination, ECG, ECHO, and treadmill test were done in all patients. P-wave dispersion (PD) was found to be statistically significantly high in obese patients. In ECHO analysis, we found that end-diastolic diameter, end-systolic diameter, left ventricle posterior wall thickness, and interventricular septum were significantly greater in obese children. In treadmill test, exercise capacity was found to be significantly lower and the hemodynamic response to exercise was found to be defective in obese children. Various cardiac structural and functional changes occur in childhood obesity and this condition includes important cardiovascular risks. PD, left ventricle end-systolic and end-diastolic diameter, left ventricle posterior wall thickness, interventricular septum thickness, exercise capacity, and hemodynamic and ECG measurements during exercise testing are useful tests to determine cardiac dysfunctions and potential arrhythmias even in early stages of childhood obesity. Early recognition and taking precautions for obesity during childhood is very important to intercept complications that will occur in adulthood.

  15. Cytoskeletal Basis of Ion Channel Function in Cardiac Muscle

    PubMed Central

    Vatta, Matteo; Faulkner, Georgine

    2009-01-01

    Summary The heart is a force-generating organ that responds to self-generated electrical stimuli from specialized cardiomyocytes. This function is modulated by sympathetic and parasympathetic activity. In order to contract and accommodate the repetitive morphological changes induced by the cardiac cycle, cardiomyocytes depend on their highly evolved and specialized cytoskeletal apparatus. Defects in components of the cytoskeleton, in the long term, affect the ability of the cell to compensate at both functional and structural levels. In addition to the structural remodeling, the myocardium becomes increasingly susceptible to altered electrical activity leading to arrhythmogenesis. The development of arrhythmias secondary to structural remodeling defects has been noted, although the detailed molecular mechanisms are still elusive. Here I will review the current knowledge of the molecular and functional relationships between the cytoskeleton and ion channels and, I will discuss the future impact of new data on molecular cardiology research and clinical practice. PMID:19774097

  16. Influence of basal nitric oxide secretion on cardiac function in man.

    PubMed Central

    Clarkson, P B; Lim, P O; MacDonald, T M

    1995-01-01

    1. Nitric oxide is recognised as an important biological mediator, which is thought to be involved in cardiovascular homeostasis. The purpose of this study was to investigate the effects of basal nitric oxide synthesis on cardiac function in man, by blocking nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA). 2. Eight normal volunteers were studied on two separate occasions. Measurements of heart rate, blood pressure and echocardiographic indices of left ventricular systolic and diastolic function were made at baseline on each day and every 20 min during incremental infusion of L-NMMA (0.1, 0.2, 0.5, 1.0 and 2.0 mg kg-1 h-1) or placebo. 3. A trend towards reduction in heart rate was observed with L-NMMA infusion although this did not reach statistical significance, whereas significant increases in both systolic blood pressure (at 2.0 mg kg-1 h-1) and systemic vascular resistance index (at 0.5 mg kg-1 h-1) were seen. 4. L-NMMA infusion caused significant reductions in stroke distance and cardiac index, although there was no change in the ratio of end systolic wall stress/end systolic volume index (an afterload independent index of left ventricular systolic performance). 5. The isovolumic relaxation time significantly increased with L-NMMA infusion, together with a significant reduction in the 'E' wave flow velocity integral. Reductions in both peak E/A ratio and E/A flow velocity integral ratio were also seen, although these failed to reach statistical significance. 6. In conclusion, the basal generation of nitric oxide in man appears to maintain a vasodilated state, and modifies left ventricular diastolic filling parameters. PMID:8554930

  17. Cardiac myosin-binding protein C decorates F-actin: Implications for cardiac function

    PubMed Central

    Whitten, Andrew E.; Jeffries, Cy M.; Harris, Samantha P.; Trewhella, Jill

    2008-01-01

    Cardiac myosin-binding protein C (cMyBP-C) is an accessory protein of striated muscle sarcomeres that is vital for maintaining regular heart function. Its 4 N-terminal regulatory domains, C0-C1-m-C2 (C0C2), influence actin and myosin interactions, the basic contractile proteins of muscle. Using neutron contrast variation data, we have determined that C0C2 forms a repeating assembly with filamentous actin, where the C0 and C1 domains of C0C2 attach near the DNase I-binding loop and subdomain 1 of adjacent actin monomers. Direct interactions between the N terminus of cMyBP-C and actin thereby provide a mechanism to modulate the contractile cycle by affecting the regulatory state of the thin filament and its ability to interact with myosin. PMID:19011110

  18. Wave intensity analysis in mice: age-related changes in WIA peaks and correlation with cardiac indexes.

    PubMed

    Di Lascio, Nicole; Kusmic, Claudia; Stea, Francesco; Faita, Francesco

    2016-11-03

    Mouse models are increasingly employed in the comprehension of cardiovascular disease. Wave Intensity Analysis (WIA) can provide information about the interaction between the vascular and the cardiac system. We investigate age-associated changes in WIA-derived parameters in mice and correlate them with biomarkers of cardiac function. Sixteen wild-type male mice were imaged with high-resolution ultrasound (US) at 8 weeks (T 0) and 25 weeks (T 1) of age. Carotid pulse wave velocity (PWV) was calculated from US images using the diameter-velocity loop and employed to evaluate WIA. Amplitudes of the first (W 1) and the second (W 2) local maxima, local minimum (W b) and the reflection index (RI = W b/W 1) were assessed. Cardiac output (CO), ejection fraction (EF), fractional shortening (FS) and stroke volume (SV) were evaluated; longitudinal, radial and circumferential strain and strain rate values (LS, LSR, RS, RSR, CS, CSR) were obtained through strain analysis. W 1 (T 0: 4.42e-07 ± 2.32e-07 m(2)/s; T 1: 2.21e-07 ± 9.77 m(2)/s), W 2 (T 0: 2.45e-08 ± 9.63e-09 m(2)/s; T 1: 1.78e-08 ± 7.82 m(2)/s), W b (T 0: -8.75e-08 ± 5.45e-08 m(2)/s; T 1: -4.28e-08 ± 2.22e-08 m(2)/s), CO (T 0: 19.27 ± 4.33 ml/min; T 1: 16.71 ± 2.88 ml/min), LS (T 0: 17.55 ± 3.67%; T 1: 15.05 ± 2.89%), LSR (T 0: 6.02 ± 1.39 s(-1); T 1: 5.02 ± 1.25 s(-1)), CS (T 0: 27.5 ± 5.18%; T 1: 22.66 ± 3.09%) and CSR (T 0: 10.03 ± 2.55 s(-1); T 1: 7.50 ± 1.84 s(-1)) significantly reduced with age. W 1 was significantly correlated with CO (R = 0.58), EF (R = 0.72), LS (R = 0.65), LSR (R = 0.89), CS (R = 0.61), CSR (R = 0.70) at T 0; correlations were lost at T 1. The decrease in W 1 and W 2 suggests a cardiac performance reduction, while that in Wb, considering unchanged RI, might indicate a wave energy decrease. The loss of correlation between WIA-derived and cardiac parameters might reflect an alteration in cardiovascular interaction.

  19. Digoxin Induces Cardiac Hypertrophy Without Negative Effects on Cardiac Function and Physical Performance in Trained Normotensive Rats.

    PubMed

    Neves, Claodete Hasselstrom; Tibana, Ramires Alsamir; Prestes, Jonato; Voltarelli, Fabricio Azevedo; Aguiar, Andreo Fernando; Ferreira Mota, Gustavo Augusto; de Sousa, Sergio Luiz Borges; Leopoldo, Andre Soares; Leopoldo, Ana Paula Lima; Mueller, Andre; Aguiar, Danilo Henrique; Navalta, James Wilfred; Sugizaki, Mario Mateus

    2017-04-01

    Cardiotonic drugs and exercise training promote cardiac inotropic effects, which may affect training-induced cardiac adaptations. This study investigated the effects of long-term administration of digoxin on heart structure and function, and physical performance of rats submitted to high-intensity interval training (HIIT). Male Wistar rats, 60 days old, were divided into control (C), digoxin (DIGO), trained (T), and trained with digoxin (TDIGO). Digoxin was administered by gavage (30 µg/kg/day) for 75 days. The HIIT program consisted of treadmill running 60 min/day (8 min at 80% of the maximum speed (MS) and 2 min at 20% of the MS), 5 days per week during 60 days. The main cardiac parameters were evaluated by echocardiograph and cardiomyocyte area was determined by histology. There were no group x time effects of digoxin, HIIT or interactions (digoxin and HIIT) on functional echocardiographic parameters (heart rate; ejection fraction) or in the maximum exercise test. There was a group x time interaction, as evidenced by observed cardiac hypertrophy in the TDIGO group evaluated by ratio of left ventricle weight to body weight (p<0.002) and cardiomyocyte area (p<0.000002). Long-term administration of digoxin promoted cardiac hypertrophy without affecting cardiac function and physical performance in rats submitted to HIIT.

  20. Cardiac Cyclic Nucleotide Phosphodiesterases: Function, Regulation, and Therapeutic Prospects

    PubMed Central

    Knight, W. E.; Yan, C.

    2014-01-01

    The second messengers cAMP and cGMP exist in multiple discrete compartments and regulate a variety of biological processes in the heart. The cyclic nucleotide phosphodiesterases, by catalyzing the hydrolysis of cAMP and cGMP, play crucial roles in controlling the amplitude, duration, and compartmentalization of cyclic nucleotide signaling. Over 60 phosphodiesterase isoforms, grouped into 11 families, have been discovered to date. In the heart, both cAMP- and cGMP-hydrolyzing phosphodiesterases play important roles in physiology and pathology. At least 7 of the 11 phosphodiesterase family members appear to be expressed in the myocardium, and evidence supports phosphodiesterase involvement in regulation of many processes important for normal cardiac function including pacemaking and contractility, as well as many pathological processes including remodeling and myocyte apoptosis. Pharmacological inhibitors for a number of phosphodiesterase families have also been used clinically or preclinically to treat several types of cardiovascular disease. In addition, phosphodiesterase inhibitors are also being considered for treatment of many forms of disease outside the cardiovascular system, raising the possibility of cardiovascular side effects of such agents. This review will discuss the roles of phosphodiesterases in the heart, in terms of expression patterns, regulation, and involvement in physiological and pathological functions. Additionally, the cardiac effects of various phosphodiesterase inhibitors, both potentially beneficial and detrimental, will be discussed. PMID:22951903

  1. Increased epicardial fat thickness is associated with cardiac functional changes in healthy women.

    PubMed

    Kilicaslan, Baris; Ozdogan, Oner; Aydin, Mehmet; Dursun, Huseyin; Susam, Ibrahim; Ertas, Faruk

    2012-01-01

    Epicardial fat tissue is a visceral fat depot with anatomical and functional contiguity to the myocardium and coronary arteries. The objective of this study was to evaluate the association between epicardial fat thickness (EFT) and cardiac changes in healthy female subjects. The study population consisted of ninety-six consecutive healthy female (mean age 31.1 ± 6.7 years) who underwent transthoracic echocardiography. EFT was measured by echocardiography. Subjects were divided into two groups according to the EFT; EFT < 6 mm and EFT ≥ 6 mm. The cardiac structural changes, increased left atrial volume indices (LAVI) (41.2 ± 9.9 vs. 52.6 ± 12.5, p = 0.001) and left ventricular mass indices (LVMI) (129.6 ± 32.1 vs. 155.6 ± 31.6 p < 0.05), were observed in patients with increased EFT. Myocardial tei index (MTI), which was used to evaluate both systolic and diastolic functions, was higher with increased EFT (0.44 ± 0.07 vs. 0.48 ± 0.08, p = 0.02). The correlation analysis revealed significant correlation between EFT and each of LAVI (r = 0.312, p = 0.002), LVMI (r = 0.301, p = 0.003), body mass index (BMI) (r = 0.8, p < 0.001), and MTI (r = 0.27, p = 0.005). Multivariate regression analysis demonstrated that EFT was associated with BMI (t = 5.28, p = 0.001), MTI (r = 2.39, p = 0.019), LVMI (r = 2.16, p = 0.01), and LAVI (r = 3.21, p = 0.002). In conclusion, EFT is an important predictor of cardiac alterations in women who are prone to obesity.

  2. Diastolic Function in Paced Children with Cardiac Defects: Septum vs Apex

    PubMed Central

    Ortega, Michel Cabrera; Morejon, Adel Eladio Gonzalez; Serrano, Giselle Ricardo; Ramos, Dunia Barbara Benitez

    2015-01-01

    In children with structural congenital heart disease (CHD), the effects of chronic ventricular pacing on diastolic function are not well known. On the other hand, the beneficial effect of septal pacing over apical pacing is still controversial. The aim of this study was to evaluate the influence of different right ventricular (RV) pacing site on left ventricular (LV) diastolic function in children with cardiac defects. Twenty-nine pediatric patients with complete atrioventricular block (CAVB) and CHD undergoing permanent pacing were prospectively studied. Pacing sites were RV apex (n = 16) and RV septum (n = 13). Echocardiographic assessment was performed before pacemaker implantation and after it, during a mean follow‑up of 4.9 years. Compared to RV septum, transmitral E-wave was significantly affected in RV apical pacing (95.38 ± 9.19 vs 83 ± 18.75, p = 0.038). Likewise, parameters at the lateral annular tissue Doppler imaging (TDI) were significantly affected in children paced at the RV apex. The E´ wave correlated inversely with TDI lateral myocardial performance index (Tei index) (R2= 0.9849, p ≤ 0.001). RV apex pacing (Odds ratio, 0.648; confidence interval, 0.067-0.652; p = 0.003) and TDI lateral Tei index (Odds ratio, 31.21; confidence interval, 54.6-177.4; p = 0.025) predicted significantly decreased LV diastolic function. Of the two sites studied, RV septum prevents pacing-induced reduction of LV diastolic function. PMID:26352178

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

    PubMed

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

    1998-11-01

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

  4. Cardiac function adaptations in hibernating grizzly bears (Ursus arctos horribilis).

    PubMed

    Nelson, O Lynne; Robbins, Charles T

    2010-03-01

    Research on the cardiovascular physiology of hibernating mammals may provide insight into evolutionary adaptations; however, anesthesia used to handle wild animals may affect the cardiovascular parameters of interest. To overcome these potential biases, we investigated the functional cardiac phenotype of the hibernating grizzly bear (Ursus arctos horribilis) during the active, transitional and hibernating phases over a 4 year period in conscious rather than anesthetized bears. The bears were captive born and serially studied from the age of 5 months to 4 years. Heart rate was significantly different from active (82.6 +/- 7.7 beats/min) to hibernating states (17.8 +/- 2.8 beats/min). There was no difference from the active to the hibernating state in diastolic and stroke volume parameters or in left atrial area. Left ventricular volume:mass was significantly increased during hibernation indicating decreased ventricular mass. Ejection fraction of the left ventricle was not different between active and hibernating states. In contrast, total left atrial emptying fraction was significantly reduced during hibernation (17.8 +/- 2.8%) as compared to the active state (40.8 +/- 1.9%). Reduced atrial chamber function was also supported by reduced atrial contraction blood flow velocities and atrial contraction ejection fraction during hibernation; 7.1 +/- 2.8% as compared to 20.7 +/- 3% during the active state. Changes in the diastolic cardiac filling cycle, especially atrial chamber contribution to ventricular filling, appear to be the most prominent macroscopic functional change during hibernation. Thus, we propose that these changes in atrial chamber function constitute a major adaptation during hibernation which allows the myocardium to conserve energy, avoid chamber dilation and remain healthy during a period of extremely low heart rates. These findings will aid in rational approaches to identifying underlying molecular mechanisms.

  5. Low-dose dasatinib rescues cardiac function in Noonan syndrome

    PubMed Central

    Yi, Jae-Sung; Huang, Yan; Kwaczala, Andrea T.; Kuo, Ivana Y.; Ehrlich, Barbara E.; Campbell, Stuart G.; Giordano, Frank J.; Bennett, Anton M.

    2016-01-01

    Noonan syndrome (NS) is a common autosomal dominant disorder that presents with short stature, craniofacial dysmorphism, and cardiac abnormalities. Activating mutations in the PTPN11 gene encoding for the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2 (SHP2) causes approximately 50% of NS cases. In contrast, NS with multiple lentigines (NSML) is caused by mutations that inactivate SHP2, but it exhibits some overlapping abnormalities with NS. Protein zero-related (PZR) is a SHP2-binding protein that is hyper-tyrosyl phosphorylated in the hearts of mice from NS and NSML, suggesting that PZR and the tyrosine kinase that catalyzes its phosphorylation represent common targets for these diseases. We show that the tyrosine kinase inhibitor, dasatinib, at doses orders of magnitude lower than that used for its anticancer activities inhibited PZR tyrosyl phosphorylation in the hearts of NS mice. Low-dose dasatinib treatment of NS mice markedly improved cardiomyocyte contractility and functionality. Remarkably, a low dose of dasatinib reversed the expression levels of molecular markers of cardiomyopathy and reduced cardiac fibrosis in NS and NSML mice. These results suggest that PZR/SHP2 signaling is a common target of both NS and NSML and that low-dose dasatinib may represent a unifying therapy for the treatment of PTPN11-related cardiomyopathies. PMID:27942593

  6. The Transfer Functions of Cardiac Tissue during Stochastic Pacing

    PubMed Central

    de Lange, Enno; Kucera, Jan P.

    2009-01-01

    Abstract The restitution properties of cardiac action potential duration (APD) and conduction velocity (CV) are important factors in arrhythmogenesis. They determine alternans, wavebreak, and the patterns of reentrant arrhythmias. We developed a novel approach to characterize restitution using transfer functions. Transfer functions relate an input and an output quantity in terms of gain and phase shift in the complex frequency domain. We derived an analytical expression for the transfer function of interbeat intervals (IBIs) during conduction from one site (input) to another site downstream (output). Transfer functions can be efficiently obtained using a stochastic pacing protocol. Using simulations of conduction and extracellular mapping of strands of neonatal rat ventricular myocytes, we show that transfer functions permit the quantification of APD and CV restitution slopes when it is difficult to measure APD directly. We find that the normally positive CV restitution slope attenuates IBI variations. In contrast, a negative CV restitution slope (induced by decreasing extracellular [K+]) amplifies IBI variations with a maximum at the frequency of alternans. Hence, it potentiates alternans and renders conduction unstable, even in the absence of APD restitution. Thus, stochastic pacing and transfer function analysis represent a powerful strategy to evaluate restitution and the stability of conduction. PMID:19134481

  7. Targeted inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis and Preserves Heart Function in Adverse Cardiac Remodeling

    PubMed Central

    Zhang, Jie; Fan, Guangpu; Zhao, Hui; Wang, Zhiwei; Li, Fei; Zhang, Peide; Zhang, Jing; Wang, Xu; Wang, Wei

    2017-01-01

    Cardiac fibrosis in post-myocardial infarction (MI), seen in both infarcted and non-infarcted myocardium, is beneficial to the recovery of heart function. But progressively pathological fibrosis impairs ventricular function and leads to poor prognosis. FAK has recently received attention as a potential mediator of fibrosis, our previous study reported that pharmacological inhibition of FAK can attenuate cardiac fibrosis in post MI models. However, the long-term effects on cardiac function and adverse cardiac remodelling were not clearly investigated. In this study, we tried to determine the preliminary mechanisms in regulating CF transformation to myofibroblasts and ECM synthesis relevant to the development of adverse cardiac remolding in vivo and in vitro. Our study provides even more evidence that FAK is directly related to the activation of CF in hypoxia condition in a dose-dependent and time-dependent manner. Pharmacological inhibition of FAK significantly reduces myofibroblast differentiation; our in vivo data demonstrated that a FAK inhibitor significantly decreases fibrotic score, and preserves partial left ventricular function. Both PI3K/AKT signalling and ERK1/2 are necessary for hypoxia-induced CF differentiation and ECM synthesis; this process also involves lysyl oxidase (LOX). These findings suggest that pharmacological inhibition of FAK may become an effective therapeutic strategy against adverse fibrosis. PMID:28225063

  8. Cardiac function and myocardial perfusion immediately following maximal treadmill exercise inside the MRI room

    PubMed Central

    Jekic, Mihaela; Foster, Eric L; Ballinger, Michelle R; Raman, Subha V; Simonetti, Orlando P

    2008-01-01

    Treadmill exercise stress testing is an essential tool in the prevention, detection, and treatment of a broad spectrum of cardiovascular disease. After maximal exercise, cardiac images at peak stress are typically acquired using nuclear scintigraphy or echocardiography, both of which have inherent limitations. Although CMR offers superior image quality, the lack of MRI-compatible exercise and monitoring equipment has prevented the realization of treadmill exercise CMR. It is critical to commence imaging as quickly as possible after exercise to capture exercise-induced cardiac wall motion abnormalities. We modified a commercial treadmill such that it could be safely positioned inside the MRI room to minimize the distance between the treadmill and the scan table. We optimized the treadmill exercise CMR protocol in 20 healthy volunteers and successfully imaged cardiac function and myocardial perfusion at peak stress, followed by viability imaging at rest. Imaging commenced an average of 30 seconds after maximal exercise. Real-time cine of seven slices with no breath-hold and no ECG-gating was completed within 45 seconds of exercise, immediately followed by stress perfusion imaging of three short-axis slices which showed an average time to peak enhancement within 57 seconds of exercise. We observed a 3.1-fold increase in cardiac output and a myocardial perfusion reserve index of 1.9, which agree with reported values for healthy subjects at peak stress. This study successfully demonstrates in-room treadmill exercise CMR in healthy volunteers, but confirmation of feasibility in patients with heart disease is still needed. PMID:18272005

  9. Goal-Directed Resuscitation Aiming Cardiac Index Masks Residual Hypovolemia: An Animal Experiment.

    PubMed

    Tánczos, Krisztián; Németh, Márton; Trásy, Domonkos; László, Ildikó; Palágyi, Péter; Szabó, Zsolt; Varga, Gabriella; Kaszaki, József

    2015-01-01

    The aim of this study was to compare stroke volume (SVI) to cardiac index (CI) guided resuscitation in a bleeding-resuscitation experiment. Twenty six pigs were randomized and bled in both groups till baseline SVI (T bsl) dropped by 50% (T 0), followed by resuscitation with crystalloid solution until initial SVI or CI was reached (T 4). Similar amount of blood was shed but animals received significantly less fluid in the CI-group as in the SVI-group: median = 900 (interquartile range: 850-1780) versus 1965 (1584-2165) mL, p = 0.02, respectively. In the SVI-group all variables returned to their baseline values, but in the CI-group animals remained underresuscitated as indicated by SVI, heart rate (HR) and stroke volume variation (SVV), and central venous oxygen saturation (ScvO2) at T 4 as compared to T bsl: SVI = 23.8 ± 5.9 versus 31.4 ± 4.7 mL, HR: 117 ± 35 versus 89 ± 11/min SVV: 17.4 ± 7.6 versus 11.5 ± 5.3%, and ScvO2: 64.1 ± 11.6 versus 79.2 ± 8.1%, p < 0.05, respectively. Our results indicate that CI-based goal-directed resuscitation may result in residual hypovolaemia, as bleeding caused stress induced tachycardia "normalizes" CI, without restoring adequate SVI. As the SVI-guided approach normalized most hemodynamic variables, we recommend using SVI instead of CI as the primary goal of resuscitation during acute bleeding.

  10. Modeling the relation between cardiac pump function and myofiber mechanics.

    PubMed

    Arts, T; Bovendeerd, P; Delhaas, T; Prinzen, F

    2003-05-01

    Complexity of the geometry and structure of the heart hampers easy modeling of cardiac mechanics. The modeling can however be simplified considerably when using the hypothesis that in the normal heart myofiber structure and geometry adapt, until load is evenly distributed. A simple and realistic relationship is found between the hemodynamic variables cavity pressure and volume, and myofiber load parameters stress and strain. The most important geometric parameter in the latter relation is the ratio of cavity volume to wall volume, while actual geometry appears practically irrelevant. Applying the found relationship, a realistic maximum is set to left ventricular pressure after chronic pressure load. Pressures exceeding this level are likely to cause decompensation and heart failure. Furthermore, model is presented to simulate left and right ventricular pump function with left-right interaction.

  11. Cardiac morphology and function in patients with and without residual diuresis on hemodialysis.

    PubMed

    Araujo, Salustiano; Lemes, Helton P; Cunha, Danny A; Queiroz, Vinicius S; Nascimento, Daniela D; Ferreira Filho, Sebastião Rodrigues

    2011-03-01

    In patients with chronic renal failure on hemodialysis, left ventricular hypertrophy is related to the increase in total peripheral vascular resistance and volume overload. The presence of residual diuresis enables greater control of the volemia of these. We evaluated the morpho-functional changes of the left ventricle in patients with chronic kidney disease on hemodyalisis treatment with and without residual diuresis. A total of 31 non diabetic patients were studied and they were divided into two groups: with residual diuresis (RD+) (n = 17) and without residual diuresis (RD-) (n = 14). In both groups, RD+ vs. RD-, using data from a Doppler echocardiogram differences were found, respectively, in the cardiac index (3.9 ± 0.2 vs. 3.0 ± 0.2 L/min/m²; p = 0.0056), systolic index (54 ± 2.9 vs. 45 ± 3.3 mL/b/m²; p = 0.04), end diastolic volume (141 ± 6.7 vs. 112 ± 7.6 mL; p = 0.008), end diastolic diameter (52 ± 0.7 vs. 48 ± 1.1 mm; p = 0.0072) and total peripheral resistance index (1121 ± 56 vs. 1529 ± 111 dyne.sec.cm-5; p = 0.001). RD+ had lower relative wall thickness than RD- (0.38 ± 0.01 vs. 0.45 ± 0.01; p = 0.0008). The ejection fraction and the left ventricular mass index were similar in both groups. The urinary 24-hour volume correlated with the relative wall thickness (r = -0.42; p = 0.0186) and with peripheral resistance index (r = -0.48; p = 0.0059). In conclusion, there were distinct ventricular geometric patterns and different functional performances between RD+ and RD- groups. The presence of residual diuresis can be responsible by these modifications in systolic function.

  12. In vivo assessment of cardiac metabolism and function in the abdominal aortic banding model of compensated cardiac hypertrophy

    PubMed Central

    Seymour, Anne-Marie L.; Giles, Lucia; Ball, Vicky; Miller, Jack J.; Clarke, Kieran; Carr, Carolyn A.; Tyler, Damian J.

    2015-01-01

    Aims Left ventricular hypertrophy is an adaptive response of the heart to chronic mechanical overload and can lead to functional deterioration and heart failure. Changes in cardiac energy metabolism are considered as key to the hypertrophic remodelling process. The concurrence of obesity and hypertrophy has been associated with contractile dysfunction, and this work therefore aimed to investigate the in vivo structural, functional, and metabolic remodelling that occurs in the hypertrophied heart in the setting of a high-fat, high-sucrose, Western diet (WD). Methods and results Following induction of cardiac hypertrophy through abdominal aortic banding, male Sprague Dawley rats were exposed to either a standard diet or a WD (containing 45% fat and 16% sucrose) for up to 14 weeks. Cardiac structural and functional characteristics were determined by CINE MRI, and in vivo metabolism was investigated using hyperpolarized 13C-labelled pyruvate. Cardiac hypertrophy was observed at all time points, irrespective of dietary manipulation, with no evidence of cardiac dysfunction. Pyruvate dehydrogenase flux was unchanged in the hypertrophied animals at any time point, but increased incorporation of the 13C label into lactate was observed by 9 weeks and maintained at 14 weeks, indicative of enhanced glycolysis. Conclusion Hypertrophied hearts revealed little evidence of a switch towards increased glucose oxidation but rather an uncoupling of glycolytic metabolism from glucose oxidation. This was maintained under conditions of dietary stress provided by a WD but, at this compensated phase of hypertrophy, did not result in any contractile dysfunction. PMID:25750189

  13. Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

    NASA Technical Reports Server (NTRS)

    Levine, Benjamin D.; Bungo, Michael W.; Platts, Steven H.; Hamilton, Douglas R.; Johnston, Smith L.

    2009-01-01

    Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.

  14. Exposure to occupational air pollution and cardiac function in workers of the Esfahan Steel Industry, Iran.

    PubMed

    Golshahi, Jafar; Sadeghi, Masoumeh; Saqira, Mohammad; Zavar, Reihaneh; Sadeghifar, Mostafa; Roohafza, Hamidreza

    2016-06-01

    Air pollution is recognized as an important risk factor for cardiovascular disease. We investigated association of exposure to occupational air pollution and cardiac function in the workers of the steel industry. Fifty male workers of the agglomeration and coke-making parts of the Esfahan Steel Company were randomly selected (n = 50). Workers in the administrative parts were studied as controls (n = 50). Those with known history of hypertension, dyslipidemia, or diabetes, and active smokers were not included. Data of age, body mass index, employment duration, blood pressure, fasting blood sugar, and lipid profile were gathered. Echocardiography was performed to evaluate cardiac function. Left ventricular ejection fraction was lower in workers of the agglomeration/coke-making parts than in controls (mean difference = 5 to 5.5 %, P < 0.001). Mild right ventricular dilatation and grade I pulmonary hypertension were present in three (12 %) workers of the coke-making part, but none of the controls (P = 0.010). According to these results, occupational air pollution exposure in workers of the steel industry is associated with left heart systolic dysfunction. Possible right heart insults due to air pollution exposure warrant further investigations.

  15. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats

    PubMed Central

    Vieira, Fabricio Furtado; Olivoto, Robson Ruiz; da Silva, Priscyla Oliveira; Francisco, Julio Cesar; Fogaça, Rosalvo Tadeu Hochmuller

    2016-01-01

    Background Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX) in the cardiac muscle. Objectives To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. Methods We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt) and relaxation (-df/dt), contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP), and contraction force induced by caffeine. Results In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05), increased +df/dt and -df/dt (p < 0.001), low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001), reduction of the maximum force in caffeine-induced contraction (p < 0.003), and decreased total contraction time (p < 0.001). The maximal contraction force did not differ significantly between groups (p = 0.973). Conclusion We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

  16. Physiologically inspired cardiac scaffolds for tailored in vivo function and heart regeneration

    PubMed Central

    Kaiser, Nicholas J; Coulombe, Kareen L K

    2015-01-01

    Tissue engineering is well suited for the treatment of cardiac disease due to the limited regenerative capacity of native cardiac tissue and the loss of function associated with endemic cardiac pathologies, such as myocardial infarction and congenital heart defects. However, the physiological complexity of the myocardium imposes extensive requirements on tissue therapies intended for these applications. In recent years, the field of cardiac tissue engineering has been characterized by great innovation and diversity in the fabrication of engineered tissue scaffolds for cardiac repair and regeneration to address these problems. From early approaches that attempted only to deliver cardiac cells in a hydrogel vessel, significant progress has been made in understanding the role of each major component of cardiac living tissue constructs (namely cells, scaffolds, and signaling mechanisms) as they relate to mechanical, biological, and electrical in vivo performance. This improved insight, accompanied by modern material science techniques, allows for the informed development of complex scaffold materials that are optimally designed for cardiac applications. This review provides a background on cardiac physiology as it relates to critical cardiac scaffold characteristics, the degree to which common cardiac scaffold materials fulfill these criteria, and finally an overview of recent in vivo studies that have employed this type of approach. PMID:25970645

  17. High Interleukin 17 Expression Is Correlated With Better Cardiac Function in Human Chagas Disease

    PubMed Central

    Magalhães, Luisa M. D.; Villani, Fernanda N. A.; Nunes, Maria do Carmo P.; Gollob, Kenneth J.; Rocha, Manoel O. C.; Dutra, Walderez O.

    2013-01-01

    This study was designed to investigate whether the expression of interleukin 17 (IL-17) is associated with the indeterminate or cardiac clinical forms of Chagas disease and whether IL-17 expression can be correlated with patients' cardiac function. Our results demonstrated that cardiac Chagas patients have a lower intensity of expression of IL-17 by total lymphocytes and lower frequency of circulating T helper 17 cells. Correlative analysis showed that high IL-17 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Therefore, IL-17 expression can be a protective factor to prevent myocardial damage in human Chagas disease. PMID:23204182

  18. Acute effects of intravenous dronedarone on electrocardiograms, hemodynamics and cardiac functions in anesthetized dogs.

    PubMed

    Saengklub, Nakkawee; Limprasutr, Vudhiporn; Sawangkoon, Suwanakiet; Buranakarl, Chollada; Hamlin, Robert L; Kijtawornrat, Anusak

    2016-02-01

    Dronedarone is a class III antiarrhythmic that has been used for management of atrial fibrillation in humans, but limited information was found in dogs. The objective of this study was to determine the acute effects of escalating concentrations of dronedarone on electrocardiograms (ECG), hemodynamics and cardiac mechanics in healthy dogs. A total of 7 beagle dogs were anesthetized with isoflurane and instrumented to obtain lead II ECG, pressures at ascending aorta, right atrium, pulmonary artery and left ventricle, and left ventricular pressure-volume relationship. Five dogs were given vehicle and followed by escalating doses of dronedarone (0.5, 1.0 and 2.5 mg/kg, 15 min for each dose), and two dogs were used as a vehicle-treated control. All parameters were measured at 15 min after the end of each dose. The results showed that all parameters in vehicle-treated dogs were unaltered. Dronedarone at 2.5 mg/kg significantly lengthened PQ interval (P<0.01), reduced cardiac output (P<0.01) and increased systemic vascular resistance (P<0.01). Dronedarone produced negative inotropy assessed by significantly lowered end-systolic pressure-volume relationship, preload recruitable stroke work, contractility index and dP/dtmax. It also impaired diastolic function by significantly increased end-diastolic pressure-volume relationship, tau and dP/dtmin. These results suggested that acute effects of dronedarone produced negative dromotropy, inotropy and lusitropy in anesthetized dogs. Care should be taken when given dronedarone to dogs, especially when the patients have impaired cardiac function.

  19. Forward ejection fraction: a new index of left ventricular function in mitral regurgitation.

    PubMed

    Clancy, K F; Hakki, A H; Iskandrian, A S; Hadjimiltiades, S; Mundth, E D; Hakki, A H; Bemis, C E; Nestico, P F; DePace, N L; Segal, B L

    1985-09-01

    Previous studies have shown that a normal LVEF is not a reliable index of LV function in MR. We hypothesized that the forward EF, which is the forward stroke volume (measured by Fick or thermodilution) divided by end-diastolic volume (measured by contrast ventriculography) may be a useful index of LV function, since it represents LV emptying into the aorta. This index was examined in 54 patients with chronic MR who had normal EF (greater than or equal to 50%). There were significant correlations between the forward EF and the end-diastolic volume index (r = -0.69, p less than 0.001), end-systolic volume index (r = -0.64, p less than 0.001), cardiac index (r = 0.43, p less than 0.01), and the ratio of systolic pressure-to-end-systolic volume (r = 0.65, p less than 0.001). Patients were divided into two groups according to the forward EF: group I (n = 34) had forward EF less than or equal to 35%; and group II (n = 20) had forward EF greater than 35%. Of the 32 patients who subsequently underwent mitral valve replacement, 24 patients were in group I and eight patients were in group II. At a mean follow-up of 35 months, four patients died; all of them were in group I. Improvement in functional class occurred in 75% of surgical survivors (80% in group I and 63% in group II, p = NS). These preliminary data suggest that forward EF may be a useful index of LV performance in patients with MR who have normal EF.

  20. Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues

    PubMed Central

    Liau, Brian; Jackman, Christopher P.; Li, Yanzhen; Bursac, Nenad

    2017-01-01

    We investigated whether the developmental stage of mouse cardiac fibroblasts (CFs) influences the formation and function of engineered cardiac tissues made of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs). Engineered cardiac tissue patches were fabricated by encapsulating pure mESC-CMs, mESC-CMs + adult CFs, or mESC-CMs + fetal CFs in fibrin-based hydrogel. Tissue patches containing fetal CFs exhibited higher velocity of action potential propagation and contractile force amplitude compared to patches containing adult CFs, while pure mESC-CM patches did not form functional syncytium. The functional improvements in mESC-CM + fetal CF patches were associated with differences in structural remodeling and increased expression of proteins involved in cardiac function. To determine role of paracrine signaling, we cultured pure mESC-CMs within miniature tissue “micro-patches” supplemented with media conditioned by adult or fetal CFs. Fetal CF-conditioned media distinctly enhanced CM spreading and contractile activity, which was shown by pathway inhibitor experiments and Western blot analysis to be mediated via MEK-ERK signaling. In mESC-CM monolayers, CF-conditioned media did not alter CM spreading or MEK-ERK activation. Collectively, our studies show that 3D co-culture of mESC-CMs with embryonic CFs is superior to co-culture with adult CFs for in vitro generation of functional myocardium. Ensuring consistent developmental stages of cardiomyocytes and supporting non-myocytes may be a critical factor for promoting functional maturation of engineered cardiac tissues. PMID:28181589

  1. Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs.

    PubMed

    Matsuura, Timothy R; Bartos, Jason A; Tsangaris, Adamantios; Shekar, Kadambari Chandra; Olson, Matthew D; Riess, Matthias L; Bienengraeber, Martin; Aufderheide, Tom P; Neumar, Robert W; Rees, Jennifer N; McKnite, Scott H; Dikalova, Anna E; Dikalov, Sergey I; Douglas, Hunter F; Yannopoulos, Demetris

    2017-04-10

    Background Out-of-hospital cardiac arrest (CA) is a prevalent medical crisis resulting in severe injury to the heart and brain and an overall survival of less than 10 percent. Mitochondrial dysfunction is predicted to be a key determinant of poor outcomes following prolonged CA. However, the onset and severity of mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) is not fully understood. Ischemic postconditioning (IPC), controlled pauses during the initiation of CPR, has been shown to improve cardiac function and neurologically favorable outcomes after fifteen minutes of CA. We tested the hypothesis that mitochondrial dysfunction develops during prolonged CA and can be rescued with IPC during CPR (IPC-CPR).

  2. The Vascular Quality Initiative Cardiac Risk Index for prediction of myocardial infarction after vascular surgery

    PubMed Central

    Schanzer, Andres; Scali, Salvatore T.; Goodney, Philip P.; Eldrup-Jorgensen, Jens; Cronenwett, Jack L.

    2016-01-01

    Objective The objective of this study was to develop and to validate the Vascular Quality Initiative (VQI) Cardiac Risk Index (CRI) for prediction of postoperative myocardial infarction (POMI) after vascular surgery. Methods We developed risk models for in-hospital POMI after 88,791 nonemergent operations from the VQI registry, including carotid endarterectomy (CEA; n = 45,340), infrainguinal bypass (INFRA; n = 18,054), suprainguinal bypass (SUPRA; n = 2678), endovascular aneurysm repair (EVAR; n = 18,539), and open abdominal aortic aneurysm repair (OAAA repair; n = 4180). Multivariable logistic regression was used to create an all-procedure and four procedure-specific risk calculators based on the derivation cohort from 2012 to 2014 (N = 61,236). Generalizability of the all-procedure model was evaluated by applying it to each procedure subtype. The models were validated using a cohort (N = 27,555) from January 2015 to February 2016. Model discrimination was measured by area under the receiver operating characteristic curve (AUC), and performance was validated by bootstrapping 5000 iterations. The VQI CRI calculator was made available on the Internet and as a free smart phone app available through QxCalculate. Results Overall POMI incidence was 1.6%, with variation by procedure type as follows: CEA, 0.8%; EVAR, 1.0%; INFRA, 2.6%; SUPRA, 3.1%; and OAAA repair, 4.3% (P < .001). Predictors of POMI in the all-procedure model included age, operation type, coronary artery disease, congestive heart failure, diabetes, creatinine concentration >1.8 mg/dL, stress test status, and body mass index (AUC, 0.75; 95% confidence interval =CI], 0.73-0.76). The all-procedure model demonstrated only minimally reduced accuracy when it was applied to each procedure, with the following AUCs: CEA, 0.65 (95% CI, 0.59-0.70); INFRA, 0.69 (95% CI, 0.64-0.73); EVAR, 0.72 (95% CI, 0.65-0.80); SUPRA, 0.62 (95% CI, 0.52-0.72); and OAAA, 0.63 (95% CI, 0.56-0.70). Procedure-specific models had

  3. Invasive Hemodynamic Assessment of Cardiac Output State after MitraClip Therapy in Nonanaesthetized Patients with Functional Mitral Regurgitation

    PubMed Central

    Budesinsky, Tomas; Linkova, Hana

    2016-01-01

    Background. Surgical correction of mitral regurgitation (MR) can lead to postoperative low cardiac output state. We aimed to assess the acute hemodynamic changes after percutaneous MitraClip therapy (a unique model without influence of factors linked to surgical procedure) in patients with functional MR without the influence of general anaesthesia. Methods. We studied invasive hemodynamic parameters in 23 patients before procedure (conscious, nonsedated patients), during procedure (intubated patients), and the first day after MitraClip implantation (conscious, extubated patients). Results. Mitral valve clipping significantly increased cardiac index (CI) (from 2.0 ± 0.5 to 3.3 ± 0.6 L/min/m2; p < 0.01). Conversely, there was significant reduction in the mean pulmonary capillary wedge pressure (PCWP) (from 18.6 ± 5.7 to 10.5 ± 3.8 mmHg; p < 0.01), mean pulmonary artery pressure (from 29.8 ± 10.9 to 25.2 ± 10.3 mmHg; p = 0.03), and pulmonary vascular resistance index (from 531 ± 359 to 365 ± 193 dyn·s·cm−5/m2; p = 0.03). Conclusions. The functional MR therapy with percutaneous MitraClip device results in significant increase in CI (+66%) and concomitant decrease in PCWP (−42%). None of our patients developed low cardiac output state. Our results support the idea that significant part of low cardiac output state after cardiac surgery is due to surgery related factors rather than due to increase in afterload after MR elimination. PMID:28058260

  4. Haemoglobin, blood volume, cardiac function, and aerobic power.

    PubMed

    Gledhill, N; Warburton, D; Jamnik, V

    1999-02-01

    Alterations in [Hb], which are mediated through changes in arterial oxygen content, and alterations in BV, which are mediated through changes in cardiac output (Q), have a significant effect on both VO2max and aerobic performance. If BV is held constant, a decrease in [Hb] (anaemia) causes a decrease in VO2max and aerobic performance, while an increase in [Hb] (blood doping) causes an increase in VO2max and aerobic performance. If [Hb] is held constant, an increase in BV can cause and increase in both VO2max and aerobic performance, while a decrease in BV can cause a decrease in VO2max and aerobic performance. In addition, an increase in BV can compensate for moderate reductions in [Hb] through increase in Q, allowing VO2max to remain unchanged or even increase. Also, a large portion of the difference in the enhanced cardiovascular function of endurance athletes is due to their high BV and the resultant enhancement of diastolic function. Hence, optimizing both [Hb] and BV is a very important consideration for endurance performance.

  5. Metoprolol Improves Endothelial Function in Patients with Cardiac Syndrome X

    PubMed Central

    Majidinia, Maryam; Rasmi, Yousef; Khadem Ansari, Mohammad Hassan; Seyed-Mohammadzad, MirHossein; Saboory, Ehsan; Shirpoor, Alireza

    2016-01-01

    Endothelial dysfunction which is manifested by the loss of nitric oxide bioavailability, is an increasingly recognized cause of cardiac syndrome X (CSX) and beta blockers are used for the treatment of this syndrome. Thus, the aim of this study was to investigate effects of metoprolol, as a beta blocker, on endothelial function in CSX patients. The study included 25 CSX patients (20 female/ 5 male, mean age: 55.36±10.31 years) who received metoprolol (50 mg BID) for one month. In addition, 25 healthy controls (20 female/ 5 male, mean age: 54.32 ±9.27 years) were enrolled. Levels of endothelin-1, E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) in controls and CSX patients were measured, both at the baseline and after the treatment, by the enzyme-linked immunosorbent assay. In CSX patients, at the baseline, levels of E-selectin and VCAM-1 were significantly higher than those of the controls. In addition, levels of these biomarkers in CSX patients after the treatment significantly decreased compared to the baseline. In spite of similar tendency, these differences were not significant for endothelin-1. In conclusion, metoprolol therapy improves endothelial function. Thus, it may be a suggested choice for CSX treatment. However, further studies are needed to confirm the clinical significance of metoprolol therapy for CSX patients. PMID:27980592

  6. Reduced Right Ventricular Function Predicts Long-Term Cardiac Re-Hospitalization after Cardiac Surgery

    PubMed Central

    Goldsmith, Yulia; Chan, Jacqueline; Iskandir, Marina; Gulkarov, Iosif; Tortolani, Anthony; Brener, Sorin J.; Sacchi, Terrence J.; Heitner, John F.

    2015-01-01

    Background The significance of right ventricular ejection fraction (RVEF), independent of left ventricular ejection fraction (LVEF), following isolated coronary artery bypass grafting (CABG) and valve procedures remains unknown. The aim of this study is to examine the significance of abnormal RVEF by cardiac magnetic resonance (CMR), independent of LVEF in predicting outcomes of patients undergoing isolated CABG and valve surgery. Methods From 2007 to 2009, 109 consecutive patients (mean age, 66 years; 38% female) were referred for pre-operative CMR. Abnormal RVEF and LVEF were considered <35% and <45%, respectively. Elective primary procedures include CABG (56%) and valve (44%). Thirty-day outcomes were perioperative complications, length of stay, cardiac re-hospitalizations and early mortaility; long-term (> 30 days) outcomes included, cardiac re-hospitalization, worsening congestive heart failure and mortality. Mean clinical follow up was 14 months. Findings Forty-eight patients had reduced RVEF (mean 25%) and 61 patients had normal RVEF (mean 50%) (p<0.001). Fifty-four patients had reduced LVEF (mean 30%) and 55 patients had normal LVEF (mean 59%) (p<0.001). Patients with reduced RVEF had a higher incidence of long-term cardiac re-hospitalization vs. patients with normal RVEF (31% vs.13%, p<0.05). Abnormal RVEF was a predictor for long-term cardiac re-hospitalization (HR 3.01 [CI 1.5-7.9], p<0.03). Reduced LVEF did not influence long-term cardiac re-hospitalization. Conclusion Abnormal RVEF is a stronger predictor for long-term cardiac re-hospitalization than abnormal LVEF in patients undergoing isolated CABG and valve procedures. PMID:26197273

  7. A review of the foot function index and the foot function index – revised

    PubMed Central

    2013-01-01

    Background The Foot Function Index (FFI) is a self-report, foot-specific instrument measuring pain and disability and has been widely used to measure foot health for over twenty years. A revised FFI (FFI-R) was developed in response to criticism of the FFI. The purpose of this review was to assess the uses of FFI and FFI-R as were reported in medical and surgical literature and address the suggestions found in the literature to improve the metrics of FFI-R. Methods A systematic literature search of PubMed/Medline and Embase databases from October 1991 through December 2010 comprised the main sources of literature. To enrich the bibliography, the search was extended to BioMedLib and Scopus search engines and manual search methods. Search terms included FFI, FFI scores, FFI-R. Requirements included abstracts/full length articles, English-language publications, and articles containing the term "foot complaints/problems." Articles selected were scrutinized; EBM abstracted data from literature and collected into tables designed for this review. EBM analyzed tables, KJC, JM, RMS reviewed and confirmed table contents. KJC and JM reanalyzed the original database of FFI-R to improve metrics. Results Seventy-eight articles qualified for this review, abstracts were compiled into 12 tables. FFI and FFI-R were used in studies of foot and ankle disorders in 4700 people worldwide. FFI Full scale or the Subscales and FFI-R were used as outcome measures in various studies; new instruments were developed based on FFI subscales. FFI Full scale was adapted/translated into other cultures. FFI and FFI-R psychometric properties are reported in this review. Reanalysis of FFI-R subscales' confirmed unidimensionality, and the FFI-R questionnaires' response categories were edited into four responses for ease of use. Conclusion This review was limited to articles published in English in the past twenty years. FFI is used extensively worldwide; this instrument pioneered a quantifiable measure

  8. Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

    PubMed Central

    O’Connell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.

    2014-01-01

    Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha1-ARs signal through Gαq, and signaling through Gq, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha1-ARs mediate important protective and adaptive functions in the heart, although alpha1-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha1-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha1-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate “inside-out” signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha1-AR expression is similar to that in the mouse, where alpha1-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha1-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha1-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha1-AR function and suggest that activation of cardiac alpha1-AR might be a viable therapeutic strategy in heart failure. PMID:24368739

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

    PubMed Central

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

    2016-01-01

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

  10. Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice.

    PubMed

    Hart, C Y; Burnett, J C; Redfield, M M

    2001-11-01

    Anesthetic regimens commonly administered during studies that assess cardiac structure and function in mice are xylazine-ketamine (XK) and avertin (AV). While it is known that XK anesthesia produces more bradycardia in the mouse, the effects of XK and AV on cardiac function have not been compared. We anesthetized normal adult male Swiss Webster mice with XK or AV. Transthoracic echocardiography and closed-chest cardiac catheterization were performed to assess heart rate (HR), left ventricular (LV) dimensions at end diastole and end systole (LVDd and LVDs, respectively), fractional shortening (FS), LV end-diastolic pressure (LVEDP), the time constant of isovolumic relaxation (tau), and the first derivatives of LV pressure rise and fall (dP/dt(max) and dP/dt(min), respectively). During echocardiography, HR was lower in XK than AV mice (250 +/- 14 beats/min in XK vs. 453 +/- 24 beats/min in AV, P < 0.05). Preload was increased in XK mice (LVDd: 4.1 +/- 0.08 mm in XK vs. 3.8 +/- 0.09 mm in AV, P < 0.05). FS, a load-dependent index of systolic function, was increased in XK mice (45 +/- 1.2% in XK vs. 40 +/- 0.8% in AV, P < 0.05). At LV catheterization, the difference in HR with AV (453 +/- 24 beats/min) and XK (342 +/- 30 beats/min, P < 0.05) anesthesia was more variable, and no significant differences in systolic or diastolic function were seen in the group as a whole. However, in XK mice with HR <300 beats/min, LVEDP was increased (28 +/- 5 vs. 6.2 +/- 2 mmHg in mice with HR >300 beats/min, P < 0.05), whereas systolic (LV dP/dt(max): 4,402 +/- 798 vs. 8,250 +/- 415 mmHg/s in mice with HR >300 beats/min, P < 0.05) and diastolic (tau: 23 +/- 2 vs. 14 +/- 1 ms in mice with HR >300 beats/min, P < 0.05) function were impaired. Compared with AV, XK produces profound bradycardia with effects on loading conditions and ventricular function. The disparate findings at echocardiography and LV catheterization underscore the importance of comprehensive assessment of LV function in

  11. New developments in paediatric cardiac functional ultrasound imaging.

    PubMed

    de Korte, Chris L; Nillesen, Maartje M; Saris, Anne E C M; Lopata, Richard G P; Thijssen, Johan M; Kapusta, Livia

    2014-07-01

    Ultrasound imaging can be used to estimate the morphology as well as the motion and deformation of tissues. If the interrogated tissue is actively deforming, this deformation is directly related to its function and quantification of this deformation is normally referred as 'strain imaging'. Tissue can also be deformed by applying an internal or external force and the resulting, induced deformation is a function of the mechanical tissue characteristics. In combination with the load applied, these strain maps can be used to estimate or reconstruct the mechanical properties of tissue. This technique was named 'elastography' by Ophir et al. in 1991. Elastography can be used for atherosclerotic plaque characterisation, while the contractility of the heart or skeletal muscles can be assessed with strain imaging. Rather than using the conventional video format (DICOM) image information, radio frequency (RF)-based ultrasound methods enable estimation of the deformation at higher resolution and with higher precision than commercial methods using Doppler (tissue Doppler imaging) or video image data (2D speckle tracking methods). However, the improvement in accuracy is mainly achieved when measuring strain along the ultrasound beam direction, so it has to be considered a 1D technique. Recently, this method has been extended to multiple directions and precision further improved by using spatial compounding of data acquired at multiple beam steered angles. Using similar techniques, the blood velocity and flow can be determined. RF-based techniques are also beneficial for automated segmentation of the ventricular cavities. In this paper, new developments in different techniques of quantifying cardiac function by strain imaging, automated segmentation, and methods of performing blood flow imaging are reviewed and their application in paediatric cardiology is discussed.

  12. The functional morphology and role of cardiac telocytes in myocardium regeneration.

    PubMed

    Varga, Ivan; Danisovic, Lubos; Kyselovic, Jan; Gazova, Andrea; Musil, Peter; Miko, Michal; Polak, Stefan

    2016-05-19

    Key morphological discoveries in recent years have included the discovery of new cell populations inside the heart called cardiac telocytes. These newly described cells of the connective tissue have extremely long cytoplasmic processes through which they form functionally connected three-dimensional networks that connect cells of the immune system, nerve fibers, cardiac stem cells, and cardiac muscle cells. Based on their functions, telocytes are also referred to as "connecting cells" or "nurse cells" for cardiac progenitor stem cells. In this critical review, we provide a summary of the latest research on cardiac telocytes localized in all layers of the heart - from the historical background of their discovery, through ultrastructural, immunohistochemical, and functional characterizations, to the application of this knowledge to the fields of cardiology, stem cell research, and regenerative medicine.

  13. Effects of Obesity on Cardiovascular Hemodynamics, Cardiac Morphology, and Ventricular Function.

    PubMed

    Alpert, Martin A; Omran, Jad; Bostick, Brian P

    2016-12-01

    Obesity produces a variety of hemodynamic alterations that may cause changes in cardiac morphology which predispose to left and right ventricular dysfunction. Various neurohormonal and metabolic alterations commonly associated with obesity may contribute to these abnormalities of cardiac structure and function. These changes in cardiovascular hemodynamics, cardiac morphology, and ventricular function may, in severely obese patients, predispose to heart failure, even in the absence of other forms of heart disease (obesity cardiomyopathy). In normotensive obese patients, cardiac involvement is commonly characterized by elevated cardiac output, low peripheral vascular resistance, and increased left ventricular (LV) end-diastolic pressure. Sleep-disordered breathing may lead to pulmonary arterial hypertension and, in association with left heart failure, may contribute to elevation of right heart pressures. These alterations, in association with various neurohormonal and metabolic abnormalities, may produce LV hypertrophy; impaired LV diastolic function; and less commonly, LV systolic dysfunction. Many of these alterations are reversible with substantial voluntary weight loss.

  14. Respiratory and cardiac function in congenital muscular dystrophies with alpha dystroglycan deficiency.

    PubMed

    Pane, M; Messina, S; Vasco, G; Foley, A R; Morandi, L; Pegoraro, E; Mongini, T; D'Amico, A; Bianco, F; Lombardo, M E; Scalise, R; Bruno, C; Berardinelli, A; Pini, A; Moroni, I; Mora, M; Toscano, A; Moggio, M; Comi, G; Santorelli, F M; Bertini, E; Muntoni, F; Mercuri, E

    2012-08-01

    The aim of this retrospective study was to assess respiratory and cardiac function in a large cohort of patients with congenital muscular dystrophies (CMD) with reduced glycosylation of alphadystroglycan (α-DG). Thirteen of the 115 patients included in the study died between the age of 1 month and 20 years. The age at last follow up of the surviving 102 ranged between 1 year and 68 years (median: 9.3 years). Cardiac involvement was found in 7 of the 115 (6%), 5 with dilated cardiomyopathy, 1 cardiac conductions defects and 1 mitral regurgitation. Respiratory function was impaired in 14 (12%). Ten of the 14 required non invasive nocturnal respiratory support, while the other four required invasive ventilation. Cardiac or respiratory involvement was found in patients with mutations in FKRP, POMT1, POMT2. All of the patients in whom mutation in POMGnT1 were identified had normal cardiac and respiratory function.

  15. Qishen Yiqi Drop Pill improves cardiac function after myocardial ischemia

    PubMed Central

    JianXin, Chen; Xue, Xu; ZhongFeng, Li; Kuo, Gao; FeiLong, Zhang; ZhiHong, Li; Xian, Wang; HongCai, Shang

    2016-01-01

    Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divided into four groups: MI model group, sham operation group, QYDP treatment group and Fosinopril treatment group. Echocardiography results showed that QYDP exhibited significantly larger LV end-diastolic dimension (LVEDd) and LV end-systolic dimension (LVEDs), compared with the MI model group, indicating the improved cardiac function by QYDP. 1H-NMR based metabonomics further identify 9 significantly changed metabolites in the QYDP treatment group, and the QYDP-related proteins based on the protein-metabolite interaction networks and the corresponding pathways were explored, involving the pyruvate metabolism pathway, the retinol metabolism pathway, the tyrosine metabolism pathway and the purine metabolism pathway, suggesting that QYDP was closely associated with blood circulation. ELISA tests were further employed to identify NO synthase (iNOS) and cathepsin K (CTSK) in the networks. For the first time, our work combined experimental and computational methods to study the mechanism of the formula of traditional Chinese medicine. PMID:27075394

  16. Effect of hypokinesia on contractile function of cardiac muscle

    NASA Technical Reports Server (NTRS)

    Meyerson, F. Z.; Kapelko, V. I.; Trikhpoyeva, A. M.; Gorina, M. S.

    1980-01-01

    Rats were subjected to hypokinesia for two months and the contractile function of isolated papillary muscle was studied. Hypokinesia reduced significantly the isotonic contraction rate which depended on the ATPase activity of the myofibrils; it also reduced the rate and index of relaxation which depended on the functional capacity of the Ca(++) pump of the sarcoplasmic reticulum. The maximum force of isometric contraction determined by the quantity of actomyosin bridges in the myofibrils did not change after hypokinesia. This complex of changes is contrary to that observed in adaptation to exercise when the rate of isotonic contraction and relaxation increases while the force of isometric contraction does not change. The possible mechanism of this stability of the contractile force during adaptation and readaptation of the heart is discussed.

  17. Single-index varying coefficient model for functional responses.

    PubMed

    Luo, Xinchao; Zhu, Lixing; Zhu, Hongtu

    2016-12-01

    Recently, massive functional data have been widely collected over space across a set of grid points in various imaging studies. It is interesting to correlate functional data with various clinical variables, such as age and gender, in order to address scientific questions of interest. The aim of this article is to develop a single-index varying coefficient (SIVC) model for establishing a varying association between functional responses (e.g., image) and a set of covariates. It enjoys several unique features of both varying-coefficient and single-index models. An estimation procedure is developed to estimate varying coefficient functions, the index function, and the covariance function of individual functions. The optimal integration of information across different grid points is systematically delineated and the asymptotic properties (e.g., consistency and convergence rate) of all estimators are examined. Simulation studies are conducted to assess the finite-sample performance of the proposed estimation procedure. Furthermore, our real data analysis of a white matter tract dataset obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study confirms the advantage and accuracy of SIVC model over the popular varying coefficient model.

  18. Residential Proximity to Major Roadways Is Not Associated with Cardiac Function in African Americans: Results from the Jackson Heart Study

    PubMed Central

    Weaver, Anne M.; Wellenius, Gregory A.; Wu, Wen-Chih; Hickson, DeMarc A.; Kamalesh, Masoor; Wang, Yi

    2016-01-01

    Cardiovascular disease (CVD), including heart failure, is a major cause of morbidity and mortality, particularly among African Americans. Exposure to ambient air pollution, such as that produced by vehicular traffic, is believed to be associated with heart failure, possibly by impairing cardiac function. We evaluated the cross-sectional association between residential proximity to major roads, a marker of long-term exposure to traffic-related pollution, and echocardiographic indicators of left and pulmonary vascular function in African Americans enrolled in the Jackson Heart Study (JHS): left ventricular ejection fraction, E-wave velocity, isovolumic relaxation time, left atrial diameter index, and pulmonary artery systolic pressure. We examined these associations using multivariable linear or logistic regression, adjusting for potential confounders. Of 4866 participants at study enrollment, 106 lived <150 m, 159 lived 150–299 m, 1161 lived 300–999 m, and 3440 lived ≥1000 m from a major roadway. We did not observe any associations between residential distance to major roads and these markers of cardiac function. Results were similar with additional adjustment for diabetes and hypertension, when considering varying definitions of major roadways, or when limiting analyses to those free from cardiovascular disease at baseline. Overall, we observed little evidence that residential proximity to major roads was associated with cardiac function among African Americans. PMID:27304962

  19. Relation of reduced preclinical left ventricular diastolic function and cardiac remodeling in overweight youth to insulin resistance and inflammation.

    PubMed

    Dahiya, Rachana; Shultz, Sarah P; Dahiya, Arun; Fu, Jinlin; Flatley, Christopher; Duncan, Danusia; Cardinal, John; Kostner, Karam M; Byrne, Nuala M; Hills, Andrew P; Harris, Mark; Conwell, Louise S; Leong, Gary M

    2015-05-01

    Insulin resistance (IR) and inflammation are associated with an increased risk of cardiovascular disease and may contribute to obesity cardiomyopathy. The earliest sign of obesity cardiomyopathy is impaired left ventricular (LV) diastolic function, which may be evident in obese children and adolescents. However, the precise metabolic basis of the impaired LV diastolic function remains unknown. The aims of this study were to evaluate cardiac structure and LV diastolic function by tissue Doppler imaging in overweight and obese (OW) youth and to assess the relative individual contributions of adiposity, IR, and inflammation to alterations in cardiac structure and function. We studied 35 OW (body mass index standard deviation score 2.0±0.8; non-IR n=19, IR n=16) and 34 non-OW youth (body mass index standard deviation score 0.1±0.7). LV diastolic function was reduced in OW youth compared with non-OW controls, as indicated by lower peak myocardial relaxation velocities (p<0.001) and greater filling pressures (p<0.001). OW youth also had greater LV mass index (p<0.001), left atrial volume index, and LV interventricular septal thickness (LV-IVS; both p=0.02). IR-OW youth had the highest LV filling pressures, LV-IVS, and relative wall thickness (all p<0.05). Homeostasis model of assessment-insulin resistance and C-reactive protein were negative determinants of peak myocardial relaxation velocity and positive predictors of filling pressure. Adiponectin was a negative determinant of LV-IVS, independent of obesity. In conclusion, OW youth with IR and inflammation are more likely to have adverse changes to cardiovascular structure and function which may predispose to premature cardiovascular disease in adulthood.

  20. Cardiac resynchronization therapy improves the uptake of MIBI-99mTc and cardiac function.

    PubMed

    Brandão, Simone Cristina Soares; Giorgi, Maria Clementina; Nishioka, Silvana D'Orio; Martinelli Filho, Martino; Soares, José; Meneghetti, José Cláudio

    2008-09-01

    This case shows the improvement promoted by cardiac resynchronization therapy (CRT) on myocardial perfusion and left ventricular (LV) performance assessed by gated myocardial perfusion scintigraphy. The patient had idiopathic dilated cardiomyopathy, left bundle branch block and severe heart failure despite optimized medical treatment. After CRT, clinical improvement, QRS reduction and improvement of previously hypoperfused anterior and septal walls were observed. There was also decrease in LV end-diastolic and systolic volumes and increase in LV ejection fraction.

  1. Disruption of ROCK1 gene attenuates cardiac dilation and improves contractile function in pathological cardiac hypertrophy.

    PubMed

    Shi, Jianjian; Zhang, Yi-Wei; Summers, Lelia J; Dorn, Gerald W; Wei, Lei

    2008-03-01

    The development of left ventricular cardiomyocyte hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response. However, persistent stress eventually leads to dilated heart failure, which is a common cause of heart failure in human hypertensive and valvular heart disease. We have recently reported that Rho-associated coiled-coil containing protein kinase 1 (ROCK1) homozygous knockout mice exhibited reduced cardiac fibrosis and cardiomyocyte apoptosis, while displaying a preserved compensatory hypertrophic response to pressure overload. In this study, we have tested the effects of ROCK1 deficiency on cardiac hypertrophy, dilation, and dysfunction. We have shown that ROCK1 deletion attenuated left ventricular dilation and contractile dysfunction, but not hypertrophy, in a transgenic model of Galphaq overexpression-induced hypertrophy which represents a well-characterized and highly relevant genetic mouse model of pathological hypertrophy. Although the development of cardiomyocyte hypertrophy was not affected, ROCK1 deletion in Galphaq mice resulted in a concentric hypertrophic phenotype associated with reduced induction of hypertrophic markers indicating that ROCK1 deletion could favorably modify hypertrophy without inhibiting it. Furthermore, ROCK1 deletion also improved contractile response to beta-adrenergic stimulation in Galphaq transgenic mice. Consistent with this observation, ROCK1 deletion prevented down-regulation of type V/VI adenylyl cyclase expression, which is associated with the impaired beta-adrenergic signaling in Galphaq mice. The present study establishes for the first time a role for ROCK1 in cardiac dilation and contractile dysfunction.

  2. Effects of interleukin-37 on cardiac function after myocardial infarction in mice

    PubMed Central

    Xu, Daoying; Wang, Aiqin; Jiang, Fengqin; Hu, Junhong; Zhang, Xiuzhou

    2015-01-01

    Background: Interleukin-37 (IL-37) is a new discovered member of the interleukin family and plays anti-inflammatory effect in some inflammatory disease. A recent study found that IL-37 elevated significantly in peripheral blood of patients with acute myocardial infarction. We aimed to explore the effect IL-37 on cardiac function after mice myocardial infarction (MI) and its mechanism. Methods: Acute MI mouse model was established and divided into three groups: sham group, MI group and IL-37 treatment group. MPO expression was detected by immunohistochemistry; NF-κB signaling pathway was tested by Western blot; and cardiac function was measured by echocardiography. Results: Compared with MI mice, IL-37 treatment showed an obvious decrease of MPO expression, suppression of p-p65 expression, and improved cardiac function by decreasing left ventricular shortening fraction (LVFS). Conclusion: IL-37 may improve MI mice cardiac function via inhibition of inflammatory NF-κB signaling pathway. PMID:26191225

  3. Vortex Formation Time is Not an Index of Ventricular Function

    PubMed Central

    Vlachos, Pavlos P.; Little, William C.

    2015-01-01

    The diastolic intraventricular ring vortex formation and pinch-off process may provide clinically useful insights into diastolic function in health and disease. The vortex ring formation time (FT) concept, based on hydrodynamic experiments dealing with unconfined (large tank) flow, has attracted considerable attention and popularity. Dynamic conditions evolving within the very confined space of a filling, expansible ventricular chamber with relaxing and rebounding viscoelastic muscular boundaries, diverge from unconfined (large tank) flow and encompass rebounding walls’ suction and myocardial relaxation. Indeed, clinical/physiological findings seeking validation in vivo failed to support the notion that FT is an index of normal/abnormal diastolic ventricular function. Therefore, FT as originally proposed cannot and should not be utilized as such an index. Evidently, physiologically accurate models accounting for coupled hydrodynamic and (patho)physiological myocardial wall interactions with the intraventricular flow are still needed to enhance our understanding and yield diastolic function indices useful and reliable in the clinical setting. PMID:25609509

  4. Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism.

    PubMed

    Sassoon, Daniel J; Goodwill, Adam G; Noblet, Jillian N; Conteh, Abass M; Herring, B Paul; McClintick, Jeanette N; Tune, Johnathan D; Mather, Kieren J

    2016-07-01

    This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miRNA) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-minutes coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect the blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca(2+) binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion.

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

    PubMed

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

    2015-01-01

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

  6. Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function.

    PubMed

    Hurwitz, Barry E; Coryell, Virginia T; Parker, Meela; Martin, Pedro; Laperriere, Arthur; Klimas, Nancy G; Sfakianakis, George N; Bilsker, Martin S

    2009-10-19

    The study examined whether deficits in cardiac output and blood volume in a CFS (chronic fatigue syndrome) cohort were present and linked to illness severity and sedentary lifestyle. Follow-up analyses assessed whether differences in cardiac output levels between CFS and control groups were corrected by controlling for cardiac contractility and TBV (total blood volume). The 146 participants were subdivided into two CFS groups based on symptom severity data, severe (n=30) and non-severe (n=26), and two healthy non-CFS control groups based on physical activity, sedentary (n=58) and non-sedentary (n=32). Controls were matched to CFS participants using age, gender, ethnicity and body mass. Echocardiographic measures indicated that the severe CFS participants had 10.2% lower cardiac volume (i.e. stroke index and end-diastolic volume) and 25.1% lower contractility (velocity of circumferential shortening corrected by heart rate) than the control groups. Dual tag blood volume assessments indicated that the CFS groups had lower TBV, PV (plasma volume) and RBCV (red blood cell volume) than control groups. Of the CFS subjects with a TBV deficit (i.e. > or = 8% below ideal levels), the mean+/-S.D. percentage deficit in TBV, PV and RBCV were -15.4+/-4.0, -13.2+/-5.0 and -19.1+/-6.3% respectively. Lower cardiac volume levels in CFS were substantially corrected by controlling for prevailing TBV deficits, but were not affected by controlling for cardiac contractility levels. Analyses indicated that the TBV deficit explained 91-94% of the group differences in cardiac volume indices. Group differences in cardiac structure were offsetting and, hence, no differences emerged for left ventricular mass index. Therefore the findings indicate that lower cardiac volume levels, displayed primarily by subjects with severe CFS, were not linked to diminished cardiac contractility levels, but were probably a consequence of a co-morbid hypovolaemic condition. Further study is needed to address

  7. A portable cadmium telluride multidetector probe for cardiac function monitoring

    NASA Astrophysics Data System (ADS)

    Arntz, Y.; Chambron, J.; Dumitresco, B.; Eclancher, B.; Prat, V.

    1999-06-01

    A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5×5×2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) which well depicted the filling and ejection of the cardiac beats, allowing to compare the clinically relevant parameters of the cardiac performance, proportional variables of the stroke volume (SV), ejection fraction (EF) and ventricular flow-rate with the known absolute values programmed on the model. The portable system is now in operation for clinical assessment of cardiac patients.

  8. Anesthetics alter the physical and functional properties of the Ca-ATPase in cardiac sarcoplasmic reticulum.

    PubMed Central

    Karon, B S; Geddis, L M; Kutchai, H; Thomas, D D

    1995-01-01

    We have studied the effects of the local anesthetic lidocaine, and the general anesthetic halothane, on the function and oligomeric state of the CA-ATPase in cardiac sarcoplasmic reticulum (SR). Oligomeric changes were detected by time-resolved phosphorescence anisotropy (TPA). Lidocaine inhibited and aggregated the Ca-ATPase in cardiac SR. Micromolar calcium or 0.5 M lithium chloride protected against lidocaine-induced inhibition, indicating that electrostatic interactions are essential to lidocaine inhibition of the Ca-ATPase. The phospholamban (PLB) antibody 2D12, which mimics PLB phosphorylation, had no effect on lidocaine inhibition of the Ca-ATPase in cardiac SR. Inhibition and aggregation of the Ca-ATPase in cardiac SR occurred at lower concentrations of lidocaine than necessary to inhibit and aggregate the Ca-ATPase in skeletal SR, suggesting that the cardiac isoform of the enzyme has a higher affinity for lidocaine. Halothane inhibited and aggregated the Ca-ATPase in cardiac SR. Both inhibition and aggregation of the Ca-ATPase by halothane were much greater in the presence of PLB antibody or when PLB was phosphorylated, indicating a protective effect of PLB on halothane-induced inhibition and aggregation. The effects of halothane on cardiac SR are opposite from the effects of halothane observed in skeletal SR, where halothane activates and dissociates the Ca-ATPase. These results underscore the crucial role of protein-protein interactions on Ca-ATPase regulation and anesthetic perturbation of cardiac SR. PMID:7756557

  9. Rationally engineered Troponin C modulates in vivo cardiac function and performance in health and disease

    PubMed Central

    Shettigar, Vikram; Zhang, Bo; Little, Sean C.; Salhi, Hussam E.; Hansen, Brian J.; Li, Ning; Zhang, Jianchao; Roof, Steve R.; Ho, Hsiang-Ting; Brunello, Lucia; Lerch, Jessica K.; Weisleder, Noah; Fedorov, Vadim V.; Accornero, Federica; Rafael-Fortney, Jill A.; Gyorke, Sandor; Janssen, Paul M. L.; Biesiadecki, Brandon J.; Ziolo, Mark T.; Davis, Jonathan P.

    2016-01-01

    Treatment for heart disease, the leading cause of death in the world, has progressed little for several decades. Here we develop a protein engineering approach to directly tune in vivo cardiac contractility by tailoring the ability of the heart to respond to the Ca2+ signal. Promisingly, our smartly formulated Ca2+-sensitizing TnC (L48Q) enhances heart function without any adverse effects that are commonly observed with positive inotropes. In a myocardial infarction (MI) model of heart failure, expression of TnC L48Q before the MI preserves cardiac function and performance. Moreover, expression of TnC L48Q after the MI therapeutically enhances cardiac function and performance, without compromising survival. We demonstrate engineering TnC can specifically and precisely modulate cardiac contractility that when combined with gene therapy can be employed as a therapeutic strategy for heart disease. PMID:26908229

  10. Tetralogy of Fallot Cardiac Function Evaluation and Intelligent Diagnosis Based on Dual-Source Computed Tomography Cardiac Images.

    PubMed

    Cai, Ken; Rongqian, Yang; Li, Lihua; Xie, Zi; Ou, Shanxing; Chen, Yuke; Dou, Jianhong

    2016-05-01

    Tetralogy of Fallot (TOF) is the most common complex congenital heart disease (CHD) of the cyanotic type. Studies on ventricular functions have received an increasing amount of attention as the development of diagnosis and treatment technology for CHD continues to advance. Reasonable options for imaging examination and accurate assessment of preoperative and postoperative left ventricular functions of TOF patients are important in improving the cure rate of TOF radical operation, therapeutic evaluation, and judgment prognosis. Therefore, with the aid of dual-source computed tomography (DSCT), cardiac images with high temporal resolution and high definition, we measured the left ventricular time-volume curve using image data and calculating the left ventricular function parameters to conduct the preliminary evaluation on TOF patients. To comprehensively evaluate the cardiac function, the segmental ventricular wall function parameters were measured, and the measurement results were mapped to a bull's eye diagram to realize the standardization of segmental ventricular wall function evaluation. Finally, we introduced a new clustering method based on auto-regression model parameters and combined this method with Euclidean distance measurements to establish an intelligent diagnosis of TOF. The results of this experiment show that the TOF evaluation and the intelligent diagnostic methods proposed in this article are feasible.

  11. The whistler mode refractive index as a function of gyrofrequency

    SciTech Connect

    Albert, J. M.

    2011-08-15

    The refractive index for a constant-frequency whistler mode wave in an electron-proton plasma is considered as a function of position, through the local gyrofrequencies {Omega}{sub e,i}. The full cold plasma dispersion relation is used. The wave frequency can take any value up to the smaller of {Omega}{sub e} and the plasma frequency {omega}{sub pe}, but {omega}{sub pe} is allowed to take any fixed value, as is the wavenormal angle. It is rigorously established that the refractive index is a decreasing function of {Omega}{sub e}. One application of this is to finding locations of Landau and cyclotron resonances, to evaluate the effects of whistler mode waves on radiation belt electrons.

  12. Effect of initial temperature changes on myocardial enzyme levels and cardiac function in acute myocardial infarction.

    PubMed

    Qian, Yuanyu; Liu, Jie; Ma, Jinling; Meng, Qingyi; Peng, Chaoying

    2014-07-01

    In the present study, the effect of initial body temperature changes on myocardial enzyme levels and cardiac function in acute myocardial infarction (AMI) patients was investigated. A total of 315 AMI patients were enrolled and the mean temperature was calculated based on their body temperature within 24 h of admission to hospital. The patients were divided into four groups according to their normal body temperature: Group A, <36.5°C; group B, ≥36.5°C and <37.0°C; group C, ≥37.0°C and <37.5°C and group D, ≥37.5°C. The levels of percutaneous coronary intervention, myocardial enzymes and troponin T (TNT), as well as cardiac ultrasound images, were analyzed. Statistically significant differences in the quantity of creatine kinase at 12 and 24 h following admission were identified between group A and groups C and D (P<0.01). A significant difference in TNT at 12 h following admission was observed between groups A and D (P<0.05), however, this difference was not observed with groups B and C. The difference in TNT between the groups at 24 h following admission was not statistically significant (P>0.05). Significant differences in lactate dehydrogenase at 12 and 24 h following admission were observed between groups A and D (P<0.05), however, differences were not observed with groups B and C (P>0.05). Significant differences in glutamic-oxaloacetic transaminase at 12 and 24 h following admission were observed between groups A and D (P<0.05), however, differences were not observed in groups B and C (P>0.05). However, no significant differences were identified in cardiac function index between all the groups. Therefore, the results of the present study indicated that AMI patients with low initial body temperatures exhibited decreased levels of myocardial enzymes and TNT. Thus, the observation of an initially low body temperature may be used as a protective factor for AMI and may improve the existing clinical program.

  13. The pulsatility volume index: an indicator of cerebrovascular compliance based on fast magnetic resonance imaging of cardiac and respiratory pulsatility.

    PubMed

    Bianciardi, Marta; Toschi, Nicola; Polimeni, Jonathan R; Evans, Karleyton C; Bhat, Himanshu; Keil, Boris; Rosen, Bruce R; Boas, David A; Wald, Lawrence L

    2016-05-13

    The influence of cardiac activity on the viscoelastic properties of intracranial tissue is one of the mechanisms through which brain-heart interactions take place, and is implicated in cerebrovascular disease. Cerebrovascular disease risk is not fully explained by current risk factors, including arterial compliance. Cerebrovascular compliance is currently estimated indirectly through Doppler sonography and magnetic resonance imaging (MRI) measures of blood velocity changes. In order to meet the need for novel cerebrovascular disease risk factors, we aimed to design and validate an MRI indicator of cerebrovascular compliance based on direct endogenous measures of blood volume changes. We implemented a fast non-gated two-dimensional MRI pulse sequence based on echo-planar imaging (EPI) with ultra-short repetition time (approx. 30-50 ms), which stepped through slices every approximately 20 s. We constrained the solution of the Bloch equations for spins moving faster than a critical speed to produce an endogenous contrast primarily dependent on spin volume changes, and an approximately sixfold signal gain compared with Ernst angle acquisitions achieved by the use of a 90° flip angle. Using cardiac and respiratory peaks detected on physiological recordings, average cardiac and respiratory MRI pulse waveforms in several brain compartments were obtained at 7 Tesla, and used to derive a compliance indicator, the pulsatility volume index (pVI). The pVI, evaluated in larger cerebral arteries, displayed significant variation within and across vessels. Multi-echo EPI showed the presence of significant pulsatility effects in both S0 and [Formula: see text] signals, compatible with blood volume changes. Lastly, the pVI dynamically varied during breath-holding compared with normal breathing, as expected for a compliance indicator. In summary, we characterized and performed an initial validation of a novel MRI indicator of cerebrovascular compliance, which might prove useful

  14. Scaffold Proteins Regulating Extracellular Regulated Kinase Function in Cardiac Hypertrophy and Disease

    PubMed Central

    Liang, Yan; Sheikh, Farah

    2016-01-01

    The mitogen activated protein kinase (MAPK)-extracellular regulated kinase 1/2 (ERK1/2) pathway is a central downstream signaling pathway that is activated in cardiac muscle cells during mechanical and agonist-mediated hypertrophy. Studies in genetic mouse models deficient in ERK-associated MAPK components pathway have further reinforced a direct role for this pathway in stress-induced cardiac hypertrophy and disease. However, more recent studies have highlighted that these signaling pathways may exert their regulatory functions in a more compartmentalized manner in cardiac muscle. Emerging data has uncovered specific MAPK scaffolding proteins that tether MAPK/ERK signaling specifically at the sarcomere and plasma membrane in cardiac muscle and show that deficiencies in these scaffolding proteins alter ERK activity and phosphorylation, which are then critical in altering the cardiac myocyte response to stress-induced hypertrophy and disease progression. In this review, we provide insights on ERK-associated scaffolding proteins regulating cardiac myofilament function and their impact on cardiac hypertrophy and disease. PMID:26973524

  15. Xinfuli improves cardiac function, histopathological changes and attenuate cardiomyocyte apoptosis in rats with doxorubicin-induced cardiotoxicity

    PubMed Central

    Lu, Pei-Pei; Ma, Jie; Liang, Xiao-Peng; Guo, Cai-Xia; Yang, Yan-Kun; Yang, Kun-Qi; Shen, Qi-Ming; Ma, Li-Hong; Zhou, Xian-Liang

    2016-01-01

    Background Xinfuli Granule (XG), a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with doxorubicin-induced cardiotoxicity. Methods Sprague–Dawley rats were treated with intraperitoneal injection of Doxorubicin (DOX, 2.5 mg/kg per week) for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline (control group) or different dosage of XG (0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively) for six weeks. Transthoracic echocardiography was performed to evaluate the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining. Results Compared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax. Conclusions Administration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression. PMID:28321239

  16. Cardiac tamponade in a neonate: a dreadful condition—need for functional echo

    PubMed Central

    Iyer, Venkatesh Harohalli Aswathanarayana; Sharma, Deepa Mohan; Charki, Siddhu; Mohanty, Pankaj Kumar

    2014-01-01

    Cardiac tamponade is a clinical emergency. Detection of a swinging heart rate is one of the earliest markers of large pericardial effusion, in which the four cardiac chambers are free to float in a phasic manner. We present a case of a preterm baby, one of the twins, who developed sudden onset of deterioration in the form of swinging heart rate, fluctuation in blood pressure and desaturation, requiring emergency intubation and inotropic support. Bedside functional echo was performed, which demonstrated cardiac tamponade; an immediate echocardiography-guided tap was initiated and fluid was aspirated from the pericardial space. PMID:25535228

  17. Analysis of Cardiac Myocyte Maturation Using CASAAV, A Platform for Rapid Dissection of Cardiac Myocyte Gene Function In Vivo.

    PubMed

    Guo, Yuxuan; VanDusen, Nathan J; Zhang, Lina; Gu, Weiliang; Sethi, Isha; Guatimosim, Silvia; Ma, Qing; Jardin, Blake D; Ai, Yulan; Zhang, Donghui; Chen, Biyi; Guo, Ang; Yuan, Guo-Cheng; Song, Long-Sheng; Pu, William T

    2017-03-29

    Rationale: Loss-of-function studies in cardiac myocytes (CMs) are currently limited by the need for appropriate conditional knockout alleles. The factors that regulate CM maturation are poorly understood. Prior studies on CM maturation have been confounded by heart dysfunction caused by whole organ gene inactivation. Objective: To develop a new technical platform to rapidly characterize cell-autonomous gene function in postnatal murine CMs and apply it to identify genes that regulate T-tubules, a hallmark of mature cardiac myocytes. Methods and Results: We developed CASAAV (CRISPR/Cas9-AAV9-based somatic mutagenesis), a platform in which AAV9 delivers tandem guide RNAs targeting a gene of interest and cardiac troponin T promoter (cTNT)-driven Cre to Rosa(Cas9GFP/Cas9GFP) neonatal mice. When directed against junctophilin-2 (Jph2), a gene previously implicated in T-tubule maturation, we achieved efficient, rapid, and CM-specific JPH2 depletion. High-dose AAV9 ablated JPH2 in 64% CMs and caused lethal heart failure, whereas low-dose AAV9 ablated JPH2 in 22% CMs and preserved normal heart function. In the context of preserved heart function, CMs lacking JPH2 developed T-tubules that were nearly morphologically normal, indicating that JPH2 does not have a major, cell-autonomous role in T-tubule maturation. However, in hearts with severe dysfunction, both AAV-transduced and non-transduced CMs exhibited T-tubule disruption, which was more severe in the transduced subset. These data indicate that cardiac dysfunction disrupts T-tubule structure, and that JPH2 protects T-tubules in this context. We then used CASAAV to screen 8 additional genes for required, cell-autonomous roles in T-tubule formation. We identified ryanodine receptor 2 (RYR2) as a novel, cell-autonomously required T-tubule maturation factor. Conclusions: CASAAV is a powerful tool to study cell-autonomous gene functions. Genetic mosaics are invaluable to accurately define cell-autonomous gene function. JPH2

  18. Early postnatal rat ventricle resection leads to long‐term preserved cardiac function despite tissue hypoperfusion

    PubMed Central

    Zogbi, Camila; Saturi de Carvalho, Ana E. T.; Nakamuta, Juliana S.; Caceres, Viviane de M.; Prando, Silvana; Giorgi, Maria C. P.; Rochitte, Carlos E.; Meneghetti, Jose C.; Krieger, Jose E.

    2014-01-01

    Abstract One‐day‐old mice display a brief capacity for heart regeneration after apex resection. We sought to examine this response in a different model and to determine the impact of this early process on long‐term tissue perfusion and overall cardiac function in response to stress. Apical resection of postnatal rats at day 1 (P1) and 7 (P7) rendered 18 ± 1.0% and 16 ± 1.3% loss of cardiac area estimated by magnetic resonance imaging (MRI), respectively (P > 0.05). P1 was associated with evidence of cardiac neoformation as indicated by Troponin I and Connexin 43 expression at 21 days postresection, while in the P7 group mainly scar tissue replacement ensued. Interestingly, there was an apparent lack of uniform alignment of newly formed cells in P1, and we detected cardiac tissue hypoperfusion for both groups at 21 and 60 days postresection using SPECT scanning. Direct basal cardiac function at 60 days, when the early lesion is undetectable, was preserved in all groups, whereas under hemodynamic stress the degree of change on LVDEP, Stroke Volume and Stroke Work indicated diminished overall cardiac function in P7 (P < 0.05). Furthermore, the End‐Diastolic Pressure–Volume relationship and increased interstitial collagen deposition in P7 is consistent with increased chamber stiffness. Taken together, we provide evidence that early cardiac repair response to apex resection in rats also leads to cardiomyocyte neoformation and is associated to long‐term preservation of cardiac function despite tissue hypoperfusion. PMID:25168870

  19. c-Cbl Inhibition Improves Cardiac function and Survival in Response to Myocardial Ischemia

    PubMed Central

    Rafiq, Khadija; Kolpakov, Mikhail A; Seqqat, Rachid; Guo, Jianfen; Guo, Xinji; Qi, Zhao; Yu, Daohai; Mohapatra, Bhopal; Zutshi, Neha; An, Wei; Band, Hamid; Sanjay, Archana; Houser, Steven R; Sabri, Abdelkarim

    2014-01-01

    Background The proto-oncogene Casitas b-lineage lymphoma (c-Cbl) is an adaptor protein with an intrinsic E3 ubiquitin ligase activity that targets receptor and non-receptor tyrosine kinases, resulting in their ubiquitination and down-regulation. However, the function of c-Cbl in the control of cardiac function is currently unknown. In this study, we examined the role of c-Cbl in myocyte death and cardiac function after myocardial ischemia. Methods and Results We show increased c-Cbl expression in human ischemic and dilated cardiomyopathy hearts and in response to pathological stress stimuli in mice. c-Cbl deficient mice demonstrated a more robust functional recovery after myocardial ischemia reperfusion injury, as well as significantly reduced myocyte apoptosis and improved cardiac function. Ubiquitination and downregulation of key survival c-Cbl targets, epidermal growth factor receptors and focal adhesion kinase, were significantly reduced in c-Cbl knockout mice. Inhibition of c-Cbl expression or its ubiquitin ligase activity in cardiac myocytes offered protection against H2O2 stress. Interestingly, c-Cbl deletion reduced the risk of death and increased cardiac functional recovery after chronic myocardial ischemia. This beneficial effect of c-Cbl deletion was associated with enhanced neoangiogenesis and increased expression of vascular endothelial growth factor (VEGF)-a and VEGF receptor type 2 in the infarcted region. Conclusions c-Cbl activation promotes myocyte apoptosis, inhibits angiogenesis and causes adverse cardiac remodeling after myocardial infarction. These findings point to c-Cbl as a potential therapeutic target for the maintenance of cardiac function and remodeling after myocardial ischemia. PMID:24583314

  20. Cardiac function and tolerance to ischemia–reperfusion injury in chronic kidney disease

    PubMed Central

    Kuczmarski, James M.; Martens, Christopher R.; Lennon-Edwards, Shannon L.; Edwards, David G.

    2014-01-01

    Background Cardiac dysfunction is an independent risk factor of ischemic heart disease and mortality in chronic kidney disease (CKD) patients, yet the relationship between impaired cardiac function and tolerance to ischemia–reperfusion (IR) injury in experimental CKD remains unclear. Methods Cardiac function was assessed in 5/6 ablation–infarction (AI) and sham male Sprague–Dawley rats at 20 weeks of age, 8 weeks post-surgery using an isolated working heart system. This included measures taken during manipulation of preload and afterload to produce left ventricular (LV) function curves as well as during reperfusion following a 15-min ischemic bout. In addition, LV tissue was used for biochemical tissue analysis. Results Cardiac function was impaired in AI animals during preload and afterload manipulations. Cardiac functional impairments persisted post-ischemia in the AI animals, and 36% of AI animals did not recover sufficiently to achieve aortic overflow following ischemia (versus 0% of sham animals). However, for those animals able to withstand the ischemic perturbation, no difference was observed in percent recovery of post-ischemic cardiac function between groups. Urinary NOx (nitrite + nitrate) excretion was lower in AI animals and accompanied by reduced LV endothelial nitric oxide synthase and NOx. LV antioxidants superoxide dismutase-1 and -2 were reduced in AI animals, whereas glutathione peroxidase-1/2 as well as NADPH-oxidase-4 and H2O2 were increased in these animals. Conclusions Impaired cardiac function appears to predispose AI rats to poor outcomes following short-duration ischemic insult. These findings could be, in part, mediated by increased oxidative stress via nitric oxide-dependent and -independent mechanisms. PMID:24151020

  1. The profound effects of microcystin on cardiac antioxidant enzymes, mitochondrial function and cardiac toxicity in rat.

    PubMed

    Qiu, Tong; Xie, Ping; Liu, Ying; Li, Guangyu; Xiong, Qian; Hao, Le; Li, Huiying

    2009-03-04

    Deaths from microcystin toxication have widely been attributed to hypovolemic shock due to hepatic interstitial hemorrhage, while some recent studies suggest that cardiogenic complication is also involved. So far, information on cardiotoxic effects of MC has been rare and the underlying mechanism is still puzzling. The present study examined toxic effects of microcystins on heart muscle of rats intravenously injected with extracted MC at two doses, 0.16LD(50) (14 microg MC-LReq kg(-1) body weight) and 1LD(50) (87 microg MC-LReq kg(-1) body weight). In the dead rats, both TTC staining and maximum elevations of troponin I levels confirmed myocardial infarction after MC exposure, besides a serious interstitial hemorrhage in liver. In the 1LD(50) dose group, the coincident falls in heart rate and blood pressure were related to mitochondria dysfunction in heart, while increases in creatine kinase and troponin I levels indicated cardiac cell injury. The corresponding pathological alterations were mainly characterized as loss of adherence between cardiac myocytes and swollen or ruptured mitochondria at the ultrastructural level. MC administration at a dose of 1LD(50) not only enhanced activities and up-regulated mRNA transcription levels of antioxidant enzymes, but also increased GSH content. At both doses, level of lipid peroxides increased obviously, suggesting serious oxidative stress in mitochondria. Simultaneously, complex I and III were significantly inhibited, indicating blocks in electron flow along the mitochondrial respiratory chain in heart. In conclusion, the findings of this study implicate a role for MC-induced cardiotoxicity as a potential factor that should be considered when evaluating the mechanisms of death associated with microcystin intoxication in Brazil.

  2. Evaluation of cardiac functions of cirrhotic children using serum brain natriuretic peptide and tissue Doppler imaging

    PubMed Central

    Fattouh, Aya M; El-Shabrawi, Mortada H; Mahmoud, Enas H; Ahmed, Wafaa O

    2016-01-01

    Background: Cirrhotic cardiomyopathy (CCM) is described as the presence of cardiac dysfunction in cirrhotic patients. In children with chronic liver disease, CCM has been very rarely investigated. The Aim of the Study: Is to evaluate the cardiac function of cirrhotic children to identify those with CCM. Patients and Methods: Fifty-two cirrhotic patients and 53 age and sex matched controls were assessed using serum brain-type natriuretic peptide (BNP), conventional echocardiography, and tissue Doppler imaging. Results: Patients’ mean ages were 7.66 ± 4.16 years (vs. 6.88 ± 3.04 years for the controls). The study included 27 males and 25 females (28 and 25 respectively for the controls). Patients had larger left atrium and right ventricle (RV) (P value 0.05) and increased LV posterior wall thickness than controls (P value 0.04). They had higher late atrial diastolic filling velocity (A) of tricuspid valve (TV) inflow (0.59 ± 0.17 vs. 0.5 ± 0.1 m/s, P < 0.001) and lower ratios between the early diastolic filling velocity (E) and A wave velocity (E/A) of both mitral valve and TV inflow (1.7 ± 0.35 vs. 1.87 ± 0.34 and 1.3 ± 0.3 vs. 1.5 ± 0.3, P < 0.005 and 0.0008, respectively). Patients had significantly longer isovolumic relaxation time of LV (45.5 ± 11.1 vs. 40.5 ± 7.7 ms P 0.008), higher late diastolic peak myocardial velocity (A’) (11.8 ± 3.6 vs. 9.5 ± 2.7 ms, P 0.0003) and systolic velocity (S’) of the RV (14.5 ± 2.7 vs. 13.2 ± 2.9, P 0.01) and significantly higher myocardial performance index of both LV and RV (P 0.001 and 0.01). BNP levels were significantly higher in cases than controls (5.25 ng/l vs. 3.75 ng/l, P < 0.04) and was correlated with the E wave velocity of the TV (r 0.004) and the E/E’ ratio of the RV (r 0.001). None of the clinical or laboratory data were correlated with the BNP level. Conclusion Cirrhotic children have cardiac dysfunction mainly in the form of diastolic dysfunction. There is a need that CCM be more accurately

  3. Cardiac autonomic function in patients with diabetes improves with practice of comprehensive yogic breathing program

    PubMed Central

    Jyotsna, Viveka P.; Ambekar, Smita; Singla, Rajiv; Joshi, Ansumali; Dhawan, Anju; Kumar, Neeta; Deepak, K. K.; Sreenivas, V.

    2013-01-01

    Background: The aim of this study was to observe the effect comprehensive yogic breathing (Sudarshan Kriya Yoga [SKY] and Pranayam) had on cardiac autonomic functions in patients with diabetes. Materials and Methods: This is a prospective randomized controlled intervention trial. Cardiac autonomic functions were assessed in 64 diabetics. Patients were randomized into two groups, one group receiving standard therapy for diabetes and the other group receiving standard therapy for diabetes and comprehensive yogic breathing program. Standard therapy included dietary advice, brisk walking for 45 min daily, and administration of oral antidiabetic drugs. Comprehensive yogic breathing program was introduced to the participants through a course of 12 h spread over 3 days. It was an interactive session in which SKY, a rhythmic cyclical breathing, preceded by Pranayam is taught under the guidance of a certified teacher. Cardiac autonomic function tests were done before and after 6 months of intervention. Results: In the intervention group, after practicing the breathing techniques for 6 months, the improvement in sympathetic functions was statistically significant (P 0.04). The change in sympathetic functions in the standard therapy group was not significant (P 0.75). Parasympathetic functions did not show any significant change in either group. When both parasympathetic and sympathetic cardiac autonomic functions were considered, there was a trend toward improvement in patients following comprehensive yogic breathing program (P 0.06). In the standard therapy group, no change in cardiac autonomic functions was noted (P 0.99). Conclusion: Cardiac autonomic functions improved in patients with diabetes on standard treatment who followed the comprehensive yogic breathing program compared to patients who were on standard therapy alone. PMID:23869306

  4. Evaluation of cardiac function using transthoracic echocardiography in patients with myocardial injury secondary to methomyl poisoning.

    PubMed

    Lee, Dong Keon; Cho, Nam Hyub; Kim, Oh Hyun; Go, Jin; Kim, Tae Hoon; Cha, Kyoung Chul; Kim, Hyun; Lee, Kang Hyun; Hwang, Sung Oh; Cha, Yong Sung

    2015-07-01

    Generally, the mortality rate for cases of carbamate poisoning is low, but fatalities secondary to methomyl poisoning have been reported including a case report of cardiac toxicity following short-term exposure to methomyl. There have been no reports, however, regarding patterns of cardiac toxicity after exposure to methomyl. Therefore, we investigated the prevalence and patterns of myocardial injury using a biochemical marker, troponin I (TnI), and evaluated cardiac function using transthoracic echocardiography (TTE). We conducted a retrospective review of 14 consecutive methomyl poisoning cases that were diagnosed and treated at the emergency department of the Wonju Severance Christian Hospital between January 2009 and December 2013. On ECG analysis, ST depression and T-wave inversion were seen in five patients (35.7%) and one patient (7.1%), respectively. On cardiac biochemical marker analysis, initial TnI was elevated in 11 patients (78.6%). TTE was performed in nine patients among the 11 patients in whom TnI was found to be elevated. Of the nine patients that underwent TTE, three patients (33.3%) showed a reduced ejection fraction (EF), and RWMA was noted in two patients. There were two patients (22.2%) that had both reduced systolic function and RWMA. One patient did not regain normal systolic function on admission. None of the three patients with reduced EF received any specific treatment to support cardiac function. One patient expired due to pneumonia, and one patient was transferred as moribund. We followed up on 12 patients who survived to discharge for 6-44 months. One patient (8.3%) was died to follow-up, and 11 patients survived without any further complications. Methomyl exposure can cause direct myocardial injury and reversible cardiac dysfunction. Monitoring of TnI levels and TTE for evaluation of cardiac function may be useful in the workup of patients suffering from methomyl poisoning.

  5. Size dependence of complex refractive index function of growing nanoparticles

    NASA Astrophysics Data System (ADS)

    Eremin, A.; Gurentsov, E.; Popova, E.; Priemchenko, K.

    2011-08-01

    The evidence of the change of the complex refractive index function E( m) of carbon and iron nanoparticles as a function of their size was found from two-color time-resolved laser-induced incandescence (TiRe-LII) measurements. Growing carbon particles were observed from acetylene pyrolysis behind a shock wave and iron particles were synthesized by pulse Kr-F excimer laser photo-dissociation of Fe(CO)5. The magnitudes of refractive index function were found through the fitting of two independently measured values of particle heat up temperature, determined by two-color pyrometry and from the known energy of the laser pulse and the E( m) variation. Small carbon particles of about 1-14 nm in diameter had a low value of E( m)˜0.05-0.07, which tends to increase up to a value of 0.2-0.25 during particle growth up to 20 nm. Similar behavior for iron particles resulted in E( m) rise from ˜0.1 for particles 1-3 nm in diameter up to ˜0.2 for particles >12 nm in diameter.

  6. Precise determination of the refractive index of suspended particles: light transmission as a function of refractive index mismatch

    NASA Astrophysics Data System (ADS)

    McClymer, J. P.

    2016-08-01

    Many fluids appear white because refractive index differences lead to multiple scattering. In this paper, we use safe, low-cost commercial index matching fluids to quantitatively study light transmission as a function of index mismatch, reduce multiple scattering to allow single scattering probes, and to precisely determine the index of refraction of suspended material. The transmission profile is compared with Rayleigh-Gans and Mie theory predictions. The procedure is accessible as a student laboratory project, while providing advantages over other standard methods of measuring the refractive index of an unknown nanoparticle, making it valuable to researchers.

  7. Electromechanical Conditioning of Adult Progenitor Cells Improves Recovery of Cardiac Function After Myocardial Infarction.

    PubMed

    Llucià-Valldeperas, Aida; Soler-Botija, Carolina; Gálvez-Montón, Carolina; Roura, Santiago; Prat-Vidal, Cristina; Perea-Gil, Isaac; Sanchez, Benjamin; Bragos, Ramon; Vunjak-Novakovic, Gordana; Bayes-Genis, Antoni

    2017-03-01

    Cardiac cells are subjected to mechanical and electrical forces, which regulate gene expression and cellular function. Therefore, in vitro electromechanical stimuli could benefit further integration of therapeutic cells into the myocardium. Our goals were (a) to study the viability of a tissue-engineered construct with cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs) and (b) to examine the effect of electromechanically stimulated cardiac ATDPCs within a myocardial infarction (MI) model in mice for the first time. Cardiac ATDPCs were electromechanically stimulated at 2-millisecond pulses of 50 mV/cm at 1 Hz and 10% stretching during 7 days. The cells were harvested, labeled, embedded in a fibrin hydrogel, and implanted over the infarcted area of the murine heart. A total of 39 animals were randomly distributed and sacrificed at 21 days: groups of grafts without cells and with stimulated or nonstimulated cells. Echocardiography and gene and protein analyses were also carried out. Physiologically stimulated ATDPCs showed increased expression of cardiac transcription factors, structural genes, and calcium handling genes. At 21 days after implantation, cardiac function (measured as left ventricle ejection fraction between presacrifice and post-MI) increased up to 12% in stimulated grafts relative to nontreated animals. Vascularization and integration with the host blood supply of grafts with stimulated cells resulted in increased vessel density in the infarct border region. Trained cells within the implanted fibrin patch expressed main cardiac markers and migrated into the underlying ischemic myocardium. To conclude, synchronous electromechanical cell conditioning before delivery may be a preferred alternative when considering strategies for heart repair after myocardial infarction. Stem Cells Translational Medicine 2017;6:970-981.

  8. Embryonic stem cells improve cardiac function in Doxorubicin-induced cardiomyopathy mediated through multiple mechanisms.

    PubMed

    Singla, Dinender K; Ahmed, Aisha; Singla, Reetu; Yan, Binbin

    2012-01-01

    Doxorubicin (DOX) is an effective antineoplastic agent used for the treatment of a variety of cancers. Unfortunately, its use is limited as this drug induces cardiotoxicity and heart failure as a side effect. There is no report that describes whether transplanted embryonic stem (ES) cells or their conditioned medium (CM) in DOX-induced cardiomyopathy (DIC) can repair and regenerate myocardium. Therefore, we transplanted ES cells or CM in DIC to examine apoptosis, fibrosis, cytoplasmic vacuolization, and myofibrillar loss and their associated Akt and ERK pathway. Moreover, we also determined activation of endogenous c-kit(+ve) cardiac stem cells (CSCs), levels of HGF and IGF-1, growth factors required for c-kit cell activation, and their differentiation into cardiac myocytes, which also contributes in cardiac regeneration and improved heart function. We generated DIC in C57Bl/6 mice (cumulative dose of DOX 12 mg/kg body weight, IP), and animals were treated with ES cells, CM, or cell culture medium in controls. Two weeks post-DIC, ES cells or CM transplanted hearts showed a significant (p < 0.05) decrease in cardiac apoptotic nuclei and their regulation with Akt and ERK pathway. Cardiac fibrosis observed in the ES cell or CM groups was significantly less compared with DOX and cell culture medium groups (p < 0.05). Next, cytoplasmic vacuolization and myofibrillar loss was reduced (p < 0.05) following treatment with ES cells or CM. Moreover, our data also demonstrated increased levels of c-kit(+ve) CSCs in ES cells or CM hearts and differentiated cardiac myocytes from these CSCs, suggesting endogenous cardiac regeneration. Importantly, the levels of HFG and IGF-1 were significantly increased in ES cells or CM transplanted hearts. In conclusion, we reported that transplanted ES cells or CM in DIC hearts significantly decreases various adverse pathological mechanisms as well as enhances cardiac regeneration that effectively contributes to improved heart function.

  9. Nicotine depresses the functions of multiple cardiac potassium channels.

    PubMed

    Wang, H; Shi, H; Wang, Z

    1999-01-01

    Nicotine is the main constituent of tobacco smoke responsible for the elevated risk of the cardiovascular disease and sudden coronary death associated with smoking, presumably by provoking cardiac arrhythmias. The cellular mechanisms may be related to the ability of nicotine to prolong action potentials and to depolarize membrane potential. However, the underlying ionic mechanisms remained unknown. We showed here that nicotine blocked multiple types of K+ currents, including the native currents in canine ventricular myocytes and the cloned channels expressed in Xenopus oocytes: A-type K+ currents (I(to)/Kv4.3), delayed rectifier K+ currents (I(Kr)/HERG) and inward rectifier K+ currents (I(K1)/Kir2.1). Most noticeably, nicotine at a concentration as low as of 10 nM significantly suppressed I(to) and Kv4.3 by approximately 20%. The effects of nicotine were independent of nicotinic receptor simulation or catecholamine release. Our results indicate that nicotine is a non-specific blocker of K+ channels and the inhibitory effects are the consequence of direct interactions between nicotine molecules and the channel proteins. Our study provided for the first time the evidence for the direct inhibition of cardiac K+ channels by nicotine and established a novel aspect of nicotine pharmacology.

  10. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct

    PubMed Central

    Valarmathi, Mani T.; Fuseler, John W.; Davis, Jeffrey M.; Price, Robert L.

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty. PMID:28194397

  11. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct.

    PubMed

    Valarmathi, Mani T; Fuseler, John W; Davis, Jeffrey M; Price, Robert L

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty.

  12. Effect of polysaccharides extract of rhizoma atractylodis macrocephalae on thymus, spleen and cardiac indexes, caspase-3 activity ratio, Smac/DIABLO and HtrA2/Omi protein and mRNA expression levels in aged rats.

    PubMed

    Guo, Ling; Sun, Yong Le; Wang, Ai Hong; Xu, Chong En; Zhang, Meng Yuan

    2012-10-01

    This study was designed to determine the possible protective effect of polysaccharides extract of rhizoma atractylodis macrocephalae on heart function in aged rats. Polysaccharides extract of rhizoma atractylodis macrocephalae was administered to aged rats. Results showed that thymus, spleen and cardiac indexs were significantly increased, whereas caspase-3 activity ratio, Smac/DIABLO and HtrA2/Omi protein expression, Smac/DIABLO and HtrA2/Omi mRNA expression levels were markedly reduced. It can be concluded that polysaccharides extract of rhizoma atractylodis macrocephalae may enhance immunity and improve heart function in aged rats.

  13. Utility of comprehensive assessment of strain dyssynchrony index by speckle tracking imaging for predicting response to cardiac resynchronization therapy.

    PubMed

    Tatsumi, Kazuhiro; Tanaka, Hidekazu; Yamawaki, Kouhei; Ryo, Keiko; Omar, Alaa Mabrouk Salem; Fukuda, Yuko; Norisada, Kazuko; Matsumoto, Kensuke; Onishi, Tetsuari; Gorcsan, John; Yoshida, Akihiro; Kawai, Hiroya; Hirata, Ken-ichi

    2011-02-01

    The strain delay index is reportedly a marker of dyssynchrony and residual myocardial contractility. The aim of this study was to test the hypothesis that a relatively simple version of the strain dyssynchrony index (SDI) can predict response to cardiac resynchronization therapy (CRT) and that combining assessment of radial, circumferential, and longitudinal SDI can further improve the prediction of responders. A total of 52 patients who underwent CRT were studied. The SDI was calculated as the average difference between peak and end-systolic strain from 6 segments for radial and circumferential SDI and 18 segments for longitudinal SDI. Conventional dyssynchrony measures were assessed by interventricular mechanical delay, the Yu index, and radial dyssynchrony by speckle tracking strain. Response was defined as a ≥15% decrease in end-systolic volume after 3 months. Of the individual parameters, radial SDI ≥6.5% was the best predictor of response to CRT, with sensitivity of 81%, specificity of 81%, and an area under the curve of 0.87 (p <0.001). Circumferential SDI ≥3.2% and longitudinal SDI ≥3.6% were also found to be predictive of response to CRT, with areas under the curve of 0.81 and 0.80, respectively (p <0.001). Moreover, radial, circumferential, and longitudinal SDI at baseline were correlated with reduction of end-systolic volume with CRT. In addition, the response rate in patients with 3 positive SDIs was 100%. In contrast, rates in patients with either 1 or no positive SDIs were 42% and 22%, respectively (p <0.005 and p <0.001 vs 3 positive SDIs). In conclusion, the SDI can successfully predict response to CRT, and the combined approach leads to more accurate prediction than using individual parameters.

  14. Cardiac function after acute support with direct mechanical ventricular actuation in chronic heart failure.

    PubMed

    McConnell, Patrick I; Anstadt, Mark P; Del Rio, Carlos L; Preston, Thomas J; Ueyama, Yukie; Youngblood, Brad L

    2014-01-01

    Direct mechanical ventricular actuation (DMVA) exerts direct cardiac compression/decompression and does not require blood contact. The safety and effects of DMVA support in chronically dysfunctional beating hearts in vivo have not been established. This study evaluated hemodynamics and load-independent systolic/diastolic cardiac function before/after acute support (2 hours) using DMVA in small hearts with induced chronic failure. Chronic heart failure was created in seven small dogs (15 ± 2 kg) via either serial coronary microembolizations or right-ventricular overdrive pacing. Dogs were instrumented to measure cardiac output, hemodynamic pressures, left ventricular volumes for pressure-volume analysis via preload reduction. Temporary cardiac support using a DMVA device was instituted for 2 hours. Hemodynamic and mechanical assessments, including dobutamine dose-responses, were compared both before and after support. Hemodynamic indices were preserved with support. Both left-ventricular systolic and diastolic function were improved postsupport, as the slopes of the preload-recruitable stroke work (+29 ± 7%, p < 0.05) and the end-diastolic pressure-volume relationship (EDPVR: -28 ± 9%, p < 0.05) improved post-DMVA support. Diastolic/systolic myocardial reserve, as assessed by responsiveness to dobutamine challenges, was preserved after DMVA support. Short-term DMVA support can safely and effectively sustain hemodynamics, whereas triggering favorable effects on cardiac function in the setting of chronic heart failure. In particular, DMVA support preserved load-independent diastolic function and reserve.

  15. Older Adults in Cardiac Rehabilitation: A New Strategy for Enhancing Physical Function.

    ERIC Educational Resources Information Center

    Rejeski, W. Jack; Foy, Capri Gabrielle; Brawley, Lawrence R.; Brubaker, Peter H.; Focht, Brian C.; Norris, James L., III; Smith, Marci L.

    2002-01-01

    Contrasted the effect of a group-mediated cognitive- behavioral intervention (GMCB) versus traditional cardiac rehabilitation (CRP) upon changes in objective and self-reported physical function of older adults after 3 months of exercise therapy. Both groups improved significantly. Adults with lower function at the outset of the intervention…

  16. Impact of Peri-Operative Acute Kidney Injury as a Severity Index for 30-day Readmission After Cardiac Surgery

    PubMed Central

    Brown, Jeremiah R.; Parikh, Chirag R.; Ross, Cathy S.; Kramer, Robert S.; Magnus, Patrick C.; Chaisson, Kristine; Boss, Richard A.; Helm, Robert E.; Horton, Susan R.; Hofmaster, Patricia; Desaulniers, Helen; Blajda, Pamela; Westbrook, Benjamin M.; Duquette, Dennis; LeBlond, Kelly; Quinn, Reed D.; Jones, Cheryl; DiScipio, Anthony W.; Malenka, David J.

    2014-01-01

    Background Of patients undergoing cardiac surgery in the United States, 15–20% are re-hospitalized within 30-days. Current models to predict readmission have not evaluated the association between severity of post-operative acute kidney injury (AKI) and 30-day readmissions. Methods We collected data from 2,209 consecutive patients who underwent either coronary artery bypass (CABG) or valve surgery at seven member hospitals of the Northern New England Cardiovascular Disease Study Group Cardiac Surgery Registry (NNE) between July 2008 and December 2010. Administrative data at each hospital was searched to identify all patients readmitted to the index hospital within 30 days of discharge. We defined AKI Stages by the AKI Network definition of 0.3 or 50% increase (Stage 1), 2-fold increase (stage 2) and a 3-fold or 0.5 increase if the baseline serum creatinine was at least 4.0 (mg/dL) or new dialysis (stage 3). We evaluate the association between stages of AKI and 30-day readmission using multivariate logistic regression. Results There were 260 patients readmitted within 30-days (12.1%). The median time to readmission was 9 (IQR 4–16) days. Patients not developing AKI following cardiac surgery had a 30-day readmission rate of 9.3% compared to patients developing AKI stage 1 (16.1%), AKI stage 2 (21.8%) and AKI stage 3 (28.6%, p <0.001). Adjusted odds ratios for AKI stage 1 (1.81; 1.35, 2.44), stage 2 (2.39; 1.38, 4.14) and stage 3 (3.47; 1.85–6.50). Models to predict readmission were significantly improved with the addition of AKI stage (c-statistic 0.65, p = 0.001) and net reclassification rate of 14.6% (95%CI: 5.05% to 24.14%, p = .003). Conclusions In addition to more traditional patient characteristics, the severity of post-operative AKI should be used when assessing a patient’s risk for readmission. PMID:24119985

  17. Short-Term Effects of Transjugular Intrahepatic Shunt on Cardiac Function Assessed by Cardiac MRI: Preliminary Results

    SciTech Connect

    Kovacs, A.; Schepke, M.; Heller, J.; Schild, H. H.; Flacke, S.

    2010-04-15

    The purpose of this study was to assess short-term effects of transjugular intrahepatic shunt (TIPS) on cardiac function with cardiac magnetic resonance imaging (MRI) in patients with liver cirrhosis. Eleven patients (six males and five females) with intractable esophageal varices or refractory ascites were imaged with MRI at 1.5 T prior to, within 24 h after, and 4-6 months after TIPS creation (n = 5). Invasive pressures were registered during TIPS creation. MRI consisted of a stack of contiguous slices as well as phase contrast images at all four valve planes and perpendicular to the portal vein. Imaging data were analyzed through time-volume curves and first derivatives. The portoatrial pressure gradient decreased from 19.8 {+-} 2.3 to 6.6 {+-} 2.3, accompanied by a nearly two fold increase in central pressures and pulmonary capillary wedge pressure immediately after TIPS creation. Left and right end diastolic volumes and stroke volumes increased by 11, 13, and 24%, respectively (p < 0.001), but dropped back to baseline at follow-up. End systolic volumes remained unchanged. E/A ratios remained within normal range. During follow-up the left ventricular mass was larger than baseline values in all patients, with an average increase of 7.9 g (p < 0.001). In conclusion, the increased volume load shunted to the heart after TIPS creation transiently exceeded the preload reserve of the right and left ventricle, leading to significantly increased pulmonary wedge pressures and persistent enlargement of the left and right atria. Normalization of cardiac dimensions was observed after months together with mild left ventricular hypertrophy.

  18. Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

    PubMed Central

    Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2017-01-01

    Intracellular calcium [Ca2+]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca2+]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca2+]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca2+]i homeostasis, only DFP + NAC restored cardiac [Ca2+]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca2+]i homeostasis, leading to restored myocardial contractility in iron-overloaded rats. PMID:28287621

  19. Gravity Reception and Cardiac Function in the Spider

    NASA Technical Reports Server (NTRS)

    Finck, A.

    1985-01-01

    The following features of the arachnid gravity system were studied. (1) the absolute threshold to hyper-gz is quite low indicating fine proprioreceptive properties of the lyriform organ, the Gz/vibration detector; (2) the neurogenic heart of the spider is a good dependent variable for assessing its behavior to Gz and other stimuli which produce mechanical effects on the exoskeleton; (3) Not only is the cardiac response useful but it is now understood to be an integral part of the system which compensates for the consequences of gravity in the spider (an hydraulic leg extension); and (4) a theoretical model was proposed in which a mechanical amplifier, the leg lever, converts a weak force (at the tarsus) to a strong force (at the patella), capable of compressing the exoskeleton and consequently the lyriform receptor.

  20. Pancreatic functions in adolescents with beta thalassemia major could predict cardiac and hepatic iron loading: relation to T2-star (T2*) magnetic resonance imaging.

    PubMed

    Mokhtar, Galila M; Ibrahim, Wafaa E; Elbarbary, Nancy S; Matter, Randa M; Ibrahim, Ahmed S; Sayed, Safa M

    2016-03-01

    The aim of this study is to assess the correlation between cardiac and hepatic T2* MRI findings with the endocrine and exocrine pancreatic functions in known patients with β-thalassaemia major (β-TM). A total of 50 adolescent patients with β-TM and 44 healthy controls were investigated via: serum amylase, lipase, triglyceride index, oral glucose tolerance test and T2* MRI, to assess iron content in the heart and liver. Diabetes was found in 20%, and 40% of patients had impaired fasting glucose (IFG). Cardiac T2* was less than 10 ms in 22% indicating heavy load with iron in cardiac tissues. There was a significant decrease in median serum amylase (63.5 vs 87.5 IU/L, p=0.003) and lipase (63 vs 90 IU/L, p=0.017) among patients in comparison with the control group. Patients with β-TM and diabetes had lower serum amylase (32 vs 68 IU/L), lipase (28 vs 79 IU/L), cardiac and hepatic T2* MRI (7 vs 25.5 ms; 3 vs 6 ms, p<0.001 for all) than those without diabetes. Similar results were found among patients with IFG when compared with others (p<0.001 for all). Cardiac and hepatic T2* were inversely correlated to triglyceride index (r=-0.376, p=0.014 and r=-0.475, p=0.001, respectively) and positively correlated to amylase (r=0.791 and r=0.790) and lipase (r=0.784 and r=0.783; p<0.001 for all). The endocrine and exocrine pancreatic functions might become an equivalent predictor to cardiac and hepatic iron overload, especially in countries where MRI is not available or where it is expensive. The early occurrence of these abnormalities warrants more intensive chelation therapy.

  1. Indexing Consistency: The Input/Output Function of Thesauri.

    ERIC Educational Resources Information Center

    Reich, Phyllis; Biever, Erik J.

    1991-01-01

    Describes a study that was conducted to determine how well subject authority lists, or thesauri, control indexing vocabulary. Indexer consistency using the Commonwealth Agricultural Bureaux (CAB) thesaurus was tested by comparing indexing done by CAB and by National Agricultural Library (NAL) indexers. (six references) (LRW)

  2. Transplantation of multipotent Isl1+ cardiac progenitor cells preserves infarcted heart function in mice

    PubMed Central

    Li, Yunpeng; Tian, Shuo; Lei, Ienglam; Liu, Liu; Ma, Peter; Wang, Zhong

    2017-01-01

    Cell-based cardiac therapy is a promising therapeutic strategy to restore heart function after myocardial infarction (MI). However, the cell type selection and ensuing effects remain controversial. Here, we intramyocardially injected Isl1+ cardiac progenitor cells (CPCs) derived from EGFP/luciferase double-tagged mouse embryonic stem (dt-mES) cells with vehicle (fibrin gel) or phosphate-buffered saline (PBS) into the infarcted area in nude mice to assess the contribution of CPCs to the recovery of cardiac function post-MI. Our results showed that Isl1+ CPCs differentiated normally into three cardiac lineages (cardiomyocytes (CMs), endothelial cells and smooth muscle cells) both on cell culture plates and in fibrin gel. Cell retention was significantly increased when the transplanted cells were injected with vehicle. Importantly, 28 days after injection, CPCs were observed to differentiate into CMs within the infarcted area. Moreover, numerous CD31+ endothelial cells derived from endogenous revascularization and differentiation of the injected CPCs were detected. SMMHC-, Ki67- and CX-43-positive cells were identified in the injected CPC population, further demonstrating the proliferation, differentiation and integration of the transplanted CPCs in host cells. Furthermore, animal hearts injected with CPCs showed increased angiogenesis, decreased infarct size, and improved heart function. In conclusion, our studies showed that Isl1+ CPCs, when combined with a suitable vehicle, can produce notable therapeutic effects in the infarcted heart, suggesting that CPCs might be an ideal cell source for cardiac therapy. PMID:28386378

  3. Transplantation of multipotent Isl1+ cardiac progenitor cells preserves infarcted heart function in mice.

    PubMed

    Li, Yunpeng; Tian, Shuo; Lei, Ienglam; Liu, Liu; Ma, Peter; Wang, Zhong

    2017-01-01

    Cell-based cardiac therapy is a promising therapeutic strategy to restore heart function after myocardial infarction (MI). However, the cell type selection and ensuing effects remain controversial. Here, we intramyocardially injected Isl1+ cardiac progenitor cells (CPCs) derived from EGFP/luciferase double-tagged mouse embryonic stem (dt-mES) cells with vehicle (fibrin gel) or phosphate-buffered saline (PBS) into the infarcted area in nude mice to assess the contribution of CPCs to the recovery of cardiac function post-MI. Our results showed that Isl1+ CPCs differentiated normally into three cardiac lineages (cardiomyocytes (CMs), endothelial cells and smooth muscle cells) both on cell culture plates and in fibrin gel. Cell retention was significantly increased when the transplanted cells were injected with vehicle. Importantly, 28 days after injection, CPCs were observed to differentiate into CMs within the infarcted area. Moreover, numerous CD31+ endothelial cells derived from endogenous revascularization and differentiation of the injected CPCs were detected. SMMHC-, Ki67- and CX-43-positive cells were identified in the injected CPC population, further demonstrating the proliferation, differentiation and integration of the transplanted CPCs in host cells. Furthermore, animal hearts injected with CPCs showed increased angiogenesis, decreased infarct size, and improved heart function. In conclusion, our studies showed that Isl1+ CPCs, when combined with a suitable vehicle, can produce notable therapeutic effects in the infarcted heart, suggesting that CPCs might be an ideal cell source for cardiac therapy.

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

    PubMed

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

    2014-09-01

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

  5. Cardiac autonomic denervation and functional response to neurotoxins during acute experimental Chagas' disease in rats.

    PubMed

    Teixeira, A L; Fontoura, B F; Freire-Maia, L; Chiari, E; Machado, C R; Teixeira, M M; Camargos, E R

    2001-06-20

    Severe cardiac autonomic denervation occurs in the acute Chagas' disease in rats. The present study aims at verifying whether this denervation was accompanied by impairment of heart function. Scorpionic (Tityus serrulatus) crude venom was used for neurotransmitter release in isolated hearts (Langendorff's preparation). In control hearts, the venom induced significant bradycardia followed by tachycardia. In infected animals, despite the severe (sympathetic) or moderate (parasympathetic) cardiac denervation, the venom provoked similar bradycardia but the tachycardia was higher. The hearts of infected animals beat at significantly lower rate. Atropine prevented this lower rate. Our results demonstrated sympathetic dysfunction during the acute phase of Trypanosoma cruzi infection in rats, the parasympathetic function being spared.

  6. Patient and Societal Value Functions for the Testing Morbidities Index

    PubMed Central

    Swan, John Shannon; Kong, Chung Yin; Lee, Janie M.; Akinyemi, Omosalewa; Halpern, Elkan F.; Lee, Pablo; Vavinskiy, Sergey; Williams, Olubunmi; Zoltick, Emilie S.; Donelan, Karen

    2013-01-01

    Background We developed preference-based and summated scale scoring for the Testing Morbidities Index (TMI) classification, which addresses short-term effects on quality of life from diagnostic testing before, during and after a testing procedure. Methods The two TMI value functions utilize multiattribute value techniques; one is patient-based and the other has a societal perspective. 206 breast biopsy patients and 466 (societal) subjects informed the models. Due to a lack of standard short-term methods for this application, we utilized the visual analog scale (VAS). Waiting trade-off (WTO) tolls provided an additional option for linear transformation of the TMI. We randomized participants to one of three surveys: the first derived weights for generic testing morbidity attributes and levels of severity with the VAS; a second developed VAS values and WTO tolls for linear transformation of the TMI to a death-healthy scale; the third addressed initial validation in a specific test (breast biopsy). 188 patients and 425 community subjects participated in initial validation, comparing direct VAS and WTO values to the TMI. Alternative TMI scoring as a non-preference summated scale was included, given evidence of construct and content validity. Results The patient model can use an additive function, while the societal model is multiplicative. Direct VAS and the VAS-scaled TMI were correlated across modeling groups (r=0.45 to 0.62) and agreement was comparable to the value function validation of the Health Utilities Index 2. Mean Absolute Difference (MAD) calculations showed a range of 0.07–0.10 in patients and 0.11–0.17 in subjects. MAD for direct WTO tolls compared to the WTO-scaled TMI varied closely around one quality-adjusted life day. Conclusions The TMI shows initial promise in measuring short-term testing-related health states. PMID:23689044

  7. Cardiac tamponade as an independent condition affecting the relationship between the plasma B-type natriuretic peptide levels and cardiac function.

    PubMed

    Minai, Kosuke; Komukai, Kimiaki; Arase, Satoshi; Nagoshi, Tomohisa; Matsuo, Seiichiro; Ogawa, Kazuo; Kayama, Yosuke; Inada, Keiichi; Tanigawa, Shin-Ichi; Takemoto, Tomoyuki; Sekiyama, Hiroshi; Date, Taro; Ogawa, Takayuki; Taniguchi, Ikuo; Yoshimura, Michihiro

    2013-07-01

    Plasma B-type natriuretic peptide (BNP) is finely regulated by the cardiac function and several extracardiac factors. Therefore, the relationship between the plasma BNP levels and the severity of heart failure sometimes seems inconsistent. The purpose of the present study was to investigate the plasma BNP levels in patients with cardiac tamponade and their changes after pericardial drainage. This study included 14 patients with cardiac tamponade who underwent pericardiocentesis. The cardiac tamponade was due to malignant diseases in 13 patients and uremia in 1 patient. The plasma BNP levels were measured before and 24-48 h after drainage. Although the patients reported severe symptoms of heart failure, their plasma BNP levels were only 71.2 ± 11.1 pg/ml before drainage. After appropriate drainage, the plasma BNP levels increased to 186.0 ± 22.5 pg/ml, which was significantly higher than that before drainage (P = 0.0002). In patients with cardiac tamponade, the plasma BNP levels were low, probably because of impaired ventricular stretching, and the levels significantly increased in response to the primary condition after drainage. This study demonstrates an additional condition that affects the relationship between the plasma BNP levels and cardiac function. If inconsistency is seen in the relationship between the plasma BNP levels and clinical signs of heart failure, the presence of cardiac tamponade should therefore be considered.

  8. Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass†

    PubMed Central

    Aass, Terje; Stangeland, Lodve; Moen, Christian Arvei; Salminen, Pirjo-Riitta; Dahle, Geir Olav; Chambers, David J.; Markou, Thomais; Eliassen, Finn; Urban, Malte; Haaverstad, Rune; Matre, Knut; Grong, Ketil

    2016-01-01

    OBJECTIVES Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable myocardial protection in a clinically relevant animal model. METHODS Twenty anaesthetized young pigs, 42 ± 2 (standard deviation) kg on standardized tepid cardiopulmonary bypass (CPB) were randomized (10 per group) to depolarizing or polarizing cardiac arrest for 60 min with cardioplegia administered in the aortic root every 20 min as freshly mixed cold, intermittent, oxygenated blood. Global and local baseline and postoperative cardiac function 60, 120 and 180 min after myocardial reperfusion was evaluated with pressure–conductance catheter and strain by Tissue Doppler Imaging. Regional tissue blood flow, cleaved caspase-3 activity, GRK2 phosphorylation and mitochondrial function and ultrastructure were evaluated in myocardial tissue samples. RESULTS Left ventricular function and general haemodynamics did not differ between groups before CPB. Cardiac asystole was obtained and maintained during aortic cross-clamping. Compared with baseline, heart rate was increased and left ventricular end-systolic and end-diastolic pressures decreased in both groups after weaning. Cardiac index, systolic pressure and radial peak systolic strain did not differ between groups. Contractility, evaluated as dP/dtmax, gradually increased from 120 to 180 min after declamping in animals with polarizing cardioplegia and was significantly higher, 1871 ± 160 (standard error) mmHg/s, compared with standard potassium-based cardioplegic arrest, 1351 ± 70 mmHg/s, after 180 min of reperfusion (P = 0

  9. Engineering the heart: evaluation of conductive nanomaterials for improving implant integration and cardiac function.

    PubMed

    Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; Mengqiu Xing, Malcolm; Wang, Changyong

    2014-01-16

    Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction.

  10. Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

    PubMed Central

    Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; (Mengqiu) Xing, Malcolm; Wang, Changyong

    2014-01-01

    Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction. PMID:24429673

  11. Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

    NASA Astrophysics Data System (ADS)

    Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; (Mengqiu) Xing, Malcolm; Wang, Changyong

    2014-01-01

    Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction.

  12. Chitosan hydrogel improves mesenchymal stem cell transplant survival and cardiac function following myocardial infarction in rats

    PubMed Central

    Xu, Bin; Li, Yang; Deng, Bo; Liu, Xiaojing; Wang, Lin; Zhu, Qing-Lei

    2017-01-01

    Myocardial infarction (MI) remains the leading cause of cardiovascular-associated mortality and morbidity. Improving the retention rate, survival and cardiomyocyte differentiation of mesenchymal stem cells (MSCs) is important in improving the treatment of patients with MI. In the present study, temperature-responsive chitosan hydrogel, an injectable scaffold, was used to deliver MSCs directly into the infarcted myocardium of rats following MI. Histopathology and immunohistochemical staining were used to evaluate cardiac cell survival and regeneration, and cardiac function was assessed using an echocardiograph. It was demonstrated that chitosan hydrogel increased graft size and cell retention in the ischemic heart, promoted MSCs to differentiate into cardiomyocytes and increased the effects of MSCs on neovasculature formation. Furthermore, chitosan hydrogel enhanced the effect of MSCs on the improvement of cardiac function and hemodynamics in the infarcted area of rats following MI. These findings suggest that chitosan hydrogel is an appropriate material to deliver MSCs into infarcted myocardium. PMID:28352335

  13. Time Course of Atrophic Remodeling: Effects of Exercise on Cardiac Morpology and Function

    NASA Technical Reports Server (NTRS)

    Scott, J. M.; Martin, D.; Caine, T.; Matz, T.; Ploutz-Snyder, L. L.

    2014-01-01

    Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. Exercise training is one intervention that has been shown to confer favorable improvements in LV mass and function during unloading. However, the format and intensity of exercise required to induce optimal cardiac improvements has not been investigated. PURPOSE: This randomized, controlled trial was designed to 1) comprehensively characterize the time course of unloading-induced morpho-functional remodeling, and 2) examine the effects of high intensity exercise training on cardiac structural and functional parameters during unloading. METHODS: Twenty six subjects completed 70 days of head down tilt bed rest (HDBR): 17 were randomized to exercise training (ExBR) and 9 remained sedentary. Exercise consisted of integrated high intensity, continuous, and resistance exercise. We assessed cardiac morphology (left ventricular mass; LVM) and function (speckle-tracking assessment of longitudinal, radial, and circumferential strain and twist) before (BR-2), during (BR7,21,31,70), and following (BR+0, +3) HDBR. Cardiorespiratory fitness (VO2max) was evaluated before (BR- 3), during (BR4,25,46,68) and following (BR+0) HDBR. RESULTS: Sedentary HDBR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain, and an increase in twist. ExBR mitigated decreases in LVM and function. Change in twist was significantly related to change in VO2max (R=0.68, p<0.01). CONCLUSIONS: Alterations in cardiac morphology and function begin early during unloading. High-intensity exercise attenuates atrophic morphological and functional remodeling.

  14. Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects?

    PubMed

    Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Peterson, Lindsy M; Mai, Katherine; McHale, Quinn; Jenkins, Michael W; Linask, Kersti K; Rollins, Andrew M; Watanabe, Michiko

    2014-02-01

    Alcohol-induced congenital heart defects are frequently among the most life threatening and require surgical correction in newborns. The etiology of these defects, collectively known as fetal alcohol syndrome, has been the focus of much study, particularly involving cellular and molecular mechanisms. Few studies have addressed the influential role of altered cardiac function in early embryogenesis because of a lack of tools with the capability to assay tiny beating hearts. To overcome this gap in our understanding, we used optical coherence tomography (OCT), a nondestructive imaging modality capable of micrometer-scale resolution imaging, to rapidly and accurately map cardiovascular structure and hemodynamics in real time under physiological conditions. In this study, we exposed avian embryos to a single dose of alcohol/ethanol at gastrulation when the embryo is sensitive to the induction of birth defects. Late-stage hearts were analyzed using standard histological analysis with a focus on the atrio-ventricular valves. Early cardiac function was assayed using Doppler OCT, and structural analysis of the cardiac cushions was performed using OCT imaging. Our results indicated that ethanol-exposed embryos developed late-stage valvuloseptal defects. At early stages, they exhibited increased regurgitant flow and developed smaller atrio-ventricular cardiac cushions, compared with controls (uninjected and saline-injected embryos). The embryos also exhibited abnormal flexion/torsion of the body. Our evidence suggests that ethanol-induced alterations in early cardiac function have the potential to contribute to late-stage valve and septal defects, thus demonstrating that functional parameters may serve as early and sensitive gauges of cardiac normalcy and abnormalities.

  15. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

    PubMed Central

    Luck, Christian; DeMarco, Vincent G.; Mahmood, Abuzar; Gavini, Madhavi P.

    2017-01-01

    Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes.

  16. In vivo imaging of cardiac development and function in zebrafish using light sheet microscopy.

    PubMed

    Weber, Michael; Huisken, Jan

    2015-01-01

    Detailed studies of heart development and function are crucial for our understanding of cardiac failures and pave the way for better diagnostics and treatment. However, the constant motion and close incorporation into the cardiovascular system prevent in vivo studies of the living, unperturbed heart. The complementary strengths of the zebrafish model and light sheet microscopy provide a useful platform to fill this gap. High-resolution images of the embryonic vertebrate heart are now recorded from within the living animal: deep inside the unperturbed heart we can follow cardiac contractions and measure action potentials and calcium transients. Three-dimensional reconstructions of the entire beating heart with cellular resolution give new insights into its ever-changing morphology and facilitate studies into how individual cells form the complex cardiac network. In addition, cardiac dynamics and robustness are now examined with targeted optical manipulation. Overall, the combination of zebrafish and light sheet microscopy represents a promising addition for cardiac research and opens the door to a better understanding of heart function and development.

  17. The Value of Attenuation Correction in Hybrid Cardiac SPECT/CT on Inferior Wall According to Body Mass Index

    PubMed Central

    Tamam, Muge; Mulazimoglu, Mehmet; Edis, Nurcan; Ozpacaci, Tevfik

    2016-01-01

    The purpose of this study was to evaluate the diagnostic value of attenuation-corrected single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) on the inferior wall compared to uncorrected (NC) SPECT MPI between obese and nonobese patients. A total of 157 consecutive patients (122 males and 35 females, with median age: 57.4 ± 11 years) who underwent AC technetium 99m-methoxyisobutylisonitrile (AC Tc99m-sestamibi) SPECT MPI were included to the study. A hybrid SPECT and transmission computed tomography (CT) system was used for the diagnosis with 1-day protocol, and stress imaging was performed first. During attenuation correction (AC) processing on a Xeleris Workstation using Myovation cardiac software with ordered subset expectation maximization (OSEM), iterative reconstruction with attenuation correction (IRAC) and NC images filtered back projection (FBP) were used. For statistical purposes, P < 0.05 was considered significant. This study included 73 patients with body mass index (BMI) <30 and 84 patients with BMI ≥ 30. In patients with higher BMI, increased amount of both visual and semiquantitative attenuation of the inferior wall was detected. IRAC reconstruction corrects the diaphragm attenuation of the inferior wall better than FBP. AC with OSEM iterative reconstruction significantly improves the diagnostic value of stress-only SPECT MPI in patients with normal weight and those who are obese, but the improvements are significantly greater in obese patients. Stress-only SPECT imaging with AC provides shorter and lower radiation exposure. PMID:26912974

  18. The Value of Attenuation Correction in Hybrid Cardiac SPECT/CT on Inferior Wall According to Body Mass Index.

    PubMed

    Tamam, Muge; Mulazimoglu, Mehmet; Edis, Nurcan; Ozpacaci, Tevfik

    2016-01-01

    The purpose of this study was to evaluate the diagnostic value of attenuation-corrected single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) on the inferior wall compared to uncorrected (NC) SPECT MPI between obese and nonobese patients. A total of 157 consecutive patients (122 males and 35 females, with median age: 57.4 ± 11 years) who underwent AC technetium 99m-methoxyisobutylisonitrile (AC Tc99m-sestamibi) SPECT MPI were included to the study. A hybrid SPECT and transmission computed tomography (CT) system was used for the diagnosis with 1-day protocol, and stress imaging was performed first. During attenuation correction (AC) processing on a Xeleris Workstation using Myovation cardiac software with ordered subset expectation maximization (OSEM), iterative reconstruction with attenuation correction (IRAC) and NC images filtered back projection (FBP) were used. For statistical purposes, P < 0.05 was considered significant. This study included 73 patients with body mass index (BMI) <30 and 84 patients with BMI ≥ 30. In patients with higher BMI, increased amount of both visual and semiquantitative attenuation of the inferior wall was detected. IRAC reconstruction corrects the diaphragm attenuation of the inferior wall better than FBP. AC with OSEM iterative reconstruction significantly improves the diagnostic value of stress-only SPECT MPI in patients with normal weight and those who are obese, but the improvements are significantly greater in obese patients. Stress-only SPECT imaging with AC provides shorter and lower radiation exposure.

  19. Validation of a Spanish version of the Spine Functional Index

    PubMed Central

    2014-01-01

    Background The Spine Functional Index (SFI) is a recently published, robust and clinimetrically valid patient reported outcome measure. Objectives The purpose of this study was the adaptation and validation of a Spanish-version (SFI-Sp) with cultural and linguistic equivalence. Methods A two stage observational study was conducted. The SFI was cross-culturally adapted to Spanish through double forward and backward translation then validated for its psychometric characteristics. Participants (n = 226) with various spine conditions of >12 weeks duration completed the SFI-Sp and a region specific measure: for the back, the Roland Morris Questionnaire (RMQ) and Backache Index (BADIX); for the neck, the Neck Disability Index (NDI); for general health the EQ-5D and SF-12. The full sample was employed to determine internal consistency, concurrent criterion validity by region and health, construct validity and factor structure. A subgroup (n = 51) was used to determine reliability at seven days. Results The SFI-Sp demonstrated high internal consistency (α = 0.85) and reliability (r = 0.96). The factor structure was one-dimensional and supported construct validity. Criterion specific validity for function was high with the RMQ (r = 0.79), moderate with the BADIX (r = 0.59) and low with the NDI (r = 0.46). For general health it was low with the EQ-5D and inversely correlated (r = −0.42) and fair with the Physical and Mental Components of the SF-12 and inversely correlated (r = −0.56 and r = −0.48), respectively. The study limitations included the lack of longitudinal data regarding other psychometric properties, specifically responsiveness. Conclusions The SFI-Sp was demonstrated as a valid and reliable spine-regional outcome measure. The psychometric properties were comparable to and supported those of the English-version, however further longitudinal investigations are required. PMID:24972525

  20. Influence of nutrients on cardiac autonomic function in nondiabetic overweight subjects.

    PubMed

    Valensi, Paul; Pariès, Jacques; Lormeau, Boris; Attia, Sandra; Attali, Jean-Raymond

    2005-10-01

    The current study sought to determine whether there is a link between cardiac autonomic dysfunction and food intake in overweight subjects. One hundred five nondiabetic overweight (body mass index >27 kg/m2) subjects were studied. Heart rate variations were analyzed during 3 bedside standard tests investigating mainly vagal control: deep breathing, lying-to-standing, and Valsalva tests. The resting metabolic rate and substrate oxidation rates were measured by indirect calorimetry. Dietary intake was estimated from a 3-day recall of food intake. Cardiac parasympathetic dysfunction (PSD) was found in 39 subjects. The sex ratio, age, anthropometric parameters, biochemical parameters and insulin resistance index, resting metabolic rate, and substrate oxidation rates did not differ in the subjects with or without PSD. The total 24-hour energy intake was similar, but the carbohydrate intake was significantly higher in the subjects with PSD (P = .006), and the fat and protein intakes were significantly lower (P = .026 and .045, respectively). In the logistic regression analyses, PSD correlated with carbohydrate and fat intake, independently of serum insulin levels. Glucose oxidation rate correlated negatively with fasting and postglucose serum insulin levels only in the subjects with PSD (P = .006 and .005, respectively). Cardiac parasympathetic dysfunction is associated with higher carbohydrate intake and lower fat and protein intakes in overweight subjects. A sympathetic override may contribute to reducing the glucose oxidation rate in subjects with PSD.

  1. Cardiac Morphology and Function, and Blood Gas Transport in Aquaporin-1 Knockout Mice

    PubMed Central

    Al-Samir, Samer; Wang, Yong; Meissner, Joachim D.; Gros, Gerolf; Endeward, Volker

    2016-01-01

    We have studied cardiac and respiratory functions of aquaporin-1-deficient mice by the Pressure-Volume-loop technique and by blood gas analysis. In addition, the morphological properties of the animals' hearts were analyzed. In anesthesia under maximal dobutamine stimulation, the mice exhibit a moderately elevated heart rate of < 600 min−1 and an O2 consumption of ~0.6 ml/min/g, which is about twice the basal rate. In this state, which is similar to the resting state of the conscious animal, all cardiac functions including stroke volume and cardiac output exhibited resting values and were identical between deficient and wildtype animals. Likewise, pulmonary and peripheral exchange of O2 and CO2 were normal. In contrast, several morphological parameters of the heart tissue of deficient mice were altered: (1) left ventricular wall thickness was reduced by 12%, (2) left ventricular mass, normalized to tibia length, was reduced by 10–20%, (3) cardiac muscle fiber cross sectional area was decreased by 17%, and (4) capillary density was diminished by 10%. As the P-V-loop technique yielded normal end-diastolic and end-systolic left ventricular volumes, the deficient hearts are characterized by thin ventricular walls in combination with normal intraventricular volumes. The aquaporin-1-deficient heart thus seems to be at a disadvantage compared to the wild-type heart by a reduced left-ventricular wall thickness and an increased diffusion distance between blood capillaries and muscle mitochondria. While under the present quasi-resting conditions these morphological alterations have no consequences for cardiac function, we expect that the deficient hearts will show a reduced maximal cardiac output. PMID:27252655

  2. Body adiposity dictates different mechanisms of increased coronary reactivity related to improved in vivo cardiac function

    PubMed Central

    2014-01-01

    Background Saturated fatty acid-rich high fat (HF) diets trigger abdominal adiposity, insulin resistance, type 2 diabetes and cardiac dysfunction. This study was aimed at evaluating the effects of nascent obesity on the cardiac function of animals fed a high-fat diet and at analyzing the mechanisms by which these alterations occurred at the level of coronary reserve. Materials and methods Rats were fed a control (C) or a HF diet containing high proportions of saturated fatty acids for 3 months. Thereafter, their cardiac function was evaluated in vivo using a pressure probe inserted into the cavity of the left ventricle. Their heart was isolated, perfused iso-volumetrically according to the Langendorff mode and the coronary reserve was evaluated by determining the endothelial-dependent (EDV) and endothelial-independent (EIV) vasodilatations in the absence and presence of endothelial nitric oxide synthase and cyclooxygenase inhibitors (L-NAME and indomethacin). The fatty acid composition of cardiac phospholipids was then evaluated. Results Although all the HF-fed rats increased their abdominal adiposity, some of them did not gain body weight (HF- group) compared to the C group whereas other ones had a higher body weight (HF+). All HF rats displayed a higher in vivo cardiac activity associated with an increased EDV. In the HF- group, the improved EDV was due to an increase in the endothelial cell vasodilatation activity whereas in the HF+ group, the enhanced EDV resulted from an improved sensitivity of coronary smooth muscle cells to nitric oxide. Furthermore, in the HF- group the main pathway implicated in the EDV was the NOS pathway while in the HF+ group the COX pathway. Conclusions Nascent obesity-induced improvement of cardiac function may be supported by an enhanced coronary reserve occurring via different mechanisms. These mechanisms implicate either the endothelial cells activity or the smooth muscle cells sensitivity depending on the body adiposity of

  3. Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

    ERIC Educational Resources Information Center

    Junqueira, Luiz Fernando, Jr.

    2008-01-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

  4. Cardiac Autonomic Function during Submaximal Treadmill Exercise in Adults with Down Syndrome

    ERIC Educational Resources Information Center

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

    2011-01-01

    This study determined whether the cardiac autonomic function of adults with Down syndrome (DS) differs from that of nondisabled persons during submaximal dynamic exercise. Thirteen participants with DS and 12 nondisabled individuals performed maximal and submaximal treadmill tests with metabolic and heart rate (HR) measurements. Spectral analysis…

  5. Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery

    PubMed Central

    Cordeiro, André Luiz Lisboa; de Melo, Thiago Araújo; Neves, Daniela; Luna, Julianne; Esquivel, Mateus Souza; Guimarães, André Raimundo França; Borges, Daniel Lago; Petto, Jefferson

    2016-01-01

    Introduction Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. Objective To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. Methods This is a clinical randomized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia. Patients were divided into two groups: control group and training. Preoperatively, were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test. From the third postoperative day, the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge. Results 50 patients, 27 (54%) males were included, with a mean age of 56.7±13.9 years. After the analysis, the training group had significant increase in maximum inspiratory pressure (69.5±14.9 vs. 83.1±19.1 cmH2O, P=0.0073) and 6-minute walk test (422.4±102.8 vs. 502.4±112.8 m, P=0.0031). Conclusion We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery. PMID:27556313

  6. Sympathetic- and Parasympathetic-Linked Cardiac Function and Prediction of Externalizing Behavior, Emotion Regulation, and Prosocial Behavior among Preschoolers Treated for ADHD

    ERIC Educational Resources Information Center

    Beauchaine, Theodore P.; Gatzke-Kopp, Lisa; Neuhaus, Emily; Chipman, Jane; Reid, M. Jamila; Webster-Stratton, Carolyn

    2013-01-01

    Objective: To evaluate measures of cardiac activity and reactivity as prospective biomarkers of treatment response to an empirically supported behavioral intervention for attention-deficit/hyperactivity disorder (ADHD). Method: Cardiac preejection period (PEP), an index of sympathetic-linked cardiac activity, and respiratory sinus arrhythmia…

  7. Generation of Functional Human Cardiac Progenitor Cells by High-Efficiency Protein Transduction

    PubMed Central

    Li, Xiao-Hong; Li, Qianqian; Jiang, Lin; Deng, Chunyu; Liu, Zaiyi; Fu, Yongheng; Zhang, Mengzhen; Tan, Honghong; Feng, Yuliang; Shan, Zhixin

    2015-01-01

    The reprogramming of fibroblasts to induced pluripotent stem cells raises the possibility that somatic cells could be directly reprogrammed to cardiac progenitor cells (CPCs). The present study aimed to assess highly efficient protein-based approaches to reduce or eliminate the genetic manipulations to generate CPCs for cardiac regeneration therapy. A combination of QQ-reagent-modified Gata4, Hand2, Mef2c, and Tbx5 and three cytokines rapidly and efficiently reprogrammed human dermal fibroblasts (HDFs) into CPCs. This reprogramming process enriched trimethylated histone H3 lysine 4, monoacetylated histone H3 lysine 9, and Baf60c at the Nkx2.5 cardiac enhancer region by the chromatin immunoprecipitation quantitative polymerase chain reaction assay. Protein-induced CPCs transplanted into rat hearts after myocardial infarction improved cardiac function, and this was related to differentiation into cardiomyocyte-like cells. These findings demonstrate that the highly efficient protein-transduction method can directly reprogram HDFs into CPCs. This protein reprogramming strategy lays the foundation for future refinements both in vitro and in vivo and might provide a source of CPCs for regenerative approaches. Significance The findings from the present study have demonstrated an efficient protein-transduction method of directly reprogramming fibroblasts into cardiac progenitor cells. These results have great potential in cell-based therapy for cardiovascular diseases. PMID:26564862

  8. MT1-MMP-dependent remodeling of cardiac extracellular matrix structure and function following myocardial infarction.

    PubMed

    Koenig, Gerald C; Rowe, R Grant; Day, Sharlene M; Sabeh, Farideh; Atkinson, Jeffrey J; Cooke, Kenneth R; Weiss, Stephen J

    2012-05-01

    The myocardial extracellular matrix (ECM), an interwoven meshwork of proteins, glycoproteins, proteoglycans, and glycosaminoglycans that is dominated by polymeric fibrils of type I collagen, serves as the mechanical scaffold on which myocytes are arrayed for coordinated and synergistic force transduction. Following ischemic injury, cardiac ECM remodeling is initiated via localized proteolysis, the bulk of which has been assigned to matrix metalloproteinase (MMP) family members. Nevertheless, the key effector(s) of myocardial type I collagenolysis both in vitro and in vivo have remained unidentified. In this study, using cardiac explants from mice deficient in each of the major type I collagenolytic MMPs, including MMP-13, MMP-8, MMP-2, MMP-9, or MT1-MMP, we identify the membrane-anchored MMP, MT1-MMP, as the dominant collagenase that is operative within myocardial tissues in vitro. Extending these observations to an in vivo setting, mice heterozygous for an MT1-MMP-null allele display a distinct survival advantage and retain myocardial function relative to wild-type littermates in an experimental model of myocardial infarction, effects associated with preservation of the myocardial type I collagen network as a consequence of the decreased collagenolytic potential of cardiac fibroblasts. This study identifies MT1-MMP as a key MMP responsible for effecting postinfarction cardiac ECM remodeling and cardiac dysfunction.

  9. Maturation status of sarcomere structure and function in human iPSC-derived cardiac myocytes.

    PubMed

    Bedada, Fikru B; Wheelwright, Matthew; Metzger, Joseph M

    2016-07-01

    Human heart failure due to myocardial infarction is a major health concern. The paucity of organs for transplantation limits curative approaches for the diseased and failing adult heart. Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) have the potential to provide a long-term, viable, regenerative-medicine alternative. Significant progress has been made with regard to efficient cardiac myocyte generation from hiPSCs. However, directing hiPSC-CMs to acquire the physiological structure, gene expression profile and function akin to mature cardiac tissue remains a major obstacle. Thus, hiPSC-CMs have several hurdles to overcome before they find their way into translational medicine. In this review, we address the progress that has been made, the void in knowledge and the challenges that remain. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  10. Estimation of cardiac reserve by peak power: validation and initial application of a simplified index

    NASA Technical Reports Server (NTRS)

    Armstrong, G. P.; Carlier, S. G.; Fukamachi, K.; Thomas, J. D.; Marwick, T. H.

    1999-01-01

    OBJECTIVES: To validate a simplified estimate of peak power (SPP) against true (invasively measured) peak instantaneous power (TPP), to assess the feasibility of measuring SPP during exercise and to correlate this with functional capacity. DESIGN: Development of a simplified method of measurement and observational study. SETTING: Tertiary referral centre for cardiothoracic disease. SUBJECTS: For validation of SPP with TPP, seven normal dogs and four dogs with dilated cardiomyopathy were studied. To assess feasibility and clinical significance in humans, 40 subjects were studied (26 patients; 14 normal controls). METHODS: In the animal validation study, TPP was derived from ascending aortic pressure and flow probe, and from Doppler measurements of flow. SPP, calculated using the different flow measures, was compared with peak instantaneous power under different loading conditions. For the assessment in humans, SPP was measured at rest and during maximum exercise. Peak aortic flow was measured with transthoracic continuous wave Doppler, and systolic and diastolic blood pressures were derived from brachial sphygmomanometry. The difference between exercise and rest simplified peak power (Delta SPP) was compared with maximum oxygen uptake (VO(2)max), measured from expired gas analysis. RESULTS: SPP estimates using peak flow measures correlated well with true peak instantaneous power (r = 0.89 to 0.97), despite marked changes in systemic pressure and flow induced by manipulation of loading conditions. In the human study, VO(2)max correlated with Delta SPP (r = 0.78) better than Delta ejection fraction (r = 0.18) and Delta rate-pressure product (r = 0.59). CONCLUSIONS: The simple product of mean arterial pressure and peak aortic flow (simplified peak power, SPP) correlates with peak instantaneous power over a range of loading conditions in dogs. In humans, it can be estimated during exercise echocardiography, and correlates with maximum oxygen uptake better than ejection

  11. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium

    PubMed Central

    Turnbull, Irene C.; Karakikes, Ioannis; Serrao, Gregory W.; Backeris, Peter; Lee, Jia-Jye; Xie, Chaoqin; Senyei, Grant; Gordon, Ronald E.; Li, Ronald A.; Akar, Fadi G.; Hajjar, Roger J.; Hulot, Jean-Sébastien; Costa, Kevin D.

    2014-01-01

    Cardiac experimental biology and translational research would benefit from an in vitro surrogate for human heart muscle. This study investigated structural and functional properties and interventional responses of human engineered cardiac tissues (hECTs) compared to human myocardium. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs, >90% troponin-positive) were mixed with collagen and cultured on force-sensing elastomer devices. hECTs resembled trabecular muscle and beat spontaneously (1.18±0.48 Hz). Microstructural features and mRNA expression of cardiac-specific genes (α-MHC, SERCA2a, and ACTC1) were comparable to human myocardium. Optical mapping revealed cardiac refractoriness with loss of 1:1 capture above 3 Hz, and cycle length dependence of the action potential duration, recapitulating key features of cardiac electrophysiology. hECTs reconstituted the Frank-Starling mechanism, generating an average maximum twitch stress of 660 μN/mm2 at Lmax, approaching values in newborn human myocardium. Dose-response curves followed exponential pharmacodynamics models for calcium chloride (EC50 1.8 mM) and verapamil (IC50 0.61 μM); isoproterenol elicited a positive chronotropic but negligible inotropic response, suggesting sarcoplasmic reticulum immaturity. hECTs were amenable to gene transfer, demonstrated by successful transduction with Ad.GFP. Such 3-D hECTs recapitulate an early developmental stage of human myocardium and promise to offer an alternative preclinical model for cardiology research.—Turnbull, I. C., Karakikes, I., Serrao, G. W., Backeris, P., Lee, J.-J., Xie, C., Senyei, G., Gordon, R. E., Li, R. A., Akar, F. G., Hajjar, R. J., Hulot, J.-S., Costa, K. D. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium. PMID:24174427

  12. Cross talk between cardiac myocytes and fibroblasts: from multiscale investigative approaches to mechanisms and functional consequences.

    PubMed

    Zhang, P; Su, J; Mende, U

    2012-12-15

    The heart is comprised of a syncytium of cardiac myocytes (CM) and surrounding nonmyocytes, the majority of which are cardiac fibroblasts (CF). CM and CF are highly interspersed in the myocardium with one CM being surrounded by one or more CF. Bidirectional cross talk between CM and CF plays important roles in determining cardiac mechanical and electrical function in both normal and diseased hearts. Genetically engineered animal models and in vitro studies have provided evidence that CM and CF can regulate each other's function. Their cross talk contributes to structural and electrical remodeling in both atria and ventricles and appears to be involved in the pathogenesis of various heart diseases that lead to heart failure and arrhythmia disorders. Mechanisms of CM-CF cross talk, which are not yet fully understood, include release of paracrine factors, direct cell-cell interactions via gap junctions and potentially adherens junctions and nanotubes, and cell interactions with the extracellular matrix. In this article, we provide an overview of the existing multiscale experimental and computational approaches for the investigation of cross talk between CM and CF and review recent progress in our understanding of the functional consequences and underlying mechanisms. Targeting cross talk between CM and CF could potentially be used therapeutically for the modulation of the cardiac remodeling response in the diseased heart and may lead to new strategies for the treatment of heart failure or rhythm disturbances.

  13. Heart-specific Rpd3 downregulation enhances cardiac function and longevity

    PubMed Central

    Kopp, Zachary A.; Hsieh, Jo-Lin; Li, Andrew; Wang, William; Bhatt, Dhelni T.; Lee, Angela; Kim, Sae Yeon; Fan, David; Shah, Veevek; Siddiqui, Emaad; Ragam, Radhika; Park, Kristen; Ardeshna, Dev; Park, Kunwoo; Wu, Rachel; Parikh, Hardik; Parikh, Ayush; Lin, Yuh-Ru; Park, Yongkyu

    2015-01-01

    Downregulation of Rpd3, a homologue of mammalian Histone Deacetylase 1 (HDAC1), extends lifespan in Drosophila melanogaster. Once revealed that long-lived fruit flies exhibit limited cardiac decline, we investigated whether Rpd3 downregulation would improve stress resistance and/or lifespan when targeted in the heart. Contested against three different stressors (oxidation, starvation and heat), heart-specific Rpd3 downregulation significantly enhanced stress resistance in flies. However, these higher levels of resistance were not observed when Rpd3 downregulation was targeted in other tissues or when other long-lived flies were tested in the heart-specific manner. Interestingly, the expressions of anti-aging genes such as sod2, foxo and Thor, were systemically increased as a consequence of heart-specific Rpd3 downregulation. Showing higher resistance to oxidative stress, the heart-specific Rpd3 downregulation concurrently exhibited improved cardiac functions, demonstrating an increased heart rate, decreased heart failure and accelerated heart recovery. Conversely, Rpd3 upregulation in cardiac tissue reduced systemic resistance against heat stress with decreased heart function, also specifying phosphorylated Rpd3 levels as a significant modulator. Continual downregulation of Rpd3 throughout aging increased lifespan, implicating that Rpd3 deacetylase in the heart plays a significant role in cardiac function and longevity to systemically modulate the fly's response to the environment. PMID:26399365

  14. Embryonic stem cell-based cardiopatches improve cardiac function in infarcted rats.

    PubMed

    Vallée, Jean-Paul; Hauwel, Mathieu; Lepetit-Coiffé, Matthieu; Bei, Wang; Montet-Abou, Karin; Meda, Paolo; Gardier, Stephany; Zammaretti, Prisca; Kraehenbuehl, Thomas P; Herrmann, Francois; Hubbell, Jeffrey A; Jaconi, Marisa E

    2012-03-01

    Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2-positive cardiac-committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31-positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell-based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction.

  15. Update on the slow delayed rectifier potassium current (I(Ks)): role in modulating cardiac function.

    PubMed

    Liu, Zhenzhen; Du, Lupei; Li, Minyong

    2012-01-01

    The slow delayed rectifier current (I(Ks)) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. I(Ks) channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of I(Ks) channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of I(Ks) channel in modulating cardiac function and donate some instructions to the progression of I(Ks) blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of I(Ks).

  16. High-Resolution MRI of Cardiac Function With Projection Reconstruction and Steady-State Free Precession

    PubMed Central

    Peters, Dana C.; Ennis, Daniel B.; McVeigh, Elliot R.

    2007-01-01

    The purpose of this study was to investigate the trabecular structure of the endocardial wall of the living human heart, and the effect of that structure on the measurement of myocardial function using MRI. High-resolution MR images (0.8 × 0.8 × 8 mm voxels) of cardiac function were obtained in five volunteers using a combination of undersampled projection reconstruction (PR) and steady-state free precession (SSFP) contrast in ECG-gated breath-held scans. These images provide movies of cardiac function with new levels of endocardial detail. The trabecular-papillary muscle complex, consisting of a mixture of blood and endocardial structures, is measured to constitute as much as 50% of the myocardial wall in some sectors. Myocardial wall strain measurements derived from tagged MR images show correlation between regions of trabeculae and papillary muscles and regions of high strain, leading to an overestimation of function in the lateral wall. PMID:12111934

  17. Accumulation of Mitochondrial DNA Mutations Disrupts Cardiac Progenitor Cell Function and Reduces Survival.

    PubMed

    Orogo, Amabel M; Gonzalez, Eileen R; Kubli, Dieter A; Baptista, Igor L; Ong, Sang-Bing; Prolla, Tomas A; Sussman, Mark A; Murphy, Anne N; Gustafsson, Åsa B

    2015-09-04

    Transfer of cardiac progenitor cells (CPCs) improves cardiac function in heart failure patients. However, CPC function is reduced with age, limiting their regenerative potential. Aging is associated with numerous changes in cells including accumulation of mitochondrial DNA (mtDNA) mutations, but it is unknown how this impacts CPC function. Here, we demonstrate that acquisition of mtDNA mutations disrupts mitochondrial function, enhances mitophagy, and reduces the replicative and regenerative capacities of the CPCs. We show that activation of differentiation in CPCs is associated with expansion of the mitochondrial network and increased mitochondrial oxidative phosphorylation. Interestingly, mutant CPCs are deficient in mitochondrial respiration and rely on glycolysis for energy. In response to differentiation, these cells fail to activate mitochondrial respiration. This inability to meet the increased energy demand leads to activation of cell death. These findings demonstrate the consequences of accumulating mtDNA mutations and the importance of mtDNA integrity in CPC homeostasis and regenerative potential.

  18. RNA splicing regulated by RBFOX1 is essential for cardiac function in zebrafish.

    PubMed

    Frese, Karen S; Meder, Benjamin; Keller, Andreas; Just, Steffen; Haas, Jan; Vogel, Britta; Fischer, Simon; Backes, Christina; Matzas, Mark; Köhler, Doreen; Benes, Vladimir; Katus, Hugo A; Rottbauer, Wolfgang

    2015-08-15

    Alternative splicing is one of the major mechanisms through which the proteomic and functional diversity of eukaryotes is achieved. However, the complex nature of the splicing machinery, its associated splicing regulators and the functional implications of alternatively spliced transcripts are only poorly understood. Here, we investigated the functional role of the splicing regulator rbfox1 in vivo using the zebrafish as a model system. We found that loss of rbfox1 led to progressive cardiac contractile dysfunction and heart failure. By using deep-transcriptome sequencing and quantitative real-time PCR, we show that depletion of rbfox1 in zebrafish results in an altered isoform expression of several crucial target genes, such as actn3a and hug. This study underlines that tightly regulated splicing is necessary for unconstrained cardiac function and renders the splicing regulator rbfox1 an interesting target for investigation in human heart failure and cardiomyopathy.

  19. Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress

    PubMed Central

    Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

    2016-01-01

    Objective The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Methods Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Results Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=−0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=−0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=−0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction

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

    PubMed

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

    2014-01-01

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

  1. Massive nitrogen loss in critical surgical illness: effect on cardiac mass and function.

    PubMed Central

    Hill, A A; Plank, L D; Finn, P J; Whalley, G A; Sharpe, N; Clark, M A; Hill, G L

    1997-01-01

    OBJECTIVE: The authors measured cardiac mass and function to determine whether these changed in patients who were critically ill who were losing large amounts of nitrogen from the body. SUMMARY BACKGROUND DATA: The large losses of body nitrogen that occur in patients with protein-energy malnutrition are associated with a loss of cardiac mass and function. It is not known if this also occurs in patients who were critically ill who are losing massive amounts of nitrogen. METHODS: Once hemodynamically stable, 13 patients who were critically ill underwent sequential measurements of left ventricular mass (LVM) and function, total body nitrogen (TBN), total body potassium, body weight, fat-free mass, and limb muscle mass. RESULTS: Over a 21-day study period, there was no change in LVM or function despite falls of 14% and 21% in TBN and total body potassium, respectively, a 21% fall in limb muscle mass, and a deterioration in skeletal muscle function by approximately 40%. CONCLUSIONS: In patients who were critically ill, cardiac mass does not decrease and function does not deteriorate after hemodynamic stability has been achieved despite massive losses of protein from the body. PMID:9296513

  2. Assessing cardiac pumping capability by exercise testing and inotropic stimulation.

    PubMed Central

    Tan, L B; Bain, R J; Littler, W A

    1989-01-01

    In heart failure both functional capacity and prognosis are primarily determined by the degree of pump dysfunction. Although data on haemodynamic function at rest may indicate impaired cardiac function, they do not assess the capacity of the heart to respond to stress. Maximal bicycle ergometry and incremental intravenous inotropic stimulation in 31 patients with moderately severe heart failure were evaluated as methods of stressing the heart to determine cardiac pumping capability, which is defined as the cardiac power obtained during maximal stimulation. There was good agreement between the cardiac pumping capabilities assessed by these two methods. Maximal cardiac power output was better than maximal cardiac output and left ventricular stroke work index in representing cardiac pumping capability, because it was less dependent on the type of stimulation used during evaluation. Inotropic challenge is at least as effective as exercise testing in assessing cardiac pumping capability in heart failure, and may be a better method in patients who find physical exercise difficult. PMID:2757870

  3. Left ventricular diastolic function in workers occupationally exposed to mercury vapour without clinical presentation of cardiac involvement

    SciTech Connect

    Poręba, Rafał Skoczyńska, Anna; Gać, Paweł; Turczyn, Barbara; Wojakowska, Anna

    2012-09-15

    The aim of the study was to evaluate left ventricular diastolic function in workers occupationally exposed to mercury vapour without clinical presentation of cardiac involvement. The studies included 115 workers (92 men and 23 women) occupationally exposed to mercury vapour without clinical presentation of cardiac involvement (mean age: 47.83 ± 8.29). Blood samples were taken to determine blood lipid profile, urine was collected to estimate mercury concentration (Hg-U) and echocardiographic examination was performed to evaluate diastolic function of the left ventricle. In the entire group of workers occupationally exposed to mercury vapour without clinical presentation of cardiac involvement, Spearman correlations analysis demonstrated the following significant linear relationships: between body mass index (BMI) and ratio of maximal early diastolic mitral flow velocity/early diastolic mitral annular velocity (E/E') (r = 0.32, p < 0.05), between serum HDL concentration and E/E' (r = − 0.22, p < 0.05), between Hg-U and E/E' (r = 0.35, p < 0.05), between Hg-U and isovolumetric relaxation time (IVRT') (r = 0.41, p < 0.05), between Hg-U and ratio of maximal early diastolic mitral flow velocity/maximal late diastolic mitral flow velocity (E/A) (r = − 0.31, p < 0.05) and between serum HDL concentration and E/A (r = 0.43, p < 0,05). In logistic regression analysis it as shown that independent factors of left ventricular diastolic dysfunction risk in the study group included a higher urine mercury concentration, a higher value of BMI and a lower serum HDL concentration (OR{sub Hg}-{sub U} = 1.071, OR{sub BMI} = 1.200, OR{sub HDL} = 0.896, p < 0.05). Summing up, occupational exposure to mercury vapour may be linked to impaired left ventricular diastolic function in workers without clinical presentation of cardiac involvement. -- Highlights: ► Study aimed at evaluation of LVDD in workers occupationally exposed to Hg. ► There was significant linear relationships

  4. Yoga respiratory training improves respiratory function and cardiac sympathovagal balance in elderly subjects: a randomised controlled trial

    PubMed Central

    Santaella, Danilo F; Devesa, Cesar R S; Rojo, Marcos R; Amato, Marcelo B P; Drager, Luciano F; Casali, Karina R; Montano, Nicola

    2011-01-01

    Objectives Since ageing is associated with a decline in pulmonary function, heart rate variability and spontaneous baroreflex, and recent studies suggest that yoga respiratory exercises may improve respiratory and cardiovascular function, we hypothesised that yoga respiratory training may improve respiratory function and cardiac autonomic modulation in healthy elderly subjects. Design 76 healthy elderly subjects were enrolled in a randomised control trial in Brazil and 29 completed the study (age 68±6 years, 34% males, body mass index 25±3 kg/m2). Subjects were randomised into a 4-month training program (2 classes/week plus home exercises) of either stretching (control, n=14) or respiratory exercises (yoga, n=15). Yoga respiratory exercises (Bhastrika) consisted of rapid forced expirations followed by inspiration through the right nostril, inspiratory apnoea with generation of intrathoracic negative pressure, and expiration through the left nostril. Pulmonary function, maximum expiratory and inspiratory pressures (PEmax and PImax, respectively), heart rate variability and blood pressure variability for spontaneous baroreflex determination were determined at baseline and after 4 months. Results Subjects in both groups had similar demographic parameters. Physiological variables did not change after 4 months in the control group. However, in the yoga group, there were significant increases in PEmax (34%, p<0.0001) and PImax (26%, p<0.0001) and a significant decrease in the low frequency component (a marker of cardiac sympathetic modulation) and low frequency/high frequency ratio (marker of sympathovagal balance) of heart rate variability (40%, p<0.001). Spontaneous baroreflex did not change, and quality of life only marginally increased in the yoga group. Conclusion Respiratory yoga training may be beneficial for the elderly healthy population by improving respiratory function and sympathovagal balance. Trial Registration CinicalTrials.gov identifier: NCT

  5. Multi-attribute preference functions. Health Utilities Index.

    PubMed

    Torrance, G W; Furlong, W; Feeny, D; Boyle, M

    1995-06-01

    Multi-attribute utility theory, an extension of conventional utility theory, can be applied to model preference scores for health states defined by multi-attribute health status classification systems. The type of preference independence among the attributes determines the type of preference function required: additive, multiplicative or multilinear. In addition, the type of measurement instrument used determines the type of preference score obtained: value or utility. Multi-attribute utility theory has been applied to 2 recently developed multi-attribute health status classification systems, the Health Utilities Index (HUI) Mark II and Mark III systems. Results are presented for the Mark II system, and ongoing research is described for the Mark III system. The theory is also discussed in the context of other well known multi-attribute systems. The HUI system is an efficient method of determining a general public-based utility score for a specified health outcome or for the health status of an individual. In clinical populations, the scores can be used to provide a single summary measure of health-related quality of life. In cost-utility analyses, the scores can be used as quality weights for calculating quality-adjusted life years. In general populations, the measure can be used as quality weights for determining population health expectancy.

  6. Mesodermal iPSC–derived progenitor cells functionally regenerate cardiac and skeletal muscle

    PubMed Central

    Quattrocelli, Mattia; Swinnen, Melissa; Giacomazzi, Giorgia; Camps, Jordi; Barthélemy, Ines; Ceccarelli, Gabriele; Caluwé, Ellen; Grosemans, Hanne; Thorrez, Lieven; Pelizzo, Gloria; Muijtjens, Manja; Verfaillie, Catherine M.; Blot, Stephane; Janssens, Stefan; Sampaolesi, Maurilio

    2015-01-01

    Conditions such as muscular dystrophies (MDs) that affect both cardiac and skeletal muscles would benefit from therapeutic strategies that enable regeneration of both of these striated muscle types. Protocols have been developed to promote induced pluripotent stem cells (iPSCs) to differentiate toward cardiac or skeletal muscle; however, there are currently no strategies to simultaneously target both muscle types. Tissues exhibit specific epigenetic alterations; therefore, source-related lineage biases have the potential to improve iPSC-driven multilineage differentiation. Here, we determined that differential myogenic propensity influences the commitment of isogenic iPSCs and a specifically isolated pool of mesodermal iPSC-derived progenitors (MiPs) toward the striated muscle lineages. Differential myogenic propensity did not influence pluripotency, but did selectively enhance chimerism of MiP-derived tissue in both fetal and adult skeletal muscle. When injected into dystrophic mice, MiPs engrafted and repaired both skeletal and cardiac muscle, reducing functional defects. Similarly, engraftment into dystrophic mice of canine MiPs from dystrophic dogs that had undergone TALEN-mediated correction of the MD-associated mutation also resulted in functional striatal muscle regeneration. Moreover, human MiPs exhibited the same capacity for the dual differentiation observed in murine and canine MiPs. The findings of this study suggest that MiPs should be further explored for combined therapy of cardiac and skeletal muscles. PMID:26571398

  7. Cardiac function and survival are affected by crude oil in larval red drum, Sciaenops ocellatus.

    PubMed

    Khursigara, Alexis J; Perrichon, Prescilla; Martinez Bautista, Naim; Burggren, Warren W; Esbaugh, Andrew J

    2017-02-01

    Following exposure to weathered and non-weathered oil, lethal and sub-lethal impacts on red drum larvae were assessed using survival, morphological, and cardiotoxicity assays. The LC50 for red drum ranged from 14.6 (10.3-20.9) to 21.3 (19.1-23.8) μgl(-1) ΣPAH with no effect of exposure timing during the pre-hatch window or oil weathering. Similarly, morphological deformities showed dose responses in the low ppb range. Cardiac output showed similar sensitivity resulting in a major 70% reduction after exposure to 2.6μgl(-1) ΣPAH. This cardiac failure was driven by reduced stroke volume rather than bradycardia, meaning that in some species, cardiac function is more sensitive than previously thought. After the Deepwater Horizon oil spill, much of this type of work has primarily focused on pelagic species with little known about fast developing estuarine species. These results demonstrate similarity sensitivity of the red drum as their pelagic counter parts, and more importantly, that cardiac function is dramatically reduced in concert with pericardial edema.

  8. Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature.

    PubMed

    Maagaard, Marie; Heiberg, Johan

    2016-09-01

    Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3-168 patients, mean age-ranges of 5-33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22-34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac

  9. Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature

    PubMed Central

    Heiberg, Johan

    2016-01-01

    Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3–168 patients, mean age-ranges of 5–33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22–34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac

  10. Sudden Cardiac Arrest in Patients with Preserved Left Ventricular Systolic Function: A Clinical Dilemma

    PubMed Central

    Sawhney, Navinder; Narayan, Sanjiv M.

    2009-01-01

    Stratifying the risk for sudden cardiac arrest (SCA) in individuals with preserved systolic function remains a pressing public health problem. Current guidelines for the implantation of cardiac defibrillators largely ignore patients with preserved systolic function, even though they account for the majority of cases. However, risk stratification for such individuals is increasingly feasible. Notably, most individuals who experience SCA have structural heart disease, even if undiagnosed. Thus, clinical risk scores have been developed to identify high risk. Moreover, there are now promising data that T-Wave Alternans (TWA), alone and in combination with other indices, effectively predicts SCA in this population. This article presents our current understanding of SCA due to ventricular arrhythmias in patients with preserved LV systolic function, and attempts to build a framework to predict risk in this population. PMID:19251226

  11. Automatic functional analysis of left ventricle in cardiac cine MRI

    PubMed Central

    Lu, Ying-Li; Connelly, Kim A.; Dick, Alexander J.; Wright, Graham A.

    2013-01-01

    Rationale and objectives A fully automated left ventricle segmentation method for the functional analysis of cine short axis (SAX) magnetic resonance (MR) images was developed, and its performance evaluated with 133 studies of subjects with diverse pathology: ischemic heart failure (n=34), non-ischemic heart failure (n=30), hypertrophy (n=32), and healthy (n=37). Materials and methods The proposed automatic method locates the left ventricle (LV), then for each image detects the contours of the endocardium, epicardium, papillary muscles and trabeculations. Manually and automatically determined contours and functional parameters were compared quantitatively. Results There was no significant difference between automatically and manually determined end systolic volume (ESV), end diastolic volume (EDV), ejection fraction (EF) and left ventricular mass (LVM) for each of the four groups (paired sample t-test, α=0.05). The automatically determined functional parameters showed high correlations with those derived from manual contours, and the Bland-Altman analysis biases were small (1.51 mL, 1.69 mL, –0.02%, –0.66 g for ESV, EDV, EF and LVM, respectively). Conclusions The proposed technique automatically and rapidly detects endocardial, epicardial, papillary muscles’ and trabeculations’ contours providing accurate and reproducible quantitative MRI parameters, including LV mass and EF. PMID:24040616

  12. Subclinical Cardiac Abnormalities and Kidney Function Decline: The Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Shlipak, Michael G.; Katz, Ronit; Agarwal, Subhashish; Ix, Joachim H.; Hsu, Chi-yuan; Peralta, Carmen A.

    2012-01-01

    Summary Background and objectives Clinical heart failure (HF) is associated with CKD and faster rates of kidney function decline. Whether subclinical abnormalities of cardiac structure are associated with faster kidney function decline is not known. The association between cardiac concentricity and kidney function decline was evaluated. Design, setting, participants, & measurements This is a longitudinal study of 3866 individuals from the Multi-Ethnic Study of Atherosclerosis (2000–2007) who were free of clinical cardiovascular disease, with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m2 at baseline and 5 years of follow-up. Concentricity, a measurement of abnormal cardiac size, was assessed by magnetic resonance imaging and evaluated as a continuous measurement and in quartiles. GFR was estimated by creatinine (eGFRcr) and cystatin C (eGFRcys). The association of concentricity with annual eGFR decline, incident CKD, and rapid kidney function decline (>5% per year) was investigated using linear mixed models as well as Poisson and logistic regression, respectively. Analyses adjusted for demographics, BP, diabetes, and inflammatory markers. Results Median decline was −0.8 (interquartile range, −3.1, −0.5) by eGFRcr. Compared with the lowest quartile of concentricity, persons in the highest quartile had an additional 21% (9%–32%) decline in mean eGFRcr in fully adjusted models. Concentricity was also associated with incident CKD and with rapid kidney function decline after adjustment. Conclusions Subclinical abnormalities in cardiac structure are associated with longitudinal kidney function decline independent of diabetes and hypertension. Future studies should examine mechanisms to explain these associations. PMID:22580783

  13. Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models.

    PubMed

    Wang, Louis W; Huttner, Inken G; Santiago, Celine F; Kesteven, Scott H; Yu, Ze-Yan; Feneley, Michael P; Fatkin, Diane

    2017-01-01

    The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l(-1) having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high frequency

  14. Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models

    PubMed Central

    Wang, Louis W.; Huttner, Inken G.; Santiago, Celine F.; Kesteven, Scott H.; Yu, Ze-Yan; Feneley, Michael P.

    2017-01-01

    ABSTRACT The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l−1 having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high

  15. Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues.

    PubMed

    Marsano, Anna; Conficconi, Chiara; Lemme, Marta; Occhetta, Paola; Gaudiello, Emanuele; Votta, Emiliano; Cerino, Giulia; Redaelli, Alberto; Rasponi, Marco

    2016-02-07

    In the past few years, microfluidic-based technology has developed microscale models recapitulating key physical and biological cues typical of the native myocardium. However, the application of controlled physiological uniaxial cyclic strains on a defined three-dimension cellular environment is not yet possible. Two-dimension mechanical stimulation was particularly investigated, neglecting the complex three-dimensional cell-cell and cell-matrix interactions. For this purpose, we developed a heart-on-a-chip platform, which recapitulates the physiologic mechanical environment experienced by cells in the native myocardium. The device includes an array of hanging posts to confine cell-laden gels, and a pneumatic actuation system to induce homogeneous uniaxial cyclic strains to the 3D cell constructs during culture. The device was used to generate mature and highly functional micro-engineered cardiac tissues (μECTs), from both neonatal rat and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), strongly suggesting the robustness of our engineered cardiac micro-niche. Our results demonstrated that the cyclic strain was effectively highly uniaxial and uniformly transferred to cells in culture. As compared to control, stimulated μECTs showed superior cardiac differentiation, as well as electrical and mechanical coupling, owing to a remarkable increase in junction complexes. Mechanical stimulation also promoted early spontaneous synchronous beating and better contractile capability in response to electric pacing. Pacing analyses of hiPSC-CM constructs upon controlled administration of isoprenaline showed further promising applications of our platform in drug discovery, delivery and toxicology fields. The proposed heart-on-a-chip device represents a relevant step forward in the field, providing a standard functional three-dimensional cardiac model to possibly predict signs of hypertrophic changes in cardiac phenotype by mechanical and biochemical co-stimulation.

  16. Effect of monomeric adiponectin on cardiac function and perfusion in anesthetized pig.

    PubMed

    Grossini, Elena; Prodam, Flavia; Walker, Gillian Elisabeth; Sigaudo, Lorenzo; Farruggio, Serena; Bellofatto, Kevin; Marotta, Patrizia; Molinari, Claudio; Mary, David; Bona, Gianni; Vacca, Giovanni

    2014-07-01

    Adiponectin, the most abundant adipokine released by adipose tissue, appears to play an important role in the regulation of vascular endothelial and cardiac function. To date, however, the physiological effects of human monomeric adiponectin on the coronary vasculature and myocardial systo-diastolic function, as well as on parasympathetic/sympathetic involvement and nitric oxide (NO) release, have not yet been investigated. Thus, we planned to determine the primary in vivo effects of human monomeric adiponectin on coronary blood flow and cardiac contractility/relaxation and the related role of autonomic nervous system, adiponectin receptors, and NO. In 30 anesthetized pigs, human monomeric adiponectin was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure, and the effects on coronary blood flow, left ventricular systo-diastolic function, myocardial oxygen metabolism, and NO release were examined. The mechanisms of the observed hemodynamic responses were also analyzed by repeating the highest dose of human monomeric adiponectin infusion after autonomic nervous system and NO blockade, and after specific adiponectin 1 receptor antagonist administration. Intracoronary human monomeric adiponectin caused dose-related increases of coronary blood flow and cardiac function. Those effects were accompanied by increased coronary NO release and coronary adiponectin levels. Moreover, the vascular effects of the peptide were prevented by blockade of β2-adrenoceptors and NO synthase, whereas all effects of human monomeric adiponectin were prevented by adiponectin 1 receptor inhibitor. In conclusion, human monomeric adiponectin primarily increased coronary blood flow and cardiac systo-diastolic function through the involvement of specific receptors, β2-adrenoceptors, and NO release.

  17. Recovering refractive index correlation function from measurement of tissue scattering phase function (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Rogers, Jeremy D.

    2016-03-01

    Numerous methods have been developed to quantify the light scattering properties of tissue. These properties are of interest in diagnostic and screening applications due to sensitivity to changes in tissue ultrastructure and changes associated with disease such as cancer. Tissue is considered a weak scatterer because that the mean free path is much larger than the correlation length. When this is the case, all scattering properties can be calculated from the refractive index correlation function Bn(r). Direct measurement of Bn(r) is challenging because it requires refractive index measurement at high resolution over a large tissue volume. Instead, a model is usually assumed. One particularly useful model, the Whittle-Matern function includes several realistic function types such as mass fractal and exponential. Optical scattering properties for weakly scattering media can be determined analytically from Bn(r) by applying the Rayleigh-Gans-Debye (RGD) or Born Approximation, and so measured scattering properties are used to fit parameters of the model function. Direct measurement of Bn(r) would provide confirmation that the function is a good representation of tissue or help in identifying the length scale at which changes occur. The RGD approximation relates the scattering phase function to the refractive index correlation function through a Fourier transform. This can be inverted without approximation, so goniometric measurement of the scattering can be converted to Bn(r). However, geometric constraints of the measurement of the phase function, angular resolution, and wavelength result in a band limited measurement of Bn(r). These limits are discussed and example measurements are described.

  18. Systems analysis of the mechanisms of cardiac diastolic function changes after microgravity exposure

    NASA Astrophysics Data System (ADS)

    Summers, Richard; Coleman, Thomas; Steven, Platts; Martin, David

    Detailed information concerning cardiac function was collected by two-dimensional and M-mode echocardiography at 10 days before flight and 3h after landing in astronauts returning from shuttle missions. A comparative analysis of this data suggests that cardiac diastolic function is reduced after microgravity exposure with little or no change in systolic function as measured by ejection fraction However, the mechanisms responsible for these adaptations have not been determined. In this study, an integrative computer model of human physiology that forms the framework for the Digital Astronaut Project (Guyton/Coleman/Summers Model) was used in a systems analysis of the echocardiographic data in the context of general cardiovascular physiologic functioning. The physiologic mechanisms involved in the observed changes were then determined by a dissection of model interrelationships. The systems analysis of possible physiologic mechanisms involved reveals that a loss of fluid from the myocardial interstitial space may lead to a stiffening of the myocardium and could potentially result in some of the cardiac diastolic dysfunction seen postflight. The cardiovascular dynamics may be different during spaceflight.

  19. Integrative computed tomographic imaging of cardiac structure, function, perfusion, and viability.

    PubMed

    Thilo, Christian; Hanley, Michael; Bastarrika, Gorka; Ruzsics, Balazs; Schoepf, U Joseph

    2010-01-01

    Recent advances in multidetector-row computed tomography (MDCT) technology have created new opportunities in cardiac imaging and provided new insights into a variety of disease states. Use of 64-slice coronary computed tomography angiography has been validated for the evaluation of clinically relevant coronary artery stenosis with high negative predictive values for ruling out significant obstructive disease. This technology has also advanced the care of patients with acute chest pain by simultaneous assessment of acute coronary syndrome, pulmonary embolism, and acute aortic syndrome ("triple rule out"). Although MDCT has been instrumental in the advancement of cardiac imaging, there are still limitations in patients with high or irregular heart rates. Newer MDCT scanner generations hold promise to improve some of these limitations for noninvasive cardiac imaging. The evaluation of coronary artery stenosis remains the primary clinical indication for cardiac computed tomography angiography. However, the use of MDCT for simultaneous assessment of coronary artery stenosis, atherosclerotic plaque formation, ventricular function, myocardial perfusion, and viability with a single modality is under intense investigation. Recent technical developments hold promise for accomplishing this goal and establishing MDCT as a comprehensive stand-alone test for integrative imaging of coronary heart disease.

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

    SciTech Connect

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

    1997-03-01

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

  1. STRUCTURAL AND FUNCTIONAL BASES OF CARDIAC FIBRILLATION. DIFFERENCES AND SIMILARITIES BETWEEN ATRIA AND VENTRICLES

    PubMed Central

    Filgueiras-Rama, David; Jalife, José

    2016-01-01

    Evidence accumulated over the last 25 years suggests that, whether in the atria or ventricles, fibrillation may be explained by the self-organization of the cardiac electrical activity into rapidly spinning rotors giving way to spiral waves that break intermittently and result in fibrillatory conduction. The dynamics and frequency of such rotors depend on the ion channel composition, excitability and refractory properties of the tissues involved, as well as on the thickness and respective three-dimensional fiber structure of the atrial and ventricular chambers. Therefore, improving the understanding of fibrillation has required the use of multidisciplinary research approaches, including optical mapping, patch clamping and molecular biology, and the application of concepts derived from the theory of wave propagation in excitable media. Moreover, translation of such concepts to the clinic has recently opened new opportunities to apply novel mechanistic approaches to therapy, particularly during atrial fibrillation ablation. Here we review the current understanding of the manner in which the underlying myocardial structure and function influence rotor initiation and maintenance during cardiac fibrillation. We also examine relevant underlying differences and similarities between atrial fibrillation and ventricular fibrillation and evaluate the latest clinical mapping technologies used to identify rotors in either arrhythmia. Altogether, the data being discussed have significantly improved our understanding of the cellular and structural bases of cardiac fibrillation and pointed toward potentially exciting new avenues for more efficient and effective identification and therapy of the most complex cardiac arrhythmias. PMID:27042693

  2. STRUCTURAL AND FUNCTIONAL BASES OF CARDIAC FIBRILLATION. DIFFERENCES AND SIMILARITIES BETWEEN ATRIA AND VENTRICLES.

    PubMed

    Filgueiras-Rama, David; Jalife, José

    2016-02-01

    Evidence accumulated over the last 25 years suggests that, whether in the atria or ventricles, fibrillation may be explained by the self-organization of the cardiac electrical activity into rapidly spinning rotors giving way to spiral waves that break intermittently and result in fibrillatory conduction. The dynamics and frequency of such rotors depend on the ion channel composition, excitability and refractory properties of the tissues involved, as well as on the thickness and respective three-dimensional fiber structure of the atrial and ventricular chambers. Therefore, improving the understanding of fibrillation has required the use of multidisciplinary research approaches, including optical mapping, patch clamping and molecular biology, and the application of concepts derived from the theory of wave propagation in excitable media. Moreover, translation of such concepts to the clinic has recently opened new opportunities to apply novel mechanistic approaches to therapy, particularly during atrial fibrillation ablation. Here we review the current understanding of the manner in which the underlying myocardial structure and function influence rotor initiation and maintenance during cardiac fibrillation. We also examine relevant underlying differences and similarities between atrial fibrillation and ventricular fibrillation and evaluate the latest clinical mapping technologies used to identify rotors in either arrhythmia. Altogether, the data being discussed have significantly improved our understanding of the cellular and structural bases of cardiac fibrillation and pointed toward potentially exciting new avenues for more efficient and effective identification and therapy of the most complex cardiac arrhythmias.

  3. Treadmill performance and cardiac function in selected patients with coronary heart disease

    SciTech Connect

    McKirnan, M.D.; Sullivan, M.; Jensen, D.; Froelicher, V.F.

    1984-02-01

    To investigate the cardiac determinants of treadmill performance in patients able to exercise to volitional fatigue, 88 patients with coronary heart disease free of angina pectoris were tested. The exercise tests included supine bicycle radionuclide ventriculography, thallium scintigraphy and treadmill testing with expired gas analysis. The number of abnormal Q wave locations, ejection fraction, end-diastolic volume, cardiac output, exercise-induced ST segment depression and thallium scar and ischemia scores were the cardiac variables considered. Rest and exercise ejection fractions were highly correlated to thallium scar score (r . -0.72 to -0.75, p less than 0.001), but not to maximal oxygen consumption (r . 0.19 to 0.25, p less than 0.05). Fifty-five percent of the variability in predicting treadmill time or estimated maximal oxygen consumption was explained by treadmill test-induced change in heart rate (39%), thallium ischemia score (12%) and cardiac output at rest (4%). The change in heart rate induced by the treadmill test explained only 27% of the variability in measured maximal oxygen consumption. Myocardial damage predicted ejection fraction at rest and the ability to increase heart rate with treadmill exercise appeared as an essential component of exercise capacity. Exercise capacity was only minimally affected by asymptomatic ischemia and was relatively independent of ventricular function.

  4. Effects of cardiotrophin-1 on haemodynamics and cardiac function in conscious rats.

    PubMed

    Jin, H; Yang, R; Ko, A; Pennica, D; Wood, W I; Paoni, N F

    1998-01-01

    Cardiotrophin-1 (CT-1), a newly discovered cytokine, has been shown to induce cardiac hypertrophy in vitro and in vivo. The present study examined the effects of CT-1 on haemodynamics and cardiac function. The measurements of haemodynamic parameters were made using in-dwelling catheters and flow probes in conscious, unrestrained rats. Intravenous administration of CT-1 caused a dose-dependent decrease in mean arterial pressure (MAP), and an increase in heart rate (HR). CT-1 (100 micrograms/kg) significantly elevated cardiac output and HR, and decreased MAP and systemic vascular resistance. Stroke volume was unaltered, suggesting that the CT-1 induced increase in cardiac output was secondary to increased HR. There was no significant difference in left ventricular maximal dP/dt between the CT-1-treated and vehicle-treated groups, suggesting that CT-1 might not induce a meaningful change in ventricular contractility. Pretreatment with intravenous N omega-nitro-L-arginine methyl ester, a specific inhibitor of nitric oxide synthase, significantly attenuated the depressor and tachycardic responses to CT-1. These results indicate that nitric oxide plays an important role in mediating the haemodynamic effects of CT-1.

  5. Cardiac baroreflex function and dynamic cerebral autoregulation in elderly Masters athletes.

    PubMed

    Aengevaeren, Vincent L; Claassen, Jurgen A H R; Levine, Benjamin D; Zhang, Rong

    2013-01-15

    Cerebral blood flow (CBF) is stably maintained through the combined effects of blood pressure (BP) regulation and cerebral autoregulation. Previous studies suggest that aerobic exercise training improves cardiac baroreflex function and beneficially affects BP regulation, but may negatively affect cerebral autoregulation. The purpose of this study was to reveal the impact of lifelong exercise on cardiac baroreflex function and dynamic cerebral autoregulation (CA) in older adults. Eleven Masters athletes (MA) (8 men, 3 women; mean age 73 ± 6 yr; aerobic training >15 yr) and 12 healthy sedentary elderly (SE) (7 men, 5 women; mean age 71 ± 6 yr) participated in this study. BP, CBF velocity (CBFV), and heart rate were measured during resting conditions and repeated sit-stand maneuvers to enhance BP variability. Baroreflex gain was assessed using transfer function analysis of spontaneous changes in systolic BP and R-R interval in the low frequency range (0.05-0.15 Hz). Dynamic CA was assessed during sit-stand-induced changes in mean BP and CBFV at 0.05 Hz (10 s sit, 10 s stand). Cardiac baroreflex gain was more than doubled in MA compared with SE (MA, 7.69 ± 7.95; SE, 3.18 ± 1.29 ms/mmHg; P = 0.018). However, dynamic CA was similar in the two groups (normalized gain: MA, 1.50 ± 0.56; SE, 1.56 ± 0.42% CBFV/mmHg; P = 0.792). These findings suggest that lifelong exercise improves cardiac baroreflex function, but does not alter dynamic CA. Thus, beneficial effects of exercise training on BP regulation can be achieved in older adults without compromising dynamic regulation of CBF.

  6. Mechanography: a non-invasive technique for the evaluation of cardiac function in children

    PubMed Central

    Spitaels, Silja; Fouron, Jean-Claude; Davignon, André

    1972-01-01

    Experience in the pediatric age group with mechanography, an indirect method of cardiovascular investigation, is described with emphasis on the recording technique and on the analysis of the tracings. A few examples are presented with comments on the morphological aspects and the time characteristics of the pulse curves, showing how much information about cardiac disease and especially myocardial function in children may be obtained. PMID:4640813

  7. Cardiac mitochondrial biogenesis in endotoxemia is not accompanied by mitochondrial function recovery.

    PubMed

    Vanasco, Virginia; Saez, Trinidad; Magnani, Natalia D; Pereyra, Leonardo; Marchini, Timoteo; Corach, Alejandra; Vaccaro, María Inés; Corach, Daniel; Evelson, Pablo; Alvarez, Silvia

    2014-12-01

    Mitochondrial biogenesis emerges as a compensatory mechanism involved in the recovery process in endotoxemia and sepsis. The aim of this work was to analyze the time course of the cardiac mitochondrial biogenesis process occurring during endotoxemia, with emphasis on the quantitative analysis of mitochondrial function. Female Sprague-Dawley rats (45 days old) were ip injected with LPS (10 mg/kg). Measurements were performed at 0-24 h after LPS administration. PGC-1α and mtTFA expression for biogenesis and p62 and LC3 expression for autophagy were analyzed by Western blot; mitochondrial DNA levels by qPCR, and mitochondrial morphology by transmission electron microscopy. Mitochondrial function was evaluated as oxygen consumption and respiratory chain complex activity. PGC-1α and mtTFA expression significantly increased in every time point analyzed, and mitochondrial mass was increased by 20% (P<0.05) at 24 h. p62 expression was significantly decreased in a time-dependent manner. LC3-II expression was significantly increased at all time points analyzed. Ultrastructurally, mitochondria displayed several abnormalities (internal vesicles, cristae disruption, and swelling) at 6 and 18 h. Structures compatible with fusion/fission processes were observed at 24 h. A significant decrease in state 3 respiration was observed in every time point analyzed (LPS 6h: 20%, P<0.05). Mitochondrial complex I activity was found decreased by 30% in LPS-treated animals at 6 and 24h. Complex II and complex IV showed decreased activity only at 24 h. The present results show that partial restoration of cardiac mitochondrial architecture is not accompanied by improvement of mitochondrial function in acute endotoxemia. The key implication of our study is that cardiac failure due to bioenergetic dysfunction will be overcome by therapeutic interventions aimed to restore cardiac mitochondrial function.

  8. Alkaline Phosphatase: A Biomarker of Cardiac Function in Pediatric Patients.

    PubMed

    Makil, Elizabeth S; Tang, Xinyu; Frazier, Elizabeth A; Collins, R Thomas

    2017-02-09

    Myocardial dysfunction and heart failure are common in pediatric patients with congenital and acquired heart disease. Alkaline phosphatase (AP) has been suggested as a biomarker for myocardial dysfunction after Fontan operation. We hypothesized that pediatric patients with myocardial dysfunction requiring orthotopic heart transplant (OHT) have diminished AP compared to normal. A retrospective review was performed in all patients who underwent OHT at Arkansas Children's Hospital between January 2007 and October 2012. Anatomic diagnoses, therapeutic interventions, and ventricular ejection fraction (EF) were recorded. Z scores for AP levels in the study group were determined by comparing the observed AP levels to age- and gender-matched normative values. T tests were performed to compare the mean AP Z score prior to and after OHT. p values <0.05 were considered statistically significant. During the study period, 124 OHTs were performed. Complete study data were available and analyzed from 71/124 patients (mean age at OHT 3.9 years; 51% female). The mean AP Z score was significantly lower in the study group prior to OHT compared to normal (p < 0.0001). The initiation of ACE inhibitor therapy prior to OHT was associated with a significant increase in AP and the ventricular EF (p < 0.001 for both). Treatment with milrinone was associated with an increase in EF. AP is significantly lower in pediatric patients with myocardial dysfunction prior to OHT compared to normal. AP increases significantly after the initiation of therapies to improve myocardial function. Diminished AP is an indicator of myocardial dysfunction in pediatric patients.

  9. About Cardiac Arrest

    MedlinePlus

    ... Thromboembolism Aortic Aneurysm More About Cardiac Arrest Updated:Mar 10,2017 What is cardiac arrest? Cardiac arrest is the abrupt loss of heart function in a person who may or may not have diagnosed heart ...

  10. Cell-cell junction remodeling in the heart: possible role in cardiac conduction system function and arrhythmias?

    PubMed

    Mezzano, Valeria; Sheikh, Farah

    2012-02-27

    Anchoring cell-cell junctions (desmosomes, fascia adherens) play crucial roles in maintaining mechanical integrity of cardiac muscle cells and tissue. Genetic mutations and/or loss of critical components in these macromolecular structures are increasingly being associated with arrhythmogenic cardiomyopathies; however, their specific roles have been primarily attributed to effects within the working (ventricular) cardiac muscle. Growing evidence also points to a key role for anchoring cell-cell junction components in cardiac muscle cells of the cardiac conduction system. This is not only evidenced by the molecular and ultra-structural presence of anchoring cell junctions in specific compartments/structures of the cardiac conduction system (sinoatrial node, atrioventricular node, His-Purkinje system), but also because conduction system-related arrhythmias can be found in humans and mouse models of cardiomyopathies harboring defects and/or mutations in key anchoring cell-cell junction proteins. These studies emphasize the clinical need to understand the molecular and cellular role(s) for anchoring cell-cell junctions in cardiac conduction system function and arrhythmias. This review will focus on (i) experimental findings that underline an important role for anchoring cell-cell junctions in the cardiac conduction system, (ii) insights regarding involvement of these structures in age-related cardiac remodeling of the conduction system, (iii) summarizing available genetic mouse models that can target cardiac conduction system structures and (iv) implications of these findings on future therapies for arrhythmogenic heart diseases.

  11. Assessment of Cardiac Functions in Infants with Cow’s Milk Allergy

    PubMed Central

    Ece, İbrahim; Demirören, Kaan; Demir, Nihat; Uner, Abdurrahman; Balli, Sevket

    2014-01-01

    Background Cow’s milk allergy is the most common food allergy in children, with rates estimated at 1.9% to 4.9%. Clinical phenotypes of cow’s milk allergy are varied and involve 1 or more target organs, with the main targets being the skin, respiratory system, and gastrointestinal tract. To date, no studies have investigated detailed cardiac function in children with cow’s milk allergy. The current study aimed to investigate cardiac function in infants with cow’s milk allergy. Material/Methods We studied 42 infants with cow’s milk allergy and 30 age- and sex-matched healthy subjects. Cardiac functions were evaluated by M-mode, pulsed-wave, and tissue Doppler echocardiography. Results There were no significant differences in ejection fraction or mitral and tricuspid annular plane systolic excursion between the 2 groups. Pulsed-wave Doppler-derived E/A ratios in mitral and tricuspid valves were similar in both groups. Ea/Aa ratios in the left ventricle posterior wall and right ventricle free wall were lower in patients with cow’s milk allergy than in the control group. The E/Ea ratio in the left ventricle, isovolumic relaxation time, deceleration time, and right and left ventricular myocardial performance indices were higher in patients in the study group. Conclusions Our study identified reduced early diastolic tissue Doppler velocities in infants with cow’s milk allergy. PMID:25098395

  12. Echocardiographic evaluation of the effects of dexmedetomidine on cardiac function during total intravenous anaesthesia.

    PubMed

    Lee, S H; Choi, Y S; Hong, G R; Oh, Y J

    2015-09-01

    The purpose of this study was to investigate the effects of dexmedetomidine on biventricular systolic and diastolic function using transoesophageal echocardiography. Cardiac function was assessed in 30 healthy patients who received total intravenous anaesthesia with propofol and remifentanil. The echocardiographic examinations were performed just before and 20, 40 and 60 min after dexmedetomidine or saline administration. Patients who received dexmedetomidine, compared with saline after 20 min, had a lower mean (SD) heart rate (56.7 (5.2) vs. 67.1 (7.1) beats.min(-1) ), higher systolic blood pressure (125.7 (18.9) vs. 109 (7.9) mmHg), and lower cardiac output (2.9 (0.5) vs. 3.7 (1.0) l.min(-1) ), respectively (all p < 0.05). In contrast, no changes were observed in biventricular systolic and diastolic indices in either group, and there were no inter-group differences at any time point. Dexmedetomidine, as an adjuvant to total intravenous anaesthesia, does not impair biventricular systolic and diastolic function in healthy patients, but decreases cardiac output by reducing heart rate.

  13. The Probability of Inconstancy in Assessment of Cardiac Function Post-Myocardial Infarction in Mice

    PubMed Central

    Chen, Jiqiu; Hammoudi, Nadjib; Benard, Ludovic; Ceholski, Delaine K; Zhang, Shihong; Lebeche, Djamel; Hajjar, Roger J

    2016-01-01

    In the present study, we explore the inherent variability that leads to overlaps in cardiac functional parameters between control and post-myocardial infarction (MI) mice. Heart failure was induced by Left Coronary Artery (LCA) ligation in mice. Average Ejection Fraction (EF) measured by echocardiography was lower in MI mice compared to control, but exhibited higher Standard Deviation (SD) and Standard Error (SEM), notably in 2D mode. Fractional Shortening (FS) showed a higher degree of overlap between MI and control mice even though the mean values were significantly different. Hemodynamic measurements of EF resulted in greater SD, SEM, ± 95% confidence intervals, and effect size. In comparing echocardiography at different time points, EF and FS were consistent by mean, but had apparent fluctuation in individual tracks, which were more obvious in MI than control mice. Hemodynamic measurements showed more complexity in data collection in mice in vivo. MI size showed variability that correlated with severity of cardiac function. These studies show that there is inherent variability in functional cardiac parameters after induction of heart failure by MI in mice. Analysis of these parameters by traditional statistical methods is insufficient, and we propose a more robust statistical analysis for proper data interpretation. PMID:27917392

  14. Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade.

    PubMed

    Hathaway, Catherine K; Grant, Ruriko; Hagaman, John R; Hiller, Sylvia; Li, Feng; Xu, Longquan; Chang, Albert S; Madden, Victoria J; Bagnell, C Robert; Rojas, Mauricio; Kim, Hyung-Suk; Wu, Bingruo; Zhou, Bin; Smithies, Oliver; Kakoki, Masao

    2015-04-21

    We have generated low-expressing and high-expressing endothelin-1 genes (L and H) and have bred mice with four levels of expression: L/L, ∼20%; L/+, ∼65%; +/+ (wild type), 100%; and H/+, ∼350%. The hypomorphic L allele can be spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination. Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and increased plasma volumes, together with increased ventricular superoxide levels, increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular stiffness. H/+ mice have decreased plasma volumes and significantly heavy stiff hearts. Global or cardiomyocyte-specific switching expression from L to H normalized the abnormalities already present in young adult L/L mice. An epithelial sodium channel antagonist normalized plasma volume and blood pressure, but only partially corrected the cardiomyopathy. A superoxide dismutase mimetic made superoxide levels subnormal, reduced Mmp9 overexpression, and substantially improved cardiac function. Genetic absence of Mmp9 also improved cardiac function, but increased superoxide remained. We conclude that endothelin-1 is critical for maintaining normal contractile function, for controlling superoxide and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to prevent overstretching. Even a modest (∼35%) decrease in endothelin-1 gene (Edn1) expression is sufficient to cause cardiac dysfunction.

  15. Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade

    PubMed Central

    Hathaway, Catherine K.; Grant, Ruriko; Hagaman, John R.; Hiller, Sylvia; Li, Feng; Xu, Longquan; Chang, Albert S.; Madden, Victoria J.; Bagnell, C. Robert; Rojas, Mauricio; Kim, Hyung-Suk; Wu, Bingruo; Zhou, Bin; Smithies, Oliver; Kakoki, Masao

    2015-01-01

    We have generated low-expressing and high-expressing endothelin-1 genes (L and H) and have bred mice with four levels of expression: L/L, ∼20%; L/+, ∼65%; +/+ (wild type), 100%; and H/+, ∼350%. The hypomorphic L allele can be spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination. Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and increased plasma volumes, together with increased ventricular superoxide levels, increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular stiffness. H/+ mice have decreased plasma volumes and significantly heavy stiff hearts. Global or cardiomyocyte-specific switching expression from L to H normalized the abnormalities already present in young adult L/L mice. An epithelial sodium channel antagonist normalized plasma volume and blood pressure, but only partially corrected the cardiomyopathy. A superoxide dismutase mimetic made superoxide levels subnormal, reduced Mmp9 overexpression, and substantially improved cardiac function. Genetic absence of Mmp9 also improved cardiac function, but increased superoxide remained. We conclude that endothelin-1 is critical for maintaining normal contractile function, for controlling superoxide and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to prevent overstretching. Even a modest (∼35%) decrease in endothelin-1 gene (Edn1) expression is sufficient to cause cardiac dysfunction. PMID:25848038

  16. Electroacupuncture improves cardiac function and remodeling by inhibition of sympathoexcitation in chronic heart failure rats.

    PubMed

    Ma, Luyao; Cui, Baiping; Shao, Yongfeng; Ni, Buqing; Zhang, Weiran; Luo, Yonggang; Zhang, Shijiang

    2014-05-15

    Chronic heart failure (CHF) is responsible for significant morbidity and mortality worldwide, mainly as a result of neurohumoral activation. Acupuncture has been used to treat a wide range of diseases and conditions. In this study, we investigated the effects of electroacupuncture (EA) on the sympathetic nerve activity, heart function, and remodeling in CHF rats after ligation of the left anterior descending coronary artery. CHF rats were randomly selected to EA and control groups for acute and chronic experiments. In the acute experiment, both the renal sympathetic nerve activity and cardiac sympathetic afferent reflex elicited by epicardial application of capsaicin were recorded. In the chronic experiment, we performed EA for 30 min once a day for 1 wk to test the long-term EA effects on heart function, remodeling, as well as infarct size in CHF rats. The results show EA significantly decreased the renal sympathetic nerve activity effectively, inhibited cardiac sympathetic afferent reflex, and lowered the blood pressure of CHF rats. Treating CHF rats with EA for 1 wk dramatically increased left ventricular ejection fraction and left ventricular fraction shortening, reversed the enlargement of left ventricular end-systolic dimension and left ventricular end-diastolic dimension, and shrunk the infarct size. In this experiment, we demonstrated EA attenuates sympathetic overactivity. Additionally, long-term EA improves cardiac function and remodeling and reduces infarct size in CHF rats. EA is a novel and potentially useful therapy for treating CHF.

  17. A role for matrix stiffness in the regulation of cardiac side population cell function.

    PubMed

    Qiu, Yiling; Bayomy, Ahmad F; Gomez, Marcus V; Bauer, Michael; Du, Ping; Yang, Yanfei; Zhang, Xin; Liao, Ronglih

    2015-05-01

    The mechanical properties of the local microenvironment may have important influence on the fate and function of adult tissue progenitor cells, altering the regenerative process. This is particularly critical following a myocardial infarction, in which the normal, compliant myocardial tissue is replaced with fibrotic, stiff scar tissue. In this study, we examined the effects of matrix stiffness on adult cardiac side population (CSP) progenitor cell behavior. Ovine and murine CSP cells were isolated and cultured on polydimethylsiloxane substrates, replicating the elastic moduli of normal and fibrotic myocardium. Proliferation capacity and cell cycling were increased in CSP cells cultured on the stiff substrate with an associated reduction in cardiomyogeneic differentiation and accelerated cell ageing. In addition, culture on stiff substrate stimulated upregulation of extracellular matrix and adhesion proteins gene expression in CSP cells. Collectively, we demonstrate that microenvironment properties, including matrix stiffness, play a critical role in regulating progenitor cell functions of endogenous resident CSP cells. Understanding the effects of the tissue microenvironment on resident cardiac progenitor cells is a critical step toward achieving functional cardiac regeneration.

  18. Functional Cardiac Lipolysis in Mice Critically Depends on Comparative Gene Identification-58*

    PubMed Central

    Zierler, Kathrin A.; Jaeger, Doris; Pollak, Nina M.; Eder, Sandra; Rechberger, Gerald N.; Radner, Franz P. W.; Woelkart, Gerald; Kolb, Dagmar; Schmidt, Albrecht; Kumari, Manju; Preiss-Landl, Karina; Pieske, Burkert; Mayer, Bernd; Zimmermann, Robert; Lass, Achim; Zechner, Rudolf; Haemmerle, Guenter

    2013-01-01

    Efficient catabolism of cellular triacylglycerol (TG) stores requires the TG hydrolytic activity of adipose triglyceride lipase (ATGL). The presence of comparative gene identification-58 (CGI-58) strongly increased ATGL-mediated TG catabolism in cell culture experiments. Mutations in the genes coding for ATGL or CGI-58 in humans cause neutral lipid storage disease characterized by TG accumulation in multiple tissues. ATGL gene mutations cause a severe phenotype especially in cardiac muscle leading to cardiomyopathy that can be lethal. In contrast, CGI-58 gene mutations provoke severe ichthyosis and hepatosteatosis in humans and mice, whereas the role of CGI-58 in muscle energy metabolism is less understood. Here we show that mice lacking CGI-58 exclusively in muscle (CGI-58KOM) developed severe cardiac steatosis and cardiomyopathy linked to impaired TG catabolism and mitochondrial fatty acid oxidation. The marked increase in ATGL protein levels in cardiac muscle of CGI-58KOM mice was unable to compensate the lack of CGI-58. The addition of recombinant CGI-58 to cardiac lysates of CGI-58KOM mice completely reconstituted TG hydrolytic activities. In skeletal muscle, the lack of CGI-58 similarly provoked TG accumulation. The addition of recombinant CGI-58 increased TG hydrolytic activities in control and CGI-58KOM tissue lysates, elucidating the limiting role of CGI-58 in skeletal muscle TG catabolism. Finally, muscle CGI-58 deficiency affected whole body energy homeostasis, which is caused by impaired muscle TG catabolism and increased cardiac glucose uptake. In summary, this study demonstrates that functional muscle lipolysis depends on both CGI-58 and ATGL. PMID:23413028

  19. Assessment of cardiac autonomic functions by heart rate recovery, heart rate variability and QT dynamicity parameters in patients with acromegaly.

    PubMed

    Dural, Muhammet; Kabakcı, Giray; Cınar, Neşe; Erbaş, Tomris; Canpolat, Uğur; Gürses, Kadri Murat; Tokgözoğlu, Lale; Oto, Ali; Kaya, Ergün Barış; Yorgun, Hikmet; Sahiner, Levent; Dağdelen, Selçuk; Aytemir, Kudret

    2014-04-01

    Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with

  20. Radiographic and electrocardiographic evaluation of cardiac morphology and function in captive cheetahs (Acinonyx jubatus).

    PubMed

    Schumacher, Juergen; Snyder, Patti; Citino, Scott B; Bennett, R Avery; Dvorak, Laura D

    2003-12-01

    In a prospective study, eight (four males and four females) healthy, adult captive cheetahs (Acinonyx jubatus) were immobilized with a combination of tiletamine-zolazepam (4 mg/kg, i.m.), administered with a remote drug delivery system, to define normal cardiac morphology and function. Standard lateral and ventrodorsal (VD) radiographs were then taken to measure heart and thorax using a metric and vertebral scale system. Standard six-lead electrocardiograms were obtained with the animals in right lateral recumbency under isoflurane anesthesia. Mean chest depth and width was 18.7 +/- 1.3 cm and 13.0 +/- 0.6 cm, respectively. The mean lateral cardiac short axis (X) was 9.1 +/- 0.6 cm. the mean cardiac long axis (Y) was 13.6 +/- 0.7 cm, and the mean lateral heart sum (X + Y) was 22.6 +/- 1.2 cm. In the VD projection, mean cardiac short axis (V) was 10.1 +/- 0.7 cm, mean cardiac long axis (W) was 14.9 +/- 1.2 cm, and the heart sum (V + W) was 24.9 +/- 1.8 cm. The vertebral heart size was 8.2 +/- 0.9. All cheetahs had sinus rhythm, and no arrhythmias were noted. Mean heart rate was 126 +/- 15 beats/min, and the mean electrical axis was 82 + 5 degrees. P waves were always positive on lead II and had a width of 0.04 +/- 0.01 sec and a height between 0.1 and 0.3 mV. PR intervals were 0.11 +/- 0.01 sec. The height of the QRS complex was 1.25 +/- 0.24 mV and the width 0.06 +/- 0.01 sec. The ST segment was 0.04 sec, and the T wave (height: 0.25 +/- 0.05 mV) was positive in all cheetahs examined. Although these cardiac and thoracic measurements were larger than those of domestic cats (Felis catus), ratios of cardiac parameters were similar in both species. Electrocardiographic findings were similar to those reported from domestic cats.

  1. A Four-Way Comparison of Cardiac Function with Normobaric Normoxia, Normobaric Hypoxia, Hypobaric Hypoxia and Genuine High Altitude

    PubMed Central

    Boos, Christopher John; O’Hara, John Paul; Mellor, Adrian; Hodkinson, Peter David; Tsakirides, Costas; Reeve, Nicola; Gallagher, Liam; Green, Nicholas Donald Charles; Woods, David Richard

    2016-01-01

    Background There has been considerable debate as to whether different modalities of simulated hypoxia induce similar cardiac responses. Materials and Methods This was a prospective observational study of 14 healthy subjects aged 22–35 years. Echocardiography was performed at rest and at 15 and 120 minutes following two hours exercise under normobaric normoxia (NN) and under similar PiO2 following genuine high altitude (GHA) at 3,375m, normobaric hypoxia (NH) and hypobaric hypoxia (HH) to simulate the equivalent hypoxic stimulus to GHA. Results All 14 subjects completed the experiment at GHA, 11 at NN, 12 under NH, and 6 under HH. The four groups were similar in age, sex and baseline demographics. At baseline rest right ventricular (RV) systolic pressure (RVSP, p = 0.0002), pulmonary vascular resistance (p = 0.0002) and acute mountain sickness (AMS) scores were higher and the SpO2 lower (p<0.0001) among all three hypoxic groups (GHA, NH and HH) compared with NN. At both 15 minutes and 120 minutes post exercise, AMS scores, Cardiac output, septal S’, lateral S’, tricuspid S’ and A’ velocities and RVSP were higher and SpO2 lower with all forms of hypoxia compared with NN. On post-test analysis, among the three hypoxia groups, SpO2 was lower at baseline and 15 minutes post exercise with GHA (89.3±3.4% and 89.3±2.2%) and HH (89.0±3.1 and (89.8±5.0) compared with NH (92.9±1.7 and 93.6±2.5%). The RV Myocardial Performance (Tei) Index and RVSP were significantly higher with HH than NH at 15 and 120 minutes post exercise respectively and tricuspid A’ was higher with GHA compared with NH at 15 minutes post exercise. Conclusions GHA, NH and HH produce similar cardiac adaptations over short duration rest despite lower SpO2 levels with GHA and HH compared with NH. Notable differences emerge following exercise in SpO2, RVSP and RV cardiac function. PMID:27100313

  2. Functional Cardiac Magnetic Resonance Imaging (MRI) in the Assessment of Myocardial Viability and Perfusion

    PubMed Central

    2003-01-01

    Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness safety and cost-effectiveness of using functional cardiac magnetic resonance imaging (MRI) for the assessment of myocardial viability and perfusion in patients with coronary artery disease and left ventricular dysfunction. Results Functional MRI has become increasingly investigated as a noninvasive method for assessing myocardial viability and perfusion. Most patients in the published literature have mild to moderate impaired LV function. It is possible that the severity of LV dysfunction may be an important factor that can alter the diagnostic accuracy of imaging techniques. There is some evidence of comparable or better performance of functional cardiac MRI for the assessment of myocardial viability and perfusion compared with other imaging techniques. However limitations to most of the studies included: Functional cardiac MRI studies that assess myocardial viability and perfusion have had small sample sizes. Some studies assessed myocardial viability/perfusion in patients who had already undergone revascularization, or excluded patients with a prior MI (Schwitter et al., 2001). Lack of explicit detail of patient recruitment. Patients with LVEF >35%. Interstudy variability in post MI imaging time(including acute or chronic MI), when patients with a prior MI were included. Poor interobserver agreement (kappa statistic) in the interpretation of the results. Traditionally, 0.80 is considered “good”. Cardiac MRI measurement of myocardial perfusion to as an adjunct tool to help diagnose CAD (prior to a definitive coronary angiography) has also been examined in some studies, with methodological limitations, yielding comparable results. Many studies examining myocardial viability and perfusion report on the accuracy of imaging methods with limited data on long-term patient outcome and management. Kim et al. (2000) revealed that the transmural

  3. Distinct conformational and functional effects of two adjacent pathogenic mutations in cardiac troponin I at the interface with troponin T.

    PubMed

    Akhter, Shirin; Jin, J-P

    2015-01-01

    The α-helix in troponin I (TnI) at the interface with troponin T (TnT) is a highly conserved structure. A point mutation in this region, A116G, was found in human cardiac TnI in a case of cardiomyopathy. An adjacent dominantly negative mutation found in turkey cardiac TnI (R111C, equivalent to K117C in human and K118C in mouse) decreased diastolic function and blunted beta-adrenergic response in transgenic mice. To investigate the functional importance of the TnI-TnT interface and pathological impact of the cardiac TnI mutations, we engineered K118C and A117G mutations in mouse cardiac TnI for functional studies. Despite their adjacent locations, A117G substitution results in faster mobility of cardiac TnI in SDS-PAGE whereas K118C decreases gel mobility, indicating significant and distinct changes in overall protein conformation. Consistently, monoclonal antibody epitope analysis demonstrated distinct local and remote conformational alterations in the two mutant proteins. Protein binding assays showed that K118C, but not A117G, decreased the relative binding affinity of cardiac TnI for TnT. K118C mutation decreased binding affinity for troponin C in a Ca(2+)-dependent manner, whereas A117G had a similar but less profound effect. Protein kinase A phosphorylation or truncation to remove the cardiac specific N-terminal extension of cardiac TnI resulted in similar conformational changes in the region interfacing with TnT and minimized the functional impacts of the mutations. The data demonstrate potent conformational and functional impacts of the TnT-interfacing helix in TnI and suggest a role of the N-terminal extension of cardiac TnI in modulating TnI-TnT interface functions.

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

    PubMed Central

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

    2014-01-01

    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 Ca2+ were measured. We observed the modulation of twitch force, but not of intracellular Ca2+, by both extracellular [Ca2+] 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 Ca2+ 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. PMID:24591576

  5. Dysregulation of cardiac autonomic function in offspring exposed to alcohol during antenatal period.

    PubMed

    Chandran, Sajish; Abhishekh, Hulegar A; Murthy, Pratima; Raju, Trichur R; Sathyaprabha, Talakad N

    2015-10-01

    Several lines of investigations have shown the deleterious effect of an alcohol on the autonomic nervous system. Recent evidence shows that infants exposed to alcohol during the antenatal period displayed aberration in the cardiac autonomic function after the birth. However, there is dearth of literature on the long term influence of antenatal alcohol exposure. In this study we measured the cardiac autonomic functions in children who were exposed to alcohol in the antenatal period and compared them with non-exposed control children. Twenty eight children (age: 9±2 years) in the antenatal alcohol exposed group and age, gender matched 30 non exposed healthy volunteers as a control (age: 10±2 years) were recruited. Electrocardiogram was recorded in all subjects at rest in the supine position. HRV parameters were analyzed in the time and frequency domains using customized software. The average heart rate was similar between both the groups. There was no statistical significant difference in the time domain measures between the groups. However, the low frequency power, normalized units and low frequency to high frequency ratio were significantly higher in the antenatal alcohol exposed children compared to the controls. This suggests sympathetic predominance in children who were exposed to alcohol in the antenatal period. In this study we provide evidence for the deleterious long lasting effect of antenatal exposure of alcohol on cardiac autonomic regulation. Further prospective studies are needed to confirm the causal relationship between antenatal alcohol exposure and autonomic dysregulation.

  6. Smyd1b is required for skeletal and cardiac muscle function in zebrafish

    PubMed Central

    Li, Huiqing; Zhong, Yongwang; Wang, Zengfeng; Gao, Jie; Xu, Jin; Chu, Wuying; Zhang, Jianshe; Fang, Shenyun; Du, Shao Jun

    2013-01-01

    Smyd1b is a member of the Smyd family that is specifically expressed in skeletal and cardiac muscles. Smyd1b plays a key role in thick filament assembly during myofibrillogenesis in skeletal muscles of zebrafish embryos. To better characterize Smyd1b function and its mechanism of action in myofibrillogenesis, we analyzed the effects of smyd1b knockdown on myofibrillogenesis in skeletal and cardiac muscles of zebrafish embryos. The results show that knockdown of smyd1b causes significant disruption of myofibril organization in both skeletal and cardiac muscles of zebrafish embryos. Microarray and quantitative reverse transcription-PCR analyses show that knockdown of smyd1b up-regulates heat shock protein 90 (hsp90) and unc45b gene expression. Biochemical analysis reveals that Smyd1b can be coimmunoprecipitated with heat shock protein 90 α-1 and Unc45b, two myosin chaperones expressed in muscle cells. Consistent with its potential function in myosin folding and assembly, knockdown of smyd1b significantly reduces myosin protein accumulation without affecting mRNA expression. This likely results from increased myosin degradation involving unc45b overexpression. Together these data support the idea that Smyd1b may work together with myosin chaperones to control myosin folding, degradation, and assembly into sarcomeres during myofibrillogenesis. PMID:24068325

  7. Low-Intensity Pulsed Ultrasound Improves the Functional Properties of Cardiac Mesoangioblasts.

    PubMed

    Bernal, Aurora; Pérez, Laura M; De Lucas, Beatriz; Martín, Nuria San; Kadow-Romacker, Anke; Plaza, Gustavo; Raum, Kay; Gálvez, Beatriz G

    2015-12-01

    Cell-based therapy is a promising approach for many diseases, including ischemic heart disease. Cardiac mesoangioblasts are committed vessel-associated progenitors that can restore to a significant, although partial, extent, heart structure and function in a murine model of myocardial infarction. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive form of mechanical energy that can be delivered into biological tissues as acoustic pressure waves, and is widely used for clinical applications including bone fracture healing. We hypothesized that the positive effects of LIPUS on bone and soft tissue, such as increased cell differentiation and cytoskeleton reorganization, could be applied to increase the therapeutic potential of mesoangioblasts for heart repair. In this work, we show that LIPUS stimulation of cardiac mesoangioblasts isolated from mouse and human heart results in significant cellular modifications that provide beneficial effects to the cells, including increased malleability and improved motility. Additionally, LIPUS stimulation increased the number of binucleated cells and induced cardiac differentiation to an extent comparable with 5'-azacytidine treatment. Mechanistically, LIPUS stimulation activated the BMP-Smad signalling pathway and increased the expression of myosin light chain-2 together with upregulation of β1 integrin and RhoA, highlighting a potentially important role for cytoskeleton reorganization. Taken together, these results provide functional evidence that LIPUS might be a useful tool to explore in the field of heart cell therapy.

  8. Impact of dispersed fuel oil on cardiac mitochondrial function in polar cod Boreogadus saida.

    PubMed

    Dussauze, Matthieu; Camus, Lionel; Le Floch, Stéphane; Pichavant-Rafini, Karine; Geraudie, Perrine; Coquillé, Nathalie; Amérand, Aline; Lemaire, Philippe; Theron, Michael

    2014-12-01

    In this study, impact of dispersed oil on cardiac mitochondrial function was assessed in a key species of Arctic marine ecosystem, the polar cod Boreogadus saida. Mature polar cod were exposed during 48 h to dispersed oil (mechanically and chemically) and dispersants alone. The increase observed in ethoxyresorufin-O-deethylase activity and polycyclic aromatic hydrocarbon metabolites in bile indicated no difference in contamination level between fish exposed to chemical or mechanical dispersion of oil. Oil induced alterations of O2 consumption of permeabilised cardiac fibres showing inhibitions of complexes I and IV of the respiratory chain. Oil did not induce any modification of mitochondrial proton leak. Dispersants did not induce alteration of mitochondrial activity and did not increase oil toxicity. These data suggest that oil exposure may limit the fitness of polar cod and consequently could lead to major disruption in the energy flow of polar ecosystem.

  9. The functional diversity of essential genes required for mammalian cardiac development.

    PubMed

    Clowes, Christopher; Boylan, Michael G S; Ridge, Liam A; Barnes, Emma; Wright, Jayne A; Hentges, Kathryn E

    2014-08-01

    Genes required for an organism to develop to maturity (for which no other gene can compensate) are considered essential. The continuing functional annotation of the mouse genome has enabled the identification of many essential genes required for specific developmental processes including cardiac development. Patterns are now emerging regarding the functional nature of genes required at specific points throughout gestation. Essential genes required for development beyond cardiac progenitor cell migration and induction include a small and functionally homogenous group encoding transcription factors, ligands and receptors. Actions of core cardiogenic transcription factors from the Gata, Nkx, Mef, Hand, and Tbx families trigger a marked expansion in the functional diversity of essential genes from midgestation onwards. As the embryo grows in size and complexity, genes required to maintain a functional heartbeat and to provide muscular strength and regulate blood flow are well represented. These essential genes regulate further specialization and polarization of cell types along with proliferative, migratory, adhesive, contractile, and structural processes. The identification of patterns regarding the functional nature of essential genes across numerous developmental systems may aid prediction of further essential genes and those important to development and/or progression of disease.

  10. Determinants of biventricular cardiac function: a mathematical model study on geometry and myofiber orientation.

    PubMed

    Pluijmert, Marieke; Delhaas, Tammo; de la Parra, Adrián Flores; Kroon, Wilco; Prinzen, Frits W; Bovendeerd, Peter H M

    2017-04-01

    In patient-specific mathematical models of cardiac electromechanics, usually a patient-specific geometry and a generic myofiber orientation field are used as input, upon which myocardial tissue properties are tuned to clinical data. It remains unclear to what extent deviations in myofiber orientation and geometry between model and patient influence model predictions on cardiac function. Therefore, we evaluated the sensitivity of cardiac function for geometry and myofiber orientation in a biventricular (BiV) finite element model of cardiac mechanics. Starting out from a reference geometry in which myofiber orientation had no transmural component, two new geometries were defined with either a 27 % decrease in LV short- to long-axis ratio, or a 16 % decrease of RV length, but identical LV and RV cavity and wall volumes. These variations in geometry caused differences in both local myofiber and global pump work below 6 %. Variation of fiber orientation was induced through adaptive myofiber reorientation that caused an average change in fiber orientation of [Formula: see text] predominantly through the formation of a component in transmural direction. Reorientation caused a considerable increase in local myofiber work [Formula: see text] and in global pump work [Formula: see text] in all three geometries, while differences between geometries were below 5 %. The findings suggest that implementing a realistic myofiber orientation is at least as important as defining a patient-specific geometry. The model for remodeling of myofiber orientation seems a useful approach to estimate myofiber orientation in the absence of accurate patient-specific information.

  11. Cardiac resynchronization therapy modulation of exercise left ventricular function and pulmonary O₂ uptake in heart failure.

    PubMed

    Tomczak, Corey R; Paterson, Ian; Haykowsky, Mark J; Lawrance, Richard; Martellotto, Andres; Pantano, Alfredo; Gulamhusein, Sajad; Haennel, Robert G

    2012-06-15

    To better understand the mechanisms contributing to improved exercise capacity with cardiac resynchronization therapy (CRT), we studied the effects of 6 mo of CRT on pulmonary O(2) uptake (Vo(2)) kinetics, exercise left ventricular (LV) function, and peak Vo(2) in 12 subjects (age: 56 ± 15 yr, peak Vo(2): 12.9 ± 3.2 ml·kg(-1)·min(-1), ejection fraction: 18 ± 3%) with heart failure. We hypothesized that CRT would speed Vo(2) kinetics due to an increase in stroke volume secondary to a reduction in LV end-systolic volume (ESV) and that the increase in peak Vo(2) would be related to an increase in cardiac output reserve. We found that Vo(2) kinetics were faster during the transition to moderate-intensity exercise after CRT (pre-CRT: 69 ± 21 s vs. post-CRT: 54 ± 17 s, P < 0.05). During moderate-intensity exercise, LV ESV reserve (exercise - resting) increased 9 ± 7 ml (vs. a 3 ± 9-ml decrease pre-CRT, P < 0.05), and steady-state stroke volume increased (pre-CRT: 42 ± 8 ml vs. post-CRT: 61 ± 12 ml, P < 0.05). LV end-diastolic volume did not change from rest to steady-state exercise post-CRT (P > 0.05). CRT improved heart rate, measured as a lower resting and steady-state exercise heart rate and as faster heart rate kinetics after CRT (pre-CRT: 89 ± 12 s vs. post-CRT: 69 ± 21 s, P < 0.05). For peak exercise, cardiac output reserve increased significantly post-CRT and was 22% higher at peak exercise post-CRT (both P < 0.05). The increase in cardiac output was due to both a significant increase in peak and reserve stroke volume and to a nonsignificant increase in heart rate reserve. Similar patterns in LV volumes as moderate-intensity exercise were observed at peak exercise. Cardiac output reserve was related to peak Vo(2) (r = 0.48, P < 0.05). These findings demonstrate the chronic CRT-mediated cardiac factors that contribute, in part, to the speeding in Vo(2) kinetics and increase in peak Vo(2) in clinically stable heart failure patients.

  12. Impaired contractile function due to decreased cardiac myosin binding protein C content in the sarcomere

    PubMed Central

    Cheng, Y.; Wan, X.; McElfresh, T. A.; Chen, X.; Gresham, K. S.; Rosenbaum, D. S.; Chandler, M. P.

    2013-01-01

    Mutations in cardiac myosin binding protein C (MyBP-C) are a common cause of familial hypertrophic cardiomyopathy (FHC). The majority of MyBP-C mutations are expected to reduce MyBP-C expression; however, the consequences of MyBP-C deficiency on the regulation of myofilament function, Ca2+ homeostasis, and in vivo cardiac function are unknown. To elucidate the effects of decreased MyBP-C expression on cardiac function, we employed MyBP-C heterozygous null (MyBP-C+/−) mice presenting decreases in MyBP-C expression (32%) similar to those of FHC patients carrying MyBP-C mutations. The levels of MyBP-C phosphorylation were reduced 53% in MyBP-C+/− hearts compared with wild-type hearts. Skinned myocardium isolated from MyBP-C+/− hearts displayed decreased cross-bridge stiffness at half-maximal Ca2+ activations, increased steady-state force generation, and accelerated rates of cross-bridge recruitment at low Ca2+ activations (<15% and <25% of maximum, respectively). Protein kinase A treatment abolished basal differences in rates of cross-bridge recruitment between MyBP-C+/− and wild-type myocardium. Intact ventricular myocytes from MyBP-C+/− hearts displayed abnormal sarcomere shortening but unchanged Ca2+ transient kinetics. Despite a lack of left ventricular hypertrophy, MyBP-C+/− hearts exhibited elevated end-diastolic pressure and decreased peak rate of LV pressure rise, which was normalized following dobutamine infusion. Furthermore, electrocardiogram recordings in conscious MyBP-C+/− mice revealed prolonged QRS and QT intervals, which are known risk factors for cardiac arrhythmia. Collectively, our data show that reduced MyBP-C expression and phosphorylation in the sarcomere result in myofilament dysfunction, contributing to contractile dysfunction that precedes compensatory adaptations in Ca2+ handling, and chamber remodeling. Perturbations in mechanical and electrical activity in MyBP-C+/− mice could increase their susceptibility to cardiac

  13. The heart's ‘little brain’ controlling cardiac function in the rabbit

    PubMed Central

    Brack, Kieran E

    2015-01-01

    New Findings •What is the topic of this review? The topic of the review is the intrinsic cardiac nervous system in the rabbit. •What advances does it highlight? The anatomy of rabbit intrinsic ganglia is similar to that of other species, including humans. Immunohistochemistry confirms the presence of cholinergic and adrenergic neurones, with a striking arrangement of neuronal nitric oxide synthase-positive cell bodies. Activation of atrial ganglia produces effects on local and remote regions. Heart disease is a primary cause of mortality in the developed world, and it is well recognized that neural mechanisms play an important role in many cardiac pathologies. The role of extrinsic autonomic nerves has traditionally attracted the most attention. However, there is a rich intrinsic innervation of the heart, including numerous cardiac ganglia (ganglionic plexuses), that has the potential to affect cardiac function independently as well as to influence the actions of the extrinsic nerves. To investigate this, an isolated, perfused, innervated rabbit Langendorff heart preparation was considered the best option. Although ganglionic plexuses have been well described for several species, there was no full description of the anatomy and histochemistry of rabbit hearts. To this end, rabbit intrinsic ganglia were located using acetylcholinesterase histology (n = 33 hearts). This revealed six generalized ganglionic regions, defined as a left neuronal complex above the left pulmonary vein, a right neuronal complex around the base of right cranial vein, three scattered in the dorsal right atrium and a region containing numerous ventricular ganglia located on the conus arteriosus. Using immunohistochemistry, neurons were found to contain choline acetyltransferase or tyrosine hydroxylase and/or neuronal nitric oxide synthase in differing amounts (choline acetyltransferase > tyrosine hydroxylase > neuronal nitric oxide synthase). The function of rabbit intrinsic ganglia

  14. Long-term wheel running compromises diaphragm function but improves cardiac and plantarflexor function in the mdx mouse.

    PubMed

    Selsby, Joshua T; Acosta, Pedro; Sleeper, Meg M; Barton, Elisabeth R; Sweeney, H Lee

    2013-09-01

    Dystrophin-deficient muscles suffer from free radical injury, mitochondrial dysfunction, apoptosis, and inflammation, among other pathologies that contribute to muscle fiber injury and loss, leading to wheelchair confinement and death in the patient. For some time, it has been appreciated that endurance training has the potential to counter many of these contributing factors. Correspondingly, numerous investigations have shown improvements in limb muscle function following endurance training in mdx mice. However, the effect of long-term volitional wheel running on diaphragm and cardiac function is largely unknown. Our purpose was to determine the extent to which long-term endurance exercise affected dystrophic limb, diaphragm, and cardiac function. Diaphragm specific tension was reduced by 60% (P < 0.05) in mice that performed 1 yr of volitional wheel running compared with sedentary mdx mice. Dorsiflexor mass (extensor digitorum longus and tibialis anterior) and function (extensor digitorum longus) were not altered by endurance training. In mice that performed 1 yr of volitional wheel running, plantarflexor mass (soleus and gastrocnemius) was increased and soleus tetanic force was increased 36%, while specific tension was similar in wheel-running and sedentary groups. Cardiac mass was increased 15%, left ventricle chamber size was increased 20% (diastole) and 18% (systole), and stroke volume was increased twofold in wheel-running compared with sedentary mdx mice. These data suggest that the dystrophic heart may undergo positive exercise-induced remodeling and that limb muscle function is largely unaffected. Most importantly, however, as the diaphragm most closely recapitulates the human disease, these data raise the possibility of exercise-mediated injury in dystrophic skeletal muscle.

  15. Carotid body denervation improves autonomic and cardiac function and attenuates disordered breathing in congestive heart failure

    PubMed Central

    Marcus, Noah J; Rio, Rodrigo; Schultz, Evan P; Xia, Xiao-Hong; Schultz, Harold D

    2014-01-01

    In congestive heart failure (CHF), carotid body (CB) chemoreceptor activity is enhanced and is associated with oscillatory (Cheyne–Stokes) breathing patterns, increased sympathetic nerve activity (SNA) and increased arrhythmia incidence. We hypothesized that denervation of the CB (CBD) chemoreceptors would reduce SNA, reduce apnoea and arrhythmia incidence and improve ventricular function in pacing-induced CHF rabbits. Resting breathing, renal SNA (RSNA) and arrhythmia incidence were measured in three groups of animals: (1) sham CHF/sham–CBD (sham–sham); (2) CHF/sham–CBD (CHF–sham); and (3) CHF/CBD (CHF–CBD). Chemoreflex sensitivity was measured as the RSNA and minute ventilatory () responses to hypoxia and hypercapnia. Respiratory pattern was measured by plethysmography and quantified by an apnoea–hypopnoea index, respiratory rate variability index and the coefficient of variation of tidal volume. Sympatho-respiratory coupling (SRC) was assessed using power spectral analysis and the magnitude of the peak coherence function between tidal volume and RSNA frequency spectra. Arrhythmia incidence and low frequency/high frequency ratio of heart rate variability were assessed using ECG and blood pressure waveforms, respectively. RSNA and responses to hypoxia were augmented in CHF–sham and abolished in CHF–CBD animals. Resting RSNA was greater in CHF–sham compared to sham–sham animals (43 ± 5% max vs. 23 ± 2% max, P < 0.05), and this increase was not found in CHF–CBD animals (25 ± 1% max, P < 0.05 vs. CHF–sham). Low frequency/high frequency heart rate variability ratio was similarly increased in CHF and reduced by CBD (P < 0.05). Respiratory rate variability index, coefficient of variation of tidal volume and apnoea–hypopnoea index were increased in CHF–sham animals and reduced in CHF–CBD animals (P < 0.05). SRC (peak coherence) was increased in CHF–sham animals (sham–sham 0.49 ± 0.05; CHF–sham 0.79

  16. On site assessment of cardiac function and neural regulation in amateur half marathon runners

    PubMed Central

    Dalla Vecchia, Laura; Traversi, Egidio; Porta, Alberto; Lucini, Daniela; Pagani, Massimo

    2014-01-01

    Objective Strenuous exercise variably modifies cardiovascular function. Only few data are available on intermediate levels of effort. We therefore planned a study in order to address the hypothesis that a half marathon distance would result in transient changes of cardiac mechanics, neural regulation and biochemical profile suggestive of a complex, integrated adaptation. Methods We enrolled 35 amateur athletes (42±7 years). Supine and standing heart rate variability and a complete echocardiographic evaluation were assessed on site after the completion of a half marathon (postrace) and about 1 month after (baseline). Biochemical tests were also measured postrace. Results Compared to baseline, the postrace left ventricular end-diastolic volume was smaller, peak velocity of E wave was lower, peak velocity of A wave higher, and accordingly the E/A ratio lower. The postrace heart and respiratory rate were higher and variance of RR interval lower, together with a clear shift towards a sympathetic predominance in supine position and a preserved response to orthostasis. At baseline, athletes were characterised by a lower, although still predominant, sympathetic drive with a preserved physiological response to standing. Conclusions Immediately after a half marathon there are clear marks that an elevated sympathetic cardiac drive outlasts the performance, together with decreased left ventricular diastolic volumes and slight modifications of the left ventricular filling pattern without additional signs of diastolic dysfunction or indices of transient left or right ventricular systolic abnormalities. Furthermore, no biochemical indices of any permanent cardiac damage were found. PMID:25332775

  17. Cardiac structure and function in humans: a new cardiovascular physiology laboratory

    PubMed Central

    Song, Su; Burleson, Paul D.; Passo, Stanley; Messina, Edward J.; Levine, Norman; Thompson, Carl I.; Belloni, Francis L.; Recchia, Fabio A.; Ojaimi, Caroline; Kaley, Gabor

    2009-01-01

    As the traditional cardiovascular control laboratory has disappeared from the first-year medical school curriculum, we have recognized the need to develop another “hands-on” experience as a vehicle for wide-ranging discussions of cardiovascular control mechanisms. Using an echocardiograph, an automatic blood pressure cuff, and a reclining bicycle, we developed protocols to illustrate the changes in cardiac and vascular function that occur with changes in posture, venous return, and graded exercise. We use medical student volunteers and a professional echocardiographer to generate and acquire data, respectively. In small-group sessions, we developed an interactive approach to discuss the data and to make a large number of calculations from a limited number of measurements. The sequence of cardiac events and cardiac structure in vivo were illustrated with the volunteers lying down, standing, and then with their legs raised passively above the heart to increase venous return. Volunteers were then asked to peddle the bicycle to achieve steady-state heart rates of 110 and 150 beats/min. Data were collected in all these states, and calculations were performed and used as the basis of a small-group discussion to illustrate physiological principles. Information related to a surprisingly large number of cardiovascular control mechanisms was derived, and its relevance to cardiovascular dysfunction was explored. This communication describes our experience in developing a new cardiovascular control laboratory to reinforce didactic material presented in lectures and small-group sessions. PMID:19745049

  18. Critical Care Management Focused on Optimizing Brain Function After Cardiac Arrest.

    PubMed

    Nakashima, Ryuta; Hifumi, Toru; Kawakita, Kenya; Okazaki, Tomoya; Egawa, Satoshi; Inoue, Akihiko; Seo, Ryutaro; Inagaki, Nobuhiro; Kuroda, Yasuhiro

    2017-03-24

    The discussion of neurocritical care management in post-cardiac arrest syndrome (PCAS) has generally focused on target values used for targeted temperature management (TTM). There has been less attention paid to target values for systemic and cerebral parameters to minimize secondary brain damage in PCAS. And the neurologic indications for TTM to produce a favorable neurologic outcome remain to be determined. Critical care management of PCAS patients is fundamental and essential for both cardiologists and general intensivists to improve neurologic outcome, because definitive therapy of PCAS includes both special management of the cause of cardiac arrest, such as coronary intervention to ischemic heart disease, and intensive management of the results of cardiac arrest, such as ventilation strategies to avoid brain ischemia. We reviewed the literature and the latest research about the following issues and propose practical care recommendations. Issues are (1) prediction of TTM candidate on admission, (2) cerebral blood flow and metabolism and target value of them, (3) seizure management using continuous electroencephalography, (4) target value of hemodynamic stabilization and its method, (5) management and analysis of respiration, (6) sedation and its monitoring, (7) shivering control and its monitoring, and (8) glucose management. We hope to establish standards of neurocritical care to optimize brain function and produce a favorable neurologic outcome.

  19. Shrink-induced biomimetic wrinkled substrates for functional cardiac cell alignment and culture.

    PubMed

    Mendoza, Nicole; Tu, Roger; Chen, Aaron; Lee, Eugene; Khine, Michelle

    2014-01-01

    The anisotropic alignment of cardiomyocytes in native myocardium tissue is a functional feature that is absent in traditional in vitro cardiac cell culture. Microenvironmental factors cue structural organization of the myocardium, which promotes the mechanical contractile properties and electrophysiological patterns seen in mature cardiomyocytes. Current nano- and microfabrication techniques, such as photolithography, generate simplified cell culture topographies that are not truly representative of the multifaceted and multi-scale fibrils of the cardiac extracellular matrix. In addition, such technologies are costly and require a clean room for fabrication. This chapter offers an easy, fast, robust, and inexpensive fabrication of biomimetic multi-scale wrinkled surfaces through the process of plasma treating and shrinking prestressed thermoplastic. Additionally, this chapter includes techniques for culturing stem cells and their cardiac derivatives on these substrates. Importantly, this wrinkled cell culture platform is compatible with both fluorescence and bright-field imaging; real-time physiological monitoring of CM action potential propagation and contraction properties can elucidate cardiotoxicity drug effects.

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

    PubMed

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

    2016-01-01

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

  1. Effect of aerobic training on baroreflex regulation of cardiac and sympathetic function.

    PubMed

    Sheldahl, L M; Ebert, T J; Cox, B; Tristani, F E

    1994-01-01

    To investigate the effect of aerobic exercise training on baroreflex regulation of muscle sympathetic nerve activity (MSNA) and cardiac R-R intervals in a middle-aged to older population, 10 healthy men > 40 yr of age underwent tests of autonomic function before and after 12 wk of high-intensity training. Cardiac and peripheral baroslopes were determined from the R-R interval vs. mean arterial pressure (MAP) and peroneal MSNA vs. diastolic pressure relationships, respectively, during sequential bolus injections of nitroprusside and phenylephrine. Maximal oxygen uptake increased (P < 0.05) 17% with training. Resting R-R interval increased (881 +/- 23 to 956 +/- 38 ms, P < 0.05), MAP decreased (96 +/- 2 to 91 +/- 3 mmHg, P < 0.05), and MSNA was unaltered (23.1 +/- 2.3 to 23.6 +/- 1.9 bursts/min) with training. Before and after training, respectively, cardiac baroslopes determined with decreasing (8.7 +/- 0.9 to 9.9 +/- 5.5 ms/mmHg) and increasing MAP (9.6 +/- 2.1 to 9.9 +/- 2.2 ms/mmHg) and the peripheral sympathetic baroslope (-3.3 +/- 0.4 to -3.5 +/- 0.6 bursts.min-1 x mmHg-1) did not differ. The results suggest that short-term aerobic training does not alter resting MSNA or neurocirculatory responses to baroreceptor challenges in middle-aged and older men.

  2. De Vega annuloplasty for functional tricupsid regurgitation: concept of tricuspid valve orifice index to optimize tricuspid valve annular reduction.

    PubMed

    Hwang, Ho Young; Chang, Hyoung Woo; Jeong, Dong Seop; Ahn, Hyuk

    2013-12-01

    We evaluated long-term results of De Vega annuloplasty measured by cylindrical sizers for functional tricuspid regurgitation (FTR) and analyzed the impact of measured annular size on the late recurrence of tricuspid valve regurgitation. Between 2001 and 2011, 177 patients (57.9±10.5 yr) underwent De Vega annuloplasty for FTR. Three cylindrical sizers (actual diameters of 29.5, 31.5, and 33.5 mm) were used to reproducibly reduce the tricuspid annulus. Long-term outcomes were evaluated and risk factor analyses for the recurrence of FTR ≥3+ were performed. Measured annular diameter indexed by patient's body surface area was included in the analyses as a possible risk factor. Operative mortality occurred in 8 patients (4.5%). Ten-year overall and cardiac death-free survivals were 80.5% and 90.8%, respectively. Five and 10-yr freedom rates from recurrent FTR were 96.5% and 93.1%, respectively. Cox proportional hazard model revealed that higher indexed annular size was the only risk factor for the recurrence of FTR (P=0.006). A minimal P value approach demonstrated that indexed annular diameter of 22.5 mm/m(2) was a cut-off value predicting the recurrence of FTR. De Vega annuloplasty for FTR results in low rates of recurrent FTR in the long-term. Tricuspid annulus should be reduced appropriately considering patients' body size to prevent recurrent FTR.

  3. The effects of pre-pregnancy obesity on fetal cardiac functions.

    PubMed

    Ece, Ibrahim; Uner, Abdurrahman; Balli, Sevket; Kibar, Ayse Esin; Oflaz, Mehmet Burhan; Kurdoglu, Mertihan

    2014-06-01

    Obesity is a substantial public health problem with a rapidly increasing prevalence in numerous industrialized nations. The objective of this study was to evaluate the effects of maternal pre-pregnancy obesity on fetal cardiac functions. We studied 55 fetuses of obese mothers and 44 fetuses of healthy mothers at 26-38 weeks of gestation. Cardiac functions were evaluated by M-mode, pulsed-wave, and tissue Doppler echocardiography. The two groups were similar in terms of maternal age, gravidity, parity, gestational age, estimated birth weight, serum lipids, and systolic-diastolic blood pressure. Fetal heart rate, diameters of the aortic and pulmonary valve annulus, aortic and pulmonary peak systolic velocities, ventricular systolic function, and cardiothoracic ratio were similar in the two groups. Pulsed-wave Doppler-derived E/A ratios in the mitral and tricuspid valves were similar in the two groups. The deceleration time of early mitral inflow was prolonged in the fetuses of the obese mothers. In the interventricular septum, left ventricle posterior wall, and right ventricle free wall, the E a and A a were higher, and E a/A a ratios were significantly lower in the study group than in the control group. The E/E a ratio was higher in the obese group than in the control group. The isovolumic relaxation time and the right and left ventricle myocardial performance indices were higher in the fetuses of the obese mothers than in the fetuses of the healthy mothers. We believe that maternal obesity has an important influence on fetal cardiac diastolic functions.

  4. Transfer function of long spliced graded-index fibers with mode scramblers.

    PubMed

    Ikeda, M; Kitayama, K

    1978-01-01

    Transfer functions of long spliced graded-index fibers are described. The transfer function of a spliced graded-index fiber is determined with the steady state mode exciter and the mode scramblers loaded just after each splicing. Under these conditions, the total transfer function calculated by the linear combination of each fiber's transfer function is in good agreement with the measurement results. It has been found that the transmission bandwidth can be widened by using mode scramblers.

  5. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure.

    PubMed

    Yin, Meimei; van der Horst, Iwan C C; van Melle, Joost P; Qian, Cheng; van Gilst, Wiek H; Silljé, Herman H W; de Boer, Rudolf A

    2011-08-01

    Metformin is the first choice drug for the treatment of patients with diabetes, but its use is debated in patients with advanced cardiorenal disease. Epidemiological data suggest that metformin may reduce cardiac events, in patients both with and without heart failure. Experimental evidence suggests that metformin reduces cardiac ischemia-reperfusion injury. It is unknown whether metformin improves cardiac function (remodeling) in a long-term post-MI remodeling model. We therefore studied male, nondiabetic, Sprague-Dawley rats that were subjected to either myocardial infarction (MI) or sham operation. Animals were randomly allocated to treatment with normal water or metformin-containing water (250 mg·kg(-1)·day(-1)). At baseline, 6 wk, and 12 wk, metabolic parameters were analyzed and oral glucose tolerance tests (OGTT) were performed. Echocardiography and hemodynamic parameters were assessed 12 wk after MI. In the MI model, infarct size was significantly smaller after 12-wk metformin treatment (29.6 ± 3.2 vs. 38.0 ± 2.2%, P < 0.05). Moreover, metformin resulted in less left ventricular dilatation (6.0 ± 0.4 vs. 7.6 ± 0.6 mm, P < 0.05) and preservation of left ventricular ejection fraction (65.8 ± 3.7% vs. 48.6 ± 5.6%, P < 0.05) compared with MI control. The improved cardiac function was associated with decreased atrial natriuretic peptide mRNA levels in the metformin-treated group (50% reduction compared with MI, P < 0.05). Insulin resistance did not occur during cardiac remodeling (as indicated by normal OGTT) and fasting glucose levels and the pattern of the OGTT were not affected by metformin. Molecular analyses suggested that altered AMP kinase phosphorylation status and low insulin levels mediate the salutary effects of metformin. Altogether our results indicate that metformin may have potential to attenuate heart failure development after myocardial infarction, in the absence of diabetes and independent of systemic glucose levels.

  6. Frequency components of systolic blood pressure variability reflect vasomotor and cardiac sympathetic functions in conscious rats.

    PubMed

    Yoshimoto, Takahiko; Eguchi, Kunihiro; Sakurai, Hiroki; Ohmichi, Yusuke; Hashimoto, Tatsuyuki; Ohmichi, Mika; Morimoto, Atsuko; Yamaguchi, Yoshiko; Ushida, Takahiro; Iwase, Satoshi; Sugenoya, Junichi; Kumazawa, Takao

    2011-09-01

    In this study, after confirming the suppression of autonomic nervous function by isoflurane anesthesia using autonomic antagonists, we pharmacologically investigated the involvement of vasomotor and cardiac sympathetic functions in systolic blood pressure variability (SBPV) frequency components in conscious rats at rest and during exposure to low-ambient temperature (LT-exposure, 9°C for 90 min). Under unanesthesia, phentolamine administration (α-adrenoceptor antagonist, 10 mg/kg) decreased the mid-frequency component (MF 0.33-0.73 Hz) and inversely increased the high-frequency component (HF 1.3-2.5 Hz). The increased HF was suppressed by subsequent treatment with atenolol (β-adrenoceptor antagonist, 10 mg/kg), but not with atropine (muscarinic receptor antagonist, 10 mg/kg). Moreover, phentolamine administration after atenolol decreased MF, but did not increase HF. LT-exposure increased MF and HF; however, phentolamine pretreatment suppressed the increased MF during LT-exposure, and atenolol pretreatment dose-dependently decreased the increased HF. These results suggest that MF and HF of SBPV may reflect α-adrenoceptor-mediated vasomotor function and β-adrenoceptor-mediated cardiac sympathetic function, respectively, in the conscious state.

  7. Cardiac catheterization

    MedlinePlus

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

  8. The microvascular effects of insulin resistance and diabetes on cardiac structure, function, and perfusion: a cardiovascular magnetic resonance study

    PubMed Central

    Larghat, Abdulghani M.; Swoboda, Peter P.; Biglands, John D.; Kearney, Mark T.; Greenwood, John P.; Plein, Sven

    2014-01-01

    Aims Type 2 diabetes mellitus is an independent risk factor for the development of heart failure. To better understand the mechanism by which this occurs, we investigated cardiac structure, function, and perfusion in patients with and without diabetes. Methods and results Sixty-five patients with no stenosis >30% on invasive coronary angiography were categorized into diabetes (19) and non-diabetes (46) which was further categorized into prediabetes (30) and controls (16) according to the American Diabetes Association guidelines. Each patient underwent comprehensive cardiovascular magnetic resonance assessment. Left-ventricular (LV) mass, relative wall mass (RWM), Lagrangian circumferential strain, LV torsion, and myocardial perfusion reserve (MPR) were calculated. LV mass was higher in diabetics than non-diabetics (112.8 ± 39.7 vs. 91.5 ± 21.3 g, P = 0.01) and in diabetics than prediabetics (112.8 ± 39.7 vs. 90.3 ± 18.7 g, P = 0.02). LV torsion angle was higher in diabetics than non-diabetics (9.65 ± 1.90 vs. 8.59 ± 1.91°, P = 0.047), and MPR was lower in diabetics than non-diabetics (2.10 ± 0.76 vs. 2.84 ± 1.25 mL/g/min, P = 0.01). There was significant correlation between MPR and early diastolic strain rate (r = −0.310, P = 0.01) and LV torsion (r = −0.306, P = 0.01). In multivariable linear regression analysis, non-diabetics waist–hip ratio, but not body mass index, had a significant association with RWM (Beta = 0.34, P = 0.02). Conclusion Patients with diabetes have increased LV mass, LV torsion, and decreased MPR. There is a significant association between decreased MPR and increased LV torsion suggesting a possible mechanistic link between microvascular disease and cardiac dysfunction in diabetes. PMID:25117473

  9. Relations among several nuclear and electronic density functional reactivity indexes

    NASA Astrophysics Data System (ADS)

    Torrent-Sucarrat, Miquel; Luis, Josep M.; Duran, Miquel; Toro-Labbé, Alejandro; Solà, Miquel

    2003-11-01

    An expansion of the energy functional in terms of the total number of electrons and the normal coordinates within the canonical ensemble is presented. A comparison of this expansion with the expansion of the energy in terms of the total number of electrons and the external potential leads to new relations among common density functional reactivity descriptors. The formulas obtained provide explicit links between important quantities related to the chemical reactivity of a system. In particular, the relation between the nuclear and the electronic Fukui functions is recovered. The connection between the derivatives of the electronic energy and the nuclear repulsion energy with respect to the external potential offers a proof for the "Quantum Chemical le Chatelier Principle." Finally, the nuclear linear response function is defined and the relation of this function with the electronic linear response function is given.

  10. Statistical functions and relevant correlation coefficients of clearness index

    NASA Astrophysics Data System (ADS)

    Pavanello, Diego; Zaaiman, Willem; Colli, Alessandra; Heiser, John; Smith, Scott

    2015-08-01

    This article presents a statistical analysis of the sky conditions, during years from 2010 to 2012, for three different locations: the Joint Research Centre site in Ispra (Italy, European Solar Test Installation - ESTI laboratories), the site of National Renewable Energy Laboratory in Golden (Colorado, USA) and the site of Brookhaven National Laboratories in Upton (New York, USA). The key parameter is the clearness index kT, a dimensionless expression of the global irradiance impinging upon a horizontal surface at a given instant of time. In the first part, the sky conditions are characterized using daily averages, giving a general overview of the three sites. In the second part the analysis is performed using data sets with a short-term resolution of 1 sample per minute, demonstrating remarkable properties of the statistical distributions of the clearness index, reinforced by a proof using fuzzy logic methods. Successively some time-dependent correlations between different meteorological variables are presented in terms of Pearson and Spearman correlation coefficients, and introducing a new one.

  11. Invasive surgery reduces infarct size and preserves cardiac function in a porcine model of myocardial infarction

    PubMed Central

    van Hout, Gerardus PJ; Teuben, Michel PJ; Heeres, Marjolein; de Maat, Steven; de Jong, Renate; Maas, Coen; Kouwenberg, Lisanne HJA; Koenderman, Leo; van Solinge, Wouter W; de Jager, Saskia CA; Pasterkamp, Gerard; Hoefer, Imo E

    2015-01-01

    Reperfusion injury following myocardial infarction (MI) increases infarct size (IS) and deteriorates cardiac function. Cardioprotective strategies in large animal MI models often failed in clinical trials, suggesting translational failure. Experimentally, MI is induced artificially and the effect of the experimental procedures may influence outcome and thus clinical applicability. The aim of this study was to investigate if invasive surgery, as in the common open chest MI model affects IS and cardiac function. Twenty female landrace pigs were subjected to MI by transluminal balloon occlusion. In 10 of 20 pigs, balloon occlusion was preceded by invasive surgery (medial sternotomy). After 72 hrs, pigs were subjected to echocardiography and Evans blue/triphenyl tetrazoliumchloride double staining to determine IS and area at risk. Quantification of IS showed a significant IS reduction in the open chest group compared to the closed chest group (IS versus area at risk: 50.9 ± 5.4% versus 69.9 ± 3.4%, P = 0.007). End systolic LV volume and LV ejection fraction measured by echocardiography at follow-up differed significantly between both groups (51 ± 5 ml versus 65 ± 3 ml, P = 0.033; 47.5 ± 2.6% versus 38.8 ± 1.2%, P = 0.005). The inflammatory response in the damaged myocardium did not differ between groups. This study indicates that invasive surgery reduces IS and preserves cardiac function in a porcine MI model. Future studies need to elucidate the effect of infarct induction technique on the efficacy of pharmacological therapies in large animal cardioprotection studies. PMID:26282710

  12. The TRPM4 channel is functionally important for the beneficial cardiac remodeling induced by endurance training.

    PubMed

    Gueffier, Mélanie; Zintz, Justin; Lambert, Karen; Finan, Amanda; Aimond, Franck; Chakouri, Nourdine; Hédon, Christophe; Granier, Mathieu; Launay, Pierre; Thireau, Jérôme; Richard, Sylvain; Demion, Marie

    2017-02-21

    Cardiac hypertrophy (CH) is an adaptive process that exists in two distinct forms and allows the heart to adequately respond to an organism's needs. The first form of CH is physiological, adaptive and reversible. The second is pathological, irreversible and associated with fibrosis and cardiomyocyte death. CH involves multiple molecular mechanisms that are still not completely defined but it is now accepted that physiological CH is associated more with the PI3-K/Akt pathway while the main signaling cascade activated in pathological CH involves the Calcineurin-NFAT pathway. It was recently demonstrated that the TRPM4 channel may act as a negative regulator of pathological CH by regulating calcium entry and thus the Cn-NFAT pathway. In this study, we examined if the TRPM4 channel is involved in the physiological CH process. We evaluated the effects of 4 weeks endurance training on the hearts of Trpm4 (+/+) and Trpm4 (-/-) mice. We identified an elevated functional expression of the TRPM4 channel in cardiomyocytes after endurance training suggesting a potential role for the channel in physiological CH. We then observed that Trpm4 (+/+) mice displayed left ventricular hypertrophy after endurance training associated with enhanced cardiac function. By contrast, Trpm4 (-/-) mice did not develop these adaptions. While Trpm4 (-/-) mice did not develop gross cardiac hypertrophy, the cardiomyocyte surface area was larger and associated with an increase of Tunel positive cells. Endurance training in Trpm4 (+/+) mice did not increase DNA fragmentation in the heart. Endurance training in Trpm4 (+/+) mice was associated with activation of the classical physiological CH Akt pathway while Trpm4 (-/-) favored the Calcineurin pathway. Calcium studies demonstrated that TRPM4 channel negatively regulates calcium entry providing support for activation of the Cn-NFAT pathway in Trpm4 (-/-) mice. In conclusion, we provide evidence for the functional expression of TRPM4 channel in response

  13. Reduction of Leukocyte Counts by Hydroxyurea Improves Cardiac Function in Rats with Acute Myocardial Infarction.

    PubMed

    Zhu, Guiyue; Yao, Yucai; Pan, Lingyun; Zhu, Wei; Yan, Suhua

    2015-12-17

    BACKGROUND This study aimed to decrease leukocytes counts by hydroxyurea (Hu) in an acute myocardial infarction (AMI) rat model and examine its effect on the inflammatory response of myocardial infarction and cardiac functions. MATERIAL AND METHODS AMI was successfully caused in 36 rats, and 12 control rats received sham operation. Rats in the AMI group were then randomly divided into Hu and vehicle group with 18 rats each. Rats in the Hu AMI group received Hu (200 mg/kg) intragastrically while vehicle AMI group received saline. Leukocytes counts, cardiac functions, myocardial tissue morphology, and levels of soluble intercellular adhesion molecule-1 (sICAM), P-selectin and platelet activating factor (PAF) were measured and compared among the three groups four weeks after AMI induction. RESULTS Leukocytes, neutrophils, and leukomonocyte counts in vehicle AMI rats were significantly higher than that of the normal control group (p<0.05). However, Hu treatment decreased their counts significantly (p<0.05). sICAM, P-selectin, and PAF level in vehicle AMI group were significantly higher than those of the normal group, and their level was also decreased by Hu treatment (p<0.05). Echocardiography analysis showed that Hu treatment increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) compared to that of vehicle AMI group (p<0.05). Histopathological examination showed that Hu significantly reduced the swelling of the heart muscle fiber in necrotic foci and the number of inflammatory cells infiltrated into myocardial interstitium compared to vehicle AMI group. CONCLUSIONS Decrease leukocytes counts by Hu significantly reduced inflammatory reaction and improved cardiac functions in AMI rats.

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

    PubMed Central

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

    2015-01-01

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

  15. Molecular mechanisms of neuronal nitric oxide synthase in cardiac function and pathophysiology

    PubMed Central

    Zhang, Yin Hua; Jin, Chun Zi; Jang, Ji Hyun; Wang, Yue

    2014-01-01

    Neuronal nitric oxide synthase (nNOS or NOS1) is the major endogenous source of myocardial nitric oxide (NO), which facilitates cardiac relaxation and modulates contraction. In the healthy heart it regulates intracellular Ca2+, signalling pathways and oxidative homeostasis and is upregulated from early phases upon pathogenic insult. nNOS plays pivotal roles in protecting the myocardium from increased oxidative stress, systolic/diastolic dysfunction, adverse structural remodelling and arrhythmias in the failing heart. Here, we show that the downstream target proteins of nNOS and underlying post-transcriptional modifications are shifted during disease progression from Ca2+-handling proteins [e.g. PKA-dependent phospholamban phosphorylation (PLN-Ser16)] in the healthy heart to cGMP/PKG-dependent PLN-Ser16 with acute angiotensin II (Ang II) treatment. In early hypertension, nNOS-derived NO is involved in increases of cGMP/PKG-dependent troponin I (TnI-Ser23/24) and cardiac myosin binding protein C (cMBP-C-Ser273). However, nNOS-derived NO is shown to increase S-nitrosylation of various Ca2+-handling proteins in failing myocardium. The spatial compartmentation of nNOS and its translocation for diverse binding partners in the diseased heart or various nNOS splicing variants and regulation in response to pathological stress may be responsible for varied underlying mechanisms and functions. In this review, we endeavour to outline recent advances in knowledge of the molecular mechanisms mediating the functions of nNOS in the myocardium in both normal and diseased hearts. Insights into nNOS gene regulation in various tissues are discussed. Overall, nNOS is an important cardiac protector in the diseased heart. The dynamic localization and various mediating mechanisms of nNOS ensure that it is able to regulate functions effectively in the heart under stress. PMID:24756636

  16. Improvement of early postburn cardiac function by use of Panax notoginseng and immediate total eschar excision in one operation.

    PubMed

    Huang, Y S; Yang, Z C; Yan, B G; Hu, X C; Li, A N; Crowther, R S

    1999-02-01

    Cardiac dysfunction development in the early stage postburn has been an important problem in burn treatment. However, no effective therapies are available for use in clinical practice. In this study, we sought to determine whether early total eschar excision (EEE) in one operation and the traditional Chinese herb Panax notoginseng (PNS) would be helpful in improving early postburn cardiac function. 160 Wistar rats were randomly divided into burn (burn group, n = 50), burn treated with EEE (EEE group, n = 50), burn treated with PNS (PNS group, n = 50) groups and normal controls (n = 10). All rats except the normal control were given a 30% TBSA full skin thickness burn and resuscitated with Ringer's lactate. EEE was performed immediately after the burn group received the first intraperitoneal injection of Ringer's lactate. The wound was covered with homoskin from normal rats. In the PNS group, two doses of PNS (200 mg/kg for each dose) were given intraperitoneally immediately and 4 h postburn. Cardiac contractile function and cardiac troponin T (TnT) were determined at 1, 3, 6, 12 and 24 h postburn. Results showed that cardiac contractile parameters including AOSP, AODP, LVSP and +dp/dt(max) all declined and were still significantly lower than the control values at 24 h postburn. Cardiac TnT was elevated markedly and reached a level 25 times higher than control at 12 h postburn. In EEE and PNS groups, the reduction of cardiac contractile function was limited as compared with that in the burn group. Levels of TnT in both EEE and PNS groups were significantly lower than in the burn group 6 h postburn later. The findings of this study demonstrated that both EEE and PNS were effective in improving early postburn cardiac function.

  17. Beneficial Effects of Schisandrin B on the Cardiac Function in Mice Model of Myocardial Infarction

    PubMed Central

    Chen, Pengsheng; Pang, Sisi; Yang, Naiquan; Meng, Haoyu; Liu, Jia; Zhou, Ningtian; Zhang, Min; Xu, Zhihui; Gao, Wei; Chen, Bo; Tao, Zhengxian; Wang, Liansheng; Yang, Zhijian

    2013-01-01

    The fruit of Schisandra chinensis has been used in the traditional Chinese medicine for thousands of years. Accumulating evidence suggests that Schisandrin B (Sch B) has cardioprotection effect on myocardial ischemia in vitro. However, it is unclear whether Sch B has beneficial effects on continuous myocardial ischemia in vivo. The aim of the present study was to investigate whether Sch B could improve cardiac function and attenuate myocardial remodeling after myocardial infarction (MI) in mice. Mice model of MI was established by permanent ligation of the left anterior descending (LAD) coronary artery. Then the MI mice were randomly treated with Sch B or vehicle alone. After treatment for 3 weeks, Sch B could increase survival rate, improve heart function and decrease infarct size compared with vehicle. Moreover, Sch B could down-regulate some inflammatory cytokines, activate eNOS pathway, inhibit cell apoptosis, and enhance cell proliferation. Further in vitro study on H9c2 cells showed similar effects of Sch B on prevention of hypoxia-induced inflammation and cell apoptosis. Taken together, our results demonstrate that Sch B can reduce inflammation, inhibit apoptosis, and improve cardiac function after ischemic injury. It represents a potential novel therapeutic approach for treatment of ischemic heart disease. PMID:24260217

  18. Functional Coupling of Ca2+ Channels and Ryanodine Receptors in Cardiac Myocytes

    NASA Astrophysics Data System (ADS)

    Sham, James S. K.; Cleemann, Lars; Morad, Martin

    1995-01-01

    In skeletal muscle, dihydropyridine receptors are functionally coupled to ryanodine receptors of the sarcoplasmic reticulum in triadic or diadic junctional complexes. In cardiac muscle direct physical or functional couplings have not been demonstrated. We have tested the hypothesis of functional coupling of L-type Ca2+ channels and ryanodine receptors in rat cardiac myocytes by comparing the efficacies of Ca2+ in triggering Ca2+ release when the ion enters the cell via the Ca2+ channels or the Na^+/Ca2+ exchanger. Ca2+ transported through the Ca2+ channels was 20-160 times more effective than Ca2+ influx via the Na^+/Ca2+ exchanger in gating Ca2+ release from the sarcoplasmic reticulum, suggesting privileged communication between Ca2+ channels and ryanodine receptors. In support of this hypothesis we found that Ca2+ channels were inactivated by Ca2+ release from the sarcoplasmic reticulum, even though the myoplasmic Ca2+ concentrations were buffered with 10 mM EGTA. The data thus suggest privileged cross signaling between the dihydropyridine and ryanodine receptors such that Ca2+ flux through either the Ca2+ channel or the ryanodine receptor alters the gating kinetics of the other channel.

  19. Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years

    PubMed Central

    Piccirillo, Gianfranco; Ottaviani, Cristina; Fiorucci, Claudia; Petrocchi, Nicola; Moscucci, Federica; Di Iorio, Claudia; Mastropietri, Fabiola; Parrotta, Ilaria; Pascucci, Matteo; Magrì, Damiano

    2016-01-01

    Background Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS) responses. Objective The objective of this report is to evaluate whether anodal transcranial direct current stimulation (tDCS) over the temporal cortex influences short-period temporal ventricular repolarization dispersion and cardiovascular ANS control in elderly subjects. Subjects and methods In 50 healthy subjects (29 subjects younger than 60 years and 21 subjects older than 60 years) matched for gender, short-period RR and systolic blood pressure spectral variability, QT variability index (QTVI), and noninvasive hemodynamic data were obtained during anodal tDCS or sham stimulation. Results In the older group, the QTVI, low-frequency (LF) power expressed in normalized units, the ratio between LF and high-frequency (HF) power, and systemic peripheral resistances decreased, whereas HF power expressed in normalized units and α HF power increased during the active compared to the sham condition (P<0.05). Conclusion In healthy subjects older than 60 years, tDCS elicits cardiovascular and autonomic changes. Particularly, it improves temporal ventricular repolarization dispersion, reduces sinus sympathetic activity and systemic peripheral resistance, and increases vagal sinus activity and baroreflex sensitivity. PMID:27895475

  20. Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy

    PubMed Central

    Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

    2013-01-01

    Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n= 8; 0.5, 0.3, 0.1 μg g−1) or D with vitamins C and E (DCE; n= 8; 200 and 100 mg kg−1, respectively) on postnatal days 1–3 (P1–3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n= 8). A fourth group received vitamins alone (CCE; n= 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μm), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (Δcardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min−1) or afterload (Δcardiac output: −5.3 ± 2.0 vs.1.4 ± 1.2 ml min−1); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes

  1. Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne Muscular Dystrophy

    PubMed Central

    Galindo, Cristi L.; Soslow, Jonathan H.; Brinkmeyer-Langford, Candice L.; Gupte, Manisha; Smith, Holly M.; Sengsayadeth, Seng; Sawyer, Douglas B.; Benson, D. Woodrow; Kornegay, Joe N.; Markham, Larry W.

    2016-01-01

    Background In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. Methods We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ months) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. Results We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. Conclusion These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively. PMID:26672735

  2. Theory of two-index Bessel functions and applications to physical problems

    NASA Astrophysics Data System (ADS)

    Dattoli, G.; Lorenzutta, S.; Maino, G.; Torre, A.; Voykov, G.; Chiccoli, C.

    1994-07-01

    In this article the theory of two-index Bessel functions is presented. Their generating function, series expansion, and integral representations are discussed. Their usefulness in physical problems is also discussed in the context of analysis of radiation emitted by relativistic electrons in two-frequency undulators. Finally, the theoretical analysis proving addition and multiplication theorems for two-index Bessel functions are completed and their modified forms are introduced.

  3. The Lower Limb Functional Index - A reliable and valid functional outcome assessment in burns.

    PubMed

    Gittings, Paul M; Heberlien, Nicholas; Devenish, Neale; Parker, Matthew; Phillips, Michael; Wood, Fiona M; Edgar, Dale W

    2016-09-01

    Lower limb injuries account for up to 40% of all burns in Western Australia and affect physical function. Lower limb specific functional assessments are available to monitor recovery, yet no scale has been assessed for use in burns. The Lower Limb Functional Index (LLFI) which is validated in musculoskeletal patients was investigated for applicability in burn. Reliability was assessed using Cronbach's alpha, principal components analysis and Rasch analysis. Validity was assessed using Spearman's correlation coefficient with quality of life assessments (BSHS-B & SF-36) and physical assessments (TUG & ankle ROM). Regression analysis was performed with burn severity measures, time of recovery and location of the burn. The LLFI-10 was applied 1368 times on 739 patients at regular time points. It was internally consistent (α>0.8) and unidimensional. Associations were demonstrated with the BSHS-B and SF-36 (rho=-0.56 to -0.72, p<0.001), TUG (rho=0.41, p<0.001) and ankle ROM (rho=-0.31 to -0.35, p<0.001). The LLFI-10 also showed associations (p<0.001) with time since injury (rho=-0.29), age (rho=0.12) and TBSA (rho=0.12). The LLFI-10 is a reliable and valid tool to assess function in lower limb burns. This study supports the use of the LLFI-10 as part of a battery of assessment for lower limb burn recovery.

  4. Modifications of myofilament protein phosphorylation and function in response to cardiac arrest induced in a swine model

    PubMed Central

    Woodward, Mike; Previs, Michael J.; Mader, Timothy J.; Debold, Edward P.

    2015-01-01

    Cardiac arrest is a prevalent condition with a poor prognosis, attributable in part to persistent myocardial dysfunction following resuscitation. The molecular basis of this dysfunction remains unclear. We induced cardiac arrest in a porcine model of acute sudden death and assessed the impact of ischemia and reperfusion on the molecular function of isolated cardiac contractile proteins. Cardiac arrest was electrically induced, left untreated for 12 min, and followed by a resuscitation protocol. With successful resuscitations, the heart was reperfused for 2 h (IR2) and the muscle harvested. In failed resuscitations, tissue samples were taken following the failed efforts (IDNR). Actin filament velocity, using myosin isolated from IR2 or IDNR cardiac tissue, was nearly identical to myosin from the control tissue in a motility assay. However, both maximal velocity (25% faster than control) and calcium sensitivity (pCa50 6.57 ± 0.04 IDNR vs. 6.34 ± 0.07 control) were significantly (p < 0.05) enhanced using native thin filaments (actin+troponin+tropomyosin) from IDNR samples, suggesting that the enhanced velocity is mediated through an alteration in muscle regulatory proteins (troponin+tropomyosin). Mass spectrometry analysis showed that only samples from the IR2 had an increase in total phosphorylation levels of troponin (Tn) and tropomyosin (Tm), but both IR2 and IDNR samples demonstrated a significant shift from mono-phosphorylated to bis-phosphorylated forms of the inhibitory subunit of Tn (TnI) compared to control. This suggests that the shift to bis-phosphorylation of TnI is associated with the enhanced function in IDNR, but this effect may be attenuated when phosphorylation of Tm is increased in tandem, as observed for IR2. There are likely many other molecular changes induced following cardiac arrest, but to our knowledge, these data provide the first evidence that this form cardiac arrest can alter the in vitro function of the cardiac contractile proteins

  5. Can Functional Cardiac Age be Predicted from ECG in a Normal Healthy Population

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd; Starc, Vito; Leban, Manja; Sinigoj, Petra; Vrhovec, Milos

    2011-01-01

    In a normal healthy population, we desired to determine the most age-dependent conventional and advanced ECG parameters. We hypothesized that changes in several ECG parameters might correlate with age and together reliably characterize the functional age of the heart. Methods: An initial study population of 313 apparently healthy subjects was ultimately reduced to 148 subjects (74 men, 84 women, in the range from 10 to 75 years of age) after exclusion criteria. In all subjects, ECG recordings (resting 5-minute 12-lead high frequency ECG) were evaluated via custom software programs to calculate up to 85 different conventional and advanced ECG parameters including beat-to-beat QT and RR variability, waveform complexity, and signal-averaged, high-frequency and spatial/spatiotemporal ECG parameters. The prediction of functional age was evaluated by multiple linear regression analysis using the best 5 univariate predictors. Results: Ignoring what were ultimately small differences between males and females, the functional age was found to be predicted (R2= 0.69, P < 0.001) from a linear combination of 5 independent variables: QRS elevation in the frontal plane (p<0.001), a new repolarization parameter QTcorr (p<0.001), mean high frequency QRS amplitude (p=0.009), the variability parameter % VLF of RRV (p=0.021) and the P-wave width (p=0.10). Here, QTcorr represents the correlation between the calculated QT and the measured QT signal. Conclusions: In apparently healthy subjects with normal conventional ECGs, functional cardiac age can be estimated by multiple linear regression analysis of mostly advanced ECG results. Because some parameters in the regression formula, such as QTcorr, high frequency QRS amplitude and P-wave width also change with disease in the same direction as with increased age, increased functional age of the heart may reflect subtle age-related pathologies in cardiac electrical function that are usually hidden on conventional ECG.

  6. Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

    PubMed

    Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

    2015-11-15

    Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy.

  7. Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function

    PubMed Central

    Rajendran, Pradeep S.; Nier, Heath A.; KenKnight, Bruce H.; Armour, J. Andrew

    2015-01-01

    Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. PMID:26371171

  8. Interspecies Differences in Virus Uptake versus Cardiac Function of the Coxsackievirus and Adenovirus Receptor

    PubMed Central

    Freiberg, Fabian; Sauter, Martina; Pinkert, Sandra; Govindarajan, Thirupugal; Kaldrack, Joanna; Thakkar, Meghna; Fechner, Henry; Klingel, Karin

    2014-01-01

    ABSTRACT The coxsackievirus and adenovirus receptor (CAR) is a cell contact protein with an important role in virus uptake. Its extracellular immunoglobulin domains mediate the binding to coxsackievirus and adenovirus as well as homophilic and heterophilic interactions between cells. The cytoplasmic tail links CAR to the cytoskeleton and intracellular signaling cascades. In the heart, CAR is crucial for embryonic development, electrophysiology, and coxsackievirus B infection. Noncardiac functions are less well understood, in part due to the lack of suitable animal models. Here, we generated a transgenic mouse that rescued the otherwise embryonic-lethal CAR knockout (KO) phenotype by expressing chicken CAR exclusively in the heart. Using this rescue model, we addressed interspecies differences in coxsackievirus uptake and noncardiac functions of CAR. Survival of the noncardiac CAR KO (ncKO) mouse indicates an essential role for CAR in the developing heart but not in other tissues. In adult animals, cardiac activity was normal, suggesting that chicken CAR can replace the physiological functions of mouse CAR in the cardiomyocyte. However, chicken CAR did not mediate virus entry in vivo, so that hearts expressing chicken instead of mouse CAR were protected from infection and myocarditis. Comparison of sequence homology and modeling of the D1 domain indicate differences between mammalian and chicken CAR that relate to the sites important for virus binding but not those involved in homodimerization. Thus, CAR-directed anticoxsackievirus therapy with only minor adverse effects in noncardiac tissue could be further improved by selectively targeting the virus-host interaction while maintaining cardiac function. IMPORTANCE Coxsackievirus B3 (CVB3) is one of the most common human pathogens causing myocarditis. Its receptor, the coxsackievirus and adenovirus receptor (CAR), not only mediates virus uptake but also relates to cytoskeletal organization and intracellular signaling

  9. Pressor response to intravenous tyramine is a marker of cardiac, but not vascular, adrenergic function

    NASA Technical Reports Server (NTRS)

    Meck, Janice V.; Martin, David S.; D'Aunno, Dominick S.; Waters, Wendy W.

    2003-01-01

    Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

  10. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review

    PubMed Central

    Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R.

    2015-01-01

    The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed. PMID:26109634

  11. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

    PubMed

    Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

    2015-07-06

    The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

  12. Ginsenoside Rg3 Improves Cardiac Function after Myocardial Ischemia/Reperfusion via Attenuating Apoptosis and Inflammation

    PubMed Central

    Zhang, Li-ping; Jiang, Yi-chuan; Yu, Xiao-feng; Xu, Hua-li; Li, Min

    2016-01-01

    Objectives. Ginsenoside Rg3 is one of the ginsenosides which are the main constituents isolated from Panax ginseng. Previous study demonstrated that ginsenoside Rg3 had a protective effect against myocardial ischemia/reperfusion- (I/R-) induced injury. Objective. This study was designed to evaluate the effect of ginsenoside Rg3 on cardiac function impairment induced by myocardial I/R in rats. Methods. Sprague-Dawley rats were subjected to myocardial I/R. Echocardiographic and hemodynamic parameters and histopathological examination were carried out. The expressions of P53, Bcl-2, Bax, and cleaved caspase-3 and the levels of TNF-α and IL-1β in the left ventricles were measured. Results. Ginsenoside Rg3 increased a left ventricular fractional shortening and left ventricular ejection fraction. Treatment with ginsenoside Rg3 also alleviated increases of left ventricular end diastolic pressure and decreases of left ventricular systolic pressure and ±dp/dt in myocardial I/R-rats. Ginsenoside Rg3 decreased apoptosis cells through inhibiting the activation of caspase-3. Ginsenoside Rg3 also caused significant reductions of the contents of TNF-α and IL-1β in left ventricles of myocardial I/R-rats. Conclusion. The findings suggested that ginsenoside Rg3 possessed the effect of improving myocardial I/R-induced cardiac function impairment and that the mechanism of pharmacological action of ginsenoside Rg3 was related to its properties of antiapoptosis and anti-inflammation. PMID:28105061

  13. Morphological and Functional Evaluation of Quadricuspid Aortic Valves Using Cardiac Computed Tomography

    PubMed Central

    Song, Inyoung; Park, Jung Ah; Choi, Bo Hwa; Shin, Je Kyoun; Chee, Hyun Keun; Kim, Jun Seok

    2016-01-01

    Objective The aim of this study was to identify the morphological and functional characteristics of quadricuspid aortic valves (QAV) on cardiac computed tomography (CCT). Materials and Methods We retrospectively enrolled 11 patients with QAV. All patients underwent CCT and transthoracic echocardiography (TTE), and 7 patients underwent cardiovascular magnetic resonance (CMR). The presence and classification of QAV assessed by CCT was compared with that of TTE and intraoperative findings. The regurgitant orifice area (ROA) measured by CCT was compared with severity of aortic regurgitation (AR) by TTE and the regurgitant fraction (RF) by CMR. Results All of the patients had AR; 9 had pure AR, 1 had combined aortic stenosis and regurgitation, and 1 had combined subaortic stenosis and regurgitation. Two patients had a subaortic fibrotic membrane and 1 of them showed a subaortic stenosis. One QAV was misdiagnosed as tricuspid aortic valve on TTE. In accordance with the Hurwitz and Robert's classification, consensus was reached on the QAV classification between the CCT and TTE findings in 7 of 10 patients. The patients were classified as type A (n = 1), type B (n = 3), type C (n = 1), type D (n = 4), and type F (n = 2) on CCT. A very high correlation existed between ROA by CCT and RF by CMR (r = 0.99) but a good correlation existed between ROA by CCT and regurgitant severity by TTE (r = 0.62). Conclusion Cardiac computed tomography provides comprehensive anatomical and functional information about the QAV. PMID:27390538

  14. 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

  15. Respiratory, metabolic and cardiac functions are altered by disinhibition of subregions of the medial prefrontal cortex

    PubMed Central

    Hassan, Sarah F; Cornish, Jennifer L; Goodchild, Ann K

    2013-01-01

    The prefrontal cortex (PFC) is referred to as the visceral motor cortex; however, little is known about whether this region influences respiratory or metabolic outflows. The aim of this study was to describe simultaneous changes in respiratory, metabolic and cardiovascular functions evoked by disinhibition of the medial PFC (mPFC) and adjacent lateral septal nucleus (LSN). In urethane-anaesthetized rats, bicuculline methiodide was microinjected (2 mm; GABA-A receptor antagonist) into 90 sites in the mPFC at 0.72–4.00 mm from bregma. Phrenic nerve amplitude and frequency, arterial pressure, heart rate, splanchnic and lumbar sympathetic nerve activities (SNA), expired CO2, and core and brown adipose tissue temperatures were measured. Novel findings included disturbances to respiratory rhythm evoked from all subregions of the mPFC. Injections into the cingulate cortex evoked reductions in central respiratory function exclusively, whereas in ventral sites, particularly the infralimbic region, increases in respiratory drive and frequency, and metabolic and cardiac outflows were evoked. Disinhibition of sites in surrounding regions revealed that the LSN could evoke cardiovascular changes accompanied by distinct oscillations in SNA, as well as increases in respiratory amplitude. We show that activation of neurons within the mPFC and LSN influence respiratory, metabolic and cardiac outflows in a site-dependent manner. This study has implications with respect to the altered PFC neuronal activity seen in stress-related and mental health disorders, and suggests how basic physiological systems may be affected. PMID:24042503

  16. Nitric oxide control of cardiac function: is neuronal nitric oxide synthase a key component?

    PubMed Central

    Sears, Claire E; Ashley, Euan A; Casadei, Barbara

    2004-01-01

    Nitric oxide (NO) has been shown to regulate cardiac function, both in physiological conditions and in disease states. However, several aspects of NO signalling in the myocardium remain poorly understood. It is becoming increasingly apparent that the disparate functions ascribed to NO result from its generation by different isoforms of the NO synthase (NOS) enzyme, the varying subcellular localization and regulation of NOS isoforms and their effector proteins. Some apparently contrasting findings may have arisen from the use of non-isoform-specific inhibitors of NOS, and from the assumption that NO donors may be able to mimic the actions of endogenously produced NO. In recent years an at least partial explanation for some of the disagreements, although by no means all, may be found from studies that have focused on the role of the neuronal NOS (nNOS) isoform. These data have shown a key role for nNOS in the control of basal and adrenergically stimulated cardiac contractility and in the autonomic control of heart rate. Whether or not the role of nNOS carries implications for cardiovascular disease remains an intriguing possibility requiring future study. PMID:15306414

  17. PPARα augments heart function and cardiac fatty acid oxidation in early experimental polymicrobial sepsis.

    PubMed

    Standage, Stephen W; Bennion, Brock G; Knowles, Taft O; Ledee, Dolena R; Portman, Michael A; McGuire, John K; Liles, W Conrad; Olson, Aaron K

    2017-02-01

    Children with sepsis and multisystem organ failure have downregulated leukocyte gene expression of peroxisome proliferator-activated receptor-α (PPARα), a nuclear hormone receptor transcription factor that regulates inflammation and lipid metabolism. Mouse models of sepsis have likewise demonstrated that the absence of PPARα is associated with decreased survival and organ injury, specifically of the heart. Using a clinically relevant mouse model of early sepsis, we found that heart function increases in wild-type (WT) mice over the first 24 h of sepsis, but that mice lacking PPARα (Ppara(-/-)) cannot sustain the elevated heart function necessary to compensate for sepsis pathophysiology. Left ventricular shortening fraction, measured 24 h after initiation of sepsis by echocardiography, was higher in WT mice than in Ppara(-/-) mice. Ex vivo working heart studies demonstrated greater developed pressure, contractility, and aortic outflow in WT compared with Ppara(-/-) mice. Furthermore, cardiac fatty acid oxidation was increased in WT but not in Ppara(-/-) mice. Regulatory pathways controlling pyruvate incorporation into the citric acid cycle were inhibited by sepsis in both genotypes, but the regulatory state of enzymes controlling fatty acid oxidation appeared to be permissive in WT mice only. Mitochondrial ultrastructure was not altered in either genotype indicating that severe mitochondrial dysfunction is unlikely at this stage of sepsis. These data suggest that PPARα expression supports the hyperdynamic cardiac response early in the course of sepsis and that increased fatty acid oxidation may prevent morbidity and mortality.

  18. Evaluation of cardiac function during left ventricular assist by a centrifugal blood pump.

    PubMed

    Kikugawa, D

    2000-08-01

    In this study, the effects on varying cardiac function during a left ventricular (LV) bypass from the apex to the descending aorta using a centrifugal blood pump were evaluated by analyzing the left ventricular pressure and the motor current of the centrifugal pump in a mock circulatory loop. Failing heart models (preload 15 mm Hg, afterload 40 mm Hg) and normal heart models (preload 5 mm Hg, afterload 100 mm Hg) were simulated by adjusting the contractility of the latex rubber left ventricle. In Study 1, the bypass flow rate, left ventricular pressure, aortic pressure, and motor current levels were measured in each model as the centrifugal pump rpm were increased from 1,000 to 1,500 to 2,000. In Study 2, the pump rpm were fixed at 1,300, 1,500, and 1,700, and at each rpm, the left ventricular peak pressure was increased from 40 to 140 mm Hg by steps of 20 mm Hg. The same measurements as in Study 1 were performed. In Study 1, the bypass flow rate and mean aortic pressure both increased with the increase in pump rpm while the mean left ventricular pressure decreased. In Study 2, a fairly good correlation between the left ventricular pressure and the motor current of the centrifugal pump was obtained. These results suggest that cardiac function as indicated by left ventricular pressure may be estimated from a motor current analysis of the centrifugal blood pump during left heart bypass.

  19. Skeletal myoblasts for heart regeneration and repair: state of the art and perspectives on the mechanisms for functional cardiac benefits.

    PubMed

    Formigli, L; Zecchi-Orlandini, S; Meacci, E; Bani, D

    2010-01-01

    Until recently, skeletal myoblasts (SkMBs) have been the most widely used cells in basic research and clinical trials of cell based therapy for cardiac repair and regeneration. Although SkMB engraftment into the post-infarcted heart has been consistently found to improve cardiac contractile function, the underlying therapeutic mechanisms remain still a matter of controversy and debate. This is basically because SkMBs do not attain a cardiac-like phenotype once homed into the diseased heart nor they form a contractile tissue functionally coupled with the surrounding viable myocardium. This issue of concern has generated the idea that the cardiotropic action of SkMBs may depend on the release of paracrine factors. However, the paracrine hypothesis still remains ill-defined, particularly concerning the identification of the whole spectrum of cell-derived soluble factors and details on their cardiac effects. In this context, the possibility to genetically engineering SkMBs to potentate their paracrine attitudes appears particularly attractive and is actually raising great expectation. Aim of the present review is not to cover all the aspects of cell-based therapy with SkMBs, as this has been the object of previous exhaustive reviews in this field. Rather, we focused on novel aspects underlying the interactions between SkMBs and the host cardiac tissues which may be relevant for directing the future basic and applied research on SkMB transplantation for post ischemic cardiac dysfunction.

  20. Cardiac autonomic function and vascular profile in subclinical hypothyroidism: Increased beat-to-beat QT variability

    PubMed Central

    Kalra, Pramila; Yeragani, Vikram K.; Prasanna Kumar, K. M.

    2016-01-01

    Background: Patients with subclinical hypothyroidism (SH) may have higher incidence of coronary heart disease and autonomic dysfunction. Design of the Study: Prospective case control study. Aim and Objectives: To evaluate beat-to-beat QT variability and vascular stiffness in patients with SH compared to normal controls. Materials and Methods: We compared linear and nonlinear measures of cardiac repolarization liability using beat-to-beat QT intervals derived from the surface electrocardiogram during supine posture and vascular indices including pulse wave velocity and ankle-brachial index (ABI) during supine posture between female patients with SH and age- and sex-matched normal controls. Spectral analysis was done at very low frequency (LF) (0.003–0.04 Hz), Low frequency (LF) (0.04–0.15 Hz), and high frequency (HF) (0.15–0.4 Hz). The HF represents vagal regulation (parasympathetic) and LF represents both parasympathetic and sympathetic regulation. Results: We recruited 58 women with a mean age of 31.83 ± 8.9 years and 49 controls with mean age of 32.4 ± 9.9 years (P = NS). QT variability index (QTvi) was higher in cases compared to controls (P = 0.01). The ratio of LF/HF of R-R interval which is an index of sympathovagal tone was significantly more in cases compared to controls (P = 0.02). The difference in the left minus the right ABI was significant between cases and controls (P = 0.03). Conclusions: The cases had lower parasympathetic activity as compared to controls, and there was a predominance of sympathetic activity in cases. QTvi may be an important noninvasive tool in this group of patients to study the risk of cardiovascular mortality. PMID:27730068

  1. The Natural History of Cardiac and Pulmonary Function Decline in Patients with Duchenne Muscular Dystrophy

    PubMed Central

    Roberto, Rolando; Fritz, Anto; Hagar, Yolanda; Boice, Braden; Skalsky, Andrew; Hwang, HoSun; Beckett, Laurel; McDonald, Craig; Gupta, Munish

    2010-01-01

    Study Design Retrospective review of scoliosis progression, pulmonary and cardiac function in a series of patients with Duchenne Muscular Dystrophy (DMD). Objective To determine whether operative treatment of scoliosis decreases the rate of pulmonary function loss in patients with DMD. Summary of Background Data It is generally accepted that surgical intervention should be undertaken in DMD scoliosis once curve sizes reach 35 degrees to allow intervention before critical respiratory decline has occurred. There are conflicting reports, however, regarding the effect of scoliosis stabilization on the rate of pulmonary function decline when compared to non operative cohorts. Methods We reviewed spinal radiographs, echocardiograms, and spirometry, hospital, and operative records of all patients seen at our tertiary referral center from July 1, 1992 to June 1, 2007 Data was recorded to Microsoft Excel and analyzed with SAS and R statistical processing software. Results The percent predicted forced vital capacity (PPFVC) decreased 5% /year prior to operation. The mean PPFVC was 54% (sd=21%) prior to operation with a mean postoperative PPFVC of 43% (sd=14%). Surgical treatment was associated with a 12% decline in PPFVC independent of other treatment variables. PPFVC after operation declined at a rate of 1% per year and while this rate was lower, it was not significantly different than the rate of decline present prior to operation (p=0.18). Cardiac function as measured by left ventricular fractional shortening declined at a rate of 1%/year with most individuals exhibiting an LVFS rate of >30 prior to operation. Conclusion Operative treatment of scoliosis in DMD using the Luque Galveston method was associated with a reduction of FVC related to operation. The rate of pulmonary function decline after operation was not significantly reduced when compared to the rate of preoperative FVC decline. PMID:21289561

  2. Distinct Functional Roles of Cardiac Mitochondrial Subpopulations Revealed by a 3D Simulation Model

    PubMed Central

    Hatano, Asuka; Okada, Jun-ichi; Washio, Takumi; Hisada, Toshiaki; Sugiura, Seiryo

    2015-01-01

    Experimental characterization of two cardiac mitochondrial subpopulations, namely, subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM), has been hampered by technical difficulties, and an alternative approach is eagerly awaited. We previously developed a three-dimensional computational cardiomyocyte model that integrates electrophysiology, metabolism, and mechanics with subcellular structure. In this study, we further developed our model to include intracellular oxygen diffusion, and determined whether mitochondrial localization or intrinsic properties cause functional variations. For this purpose, we created two models: one with equal SSM and IFM properties and one with IFM having higher activity levels. Using these two models to compare the SSM and IFM responses of [Ca2+], tricarboxylic acid cycle activity, [NADH], and mitochondrial inner membrane potential to abrupt changes in pacing frequency (0.25–2 Hz), we found that the reported functional differences between these subpopulations appear to be mostly related to local [Ca2+] heterogeneity, and variations in intrinsic properties only serve to augment these differences. We also examined the effect of hypoxia on mitochondrial function. Under normoxic conditions, intracellular oxygen is much higher throughout the cell than the half-saturation concentration for oxidative phosphorylation. However, under limited oxygen supply, oxygen is mostly exhausted in SSM, leaving the core region in an anoxic condition. Reflecting this heterogeneous oxygen environment, the inner membrane potential continues to decrease in IFM, whereas it is maintained to nearly normal levels in SSM, thereby ensuring ATP supply to this region. Our simulation results provide clues to understanding the origin of functional variations in two cardiac mitochondrial subpopulations and their differential roles in maintaining cardiomyocyte function as a whole. PMID:26039174

  3. Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model

    PubMed Central

    Das, Hiranmoy; George, Jon C.; Joseph, Matthew; Das, Manjusri; Abdulhameed, Nasreen; Blitz, Anna; Khan, Mahmood; Sakthivel, Ramasamy; Mao, Hai-Quan; Hoit, Brian D.; Kuppusamy, Periannan; Pompili, Vincent J.

    2009-01-01

    Background Therapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+/CD34+) genetically modified with VEGF plus PDGF genes (VIP). Methods and Findings Myocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue velocity, wall motion score index, strain and strain rate in animals treated with VEGF plus PDGF overexpressed stem cells (VIP) compared to nanofiber expanded cells (Exp), freshly isolated cells (FCB) or media control (Media). Improvement observed was as follows: VIP>Exp> FCB>media. Similar trend was noticed in the exercise capacity of rats on a treadmill. These findings correlated with significantly increased neovascularization in ischemic tissue and markedly reduced infarct area in animals in the VIP group. Stem cells in addition to their usual homing sites such as lung, spleen, bone marrow and liver, also migrated to sites of myocardial ischemia. The improvement of cardiac function correlated with expression of heart tissue connexin 43, a gap junctional protein, and heart tissue angiogenesis related protein molecules like VEGF, pNOS3, NOS2 and GSK3. There was no evidence of upregulation in the molecules of oncogenic potential in genetically modified or other stem cell therapy groups. Conclusion Regenerative therapy using nanofiber-expanded hematopoietic stem cells with overexpression of VEGF and PDGF has a favorable impact on the improvement of rat myocardial function accompanied by upregulation of tissue connexin 43 and pro-angiogenic molecules after infarction. PMID:19809493

  4. Nuclear cardiac

    SciTech Connect

    Slutsky, R.; Ashburn, W.L.

    1982-01-01

    The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques. (KRM)

  5. Cardiac pacemakers: design, function and problems. January, 1976-May, 1981 (citations from the International Information Service for the Physics and Engineering Communities data base). Report for January 1976-May 1981

    SciTech Connect

    Not Available

    1981-05-01

    This retrospective bibliography contains citations concerning the design, function, and problems of fixed rate and demand implanted cardiac pacemakers. The susceptibility of pacemakers to electromagnetic interference, and the effects of radiation therapy and microwave interception are considered. The reliability of batteries, types of batteries, and other power sources are all discussed. Nondestructive methods for the assessment of cells and pacemaker are included. (Contains 107 citations fully indexed and including a title list.)

  6. Evaluation of Cardiac Functions in Children and Adolescents with Type 1 Diabetes

    PubMed Central

    M Abd-El Aziz, Faten; Abdelghaffar, Shereen; M Hussien, Eman

    2017-01-01

    Background Cardiac dysfunction in patients with type 1 diabetes (T1D) represents one of the serious complications. To evaluate the cardiac function in children with T1D by conventional echocardiography and tissue Doppler imaging (TDI). Methods The study included 40 T1D patients (age between 6 and 16 years) with > 5 years duration of diabetes and 42 healthy control children. The patients were subjected to clinical evaluation and laboratory investigations [glycosylated hemoglobin A1c (HbA1c), serum lipids and lipoproteins]. Conventional echocardiography and TDI were performed to patients and controls. Results The patients had lower early diastolic filling velocity (E wave) of the tricuspid valve and mitral valves with a p value of (0.000 and 0.006, respectively). TDI revealed that patients had lower S′velocity of the T1D, shorter isovolumic contraction time, longer isovolumic relaxation time and lower E/E′ of the right ventricle than controls (p value 0.002, 0.001, 0.004, 0.003, and 0.016, respectively). The left ventricle (LV)-T1D of the patients was significantly higher (p value 0.02). Twenty eight patients had poor glycemic control without significant differences between them and those with good glycemic control regarding echocardiographic data. Patients with dyslipidemia (13 patients) had higher late diastolic filling velocity of the mitral valve (A) and the lower LV late tissue velocity (A′) (p wave 0.047 and 0.015). No correlation existed between the duration of illness or the level of HbA1c and the echocardiographic parameters. Conclusion Diabetic children have evidence of echocardiographic diastolic dysfunctions. Periodic cardiac evaluation with both conventional and tissue Doppler echocardiography is recommended for early detection of this dysfunction.

  7. Intraoperative Magnesium Administration Does Not Improve Neurocognitive Function Following Cardiac Surgery

    PubMed Central

    Mathew, Joseph P.; White, William D.; Schinderle, David B.; Podgoreanu, Mihai V.; Berger, Miles; Milano, Carmelo A.; Laskowitz, Daniel T.; Stafford-Smith, Mark; Blumenthal, James A.; Newman, Mark F.

    2014-01-01

    Background and Purpose Neurocognitive decline occurs frequently after cardiac surgery and persists in a significant number of patients. Magnesium is thought to provide neuroprotection through preservation of cellular energy metabolism, blockade of the N-methyl-D-aspartate receptor, diminution of the inflammatory response, and inhibition of platelet activation. We therefore hypothesized that intraoperative magnesium administration would decrease postoperative cognitive impairment. Methods Following IRB approval, 389 patients undergoing cardiac surgery were enrolled into this prospective, randomized, double-blinded placebo controlled clinical trial. Subjects were randomized to receive: 1) Magnesium as a 50 mg/kg bolus followed by another 50 mg/kg infusion over 3 hours or 2) Placebo bolus and infusion. Cognitive function was assessed preoperatively and again at 6 weeks postoperatively using a standardized test battery. Mean CD11b fluorescence and percentage of platelets expressing CD62P, markers of leukocyte and platelet activation respectively, were assessed by flow cytometry as a secondary outcome. The effect of magnesium on postoperative cognition was tested using multivariable regression modeling, adjusting for age, years of education, baseline cognition, gender, race and weight. Results Among the 389 allocated subjects (Magnesium: N=198; Placebo: N=191), the incidence of cognitive deficit in the magnesium group was 44.4% compared to 44.9% in the placebo group (p=0.93). The cognitive change score and platelet and leukocyte activation were also not different between groups. Multivariable analysis revealed a marginal interaction between treatment group and weight, such that heavier subjects receiving magnesium were less likely to suffer cognitive deficit (p=0.06). Conclusions Magnesium administered intravenously during cardiac surgery does not reduce postoperative cognitive dysfunction. Clinical Trials Registration–URL http://clinicaltrials.gov/ Unique identifier

  8. Maximal exercise limitation in functionally overreached triathletes: role of cardiac adrenergic stimulation.

    PubMed

    Le Meur, Yann; Louis, Julien; Aubry, Anaël; Guéneron, Jacques; Pichon, Aurélien; Schaal, Karine; Corcuff, Jean-Benoît; Hatem, Stéphane N; Isnard, Richard; Hausswirth, Christophe

    2014-08-01

    Functional overreaching (F-OR) induced by heavy load endurance training programs has been associated with reduced heart rate values both at rest and during exercise. Because this phenomenon may reflect an impairment of cardiac response, this research was conducted to test this hypothesis. Thirty-five experienced male triathletes were tested (11 control and 24 overload subjects) before overloading (Pre), immediately after overloading (Mid), and after a 2-wk taper period (Post). Physiological responses were assessed during an incremental cycling protocol to volitional exhaustion, including catecholamines release, oxygen uptake (V̇o2), arteriovenous O2 difference, cardiac output (Q̇), and systolic (SBP) and diastolic blood pressure (DBP). Twelve subjects of the overload group developed signs of F-OR at Mid (decreased performance with concomitant high perceived fatigue), while 12 others did not [acute fatigue group (AF)]. V̇o2max was reduced only in F-OR subjects at Mid. Lower Q̇ and SBP values with greater arteriovenous O2 difference were reported in F-OR subjects at all exercising intensities, while no significant change was observed in the control and AF groups. A concomitant decrease in epinephrine excretion was reported only in the F-OR group. All values returned to baseline at Post. Following an overload endurance training program leading to F-OR, the cardiac response to exhaustive exercise is transiently impaired, possibly due to reduced epinephrine excretion. This finding is likely to explain the complex process of underperformance syndrome experienced by F-OR endurance athletes during heavy load programs.

  9. A novel urotensin II receptor antagonist, KR-36996, improved cardiac function and attenuated cardiac hypertrophy in experimental heart failure.

    PubMed

    Oh, Kwang-Seok; Lee, Jeong Hyun; Yi, Kyu Yang; Lim, Chae Jo; Park, Byung Kil; Seo, Ho Won; Lee, Byung Ho

    2017-03-15

    Urotensin II and its receptor are thought to be involved in various cardiovascular diseases such as heart failure, pulmonary hypertension and atherosclerosis. Since the regulation of the urotensin II/urotensin II receptor offers a great potential for therapeutic strategies related to the treatment of cardiovascular diseases, the study of selective and potent antagonists for urotensin II receptor is more fascinating. This study was designed to determine the potential therapeutic effects of a newly developed novel urotensin II receptor antagonist, N-(1-(3-bromo-4-(piperidin-4-yloxy)benzyl)piperidin-4-yl)benzo[b]thiophene-3-carboxamide (KR-36996), in experimental models of heart failure. KR-36996 displayed a high binding affinity (Ki=4.44±0.67nM) and selectivity for urotensin II receptor. In cell-based study, KR-36996 significantly inhibited urotensin II-induced stress fiber formation and cellular hypertrophy in H9c2UT cells. In transverse aortic constriction-induced cardiac hypertrophy model in mice, the daily oral administration of KR-36996 (30mg/kg) for 14 days significantly decreased left ventricular weight by 40% (P<0.05). In myocardial infarction-induced chronic heart failure model in rats, repeated echocardiography and hemodynamic measurements demonstrated remarkable improvement of the cardiac performance by KR-36996 treatment (25 and 50mg/kg/day, p.o.) for 12 weeks. Moreover, KR-36996 decreased interstitial fibrosis and cardiomyocyte hypertrophy in the infarct border zone. These results suggest that potent and selective urotensin II receptor antagonist could efficiently attenuate both cardiac hypertrophy and dysfunction in experimental heart failure. KR-36996 may be useful as an effective urotensin II receptor antagonist for pharmaceutical or clinical applications.

  10. Endurance training prevents negative effects of the hypoxia mimetic dimethyloxalylglycine on cardiac and skeletal muscle function.

    PubMed

    Favier, Francois B; Britto, Florian A; Ponçon, Benjamin; Begue, Gwenaelle; Chabi, Beatrice; Reboul, Cyril; Meyer, Gregory; Py, Guillaume

    2016-02-15

    Hypoxic preconditioning is a promising strategy to prevent hypoxia-induced damages to several tissues. This effect is related to prior stabilization of the hypoxia-inducible factor-1α via inhibition of the prolyl-hydroxylases (PHDs), which are responsible for its degradation under normoxia. Although PHD inhibition has been shown to increase endurance performance in rodents, potential side effects of such a therapy have not been explored. Here, we investigated the effects of 1 wk of dimethyloxalylglycine (DMOG) treatment (150 mg/kg) on exercise capacity, as well as on cardiac and skeletal muscle function in sedentary and endurance-trained rats. DMOG improved maximal aerobic velocity and endurance in both sedentary and trained rats. This effect was associated with an increase in red blood cells without significant alteration of skeletal muscle contractile properties. In sedentary rats, DMOG treatment resulted in enhanced left ventricle (LV) weight together with impairment in diastolic function, LV relaxation, and pulse pressure. Moreover, DMOG decreased maximal oxygen uptake (state 3) of isolated mitochondria from skeletal muscle. Importantly, endurance training reversed the negative effects of DMOG treatment on cardiac function and restored maximal mitochondrial oxygen uptake to the level of sedentary placebo-treated rats. In conclusion, we provide here evidence that the PHD inhibitor DMOG has detrimental influence on myocardial and mitochondrial function in healthy rats. However, one may suppose that the deleterious influence of PHD inhibition would be potentiated in patients with already poor physical condition. Therefore, the present results prompt us to take into consideration the potential side effects of PHD inhibitors when administrated to patients.

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

    PubMed Central

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

    1997-01-01

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

  12. Independent and Interactive Effects of Blood Pressure and Cardiac Function on Brain Volume and White Matter Hyperintensities in Heart Failure

    PubMed Central

    Alosco, Michael L.; Brickman, Adam M.; Spitznagel, Mary Beth; Griffith, Erica Y.; Narkhede, Atul; Raz, Naftali; Cohen, Ronald; Sweet, Lawrence H.; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2013-01-01

    Background Reduced systemic perfusion and comorbid medical conditions are key contributors to adverse brain changes in heart failure (HF). Hypertension, the most common co-occurring condition in HF, accelerates brain atrophy in aging populations. However, the independent and interactive effects of blood pressure and systemic perfusion on brain structure in HF have yet to be investigated. Methods Forty-eight older adults with HF underwent impedance cardiography to assess current systolic blood pressure status, and cardiac index to quantify systemic perfusion. All participants underwent brain magnetic resonance imaging to quantify total brain, total and subcortical gray matter volume, and white matter hyperintensities (WMH) volume. Results Regression analyses adjusting for medical and demographic factors showed decreased cardiac index was associated with smaller subcortical gray matter volume (p < .01) and higher systolic blood pressure predicted reduced total gray matter volume (p = .03). The combination of higher blood pressure and lower cardiac index exacerbated WMH (p = .048). Conclusions Higher blood pressure and systemic hypoperfusion are associated with smaller brain volume and these factors interact to exacerbate WMH in HF. Prospective studies are needed to clarify the effects of blood pressure on the brain in HF, including the role of long-term blood pressure fluctuations. PMID:23735419

  13. miR-300 mediates Bmi1 function and regulates differentiation in primitive cardiac progenitors.

    PubMed

    Cruz, F M; Tomé, M; Bernal, J A; Bernad, A

    2015-10-29

    B lymphoma Mo-MLV insertion region 1 (Bmi1) is a polycomb-family transcriptional factor critical for self-renewal in many adult stem cells and human neoplasia. We sought to identify microRNAs regulated by Bmi1 that could play a role in multipotent cardiac progenitor cell (CPC) decisions. We found that miR-300, a poorly characterized microRNA mapping in the Dlk1-Dio3 microRNA cluster, was positively regulated by Bmi1 in CPCs. Forced expression of miR-300 in CPCs promoted an improved stemness signature with a significant increase in Oct4 levels, a reduction in senescence progression and an enhanced proliferative status via p19 activation and inhibition of p16 accumulation. Endothelial and cardiogenic differentiation were clearly compromised by sustained miR-300 expression. Additionally, RNA and protein analysis revealed a significant reduction in key cardiac transcription factors, including Nkx2.5 and Tbx5. Collectively, these results suggest that some functions attributed to Bmi1 are due to induction of miR-300, which decreases the cardiogenic differentiation potential of multipotent CPCs in vitro and promotes self-renewal.

  14. Echocardiographic assessment of cardiac function in shocked very low birthweight infants.

    PubMed Central

    Gill, A B; Weindling, A M

    1993-01-01

    The contribution of abnormal cardiac function to hypotension and metabolic acidosis, which affect approximately 40% of ventilated very low birthweight infants in the first 24 hours after birth was assessed using M mode, two dimensional, and Doppler echocardiography in 75 very low birthweight infants during the first few hours after birth. Thirty four infants whose blood pressure was less than the 10th centile or who had a metabolic acidosis in the first 24 hours were compared with 41 who showed neither feature. The median shortening fraction was significantly lower in the hypotensive/acidotic (shocked) group than in the controls. In 16 of 34 (47%) shocked infants left ventricular contractility and output were significantly worse than in the control subjects. One and five minute Apgar scores were also significantly lower in the shock group when compared with controls. Cardiac dysfunction was an important feature in the shocked very low birthweight infants. It is speculated that volume expansion may not always be the most appropriate first line treatment for such infants. PMID:8439190

  15. Sustaining Cardiac Claudin-5 Levels Prevents Functional Hallmarks of Cardiomyopathy in a Muscular Dystrophy Mouse Model

    PubMed Central

    Delfín, Dawn A; Xu, Ying; Schill, Kevin E; Mays, Tessily A; Canan, Benjamin D; Zang, Kara E; Barnum, Jamie A; Janssen, Paul ML; Rafael-Fortney, Jill A

    2012-01-01

    Identification of new molecular targets in heart failure could ultimately have a substantial positive impact on both the health and financial aspects of treating the large heart failure population. We originally identified reduced levels of the cell junction protein claudin-5 specifically in heart in the dystrophin/utrophin-deficient (Dmdmdx;Utrn−/−) mouse model of muscular dystrophy and cardiomyopathy, which demonstrates physiological hallmarks of heart failure. We then showed that at least 60% of cardiac explant samples from patients with heart failure resulting from diverse etiologies also have reduced claudin-5 levels. These claudin-5 reductions were independent of changes in other cell junction proteins previously linked to heart failure. The goal of this study was to determine whether sustaining claudin-5 levels is sufficient to prevent the onset of histological and functional indicators of heart failure. Here, we show the proof-of-concept rescue experiment in the Dmdmdx;Utrn−/− model, in which claudin-5 reductions were originally identified. Expression of claudin-5 4 weeks after a single administration of recombinant adeno-associated virus (rAAV) containing a claudin-5 expression cassette prevented the onset of physiological hallmarks of cardiomyopathy and improved histological signs of cardiac damage. This experiment demonstrates that claudin-5 may represent a novel treatment target for prevention of heart failure. PMID:22547149

  16. Sustaining cardiac claudin-5 levels prevents functional hallmarks of cardiomyopathy in a muscular dystrophy mouse model.

    PubMed

    Delfín, Dawn A; Xu, Ying; Schill, Kevin E; Mays, Tessily A; Canan, Benjamin D; Zang, Kara E; Barnum, Jamie A; Janssen, Paul M L; Rafael-Fortney, Jill A

    2012-07-01

    Identification of new molecular targets in heart failure could ultimately have a substantial positive impact on both the health and financial aspects of treating the large heart failure population. We originally identified reduced levels of the cell junction protein claudin-5 specifically in heart in the dystrophin/utrophin-deficient (Dmd(mdx);Utrn(-/-)) mouse model of muscular dystrophy and cardiomyopathy, which demonstrates physiological hallmarks of heart failure. We then showed that at least 60% of cardiac explant samples from patients with heart failure resulting from diverse etiologies also have reduced claudin-5 levels. These claudin-5 reductions were independent of changes in other cell junction proteins previously linked to heart failure. The goal of this study was to determine whether sustaining claudin-5 levels is sufficient to prevent the onset of histological and functional indicators of heart failure. Here, we show the proof-of-concept rescue experiment in the Dmd(mdx);Utrn(-/-) model, in which claudin-5 reductions were originally identified. Expression of claudin-5 4 weeks after a single administration of recombinant adeno-associated virus (rAAV) containing a claudin-5 expression cassette prevented the onset of physiological hallmarks of cardiomyopathy and improved histological signs of cardiac damage. This experiment demonstrates that claudin-5 may represent a novel treatment target for prevention of heart failure.

  17. Reducing the 4d index to the S 3 partition function

    NASA Astrophysics Data System (ADS)

    Gadde, Abhijit; Yan, Wenbin

    2012-12-01

    The superconformal index of a 4 d gauge theory is computed by a matrix integral arising from localization of the supersymmetric path integral on S 3 × S 1. As the radius of the circle goes to zero, it is natural to expect that the 4 d path integral becomes the partition function of dimensionally reduced gauge theory on S 3. We show that this is indeed the case and recover the matrix integral of Kapustin, Willett and Yaakov from the matrix integral that computes the superconformal index. Remarkably, the superconformal index of the "parent" 4 d theory can be thought of as the q-deformation of the 3 d partition function.

  18. A Tocotrienol-Enriched Formulation Protects against Radiation-Induced Changes in Cardiac Mitochondria without Modifying Late Cardiac Function or Structure

    PubMed Central

    Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K.; Moros, Eduardo G.; Melnyk, Stepan B.; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan

    2015-01-01

    Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling. PMID:25710576

  19. Inhibition of leukotriene B4 receptor 1 attenuates lipopolysaccharide-induced cardiac dysfunction: role of AMPK-regulated mitochondrial function

    PubMed Central

    Sun, Meng; Wang, Rui; Han, Qinghua

    2017-01-01

    Leukotriene B4 (LTB4)-mediated leukocyte recruitment and inflammatory cytokine production make crucial contributions to chronic inflammation and sepsis; however, the role of LTB4 in lipopolysaccharide (LPS)-induced cardiac dysfunction remains unclear. Therefore, the present study addressed this issue using an LTB4 receptor 1 (BLT1) inhibitor. Administration of LPS to mice resulted in decreased cardiovascular function. Inhibition of LTB4/BLT1 with the BLT1 inhibitor U75302 significantly improved survival and attenuated the LPS-induced acute cardiac dysfunction. During LPS challenge, the phosphorylated AMPK/ACC signaling pathway was slightly activated, and this effect was enhanced by U75302. Additionally, pNF-κB, Bax and cleaved caspase-3 were upregulated by LPS, and Bcl-2, IκB-α, mitochondrial complex I, complex II, and OPA1 were downregulated; however, these effects were reversed by U75302. The results indicated that the BLT1 antagonist suppressed cardiac apoptosis, inflammation, and mitochondrial impairment. Furthermore, the protection provided by the BLT1 inhibitor against LPS-induced cardiac dysfunction was significantly reversed by the AMPK inhibitor Compound C. In conclusion, inhibiting the LTB4/BLT1 signaling pathway via AMPK activation is a potential treatment strategy for septic cardiac dysfunction because it efficiently attenuates cardiac apoptosis, which may occur via the inhibition of inflammation and mitochondrial dysfunction. PMID:28290498

  20. Cardiac Non-myocyte Cells Show Enhanced Pharmacological Function Suggestive of Contractile Maturity in Stem Cell Derived Cardiomyocyte Microtissues

    PubMed Central

    Ravenscroft, Stephanie M.; Pointon, Amy; Williams, Awel W.; Cross, Michael J.; Sidaway, James E.

    2016-01-01

    The immature phenotype of stem cell derived cardiomyocytes is a significant barrier to their use in translational medicine and pre-clinical in vitro drug toxicity and pharmacological analysis. Here we have assessed the contribution of non-myocyte cells on the contractile function of co-cultured human embryonic stem cell derived cardiomyocytes (hESC-CMs) in spheroid microtissue format. Microtissues were formed using a scaffold free 96-well cell suspension method from hESC-CM cultured alone (CM microtissues) or in combination with human primary cardiac microvascular endothelial cells and cardiac fibroblasts (CMEF microtissues). Contractility was characterized with fluorescence and video-based edge detection. CMEF microtissues displayed greater Ca2+ transient amplitudes, enhanced spontaneous contraction rate and remarkably enhanced contractile function in response to both positive and negative inotropic drugs, suggesting a more mature contractile phenotype than CM microtissues. In addition, for several drugs the enhanced contractile response was not apparent when endothelial cell or fibroblasts from a non-cardiac tissue were used as the ancillary cells. Further evidence of maturity for CMEF microtissues was shown with increased expression of genes that encode proteins critical in cardiac Ca2+ handling (S100A1), sarcomere assembly (telethonin/TCAP) and β-adrenergic receptor signalling. Our data shows that compared with single cell-type cardiomyocyte in vitro models, CMEF microtissues are superior at predicting the inotropic effects of drugs, demonstrating the critical contribution of cardiac non-myocyte cells in mediating functional cardiotoxicity. PMID:27125969

  1. Connective Tissue Growth Factor Regulates Cardiac Function and Tissue Remodeling in a Mouse Model of Dilated Cardiomyopathy

    PubMed Central

    Koshman, Yevgeniya E.; Sternlicht, Mark D.; Kim, Taehoon; O'Hara, Christopher P.; Koczor, Christopher A.; Lewis, William; Seeley, Todd W.; Lipson, Kenneth E.; Samarel, Allen M.

    2015-01-01

    Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective Tissue Growth Factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. Our aim was to test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase Cε (PKCε) mouse model of DCM. Transgenic mice expressing constitutively active PKCε in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to cardiac fibrosis, heart failure, and increased mortality. Beginning at 3 months of age, PKCε mice were treated with a neutralizing monoclonal antibody to CTGF (FG-3149) for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic function in PKCε mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling were elevated in PKCε mice, but significantly decreased by CTGF inhibition. However total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKCε mice suggests that CTGF inhibition may benefit patients with DCM. Additional studies to explore this potential are warranted. PMID:26549358

  2. 8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish

    SciTech Connect

    Yan, Lifeng; Zhou, Yong; Yu, Shanhe; Ji, Guixiang; Liu, Wei; Gu, Aihua

    2013-11-15

    Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes and nkx2.5{sup +} cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits. - Highlights: • A key DNA repair enzyme ogg1 is expressed in the embryonic heart in zebrafish. • We found that ogg1 is essential for normal cardiac morphogenesis in zebrafish. • The production of embryonic cardiomyocytes requires appropriate ogg1 expression. • Ogg1 critically regulated proliferation of cardiac progenitor cells in zebrafish. • foxh1 is a partner of ogg1 in the cardiac development in response to DNA damage.

  3. Carbon nanotubes instruct physiological growth and functionally mature syncytia: nongenetic engineering of cardiac myocytes.

    PubMed

    Martinelli, Valentina; Cellot, Giada; Toma, Francesca Maria; Long, Carlin S; Caldwell, John H; Zentilin, Lorena; Giacca, Mauro; Turco, Antonio; Prato, Maurizio; Ballerini, Laura; Mestroni, Luisa

    2013-07-23

    Myocardial tissue engineering currently represents one of the most realistic strategies for cardiac repair. We have recently discovered the ability of carbon nanotube scaffolds to promote cell division and maturation in cardiomyocytes. Here, we test the hypothesis that carbon nanotube scaffolds promote cardiomyocyte growth and maturation by altering the gene expression program, implementing the cell electrophysiological properties and improving networking and maturation of functional syncytia. In our study, we combine microscopy, biological and electrophysiological methodologies, and calcium imaging, to verify whether neonatal rat ventricular myocytes cultured on substrates of multiwall carbon nanotubes acquire a physiologically more mature phenotype compared to control (gelatin). We show that the carbon nanotube substrate stimulates the induction of a gene expression profile characteristic of terminal differentiation and physiological growth, with a 2-fold increase of α-myosin heavy chain (P < 0.001) and upregulation of sarcoplasmic reticulum Ca(2+) ATPase 2a. In contrast, markers of pathological hypertrophy remain unchanged (β-myosin heavy chain, skeletal α-actin, atrial natriuretic peptide). These modifications are paralleled by an increase of connexin-43 gene expression, gap junctions and functional syncytia. Moreover, carbon nanotubes appear to exert a protective effect against the pathologic stimulus of phenylephrine. Finally, cardiomyocytes on carbon nanotubes demonstrate a more mature electrophysiological phenotype of syncytia and intracellular calcium signaling. Thus, carbon nanotubes interacting with cardiomyocytes have the ability to promote physiological growth and functional maturation. These properties are unique in the current vexing field of tissue engineering, and offer unprecedented perspectives in the development of innovative therapies for cardiac repair.

  4. Sustained delivery of VEGF from designer self-assembling peptides improves cardiac function after myocardial infarction

    SciTech Connect

    Guo, Hai-dong; Cui, Guo-hong; Yang, Jia-jun; Wang, Cun; Zhu, Jing; Zhang, Li-sheng; Jiang, Jun; Shao, Shui-jin

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer The designer peptide LRKKLGKA could self-assemble into nanofibers. Black-Right-Pointing-Pointer Injection of LRKKLGKA peptides could promote the sustained delivery of VEGF. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides lead to sufficient angiogenesis. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides improves heart function. -- Abstract: Poor vascularization and insufficient oxygen supply are detrimental to the survival of residual cardiomyocytes or transplanted stem cells after myocardial infarction. To prolong and slow the release of angiogenic factors, which stimulate both angiogenesis and vasculogenesis, we constructed a novel self-assembling peptide by attaching the heparin-binding domain sequence LRKKLGKA to the self-assembling peptide RADA16. This designer self-assembling peptide self-assembled into nanofiber scaffolds under physiological conditions, as observed by atomic force microscopy. The injection of designer self-assembling peptides can efficiently provide the sustained delivery of VEGF for at least 1 month. At 4 weeks after transplantation, cardiac function was improved, and scar size and collagen deposition were markedly reduced in the group receiving VEGF with the LRKKLGKA scaffolds compared with groups receiving VEGF alone, LRKKLGKA scaffolds alone or VEGF with RADA16 scaffolds. The microvessel density in the VEGF with LRKKLGKA group was higher than that in the VEGF with RADA16 group. TUNEL and cleaved caspase-3 expression assays showed that the transplantation of VEGF with LRKKLGKA enhanced cell survival in the infarcted heart. These results present the tailor-made peptide scaffolds as a new generation of sustained-release biomimetic biomaterials and suggest that the use of angiogenic factors along with designer self-assembling peptides can lead to myocardial protection, sufficient angiogenesis, and improvement in cardiac function.

  5. Effect of Head-Down Bed Rest and Artificial Gravity Countermeasure on Cardiac Autonomic and Advanced Electrocardiographic Function

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Platts, S.; Stenger, M.; Ribeiro, C.; Natapoff, A.; Howarth, M.; Evans, J.

    2007-01-01

    ); and 4) QTV index was also significantly more changed (increased) in the AG-treated group than in the HDBR-only group, although this was clearly due to a greater decrease in generalized HRV and not to a greater increase in QTV proper because there was no relevant HDBR*group effect for either the SDNN or the RMSSD of QTV. Brief daily AG treatment by short-arm centrifuge during each of 21 days of HDBR does not appear to protect against HDBR-related losses of cardiac autonomic function or of LV mass as estimated by ECG.

  6. Aging Impairs Myocardial Fatty Acid and Ketone Oxidation and Modifies Cardiac Functional and Metabolic Responses to Insulin in Mice

    SciTech Connect

    Hyyti, Outi M.; Ledee, Dolena; Ning, Xue-Han; Ge, Ming; Portman, Michael A.

    2010-07-02

    Aging presumably initiates shifts in substrate oxidation mediated in part by changes in insulin sensitivity. Similar shifts occur with cardiac hypertrophy and may contribute to contractile dysfunction. We tested the hypothesis that aging modifies substrate utilization and alters insulin sensitivity in mouse heart when provided multiple substrates. In vivo cardiac function was measured with microtipped pressure transducers in the left ventricle from control (4–6 mo) and aged (22–24 mo) mice. Cardiac function was also measured in isolated working hearts along with substrate and anaplerotic fractional contributions to the citric acid cycle (CAC) by using perfusate containing 13C-labeled free fatty acids (FFA), acetoacetate, lactate, and unlabeled glucose. Stroke volume and cardiac output were diminished in aged mice in vivo, but pressure development was preserved. Systolic and diastolic functions were maintained in aged isolated hearts. Insulin prompted an increase in systolic function in aged hearts, resulting in an increase in cardiac efficiency. FFA and ketone flux were present but were markedly impaired in aged hearts. These changes in myocardial substrate utilization corresponded to alterations in circulating lipids, thyroid hormone, and reductions in protein expression for peroxisome proliferator-activated receptor (PPAR)α and pyruvate dehydrogenase kinase (PDK)4. Insulin further suppressed FFA oxidation in the aged. Insulin stimulation of anaplerosis in control hearts was absent in the aged. The aged heart shows metabolic plasticity by accessing multiple substrates to maintain function. However, fatty acid oxidation capacity is limited. Impaired insulin-stimulated anaplerosis may contribute to elevated cardiac efficiency, but may also limit response to acute stress through depletion of CAC intermediates.

  7. Resting cardiac function in adolescent non-suicidal self-injury: The impact of borderline personality disorder symptoms and psychosocial functioning.

    PubMed

    Koenig, Julian; Rinnewitz, Lena; Parzer, Peter; Resch, Franz; Thayer, Julian F; Kaess, Michael

    2017-02-01

    Vagally mediated heart rate variability (vmHRV) is reduced in borderline personality disorder (BPD). Non-suicidal self-injury (NSSI) is associated with comorbid psychopathology, in particular BPD. We aimed to examine differences in cardiac function (vmHRV and heart rate [HR]) comparing adolescents (12-17 years) engaging in NSSI (n=30) and healthy controls (n=30). Further, we aimed to determine clinical concomitants of cardiac function in patients with NSSI. Analyses showed no significant group differences on cardiac function. Controlling for a host of confounding variables resting state HR and vmHRV in adolescents with NSSI were significantly correlated with BPD symptoms and the current level of functioning.

  8. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    SciTech Connect

    Haddad, Rami; Kasneci, Amanda; Mepham, Kathryn; Sebag, Igal A.; and others

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  9. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment

    SciTech Connect

    Iso, Yoshitaka; Spees, Jeffrey L.; E-mail: Jeffrey.Spees@uvm.edu; Serrano, Claudia; Bakondi, Benjamin; Pochampally, Radhika; Song, Yao-Hua; Sobel, Burton E.; Delafontaine, Patrick; Prockop, Darwin J. . E-mail: dprocko@tulane.edu

    2007-03-16

    The aim of this study was to determine whether intravenously administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group were significantly improved compared with controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion.

  10. Extracellular Matrix Mediated Maturation of Human Pluripotent Stem Cell Derived Cardiac Monolayer Structure and Electrophysiological Function

    PubMed Central

    Herron, Todd J.; Rocha, Andre Monteiro Da; Campbell, Katherine; Ponce-Balbuena, Daniela; Willis, B. Cicero; Guerrero-Serna, Guadalupe; Liu, Qinghua; Klos, Matt; Musa, Hassan; Zarzoso, Manuel; Bizy, Alexandra; Furness, Jamie; Anumonwo, Justus; Mironov, Sergey; Jalife, José

    2016-01-01

    Background Human pluripotent stem cell-derived cardiomyocyte (hPSC-CMs) monolayers generated to date display an immature embryonic-like functional and structural phenotype that limits their utility for research and cardiac regeneration. In particular, the electrophysiological function of hPSC-CM monolayers and bioengineered constructs used to date are characterized by slow electrical impulse propagation velocity and immature action potential profiles. Methods and Results Here we have identified an optimal extracellular matrix (ECM) for significant electrophysiological and structural maturation of hPSC-CM monolayers. hPSC-CM plated in the optimal ECM combination have impulse propagation velocities ~2X faster than previously reported (43.6±7.0 cm·s−1 n=9) and have mature cardiomyocyte action potential profiles including hyperpolarized diastolic potential and rapid action potential upstroke velocity (146.5±17.7 V/s, N=5 monolayers). In addition the optimal ECM promoted hypertrophic growth of cardiomyocytes and the expression of key mature sarcolemmal (SCN5A, Kir2.1 and Connexin43) and myofilament markers (cTroponin I). The maturation process reported here relies on activation of integrin signaling pathways: neutralization of β1 integrin receptors via blocking antibodies and pharmacological blockade of focal adhesion kinase (FAK) activation prevented structural maturation. Conclusions Maturation of human stem cell derived cardiomyocyte monolayers is achieved in a one week period by plating cardiomyocytes on PDMS coverslips rather than on conventional 2D cell culture formats such as glass coverslips or plastic dishes. Activation of integrin signaling and FAK are essential for significant maturation of human cardiac monolayers. PMID:27069088

  11. Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction

    SciTech Connect

    Muthu, Priya; Wang, Li; Yuan, Chen-Ching; Kazmierczak, Katarzyna; Huang, Wenrui; Hernandez, Olga M.; Kawai, Masataka; Irving, Thomas C.; Szczesna-Cordary, Danuta

    2012-04-02

    The myosin essential light chain (ELC) is a structural component of the actomyosin cross-bridge, but its function is poorly understood, especially the role of the cardiac specific N-terminal extension in modulating actomyosin interaction. Here, we generated transgenic (Tg) mice expressing the A57G (alanine to glycine) mutation in the cardiac ELC known to cause familial hypertrophic cardiomyopathy (FHC). The function of the ELC N-terminal extension was investigated with the Tg-{Delta}43 mouse model, whose myocardium expresses a truncated ELC. Low-angle X-ray diffraction studies on papillary muscle fibers in rigor revealed a decreased interfilament spacing ({approx} 1.5 nm) and no alterations in cross-bridge mass distribution in Tg-A57G mice compared to Tg-WT, expressing the full-length nonmutated ELC. The truncation mutation showed a 1.3-fold increase in I{sub 1,1}/I{sub 1,0}, indicating a shift of cross-bridge mass from the thick filament backbone toward the thin filaments. Mechanical studies demonstrated increased stiffness in Tg-A57G muscle fibers compared to Tg-WT or Tg-{Delta}43. The equilibrium constant for the cross-bridge force generation step was smallest in Tg-{Delta}43. These results support an important role for the N-terminal ELC extension in prepositioning the cross-bridge for optimal force production. Subtle changes in the ELC sequence were sufficient to alter cross-bridge properties and lead to pathological phenotypes.

  12. Functional Outcome Trajectories after Out-of Hospital Pediatric Cardiac Arrest

    PubMed Central

    Silverstein, Faye S; Slomine, Beth; Christensen, James; Holubkov, Richard; Page, Kent; Dean, J. Michael; Moler, Frank

    2016-01-01

    Objective To analyze functional performance measures collected prospectively during the conduct of a clinical trial that enrolled children (up to age 18 years), resuscitated after out-of-hospital cardiac arrest, who were at high risk for poor outcomes. Design Children with Glasgow Motor Scales <5, within 6 hours of resuscitation, were enrolled in a clinical trial that compared two targeted temperature management interventions (THAPCA-OH, NCT00878644). The primary outcome, 12-month survival with Vineland Adaptive Behavior Scales, second edition (VABS-II) score ≥70, did not differ between groups. Setting 38 North American pediatric ICU’s. Participants 295 children were enrolled; 270/295 had baseline VABS-II scores ≥70; 87/270 survived one year. Interventions Targeted temperatures were 33.0°C and 36.8°C for hypothermia and normothermia groups. Measurements and Main Results Baseline measures included VABS-II, Pediatric Cerebral Performance Category(PCPC), and Pediatric Overall Performance Category (POPC). PCPC and POPC were rescored at hospital discharges; all three were scored at 3 and 12 months. In survivors with baseline VABS-II scores ≥70, we evaluated relationships of hospital discharge PCPC with 3 and 12 month scores, and between 3 and 12 month VABS-II scores. Hospital discharge PCPC scores strongly predicted 3 and 12 month PCPC (r=0.82,0.79; p<0.0001) and VABS-II scores (r=−0.81,−0.77; p<0.0001) Three month VABS-II scores strongly predicted 12 month performance (r=0.95, p<0.0001). Hypothermia treatment did not alter these relationships. Conclusions In comatose children, with Glasgow Motor Scales <5 in the initial hours after out-of-hospital cardiac arrest resuscitation, function scores at hospital discharge and at 3 months predicted 12-month performance well in the majority of survivors. PMID:27509385

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

    PubMed Central

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

    2016-01-01

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

  14. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult

    PubMed Central

    Carreira, Vinicius S.; Fan, Yunxia; Kurita, Hisaka; Wang, Qin; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro

    2015-01-01

    The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease. PMID:26555816

  15. Asiatic acid inhibits left ventricular remodeling and improves cardiac function in a rat model of myocardial infarction

    PubMed Central

    HUO, LIANYING; SHI, WENBING; CHONG, LING; WANG, JINLONG; ZHANG, KAI; LI, YUFENG

    2016-01-01

    Left ventricular remodeling results in cardiac dysfunction and accounts for the majority of the morbidity and mortality following myocardial infarction (MI). The aim of the present study was to investigate the effect of asiatic acid (AA) on cardiac function and left ventricular remodeling in a rat model of MI and explore the underlying mechanisms. Rats were subjected to coronary artery ligation to model MI and orally treated with AA. After 4 weeks, cardiac function was assessed by echocardiography. Cardiomyocyte cross-sectional area was recorded, and the expression levels of a number of inflammatory cytokines were detected using ELISA. The degree of interstitial fibrosis was determined by evaluating the mRNA expression levels of collagen II and III. Western blot analysis was performed to detect the expression levels of total and phosphorylated p38 MAPK and ERK1/2, to investigate whether they are involved in the mechanism underlying the effect of AA on the heart. Rats subjected to MI displayed significantly impaired cardiac function compared with those subjected to a sham procedure, while this change was reversed by treatment with AA. Furthermore, AA markedly inhibited cardiac hypertrophy, reduced the mRNA expression levels of inflammatory cytokines and decreased interstitial fibrosis in the infarct border zone of MI model rats compared with those in vehicle-treated MI model rats. Furthermore, the phosphorylation of p38 MAPK and ERK1/2 was blocked by AA in the MI rats but not in the sham rats. In summary, AA treatment preserved cardiac function and inhibited left ventricular remodeling, potentially by blocking the phosphorylation of p38 MAPK and ERK1/2 in the infarct border zone of the ischemic myocardium, indicating that AA may be a novel candidate for development as a therapy for MI. PMID:26889217

  16. Effects of pulsatile perfusion during cardiopulmonary bypass on biochemical markers and kidney function in patients undergoing cardiac surgeries.

    PubMed

    Mohammadzadeh, Alireza; Jafari, Naser; Hasanpour, Mohammad; Sahandifar, Soheil; Ghafari, Masoud; Alaei, Vahed

    2013-01-01

    For several years there is no conclusive guideline on the effectiveness of pulsatile or non-pulsatile perfusion during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgeries. In this study, we evaluated the effect of pulsatile versus continuous perfusion on the myocardial release of the cardiac biochemical markers including, creatine phosphokinase (CPK), cardiac creatine kinase (CK-MB), and lactate dehydrogenase (LDH), and also kidney function tests including: blood urea nitrogen test (BUN) and creatinine test (Cr) in patients that underwent both pulsatile and non-pulsatile methods before and after heart surgeries. A total of 80 patients were enrolled in this study, 40 patients in each pulsatile and non-pulsatile group. Venous blood samples were drown from each patient in two groups before operation and after operation at, 24, 48, and 72 h and analyzed separately for CPK, its cardiac isoenzyme (CK-MB), LDH, BUN and Cr. There were no significant differences between the two groups with regard to preoperative parameters such as sex, age, and body surface area. Our study shows that the effect of pulsatile perfusion on cardiac and kidney function is better than the non-pulsatile method.

  17. ACP1 Genetic Polymorphism and Coronary Artery Disease: Evidence of Effects on Clinical Parameters of Cardiac Function

    PubMed Central

    Gloria-Bottini, Fulvia; Banci, Maria; Saccucci, Patrizia; Nardi, Paolo; Scognamiglio, Mattia; Papetti, Federica; Adanti, Sara; Magrini, Andrea; Pellegrino, Antonio; Bottini, Egidio; Chiariello, Luigi

    2013-01-01

    Background Kinases and phosphatases have an important role in the susceptibility and clinical variability of cardiac diseases. We have recently reported an association between a phosphoprotein phosphatase controlled by Acid Phosphatase locus 1 (ACP1), and Coronary artery disease (CAD) suggesting an effect on the susceptibility to this disease. In the present note we have investigated a possible role of ACP1 in the variability of clinical parameters of cardiac function. Methods We have studied 345 subjects admitted to Valmontone Hospital for cardiovascular diseases: 202 subjects with CAD and 143 without CAD, 53 subjects admitted to Cardiac Surgery Division of Tor Vergata University were also considered. Results In diabetic patients with CAD there is a significant negative association between Left ventricular ejection fraction (LVEF) and ACP1 S isoform concentration. Genotypes with high S isoform concentration show a lower value of LVEF as compared to genotypes with low S isoform concentration. We have also found a significant positive association between cNYHA class and ACP1 S isoform. After surgical intervention, in subjects with high S isoform concentration the decrease of LVEF is more marked as compared to subjects with low S isoform concentration. Overall these observations indicate that high S isoform activity has negative effects on cardiac function. The observation in patients undergoing cardiac surgery confirms the negative association between high S isoform activity and LVEF. Conclusions The present study suggests that ACP1 influences both susceptibility to CAD and clinical manifestations of the disease.

  18. Endoplasmic Reticulum Resident Protein 44 (ERp44) Deficiency in Mice and Zebrafish Leads to Cardiac Developmental and Functional Defects

    PubMed Central

    Wang, Ding‐Yan; Abbasi, Cynthia; El‐Rass, Suzan; Li, Jamie Yuanjun; Dawood, Fayez; Naito, Kotaro; Sharma, Parveen; Bousette, Nicolas; Singh, Shalini; Backx, Peter H.; Cox, Brian; Wen, Xiao‐Yan; Liu, Peter P.; Gramolini, Anthony O.

    2014-01-01

    Background Endoplasmic reticulum (ER) resident protein 44 (ERp44) is a member of the protein disulfide isomerase family, is induced during ER stress, and may be involved in regulating Ca2+ homeostasis. However, the role of ERp44 in cardiac development and function is unknown. The aim of this study was to investigate the role of ERp44 in cardiac development and function in mice, zebrafish, and embryonic stem cell (ESC)‐derived cardiomyocytes to determine the underlying role of ERp44. Methods and Results We generated and characterized ERp44−/− mice, ERp44 morphant zebrafish embryos, and ERp44−/− ESC‐derived cardiomyocytes. Deletion of ERp44 in mouse and zebrafish caused significant embryonic lethality, abnormal heart development, altered Ca2+ dynamics, reactive oxygen species generation, activated ER stress gene profiles, and apoptotic cell death. We also determined the cardiac phenotype in pressure overloaded, aortic‐banded ERp44+/− mice: enhanced ER stress activation and increased mortality, as well as diastolic cardiac dysfunction with a significantly lower fractional shortening. Confocal and LacZ histochemical staining showed a significant transmural gradient for ERp44 in the adult heart, in which high expression of ERp44 was observed in the outer subepicardial region of the myocardium. Conclusions ERp44 plays a critical role in embryonic heart development and is crucial in regulating cardiac cell Ca2+ signaling, ER stress, ROS‐induced oxidative stress, and activation of the intrinsic mitochondrial apoptosis pathway. PMID:25332179

  19. A functional comparison of cardiac troponin C from representatives of three vertebrate taxa: Linking phylogeny and protein function.

    PubMed

    Sears, Elizabeth J; Gillis, Todd E

    2016-12-01

    The Ca(2+) affinity of cardiac troponin C (cTnC) from rainbow trout is significantly greater than that of cTnC from mammalian species. This high affinity is thought to enable cardiac function in trout at low physiological temperatures and is due to residues Asn(2), Ile(28), Gln(29), and Asp(30) (Gillis et al., 2005, Physiol Genomics, 22, 1-7). Interestingly, the cTnC of the African clawed frog Xenopus laevis (frog cTnC) contains Gln(29) and Asp(30) but the residues at positions 2 and 28 are those found in all mammalian cTnC isoforms (Asp(2) and Val(28)). The purpose of this study was to determine the Ca(2+) affinity of frog cTnC, and to determine how these three protein orthologs influence the function of complete troponin complexes. Measurements of Ca(2+) affinity and the rate of Ca(2+) dissociation from the cTnC isoforms and cTn complexes were made by monitoring the fluorescence of anilinonapthalenesulfote iodoacetamide (IAANS) engineered into the cTnC isoforms to report changes in protein conformation. The results demonstrate that the Ca(2+) affinity of frog cTnC is greater than that of trout cTnC and human cTnC. We also found that replacing human cTnC with frog cTnC in a mammalian cTn complex increased the Ca(2+) affinity of the complex by 5-fold, which is also greater than complexes containing trout cTnC. Together these results suggest that frog cTnC has the potential to increase the Ca(2+) sensitivity of force generation by the mammalian heart.

  20. Saturated high-fat diet-induced obesity increases adenylate cyclase of myocardial β-adrenergic system and does not compromise cardiac function.

    PubMed

    Vileigas, Danielle F; de Deus, Adriana F; da Silva, Danielle C T; de Tomasi, Loreta C; de Campos, Dijon H S; Adorni, Caroline S; de Oliveira, Scarlet M; Sant'Ana, Paula G; Okoshi, Katashi; Padovani, Carlos R; Cicogna, Antonio C

    2016-09-01

    Obesity is a worldwide pandemic associated with high incidence of cardiovascular disease. The mechanisms by which the obesity leads cardiac dysfunction are not fully elucidated and few studies have evaluated the relationship between obesity and proteins involved in myocardial β-adrenergic (βA) system. The purpose of this study was to evaluate the cardiac function and βA pathway components in myocardium of obese rats. Male Wistar rats were distributed into two groups: control (n = 17; standard diet) and obese (n = 17; saturated high-fat diet) fed for 33 weeks. Nutritional profile and comorbidities were assessed. Cardiac structure and function was evaluated by macroscopic postmortem, echocardiographic and isolated papillary muscle analyzes. Myocardial protein expression of β1- and β2-adrenergic receptors, Gαs protein, adenylate cyclase (AC) and protein kinase A (PKA) was performed by Western blot. Cardiac cyclic adenosine monophosphate (cAMP) levels and PKA activity were assessed by ELISA Obese rats showed increased adiposity index (P < 0.001) and several comorbidities as hypertension, glucose intolerance, insulin resistance, and dyslipidemia compared with control rats. Echocardiographic assessment revealed increased left atrium diameter (C: 4.98 ± 0.38 vs. Ob: 5.47 ± 0.53, P = 0.024) and posterior wall shortening velocity (C: 37.1 ± 3.6 vs. Ob: 41.8 ± 3.8, P = 0.007) in obese group. Papillary muscle evaluation indicated that baseline data and myocardial responsiveness to isoproterenol stimulation were similar between the groups. Protein expression of myocardial AC was higher in obese group than in the control (C: 1.00 ± 0.21 vs. Ob: 1.25 ± 0.10, P = 0.025), whereas the other components were unchanged. These results suggest that saturated high-fat diet-induced obesity was not effective in triggering cardiac dysfunction and impair the beta-adrenergic signaling.

  1. Maternal high-fat diet impairs cardiac function in offspring of diabetic pregnancy through metabolic stress and mitochondrial dysfunction

    PubMed Central

    Mdaki, Kennedy S.; Larsen, Tricia D.; Wachal, Angela L.; Schimelpfenig, Michelle D.; Weaver, Lucinda J.; Dooyema, Samuel D. R.; Louwagie, Eli J.

    2016-01-01

    Offspring of diabetic pregnancies are at risk of cardiovascular disease at birth and throughout life, purportedly through fuel-mediated influences on the developing heart. Preventative measures focus on glycemic control, but the contribution of additional offenders, including lipids, is not understood. Cellular bioenergetics can be influenced by both diabetes and hyperlipidemia and play a pivotal role in the pathophysiology of adult cardiovascular disease. This study investigated whether a maternal high-fat diet, independently or additively with diabetes, could impair fuel metabolism, mitochondrial function, and cardiac physiology in the developing offspring's heart. Sprague-Dawley rats fed a control or high-fat diet were administered placebo or streptozotocin to induce diabetes during pregnancy and then delivered offspring from four groups: control, diabetes exposed, diet exposed, and combination exposed. Cardiac function, cellular bioenergetics (mitochondrial stress test, glycolytic stress test, and palmitate oxidation assay), lipid peroxidation, mitochondrial histology, and copy number were determined. Diabetes-exposed offspring had impaired glycolytic and respiratory capacity and a reduced proton leak. High-fat diet-exposed offspring had increased mitochondrial copy number, increased lipid peroxidation, and evidence of mitochondrial dysfunction. Combination-exposed pups were most severely affected and demonstrated cardiac lipid droplet accumulation and diastolic/systolic cardiac dysfunction that mimics that of adult diabetic cardiomyopathy. This study is the first to demonstrate that a maternal high-fat diet impairs cardiac function in offspring of diabetic pregnancies through metabolic stress and serves as a critical step in understanding the role of cellular bioenergetics in developmentally programmed cardiac disease. PMID:26801311

  2. Cell number per spheroid and electrical conductivity of nanowires influence the function of silicon nanowired human cardiac spheroids.

    PubMed

    Tan, Yu; Richards, Dylan; Coyle, Robert C; Yao, Jenny; Xu, Ruoyu; Gou, Wenyu; Wang, Hongjun; Menick, Donald R; Tian, Bozhi; Mei, Ying

    2017-03-15

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide an unlimited cell source to treat cardiovascular diseases, the leading cause of death worldwide. However, current hiPSC-CMs retain an immature phenotype that leads to difficulties for integration with adult myocardium after transplantation. To address this, we recently utilized electrically conductive silicon nanowires (e-SiNWs) to facilitate self-assembly of hiPSC-CMs to form nanowired hiPSC cardiac spheroids. Our previous results showed addition of e-SiNWs effectively enhanced the functions of the cardiac spheroids and improved the cellular maturation of hiPSC-CMs. Here, we examined two important factors that can affect functions of the nanowired hiPSC cardiac spheroids: (1) cell number per spheroid (i.e., size of the spheroids), and (2) the electrical conductivity of the e-SiNWs. To examine the first factor, we prepared hiPSC cardiac spheroids with four different sizes by varying cell number per spheroid (∼0.5k, ∼1k, ∼3k, ∼7k cells/spheroid). Spheroids with ∼3k cells/spheroid was found to maximize the beneficial effects of the 3D spheroid microenvironment. This result was explained with a semi-quantitative theory that considers two competing factors: 1) the improved 3D cell-cell adhesion, and 2) the reduced oxygen supply to the center of spheroids with the increase of cell number. Also, the critical role of electrical conductivity of silicon nanowires has been confirmed in improving tissue function of hiPSC cardiac spheroids. These results lay down a solid foundation to develop suitable nanowired hiPSC cardiac spheroids as an innovative cell delivery system to treat cardiovascular diseases.

  3. EFFECTS OF INSTILLATION OF RESIDUAL OIL FLY ASH ON INDICES OF CARDIAC, PULMONARY, AND THERMOREGULATORY FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS

    EPA Science Inventory


    EFFECTS OF INSTILLED RESIDUAL OIL FLY ASH (ROFA) ON INDICES OF CARDIAC, PULMONARY, AND THERMOREGULATORY FUNCTION IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS. LB Wichers1, JP Nolan2, UP Kodavanti2, MCJ Schladweiler2, R Hauser3, DW Winsett2, DL Costa2, and WP Watkinson2. 1UNC Sch...

  4. Assessment of cardiac function using myocardial perfusion imaging technique on SPECT with 99mTc sestamibi

    NASA Astrophysics Data System (ADS)

    Gani, M. R. A.; Nazir, F.; Pawiro, S. A.; Soejoko, D. S.

    2016-03-01

    Suspicion on coronary heart disease can be confirmed by observing the function of left ventricle cardiac muscle with Myocardial Perfusion Imaging techniques. The function perfusion itself is indicated by the uptake of radiopharmaceutical tracer. The 31 patients were studied undergoing the MPI examination on Gatot Soebroto Hospital using 99mTc-sestamibi radiopharmaceutical with stress and rest conditions. Stress was stimulated by physical exercise or pharmacological agent. After two hours, the patient did rest condition on the same day. The difference of uptake percentage between stress and rest conditions will be used to determine the malfunction of perfusion due to ischemic or infarct. Degradation of cardiac function was determined based on the image-based assessment of five segments of left ventricle cardiac. As a result, 8 (25.8%) patients had normal myocardial perfusion and 11 (35.5%) patients suspected for having partial ischemia. Total ischemia occurred to 8 (25.8%) patients with reversible and irreversible ischemia and the remaining 4 (12.9%) patients for partial infarct with characteristic the percentage of perfusion ≤50%. It is concluded that MPI technique of image-based assessment on uptake percentage difference between stress and rest conditions can be employed to predict abnormal perfusion as complementary information to diagnose the cardiac function.

  5. Progressive Dystrophic Pathology in Diaphragm and Impairment of Cardiac Function in FKRP P448L Mutant Mice

    PubMed Central

    Blaeser, Anthony; Awano, Hiroyuki; Wu, Bo; Lu, Qi-Long

    2016-01-01

    Mutations in the gene for fukutin-related protein represent a subset of muscular dystrophies known as dystroglycanopathies characterized by loss of functionally-glycosylated-alpha-dystroglycan and a wide range of dystrophic phenotypes. Mice generated by our lab containing the P448L mutation in the fukutin-related protein gene demonstrate the dystrophic phenotype similar to that of LGMD2I. Here we examined the morphology of the heart and diaphragm, focusing on pathology of diaphragm and cardiac function of the mutant mice for up to 12 months. Both diaphragm and heart lack clear expression of functionally-glycosylated-alpha-dystroglycan throughout the observed period. The diaphragm undergoes progressive deterioration in histology with increasing amount of centranucleation and inflammation. Large areas of mononuclear cell infiltration and fibrosis of up to 60% of tissue area were detected as early as 6 months of age. Despite a less severe morphology with only patches of mononuclear cell infiltration and fibrosis of ~5% by 12 months of age in the heart, cardiac function is clearly affected. High frequency ultrasound reveals a smaller heart size up to 10 months of age. There are significant increases in myocardial thickness and decrease in cardiac output through 12 months. Dysfunction in the heart represents a key marker for evaluating experimental therapies aimed at cardiac muscle. PMID:27711214

  6. Modelling passive diastolic mechanics with quantitative MRI of cardiac structure and function.

    PubMed

    Wang, Vicky Y; Lam, H I; Ennis, Daniel B; Cowan, Brett R; Young, Alistair A; Nash, Martyn P

    2009-10-01

    The majority of patients with clinically diagnosed heart failure have normal systolic pump function and are commonly categorized as suffering from diastolic heart failure. The left ventricle (LV) remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions, which in turn can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element (FE) model was customized to geometric data segmented from in vivo tagged magnetic resonance images (MRI) data and myofibre orientation derived from ex vivo diffusion tensor MRI (DTMRI) of a canine heart using nonlinear finite element fitting techniques. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion in each voxel of a DTMRI directly corresponds to the local myocardial fibre orientation. Due to differences in myocardial geometry between in vivo and ex vivo imaging, myofibre orientations were mapped into the geometric FE model using host mesh fitting (a free form deformation technique). Pressure recordings, temporally synchronized to the tagging data, were used as the loading constraints to simulate the LV deformation during diastole. Simulation of diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. Integrated physiological modelling of this kind will allow more insight into mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction under pathological conditions.

  7. Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function

    PubMed Central

    Sadhukhan, Sushabhan; Liu, Xiaojing; Ryu, Dongryeol; Nelson, Ornella D.; Stupinski, John A.; Li, Zhi; Chen, Wei; Zhang, Sheng; Weiss, Robert S.; Auwerx, Johan; Lin, Hening

    2016-01-01

    Cellular metabolites, such as acyl-CoA, can modify proteins, leading to protein posttranslational modifications (PTMs). One such PTM is lysine succinylation, which is regulated by sirtuin 5 (SIRT5). Although numerous proteins are modified by lysine succinylation, the physiological significance of lysine succinylation and SIRT5 remains elusive. Here, by profiling acyl-CoA molecules in various mouse tissues, we have discovered that different tissues have different acyl-CoA profiles and that succinyl-CoA is the most abundant acyl-CoA molecule in the heart. This interesting observation has prompted us to examine protein lysine succinylation in different mouse tissues in the presence and absence of SIRT5. Protein lysine succinylation predominantly accumulates in the heart when Sirt5 is deleted. Using proteomic studies, we have identified many cardiac proteins regulated by SIRT5. Our data suggest that ECHA, a protein involved in fatty acid oxidation, is a major enzyme that is regulated by SIRT5 and affects heart function. Sirt5 knockout (KO) mice have lower ECHA activity, increased long-chain acyl-CoAs, and decreased ATP in the heart under fasting conditions. Sirt5 KO mice develop hypertrophic cardiomyopathy, as evident from the increased heart weight relative to body weight, as well as reduced shortening and ejection fractions. These findings establish that regulating heart metabolism and function is a major physiological function of lysine succinylation and SIRT5. PMID:27051063

  8. Gain-of-function mutation in TASK-4 channels and severe cardiac conduction disorder.

    PubMed

    Friedrich, Corinna; Rinné, Susanne; Zumhagen, Sven; Kiper, Aytug K; Silbernagel, Nicole; Netter, Michael F; Stallmeyer, Birgit; Schulze-Bahr, Eric; Decher, Niels

    2014-07-01

    Analyzing a patient with progressive and severe cardiac conduction disorder combined with idiopathic ventricular fibrillation (IVF), we identified a splice site mutation in the sodium channel gene SCN5A. Due to the severe phenotype, we performed whole-exome sequencing (WES) and identified an additional mutation in the KCNK17 gene encoding the K2P potassium channel TASK-4. The heterozygous change (c.262G>A) resulted in the p.Gly88Arg mutation in the first extracellular pore loop. Mutant TASK-4 channels generated threefold increased currents, while surface expression was unchanged, indicating enhanced conductivity. When co-expressed with wild-type channels, the gain-of-function by G88R was conferred in a dominant-active manner. We demonstrate that KCNK17 is strongly expressed in human Purkinje cells and that overexpression of G88R leads to a hyperpolarization and strong slowing of the upstroke velocity of spontaneously beating HL-1 cells. Thus, we propose that a gain-of-function by TASK-4 in the conduction system might aggravate slowed conductivity by the loss of sodium channel function. Moreover, WES supports a second hit-hypothesis in severe arrhythmia cases and identified KCNK17 as a novel arrhythmia gene.

  9. Gain-of-function mutation in TASK-4 channels and severe cardiac conduction disorder

    PubMed Central

    Friedrich, Corinna; Rinné, Susanne; Zumhagen, Sven; Kiper, Aytug K; Silbernagel, Nicole; Netter, Michael F; Stallmeyer, Birgit; Schulze-Bahr, Eric; Decher, Niels

    2014-01-01

    Analyzing a patient with progressive and severe cardiac conduction disorder combined with idiopathic ventricular fibrillation (IVF), we identified a splice site mutation in the sodium channel gene SCN5A. Due to the severe phenotype, we performed whole-exome sequencing (WES) and identified an additional mutation in the KCNK17 gene encoding the K2P potassium channel TASK-4. The heterozygous change (c.262G>A) resulted in the p.Gly88Arg mutation in the first extracellular pore loop. Mutant TASK-4 channels generated threefold increased currents, while surface expression was unchanged, indicating enhanced conductivity. When co-expressed with wild-type channels, the gain-of-function by G88R was conferred in a dominant-active manner. We demonstrate that KCNK17 is strongly expressed in human Purkinje cells and that overexpression of G88R leads to a hyperpolarization and strong slowing of the upstroke velocity of spontaneously beating HL-1 cells. Thus, we propose that a gain-of-function by TASK-4 in the conduction system might aggravate slowed conductivity by the loss of sodium channel function. Moreover, WES supports a second hit-hypothesis in severe arrhythmia cases and identified KCNK17 as a novel arrhythmia gene. PMID:24972929

  10. Arterial-cardiac baroreflex function: insights from repeated squat-stand maneuvers.

    PubMed

    Zhang, Rong; Claassen, Jurgen A H R; Shibata, Shigeki; Kilic, Sinem; Martin-Cook, Kristin; Diaz-Arrastia, Ramon; Levine, Benjamin D

    2009-07-01

    To assess baroreflex function under closed-loop conditions, a new approach was used to generate large and physiological perturbations in arterial pressure. Blood pressure (BP) and R-R interval were recorded continuously in 20 healthy young (33 +/- 8 yr) and eight elderly subjects (66 +/- 6 yr). Repeated squat-stand maneuvers at the frequencies of 0.05 and 0.1 Hz were performed to produce periodic oscillations in BP to provoke the baroreflex. To assess the effects of the muscle reflex and/or central command on the baroreflex, passive squat-stand maneuvers were conducted using a pulley system to assist changes in body position. Transfer function between changes in BP and R-R interval was estimated to assess the arterial-cardiac baroreflex. Relative to resting conditions, large and coherent oscillations in BP and R-R interval were produced during both active and passive squat-stand maneuvers. However, changes in BP were smaller during passive than during active maneuvers. Changes in R-R interval were reduced commensurately. Therefore, transfer function gain did not change between the two maneuvers. Compared with the young, transfer function gain was reduced and the phase became more negative in the elderly, demonstrating the well-known effects of aging on reducing baroreflex sensitivity. Collectively, these findings suggest that the changes in R-R interval elicited by BP perturbations during squat-stand maneuvers are mediated primarily by a baroreflex mechanism. Furthermore, baroreflex function can be assessed using the transfer function method during large perturbations in arterial pressure.

  11. Effects of left ventricular assist device on cardiac function: experimental study of relationship between pump flow and left ventricular diastolic function.

    PubMed

    Saito, A; Shiono, M; Orime, Y; Yagi, S; Nakata, K I; Eda, K; Hattori, T; Funahashi, M; Taniguchi, Y; Negishi, N; Sezai, Y

    2001-09-01

    The left ventricular assist device (LVAD) with centrifugal pump has two characteristics. One is a pump flow wave of the centrifugal pump, consisting of the pulsatile flow of the native heart and the nonpulsatile flow of the centrifugal pump. The other is that the centrifugal pump fills from the native heart not only in the systolic phase, but also in the diastolic phase. In the case of the apex outlet LVAD with centrifugal pump, blood flows from the left atrium through the left ventricle to the pump. Pump flow is regulated by preload, and preload is regulated by diastolic hemodynamics. The aim of this study is to analyze the relationship between pump flow and the diastolic hemodynamics of the native heart. Ten anesthetized intact pigs were studied after placement of an LVAD. Data were recorded with the LVAD off (control) and the LVAD on. The assist rate was changed to 25%, 50%, and 75%. The indexes of left ventricular (LV) diastolic function included LV myocardial relaxation (time constant of isovolumic pressure decay [Tau] and maximum negative dP/dt [LV dP/dt min]) and LV filling (peak filling rate [PFR], time to peak filling rate [tPFR], and diastolic filling time [DFT]). Stroke volume decreased significantly in 75% assist. LV end-systolic pressure decreased significantly in 50% and 75% assist. LV end-diastolic volume decreased as assist rate increased, but there were no significant changes. Stroke work decreased significantly in 50% and 75% assist. LV dP/dt min decreased significantly in 50% and 75% assist. Tau prolonged as assist rate increased, but there were no significant changes. DFT shortened significantly in 75% assist. PFR increased significantly in 75% assist. tPFR shortened significantly in 50% and 75% assist. In this study, LV relaxation delayed as an increasing of pump assist rate, but it suggested a result of reduction of cardiac work. Also, it was suggested that LVAD increases the pressure difference between the left atrium and the left ventricle

  12. Live dynamic OCT imaging of cardiac structure and function in mouse embryos with 43 Hz direct volumetric data acquisition

    NASA Astrophysics Data System (ADS)

    Wang, Shang; Singh, Manmohan; Lopez, Andrew L.; Wu, Chen; Raghunathan, Raksha; Schill, Alexander; Li, Jiasong; Larin, Kirill V.; Larina, Irina V.

    2016-03-01

    Efficient phenotyping of cardiac dynamics in live mouse embryos has significant implications on understanding of early mammalian heart development and congenital cardiac defects. Recent studies established optical coherence tomography (OCT) as a powerful tool for live embryonic heart imaging in various animal models. However, current four-dimensional (4D) OCT imaging of the beating embryonic heart largely relies on gated data acquisition or postacquisition synchronization, which brings errors when cardiac cycles lack perfect periodicity and is time consuming and computationally expensive. Here, we report direct 4D OCT imaging of the structure and function of cardiac dynamics in live mouse embryos achieved by employing a Fourier domain mode-locking swept laser source that enables ~1.5 MHz A-line rate. Through utilizing both forward and backward scans of a resonant mirror, we obtained a ~6.4 kHz frame rate, which allows for a direct volumetric data acquisition speed of ~43 Hz, around 20 times of the early-stage mouse embryonic heart rate. Our experiments were performed on mouse embryos at embryonic day 9.5. Time-resolved 3D cardiodynamics clearly shows the heart structure in motion. We present analysis of cardiac wall movement and its velocity from the primitive atrium and ventricle. Our results suggest that the combination of ultrahigh-speed OCT imaging with live embryo culture could be a useful embryonic heart phenotyping approach for mouse mutants modeling human congenital heart diseases.

  13. The Function of the MEF2 Family of Transcription Factors in Cardiac Development, Cardiogenomics, and Direct Reprogramming

    PubMed Central

    Desjardins, Cody A.; Naya, Francisco J.

    2016-01-01

    Proper formation of the mammalian heart requires precise spatiotemporal transcriptional regulation of gene programs in cardiomyocytes. Sophisticated regulatory networks have evolved to not only integrate the activities of distinct transcription factors to control tissue-specific gene programs but also, in many instances, to incorporate multiple members within these transcription factor families to ensure accuracy and specificity in the system. Unsurprisingly, perturbations in this elaborate transcriptional circuitry can lead to severe cardiac abnormalities. Myocyte enhancer factor–2 (MEF2) transcription factor belongs to the evolutionarily conserved cardiac gene regulatory network. Given its central role in muscle gene regulation and its evolutionary conservation, MEF2 is considered one of only a few core cardiac transcription factors. In addition to its firmly established role as a differentiation factor, MEF2 regulates wide variety of, sometimes antagonistic, cellular processes such as cell survival and death. Vertebrate genomes encode multiple MEF2 family members thereby expanding the transcriptional potential of this core transcription factor in the heart. This review highlights the requirement of the MEF2 family and their orthologs in cardiac development in diverse animal model systems. Furthermore, we describe the recently characterized role of MEF2 in direct reprogramming and genome-wide cardiomyocyte gene regulation. A thorough understanding of the regulatory functions of the MEF2 family in cardiac development and cardiogenomics is required in order to develop effective therapeutic strategies to repair the diseased heart. PMID:27630998

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

    PubMed

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

    2008-11-12

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

  15. Waon therapy improves quality of life as well as cardiac function and exercise capacity in patients with chronic heart failure.

    PubMed

    Sobajima, Mitsuo; Nozawa, Takashi; Fukui, Yasutaka; Ihori, Hiroyuki; Ohori, Takashi; Fujii, Nozomu; Inoue, Hiroshi

    2015-01-01

    Waon therapy (WT), which in Japanese means soothing warmth, is a repeated sauna therapy that improves cardiac and vascular endothelial function in patients with chronic heart failure (CHF). We investigated whether WT could improve the quality of life (QOL) of CHF patients in addition to improving cardiac function and exercise capacity.A total of 49 CHF patients (69 ± 14 years old) were treated with a 60°C far infrared-ray dry sauna bath for 15 minutes and then kept in a bed covered with blankets for 30 minutes once a day for 3 weeks. At baseline and 3 weeks after starting WT, cardiac function, 6-minute walk distance (6MWD), flow mediated dilation (FMD) of the brachial artery, and SF36-QOL scores were determined.WT significantly improved left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), 6MWD, and FMD (3.6 ± 2.3 to 5.1 ± 2.8%, P < 0.01). Moreover, WT significantly improved not only the physical (PC) but also mental component (MC) of the QOL scores. WT-induced improvement of PC was negatively correlated with changes in BNP (r = -0.327, P < 0.05), but MC improvement was not related directly to changes in BNP, LVEF, or 6MWD. WT-induced changes in MC were not parallel to PC improvement.WT improved QOL as well as cardiac function and exercise capacity in patients with CHF. Mental QOL improved independently of WT-induced improvement of cardiac function and exercise capacity.

  16. Cardiac-Restricted Expression of VCP/TER94 RNAi or Disease Alleles Perturbs Drosophila Heart Structure and Impairs Function

    PubMed Central

    Viswanathan, Meera C.; Blice-Baum, Anna C.; Sang, Tzu-Kang; Cammarato, Anthony

    2016-01-01

    Valosin-containing protein (VCP) is a highly conserved mechanoenzyme that helps maintain protein homeostasis in all cells and serves specialized functions in distinct cell types. In skeletal muscle, it is critical for myofibrillogenesis and atrophy. However, little is known about VCP's role(s) in the heart. Its functional diversity is determined by differential binding of distinct cofactors/adapters, which is likely disrupted during disease. VCP mutations cause multisystem proteinopathy (MSP), a pleiotropic degenerative disorder that involves inclusion body myopathy. MSP patients display progressive muscle weakness. They also exhibit cardiomyopathy and die from cardiac and respiratory failure, which are consistent with critical myocardial roles for the enzyme. Nonetheless, efficient models to interrogate VCP in cardiac muscle remain underdeveloped and poorly studied. Here, we investigated the significance of VCP and mutant VCP in the Drosophila heart. Cardiac-restricted RNAi-mediated knockdown of TER94, the Drosophila VCP homolog, severely perturbed myofibrillar organization and heart function in adult flies. Furthermore, expression of MSP disease-causing alleles engendered cardiomyopathy in adults and structural defects in embryonic hearts. Drosophila may therefore serve as a valuable model for examining role(s) of VCP in cardiogenesis and for identifying novel heart-specific VCP interactions, which when disrupted via mutation, contribute to or elicit cardiac pathology. PMID:27500162

  17. Molecular Mechanisms for Exercise Training-Induced Changes in Vascular Structure and Function: Skeletal Muscle, Cardiac Muscle, and the Brain.

    PubMed

    Olver, T Dylan; Ferguson, Brian S; Laughlin, M Harold

    2015-01-01

    Compared with resting conditions, during incremental exercise, cardiac output in humans is elevated from ~5 to 25 L min(-1). In conjunction with this increase, the proportion of cardiac output directed toward skeletal muscle increases from ~20% to 85%, while blood flow to cardiac muscle increases 500% and blood flow to specific brain structures increases nearly 200%. Based on existing evidence, researchers believe that blood flow in these tissues is matched to the increases in metabolic rate during exercise. This phenomenon, the matching of blood flow to metabolic requirement, is often referred to as functional hyperemia. This chapter summarizes mechanical and metabolic factors that regulate functional hyperemia as well as other exercise-induced signals, which are also potent stimuli for chronic adaptations in vascular biology. Repeated exposure to exercise-induced increases in shear stress and the induction of angiogenic factors alter vascular cell gene expression and mediate changes in vascular volume and blood flow control. The magnitude and regulation of this coordinated response appear to be tissue specific and coupled to other factors such as hypertrophy and hyperplasia. The cumulative effects of these adaptations contribute to increased exercise capacity, reduced relative challenge of a given submaximal exercise bout and ameliorated vascular outcomes in patient populations with pathological conditions. In the subsequent discussion, this chapter explores exercise as a regulator of vascular biology and summarizes the molecular mechanisms responsible for exercise training-induced changes in vascular structure and function in skeletal and cardiac muscle as well as the brain.

  18. Association of Cardiac Troponin T With Left Ventricular Structure and Function in CKD

    PubMed Central

    Mishra, Rakesh K.; Li, Yongmei; DeFilippi, Christopher; Fischer, Michael J.; Yang, Wei; Keane, Martin; Chen, Jing; He, Jiang; Kallem, Radhakrishna; Horwitz, Ed; Rafey, Mohammad; Raj, Dominic S.; Go, Alan S.; Shlipak, Michael G.

    2013-01-01

    Background Serum cardiac troponin T (cTnT) is associated with increased risk of heart failure and cardiovascular death in several population settings. We evaluated associations of cTnT with cardiac structural and functional abnormalities in a cohort of chronic kidney disease (CKD) patients without heart failure. Study Design Cross-sectional. Setting & Participants Chronic Renal Insufficiency Cohort (CRIC; N= 3,243) Predictor The primary predictor was cTnT. Secondary predictors included demographic and clinical characteristics, hemoglobin level, high-sensitivity C-reactive protein, and estimated glomerular filtration rate using cystatin C. Outcomes Echocardiography was used to determine left ventricular (LV) mass and LV systolic and diastolic function. Measurements Circulating cTnT was measured in stored sera using the highly sensitive assay. Logistic and linear regression models were used to examine associations of cTnT with each echocardiographic outcome. Results cTnT was detectable in 2,735 (84%) persons; the median was 13.3 (IQR, 7.7–23.8) pg/mL. Compared with undetectable cTnT (<3.0 pg/mL), the highest quartile (23.9 – 738.7 pg/mL) was associated with approximately two times as likely to experience LV hypertrophy (OR, 2.43; 95% CI, 1.44–4.09) in the fully adjusted model. cTnT had a more modest association with LV systolic dysfunction; as a log-linear variable, a significant association was present in the fully adjusted model (OR of 1.4 [95% CI, 1.1–1.7] per 1-log unit; p<0.01). There was no significant independent association between cTnT and LV diastolic dysfunction. When evaluated as a screening test, cTnT functioned only modestly for LV hypertrophy and concentric hypertrophy detection (area under the curve, 0.64 for both) with weaker areas under the curve for the other outcomes. Limitations The presence of coronary artery disease was not formally assessed using either noninvasive or angiographic techniques in this study. Conclusions In this large CKD

  19. On the averaging of cardiac diffusion tensor MRI data: the effect of distance function selection

    NASA Astrophysics Data System (ADS)

    Giannakidis, Archontis; Melkus, Gerd; Yang, Guang; Gullberg, Grant T.

    2016-11-01

    Diffusion tensor magnetic resonance imaging (DT-MRI) allows a unique insight into the microstructure of highly-directional tissues. The selection of the most proper distance function for the space of diffusion tensors is crucial in enhancing the clinical application of this imaging modality. Both linear and nonlinear metrics have been proposed in the literature over the years. The debate on the most appropriate DT-MRI distance function is still ongoing. In this paper, we presented a framework to compare the Euclidean, affine-invariant Riemannian and log-Euclidean metrics using actual high-resolution DT-MRI rat heart data. We employed temporal averaging at the diffusion tensor level of three consecutive and identically-acquired DT-MRI datasets from each of five rat hearts as a means to rectify the background noise-induced loss of myocyte directional regularity. This procedure is applied here for the first time in the context of tensor distance function selection. When compared with previous studies that used a different concrete application to juxtapose the various DT-MRI distance functions, this work is unique in that it combined the following: (i) metrics were judged by quantitative—rather than qualitative—criteria, (ii) the comparison tools were non-biased, (iii) a longitudinal comparison operation was used on a same-voxel basis. The statistical analyses of the comparison showed that the three DT-MRI distance functions tend to provide equivalent results. Hence, we came to the conclusion that the tensor manifold for cardiac DT-MRI studies is a curved space of almost zero curvature. The signal to noise ratio dependence of the operations was investigated through simulations. Finally, the ‘swelling effect’ occurrence following Euclidean averaging was found to be too unimportant to be worth consideration.

  20. Effect of CPAP on Cardiac Function in Minimally Symptomatic Patients with OSA: Results from a Subset of the MOSAIC Randomized Trial

    PubMed Central

    Craig, Sonya; Kylintireas, Ilias; Kohler, Malcolm; Nicoll, Debby; Bratton, Daniel J.; Nunn, Andrew J.; Leeson, Paul; Neubauer, Stefan; Stradling, John R.

    2015-01-01

    Study Objectives: Minimally symptomatic obstructive sleep apnea (OSA) is highly prevalent, and the effects of continuous positive airway pressure (CPAP) on myocardial function in these patients are unknown. The MOSAIC randomized, controlled trial of CPAP for minimally symptomatic OSA assessed the effect of CPAP on myocardial function in a subset of patients. Methods: Two centers taking part in the MOSAIC trial randomized 238 patients in parallel to 6 months of CPAP (120) or standard care (118). Of these, 168 patients had echocardiograms, and 68 patients had a cardiac magnetic resonance scan (CMR). A larger group (314) from 4 centers had brain natriuretic peptide (BNP) measured. Results: Mean (SD) baseline oxygen desaturation index (ODI) and Epworth sleepiness score (ESS) were 13.5 (13.2), and 8.4 (4.0), respectively. CPAP significantly reduced ESS and ODI. Baseline LV ejection fraction (LVEF) was well preserved (60.4%). CPAP had no significant effect on echo-derived left atrial (LA) area (−1.0 cm2, 95% CI −2.6 to +0.6, p = 0.23) or early to late left ventricular filling velocity (E/A) ratio (−0.01, 95% CI −0.07 to +0.05, p = 0.79). There was a small change in echo-derived LV end diastolic volume (EDV) with CPAP (−5.9 mL, 95% CI −10.6 to −1.2, p = 0.015). No significant changes were detected by CMR on LV mass index (+1.1 g/m2, 95% CI −5.9 to +8.0, p = 0.76) or LVEF (+0.8%, 95% CI −1.2 to +2.8, p = 0.41). CPAP did not affect BNP levels (p = 0.16). Conclusions: Six months of CPAP therapy does not change cardiac functional or structural parameters measured by echocardiogram or CMR in patients with minimally symptomatic mild-to-moderate OSA. Clinical Trial Registration: ISRCTN 34164388 (http://isrctn.org). Citation: Craig S, Kylintireas I, Kohler M, Nicoll D, Bratton DJ, Nunn AJ, Leeson P, Neubauer S, Stradling JR. Effect of CPAP on cardiac function in minimally symptomatic patients with OSA: results from a subset of the MOSAIC randomized trial. J Clin

  1. Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients.

    PubMed

    Zoccali, C; Mallamaci, F; Benedetto, F A; Tripepi, G; Parlongo, S; Cataliotti, A; Cutrupi, S; Giacone, G; Bellanuova, I; Cottini, E; Malatino, L S

    2001-07-01

    This study was designed to investigate the relationship among brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) and left ventricular mass (LVM), ejection fraction, and LV geometry in a large cohort of dialysis patients without heart failure (n = 246) and to test the prediction power of these peptides for total and cardiovascular mortality. In separate multivariate models of LVM, BNP and ANP were the strongest independent correlates of the LVM index. In these models, the predictive power of BNP was slightly stronger than that of ANP. Both natriuretic peptides also were the strongest independent predictors of ejection fraction, and again BNP was a slightly better predictor of ejection fraction than ANP. In separate multivariate Cox models, the relative risk of death was significantly higher in patients of the third tertile of the distribution of BNP and ANP than in those of the first tertile (BNP, 7.14 [95% confidence interval (CI), 2.83 to 18.01, P = 0.00001]; ANP, 4.22 [95% CI, 1.79 to 9.92, P = 0.001]), and a similar difference was found for cardiovascular death (BNP, 6.72 [95% CI, 2.44 to 18.54, P = 0.0002]; ANP, 3.80 [95% CI, 1.44 to 10.03, P = 0.007]). BNP but not ANP remained as an independent predictor of death in a Cox's model including LVM and ejection fraction. Cardiac natriuretic peptides are linked independently to LVM and function in dialysis patients and predict overall and cardiovascular mortality. The measurement of the plasma concentration of BNP and ANP may be useful for risk stratification in these patients.

  2. Connecting Teratogen-Induced Congenital Heart Defects to Neural Crest Cells and Their Effect on Cardiac Function

    PubMed Central

    Karunamuni, Ganga H.; Ma, Pei; Gu, Shi; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

    2014-01-01

    Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest is in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies. PMID:25220155

  3. Connecting teratogen-induced congenital heart defects to neural crest cells and their effect on cardiac function.

    PubMed

    Karunamuni, Ganga H; Ma, Pei; Gu, Shi; Rollins, Andrew M; Jenkins, Michael W; Watanabe, Michiko

    2014-09-01

    Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies.

  4. Adrenergic responsiveness is reduced, while baseline cardiac function is preserved in old adult conscious monkeys

    NASA Technical Reports Server (NTRS)

    Sato, N.; Kiuchi, K.; Shen, Y. T.; Vatner, S. F.; Vatner, D. E.

    1995-01-01

    To examine the physiological deficit to adrenergic stimulation with aging, five younger adult (3 +/- 1 yr old) and nine older adult (17 +/- 1 yr old) healthy monkeys were studied after instrumentation with a left ventricular (LV) pressure gauge, aortic and left atrial catheters, and aortic flow probes to measure cardiac output directly. There were no significant changes in baseline hemodynamics in conscious older monkeys. For example, an index of contractility, the first derivative of LV pressure (LV dP/dt) was similar (3,191 +/- 240, young vs. 3,225 +/- 71 mmHg/s, old) as well as in isovolumic relaxation, tau (24.3 +/- 1.7 ms, young vs. 23.0 +/- 1.0 ms, old) was similar. However, inotropic, lusitropic, and chronotropic responses to isoproterenol (Iso; 0.1 micrograms/kg), norepinephrine (NE; 0.4 micrograms/kg), and forskolin (For; 75 nmol/kg) were significantly (P < 0.05) depressed in older monkeys. For example. Iso increased LV dP/dt by by 146 +/- 14% in younger monkeys and by only 70 +/- 5% in older monkeys. Iso also reduced tau more in younger monkeys (-28 +/- 7%) compared with older monkeys (-13 +/- 3%). Furthermore, peripheral vascular responsiveness to Iso, NE, For, and phenylephrine (PE; 5 micrograms/kg) was significantly (P < 0.05) reduced in older monkeys. For example, phenylephrine (5 micrograms/kg) increased total peripheral resistence by 69 +/- 4% in younger monkeys and by only 45 +/- 3% in older monkeys. Thus in older monkeys without associated cardiovascular disease, baseline hemodynamics are preserved, but adrenergic receptor responsiveness is reduced systemically, not just in the heart.

  5. Cardiac and Vascular Function in Bedrested Volunteers: Effects of Artificial Gravity Training

    NASA Technical Reports Server (NTRS)

    Meng, M.; Platts, S.; Stenger, M.; Diedrich, A.; Schlegel, T.; Natapoff, A.; Knapp, C.; Evans, J.

    2007-01-01

    Cardiovascular effects of an artificial gravity (AG) countermeasure on deconditioned male volunteers were studied. In two groups of men we measured cardiovascular parameters at rest and in response to 30 minutes of 80 deg. head up tilt (HUT) before, at the end of, and four days following 21 days of 6 deg. head down bed rest (HDBR). One group (N=7) underwent no countermeasure while the other (N=8) received a daily, one hour, dose (2.5 gz at the foot, decreasing to 1.0 gz at the heart) of AG training on the Johnson Space Center short radius centrifuge. Cardiovascular parameters measured included heart rate, blood pressure, stroke volume, cardiac output, peripheral vascular resistance, plasma volume shifts, and vasoactive hormones. Untrained subjects exhibited shorter tilt survival (on average 8 minutes shorter) compared to trained subjects. By the end of bed rest, mean heart rate (MHR) was elevated in both groups (both supine and during tilt). In addition, treated subjects demonstrated lower, tilt-induced, increases in MHR four days following HDBR, indicating a more rapid return to pre bed rest conditions. Results from an index of autonomic balance (percentage of MHR spectral power in the respiratory frequency range) in control of heart rate are consistent with the interpretation that parasympathetic nervous system withdrawal was responsible for both tilt- and bed rest-induced increases in MHR. Our data support our pre-study hypothesis that AG treatment would lessen cardiovascular effects of deconditioning in bed rested men and suggest that AG should be further pursued as a space flight countermeasure.

  6. Horizontal Long Axis Imaging Plane for Evaluation of Right Ventricular Function on Cardiac Magnetic Resonance Imaging

    PubMed Central

    Chaturvedi, Abhishek; Whitnah, Joseph; Maki, Jeffrey H; Baran, Timothy; Mitsumori, Lee M

    2016-01-01

    Purpose: The purpose of this study was to evaluate a horizontal long axis (HLA) magnetic resonance imaging (MRI) plane aligned to the long axis of the right ventricular (RV) cavity for functional analysis by comparing the measurement variability and time required for the analysis with that using a short-axis (SAX) image orientation. Materials and Methods: Thirty-four cardiac MRI exams with cine balanced steady-state free precession image stacks in both the SAX and the HLA of the RV (RHLA) were evaluated. Two reviewers independently traced RV endocardial borders on each image of the cine stacks. The time required to complete each set of traces was recorded, and the RV end-diastolic volume, end-systolic volume, and ejection fraction were calculated. Analysis times and RV measurements were compared between the two orientations. Results: Analysis time for each reviewer was significantly shorter for the RHLA stack (reviewer 1 = 6.4 ± 1.8 min, reviewer 2 = 6.0 ± 3.3 min) than for the SAX stack (7.5 ± 2.1 and 6.9 ± 3.6 min, respectively; P < 0.002). Bland–Altman analysis revealed lower mean differences, limits of agreement, and coefficients of variation for RV measurements obtained with the RHLA stack. Conclusions: RV functional analysis using a RHLA stack resulted in shorter analysis times and lower measurement variability than for a SAX stack orientation. PMID:28123842

  7. Functional coupling as a basic mechanism of feedback regulation of cardiac energy metabolism.

    PubMed

    Saks, V A; Kuznetsov, A V; Vendelin, M; Guerrero, K; Kay, L; Seppet, E K

    2004-01-01

    In this review we analyze the concepts and the experimental data on the mechanisms of the regulation of energy metabolism in muscle cells. Muscular energetics is based on the force-length relationship, which in the whole heart is expressed as a Frank-Starling law, by which the alterations of left ventricle diastolic volume change linearly both the cardiac work and oxygen consumption. The second basic characteristics of the heart is the metabolic stability--almost constant levels of high energy phosphates, ATP and phosphocreatine, which are practically independent of the workload and the rate of oxygen consumption, in contrast to the fast-twitch skeletal muscle with no metabolic stability and rapid fatigue. Analysis of the literature shows that an increase in the rate of oxygen consumption by order of magnitude, due to Frank-Starling law, is observed without any significant changes in the intracellular calcium transients. Therefore, parallel activation of contraction and mitochondrial respiration by calcium ions may play only a minor role in regulation of respiration in the cells. The effective regulation of the respiration under the effect of Frank-Starling law and metabolic stability of the heart are explained by the mechanisms of functional coupling within supramolecular complexes in mitochondria, and at the subcellular level within the intracellular energetic units. Such a complex structural and functional organisation of heart energy metabolism can be described quantitatively by mathematical models.

  8. Intracoronary secretin increases cardiac perfusion and function in anaesthetized pigs through pathways involving β-adrenoceptors and nitric oxide.

    PubMed

    Grossini, Elena; Molinari, Claudio; Morsanuto, Vera; Mary, David A S G; Vacca, Giovanni

    2013-05-01

    Secretin has been implicated in cardiovascular regulation through its specific receptors, as well as through β-adrenoceptors and nitric oxide, although data on its direct effect on coronary blood flow and cardiac function have remained scarce. The present study aimed to determine the primary in vivo effect of secretin on cardiac function and perfusion and the mechanisms related to the autonomic nervous system, secretin receptors and NO. In addition, in coronary endothelial cells the intracellular pathways involved in the effects of secretin on NO release were also examined. In 30 pigs, intracoronary secretin infusion at 2.97 pg for each millilitre per minute of coronary blood flow at constant heart rate and aortic blood pressure increased coronary blood flow, maximal rate of change of left ventricular pressure, segmental shortening, cardiac output and coronary NO release (P<0.05). These responses were graded in a further five pigs. Moreover, while blockade of muscarinic cholinoreceptors (n=5) and of α-adrenoceptors (n=5) did not abolish the observed responses to secretin, blockade of β1-adrenoceptors (n=5) prevented the effects of secretin on cardiac function. In addition, blockade of β2-adrenoceptors (n=5) and NO synthase inhibition (n=5) prevented the coronary response and the effect of secretin on NO release. All these effects were abolished by a secretin receptor inhibitor (n=5). In coronary endothelial cells, the increased NO production caused by secretin was found to be related to cAMP/protein kinase A signalling activated as downstream effectors of stimulation of secretin receptors and β2-adrenoceptors. In conclusion, in anaesthetized pigs secretin primarily increased cardiac function and perfusion through the involvement of specific receptors, β-adrenoceptors and NO release.

  9. Explicit expressions of the Pietra index for the generalized function for the size distribution of income

    NASA Astrophysics Data System (ADS)

    Sarabia, José María; Jordá, Vanesa

    2014-12-01

    The importance of the Pietra index in socioeconomic systems and econophysics has been highlighted by Eliazar and Sokolov (2010). In this paper, we obtain closed expressions for the Pietra index for the generalized function for the size of income proposed by McDonald (1984). This family is composed of three classes of distributions: the generalized gamma distribution (GG), the generalized beta of the first kind (GB1) and the generalized beta of the second kind (GB2). For the different distributions, we obtain closed and simple expressions of the Pietra index, which can be easily computed. We also obtain the Pietra index for other relevant income models including finite mixtures of distributions and the κ-generalized distribution (Clementi et al., 2008). Finally, two empirical applications with real income data are given.

  10. Acute Radiation Effects on Cardiac Function Detected by Strain Rate Imaging in Breast Cancer Patients

    SciTech Connect

    Erven, Katrien; Jurcut, Ruxandra; Weltens, Caroline; Giusca, Sorin; Ector, Joris; Wildiers, Hans; Van den Bogaert, Walter; Voigt, Jens-Uwe

    2011-04-01

    Purpose: To investigate the occurrence of early radiation-induced changes in regional cardiac function using strain rate imaging (SRI) by tissue Doppler echocardiography. Methods and Materials: We included 20 left-sided and 10 right-sided breast cancer patients receiving radiotherapy (RT) to the breast or chest wall. Standard echocardiography and SRI were performed before RT (baseline), immediately after RT (post-RT), and at 2 months follow-up (FUP) after RT. Regional strain (S) and strain rate (SR) values were obtained from all 18 left ventricular (LV) segments. Data were compared to the regional radiation dose. Results: A reduction in S was observed post-RT and at FUP in left-sided patients (S{sub post-RT}: -17.6 {+-} 1.5%, and S{sub FUP}: -17.4 {+-} 2.3%, vs. S{sub baseline}: -19.5 {+-} 2.1%, p < 0.001) but not in right-sided patients. Within the left-sided patient group, S and SR were significantly reduced after RT in apical LV segments (S{sub post-RT}: -15.3 {+-} 2.5%, and S{sub FUP}: -14.3 {+-} 3.7%, vs. S{sub baseline}: -19.3 {+-} 3.0%, p < 0.01; and SR{sub post-RT}: -1.06 {+-} 0.15 s {sup -1}, and SR{sub FUP}: -1.16 {+-} 0.28 s {sup -1}, vs. SR{sub baseline}: -1.29 {+-} 0.27s {sup -1}, p = 0.01), but not in mid- or basal segments. Furthermore, we observed that segments exposed to more than 3 Gy showed a significant decrease in S after RT (S{sub post-RT}: -16.1 {+-} 1.6%, and S{sub FUP}: -15.8 {+-} 3.4%, vs. S{sub baseline}: -18.9 {+-} 2.6%, p < 0.001). This could not be observed in segments receiving less than 3 Gy. Conclusions: SRI shows a dose-related regional decrease in myocardial function after RT. It might be a useful tool in the evaluation of modern RT techniques, with respect to cardiac toxicity.

  11. Correlation between mobility assessed by the Modified Rivermead Mobility Index and physical function in stroke patients

    PubMed Central

    Park, Gi-Tae; Kim, Mihyun

    2016-01-01

    [Purpose] The purpose of this study was to investigate the relationship between mobility assessed by the Modified Rivermead Mobility Index and variables associated with physical function in stroke patients. [Subjects and Methods] One hundred stroke patients (35 males and 65 females; age 58.60 ± 13.91 years) participated in this study. Modified Rivermead Mobility Index, muscle strength (manual muscle test), muscle tone (Modified Ashworth Scale), range of motion of lower extremity, sensory function (light touch and proprioception tests), and coordination (heel to shin and lower-extremity motor coordination tests) were assessed. [Results] The Modified Rivermead Mobility Index was correlated with all the physical function variables assessed, except the degree of knee extension. In addition, stepwise linear regression analysis revealed that coordination (heel to shin test) was the explanatory variable closely associated with mobility in stroke patients. [Conclusion] The Modified Rivermead Mobility Index score was significantly correlated with all the physical function variables. Coordination (heel to shin test) was closely related to mobility function. These results may be useful in developing rehabilitation programs for stroke patients. PMID:27630440

  12. Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines.

    PubMed

    Barac, Ana; Lynce, Filipa; Smith, Karen L; Mete, Mihriye; Shara, Nawar M; Asch, Federico M; Nardacci, Madeline P; Wray, Lynette; Herbolsheimer, Pia; Nunes, Raquel A; Swain, Sandra M; Warren, Robert; Peshkin, Beth N; Isaacs, Claudine

    2016-01-01

    Animal data suggest that defects in BRCA1/2 genes significantly increase the risk of heart failure and mortality in mice exposed to doxorubicine. Women with BRCA1/2 mutations who develop breast cancer (BC) may receive anthracyclines but their risk of cardiac dysfunction has not been investigated. Our study tested the hypothesis that women with history of BRCA1/2 mutation-associated BC treated with anthracyclines have impaired parameters of cardiac function compared to similarly treated women with history of sporadic BC. Women with history of BC and anthracycline treatment underwent an echocardiographic exam for assessment of primary outcomes, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). The sample size of 81 provided 79 % power with two-sided two-sample t test and alpha of 0.05 to detect a clinically meaningful difference in cardiac function of absolute 5 % points difference for LVEF and 2 % points difference for GLS. Of 81 normotensive participants, 39 were BRCA1/2 mutation carriers and 42 in the sporadic group. Mean age was 50 ± 9 years in both groups (P = 0.99) but BRCA1/2 mutation carriers had longer anthracycline treatment-to-enrollment time (7.5 ± 5.3 vs. 4.2 ± 3.3 years, P = 0.001). There were no significant differences in LVEF (P = 0.227) or GLS (P = 0.53) between the groups. LVEF was normal in 91 % of women and subclinical cardiac dysfunction defined as absolute GLS value <18.9 % was seen in 4 (10 %) BRCA1/2 mutation carriers and 7 (17 %) sporadic participants. In this first prospective examination of cardiac function in BRCA1/2 mutation carriers, we found no significant differences in sensitive echocardiographic parameters of cardiac function between BRCA1/2 mutation carriers and women with history of sporadic BC who received anthracycline treatment. In contrast to laboratory animal data, our findings indicate lack of elevated cardiac risk with the use of standard-doses of adjuvant anthracyclines in treatment of BRCA1

  13. Resveratrol Treatment Reduces Cardiac Progenitor Cell Dysfunction and Prevents Morpho-Functional Ventricular Remodeling in Type-1 Diabetic Rats

    PubMed Central

    Delucchi, Francesca; Berni, Roberta; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Sala, Roberto; Chaponnier, Christine; Gabbiani, Giulio; Calani, Luca; Rio, Daniele Del; Bocchi, Leonardo; Lagrasta, Costanza; Quaini, Federico; Stilli, Donatella

    2012-01-01

    Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n = 128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n = 54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n = 64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic “milieu” on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing

  14. The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel capsules on cell survival, post-ischemic cell retention and cardiac function.

    PubMed

    Mayfield, Audrey E; Tilokee, Everad L; Latham, Nicholas; McNeill, Brian; Lam, Bu-Khanh; Ruel, Marc; Suuronen, Erik J; Courtman, David W; Stewart, Duncan J; Davis, Darryl R

    2014-01-01

    Transplantation of ex vivo proliferated cardiac stem cells (CSCs) is an emerging therapy for ischemic cardiomyopathy but outcomes are limited by modest engraftment and poor long-term survival. As such, we explored the effect of single cell microencapsulation to increase CSC engraftment and survival after myocardial injection. Transcript and protein profiling of human atrial appendage sourced CSCs revealed strong expression the pro-survival integrin dimers αVβ3 and α5β1- thus rationalizing the integration of fibronectin and fibrinogen into a supportive intra-capsular matrix. Encapsulation maintained CSC viability under hypoxic stress conditions and, when compared to standard suspended CSC, media conditioned by encapsulated CSCs demonstrated superior production of pro-angiogenic/cardioprotective cytokines, angiogenesis and recruitment of circulating angiogenic cells. Intra-myocardial injection of encapsulated CSCs after experimental myocardial infarction favorably affected long-term retention of CSCs, cardiac structure and function. Single cell encapsulation prevents detachment induced cell death while boosting the mechanical retention of CSCs to enhance repair of damaged myocardium.

  15. Development of a Preference-Based Index from the National Eye Institute Visual Function Questionnaire-25

    PubMed Central

    Rentz, Anne M.; Kowalski, Jonathan W.; Walt, John G.; Hays, Ron D.; Brazier, John E.; Yu, Ren; Lee, Paul; Bressler, Neil; Revicki, Dennis A.

    2015-01-01

    Importance Understanding how individuals value health states is central to patient-centered care and to health policy decision making. Generic preference-based measures of health may not effectively capture the impact of ocular diseases. Recently, 6 items from the National Eye Institute Visual Function Questionnaire-25 were used to develop the Visual Function Questionnaire-Utility Index health state classification, which defines visual function health states. Objective To describe elicitation of preferences for health states generated from the Visual Function Questionnaire-Utility Index health state classification and development of an algorithm to estimate health preference scores for any health state. Design Non-intervention, cross-sectional study. Setting General community in four countries (Australia, Canada, United Kingdom, and United States) Participants 607 adult participants recruited from local newspaper advertisements. In the United Kingdom, an existing database of participants from previous studies was used for recruitment. Interventions Eight out of 15,625 possible health states from the Visual Function Questionnaire-Utility Index were valued using time trade-off technique. Main Outcome Measures A theta severity score was calculated for Visual Function Questionnaire-Utility Index–defined health states using item response theory analysis. Regression models were then used to develop an algorithm to assign health state preference values for all potential health states defined by the Visual Function Questionnaire-Utility Index. Results Health state preference values for the 8 states ranged from 0.343 (standard deviation, 0.395) to 0.956 (0.124). As expected, preference values declined with worsening visual function. Results indicate that the Visual Function Questionnaire-Utility Index describes states that participants view as spanning most of continuum from full health to dead. Conclusions and Relevance Visual Function Questionnaire-Utility Index health

  16. Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.

    PubMed

    Buscariollo, Daniela L; Fang, Xiefan; Greenwood, Victoria; Xue, Huiling; Rivkees, Scott A; Wendler, Christopher C

    2014-01-01

    Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.

  17. Intracoronary gastrin 17 increases cardiac perfusion and function through autonomic nervous system, CCK receptors, and nitric oxide in anesthetized pigs.

    PubMed

    Grossini, Elena; Caimmi, Philippe; Molinari, Claudio; Uberti, Francesca; Mary, David; Vacca, Giovanni

    2011-01-01

    The release of gastrointestinal hormones has been reported to modulate reflex cardiovascular responses caused by gastric distension, although the role played by gastrin 17 is as yet unknown. The present study was therefore planned to determine the primary in vivo effect of gastrin 17 on coronary blood flow and cardiac function and the involvement of autonomic nervous system, CCK1/2 receptors, and nitric oxide (NO). In 40 anesthetized pigs, gastrin 17 was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure. In 35 of the 40 pigs, the mechanisms of the observed hemodynamic responses were analyzed by repeating gastrin 17 infusion after autonomic nervous system and NO blockade, and after specific CCK receptors agonists/antagonists administration. Intracoronary gastrin 17 administration caused dose-related increases of both coronary blood flow and cardiac function. The intracoronary co-administration of CCK33/pentagastrin and gastrin 17 potentiated the coronary effects observed when the above agents were given alone (P <0.05). The potentiation of the cardiac response was observed only with the co-administration of pentagastrin and gastrin 17 (P <0.05). Moreover, blockade of muscarinic cholinoceptors (intravenous atropine) and of α-adrenoceptors (intravenous phentolamine) did not abolish the hemodynamic responses to gastrin 17. The cardiac and vascular effects of the hormone were prevented by blockade of β-adrenoceptors (intravenous atenolol and butoxamine), CCK1/2 receptors (intracoronary lorglumide and CAM-1028), and NO synthase (intracoronary Nω-nitro-l-arginine methyl ester). In conclusion, gastrin 17 primarily increased coronary blood flow and cardiac function through the involvement of CCK receptors, β-adrenoceptors, and NO release.

  18. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    SciTech Connect

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; May, Dalit; Johnson, Rory; Dauvillier, Jérôme; Pennacchio, Len A.; Pedrazzini, Thierry

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.

  19. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    DOE PAGES

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; ...

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Throughmore » a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.« less

  20. Everyday cognitive functioning in cardiac patients: relationships between self-report, report of a significant other and cognitive test performance.

    PubMed

    Elliott, Peter C; Smith, Geoff; Ernest, Christine S; Murphy, Barbara M; Worcester, Marian U C; Higgins, Rosemary O; Le Grande, Michael R; Goble, Alan J; Andrewes, David; Tatoulis, James

    2010-01-01

    Candidates for cardiac bypass surgery often experience cognitive decline. Such decline is likely to affect their everyday cognitive functioning. The aim of the present study was to compare cardiac patients' ratings of their everyday cognitive functioning against significant others' ratings and selected neuropsychological tests. Sixty-nine patients completed a battery of standardised cognitive tests. Patients and significant others also completed the Everyday Function Questionnaire independently of each other. Patient and significant other ratings of patients' everyday cognitive difficulties were found to be similar. Despite the similarities in ratings of difficulties, some everyday cognitive tasks were attributed to different processes. Patients' and significant others' ratings were most closely associated with the neuropsychological test of visual memory. Tests of the patients' verbal memory and fluency were only related to significant others' ratings. Test scores of attention and planning were largely unrelated to ratings by either patients or their significant others.

  1. Cognitive Function in Ambulatory Patients with Systolic Heart Failure: Insights from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

    PubMed Central

    Graham, Susan; Ye, Siqin; Qian, Min; Sanford, Alexandra R.; Di Tullio, Marco R.; Sacco, Ralph L.; Mann, Douglas L.; Levin, Bruce; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Mohr, J. P.; Labovitz, Arthur J.; Lip, Gregory Y. H.; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.; Thompson, John L. P.; Homma, Shunichi

    2014-01-01

    We sought to determine whether cognitive function in stable outpatients with heart failure (HF) is affected by HF severity. A retrospective, cross-sectional analysis was performed using data from 2, 043 outpatients with systolic HF and without prior stroke enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial. Multivariable regression analysis was used to assess the relationship between cognitive function measured using the Mini-Mental Status Exam (MMSE) and markers of HF severity (left ventricular ejection fraction [LVEF], New York Heart Association [NYHA] functional class, and 6-minute walk distance). The mean (SD) for the MMSE was 28.6 (2.0), with 64 (3.1%) of the 2,043 patients meeting the cut-off of MMSE <24 that indicates need for further evaluation of cognitive impairment. After adjustment for demographic and clinical covariates, 6-minute walk distance (β-coefficient 0.002, p<0.0001), but not LVEF or NYHA functional class, was independently associated with the MMSE as a continuous measure. Age, education, smoking status, body mass index, and hemoglobin level were also independently associated with the MMSE. In conclusion, six-minute walk distance, but not LVEF or NYHA functional class, was an important predictor of cognitive function in ambulatory patients with systolic heart failure. PMID:25426862

  2. Injectable biodegradable hydrogels for embryonic stem cell transplantation: improved cardiac remodelling and function of myocardial infarction.

    PubMed

    Wang, Haibin; Liu, Zhiqiang; Li, Dexue; Guo, Xuan; Kasper, F Kurtis; Duan, Cuimi; Zhou, Jin; Mikos, Antonios G; Wang, Changyong

    2012-06-01

    In this study, an injectable, biodegradable hydrogel composite of oligo[poly(ethylene glycol) fumarate] (OPF) was investigated as a carrier of mouse embryonic stem cells (mESCs) for the treatment of myocardial infarction (MI). The OPF hydrogels were used to encapsulate mESCs. The cell differentiation in vitro over 14 days was determined via immunohistochemical examination. Then, mESCs encapsulated in OPF hydrogels were injected into the LV wall of a rat MI model. Detailed histological analysis and echocardiography were used to determine the structural and functional consequences after 4 weeks of transplantation. With ascorbic acid induction, mESCs could differentiate into cardiomyocytes and other cell types in all three lineages in the OPF hydrogel. After transplantation, both the 24-hr cell retention and 4-week graft size were significantly greater in the OPF + ESC group than that of the PBS + ESC group (P < 0.01). Four weeks after transplantation, OPF hydrogel alone significantly reduced the infarct size and collagen deposition and improved the cardiac function. The heart function and revascularization improved significantly, while the infarct size and fibrotic area decreased significantly in the OPF + ESC group compared with that of the PBS + ESC, OPF and PBS groups (P < 0.01). All treatments had significantly reduced MMP2 and MMP9 protein levels compared to the PBS control group, and the OPF + ESC group decreased most by Western blotting. Transplanted mESCs expressed cardiovascular markers. This study suggests the potential of a method for heart regeneration involving OPF hydrogels for stem cell encapsulation and transplantation.

  3. Impaired Cerebrovascular Function in Coronary Artery Disease Patients and Recovery Following Cardiac Rehabilitation

    PubMed Central

    Anazodo, Udunna C.; Shoemaker, J. K.; Suskin, Neville; Ssali, Tracy; Wang, Danny J. J.; St. Lawrence, Keith S.

    2016-01-01

    Coronary artery disease (CAD) poses a risk to the cerebrovascular function of older adults and has been linked to impaired cognitive abilities. Using magnetic resonance perfusion imaging, we investigated changes in resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to hypercapnia in 34 CAD patients and 21 age-matched controls. Gray matter volume (GMV) images were acquired and used as a confounding variable to separate changes in structure from function. Compared to healthy controls, CAD patients demonstrated reduced CBF in the superior frontal, anterior cingulate (AC), insular, pre- and post-central gyri, middle temporal, and superior temporal regions. Subsequent analysis of these regions demonstrated decreased CVR in the AC, insula, post-central and superior frontal regions. Except in the superior frontal and precentral regions, regional reductions in CBF and CVR were identified in brain areas where no detectable reductions in GMV were observed, demonstrating that these vascular changes were independent of brain atrophy. Because aerobic fitness training can improve brain function, potential changes in regional CBF were investigated in the CAD patients after completion of a 6-months exercise-based cardiac rehabilitation program. Increased CBF was observed in the bilateral AC, as well as recovery of CBF in the dorsal aspect of the right AC, where the magnitude of increased CBF was roughly equal to the reduction in CBF at baseline compared to controls. These exercise-related improvements in CBF in the AC is intriguing given the role of this area in cognitive processing and regulation of cardiovascular autonomic control. PMID:26779011

  4. Temporal alterations in cardiac fibroblast function following induction of pressure overload

    PubMed Central

    Stewart, James A.; Massey, Erin P.; Fix, Charity; Zhu, Jinyu; Goldsmith, Edie C.

    2014-01-01

    Increases in cardiovascular load (pressure overload) are known to elicit ventricular remodeling including cardiomyocyte hypertrophy and interstitial fibrosis. While numerous studies have focused on the mechanisms of myocyte hypertrophy, comparatively little is known regarding the response of the interstitial fibroblasts to increased cardiovascular load. Fibroblasts are the most numerous cell type in the mammalian myocardium and have long been recognized as producing the majority of the myocardial extracellular matrix. It is only now becoming appreciated that other aspects of fibroblast behavior are important to overall cardiac function. The present studies were performed to examine the temporal alterations in fibroblast activity in response to increased cardiovascular load. Rat myocardial fibroblasts were isolated at specific time-points (3, 7, 14, and 28 days) after induction of pressure overload by abdominal aortic constriction. Bioassays were performed to measure specific parameters of fibroblast function including remodeling and contraction of 3-dimensional collagen gels, migration, and proliferation. In addition, the expression of extracellular matrix receptors of the integrin family was examined. Myocardial hypertrophy and fibrosis were evident within 7 days after constriction of the abdominal aorta. Collagen gel contraction, migration, and proliferation were enhanced in fibroblasts from pressure-overloaded animals compared to fibroblasts from sham animals. Differences in fibroblast function and protein expression were evident within 7 days of aortic constriction, concurrent with the onset of hypertrophy and fibrosis of the intact myocardium. These data provide further support for the idea that rapid and dynamic changes in fibroblast phenotype accompany and contribute to the progression of cardiovascular disease. PMID:20217135

  5. Acute pulmonary function response to ozone in young adults as a function of body mass index

    EPA Science Inventory

    Recent studies have shown enhanced responsiveness to ozone in obese mice. Adiposity has not been examined as a possible modulator of ozone response in humans. We therefore examined the relationship between body mass index and the acute spirometric response to ozone (O(3)) exposur...

  6. Application of a Functional Mathematical Index for Antibacterial and Anticarcinogenic Effects of Tea Catechins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tea leaves produce secondary metabolites that are involved in the defense of the plants against invading pathogens. In the case of green teas, these metabolites are polyphenolic compounds called catechins. In previous studies, we developed a mathematical formula called functional mathematical index ...

  7. The Relationships among Body Image, Body Mass Index, Exercise, and Sexual Functioning in Heterosexual Women

    ERIC Educational Resources Information Center

    Weaver, Angela D.; Byers, E. Sandra

    2006-01-01

    Problems related to negative body image are very common among young women. In this study, we examined the relationship between women's body image and their sexual functioning over and above the effects of physical exercise and body mass index (BMI) in a sample of 214 university women. Low situational body image dysphoria and low body…

  8. Combined baseline strain dyssynchrony index and its acute reduction predicts mid-term left ventricular reverse remodeling and long-term outcome after cardiac resynchronization therapy.

    PubMed

    Tatsumi, Kazuhiro; Tanaka, Hidekazu; Matsumoto, Kensuke; Miyoshi, Tatsuya; Hiraishi, Mana; Tsuji, Takayuki; Kaneko, Akihiro; Ryo, Keiko; Fukuda, Yuko; Norisada, Kazuko; Onishi, Tetsuari; Yoshida, Akihiro; Kawai, Hiroya; Hirata, Ken-ichi

    2014-04-01

    The objective of this study was to test the hypothesis that combining assessment of baseline radial strain dyssynchrony index (SDI), that expressed both left ventricular (LV) dyssynchrony and residual myocardial contractility, and of acute changes in this index can yield more accurate prediction of mid-term responders and long-term outcome after cardiac resynchronization therapy (CRT). Radial SDI for 75 CRT patients was calculated as the average difference between peak and end-systolic speckle tracking strain from 6 segments of the mid-LV short-axis view before and 8 ± 2 days after CRT. Mid-term responder was defined as ≥ 15% decrease in LV end-systolic volume 6 ± 2 months after CRT. Long-term outcome was tracked over 5 years. Baseline radial SDI ≥ 6.5% is considered predictive of responder and favorable outcome, as previously reported. Acute reduction in radial SDI ≥ 1.5% was found to be the best predictor of mid-term responders with CRT. Furthermore, patients with acute reductions in radial SDI ≥1.5% were associated with a significantly more favorable long-term outcome after CRT than those with radial SDI <1.5% (log rank P < 0.001). An important findings were that baseline radial SDI ≥6.5% and acute reductions in radial SDI ≥ 1.5% in 42 patients were associated with the highest event-free survival rate of 92%, whereas, 21 patients corresponding values of <6.5% and <1.5% were associated with low event-free survival rate of 46% (log rank P < 0.001). Combined assessment of baseline radial SDI and its acute reduction after CRT may have clinical implications for predicting responders and thus patients' care.

  9. Effects of adrenaline on circulatory dynamics and cardiac function in rats administered chlorpromazine.

    PubMed

    Sakai, Arisa; Sunada, Katsuhisa

    2017-01-01

    We aimed to elucidate changes in circulatory dynamics and cardiac function during concomitant use of chlorpromazine (CPZ) and adrenaline (AD). An arterial line and left intraventricular pressure-volume measurement catheter were inserted in rats. CPZ 10 mg/kg was administered to the left great adductor muscle, followed by normal saline (NS) or AD 50 μg/kg through the tongue 20 min later. End-diastolic volume (V ed), end-systolic pressure (P es), stroke volume (SV), stroke work (SW), end-systolic volume elastance (E es), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate (PR) were measured. Following AD administration, V ed significantly decreased at 2-4 and 10 min than that in control rats; P es significantly decreased at 1 min; E es significantly increased from 2 to 10 min; SV did not change significantly, and SW significantly reduced at 1 and 2 min; SBP and DBP were lower at 1-3 min than in the control; and PR increased at 10 min. These findings suggest that when AD-containing local anesthetics are administered during dental treatment of patients taking CPZ, there is a risk of a temporary drop in blood pressure. However, the blood pressure is recovered a few minutes later by the increase in afterload and the myocardial contractile force.

  10. Astragalus polysaccharide improves cardiac function in doxorubicin-induced cardiomyopathy through ROS-p38 signaling

    PubMed Central

    Zhou, Liangliang; Chen, Lanping; Wang, Jing; Deng, Yijun

    2015-01-01

    Doxorubicin (DOX) is widely used as an antitumor agent, but it is significantly challenged by clinical workers due to the severe and acute cardiotoxitity. Astragalus polysaccharide (APS) is characterized by an anti-inflammation and anti-oxidant features. In the current study, we explored the effects and specific mechanisms of APS on DOX-induced-cardiomyopathy in mouse primary myocardial cells. To explore the effect of DOX on ROS production, DHE staining and flow cytometry analysis were used in primary cardiomyocytes treated with 1 μM DOX for 24 h. MTT assay was applied to determine the effect of DOX on cell viability. The effects of DOX on rat cardiomyocytes apoptosis by Hoechst staining and annexin V-PI staining, while caspase3 activity was determined using an assay kit. Two-dimensional echocardiography of rats was performed to determine left ventricular fraction and relative wall thickness. Activation of p38 and Akt was analyzed using western blot. ROS production was significantly enhanced by DOX stimulation in primary cardiomyocytes. DOX reduced rat cardiomyocytes viability in a time- and dose-dependent manner. DOX induced apoptosis in rat cardiomyocytes via activation of caspase-3. Cardiac function was significantly impaired by enhanced p38 activation. APS treatment reduced DOX-induced rat cardiomyocytes apoptosis by decreasing ROS production. To conclude, APS reduced DOX-induced cell apoptosis and ROS production by reduced activation of p38 signaling pathway. PMID:26885153

  11. Noninvasive ventilation improves cardiac function in patients with chronic heart failure

    PubMed Central

    Cheng, Jing; Liu, Yanping; Li, Guishuang; Zhang, Zhongwen; Ma, Lianyue; Yang, Xiaoyan; Yang, Jianmin; Zhang, Kai; Kong, Jing; Dong, Mei; Zhang, Meng; Xu, Xingli; Sui, Wenhai; Wang, Jiali; Shang, Rui; Ji, Xiaoping; Zhang, Yun; Zhang, Cheng; Hao, Panpan

    2016-01-01

    Chronic heart failure (CHF) has been shown to be associated with an increased incidence of sleep-disordered breathing. Whether treatment with noninvasivepositive-pressure ventilation (NPPV), including continuous positive airway pressure, bi-level positive airway pressure and adaptive servo-ventilation, improves clinical outcomes of CHF patients is still debated. 2,832 CHF patients were enrolled in our analysis. NPPV was significantly associated with improvement in left ventricular ejection fraction (39.39% vs. 34.24%; WMD, 5.06; 95% CI, 3.30-6.81; P < 0.00001) and plasma brain natriuretic peptide level (268.23 pg/ml vs. 455.55 pg/ml; WMD, −105.66; 95% CI, [−169.19]-[−42.13]; P = 0.001). However, NPPV did not reduce all-cause mortality (0.26% vs. 0.24%; OR, 1.13; 95% CI, 0.93-1.37; P = 0.22) or re-hospitalization rate (57.86% vs. 59.38%; OR, 0.47; 95% CI, 0.19-1.19; P = 0.02) as compared with conventional therapy. Despite no benefits on hard endpoints, NPPV may improve cardiac function of CHF patients. These data highlight the important role of NPPV in the therapy of CHF. PMID:27391436

  12. Impaired Cardiac Autonomic Nervous System Function is Associated with Pediatric Hypertension Independent of Adiposity

    PubMed Central

    Ryder, Justin R.; O’Connell, Michael; Bosch, Tyler A.; Chow, Lisa; Rudser, Kyle D.; Dengel, Donald R.; Fox, Claudia K.; Steinberger, Julia; Kelly, Aaron S.

    2015-01-01

    Background We examined whether sympathetic nervous system activity influences hypertension status and systolic blood pressure (SBP) independent of adiposity in youth ranging from normal-weight to severe obesity. Methods We examined the association of heart rate variability (HRV) with hypertension status and SBP among youth (6-18 years old; n = 188; 103 female). Seated SBP was measured using an automated cuff. Pre-hypertension (SBP percentile≤90th-<95th) and hypertension (SBP percentile≤95th) were defined by age-, sex-, and height-norms. Autonomic nervous system activity was measured using HRV via SphygmoCorTM MM3 system and analyzed for time- and frequency-domains. Total body fat was measured via dual-energy X-ray absorptiometry. Results Logistic regression models demonstrated lower values in each time-domain HRV measure and larger LF:HF ratio to be significantly associated with higher odds of being pre-hypertensive/hypertensive (11-47% higher odds) independent of total body fat (p<0.05). In linear regression analysis, lower time-domain, but not frequency-domain, HRV measures were significantly associated with higher SBP independent of total body fat (p<0.05). Conclusion These data suggest that impaired cardiac autonomic nervous system function, at rest, is associated with higher odds of being pre-hypertensive/hypertensive and higher SBP which may be independent of adiposity in youth. PMID:26389821

  13. A flatness-based control approach to drug infusion for cardiac function regulation

    NASA Astrophysics Data System (ADS)

    Rigatos, Gerasimos; Zervos, Nikolaos; Melkikh, Alexey

    2016-12-01

    A new control method based on differential flatness theory is developed in this article, aiming at solving the problem of regulation of haemodynamic parameters, Actually control of the cardiac output (volume of blood pumped out by heart per unit of time) and of the arterial blood pressure is achieved through the administered infusion of cardiovascular drugs, such as dopamine and sodium nitroprusside. Time delays between the control inputs and the system's outputs are taken into account. Using the principle of dynamic extension, which means that by considering certain control inputs and their derivatives as additional state variables, a state-space description for the heart's function is obtained. It is proven that the dynamic model of the heart is a differentially flat one. This enables its transformation into a linear canonical and decoupled form, for which the design of a stabilizing feedback controller becomes possible. The proposed feedback controller is of proven stability and assures fast and accurate tracking of the reference setpoints by the outputs of the heart's dynamic model. Moreover, by using a Kalman Filter-based disturbances' estimator, it becomes possible to estimate in real-time and compensate for the model uncertainty and external perturbation inputs that affect the heart's model.

  14. Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations.

    PubMed

    Hsueh, Chia-Hsiang; Chen, Wen-Pin; Lin, Jiunn-Lee; Tsai, Chia-Ti; Liu, Yen-Bin; Juang, Jyh-Ming; Tsao, Hsuan-Ming; Su, Ming-Jai; Lai, Ling-Ping

    2009-02-20

    The Brugada syndrome is characterized by ST segment elevation in the right precodial leads V1-V3 on surface ECG accompanied by episodes of ventricular fibrillation causing syncope or even sudden death. The molecular and cellular mechanisms that lead to Brugada syndrome are not yet completely understood. However, SCN5A is the most well known responsible gene that causes Brugada syndrome. Until now, more than a hundred mutations in SCN5A responsible for Brugada syndrome have been described. Functional studies of some of the mutations have been performed and show that a reduction of human cardiac sodium current accounts for the pathogenesis of Brugada syndrome. Here we reported three novel SCN5A mutations identified in patients with Brugada syndrome in Taiwan (p.I848fs, p.R965C, and p.1876insM). Their electrophysiological properties were altered by patch clamp analysis. The p.I848fs mutant generated no sodium current. The p.R965C and p.1876insM mutants produced channels with steady state inactivation shifted to a more negative potential (9.4 mV and 8.5 mV respectively), and slower recovery from inactivation. Besides, the steady state activation of p.1876insM was altered and was shifted to a more positive potential (7.69 mV). In conclusion, the SCN5A channel defect related to Brugada syndrome might be diverse but all resulted in a decrease of sodium current.

  15. TGF-{beta}{sub 1}-induced cardiac myofibroblasts are nonproliferating functional cells carrying DNA damages

    SciTech Connect

    Petrov, Victor V. Pelt, Jos F. van; Vermeesch, Joris R.; Van Duppen, Viktor J.; Vekemans, Katrien; Fagard, Robert H.; Lijnen, Paul J.

    2008-04-15

    TGF-{beta}{sub 1} induces differentiation and total inhibition of cardiac MyoFb cell division and DNA synthesis. These effects of TGF-{beta}{sub 1} are irreversible. Inhibition of MyoFb proliferation is accompanied with the expression of Smad1, Mad1, p15Ink4B and total inhibition of telomerase activity. Surprisingly, TGF-{beta}{sub 1}-activated MyoFbs are growth-arrested not only at G1-phase but also at S-phase of the cell cycle. Staining with TUNEL indicates that these cells carry DNA damages. However, the absolute majority of MyoFbs are non-apoptotic cells as established with two apoptosis-specific methods, flow cytometry and caspase-dependent cleavage of cytokeratin 18. Expression in MyoFbs of proliferative cell nuclear antigen even in the absence of serum confirms that these MyoFbs perform repair of DNA damages. These results suggest that TGF-{beta}{sub 1}-activated MyoFbs can be growth-arrested by two checkpoints, the G1/S checkpoint, which prevents cells from entering S-phase and the intra-S checkpoint, which is activated by encountering DNA damage during the S phase or by unrepaired damage that escapes the G1/S checkpoint. Despite carrying of the DNA damages TGF-{beta}{sub 1}-activated MyoFbs are highly functional cells producing lysyl oxidase and contracting the collagen matrix.

  16. A new algorithm for estimating the ν-index using sinusoidal basis functions.

    PubMed

    Roonizi, Ebadollah Kheirati; Mainardi, Luca T; Sassi, Roberto

    2015-01-01

    Recently it was shown that the spatial dispersion of ventricular repolarization (SHVR) can be assessed from the surface ECG using a metric termed ν-index. In this paper, a new algorithm is presented for estimating the ν-index, allowing the inclusion of higher order terms with ease, even in the presence of noise, leading to more accurate estimates. We first introduced a new analytical model for the derivative of the average transmembrane potentials during repolarization (the dominant T-wave) based on trigonometric functions. This functional set is closed under the operation of derivation. Therefore, the nonlinear iterative optimization required by previous methods is no longer necessary. Then, we suggested an iterative linear matrix factorization method to properly estimate the leads factors and the ν-index. Several synthetic SHVR (in the range 20 to 70 ms) were simulated, employing a publicly-available forward electrophysiological model (ECGSIM), leading to a total of 240 synthetic 8-lead electrocardiographical recordings (ECG), each composed of 128 beats. Then the ν-index was estimated with the newly introduced method and compared (root mean square error, RMSE) with the theoretical values, available for each series. The simulation results confirmed the theoretical expectations and indeed showed that the ν-index estimates were improved by increasing the number of lead factors included (RMSE=0:295±0:037 vs 0:280±0:038 for 2 and 8 lead factors respectively).

  17. Microbial Diversity Indexes Can Explain Soil Carbon Dynamics as a Function of Carbon Source

    PubMed Central

    Maron, Pierre-Alain; Menasseri-Aubry, Safya; Sarr, Amadou; Lévêque, Jean; Mathieu, Olivier; Jolivet, Claudy; Leterme, Philippe; Viaud, Valérie

    2016-01-01

    Mathematical models do not explicitly represent the influence of soil microbial diversity on soil organic carbon (SOC) dynamics despite recent evidence of relationships between them. The objective of the present study was to statistically investigate relationships between bacterial and fungal diversity indexes (richness, evenness, Shannon index, inverse Simpson index) and decomposition of different pools of soil organic carbon by measuring dynamics of CO2 emissions under controlled conditions. To this end, 20 soils from two different land uses (cropland and grassland) were incubated with or without incorporation of 13C-labelled wheat-straw residue. 13C-labelling allowed us to study residue mineralisation, basal respiration and the priming effect independently. An innovative data-mining approach was applied, based on generalized additive models and a predictive criterion. Results showed that microbial diversity indexes can be good covariates to integrate in SOC dynamics models, depending on the C source and the processes considered (native soil organic carbon vs. fresh wheat residue). Specifically, microbial diversity indexes were good candidates to help explain mineralisation of native soil organic carbon, while priming effect processes seemed to be explained much more by microbial composition, and no microbial diversity indexes were found associated with residue mineralisation. Investigation of relationships between diversity and mineralisation showed that higher diversity, as measured by the microbial diversity indexes, seemed to be related to decreased CO2 emissions in the control soil. We suggest that this relationship can be explained by an increase in carbon yield assimilation as microbial diversity increases. Thus, the parameter for carbon yield assimilation in mathematical models could be calculated as a function of microbial diversity indexes. Nonetheless, given limitations of the methods used, these observations should be considered with caution and

  18. Inhalation of Photochemically Altered Urban Mixtures Depresses Cardiac Function in Mice

    EPA Science Inventory

    Rationale: Epidemiological studies have indicated an association between urban air pollution exposure and cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of inhaled photochemical products in urban mixtures in a murine model. ...

  19. Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction

    PubMed Central

    Nakajima, Kazuaki; Fujita, Jun; Matsui, Makoto; Tohyama, Shugo; Tamura, Noriko; Kanazawa, Hideaki; Seki, Tomohisa; Kishino, Yoshikazu; Hirano, Akinori; Okada, Marina; Tabei, Ryota; Sano, Motoaki; Goto, Shinya; Tabata, Yasuhiko; Fukuda, Keiichi

    2015-01-01

    Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×106 or 1x106 cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×106 CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05), only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05). Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01) and angiogenesis was significantly enhanced (p<0.05) in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05). Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH improved cardiac

  20. [Abnormal cardiac index measured by means of systolic time intervals and the effect of co-enzyme Q10 in thyroid disorders].

    PubMed

    Naito, T

    1986-05-20

    By using the pre-ejection period (PEP), the left ventricular ejection time (LVET) and LVET/PEP ratio, cardiac function was investigated in 35 patients with Graves' disease (mild and severe), 13 patients with primary hypothyroidism and 35 normal subjects. The effect of treatment with antithyroid drugs, T4 or Co-Q10 was also evaluated. Before treatment, PEP was significantly shorter and the LVET/PEP ratio was greater in mild thyrotoxic patients than in the control subjects. PEP and LVET/PEP ratio returned to control levels after the euthyroid state was maintained with antithyroid drugs. In severe thyrotoxic patients, PEP and LVET/PEP ratio did not show any significant change compared with the control subjects, although LVET was significantly shorter. In hypothyroid patients, marked prolongation of PEP, shortening of LVET and decrease in LVET/PEP ratio were shown and returned to control levels after the euthyroid state was maintained with T4. PEP correlated curvilinearly with serum T3 and T4 concentrations. However, LVET/PEP ratio increased linearly from hypothyroid to mild thyrotoxic patients and decreased gradually in severe thyrotoxic patients. The inverse correlations between serum Co-Q10 and T3 and T4 concentrations were shown in patients suffering from hypothyroidism to mild thyrotoxicosis. After the administration of 120 mg Co-Q10 for 7 days in mild untreated thyrotoxic patients, a significant shortening of PEP and an increase in LVET/PEP ratio and stroke volume were shown. These data indicate that cardiac function in terms of PEP and LVET/PEP ratio is markedly influenced by serum thyroid hormone concentrations and Co-Q10 modulates it.

  1. In vivo assessment of coronary flow and cardiac function after bolus adenosine injection in adenosine receptor knockout mice.

    PubMed

    Teng, Bunyen; Tilley, Stephen L; Ledent, Catherine; Mustafa, S Jamal

    2016-06-01

    Bolus injections of adenosine and the A2A adenosine receptor (AR) selective agonist (regadenoson) are used clinically as a substitute for a stress test in people who cannot exercise. Using isolated tissue preparations, our lab has shown that coronary flow and cardiac effects of adenosine are mostly regulated by the AR subtypes A1, A2A, and A2B In this study, we used ultrasound imaging to measure the in vivo effects of adenosine on coronary blood flow (left coronary artery) and cardiac function in anesthetized wild-type, A1 knockout (KO), A2AKO, A2BKO, A3KO, A1, and A3 double KO (A1/3 DKO) and A2A and A2B double KO (A2A/2B DKO) mice in real time. Echocardiographic and Doppler studies were performed using a Visualsonic Vevo 2100 ultrasound system. Coronary blood flow (CBF) baseline data were obtained when animals were anesthetized with 1% isoflourane. Diameter (D) and velocity time integral (VTI) were measured on the left coronary arteries (CBF = ((π/4) × D(2) × VTI × HR)/1000). CBF changes were the highest within 2 min of injection (about 10 mg/kg). Heart rate, cardiac output, and stroke volume were measured by tracing the left ventricle long axis. Our data support a role for the A2 AR in CBF and further support our conclusions of previous studies from isolated tissues. Adenosine-mediated decreases in cardiac output and stroke volume may be A2B and/or A3 AR-mediated; however, the A1 and A2 ARs also play roles in overall cardiac function. These data further provide a powerful translational tool in studying the cardiovascular effects of adenosine in disease states.

  2. Dietary omega-6 fatty acid replacement selectively impairs cardiac functional recovery after ischemia in female (but not male) rats.

    PubMed

    Ip, Wendy T K; McAlindon, Andrew; Miller, Sarah E; Bell, James R; Curl, Claire L; Huggins, Catherine E; Mellor, Kimberley M; Raaijmakers, Antonia J A; Bienvenu, Laura A; McLennan, Peter L; Pepe, Salvatore; Delbridge, Lea M D

    2016-09-01

    A definitive understanding of the role of dietary lipids in determining cardioprotection (or cardiodetriment) has been elusive. Randomized trial findings have been variable and sex specificity of dietary interventions has not been determined. In this investigation the sex-selective cardiac functional effects of three diets enriched by omega-3 or omega-6 polyunsaturated fatty acids (PUFA) or enriched to an equivalent extent in saturated fatty acid components were examined in rats after an 8-wk treatment period. In females the myocardial membrane omega-6:omega-3 PUFA ratio was twofold higher than males in the omega-6 diet replacement group. In diets specified to be high in omega-3 PUFA or in saturated fat, this sex difference was not apparent. Isolated cardiomyocyte and heart Langendorff perfusion experiments were performed, and molecular measures of cell viability were assessed. Under basal conditions the contractile performance of omega-6 fed female cardiomyocytes and hearts was reduced compared with males. Omega-6 fed females exhibited impaired systolic resilience after ischemic insult. This response was associated with increased postischemia necrotic cell damage evaluated by coronary lactate dehydrogenase during reperfusion in omega-6 fed females. Cardiac and myocyte functional parameters were not different between omega-3 and saturated fat dietary groups and within these groups there were no discernible sex differences. Our data provide evidence at both the cardiac and cardiomyocyte levels that dietary saturated fatty acid intake replacement with an omega-6 (but not omega-3) enriched diet has selective adverse cardiac effect in females. This finding has potential relevance in relation to women, cardiac risk, and dietary management.

  3. Patterns and determinants of functional and absolute iron deficiency in patients undergoing cardiac rehabilitation following heart surgery.

    PubMed

    Tramarin, Roberto; Pistuddi, Valeria; Maresca, Luigi; Pavesi, Marco; Castelvecchio, Serenella; Menicanti, Lorenzo; de Vincentiis, Carlo; Ranucci, Marco

    2017-01-01

    Background Anaemia and iron deficiency are frequent following major surgery. The present study aims to identify the iron deficiency patterns in cardiac surgery patients at their admission to a cardiac rehabilitation programme, and to determine which perioperative risk factor(s) may be associated with functional and absolute iron deficiency. Design This was a retrospective study on prospectively collected data. Methods The patient population included 339 patients. Functional iron deficiency was defined in the presence of transferrin saturation <20% and serum ferritin ≥100 µg/l. Absolute iron deficiency was defined in the presence of serum ferritin values <100 µg/l. Results Functional iron deficiency was found in 62.9% of patients and absolute iron deficiency in 10% of the patients. At a multivariable analysis, absolute iron deficiency was significantly ( p = 0.001) associated with mechanical prosthesis mitral valve replacement (odds ratio 5.4, 95% confidence interval 1.9-15) and tissue valve aortic valve replacement (odds ratio 4.5, 95% confidence interval 1.9-11). In mitral valve surgery, mitral repair carried a significant ( p = 0.013) lower risk of absolute iron deficiency (4.4%) than mitral valve replacement with tissue valves (8.3%) or mechanical prostheses (22.5%). Postoperative outcome did not differ between patients with functional iron deficiency and patients without iron deficiency; patients with absolute iron deficiency had a significantly ( p = 0.017) longer postoperative hospital stay (median 11 days) than patients without iron deficiency (median nine days) or with functional iron deficiency (median eight days). Conclusions Absolute iron deficiency following cardiac surgery is more frequent in heart valve surgery and is associated with a prolonged hospital stay. Routine screening for iron deficiency at admission in the cardiac rehabilitation unit is suggested.

  4. Interferon Regulatory Factor 7 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

    PubMed Central

    Jiang, Ding-Sheng; Liu, Yu; Zhou, Heng; Zhang, Yan; Zhang, Xiao-Dong; Zhang, Xiao-Fei; Chen, Ke; Gao, Lu; Peng, Juan; Gong, Hui; Chen, Yingjie; Yang, Qinglin; Liu, Peter P.; Fan, Guo-Chang; Zou, Yunzeng; Li, Hongliang

    2017-01-01

    Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding–induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload–induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II–induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBαS32A/S36A super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-βS177E/S181E (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy. PMID:24396025

  5. Amino-Functionalization of Carbon Nanotubes by Using a Factorial Design: Human Cardiac Troponin T Immunosensing Application

    PubMed Central

    Freitas, Tatianny A.; Mattos, Alessandra B.; Silva, Bárbara V. M.; Dutra, Rosa F.

    2014-01-01

    A simple amino-functionalization method for carbon nanotubes and its application in an electrochemical immunosensor for detection of the human cardiac troponin T are described. Amino-functionalized carbon nanotubes allow oriented antibodies immobilization via their Fc regions, improving the performance of an immunosensor. Herein multiwalled carbon nanotubes were amino-functionalized by using the ethylenediamine reagent and assays were designed by fractional factorial study associated with Doehlert matrix. Structural modifications in the carbon nanotubes were confirmed by Fourier transform infrared spectroscopy. After amino-functionalization the carbon nanotubes were attached to screen-printed carbon electrode and a sandwich-type immunoassay was performed for measuring the cardiac troponin T. The electrochemical measurements were obtained through hydrogen peroxide reaction with peroxidase conjugated to the secondary antibody. Under optimal conditions, troponin T immunosensor was evaluated in serum samples, which showed a broad linear range (0.02 to 0.32 ng mL−1) and a low limit of detection, 0.016 ng mL−1. This amino platform can be properly used as clinical tool for cardiac troponin T detection in the acute myocardial infarction diagnosis. PMID:25133185

  6. A comparative serial echocardiographic analysis of cardiac structure and function in rats subjected to pressure or volume overload.

    PubMed

    Cantor, Elliott J F; Babick, Andrea P; Vasanji, Zainisha; Dhalla, Naranjan S; Netticadan, Thomas

    2005-05-01

    Heart failure is a leading cause of death that is reaching epidemic proportions. It is a clinical syndrome attributable to a multitude of factors that begins with a compensatory response known as hypertrophy, followed by a decompensatory response that eventually results in failure. Heart failure can be triggered when the heart is subjected to extended periods of pathological pressure overload (PO) or volume overload (VO). To date there have been no comparative serial echocardiographic studies outlining the progression of hypertrophy in PO versus VO rats. We hypothesized that PO or VO would induce differential cardiac remodeling leading to contractile dysfunction with subsequent heart failure. To address this hypothesis we used echocardiography to study the serial progression of heart structure and function in rat models of both PO- and VO-induced hypertrophy. PO or VO were induced by performing abdominal aortic banding or aortocaval shunt procedures, respectively, while cardiac structure and function were assessed in both models by M-mode and Doppler echocardiography at key time intervals. PO rats showed progressive wall thickening consistent with concentric hypertrophy, while VO rats showed marked left ventricular dilatation consistent with eccentric hypertrophy. Systolic dysfunction occurred early in VO compared to PO. Diastolic dysfunction was evident in PO, while VO showed signs of enhanced diastolic function. PO and VO induced differential changes in cardiac structure and function during the progression of compensated hypertrophy to decompensated heart failure.

  7. Effects of injectable anesthetic combinations on left ventricular function and cardiac morphology in Sprague-Dawley rats.

    PubMed

    Sabatini, Carla F; O'Sullivan, M Lynne; Valcour, James E; Sears, William; Johnson, Ron J

    2013-01-01

    Novel anesthetic agents or combinations may provide superior general anesthesia for echocardiography in rodents with the potential for reduced adverse effects. This study sought to characterize the effects of 3 injectable anesthetics on left ventricular (LV) systolic function and cardiac morphology in healthy male and female rats. Rats underwent echocardiographic assessment after general anesthesia via pentobarbital or combinations of ketamine and medetomidine (KME) and ketamine and midazolam (KMI) according to a crossover Latin-square design. Blood samples for serum estradiol measurements were obtained from all females after echocardiography with each anesthetic. Rats given KMI showed superior LV systolic function with the highest values for fractional shortening (FS), ejection fraction (EF) and stroke volume, whereas heart rate was greatest with pentobarbital, followed by KMI and then KME. KME produced the greatest effects on cardiac morphology, most notably during systole, including reduced septal and posterior wall thickness and increased LV chamber dimensions and volumes. In addition, KME had the greatest cardiac-depressing effects on LV systolic function, including reduced FS, EF, and heart rate values. Compared with male rats, female rats had superior LV function with greater EF and FS values, whereas male rats showed higher heart rate. Significant negative correlations were noted between serum estradiol levels and FS and EF values in female rats receiving KME. We conclude that the combination of KMI may be a superior anesthetic for use in male and female rats undergoing echocardiography.

  8. Intramyocardial Delivery of Mesenchymal Stem Cell-Seeded Hydrogel Preserves Cardiac Function and Attenuates Ventricular Remodeling after Myocardial Infarction

    PubMed Central

    Mathieu, Eva; Lamirault, Guillaume; Toquet, Claire; Lhommet, Pierre; Rederstorff, Emilie; Sourice, Sophie; Biteau, Kevin; Hulin, Philippe; Forest, Virginie; Weiss, Pierre

    2012-01-01

    Background To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC) therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) hydrogel seeded with MSC (MSC+hydrogel) could preserve cardiac function and attenuate left ventricular (LV) remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI). Methodology/Principal Finding Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. Conclusion/Significance These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium. PMID:23284842

  9. Implications for Cardiac Function Following Rescue of the Dystrophic Diaphragm in a Mouse Model of Duchenne Muscular Dystrophy.

    PubMed

    Betts, Corinne A; Saleh, Amer F; Carr, Carolyn A; Muses, Sofia; Wells, Kim E; Hammond, Suzan M; Godfrey, Caroline; McClorey, Graham; Woffindale, Caroline; Clarke, Kieran; Wells, Dominic J; Gait, Michael J; Wood, Matthew J A

    2015-06-26

    Duchenne muscular dystrophy (DMD) is caused by absence of the integral structural protein, dystrophin, which renders muscle fibres susceptible to injury and degeneration. This ultimately results in cardiorespiratory dysfunction, which is the predominant cause of death in DMD patients, and highlights the importance of therapeutic targeting of the cardiorespiratory system. While there is some evidence to suggest that restoring dystrophin in the diaphragm improves both respiratory and cardiac function, the role of the diaphragm is not well understood. Here using exon skipping oligonucleotides we predominantly restored dystrophin in the diaphragm and assessed cardiac function by MRI. This approach reduced diaphragmatic pathophysiology and markedly improved diaphragm function but did not improve cardiac function or pathophysiology, with or without exercise. Interestingly, exercise resulted in a reduction of dystrophin protein and exon skipping in the diaphragm. This suggests that treatment regimens may require modification in more active patients. In conclusion, whilst the diaphragm is an important respiratory muscle, it is likely that dystrophin needs to be restored in other tissues, including multiple accessory respiratory muscles, and of course the heart itself for appropriate therapeutic outcomes. This supports the requirement of a body-wide therapy to treat DMD.

  10. Physical Activity Measured by Accelerometry and its Associations With Cardiac Structure and Vascular Function in Young and Middle‐Aged Adults

    PubMed Central

    Andersson, Charlotte; Lyass, Asya; Larson, Martin G.; Spartano, Nicole L.; Vita, Joseph A.; Benjamin, Emelia J.; Murabito, Joanne M.; Esliger, Dale W.; Blease, Susan J.; Hamburg, Naomi M.; Mitchell, Gary F.; Vasan, Ramachandran S.

    2015-01-01

    Background Physical activity is associated with several health benefits, including lower cardiovascular disease risk. The independent influence of physical activity on cardiac and vascular function in the community, however, has been sparsely investigated. Measures and Results We related objective measures of moderate‐ to vigorous‐intensity physical activity (MVPA, assessed by accelerometry) to cardiac and vascular indices in 2376 participants of the Framingham Heart Study third generation cohort (54% women, mean age 47 years). Using multivariable regression models, we related MVPA to the following echocardiographic and vascular measures: left ventricular mass, left atrial and aortic root sizes, carotid–femoral pulse wave velocity, augmentation index, and forward pressure wave. Men and women engaged in MVPA 29.9±21.4 and 25.5±19.4 min/day, respectively. Higher values of MVPA (per 10‐minute increment) were associated with lower carotid–femoral pulse wave velocity (estimate −0.53 ms/m; P=0.006) and lower forward pressure wave (estimate −0.23 mm Hg; P=0.03) but were not associated with augmentation index (estimate 0.13%; P=0.25). MVPA was associated positively with loge left ventricular mass (estimate 0.006 loge [g/m2]; P=0.0003), left ventricular wall thickness (estimate 0.07 mm; P=0.0001), and left atrial dimension (estimate 0.10 mm; P=0.01). MVPA also tended to be positively associated with aortic root dimension (estimate 0.05 mm; P=0.052). Associations of MVPA with cardiovascular measures were similar, in general, for bouts lasting <10 versus ≥10 minutes. Conclusions In our community‐based sample, greater physical activity was associated with lower vascular stiffness but with higher echocardiographic left ventricular mass and left atrial size. These findings suggest complex relations of usual levels of physical activity and cardiovascular remodeling. PMID:25792127

  11. Effect of mediastinal irradiation on cardiac function of patients treated during childhood and adolescence for Hodgkin's disease

    SciTech Connect

    Green, D.M.; Gingell, R.L.; Pearce, J.; Panahon, A.M.; Ghoorah, J.

    1987-02-01

    To determine the frequency of cardiac dysfunction in patients treated during childhood or adolescence with mediastinal irradiation for Hodgkin's disease (HD), 28 patients underwent cardiac evaluation 19 to 182 months (median, 90 months) after the completion of radiation therapy. No patient had symptoms of cardiac disease. All were normotensive. All patients had a normal cardiothoracic ratio. There were no abnormalities of voltage or rhythm in the ECGs. The left ventricular end diastolic volume was increased in 19.2% of patients, none of whom had evidence of impaired left ventricular function. The left ventricular ejection fraction (LVEF) was increased in 15.3% of patients. No patient had a decreased LVEF. Pericardial thickening was demonstrated on echocardiograms from 12 of 28 patients (42.9%). Thickening was more frequent among those patients observed for 72 or more months (47.1%; eight of 17) than among those with shorter periods of follow-up (36.4%; four of 11). This study demonstrates that cardiac dysfunction is an infrequent sequela of mediastinal irradiation following treatment using an equally weighted, anterior-posterior technique. Longitudinal study of these patients will be necessary to determine the clinical significance and evolution of the occult pericardial thickening that was identified.

  12. The Modulation of Cardiac Contractile Function by the Pharmacological and Toxicological Effects of Urocortin2

    PubMed Central

    Chen, Si; Wang, Zhenhua; Xu, Bo; Mi, Xiangquan; Sun, Wanqing; Quan, Nanhu; Wang, Lin; Chen, Xingchi; Liu, Quan; Zheng, Yang; Leng, Jiyan; Li, Ji

    2015-01-01

    Urocortin2 (Ucn2) has been revealed to enhance cardiac function in heart failure. However, the pharmacological and toxicological effects of Ucn2 on cardiomyocytes are incompletely understood. In this study, we investigated the possible mechanisms of Ucn2 on mediating the contractility of cardiomyocytes. Mechanical properties and intracellular Ca2+ properties were measured in isolated cardiomyocytes from different treatment groups. The stress signaling was evaluated using Western blot. The results demonstrated that Ucn2 induced maximal velocity of shortening (+dL/dt), peak height, peak shortening (PS) amplitude, maximal velocity of relengthening (−dL/dt), accompanied by a significant rise in intracellular Ca2+ level and a fall of the mean time constant of Ca2+ transient decay (Tau) in WT cardiomyocytes. However, these effects were abolished by preincubation of type 2 CRF receptors (CRFR2) antagonist anti-sauvagine 30 (a-SVG-30). We also found that Ucn2 treatment activated the AMPK pathway in isolated cardiomyocytes via CRFR2. Furthermore, Ucn2 induced protein kinase A (PKA) and phospholamban (PLN) phosphorylation. Pretreatment of PKA inhibitor H89 reduced the inotropic and lusitropic effects of Ucn2 as well as decreased the intracellular Ca2+ load and slowed down the Ca2+ transient decay. We also showed that preincubation of Compound C, an inhibitor of AMPK, inhibited the phosphorylation of PKA and the intracellular Ca2+ level in cardiomyocytes without affecting the contractile function and the Tau of cardiomyocytes. Taken together, it suggests that Ucn2 facilitate the contractility of cardiomyocytes via activating both AMPK and PKA. PMID:26342213

  13. Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction

    SciTech Connect

    McGhie, A.I.; Corbett, J.R.; Akers, M.S.; Kulkarni, P.; Sills, M.N.; Kremers, M.; Buja, L.M.; Durant-Reville, M.; Parkey, R.W.; Willerson, J.T. )

    1991-02-01

    The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036.

  14. Cardiac structure and function in adolescent Sherpa; effect of habitual altitude and developmental stage.

    PubMed

    Stembridge, Mike; Ainslie, Philip N; Donnelly, Joseph; MacLeod, Nicholas T; Joshi, Suchita; Hughes, Michael G; Sherpa, Kami; Shave, Rob

    2016-03-15

    The purpose of this study was to examine ventricular structure and function in Sherpa adolescents to determine whether age-specific differences in oxygen saturation (SpO2 ) and pulmonary artery systolic pressure (PASP) influence cardiac adaptation to chronic hypoxia early in life. Two-dimensional, Doppler, and speckle-tracking echocardiography were performed on adolescent (9-16 yr) highland Sherpa (HLS; 3,840 m; n = 26) and compared with age-matched lowland Sherpa (LLS; 1,400 m; n = 10) and lowland Caucasian controls (LLC; sea level; n = 30). The HLS were subdivided into pre- and postadolescence; SpO2 was also recorded. Only HLS exhibited a smaller relative left ventricular (LV) end-diastolic volume; however, both HLS and LLS demonstrated a lower peak LV untwisting velocity compared with LLC (92 ± 26 and 100 ± 45 vs. 130 ± 43°/s, P < 0.05). Although SpO2 was similar between groups, PASP was higher in post- vs. preadolescent HLS (30 ± 5 vs. 25 ± 5 mmHg, P < 0.05), which negatively correlated with right ventricular strain rate (r = 0.50, P < 0.01). Much like their adult counterparts, HLS and LLS adolescents exhibit slower LV diastolic relaxation, despite residing at different altitudes. These findings suggest fundamental differences exist in the diastolic function of Sherpa that are present at an early age and may be retained after migration to lower altitudes. The higher PASP in postadolescent Sherpa is in contrast to previous reports of lowland children at high altitude and, unlike that in lowlanders, was not explained by differences in SpO2 ; thus different regulatory mechanisms seem to exist between these two distinct populations.

  15. Short-axis epicardial volume change is a measure of cardiac left ventricular short-axis function, which is independent of myocardial wall thickness.

    PubMed

    Ugander, Martin; Carlsson, Marcus; Arheden, Håkan

    2010-02-01

    Fractional shortening (FS) by echocardiography is considered to represent the short-axis contribution to the stroke volume (SV), also called short-axis function. However, FS is mathematically coupled to the amount of myocardium, since it rearranges during atrioventricular plane displacement (AVPD). The SV is the sum of the volumes generated by 1) reduction in outer volume of the heart, and 2) inner AVPD. The long-axis contribution to the SV is generated by AVPD, and thus the short-axis contribution is the remaining outer volume change of the heart, which should be unrelated to myocardial wall thickness. We hypothesized that both endocardial and midwall shortening indexed to SV are dependent on myocardial wall thickness, whereas epicardial volume change (EVC) indexed to SV is not. Twelve healthy volunteers (normals), 12 athletes, and 12 patients with dilated cardiomyopathy (ejection fraction < 30%) underwent cine cardiac magnetic resonance imaging. Left ventricular long-axis function was measured as the portion of the SV, in milliliters, generated by AVPD. EVC was defined as SV minus long-axis function. Endocardial and midwall shortening were measured in a midventri