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Sample records for improved cardiac function

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  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. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  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. 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.

  13. 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.

  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. 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.

  16. Metformin improves cardiac function in mice with heart failure after myocardial infarction by regulating mitochondrial energy metabolism.

    PubMed

    Sun, Dan; Yang, Fei

    2017-03-14

    To investigate whether metformin can improve the cardiac function through improving the mitochondrial function in model of heart failure after myocardial infarction. Male C57/BL6 mice aged about 8 weeks were selected and the anterior descending branch was ligatured to establish the heart failure model after myocardial infarction. The cardiac function was evaluated via ultrasound after 3 days to determine the modeling was successful, and the mice were randomly divided into two groups. Saline group (Saline) received the intragastric administration of normal saline for 4 weeks, and metformin group (Met) received the intragastric administration of metformin for 4 weeks. At the same time, Shame group (Sham) was set up. Changes in cardiac function in mice were detected at 4 weeks after operation. Hearts were taken from mice after 4 weeks, and cell apoptosis in myocardial tissue was detected using TUNEL method; fresh mitochondria were taken and changes in oxygen consumption rate (OCR) and respiratory control rate (RCR) of mitochondria in each group were detected using bio-energy metabolism tester, and change in mitochondrial membrane potential (MMP) of myocardial tissue was detected via JC-1 staining; the expressions and changes in Bcl-2, Bax, Sirt3, PGC-1α and acetylated PGC-1α in myocardial tissue were detected by Western blot. RT-PCR was used to detect mRNA levels in Sirt3 in myocardial tissues. Metformin improved the systolic function of heart failure model rats after myocardial infarction and reduced the apoptosis of myocardial cells after myocardial infarction. Myocardial mitochondrial respiratory function and membrane potential were decreased after myocardial infarction, and metformin treatment significantly improved the mitochondrial respiratory function and mitochondrial membrane potential; Metformin up-regulated the expression of Sirt3 and the activity of PGC-1α in myocardial tissue of heart failure after myocardial infarction. Metformin decreases the

  17. 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

  18. Weight reduction via life-style modifications results in reverse remodelling and cardiac functional improvement in a patient with obesity.

    PubMed

    Hou, Chang; Zheng, Bo; Yang, Ying; Wang, Xin-Gang; Zhang, Bin; Shi, Qiu-Ping; Chen, Ming

    2017-03-09

    The prevalence of obesity has increased strikingly in recent years. Obesity is associated with increased left ventricular end-diastolic dimension (LVEDD), ventricular wall thickness, left ventricular (LV) mass, left atrial diameter, subtle myocardial systolic as well as diastolic dysfunction and has been identified as an independent predictor of these changes. It's convinced that weight reduction results in cardiac reverse remodelling, while the functional changes after weight reduction are variable. Here, we present a recent case of man with moderate obesity who acquires favourable regression in chamber size, wall thickness and significant improvement in cardiac function. Briefly, after life-style modifications and comprehensive secondary prevention, great amounts of weight loss was achieved simultaneously with decreased LVEDD and increased LV ejection fraction. As dietary intervention and regular physical activity are pivotal for these benefits, this non-invasive approach for weight loss should be advocated in selected patients.

  19. 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

  20. Controlled Release of Collagen-Binding SDF-1α Improves Cardiac Function after Myocardial Infarction by Recruiting Endogenous Stem Cells

    PubMed Central

    Sun, Jie; Zhao, Yannan; Li, Qingguo; Chen, Bing; Hou, Xianglin; Xiao, Zhifeng; Dai, Jianwu

    2016-01-01

    Stromal cell-derived factor-1α (SDF-1α) is a well-characterized chemokine that mobilizes stem cells homing to the ischemic heart, which is beneficial for cardiac regeneration. However, clinically administered native SDF-1α diffuses quickly, thus decreasing its local concentration, and results in side effects. Thus, a controlled release system for SDF-1α is required to produce an effective local concentration in the ischemic heart. In this study, we developed a recombinant chemokine, consisting of SDF-1α and a collagen-binding domain, which retains both the SDF-1α and collagen-binding activity (CBD-SDF-1α). In an in vitro assay, CBD-SDF-1α could specifically bind to a collagen gel and achieve sustained release. An intramyocardial injection of CBD-SDF-1α after acute myocardial infarction demonstrated that the protein was largely tethered in the ischemic area and that controlled release had been achieved. Furthermore, CBD-SDF-1α enhanced the recruitment of c-kit positive (c-kit+) stem cells, increased capillary density and improved cardiac function, whereas NAT-SDF-1α had no such beneficial effects. Our findings demonstrate that CBD-SDF-1α can specifically bind to collagen and achieve controlled release both in vitro and in vivo. Local delivery of this protein could mobilize endogenous stem cells homing to the ischemic heart and improve cardiac function after myocardial infarction. PMID:27226084

  1. 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

  2. Controlled Release of Collagen-Binding SDF-1α Improves Cardiac Function after Myocardial Infarction by Recruiting Endogenous Stem Cells.

    PubMed

    Sun, Jie; Zhao, Yannan; Li, Qingguo; Chen, Bing; Hou, Xianglin; Xiao, Zhifeng; Dai, Jianwu

    2016-05-26

    Stromal cell-derived factor-1α (SDF-1α) is a well-characterized chemokine that mobilizes stem cells homing to the ischemic heart, which is beneficial for cardiac regeneration. However, clinically administered native SDF-1α diffuses quickly, thus decreasing its local concentration, and results in side effects. Thus, a controlled release system for SDF-1α is required to produce an effective local concentration in the ischemic heart. In this study, we developed a recombinant chemokine, consisting of SDF-1α and a collagen-binding domain, which retains both the SDF-1α and collagen-binding activity (CBD-SDF-1α). In an in vitro assay, CBD-SDF-1α could specifically bind to a collagen gel and achieve sustained release. An intramyocardial injection of CBD-SDF-1α after acute myocardial infarction demonstrated that the protein was largely tethered in the ischemic area and that controlled release had been achieved. Furthermore, CBD-SDF-1α enhanced the recruitment of c-kit positive (c-kit(+)) stem cells, increased capillary density and improved cardiac function, whereas NAT-SDF-1α had no such beneficial effects. Our findings demonstrate that CBD-SDF-1α can specifically bind to collagen and achieve controlled release both in vitro and in vivo. Local delivery of this protein could mobilize endogenous stem cells homing to the ischemic heart and improve cardiac function after myocardial infarction.

  3. 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

    ± 0.06), and was attenuated in CHF–CBD animals (0.59 ± 0.05) (P < 0.05 for all comparisons). Arrhythmia incidence was increased in CHF–sham and reduced in CHF–CBD animals (213 ± 58 events h–1 CHF, 108 ± 48 events h–1 CHF–CBD, P < 0.05). Furthermore, ventricular systolic (3.8 ± 0.7 vs. 6.3 ± 0.5 ml, P < 0.05) and diastolic (6.3 ± 1.0 vs. 9.1 ± 0.5 ml, P < 0.05) volumes were reduced, and ejection fraction preserved (41 ± 5% vs. 54 ± 2% reduction from pre-pace, P < 0.05) in CHF–CBD compared to CHF–sham rabbits. Similar patterns of changes were observed longitudinally within the CHF–CBD group before and after CBD. In conclusion, CBD is effective in reducing RSNA, SRC and arrhythmia incidence, while improving breathing stability and cardiac function in pacing-induced CHF rabbits. Key points A strong correlation between disordered breathing patterns, elevated sympathetic nerve activity and enhanced chemoreflex sensitivity exists in patients with heart failure. Evidence indicates that disordered breathing patterns and increased sympathetic nerve activity increases arrhythmia incidence in patients with heart failure. Enhanced coupling between sympathetic and respiratory neural drive underlies elevated sympathetic nerve activity in an animal model of sleep apnoea. We investigated the impact of carotid body chemoreceptor denervation on sympathetic nerve activity, disordered breathing and sympatho-respiratory coupling in an animal model of heart failure. Renal sympathetic nerve activity, apnoea/hypopnoea incidence, variability measures of tidal volume and respiratory rate and arrhythmia incidence were quantified during resting breathing in heart failure animals with and without carotid body ablation. Our results indicate that carotid body chemoreceptor denervation reduces sympathetic nerve activity, disordered breathing patterns, arrhythmia incidence and sympatho-respiratory coupling in

  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. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

    PubMed

    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-03-21

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia/reperfusion injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. Here we found that glucose uptake was remarkably diminished in myocardium following reperfusion in Sprague-Dawley rats as detected by 18F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by 3 folds and GLUT4 translocation remained unchanged compared with those of sham rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated ischemia/reperfusion injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, while its knockdown increased glucose uptake, suggesting a role of PDK4 in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial ischemia/reperfusion. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial ischemia/reperfusion injury.

  6. 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

  7. 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

  8. Tissue kallikrein promotes neovascularization and improves cardiac function by the Akt-glycogen synthase kinase-3β pathway

    PubMed Central

    Yao, Yu-Yu; Yin, Hang; Shen, Bo; Smith, Robert S.; Liu, Yuying; Gao, Lin; Chao, Lee; Chao, Julie

    2008-01-01

    Aims We investigated the role of the Akt-glycogen synthase kinase (GSK)-3β signalling pathway in mediating the protective effects of tissue kallikrein on myocardial injury by promoting angiogenesis and blood flow in rats after myocardial infarction (MI). Methods and results Human tissue kallikrein gene in an adenoviral vector, with or without co-administration of dominant-negative Akt (Ad.DN-Akt) or constitutively active GSK-3β (Ad.GSK-3βS9A), was injected into rat myocardium after MI. The expression of recombinant human kallikrein in rat heart significantly improved cardiac function and reduced infarct size 10 days after gene delivery. Kallikrein administration significantly increased myocardial blood flow as well as capillary and arteriole densities in the infarcted myocardium. Kallikrein increased cardiac Akt and GSK-3β phosphorylation in conjunction with decreased GSK-3β activity and the upregulation of vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2). All of kallikrein’s effects on the myocardium were abrogated by Ad.DN-Akt and Ad.GSK-3βS9A. Moreover, in cultured human aortic endothelial cells, tissue kallikrein stimulated capillary tube formation and promoted cell migration; however, these effects were blocked by Ad.DN-Akt, Ad.GSK-3βS9A, icatibant (a kinin B2 receptor antagonist), Tki (a VEGF receptor tyrosine kinase inhibitor), and a neutralizing VEGF antibody. In addition, tissue kallikrein decreased GSK-3β activity via the phosphatidylinositol 3-kinase-Akt pathway and enhanced VEGF and VEGFR-2 expression in endothelial cells. Conclusion These data provide the first direct evidence that tissue kallikrein protects against acute-phase MI by promoting neovascularization, restoring regional blood flow and improving cardiac function through the kinin B2 receptor-Akt-GSK-3β and VEGF signalling pathways. PMID:18689794

  9. Improved hepatic arterial fraction estimation using cardiac output correction of arterial input functions for liver DCE MRI

    NASA Astrophysics Data System (ADS)

    Chouhan, Manil D.; Bainbridge, Alan; Atkinson, David; Punwani, Shonit; Mookerjee, Rajeshwar P.; Lythgoe, Mark F.; Taylor, Stuart A.

    2017-02-01

    Liver dynamic contrast enhanced (DCE) MRI pharmacokinetic modelling could be useful in the assessment of diffuse liver disease and focal liver lesions, but is compromised by errors in arterial input function (AIF) sampling. In this study, we apply cardiac output correction to arterial input functions (AIFs) for liver DCE MRI and investigate the effect on dual-input single compartment hepatic perfusion parameter estimation and reproducibility. Thirteen healthy volunteers (28.7  ±  1.94 years, seven males) underwent liver DCE MRI and cardiac output measurement using aortic root phase contrast MRI (PCMRI), with reproducibility (n  =  9) measured at 7 d. Cardiac output AIF correction was undertaken by constraining the first pass AIF enhancement curve using the indicator-dilution principle. Hepatic perfusion parameters with and without cardiac output AIF correction were compared and 7 d reproducibility assessed. Differences between cardiac output corrected and uncorrected liver DCE MRI portal venous (PV) perfusion (p  =  0.066), total liver blood flow (TLBF) (p  =  0.101), hepatic arterial (HA) fraction (p  =  0.895), mean transit time (MTT) (p  =  0.646), distribution volume (DV) (p  =  0.890) were not significantly different. Seven day corrected HA fraction reproducibility was improved (mean difference 0.3%, Bland–Altman 95% limits-of-agreement (BA95%LoA)  ±27.9%, coefficient of variation (CoV) 61.4% versus 9.3%, ±35.5%, 81.7% respectively without correction). Seven day uncorrected PV perfusion was also improved (mean difference 9.3 ml min‑1/100 g, BA95%LoA  ±506.1 ml min‑1/100 g, CoV 64.1% versus 0.9 ml min‑1/100 g, ±562.8 ml min‑1/100 g, 65.1% respectively with correction) as was uncorrected TLBF (mean difference 43.8 ml min‑1/100 g, BA95%LoA  ±586.7 ml min‑1/ 100 g, CoV 58.3% versus 13.3 ml min‑1/100 g, ±661.5 ml min‑1/100 g, 60

  10. Inhibition of let-7 augments the recruitment of epicardial cells and improves cardiac function after myocardial infarction.

    PubMed

    Seeger, Timon; Xu, Quan-Fu; Muhly-Reinholz, Marion; Fischer, Ariane; Kremp, Eva-Maria; Zeiher, Andreas M; Dimmeler, Stefanie

    2016-05-01

    Heart failure due to myocardial infarction is a major cause of mortality. The microRNA (miR) family let-7 is expressed during embryonic development and is up-regulated in differentiated cells. The aim of this study was to study the role of let-7 after acute myocardial infarction (AMI). We designed an antimiR to inhibit the highest expressed members of the let-7 family, let-7 a, b and c. Administration at day 0 and day 2 after AMI resulted in sustained knockdown of let-7 after 28days. Let-7 inhibition prevented deterioration of cardiac functions compared to control treatment which was especially due to improvements in the infarcted, apical cardiac segments. We observed higher contents of fibrosis in the border zone as well as increased numbers of cells positive for TCF21, which is also expressed in epicardial cells. Markers were augmented after let-7 inhibition and let-7 blocked EMT in epicardial cells in vitro. Lineage tracing in TCF21(iCre/+):R26R(tdT) mice showed abundant tomato positive cells in the infarct and border zone. In conclusion, let-7 inhibition resulted in functional benefits due to an increase in recruitment of epicardial cells and EMT.

  11. Mitochondria-targeted ROS scavenger improves post-ischemic recovery of cardiac function and attenuates mitochondrial abnormalities in aged rats.

    PubMed

    Escobales, Nelson; Nuñez, Rebeca E; Jang, Sehwan; Parodi-Rullan, Rebecca; Ayala-Peña, Sylvette; Sacher, Joshua R; Skoda, Erin M; Wipf, Peter; Frontera, Walter; Javadov, Sabzali

    2014-12-01

    Mitochondria-generated reactive oxygen species (ROS) play a crucial role in the pathogenesis of aging and age-associated diseases. In this study, we evaluated the effects of XJB-5-131 (XJB), a mitochondria-targeted ROS and electron scavenger, on cardiac resistance to ischemia-reperfusion (IR)-induced oxidative stress in aged rats. Male adult (5-month old, n=17) and aged (29-month old, n=19) Fischer Brown Norway (F344/BN) rats were randomly assigned to the following groups: adult (A), adult+XJB (AX), aged (O), and aged+XJB (OX). XJB was administered 3 times per week (3mg/kg body weight, IP) for four weeks. At the end of the treatment period, cardiac function was continuously monitored in excised hearts using the Langendorff technique for 30 min, followed by 20 min of global ischemia, and 60-min reperfusion. XJB improved post-ischemic recovery of aged hearts, as evidenced by greater left ventricular developed-pressures and rate-pressure products than the untreated, aged-matched group. The state 3 respiration rates at complexes I, II and IV of mitochondria isolated from XJB-treated aged hearts were 57% (P<0.05), 25% (P<0.05) and 28% (P<0.05), respectively, higher than controls. Ca(2+)-induced swelling, an indicator of permeability transition pore opening, was reduced in the mitochondria of XJB-treated aged rats. In addition, XJB significantly attenuated the H2O2-induced depolarization of the mitochondrial inner membrane as well as the total and mitochondrial ROS levels in cultured cardiomyocytes. This study underlines the importance of mitochondrial ROS in aging-induced cardiac dysfunction and suggests that targeting mitochondrial ROS may be an effective therapeutic approach to protect the aged heart against IR injury.

  12. Elevated catalase and heme oxygenase-1 may contribute to improved postischaemic cardiac function in long-term type 1 diabetes.

    PubMed

    Shen, Wei-Li; Zhong, Mei-Fang; Ding, Wen-Long; Wang, Jian; Zheng, Lin; Zhu, Ping; Wang, Bing-Shun; Higashino, Hideaki; Chen, Hong

    2008-07-01

    1. Although increased oxidative stress has been shown repeatedly to be implicated in diabetes, the cardiovascular anti-oxidant state and heart response to ischaemia in long-term Type 1 diabetes remain largely unknown. The present study was designed to observe heart tolerance to ischaemia-reperfusion and endogenous anti-oxidants in the cardiovascular system in long-term hyperglycaemic rats. 2. Hearts from Sprague-Dawley rats surviving up to 6 months with streptozocin-induced severe hyperglycaemia (blood glucose > 20 mmol/L) were isolated and subjected to global ischaemia and reperfusion. Cardiac function, electrocardiogram and anti-oxidants in the myocardium and aorta were examined. In addition, the morphology of the myocardial mitochondria and the in vitro function of aortic vessels were assessed. 3. Hearts from diabetic rats demonstrated lower baseline heart function but had higher postischaemic coronary flow and left ventricular developed pressure compared with their respective controls (P < 0.05). In addition, hearts from diabetic animals had fewer arrhythmias (P < 0.01) and lower left ventricular end-diastolic pressure during reperfusion (P < 0.05). Higher catalase and heme oxygenase-1 content was found in the aorta and myocardium from diabetic rats (P < 0.01). In aortas from diabetic animals, acetylcholine-induced vasodilatation was enhanced and was approximately 15% after inhibition of nitric oxide synthase, compared with 0% in controls. The 15% relaxation was abrogated by heme oxygenase blockade. Mitochondria from the myocardium of diabetic rats showed significant increases in both size and number (P < 0.05). 4. Hearts of long-term Type 1 diabetic rats demonstrated improved recovery of postischaemic cardiac function and reduced reperfusion arrhythmia. Hyperglycaemia may enhance cardiovascular anti-oxidant capacity and mitochondrial neogenesis, which renders the heart resistant to ischaemia and oxidative injury.

  13. A novel, biodegradable, thermoresponsive hydrogel attenuates ventricular remodeling and improves cardiac function following myocardial infarction - a review.

    PubMed

    Yi, Xin; Li, Xiaoyan; Ren, Shan; He, Yiyu; Wan, Weiguo; Wen, Ying; Jiang, Xuejun

    2014-01-01

    Myocardial infarction (MI) and the subsequent heart failure remain among of the leading causes of morbidity and mortality in world wide. A number of studies have demonstrated that intramyocardial biomaterials injections improve cardiac function after implantation because of their angiogenic potential. Thermoresponsive hydrogels, one member of the hydrogels family, are a kind of biomaterial whose structure is similar to that of extracellular matrix. These hydrogels have been interesting for biomedical uses as they can swell in situ under physiological conditions and provide the advantage of convenient administration. The hydrogel that our team is interested in is a novel biodegradable injectable thermoresponsive hydrogel-the copolymer dextran-poly (ε-caprolactone) -2-hydroxylethyl methacrylatepoly (N-isopropylacrylaminde) (Dex-PCL-HEMA/PNIPAAm). Thus, this review will focus on requirements and challenges of injectable synthetic material, and possible mechanism of thermoresponsive hydrogel in treating MI. The main emphases are on the work done and future interesting studies in our laboratory.

  14. Improving Survival after Cardiac Arrest.

    PubMed

    Bjørshol, Conrad Arnfinn; Søreide, Eldar

    2017-02-01

    Each year, approximately half a million people suffer out-of-hospital cardiac arrest (CA) in Europe: The majority die. Survival after CA varies greatly between regions and countries. The authors give an overview of the important elements necessary to promote improved survival after CA as a function of the chain of survival and formula for survival concepts. The chain of survival incorporates bystanders (who identify warning symptoms, call the emergency dispatch center, initiate cardiopulmonary resuscitation [CPR]), dispatchers (who identify CA, and instruct and reassure the caller), first responders (who provide high-quality CPR, early defibrillation), paramedics and other prehospital care providers (who continue high-quality CPR, and provide timely defibrillation and advanced life support, transport to CA center), and hospitals (targeted temperature management, percutaneous coronary intervention, delayed prognostication). The formula for survival concept consists of (1) medical science (international guidelines), (2) educational efficiency (e.g., low-dose, high-frequency training for lay people, first responders, and professionals; and (3) local implementation of all factors in the chain of survival and formula for survival. Survival rates after CA can be advanced through the improvement of the different factors in both the chain of survival and the formula for survival. Importantly, the neurologic outcome in the majority of CA survivors has continued to improve.

  15. Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function.

    PubMed

    Pischke, Soeren E; Gustavsen, A; Orrem, H L; Egge, K H; Courivaud, F; Fontenelle, H; Despont, A; Bongoni, A K; Rieben, R; Tønnessen, T I; Nunn, M A; Scott, H; Skulstad, H; Barratt-Due, A; Mollnes, T E

    2017-05-01

    Inhibition of complement factor 5 (C5) reduced myocardial infarction in animal studies, while no benefit was found in clinical studies. Due to lack of cross-reactivity of clinically used C5 antibodies, different inhibitors were used in animal and clinical studies. Coversin (Ornithodoros moubata complement inhibitor, OmCI) blocks C5 cleavage and binds leukotriene B4 in humans and pigs. We hypothesized that inhibition of C5 before reperfusion will decrease infarct size and improve ventricular function in a porcine model of myocardial infarction. In pigs (Sus scrofa), the left anterior descending coronary artery was occluded (40 min) and reperfused (240 min). Coversin or placebo was infused 20 min after occlusion and throughout reperfusion in 16 blindly randomized pigs. Coversin significantly reduced myocardial infarction in the area at risk by 39% (p = 0.03, triphenyl tetrazolium chloride staining) and by 19% (p = 0.02) using magnetic resonance imaging. The methods correlated significantly (R = 0.92, p < 0.01). Tissue Doppler echocardiography showed increased systolic displacement (31%, p < 0.01) and increased systolic velocity (29%, p = 0.01) in coversin treated pigs. Interleukin-1β in myocardial microdialysis fluid was significantly reduced (31%, p < 0.05) and tissue E-selectin expression was significantly reduced (p = 0.01) in the non-infarcted area at risk by coversin treatment. Coversin ablated plasma C5 activation throughout the reperfusion period and decreased myocardial C5b-9 deposition, while neither plasma nor myocardial LTB4 were significantly reduced. Coversin substantially reduced the size of infarction, improved ventricular function, and attenuated interleukin-1β and E-selectin in this porcine model by inhibiting C5. We conclude that inhibition of C5 in myocardial infarction should be reconsidered.

  16. Lowering body weight in obese mice with diastolic heart failure improves cardiac insulin sensitivity and function: implications for the obesity paradox.

    PubMed

    Sankaralingam, Sowndramalingam; Abo Alrob, Osama; Zhang, Liyan; Jaswal, Jagdip S; Wagg, Cory S; Fukushima, Arata; Padwal, Raj S; Johnstone, David E; Sharma, Arya M; Lopaschuk, Gary D

    2015-05-01

    Recent studies suggest improved outcomes and survival in obese heart failure patients (i.e., the obesity paradox), although obesity and heart failure unfavorably alter cardiac function and metabolism. We investigated the effects of weight loss on cardiac function and metabolism in obese heart failure mice. Obesity and heart failure were induced by feeding mice a high-fat (HF) diet (60% kcal from fat) for 4 weeks, following which an abdominal aortic constriction (AAC) was produced. Four weeks post-AAC, mice were switched to a low-fat (LF) diet (12% kcal from fat; HF AAC LF) or maintained on an HF (HF AAC HF) for a further 10 weeks. After 18 weeks, HF AAC LF mice weighed less than HF AAC HF mice. Diastolic function was improved in HF AAC LF mice, while cardiac hypertrophy was decreased and accompanied by decreased SIRT1 expression, increased FOXO1 acetylation, and increased atrogin-1 expression compared with HF AAC HF mice. Insulin-stimulated glucose oxidation was increased in hearts from HF AAC LF mice, compared with HF AAC HF mice. Thus lowering body weight by switching to LF diet in obese mice with heart failure is associated with decreased cardiac hypertrophy and improvements in both cardiac insulin sensitivity and diastolic function, suggesting that weight loss does not negatively impact heart function in the setting of obesity.

  17. Right ventricular free wall pacing improves cardiac pump function in severe pulmonary arterial hypertension: a computer simulation analysis.

    PubMed

    Lumens, Joost; Arts, Theo; Broers, Bernard; Boomars, Karin A; van Paassen, Pieter; Prinzen, Frits W; Delhaas, Tammo

    2009-12-01

    In pulmonary arterial hypertension (PAH), duration of myofiber shortening is prolonged in the right ventricular (RV) free wall (RVfw) compared with that in the interventricular septum and left ventricular free wall. This interventricular mechanical asynchrony eventually leads to right heart failure. We investigated by computer simulation whether, in PAH, early RVfw pacing may improve interventricular mechanical synchrony and, hence, cardiac pump function. A mathematical model of the human heart and circulation was used to simulate left ventricular and RV pump mechanics and myofiber mechanics. First, we simulated cardiovascular mechanics of a healthy adult at rest. Size and mass of heart and blood vessels were adapted so that mechanical tissue load was normalized. Second, compensated PAH was simulated by increasing mean pulmonary artery pressure to 32 mmHg while applying load adaptation. Third, decompensated PAH was simulated by increasing mean pulmonary artery pressure further to 79 mmHg without further adaptation. Finally, early RVfw pacing was simulated in severely decompensated PAH. Time courses of circumferential strain in the ventricular walls as simulated were similar to the ones measured in healthy subjects (uniform strain patterns) and in PAH patients (prolonged RVfw shortening). When simulating pacing in decompensated PAH, RV pump function was best upon 40-ms RVfw preexcitation, as evidenced by maximal decrease of RV end-diastolic volume, reduced RVfw myofiber work, and most homogeneous distribution of workload over the ventricular walls. Thus our simulations indicate that, in decompensated PAH, RVfw pacing may improve RV pump function and may homogenize workload over the ventricular walls.

  18. Nanosecond pulsed platelet-rich plasma (nsPRP) improves mechanical and electrical cardiac function following myocardial reperfusion injury.

    PubMed

    Hargrave, Barbara; Varghese, Frency; Barabutis, Nektarios; Catravas, John; Zemlin, Christian

    2016-02-01

    Ischemia and reperfusion (I/R) of the heart is associated with biochemical and ionic changes that result in cardiac contractile and electrical dysfunction. In rabbits, platelet-rich plasma activated using nanosecond pulsed electric fields (nsPRP) has been shown to improve left ventricular pumping. Here, we demonstrate that nsPRP causes a similar improvement in mouse left ventricular function. We also show that nsPRP injection recovers electrical activity even before reperfusion begins. To uncover the mechanism of nsPRP action, we studied whether the enhanced left ventricular function in nsPRP rabbit and mouse hearts was associated with increased expression of heat-shock proteins and altered mitochondrial function under conditions of oxidative stress. Mouse hearts underwent 30 min of global ischemia and 1 h of reperfusion in situ. Rabbit hearts underwent 30 min of ischemia in vivo and were reperfused for 14 days. Hearts treated with nsPRP expressed significantly higher levels of Hsp27 and Hsp70 compared to hearts treated with vehicle. Also, pretreatment of cultured H9c2 cells with nsPRP significantly enhanced the "spare respiratory capacity (SRC)" also referred to as "respiratory reserve capacity" and ATP production in response to the uncoupler FCCP. These results suggest a cardioprotective effect of nsPRP on the ischemic heart during reperfusion.

  19. 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

  20. 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.

  1. Cardiac rehabilitation improves the blood plasma properties of cardiac patients.

    PubMed

    Gwoździński, Krzysztof; Pieniążek, Anna; Czepas, Jan; Brzeszczyńska, Joanna; Jegier, Anna; Pawlicki, Lucjan

    2016-11-01

    Cardiac rehabilitation (CR) improves exercise tolerance and general function. However, its effects on blood plasma in cardiac patients remain uncertain. Our aim was to examine the effect of comprehensive CR on the oxidative stress parameters and antioxidant plasma status in patients with coronary artery disease (CAD) after cardiac interventions. Exercise-based rehabilitation was established as ergometer training, adjusted for individual patients' physical efficiency. Training was repeated three times a week for two months. The standard biochemical (total cholesterol, HDL, LDL, triglycerides and erythrocyte sedimentation rate) and metabolic parameters (peak oxygen uptake [VO2] and peak workload) were determined. We assessed plasma viscosity, lipid peroxidation, carbonyl compounds levels, glutathione (GSH) and ascorbate (ASC) levels and the non-enzymatic antioxidant capacity of plasma in 12 patients with CAD before and after CR. Parameters were examined before exercise, immediately after exercise, and 1 h later. We also compared morphological and biochemical parameters of blood, as well as other parameters such as heart rate and blood pressure (resting and exercise), VO2max and peak workload (W) before and after CR. Before CR, a significant decrease in GSH concentration was observed 1 h after exercise. Conversely, after CR, GSH, and ASC levels remained unchanged immediately after exercise. However, ASC increased after CR after exercise and 1 h later in comparison to before CR. There was a significant increase in ferric reduction ability of plasma immediately after exercise after CR, when compared with before CR. CR improved several blood biochemical parameters, peak VO2, induced an increase in systolic blood pressure peak, and patients' peak workload. After CR, improvements were detected in oxidative stress parameters, except in the level of carbonyls. These changes may contribute to the increased functional heart capacity and better tolerance to exercise and

  2. Histamine H3 receptor blockade improves cardiac function in canine anaphylaxis.

    PubMed

    Chrusch, C; Sharma, S; Unruh, H; Bautista, E; Duke, K; Becker, A; Kepron, W; Mink, S N

    1999-10-01

    In anaphylactic shock (AS), the relative effects of the autacoids including histamine, prostaglandins, and leukotrienes on causing cardiovascular collapse and the extent to which receptor blocking agents and pathway inhibitors may prevent this collapse are not clear. In a ragweed model of anaphylaxis, we examined whether pretreatment with H1, H2, H3 receptor blockers, and cyclooxygenase and leukotriene pathway inhibitors was useful in preventing the depression in left ventricular (LV) contractility known to occur in this model. The dose of allergen was varied to produce similar degrees of shock between treatments. The animals were studied under pentobarbital anesthesia in which the treatment studies were approximately 3 wk apart. LV volumes were measured by sonomicrometric techniques. During challenge, mean arterial blood pressure (Pa), cardiac output (Q), and LV end-diastolic pressure (LVEDP) decreased approximately 50% compared with preshock values in all treatments. Histamine H3 receptor blockade was associated with higher heart rates (HR) and higher stroke work (SW) (p < 0.05) as compared with the other treatment studies. We conclude that histamine H3 activation by inhibiting adrenergic neural norepinephrine release contributes to cardiovascular collapse in AS.

  3. Puerarin accelerate scardiac angiogenesis and improves cardiac function of myocardial infarction by upregulating VEGFA, Ang-1 and Ang-2 in rats

    PubMed Central

    Ai, Fen; Chen, Manhua; Yu, Bo; Yang, Yang; Xu, Guizhong; Gui, Feng; Liu, Zhenxing; Bai, Xiangyan; Chen, Zhen

    2015-01-01

    Objective: The traditional Chinese medicinal puerarin, has long been used to treat cardiovascular diseases, however, the mechanism underlying its effects remain unclear. Here, this study would to investigate the role of puerarin on cardiac angiogenesis and myocardial function induced by myocardial infarction. Methods: Puerarin was treated in rats after left anterior descending coronary artery (LAD) ligation and maintained for 4 weeks (diets containing about 50 mg/kg/day or 100 mg/kg/day). After treatment, cardiac function was evaluated by echocardiography and markers of heart failure. Paraffin sections of the heart tissues were used for isolect in GS-IB4 staining. The Mrna and protein expression levels of VEGFA, Ang-1 and Ang-2 were detected by real-time polymerase chain reaction and western blot. Results: Significantly damaged angiogenesis and slightly increase of VEGFA, Ang-1 and Ang-2 were showed after LAD ligation. Impaired angiogenesis and cardiac function were remarkably improved in puerarin treatment rats with great increase of VEGFA, Ang-1 and Ang-2. Conclusion: The above results demonstrated that puerarin could accelerate cardiac angiogenesis and improve cardiac function of myocardial infarction rats by upregulating VEGFA, Ang-1 and Ang-2. PMID:26885006

  4. 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

  5. The Alberta Cardiac Access Collaborative: improving the cardiac patient journey.

    PubMed

    Blackadar, Robyn; Houle, Mishaela

    2009-01-01

    The Alberta Cardiac Access Collaborative (ACAC) is a joint initiative of Alberta's health system to improve access to adult cardiac services across the patient journey. ACAC has created new care delivery models and implemented best practices across Alberta in four streams across the continuum: heart attack, patient navigation, heart failure and arrhythmia. Emergency medical providers, nurses, primary care physicians, hospitals, cardiac specialists and clinicians are all working together to integrate services, bridge jurisdictions and geography with one aim--improving the patient journey for adults in need of cardiac care.

  6. Diacerein Improves Left Ventricular Remodeling and Cardiac Function by Reducing the Inflammatory Response after Myocardial Infarction

    PubMed Central

    Torina, Anali Galluce; Reichert, Karla; Lima, Fany; de Souza Vilarinho, Karlos Alexandre; de Oliveira, Pedro Paulo Martins; do Carmo, Helison Rafael Pereira; de Carvalho, Daniela Diógenes; Saad, Mário José Abdalla; Sposito, Andrei Carvalho; Petrucci, Orlando

    2015-01-01

    Background The inflammatory response has been implicated in the pathogenesis of left ventricular (LV) remodeling after myocardial infarction (MI). An anthraquinone compound with anti-inflammatory properties, diacerein inhibits the synthesis and activity of pro-inflammatory cytokines, such as tumor necrosis factor and interleukins 1 and 6. The purpose of this study was to investigate the effects of diacerein on ventricular remodeling in vivo. Methods and Results Ligation of the left anterior descending artery was used to induce MI in an experimental rat model. Rats were divided into two groups: a control group that received saline solution (n = 16) and a group that received diacerein (80 mg/kg) daily (n = 10). After 4 weeks, the LV volume, cellular signaling, caspase 3 activity, and nuclear factor kappa B (NF-κB) transcription were compared between the two groups. After 4 weeks, end-diastolic and end-systolic LV volumes were reduced in the treatment group compared to the control group (p < .01 and p < .01, respectively). Compared to control rats, diacerein-treated rats exhibited less fibrosis in the LV (14.65%± 7.27% vs. 22.57%± 8.94%; p < .01), lower levels of caspase-3 activity, and lower levels of NF-κB p65 transcription. Conclusions Treatment with diacerein once a day for 4 weeks after MI improved ventricular remodeling by promoting lower end-systolic and end-diastolic LV volumes. Diacerein also reduced fibrosis in the LV. These effects might be associated with partial blockage of the NF-κB pathway. PMID:25816098

  7. 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.

  8. PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.

    PubMed

    Zhang, Hao; Wang, Zheng; Feng, Shou-Jie; Xu, Lei; Shi, He-Xian; Chen, Li-Li; Yuan, Guang-Da; Yan, Wei; Zhuang, Wei; Zhang, Yi-Qian; Zhang, Zhong-Ming; Dong, Hong-Yan

    2015-03-11

    Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.

  9. Myocardial Adeno-Associated Virus Serotype 6–βARKct Gene Therapy Improves Cardiac Function and Normalizes the Neurohormonal Axis in Chronic Heart Failure

    PubMed Central

    Rengo, Giuseppe; Lymperopoulos, Anastasios; Zincarelli, Carmela; Donniacuo, Maria; Soltys, Stephen; Rabinowitz, Joseph E.; Koch, Walter J.

    2009-01-01

    Background The upregulation of G protein–coupled receptor kinase 2 in failing myocardium appears to contribute to dysfunctional β-adrenergic receptor (βAR) signaling and cardiac function. The peptide βARKct, which can inhibit the activation of G protein–coupled receptor kinase 2 and improve βAR signaling, has been shown in transgenic models and short-term gene transfer experiments to rescue heart failure (HF). This study was designed to evaluate long-term βARKct expression in HF with the use of stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). Methods and Results In HF rats, we delivered βARKct or green fluorescent protein as a control via AAV6-mediated direct intramyocardial injection. We also treated groups with concurrent administration of the β-blocker metoprolol. We found robust and long-term transgene expression in the left ventricle at least 12 weeks after delivery. βARKct significantly improved cardiac contractility and reversed left ventricular remodeling, which was accompanied by a normalization of the neurohormonal (catecholamines and aldosterone) status of the chronic HF animals, including normalization of cardiac βAR signaling. Addition of metoprolol neither enhanced nor decreased βARKct-mediated beneficial effects, although metoprolol alone, despite not improving contractility, prevented further deterioration of the left ventricle. Conclusions Long-term cardiac AAV6-βARKct gene therapy in HF results in sustained improvement of global cardiac function and reversal of remodeling at least in part as a result of a normalization of the neurohormonal signaling axis. In addition, βARKct alone improves outcomes more than a β-blocker alone, whereas both treatments are compatible. These findings show that βARKct gene therapy can be of long-term therapeutic value in HF. PMID:19103992

  10. Exogenous apelin changes alpha and beta myosin heavy chain mRNA expression and improves cardiac function in PTU-induced hypothyroid rats.

    PubMed

    Faraji Shahrivar, Farzaneh; Badavi, Mohammad; Dianat, Mahin; Mard, Ali; Ahangarpour, Akram; Samarbaf-Zadeh, Alireza

    2016-12-20

    The most important conditions associated with hypothyroidism is the cardiac dysfunction. Apelin is an endogenous ligand, involved in energy storage and metabolism which improves cardiac contractility. This study was done to evaluate the effects of apelin, l-Thyroxin (T4) or a combination of both, on cardiac function and mRNA expression of two contractile proteins, α and β myosin heavy chain (α-MHC and β-MHC), in 6-propyl-2-thiouracil (PTU)-induced hypothyroid rats. Forty male Wistar rats were randomly assigned into five groups: Ctrl (Control), and 4 hypothyroid groups (H, HA, HT, and HAT). The Hypothyroid (H) group received 0.05% PTU in the drinking water for six weeks; the next 3 groups, along with PTU, received apelin (HA, 200μg/kg/day, ip), T4 (HT, 20μg/kg/day, gavage), or a combination of both drugs (HAT) for the last 2weeks (weeks 5 and 6). TSH and T4 were measured using ELISA kit. Isolated hearts of animals were perfused in Langendorff apparatus and left ventricular developed pressure, cardiac contractility, heart rate, rate pressure product and perfusion pressure were assessed using PowerLab ADInstruments. In addition α-MHC and β-MHC mRNA expression were evaluated by RT-PCR method in heart tissue. Apelin alone or accompanied by T4 significantly increased cardiac contractility and performance as compared to hypothyroid group. Apelin also significantly increased the alpha-MHC mRNA expression and in the presence of T4 significantly decreased beta-MHC mRNA expression. It seems that apelin alone may improve cardiac function in hypothyroid rats via genomic pathways.

  11. A novel antidote-controlled anticoagulant reduces thrombin generation and inflammation and improves cardiac function in cardiopulmonary bypass surgery.

    PubMed

    Nimjee, Shahid M; Keys, J R; Pitoc, G A; Quick, G; Rusconi, C P; Sullenger, Bruce A

    2006-09-01

    Heparin and protamine are the standard anticoagulant-antidote regimen used in almost every cardiopulmonary bypass (CPB) procedure even though both are associated with an array of complications and toxicities. Here we demonstrate that an anticoagulant aptamer-antidote pair targeting factor IXa can replace heparin and protamine in a porcine CPB model and also limit the adverse effects on thrombin generation, inflammation, and cardiac physiology associated with heparin and protamine use. These results demonstrate that targeting clotting factors upstream of thrombin in the coagulation cascade can potentially reduce the perioperative pathologies associated with CPB and suggest that the aptamer-antidote pair to FIXa may improve the outcome of patients undergoing CPB. In particular, this novel anticoagulant-antidote pair may prove to be useful in patients diagnosed with heparin-induced thrombocytopenia or those who have been sensitized to protamine, particularly patients who have insulin-dependent diabetes.

  12. Acute in vivo administration of a fish oil-containing emulsion improves post-ischemic cardiac function in n-3-depleted rats.

    PubMed

    Peltier, S; Malaisse, W J; Portois, L; Demaison, L; Novel-Chate, V; Chardigny, J M; Sebedio, J L; Carpentier, Y A; Leverve, X M

    2006-10-01

    A novel i.v. lipid preparation (MCT:FO) containing 80% medium chain-triacylglycerols and 20% fish oil was recently developed to rapidly replenish cell membrane phospholipids with omega 3 (n-3) polyunsaturated fatty acids (PUFA). In regard of this property, we investigated the effect of a single i.v. administration of MCT:FO on the recovery of cardiac function after ischemia in control and n-3-depleted rats. Results were compared with those obtained either with a control preparation, where FO was replaced by triolein (MCT:OO), or with saline. Saline (1 ml) or lipid preparation (also 1 ml) was injected as a bolus via the left saphenous vein. After 60 min the heart was removed and perfused for 20 min in normoxic conditions according to Langendorff. Thereafter, the heart was subjected to a 20 min zero-flow normothermic ischemia, followed by 40 min reperfusion. Cardiac mechanical and metabolic functions were monitored. In control rats, the previous administration of a lipid preparation (MCT:FO or MCT:OO) versus saline improved cardiac function during aerobic reperfusion post-ischemia. N-3-depleted rats showed decreased basal cardiac function and impaired recovery following ischemia. However, the bolus injection of MCT:FO opposed the deleterious effect of long-term n-3-deficiency and, in this respect, was superior to MCT:OO over the first 20 min of reperfusion. This novel approach to rapidly correct n-3 PUFA-deficiency might be clinically relevant and offer interesting perspectives in the management of acute ischemic accidents.

  13. 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

  14. Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model.

    PubMed

    Gautam, Milan; Fujita, Daiki; Kimura, Kazuhiro; Ichikawa, Hinako; Izawa, Atsushi; Hirose, Masamichi; Kashihara, Toshihide; Yamada, Mitsuhiko; Takahashi, Masafumi; Ikeda, Uichi; Shiba, Yuji

    2015-04-01

    The transplantation of adipose tissue-derived stem cells (ADSCs) improves cardiac contractility after myocardial infarction (MI); however, little is known about the electrophysiological consequences of transplantation. The purpose of this study was to clarify whether the transplantation of ADSCs increases or decreases the incidence of ventricular tachyarrhythmias (VT) in a rat model of MI. MI was induced experimentally by permanent occlusion of the left anterior descending artery of Lewis rats. ADSCs were harvested from GFP-transgenic rats, and were cultured until passage four. ADSCs (10×10(6)) resuspended in 100μL saline or pro-survival cocktail (PSC), which enhances cardiac graft survival, were injected directly into syngeneic rat hearts 1week after MI. The recipients of ADSCs suspended in PSC had a larger graft area compared with those receiving ASDCs suspended in saline at 1week post-transplantation (number of graft cells/section: 148.7±10.6 vs. 22.4±3.4, p<0.05, n=5/group). Thereafter, all ADSC recipients were transplanted with ASDCs in PSC. ADSCs were transplanted into infarcted hearts, and the mechanical and electrophysiological functions were assessed. Echocardiography revealed that ADSC recipients had improved contractile function compared with those receiving PSC vehicle (fractional shortening: 21.1±0.9 vs. 14.1±1.2, p<0.05, n≥12/group). Four weeks post-transplantation, VT was induced via in vivo programmed electrical stimulation. The recipients of ADSCs showed a significantly lower incidence of induced VT compared with the control (31.3% vs. 83.3%, p<0.05, n≥12/group). To understand the electrical activity following transplantation, we performed ex vivo optical mapping using a voltage sensitive dye, and found that ADSC transplantation decreased conduction velocity and its dispersion in the peri-infarct area. These results suggest that ADSC transplantation improved cardiac mechanical and electrophysiological functions in subacute MI.

  15. Prednisolone attenuates improvement of cardiac and skeletal contractile function and histopathology by lisinopril and spironolactone in the mdx mouse model of Duchenne muscular dystrophy.

    PubMed

    Janssen, Paul M L; Murray, Jason D; Schill, Kevin E; Rastogi, Neha; Schultz, Eric J; Tran, Tam; Raman, Subha V; Rafael-Fortney, Jill A

    2014-01-01

    Duchenne muscular dystrophy (DMD) is an inherited disease that causes striated muscle weakness. Recently, we showed therapeutic effects of the combination of lisinopril (L), an angiotensin converting enzyme (ACE) inhibitor, and spironolactone (S), an aldosterone antagonist, in mice lacking dystrophin and haploinsufficient for utrophin (utrn(+/-);mdx, het mice); both cardiac and skeletal muscle function and histology were improved when these mice were treated early with LS. It was unknown to what extent LS treatment is effective in the most commonly used DMD murine model, the mdx mouse. In addition, current standard-of-care treatment for DMD is limited to corticosteroids. Therefore, potentially useful alternative or additive drugs need to be both compared directly to corticosteroids and tested in presence of corticosteroids. We evaluated the effectiveness of this LS combination in the mdx mouse model both compared with corticosteroid treatment (prednisolone, P) or in combination (LSP). We tested the additional combinatorial treatment containing the angiotensin II receptor blocker losartan (T), which is widely used to halt and treat the developing cardiac dysfunction in DMD patients as an alternative to an ACE inhibitor. Peak myocardial strain rate, assessed by magnetic resonance imaging, showed a negative impact of P, whereas in both diaphragm and extensor digitorum longus (EDL) muscle contractile function was not significantly impaired by P. Histologically, P generally increased cardiac damage, estimated by percentage area infiltrated by IgG as well as by collagen staining. In general, groups that only differed in the presence or absence of P (i.e. mdx vs. P, LS vs. LSP, and TS vs. TSP) demonstrated a significant detrimental impact of P on many assessed parameters, with the most profound impact on cardiac pathology.

  16. Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats.

    PubMed

    Dolinsky, Vernon W; Jones, Kelvin E; Sidhu, Robinder S; Haykowsky, Mark; Czubryt, Michael P; Gordon, Tessa; Dyck, Jason R B

    2012-06-01

    Exercise training (ET) improves endurance capacity by increasing both skeletal muscle mitochondrial number and function, as well as contributing to favourable cardiac remodelling.Interestingly, some of the benefits of regular exercise can also be mimicked by the naturally occurring polyphenol, resveratrol (RESV). However, it is not known whether RESV enhances physiological adaptations to ET. To investigate this, male Wistar rats were randomly assigned to a control chow diet or a chow diet that contained RESV (4 g kg⁻¹ of diet) and subsequently subjected to a programme of progressive treadmill running for 12 weeks. ET-induced improvements in exercise performance were enhanced by 21% (P <0.001) by the addition of RESV to the diet. In soleus muscle, ET+RESV increased both the twitch (1.8-fold; P <0.05) and tetanic(1.2-fold; P <0.05) forces generated during isometric contraction, compared to ET alone. In vivo echocardiography demonstrated that ET+RESV also increased the resting left ventricular ejection fraction by 10% (P <0.05), and reduced left ventricular wall stress compared to ET alone.These functional changes were accompanied by increased cardiac fatty acid oxidation (1.2-fold;P <0.05) and favourable changes in cardiac gene expression and signal transduction pathways that optimized the utilization of fatty acids in ET+RESV compared to ET alone. Overall, our findings provide evidence that the capacity for fatty acid oxidation is augmented by the addition of RESV to the diet during ET, and that this may contribute to the improved physical performance of rats following ET.

  17. Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

    NASA Astrophysics Data System (ADS)

    Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

    2016-05-01

    Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.

  18. Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

    PubMed Central

    Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

    2016-01-01

    Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials. PMID:27184924

  19. 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.

  20. Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

    PubMed

    Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

    2016-09-01

    Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001), respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance.

  1. Soluble epoxide hydrolase inhibition improves coronary endothelial function and prevents the development of cardiac alterations in obese insulin-resistant mice

    PubMed Central

    Roche, Clothilde; Besnier, Marie; Cassel, Roméo; Harouki, Najah; Coquerel, David; Guerrot, Dominique; Nicol, Lionel; Loizon, Emmanuelle; Remy-Jouet, Isabelle; Morisseau, Christophe; Mulder, Paul; Ouvrard-Pascaud, Antoine; Madec, Anne-Marie; Richard, Vincent

    2015-01-01

    This study addressed the hypothesis that inhibiting the soluble epoxide hydrolase (sEH)-mediated degradation of epoxy-fatty acids, notably epoxyeicosatrienoic acids, has an additional impact against cardiovascular damage in insulin resistance, beyond its previously demonstrated beneficial effect on glucose homeostasis. The cardiovascular and metabolic effects of the sEH inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB; 10 mg/l in drinking water) were compared with those of the sulfonylurea glibenclamide (80 mg/l), both administered for 8 wk in FVB mice subjected to a high-fat diet (HFD; 60% fat) for 16 wk. Mice on control chow diet (10% fat) and nontreated HFD mice served as controls. Glibenclamide and t-AUCB similarly prevented the increased fasting glycemia in HFD mice, but only t-AUCB improved glucose tolerance and decreased gluconeogenesis, without modifying weight gain. Moreover, t-AUCB reduced adipose tissue inflammation, plasma free fatty acids, and LDL cholesterol and prevented hepatic steatosis. Furthermore, only the sEH inhibitor improved endothelium-dependent relaxations to acetylcholine, assessed by myography in isolated coronary arteries. This improvement was related to a restoration of epoxyeicosatrienoic acid and nitric oxide pathways, as shown by the increased inhibitory effects of the nitric oxide synthase and cytochrome P-450 epoxygenase inhibitors l-NA and MSPPOH on these relaxations. Moreover, t-AUCB decreased cardiac hypertrophy, fibrosis, and inflammation and improved diastolic function, as demonstrated by the increased E/A ratio (echocardiography) and decreased slope of the end-diastolic pressure-volume relation (invasive hemodynamics). These results demonstrate that sEH inhibition improves coronary endothelial function and prevents cardiac remodeling and diastolic dysfunction in obese insulin-resistant mice. PMID:25724490

  2. Spliced stromal cell-derived factor-1α analog stimulates endothelial progenitor cell migration and improves cardiac function in a dose-dependent manner after myocardial infarction

    PubMed Central

    Hiesinger, William; Frederick, John R.; Atluri, Pavan; McCormick, Ryan C.; Marotta, Nicole; Muenzer, Jeffrey R.; Woo, Y. Joseph

    2011-01-01

    Objectives Stromal cell-derived factor (SDF)-1α is a potent endogenous endothelial progenitor cell (EPC) chemokine and key angiogenic precursor. Recombinant SDF-1α has been demonstrated to improve neovasculogenesis and cardiac function after myocardial infarction (MI) but SDF-1α is a bulky protein with a short half-life. Small peptide analogs might provide translational advantages, including ease of synthesis, low manufacturing costs, and the potential to control delivery within tissues using engineered biomaterials. We hypothesized that a minimized peptide analog of SDF-1α, designed by splicing the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a truncated amino acid linker, would induce EPC migration and preserve ventricular function after MI. Methods EPC migration was first determined in vitro using a Boyden chamber assay. For in vivo analysis, male rats (n=48) underwent left anterior descending coronary artery ligation. At infarction, the rats were randomized into 4 groups and received peri-infarct intramyocardial injections of saline, 3 μg/kg of SDF-1α, 3 μg/kg of spliced SDF analog, or 6 μg/kg spliced SDF analog. After 4 weeks, the rats underwent closed chest pressure volume conductance catheter analysis. Results EPCs showed significantly increased migration when placed in both a recombinant SDF-1α and spliced SDF analog gradient. The rats treated with spliced SDF analog at MI demonstrated a significant dose-dependent improvement in end-diastolic pressure, stroke volume, ejection fraction, cardiac output, and stroke work compared with the control rats. Conclusions A spliced peptide analog of SDF-1α containing both the N- and C- termini of the native protein induced EPC migration, improved ventricular function after acute MI, and provided translational advantages compared with recombinant human SDF-1α. PMID:20951261

  3. p27 kip1 haplo-insufficiency improves cardiac function in early-stages of myocardial infarction by protecting myocardium and increasing angiogenesis by promoting IKK activation.

    PubMed

    Zhou, Ningtian; Fu, Yuxuan; Wang, Yunle; Chen, Pengsheng; Meng, Haoyu; Guo, Shouyu; Zhang, Min; Yang, Zhijian; Ge, Yingbin

    2014-08-07

    p27(kip1) (p27) is widely known as a potent cell cycle inhibitor in several organs, especially in the heart. However, its role has not been fully defined during the early phase of myocardial infarction (MI). In this study, we investigated the relationships between p27, vascular endothelial growth factor/hepatocyte growth factor (VEGF/HGF) and NF-κB in post-MI cardiac function repair both in vivo and in the hypoxia/ischemia-induced rat myocardiocyte model. In vivo, haplo-insufficiency of p27 improved cardiac function, diminished the infarct zone, protected myocardiocytes and increased angiogenesis by enhancing the production of VEGF/HGF. In vitro, the presence of conditioned medium from hypoxia/ischemia-induced p27 knockdown myocardiocytes reduced the injury caused by hypoxia/ischemia in myocardiocytes, and this effect was reversed by VEGF/HGF neutralizing antibodies, consistent with the cardioprotection being due to VEGF/HGF secretion. We also observed that p27 bound to IKK and that p27 haplo-insufficiency promoted IKK/p65 activation both in vivo and in vitro, thereby inducing the NF-κB downstream regulator, VEGF/HGF. Furthermore, IKKi and IKK inhibitor negated the effect of VEGF/HGF. Therefore, we conclude that p27 haplo-insufficiency protects against heart injury by VEGF/HGF mediated cardioprotection and increased angiogenesis through promoting IKK activation.

  4. Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes.

    PubMed

    Habibi, Javad; Aroor, Annayya R; Sowers, James R; Jia, Guanghong; Hayden, Melvin R; Garro, Mona; Barron, Brady; Mayoux, Eric; Rector, R Scott; Whaley-Connell, Adam; DeMarco, Vincent G

    2017-01-13

    Obese and diabetic individuals are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction. The impairments in diastolic relaxation are especially pronounced in obese and diabetic women and predict future cardiovascular disease (CVD) events in this population. Recent clinical data suggest sodium glucose transporter-2 (SGLT2) inhibition reduces CVD events in diabetic individuals, but the mechanisms of this CVD protection are unknown. To determine whether targeting SGLT2 improves diastolic relaxation, we utilized empagliflozin (EMPA) in female db/db mice. Eleven week old female db/db mice were fed normal mouse chow, with or without EMPA, for 5 weeks. Blood pressure (BP), HbA1c and fasting glucose were significantly increased in untreated db/db mice (DbC) (P < 0.01). EMPA treatment (DbE) improved glycemic indices (P < 0.05), but not BP (P > 0.05). At baseline, DbC and DbE had already established impaired diastolic relaxation as indicated by impaired septal wall motion (>tissue Doppler derived E'/A' ratio) and increased left ventricular (LV) filling pressure (function improved with EMPA treatment. In DbC, myocardial fibrosis was accompanied by increased expression of profibrotic/prohypertrophic proteins, serum/glucocorticoid regulated kinase 1 (SGK1) and the epithelial sodium channel (ENaC), and the development of these abnormalities were reduced with EMPA. DbC exhibited eccentric LV hypertrophy that was slightly improved by EMPA, indicated by a reduction in cardiomyocyte cross sectional area. In summary, EMPA improved glycemic indices along with diastolic relaxation, as well as SGK1/ENaC profibrosis signaling and associated interstitial fibrosis, all of which occurred in the absence of any changes in BP.

  5. Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: a randomized controlled trial.

    PubMed

    Hallsworth, Kate; Thoma, Christian; Hollingsworth, Kieren G; Cassidy, Sophie; Anstee, Quentin M; Day, Christopher P; Trenell, Michael I

    2015-12-01

    Although lifestyle changes encompassing weight loss and exercise remain the cornerstone of non-alcoholic fatty liver disease (NAFLD) management, the effect of different types of exercise on NAFLD is unknown. This study defines the effect of modified high-intensity interval training (HIIT) on liver fat, cardiac function and metabolic control in adults with NAFLD. Twenty-three patients with NAFLD [age 54±10 years, body mass index (BMI) 31±4 kg/m(2), intra-hepatic lipid >5%) were assigned to either 12 weeks HIIT or standard care (controls). HIIT involved thrice weekly cycle ergometry for 30-40 min. MRI and spectroscopy were used to assess liver fat, abdominal fat and cardiac structure/function/energetics. Glucose control was assessed by oral glucose tolerance test and body composition by air displacement plethysmography. Relative to control, HIIT decreased liver fat (11±5% to 8±2% compared with 10±4% to 10±4% P=0.019), whole-body fat mass (35±7 kg to 33±8 kg compared with 31±9 kg to 32±9 kg, P=0.013), alanine (52±29 units/l to 42±20 units/l compared with 47±22 units/l to 51±24 units/l, P=0.016) and aspartate aminotransferase (AST; 36±18 units/l to 33±15 units/l compared with 31±8 units/l to 35±8 units/l, P=0.017) and increased early diastolic filling rate (244±84 ml/s to 302±107 ml/s compared with 255±82 ml/s to 251±82 ml/s, P=0.018). There were no between groups differences in glucose control. Modified HIIT reduces liver fat and improves body composition alongside benefits to cardiac function in patients with NAFLD and should be considered as part of the broader treatment regimen by clinical care teams. ISRCTN trial ID: ISRCTN78698481.

  6. Improving safety for children with cardiac disease.

    PubMed

    Thiagarajan, Ravi R; Bird, Geoffrey L; Harrington, Karen; Charpie, John R; Ohye, Richard C; Steven, James M; Epstein, Michael; Laussen, Peter C

    2007-09-01

    improve the safety of patients include the leadership for the programme, the implementation of process design based on human limitations, the promotion of teamwork and function, the anticipation of unexpected events, and the creation of a learning environment. Much is yet to be learned about the risk and incidence of adverse events during hospitalization of children with congenital cardiac disease. Errors due to human factors, such as poor communication, poor coordination, and suboptimal team work, have shown to be important causes of adverse outcomes in children undergoing cardiac surgery, and should be a focus for improvement. Future research on evaluating causes and prevention of medical errors and adverse events in this population at high risk, and consuming high resources, is essential. Issues of inadequate safeguards for patients have been prominent in the media, and have been highlighted in reports from the Institute of Medicine. Our review discusses research on the causes of medical error, and proposes concepts to design successful programmes to improve safety for the patients on a local level.

  7. Tissue kallikrein-modified human endothelial progenitor cell implantation improves cardiac function via enhanced activation of akt and increased angiogenesis.

    PubMed

    Yao, Yuyu; Sheng, Zulong; Li, YeFei; Fu, Cong; Ma, Genshan; Liu, Naifeng; Chao, Julie; Chao, Lee

    2013-05-01

    Endothelial progenitor cells (EPCs) have been shown to enhance angiogenesis not only by incorporating into the vasculature but also by secreting cytokines, thereby serving as an ideal vehicle for gene transfer. As tissue kallikrein (TK) has pleiotropic effects in inhibiting apoptosis and oxidative stress, and promoting angiogenesis, we evaluated the salutary potential of kallikrein-modified human EPCs (hEPCs; Ad.hTK-hEPCs) after acute myocardial infarction (MI). We genetically modified hEPCs with a TK gene and evaluated cell survival, engraftment, revascularization, and functional improvement in a nude mouse left anterior descending ligation model. hEPCs were manipulated to overexpress the TK gene. In vitro, the antiapoptotic and paracrine effects were assessed under oxidative stress. TK protects hEPCs from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and -9, induction of Akt phosphorylation, and secretion of vascular endothelial growth factor. In vivo, the Ad.hTK-hEPCs were transplanted after MI via intracardiac injection. The surviving cells were tracked after transplantation using near-infrared optical imaging. Left ventricular (LV) function was evaluated by transthoracic echocardiography. Capillary density was quantified using immunohistochemical staining. Engrafted Ad.hTK-hEPCs exhibited advanced protection against ischemia by increasing LV ejection fraction. Compared with Ad.Null-hEPCs, transplantation with Ad.hTK-hEPCs significantly decreased cardiomyocyte apoptosis in association with increased retention of transplanted EPCs in the myocardium. Capillary density and arteriolar density in the infarct border zone was significantly higher in Ad.hTK-hEPC-transplanted mice than in Ad.Null-hEPC-treated mice. Transplanted hEPCs were clearly incorporated into CD31(+) capillaries. These results indicate that implantation of kallikrein-modified EPCs in the heart provides advanced benefits in protection against ischemia-induced MI by

  8. Improvement of cardiac screening in amateur athletes.

    PubMed

    Schmied, Christian M

    2015-01-01

    Although not performing on a professional level, amateur athletes, nevertheless, are participating in competitive sports and thus underlie a relevant risk for exercise-related SCD which implicates the need for an adequate pre-competition cardiac screening. As many amateur athletes belong to the category of "older" individuals, particularly CAD among male athletes with risk factors has to be targeted by the screening. However, the detection of clinically silent underlying coronary heart disease is challenging and cannot be accurately achieved by a standard screening provided to young athletes (history, clinical status, ECG). An extended work-up, at least, mandates the detection of cholesterol levels to estimate the individual cardiovascular risk. The fact that only less than 10% of Swiss amateur athletes have undergone cardiac screening led to various promising approaches to improve the awareness of the issue. Exemplarily, we successfully invented an "on-site" prevention campaign that positively influenced the attitude of the athletes towards cardiac screening.

  9. 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.

  10. 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

  11. Xenotransplantation of Human Cardiomyocyte Progenitor Cells Does Not Improve Cardiac Function in a Porcine Model of Chronic Ischemic Heart Failure. Results from a Randomized, Blinded, Placebo Controlled Trial

    PubMed Central

    Jansen of Lorkeers, Sanne J.; Gho, Johannes M. I. H.; Koudstaal, Stefan; van Hout, Gerardus P. J.; Zwetsloot, Peter Paul M.; van Oorschot, Joep W. M.; van Eeuwijk, Esther C. M.; Leiner, Tim; Hoefer, Imo E.; Goumans, Marie-José; Doevendans, Pieter A.; Sluijter, Joost P. G.; Chamuleau, Steven A. J.

    2015-01-01

    Background Recently cardiomyocyte progenitor cells (CMPCs) were successfully isolated from fetal and adult human hearts. Direct intramyocardial injection of human CMPCs (hCMPCs) in experimental mouse models of acute myocardial infarction significantly improved cardiac function compared to controls. Aim Here, our aim was to investigate whether xenotransplantation via intracoronary infusion of fetal hCMPCs in a pig model of chronic myocardial infarction is safe and efficacious, in view of translation purposes. Methods & Results We performed a randomized, blinded, placebo controlled trial. Four weeks after ischemia/reperfusion injury by 90 minutes of percutaneous left anterior descending artery occlusion, pigs (n = 16, 68.5 ± 5.4 kg) received intracoronary infusion of 10 million fetal hCMPCs or placebo. All animals were immunosuppressed by cyclosporin (CsA). Four weeks after infusion, endpoint analysis by MRI displayed no difference in left ventricular ejection fraction, left ventricular end diastolic and left ventricular end systolic volumes between both groups. Serial pressure volume (PV-)loop and echocardiography showed no differences in functional parameters between groups at any timepoint. Infarct size at follow-up, measured by late gadolinium enhancement MRI showed no difference between groups. Intracoronary pressure and flow measurements showed no signs of coronary obstruction 30 minutes after cell infusion. No premature death occurred in cell treated animals. Conclusion Xenotransplantation via intracoronary infusion of hCMPCs is feasible and safe, but not associated with improved left ventricular performance and infarct size compared to placebo in a porcine model of chronic myocardial infarction. PMID:26678993

  12. 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

  13. Transgenic overexpression of ribonucleotide reductase improves cardiac performance

    PubMed Central

    Nowakowski, Sarah G.; Kolwicz, Stephen C.; Korte, Frederick Steven; Luo, Zhaoxiong; Robinson-Hamm, Jacqueline N.; Page, Jennifer L.; Brozovich, Frank; Weiss, Robert S.; Tian, Rong; Murry, Charles E.; Regnier, Michael

    2013-01-01

    We previously demonstrated that cardiac myosin can use 2-deoxy-ATP (dATP) as an energy substrate, that it enhances contraction and relaxation with minimal effect on calcium-handling properties in vitro, and that contractile enhancement occurs with only minor elevation of cellular [dATP]. Here, we report the effect of chronically enhanced dATP concentration on cardiac function using a transgenic mouse that overexpresses the enzyme ribonucleotide reductase (TgRR), which catalyzes the rate-limiting step in de novo deoxyribonucleotide biosynthesis. Hearts from TgRR mice had elevated left ventricular systolic function compared with wild-type (WT) mice, both in vivo and in vitro, without signs of hypertrophy or altered diastolic function. Isolated cardiomyocytes from TgRR mice had enhanced contraction and relaxation, with no change in Ca2+ transients, suggesting targeted improvement of myofilament function. TgRR hearts had normal ATP and only slightly decreased phosphocreatine levels by 31P NMR spectroscopy, and they maintained rate responsiveness to dobutamine challenge. These data demonstrate long-term (at least 5-mo) elevation of cardiac [dATP] results in sustained elevation of basal left ventricular performance, with maintained β-adrenergic responsiveness and energetic reserves. Combined with results from previous studies, we conclude that this occurs primarily via enhanced myofilament activation and contraction, with similar or faster ability to relax. The data are sufficiently compelling to consider elevated cardiac [dATP] as a therapeutic option to treat systolic dysfunction. PMID:23530224

  14. Cardiac Resynchronization Therapy Leads to Improvements in Handgrip Strength

    PubMed Central

    Warriner, David R.; Lawford, Patricia; Sheridan, Paul J.

    2016-01-01

    Background A reduction in skeletal muscle performance measured by handgrip strength is common in heart failure. No trial has investigated the role of cardiac resynchronization therapy, which leads to improvements in cardiac performance, on the function of skeletal muscle in patients with heart failure. Methods Nineteen patients were recruited, 18 male, age 69 ± 8 years, New York Heart Association class II-IV, QRS duration 173 ± 21 ms and left ventricular ejection fraction 26±8%. Handgrip strength was measured at baseline before, and 6 and 12 months, following cardiac resynchronization therapy. Response was assessed using quality of life questionnaire, 6-minute walk distance, left ventricular end-diastolic volume, and cardiopulmonary exercise testing at the same time points. Results Fourteen patients were identified as responders, demonstrating significant improvements in all four markers of response. There was no significant difference at baseline in left or right handgrip strength between responders and non-responders. Compared to baseline, handgrip strength significantly increased in responders during follow-up, left (34.4 ± 11.4 to 40.3 ± 11.3 kgf, P < 0.001) and right (35.7 ± 12.5 to 42.2 ± 11.5 kgf, P < 0.001) at 12 months. No such improvement was seen in non-responders. Conclusions This study demonstrates that positive response to cardiac resynchronization therapy is associated with significant gains in handgrip strength, suggesting that cardiac resynchronization therapy may indirectly lead to secondary gains in skeletal muscle function. PMID:28197275

  15. Rapid Surface Cooling by ThermoSuit System Dramatically Reduces Scar Size, Prevents Post-Infarction Adverse Left Ventricular Remodeling, and Improves Cardiac Function in Rats

    PubMed Central

    Dai, Wangde; Herring, Michael J; Hale, Sharon L; Kloner, Robert A

    2015-01-01

    Background The long-term effects of transient hypothermia by the non-invasive ThermoSuit apparatus on myocardial infarct (MI) scar size, left ventricular (LV) remodeling, and LV function were assessed in rat MI model. Methods and Results Rats were randomized to normothermic or hypothermic groups (n=14 in each group) and subjected to 30 minutes coronary artery occlusion and 6 weeks of reperfusion. For hypothermia therapy, rats were placed into the ThermoSuit apparatus at 2 minutes after the onset of coronary artery occlusion, were taken out of the apparatus when the core body temperature reached 32°C (in ≈8 minutes), and were then allowed to rewarm. After 6 weeks of recovery, rats treated with hypothermia demonstrated markedly reduced scar size (expressed as % of left ventricular area: hypothermia, 6.5±1.1%; normothermia, 19.4±1.7%; P=1.3×10−6); and thicker anterior LV wall (hypothermia, 1.57±0.09 mm; normothermia, 1.07±0.05 mm; P=3.4×10−5); decreased postmortem left ventricular volume (hypothermia, 0.45±0.04 mL; normothermia, 0.6±0.03 mL; P=0.028); and better LV fractional shortening by echocardiography (hypothermia, 37.2±2.8%; normothermia, 18.9±2.3%; P=0.0002) and LV ejection fraction by LV contrast ventriculography (hypothermia, 66.8±2.3%; normothermia, 56.0±2.0%; P=0.0014). Conclusions Rapid, transient non-invasive surface cooling with the ThermoSuit apparatus in the acute phase of MI decreased scar size by 66.5%, attenuated adverse post-infarct left ventricular dilation and remodeling, and improved cardiac function in the chronic phase of experimental MI. PMID:26116692

  16. Improving Cell Engraftment in Cardiac Stem Cell Therapy

    PubMed Central

    Xie, Xiaoyun

    2016-01-01

    Myocardial infarction (MI) affects millions of people worldwide. MI causes massive cardiac cell death and heart function decrease. However, heart tissue cannot effectively regenerate by itself. While stem cell therapy has been considered an effective approach for regeneration, the efficacy of cardiac stem cell therapy remains low due to inferior cell engraftment in the infarcted region. This is mainly a result of low cell retention in the tissue and poor cell survival under ischemic, immune rejection and inflammatory conditions. Various approaches have been explored to improve cell engraftment: increase of cell retention using biomaterials as cell carriers; augmentation of cell survival under ischemic conditions by preconditioning cells, genetic modification of cells, and controlled release of growth factors and oxygen; and enhancement of cell survival by protecting cells from excessive inflammation and immune surveillance. In this paper, we review current progress, advantages, disadvantages, and potential solutions of these approaches. PMID:26783405

  17. 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.

  18. Cardiac shockwave therapy improves myocardial function in patients with refractory coronary artery disease by promoting VEGF and IL-8 secretion to mediate the proliferation of endothelial progenitor cells

    PubMed Central

    CAI, HONG-YAN; LI, LIN; GUO, TAO; WANG, YU; MA, TIE-KUN; XIAO, JIAN-MING; ZHAO, LING; FANG, YIN; YANG, PING; ZHAO, HU

    2015-01-01

    Cardiac shockwave therapy (CSWT) is a potential and effective remedy to promote revascularization in the ischemic myocardium of patients with refractory coronary heart disease (CHD). The technique is both safe and non-invasive; however, the underlying molecular mechanism remains unclear. The aim of this study was to evaluate the efficacy of CSWT in treating CHD patients and investigate a potential mechanism. A total of 26 patients with CHD were enrolled in the study, and CSWT was performed over a 3-month period. The efficacy of CSWT was assessed using several clinical parameters. Peripheral blood (PB) was collected prior to and following treatment. The number of circulating endothelial progenitor cells (EPCs) in the PB was counted using a flow cytometer, and the levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), stromal cell-derived factor 1 and matrix metalloproteinase 9 in the PB were analyzed. Mononuclear cells were isolated from the PB and cultured in vitro. The EPCs and EPC-colony forming units (EPC-CFUs) in the PB mononuclear cell culture were counted using an inverted phase contrast microscope. Following CSWT, the tested clinical parameters were significantly improved. The levels of circulating EPCs, VEGF and IL-8 in the PB were significantly increased, as were the EPCs and EPC-CFUs from the PB mononuclear cell culture. We suggest that EPC proliferation, mediated by VEGF and IL-8 secretion, may be among the potential mechanisms associated with CSWT. PMID:26668649

  19. Beetroot juice reduces infarct size and improves cardiac function following ischemia-reperfusion injury: Possible involvement of endogenous H2S.

    PubMed

    Salloum, Fadi N; Sturz, Gregory R; Yin, Chang; Rehman, Shabina; Hoke, Nicholas N; Kukreja, Rakesh C; Xi, Lei

    2015-05-01

    Ingestion of high dietary nitrate in the form of beetroot juice (BRJ) has been shown to exert antihypertensive effects in humans through increasing cyclic guanosine monophosphate (cGMP) levels. Since enhanced cGMP protects against myocardial ischemia-reperfusion (I/R) injury through upregulation of hydrogen sulfide (H2S), we tested the hypothesis that BRJ protects against I/R injury via H2S. Adult male CD-1 mice received either regular drinking water or those dissolved with BRJ powder (10 g/L, containing ∼ 0.7 mM nitrate). Seven days later, the hearts were explanted for molecular analyses. Subsets of mice were subjected to I/R injury by occlusion of the left coronary artery for 30 min and reperfusion for 24 h. A specific inhibitor of H2S producing enzyme--cystathionine-γ-lyase (CSE), DL-propargylglycine (PAG, 50 mg/kg) was given i.p. 30 min before ischemia. Myocardial infarct size was significantly reduced in BRJ-fed mice (15.8 ± 3.2%) versus controls (46.5 ± 3.5%, mean ± standard error [SE], n = 6/group, P < .05). PAG completely blocked the infarct-limiting effect of BRJ. Moreover, BRJ significantly preserved ventricular function following I/R. Myocardial levels of H2S and its putative protein target--vascular endothelial growth factor receptor 2 (VEGFR2) were significantly increased by BRJ intake, whereas CSE mRNA and protein content did not change. Interestingly, the BRJ-induced cardioprotection was not associated with elevated blood nitrate-nitrite levels following I/R nor induction of cardiac peroxiredoxin 5, a mitochondrial antioxidant enzyme previously linked to nitrate-induced cardioprotection. We conclude that BRJ ingestion protects against post-I/R myocardial infarction and ventricular dysfunction possibly through CSE-mediated endogenous H2S generation. BRJ could be a promising natural and inexpensive nutraceutical supplement to reduce cardiac I/R injury in patients.

  20. 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

  1. Electrospun nanofibrous sheets of collagen/elastin/polycaprolactone improve cardiac repair after myocardial infarction

    PubMed Central

    Liu, Yang; Xu, Yachen; Wang, Zhenhua; Wen, Dezhong; Zhang, Wentian; Schmull, Sebastian; Li, Haiyan; Chen, Yao; Xue, Song

    2016-01-01

    Electrospun nanofibrous sheets get increasing attention in myocardial infarction (MI) treatment due to their good cytocompatibility to deliver transplanted stem cells to infarcted areas and due to mechanical characteristics to support damaged tissue. Cardiac extracellular matrix is essential for implanted cells since it provides the cardiac microenvironment. In this study, we hypothesized high concentrations of cardiac nature protein (NP), namely elastin and collagen, in hybrid polycaprolactone (PCL) electrospun nanofibrous sheets could be effective as cardiac-mimicking patch. Optimal ratio of elastin and collagen with PCL in electrospun sheets (80% NP/PCL) was selected based on cytocompatibility and mechanical characteristics. Bone-marrow (BM) c-kit+ cells anchoring onto NP/PCL sheets exhibited increased proliferative capacity compared with those seeded on PCL in vitro. Moreover, we examined the improvement of cardiac function in MI mice by cell-seeded cardiac patch. Green Fluorescent Protein (GFP)-labeled BM c-kit+ cells were loaded on 80% NP/PCL sheets which was transplanted into MI mice. Both 80% NP/PCL and c-kit+-seeded 80% NP/PCL effectively improved cardiac function after 4 weeks of transplantation, with reduced infarction area and restricted LV remodeling. C-kit+-seeded 80% NP/PCL was even superior to the 80% NP/PCL alone and both superior to PCL. GFP+ cells were identified both in the sheets and local infarcted area where transplanted cells underwent cardiac differentiation after 4 weeks. To the best of our knowledge, this is the first report that sheets with high concentrations of nature proteins loaded with BM c-kit+ cells might be a novel promising candidate for tissue-engineered cardiac patch to improve cardiac repair after MI. PMID:27186292

  2. 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

  3. 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

  4. 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

  5. Tomato (Lycopersicon esculentum) Supplementation Induces Changes in Cardiac miRNA Expression, Reduces Oxidative Stress and Left Ventricular Mass, and Improves Diastolic Function

    PubMed Central

    Pereira, Bruna L. B.; Arruda, Fernanda C. O.; Reis, Patrícia P.; Felix, Tainara F.; Santos, Priscila P.; Rafacho, Bruna P.; Gonçalves, Andrea F.; Claro, Renan T.; Azevedo, Paula S.; Polegato, Bertha F.; Okoshi, Katashi; Fernandes, Ana A. H.; Paiva, Sergio A. R.; Zornoff, Leonardo A. M.; Minicucci, Marcos F.

    2015-01-01

    The aim of this study was to evaluate the effects of tomato supplementation on the normal rat heart and the role of oxidative stress in this scenario. Male Wistar rats were assigned to two groups: a control group (C; n = 16), in which animals received a control diet + 0.5 mL of corn oil/kg body weight/day, and a tomato group (T; n = 16), in which animals received a control diet supplemented with tomato +0.5 mL of corn oil/kg body weight/day. After three months, morphological, functional, and biochemical analyses were performed. Animals supplemented with tomato had a smaller left atrium diameter and myocyte cross-sectional area (CSA) compared to the control group (C group: 474 (415–539); T group: 273 (258–297) µm2; p = 0.004). Diastolic function was improved in rats supplemented with tomato. In addition, lipid hydroperoxide was lower (C group: 267 ± 46.7; T group: 219 ± 23.0 nmol/g; p = 0.039) in the myocardium of rats supplemented with tomato. Tomato intake was also associated with up-regulation of miR-107 and miR-486 and down-regulation of miR-350 and miR-872. In conclusion, tomato supplementation induces changes in miRNA expression and reduces oxidative stress. In addition, these alterations may be responsible for CSA reduction and diastolic function improvement. PMID:26610560

  6. Tomato (Lycopersicon esculentum) Supplementation Induces Changes in Cardiac miRNA Expression, Reduces Oxidative Stress and Left Ventricular Mass, and Improves Diastolic Function.

    PubMed

    Pereira, Bruna L B; Arruda, Fernanda C O; Reis, Patrícia P; Felix, Tainara F; Santos, Priscila P; Rafacho, Bruna P; Gonçalves, Andrea F; Claro, Renan T; Azevedo, Paula S; Polegato, Bertha F; Okoshi, Katashi; Fernandes, Ana A H; Paiva, Sergio A R; Zornoff, Leonardo A M; Minicucci, Marcos F

    2015-11-19

    The aim of this study was to evaluate the effects of tomato supplementation on the normal rat heart and the role of oxidative stress in this scenario. Male Wistar rats were assigned to two groups: a control group (C; n = 16), in which animals received a control diet + 0.5 mL of corn oil/kg body weight/day, and a tomato group (T; n = 16), in which animals received a control diet supplemented with tomato +0.5 mL of corn oil/kg body weight/day. After three months, morphological, functional, and biochemical analyses were performed. Animals supplemented with tomato had a smaller left atrium diameter and myocyte cross-sectional area (CSA) compared to the control group (C group: 474 (415-539); T group: 273 (258-297) µm²; p = 0.004). Diastolic function was improved in rats supplemented with tomato. In addition, lipid hydroperoxide was lower (C group: 267 ± 46.7; T group: 219 ± 23.0 nmol/g; p = 0.039) in the myocardium of rats supplemented with tomato. Tomato intake was also associated with up-regulation of miR-107 and miR-486 and down-regulation of miR-350 and miR-872. In conclusion, tomato supplementation induces changes in miRNA expression and reduces oxidative stress. In addition, these alterations may be responsible for CSA reduction and diastolic function improvement.

  7. 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

  8. 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).

  9. 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.

  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. 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.

  12. Mimicking isovolumic contraction with combined electromechanical stimulation improves the development of engineered cardiac constructs.

    PubMed

    Morgan, Kathy Ye; Black, Lauren Deems

    2014-06-01

    Electrical and mechanical stimulation have both been used extensively to improve the function of cardiac engineered tissue as each of these stimuli is present in the physical environment during normal development in vivo. However, to date, there has been no direct comparison between electrical and mechanical stimulation and current published data are difficult to compare due to the different systems used to create the engineered cardiac tissue and the different measures of functionality studied as outcomes. The goals of this study were twofold. First, we sought to directly compare the effects of mechanical and electrical stimulation on engineered cardiac tissue. Second, we aimed to determine the importance of the timing of the two stimuli in relation to each other in combined electromechanical stimulation. We hypothesized that delaying electrical stimulation after the beginning of mechanical stimulation to mimic the biophysical environment present during isovolumic contraction would improve construct function by improving proteins responsible for cell-cell communication and contractility. To test this hypothesis, we created a bioreactor system that would allow us to electromechanically stimulate engineered tissue created from neonatal rat cardiac cells entrapped in fibrin gel during 2 weeks in culture. Contraction force was higher for all stimulation groups as compared with the static controls, with the delayed combined stimulation constructs having the highest forces. Mechanical stimulation alone displayed increased final cell numbers but there were no other differences between electrical and mechanical stimulation alone. Delayed combined stimulation resulted in an increase in SERCA2a and troponin T expression levels, which did not happen with synchronous combined stimulation, indicating that the timing of combined stimulation is important to maximize the beneficial effect. Increases in Akt protein expression levels suggest that the improvements are at least in

  13. Mimicking Isovolumic Contraction with Combined Electromechanical Stimulation Improves the Development of Engineered Cardiac Constructs

    PubMed Central

    Morgan, Kathy Ye

    2014-01-01

    Electrical and mechanical stimulation have both been used extensively to improve the function of cardiac engineered tissue as each of these stimuli is present in the physical environment during normal development in vivo. However, to date, there has been no direct comparison between electrical and mechanical stimulation and current published data are difficult to compare due to the different systems used to create the engineered cardiac tissue and the different measures of functionality studied as outcomes. The goals of this study were twofold. First, we sought to directly compare the effects of mechanical and electrical stimulation on engineered cardiac tissue. Second, we aimed to determine the importance of the timing of the two stimuli in relation to each other in combined electromechanical stimulation. We hypothesized that delaying electrical stimulation after the beginning of mechanical stimulation to mimic the biophysical environment present during isovolumic contraction would improve construct function by improving proteins responsible for cell–cell communication and contractility. To test this hypothesis, we created a bioreactor system that would allow us to electromechanically stimulate engineered tissue created from neonatal rat cardiac cells entrapped in fibrin gel during 2 weeks in culture. Contraction force was higher for all stimulation groups as compared with the static controls, with the delayed combined stimulation constructs having the highest forces. Mechanical stimulation alone displayed increased final cell numbers but there were no other differences between electrical and mechanical stimulation alone. Delayed combined stimulation resulted in an increase in SERCA2a and troponin T expression levels, which did not happen with synchronous combined stimulation, indicating that the timing of combined stimulation is important to maximize the beneficial effect. Increases in Akt protein expression levels suggest that the improvements are at least in

  14. 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

  15. 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

  16. Cardiac auscultation in sports medicine: strategies to improve clinical care.

    PubMed

    Barrett, Michael J; Ayub, Bilal; Martinez, Matthew W

    2012-01-01

    Cardiac auscultation is an important part of the preparticipation physical examination of athletes. Sudden death remains a rare but tragic event among athletes. The most common cause of sudden death among young athletes in the United States continues to be hypertrophic cardiomyopathy, which may or may not present with a typical heart murmur. Many clinicians do not possess sufficient proficiency in recognizing abnormal heart murmurs. New insights in the field of auditory learning suggest that cardiac auscultation is more of a technical skill than an intellectual one. Intensive repetition of abnormal heart murmurs has been shown to improve proficiency in cardiac auscultation markedly. Sample audio files of two important murmurs, i.e., an innocent murmur and hypertrophic cardiomyopathy, are provided online with this review.

  17. Resuscitation review to improve nursing performance during cardiac arrest.

    PubMed

    Carpico, Bronwynne; Jenkins, Peggy

    2011-01-01

    The purpose of this study was to evaluate the effect of Resuscitation Review Simulation Education (RRSE) on improving adherence to hospital protocols and American Heart Association (AHA) resuscitation standards. Prior to implementing the RRSE on two nursing units, performance was evaluated during a simulated cardiac arrest using a mannequin and comparing performance against AHA algorithms. Performance was measured at two separate periods: preintervention and 3 months after the intervention. Both units improved overall scores after the RRSE.

  18. 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.

  19. 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

  20. 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…

  1. Rosuvastatin improves myocardial and neurological outcomes after asphyxial cardiac arrest and cardiopulmonary resuscitation in rats.

    PubMed

    Qiu, Yun; Wu, Yichen; Meng, Min; Luo, Man; Zhao, Hongmei; Sun, Hong; Gao, Sumin

    2017-03-01

    Rosuvastatin, a potent HMG-CoA reductase inhibitor, is cholesterol-lowering drugs and reduce the risk of myocardial infarction and stroke. This study is to explore whether rosuvastatin improves outcomes after cardiac arrest in rats. Male Sprague-Dawley rats were subjected to 8min of cardiac arrest (CA) by asphyxia and randomly assigned to three experimental groups immediately following successful resuscitation: Sham; Control; and Rosuvastatin. The survival, hemodynamics, myocardial function, neurological outcomes and apoptosis were assessed. The 7-d survival rate was greater in the rosuvastatin treated group compared to the Control group (P=0.019 by log-rank test). Myocardial function, as measured by cardiac output and ejection fraction, was significantly impaired after CA and notably improved in the animals treated with rosuvastatin beginning at 60min after return of spontaneous circulation (ROSC) (P<0.05). Moreover, rosuvastatin treatment significantly ameliorated brain injury after ROSC, which was characterized by the increase of neurological function scores, and reduction of brain edema in cortex and hippocampus (P<0.05). Meanwhile, the levels of cardiac troponin T and neuron-specific enolase and the caspase-3 activity were significantly decreased in the Rosuvastatin group when compared with the Control group (P<0.05). In conclusion, rosuvastatin treatment substantially improves the 7-d survival rate as well as myocardial function and neurological outcomes after ROSC.

  2. Using Data to Improve Quality: the Pediatric Cardiac Care Consortium.

    PubMed

    Moller, James H

    2016-01-01

    A program to collect and analyze cardiac catheterization, electrophysiologic studies and cardiac operations in children was initiated in 1982. The purpose was to help centers compare their experience and outcomes with a group of centers to determine areas where their performance might improve. Cardiac centers became members of the Pediatric Cardiac Care Consortium and submitted demographic data and copies of procedure reports regularly to a central office. Data were extracted from the reports, coded by trained coders and entered into a computer database. Annually, the data were analyzed to compare the experience of an individual center with that of the entire group of centers. The annual data were adjusted for severity on the basis of eight factors selected after discussion with participants in the Consortium. Adjustment was by multivariate analysis. Reports were prepared for each center and distributed at an annual meeting. The data were used by centers to review operations where the mortality rate exceeded +2 standard deviations of the group. With discussion, the center staff often initiated changes to improve outcome. The outcome could then be monitored by the annual reports. Our data were also utilized in the creation of the Risk Adjustment for Surgery for Congenital Heart Disease (RACHS)-1 categories of disease severity. The mortality rates of our centers were comparable with the combined hospital discharge data from New York, Massachusetts, and California. From 1982 through 2007, the mortality rates of our centers dropped for each RACHS-1 category, falling to less than 1% for categories 1 and 2 for the last 5-year period. During the 25 years, we received data from 52 centers about 137 654 patients who underwent 117 756 cardiac operations.

  3. 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.

  4. Improvements in kidney transplantation from donors after cardiac death.

    PubMed

    Hoogland, E R Pieter; Snoeijs, Maarten G J; Habets, Margot A W; Brandsma, D Steven; Peutz-Kootstra, Carine J; Christiaans, Maarten H L; van Heurn, L W Ernest

    2013-01-01

    To reduce the growing waiting list for kidney transplantation, we explored the limits of kidney transplantation from donors after cardiac death by liberally accepting marginal donor kidneys for transplantation. As the percentage of primary non-function (PNF) increased, we evaluated our transplantation program and implemented changes to reduce the high percentage of PNF in 2005, followed by a second evaluation over the period 2006-2009. Recipients of a kidney from a donor after cardiac death between 1998 and 2005 were analyzed, with PNF as outcome measure. During the period 2002-2005, the percentage of PNF increased and crossed the upper control limits of 12% which was considered as unacceptably high. After implementation of changes, this percentage was reduced to 5%, without changing the number of kidney transplantations from donors after cardiac death. Continuous monitoring of the quality of care is essential as the boundaries of organ donation and transplantation are sought. Meticulous donor, preservation, and recipient management make extension of the donor potential possible, with good results for the individual recipient. Liberal use of kidneys from donors after cardiac death may contribute to a reduction in the waiting list for kidney transplantation and dialysis associated mortality.

  5. Direct cardiac injection of G-CSF mobilized bone-marrow stem-cells improves ventricular function in old myocardial infarction.

    PubMed

    Archundia, Abel; Aceves, José Luis; López-Hernández, Manuel; Alvarado, Martha; Rodriguez, Emma; Díaz Quiroz, Guillermo; Páez, Araceli; Rojas, Felipe Masso; Montaño, Luis Felipe

    2005-12-05

    Autologous transplant of bone marrow stem cells (BMSC), although extremely useful after acute myocardial events, has not been evaluated in patients with old (>one-year-old) myocardial infarction. Our aim was to determine if CD34(+)-enriched peripheral-blood cells, obtained by apheresis, injected directly into the severely damaged myocardium of five patients with old myocardial infarction could restore depressed myocardial function. We found that 28 weeks after revascularization and peri-infarction injection of the enriched CD34(+) peripheral mononuclear cells, ventricular hemodynamic parameters that included left ventricular ejection fraction, left ventricular diastolic volume, ventricular systolic volume and left ventricular diastolic diameter approximated normal values and there was no restenosis; two patients have been followed for >52 weeks and their parameters are within normal values. In conclusion, intramyocardial injection of easily obtained CD34(+) enriched peripheral blood cells represent an encouraging procedure for patients with severely scarred and dysfunctional myocardium.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. Pulsatile reperfusion after cardiac arrest improves neurologic outcome.

    PubMed Central

    Anstadt, M P; Stonnington, M J; Tedder, M; Crain, B J; Brothers, M F; Hilleren, D J; Rahija, R J; Menius, J A; Lowe, J E

    1991-01-01

    Cardiopulmonary bypass (CPB) using nonpulsatile flow (NPF) is advocated for refractory cardiac arrest. This study examined cerebral outcome after resuscitation with pulsatile flow (PF) versus NPF. Dogs arrested for 12.5 minute were reperfused with NPF (n = 11) using roller pump CPB or PF (n = 11) using mechanical biventricular cardiac massage. Pump flows were similar between groups; however early arterial pressures were greater during PF versus NPF, *p less than 0.05. Circulatory support was weaned at 60 minutes' reperfusion. Neurologic recovery of survivors (n = 16) was significantly better after PF versus NPF, *p = 0.01. The presence of brain lesions on magnetic resonance images did not significantly differ between groups at 7 days. Brain then were removed and regions examined for ischemic changes. Loss of CA1 pyramidal neurons was more severe after NPF versus PF, +p = 0.009. Ischemic changes were more frequent after NPF in the caudate nucleus (+p = 0.009) and watershed regions of the cerebral cortex (+p = 0.062), compared with PF. These results demonstrate that PF improves cerebral resuscitation when treating cardiac arrest with mechanical circulatory support (* = MANOVA with repeated measures, + = categorical data analysis. Images Fig. 5. Fig. 7. PMID:1953100

  15. Improving Cardiac Surgical Care: A Work Systems Approach

    PubMed Central

    Wiegmann, Douglas A.; Eggman, Ashley A.; ElBardissi, Andrew W.; Henrickson, Sarah E.; Sundt, Thoralf M.

    2010-01-01

    Over the past 50 years, significant improvements in cardiac surgical care have been achieved. Nevertheless, surgical errors that significantly impact patient safety continue to occur. In order to further improve surgical outcomes, patient safety programs must focus on rectifying work system factors in the operating room (OR) that negatively impact the delivery of reliable surgical care. The goal of this paper is to provide an integrative review of specific work system factors in the OR that may directly impact surgical care processes, as well as the subsequent recommendations that have been put forth to improve surgical outcomes and patient safety. The important role that surgeons can play in facilitating work system changes in the OR is also discussed. The paper concludes with a discussion of the challenges involved in assessing the impact that interventions have on improving surgical care. Opportunities for future research are also highlighted throughout the paper. PMID:20202623

  16. Biologically improved nanofibrous scaffolds for cardiac tissue engineering.

    PubMed

    Bhaarathy, V; Venugopal, J; Gandhimathi, C; Ponpandian, N; Mangalaraj, D; Ramakrishna, S

    2014-11-01

    Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(l-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering.

  17. Music Improves Subjective Feelings Leading to Cardiac Autonomic Nervous Modulation: A Pilot Study

    PubMed Central

    Kume, Satoshi; Nishimura, Yukako; Mizuno, Kei; Sakimoto, Nae; Hori, Hiroshi; Tamura, Yasuhisa; Yamato, Masanori; Mitsuhashi, Rika; Akiba, Keigo; Koizumi, Jun-ichi; Watanabe, Yasuyoshi; Kataoka, Yosky

    2017-01-01

    It is widely accepted that listening to music improves subjective feelings and reduces fatigue sensations, and different kinds of music lead to different activations of these feelings. Recently, cardiac autonomic nervous modulation has been proposed as a useful objective indicator of fatigue. However, scientific considerations of the relation between feelings of fatigue and cardiac autonomic nervous modulation while listening to music are still lacking. In this study, we examined which subjective feelings of fatigue are related to participants' cardiac autonomic nervous function while they listen to music. We used an album of comfortable and relaxing environmental music, with blended sounds from a piano and violin as well as natural sound sources. We performed a crossover trial of environmental music and silent sessions for 20 healthy subjects, 12 females, and 8 males, after their daily work shift. We measured changes in eight types of subjective feelings, including healing, fatigue, sleepiness, relaxation, and refreshment, using the KOKORO scale, a subjective mood measurement system for self-reported feelings. Further, we obtained measures of cardiac autonomic nervous function on the basis of heart rate variability before and after the sessions. During the music session, subjective feelings significantly shifted toward healing and a secure/relaxed feeling and these changes were greater than those in the silent session. Heart rates (ΔHR) in the music session significantly decreased compared with those in the silent session. Other cardiac autonomic parameters such as high-frequency (HF) component and the ratio of low-frequency (LF) and HF components (LF/HF) were similar in the two sessions. In the linear regression analysis of the feelings with ΔHR and changes in LF/HF (ΔLF/HF), increases and decreases in ΔHR were correlated to the feeling axes of Fatigue-Healing and Anxiety/Tension–Security/Relaxation, whereas those in ΔLF/HF were related to the feeling axes

  18. Music Improves Subjective Feelings Leading to Cardiac Autonomic Nervous Modulation: A Pilot Study.

    PubMed

    Kume, Satoshi; Nishimura, Yukako; Mizuno, Kei; Sakimoto, Nae; Hori, Hiroshi; Tamura, Yasuhisa; Yamato, Masanori; Mitsuhashi, Rika; Akiba, Keigo; Koizumi, Jun-Ichi; Watanabe, Yasuyoshi; Kataoka, Yosky

    2017-01-01

    It is widely accepted that listening to music improves subjective feelings and reduces fatigue sensations, and different kinds of music lead to different activations of these feelings. Recently, cardiac autonomic nervous modulation has been proposed as a useful objective indicator of fatigue. However, scientific considerations of the relation between feelings of fatigue and cardiac autonomic nervous modulation while listening to music are still lacking. In this study, we examined which subjective feelings of fatigue are related to participants' cardiac autonomic nervous function while they listen to music. We used an album of comfortable and relaxing environmental music, with blended sounds from a piano and violin as well as natural sound sources. We performed a crossover trial of environmental music and silent sessions for 20 healthy subjects, 12 females, and 8 males, after their daily work shift. We measured changes in eight types of subjective feelings, including healing, fatigue, sleepiness, relaxation, and refreshment, using the KOKORO scale, a subjective mood measurement system for self-reported feelings. Further, we obtained measures of cardiac autonomic nervous function on the basis of heart rate variability before and after the sessions. During the music session, subjective feelings significantly shifted toward healing and a secure/relaxed feeling and these changes were greater than those in the silent session. Heart rates (ΔHR) in the music session significantly decreased compared with those in the silent session. Other cardiac autonomic parameters such as high-frequency (HF) component and the ratio of low-frequency (LF) and HF components (LF/HF) were similar in the two sessions. In the linear regression analysis of the feelings with ΔHR and changes in LF/HF (ΔLF/HF), increases and decreases in ΔHR were correlated to the feeling axes of Fatigue-Healing and Anxiety/Tension-Security/Relaxation, whereas those in ΔLF/HF were related to the feeling axes

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Remote Postconditioning Alone and Combined with Hypothermia Improved Postresuscitation Cardiac and Neurological Outcomes in Swine.

    PubMed

    Xu, Jiefeng; Huang, Zeng; Ye, Sen; Wang, Moli; Fang, Ya; Li, Zilong

    2016-01-01

    Objective. Previously, we demonstrated that remote ischemic postconditioning (RIpostC) improved postresuscitation myocardial and cerebral functions in rat. Here, we investigated the effects of RIpostC alone and combined with therapeutic hypothermia (TH) on cardiac and neurological outcomes after CPR in swine. Methods. Twenty-one pigs were subjected to 10 mins of VF and then 5 mins of CPR. The animals were randomized to receive RIpostC alone, or its combination with TH, or sham control. RIpostC was induced by 4 cycles of limb ischemia followed by reperfusion. TH was implemented by surface cooling to reach a temperature of 32-34°C. Results. During 72 hrs after resuscitation, lower level of cardiac troponin I and greater stroke volume and global ejection fraction were observed in animals that received RIpostC when compared to the control. RIpostC also decreased serum levels of neuron-specific enolase and S100B and increased neurologic alertness score after resuscitation. The combination of RIpostC and TH resulted in greater improvement in cardiac and neurological outcomes than RIpostC alone. Conclusion. RIpostC was conducive to improving postresuscitation myocardial and cerebral functions and reducing their organ injuries. Its combination with TH further enhanced its protective effects.

  10. Remote Postconditioning Alone and Combined with Hypothermia Improved Postresuscitation Cardiac and Neurological Outcomes in Swine

    PubMed Central

    Xu, Jiefeng; Huang, Zeng; Ye, Sen; Wang, Moli; Fang, Ya

    2016-01-01

    Objective. Previously, we demonstrated that remote ischemic postconditioning (RIpostC) improved postresuscitation myocardial and cerebral functions in rat. Here, we investigated the effects of RIpostC alone and combined with therapeutic hypothermia (TH) on cardiac and neurological outcomes after CPR in swine. Methods. Twenty-one pigs were subjected to 10 mins of VF and then 5 mins of CPR. The animals were randomized to receive RIpostC alone, or its combination with TH, or sham control. RIpostC was induced by 4 cycles of limb ischemia followed by reperfusion. TH was implemented by surface cooling to reach a temperature of 32–34°C. Results. During 72 hrs after resuscitation, lower level of cardiac troponin I and greater stroke volume and global ejection fraction were observed in animals that received RIpostC when compared to the control. RIpostC also decreased serum levels of neuron-specific enolase and S100B and increased neurologic alertness score after resuscitation. The combination of RIpostC and TH resulted in greater improvement in cardiac and neurological outcomes than RIpostC alone. Conclusion. RIpostC was conducive to improving postresuscitation myocardial and cerebral functions and reducing their organ injuries. Its combination with TH further enhanced its protective effects. PMID:28097144

  11. 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

  12. 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

  13. Does repair of pectus excavatum improve cardiopulmonary function?

    PubMed

    Jayaramakrishnan, Kumara; Wotton, Robin; Bradley, Amy; Naidu, Babu

    2013-06-01

    A best evidence topic was written according to a structured protocol. The question addressed was 'Does repair of pectus excavatum (PE) improve cardiopulmonary function?' One hundred and sixty-eight papers were found using the reported search, 19 level III evidence papers and three meta-analyses were relevant. Studies were divided into four groups based on the surgical technique applied and pulmonary and cardiac functions in these groups were analysed. The meta-analyses show conflicting results for improvements in pulmonary and cardiac functions when comparing surgical techniques, while four more recent studies show improved long-term results using the Nuss technique. The best evidence of papers studying the PE repair using the minimally invasive Nuss technique demonstrates a decrease in pulmonary function during the early postoperative period, however, there is a small but significant improvement during the late postoperative period and after bar removal. The best evidence for cardiac function in this group suggests an early improvement that is sustained during further follow-up. The best evidence of papers studying the PE repair using the Ravitch technique shows that pulmonary function decreased during the early postoperative period, however, there is a small but significant improvement during the late postoperative period. The best evidence for cardiac function in this group suggests an early improvement that is sustained during further follow-up. The best evidence of papers studying the PE repair using other techniques (modified Daniel's technique, modified Baronofsky's technique, sterno-costal turn-over technique and sterno-costal elevation technique) or where surgical techniques used were not described (preceding year 1985) suggests that there is no improvement in pulmonary function after surgery. There is some evidence that certain aspects of cardiac function improved after surgery in this group.

  14. Snf1-related kinase improves cardiac mitochondrial efficiency and decreases mitochondrial uncoupling

    PubMed Central

    Rines, Amy K.; Chang, Hsiang-Chun; Wu, Rongxue; Sato, Tatsuya; Khechaduri, Arineh; Kouzu, Hidemichi; Shapiro, Jason; Shang, Meng; Burke, Michael A.; Jiang, Xinghang; Chen, Chunlei; Rawlings, Tenley A.; Lopaschuk, Gary D.; Schumacker, Paul T.; Abel, E. Dale; Ardehali, Hossein

    2017-01-01

    Ischaemic heart disease limits oxygen and metabolic substrate availability to the heart, resulting in tissue death. Here, we demonstrate that the AMP-activated protein kinase (AMPK)-related protein Snf1-related kinase (SNRK) decreases cardiac metabolic substrate usage and mitochondrial uncoupling, and protects against ischaemia/reperfusion. Hearts from transgenic mice overexpressing SNRK have decreased glucose and palmitate metabolism and oxygen consumption, but maintained power and function. They also exhibit decreased uncoupling protein 3 (UCP3) and mitochondrial uncoupling. Conversely, Snrk knockout mouse hearts have increased glucose and palmitate oxidation and UCP3. SNRK knockdown in cardiac cells decreases mitochondrial efficiency, which is abolished with UCP3 knockdown. We show that Tribbles homologue 3 (Trib3) binds to SNRK, and downregulates UCP3 through PPARα. Finally, SNRK is increased in cardiomyopathy patients, and SNRK reduces infarct size after ischaemia/reperfusion. SNRK also decreases cardiac cell death in a UCP3-dependent manner. Our results suggest that SNRK improves cardiac mitochondrial efficiency and ischaemic protection. PMID:28117339

  15. Human heart valve-derived scaffold improves cardiac repair in a murine model of myocardial infarction

    PubMed Central

    Wan, Long; Chen, Yao; Wang, Zhenhua; Wang, Weijun; Schmull, Sebastian; Dong, Jun; Xue, Song; Imboden, Hans; Li, Jun

    2017-01-01

    Cardiac tissue engineering using biomaterials with or without combination of stem cell therapy offers a new option for repairing infarcted heart. However, the bioactivity of biomaterials remains to be optimized because currently available biomaterials do not mimic the biochemical components as well as the structural properties of native myocardial extracellular matrix. Here we hypothesized that human heart valve-derived scaffold (hHVS), as a clinically relevant novel biomaterial, may provide the proper microenvironment of native myocardial extracellular matrix for cardiac repair. In this study, human heart valve tissue was sliced into 100 μm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function and reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first clinically relevant evidence for translating the hHVS-based biomaterials into clinical strategies to treat myocardial infarction. PMID:28051180

  16. Adaptive servo ventilation improves cardiac dysfunction and prognosis in chronic heart failure patients with Cheyne-Stokes respiration.

    PubMed

    Yoshihisa, Akiomi; Shimizu, Takeshi; Owada, Takashi; Nakamura, Yuichi; Iwaya, Shoji; Yamauchi, Hiroyuki; Miyata, Makiko; Hoshino, Yasuto; Sato, Takamasa; Suzuki, Satoshi; Sugimoto, Koichi; Yamaki, Takayoshi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

    2011-01-01

    Cheyne-Stokes respiration (CSR) is often observed in patients with chronic heart failure (CHF). Although adaptive servo ventilation (ASV) is effective for CSR, it remains unclear whether ASV improves the cardiac function and prognosis of patients with CHF and CSR.Sixty patients with CHF and CSR (mean left ventricular ejection fraction 38.7%, mean apnea hypopnea index 36.8 times/hour, mean central apnea index 19.1 times/hour) were enrolled in this study. Patients were divided into two groups: 23 patients treated with ASV (ASV group) and 37 patients treated without ASV (Non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels and echocardiography were performed before, 3 and 6 months after treatments in each group. Patients were followed-up for cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, NYHA functional class, BNP levels, cardiac systolic and diastolic function were significantly improved with ASV treatment for 6 months. In contrast, none of these parameters changed in the Non-ASV group. Importantly, Kaplan-Meier analysis clearly demonstrated that the event-free rate was significantly higher in the ASV group than in the Non-ASV group.Adaptive servo ventilation improves cardiac function and prognosis in patients with chronic heart failure and Cheyne-Stokes respiration.

  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. 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

  19. Endothelial p53 Deletion Improves Angiogenesis and Prevents Cardiac Fibrosis and Heart Failure Induced by Pressure Overload in Mice

    PubMed Central

    Gogiraju, Rajinikanth; Xu, Xingbo; Bochenek, Magdalena L.; Steinbrecher, Julia H.; Lehnart, Stephan E.; Wenzel, Philip; Kessel, Michael; Zeisberg, Elisabeth M.; Dobbelstein, Matthias; Schäfer, Katrin

    2015-01-01

    Background Cardiac dysfunction developing in response to chronic pressure overload is associated with apoptotic cell death and myocardial vessel rarefaction. We examined whether deletion of tumor suppressor p53 in endothelial cells may prevent the transition from cardiac hypertrophy to heart failure. Methods and Results Mice with endothelial‐specific deletion of p53 (End.p53‐KO) were generated by crossing p53fl/fl mice with mice expressing Cre recombinase under control of an inducible Tie2 promoter. Cardiac hypertrophy was induced by transverse aortic constriction. Serial echocardiography measurements revealed improved cardiac function in End.p53‐KO mice that also exhibited better survival. Cardiac hypertrophy was associated with increased p53 levels in End.p53‐WT controls, whereas banded hearts of End.p53‐KO mice exhibited lower numbers of apoptotic endothelial and non‐endothelial cells and altered mRNA levels of genes regulating cell cycle progression (p21), apoptosis (Puma), or proliferation (Pcna). A higher cardiac capillary density and improved myocardial perfusion was observed, and pharmacological inhibition or genetic deletion of p53 also promoted endothelial sprouting in vitro and new vessel formation following hindlimb ischemia in vivo. Hearts of End.p53‐KO mice exhibited markedly less fibrosis compared with End.p53‐WT controls, and lower mRNA levels of p53‐regulated genes involved in extracellular matrix production and turnover (eg, Bmp‐7, Ctgf, or Pai‐1), or of transcription factors involved in controlling mesenchymal differentiation were observed. Conclusions Our analyses reveal that accumulation of p53 in endothelial cells contributes to blood vessel rarefaction and fibrosis during chronic cardiac pressure overload and suggest that endothelial cells may be a therapeutic target for preserving cardiac function during hypertrophy. PMID:25713289

  20. 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.

  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. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Moxonidine improves cardiac structure and performance in SHR through inhibition of cytokines, p38 MAPK and Akt

    PubMed Central

    Aceros, H; Farah, G; Cobos-Puc, L; Stabile, AM; Noiseux, N; Mukaddam-Daher, S

    2011-01-01

    BACKGROUND AND PURPOSE Regression of left ventricular hypertrophy by moxonidine, a centrally acting sympatholytic imidazoline compound, results from a sustained reduction of DNA synthesis and transient stimulation of DNA fragmentation. Because apoptosis of cardiomyocytes may lead to contractile dysfunction, we investigated in spontaneously hypertensive rats (SHR), time- and dose-dependent effects of in vivo moxonidine treatment on cardiac structure and function as well as on the inflammatory process and signalling proteins involved in cardiac cell survival/death. EXPERIMENTAL APPROACH 12 week old SHR received moxonidine at 0, 100 and 400 µg·kg−1·h−1, s.c., for 1 and 4 weeks. Cardiac function was evaluated by echocardiography; plasma cytokines were measured by elisa and hearts were collected for histological assessment of fibrosis and measurement of cardiac proteins by Western blotting. Direct effects of moxonidine on cardiac cell death and underlying mechanisms were investigated in vitro by flow cytometry and Western blotting. KEY RESULTS After 4 weeks, the sub-hypotensive dose of moxonidine (100 µg) reduced heart rate and improved global cardiac performance, reduced collagen deposition, regressed left ventricular hypertrophy, inhibited Akt and p38 MAPK phosphorylation, and attenuated circulating and cardiac cytokines. The 400 µg dose resulted in similar effects but of a greater magnitude, associated with blood pressure reduction. In vitro, moxonidine inhibited norepinephrine-induced neonatal cardiomyocyte mortality but increased fibroblast mortality, through I1-receptor activation and differential effects on downstream Akt and p38 MAPK. CONCLUSIONS AND IMPLICATIONS While the antihypertensive action of centrally acting imidazoline compounds is appreciated, new cardiac-selective I1-receptor agonists may confer additional benefit. PMID:21426316

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. The Society of Thoracic Surgeons Adult Cardiac Surgery Database: The Driving Force for Improvement in Cardiac Surgery.

    PubMed

    Winkley Shroyer, Annie Laurie; Bakaeen, Faisal; Shahian, David M; Carr, Brendan M; Prager, Richard L; Jacobs, Jeffrey P; Ferraris, Victor; Edwards, Fred; Grover, Frederick L

    2015-01-01

    Initiated in 1989, the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) includes more than 1085 participating centers, representing 90%-95% of current US-based adult cardiac surgery hospitals. Since its inception, the primary goal of the STS ACSD has been to use clinical data to track and improve cardiac surgical outcomes. Patients' preoperative risk characteristics, procedure-related processes of care, and clinical outcomes data have been captured and analyzed, with timely risk-adjusted feedback reports to participating providers. In 2006, STS initiated an external audit process to evaluate STS ACSD completeness and accuracy. Given the extremely high inter-rater reliability and completeness rates of STS ACSD, it is widely regarded as the "gold standard" for benchmarking cardiac surgery risk-adjusted outcomes. Over time, STS ACSD has expanded its quality horizons beyond the traditional focus on isolated, risk-adjusted short-term outcomes such as perioperative morbidity and mortality. New quality indicators have evolved including composite measures of key processes of care and outcomes (risk-adjusted morbidity and risk-adjusted mortality), longer-term outcomes, and readmissions. Resource use and patient-reported outcomes would be added in the future. These additional metrics provide a more comprehensive perspective on quality as well as additional end points. Widespread acceptance and use of STS ACSD has led to a cultural transformation within cardiac surgery by providing nationally benchmarked data for internal quality assessment, aiding data-driven quality improvement activities, serving as the basis for a voluntary public reporting program, advancing cardiac surgery care through STS ACSD-based research, and facilitating data-driven informed consent dialogues and alternative treatment-related discussions.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death

    PubMed Central

    Toldo, Stefano; Quader, Mohammed; Salloum, Fadi N.; Mezzaroma, Eleonora; Abbate, Antonio

    2016-01-01

    Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response. PMID:27322252

  5. Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death.

    PubMed

    Toldo, Stefano; Quader, Mohammed; Salloum, Fadi N; Mezzaroma, Eleonora; Abbate, Antonio

    2016-06-17

    Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response.

  6. 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.

  7. A recirculating cooling system for improved topical cardiac hypothermia.

    PubMed

    Rosenfeldt, F L; Fambiatos, A; Pastoriza-Pinol, J; Stirling, G R

    1981-10-01

    A simple system is described that recirculates cooling fluid for topical cardiac hypothermia. This disposable system can produce a flow of 1,500 ml/min at 2 degrees to 4 degrees C. The recirculating cooler produced significantly lower myocardial temperatures than a conventional fluid-discard system in 22 patients having coronary operation. This system has been used as part of the technique of hypothermic cardioplegia in more than 600 patients. During various cardiac procedures, septal temperatures were maintained well below 20 degrees C for 60 minutes or more without the need to reinfuse the cardioplegic solution.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Leonurine (SCM-198) improves cardiac recovery in rat during chronic infarction.

    PubMed

    Liu, XinHua; Pan, LiLong; Gong, QiHai; Zhu, YiZhun

    2010-12-15

    Leonurine, an alkaloid typically found in Herba leonuri, is known to have both antioxidant and cardioprotective properties. In the present study, we investigated the cardioprotective mechanism of leonurine the in vivo rat model of chronic myocardial ischemia and in vitro H9c2 cardiac myocyte model of oxidative stress. Myocardial ischemia was induced by ligating the left anterior descending coronary artery. Rats were divided into sham, myocardial ischemia+saline, and myocardial ischemia+leonurine (15 mg/kg/day). Cardiac function was recorded by catheterization. Apoptosis-related factor vascular endothelial growth factor (VEGF), survivin, Bcl-2 and Bax and pro-survival signaling pathways Akt, hypoxia inducible factor (HIF)-1α were measured by Western blotting or RT-PCR. Our results showed leonurine significantly improved myocardial function as evidenced by the decreased left ventricle end-diastolic pressure and the increased +dP/dt. Interestingly, leonurine increased the phosphorylation of Akt, the protein and gene expression of Bcl-2, but it reduced the protein and gene expression of Bax in vivo. Meanwhile leonurine significantly increased Akt phosphorylation in a concentration-dependent manner in H9c2 cardiac myocyte induced by oxidative stress in vitro, which was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. Furthermore, leonurine not only increased the expression of HIF-1α but also the expression of survivin and VEGF. The results of present study demonstrated, for the first time that leonurine has potent anti-apoptotic effects after chronic myocardial ischemia mediated by activating the PI3K/Akt signaling pathway. Angiogenic mechanisms may be partially responsible for such an effect, which needs to be studied further.

  19. 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

  20. 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

    index (LV-ESVI). This improved to 91.9% with inclusion of the RMS-P2PD biomarker and was congruent with improvements in both sensitivity for classifying patients and specificity for identifying asymptomatic controls from 82.6% up to 95.7%. RMS-P2PD, when contrasted against a collective normal reference, is a promising biomarker to investigate further in its utility for identifying quantitative signs of pathological endocardial function which may boost standard image makers as precursors of declining cardiac performance.

  1. 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.

  2. 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

  3. Macrophage Migration Inhibitory Factor (MIF) Deficiency Exacerbates Aging-Induced Cardiac Remodeling and Dysfunction Despite Improved Inflammation: Role of Autophagy Regulation

    PubMed Central

    Xu, Xihui; Pang, Jiaojiao; Chen, Yuguo; Bucala, Richard; Zhang, Yingmei; Ren, Jun

    2016-01-01

    Aging leads to unfavorable geometric and functional sequelae in the heart. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) plays a role in the maintenance of cardiac homeostasis under stress conditions although its impact in cardiac aging remains elusive. This study was designed to evaluate the role of MIF in aging-induced cardiac anomalies and the underlying mechanism involved. Cardiac geometry, contractile and intracellular Ca2+ properties were examined in young (3–4 mo) or old (24 mo) wild type and MIF knockout (MIF−/−) mice. Our data revealed that MIF knockout exacerbated aging-induced unfavorable structural and functional changes in the heart. The detrimental effect of MIF knockout was associated with accentuated loss in cardiac autophagy with aging. Aging promoted cardiac inflammation, the effect was attenuated by MIF knockout. Intriguingly, aging-induced unfavorable responses were reversed by treatment with the autophagy inducer rapamycin, with improved myocardial ATP availability in aged WT and MIF−/− mice. Using an in vitro model of senescence, MIF knockdown exacerbated doxorubicin-induced premature senescence in H9C2 myoblasts, the effect was ablated by MIF replenishment. Our data indicated that MIF knockout exacerbates aging-induced cardiac remodeling and functional anomalies despite improved inflammation, probably through attenuating loss of autophagy and ATP availability in the heart. PMID:26940544

  4. Macrophage Migration Inhibitory Factor (MIF) Deficiency Exacerbates Aging-Induced Cardiac Remodeling and Dysfunction Despite Improved Inflammation: Role of Autophagy Regulation.

    PubMed

    Xu, Xihui; Pang, Jiaojiao; Chen, Yuguo; Bucala, Richard; Zhang, Yingmei; Ren, Jun

    2016-03-04

    Aging leads to unfavorable geometric and functional sequelae in the heart. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) plays a role in the maintenance of cardiac homeostasis under stress conditions although its impact in cardiac aging remains elusive. This study was designed to evaluate the role of MIF in aging-induced cardiac anomalies and the underlying mechanism involved. Cardiac geometry, contractile and intracellular Ca(2+) properties were examined in young (3-4 mo) or old (24 mo) wild type and MIF knockout (MIF(-/-)) mice. Our data revealed that MIF knockout exacerbated aging-induced unfavorable structural and functional changes in the heart. The detrimental effect of MIF knockout was associated with accentuated loss in cardiac autophagy with aging. Aging promoted cardiac inflammation, the effect was attenuated by MIF knockout. Intriguingly, aging-induced unfavorable responses were reversed by treatment with the autophagy inducer rapamycin, with improved myocardial ATP availability in aged WT and MIF(-/-) mice. Using an in vitro model of senescence, MIF knockdown exacerbated doxorubicin-induced premature senescence in H9C2 myoblasts, the effect was ablated by MIF replenishment. Our data indicated that MIF knockout exacerbates aging-induced cardiac remodeling and functional anomalies despite improved inflammation, probably through attenuating loss of autophagy and ATP availability in the heart.

  5. 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.

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

    PubMed Central

    2003-01-01

    extent of hyperenhancement was significantly related to the likelihood of improvement in contractility after revascularization. However, the LVEF in the patient population was 43% prior to revascularization. It is important to know whether the technique has the same degree of accuracy in patients who have more severe LV dysfunction and who would most benefit from an assessment of myocardial viability. “Substantial” viability used as a measure of a patient’s ability to recover after revascularization has not been definitively reported (how much viability is enough?). Patients with severe LV dysfunction are more likely to have mixtures of surviving myocardium, including normal, infarcted, stunned and hibernating myocardium (Cowley et al., 1999). This may lead to a lack of homogeneity of response to testing and to revascularization and contribute to inter- and intra-study differences. There is a need for a large prospective study with adequate follow-up time for patients with CAD and LV dysfunction (LVEF<35%) comparing MRI and an alternate imaging technique. There is some evidence that MRI has comparable sensitivity, specificity and accuracy to PET for determining myocardial viability. However, there is a lack of evidence comparing the accuracy of these two techniques to predict LV function recovery. In addition, some studies refer to PET as the gold standard for the assessment of myocardial viability. Therefore, PET may be an ideal noninvasive imaging comparator to MRI for a prospective study with follow-up. To date, there is a lack of cost-effectiveness analyses (or any economic analyses) of functional cardiac MRI versus an alternate noninvasive imaging method for the assessment of myocardial viability/perfusion. Conclusion There is some evidence that the accuracy of functional cardiac MRI compares favourably with alternate imaging techniques for the assessment of myocardial viability and perfusion. There is insufficient evidence whether functional cardiac MRI can

  7. 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

  8. 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.

  9. Overexpression of connexin 43 using a retroviral vector improves electrical coupling of skeletal myoblasts with cardiac myocytes in vitro

    PubMed Central

    Tolmachov, Oleg; Ma, Yu-Ling; Themis, Michael; Patel, Pravina; Spohr, Hilmar; MacLeod, Kenneth T; Ullrich, Nina D; Kienast, Yvonne; Coutelle, Charles; Peters, Nicholas S

    2006-01-01

    Background Organ transplantation is presently often the only available option to repair a damaged heart. As heart donors are scarce, engineering of cardiac grafts from autologous skeletal myoblasts is a promising novel therapeutic strategy. The functionality of skeletal muscle cells in the heart milieu is, however, limited because of their inability to integrate electrically and mechanically into the myocardium. Therefore, in pursuit of improved cardiac integration of skeletal muscle grafts we sought to modify primary skeletal myoblasts by overexpression of the main gap-junctional protein connexin 43 and to study electrical coupling of connexin 43 overexpressing myoblasts to cardiac myocytes in vitro. Methods To create an efficient means for overexpression of connexin 43 in skeletal myoblasts we constructed a bicistronic retroviral vector MLV-CX43-EGFP expressing the human connexin 43 cDNA and the marker EGFP gene. This vector was employed to transduce primary rat skeletal myoblasts in optimised conditions involving a concomitant use of the retrovirus immobilising protein RetroNectin® and the polycation transduction enhancer Transfectam®. The EGFP-positive transduced cells were then enriched by flow cytometry. Results More than four-fold overexpression of connexin 43 in the transduced skeletal myoblasts, compared with non-transduced cells, was shown by Western blotting. Functionality of the overexpressed connexin 43 was demonstrated by microinjection of a fluorescent dye showing enhanced gap-junctional intercellular transfer in connexin 43 transduced myoblasts compared with transfer in non-transduced myoblasts. Rat cardiac myocytes were cultured in multielectrode array culture dishes together with connexin 43/EGFP transduced skeletal myoblasts, control non-transduced skeletal myoblasts or alone. Extracellular field action potential activation rates in the co-cultures of connexin 43 transduced skeletal myoblasts with cardiac myocytes were significantly higher than

  10. Haemodynamic improvement of older, previously replaced mechanical mitral valves by removal of the subvalvular pannus in redo cardiac surgery.

    PubMed

    Kim, Jong Hun; Kim, Tae Youn; Choi, Jong Bum; Kuh, Ja Hong

    2017-01-01

    Patients requiring redo cardiac surgery for diseased heart valves other than mitral valves may show increased pressure gradients and reduced valve areas of previously placed mechanical mitral valves due to subvalvular pannus formation. We treated four women who had mechanical mitral valves inserted greater than or equal to 20 years earlier and who presented with circular pannus that protruded into the lower margin of the valve ring but did not impede leaflet motion. Pannus removal improved the haemodynamic function of the mitral valve.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Combination of European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Cardiac Surgery Score (CASUS) to Improve Outcome Prediction in Cardiac Surgery

    PubMed Central

    Doerr, Fabian; Heldwein, Matthias B.; Bayer, Ole; Sabashnikov, Anton; Weymann, Alexander; Dohmen, Pascal M.; Wahlers, Thorsten; Hekmat, Khosro

    2015-01-01

    Background We hypothesized that the combination of a preoperative and a postoperative scoring system would improve the accuracy of mortality prediction and therefore combined the preoperative ‘additive EuroSCORE‘ (European system for cardiac operative risk evaluation) with the postoperative ‘additive CASUS’ (Cardiac Surgery Score) to form the ‘modified CASUS’. Material/Methods We included all consecutive adult patients after cardiac surgery during January 2007 and December 2010 in our prospective study. Our single-centre study was conducted in a German general referral university hospital. The original additive and the ‘modified CASUS’ were tested using calibration and discrimination statistics. We compared the area under the curve (AUC) of the receiver characteristic curves (ROC) by DeLong’s method and calculated overall correct classification (OCC) values. Results The mean age among the total of 5207 patients was 67.2±10.9 years. Whilst the ICU mortality was 5.9% we observed a mean length of ICU stay of 4.6±7.0 days. Both models demonstrated excellent discriminatory power (mean AUC of ‘modified CASUS’: ≥0.929; ‘additive CASUS’: ≥0.920), with no significant differences according to DeLong. Neither model showed a significant p-value (<0.05) in calibration. We detected the best OCC during the 2nd day (modified: 96.5%; original: 96.6%). Conclusions Our ‘additive’ and ‘modified’ CASUS are reasonable overall predictors. We could not detect any improvement in the accuracy of mortality prediction in cardiac surgery by combining a preoperative and a postoperative scoring system. A separate calculation of the two individual elements is therefore recommended. PMID:26279053

  17. Combination of European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Cardiac Surgery Score (CASUS) to Improve Outcome Prediction in Cardiac Surgery.

    PubMed

    Doerr, Fabian; Heldwein, Matthias B; Bayer, Ole; Sabashnikov, Anton; Weymann, Alexander; Dohmen, Pascal M; Wahlers, Thorsten; Hekmat, Khosro

    2015-08-17

    BACKGROUND We hypothesized that the combination of a preoperative and a postoperative scoring system would improve the accuracy of mortality prediction and therefore combined the preoperative 'additive EuroSCORE' (European system for cardiac operative risk evaluation) with the postoperative 'additive CASUS' (Cardiac Surgery Score) to form the 'modified CASUS'. MATERIAL AND METHODS We included all consecutive adult patients after cardiac surgery during January 2007 and December 2010 in our prospective study. Our single-centre study was conducted in a German general referral university hospital. The original additive and the 'modified CASUS' were tested using calibration and discrimination statistics. We compared the area under the curve (AUC) of the receiver characteristic curves (ROC) by DeLong's method and calculated overall correct classification (OCC) values. RESULTS The mean age among the total of 5207 patients was 67.2 ± 10.9 years. Whilst the ICU mortality was 5.9% we observed a mean length of ICU stay of 4.6 ± 7.0 days. Both models demonstrated excellent discriminatory power (mean AUC of 'modified CASUS': ≥ 0.929; 'additive CASUS': ≥ 0.920), with no significant differences according to DeLong. Neither model showed a significant p-value (<0.05) in calibration. We detected the best OCC during the 2nd day (modified: 96.5%; original: 96.6%). CONCLUSIONS Our 'additive' and 'modified' CASUS are reasonable overall predictors. We could not detect any improvement in the accuracy of mortality prediction in cardiac surgery by combining a preoperative and a postoperative scoring system. A separate calculation of the two individual elements is therefore recommended.

  18. 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.

  19. 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.

  20. 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.

  1. Brain-derived neurotrophic factor does not improve recovery after cardiac arrest in rats.

    PubMed

    Callaway, Clifton W; Ramos, Ramiro; Logue, Eric S; Betz, Amy E; Wheeler, Matthew; Repine, Melissa J

    2008-11-07

    Increased brain-derived neurotrophic factor (BDNF) levels and extracellular-signal regulated kinase (ERK) signaling are associated with reduced brain injury after cerebral ischemia. In particular, mild hypothermia after cardiac arrest increases BDNF and ERK signaling. This study tested whether intracerebroventricular infusions (0.025 microg/h x 3 days) of BDNF also improved recovery of rats resuscitated from cardiac arrest and maintained at 37 degrees C. BDNF infusions initiated at the time of cardiac arrest did not alter survival, neurological recovery, or histological injury. Separate experiments confirmed that BDNF infusions increased tissue levels of BDNF. However, these infusions did not increase ERK activation in hippocampus. These data suggest that increased BDNF levels are not sufficient to explain the beneficial effects of mild hypothermia after cardiac arrest, and that exogenous BDNF administration does not increase extracellular ERK signaling.

  2. Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: Modulation of cardiac PPAR-{alpha}-mediated transcription of fatty acid metabolic genes

    SciTech Connect

    Huang, Tom H.-W.; Yang Qinglin; Harada, Masaki; Uberai, Jasna; Radford, Jane; Li, George Q.; Yamahara, Johji; Roufogalis, Basil D.; Li Yuhao . E-mail: yuhao@pharm.usyd.edu.au

    2006-01-15

    Excess cardiac triglyceride accumulation in diabetes and obesity induces lipotoxicity, which predisposes the myocytes to death. On the other hand, increased cardiac fatty acid (FA) oxidation plays a role in the development of myocardial dysfunction in diabetes. PPAR-{alpha} plays an important role in maintaining homeostasis of lipid metabolism. We have previously demonstrated that the extract from Salacia oblonga root (SOE), an Ayurvedic anti-diabetic and anti-obesity medicine, improves hyperlipidemia in Zucker diabetic fatty (ZDF) rats (a genetic model of type 2 diabetes and obesity) and possesses PPAR-{alpha} activating properties. Here we demonstrate that chronic oral administration of SOE reduces cardiac triglyceride and FA contents and decreases the Oil red O-stained area in the myocardium of ZDF rats, which parallels the effects on plasma triglyceride and FA levels. Furthermore, the treatment suppressed cardiac overexpression of both FA transporter protein-1 mRNA and protein in ZDF rats, suggesting inhibition of increased cardiac FA uptake as the basis for decreased cardiac FA levels. Additionally, the treatment also inhibited overexpression in ZDF rat heart of PPAR-{alpha} mRNA and protein and carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase mRNAs and restored the downregulated acetyl-CoA carboxylase mRNA. These results suggest that SOE inhibits cardiac FA oxidation in ZDF rats. Thus, our findings suggest that improvement by SOE of excess cardiac lipid accumulation and increased cardiac FA oxidation in diabetes and obesity occurs by reduction of cardiac FA uptake, thereby modulating cardiac PPAR-{alpha}-mediated FA metabolic gene transcription.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Short Duration Combined Mild Hypothermia Improves Resuscitation Outcomes in a Porcine Model of Prolonged Cardiac Arrest

    PubMed Central

    Yu, Tao; Yang, Zhengfei; Li, Heng; Ding, Youde; Huang, Zitong; Li, Yongqin

    2015-01-01

    Objective. In this study, our aim was to investigate the effects of combined hypothermia with short duration maintenance on the resuscitation outcomes in a porcine model of ventricular fibrillation (VF). Methods. Fourteen porcine models were electrically induced with VF and untreated for 11 mins. All animals were successfully resuscitated manually and then randomized into two groups: combined mild hypothermia (CH group) and normothermia group (NT group). A combined hypothermia of ice cold saline infusion and surface cooling was implemented in the animals of the CH group and maintained for 4 hours. The survival outcomes and neurological function were evaluated every 24 hours until a maximum of 96 hours. Neuron apoptosis in hippocampus was analyzed. Results. There were no significant differences in baseline physiologies and primary resuscitation outcomes between both groups. Obvious improvements of cardiac output were observed in the CH group at 120, 180, and 240 mins following resuscitation. The animals demonstrated better survival at 96 hours in the CH group when compared to the NT group. In comparison with the NT group, favorable neurological functions were observed in the CH group. Conclusion. Short duration combined cooling initiated after resuscitation improves survival and neurological outcomes in a porcine model of prolonged VF. PMID:26558261

  8. Using motion correction to improve real-time cardiac MRI reconstruction

    NASA Astrophysics Data System (ADS)

    Bilgazyev, E.; Uyanik, I.; Unan, M.; Shah, Dipan; Tsekos, Nikolaos V.; Leiss, E. L.

    2013-12-01

    Cardiac gating or breath-hold MRI acquisition is challenging. In particular, data collected in a short amount of time might be insufficient for the diagnosis of patients with impaired breath-holding capabilities and/or arrhythmia. A major challenge in cardiac MRI is the motion of the heart itself, the pulsate blood flow, and the respiratory motion. Furthermore, the motion of the diaphragm in the chest moving up and down gets translated to the heart when a patient breathes. Therefore, artifacts arise due to the changes in signal intensity or phase as a function of time, resulting in blurry images. This paper describes a novel reconstruction strategy for real time cardiac MRI without requiring the use of an electro-cardiogram or of breath holding. In this research we focused on automation and evaluation of the performance of our proposed method in real time MRI data to ensure a good basis for the signal extraction. Hence, it assists in the reconstruction. The proposed method enables one to extract cardiac beating waveforms directly from real-time cardiac MRI series collected from freely breathing patients and without cardiac gating. Our method only requires minimal user involvement as initialization step. Thereafter, the method follows the registered area in every frame and updates itself.

  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. 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

  11. 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.

  12. Improved outcomes of renal transplantation from cardiac death donors: a 30-year single center experience.

    PubMed

    Tojimbara, T; Fuchinoue, S; Iwadoh, K; Koyama, I; Sannomiya, A; Kato, Y; Nanmoku, K; Kai, K; Nakajima, I; Toma, H; Teraoka, S

    2007-03-01

    Outcomes of renal transplantation from donation after cardiac death (DCD) donors over 30 years were analyzed. Between 1975 and 2004, 256 renal transplantations from DCD donors were performed. The recipients were divided into four groups according to a time period as follows: 1975-1979 (Group 1; n = 18), 1980-1989 (Group 2; n = 81), 1990-1999 (Group 3; n = 84) and 2000-2004 (Group 4; n = 73). Of the 256 transplanted kidneys from DCD donors, 38 (15%) functioned immediately after transplantation. The incidence of delayed graft function (DGF) was 72%. Warm ischemic time and total ischemic time were 7.4 +/- 9.4 min and 11.9 +/- 5.6 h, respectively. The overall graft survival rates at 1, 5 and 10 years were 80%, 72% and 53%, respectively. Graft survival rates in each group have continually improved over time (5-year graft survival; 23% vs. 64% vs. 74% vs. 91%, respectively). However, there was no significant difference in graft survival rates between the groups of patients who survived with a functioning graft for more than 1 year. A multivariate Cox regression analysis showed acute rejection and donor age to be independently associated with graft outcome. DCD donors are a valuable source of kidneys for transplantation with promising long-term outcomes.

  13. 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.

  14. 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

  15. 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

  16. Helping Family Physicians Improve Their Cardiac Auscultation Skills with an Interactive CD-ROM.

    ERIC Educational Resources Information Center

    Roy, Douglas; Sargeant, Joan; Gray, Jean; Hoyt, Brian; Allen, Michael; Fleming, Michael

    2002-01-01

    Physicians (n=42) studied cardiac auscultation using a 15-hour CD-ROM program. Nine months later, 21 who completed a posttest showed significant improvement in identifying heart sounds. CDs were valued for opportunities to review material at an individual pace. Lack of computer skills hindered use. (Contains 26 references.) (SK)

  17. 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

  18. 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

  19. 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

  20. 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

  1. Thermodynamic analysis questions claims of improved cardiac efficiency by dietary fish oil

    PubMed Central

    Goo, Eden; Chapman, Brian; Hickey, Anthony J.R.

    2016-01-01

    Studies in the literature describe the ability of dietary supplementation by omega-3 fish oil to increase the pumping efficiency of the left ventricle. Here we attempt to reconcile such studies with our own null results. We undertake a quantitative analysis of the improvement that could be expected theoretically, subject to physiological constraints, by posing the following question: By how much could efficiency be expected to increase if inefficiencies could be eliminated? Our approach utilizes thermodynamic analyses to investigate the contributions, both singly and collectively, of the major components of cardiac energetics to total cardiac efficiency. We conclude that it is unlikely that fish oils could achieve the required diminution of inefficiencies without greatly compromising cardiac performance. PMID:27574288

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity

    PubMed Central

    Lovelock, Joshua D.; Monasky, Michelle M.; Jeong, Euy-Myoung; Lardin, Harvey A.; Liu, Hong; Patel, Bindiya G.; Taglieri, Domenico M.; Gu, Lianzhi; Kumar, Praveen; Pokhrel, Narayan; Zeng, Dewan; Belardinelli, Luiz; Sorescu, Dan; Solaro, R. John; Dudley, Samuel C.

    2012-01-01

    Rationale Previously, we demonstrated that a deoxycorticosterone acetate (DOCA)-salt hypertensive mouse model produces cardiac oxidative stress and diastolic dysfunction with preserved systolic function. Oxidative stress has been shown to increase late inward sodium current (INa), reducing the net cytosolic Ca2+ efflux. Objective Oxidative stress in the DOCA-salt model may increase late INa resulting in diastolic dysfunction amenable to treatment with ranolazine. Methods and Results Echocardiography detected evidence of diastolic dysfunction in hypertensive mice that improved after treatment with ranolazine (E/E′, sham 31.9 ± 2.8, sham+ranolazine 30.2 ± 1.9, DOCA-salt 41.8 ± 2.6, and DOCA-salt+ranolazine 31.9 ± 2.6, p = 0.018). The end diastolic pressure volume relationship slope was elevated in DOCA-salt mice, improving to sham levels with treatment (sham 0.16 ± 0.01 vs. sham+ranolazine 0.18 ± 0.01 vs. DOCA-salt 0.23 ± 0.2 vs. DOCA-salt+ranolazine 0.17 ± 0.01 mm Hg/L, p < 0.005). DOCA-salt myocytes demonstrated impaired relaxation, τ, improving with ranolazine (DOCA-salt 0.18 ± 0.02, DOCA-salt + ranolazine 0.13 ± 0.01, Sham 0.11 ± 0.01, Sham + ranolazine 0.09 ± 0.02 s, p = 0.0004). Neither late INa nor the Ca2+ transients were different from sham myocytes. Detergent extracted fiber bundles from DOCA-salt hearts demonstrated increased myofilament response to Ca2+ with glutathionylation of myosin binding protein C. Treatment with ranolazine ameliorated the Ca2+ response and cross-bridge kinetics. Conclusions Therefore, diastolic dysfunction could be reversed by ranolazine, likely resulting from a direct effect on myofilaments, indicating that cardiac oxidative stress may mediate diastolic dysfunction through altering the contractile apparatus. PMID:22343711

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  12. Early upregulation of myocardial CXCR4 expression is critical for dimethyloxalylglycine-induced cardiac improvement in acute myocardial infarction.

    PubMed

    Mayorga, Mari; Kiedrowski, Matthew; Shamhart, Patricia; Forudi, Farhad; Weber, Kristal; Chilian, William M; Penn, Marc S; Dong, Feng

    2016-01-01

    The stromal cell-derived factor-1 (SDF-1):CXCR4 is important in myocardial repair. In this study we tested the hypothesis that early upregulation of cardiomyocyte CXCR4 (CM-CXCR4) at a time of high myocardial SDF-1 expression could be a strategy to engage the SDF-1:CXCR4 axis and improve cardiac repair. The effects of the hypoxia inducible factor (HIF) hydroxylase inhibitor dimethyloxalylglycine (DMOG) on CXCR4 expression was tested on H9c2 cells. In mice a myocardial infarction (MI) was produced in CM-CXCR4 null and wild-type controls. Mice were randomized to receive injection of DMOG (DMOG group) or saline (Saline group) into the border zone after MI. Protein and mRNA expression of CM-CXCR4 were quantified. Echocardiography was used to assess cardiac function. During hypoxia, DMOG treatment increased CXCR4 expression of H9c2 cells by 29 and 42% at 15 and 24 h, respectively. In vivo DMOG treatment increased CM-CXCR4 expression at 15 h post-MI in control mice but not in CM-CXCR4 null mice. DMOG resulted in increased ejection fraction in control mice but not in CM-CXCR4 null mice 21 days after MI. Consistent with greater cardiomyocyte survival with DMOG treatment, we observed a significant increase in cardiac myosin-positive area within the infarct zone after DMOG treatment in control mice, but no increase in CM-CXCR4 null mice. Inhibition of cardiomyocyte death in MI through the stabilization of HIF-1α requires downstream CM-CXCR4 expression. These data suggest that engagement of the SDF-1:CXCR4 axis through the early upregulation of CM-CXCR4 is a strategy for improving cardiac repair after MI.

  13. 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.

  14. 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.

  15. Simulation-guided cardiac auscultation improves medical students' clinical skills: the Pavia pilot experience.

    PubMed

    Perlini, Stefano; Salinaro, Francesco; Santalucia, Paola; Musca, Francesco

    2014-03-01

    Clinical evaluation is the cornerstone of any cardiac diagnosis, although excessive over-specialisation often leads students to disregard the value of clinical skills, and to overemphasize the approach to instrumental cardiac diagnosis. Time restraints, low availability of "typical" cardiac patients on whom to perform effective bedside teaching, patients' respect and the underscoring of the value of clinical skills all lead to a progressive decay in teaching. Simulation-guided cardiac auscultation may improve clinical training in medical students and residents. Harvey(©) is a mannequin encompassing more than 50 cardiac diagnoses that was designed and developed at the University of Miami (Florida, USA). One of the advantages of Harvey(©) simulation resides in the possibility of listening, comparing and discussing "real" murmurs. To objectively assess its teaching performance, the capability to identify five different cardiac diagnoses (atrial septal defect, normal young subject, mitral stenosis with tricuspid regurgitation, chronic mitral regurgitation, and pericarditis) out of more than 50 diagnostic possibilities was assessed in 523 III-year medical students (i.e. at the very beginning of their clinical experience), in 92 VI-year students, and in 42 residents before and after a formal 10-h teaching session with Harvey(©). None of them had previously experienced simulation-based cardiac auscultation in addition to formal lecturing (all three groups) and bedside teaching (VI-year students and residents). In order to assess the "persistence" of the acquired knowledge over time, the test was repeated after 3 years in 85 students, who did not repeat the formal 10-h teaching session with Harvey(©) after the III year. As expected, the overall response was poor in the "beginners" who correctly identified 11.0 % of the administered cardiac murmurs. After simulation-guided training, the ability to recognise the correct cardiac diagnoses was much better (72.0 %; p < 0

  16. 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

  17. 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

  18. Cardiac conduction improvement in two heterozygotes for primary carnitine deficiency on L-carnitine supplementation.

    PubMed

    Sarafoglou, K; Tridgell, A H C; Bentler, K; Redlinger-Grosse, K; Berry, S A; Schimmenti, L A

    2010-08-01

    Expanded newborn screening (NBS) for free carnitine levels has led to the identification of a larger number of heterozygous infants of undiagnosed mothers affected with systemic primary carnitine deficiency (PCD), which in turn leads to the identification of other undiagnosed heterozygous family members. There is an increasing recognition that individuals heterozygous for mutations of genes involved in fatty acid oxidation (FAO) may become symptomatic under environmental stress (fasting, prolonged exercise and illness). Considering the importance of carnitine in FAO, its role in heart and bowel function and in lipid metabolism, what is still little known is the phenotypic variability, biochemical parameters and clinical course of PCD heterozygotes with consistently low-to-normal levels to low levels of carnitine over a lifetime. We report on three generations of a family--an asymptomatic PCD heterozygous infant identified through NBS that led to the diagnosis of her asymptomatic PCD-affected mother and the heterozygous status of the maternal grandparents who report some cardiac symptoms that overlap with PCD that improved with L-carnitine supplementation.

  19. 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.

  20. Use of cardiac biomarkers in neonatology.

    PubMed

    Vijlbrief, Daniel C; Benders, Manon J N L; Kemperman, Hans; van Bel, Frank; de Vries, Willem B

    2012-10-01

    Cardiac biomarkers are used to identify cardiac disease in term and preterm infants. This review discusses the roles of natriuretic peptides and cardiac troponins. Natriuretic peptide levels are elevated during atrial strain (atrial natriuretic peptide (ANP)) or ventricular strain (B-type natriuretic peptide (BNP)). These markers correspond well with cardiac function and can be used to identify cardiac disease. Cardiac troponins are used to assess cardiomyocyte compromise. Affected cardiomyocytes release troponin into the bloodstream, resulting in elevated levels of cardiac troponin. Cardiac biomarkers are being increasingly incorporated into clinical trials as indicators of myocardial strain. Furthermore, cardiac biomarkers can possibly be used to guide therapy and improve outcome. Natriuretic peptides and cardiac troponins are potential tools in the diagnosis and treatment of neonatal disease that is complicated by circulatory compromise. However, clear reference ranges need to be set and validation needs to be carried out in a population of interest.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Does Glucagon Improve Survival in a Porcine (Sus Scrofa) of Adult Asphyxial Cardiac Arrest in Addition to Standard Epinephrine Therapy?

    DTIC Science & Technology

    2012-01-17

    UDIIILI: oa. I..UN I ItA!.. I NUMDI:It Does Glucagon improve survival in a porcine (Sus Scrofa ) of adult asphyxial cardiac arrest in addition to...EXPIRATION DATE: 25 Mar 13 PROTOCOL TITLE: Does Glucagon Improve Survival in a Porcine (Sus scrofa ) Model of Adult Asphyxial Cardiac Arrest in Addition...Additions: Deletions: 2 Protocol No: A-2007-03 Protocol Title: Does Glucagon Improve Survival in a Porcine (Sus scrofa ) Model of Adult Asphyxial

  6. 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.

  7. Ad-HGF improves the cardiac remodeling of rat following myocardial infarction by upregulating autophagy and necroptosis and inhibiting apoptosis

    PubMed Central

    Liu, Jiabao; Wu, Peng; Wang, Yunle; Du, Yingqiang; A, Nan; Liu, Shuiyuan; Zhang, Yiming; Zhou, Ningtian; Xu, Zhihui; Yang, Zhijian

    2016-01-01

    Cell death in MI is the most critical determinant of subsequent left ventricular remodeling and heart failure. Besides apoptosis, autophagy and necroptosis have been recently found to be another two regulated cell death styles. HGF has been reported to have a protective role in MI, but its impact on the three death styles remains unclear. Thus, our study was performed to investigate the distribution of autophagy, apoptosis and necroptosis in cardiac tissues after MI and explore the role and mechanism of Ad-HGF on cardiac remodeling by regulating the three death styles. We firstly showed the distribution of autophagy, apoptosis and necroptosis differs in temporal and spatial context after MI using immunofluorescence. Notably, Ad-HGF treatment improves the cardiac remodeling of SD rats following MI by preserving the heart function, reducing the scar size and aggresomes. Further mechanism study reveals Ad-HGF promotes autophagy and necroptosis and inhibits apoptosis in vivo and in vitro. Co-immunoprecipitation assays showed Ad-HGF treatment significantly decreased the binding of Bcl-2 to Beclin1 but enhanced Bcl-2 binding to Bax in H9c2 cells under hypoxia. Moreover, HGF-induced sequestration of Bax by Bcl-2 allows Bax to become inactive, thereby inhibiting apoptosis. In addition, Ad-HGF markedly increased the formation of Beclin1-Vps34-Atg14L complex, which accounted for promoting autophagy. Both the western blot and activity assay showed Ad-HGF significantly decreased the caspase 8 protein and activity levels, which obligated the cell to undergo necroptosis under hypoxia and block apoptosis. Thus, our findings offer new evidence and strategies for the treatment of MI and post-MI cardiac remodeling. PMID:27904666

  8. Ad-HGF improves the cardiac remodeling of rat following myocardial infarction by upregulating autophagy and necroptosis and inhibiting apoptosis.

    PubMed

    Liu, Jiabao; Wu, Peng; Wang, Yunle; Du, Yingqiang; A, Nan; Liu, Shuiyuan; Zhang, Yiming; Zhou, Ningtian; Xu, Zhihui; Yang, Zhijian

    2016-01-01

    Cell death in MI is the most critical determinant of subsequent left ventricular remodeling and heart failure. Besides apoptosis, autophagy and necroptosis have been recently found to be another two regulated cell death styles. HGF has been reported to have a protective role in MI, but its impact on the three death styles remains unclear. Thus, our study was performed to investigate the distribution of autophagy, apoptosis and necroptosis in cardiac tissues after MI and explore the role and mechanism of Ad-HGF on cardiac remodeling by regulating the three death styles. We firstly showed the distribution of autophagy, apoptosis and necroptosis differs in temporal and spatial context after MI using immunofluorescence. Notably, Ad-HGF treatment improves the cardiac remodeling of SD rats following MI by preserving the heart function, reducing the scar size and aggresomes. Further mechanism study reveals Ad-HGF promotes autophagy and necroptosis and inhibits apoptosis in vivo and in vitro. Co-immunoprecipitation assays showed Ad-HGF treatment significantly decreased the binding of Bcl-2 to Beclin1 but enhanced Bcl-2 binding to Bax in H9c2 cells under hypoxia. Moreover, HGF-induced sequestration of Bax by Bcl-2 allows Bax to become inactive, thereby inhibiting apoptosis. In addition, Ad-HGF markedly increased the formation of Beclin1-Vps34-Atg14L complex, which accounted for promoting autophagy. Both the western blot and activity assay showed Ad-HGF significantly decreased the caspase 8 protein and activity levels, which obligated the cell to undergo necroptosis under hypoxia and block apoptosis. Thus, our findings offer new evidence and strategies for the treatment of MI and post-MI cardiac remodeling.

  9. 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.

  10. Evening primrose oil ameliorates platelet aggregation and improves cardiac recovery in myocardial-infarct hypercholesterolemic rats

    PubMed Central

    Abo-Gresha, Noha M; Abel-Aziz, Eman Z; Greish, Sahar M

    2014-01-01

    Omega-6 polyunsaturated fatty acids (n-6 PUFA) are well known for their role in cardiovascular disease (CVD). We proposed that Evening prime rose oil (EPO) can improve the outcome of a heart with myocardial infarction (MI) in the presence of diet-induced hyperaggregability. This study was designed to examine its cholesterol lowering, antithrombotic and anti-inflammatory effects. High fat diet was administered for 4 weeks then MI was induced by isoproterenol (85 mg/kg/s.c./24 h). Treatment with EPO (5 or 10 gm/kg/day) for 6 weeks improved the electrocardiographic pattern, serum lipid profile, cardiac biomarkers as well as Platelet aggregation percent. We reported decreased serum level of TNF-α, IL-6 and COX-2 with attenuation of TNF-α and TGF-β in the cardiac homogenate. Moreover, histopathology revealed marked amelioration. Finally, we provide evidence that EPO improve cardiac recovery in hypercholesterolemic myocardial infarct rats. These effects are attributed to direct hypocholesterolemic effect and indirect effect on the synthesis of eicosanoids (prostaglandins, cytokines). PMID:24665356

  11. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

    The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration, a combination of these approaches could ameliorate the overall repair process to incorporate the participation of multiple cellular players. PMID:26484341

  12. Improvement of Right Ventricular Hemodynamics with Left Ventricular Endocardial Pacing during Cardiac Resynchronization Therapy

    PubMed Central

    HYDE, EOIN R.; BEHAR, JONATHAN M.; CROZIER, ANDREW; CLARIDGE, SIMON; JACKSON, TOM; SOHAL, MANAV; GILL, JASWINDER S.; O'NEILL, MARK D.; RAZAVI, REZA; RINALDI, CHRISTOPHER A.

    2016-01-01

    Background Cardiac resynchronization therapy (CRT) with biventricular epicardial (BV‐CS) or endocardial left ventricular (LV) stimulation (BV‐EN) improves LV hemodynamics. The effect of CRT on right ventricular function is less clear, particularly for BV‐EN. Our objective was to compare the simultaneous acute hemodynamic response (AHR) of the right and left ventricles (RV and LV) with BV‐CS and BV‐EN in order to determine the optimal mode of CRT delivery. Methods Nine patients with previously implanted CRT devices successfully underwent a temporary pacing study. Pressure wires measured the simultaneous AHR in both ventricles during different pacing protocols. Conventional epicardial CRT was delivered in LV‐only (LV‐CS) and BV‐CS configurations and compared with BV‐EN pacing in multiple locations using a roving decapolar catheter. Results Best BV‐EN (optimal AHR of all LV endocardial pacing sites) produced a significantly greater RV AHR compared with LV‐CS and BV‐CS pacing (P < 0.05). RV AHR had a significantly increased standard deviation compared to LV AHR (P < 0.05) with a weak correlation between RV and LV AHR (Spearman rs = −0.06). Compromised biventricular optimization, whereby RV AHR was increased at the expense of a smaller decrease in LV AHR, was achieved in 56% of cases, all with BV‐EN pacing. Conclusions BV‐EN pacing produces significant increases in both LV and RV AHR, above that achievable with conventional epicardial pacing. RV AHR cannot be used as a surrogate for optimizing LV AHR; however, compromised biventricular optimization is possible. The beneficial effect of endocardial LV pacing on RV function may have important clinical benefits beyond conventional CRT. PMID:27001004

  13. 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.

  14. 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.

  15. Evaluation of Skeletal and Cardiac Muscle Function after Chronic Administration of Thymosin β-4 in the Dystrophin Deficient Mouse

    PubMed Central

    Spurney, Christopher F.; Cha, Hee-Jae; Sali, Arpana; Pandey, Gouri S.; Pistilli, Emidio; Guerron, Alfredo D.; Gordish-Dressman, Heather; Hoffman, Eric P.; Nagaraju, Kanneboyina

    2010-01-01

    Thymosin beta-4 (Tβ4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. We studied the effects of chronic administration of Tβ4 on the skeletal and cardiac muscle of dystrophin deficient mdx mice, the mouse model of Duchenne muscular dystrophy. Female wild type (C57BL10/ScSnJ) and mdx mice, 8–10 weeks old, were treated with 150 µg of Tβ4 twice a week for 6 months. To promote muscle pathology, mice were exercised for 30 minutes twice a week. Skeletal and cardiac muscle function were assessed via grip strength and high frequency echocardiography. Localization of Tβ4 and amount of fibrosis were quantified using immunohistochemistry and Gomori's tri-chrome staining, respectively. Mdx mice treated with Tβ4 showed a significant increase in skeletal muscle regenerating fibers compared to untreated mdx mice. Tβ4 stained exclusively in the regenerating fibers of mdx mice. Although untreated mdx mice had significantly decreased skeletal muscle strength compared to untreated wild type, there were no significant improvements in mdx mice after treatment. Systolic cardiac function, measured as percent shortening fraction, was decreased in untreated mdx mice compared to untreated wild type and there was no significant difference after treatment in mdx mice. Skeletal and cardiac muscle fibrosis were also significantly increased in untreated mdx mice compared to wild type, but there was no significant improvement in treated mdx mice. In exercised dystrophin deficient mice, chronic administration of Tβ4 increased the number of regenerating fibers in skeletal muscle and could have a potential role in treatment of skeletal muscle disease in Duchenne muscular dystrophy. PMID:20126456

  16. 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.

  17. 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.

  18. 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.

  19. Inhibition of farnesyl pyrophosphate synthase improves pressure overload induced chronic cardiac remodeling

    PubMed Central

    Zhao, Chen-Ze; Zhao, Xu-Ming; Yang, Jian; Mou, Yun; Chen, Bin; Wu, Huan-Dong; Dai, Dong-Pu; Ding, Jie; Hu, Shen-Jiang

    2016-01-01

    Farnesyl pyrophosphate synthase (FPPS) is a key enzyme in the mevalonate pathway. In our previous studies, we find that inhibition of FPPS attenuates angiotensin II-induced cardiac hypertrophy and fibrosis by suppressing RhoA while FPPS and Ras are up-regulated in pressure overload rats. In this study, we evaluate the effects and mechanisms of FPPS inhibition in pressure overload mice. Male FPPS-small interfering RNA (SiRNA) transgenic (Tg) mice and non-transgenic littermate control (NLC) were randomly divided into suprarenal abdominal aortic constriction (AAC) group and sham operation group. 12 weeks following AAC, mice were sacrificed by cervical dislocation. Histological and echocardiographic assessments showed that inhibition of FPPS improved chronic cardiac remodeling which was induced by AAC. The reductions of Ras farnesylation and GTP-Ras, as well as their downstream extracellular signal-related kinases 1/2 (ERK1/2) expression were observed in the heart of Tg-AAC mice compared with NLC-AAC mice, along with the reduction of fetal gene expression. We provide here important experimental evidence that inhibition of FPPS improves AAC induced chronic cardiac remodeling and fibrosis by the reduction of farnesylated Ras and the downregulation of Ras-ERK1/2 pathway. PMID:28008986

  20. Oral administration of sodium tungstate improves cardiac performance in streptozotocin-induced diabetic rats.

    PubMed

    Nagareddy, Prabhakara Reddy; Vasudevan, Harish; McNeill, John H

    2005-05-01

    Normalization of hyperglycemia and hyperlipidemia is an important objective in preventing diabetes-induced cardiac dysfunction. Our study investigated the effects of sodium tungstate on cardiac performance in streptozotocin-induced (STZ) diabetic rats based on its potential antidiabetic and antioxidant activity. Male Wistar rats were made STZ-diabetic and then treated with tungstate in their drinking water for 9 weeks. Body mass, food and fluid intake, plasma glucose, insulin, triglyceride, and free fatty acids levels were measured. At the termination of the study period, an oral glucose tolerance test (OGTT) was performed, and cardiac performance was evaluated using an isolated working heart apparatus. Tungstate-treated STZ-diabetic rats showed a significant reduction in fluid and food intake, plasma glucose, triglycerides, and free fatty acid levels, and improved tolerance to glucose in OGTT, owing to tungstate-mediated enhancement of insulin activity rather than increased insulin levels. Left ventricular pressure development, the rate of contraction (+dP/dT), and the rate of relaxation (-dP/dT) were significantly improved in tungstate-treated diabetic rats. Apart from a decreased rate of body mass gain, no other signs of toxicity or hypoglycemic episodes were observed in tungstate-treated rats. This study extends previous observations on the antidiabetic activities of tungstate, and also reports for the first time the salutary effects in preventing diabetic cardiomyopathy.

  1. 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

  2. Improving best-phase image quality in cardiac CT by motion correction with MAM optimization

    SciTech Connect

    Rohkohl, Christopher; Bruder, Herbert; Stierstorfer, Karl; Flohr, Thomas

    2013-03-15

    Purpose: Research in image reconstruction for cardiac CT aims at using motion correction algorithms to improve the image quality of the coronary arteries. The key to those algorithms is motion estimation, which is currently based on 3-D/3-D registration to align the structures of interest in images acquired in multiple heart phases. The need for an extended scan data range covering several heart phases is critical in terms of radiation dose to the patient and limits the clinical potential of the method. Furthermore, literature reports only slight quality improvements of the motion corrected images when compared to the most quiet phase (best-phase) that was actually used for motion estimation. In this paper a motion estimation algorithm is proposed which does not require an extended scan range but works with a short scan data interval, and which markedly improves the best-phase image quality. Methods: Motion estimation is based on the definition of motion artifact metrics (MAM) to quantify motion artifacts in a 3-D reconstructed image volume. The authors use two different MAMs, entropy, and positivity. By adjusting the motion field parameters, the MAM of the resulting motion-compensated reconstruction is optimized using a gradient descent procedure. In this way motion artifacts are minimized. For a fast and practical implementation, only analytical methods are used for motion estimation and compensation. Both the MAM-optimization and a 3-D/3-D registration-based motion estimation algorithm were investigated by means of a computer-simulated vessel with a cardiac motion profile. Image quality was evaluated using normalized cross-correlation (NCC) with the ground truth template and root-mean-square deviation (RMSD). Four coronary CT angiography patient cases were reconstructed to evaluate the clinical performance of the proposed method. Results: For the MAM-approach, the best-phase image quality could be improved for all investigated heart phases, with a maximum

  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 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

  6. 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,…

  7. 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…

  8. Sodium sulfide prevents water diffusion abnormality in the brain and improves long term outcome after cardiac arrest in mice

    PubMed Central

    Kida, Kotaro; Minamishima, Shizuka; Wang, Huifang; Ren, JiaQian; Yigitkanli, Kazim; Nozari, Ala; Mandeville, Joseph B.; Liu, Philip K.; Liu, Christina H.; Ichinose, Fumito

    2012-01-01

    Aim of the study Sudden cardiac arrest (CA) is one of the leading causes of death worldwide. Previously we demonstrated that administration of sodium sulfide (Na2S), a hydrogen sulfide (H2S) donor, markedly improved the neurological outcome and survival rate at 24h after CA and cardiopulmonary resuscitation (CPR) in mice. In this study, we sought to elucidate the mechanism responsible for the neuroprotective effects of Na2S and its impact on the long-term survival after CA/CPR in mice. Methods Adult male mice were subjected to potassium-induced CA for 7.5 min at 37°C whereupon CPR was performed with chest compression and mechanical ventilation. Mice received Na2S (0.55 mg/kg i.v.) or vehicle 1 min before CPR. Results Mice that were subjected to CA/CPR and received vehicle exhibited a poor 10-day survival rate (4/12) and depressed neurological function. Cardiac arrest and CPR induced abnormal water diffusion in the vulnerable regions of the brain, as demonstrated by hyperintense diffusion-weighted imaging (DWI) 24h after CA/CPR. Extent of hyperintense DWI was associated with matrix metalloproteinase 9 (MMP-9) activation, worse neurological outcomes, and poor survival rate at 10 days after CA/CPR. Administration of Na2S prevented the development of abnormal water diffusion and MMP-9 activation and markedly improved neurological function and long-term survival (9/12, P<0.05 vs. vehicle) after CA/CPR. Conclusion These results suggest that administration of Na2S 1 min before CPR improves neurological function and survival rate at 10 days after CA/CPR by preventing water diffusion abnormality in the brain potentially via inhibiting MMP-9 activation early after resuscitation. PMID:22370005

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Fibronectin and Cyclic Strain Improve Cardiac Progenitor Cell Regenerative Potential In Vitro

    PubMed Central

    Ghosh-Choudhary, Shohini; Fierro, Marcos J.; Christman, Karen L.; Taylor, W. Robert

    2016-01-01

    Cardiac progenitor cells (CPCs) have rapidly advanced to clinical trials, yet little is known regarding their interaction with the microenvironment. Signaling cues present in the microenvironment change with development and disease. This work aims to assess the influence of two distinct signaling moieties on CPCs: cyclic biaxial strain and extracellular matrix. We evaluate four endpoints for improving CPC therapy: paracrine signaling, proliferation, connexin43 expression, and alignment. Vascular endothelial growth factor A (about 900 pg/mL) was secreted by CPCs cultured on fibronectin and collagen I. The application of mechanical strain increased vascular endothelial growth factor A secretion 2–4-fold for CPCs cultured on poly-L-lysine, laminin, or a naturally derived cardiac extracellular matrix. CPC proliferation was at least 25% higher on fibronectin than that on other matrices, especially for lower strain magnitudes. At 5% strain, connexin43 expression was highest on fibronectin. With increasing strain magnitude, connexin43 expression decreased by as much as 60% in CPCs cultured on collagen I and a naturally derived cardiac extracellular matrix. Cyclic mechanical strain induced the strongest CPC alignment when cultured on fibronectin or collagen I. This study demonstrates that culturing CPCs on fibronectin with 5% strain magnitude is optimal for their vascular endothelial growth factor A secretion, proliferation, connexin43 expression, and alignment. PMID:27610140

  14. 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.

  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. Aldehyde dehydrogenase 2 activation in heart failure restores mitochondrial function and improves ventricular function and remodelling

    PubMed Central

    Gomes, Katia M.S.; Campos, Juliane C.; Bechara, Luiz R.G.; Queliconi, Bruno; Lima, Vanessa M.; Disatnik, Marie-Helene; Magno, Paulo; Chen, Che-Hong; Brum, Patricia C.; Kowaltowski, Alicia J.; Mochly-Rosen, Daria; Ferreira, Julio C.B.

    2014-01-01

    Aims We previously demonstrated that pharmacological activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) protects the heart against acute ischaemia/reperfusion injury. Here, we determined the benefits of chronic activation of ALDH2 on the progression of heart failure (HF) using a post-myocardial infarction model. Methods and results We showed that a 6-week treatment of myocardial infarction-induced HF rats with a selective ALDH2 activator (Alda-1), starting 4 weeks after myocardial infarction at a time when ventricular remodelling and cardiac dysfunction were present, improved cardiomyocyte shortening, cardiac function, left ventricular compliance and diastolic function under basal conditions, and after isoproterenol stimulation. Importantly, sustained Alda-1 treatment showed no toxicity and promoted a cardiac anti-remodelling effect by suppressing myocardial hypertrophy and fibrosis. Moreover, accumulation of 4-hydroxynonenal (4-HNE)-protein adducts and protein carbonyls seen in HF was not observed in Alda-1-treated rats, suggesting that increasing the activity of ALDH2 contributes to the reduction of aldehydic load in failing hearts. ALDH2 activation was associated with improved mitochondrial function, including elevated mitochondrial respiratory control ratios and reduced H2O2 release. Importantly, selective ALDH2 activation decreased mitochondrial Ca2+-induced permeability transition and cytochrome c release in failing hearts. Further supporting a mitochondrial mechanism for ALDH2, Alda-1 treatment preserved mitochondrial function upon in vitro aldehydic load. Conclusions Selective activation of mitochondrial ALDH2 is sufficient to improve the HF outcome by reducing the toxic effects of aldehydic overload on mitochondrial bioenergetics and reactive oxygen species generation, suggesting that ALDH2 activators, such as Alda-1, have a potential therapeutic value for treating HF patients. PMID:24817685

  17. 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

  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. Same day admission for elective cardiac surgery: how to improve outcome with satisfaction and decrease expenses.

    PubMed

    Silvay, George; Goldberg, Andrew; Gutsche, Jacob T; T Augoustides, John G

    2016-06-01

    Admission on the day of surgery for elective cardiac and non-cardiac surgery has been established as a prevalent, critical practice. This approach realizes medical, logistical, psychological and fiscal benefits, and its success is predicated on an effective outpatient pre-operative evaluation. The establishment of a highly functional pre-operative clinic with a comprehensive set-up and efficient logistical pathways is invaluable. This notion has been expanded in recent years to include the entire peri-operative period and the concept of a 'peri-operative anesthesia/surgical home' is gaining popularity and support. Evaluating patients prior to admission for surgery, anesthesiologists can place themselves at the forefront of reducing unnecessary pre-operative hospital admissions, excess lab tests, unneeded consultations, and ultimately decrease the cancellations on the day of surgery. Furthermore, by taking a leadership role in the pre-operative clinic, anesthesiologists place themselves squarely at the forefront of the burgeoning movement for the peri-operative surgical home and continue to cement the indispensability of the anesthesiologist during the entire peri-operative course. The authors present this review as a follow-up describing the successful implementation of a pre-operative same-day cardiac surgery clinic and offer these experiences over the last 8 years as a guide to helping other anesthesiologists do the same.

  20. Effects of an 18 week walking programme on cardiac function in previously sedentary or relatively inactive adults.

    PubMed Central

    Woolf-May, K; Bird, S; Owen, A

    1997-01-01

    OBJECTIVE: To investigate the effects of an 18 week walking programme upon cardiac function. METHODS: 29 sedentary or relatively inactive but otherwise healthy subjects (15 walkers and 14 controls, aged 40-68 years) completed the study. The walkers completed a progressive 18 week walking programme which required an estimated average energy expenditure of 900 kcal week-1 for the total duration of the study and 1161 kcal week-1 during the final six weeks. Walking was carried out at an intensity of 67.8 (SD 4.99)% of maximum oxygen consumption and 73.8(6.99%) of maximum heart rate. Before and after the intervention all subjects underwent an M mode echocardiogram, graded treadmill walking test, and step test for the assessment of aerobic fitness. RESULTS: After 18 weeks the results of the control group showed no change in any of the variables measured while the walkers showed a statistically significant increase in the velocity of relaxation of the longitudinal myocardial fibres of the left ventricle and a decrease in heart rate measured during the step tests, indicating an improvement in aerobic capacity. CONCLUSIONS: Walking promotes improvements in cardiovascular fitness. Moderate forms of exercise may improve cardiac function. Images p50-a PMID:9132212

  1. Atrial natriuretic peptide affects cardiac remodeling, function, heart failure, and survival in a mouse model of dilated cardiomyopathy.

    PubMed

    Wang, Dong; Gladysheva, Inna P; Fan, Tai-Hwang M; Sullivan, Ryan; Houng, Aiilyan K; Reed, Guy L

    2014-03-01

    Dilated cardiomyopathy is a frequent cause of heart failure and death. Atrial natriuretic peptide (ANP) is a biomarker of dilated cardiomyopathy, but there is controversy whether ANP modulates the development of heart failure. Therefore, we examined whether ANP affects heart failure, cardiac remodeling, function, and survival in a well-characterized, transgenic model of dilated cardiomyopathy. Mice with dilated cardiomyopathy with normal ANP levels survived longer than mice with partial ANP (P<0.01) or full ANP deficiency (P<0.001). In dilated cardiomyopathy mice, ANP protected against the development of heart failure as indicated by reduced lung water, alveolar congestion, pleural effusions, etc. ANP improved systolic function and reduced cardiomegaly. Pathological cardiac remodeling was diminished in mice with normal ANP as indicated by decreased ventricular interstitial and perivascular fibrosis. Mice with dilated cardiomyopathy and normal ANP levels had better systolic function (P<0.001) than mice with dilated cardiomyopathy and ANP deficiency. Dilated cardiomyopathy was associated with diminished cardiac transcripts for NP receptors A and B in mice with normal ANP and ANP deficiency, but transcripts for NP receptor C and C-type natriuretic peptide were selectively altered in mice with dilated cardiomyopathy and ANP deficiency. Taken together, these data indicate that ANP has potent effects in experimental dilated cardiomyopathy that reduce the development of heart failure, prevent pathological remodeling, preserve systolic function, and reduce mortality. Despite the apparent overlap in physiological function between the NPs, these data suggest that the role of ANP in dilated cardiomyopathy and heart failure is not compensated physiologically by other NPs.

  2. Ginsenoside Rg3 improves cardiac mitochondrial population quality: Mimetic exercise training

    SciTech Connect

    Sun, Mengwei; Huang, Chenglin; Wang, Cheng; Zheng, Jianheng; Zhang, Peng; Xu, Yangshu; Chen, Hong; Shen, Weili

    2013-11-08

    Highlights: •Rg3 is an ergogenic aid. •Rg3 improves mitochondrial antioxidant capacity. •Rg3 regulates mitochondria dynamic remodeling. •Rg3 alone matches some the benefits of aerobic exercise. -- Abstract: Emerging evidence indicates exercise training could mediate mitochondrial quality control through the improvement of mitochondrial dynamics. Ginsenoside Rg3 (Rg3), one of the active ingredients in Panax ginseng, is well known in herbal medicine as a tonic and restorative agent. However, the molecular mechanism underlying the beneficial effects of Rg3 has been elusive. In the present study, we compared the effects of Rg3 administration with aerobic exercise on mitochondrial adaptation in cardiac muscle tissue of Sprague–Dawley (SD) rats. Three groups of SD rats were studied: (1) sedentary control, (2) Rg3-treated and (3) aerobic exercise trained. Both aerobic exercise training and Rg3 supplementation enhanced peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) and nuclear factor-E2-related factor 2 (Nrf2) protein levels in cardiac muscle. The activation of PGC-1α led to increased mRNA levels of mitochondrial transcription factor A (Tfam) and nuclear related factor 1(Nrf1), these changes were accompanied by increases in mitochondrial DNA copy number and complex protein levels, while activation of Nrf2 increased levels of phase II detoxifying enzymes, including nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1(NQO1), superoxide dismutase (MnSOD) and catalase. Aerobic exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of beclin1 and autophagy-related protein 7 (ATG7), these effects of aerobic exercise are comparable to that of Rg3. These results demonstrate that Rg3 mimics improved cardiac adaptations to exercise by regulating mitochondria dynamic remodeling and enhancing the quantity and quality of mitochondria.

  3. 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

  4. 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.

  5. Segmented independent component analysis for improved separation of fetal cardiac signals from nonstationary fetal magnetocardiograms

    PubMed Central

    Murta, Luiz O.; Guzo, Mauro G.; Moraes, Eder R.; Baffa, Oswaldo; Wakai, Ronald T.; Comani, Silvia

    2015-01-01

    Fetal magnetocardiograms (fMCGs) have been successfully processed with independent component analysis (ICA) to separate the fetal cardiac signals, but ICA effectiveness can be limited by signal nonstation-arities due to fetal movements. We propose an ICA-based method to improve the quality of fetal signals separated from fMCG affected by fetal movements. This technique (SegICA) includes a procedure to detect signal nonstationarities, according to which the fMCG recordings are divided in stationary segments that are then processed with ICA. The first and second statistical moments and the signal polarity reversal were used at different threshold levels to detect signal transients. SegICA effectiveness was assessed in two fMCG datasets (with and without fetal movements) by comparing the signal-to-noise ratio (SNR) of the signals extracted with ICA and with SegICA. Results showed that the SNR of fetal signals affected by fetal movements improved with SegICA, whereas the SNR gain was negligible elsewhere. The best measure to detect signal nonstationarities of physiological origin was signal polarity reversal at threshold level 0.9. The first statistical moment also provided good results at threshold level 0.6. SegICA seems a promising method to separate fetal cardiac signals of improved quality from nonstationary fMCG recordings affected by fetal movements. PMID:25781658

  6. Improving functional value of meat products.

    PubMed

    Zhang, Wangang; Xiao, Shan; Samaraweera, Himali; Lee, Eun Joo; Ahn, Dong U

    2010-09-01

    In recent years, much attention has been paid to develop meat and meat products with physiological functions to promote health conditions and prevent the risk of diseases. This review focuses on strategies to improve the functional value of meat and meat products. Value improvement can be realized by adding functional compounds including conjugated linoneleic acid, vitamin E, n3 fatty acids and selenium in animal diets to improve animal production, carcass composition and fresh meat quality. In addition, functional ingredients such as vegetable proteins, dietary fibers, herbs and spices, and lactic acid bacteria can be directly incorporated into meat products during processing to improve their functional value for consumers. Functional compounds, especially peptides, can also be generated from meat and meat products during processing such as fermentation, curing and aging, and enzymatic hydrolysis. This review further discusses the current status, consumer acceptance, and market for functional foods from the global viewpoints. Future prospects for functional meat and meat products are also discussed.

  7. 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.

  8. 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

  9. Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3 dependent mechanism in mice

    PubMed Central

    Minamishima, Shizuka; Bougaki, Masahiko; Sips, Patrick Y.; De Yu, Jia; Minamishima, Yoji Andrew; Elrod, John W.; Lefer, David J.; Bloch, Kenneth D.; Ichinose, Fumito

    2009-01-01

    Background Sudden cardiac arrest (CA) is one of the leading causes of death worldwide. We sought to evaluate the impact of hydrogen sulfide (H2S) on the outcome after CA and cardiopulmonary resuscitation (CPR) in mouse. Methods and Results Mice were subjected to 8 min of normothermic CA and resuscitated with chest compression and mechanical ventilation. Seven minutes after the onset of CA, mice received sodium sulfide (Na2S, 0.55 mg/kg i.v.) or vehicle 1 min before CPR. There was no difference in the rate of return of spontaneous circulation (ROSC), CPR time to ROSC, and left ventricular (LV) function at ROSC between groups. Administration of Na2S 1 min before CPR markedly improved survival rate at 24h after CPR (15/15) compared to vehicle (10/26, P=0.0001 vs Na2S). Administration of Na2S prevented CA/CPR-induced oxidative stress and ameliorated LV and neurological dysfunction 24h after CPR. Delayed administration of Na2S at 10 min after CPR did not improve outcomes after CA/CPR. Cardioprotective effects of Na2S were confirmed in isolated-perfused mouse hearts subjected to global ischemia and reperfusion. Cardiomyocyte-specific overexpression of cystathionine γ-lyase (CGL, an enzyme that produces H2S) markedly improved outcomes of CA/CPR. Na2S increased phosphorylation of NOS3 in LV and brain cortex, increased serum nitrite/nitrate levels, and attenuated CA-induced mitochondrial injury and cell death. NOS3 deficiency abrogated the protective effects of Na2S on the outcome of CA/CPR. Conclusions These results suggest that administration of Na2S at the time of CPR improves outcome after cardiac arrest possibly via an NOS3-dependent signaling pathway. PMID:19704099

  10. 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.

  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. 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

  14. An analysis of implantable cardiac device reliability. The case for improved postmarketing risk assessment and surveillance.

    PubMed

    Laskey, Warren; Awad, Khaled; Lum, Jeremy; Skodacek, Ken; Zimmerman, Barbara; Selzman, Kimberly; Zuckerman, Bram

    2012-07-01

    Implantable cardiac devices have become the mainstay of the treatment of patients with heart disease. However, data regarding their reliability and, inferentially, safety have been called into question. We reviewed annual reports submitted to the Food and Drug Administration Office of Device Evaluation by device manufacturers from 2003 to 2007. The annual number of implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy defibrillator (CRT-D) implants, explants, and returned devices were tabulated along with the cumulative (Cum) number of implants for each device. We derived an annual explantation rate (AER) defined as the ratio of the annual number of explants less the number of normal battery depletions/Cum (×1000). From 2003 to 2007, 256,392 CRT-D and 459,300 ICD devices were implanted in the United States. The overall mean (±SD) AERs for ICD and CRT-D devices were, respectively, 49.5 (15.6) per 1000 ICD devices and 82.6 (35.5) per 1000 CRT-D devices. The AER for each device type significantly decreased over the study period (P for trend <0.001) although the AER for CRT-D devices was 38% higher than that for ICD devices (P < 0.001). On average, 20.3% of CRT-D devices and 22.6% of ICD devices were returned to the manufacturer for analysis after explantation. The rates of explanted CRT-D and ICD devices decreased from 2003 to 2007. Notwithstanding this favorable trend, the AER for CRT-D devices was higher than that for ICD devices. Improved methods for tracking individual device histories are needed for more precise estimates of the risk of device explantation for suspected malfunction. The proportion of devices returned to the manufacturer is suboptimal and needs to be improved to better understand the mechanisms of device malfunction.

  15. Feasibility of cognitive functional assessment in cardiac arrest survivors using an abbreviated laptop-based neurocognitive battery.

    PubMed

    Iannacone, Stephen; Leary, Marion; Esposito, Emily C; Ruparel, Kosha; Savitt, Adam; Mott, Allison; Richard, Jan A; Gur, Ruben C; Abella, Benjamin S

    2014-09-01

    Cardiac arrest survivors exhibit varying degrees of neurological recovery even in the setting of targeted temperature management (TTM) use, ranging from severe impairments to making a seemingly full return to neurologic baseline function. We sought to explore the feasibility of utilizing a laptop-based neurocognitive battery to identify more subtle cognitive deficits in this population. In a convenience sample of cardiac arrest survivors discharged with a cerebral performance category (CPC) of 1, we evaluated the use of a computerized neurocognitive battery (CNB) in this group compared to a healthy control normative population. The CNB was designed to test 11 specific neurocognitive domains, including such areas as working memory and spatial processing. Testing was scored for both accuracy and speed. In a feasibility convenience sample of 29 cardiac arrest survivors, the mean age was 52.9±16.7 years; 12 patients received postarrest TTM and 17 did not receive TTM. Patients tolerated the battery well and performed at normative levels for both accuracy and speed on most of the 11 domains, but showed reduced accuracy of working memory and speed of spatial memory with large magnitudes (>1 SD), even among those receiving TTM. Across all domains, including those using speed and accuracy, 7 of the 29 subjects (24%) achieved statistically significant scores lower from the normative population in two or more domains. In this population of CPC 1 cardiac arrest survivors, a sensitive neurocognitive battery was feasible and suggests that specific cognitive deficits can be detected compared to a normative population, despite CPC 1 designation. Such testing might allow improved measurement of outcomes following TTM interventions in future trials.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Carbon Monoxide Improves Neurologic Outcomes by Mitochondrial Biogenesis after Global Cerebral Ischemia Induced by Cardiac Arrest in Rats

    PubMed Central

    Wang, Peng; Yao, Lan; Zhou, Li-li; Liu, Yuan-shan; Chen, Ming-di; Wu, Hai-dong; Chang, Rui-ming; Li, Yi; Zhou, Ming-gen; Fang, Xiang-shao; Yu, Tao; Jiang, Long-yuan; Huang, Zi-tong

    2016-01-01

    Mitochondrial dysfunction contributes to brain injury following global cerebral ischemia after cardiac arrest. Carbon monoxide treatment has shown potent cytoprotective effects in ischemia/reperfusion injury. This study aimed to investigate the effects of carbon monoxide-releasing molecules on brain mitochondrial dysfunction and brain injury following resuscitation after cardiac arrest in rats. A rat model of cardiac arrest was established by asphyxia. The animals were randomly divided into the following 3 groups: cardiac arrest and resuscitation group, cardiac arrest and resuscitation plus carbon monoxide intervention group, and sham control group (no cardiac arrest). After the return of spontaneous circulation, neurologic deficit scores (NDS) and S-100B levels were significantly decreased at 24, 48, and 72 h, but carbon monoxide treatment improved the NDS and S-100B levels at 24 h and the 3-day survival rates of the rats. This treatment also decreased the number of damaged neurons in the hippocampus CA1 area and increased the brain mitochondrial activity. In addition, it increased mitochondrial biogenesis by increasing the expression of biogenesis factors including peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, nuclear respiratory factor-2 and mitochondrial transcription factor A. Thus, this study showed that carbon monoxide treatment alleviated brain injury after cardiac arrest in rats by increased brain mitochondrial biogenesis. PMID:27489503

  2. Apocynin improving cardiac remodeling in chronic renal failure disease is associated with up-regulation of epoxyeicosatrienoic acids.

    PubMed

    Zhang, Kun; Liu, Yu; Liu, Xiaoqiang; Chen, Jie; Cai, Qingqing; Wang, Jingfeng; Huang, Hui

    2015-09-22

    Cardiac remodeling is one of the most common cardiac abnormalities and associated with a high mortality in chronic renal failure (CRF) patients. Apocynin, a nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been showed cardio-protective effects. However, whether apocynin can improve cardiac remodeling in CRF and what is the underlying mechanism are unclear. In the present study, we enrolled 94 participants. In addition, we used 5/6 nephrectomized rats to mimic cardiac remodeling in CRF. Serum levels of epoxyeicosatrienoic acids (EETs) and its mainly metabolic enzyme-soluble epoxide hydrolase (sEH) were measured. The results showed that the serum levels of EETs were significantly decreased in renocardiac syndrome participants (P < 0.05). In 5/6 nephrectomized CRF model, the ratio of left ventricular weight / body weight, left ventricular posterior wall thickness, and cardiac interstitial fibrosis were significantly increased while ejection fraction significantly decreased (P < 0.05). All these effects could partly be reversed by apocynin. Meanwhile, we found during the process of cardiac remodeling in CRF, apocynin significantly increased the reduced serum levels of EETs and decreased the mRNA and protein expressions of sEH in the heart (P < 0.05). Our findings indicated that the protective effect of apocynin on cardiac remodeling in CRF was associated with the up-regulation of EETs. EETs may be a new mediator for the injury of kidney-heart interactions.

  3. 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.

  4. 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.

  5. 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.

  6. The effect of matrix stiffness of injectable hydrogels on the preservation of cardiac function after a heart attack.

    PubMed

    Plotkin, Marian; Vaibavi, Srirangam Ramanujam; Rufaihah, Abdul Jalil; Nithya, Venkateswaran; Wang, Jing; Shachaf, Yonatan; Kofidis, Theo; Seliktar, Dror

    2014-02-01

    This study compares the effect of four injectable hydrogels with different mechanical properties on the post-myocardial infarction left ventricle (LV) remodeling process. The bioactive hydrogels were synthesized from Tetronic-fibrinogen (TF) and PEG-fibrinogen (PF) conjugates; each hydrogel was supplemented with two levels of additional cross-linker to increase the matrix stiffness as measured by the shear storage modulus (G'). Infarcts created by ligating the left anterior descending coronary artery in a rodent model were treated with the hydrogels, and all four treatment groups showed an increase in wall thickness, arterial density, and viable cardiac tissue in the peri-infarct areas of the LV. Echocardiography and hemodynamics data of the PF/TF treated groups showed significant improvement of heart function associated with the attenuated effects of the remodeling process. Multi-factorial regression analysis indicated that the group with the highest modulus exhibited the best rescue of heart function and highest neovascularization. The results of this study demonstrate that multiple properties of an injectable bioactive biomaterial, and notably the matrix stiffness, provide the multifaceted stimulation necessary to preserve cardiac function and prevent adverse remodeling following a heart attack.

  7. Effects of glycyl-glutamine dipeptide supplementation on myocardial damage and cardiac function in rats after severe burn injury.

    PubMed

    Zhang, Yong; Yan, Hong; Lv, Shang-Gun; Wang, Lin; Liang, Guang-Ping; Wan, Qian-Xue; Peng, Xi

    2013-01-01

    Glutamine decreases myocardial damage in ischemia/reperfusion injury. However, the cardioprotective effect of glutamine after burn injury remains unclear. Present study was to explore the protective effect of glycyl-glutamine dipeptide on myocardial damage in severe burn rats. Seventy-two Wistar rats were randomly divided into three groups: normal control (C), burned control (B) and glycyl-glutamine dipeptide-treated (GG) groups. B and GG groups were inflicted with 30% total body surface area of full thickness burn. The GG group was given 1.5 g/kg glycyl-glutamine dipeptide per day and the B group was given the same dose of alanine via intraperitoneal injection for 3 days. The serum CK, LDH, AST, and, blood lactic acid levels, as well as the myocardium ATP and GSH contents, were measured. The indices of cardiac contractile function and histopathological change were analyzed at 12, 24, 48, and 72 post-burn hours (PBH). The serum CK, LDH, AST and blood lactic acid levels increased, and the myocardium ATP and GSH content decreased in both burned groups. Compared with B group, the CK, LDH, AST and blood lactic acid levels reduced, myocardium ATP and GSH content increased in GG group. Moreover, the inhibition of cardiac contractile function and myocardial histopathological damage were reduced significantly in GG group. We conclude that myocardial histological structure and function were damaged significantly after burn injury, glycyl-glutamine dipeptide supplementation is beneficial to myocardial preservation by improving cardiocyte energy metabolism, increasing ATP and glutathione synthesis.

  8. Functional Effect of Pim1 Depends upon Intracellular Localization in Human Cardiac Progenitor Cells.

    PubMed

    Samse, Kaitlen; Emathinger, Jacqueline; Hariharan, Nirmala; Quijada, Pearl; Ilves, Kelli; Völkers, Mirko; Ormachea, Lucia; De La Torre, Andrea; Orogo, Amabel M; Alvarez, Roberto; Din, Shabana; Mohsin, Sadia; Monsanto, Megan; Fischer, Kimberlee M; Dembitsky, Walter P; Gustafsson, Åsa B; Sussman, Mark A

    2015-05-29

    Human cardiac progenitor cells (hCPC) improve heart function after autologous transfer in heart failure patients. Regenerative potential of hCPCs is severely limited with age, requiring genetic modification to enhance therapeutic potential. A legacy of work from our laboratory with Pim1 kinase reveals effects on proliferation, survival, metabolism, and rejuvenation of hCPCs in vitro and in vivo. We demonstrate that subcellular targeting of Pim1 bolsters the distinct cardioprotective effects of this kinase in hCPCs to increase proliferation and survival, and antagonize cellular senescence. Adult hCPCs isolated from patients undergoing left ventricular assist device implantation were engineered to overexpress Pim1 throughout the cell (PimWT) or targeted to either mitochondrial (Mito-Pim1) or nuclear (Nuc-Pim1) compartments. Nuc-Pim1 enhances stem cell youthfulness associated with decreased senescence-associated β-galactosidase activity, preserved telomere length, reduced expression of p16 and p53, and up-regulation of nucleostemin relative to PimWT hCPCs. Alternately, Mito-Pim1 enhances survival by increasing expression of Bcl-2 and Bcl-XL and decreasing cell death after H2O2 treatment, thereby preserving mitochondrial integrity superior to PimWT. Mito-Pim1 increases the proliferation rate by up-regulation of cell cycle modulators Cyclin D, CDK4, and phospho-Rb. Optimal stem cell traits such as proliferation, survival, and increased youthful properties of aged hCPCs are enhanced after targeted Pim1 localization to mitochondrial or nuclear compartments. Targeted Pim1 overexpression in hCPCs allows for selection of the desired phenotypic properties to overcome patient variability and improve specific stem cell characteristics.

  9. 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

  10. Cognitive behavioral therapy for depression improves pain and perceived control in cardiac surgery patients

    PubMed Central

    Doering, Lynn V; McGuire, Anthony; Eastwood, Jo-Ann; Chen, Belinda; Bodán, Rebecca C; Czer, Lawrence S; Irwin, Michael R

    2015-01-01

    Background Depression after cardiac surgery (CS) is associated with increased pain and decreased sleep quality. While cognitive behavioral therapy (CBT) aimed at depression is effective in relieving depressive symptoms after cardiac surgery, little is known about its ability to ameliorate other common postoperative problems that affect recovery and quality of life. Aims The purpose of this study was to evaluate the effects of CBT for depression on pain severity, pain interference, sleep, and perceived control in patients recovering from CS. Methods Depressed patients recovering from CS were randomized to receive either eight weeks of CBT or usual care. At baseline and post-intervention, patients completed questionnaires for depressive symptoms, pain, sleep, and perceived control. Group comparisons were conducted using t-tests or chi square analysis. Repeated measures analysis was used to assess the effect of the intervention in changes over time. Results The sample (n=53) included 16.9% women and had a mean age of 67.8±9.2 years. CBT for depression increased perceived control (p<0.001) and decreased pain interference (p=0.02) and pain severity (p=0.03). Group effects remained significant (p<0.05) for perceived control and pain interference and a trend was observed for pain severity (p<0.10) after controlling for variables that differed at baseline. There were no group differences in sleep disturbance over time. Conclusions A depression-focused CBT intervention yields benefits in other common postoperative problems, specifically improved perceived control and decreased pain in depressed cardiac surgery patients. PMID:26115954

  11. The Role of Cardiac Side Population Cells in Cardiac Regeneration

    PubMed Central

    Yellamilli, Amritha; van Berlo, Jop H.

    2016-01-01

    The heart has a limited ability to regenerate. It is important to identify therapeutic strategies that enhance cardiac regeneration in order to replace cardiomyocytes lost during the progression of heart failure. Cardiac progenitor cells are interesting targets for new regenerative therapies because they are self-renewing, multipotent cells located in the heart. Cardiac side population cells (cSPCs), the first cardiac progenitor cells identified in the adult heart, have the ability to differentiate into cardiomyocytes, endothelial cells, smooth muscle cells, and fibroblasts. They become activated in response to cardiac injury and transplantation of cSPCs into the injured heart improves cardiac function. In this review, we will discuss the current literature on the progenitor cell properties and therapeutic potential of cSPCs. This body of work demonstrates the great promise cSPCs hold as targets for new regenerative strategies. PMID:27679798

  12. 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 ...

  13. 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.

  14. 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

  15. 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.

  16. 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

  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. Efficacy and effects on cardiac function of radiofrequency catheter ablation vs. direct current cardioversion of persistent atrial fibrillation with left ventricular systolic dysfunction

    PubMed Central

    Wang, Maojing; Cai, Shanglang; Ding, Wei; Deng, Yujie; Zhao, Qing

    2017-01-01

    Objective To evaluate the effect of catheter ablation vs. direct current synchronized cardioversion (DCC) in patients with persistent atrial fibrillation (AF) and left ventricular systolic dysfunction, and to define baseline features of patients that will get more benefit from ablation. Methods From July 2013 to October 2014, 97 consecutive single-center patients with persistent AF and symptomatic heart failure (left ventricular ejection fraction (LVEF) <50%) underwent DCC followed by amiodarone (n = 40) or circumferential pulmonary vein isolation (PVI; n = 57) according to patient’s preference were recruited in the study. Post-ablation recurrence was treated with atrial roof and mitral isthmus lines ablation with or without PVI based on restoration or not of pulmonary vein (PV) potential conduction. Study outcomes were 12-month rate of sustained sinus rhythm (SR) and cardiac function. Baseline characteristics were compared between patients with and without cardiac function improvement post ablation. Results With similarly distributed characteristics at baseline, ablation (mean 1.8 procedures) relative to DCC yielded significantly higher level of 12-month SR maintenance rate (68.42% vs. 35%, P = 0.001); and better LVEF and New York Heart Association class. with significant effect for DCC only in maintained SR cases. Post ablation LVEF increased (>20% or to over 55%) in 31 (54.39%) patients with worse baseline cardiac function and ventricular rate control. Conclusions Catheter ablation relative to cardioversion of persistent AF with symptomatic heart failure yielded better 12-month SR maintenance and cardiac function. Compared with non-responders, patients with improved LVEF post-ablation had poorer ventricular rate control and cardiac function at baseline, suggesting a significant component of tachycardia-induced cardiomyopathy in this group. PMID:28350861

  19. 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

  20. Speeding up laboratory test reporting in Medical Emergency and Cardiac Arrest calls: a quality improvement project

    PubMed Central

    Al-Talib, Mohammed; Leslie, Isla

    2017-01-01

    Many hospitals deploy Medical Emergency (MET) and Cardiac Arrest teams to improve the management and treatment of patients who become critically ill. In many cases, blood results are key in allowing the clinicians involved in these teams to make definitive management decisions for these patients. Following anecdotal reports that these results were often delayed, we assessed the process of blood tests being reported in emergency calls, identified the key factors causing delays and sought to make improvements. The initial intervention involved implementing a new blood form that specified the nature of the call, the tests required and a contact number for laboratory staff to contact the clinical team with results. We also developed a streamlined process within the laboratory for these samples to be fast-tracked. Successive improvement cycles sought to increase awareness of the project, improve accessibility to the new forms and embed spontaneous practices that contributed to improvement. Results demonstrated an overall reduction in the time taken for blood samples in emergencies to be reported from 130 minutes to 97 minutes. This project demonstrates that using a specific blood request form for emergency calls, and tying this to a specified laboratory process, improves the time taken for these tests to be reported. In addition, the project provides some insight into challenges faced when implementing change in new departments. PMID:28243442

  1. 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.

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

    PubMed

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

    2016-12-01

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

  3. Suburban cardiac screening: improving access to specialist services within a primary care network.

    PubMed

    Jones, David C; Ludwick, Dave; Brass, Neil; Cutts, Carrie

    2011-01-01

    This article evaluates a cardiac screening program by analyzing wait times and exploring associations between administratively tracked variables and confirmed cardiac diagnosis. The findings indicate that the wait times for specialist consultation are shorter than previously reported in Alberta and age and sex have the strongest associations with a confirmed cardiac diagnosis.

  4. Improving Low-dose Cardiac CT Images based on 3D Sparse Representation

    NASA Astrophysics Data System (ADS)

    Shi, Luyao; Hu, Yining; Chen, Yang; Yin, Xindao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis

    2016-03-01

    Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images.

  5. Improving Low-dose Cardiac CT Images based on 3D Sparse Representation

    PubMed Central

    Shi, Luyao; Hu, Yining; Chen, Yang; Yin, Xindao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis

    2016-01-01

    Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images. PMID:26980176

  6. Improving Low-dose Cardiac CT Images based on 3D Sparse Representation.

    PubMed

    Shi, Luyao; Hu, Yining; Chen, Yang; Yin, Xindao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis

    2016-03-16

    Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images.

  7. Combination of principal component analysis and optical-flow motion compensation for improved cardiac MR thermometry

    NASA Astrophysics Data System (ADS)

    Toupin, S.; de Senneville, B. Denis; Ozenne, V.; Bour, P.; Lepetit-Coiffe, M.; Boissenin, M.; Jais, P.; Quesson, B.

    2017-02-01

    The use of magnetic resonance (MR) thermometry for the monitoring of thermal ablation is rapidly expanding. However, this technique remains challenging for the monitoring of the treatment of cardiac arrhythmia by radiofrequency ablation due to the heart displacement with respiration and contraction. Recent studies have addressed this problem by compensating in-plane motion in real-time with optical-flow based tracking technique. However, these algorithms are sensitive to local variation of signal intensity on magnitude images associated with tissue heating. In this study, an optical-flow algorithm was combined with a principal component analysis method to reduce the impact of such effects. The proposed method was integrated to a fully automatic cardiac MR thermometry pipeline, compatible with a future clinical workflow. It was evaluated on nine healthy volunteers under free breathing conditions, on a phantom and in vivo on the left ventricle of a sheep. The results showed that local intensity changes in magnitude images had lower impact on motion estimation with the proposed method. Using this strategy, the temperature mapping accuracy was significantly improved.

  8. 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.

  9. Exercise-induced pulmonary artery hypertension in a patient with compensated cardiac disease: hemodynamic and functional response to sildenafil therapy.

    PubMed

    Nikolaidis, Lazaros; Memon, Nabeel; O'Murchu, Brian

    2015-02-01

    We describe the case of a 54-year-old man who presented with exertional dyspnea and fatigue that had worsened over the preceding 2 years, despite a normally functioning bioprosthetic aortic valve and stable, mild left ventricular dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be explained by physical examination, an extensive biochemical profile, or multiple cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise test results and a right heart catheterization-combined with the use of a symptom-limited, bedside bicycle ergometer-revealed that the patient's exercise-induced pulmonary artery hypertension was out of proportion to his compensated left heart disease. A trial of sildenafil therapy resulted in objective improvements in hemodynamic values and functional class.

  10. Benefit Finding in Cardiac Patients: Relationships with Emotional Well-Being and Resources after Controlling for Physical Functional Impairment.

    PubMed

    Sanjuán, Pilar; García-Zamora, Cristina; Ruiz, M Ángeles; Rueda, Beatriz; Arranz, Henar; Castro, Almudena

    2016-09-19

    Benefit finding (BF) is defined as the individual's perception of positive change as a result of coping with an adverse life event. The beneficial effects of BF on well-being could be because BF favors the improvement of resources like self-efficacy, social support and effective coping. The main objective of this longitudinal 8 week study was to explore, in a sample of cardiac patients (n = 51), the combined contribution of BF and these resources to the positive affect. Moreover, we wanted to check whether these resources were derived from BF or, on the contrary, these resources were antecedents of BF. Results showed that after controlling for functional capacity, only effective coping could predict the positive affect at Time 1 (β = .32, p < .05), while the BF predicted it at Time 2 (β = .23, p < .001). Only social support predicted BF (β = .26, p < .05), but not the opposite. We discussed the desirability of promoting these processes to improve the emotional state of cardiac patients.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. New Developments in Cardiac Regeneration.

    PubMed

    Le, Thi Yen Loan; Thavapalachandran, Sujitha; Kizana, Eddy; Chong, James Jh

    2017-04-01

    Numerous pharmacological and device therapies have improved adverse cardiac remodelling and mortality in heart failure. However, none are able to regenerate damaged cardiac tissue. Stem cell based therapies using multipotent (adult) stem cells and pluripotent stem cells are new approaches that could potentially achieve the elusive goal of true cardiac regeneration. Over the past two decades, various stem cell based approaches have been shown to improve left ventricular function in pre-clinical animal models. Promising results rapidly led to clinical trials, initially using bone marrow-derived mononuclear cells, then mesenchymal stromal cell populations and, more recently, progenitor cells from the adult heart itself. These have been shown to be safe and have advanced our understanding of potential suitable recipients, cell delivery routes, and possible mechanisms of action. However, efficacy in these trials has been inconsistent. Human pluripotent stem cells (hPSCs) are another potential source of stem cells for cardiac regeneration. They could theoretically provide an unlimited source of cardiomyocytes or cardiac progenitors. Pre-clinical studies in both small and large animal models have shown robust engraftment and improvements in cardiac function. The first clinical trial using hPSC-derived cardiac derivatives has now commenced and others are imminent. In this brief review article, we summarise recent developments in stem cell therapies aimed at cardiac regeneration, including discussion of types of cell and non-cell-based strategies being explored.

  17. 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.

  18. 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.

  19. Influence of hydrotherapy on clinical and cardiac autonomic function in migraine patients

    PubMed Central

    Sujan, M. U.; Rao, M. Raghavendra; Kisan, Ravikiran; Abhishekh, Hulegar A.; Nalini, Atchayaram; Raju, Trichur R.; Sathyaprabha, T. N.

    2016-01-01

    Background: Migraine is associated with autonomic symptoms. The growing body of literature suggests that the dysfunctional autonomic nervous system might play a pivotal role in the pathogenesis of migraine. Thermal therapies have been hypothesized to modulate these changes and alleviate pain. However, data regarding the efficacy of hydrotherapy in migraine remain scant. We evaluated the effect of add on hydrotherapy procedure (a hot arm and foot bath with ice massage to head) in migraine patients. Methods: Forty chronic migraine patients fulfilling the International Classification of Headache Disorders II criteria were recruited from the neurology outpatient clinic. Patients were randomized to receive either hydrotherapy plus conventional pharmacological care (n = 20) or conventional medication only (n = 20). Hydrotherapy group received treatment with hot arm and foot bath (103°F to 110°F) and ice massage to head daily for 20 min for 45 days. Patients were assessed using headache impact test (HIT), visual analog scale for pain and cardiac autonomic function by heart rate variability (HRV) before and after intervention period. Results: There was a significant decrease in HIT score, frequency, and intensity of headaches following treatment in both the groups. However, it was more evident in add on hydrotherapy group compared to pharmacological treatment alone group. There was also significant improvement in the HRV parameters. In particular, there was a significant decrease in heart rate (P = 0.017), increase in high frequency (HF) (P = 0.014) and decrease in low frequency/HF ratio (P = 0.004) in add on hydrotherapy group. Conclusion: Our study shows that add on hydrotherapy enhanced the vagal tone in addition to reducing the frequency and intensity of headaches in migraine patients. PMID:26933356

  20. A Submaximal Running Test With Postexercise Cardiac Autonomic and Neuromuscular Function in Monitoring Endurance Training Adaptation.

    PubMed

    Vesterinen, Ville; Nummela, Ari; Laine, Tanja; Hynynen, Esa; Mikkola, Jussi; Häkkinen, Keijo

    2017-01-01

    Vesterinen, V, Nummela, A, Laine, T, Hynynen, E, Mikkola, J, and Häkkinen, K. A submaximal running test with postexercise cardiac autonomic and neuromuscular function in monitoring endurance training adaptation. J Strength Cond Res 31(1): 233-243, 2017-The aim of this study was to investigate whether a submaximal running test (SRT) with postexercise heart rate recovery (HRR), heart rate variability (HRV), and countermovement jump (CMJ) measurements could be used to monitor endurance training adaptation. Thirty-five endurance-trained men and women completed an 18-week endurance training. Maximal endurance performance and maximal oxygen uptake were measured every 8 weeks. In addition, SRTs with postexercise HRR, HRV, and CMJ measurements were carried out every 4 weeks. Submaximal running test consisted of two 6-minute stages at 70 and 80% of maximum heart rate (HRmax) and a 3-minute stage at 90% HRmax, followed by a 2-minute recovery stage for measuring postexercise HRR, HRV, and CMJ test. The highest responders according to the change of maximal endurance performance showed a significant improvement in running speeds during stages 2 and 3 in SRT, whereas no changes were observed in the lowest responders. The strongest correlation was found between the change of maximal endurance performance and running speed during stage 3, whereas no significant relationships were found between the change of maximal endurance performance and the changes of postexercise HRR, HRV, and CMJ. Running speed at 90% HRmax intensity was the most sensitive variable to monitor adaptation to endurance training. The present submaximal test showed potential to monitor endurance training adaptation. Furthermore, it may serve as a practical tool for athletes and coaches to evaluate weekly the effectiveness of training program without interfering in the normal training habits.

  1. Long-term treatment with naproxcinod significantly improves skeletal and cardiac disease phenotype in the mdx mouse model of dystrophy.

    PubMed

    Uaesoontrachoon, Kitipong; Quinn, James L; Tatem, Kathleen S; Van Der Meulen, Jack H; Yu, Qing; Phadke, Aditi; Miller, Brittany K; Gordish-Dressman, Heather; Ongini, Ennio; Miglietta, Daniela; Nagaraju, Kanneboyina

    2014-06-15

    In Duchenne muscular dystrophy (DMD) patients and the mouse model of DMD, mdx, dystrophin deficiency causes a decrease and mislocalization of muscle-specific neuronal nitric oxide synthase (nNOSμ), leading to functional impairments. Previous studies have shown that nitric oxide (NO) donation associated with anti-inflammatory action has beneficial effects in dystrophic mouse models. In this study, we have systematically investigated the effects of naproxcinod, an NO-donating naproxen derivative, on the skeletal and cardiac disease phenotype in mdx mice. Four-week-old mdx and C57BL/10 mice were treated with four different concentrations (0, 10, 21 and 41 mg/kg) of naproxcinod and 0.9 mg/kg of prednisolone in their food for 9 months. All mice were subjected to twice-weekly treadmill sessions, and functional and behavioral parameters were measured at 3, 6 and 9 months of treatment. In addition, we evaluated in vitro force contraction, optical imaging of inflammation, echocardiography and blood pressure (BP) at the 9-month endpoint prior to sacrifice. We found that naproxcinod treatment at 21 mg/kg resulted in significant improvement in hindlimb grip strength and a 30% decrease in inflammation in the fore- and hindlimbs of mdx mice. Furthermore, we found significant improvement in heart function, as evidenced by improved fraction shortening, ejection fraction and systolic BP. In addition, the long-term detrimental effects of prednisolone typically seen in mdx skeletal and heart function were not observed at the effective dose of naproxcinod. In conclusion, our results indicate that naproxcinod has significant potential as a safe therapeutic option for the treatment of muscular dystrophies.

  2. Accuracy and Robustness Improvements of Echocardiographic Particle Image Velocimetry for Routine Clinical Cardiac Evaluation

    NASA Astrophysics Data System (ADS)

    Meyers, Brett; Vlachos, Pavlos; Charonko, John; Giarra, Matthew; Goergen, Craig

    2015-11-01

    Echo Particle Image Velocimetry (echoPIV) is a recent development in flow visualization that provides improved spatial resolution with high temporal resolution in cardiac flow measurement. Despite increased interest a limited number of published echoPIV studies are clinical, demonstrating that the method is not broadly accepted within the medical community. This is due to the fact that use of contrast agents are typically reserved for subjects whose initial evaluation produced very low quality recordings. Thus high background noise and low contrast levels characterize most scans, which hinders echoPIV from producing accurate measurements. To achieve clinical acceptance it is necessary to develop processing strategies that improve accuracy and robustness. We hypothesize that using a short-time moving window ensemble (MWE) correlation can improve echoPIV flow measurements on low image quality clinical scans. To explore the potential of the short-time MWE correlation, evaluation of artificial ultrasound images was performed. Subsequently, a clinical cohort of patients with diastolic dysfunction was evaluated. Qualitative and quantitative comparisons between echoPIV measurements and Color M-mode scans were carried out to assess the improvements delivered by the proposed methodology.

  3. c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction

    PubMed Central

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.

    2015-01-01

    Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction (TAC; n = 7/group). Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes. PMID:26266538

  4. 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

  5. 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

  6. Improved Outcome of Cardiac Extracorporeal Membrane Oxygenation in Infants and Children Using Magnetic Levitation Centrifugal Pumps.

    PubMed

    Luciani, Giovanni Battista; Hoxha, Stiljan; Torre, Salvatore; Rungatscher, Alessio; Menon, Tiziano; Barozzi, Luca; Faggian, Giuseppe

    2016-01-01

    repair (P = 0.03). During a median follow-up of 34 months (range 4-62 months), there were three (23%) late deaths and two late survivors with neurological sequelae. Weaning rate (5/7 vs. 21/26, P = NS) and prevalence of renal failure requiring dialysis (4/7 vs. 13/26, P = NS) were comparable between SP and ML ECMO groups. Patients supported with ML had a trend toward higher hospital survival (1/7 vs. 12/26, P = 0.07) and significantly higher late survival (0/7 vs. 10/26, P = 0.05). The present experience shows that V-A ECMO for cardiac indications using centrifugal pumps in infants and children yields outcomes absolutely comparable to international registry (ELSO) data using mostly roller pumps. Although changes in practice may have contributed to these results, use of ML centrifugal pumps appears to further improve end-organ recovery and hospital and late survival.

  7. Hyperbaric oxygen can induce neuroplasticity and improve cognitive functions of patients suffering from anoxic brain damage

    PubMed Central

    Hadanny, A.; Golan, H.; Fishlev, G.; Bechor, Y.; Volkov, O.; Suzin, G.; Ben-Jacob, E.; Efrati, S.

    2015-01-01

    Abstract Purpose: Cognitive impairment may occur in 42–50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury. The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest. Methods: Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging. Results: The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5–7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging. Conclusions: Although further research is needed, the results demonstrate the beneficial effects of HBO2 on CCI in patients after cardiac arrest, even months to years after the acute event. PMID:26409406

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Peptide Mimetics of Apolipoproteins Improve HDL Function

    PubMed Central

    Navab, Mohamad; Anantharamaiah, G. M.; Reddy, Srinivasa T.; Van Lenten, Brian J.; Buga, Georgette M.; Fogelman, Alan M.

    2007-01-01

    Over the past decade evidence has accumulated that suggests that the anti-inflammatory properties of HDL may be at least as important as the levels of HDL-cholesterol. The recent failure of the torcetrapib clinical trails has highlighted the potential differences between HDL-cholesterol levels and HDL function. Agents to improve HDL function including HDL anti-inflammatory properties provide a new therapeutic strategy for ameliorating atherosclerosis and other chronic inflammatory conditions related to dyslipidemia. Seeking guidance from the structure of the apolipoproteins of the plasma lipoproteins has allowed the creation of a series of polypeptides that have interesting functionality with therapeutic implications. In animal models of atherosclerosis, peptide mimetics of apolipoproteins have been shown to improve the anti-inflammatory properties of HDL, significantly reduce lesions and improve vascular inflammation and function without necessarily altering HDL-cholesterol levels. Some of these are now entering the clinical arena as interventions in pharmacologic and pharmacodynamic studies. PMID:18449337

  17. 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

  18. Intracoronary administration of cardiac stem cells in mice: a new, improved technique for cell therapy in murine models.

    PubMed

    Li, Qianhong; Guo, Yiru; Ou, Qinghui; Chen, Ning; Wu, Wen-Jian; Yuan, Fangping; O'Brien, Erin; Wang, Tao; Luo, Li; Hunt, Gregory N; Zhu, Xiaoping; Bolli, Roberto

    2011-09-01

    A model of intracoronary stem cell delivery that enables transgenesis/gene targeting would be a powerful tool but is still lacking. To address this gap, we compared intracoronary and intramyocardial delivery of lin(-)/c-kit(+)/GFP(+) cardiac stem cells (CSCs) in a murine model of reperfused myocardial infarction (MI). Lin(-)/c-kit(+)/GFP(+) CSCs were successfully expanded from GFP transgenic hearts and cultured with no detectable phenotypic change for up to ten passages. Intracoronary delivery of CSCs 2 days post-MI resulted in significant alleviation of adverse LV remodeling and dysfunction, which was at least equivalent, if not superior, to that achieved with intramyocardial delivery. Compared with intramyocardial injection, intracoronary infusion was associated with a more homogeneous distribution of CSCs in the infarcted region and a greater increase in viable tissue in this region, suggesting greater formation of new cardiomyocytes. Intracoronary CSC delivery resulted in improved function in the infarcted region, as well as in improved global LV systolic and diastolic function, and in decreased LV dilation and LV expansion index; the magnitude of these effects was similar to that observed after intramyocardial injection. We conclude that, in the murine model of reperfused MI, intracoronary CSC infusion is at least as effective as intramyocardial injection in limiting LV remodeling and improving both regional and global LV function. The intracoronary route appears to be superior in terms of uniformity of cell distribution, myocyte regeneration, and amount of viable tissue in the risk region. To our knowledge, this is the first study to report that intracoronary infusion of stem cells in mice is feasible and effective.

  19. Measurement of the Red Blood Cell Distribution Width Improves the Risk Prediction in Cardiac Resynchronization Therapy

    PubMed Central

    Boros, András Mihály; Perge, Péter; Jenei, Zsigmond; Karády, Júlia; Zima, Endre; Molnár, Levente; Becker, Dávid; Gellér, László; Prohászka, Zoltán; Merkely, Béla; Széplaki, Gábor

    2016-01-01

    Objectives. Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction. Design. The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed. Results. After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n = 57). In the final model including all variables, the RDW [HR = 2.49 (1.27–4.86); p = 0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93–3.51); p = 0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model. Conclusions. Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT. PMID:26903690

  20. 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.

  1. Cardiac catheterization

    MedlinePlus

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

  2. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    PubMed

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  3. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

    SciTech Connect

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.; Bertrand, Luc

    2015-08-12

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.

  4. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

    DOE PAGES

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; ...

    2015-08-12

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.« less

  5. Influence of angiotensin converting enzyme inhibition on pump function and cardiac contractility in patients with chronic congestive heart failure.

    PubMed Central

    Baur, L H; Schipperheyn, J J; Baan, J; van der Laarse, A; Buis, B; van der Wall, E E; Manger Cats, V; van Dijk, A D; Blokland, J A; Frölich, M

    1991-01-01

    Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function. PMID:2015121

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Usefulness of case reports to improve medical knowledge regarding trigemino-cardiac reflex in skull base surgery

    PubMed Central

    2011-01-01

    We describe the discovery of the trigemino-cardiac reflex by Schaller in 1999 and the continued improvement of the knowledge about the trigemino-cardiac reflex involved in neurosurgery, especially in skull base surgery, during the past several years. The achieved medical progress could be gained only by the practical experience described by different case reports and later case series that have been published in several principal scientific journals. Additionally, we explain the scientific as well as clinical importance of the communication of the case reports on TCR. Special reference has been given to the validity of the case reports for new phenomena in clinical medicine. PMID:21496216

  12. 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.

  13. Social media in paediatric heart disease: professional use and opportunities to improve cardiac care.

    PubMed

    Schumacher, Kurt R; Lee, Joyce M; Pasquali, Sara K

    2015-12-01

    Social media is any type of communication utilising electronic technology that follows two guiding principles: free publishing or sharing of content and ideas and group collaboration and inter-connectedness. Over the last 10 years, social media technology has made tremendous inroads into all facets of communication. Modalities such as Facebook, YouTube, and Twitter are no longer viewed as new communication technologies. Owing to their tremendous usage, they are now common ways to conduct a dialogue with individuals and groups. Greater than 91% of teenagers and 89% of young adults routinely use social media. Further, 24% of teenagers reported being online "almost constantly". These forms of communication are readily used by individuals cared for in the field of paediatric cardiology; thus, they should carry significant interest for cardiology care providers; however, social media's influence on medicine extends beyond use by patients. It directly affects all medical providers, both users and non-users. Further, social media has the ability to improve care for patients with paediatric heart disease. This article details social media's current influence on paediatric cardiology, including considerations for professional use of social media and potential opportunities to improve cardiac care.

  14. 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

  15. Protective effects of a magnesium magnetic isotope (Mg25)-exchanging nanoparticle (25MgPMC16 ) on mitochondrial functional disorders in esmolol-induced cardiac arrest in rats.

    PubMed

    Adeli, S; Zarrindast, M R; Niknahad, H; Sarkar, S; Bidgoli, S A; Korani, M; Ghasemzadeh, P; Rezayat, S M

    2012-04-01

    In cardiac surgery, agents are needed to produce temporary cardiac arrest (cardioplegia). One of these agents is esmolol (ESM) which is a short-acting selective beta-1 adrenergic receptor antagonist and its overdose causes diastolic ventricular arrest. The (25) MgPMC(16) (porphyrin adducts of cyclohexil fullerene-C60) is known as a nanoparticle which has a cardioprotective effect when the heart is subjected to stressful conditions. In this study, we aimed to confirm the deleterious effects of ESM overdose on cardiac mitochondria and identify any protective effects of (25) MgPMC(16) in male Wistar rats. Esmolol 100 mg kg(-1) (LD50 = 71 mg kg(-1) ) was injected intravenously (i.v.) into tail vein to induce cardiac arrest. This dose was obtained from an ESM dose-response curve which induces at least 80% arrest in rats. (25) MgPMC(16) at three different doses (45, 90 and 224 mg kg(-1) ) was injected i.v. as pretreatment, eight hours before ESM injection. (25) MgCl(2) or (24) MgPMC(16) were used as controls. Following cardiac arrest, the heart was removed and the mitochondria extracted. Mitochondrial viability and the adenosine 5'-diphosphate sodium salt hydrate/Adenosine 5'-triphosphate disodium salt hydrate (ADP/ATP) ratio were measured as biomarkers of mitochondrial function. Results indicate that (25) MgPMC(16) caused a significant increase in mitochondrial viability and decrease in ADP/ATP ratio. No significant changes were seen with (24) MgPMC(16) or (25) MgCl(2) . It is concluded that cardiac arrest induced by ESM overdose leads to a significant decrease in mitochondrial viability and their ATP levels, whereas pretreatment by (25) MgPMC(16) can protect mitochondria by increasing ATP level through liberation of Mg into cells and the improvement of hypoxia.

  16. Improved Approximate Profile Function of Hedgehog Skyrmion

    NASA Astrophysics Data System (ADS)

    Ji, Yong-Lin; Jia, Duo-Jie; Xi, Guo-Zhu; Liu, Feng

    The profile function for Skyrme model is investigated in Hedgehog ansatz. An improved analytical solution to the Hedgehog Skyrmion is obtained by using tentative function method. It is found that ensuing calculated static energy is smaller than that in Ref. 13, and the isoscalar electric mean square radius √ {< r2>}I=0 and the isoscalar magnetic mean square radius √ {< r2>}M,I=0 well agree with experiment results.

  17. Cardiac Dysautonomia in Huntington's Disease.

    PubMed

    Abildtrup, Mads; Shattock, Michael

    2013-01-01

    Huntington's disease is a fatal, hereditary, neurodegenerative disorder best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances. Although a disease of the central nervous system, mortality surveys indicate that heart disease is a leading cause of death. The nature of such cardiac abnormalities remains unknown. Clinical findings indicate a high prevalence of autonomic nervous system dysfunction - dysautonomia - which may be a result of pathology of the central autonomic network. Dysautonomia can have profound effects on cardiac health, and pronounced autonomic dysfunction can be associated with neurogenic arrhythmias and sudden cardiac death. Significant advances in the knowledge of neural mechanisms in cardiac disease have recently been made which further aid our understanding of cardiac mortality in Huntington's disease. Even so, despite the evidence of aberrant autonomic activity the potential cardiac consequences of autonomic dysfunction have been somewhat ignored. In fact, underlying cardiac abnormalities such as arrhythmias have been part of the exclusion criteria in clinical autonomic Huntington's disease research. A comprehensive analysis of cardiac function in Huntington's disease patients is warranted. Further experimental and clinical studies are needed to clarify how the autonomic nervous system is controlled and regulated in higher, central areas of the brain - and how these regions may be altered in neurological pathology, such as Huntington's disease. Ultimately, research will hopefully result in an improvement of management with the aim of preventing early death in Huntington's disease from cardiac causes.

  18. The beneficial effects of ranolazine on cardiac function after myocardial infarction are greater in diabetic than in nondiabetic rats.

    PubMed

    Mourouzis, Iordanis; Mantzouratou, Polixeni; Galanopoulos, Georgios; Kostakou, Erietta; Dhalla, Arvinder K; Belardinelli, Luiz; Pantos, Constantinos

    2014-09-01

    Ranolazine (RAN) is known to exert both anti-ischemic and antidiabetic actions. Thus, this study has explored the hypothesis that RAN would have greater effect on the recovery of cardiac function in diabetic mellitus (DM) rat hearts following myocardial infarction (MI). Myocardial infarction was induced in nondiabetic (MI, n = 14) and diabetic (streptozotocin induced; DM-MI, n = 13) Wistar rats by permanent ligation of the left coronary artery. Cardiac function was evaluated using echocardiography (left ventricular ejection fraction %) and in isolated heart preparations by measuring left ventricular developed pressure (LVDP), and the positive and negative first derivative of LVDP (± dp/dt). Ranolazine (20 mg/kg, ip once a day) was administered 24 hours after surgical procedure for 4 weeks to nondiabetic (MI + RAN, n = 17) and diabetic rats (DM-MI + RAN, n = 15). The RAN improved the recovery of function in both the nondiabetic and the diabetic postinfarcted hearts but this effect was greater and achieved statistical significance only in the diabetic group. The RAN resulted in increased levels of phosphorylated protein kinase B (Akt) and mammalian target of rapamycin (mTOR, a component of Akt signaling) in both nondiabetic and diabetic infarcted hearts without changes in the activation of mitogen-activated protein kinases (MAPKs; p38 MAPK, c-Jun N-terminal kinase, and extracellular signal-regulated kinase). In addition, in diabetic hearts, RAN resulted in a significant increase in the ratio of sarcoplasmic Ca(2+)-ATPase/phospholamban (a target of Akt signaling, 2.0-fold increase) and increased levels of phosphorylated calcium-regulated adenosine monophosphate-activated protein kinase (AMPK; 2.0-fold increase). In diabetic animals, RAN increased insulin and lowered glucose levels in serum. In conclusion, the beneficial effect of RAN on the recovery of cardiac function after MI was greater in DM rats. This response was associated with activation of Akt/mTOR and AMPK

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. Artificial gravity with ergometric exercise preserves the cardiac, but not cerebrovascular, functions during 4 days of head-down bed rest.

    PubMed

    Yang, Chang-Bin; Wang, Yong-Chun; Gao, Yuan; Geng, Jie; Wu, Yan-Hong; Zhang, Yu; Shi, Fei; Sun, Xi-Qing

    2011-12-01

    Cardiovascular and musculoskeletal deconditioning occurring in long-term spaceflight requires new strategies to counteract these adverse effects. We previously reported that a short-arm centrifuge produced artificial gravity (AG), together with ergometer, has an approving effect on promoting cardiovascular function. The current study sought to investigate whether the cardiac and cerebrovascular functions were maintained and improved using a strategy of AG combined with exercise training on cardiovascular function during 4-day head-down bed rest (HDBR). Twelve healthy male subjects were assigned to a control group (CONT, n=6) and an AG combined with ergometric exercise training group (CM, n=6). Simultaneously, cardiac pumping and systolic functions, cerebral blood flow were measured before, during, and after HDBR. The results showed that AG combined with ergometric exercise caused an increase trend of number of tolerance, however, there was no significant difference between the two groups. After 4-day HDBR in the CONT group, heart rate increased significantly (59±6 vs 66±7 beats/min), while stroke volume (98±12 vs 68±13 mL) and cardiac output (6±1 vs 4±1 L/min) decreased significantly (p<0.05). All subjects had similar drops on cerebral vascular function. Volume regulating hormone aldosterone increased in both groups (by 119.9% in CONT group and 112.8% in the CM group), but only in the CONT group there were a significant changes (p<0.05). Angiotensin II was significantly increased by 140.5% after 4-day HDBR in the CONT group (p<0.05), while no significant changes were observed in the CM group. These results indicated that artificial gravity with ergometric exercise successfully eliminated changes induced by simulated weightlessness in heart rate, volume regulating hormones, and cardiac pumping function and partially maintained cardiac systolic function. Hence, a daily 1h alternating +1.0 and +2.0 Gz with 40 W exercise training appear to be an effective

  7. 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.

  8. 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

  9. 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.

  10. 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