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Sample records for improved cardiac function

  1. Cardiac Rehabilitation: Improving Function and Reducing Risk.

    PubMed

    Servey, Jessica T; Stephens, Mark

    2016-07-01

    Cardiac rehabilitation is a comprehensive multidisciplinary program individually tailored to the needs of patients with cardiovascular disease. The overall goals focus on improving daily function and reducing cardiovascular risk factors. Cardiac rehabilitation includes interventions aimed at lowering blood pressure and improving lipid and diabetes mellitus control, with tobacco cessation, behavioral counseling, and graded physical activity. The physical activity component typically involves 36 sessions over 12 weeks, during which patients participate in supervised exercise under cardiac monitoring. There are also intensive programs that include up to 72 sessions lasting up to 18 weeks, although these programs are not widely available. Additional components of cardiac rehabilitation include counseling on nutrition, screening for and managing depression, and assuring up-to-date immunizations. Cardiac rehabilitation is covered by Medicare and recommended for patients following myocardial infarction, bypass surgery, and stent placement, and for patients with heart failure, stable angina, and several other conditions. Despite proven benefits in mortality rates, depression, functional capacity, and medication adherence, rates of referral for cardiac rehabilitation are suboptimal. Groups less likely to be referred are older adults, women, patients who do not speak English, and persons living in areas where cardiac rehabilitation is not locally available. Additionally, primary care physicians refer patients less often than cardiologists and cardiothoracic surgeons. PMID:27386722

  2. Exercise improves cardiac autonomic function in obesity and diabetes.

    PubMed

    Voulgari, Christina; Pagoni, Stamatina; Vinik, Aaron; Poirier, Paul

    2013-05-01

    Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. PMID:23084034

  3. Losartan decreases cardiac muscle fibrosis and improves cardiac function in dystrophin-deficient mdx mice.

    PubMed

    Spurney, Christopher F; Sali, Arpana; Guerron, Alfredo D; Iantorno, Micaela; Yu, Qing; Gordish-Dressman, Heather; Rayavarapu, Sree; van der Meulen, Jack; Hoffman, Eric P; Nagaraju, Kanneboyina

    2011-03-01

    Recent studies showed that chronic administration of losartan, an angiotensin II type I receptor antagonist, improved skeletal muscle function in dystrophin-deficient mdx mice. In this study, C57BL/10ScSn-Dmd(mdx)/J female mice were either untreated or treated with losartan (n = 15) in the drinking water at a dose of 600 mg/L over a 6-month period. Cardiac function was assessed via in vivo high frequency echocardiography and skeletal muscle function was assessed using grip strength testing, Digiscan monitoring, Rotarod timing, and in vitro force testing. Fibrosis was assessed using picrosirius red staining and Image J analysis. Gene expression was evaluated using real-time polymerized chain reaction (RT-PCR). Percentage shortening fraction was significantly decreased in untreated (26.9% ± 3.5%) mice compared to losartan-treated (32.2% ± 4.2%; P < .01) mice. Systolic blood pressure was significantly reduced in losartan-treated mice (56 ± 6 vs 69 ± 7 mm Hg; P < .0005). Percentage cardiac fibrosis was significantly reduced in losartan-treated hearts (P < .05) along with diaphragm (P < .01), extensor digitorum longus (P < .05), and gastrocnemius (P < .05) muscles compared to untreated mdx mice. There were no significant differences in skeletal muscle function between treated and untreated groups. Chronic treatment with losartan decreases cardiac and skeletal muscle fibrosis and improves cardiac systolic function in dystrophin-deficient mdx mice. PMID:21304057

  4. Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction.

    PubMed

    Wang, Qingjie; Yang, Hui; Bai, Aobing; Jiang, Wei; Li, Xiuya; Wang, Xinhong; Mao, Yishen; Lu, Chao; Qian, Ruizhe; Guo, Feng; Ding, Tianling; Chen, Haiyan; Chen, Sifeng; Zhang, Jianyi; Liu, Chen; Sun, Ning

    2016-10-01

    With the advent of induced pluripotent stem cells and directed differentiation techniques, it is now feasible to derive individual-specific cardiac cells for human heart tissue engineering. Here we report the generation of functional engineered human cardiac patches using human induced pluripotent stem cells-derived cardiac cells and decellularized natural heart ECM as scaffolds. The engineered human cardiac patches can be tailored to any desired size and shape and exhibited normal contractile and electrical physiology in vitro. Further, when patching on the infarct area, these patches improved heart function of rats with acute myocardial infarction in vivo. These engineered human cardiac patches can be of great value for normal and disease-specific heart tissue engineering, drug screening, and meet the demands for individual-specific heart tissues for personalized regenerative therapy of myocardial damages in the future. PMID:27509303

  5. 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

  6. Regular Football Practice Improves Autonomic Cardiac Function in Male Children

    PubMed Central

    Fernandes, Luis; Oliveira, Jose; Soares-Miranda, Luisa; Rebelo, Antonio; Brito, Joao

    2015-01-01

    Background: The role of the autonomic nervous system (ANS) in the cardiovascular regulation is of primal importance. Since it has been associated with adverse conditions such as cardiac arrhythmias, sudden death, sleep disorders, hypertension and obesity. Objectives: The present study aimed to investigate the impact of recreational football practice on the autonomic cardiac function of male children, as measured by heart rate variability. Patients and Methods: Forty-seven male children aged 9 - 12 years were selected according to their engagement with football oriented practice outside school context. The children were divided into a football group (FG; n = 22) and a control group (CG; n = 25). The FG had regular football practices, with 2 weekly training sessions and occasional weekend matches. The CG was not engaged with any physical activity other than complementary school-based physical education classes. Data from physical activity, physical fitness, and heart rate variability measured in time and frequency domains were obtained. Results: The anthropometric and body composition characteristics were similar in both groups (P > 0.05). The groups were also similar in time spent daily on moderate-to-vigorous physical activities (FG vs. CG: 114 ± 64 vs. 87 ± 55 minutes; P > 0.05). However, the FG performed better (P < 0.05) in Yo-Yo intermittent endurance test (1394 ± 558 vs. 778 ± 408 m) and 15-m sprint test (3.06 ± 0.17 vs. 3.20 ± 0.23 s). Also, the FG presented enhanced autonomic function. Significant differences were detected (P < 0.05) between groups for low frequency normalized units (38.0 ± 15.2 vs. 47.3 ± 14.2 n.u (normalized units)), high frequency normalized units (62.1 ± 15.2 vs. 52.8 ± 14.2 n.u.), and LF:HF ratio (0.7 ± 0.4 vs. 1.1 ± 0.6 ms2). Conclusions: Children engaged with regular football practice presented enhanced physical fitness and autonomic function, by increasing vagal tone at rest. PMID:26448848

  7. Implantation of cardiac progenitor cells using self-assembling peptide improves cardiac function after myocardial infarction.

    PubMed

    Tokunaga, Masakuni; Liu, Mei-Lan; Nagai, Toshio; Iwanaga, Koji; Matsuura, Katsuhisa; Takahashi, Toshinao; Kanda, Masato; Kondo, Naomichi; Wang, Pin; Naito, Atsuhiko T; Komuro, Issei

    2010-12-01

    Implantation of various types of cells into the heart has been reported to be effective for heart failure, however, it is unknown what kinds of cells are most suitable for myocardial repair. To examine which types of cells are most effective, we injected cell-Puramatrix™ (PM) complex into the border area and overlaid the cell-PM patch on the myocardial infarction (MI) area. We compared cardiac morphology and function at 2 weeks after transplantation. Among clonal stem cell antigen-1 positive cardiac progenitors with PM (cSca-1/PM), bone marrow mononuclear cells with PM (BM/PM), skeletal myoblasts with PM (SM/PM), adipose tissue-derived mesenchymal cells with PM (AMC/PM), PM alone (PM), and non-treated MI group (MI), the infarct area of cSca-1/PM was smaller than that of BM/PM, SM/PM, PM and MI. cSca-1/PM and AMC/PM attenuated ventricular enlargement and restored cardiac function in comparison with MI. Capillary density in the infarct area of cSca-1/PM was higher than that of other five groups. The percentage of TUNEL positive cardiomyocytes in the infarct area of cSca-1/PM was lower than that of MI and PM. cSca-1 secreted VEGF and some of them differentiated into cardiomyocytes and vascular smooth muscle cells. These results suggest that transplantation of cSca-1/PM most effectively prevents cardiac remodeling and dysfunction through angiogenesis, inhibition of apoptosis and myocardial regeneration. PMID:20869968

  8. Nanowires and Electrical Stimulation Synergistically Improve Functions of hiPSC Cardiac Spheroids.

    PubMed

    Richards, Dylan J; Tan, Yu; Coyle, Robert; Li, Yang; Xu, Ruoyu; Yeung, Nelson; Parker, Arran; Menick, Donald R; Tian, Bozhi; Mei, Ying

    2016-07-13

    The advancement of human induced pluripotent stem-cell-derived cardiomyocyte (hiPSC-CM) technology has shown promising potential to provide a patient-specific, regenerative cell therapy strategy to treat cardiovascular disease. Despite the progress, the unspecific, underdeveloped phenotype of hiPSC-CMs has shown arrhythmogenic risk and limited functional improvements after transplantation. To address this, tissue engineering strategies have utilized both exogenous and endogenous stimuli to accelerate the development of hiPSC-CMs. Exogenous electrical stimulation provides a biomimetic pacemaker-like stimuli that has been shown to advance the electrical properties of tissue engineered cardiac constructs. Recently, we demonstrated that the incorporation of electrically conductive silicon nanowires to hiPSC cardiac spheroids led to advanced structural and functional development of hiPSC-CMs by improving the endogenous electrical microenvironment. Here, we reasoned that the enhanced endogenous electrical microenvironment of nanowired hiPSC cardiac spheroids would synergize with exogenous electrical stimulation to further advance the functional development of nanowired hiPSC cardiac spheroids. For the first time, we report that the combination of nanowires and electrical stimulation enhanced cell-cell junction formation, improved development of contractile machinery, and led to a significant decrease in the spontaneous beat rate of hiPSC cardiac spheroids. The advancements made here address critical challenges for the use of hiPSC-CMs in cardiac developmental and translational research and provide an advanced cell delivery vehicle for the next generation of cardiac repair. PMID:27328393

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

    PubMed Central

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

    2009-01-01

    Summary 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 Gαq 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 Gαq 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 β-adrenergic stimulation in Gαq transgenic mice. Consistent with this observation, ROCK1 deletion prevented down-regulation of type V/VI adenylyl cyclase expression, which is associated with the impaired β-adrenergic signaling in Gαq mice. The present study establishes for the first time a role for ROCK1 in cardiac dilation and contractile dysfunction. PMID:18178218

  10. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    PubMed Central

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  11. Vagus Nerve Stimulation Improves Cardiac Function by Preventing Mitochondrial Dysfunction in Obese-Insulin Resistant Rats

    PubMed Central

    Samniang, Bencharunan; Shinlapawittayatorn, Krekwit; Chunchai, Titikorn; Pongkan, Wanpitak; Kumfu, Sirinart; Chattipakorn, Siriporn C.; KenKnight, Bruce H.; Chattipakorn, Nipon

    2016-01-01

    Long-term high-fat diet (HFD) consumption leads to not only obese-insulin resistance, but also impaired left ventricular (LV) function. Vagus nerve stimulation (VNS) has been shown to exert cardioprotection. However, its effects on the heart and metabolic parameters under obese-insulin resistant condition is not known. We determined the effects of VNS on metabolic parameters, heart rate variability (HRV) and LV function in obese-insulin resistant rats. Male Wistar rats were fed with HFD for 12 weeks, and were randomly divided into sham and VNS groups. VNS was applied for the next 12 weeks. Echocardiography, blood pressure and HRV were examined. Blood samples were collected for metabolic parameters. At the end, the heart was removed for determination of apoptosis, inflammation, oxidative stress, and cardiac mitochondrial function. VNS for 12 weeks significantly decreased plasma insulin, HOMA index, total cholesterol, triglyceride, LDL and visceral fat. Serum adiponectin was significantly increased in the VNS group. VNS also significantly decreased blood pressure, improved HRV and LV function, decreased cardiac MDA, TNF-α and Bax levels, and improved cardiac mitochondrial function. VNS improves metabolic and hemodynamic parameters, and the LV function via its ability against apoptosis, inflammation and oxidative stress, and preserved cardiac mitochondrial function in obese-insulin resistant rats. PMID:26830020

  12. Proteasome inhibition slightly improves cardiac function in mice with hypertrophic cardiomyopathy

    PubMed Central

    Schlossarek, Saskia; Singh, Sonia R.; Geertz, Birgit; Schulz, Herbert; Reischmann, Silke; Hübner, Norbert; Carrier, Lucie

    2014-01-01

    A growing line of evidence indicates a dysfunctional ubiquitin-proteasome system (UPS) in cardiac diseases. Anti-hypertrophic effects and improved cardiac function have been reported after treatment with proteasome inhibitors in experimental models of cardiac hypertrophy. Here we tested whether proteasome inhibition could also reverse the disease phenotype in a genetically-modified mouse model of hypertrophic cardiomyopathy (HCM), which carries a mutation in Mybpc3, encoding the myofilament protein cardiac myosin-binding protein C. At 7 weeks of age, homozygous mutant mice (KI) have 39% higher left ventricular mass-to-body-weight ratio and 29% lower fractional area shortening (FAS) than wild-type (WT) mice. Both groups were treated with epoxomicin (0.5 mg/kg/day) or vehicle for 1 week via osmotic minipumps. Epoxomicin inhibited the chymotrypsin-like activity by ~50% in both groups. All parameters of cardiac hypertrophy (including the fetal gene program) were not affected by epoxomicin treatment in both groups. In contrast, FAS was 12% and 35% higher in epoxomicin-treated than vehicle-treated WT and KI mice, respectively. To identify which genes or pathways could be involved in this positive effect, we performed a transcriptome analysis in KI and WT neonatal cardiac myocytes, treated or not with the proteasome inhibitor MG132 (1 μM, 24 h). This revealed 103 genes (four-fold difference; 5% FDR) which are commonly regulated in both KI and WT cardiac myocytes. Thus, even in genetically-modified mice with manifest HCM, proteasome inhibition showed beneficial effects, at least with regard to cardiac function. Targeting the UPS in cardiac diseases remains therefore a therapeutic option. PMID:25566086

  13. 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

  14. 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.

  15. Anti-rat soluble IL-6 receptor antibody down-regulates cardiac IL-6 and improves cardiac function following trauma-hemorrhage.

    PubMed

    Yang, Shaolong; Hu, Shunhua; Choudhry, Mashkoor A; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

    2007-03-01

    Although anti-IL-6-mAb down-regulates cardiac IL-6 and attenuates IL-6-mediated cardiac dysfunction following trauma-hemorrhage, it is not known whether blockade of IL-6 receptor will down-regulate cardiac IL-6 and improve cardiac function under those conditions. Six groups of male adult rats (275-325 g) were used: sham/trauma-hemorrhage+vehicle, sham/trauma-hemorrhage+IgG, sham/trauma-hemorrhage+anti-rat sIL-6R. Rats underwent trauma-hemorrhage (removal of 60% of the circulating blood volume and fluid resuscitation after 90 min). Vehicle (V), normal goat IgG or anti-rat sIL-6R (16.7 microg/kg BW) was administered intra-peritoneally in the middle of resuscitation. Two hours later, cardiac function was measured by ICG dilution technique; blood samples collected, cardiomyocytes isolated, and cardiomyocyte nuclei were then extracted. Cardiac IL-6, IL-6R, gp130, IkappaB-alpha/P-IkappaB-alpha, NF-kappaB, and ICAM-1 expressions were measured by immunoblotting. Plasma IL-6 and cardiomyocyte NF-kappaB DNA-binding activity were determined by ELISA. In additional animals, heart harvested and cardiac MPO activity and CINC-1 and -3 were also measured. In another group of rats, cardiac function was measure by microspheres at 24 h following trauma-hemorrhage. Cardiac function was depressed and cardiac IL-6, P-IkappaB-alpha, NF-kappaB and its DNA-binding activity, ICAM-1, MPO activity, and CINC-1 and -3 were markedly increased after trauma-hemorrhage. Moreover, cardiac dysfunction was evident even 24 h after trauma-hemorrhage. Administration of sIL-6R following trauma-hemorrhage: (1) improved cardiac output at 2 h and 24 h (p<0.05); (2) down-regulated both cardiac IL-6 and IL-6R (p<0.05); and (3) attenuated cardiac P-IkappaB-alpha, NF-kappaB, NF-kappaB DNA-binding activity, ICAM-1, CINC-1, -3, and MPO activity (p<0.05). IgG did not significantly influence the above parameters. Thus, IL-6-mediated up-regulation of cardiac NF-kappaB, ICAM-1, CINC-1, -3, and MPO activity likely

  16. Pulsed electromagnetic field improves cardiac function in response to myocardial infarction

    PubMed Central

    Hao, Chang-Ning; Huang, Jing-Juan; Shi, Yi-Qin; Cheng, Xian-Wu; Li, Hao-Yun; Zhou, Lin; Guo, Xin-Gui; Li, Rui-Lin; Lu, Wei; Zhu, Yi-Zhun; Duan, Jun-Li

    2014-01-01

    Extracorporeal pulsed electromagnetic field (PEMF) has been shown the ability to improve regeneration in various ischemic episodes. Here, we examined whether PEMF therapy facilitate cardiac recovery in rat myocardial infarction (MI), and the cellular/molecular mechanisms underlying PEMF-related therapy was further investigated. The MI rats were exposed to active PEMF for 4 cycles per day (8 minutes/cycle, 30 ± 3 Hz, 5 mT) after MI induction. The data demonstrated that PEMF treatment significantly inhibited cardiac apoptosis and improved cardiac systolic function. Moreover, PEMF treatment increased capillary density, the levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor-1α in infarct border zone. Furthermore, the number and function of circulating endothelial progenitor cells were advanced in PEMF treating rats. In vitro, PEMF induced the degree of human umbilical venous endothelial cells tubulization and increased soluble pro-angiogenic factor secretion (VEGF and nitric oxide). In conclusion, PEMF therapy preserves cardiac systolic function, inhibits apoptosis and trigger postnatal neovascularization in ischemic myocardium. PMID:24936220

  17. Pulsed electromagnetic field improves cardiac function in response to myocardial infarction.

    PubMed

    Hao, Chang-Ning; Huang, Jing-Juan; Shi, Yi-Qin; Cheng, Xian-Wu; Li, Hao-Yun; Zhou, Lin; Guo, Xin-Gui; Li, Rui-Lin; Lu, Wei; Zhu, Yi-Zhun; Duan, Jun-Li

    2014-01-01

    Extracorporeal pulsed electromagnetic field (PEMF) has been shown the ability to improve regeneration in various ischemic episodes. Here, we examined whether PEMF therapy facilitate cardiac recovery in rat myocardial infarction (MI), and the cellular/molecular mechanisms underlying PEMF-related therapy was further investigated. The MI rats were exposed to active PEMF for 4 cycles per day (8 minutes/cycle, 30 ± 3 Hz, 5 mT) after MI induction. The data demonstrated that PEMF treatment significantly inhibited cardiac apoptosis and improved cardiac systolic function. Moreover, PEMF treatment increased capillary density, the levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor-1α in infarct border zone. Furthermore, the number and function of circulating endothelial progenitor cells were advanced in PEMF treating rats. In vitro, PEMF induced the degree of human umbilical venous endothelial cells tubulization and increased soluble pro-angiogenic factor secretion (VEGF and nitric oxide). In conclusion, PEMF therapy preserves cardiac systolic function, inhibits apoptosis and trigger postnatal neovascularization in ischemic myocardium. PMID:24936220

  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. Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stimulation.

    PubMed

    Otsuki, Yuki; Nakamura, Yoshinobu; Harada, Shingo; Yamamoto, Yasutaka; Ogino, Kazuhide; Morikawa, Kumi; Ninomiya, Haruaki; Miyagawa, Shigeru; Sawa, Yoshiki; Hisatome, Ichiro; Nishimura, Motonobu

    2015-01-01

    Adipose stem cells (ASCs) are a source of regenerative cells available for autologous transplantation to hearts. We compared protective actions of ASC sheets on rat myocardial infarction (MI) in comparison with those of skeletal myoblast cell sheets. Their effects on infarcted hearts were evaluated by biological, histochemical as well as physiological analyses. ASC sheets secreted higher concentrations of angiogenic factors (HGF, VEGF, and bFGF; P < 0.05) under normoxic and hypoxic conditions than those of myoblast cell sheets, associated with reduction of cell apoptosis (P < 0.05). Like myoblast cell sheets, ASC sheets improved cardiac function (P < 0.05) and decreased the plasma level of ANP (P < 0.05) in MI hearts. ASC sheets restored cardiac remodeling characterized by fibrosis, cardiac hypertrophy and impaired angiogenesis (P < 0.05), which was associated with increases in angiogenic factors (P < 0.05). In isolated perfused rat hearts, ASC sheets improved both systolic and diastolic functions, which was comparable to cardiac functions of myoblast cell sheets, while both cell sheets failed to restore cardiac contractile response to either isoproterenol, pimobendan or dibutyryl cAMP. These results indicated that ASC sheets improved cardiac function and remodeling of MI hearts mediated by their paracrine action and this improvement was comparable to those by myoblast cell sheets. PMID:25749147

  20. Adipose-derived stromal cell therapy improves cardiac function after coronary occlusion in rats.

    PubMed

    Bagno, Luiza L S; Werneck-de-Castro, João Pedro S; Oliveira, Patrícia F; Cunha-Abreu, Márcia S; Rocha, Nazareth N; Kasai-Brunswick, Taís H; Lago, Vivian M; Goldenberg, Regina C S; Campos-de-Carvalho, Antonio C

    2012-01-01

    Recent studies have identified adipose tissue as a new source of mesenchymal stem cells for therapy. The purpose of this study was to investigate the therapy with adipose-derived stromal cells (ASCs) in a rat model of healed myocardial infarction (MI). ASCs from inguinal subcutaneous adipose tissue of male Wistar rats were isolated by enzymatic digestion and filtration. Cells were then cultured until passage 3. Four weeks after ligation of the left coronary artery of female rats, a suspension of either 100 µl with phosphate-buffered saline (PBS) + Matrigel + 2 × 10(6) ASCs labeled with Hoechst (n = 11) or 100 µl of PBS + Matrigel (n = 10) was injected along the borders of the ventricular wall scar tissue. A sham-operated group (n = 5) was submitted to the same surgical procedure except permanent ligation of left coronary artery. Cardiac performance was assessed by electro- and echocardiogram. Echo was performed prior to injections (baseline, BL) and 6 weeks after injections (follow-up, FU), and values after treatment were normalized by values obtained before treatment. Hemodynamic measurements were performed 6 weeks after injections. All infarcted animals exhibited cardiac function impairment. Ejection fraction (EF), shortening fractional area (SFA), and left ventricular akinesia (LVA) were similar between infarcted groups before treatment. Six weeks after therapy, ASC group showed significant improvement in all three ECHO indices in comparison to vehicle group. In anesthetized animals dp/dt(+) was also significantly higher in ASCs when compared to vehicle. In agreement with functional improvement, scar area was diminished in the ASC group. We conclude that ASCs improve cardiac function in infarcted rats when administered directly to the myocardium. PMID:22472303

  1. Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs

    PubMed Central

    Lu, Huixia; Xu, Xinsheng; Zhang, Mei; Cao, Renhai; Bråkenhielm, Ebba; Li, Changjiang; Lin, Huili; Yao, Guihua; Sun, Huiwen; Qi, Lihang; Tang, Mengxiong; Dai, Hongyan; Zhang, Yanen; Su, Runyi; Bi, Yanwen; Zhang, Yun; Cao, Yihai

    2007-01-01

    Establishment of functional and stable collaterals in the ischemic myocardium is crucial to restoring cardiac function after myocardial infarction. Here, we show that only dual delivery of a combination of angiogenic and arteriogenic factors to the ischemic myocardium could significantly reestablish stable collateral networks and improve myocardial perfusion and function. A combination of FGF-2 with PDGF-BB, two factors primarily targeting endothelial cells and vascular smooth muscle cells, remarkably promotes myocardial collateral growth and stabilizes the newly formed collateral networks, which significantly restore myocardial perfusion and function. Using various members of the PDGF family together with FGF-2 in an angiogenesis assay, we demonstrate that PDGFR-α is mainly involved in angiogenic synergism, whereas PDGFR-β mediates vessel stability signals. Our findings provide conceptual guidelines for the clinical development of proangiogenic/arteriogenic factors for the treatment of ischemic heart disease. PMID:17636133

  2. Improved Cardiac Function in Patients With Obstructive Jaundice After Internal Biliary Drainage

    PubMed Central

    Padillo, Javier; Puente, Jesús; Gómez, Manuel; Dios, Francisco; Naranjo, Antonio; Vallejo, Juan A.; Miño, Gonzalo; Pera, Carlos; Sitges-Serra, Antonio

    2001-01-01

    Objective To investigate myocardial function in patients with obstructive jaundice before and after internal biliary drainage. Summary Background Data Increased plasma levels of atrial natriuretic peptide (ANP) have been found in patients with biliary obstruction. Methods Thirteen patients with newly diagnosed obstructive jaundice and no previous heart, lung, or renal disease were studied using a Swan-Ganz catheter. Hemodynamic measurements were taken before and 4 days after internal biliary drainage. Levels of ANP and brain natriuretic peptide (BNP) were obtained and liver function tests were also determined. Results Plasma levels of ANP and BNP were increased twofold to fourfold in the basal state and declined after biliary drainage. Independent variables predicting left ventricular systolic work were total bilirubin concentrations, duration of jaundice, and BNP. In addition, bilirubin concentrations correlated with pulmonary vascular resistance, mean arterial pulmonary pressure, and right ventricular systolic work. Internal biliary drainage resulted in an improvement in left ventricular systolic work. A correlation was found between decreasing ANP concentrations and increasing cardiac output. Conclusions Increased plasma levels of natriuretic peptides in patients with obstructive jaundice may reflect a subclinical myocardial dysfunction correlating with the degree of jaundice. After internal biliary drainage, there is a measurable improvement of cardiac function. PMID:11685028

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

    PubMed Central

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

    2015-01-01

    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/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. PMID:26675565

  4. Sustained delivery of VEGF from designer self-assembling peptides improves cardiac function after myocardial infarction

    SciTech Connect

    Guo, Hai-dong; Cui, Guo-hong; Yang, Jia-jun; Wang, Cun; Zhu, Jing; Zhang, Li-sheng; Jiang, Jun; Shao, Shui-jin

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer The designer peptide LRKKLGKA could self-assemble into nanofibers. Black-Right-Pointing-Pointer Injection of LRKKLGKA peptides could promote the sustained delivery of VEGF. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides lead to sufficient angiogenesis. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides improves heart function. -- Abstract: Poor vascularization and insufficient oxygen supply are detrimental to the survival of residual cardiomyocytes or transplanted stem cells after myocardial infarction. To prolong and slow the release of angiogenic factors, which stimulate both angiogenesis and vasculogenesis, we constructed a novel self-assembling peptide by attaching the heparin-binding domain sequence LRKKLGKA to the self-assembling peptide RADA16. This designer self-assembling peptide self-assembled into nanofiber scaffolds under physiological conditions, as observed by atomic force microscopy. The injection of designer self-assembling peptides can efficiently provide the sustained delivery of VEGF for at least 1 month. At 4 weeks after transplantation, cardiac function was improved, and scar size and collagen deposition were markedly reduced in the group receiving VEGF with the LRKKLGKA scaffolds compared with groups receiving VEGF alone, LRKKLGKA scaffolds alone or VEGF with RADA16 scaffolds. The microvessel density in the VEGF with LRKKLGKA group was higher than that in the VEGF with RADA16 group. TUNEL and cleaved caspase-3 expression assays showed that the transplantation of VEGF with LRKKLGKA enhanced cell survival in the infarcted heart. These results present the tailor-made peptide scaffolds as a new generation of sustained-release biomimetic biomaterials and suggest that the use of angiogenic factors along with designer self-assembling peptides can lead to myocardial protection, sufficient angiogenesis, and improvement in cardiac function.

  5. Heme Oxygenase-1 Induction Improves Cardiac Function following Myocardial Ischemia by Reducing Oxidative Stress

    PubMed Central

    Issan, Yossi; Kornowski, Ran; Aravot, Dan; Shainberg, Asher; Laniado-Schwartzman, Michal; Sodhi, Komal; Abraham, Nader G.; Hochhauser, Edith

    2014-01-01

    Background Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation. Methods In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured. Results HO-1 induction lowered release of lactate dehydrogenase (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non-diabetic mice (35±1%vs.41±2, respectively p<0.05). CoPP-treated diabetic animals improved cardiac function (43±2% p<0.01), reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01 respectively). CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p<0.05). The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p<0.05). CoPP significantly increased the expression levels of pAKT and pGSK3β (p<0.05) in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects. Conclusions HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by

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

    PubMed

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

    2013-10-15

    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 (cardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min(-1)) or afterload (cardiac 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 cardiac

  7. Cardiac Rehabilitation is Associated with Lasting Improvements in Cognitive Function in Older Adults with Heart Failure

    PubMed Central

    Alosco, Michael L.; Spitznagel, Mary Beth; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2016-01-01

    Objective Heart failure (HF) is a known risk factor for cognitive impairment. Cardiac rehabilitation (CR) may attenuate poor neurocognitive outcomes in HF via improved physical fitness—a significant promoter of cognitive function. However, no study has examined the possible acute and lasting benefits of CR on cognitive function in persons with HF. Methods and Results 52 patients with HF completed a 12-week Phase II CR program. All participants were administered neuropsychological testing and completed a brief physical fitness assessment at baseline, completion of CR (i.e. 12-weeks), and 12-month follow-up. Repeated measures analyses showed a significant time effect for both attention/executive function and memory (p < 0.05). Attention/executive function performance increased from baseline to 12-weeks and these gains remained up to 12-months; memory was unchanged from baseline to 12-weeks, but then improved between the 12-week and 12-month time points. Physical fitness improved from baseline to 12-weeks and these benefits were maintained 12-months later. Changes in physical fitness and cognitive function over time did not reach a statistically significant association, though poorer physical fitness was associated with decreased cognitive performance at the baseline and 12-month time points. Conclusions CR is associated with both acute and lasting cognitive benefits in patients with HF. Prospective studies with extended follow-ups are needed to clarify the mechanisms that underpin cognitive improvements following CR (e.g., improved cerebral perfusion) and whether CR can ultimately reduce risk for cognitive decline and conditions like Alzheimer’s disease in HF. PMID:25181916

  8. Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization

    PubMed Central

    Zhang, Ying; Ma, Xiao-juan; Guo, Chun-yu; Wang, Ming-ming; Kou, Na; Qu, Hua; Mao, Hui-min; Shi, Da-zhuo

    2016-01-01

    Aim: We have shown that a combination of ligustrazine and berberine produces more effective inhibition on platelet activation and inflammatory reactions in rat acute myocardial infarction compared with either agent alone. In this study we evaluated the beneficial effects of a combination of ligustrazine and berberine in a rat model of coronary microembolization (CME). Methods: SD rats were treated with ligustrazine, berberine, ligustrazine+berberine, or clopidogrel for 2 weeks. When the treatment completed, CME was induced by injection of sodium laurate into the left ventricular, while obstructing the ascending aorta. All rats were intubated for hemodynamic measurements. Blood samples were collected for biochemical analyses, flow cytometry, and ELISAs. Heart tissues were isolated for histopathology and subsequent protein analyses. Results: Pretreatment with the combination of ligustrazine (27 mg·kg−1·d−1) and berberine (90 mg·kg−1·d−1) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFα, IL-1β, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg·kg−1·d−1). Conclusion: The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects. PMID:26924290

  9. 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. PMID:25740582

  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. Glucagon-like peptide-1 and the exenatide analogue AC3174 improve cardiac function, cardiac remodeling, and survival in rats with chronic heart failure

    PubMed Central

    2010-01-01

    Background Accumulating evidence suggests glucagon-like peptide-1 (GLP-1) exerts cardioprotective effects in animal models of myocardial infarction (MI). We hypothesized that chronic treatment with GLP-1 or the exenatide analog AC3174 would improve cardiac function, cardiac remodeling, insulin sensitivity, and exercise capacity (EC) in rats with MI-induced chronic heart failure (CHF) caused by coronary artery ligation. Methods Two weeks post-MI, male Sprague-Dawley rats were treated with GLP-1 (2.5 or 25 pmol/kg/min), AC3174 (1.7 or 5 pmol/kg/min) or vehicle via subcutaneous infusion for 11 weeks. Cardiac function and morphology were assessed by echocardiography during treatment. Metabolic, hemodynamic, exercise-capacity, and body composition measurements were made at study end. Results Compared with vehicle-treated rats with CHF, GLP-1 or AC3174 significantly improved cardiac function, including left ventricular (LV) ejection fraction, and end diastolic pressure. Cardiac dimensions also improved as evidenced by reduced LV end diastolic and systolic volumes and reduced left atrial volume. Vehicle-treated CHF rats exhibited fasting hyperglycemia and hyperinsulinemia. In contrast, GLP-1 or AC3174 normalized fasting plasma insulin and glucose levels. GLP-1 or AC3174 also significantly reduced body fat and fluid mass and improved exercise capacity and respiratory efficiency. Four of 16 vehicle control CHF rats died during the study compared with 1 of 44 rats treated with GLP-1 or AC3174. The cellular mechanism by which GLP-1 or AC3174 exert cardioprotective effects appears unrelated to changes in GLUT1 or GLUT4 translocation or expression. Conclusions Chronic treatment with either GLP-1 or AC3174 showed promising cardioprotective effects in a rat model of CHF. Hence, GLP-1 receptor agonists may represent a novel approach for the treatment of patients with CHF or cardiovascular disease associated with type 2 diabetes. PMID:21080957

  12. Injectable biodegradable hydrogels for embryonic stem cell transplantation: improved cardiac remodelling and function of myocardial infarction

    PubMed Central

    Wang, Haibin; Liu, Zhiqiang; Li, Dexue; Guo, Xuan; Kasper, F Kurtis; Duan, Cuimi; Zhou, Jin; Mikos, Antonios G; Wang, Changyong

    2012-01-01

    Abstract 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. PMID:21838774

  13. Remote ischemic preconditioning improves post resuscitation cerebral function via overexpressing neuroglobin after cardiac arrest in rats.

    PubMed

    Fan, Ran; Yu, Tao; Lin, Jia-Li; Ren, Guang-Dong; Li, Yi; Liao, Xiao-Xing; Huang, Zi-Tong; Jiang, Chong-Hui

    2016-10-01

    In this study, we investigated the effects of remote ischemic preconditioning on post resuscitation cerebral function in a rat model of cardiac arrest and resuscitation. The animals were randomized into six groups: 1) sham operation, 2) lateral ventricle injection and sham operation, 3) cardiac arrest induced by ventricular fibrillation, 4) lateral ventricle injection and cardiac arrest, 5) remote ischemic preconditioning initiated 90min before induction of ventricular fibrillation, and 6) lateral ventricle injection and remote ischemic preconditioning before cardiac arrest. Reagent of Lateral ventricle injection is neuroglobin antisense oligodeoxynucleotides which initiated 24h before sham operation, cardiac arrest or remote ischemic preconditioning. Remote ischemic preconditioning was induced by four cycles of 5min of limb ischemia, followed by 5min of reperfusion. Ventricular fibrillation was induced by current and lasted for 6min. Defibrillation was attempted after 6min of cardiopulmonary resuscitation. The animals were then monitored for 2h and observed for an additionally maximum 70h. Post resuscitation cerebral function was evaluated by neurologic deficit score at 72h after return of spontaneous circulation. Results showed that remote ischemic preconditioning increased neurologic deficit scores. To investigate the neuroprotective effects of remote ischemic preconditioning, we observed neuronal injury at 48 and 72h after return of spontaneous circulation and found that remote ischemic preconditioning significantly decreased the occurrence of neuronal apoptosis and necrosis. To further comprehend mechanism of neuroprotection induced by remote ischemic preconditioning, we found expression of neuroglobin at 24h after return of spontaneous circulation was enhanced. Furthermore, administration of neuroglobin antisense oligodeoxynucleotides before induction of remote ischemic preconditioning showed that the level of neuroglobin was decreased then partly abrogated

  14. Diosmin pretreatment improves cardiac function and suppresses oxidative stress in rat heart after ischemia/reperfusion.

    PubMed

    Senthamizhselvan, Oomaidurai; Manivannan, Jeganathan; Silambarasan, Thangarasu; Raja, Boobalan

    2014-08-01

    Reperfusion of ischemic tissue leads to the generation of oxygen derived free radicals which plays an important role in cellular damage. Objective of the current study is to evaluate the cardio-protective and antioxidant effect of diosmin on ischemia-reperfusion related cardiac dysfunction, oxidative stress and apoptosis. Diosmin (50 and 100 mg/kg body weight (bw)) was given every day to the rats orally throughout the experimental period. Ischemia/reperfusion protocol was carried out ex vivo using langendorff perfusion method and the cardiac functional recovery was assessed in terms of percentage rate pressure product. Coronary effluents of LDH and CK-MB activities, antioxidant enzyme activities, lipid peroxidation products, activity of TCA cycle enzymes were evaluated. Moreover, in vitro superoxide anion and hydroxyl radical scavenging potential of diosmin was also quantified. Finally, quantitative real-time PCR was used for assessing Bcl-2 mRNA expression in heart. Cardiac functional recovery was impaired after reperfusion compared with continuously perfused heart. It was significantly prevented by diosmin treatment. Impaired antioxidant enzyme activities and elevated lipid peroxidation products level were also significantly suppressed. The activity of TCA cycle enzymes was protected against reperfusion stress. Down regulated Bcl-2 was also significantly increased. This study concluded that diosmin pretreatment prevents all the impaired patterns including cardiac function, oxidative stress and apoptosis associated with reperfusion in control heart by its antioxidant role. PMID:24769512

  15. Plasmid-based transient human stromal cell-derived factor-1 gene transfer improves cardiac function in chronic heart failure

    PubMed Central

    Sundararaman, S; Miller, T J; Pastore, J M; Kiedrowski, M; Aras, R; Penn, M S

    2011-01-01

    We previously demonstrated that transient stromal cell-derived factor-1 alpha (SDF-1) improved cardiac function when delivered via cell therapy in ischemic cardiomyopathy at a time remote from acute myocardial infarction (MI) rats. We hypothesized that non-viral gene transfer of naked plasmid DNA-expressing hSDF-1 could similarly improve cardiac function. To optimize plasmid delivery, we tested SDF-1 and luciferase plasmids driven by the cytomegalovirus (CMV) promoter with (pCMVe) or without (pCMV) translational enhancers or α myosin heavy chain (pMHC) promoter in a rodent model of heart failure. In vivo expression of pCMVe was 10-fold greater than pCMV and pMHC expression and continued over 30 days. We directly injected rat hearts with SDF-1 plasmid 1 month after MI and assessed heart function. At 4 weeks after plasmid injection, we observed a 35.97 and 32.65% decline in fractional shortening (FS) in control (saline) animals and pMHC-hSDF1 animals, respectively, which was sustained to 8 weeks. In contrast, we observed a significant 24.97% increase in animals injected with the pCMVe-hSDF1 vector. Immunohistochemistry of cardiac tissue revealed a significant increase in vessel density in the hSDF-1-treated animals compared with control animals. Increasing SDF-1 expression promoted angiogenesis and improved cardiac function in rats with ischemic heart failure along with evidence of scar remodeling with a trend toward decreased myocardial fibrosis. These data demonstrate that stand-alone non-viral hSDF-1 gene transfer is a strategy for improving cardiac function in ischemic cardiomyopathy. PMID:21472007

  16. Eprosartan improves cardiac function in swine working heart model of ischemia-reperfusion injury

    PubMed Central

    Weymann, Alexander; Sabashnikov, Anton; Patil, Nikhil P.; Konertz, Wolfgang; Modersohn, Diethelm; Dohmen, Pascal M.

    2014-01-01

    Background Eprosartan is an angiotensin II receptor antagonist used as an antihypertensive. We sought to evaluate the regional effect of Eprosartan on postinfarct ventricular remodeling and myocardial function in an isolated swine working heart model of ischemia-reperfusion injury. Material/Methods 22 swine hearts were perfused with the Langendorff perfusion apparatus under standard experimental conditions. Myocardial ischemia was induced by a 10-min left anterior descending artery ligation. Hearts were reperfused with either saline (control group, n=11), or Eprosartan (treatment group, n=11). Left ventricular pressure (LVP) and regional heart parameters such as intramyocardial pressure (IMP), wall thickening rate (WTh), and pressure-length-loops (PLL) were measured at baseline and after 30 min of reperfusion. Results Measured parameters were statistically similar between the 2 groups at baseline. The administration of Eprosartan led to a significantly better recovery of IMP and WTh: 44.4±2.5 mmHg vs. 51.2±3.3 mmHg, p<0.001 and 3.8±0.4 μm vs. 4.4±0.3 μm, p=0.001, respectively. PLL were also significantly higher in the treatment group following reperfusion (21694±3259 units vs. 31267±3429 units, p<0.01). There was no difference in the LVP response to Eprosartan versus controls (63.6±3.0 mmHg vs. 62.5±3.1 mmHg, p=0.400). Conclusions Pre-treatment with Eprosartan is associated with a significant improvement in regional cardiac function under ischemic conditions. Pharmacological treatment with eprosartan may exert a direct cardioprotective effect on ischemic myocardium. PMID:24762635

  17. Estrogen Therapy, Independent of Timing, Improves Cardiac Structure and Function in Oophorectomized mRen2.Lewis Rats

    PubMed Central

    Jessup, Jewell A.; Wang, Hao; MacNamara, Lindsay M.; Presley, Tennille D.; Kim-Shapiro, Daniel B.; Zhang, Lili; Chen, Alex F.; Groban, Leanne

    2013-01-01

    Objective mRen2.Lewis Rats exhibit exacerbated increases in blood pressure, left ventricular (LV) remodeling, and diastolic impairment following the loss of estrogens. In this same model, depletion of estrogens has marked effects on the cardiac biopterin profile concomitant with suppressed nitric oxide (NO) release. With respect to the establishment of overt systolic hypertension after oophorectomy (OVX), we assessed the effects of timing chronic 17 β-estradiol (E2) therapy on myocardial function, structure, and the cardiac NO system. Methods Oophrectomy (OVX; n=24) or sham-operation (Sham; n=13) was performed in 4-week-old, female mRen2.Lewis rats. Following randomization, OVX rats received E2 immediately (OVX + early E2; n=7), E2 at 11 weeks of age (OVX + late E2 N=8), or no E2 at all (OVX N=9). Results Early E2 was associated with lower body weight, less hypertension-related cardiac remodeling, and decreased LV filling pressure compared to OVX rats without E2 supplementation. Late E2 similarly attenuated the adverse effects of ovarian hormone loss on tissue-Doppler derived LV filling pressures and perivascular fibrosis, and significantly improved myocardial relaxation, or mitral annular velocity (e′). Early and late exposure to E2 decreased dihydrobiopterin, but only late E2 yielded significant increases in cardiac nitrite concentrations. Conclusions Although there were some similarities between early and late E2 treatment on preservation of diastolic function and cardiac structure after OVX, the lusitropic potential of E2 was most consistent with late supplementation. The cardioprotective effects of late E2 were independent of blood pressure and may have occurred through regulation of cardiac biopterins and NO production. PMID:23481117

  18. Dual Delivery of Hepatocyte and Vascular Endothelial Growth Factors via a Protease-Degradable Hydrogel Improves Cardiac Function in Rats

    PubMed Central

    Boopathy, Archana V.; Che, Pao-lin; Brown, Milton; García, Andrés J.; Davis, Michael E.

    2012-01-01

    Acute myocardial infarction (MI) caused by ischemia and reperfusion (IR) is the most common cause of cardiac dysfunction due to local cell death and a temporally regulated inflammatory response. Current therapeutics are limited by delivery vehicles that do not address spatial and temporal aspects of healing. The aim of this study was to engineer biotherapeutic delivery materials to harness endogenous cell repair to enhance myocardial repair and function. We have previously engineered poly(ethylene glycol) (PEG)-based hydrogels to present cell adhesive motifs and deliver VEGF to promote vascularization in vivo. In the current study, bioactive hydrogels with a protease-degradable crosslinker were loaded with hepatocyte and vascular endothelial growth factors (HGF and VEGF, respectively) and delivered to the infarcted myocardium of rats. Release of both growth factors was accelerated in the presence of collagenase due to hydrogel degradation. When delivered to the border zones following ischemia-reperfusion injury, there was no acute effect on cardiac function as measured by echocardiography. Over time there was a significant increase in angiogenesis, stem cell recruitment, and a decrease in fibrosis in the dual growth factor delivery group that was significant compared with single growth factor therapy. This led to an improvement in chronic function as measured by both invasive hemodynamics and echocardiography. These data demonstrate that dual growth factor release of HGF and VEGF from a bioactive hydrogel has the capacity to significantly improve cardiac remodeling and function following IR injury. PMID:23226440

  19. Inhibition of Let-7 microRNA attenuates myocardial remodeling and improves cardiac function postinfarction in mice

    PubMed Central

    Tolonen, Anna-Maria; Magga, Johanna; Szabó, Zoltán; Viitala, Pirkko; Gao, Erhe; Moilanen, Anne-Mari; Ohukainen, Pauli; Vainio, Laura; Koch, Walter J; Kerkelä, Risto; Ruskoaho, Heikki; Serpi, Raisa

    2014-01-01

    The members of lethal-7 (Let-7) microRNA (miRNA) family are involved in regulation of cell differentiation and reprogramming of somatic cells into induced pluripotent stem cells. However, their function in the heart is not known. In this study, we examined the effect of inhibiting the function of Let-7c miRNA on the progression of postinfarction left ventricular (LV) remodeling in mice. Myocardial infarction was induced with permanent ligation of left anterior descending coronary artery with a 4-week follow-up period. Let-7c miRNA was inhibited with a specific antagomir administered intravenously. The inhibition of Let-7c miRNA downregulated the levels of mature Let-7c miRNA and its other closely related members of Let-7 family in the heart and resulted in increased expression of pluripotency-associated genes Oct4 and Sox2 in cardiac fibroblasts in vitro and in adult mouse heart in vivo. Importantly, Let-7c inhibitor prevented the deterioration of cardiac function postinfarction, as demonstrated by preserved LV ejection fraction and elevated cardiac output. Improvement in cardiac function by Let-7c inhibitor postinfarction was associated with decreased apoptosis, reduced fibrosis, and reduction in the number of discoidin domain receptor 2–positive fibroblasts, while the number of c-kit+ cardiac stem cells and Ki-67+ proliferating cells remained unaltered. In conclusion, inhibition of Let-7 miRNA may be beneficial for the prevention of postinfarction LV remodeling and progression of heart failure. PMID:25505600

  20. Biomechanics of Cardiac Function.

    PubMed

    Voorhees, Andrew P; Han, Hai-Chao

    2015-10-01

    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

  1. Daily administration of atorvastatin and simvastatin for one week improves cardiac function in type 1 diabetic rats.

    PubMed

    Crespo, Maria J; Cruz, Nildris; Quidgley, Jose; Torres, Hector; Hernandez, Cesar; Casiano, Hector; Rivera, Karines

    2014-01-01

    Short-term administration of statins during the perioperative period has been suggested to improve cardiovascular (CV) outcomes in patients undergoing cardiac and vascular surgery. The effectiveness of this therapy, the optimal administration time and the statin best suited to improve cardiac performance under hyperglycemic conditions, however, are unknown. In this study, we compared the effects of 10 mg/kg/day simvastatin (SV), pravastatin (PV) and atorvastatin (AV), on the CV status of fully anesthetized streptozotocin-induced diabetic rats 4 weeks following diabetes induction. At this stage, cardiac function is compromised. The rats were anesthetized to mimic presurgical conditions. Cardiac status was evaluated twice by echocardiography, first 24 h after statin administration, and then after daily statin administration for 1 week. After 24 h of statin administration, CV parameters were not improved. Continued daily administration of SV and AV over a 1-week period, by contrast, significantly improved ejection fraction from 52.20 ± 2.33% before treatment to 64.89 ± 1.12% with AV and to 69.71 ± 2.30% with SV (n = 9, p < 0.05). The cardiac output index was also significantly improved from 51.13 ± 6.86 ml/min × 100 g body weight (BW) before treatment to 98.74 ± 13.78 ml/min × 100 g BW with AV and to 84.94 ± 8.64 ml/min × 100 g BW with SV. Only AV increased stroke volume from 0.50 ± 0.08 to 0.83 ± 0.13 ml (n = 9, p < 0.05). Unlike the other statins tested, PV provided no beneficial effects, regardless of the regimen of administration. Our results indicate that daily administration of AV and SV for 1 week enhances cardiac performance in fully anesthetized diabetic rats. This study of short-term statin administration may have strong clinical implications for improving perioperative outcomes in diabetic patients. PMID:24556594

  2. 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

  3. Exercise-based cardiac rehabilitation improves endothelial function assessed by flow-mediated dilation but not by pulse amplitude tonometry.

    PubMed

    Cornelissen, Véronique A; Onkelinx, Steven; Goetschalckx, Kaatje; Thomaes, Tom; Janssens, Stefan; Fagard, Robert; Verhamme, Peter; Vanhees, Luc

    2014-01-01

    We aimed to investigate the effect of exercise on endothelium-dependent vasodilator function assessed simultaneously in the brachial artery and in the distal arterial bed by flow-mediated dilation and the pulse amplitude tonometry method, respectively, in coronary artery disease patients. The study included 146 patients with stable coronary artery disease (123 men, mean age 62 ± 9 years) who participated in the Cardiac Rehabilitation and Genetics of Exercise performance study. All patients completed a 12-week supervised cardiac rehabilitation programme (three sessions per week at an intensity of 80% of the heart rate reserve). At baseline and upon completion of the training, we measured brachial artery diameters by means of ultrasound scanning (linear array transducer of 12 MHz) and simultaneously assessed pulse amplitudes in the fingertip using a pulse amplitude tonometry device both at rest and after reactive hyperaemia induced by a 5-min forearm cuff occlusion. Peak oxygen uptake significantly increased (+22%; p < 0.0001) and flow-mediated dilation improved from 10.0% to 13.1% (+37%; p < 0.0001), whereas the reactive hyperaemia index of the pulse amplitude tonometry method remained unchanged (p = 0.47) following exercise-based cardiac rehabilitation. However, the basal digital pulse amplitude (+58%; p < 0.001) increased as a result of training, as did the digital pulse amplitude after reactive hyperaemia (+22%; p < 0.05). Exercise-based cardiac rehabilitation is associated with an improvement in endothelial function, as can be measured by flow-mediated dilation but not by the reactive hyperaemia index of the pulse amplitude tonometry method. PMID:22962311

  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. Symmetry of cardiac function assessment.

    PubMed

    Bai, Xu-Fang; Ma, Amy X

    2016-09-01

    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

  6. 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

  7. Executive functions improvement following a 5-month aquaerobics program in older adults: Role of cardiac vagal control in inhibition performance.

    PubMed

    Albinet, Cédric T; Abou-Dest, Amira; André, Nathalie; Audiffren, Michel

    2016-03-01

    The aims of this study were to examine the effects of aerobic exercise on measures of executive performance and their relationships with changes in cardiorespiratory fitness, cardiac vagal control (heart rate variability) and psychological variables. Thirty-six sedentary seniors aged 60-75 years were randomly assigned to a swimming and aquaerobics program or a stretching program two times a week for 21 weeks. Executive functions (inhibition, updating of working memory and cognitive flexibility) and cardiorespiratory fitness (estimated VO2max) were assessed at the start, after 10 weeks of program and at the end of the program. Resting HRV and measures of psychological outcomes (depression, self-efficacy, decisional balance) were obtained at the start and at the end of the program. Participants of both groups significantly improved their VO2max level, their psychological state and their performance for the 2-back task. Only the participants in the aquaerobics group significantly improved their vagally-mediated HRV and their performance for the Stroop test and the verbal running-span test at the end of the program. Only improvements in cardiac vagal control and in inhibition were shown to be functionally related. These results are discussed in line with the model of neurovisceral integration. PMID:26812613

  8. Diltiazem restores cardiac output and improves renal function after hemorrhagic shock and crystalloid resuscitation.

    PubMed

    Wang, P; Ba, Z F; Meldrum, D R; Chaudry, I H

    1992-05-01

    Although calcium antagonists produce salutary effects after shock and ischemia, it is unknown whether such agents restore the depressed cardiac output (CO) and renal function in a nonheparinized model of trauma-hemorrhage and resuscitation. To study this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the maximum bleedout was returned in the form of Ringer lactate (RL). They were then resuscitated with four times the volume of shed blood with RL over 60 min. Diltiazem (400 micrograms/kg body wt) or an equal volume of saline was infused intravenously over 95 min. This infusion was started during the last 15 min of resuscitation. CO was determined by indocyanine green dilution. Glomerular filtration rate (GFR) was assessed with [3H]inulin clearance, and cortical microcirculation was examined by laser Doppler flowmetry. Results indicate that crystalloid resuscitation alone transiently restored but did not maintain CO after hemorrhage. Diltiazem infusion in conjunction with crystalloid resuscitation, however, restored and maintained CO and cortical microcirculation. Although GFR decreased in both groups, the values in diltiazem-treated animals were significantly higher than those in the sham-operated animals. Furthermore, diltiazem markedly decreased tissue water content. Thus diltiazem appears to be a promising adjunct in the treatment of hemorrhagic shock even in the absence of blood resuscitation. PMID:1590448

  9. 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

  10. Simvastatin Induces Regression of Cardiac Hypertrophy and Fibrosis and Improves Cardiac Function in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy

    PubMed Central

    Patel, Rajnikant; Nagueh, Sherif F.; Tsybouleva, Natalie; Abdellatif, Maha; Lutucuta, Silvia; Kopelen, Helen A.; Quinones, Miguel A.; Zoghbi, William A.; Entman, Mark L.; Roberts, Robert; Marian, A.J.

    2009-01-01

    Background Hypertrophic cardiomyopathy is a genetic disease characterized by cardiac hypertrophy, myocyte disarray, interstitial fibrosis, and left ventricular (LV) dysfunction. We have proposed that hypertrophy and fibrosis, the major determinants of mortality and morbidity, are potentially reversible. We tested this hypothesis in β-myosin heavy chain–Q403 transgenic rabbits. Methods and Results We randomized 24 β-myosin heavy chain–Q403 rabbits to treatment with either a placebo or simvastatin (5 mg · kg−1 · d−1) for 12 weeks and included 12 nontransgenic controls. We performed 2D and Doppler echocardiography and tissue Doppler imaging before and after treatment. Demographic data were similar among the groups. Baseline mean LV mass and interventricular septal thickness in nontransgenic, placebo, and simvastatin groups were 3.9±0.7, 6.2±2.0, and 7.5±2.1 g (P<0.001) and 2.2±0.2, 3.1±0.5, and 3.3±0.5 mm (P=0.002), respectively. Simvastatin reduced LV mass by 37%, interventricular septal thickness by 21%, and posterior wall thickness by 13%. Doppler indices of LV filling pressure were improved. Collagen volume fraction was reduced by 44% (P<0.001). Disarray was unchanged. Levels of activated extracellular signal-regulated kinase (ERK) 1/2 were increased in the placebo group and were less than normal in the simvastatin group. Levels of activated and total p38, Jun N-terminal kinase, p70S6 kinase, Ras, Rac, and RhoA and the membrane association of Ras, RhoA, and Rac1 were unchanged. Conclusions Simvastatin induced the regression of hypertrophy and fibrosis, improved cardiac function, and reduced ERK1/2 activity in the β-myosin heavy chain–Q403 rabbits. These findings highlight the need for clinical trials to determine the effects of simvastatin on cardiac hypertrophy, fibrosis, and dysfunction in humans with hypertrophic cardiomyopathy and heart failure. PMID:11457751

  11. 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. PMID:27071338

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

    PubMed Central

    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

    2014-01-01

    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 (3 mg/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. Ca2+-induced swelling, an indicator of permeability transition pore opening, was reduced in mitochondria of XJB-treated aged rats. In addition, XJB significantly attenuated the H2O2-induced depolarization of the mitochondrial inner membrane as well as 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. PMID:25451170

  13. 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. PMID:25451170

  14. Use of cardiac output to improve measurement of input function in quantitative dynamic contrast-enhanced MRI

    PubMed Central

    Zhang, Jeff L.; Rusinek, Henry; Bokacheva, Louisa; Chen, Qun; Storey, Pippa; Lee, Vivian S.

    2009-01-01

    Purpose: To validate a new method for converting MR arterial signal intensity versus time curves to arterial input functions (AIF). Materials and Methods: The method constrains AIF with patient's cardiac output (Q). Monte Carlo simulations of MR renography and tumor perfusion protocols were carried out for comparison with two alternative methods: direct measurement and population-averaged input function. MR renography was performed to assess the method's inter- and intra-day reproducibility for renal parameters. Results: In simulations of tumor perfusion, the precision of the parameters (Ktrans and ve) computed using the proposed method was improved by at least a factor of three compared to direct measurement. Similar improvements were obtained in simulations of MR renography. Volunteer study for testing inter-day reproducibility confirmed the improvement of precision in renal parameters when using the proposed method, compared to conventional methods. In another patient study (two injections within one session), the proposed method significantly increased the correlation coefficient (R) between GFR of the two exams (0.92 vs. 0.83), compared to direct measurement. Conclusion: A new method significantly improves the precision of DCE parameters. The method may be especially useful for analyzing repeated DCE examinations, such as monitoring tumor therapy or ACE-inhibitor renography. PMID:19711414

  15. Improved Estimation of Cardiac Function Parameters Using a Combination of Independent Automated Segmentation Results in Cardiovascular Magnetic Resonance Imaging.

    PubMed

    Lebenberg, Jessica; Lalande, Alain; Clarysse, Patrick; Buvat, Irene; Casta, Christopher; Cochet, Alexandre; Constantinidès, Constantin; Cousty, Jean; de Cesare, Alain; Jehan-Besson, Stephanie; Lefort, Muriel; Najman, Laurent; Roullot, Elodie; Sarry, Laurent; Tilmant, Christophe; Frouin, Frederique; Garreau, Mireille

    2015-01-01

    This work aimed at combining different segmentation approaches to produce a robust and accurate segmentation result. Three to five segmentation results of the left ventricle were combined using the STAPLE algorithm and the reliability of the resulting segmentation was evaluated in comparison with the result of each individual segmentation method. This comparison was performed using a supervised approach based on a reference method. Then, we used an unsupervised statistical evaluation, the extended Regression Without Truth (eRWT) that ranks different methods according to their accuracy in estimating a specific biomarker in a population. The segmentation accuracy was evaluated by estimating six cardiac function parameters resulting from the left ventricle contour delineation using a public cardiac cine MRI database. Eight different segmentation methods, including three expert delineations and five automated methods, were considered, and sixteen combinations of the automated methods using STAPLE were investigated. The supervised and unsupervised evaluations demonstrated that in most cases, STAPLE results provided better estimates than individual automated segmentation methods. Overall, combining different automated segmentation methods improved the reliability of the segmentation result compared to that obtained using an individual method and could achieve the accuracy of an expert. PMID:26287691

  16. Suppression of oxidative stress in endothelial progenitor cells promotes angiogenesis and improves cardiac function following myocardial infarction in diabetic mice

    PubMed Central

    JIN, PENG; LI, TAO; LI, XUEQI; SHEN, XINGHUA; ZHAO, YANRU

    2016-01-01

    Myocardial infarction is a major contributor to morbidity and mortality in diabetes, which is characterized by inadequate angiogenesis and consequent poor blood reperfusion in the diabetic ischemic heart. The aim of the present study was to investigate the effect that oxidative stress in endothelial progenitor cells (EPCs) has on cardiac angiogenesis in diabetic mice. EPCs derived from diabetic mice revealed reductions in superoxide dismutase (SOD) expression levels and activity compared with those from normal mice. An endothelial tube formation assay showed that angiogenesis was markedly delayed for diabetic EPCs, compared with normal controls. EPCs subjected to various pretreatments were tested as a cell therapy in a diabetic mouse model of myocardial infarction. Induction of oxidative stress in normal EPCs by H2O2 or small interfering RNA-mediated knockdown of SOD reduced their angiogenic activity in the ischemic myocardium of the diabetic mice. Conversely, cell therapy using EPCs from diabetic mice following SOD gene overexpression or treatment with the antioxidant Tempol normalized their ability to promote angiogenesis. These results indicate that decreased expression levels of SOD in EPCs contribute to impaired angiogenesis. In addition, normalization of diabetic EPCs by ex vivo SOD gene therapy accelerates the ability of the EPCs to promote angiogenesis and improve cardiac function when used as a cell therapy following myocardial infarction in diabetic mice. PMID:27284297

  17. Apolipoprotein epsilon 4 genotype is associated with less improvement in cognitive function five years after cardiac surgery: a retrospective cohort study

    PubMed Central

    Bartels, Karsten; Li, Yi-Ju; Li, Yen-Wei; White, William D.; Laskowitz, Daniel T.; Kertai, Miklos D.; Stafford-Smith, Mark; Podgoreanu, Mihai V.; Newman, Mark F.; Mathew, Joseph P.

    2015-01-01

    Purpose Cognitive performance after cardiac surgery can be impaired, and genetic risk factors have previously been suggested. When compared with other isoforms of the gene, the apolipoprotein epsilon 4 (APOE4) allele is associated with worse outcomes in many neurologic disorders. We hypothesized that the APOE4 allele is associated with less favourable cognitive function five years after surgery. Methods Caucasian patients enrolled in previously reported prospective cognitive trials in both cardiac and non-cardiac surgery participated in this retrospective cohort study. Neuropsychological function was assessed at baseline and five years postoperatively. The relationship between change in cognitive index score and APOE was evaluated using multivariable linear regression. An additive genetic model toward the epsilon 4 allele was applied with adjustment for baseline cognition, years of education, age, presence of diabetes in both cohorts, and presence of coronary artery disease in the non-cardiac surgery cohort. Results A total of 357 patients were included in this study. In the cardiac surgery group (n = 233), baseline cognitive index (P < 0.001), years of education (P = 0.04), age at time of surgery (P < 0.001), and the APOE4 allele (P = 0.009), were associated with a five-year change in cognitive index. Patients carrying the APOE4 allele showed less improvement in cognitive index scores five years after cardiac surgery compared with patients without the APOE4 allele. In the non-cardiac surgery (n = 124) group, no association was found between APOE4 allele status and change in cognitive index. Conclusion We report an association between APOE4 and neurocognitive function five years following cardiac surgery. Preoperative identification of patients with the APOE4 genotype may improve stratification of cardiac surgery patients at risk for a less favourable cognitive trajectory. PMID:25744138

  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. PMID:26908713

  19. Passive hind-limb cycling improves cardiac function and reduces cardiovascular disease risk in experimental spinal cord injury

    PubMed Central

    West, Christopher R; Crawford, Mark A; Poormasjedi-Meibod, Malihe-Sadat; Currie, Katharine D; Fallavollita, Andre; Yuen, Violet; McNeill, John H; Krassioukov, Andrei V

    2014-01-01

    Spinal cord injury (SCI) causes altered autonomic control and severe physical deconditioning that converge to drive maladaptive cardiac remodelling. We used a clinically relevant experimental model to investigate the cardio-metabolic responses to SCI and to establish whether passive hind-limb cycling elicits a cardio-protective effect. Initially, 21 male Wistar rats were evenly assigned to three groups: uninjured control (CON), T3 complete SCI (SCI) or T3 complete SCI plus passive hind-limb cycling (SCI-EX; 2 × 30 min day−1, 5 days week−1 for 4 weeks beginning 6 days post-SCI). On day 32, cardio-metabolic function was assessed using in vivo echocardiography, ex vivo working heart assessments, cardiac histology/molecular biology and blood lipid profiles. Twelve additional rats (n = 6 SCI and n = 6 SCI-EX) underwent in vivo echocardiography and basal haemodynamic assessments pre-SCI and at days 7, 14 and 32 post-SCI to track temporal cardiovascular changes. Compared with CON, SCI exhibited a rapid and sustained reduction in left ventricular dimensions and function that ultimately manifested as reduced contractility, increased myocardial collagen deposition and an up-regulation of transforming growth factor beta-1 (TGFβ1) and mothers against decapentaplegic homolog 3 (Smad3) mRNA. For SCI-EX, the initial reduction in left ventricular dimensions and function at day 7 post-SCI was completely reversed by day 32 post-SCI, and there were no differences in myocardial contractility between SCI-EX and CON. Collagen deposition was similar between SCI-EX and CON. TGFβ1 and Smad3 were down-regulated in SCI-EX. Blood lipid profiles were improved in SCI-EX versus SCI. We provide compelling novel evidence that passive hind-limb cycling prevents cardiac dysfunction and reduces cardiovascular disease risk in experimental SCI. PMID:24535438

  20. Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement.

    PubMed

    Zeng, Bin; Ren, Xiaofeng; Lin, Guosheng; Zhu, Chengang; Chen, Honglei; Yin, Jiechao; Jiang, Hong; Yang, Bo; Ding, Danhua

    2008-10-01

    The aim has been to determine whether the supernatants of mesenchymal stem cells (MSCs) transfected with adenovirus carrying human heme oxygenase-1 (hHO-1) gene protect cardiomyocytes from ischemic injury. We have found that hHO-1 infected MSCs (hHO-1-MSCs) increased expression of hHO-1 protein. Apoptosis of cultured hHO-1-MSCs exposed to hypoxia was suppressed. Several cytokines, including HGF, bFGF, TGF-beta, VEGF and IL-1beta, were produced by hHO-1-MSCs, some being significantly enhanced under hypoxia stimulation. Meanwhile, those cytokines reduced caspase-3 level and activity in cultured adult rat ventricular cardiomyocytes (ARVCs) exposed to hypoxia. Supernatants obtained from hHO-1-MSCs improved left ventricular function, limited myocardial infarct size, increased microvessel density, and inhibited apoptosis of cardiomyocytes in rat myocardial infarction. It can be concluded hHO-1-modified MSCs prevent myocardial cell injury via secretion of paracrine-acting mediators. PMID:18692581

  1. A novel role of exogenous carbon monoxide on protecting cardiac function and improving survival against sepsis via mitochondrial energetic metabolism pathway.

    PubMed

    Wang, Xu; Qin, Weiting; Qiu, Xuefeng; Cao, Jie; Liu, Dadong; Sun, Bingwei

    2014-01-01

    Septic cardiac dysfunction is the main cause of death in septic patients. Here we investigate whether exogenous carbon monoxide can protect cardiac function and improve survival against sepsis by interfering with mitochondrial energetic metabolism. Male C57BL/6 mice were subjected to cecal ligation and puncture to induce sepsis. Exogenous carbon monoxide delivered from Tricarbonyldichlororuthenium (II) dimer (carbon monoxide releasing molecule II, 8 mg/kg) was used intravenously as intervention. We found that carbon monoxide significantly improved cardiac function (LVEF 80.26 ± 2.37% vs. 71.21 ± 1.37%, P < 0.001; LVFS 43.52 ± 1.92% vs. 34.93 ± 1.28%, P < 0.001) and increased survival rate of septic mice (63% vs. 25%, P < 0.01). This phenomenon might be owing to the beneficial effect of carbon monoxide on abolishing the elevation of cardiac enzyme activity, cytokines levels and apoptosis rate, then attenuating cardiac injury in septic mice. Meanwhile, carbon monoxide significantly reversed the loss of mitochondrial number, effectively inhibited cardiac mitochondrial damage in septic mice by modulating glucose uptake, adenosine triphosphate and lactate content. Furthermore upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A genes in cardiac tissue were revealed in septic mice treated with carbon monoxide. Taken together, the results indicate that exogenous carbon monoxide effectively modulated mitochondrial energetic metabolisms by interfering with expression of peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A genes, consequently exerted an important improvement in sepsis-induced cardiac dysfunction. PMID:25076854

  2. 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

  3. 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

  4. Cognitive and Functional Consequence of Cardiac Arrest.

    PubMed

    Perez, Claudia A; Samudra, Niyatee; Aiyagari, Venkatesh

    2016-08-01

    Cardiac arrest is associated with high morbidity and mortality. Better-quality bystander cardiopulmonary resuscitation training, cardiocerebral resuscitation principles, and intensive post-resuscitation hospital care have improved survival. However, cognitive and functional impairment after cardiac arrest remain areas of concern. Research focus has shifted beyond prognostication in the immediate post-arrest period to identification of mechanisms for long-term brain injury and implementation of promising protocols to reduce neuronal injury. These include therapeutic temperature management (TTM), as well as pharmacologic and psychological interventions which also improve overall neurological function. Comprehensive assessment of cognitive function post-arrest is hampered by heterogeneous measures among studies. However, the domains of attention, long-term memory, spatial memory, and executive function appear to be affected. As more patients survive cardiac arrest for longer periods of time, there needs to be a greater focus on interventions that can enhance cognitive and psychosocial function post-arrest. PMID:27311306

  5. Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

    PubMed

    Kloner, Robert A; Dai, Wangde; Hale, Sharon L; Shi, Jianru

    2016-07-01

    While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function. PMID:26612091

  6. Natakalim improves post-infarction left ventricular remodeling by restoring the coordinated balance between endothelial function and cardiac hypertrophy.

    PubMed

    Zhou, Hong-Min; Zhong, Ming-Li; Zhang, Yan-Fang; Cui, Wen-Yu; Long, Chao-Liang; Wang, Hai

    2014-11-01

    Endothelial dysfunction can lead to congestive heart failure and the activation of endothelial ATP-sensitive potassium (K(ATP)) channels may contribute to endothelial protection. Therefore, the present study was carried out to investigate the hypothesis that natakalim, a novel K(ATP) channel opener, ameliorates post-infarction left ventricular remodeling and failure by correcting endothelial dysfunction. The effects of myocardial infarction were assessed 8 weeks following left anterior descending coronary artery occlusion in male Wistar rats. Depressed blood pressure, cardiac dysfunction, evidence of left ventricular remodeling and congestive heart failure were observed in the rats with myocardial infarction. Treatment with natakalim at daily oral doses of 1, 3 or 9 mg/kg/day for 8 weeks prevented these changes. Natakalim also prevented the progression to cardiac failure, which was demonstrated by the increase in right ventricular weight/body weight (RVW/BW) and relative lung weight, signs of cardiac dysfunction, as well as the overexpression of atrial and brain natriuretic peptide mRNAs. Our results also demonstrated that natakalim enhanced the downregulation of endothelium-derived nitric oxide, attenuated the upregulation of inducible nitric oxide synthase-derived nitric oxide (NO), inhibited the upregulated endothelin system and corrected the imbalance between prostacyclin and thromboxane A(2). Overall, our findings suggest that natakalim prevents post-infarction hypertrophy and cardiac failure by restoring the coordinated balance between endothelial function and cardiac hypertrophy. PMID:25215478

  7. Delivery of Nox2-NADPH oxidase siRNA with polyketal nanoparticles for improving cardiac function following myocardial infarction

    PubMed Central

    Somasuntharam, Inthirai; Boopathy, Archana V.; Khan, Raffay S.; Martinez, Mario D.; Brown, Milton E.; Murthy, Niren; Davis, Michael E.

    2013-01-01

    Myocardial infarction (MI) is the most common cause of heart failure (HF), the leading cause of death in the developed world. Oxidative stress due to excessive production of reactive oxygen species (ROS) plays a key role in the pathogenesis of cardiac remodeling leading to HF. NADPH oxidase with Nox2 as the catalytic subunit is a major source for cardiac ROS production. Nox2-NADPH expression is significantly increased in the infarcted myocardium, primarily in neutrophils, macrophages and myocytes. Moreover, mice lacking the Nox2 gene are protected from ischemic injury, implicating Nox2 as a potential therapeutic target. RNAi-mediated gene silencing holds great promise as a therapeutic owing to its high specificity and potency. However, in vivo delivery hurdles have limited its effective clinical use. Here, we demonstrate acid-degradable polyketal particles as delivery vehicles for Nox2-siRNA to the post-MI heart. In vitro, Nox2-siRNA particles are effectively taken up by macrophages and significantly knockdown Nox2 expression and activity. Following in vivo intramyocardial injection in experimental mice models of MI, Nox2-siRNA particles prevent upregulation of Nox2 and significantly recovered cardiac function. This study highlights the potential of polyketals as siRNA delivery vehicles to the MI heart and represents a viable therapeutic approach for targeting oxidative stress. PMID:23856052

  8. [Combined therapy with weight loss and amiodarone improved cardiac function in a patient with idiopathic dilated cardiomyopathy complicated with severe obesity: a case report].

    PubMed

    Tanaka, Haruki; Kawano, Shunichi; Kozai, Toshiyuki; Urabe, Yoshitoshi

    2007-08-01

    Obesity is associated with an increased risk of development of chronic heart failure, but recent epidemiological studies indicate that a higher body mass index (BMI) is associated with a better survival rate. This is described as the 'obesity paradox' or 'reverse epidemiology'. A 42-year-old male was admitted because of recurrent episodes of decompensated heart failure, and the diagnosis was idiopathic dilated cardiomyopathy complicated with severe obesity (BMI 46.0), nonsustained ventricular tachycardia, and central type sleep apnea syndrome. Combined therapy with weight loss (BMI 46.0 to 30.8) and amiodarone (200 mg/day) was instituted in addition to the previous regimen including angiotensin converting enzyme inhibitor, beta blocker, diuretics and pimobendan, improved cardiac function, exercise tolerance, and cardiac sympathetic nerve activity evaluated by cardiac 123I-metaiodobenzylguanidine scintigraphy. Furthermore, we succeeded in uptitration of carvedilol(5 to 10mg/day). This case highlights the possible beneficial effect of weight loss in patients with chronic heart failure complicated with obesity, and the resultant improvement of cardiac sympathetic nerve activity suggests that weight loss may partially mimic beta blocker effects in patients with systolic heart failure. PMID:17802698

  9. Reduced BDNF attenuates inflammation and angiogenesis to improve survival and cardiac function following myocardial infarction in mice

    PubMed Central

    Ma, Yonggang; Ramirez, Trevi A.; Zhang, Jianhua; Dai, Qiuxia; Hensler, Julie G.; Lopez, Elizabeth F.; Ghasemi, Omid; Jin, Yu-Fang; Lindsey, Merry L.

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) increases in failing hearts, but BDNF roles in cardiac remodeling following myocardial infarction (MI) are unclear. Male BDNF+/+ [wild-type (WT)] and BDNF+/− heterozygous (HET) mice at 6–9 mo of age were subjected to MI and evaluated at days 1, 3, 5, 7, or 28 post-MI. At day 28 post-MI, 76% of HET versus 40% of WT survived, whereas fractional shortening improved and neovascularization levels were reduced in the HET (all, P < 0.05). At day 1, post-MI, matrix metalloproteinase-9, and myeloperoxidase (MPO) increased in WT, but not in HET. Concomitantly, monocyte chemotactic protein-1 and -5 levels increased and vascular endothelial growth factor (VEGF)-A decreased in HET. Neutrophil infiltration peaked at days 1–3 in WT mice, and this increase was blunted in HET. To determine if MPO administration could rescue the HET phenotype, MPO was injected at 3 h post-MI. MPO restored VEGF-A levels without altering matrix metalloproteinase-9 or neutrophil content. In conclusion, reduced BDNF levels modulated the early inflammatory and neovascularization responses, leading to improved survival and reduced cardiac remodeling at day 28 post-MI. Thus reduced BDNF attenuates early inflammation following MI by modulating MPO and angiogenic response through VEGF-A. PMID:24142413

  10. Thyroid hormones improve cardiac function and decrease expression of pro-apoptotic proteins in the heart of rats 14 days after infarction.

    PubMed

    de Castro, Alexandre Luz; Fernandes, Rafael Oliveira; Ortiz, Vanessa D; Campos, Cristina; Bonetto, Jéssica H P; Fernandes, Tânia R G; Conzatti, Adriana; Siqueira, Rafaela; Tavares, Angela Vicente; Schenkel, Paulo Cavalheiro; Belló-Klein, Adriane; da Rosa Araujo, Alex Sander

    2016-02-01

    Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300-350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animals received T3 and T4 [2 and 8 µg/(100 g day)] by gavage. After this, the rats were submitted to haemodynamic and echocardiographic analysis, and then were sacrificed and the heart tissue was collected for molecular analysis. Statistical analyses included two-way ANOVA with Student-Newman-Keuls post test. Ethics Committee number: 23262. TH administration prevented the loss of ventricular wall thickness and improved cardiac function in the infarcted rats 14 days after the injury. AMI rats presented an increase in the pro-apoptotic proteins p53 and JNK. The hormonal treatment prevented this increase in AMIT rats. In addition, TH administration decreased the Bax:Bcl-2 ratio in the infarcted rats. TH administration improved cardiac functional parameters, and decreased the expression of pro-apoptotic proteins 14 days after myocardial infarction. PMID:26659365

  11. Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress

    PubMed Central

    Liu, Li; Goldberg, Ira J.

    2015-01-01

    Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function. PMID:25858561

  12. Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress.

    PubMed

    Kolwicz, Stephen C; Liu, Li; Goldberg, Ira J; Tian, Rong

    2015-08-01

    Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain-mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function. PMID:25858561

  13. VEGF165A microsphere therapy for myocardial infarction suppresses acute cytokine release and increases microvascular density but does not improve cardiac function.

    PubMed

    Uitterdijk, André; Springeling, Tirza; van Kranenburg, Matthijs; van Duin, Richard W B; Krabbendam-Peters, Ilona; Gorsse-Bakker, Charlotte; Sneep, Stefan; van Haeren, Rorry; Verrijk, Ruud; van Geuns, Robert-Jan M; van der Giessen, Willem J; Markkula, Tommi; Duncker, Dirk J; van Beusekom, Heleen M M

    2015-08-01

    Angiogenesis induced by growth factor-releasing microspheres can be an off-the-shelf and immediate alternative to stem cell therapy for acute myocardial infarction (AMI), independent of stem cell yield and comorbidity-induced dysfunction. Reliable and prolonged local delivery of intact proteins such as VEGF is, however, notoriously difficult. Our objective was to create a platform for local angiogenesis in human-sized hearts, using polyethylene-glycol/polybutylene-terephthalate (PEG-PBT) microsphere-based VEGF165A delivery. PEG-PBT microspheres were biocompatible, distribution was size dependent, and a regimen of 10 × 10(6) 15-μm microspheres at 0.5 × 10(6)/min did not induce cardiac necrosis. Efficacy, studied in a porcine model of AMI with reperfusion rather than chronic ischemia used for most reported VEGF studies, shows that microspheres were retained for at least 35 days. Acute VEGF165A release attenuated early cytokine release upon reperfusion and produced a dose-dependent increase in microvascular density at 5 wk following AMI. However, it did not improve major variables for global cardiac function, left ventricular dimensions, infarct size, or scar composition (collagen and myocyte content). Taken together, controlled VEGF165A delivery is safe, attenuates early cytokine release, and leads to a dose-dependent increase in microvascular density in the infarct zone but does not translate into changes in global or regional cardiac function and scar composition. PMID:26024685

  14. Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-β1 improves cardiac function in heart failure rats

    PubMed Central

    Lv, Y.; Liu, B.; Wang, H.P.; Zhang, L.

    2016-01-01

    The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats. PMID:27254663

  15. Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-β1 improves cardiac function in heart failure rats.

    PubMed

    Lv, Y; Liu, B; Wang, H P; Zhang, L

    2016-01-01

    The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats. PMID:27254663

  16. 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. PMID

  17. QRS pattern and improvement in right and left ventricular function after cardiac resynchronization therapy: a radionuclide study

    PubMed Central

    2012-01-01

    Background Predicting response to cardiac resynchronization therapy (CRT) remains a challenge. We evaluated the role of baseline QRS pattern to predict response in terms of improvement in biventricular ejection fraction (EF). Methods Consecutive patients (pts) undergoing CRT implantation underwent radionuclide angiography at baseline and at mid-term follow-up. The relationship between baseline QRS pattern and mechanical dyssynchrony using phase analysis was evaluated. Changes in left and right ventricular EF (LVEF and RVEF) were analyzed with regard to baseline QRS pattern. Results We enrolled 56 pts, 32 with left bundle branch block (LBBB), 4 with right bundle branch block (RBBB) and 20 with non-specific intraventricular conduction disturbance (IVCD). A total of 48 pts completed follow-up. LBBB pts had significantly greater improvement in LVEF compared to RBBB or non-specific IVCD pts (+9.6 ± 10.9% vs. +2.6 ± 7.6%, p = 0.003). Response (defined as ≥ 5% increase in LVEF) was observed in 68% of LBBB vs. 24% of non-specific IVCD pts (p = 0.006). None of the RBBB pts were responders. RVEF was significantly improved in LBBB (+5.0 ± 9.0%, p = 0.007), but not in non-specific IVCD and RBBB pts (+0.4 ± 5.8%, p = 0.76). At multivariate analysis, LBBB was the only predictor of LVEF response (OR, 7.45; 95% CI 1.80-30.94; p = 0.006), but not QRS duration or extent of mechanical dyssynchrony. Conclusions Presence of a LBBB is a marker of a positive response to CRT in terms of biventricular improvement. Pts with non-LBBB pattern show significantly less benefit from CRT than those with LBBB. PMID:22494365

  18. Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury

    PubMed Central

    Lee, Se-Yeon; Lee, Seahyoung; Choi, Eunhyun; Ham, Onju; Lee, Chang Youn; Lee, Jiyun; Seo, Hyang-Hee; Cha, Min-Ji; Mun, Bohyun; Lee, Yunmi; Yoon, Cheesoon; Hwang, Ki-Chul

    2016-01-01

    Genetic ablation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), an essential regulator of cardiac cell death, is an effective way to prevent cardiac cell death triggered by pathologic conditions. However, currently there exists no known means, such as inhibitors, to down-regulate BNIP3 in mature heart. Here, we report that a small molecule inducer of microRNA-182 (miR-182) suppressed ischemia/reperfusion (I/R)-induced cardiac cell death by down-regulating BNIP3. We first selected miR-182 as a potent BNIP3-targeting miRNA based on miRNA-target prediction databases and empirical data. The subsequent screening of small molecules for inducing miR-182 expression identified Kenpaullone as a hit compound. Both exogenous miR-182 and Kenpaullone significantly suppressed hypoxia-induced cardiomyocyte death in vitro. To investigate the effect of changing substituents of Kenpaullone on miR-182 expression, we synthesized 9 derivatives of Kenpaullone. Among these derivatives, compound 5 showed significantly improved ability to induce miR-182 expression. The results of the in vivo study showed that compound 5 significantly improved heart function following I/R-injury in rats. Our study provides strong evidence that the small molecule-mediated up-regulation of miRNAs is a viable strategy to down-regulate target proteins with no known chemical inhibitor and that compound 5 may have potential to prevent I/R-inflicted cardiac cell death. PMID:27008992

  19. Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury.

    PubMed

    Lee, Se-Yeon; Lee, Seahyoung; Choi, Eunhyun; Ham, Onju; Lee, Chang Youn; Lee, Jiyun; Seo, Hyang-Hee; Cha, Min-Ji; Mun, Bohyun; Lee, Yunmi; Yoon, Cheesoon; Hwang, Ki-Chul

    2016-01-01

    Genetic ablation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), an essential regulator of cardiac cell death, is an effective way to prevent cardiac cell death triggered by pathologic conditions. However, currently there exists no known means, such as inhibitors, to down-regulate BNIP3 in mature heart. Here, we report that a small molecule inducer of microRNA-182 (miR-182) suppressed ischemia/reperfusion (I/R)-induced cardiac cell death by down-regulating BNIP3. We first selected miR-182 as a potent BNIP3-targeting miRNA based on miRNA-target prediction databases and empirical data. The subsequent screening of small molecules for inducing miR-182 expression identified Kenpaullone as a hit compound. Both exogenous miR-182 and Kenpaullone significantly suppressed hypoxia-induced cardiomyocyte death in vitro. To investigate the effect of changing substituents of Kenpaullone on miR-182 expression, we synthesized 9 derivatives of Kenpaullone. Among these derivatives, compound 5 showed significantly improved ability to induce miR-182 expression. The results of the in vivo study showed that compound 5 significantly improved heart function following I/R-injury in rats. Our study provides strong evidence that the small molecule-mediated up-regulation of miRNAs is a viable strategy to down-regulate target proteins with no known chemical inhibitor and that compound 5 may have potential to prevent I/R-inflicted cardiac cell death. PMID:27008992

  20. In vivo transfer of soluble TNF-alpha receptor 1 gene improves cardiac function and reduces infarct size after myocardial infarction in rats.

    PubMed

    Sugano, Masahiro; Tsuchida, Keiko; Hata, Tomoji; Makino, Naoki

    2004-05-01

    Increased circulating and cardiac TNF-alpha levels during myocardial ischemia have been found in both experimental animals and patients with ischemic heart disease and advanced heart failure. Soluble TNF-alpha receptor 1 (sTNFR1) is an antagonist to TNF-alpha. In the present study, we examined whether sTNFR1 improves cardiac function in rats after myocardial infarction. Male Wistar rats were subjected to left coronary artery (LCA) ligation. Immediately after the ligation, a total of 200 microg of either the sTNFR1 or LacZ plasmid was injected into three different sites in the left ventricular wall. From 1 to 21 days after LCA ligation, TNF-alpha bioactivity in the heart was higher in rats receiving LacZ plasmid than in sham-operated rats, whereas sTNFR1 plasmid significantly suppressed the increase. The LV diastolic dimension was significantly lower, and the fractional shortening was significantly higher in rats treated with the sTNFR1 plasmid than in those treated with the LacZ plasmid. At 21 days after LCA ligation, the LV end-diastolic pressure was also significantly lower in the rats treated with the sTNFR1 plasmid. In addition, the sTNFR1 expression plasmid had significantly reduced the infarct size. In conclusion, TNF-alpha bioactivity in the heart increased during the early stage of infarction and remained elevated. This elevation seemed partially responsible for the impairment of LV function and the increased infarct size. Suppression of TNF-alpha bioactivity from the early stage of infarction with the sTNFR1 plasmid improved cardiac function and reduced infarct size. PMID:15117889

  1. Bioengineered FSTL1 Patches Restore Cardiac Function Following Myocardial Infarction.

    PubMed

    Alteköester, Ann-Kristin; Harvey, Richard P

    2015-12-01

    Improving the limited ability of the heart to regenerate after infarction is crucial. Researchers now demonstrate that delivery of follistatin-like 1 (FSTL1) into injured hearts via collagen patches stimulates cardiomyocyte proliferation and cardiac functional recovery. These findings highlight the epicardium as a source of novel regenerative factors and biomimetic nanomaterials in cardiac translational medicine. PMID:26596868

  2. Oxygen cycling in conjunction with stem cell transplantation induces NOS3 expression leading to attenuation of fibrosis and improved cardiac function

    PubMed Central

    Khan, Mahmood; Meduru, Sarath; Gogna, Rajan; Madan, Esha; Citro, Lucas; Kuppusamy, Muthulakshmi L.; Sayyid, Muzzammil; Mostafa, Mahmoud; Hamlin, Robert L.; Kuppusamy, Periannan

    2012-01-01

    Aims Myocardial infarction (MI) is associated with irreversible loss of viable cardiomyocytes. Cell therapy is a potential option to replace the lost cardiomyocytes and restore cardiac function. However, cell therapy is faced with a number of challenges, including survival of the transplanted cells in the infarct region, which is characterized by abundant levels of oxidants and lack of a pro-survival support mechanism. The goal of the present study was to evaluate the effect of supplemental oxygenation on cell engraftment and functional recovery in a rat model. Methods and results MI was induced in rats by a 60-min occlusion of the coronary artery, followed by restoration of flow. Mesenchymal stem cells (MSCs), isolated from adult rat bone marrow, were transplanted in the MI region. Rats with transplanted MSCs were exposed to hyperbaric oxygen (HBO: 100% O2, 2 atmospheres absolute) for 90 min, 5 days/week for 4 weeks. The experimental groups were: MI (control), Ox (MI + HBO), MSC (MI + MSC), and MSC + Ox (MI + MSC + HBO). HBO exposure (oxygenation) was started 3 days after induction of MI. MSCs were transplanted 1 week after induction of MI. Echocardiography showed a significant recovery of cardiac function in the MSC + Ox group, when compared with the MI or MSC group. Oxygenation increased the engraftment of MSCs and vascular density in the infarct region. Molecular analysis of infarct tissue showed a four-fold increase in NOS3 expression in the MSC + Ox group compared with the MI group. Conclusions The results showed that post-MI exposure of rats to daily cycles of hyperoxygenation (oxygen cycling) improved stem cell engraftment, cardiac function, and increased NOS3 expression. PMID:22012955

  3. Traditional Formula, Modern Application: Chinese Medicine Formula Sini Tang Improves Early Ventricular Remodeling and Cardiac Function after Myocardial Infarction in Rats

    PubMed Central

    Liu, Jiangang; Peter, Karoline; Shi, Dazhuo; Zhang, Lei; Dong, Guoju; Zhang, Dawu; Breiteneder, Heimo; Ma, Yan

    2014-01-01

    Sini Tang (SNT) is a traditional Chinese herbal formula consisting of four different herbs: the root of Aconitum carmichaelii, the bark of Cinnamomum cassia, the rhizome of Zingiber officinale, and the root of Glycyrrhiza uralensis. This study aims to evaluate the improvement of early ventricular remodeling and cardiac function in myocardial infarction (MI) rats by SNT. A MI model was established by ligation of the left anterior descending coronary artery. Following treatment for 4 weeks, ultrasonic echocardiography was performed. Myocardial histopathological changes were observed using haematoxylin and eosin staining. Collagens (type I and type III), transforming growth factor-β1 (TGF-β1), and Toll-like receptors (TLR-2 and TLR-4) were measured in plasma, serum, and myocardial tissue. SNT treatment decreased the infarct size, the left ventricular cavity area/heart cavity area ratio, and the left ventricle dimension at end systole and increased the left ventricular ejection fraction. SNT reduced the levels of TLR-2 and TLR-4 in myocardial tissue significantly and decreased the collagens content in serum and in myocardial tissue. SNT could partially reduce the level of TGF-β1 in serum and in myocardial tissue. Our data suggest that the Chinese medicine formula SNT has the potential to improve early ventricular remodeling and cardiac function after MI. PMID:24971143

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

    PubMed

    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

  5. 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

  6. 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. PMID:27346646

  7. 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

  8. Non-invasive technology that improves cardiac function after experimental myocardial infarction: Whole Body Periodic Acceleration (pGz).

    PubMed

    Uryash, Arkady; Bassuk, Jorge; Kurlansky, Paul; Altamirano, Francisco; Lopez, Jose R; Adams, Jose A

    2015-01-01

    Myocardial infarction (MI) may produce significant inflammatory changes and adverse ventricular remodeling leading to heart failure and premature death. Pharmacologic, stem cell transplantation, and exercise have not halted the inexorable rise in the prevalence and great economic costs of heart failure despite extensive investigations of such treatments. New therapeutic modalities are needed. Whole Body Periodic Acceleration (pGz) is a non-invasive technology that increases pulsatile shear stress to the endothelium thereby producing several beneficial cardiovascular effects as demonstrated in animal models, normal humans and patients with heart disease. pGz upregulates endothelial derived nitric oxide synthase (eNOS) and its phosphorylation (p-eNOS) to improve myocardial function in models of myocardial stunning and preconditioning. Here we test whether pGz applied chronically after focal myocardial infarction in rats improves functional outcomes from MI. Focal MI was produced by left coronary artery ligation. One day after ligation animals were randomized to receive daily treatments of pGz for four weeks (MI-pGz) or serve as controls (MI-CONT), with an additional group as non-infarction controls (Sham). Echocardiograms and invasive pressure volume loop analysis were carried out. Infarct transmurality, myocardial fibrosis, and markers of inflammatory and anti-inflammatory cytokines were determined along with protein analysis of eNOS, p-eNOS and inducible nitric oxide synthase (iNOS).At four weeks, survival was 80% in MI-pGz vs 50% in MI-CONT (p< 0.01). Ejection fraction and fractional shortening and invasive pressure volume relation indices of afterload and contractility were significantly better in MI-pGz. The latter where associated with decreased infarct transmurality and decreased fibrosis along with increased eNOS, p-eNOS. Additionally, MI-pGz had significantly lower levels of iNOS, inflammatory cytokines (IL-6, TNF-α), and higher level of anti

  9. Non-Invasive Technology That Improves Cardiac Function after Experimental Myocardial Infarction: Whole Body Periodic Acceleration (pGz)

    PubMed Central

    Kurlansky, Paul; Altamirano, Francisco; Lopez, Jose R.

    2015-01-01

    Myocardial infarction (MI) may produce significant inflammatory changes and adverse ventricular remodeling leading to heart failure and premature death. Pharmacologic, stem cell transplantation, and exercise have not halted the inexorable rise in the prevalence and great economic costs of heart failure despite extensive investigations of such treatments. New therapeutic modalities are needed. Whole Body Periodic Acceleration (pGz) is a non-invasive technology that increases pulsatile shear stress to the endothelium thereby producing several beneficial cardiovascular effects as demonstrated in animal models, normal humans and patients with heart disease. pGz upregulates endothelial derived nitric oxide synthase (eNOS) and its phosphorylation (p-eNOS) to improve myocardial function in models of myocardial stunning and preconditioning. Here we test whether pGz applied chronically after focal myocardial infarction in rats improves functional outcomes from MI. Focal MI was produced by left coronary artery ligation. One day after ligation animals were randomized to receive daily treatments of pGz for four weeks (MI-pGz) or serve as controls (MI-CONT), with an additional group as non-infarction controls (Sham). Echocardiograms and invasive pressure volume loop analysis were carried out. Infarct transmurality, myocardial fibrosis, and markers of inflammatory and anti-inflammatory cytokines were determined along with protein analysis of eNOS, p-eNOS and inducible nitric oxide synthase (iNOS).At four weeks, survival was 80% in MI-pGz vs 50% in MI-CONT (p< 0.01). Ejection fraction and fractional shortening and invasive pressure volume relation indices of afterload and contractility were significantly better in MI-pGz. The latter where associated with decreased infarct transmurality and decreased fibrosis along with increased eNOS, p-eNOS. Additionally, MI-pGz had significantly lower levels of iNOS, inflammatory cytokines (IL-6, TNF-α), and higher level of anti

  10. 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. PMID:26265792

  11. Ranolazine attenuated heightened plasma norepinephrine and B-Type natriuretic peptide-45 in improving cardiac function in rats with chronic ischemic heart failure.

    PubMed

    Feng, Guangqiu; Yang, Yu; Chen, Juan; Wu, Zhiyong; Zheng, Yin; Li, Wei; Dai, Wenxin; Guan, Pin; Zhong, Chunrong

    2016-01-01

    As a new anti-anginal agent, ranolazinehas been shown to play a cardioprotective role in regulating myocardial ischemic injury. Given that plasma norepinephrine (NE) and brain natriuretic peptide (BNP, also termed B-type natriuretic peptide-45 in rats) are considered neuron-hormones to indicate heart failure progression. This study aims to examine effects of ranolazine on plasma NE and BNP-45 of rats with chronic ischemic heart failure (CHF). CHF was induced by myocardial infarction following ligation of a left anterior descending artery in adult Sprague-Dawley rats. We hypothesized that ranolazine attenuates the elevated levels of NE and BNP-45 observed in CHF rats thereby leading to improvement of the left ventricular function. Results showed that levels of plasma NE and BNP-45 were increased in CHF rats 6-8 weeks after ligation of the coronary artery. Our data demonstrate for the first time that ranolazine significantly attenuated the augmented NE and BNP-45 induced by CHF (P<0.05 vs. saline control). In addition, a liner relation was observed between NE/BNP-45levels and left ventricular fractional shortening as indication of left ventricular function (r=0.91 and P<0.01 for NE; and r=0.93 and P<0.01 for BNP-45) after administration of ranolazine. In conclusion, CHF increases the expression of NE and BNP-45 in peripheral circulation and these changes are related to the left ventricular function. Ranolazine improves the left ventricular function likely by decreasing heightened NE and BNP-45 induced by CHF. Therefore, our data indicate the role played by ranolazine in improving cardiac function in rats with CHF. PMID:27158417

  12. Ranolazine attenuated heightened plasma norepinephrine and B-Type natriuretic peptide-45 in improving cardiac function in rats with chronic ischemic heart failure

    PubMed Central

    Feng, Guangqiu; Yang, Yu; Chen, Juan; Wu, Zhiyong; Zheng, Yin; Li, Wei; Dai, Wenxin; Guan, Pin; Zhong, Chunrong

    2016-01-01

    As a new anti-anginal agent, ranolazinehas been shown to play a cardioprotective role in regulating myocardial ischemic injury. Given that plasma norepinephrine (NE) and brain natriuretic peptide (BNP, also termed B-type natriuretic peptide-45 in rats) are considered neuron-hormones to indicate heart failure progression. This study aims to examine effects of ranolazine on plasma NE and BNP-45 of rats with chronic ischemic heart failure (CHF). CHF was induced by myocardial infarction following ligation of a left anterior descending artery in adult Sprague-Dawley rats. We hypothesized that ranolazine attenuates the elevated levels of NE and BNP-45 observed in CHF rats thereby leading to improvement of the left ventricular function. Results showed that levels of plasma NE and BNP-45 were increased in CHF rats 6-8 weeks after ligation of the coronary artery. Our data demonstrate for the first time that ranolazine significantly attenuated the augmented NE and BNP-45 induced by CHF (P<0.05 vs. saline control). In addition, a liner relation was observed between NE/BNP-45levels and left ventricular fractional shortening as indication of left ventricular function (r=0.91 and P<0.01 for NE; and r=0.93 and P<0.01 for BNP-45) after administration of ranolazine. In conclusion, CHF increases the expression of NE and BNP-45 in peripheral circulation and these changes are related to the left ventricular function. Ranolazine improves the left ventricular function likely by decreasing heightened NE and BNP-45 induced by CHF. Therefore, our data indicate the role played by ranolazine in improving cardiac function in rats with CHF. PMID:27158417

  13. 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. PMID:18039406

  14. Mathematical Models of Cardiac Pacemaking Function

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

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

  15. 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. PMID:25861857

  16. Cardiac Na Channels: Structure to Function.

    PubMed

    DeMarco, K R; Clancy, C E

    2016-01-01

    Heart rhythms arise from electrical activity generated by precisely timed opening and closing of ion channels in individual cardiac myocytes. Opening of the primary cardiac voltage-gated sodium (NaV1.5) channel initiates cellular depolarization and the propagation of an electrical action potential that promotes coordinated contraction of the heart. The regularity of these contractile waves is critically important since it drives the primary function of the heart: to act as a pump that delivers blood to the brain and vital organs. When electrical activity goes awry during a cardiac arrhythmia, the pump does not function, the brain does not receive oxygenated blood, and death ensues. Perturbations to NaV1.5 may alter the structure, and hence the function, of the ion channel and are associated downstream with a wide variety of cardiac conduction pathologies, such as arrhythmias. PMID:27586288

  17. Hypothermia improves outcome from cardiac arrest.

    PubMed

    Bernard, S A

    2005-12-01

    Out-of-hospital cardiac arrest is common and patients who are initially resuscitated by ambulance officers and transported to hospital are usually admitted to the intensive care unit (ICU). In the past, the treatment in the ICU consisted of supportive care only, and most patients remained unconscious due to the severe anoxic neurological injury. It was this neurological injury rather than cardiac complications that caused the high rate of morbidity and mortality. However, in the early 1990's, a series of animal experiments demonstrated convincingly that mild hypothermia induced after return of spontaneous circulation and maintained for several hours dramatically reduced the severity of the anoxic neurological injury. In the mid-1990's, preliminary human studies suggested that mild hypothermia could be induced and maintained in post-cardiac arrest patients without an increase in the rate of cardiac or other complications. In the late 1990's, two prospective, randomised, controlled trials were conducted and the results confirmed the animal data that mild hypothermia induced after resuscitation and maintained for 12 - 24 hours dramatically improved neurological and overall outcomes. On the basis of these studies, mild hypothermia was endorsed in 2003 by the International Liaison Committee on Resuscitation as a recommended treatment for comatose patients with an initial cardiac rhythm of ventricular fibrillation. However, the application of this therapy into routine clinical critical care practice has been slow. The reasons for this are uncertain, but may relate to the relative complexity of the treatment, unfamiliarity with the pathophysiology of hypothermia, lack of clear protocols and/or uncertainty of benefit in particular patients. Therefore, recent research in this area has focused on the development of feasible, inexpensive techniques for the early, rapid induction of mild hypothermia after cardiac arrest. Currently, the most promising strategy is a rapid

  18. 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

  19. Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

    PubMed Central

    Chen, Shou-Qiang; Xing, Shan-Shan; Gao, Hai-Qing

    2014-01-01

    Objective: In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring (TTM), a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service (GPRS) network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Methods: Using 2 leads (V1 and V5 leads) and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. Results: In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. Conclusions: A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes. PMID:25674124

  20. Improving cardiac myocytes performance by carbon nanotubes platforms†

    PubMed Central

    Martinelli, Valentina; Cellot, Giada; Fabbro, Alessandra; Bosi, Susanna; Mestroni, Luisa; Ballerini, Laura

    2013-01-01

    The application of nanotechnology to the cardiovascular system has increasingly caught scientists' attention as a potentially powerful tool for the development of new generation devices able to interface, repair, or boost the performance of cardiac tissue. Carbon nanotubes (CNTs) are considered as promising materials for nanomedicine applications in general and have been recently tested toward excitable cell growth. CNTs are cylindrically shaped structures made up of rolled-up graphene sheets, with unique electrical, thermal, and mechanical properties, able to effectively conducting electrical current in electrochemical interfaces. CNTs-based scaffolds have been recently found to support the in vitro growth of cardiac cells: in particular, their ability to improve cardiomyocytes proliferation, maturation, and electrical behavior are making CNTs extremely attractive for the development and exploitation of interfaces able to impact on cardiac cells physiology and function. PMID:24027533

  1. Functional cardiac imaging: positron emission tomography

    SciTech Connect

    Mullani, N.A.; Gould, K.L.

    1984-02-01

    Dynamic cardiovascular imaging plays a vital role in the diagnosis and treatment of cardiac disease by providing information about the function of the heart. During the past 30 years, cardiovascular imaging has evolved from the simple chest x-ray and fluoroscopy to such sophisticated techniques as invasive cardiac angiography and cinearteriography and, more recently, to noninvasive cardiac CT scanning, nuclear magnetic resonance, and positron emission tomography, which reflect more complex physiologic functions. As research tools, CT, NMR, and PET provide quantitative information on global as well as regional ventricular function, coronary artery stenosis, myocardial perfusion, glucose and fatty acid metabolism, or oxygen utilization, with little discomfort or risk to the patient. As imaging modalities become more sophisticated and more oriented toward clinical application, the prospect of routinely obtaining such functional information about the heart is becoming realistic. However, these advances are double-edged in that the interpretation of functional data is more complex than that of the anatomic imaging familiar to most physicians. They will require an enhanced understanding of the physiologic and biochemical processes, as well as of the instrumentation and techniques for analyzing the data. Of the new imaging modalities that provide functional information about the heart, PET is the most useful because it quantitates the regional distribution of radionuclides in vivo. Clinical applications, interpretation of data, and the impact of PET on our understanding of cardiac pathophysiology are discussed. 5 figures.

  2. Diminazene Aceturate Improves Cardiac Fibrosis and Diastolic Dysfunction in Rats with Kidney Disease

    PubMed Central

    Velkoska, Elena; Patel, Sheila K.; Griggs, Karen

    2016-01-01

    Angiotensin converting enzyme (ACE) 2 is a negative regulator of the renin angiotensin system (RAS) through its role to degrade angiotensin II. In rats with subtotal nephrectomy (STNx), adverse cardiac remodelling occurs despite elevated cardiac ACE2 activity. We hypothesised that diminazene aceturate (DIZE), which has been described as having an off-target effect to activate ACE2, would have beneficial cardiac effects in STNx rats. STNx led to hypertension, diastolic dysfunction, left ventricular hypertrophy, cardiac fibrosis, and increased cardiac ACE, ACE2, Ang II and Ang 1–7 levels. Cardiac gene expression of ADAM17 was also increased. In STNx, two-weeks of subcutaneous DIZE (15mg/kg/d) had no effect on blood pressure but improved diastolic dysfunction and cardiac fibrosis, reduced ADAM17 mRNA and shifted the cardiac RAS balance to a cardioprotective profile with reduced ACE and Ang II. There was no change in cardiac ACE2 activity or in cardiac Ang 1–7 levels with DIZE. In conclusion, our results suggest that DIZE exerts a protective effect on the heart under the pathological condition of kidney injury. This effect was not due to improved kidney function, a fall in blood pressure or a reduction in LVH but was associated with a reduction in cardiac ACE and cardiac Ang II levels. As in vitro studies showed no direct effect of DIZE on ACE2 or ACE activity, the precise mechanism of action of DIZE remains to be determined. PMID:27571511

  3. Diminazene Aceturate Improves Cardiac Fibrosis and Diastolic Dysfunction in Rats with Kidney Disease.

    PubMed

    Velkoska, Elena; Patel, Sheila K; Griggs, Karen; Burrell, Louise M

    2016-01-01

    Angiotensin converting enzyme (ACE) 2 is a negative regulator of the renin angiotensin system (RAS) through its role to degrade angiotensin II. In rats with subtotal nephrectomy (STNx), adverse cardiac remodelling occurs despite elevated cardiac ACE2 activity. We hypothesised that diminazene aceturate (DIZE), which has been described as having an off-target effect to activate ACE2, would have beneficial cardiac effects in STNx rats. STNx led to hypertension, diastolic dysfunction, left ventricular hypertrophy, cardiac fibrosis, and increased cardiac ACE, ACE2, Ang II and Ang 1-7 levels. Cardiac gene expression of ADAM17 was also increased. In STNx, two-weeks of subcutaneous DIZE (15mg/kg/d) had no effect on blood pressure but improved diastolic dysfunction and cardiac fibrosis, reduced ADAM17 mRNA and shifted the cardiac RAS balance to a cardioprotective profile with reduced ACE and Ang II. There was no change in cardiac ACE2 activity or in cardiac Ang 1-7 levels with DIZE. In conclusion, our results suggest that DIZE exerts a protective effect on the heart under the pathological condition of kidney injury. This effect was not due to improved kidney function, a fall in blood pressure or a reduction in LVH but was associated with a reduction in cardiac ACE and cardiac Ang II levels. As in vitro studies showed no direct effect of DIZE on ACE2 or ACE activity, the precise mechanism of action of DIZE remains to be determined. PMID:27571511

  4. 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

  5. Transplantation of Immortalized CD34+ and CD34- Adipose-Derived Stem Cells Improve Cardiac Function and Mitigate Systemic Pro-Inflammatory Responses

    PubMed Central

    Kim, Jong-Ho; Choi, Seung-Cheol; Park, Chi-Yeon; Park, Jae-Hyoung; Choi, Ji-Hyun; Joo, Hyung-Joon; Hong, Soon-Jun; Lim, Do-Sun

    2016-01-01

    Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34- mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34- mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34- mADSCshTERT demonstrated phenotypic characteristics and multi-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34- mADSCshTERT, whereas CD34- mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34- mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34- mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34- mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34- mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34- mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34- mADSCshTERT into endothelial cells was found in the infarcted myocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34- mADSCshTERT groups compared to the AMI-induced control group

  6. Methods to improve cardiac gene therapy expression.

    PubMed

    Scimia, Maria Cecilia; Sydnes, Kate E; Zuppo, Daniel A; Koch, Walter J

    2014-11-01

    Gene therapy strategies are becoming a valuable approach for the treatment of heart failure. Some trials are ongoing and others are being organized. Vascular access in clinical experimentation is still the chosen modality of delivery, but many other approaches are in research and development. A successful gene therapy strategy involves not only the choice of the right vector and gene, but also the correct delivery strategy that allows for transduction of the highest percentage of cardiomyocytes, limited spilling of virus into other organs and the possibility to correlate the amount of injected virus to the rate of the expression within the cardiac tissue. The authors will first concentrate on clarifying what the barriers are that the virus has to overcome in order to reach the nuclei of the target organs and methodologies that have been tested to improve the range of expression. PMID:25340284

  7. Secondary Sphere Formation Enhances the Functionality of Cardiac Progenitor Cells

    PubMed Central

    Cho, Hyun-Jai; Lee, Ho-Jae; Youn, Seock-Won; Koh, Seok-Jin; Won, Joo-Yun; Chung, Yeon-Ju; Cho, Hyun-Ju; Yoon, Chang-Hwan; Lee, Sae-Won; Lee, Eun Ju; Kwon, Yoo-Wook; Lee, Hae-Young; Lee, Sang Hun; Ho, Won-Kyung; Park, Young-Bae; Kim, Hyo-Soo

    2012-01-01

    Loss of cardiomyocytes impairs cardiac function after myocardial infarction (MI). Recent studies suggest that cardiac stem/progenitor cells could repair the damaged heart. However, cardiac progenitor cells are difficult to maintain in terms of purity and multipotency when propagated in two-dimensional culture systems. Here, we investigated a new strategy that enhances potency and enriches progenitor cells. We applied the repeated sphere formation strategy (cardiac explant → primary cardiosphere (CS) formation → sphere-derived cells (SDCs) in adherent culture condition → secondary CS formation by three-dimensional culture). Cells in secondary CS showed higher differentiation potentials than SDCs. When transplanted into the infarcted myocardium, secondary CSs engrafted robustly, improved left ventricular (LV) dysfunction, and reduced infarct sizes more than SDCs did. In addition to the cardiovascular differentiation of transplanted secondary CSs, robust vascular endothelial growth factor (VEGF) synthesis and secretion enhanced neovascularization in the infarcted myocardium. Microarray pathway analysis and blocking experiments using E-selectin knock-out hearts, specific chemicals, and small interfering RNAs (siRNAs) for each pathway revealed that E-selectin was indispensable to sphere initiation and ERK/Sp1/VEGF autoparacrine loop was responsible for sphere maturation. These results provide a simple strategy for enhancing cellular potency for cardiac repair. Furthermore, this strategy may be implemented to other types of stem/progenitor cell-based therapy. PMID:22713697

  8. 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

  9. Interplay between cardiac function and heart development.

    PubMed

    Andrés-Delgado, Laura; Mercader, Nadia

    2016-07-01

    Mechanotransduction refers to the conversion of mechanical forces into biochemical or electrical signals that initiate structural and functional remodeling in cells and tissues. The heart is a kinetic organ whose form changes considerably during development and disease. This requires cardiomyocytes to be mechanically durable and able to mount coordinated responses to a variety of environmental signals on different time scales, including cardiac pressure loading and electrical and hemodynamic forces. During physiological growth, myocytes, endocardial and epicardial cells have to adaptively remodel to these mechanical forces. Here we review some of the recent advances in the understanding of how mechanical forces influence cardiac development, with a focus on fluid flow forces. 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. PMID:26952935

  10. Controlling the Structural and Functional Anisotropy of Engineered Cardiac Tissues

    PubMed Central

    Bursac, N

    2014-01-01

    The ability to control the degree of structural and functional anisotropy in 3D engineered cardiac tissues would have high utility for both in vitro studies of cardiac muscle physiology and pathology as well as potential tissue engineering therapies for myocardial infarction. Here, we applied a high aspect ratio soft lithography technique to generate network-like tissue patches seeded with neonatal rat cardiomyocytes. Fabricating longer elliptical pores within the patch networks increased the overall cardiomyocyte and extracellular matrix (ECM) alignment within the patch. Improved uniformity of cell and matrix alignment yielded an increase in anisotropy of action potential propagation and faster longitudinal conduction velocity (LCV). Cardiac tissue patches with a higher degree of cardiomyocyte alignment and electrical anisotropy also demonstrated greater isometric twitch forces. After two weeks of culture, specific measures of electrical and contractile function (LCV = 26.8 ± 0.8 cm/s, specific twitch force = 8.9 ± 1.1 mN/mm2 for the longest pores studied) were comparable to those of neonatal rat myocardium. We have thus described methodology for engineering of highly functional 3D engineered cardiac tissues with controllable degree of anisotropy. PMID:24717534

  11. Prevascularization of cardiac patch on the omentum improves its therapeutic outcome

    PubMed Central

    Dvir, Tal; Kedem, Alon; Ruvinov, Emil; Levy, Oren; Freeman, Inbar; Landa, Natalie; Holbova, Radka; Feinberg, Micha S.; Dror, Shani; Etzion, Yoram; Leor, Jonathan; Cohen, Smadar

    2009-01-01

    The recent progress made in the bioengineering of cardiac patches offers a new therapeutic modality for regenerating the myocardium after myocardial infarction (MI). We present here a strategy for the engineering of a cardiac patch with mature vasculature by heterotopic transplantation onto the omentum. The patch was constructed by seeding neonatal cardiac cells with a mixture of prosurvival and angiogenic factors into an alginate scaffold capable of factor binding and sustained release. After 48 h in culture, the patch was vascularized for 7 days on the omentum, then explanted and transplanted onto infarcted rat hearts, 7 days after MI induction. When evaluated 28 days later, the vascularized cardiac patch showed structural and electrical integration into host myocardium. Moreover, the vascularized patch induced thicker scars, prevented further dilatation of the chamber and ventricular dysfunction. Thus, our study provides evidence that grafting prevascularized cardiac patch into infarct can improve cardiac function after MI. PMID:19706385

  12. Regulation of cardiac metabolism and function by lipogenic factors.

    PubMed

    Bednarski, Tomasz; Pyrkowska, Aleksandra; Opasińska, Agnieszka; Dobrzyń, Paweł

    2016-01-01

    The heart has a limited capacity for lipogenesis and de novo lipid synthesis. However, expression of lipogenic genes in cardiomyocytes is unexpectedly high. Recent studies showed that lipogenic genes are important factors regulating cardiac metabolism and function. Long chain fatty acids are a major source of ATP required for proper heart function, and under aerobic conditions, the heart derives 60-90% of the energy necessary for contractile function from fatty acid oxidation. On the other hand, cardiac lipid over-accumulation (e.g. ceramides, diacylglycerols) leads to heart dysfunction. Downregulation of the lipogenic genes' expression (e.g. sterol regulatory element binding protein 1, stearoyl-CoA desaturase, acetyl-CoA kwacarboxylase) decreased heart steatosis and cardiomyocyte apoptosis, improving systolic and diastolic function of the left ventricle. Lipogenic factors also regulate fatty acids and glucose utilization in the heart, underlining their important role in maintaining energetic homeostasis in pathological states. Fatty acid synthase, the enzyme catalyzing fatty acids de novo synthesis, affects cardiac calcium signaling through regulation of L-type calcium channel activity. Thus, a growing body of evidence suggests that the role of lipogenic genes in cardiomyocytes may be distinct from other tissues. Here, we review recent advances made in understanding the role of lipogenic genes in the control of heart metabolism and its involvement in the pathogenesis of lipotoxic cardiomyopathy. PMID:27333934

  13. 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

  14. 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. PMID:25361774

  15. Functional cardiac imaging by random access microscopy

    PubMed Central

    Crocini, Claudia; Coppini, Raffaele; Ferrantini, Cecilia; Pavone, Francesco S.; Sacconi, Leonardo

    2014-01-01

    Advances in the development of voltage sensitive dyes and Ca2+ sensors in combination with innovative microscopy techniques allowed researchers to perform functional measurements with an unprecedented spatial and temporal resolution. At the moment, one of the shortcomings of available technologies is their incapability of imaging multiple fast phenomena while controlling the biological determinants involved. In the near future, ultrafast deflectors can be used to rapidly scan laser beams across the sample, performing optical measurements of action potential and Ca2+ release from multiple sites within cardiac cells and tissues. The same scanning modality could also be used to control local Ca2+ release and membrane electrical activity by activation of caged compounds and light-gated ion channels. With this approach, local Ca2+ or voltage perturbations could be induced, simulating arrhythmogenic events, and their impact on physiological cell activity could be explored. The development of this optical methodology will provide fundamental insights in cardiac disease, boosting new therapeutic strategies, and, more generally, it will represent a new approach for the investigation of the physiology of excitable cells. PMID:25368580

  16. Improving neurological outcome after cardiac arrest: Therapeutic hypothermia the best treatment

    PubMed Central

    Malhotra, Suchitra; Dhama, Satyavir S.; Kumar, Mohinder; Jain, Gaurav

    2013-01-01

    Cardiac arrest, irrespective of its etiology, has a high mortality. This event is often associated with brain anoxia which frequently causes severe neurological damage and persistent vegetative state. Only one out of every six patients survives to discharge following in-hospital cardiac arrest, whereas only 2-9% of patients who experience out of hospital cardiac arrest survive to go home. Functional outcomes of survival are variable, but poor quality survival is common, with only 3-7% able to return to their previous level of functioning. Therapeutic hypothermia is an important tool for the treatment of post-anoxic coma after cardiopulmonary resuscitation. It has been shown to reduce mortality and has improved neurological outcomes after cardiac arrest. Nevertheless, hypothermia is underused in critical care units. This manuscript aims to review the mechanism of hypothermia in cardiac arrest survivors and to propose a simple protocol, feasible to be implemented in any critical care unit. PMID:25885714

  17. 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

  18. Influence of vascular function and pulsatile hemodynamics on cardiac function.

    PubMed

    Bell, Vanessa; Mitchell, Gary F

    2015-09-01

    Interactions between cardiac and vascular structure and function normally are optimized to ensure delivery of cardiac output with modest pulsatile hemodynamic overhead. Aortic stiffening with age or disease impairs optimal ventricular-vascular coupling, increases pulsatile load, and contributes to left ventricular (LV) hypertrophy, reduced systolic function, and impaired diastolic relaxation. Aortic pulse pressure and timing of peak systolic pressure are well-known measures of hemodynamic ventricular-vascular interaction. Recent work has elucidated the importance of direct, mechanical coupling between the aorta and the heart. LV systolic contraction results in displacement of aortic and mitral annuli, thereby producing longitudinal stretch in the ascending aorta and left atrium, respectively. Force associated with longitudinal stretch increases systolic load on the LV. However, the resulting energy stored in the elastic elements of the proximal aorta during systole facilitates early diastolic LV recoil and rapid filling. This review discusses current views on hemodynamics and mechanics of ventricular-vascular coupling. PMID:26164466

  19. 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

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

    PubMed

    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

  1. Measuring mitochondrial function in intact cardiac myocytes

    PubMed Central

    Dedkova, Elena N.; Blatter, Lothar A.

    2011-01-01

    Mitochondria are involved in cellular functions that go beyond the traditional role of these organelles as the power plants of the cell. Mitochondria have been implicated in several human diseases, including cardiac dysfunction, and play a role in the aging process. Many aspects of our knowledge of mitochondria stem from studies performed on the isolated organelle. Their relative inaccessibility imposes experimental difficulties to study mitochondria in their natural environment – the cytosol of intact cells – and has hampered a comprehensive understanding of the plethora of mitochondrial functions. Here we review currently available methods to study mitochondrial function in intact cardiomyocytes. These methods primarily use different flavors of fluorescent dyes and genetically encoded fluorescent proteins in conjunction with high-resolution imaging techniques. We review methods to study mitochondrial morphology, mitochondrial membrane potential, Ca2+ and Na+ signaling, mitochondrial pH regulation, redox state and ROS production, NO signaling, oxygen consumption, ATP generation and the activity of the mitochondrial permeability transition pore. Where appropriate we complement this review on intact myocytes with seminal studies that were performed on isolated mitochondria, permeabilized cells, and in whole hearts. PMID:21964191

  2. 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

  3. 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

  4. 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

  5. Improved bioavailability of targeted Curcumin delivery efficiently regressed cardiac hypertrophy by modulating apoptotic load within cardiac microenvironment.

    PubMed

    Ray, Aramita; Rana, Santanu; Banerjee, Durba; Mitra, Arkadeep; Datta, Ritwik; Naskar, Shaon; Sarkar, Sagartirtha

    2016-01-01

    Cardiomyocyte apoptosis acts as a prime modulator of cardiac hypertrophy leading to heart failure, a major cause of human mortality worldwide. Recent therapeutic interventions have focussed on translational applications of diverse pharmaceutical regimes among which, Curcumin (from Curcuma longa) is known to have an anti-hypertrophic potential but with limited pharmacological efficacies due to low aqueous solubility and poor bioavailability. In this study, Curcumin encapsulated by carboxymethyl chitosan (CMC) nanoparticle conjugated to a myocyte specific homing peptide was successfully delivered in bioactive form to pathological myocardium for effective regression of cardiac hypertrophy in a rat (Rattus norvegicus) model. Targeted nanotization showed higher cardiac bioavailability of Curcumin at a low dose of 5 mg/kg body weight compared to free Curcumin at 35 mg/kg body weight. Moreover, Curcumin/CMC-peptide treatment during hypertrophy significantly improved cardiac function by downregulating expression of hypertrophy marker genes (ANF, β-MHC), apoptotic mediators (Bax, Cytochrome-c) and activity of apoptotic markers (Caspase 3 and PARP); whereas free Curcumin in much higher dose showed minimal improvement during compromised cardiac function. Targeted Curcumin treatment significantly lowered p53 expression and activation in diseased myocardium via inhibited interaction of p53 with p300-HAT. Thus attenuated acetylation of p53 facilitated p53 ubiquitination and reduced the apoptotic load in hypertrophied cardiomyocytes; thereby limiting cardiomyocytes' need to enter the regeneration cycle during hypertrophy. This study elucidates for the first time an efficient targeted delivery regimen for Curcumin and also attributes towards probable mechanistic insight into its therapeutic potential as a cardio-protective agent for regression of cardiac hypertrophy. PMID:26612707

  6. 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

  7. 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

    2015-11-01

    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

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

    NASA Technical Reports Server (NTRS)

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

    1977-01-01

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

  9. 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

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

    PubMed

    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; Larner, Fiona; Tyler, Damian J; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A

    2015-03-10

    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. Extracellular Superoxide Dismutase Regulates Cardiac Function and Fibrosis

    PubMed Central

    Kliment, Corrine R; Suliman, Hagir B; Tobolewski, Jacob M; Reynolds, Crystal M; Day, Brian J; Zhu, Xiaodong; McTiernan, Charles F; McGaffin, Kenneth R; Piantadosi, Claude A; Oury, Tim D

    2009-01-01

    Aims Extracellular superoxide dismutase (EC-SOD) is an antioxidant that protects the heart from ischemia and the lung from inflammation and fibrosis. The role of cardiac EC-SOD under normal conditions and injury remains unclear. Cardiac toxicity, a common side effect of doxorubicin, involves oxidative stress. We hypothesize that EC-SOD is critical for normal cardiac function and protects the heart from oxidant-induced fibrosis and loss of function. Methods C57BL/6 and EC-SOD-null mice were treated with doxorubicin, 15 mg/kg (i.p.). After 15 days, echocardiography was used to assess cardiac function. Left ventricle (LV) tissue was used to assess fibrosis and inflammation by staining, western blot, and hydroxyproline analysis. Results At baseline EC-SOD-null mice have LV wall thinning and increases in LV end diastolic dimensions compared to wild type mice, but have normal cardiac function. After doxorubicin, EC-SOD-null mice have decreases in fractional shortening not apparent in WT mice. Lack of EC-SOD also leads to increases in myocardial apoptosis and significantly more LV fibrosis and inflammatory cell infiltration. Administration of the metalloporphyrin AEOL 10150 abrogates the loss of cardiac function, and potentially fibrosis, associated with doxorubicin treatment in both wild type and EC-SOD KO mice. Conclusions EC-SOD is critical for normal cardiac morphology and protects the heart from oxidant-induced fibrosis, apoptosis and loss of function. The antioxidant metalloporphyrin, AEOL 10150 effectively protects cardiac function from doxorubicin-induced oxidative stress, in vivo. These findings identify targets for the use of antioxidant agents in oxidant-induced cardiac fibrosis. PMID:19695260

  12. Aerobic exercise training reduces cardiac function in adult male offspring exposed to prenatal hypoxia.

    PubMed

    Reyes, Laura M; Kirschenman, Raven; Quon, Anita; Morton, Jude S; Shah, Amin; Davidge, Sandra T

    2015-09-01

    Intrauterine growth restriction (IUGR) has been associated with increased susceptibility to myocardial ischemia-reperfusion (I/R) injury. Exercise is an effective preventive intervention for cardiovascular diseases; however, it may be detrimental in conditions of compromised health. The aim of this study was to determine whether exercise training can improve cardiac performance after I/R injury in IUGR offspring. We used a hypoxia-induced IUGR model by exposing pregnant Sprague-Dawley rats to 21% oxygen (control) or hypoxic (11% oxygen; IUGR) conditions from gestational day 15 to 21. At 10 wk of age, offspring were randomized to a sedentary group or to a 6-wk exercise protocol. Transthoracic echocardiography assessments were performed after 6 wk. Twenty-four hours after the last bout of exercise, ex vivo cardiac function was determined using a working heart preparation. With exercise training, there was improved baseline cardiac performance in male control offspring but a reduced baseline cardiac performance in male IUGR exercised offspring (P < 0.05). In male offspring, exercise decreased superoxide generation in control offspring, while in IUGR offspring, it had the polar opposite effect (interaction P ≤ 0.05). There was no effect of IUGR or exercise on cardiac function in female offspring. In conclusion, in male IUGR offspring, exercise may be a secondary stressor on cardiac function. A reduction in cardiac performance along with an increase in superoxide production in response to exercise was observed in this susceptible group. PMID:26157059

  13. Recovery of brain function after cardiac arrest, case report and review.

    PubMed

    Nekoui, A; Tresierra, del Carmen Escalante; Abdolmohammadi, S; Charbonneau, S; Blaise, G

    2016-01-01

    Cerebral hypoxia during cardiac arrest is the leading cause of mortality and morbidity in survival victims. To reduce cerebral damage, studies focus on finding effective treatments during the resuscitation period. Our report focuses on a 36-year-old police officer who had had two cardiac arrests (one at home and one at the hospital). After acute treatment, his cardiac and brain functions recovered impressively. Neuropsychological results were normal except for mild anomia. He also reported some retrograde memory loss. Surprisingly, he also reported an improvement in a very specific capacity, his episodic memory. We here review the possible causes and mechanisms that may have affected his memory abilities. PMID:27363214

  14. Galectin-3, Cardiac Function, and Fibrosis.

    PubMed

    Meijers, Wouter C; López-Andrés, Natalia; de Boer, Rudolf A

    2016-08-01

    This Correspondence relates to the article by Frunza et al (Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis. Am J Pathol 2016, 186:1114-1127). PMID:27461364

  15. Cardiac lipid content is unresponsive to a physical activity training intervention in type 2 diabetic patients, despite improved ejection fraction

    PubMed Central

    2011-01-01

    Background Increased cardiac lipid content has been associated with diabetic cardiomyopathy. We recently showed that cardiac lipid content is reduced after 12 weeks of physical activity training in healthy overweight subjects. The beneficial effect of exercise training on cardiovascular risk is well established and the decrease in cardiac lipid content with exercise training in healthy overweight subjects was accompanied by improved ejection fraction. It is yet unclear whether diabetic patients respond similarly to physical activity training and whether a lowered lipid content in the heart is necessary for improvements in cardiac function. Here, we investigated whether exercise training is able to lower cardiac lipid content and improve cardiac function in type 2 diabetic patients. Methods Eleven overweight-to-obese male patients with type 2 diabetes mellitus (age: 58.4 ± 0.9 years, BMI: 29.9 ± 0.01 kg/m2) followed a 12-week training program (combination endurance/strength training, three sessions/week). Before and after training, maximal whole body oxygen uptake (VO2max) and insulin sensitivity (by hyperinsulinemic, euglycemic clamp) was determined. Systolic function was determined under resting conditions by CINE-MRI and cardiac lipid content in the septum of the heart by Proton Magnetic Resonance Spectroscopy. Results VO2max increased (from 27.1 ± 1.5 to 30.1 ± 1.6 ml/min/kg, p = 0.001) and insulin sensitivity improved upon training (insulin stimulated glucose disposal (delta Rd of glucose) improved from 5.8 ± 1.9 to 10.3 ± 2.0 μmol/kg/min, p = 0.02. Left-ventricular ejection fraction improved after training (from 50.5 ± 2.0 to 55.6 ± 1.5%, p = 0.01) as well as cardiac index and cardiac output. Unexpectedly, cardiac lipid content in the septum remained unchanged (from 0.80 ± 0.22% to 0.95 ± 0.21%, p = 0.15). Conclusions Twelve weeks of progressive endurance/strength training was effective in improving VO2max, insulin sensitivity and cardiac function

  16. Improving vagal activity ameliorates cardiac fibrosis induced by angiotensin II: in vivo and in vitro

    PubMed Central

    Liu, Jin-Jun; Huang, Ning; Lu, Yi; Zhao, Mei; Yu, Xiao-Jiang; Yang, Yang; Yang, Yong-hua; Zang, Wei-Jin

    2015-01-01

    Cardiac remodeling is characterized by overactivity of the renin–angiotensin system (RAS) and withdrawal of vagal activity. We hypothesized that improving vagal activity could attenuate cardiac fibrosis induced by angiotensin II (Ang II) in vivo and in vitro. Rats were subjected to abdominal aorta constriction (AAC) with or without pyridostigmine (PYR) (31 mg/kg/d). After 8 weeks, PYR significantly decreased Ang II level, AT1 protein expression, and collagen deposition in cardiac tissue and improved heart rate variability, baroreflex sensitivity and cardiac function, which were abolished by atropine. In vitro, treatment of cardiac fibroblasts (CFs) with Ang II (10−7 M) increased cell proliferation, migration, transformation, and secretory properties, which were significantly diminished by acetylcholine (ACh, 10−6 M). Subsequently, Ang II significantly increased collagen type I expression as well as metalloproteinase (MMP)-2 expression and activity. Transforming growth factor (TGF)-β1 expression and Smad3 phosphorylation presented a similar trend. Notably, the knockdown of the acetylcholine M2 receptor by siRNA could abolish ACh anti-fibrotic action. These data implicated cholinesterase inhibitor can increase vagal activity and reduce local Ang II level, and ACh inhibit Ang II pro-fibrotic effects. Our findings suggested that the parasympathetic nervous system can serve as a promising target for cardiac remodeling treatment. PMID:26596640

  17. 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…

  18. MiR-155 Knockout in Fibroblasts Improves Cardiac Remodeling by Targeting Tumor Protein p53-Inducible Nuclear Protein 1.

    PubMed

    He, Wangwei; Huang, He; Xie, Qiang; Wang, Zhiqiang; Fan, Yang; Kong, Bin; Huang, Dan; Xiao, Yali

    2016-07-01

    Cardiac remodeling caused by acute myocardial infarction (AMI) represents a major challenge for heart failure research. MiR-155 has been identified as a key mediator of cardiac inflammation and hypertrophy. In this study, we investigate the role of miR-155 in cardiac remodeling induced by AMI. We demonstrate that miR-155 expressed in cardiac fibroblasts is a potent contributor to cardiac remodeling. We reveal that in vivo, miR-155 knockout improves left ventricular function, reduces infarct size, and attenuates collagen deposition, whereas overexpression of miR-155 produces the opposite effects. MiR-155 knockout also inhibits cardiac fibroblast proliferation and differentiation into myofibroblasts. In addition, downregulation of tumor protein p53-inducible nuclear protein 1 (TP53INP1) by small interfering RNA reverses the effects of miR-155 knockout on cardiac fibroblasts. Our data reveal that knockout of miR-155 in cardiac fibroblasts improves cardiac remodeling by targeting TP53INP1, which may be a novel treatment strategy for cardiac remodeling. PMID:26589288

  19. Crystalloid flush with backward unclamping may decrease post-reperfusion cardiac arrest and improve short-term graft function when compared to portal blood flush with forward unclamping during liver transplantation.

    PubMed

    Fukazawa, Kyota; Nishida, Seigo; Hibi, Taizo; Pretto, Ernesto A

    2013-01-01

    During liver transplant (LT), the release of vasoactive substances into the systemic circulation is associated with severe hemodynamic instability that is injurious to the recipient and/or the post-ischemic graft. Crystalloid flush with backward unclamping (CB) and portal blood flush with forward unclamping (PF) are two reperfusion methods to reduce reperfusion-related cardiovascular perturbations in our center. The primary aim of this study was to compare these two methods. After institutional review board (IRB) approval, cadaveric whole LT cases performed between 2003 and 2008 were reviewed. Patients were divided into two groups based on reperfusion methods: CB or PF. After background matching with propensity score, the effect of each method on post-operative graft function was assessed in detail. In our cohort of 478 patients, CB was used in 313 grafts and PF in 165. Thirty-day graft survival was lower, and risk of retransplantation was higher in PF. Multivariable model showed that CB is an independent factor to reduce primary non-function, cardiac arrest and improve 30-d graft survival. Also, the incidence of ischemic-type biliary lesions was significantly higher in the PF group. Reperfusion methods affect intraoperative hemodynamics and post-transplant outcome. CB allows for control over temperature and composition of the perfusate, perfusion pressure, and the rate of infusion. PMID:23656400

  20. Cardiac rehabilitation

    MedlinePlus

    ... goal of cardiac rehab is to: Improve your cardiovascular function Improve your overall health and quality of ... E, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, PA: Elsevier Saunders; 2015: ...

  1. Analysis of cardiac function by MRI and stereology.

    PubMed

    Roberts, N; Cruz-Orive, L M; Bourne, M; Herfkens, R J; Karwoski, R A; Whitehouse, G H

    1997-07-01

    Design-based stereology and phase contrast magnetic resonance imaging (MRI) were combined to monitor changes in the volume of the four chambers of the human heart during the cardiac cycle. The data set consisted of 18 adjacent slices (or 'scanning levels') of 0.5 cm thickness, perpendicular to the long axis of the body, and encompassing the whole heart of a healthy volunteer. At each scanning level, a cardiac gated MR image was obtained at each of 16 equally spaced time frames within the cardiac cycle. Given stationarity with respect to time, absence of image artefacts and appropriate definition of chamber boundaries, for each time frame unbiased estimates of total blood volume in the relevant heart chambers were efficiently obtained using the Cavalieri method and point counting. Combined with a proper MRI acquisition, modern stereological methods constitute an efficient and reliable tool to quantify cardiac function noninvasively. PMID:9263438

  2. Using exercise to measure and modify cardiac function.

    PubMed

    Platt, Colin; Houstis, Nicholas; Rosenzweig, Anthony

    2015-02-01

    Exercise is the archetype of physiologic demands placed on the cardiovascular system. Acute responses provide an informative assessment of cardiovascular function and fitness, while repeated exercise promotes cardiovascular health and evokes important molecular, structural, and functional changes contributing to its effects in primary and secondary prevention. Here we examine the use of exercise in murine models, both as a phenotypic assay and as a provocative intervention. We first review the advantages and limitations of exercise testing for assessing cardiac function, then highlight the cardiac structural and cellular changes elicited by chronic exercise and key molecular pathways that mediate these effects. PMID:25651177

  3. Cardiac Function in Young and Old Little Mice

    PubMed Central

    Reddy, Anilkumar K.; Amador-Noguez, Daniel; Darlington, Gretchen J.; Scholz, Beth A.; Michael, Lloyd H.; Hartley, Craig J.; Entman, Mark L.; Taffet, George E.

    2009-01-01

    We studied cardiac function in young and old, wild-type (WT), and longer-living Little mice using cardiac flow velocities, echocardiographic measurements, and left ventricular (LV) pressure (P) to determine if enhanced reserves were in part responsible for longevity in these mice. Resting/baseline cardiac function, as measured by velocities, LV dimensions, +dP/dtmax, and −dP/dtmax, was significantly lower in young Little mice versus young WT mice. Fractional shortening (FS) increased significantly, and neither +dP/dtmax nor −dP/dtmax declined with age in Little mice. In contrast, old WT mice had no change in FS but had significantly lower +dP/dtmax and −dP/dtmax versus young WT mice. Significant decreases were observed in the velocity indices of old Little mice versus old WT mice, but other parameters were unchanged. The magnitude of dobutamine stress response remained unchanged with age in Little mice, while that in WT mice decreased. These data suggest that while resting cardiac function in Little mice versus WT mice is lower at young age, it is relatively unaltered with aging. Additionally, cardiac function in response to stress was maintained with age in Little mice but not in their WT counterparts. Thus, some mouse models of increased longevity may not be associated with enhanced reserves. PMID:18166681

  4. Catheter-based endomyocardial delivery of mesenchymal precursor cells using 3D echo guidance improves cardiac function in a chronic myocardial injury ovine model.

    PubMed

    Cheng, Yanping; Yi, Genghua; Conditt, Gerard B; Sheehy, Alexander; Kolodgie, Frank D; Tellez, Armando; Polyakov, Igor; Gu, Anguo; Aboodi, Michael S; Wallace-Bradley, David; Schuster, Michael; Martens, Timothy; Itescu, Silviu; Kaluza, Greg L; Basu, Shubhayu; Virmani, Renu; Granada, Juan F; Sherman, Warren

    2013-01-01

    The administration of bone marrow-derived stem cells may provide a new treatment option for patients with heart failure. Transcatheter cell injection may require multi-imaging modalities to optimize delivery. This study sought to evaluate whether endomyocardial injection of mesenchymal precursor cells (MPCs) could be guided by real-time 3D echocardiography (RT3DE) in treating chronic, postinfarction (MI) left ventricular (LV) dysfunction in sheep. Four weeks after induction of an anterior wall myocardial infarction in 39 sheep, allogeneic MPCs in doses of either 25 × 10(6) (n = 10), 75 × 10(6) (n = 9), or 225 × 10(6) (n = 10) cells or nonconditioned control media (n = 10) were administered intramyocardially into infarct and border zone areas using a catheter designed for combined fluoroscopic and RT3DE-guided injections. LV function was assessed before and after injection. Infarct dimension and vascular density were evaluated histologically. RT3DE-guided injection procedures were safe. Compared to controls, the highest dose MPC treatment led to increments in ejection fraction (3 ventricula 3% in 225M MPCs vs. -5 ± 4% in the control group, p < 0.01) and wall thickening in both infarct (4 ± 4% in 225M MPCs vs. -3 ± 6% in the control group, p = 0.02) and border zones (4 ± 6% in 225M MPCs vs. -8 ± 9% in the control group, p = 0.01). Histology analysis demonstrated significantly higher arteriole density in the infarct and border zones in the highest dose MPC-treated animals compared to the lower dose or control groups. Endomyocardial implantation of MPCs under RT3DE guidance was safe and without observed logistical obstacles. Significant increases in LV performance (ejection fraction and wall thickening) and neovascularization resulted from this technique, and so this technique has important implications for treating patients with postischemic LV dysfunction. PMID:23107489

  5. Influence of chronic kidney disease on cardiac structure and function.

    PubMed

    Matsushita, Kunihiro; Ballew, Shoshana H; Coresh, Josef

    2015-09-01

    Chronic kidney disease (CKD), the presence of kidney dysfunction and/or damage, is a worldwide public health issue. Although CKD is independently associated with various subtypes of cardiovascular diseases, a recent international collaborative meta-analysis demonstrates that CKD is particularly strongly associated with heart failure, suggesting its critical impact on cardiac structure and function. Although numerous studies have investigated the association of CKD and cardiac structure and function, these studies substantially vary regarding source populations and methodology (e.g., measures of CKD and/or parameters of cardiac structure and function), making it difficult to reach universal conclusions. Nevertheless, in this review, we comprehensively examine relevant studies, discuss potential mechanisms linking CKD to alteration of cardiac structure and function, and demonstrate clinical implications as well as potential future research directions. We exclusively focus on studies investigating both CKD measures, kidney function (i.e., glomerular filtration rate [GFR], creatinine clearance, or levels of filtration markers), and kidney damage represented by albuminuria, since current international clinical guidelines of CKD recommend staging CKD and assessing its clinical risk based on both GFR and albuminuria. PMID:26194332

  6. 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

  7. Sonication of Explanted Cardiac Implants Improves Microbial Detection in Cardiac Device Infections

    PubMed Central

    Oliva, Alessandra; Nguyen, Bich Lien; Mascellino, Maria T.; D'Abramo, Alessandra; Iannetta, Marco; Ciccaglioni, Antonio; Vullo, Vincenzo

    2013-01-01

    The sonication technique has been shown to be a promising tool for microbiological diagnosis of device-related infections. We evaluated the usefulness of the sonication method for pathogen detection in 80 explanted cardiac components collected from 40 patients, and the results were compared with those of conventional cultures. Forty subjects undergoing cardiac device removal were studied: 20 had cardiac device infection, and 20 subjects underwent elective generator replacement or revision in the absence of infection. Sonication of explanted devices was more sensitive than traditional culture for microbial detection (67% and 50%, respectively; P = 0.0005). The bacterial count detected in sonication fluid culture was significantly higher than that detected in traditional culture in both infected (P = 0.019) and uninfected (P = 0.029) devices. In the infected patients, sonication fluid culture yielded a significantly higher rate of pathogen detection in explanted electrodes than traditional culture (65% versus 45%; P = 0.02), while no differences were found in the generators. Ten strains were detected only through sonication fluid culture: 6 Staphylococcus epidermidis strains, 1 Staphylococcus hominis strain, 2 Corynebacterium striatum strains, and 1 Brevundimonas sp. Neither the type nor the duration of antimicrobial therapy before device removal had an effect on the diagnostic performance of sonication fluid culture (P = 0.75 and P = 0.56, respectively). In the patients without infection, sonication fluid culture was positive in 8 cases (40%), whereas conventional culture was positive in only 4 (20%). In summary, the sonication technique improves the microbiological diagnosis of explanted cardiac devices. PMID:23196364

  8. Acupuncture effects on cardiac functions measured by cardiac magnetic resonance imaging in a feline model.

    PubMed

    Lin, Jen-Hsou; Shih, Chen-Haw; Kaphle, Krishna; Wu, Leang-Shin; Tseng, Weng-Yih; Chiu, Jen-Hwey; Lee, Tzu-Chi; Wu, Ying-Ling

    2010-06-01

    The usefulness of acupuncture (AP) as a complementary and/or alternative therapy in animals is well established but more research is needed on its clinical efficacy relative to conventional therapy, and on the underlying mechanisms of the effects of AP. Cardiac magnetic resonance imaging (CMRI), an important tool in monitoring cardiovascular diseases, provides a reliable method to monitor the effects of AP on the cardiovascular system. This controlled experiment monitored the effect electro-acupuncture (EA) at bilateral acupoint Neiguan (PC6) on recovery time after ketamine/xylazine cocktail anesthesia in healthy cats. The CMRI data established the basic feline cardiac function index (CFI), including cardiac output and major vessel velocity. To evaluate the effect of EA on the functions of the autonomic nervous and cardiovascular systems, heart rate, respiration rate, electrocardiogram and pulse rate were also measured. Ketamine/xylazine cocktail anesthesia caused a transient hypertension in the cats; EA inhibited this anesthetic-induced hypertension and shortened the post-anesthesia recovery time. Our data support existing knowledge on the cardiovascular benefits of EA at PC6, and also provide strong evidence for the combination of anesthesia and EA to shorten post-anesthesia recovery time and counter the negative effects of anesthetics on cardiac physiology. PMID:18955311

  9. ROS Regulate Cardiac Function via a Distinct Paracrine Mechanism

    PubMed Central

    Lim, Hui-Ying; Wang, Weidong; Chen, Jianming; Ocorr, Karen; Bodmer, Rolf

    2014-01-01

    SUMMARY Reactive oxygen species (ROS) can act cell autonomously and in a paracrine manner by diffusing into nearby cells. Here, we reveal a ROS-mediated paracrine signaling mechanism that does not require entry of ROS into target cells. We found that under physiological conditions, nonmyocytic pericardial cells (PCs) of the Drosophila heart contain elevated levels of ROS compared to the neighboring cardiomyocytes (CMs). We show that ROS in PCs act in a paracrine manner to regulate normal cardiac function, not by diffusing into the CMs to exert their function, but by eliciting a downstream D-MKK3-D-p38 MAPK signaling cascade in PCs that acts on the CMs to regulate their function. We find that ROS-D-p38 signaling in PCs during development is also important for establishing normal adult cardiac function. Our results provide evidence for a previously unrecognized role of ROS in mediating PC/CM interactions that significantly modulates heart function. PMID:24656823

  10. LINC complex proteins in cardiac structure, function, and disease

    PubMed Central

    Stroud, Matthew J; Banerjee, Indroneal; Lowe, Jennifer; Chen, Ju

    2014-01-01

    The LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, composed of proteins within the inner and the outer nuclear membranes, connects the nuclear lamina to the cytoskeleton. The importance of this complex has been highlighted by the discovery of mutations in genes encoding LINC complex proteins, which are causative for skeletal or cardiac myopathies. Herein, this review summarizes structure, function, and interactions of major components of the LINC complex, highlights how mutations in these proteins may lead to cardiac disease, and outlines future challenges in the field. PMID:24481844

  11. New developments in paediatric cardiac functional ultrasound imaging.

    PubMed

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

    2014-07-01

    Ultrasound imaging can be used to estimate the morphology as well as the motion and deformation of tissues. If the interrogated tissue is actively deforming, this deformation is directly related to its function and quantification of this deformation is normally referred as 'strain imaging'. Tissue can also be deformed by applying an internal or external force and the resulting, induced deformation is a function of the mechanical tissue characteristics. In combination with the load applied, these strain maps can be used to estimate or reconstruct the mechanical properties of tissue. This technique was named 'elastography' by Ophir et al. in 1991. Elastography can be used for atherosclerotic plaque characterisation, while the contractility of the heart or skeletal muscles can be assessed with strain imaging. Rather than using the conventional video format (DICOM) image information, radio frequency (RF)-based ultrasound methods enable estimation of the deformation at higher resolution and with higher precision than commercial methods using Doppler (tissue Doppler imaging) or video image data (2D speckle tracking methods). However, the improvement in accuracy is mainly achieved when measuring strain along the ultrasound beam direction, so it has to be considered a 1D technique. Recently, this method has been extended to multiple directions and precision further improved by using spatial compounding of data acquired at multiple beam steered angles. Using similar techniques, the blood velocity and flow can be determined. RF-based techniques are also beneficial for automated segmentation of the ventricular cavities. In this paper, new developments in different techniques of quantifying cardiac function by strain imaging, automated segmentation, and methods of performing blood flow imaging are reviewed and their application in paediatric cardiology is discussed. PMID:27277901

  12. 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

  13. Improving cardiac surgical care: a work systems approach.

    PubMed

    Wiegmann, Douglas A; Eggman, Ashley A; Elbardissi, Andrew W; Parker, Sarah Henrickson; Sundt, Thoralf M

    2010-09-01

    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

  14. 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. PMID:26496001

  15. 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.

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

    PubMed Central

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

    2014-01-01

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

  17. Autonomic control of cardiac function and myocardial oxygen consumption during hypoxic hypoxia.

    NASA Technical Reports Server (NTRS)

    Erickson, H. H.; Stone, H. L.

    1972-01-01

    Investigation in 19 conscious dogs of the importance of the sympathetic nervous system in the coronary and cardiac response to altitude (hypoxic) hypoxia. Beta-adrenergic blockade was used to minimize the cardiac effect associated with sympathetic receptors. It is shown that the autonomic nervous system, and particularly the sympathetic nervous system, is responsible for the increase in ventricular function and myocardial oxygen consumption that occurs during hypoxia. Minimizing this response through appropriate conditioning and training may improve the operating efficiency of the heart and reduce the hazard of hypoxia and other environmental stresses, such as acceleration, which are encountered in advanced aircraft systems.

  18. Evaluation of ventricular function with gated cardiac magnetic resonance imaging.

    PubMed

    Osbakken, M; Yuschok, T

    1986-01-01

    To determine the feasibility of using planar images obtained with gated cardiac magnetic resonance imaging (MRI) techniques to evaluate ventricular contractile function, cardiac chamber volume (V), and ejection fraction (EF) were calculated using MR images obtained in five previously catheterized patients. Patients were imaged with a .15-Tesla 55-cm bore magnet using the ECG to gate the images. Spin echo pulse sequences (30/500, TE/TR) were used to produce images in the transverse (T), coronal (C), and sagittal (S) planes at end diastole (ED) and end systole (ES). Slice thickness was 1.5 cm, with 2-mm resolution. A calibration grid was imaged in each plane to determine correction factors. Cardiac chamber areas were determined via planimetry. An area-length-volume algorithm was used to obtain EDV and ESV. Three combinations of biplane images in ES and ED were used (T/C, T/S, C/S). Volume data were used to calculate EF. Contrast ventriculogram volumes tended to be greater than MRI volumes, but EFs were similar with both techniques. In conclusion, gated cardiac MR images can be used to evaluate the ventricular function parameters of volume and ejection fraction. PMID:3731263

  19. Assessment of pulmonary function tests in cardiac patients.

    PubMed

    El-Sobkey, Salwa B; Gomaa, Magdi

    2011-04-01

    This study was aimed to assess the pulmonary function tests (PFTs) in cardiac patients; with ischemic or rheumatic heart diseases as well as in patients who underwent coronary artery bypass graft (CABG) or valvular procedures. For the forty eligible participants, the pulmonary function was measured using the spirometry test before and after the cardiac surgery. Data collection sheet was used for the patient's demographic and intra-operative information. Cardiac diseases and surgeries had restrictive negative impact on PFTs. Before surgery, vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), ratio between FEV1 and FVC, and maximum voluntary ventilation (MVV) recorded lower values for rheumatic patients than ischemic patients (P values were 0.01, 0.005, 0.0001, 0.031, and 0.035, respectively). Moreover, patients who underwent valvular surgery had lower PFTs than patients who underwent CABG with significant differences for VC, FVC, FEV1, and MVV tests (P values were 0.043, 0.011, 0.040, and 0.020, respectively). No definite causative factor appeared to be responsible for those results although mechanical deficiency and incisional chest pain caused by cardiac surgery are doubtful. More comprehensive investigation is required to resolve the case. PMID:23960642

  20. 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.

  1. Accelerated MRI for the assessment of cardiac function.

    PubMed

    Axel, Leon; Otazo, Ricardo

    2016-07-01

    Heart disease is a worldwide public health problem; assessment of cardiac function is an important part of the diagnosis and management of heart disease. MRI of the heart can provide clinically useful information on cardiac function, although it is still not routinely used in clinical practice, in part because of limited imaging speed. New accelerated methods for performing cardiovascular MRI (CMR) have the potential to provide both increased imaging speed and robustness to CMR, as well as access to increased functional information. In this review, we will briefly discuss the main methods currently employed to accelerate CMR methods, such as parallel imaging, k-t undersampling and compressed sensing, as well as new approaches that extend the idea of compressed sensing and exploit sparsity to provide richer information of potential use in clinical practice. PMID:27033471

  2. Pulling on my heartstrings: mechanotransduction in cardiac development and function

    PubMed Central

    McCormick, Margaret E.; Tzima, Ellie

    2016-01-01

    Purpose of review Endothelial cells line the surface of the cardiovascular system and display a large degree of heterogeneity due to developmental origin and location. Despite this heterogeneity, all endothelial cells are exposed to wall shear stress (WSS) imparted by the frictional force of flowing blood, which plays an important role in determining the endothelial cell phenotype. Although the effects of WSS have been greatly studied in vascular endothelial cells, less is known about the role of WSS in regulating cardiac function and cardiac endothelial cells. Recent findings Recent advances in genetic and imaging technologies have enabled a more thorough investigation of cardiac hemodynamics. Using developmental models, shear stress sensing by endocardial endothelial cells has been shown to play an integral role in proper cardiac development including morphogenesis and formation of the conduction system. In the adult, less is known about hemodynamics and endocardial endothelial cells, but a clear role for WSS in the development of coronary and valvular disease is increasingly appreciated. Summary Future research will further elucidate a role for WSS in the developing and adult heart, and understanding this dynamic relationship may represent a potential therapeutic target for the treatment of cardiomyopathies. PMID:26906028

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

    PubMed

    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

    2015-09-01

    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

  4. Clinical investigation: thyroid function test abnormalities in cardiac arrest associated with acute coronary syndrome

    PubMed Central

    Iltumur, Kenan; Olmez, Gonul; Arıturk, Zuhal; Taskesen, Tuncay; Toprak, Nizamettin

    2005-01-01

    Introduction It is known that thyroid homeostasis is altered during the acute phase of cardiac arrest. However, it is not clear under what conditions, how and for how long these alterations occur. In the present study we examined thyroid function tests (TFTs) in the acute phase of cardiac arrest caused by acute coronary syndrome (ACS) and at the end of the first 2 months after the event. Method Fifty patients with cardiac arrest induced by ACS and 31 patients with acute myocardial infarction (AMI) who did not require cardioversion or cardiopulmonary resuscitation were enrolled in the study, as were 40 healthy volunteers. The patients were divided into three groups based on duration of cardiac arrest (<5 min, 5–10 min and >10 min). Blood samples were collected for thyroid-stimulating hormone (TSH), tri-iodothyronine (T3), free T3, thyroxine (T4), free T4, troponin-I and creatine kinase-MB measurements. The blood samples for TFTs were taken at 72 hours and at 2 months after the acute event in the cardiac arrest and AMI groups, but only once in the control group. Results The T3 and free T3 levels at 72 hours in the cardiac arrest group were significantly lower than in both the AMI and control groups (P < 0.0001). On the other hand, there were no significant differences between T4, free T4 and TSH levels between the three groups (P > 0.05). At the 2-month evaluation, a dramatic improvement was observed in T3 and free T3 levels in the cardiac arrest group (P < 0.0001). In those patients whose cardiac arrest duration was in excess of 10 min, levels of T3, free T3, T4 and TSH were significantly lower than those in patients whose cardiac arrest duration was under 5 min (P < 0.001, P < 0.001, P < 0.005 and P < 0.05, respectively). Conclusion TFTs are significantly altered in cardiac arrest induced by ACS. Changes in TFTs are even more pronounced in patients with longer periods of resuscitation. The changes in the surviving patients were characterized by euthyroid sick

  5. Subclinical hypothyroidism effects on cardiac function.

    PubMed

    Niafar, M; Toufan, M; Ghafoori, S; Aghamohammadzadeh, N

    2009-08-01

    To evaluate heart function in subclinical hypothyroid women in comparison with healthy subjects, a prospective study was performed on newly detected subclinical hypothyroid women presenting to endocrinology clinic of Tabriz Sina Hospital from October 2007 to February 2008. Thirty five women with Subclinical Hypothyroidism (SH) in case group were matched with 35 healthy euthyroid women in control group. All patients in both groups were studied by two dimensional echocardiography and Tissue Doppler Imaging (TDI) in Tabriz Shahid Madani Hospital. The FT4 and TSH levels were measured. Comparison of TDI results in Right Ventricle (RV) showed the significantly lower mean T(v) excursion in case group with no significant difference in other parameters. In Left Ventricle (LV), the mean A(m), A(v) and E(v)/E(m) were significantly higher and E/A was lower in the case group, but there was no significant difference in other parameters. No RV diastolic dysfunction was documented in both groups. There was no case with LV systolic dysfunction in both groups. There were 21 (60%) patients with LV diastolic dysfunction in the case group comparing with 11 (31.4%) cases in the control group (p = 0.016, OR = 0.306). Frequency of LV diastolic dysfunction was significantly higher in the case group in patients aged > or = 40 years (94.1% vs. 53.3%; p = 0.013). There was no case of pericardial effusion in the studied population. According to our results, SH may cause LV diastolic dysfunction. Likewise, minor RV systolic dysfunction might be seen in these patients. PMID:19943461

  6. Cardiac autonomic function and oesophageal acid sensitivity in patients with non-cardiac chest pain

    PubMed Central

    Tougas, G; Spaziani, R; Hollerbach, S; Djuric, V; Pang, C; Upton, A; Fallen, E; Kamath, M

    2001-01-01

    BACKGROUND—Acid reflux can elicit non-cardiac chest pain (NCCP), possibly through altered visceral sensory or autonomic function. The interactions between symptoms, autonomic function, and acid exposure are poorly understood.
AIM—To examine autonomic function in NCCP patients during exposure to oesophageal acid infusion.
SUBJECTS AND METHODS—Autonomic activity was assessed using power spectral analysis of heart rate variability (PSHRV), before and during oesophageal acidification (0.1 N HCl), in 28 NCCP patients (40.5 (10) years; 13 females) and in 10 matched healthy controls. Measured PSHRV indices included high frequency (HF) (0.15-0.5 Hz) and low frequency (LF) (0.06-0.15 Hz) power to assess vagal and sympathetic activity, respectively.
RESULTS—A total of 19/28 patients had angina-like symptoms elicited by acid. There were no significant manometric changes observed in either acid sensitive or insensitive patients. Acid sensitive patients had a higher baseline heart rate (82.9 (3.1) v 66.7 (3.5) beats/min; p<0.005) and lower baseline vagal activity (HF normalised area: 31.1 (1.9)% v 38.9 (2.3)%; p< 0.03) than acid insensitive patients. During acid infusion, vagal cardiac outflow increased (p<0.03) in acid sensitive but not in acid insensitive patients.
CONCLUSIONS—Patients with angina-like pain during acid infusion have decreased resting vagal activity. The symptoms elicited by perception of acid are further associated with a simultaneous increase in vagal activity in keeping with a vagally mediated pseudoaffective response.


Keywords: reflux disease; non-cardiac chest pain; acid reflux; autonomic nervous system; vagal response; sympathetic activity; heart rate variability; power spectrum analysis PMID:11600476

  7. Cardiac-specific miRNA in cardiogenesis, heart function, and cardiac pathology (with focus on myocardial infarction).

    PubMed

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-05-01

    Cardiac miRNAs (miR-1, miR133a, miR-208a/b, and miR-499) are abundantly expressed in the myocardium. They play a central role in cardiogenesis, heart function and pathology. While miR-1 and miR-133a predominantly control early stages of cardiogenesis supporting commitment of cardiac-specific muscle lineage from embryonic stem cells and mesodermal precursors, miR-208 and miR-499 are involved in the late cardiogenic stages mediating differentiation of cardioblasts to cardiomyocytes and fast/slow muscle fiber specification. In the heart, miR-1/133a control cardiac conductance and automaticity by regulating all phases of the cardiac action potential. miR-208/499 located in introns of the heavy chain myosin genes regulate expression of sarcomeric contractile proteins. In cardiac pathology including myocardial infarction (MI), expression of cardiac miRNAs is markedly altered that leads to deleterious effects associated with heart wounding, arrhythmia, increased apoptosis, fibrosis, hypertrophy, and tissue remodeling. In acute MI, circulating levels of cardiac miRNAs are significantly elevated making them to be a promising diagnostic marker for early diagnosis of acute MI. Great cardiospecific capacity of these miRNAs is very helpful for enhancing regenerative properties and survival of stem cell and cardiac progenitor transplants and for reprogramming of mature non-cardiac cells to cardiomyocytes. PMID:27056419

  8. Cellular and Functional Imaging of Cardiac Transplant Rejection

    PubMed Central

    Wu, Yijen L.; Ye, Qing

    2011-01-01

    Heart transplantation is now an established treatment for patients suffering from end-stage heart diseases. With the advances in immunosuppressive treatment, the survival rate for transplant patients has improved greatly. However, allograft rejection, both acute and chronic, after heart transplantation is still a limitation leading to morbidity and mortality. The current clinical gold standard for screening rejection is endomyocardial biopsy (EMB), which is not only invasive, but also error-prone, due to the limited sample size and the site location of sampling. It would be highly desirable to have reliable and noninvasive alternatives for EMB in monitoring cardiac allograft rejection. The objective of this review is to highlight how cardiovascular imaging can contribute to noninvasively detecting and to evaluating both acute and chronic allograft rejection after heart transplantation, in particular, cardiovascular MRI (CMRI); and how CMRI can assess both immune cell infiltration at the rejecting organ, and the cardiac dysfunctions resulting from allograft rejection. PMID:21359095

  9. Feeding the fibrillating heart: Dichloroacetate improves cardiac contractile dysfunction following VF.

    PubMed

    Azam, Mohammed Ali; Wagg, Cory S; Massé, Stéphane; Farid, Talha; Lai, Patrick F H; Kusha, Marjan; Asta, John; Jaimes, Rafael; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Lopaschuk, Gary D; Nanthakumar, Kumaraswamy

    2015-11-01

    Ventricular fibrillation (VF) is an important cause of sudden cardiac arrest following myocardial infarction. Following resuscitation from VF, decreased cardiac contractile function is a common problem. During and following myocardial ischemia, decreased glucose oxidation, increased anaerobic glycolysis for cardiac energy production are harmful and energetically expensive. The objective of the present study is to determine the effects of dichloroacetate (DCA), a glucose oxidation stimulator, on cardiac contractile dysfunction following ischemia-induced VF. Male Sprague-Dawley rat hearts were Langendorff perfused in Tyrode's buffer. Once stabilized, hearts were subjected to 15 min of global ischemia and 5 min of aerobic reperfusion in the presence or absence of DCA. At the 6th min of reperfusion, VF was induced electrically, and terminated. Left ventricular (LV) pressure was measured using a balloon. Pretreatment with DCA significantly improved post-VF left ventricular developed pressure (LVDP) and dp/dtmax. In DCA-pretreated hearts, post-VF lactate production and pyruvate dehydrogenase (PDH) phosphorylation were significantly reduced, indicative of stimulated glucose oxidation, and inhibited anaerobic glycolysis by activation of PDH. Epicardial NADH fluorescence was increased during global ischemia above preischemic levels, but decreased below preischemia levels following VF, with no differences between nontreated controls and DCA-pretreated hearts, whereas DCA pretreatment increased NADH production in nonischemic hearts. With exogenous fatty acids (FA) added to the perfusion solution, DCA pretreatment also resulted in improvements in post-VF LVDP and dp/dtmax, indicating that the presence of exogenous FA did not affect the beneficial actions of DCA. In conclusion, enhancement of PDH activation by DCA mitigates cardiac contractile dysfunction following ischemia-induced VF. PMID:26342067

  10. The Insular Cortex and the Regulation of Cardiac Function.

    PubMed

    Oppenheimer, Stephen; Cechetto, David

    2016-04-01

    Cortical representation of the heart challenges the orthodox view that cardiac regulation is confined to stereotyped, preprogrammed and rigid responses to exteroceptive or interoceptive environmental stimuli. The insula has been the region most studied in this regard; the results of clinical, experimental, and functional radiological studies show a complex interweave of activity with patterns dynamically varying regarding lateralization and antero-posterior distribution of responsive insular regions. Either acting alone or together with other cortical areas including the anterior cingulate, medial prefrontal, and orbito-frontal cortices as part of a concerted network, the insula can imbue perceptions with autonomic color providing emotional salience, and aiding in learning and behavioral decision choice. In these functions, cardiovascular input and the right anterior insula appear to play an important, if not pivotal role. At a more basic level, the insula gauges cardiovascular responses to exteroceptive and interoceptive stimuli, taking into account memory, cognitive, and reflexive constructs thereby ensuring appropriate survival responses and maintaining emotional and physiological homeostasis. When acquired derangements to the insula occur after stroke, during a seizure or from abnormal central processing of interoceptive or exteroceptive environmental cues as in psychiatric disorders, serious consequences can arise including cardiac electrophysiological, structural and contractile dysfunction and sudden cardiac death. PMID:27065176

  11. Electrophysiological Modeling of Cardiac Ventricular Function: From Cell to Organ

    PubMed Central

    Winslow, R. L.; Scollan, D. F.; Holmes, A.; Yung, C. K.; Zhang, J.; Jafri, M. S.

    2005-01-01

    Three topics of importance to modeling the integrative function of the heart are reviewed. The first is modeling of the ventricular myocyte. Emphasis is placed on excitation-contraction coupling and intracellular Ca2+ handling, and the interpretation of experimental data regarding interval-force relationships. Second, data on use of diffusion tensor magnetic resonance (DTMR) imaging for measuring the anatomical structure of the cardiac ventricles are presented. A method for the semi-automated reconstruction of the ventricles using a combination of gradient recalled acquisition in the steady state (GRASS) and DTMR images is described. Third, we describe how these anatomically and biophysically based models of the cardiac ventricles can be implemented on parallel computers. PMID:11701509

  12. Improving strategies for the diagnosis of cardiac amyloidosis.

    PubMed

    Kourelis, Taxiarchis V; Gertz, Morie A

    2015-01-01

    Amyloidosis refers to a group of rare but potentially fatal, protein misfolding diseases. The heart is frequently involved in the most common types, that is, immunoglobulin light chain and transthyretin amyloidosis and is the single most important predictor of patient outcomes. A major limitation in improving patient outcomes, in addition to developing novel therapeutics, is the late diagnosis of the disease. Once suspected, an organ for biopsy should be targeted and the amyloid type should be identified by mass spectrometry. An endomyocardial biopsy should be offered if cardiac involvement is in doubt. Echocardiography, MRI and nuclear imaging can provide valuable diagnostic and prognostic information and can secure the diagnosis if amyloid has been identified in an extracardiac tissue. PMID:26174181

  13. Biomimetic perfusion and electrical stimulation applied in concert improved the assembly of engineered cardiac tissue.

    PubMed

    Maidhof, Robert; Tandon, Nina; Lee, Eun Jung; Luo, Jianwen; Duan, Yi; Yeager, Keith; Konofagou, Elisa; Vunjak-Novakovic, Gordana

    2012-11-01

    Maintenance of normal myocardial function depends intimately on synchronous tissue contraction, driven by electrical activation and on adequate nutrient perfusion in support thereof. Bioreactors have been used to mimic aspects of these factors in vitro to engineer cardiac tissue but, due to design limitations, previous bioreactor systems have yet to simultaneously support nutrient perfusion, electrical stimulation and unconstrained (i.e. not isometric) tissue contraction. To the best of our knowledge, the bioreactor system described herein is the first to integrate these three key factors in concert. We present the design of our bioreactor and characterize its capability in integrated experimental and mathematical modelling studies. We then cultured cardiac cells obtained from neonatal rats in porous, channelled elastomer scaffolds with the simultaneous application of perfusion and electrical stimulation, with controls excluding either one or both of these two conditions. After 8 days of culture, constructs grown with simultaneous perfusion and electrical stimulation exhibited substantially improved functional properties, as evidenced by a significant increase in contraction amplitude (0.23 ± 0.10% vs 0.14 ± 0.05%, 0.13 ± 0.08% or 0.09 ± 0.02% in control constructs grown without stimulation, without perfusion, or either stimulation or perfusion, respectively). Consistently, these constructs had significantly improved DNA contents, cell distribution throughout the scaffold thickness, cardiac protein expression, cell morphology and overall tissue organization compared to control groups. Thus, the simultaneous application of medium perfusion and electrical conditioning enabled by the use of the novel bioreactor system may accelerate the generation of fully functional, clinically sized cardiac tissue constructs. PMID:22170772

  14. Comparative impact of AAV and enzyme replacement therapy on respiratory and cardiac function in adult Pompe mice

    PubMed Central

    Falk, Darin J; Soustek, Meghan S; Todd, Adrian Gary; Mah, Cathryn S; Cloutier, Denise A; Kelley, Jeffry S; Clement, Nathalie; Fuller, David D; Byrne, Barry J

    2015-01-01

    Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA)). Cardiac dysfunction and respiratory muscle weakness are primary features of this disorder. To attenuate the progressive and rapid accumulation of glycogen resulting in cardiorespiratory dysfunction, adult Gaa–/– mice were administered a single systemic injection of rAAV2/9-DES-hGAA (AAV9-DES) or bimonthly injections of recombinant human GAA (enzyme replacement therapy (ERT)). Assessment of cardiac function and morphology was measured 1 and 3 months after initiation of treatment while whole-body plethysmography and diaphragmatic contractile function was evaluated at 3 months post-treatment in all groups. Gaa–/– animals receiving either AAV9-DES or ERT demonstrated a significant improvement in cardiac function and diaphragmatic contractile function as compared to control animals. AAV9-DES treatment resulted in a significant reduction in cardiac dimension (end diastolic left ventricular mass/gram wet weight; EDMc) at 3 months postinjection. Neither AAV nor ERT therapy altered minute ventilation during quiet breathing (eupnea). However, breathing frequency and expiratory time were significantly improved in AAV9-DES animals. These results indicate systemic delivery of either strategy improves cardiac function but AAV9-DES alone improves respiratory parameters at 3 months post-treatment in a murine model of Pompe disease. PMID:26029718

  15. Positron emission tomographic imaging of cardiac sympathetic innervation and function

    SciTech Connect

    Goldstein, D.S.; Chang, P.C.; Eisenhofer, G.; Miletich, R.; Finn, R.; Bacher, J.; Kirk, K.L.; Bacharach, S.; Kopin, I.J. )

    1990-05-01

    Sites of uptake, storage, and metabolism of ({sup 18}F)fluorodopamine and excretion of ({sup 18}F)fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of ({sup 18}F)-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of ({sup 18}F)fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function.

  16. Proangiogenic scaffolds as functional templates for cardiac tissue engineering

    PubMed Central

    Madden, Lauran R.; Mortisen, Derek J.; Sussman, Eric M.; Dupras, Sarah K.; Fugate, James A.; Cuy, Janet L.; Hauch, Kip D.; Laflamme, Michael A.; Murry, Charles E.; Ratner, Buddy D.

    2010-01-01

    We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30–40 μm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response. PMID:20696917

  17. Resveratrol attenuated estrogen-deficient-induced cardiac dysfunction: role of AMPK, SIRT1, and mitochondrial function

    PubMed Central

    Meng, Zijun; Jing, Hongjiang; Gan, Lu; Li, Hua; Luo, Bingde

    2016-01-01

    Large epidemiological studies suggest that there are important differences in the incidence and severity of a wide variety of cardiac diseases, between premenopausal and menopausal women. Recently, it has been demonstrated that resveratrol may has similar function as estrogen. However, whether resveratrol replacement could mimic estrogen to protect heart in ovariectomized mice remains completely unknown. Firstly, the present study has used OVX/CAL model to investigate the effect of RSV on ischemic heart. Echocardiography analysis revealed that RSV administration significantly improved cardiac contractile function in estrogen-deficient mice. RSV also significantly reduced CK and LDH release, and heart infarct size in OVX/CAL group. Secondly, mitochondrial functions, including MRC activities, MDA level, and mitochondrial swelling, were evaluated in OVX mice. It was found that supplementation with RSV could restore mitochondrial function dampened by OVX. Thirdly, these protective functions mediated by RSV were mainly attributed to the enhancement of SIRT1/AMPK activity. In summary, the results support a potential role of resveratrol in the protection of cardiac functions under estrogen depletion status. PMID:27398147

  18. 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

  19. Hand2 ensures an appropriate environment for cardiac fusion by limiting Fibronectin function.

    PubMed

    Garavito-Aguilar, Zayra V; Riley, Heather E; Yelon, Deborah

    2010-10-01

    Heart formation requires the fusion of bilateral cardiomyocyte populations as they move towards the embryonic midline. The bHLH transcription factor Hand2 is essential for cardiac fusion; however, the effector genes that execute this function of Hand2 are unknown. Here, we provide in zebrafish the first evidence for a downstream component of the Hand2 pathway that mediates cardiac morphogenesis. Although hand2 is expressed in cardiomyocytes, mosaic analysis demonstrates that it plays a non-autonomous role in regulating cardiomyocyte movement. Gene expression profiles reveal heightened expression of fibronectin 1 (fn1) in hand2 mutant embryos. Reciprocally, overexpression of hand2 leads to decreased Fibronectin levels. Furthermore, reduction of fn1 function enables rescue of cardiac fusion in hand2 mutants: bilateral cardiomyocyte populations merge and exhibit improved tissue architecture, albeit without major changes in apicobasal polarity. Together, our data provide a novel example of a tissue creating a favorable environment for its morphogenesis: the Hand2 pathway establishes an appropriate environment for cardiac fusion through negative modulation of Fn1 levels. PMID:20724450

  20. 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

  1. 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.

  2. Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

    PubMed

    Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

    2007-05-01

    3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function. PMID:17284482

  3. Highly Elastic Micropatterned Hydrogel for Engineering Functional Cardiac Tissue

    PubMed Central

    Annabi, Nasim; Tsang, Kelly; Mithieux, Suzanne M.; Nikkhah, Mehdi; Ameri, Afshin

    2013-01-01

    Heart failure is a major international health issue. Myocardial mass loss and lack of contractility are precursors to heart failure. Surgical demand for effective myocardial repair is tempered by a paucity of appropriate biological materials. These materials should conveniently replicate natural human tissue components, convey persistent elasticity, promote cell attachment, growth and conformability to direct cell orientation and functional performance. Here, microfabrication techniques are applied to recombinant human tropoelastin, the resilience-imparting protein found in all elastic human tissues, to generate photocrosslinked biological materials containing well-defined micropatterns. These highly elastic substrates are then used to engineer biomimetic cardiac tissue constructs. The micropatterned hydrogels, produced through photocrosslinking of methacrylated tropoelastin (MeTro), promote the attachment, spreading, alignment, function, and intercellular communication of cardiomyocytes by providing an elastic mechanical support that mimics their dynamic mechanical properties in vivo. The fabricated MeTro hydrogels also support the synchronous beating of cardiomyocytes in response to electrical field stimulation. These novel engineered micropatterned elastic gels are designed to be amenable to 3D modular assembly and establish a versatile, adaptable foundation for the modeling and regeneration of functional cardiac tissue with potential for application to other elastic tissues. PMID:24319406

  4. 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.

  5. 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

  6. Acute response and chronic stimulus for cardiac structural and functional adaptation in a professional boxer.

    PubMed

    Oxborough, David; George, Keith; Utomi, Victor; Lord, Rachel; Morton, James; Jones, Nigel; Somauroo, John

    2014-06-01

    The individual response to acute and chronic changes in cardiac structure and function to intense exercise training is not fully understood and therefore evidence in this setting may help to improve the timing and interpretation of pre-participation cardiac screening. The following case report highlights an acute increase in right ventricular (RV) size and a reduction in left ventricular (LV) basal radial function with concomitant increase at the mid-level in response to a week's increase in training volume in a professional boxer. These adaptations settle by the second week; however, chronic physiological adaptation occurs over a 12-week period. Electrocardiographic findings demonstrate an acute lateral T-wave inversion at 1 week, which revert to baseline for the duration of training. It appears that a change in training intensity and volume generates an acute response within the RV that acts as a stimulus for chronic adaptation in this professional boxer. PMID:25988031

  7. Cardiac autonomic functions in children with familial Mediterranean fever.

    PubMed

    Şahin, Murat; Kır, Mustafa; Makay, Balahan; Keskinoğlu, Pembe; Bora, Elçin; Ünsal, Erbil; Ünal, Nurettin

    2016-05-01

    Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. The long-term effects of subclinical inflammation in FMF are not well recognized. Some studies have suggested that FMF is associated with cardiac autonomic dysfunction in adult FMF patients. The objective of this study was to investigate the cardiac autonomic functions in pediatric FMF patients by using several autonomic tests. Thirty-five patients with FMF and 35 healthy controls were enrolled in this cross-sectional study. Demographic data, disease-specific data, and orthostatic symptoms were recorded. In all participants, 12-lead electrocardiography (ECG), 24 h ambulatory electrocardiographic monitoring, transthoracic echocardiography, treadmill exercise test, and head upright tilt-table (HUTT) test were performed. The heart rate recovery (HRR) indices of the two groups were similar. Also, chronotropic response was similar in both groups. The time-domain parameters of heart rate variability (HRV) were similar in both groups, except mean RR (p = 0.024). Frequencies of ventricular and supraventricular ectopic stimuli were similar in both groups. There were no statistically significant differences between the groups in average QT and average corrected QT interval length, average QT interval dispersion, and average QT corrected dispersion. There was no significant difference between the two groups regarding the ratio of clinical dysautonomic reactions on HUTT. However, we observed a significantly higher rate of dysautonomic reactions on HUTT in patients with exertional leg pain than that in patients without (p = 0.013). When the fractal dimension of time curves were compared, FMF patients exhibited significantly lower diastolic blood pressure parameters than controls in response to HUTT. Cardiovascular autonomic dysfunction in children with FMF is not prominent. Particularly, patients with exertional leg pain are more prone to have dysautonomic features

  8. 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. PMID:27185937

  9. Sleep Disordered Breathing: Hypertension and Cardiac Structure and Function.

    PubMed

    Querejeta Roca, Gabriela; Shah, Amil M

    2015-12-01

    Obstructive sleep apnea (OSA) is a common form of sleep disordered breathing and has a relatively high prevalence in the general population. The frequency and severity of OSA is associated with age, male sex, and obesity, and OSA has been linked to cardiovascular complications and death. Importantly, OSA has a strong association with both prevalent and incidental hypertension and has a particularly high prevalence in patients with resistant hypertension. In these patients, CPAP and other OSA-directed treatments have been proposed as therapy to help control blood pressure (BP), especially in patients who have not attained optimal BP control despite maximum pharmacological therapy. OSA has also been associated with alterations in cardiac structure and function, although most studies are small and highly limited in study design. Existing data suggest an association between OSA greater left ventricle (LV) mass and hypertrophy that appears independent of confounders including hypertension and obesity. Although less clear and more controversial, OSA severity has been linked to LV systolic and diastolic function, pulmonary hypertension, and right ventricular hypertrophy. Further studies are needed to confirm the potential causal role of OSA in these observed associations with cardiac abnormalities. PMID:26493391

  10. Associations between Kidney Function and Subclinical Cardiac Abnormalities in CKD

    PubMed Central

    Hsu, Chi-yuan; Li, Yongmei; Mishra, Rakesh K.; Keane, Martin; Rosas, Sylvia E.; Dries, Daniel; Xie, Dawei; Chen, Jing; He, Jiang; Anderson, Amanda; Go, Alan S.; Shlipak, Michael G.

    2012-01-01

    Heart failure is a common consequence of CKD, and it portends high risk for mortality. However, among patients without known heart failure, the associations of different stages of estimated GFR (eGFR) with changes in cardiac structure and function are not well described. Here, we performed a cross-sectional analysis to study these associations among 3487 participants of the Chronic Renal Insufficiency Cohort Study. We estimated GFR using cystatin C. The prevalence of left ventricular hypertrophy (LVH) assessed by echocardiography was 32%, 48%, 57%, and 75% for eGFR categories ≥60, 45–59, 30–44, and <30 ml/min per 1.73 m2, respectively. In fully adjusted multivariable analyses, subjects with eGFR levels of <30 ml/min per 1.73 m2 had twofold higher odds of LVH (OR=2.20, 95% CI=1.40–3.40; P<0.001) relative to subjects with eGFR≥60 ml/min per 1.73 m2. This reduction in kidney function also significantly associated with abnormal LV geometry but not diastolic or systolic dysfunction. An eGFR of 30–44 ml/min per 1.73 m2 also significantly associated with LVH and abnormal LV geometry compared with eGFR≥60 ml/min per 1.73 m2. In summary, in this large CKD cohort, reduced kidney function associated with abnormal cardiac structure. We did not detect significant associations between kidney function and systolic or diastolic function after adjusting for potential confounding variables. PMID:22935481

  11. Dietary nitrate improves cardiac contractility via enhanced cellular Ca²⁺ signaling.

    PubMed

    Pironti, Gianluigi; Ivarsson, Niklas; Yang, Jiangning; Farinotti, Alex Bersellini; Jonsson, William; Zhang, Shi-Jin; Bas, Duygu; Svensson, Camilla I; Westerblad, Håkan; Weitzberg, Eddie; Lundberg, Jon O; Pernow, John; Lanner, Johanna; Andersson, Daniel C

    2016-05-01

    The inorganic anion nitrate (NO3 (-)), which is naturally enriched in certain vegetables (e.g., spinach and beetroot), has emerged as a dietary component that can regulate diverse bodily functions, including blood pressure, mitochondrial efficiency, and skeletal muscle force. It is not known if dietary nitrate improves cardiac contractility. To test this, mice were supplemented for 1-2 weeks with sodium nitrate in the drinking water at a dose similar to a green diet. The hearts from nitrate-treated mice showed increased left ventricular pressure and peak rate of pressure development as measured with the Langendorff heart technique. Cardiomyocytes from hearts of nitrate-treated and control animals were incubated with the fluorescent indicator Fluo-3 to measure cytoplasmic free [Ca(2+)] and fractional shortening. Cardiomyocytes from nitrate-treated mice displayed increased fractional shortening, which was linked to larger Ca(2+) transients. Moreover, nitrate hearts displayed increased protein expression of the L-type Ca(2+) channel/dihydropyridine receptor and peak L-type Ca(2+) channel currents. The nitrate-treated hearts displayed increased concentration of cAMP but unchanged levels of cGMP compared with controls. These findings provide the first evidence that dietary nitrate can affect the expression of important Ca(2+) handling proteins in the heart, resulting in increased cardiomyocyte Ca(2+) signaling and improved left ventricular contractile function. Our observation shows that dietary nitrate impacts cardiac function and adds understanding to inorganic nitrate as a physiological modulator. PMID:27071401

  12. Functional and Morphological Cardiac Magnetic Resonance Imaging of Mice Using a Cryogenic Quadrature Radiofrequency Coil

    PubMed Central

    Dieringer, Matthias Alexander; Els, Antje; Waiczies, Helmar; Waiczies, Sonia; Schulz-Menger, Jeanette; Niendorf, Thoralf

    2012-01-01

    Cardiac morphology and function assessment by magnetic resonance imaging is of increasing interest for a variety of mouse models in pre-clinical cardiac research, such as myocardial infarction models or myocardial injury/remodeling in genetically or pharmacologically induced hypertension. Signal-to-noise ratio (SNR) constraints, however, limit image quality and blood myocardium delineation, which crucially depend on high spatial resolution. Significant gains in SNR with a cryogenically cooled RF probe have been shown for mouse brain MRI, yet the potential of applying cryogenic RF coils for cardiac MR (CMR) in mice is, as of yet, untapped. This study examines the feasibility and potential benefits of CMR in mice employing a 400 MHz cryogenic RF surface coil, compared with a conventional mouse heart coil array operating at room temperature. The cryogenic RF coil affords SNR gains of 3.0 to 5.0 versus the conventional approach and hence enables an enhanced spatial resolution. This markedly improved image quality – by better deliniation of myocardial borders and enhanced depiction of papillary muscles and trabeculae – and facilitated a more accurate cardiac chamber quantification, due to reduced intraobserver variability. In summary the use of a cryogenically cooled RF probe represents a valuable means of enhancing the capabilities of CMR of mice. PMID:22870323

  13. Improved 3-Tesla cardiac cine imaging using wideband.

    PubMed

    Lee, Hsu-Lei; Shankaranarayanan, Ajit; Pohost, Gerald M; Nayak, Krishna S

    2010-06-01

    Cine balanced steady-state free precession (SSFP) is the most widely used sequence for assessing cardiac ventricular function at 1.5 T because it provides high signal-to-noise ratio efficiency and strong contrast between myocardium and blood. At 3 T, the use of SSFP is limited by susceptibility-induced off-resonance, resulting in either banding artifacts or the need to use a short-sequence pulse repetition time that limits the readout duration and hence the achievable spatial resolution. In this work, we apply wideband SSFP, a variant of SSFP that uses two alternating pulse repetition times to establish a steady state with wider band spacing in its frequency response and overcome the key limitations of SSFP. Prospectively gated cine two-dimensional imaging with wideband SSFP is evaluated in healthy volunteers and compared to conventional balanced SSFP, using quantitative metrics and qualitative interpretation by experienced clinicians. We demonstrate that by trading off temporal resolution and signal-to-noise ratio efficiency, wideband SSFP mitigates banding artifacts and enables imaging with approximately 30% higher spatial resolution compared to conventional SSFP with the same effective band spacing. PMID:20512877

  14. Long-term abdominal adiposity activates several parameters of cardiac energy function.

    PubMed

    Mourmoura, Evangelia; Rigaudière, Jean-Paul; Couturier, Karine; Hininger, Isabelle; Laillet, Brigitte; Malpuech-Brugère, Corinne; Azarnoush, Kasra; Demaison, Luc

    2016-09-01

    Abdominal obesity increases the incidence of cardiac events but reduces mortality when one of these events occurs. The phenomenon called obesity paradox might be related to myocardial energetics. This study was aimed at determining whether long-term abdominal adiposity alters cardiac energy function. Two groups of male Wistar rats were fed a standard or a Western-type (WD) diet for 8 months. The ex vivo coronary reactivity and mechanical function as well as the mitochondrial oxidative phosphorylation (mOxPhos) and hydrogen peroxide release (mH2O2r) were determined. Abdominal adiposity was augmented by the WD. This was also the case for the coronary reactivity to acetylcholine, but the rate pressure product remained roughly stable despite a reduction of the left ventricle-developed pressure partly compensated by a slight increase in heart rate. The prolonged WD administration resulted in an improvement of mOxPhos, but the mH2O2r was exaggerated which was confirmed in the whole cell by a reduced aconitase to fumarase ratio. This did not modify the plasma oxidative stress due to an increased plasma antioxidant status. In conclusion, long-term WD administration improved the cardiac fitness and might predispose the organism to the obesity paradox. Conversely, the increased mitochondrial mH2O2r can precipitate the heart toward cardiomyopathy if the WD is maintained for a longer duration. PMID:26255304

  15. 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. PMID:19940994

  16. Potential approaches to improve the outcomes of donation after cardiac death liver grafts

    PubMed Central

    Mahboub, Paria; Bozorgzadeh, Adel; Martins, Paulo N

    2016-01-01

    There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death (DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications. In order to maximize the usage of DCD livers several new preservation approaches have been proposed. Here, we will review 3 innovative organ preservation methods: (1) different ex vivo perfusion techniques; (2) persufflation with oxygen; and (3) addition of thrombolytic therapy. Improvement of the quality of DCD liver grafts could increase the pool of liver graft’s for transplantation, improve the outcomes, and decrease the mortality on the waiting list. PMID:27358776

  17. Potential approaches to improve the outcomes of donation after cardiac death liver grafts.

    PubMed

    Mahboub, Paria; Bozorgzadeh, Adel; Martins, Paulo N

    2016-06-24

    There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death (DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications. In order to maximize the usage of DCD livers several new preservation approaches have been proposed. Here, we will review 3 innovative organ preservation methods: (1) different ex vivo perfusion techniques; (2) persufflation with oxygen; and (3) addition of thrombolytic therapy. Improvement of the quality of DCD liver grafts could increase the pool of liver graft's for transplantation, improve the outcomes, and decrease the mortality on the waiting list. PMID:27358776

  18. Dietary interaction of high fat and marginal copper deficiency on cardiac contractile function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High fat and copper deficient diets impair heart function leading to cardio hypertrophy, increased lipid droplet volume and compromised contractile function, resembling liptoxic cardiac dysfunction. However, the combined effect of the two on cardiac function is unknown. The purpose or objective of t...

  19. 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

  20. Interdisciplinary ICU Cardiac Arrest Debriefing Improves Survival Outcomes

    PubMed Central

    Wolfe, Heather; Zebuhr, Carleen; Topjian, Alexis A.; Nishisaki, Akira; Niles, Dana E.; Meaney, Peter A.; Boyle, Lori; Giordano, Rita T.; Davis, Daniela; Priestley, Margaret; Apkon, Michael; Berg, Robert A.; Nadkarni, Vinay M.; Sutton, Robert M.

    2014-01-01

    Objective In-hospital cardiac arrest is an important public health problem. High-quality resuscitation improves survival but is difficult to achieve. Our objective is to evaluate the effectiveness of a novel, interdisciplinary, postevent quantitative debriefing program to improve survival outcomes after in-hospital pediatric chest compression events. Design, Setting, and Patients Single-center prospective interventional study of children who received chest compressions between December 2008 and June 2012 in the ICU. Interventions Structured, quantitative, audiovisual, interdisciplinary debriefing of chest compression events with front-line providers. Measurements and Main Results Primary outcome was survival to hospital discharge. Secondary outcomes included survival of event (return of spontaneous circulation for ≥ 20 min) and favorable neurologic outcome. Primary resuscitation quality outcome was a composite variable, termed “excellent cardiopulmonary resuscitation,” prospectively defined as a chest compression depth ≥ 38 mm, rate ≥ 100/min, ≤ 10% of chest compressions with leaning, and a chest compression fraction > 90% during a given 30-second epoch. Quantitative data were available only for patients who are 8 years old or older. There were 119 chest compression events (60 control and 59 interventional). The intervention was associated with a trend toward improved survival to hospital discharge on both univariate analysis (52% vs 33%, p = 0.054) and after controlling for confounders (adjusted odds ratio, 2.5; 95% CI, 0.91–6.8; p = 0.075), and it significantly increased survival with favorable neurologic outcome on both univariate (50% vs 29%, p = 0.036) and multivariable analyses (adjusted odds ratio, 2.75; 95% CI, 1.01–7.5; p = 0.047). Cardiopulmonary resuscitation epochs for patients who are 8 years old or older during the debriefing period were 5.6 times more likely to meet targets of excellent cardiopulmonary resuscitation (95% CI, 2.9–10

  1. Homeobox Protein Hop Functions in the Adult Cardiac Conduction System

    PubMed Central

    Ismat, Fraz A.; Zhang, Maozhen; Kook, Hyun; Huang, Bin; Zhou, Rong; Ferrari, Victor A.; Epstein, Jonathan A.; Patel, Vickas V.

    2006-01-01

    Hop is an unusual homeobox gene expressed in the embryonic and adult heart. Hop acts downstream of Nkx2–5 during development, and Nkx2–5 mutations are associated with cardiac conduction system (CCS) defects. Inactivation of Hop in the mouse is lethal in half of the expected null embryos. Here, we show that Hop is expressed strongly in the adult CCS. Hop−/− adult mice display conduction defects below the atrioventricular node (AVN) as determined by invasive electrophysiological testing. These defects are associated with decreased expression of connexin40. Our results suggest that Hop functions in the adult CCS and demonstrate conservation of molecular hierarchies between embryonic myocardium and the specialized conduction tissue of the mature heart. PMID:15790958

  2. 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

    2016-01-01

    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

  3. 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

  4. 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.

  5. Evaluation of the ACT intervention to improve nurses' cardiac triage decisions.

    PubMed

    Arslanian-Engoren, Cynthia; Hagerty, Bonnie; Eagle, Kim A

    2010-10-01

    Emergency department (ED) nurses are in a key position to initiate life-saving recommendations for myocardial infarction, which include a physician-read electrocardiogram (ECG) within 10 min of ED arrival. Using a quasi-experimental, one-group pretest-posttest design, the authors evaluated the preliminary effectiveness of the Aid to Cardiac Triage (ACT) intervention to improve ED nurses' cardiac triage decisions. Charts of all women who received an ED ECG 3 months before ( n = 171) and after (n = 184) the intervention and who were at least 18 years of age were reviewed. A 1-hr educational session was conducted to improve nurses' (n = 23) cardiac triage decisions. Postintervention, the proportion of women receiving an ECG within 10 min of ED arrival improved, as did the odds of women receiving a timely ECG. Preliminary evaluation of the ACT intervention indicates its effectiveness at improving ED nurses' cardiac triage decisions and obtaining a 10-min physician-read ECG. PMID:20634399

  6. 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.

  7. Primary Cardiac Lymphoma: Diagnosis and the Impact of Chemotherapy on Cardiac Structure and Function.

    PubMed

    Pagé, Maude; Grasso, Agata E; Carpenter, John-Paul; Sheppard, Mary N; Karwatowski, Stefan P; Mohiaddin, Raad H

    2016-07-01

    We report a case of primary cardiac lymphoma presenting as myopericarditis and rapidly deteriorating into biventricular heart failure and ventricular arrhythmias. Computed tomography and cardiac magnetic resonance (CMR) imaging showed extensive myocardial infiltration with typical patterns on tissue characterization CMR images, raising clinical suspicion. Diagnosis was confirmed by myocardial histologic examination. Marked regression of tumor burden was apparent after 6 cycles of anthracycline-based chemotherapy. This case illustrates that a high degree of suspicion for this rare entity is mandated to institute timely treatment. Rapid tumor lysis may induce life-threatening acute cardiac decompensation that requires intensive monitoring and support therapy. PMID:26755242

  8. Molecular mechanism regulating myosin and cardiac functions by ELC.

    PubMed

    Lossie, Janine; Köhncke, Clemens; Mahmoodzadeh, Shokoufeh; Steffen, Walter; Canepari, Monica; Maffei, Manuela; Taube, Martin; Larchevêque, Oriane; Baumert, Philipp; Haase, Hannelore; Bottinelli, Roberto; Regitz-Zagrosek, Vera; Morano, Ingo

    2014-07-18

    The essential myosin light chain (ELC) is involved in modulation of force generation of myosin motors and cardiac contraction, while its mechanism of action remains elusive. We hypothesized that ELC could modulate myosin stiffness which subsequently determines its force production and cardiac contraction. Therefore, we generated heterologous transgenic mouse (TgM) strains with cardiomyocyte-specific expression of ELC with human ventricular ELC (hVLC-1; TgM(hVLC-1)) or E56G-mutated hVLC-1 (hVLC-1(E56G); TgM(E56G)). hVLC-1 or hVLC-1(E56G) expression in TgM was around 39% and 41%, respectively of total VLC-1. Laser trap and in vitro motility assays showed that stiffness and actin sliding velocity of myosin with hVLC-1 prepared from TgM(hVLC-1) (1.67 pN/nm and 2.3 μm/s, respectively) were significantly higher than myosin with hVLC-1(E56G) prepared from TgM(E56G) (1.25 pN/nm and 1.7 μm/s, respectively) or myosin with mouse VLC-1 (mVLC-1) prepared from C57/BL6 (1.41 pN/nm and 1.5 μm/s, respectively). Maximal left ventricular pressure development of isolated perfused hearts in vitro prepared from TgM(hVLC-1) (80.0 mmHg) were significantly higher than hearts from TgM(E56G) (66.2 mmHg) or C57/BL6 (59.3±3.9 mmHg). These findings show that ELCs decreased myosin stiffness, in vitro motility, and thereby cardiac functions in the order hVLC-1>hVLC-1(E56G)≈mVLC-1. They also suggest a molecular pathomechanism of hypertrophic cardiomyopathy caused by hVLC-1 mutations. PMID:24911555

  9. Human placenta-derived adherent cells improve cardiac performance in mice with chronic heart failure.

    PubMed

    Chen, Hong-Jung; Chen, Chien-Hsi; Chang, Ming-Yao; Tsai, Da-Ching; Baum, Ellen Z; Hariri, Robert; Herzberg, Uri; Hsieh, Patrick C H

    2015-03-01

    Human placenta-derived adherent cells (PDACs) are a culture-expanded, undifferentiated mesenchymal-like population derived from full-term placental tissue, with immunomodulatory, anti-inflammatory, angiogenic, and neuroprotective properties. PDA-001 (cenplacel-L), an intravenous formulation of PDAC cells, is in clinical development for the treatment of autoimmune and inflammatory diseases. We tested the therapeutic effects of PDA-001 in mice with chronic heart failure (CHF). Three weeks after transaortic constriction surgery to induce CHF, the mice underwent direct intramyocardial (IM) or i.v. injection of PDA-001 at a high (0.5 × 10(6) cells per mouse), medium (0.5 × 10(5) cells per mouse), or low (0.5 × 10(4) cells per mouse) dose. The mice were sacrificed 4 weeks after treatment. Echocardiography and ventricular catheterization showed that IM injection of PDA-001 significantly improved left ventricular systolic and diastolic function compared with injection of vehicle or i.v. injection of PDA-001. IM injection of PDA-001 also decreased cardiac fibrosis, shown by trichrome staining in the vicinity of the injection sites. Low-dose treatment showed the best improvement in cardiac performance compared with the medium- and high-dose groups. In another independent study to determine the mechanism of action with bromodeoxyuridine labeling, the proliferation rates of endothelial cells and cardiomyocytes were significantly increased by low or medium IM dose PDA-001. However, no surviving PDA-001 cells were detected in the heart 1 month after injection. In vivo real-time imaging consistently revealed that the PDA-001 cells were detectable only within 2 days after IM injection of luciferase-expressing PDA-001. Together, these results have demonstrated the cardiac therapeutic potential of PDA-001, likely through a paracrine effect. PMID:25673767

  10. Normalization of Naxos plakoglobin levels restores cardiac function in mice.

    PubMed

    Zhang, Zhiwei; Stroud, Matthew J; Zhang, Jianlin; Fang, Xi; Ouyang, Kunfu; Kimura, Kensuke; Mu, Yongxin; Dalton, Nancy D; Gu, Yusu; Bradford, William H; Peterson, Kirk L; Cheng, Hongqiang; Zhou, Xinmin; Chen, Ju

    2015-04-01

    Arrhythmogenic cardiomyopathy (AC) is associated with mutations in genes encoding intercalated disc proteins and ultimately results in sudden cardiac death. A subset of patients with AC have the autosomal recessive cardiocutaneous disorder Naxos disease, which is caused by a 2-base pair deletion in the plakoglobin-encoding gene JUP that results in a truncated protein with reduced expression. In mice, cardiomyocyte-specific plakoglobin deficiency recapitulates many aspects of human AC, and overexpression of the truncated Naxos-associated plakoglobin also results in an AC-like phenotype; therefore, it is unclear whether Naxos disease results from loss or gain of function consequent to the plakoglobin mutation. Here, we generated 2 knockin mouse models in which endogenous Jup was engineered to express the Naxos-associated form of plakoglobin. In one model, Naxos plakoglobin bypassed the nonsense-mediated mRNA decay pathway, resulting in normal levels of the truncated plakoglobin. Moreover, restoration of Naxos plakoglobin to WT levels resulted in normal heart function. Together, these data indicate that a gain of function in the truncated form of the protein does not underlie the clinical phenotype of patients with Naxos disease and instead suggest that insufficiency of the truncated Naxos plakoglobin accounts for disease manifestation. Moreover, these results suggest that increasing levels of truncated or WT plakoglobin has potential as a therapeutic approach to Naxos disease. PMID:25705887

  11. Changes of Cardiac Function During Ultradistance Trail Running.

    PubMed

    Jouffroy, Romain; Caille, Vincent; Perrot, Stéphane; Vieillard-Baron, Antoine; Dubourg, Olivier; Mansencal, Nicolas

    2015-10-15

    Previous studies have noted reversible cardiac dysfunction during marathon races, but few data are available concerning ultradistance trail running. The aim of this study was to assess echocardiographic parameters during ultradistance trail running. We performed an observational study in 66 participants to the 80-km Ecotrail of Paris Ile de France. All subjects had echocardiographic examinations before the race and on arrival, and 28 of them underwent serial echocardiographic examinations during the race (21 and 53 km). A single experienced physician performed all echocardiographic examinations, and the same protocol was always used (conventional 2-dimensional and Doppler left ventricular parameters and longitudinal strain). All echocardiographic parameters of left ventricular (LV) systolic function were significantly decreased on arrival (p ≤0.002). A significant reduction of LV systolic function was observed in 48% of study subjects on arrival. No significant modification was observed at 21 or at 53 km, and only global longitudinal strain was significantly decreased (p = 0.0008). At arrival, mitral E/A ratio and average mitral tissue Doppler imaging e' wave were significantly decreased (p = 0.0001 and p = 0.0004, respectively), but these changes were observed from 21 km. In conclusion, ultradistance trail running can lead to abnormalities of LV systolic and diastolic functions in amateur runners. Diastolic dysfunction arises earlier than systolic dysfunction. Left ventricular systolic dysfunction occurred in 48% of the study subjects and was detected early by assessment of longitudinal strain. PMID:26294134

  12. Mechanisms of epoxyeicosatrienoic acids to improve cardiac remodeling in chronic renal failure disease.

    PubMed

    Zhang, Kun; Wang, Ju; Zhang, Huanji; Chen, Jie; Zuo, Zhiyi; Wang, Jingfeng; Huang, Hui

    2013-02-15

    Both clinical and basic science studies have demonstrated that cardiac remodeling in patients with chronic renal failure (CRF) is very common. It is a key feature during the course of heart failure and an important risk factor for subsequent cardiac mortality. Traditional drugs or therapies rarely have effects on cardiac regression of CRF and cardiovascular events are still the first cause of death. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acids metabolized by cytochrome P450 epoxygenases. It has been found that EETs have important biological effects including anti-hypertension and anti-inflammation. Recent data suggest that EETs are involved in regulating cardiomyocyte injury, renal dysfunction, chronic kidney disease (CKD)-related risk factors and signaling pathways, all of which play key roles in cardiac remodeling induced by CRF. This review analyzes the literature to identify the possible mechanisms for EETs to improve cardiac remodeling induced by CRF and indicates the therapeutic potential of EETs in it. PMID:23313758

  13. 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

  14. 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

  15. Sinus node function in first three weeks after cardiac transplantation.

    PubMed Central

    Mackintosh, A F; Carmichael, D J; Wren, C; Cory-Pearce, R; English, T A

    1982-01-01

    Donor sinus node function was studied in 10 patients from day 4 to day 24 after cardiac transplantation. Cycle length, atrial arrhythmias, corrected sinus node recovery time, and estimated sinoatrial conduction time were recorded daily. Five patients had at least two sets of results suggesting sinus node dysfunction (group A) while five patients had no such abnormalities (group B). The prognosis in group A was poor, with four of the five patients dying within four months of the operation; one unexpected death from arrhythmias was recorded by ambulatory electrocardiographic monitoring. All five patients in group B survived for at least eight months. In nine patients sinus node function varied from day to day, with corrected sinus node recovery time reaching a peak at 11 to 18 days after operation. The longest corrected sinus node recovery time was 11 160 ms. Neither the differences between the patients, nor the day to day variation, could be explained solely by the degree of rejection as assessed by biopsy or by the ischaemia time of the heart during procurement. Sinus node dysfunction soon after transplantation is associated with a poorer prognosis and might be the terminal event in some cases. Images PMID:6756446

  16. 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

  17. The EINTHOVEN system: toward an improved cardiac arrhythmia monitor.

    PubMed Central

    Widman, L. E.

    1991-01-01

    Contemporary cardiac arrhythmia monitors, used commonly in intensive care settings, are highly sensitive to artifact, resulting in high false alarm rates, inability to detect P waves reliably, and crude rhythm interpretation. We report on two new approaches that address these problems: a noise preprocessor that characterizes the type and degree of artifact in an ECG, and a model-based rhythm interpretation algorithm. PMID:1807639

  18. The Role of Cardiac Troponin T Quantity and Function in Cardiac Development and Dilated Cardiomyopathy

    PubMed Central

    Ahmad, Ferhaan; Banerjee, Sanjay K.; Lage, Michele L.; Huang, Xueyin N.; Smith, Stephen H.; Saba, Samir; Rager, Jennifer; Conner, David A.; Janczewski, Andrzej M.; Tobita, Kimimasa; Tinney, Joseph P.; Moskowitz, Ivan P.; Perez-Atayde, Antonio R.; Keller, Bradley B.; Mathier, Michael A.; Shroff, Sanjeev G.; Seidman, Christine E.; Seidman, J. G.

    2008-01-01

    Background Hypertrophic (HCM) and dilated (DCM) cardiomyopathies result from sarcomeric protein mutations, including cardiac troponin T (cTnT, TNNT2). We determined whether TNNT2 mutations cause cardiomyopathies by altering cTnT function or quantity; whether the severity of DCM is related to the ratio of mutant to wildtype cTnT; whether Ca2+ desensitization occurs in DCM; and whether absence of cTnT impairs early embryonic cardiogenesis. Methods and Findings We ablated Tnnt2 to produce heterozygous Tnnt2+/− mice, and crossbreeding produced homozygous null Tnnt2−/− embryos. We also generated transgenic mice overexpressing wildtype (TGWT) or DCM mutant (TGK210Δ) Tnnt2. Crossbreeding produced mice lacking one allele of Tnnt2, but carrying wildtype (Tnnt2+/−/TGWT) or mutant (Tnnt2+/−/TGK210Δ) transgenes. Tnnt2+/− mice relative to wildtype had significantly reduced transcript (0.82±0.06[SD] vs. 1.00±0.12 arbitrary units; p = 0.025), but not protein (1.01±0.20 vs. 1.00±0.13 arbitrary units; p = 0.44). Tnnt2+/− mice had normal hearts (histology, mass, left ventricular end diastolic diameter [LVEDD], fractional shortening [FS]). Moreover, whereas Tnnt2+/−/TGK210Δ mice had severe DCM, TGK210Δ mice had only mild DCM (FS 18±4 vs. 29±7%; p<0.01). The difference in severity of DCM may be attributable to a greater ratio of mutant to wildtype Tnnt2 transcript in Tnnt2+/−/TGK210Δ relative to TGK210Δ mice (2.42±0.08, p = 0.03). Tnnt2+/−/TGK210Δ muscle showed Ca2+ desensitization (pCa50 = 5.34±0.08 vs. 5.58±0.03 at sarcomere length 1.9 µm, p<0.01), but no difference in maximum force generation. Day 9.5 Tnnt2−/− embryos had normally looped hearts, but thin ventricular walls, large pericardial effusions, noncontractile hearts, and severely disorganized sarcomeres. Conclusions Absence of one Tnnt2 allele leads to a mild deficit in transcript but not protein, leading to a normal cardiac phenotype. DCM results from abnormal

  19. Altered mechanical state in the embryonic heart results in time-dependent decreases in cardiac function.

    PubMed

    Johnson, Brennan; Bark, David; Van Herck, Ilse; Garrity, Deborah; Dasi, Lakshmi Prasad

    2015-11-01

    Proper blood flow patterns are critical for normal cardiac morphogenesis, a process that occurs rapidly in order to support further development of all tissue and organs. Previously, intracardiac fluid forces have been shown to play a critical role in cardiac morphogenesis. Altered blood flow in early development can result in an array of cardiac defects including ventricular septal defects, valve malformations, and impaired cardiac looping. However, given the dynamic and highly transient nature of cardiac morphogenesis, time dependency of the mechanical environment as an epigenetic factor in relation to intracardiac forces must be significant. Here, we show that abnormal cardiac loading adversely influences cardiac morphology only during certain time windows, thus confirming that mechanical factors are a time-dependent epigenetic factor. To illustrate this, groups of zebrafish embryos were spaced at 6-h increments from 24 to 48 h post-fertilization (hpf) in which embryos were centrifuged to generate a noninvasive alteration of cardiac preload in addition to an overall hypergravity environment. We found that earlier and later treatment groups responded with altered morphology and function, while the group with altered preload from 30 to 36 hpf had no effect. These results demonstrate the inherently time-dependent nature of epigenetic factors as pertaining to intracardiac forces and external mechanical factors. Further, it underscores the highly coupled nature of programmed biology and mechanical forces during cardiac morphogenesis. Future studies with respect to surgical correction during cardiac morphogenesis must consider timing to optimize therapeutic impact. PMID:25976479

  20. Plasma-functionalized electrospun matrix for biograft development and cardiac function stabilization.

    PubMed

    Guex, A G; Frobert, A; Valentin, J; Fortunato, G; Hegemann, D; Cook, S; Carrel, T P; Tevaearai, H T; Giraud, M N

    2014-07-01

    Cardiac tissue engineering approaches can deliver large numbers of cells to the damaged myocardium and have thus increasingly been considered as a possible curative treatment to counteract the high prevalence of progressive heart failure after myocardial infarction (MI). Optimal scaffold architecture and mechanical and chemical properties, as well as immune- and bio-compatibility, need to be addressed. We demonstrated that radio-frequency plasma surface functionalized electrospun poly(ɛ-caprolactone) (PCL) fibres provide a suitable matrix for bone-marrow-derived mesenchymal stem cell (MSC) cardiac implantation. Using a rat model of chronic MI, we showed that MSC-seeded plasma-coated PCL grafts stabilized cardiac function and attenuated dilatation. Significant relative decreases of 13% of the ejection fraction (EF) and 15% of the fractional shortening (FS) were observed in sham treated animals; respective decreases of 20% and 25% were measured 4 weeks after acellular patch implantation, whereas a steadied function was observed 4 weeks after MSC-patch implantation (relative decreases of 6% for both EF and FS). PMID:24531014

  1. Cardiac cytoarchitecture - why the "hardware" is important for heart function!

    PubMed

    Ehler, Elisabeth

    2016-07-01

    Cells that constitute fully differentiated tissues are characterised by an architecture that makes them perfectly suited for the job they have to do. This is especially obvious for cardiomyocytes, which have an extremely regular shape and display a paracrystalline arrangement of their cytoplasmic components. This article will focus on the two major cytoskeletal multiprotein complexes that are found in cardiomyocytes, the myofibrils, which are responsible for contraction and the intercalated disc, which mediates mechanical and electrochemical contact between individual cardiomyocytes. Recent studies have revealed that these two sites are also crucial in sensing excessive mechanical strain. Signalling processes will be triggered that## lead to changes in gene expression and eventually lead to an altered cardiac cytoarchitecture in the diseased heart, which results in a compromised function. Thus, understanding these changes and the signals that lead to them is crucial to design treatment strategies that can attenuate these processes. 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. PMID:26577135

  2. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids.

    PubMed

    Huang, Tom Hsun-Wei; Peng, Gang; Kota, Bhavani Prasad; Li, George Qian; Yamahara, Johji; Roufogalis, Basil D; Li, Yuhao

    2005-07-01

    Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro. Long-term oral administration of PGF extract (500 mg kg(-1)) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholesterol in Zucker diabetic fatty (ZDF) rats, indicating improvement by PGF extract of abnormal cardiac TG accumulation and hyperlipidemia in this diabetic model. Treatment of ZDF rats with PGF extract lowered plasma FA levels. Furthermore, the treatment suppressed cardiac overexpression of mRNAs encoding for FA transport protein, peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase alpha2, and restored downregulated cardiac acetyl-CoA carboxylase mRNA expression in ZDF rats, whereas it showed little effect in Zucker lean rats. The results suggest that PGF extract inhibits increased cardiac FA uptake and oxidation in the diabetic condition. PGF extract and its component oleanolic acid enhanced PPAR-alpha luciferase reporter gene activity in human embryonic kidney 293 cells, and this effect was completely suppressed by a selective PPAR-alpha antagonist MK-886, consistent with the presence of PPAR-alpha activator activity in the extract and this component. Our findings suggest that PGF extract improves abnormal cardiac lipid metabolism in ZDF rats by activating PPAR-alpha and thereby lowering circulating lipid and inhibiting its cardiac uptake. PMID:15880139

  3. Anti-Thymocyte Globulin Induces Neoangiogenesis and Preserves Cardiac Function after Experimental Myocardial Infarction

    PubMed Central

    Lichtenauer, Michael; Mildner, Michael; Werba, Gregor; Beer, Lucian; Hoetzenecker, Konrad; Baumgartner, Andrea; Hasun, Matthias; Nickl, Stefanie; Mitterbauer, Andreas; Zimmermann, Matthias; Gyöngyösi, Mariann; Podesser, Bruno Karl; Klepetko, Walter; Ankersmit, Hendrik Jan

    2012-01-01

    Rationale Acute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries. Objective Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study. Methods and Results AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG. Conclusions These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI. PMID:23284885

  4. Exercise training improves vascular mitochondrial function.

    PubMed

    Park, Song-Young; Rossman, Matthew J; Gifford, Jayson R; Bharath, Leena P; Bauersachs, Johann; Richardson, Russell S; Abel, E Dale; Symons, J David; Riehle, Christian

    2016-04-01

    Exercise training is recognized to improve cardiac and skeletal muscle mitochondrial respiratory capacity; however, the impact of chronic exercise on vascular mitochondrial respiratory function is unknown. We hypothesized that exercise training concomitantly increases both vascular mitochondrial respiratory capacity and vascular function. Arteries from both sedentary (SED) and swim-trained (EX, 5 wk) mice were compared in terms of mitochondrial respiratory function, mitochondrial content, markers of mitochondrial biogenesis, redox balance, nitric oxide (NO) signaling, and vessel function. Mitochondrial complex I and complex I + II state 3 respiration and the respiratory control ratio (complex I + II state 3 respiration/complex I state 2 respiration) were greater in vessels from EX relative to SED mice, despite similar levels of arterial citrate synthase activity and mitochondrial DNA content. Furthermore, compared with the SED mice, arteries from EX mice displayed elevated transcript levels of peroxisome proliferative activated receptor-γ coactivator-1α and the downstream targets cytochrome c oxidase subunit IV isoform 1,isocitrate dehydrogenase(Idh)2, and Idh3a, increased manganese superoxide dismutase protein expression, increased endothelial NO synthase phosphorylation (Ser(1177)), and suppressed reactive oxygen species generation (all P< 0.05). Although there were no differences in EX and SED mice concerning endothelium-dependent and endothelium-independent vasorelaxation, phenylephrine-induced vasocontraction was blunted in vessels from EX compared with SED mice, and this effect was normalized by NOS inhibition. These training-induced increases in vascular mitochondrial respiratory capacity and evidence of improved redox balance, which may, at least in part, be attributable to elevated NO bioavailability, have the potential to protect against age- and disease-related challenges to arterial function. PMID:26825520

  5. Vascularisation to improve translational potential of tissue engineering systems for cardiac repair.

    PubMed

    Dilley, Rodney J; Morrison, Wayne A

    2014-11-01

    Cardiac tissue engineering is developing as an alternative approach to heart transplantation for treating heart failure. Shortage of organ donors and complications arising after orthotopic transplant remain major challenges to the modern field of heart transplantation. Engineering functional myocardium de novo requires an abundant source of cardiomyocytes, a biocompatible scaffold material and a functional vasculature to sustain the high metabolism of the construct. Progress has been made on several fronts, with cardiac cell biology, stem cells and biomaterials research particularly promising for cardiac tissue engineering, however currently employed strategies for vascularisation have lagged behind and limit the volume of tissue formed. Over ten years we have developed an in vivo tissue engineering model to construct vascularised tissue from various cell and tissue sources, including cardiac tissue. In this article we review the progress made with this approach and others, together with their potential to support a volume of engineered tissue for cardiac tissue engineering where contractile mass impacts directly on functional outcomes in translation to the clinic. It is clear that a scaled-up cardiac tissue engineering solution required for clinical treatment of heart failure will include a robust vascular supply for successful translation. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. PMID:25449260

  6. Design and formulation of functional pluripotent stem cell-derived cardiac microtissues

    PubMed Central

    Thavandiran, Nimalan; Dubois, Nicole; Mikryukov, Alexander; Massé, Stéphane; Beca, Bogdan; Simmons, Craig A.; Deshpande, Vikram S.; McGarry, J. Patrick; Chen, Christopher S.; Nanthakumar, Kumaraswamy; Keller, Gordon M.; Radisic, Milica; Zandstra, Peter W.

    2013-01-01

    Access to robust and information-rich human cardiac tissue models would accelerate drug-based strategies for treating heart disease. Despite significant effort, the generation of high-fidelity adult-like human cardiac tissue analogs remains challenging. We used computational modeling of tissue contraction and assembly mechanics in conjunction with microfabricated constraints to guide the design of aligned and functional 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues that we term cardiac microwires (CMWs). Miniaturization of the platform circumvented the need for tissue vascularization and enabled higher-throughput image-based analysis of CMW drug responsiveness. CMW tissue properties could be tuned using electromechanical stimuli and cell composition. Specifically, controlling self-assembly of 3D tissues in aligned collagen, and pacing with point stimulation electrodes, were found to promote cardiac maturation-associated gene expression and in vivo-like electrical signal propagation. Furthermore, screening a range of hPSC-derived cardiac cell ratios identified that 75% NKX2 Homeobox 5 (NKX2-5)+ cardiomyocytes and 25% Cluster of Differentiation 90 OR (CD90)+ nonmyocytes optimized tissue remodeling dynamics and yielded enhanced structural and functional properties. Finally, we demonstrate the utility of the optimized platform in a tachycardic model of arrhythmogenesis, an aspect of cardiac electrophysiology not previously recapitulated in 3D in vitro hPSC-derived cardiac microtissue models. The design criteria identified with our CMW platform should accelerate the development of predictive in vitro assays of human heart tissue function. PMID:24255110

  7. Effects of glutamine treatment on myocardial damage and cardiac function in rats after severe burn injury

    PubMed Central

    Yan, Hong; Zhang, Yong; Lv, Shang-jun; Wang, Lin; Liang, Guang-ping; Wan, Qian-xue; Peng, Xi

    2012-01-01

    Treatment with glutamine has been shown to reduce myocardial damage associated with ischemia/reperfusion injury. However, the cardioprotective effect of glutamine specifically after burn injury remains unclear. The present study explores the ability of glutamine to protect against myocardial damage in rats that have been severely burned. Seventy-two Wistar rats were randomly divided into three groups: normal controls (C), burned controls (B) and a glutamine-treated group (G). Groups B and G were subjected to full thickness burns comprising 30% of total body surface area. Group G was administered 1.5 g/ (kg•d) glutamine and group B was given the same dose of alanine via intragastric administration for 3 days. Levels of serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST) and blood lactic acid were measured, as well as myocardial ATP and glutathione (GSH) contents. Cardiac function indices and histopathological changes were analyzed at 12, 24, 48 and 72 post-burn hours. In both burned groups, levels of serum CK, LDH, AST and blood lactic acid increased significantly, while myocardial ATP and GSH contents decreased. Compared with group B, CK, LDH, and AST levels were lower and blood lactic acid, myocardial ATP and GSH levels were higher in group G. Moreover, cardiac contractile function inhibition and myocardial histopathological damage were significantly reduced in group G compared to B. Taken together, these results show that glutamine supplementation protects myocardial structure and function after burn injury by improving energy metabolism and by promotedthe synthesis of ATP and GSH in cardiac myocytes. PMID:22977661

  8. Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function

    PubMed Central

    Bibee, Kristin P.; Cheng, Ya-Jian; Ching, James K.; Marsh, Jon N.; Li, Allison J.; Keeling, Richard M.; Connolly, Anne M.; Golumbek, Paul T.; Myerson, Jacob W.; Hu, Grace; Chen, Junjie; Shannon, William D.; Lanza, Gregory M.; Weihl, Conrad C.; Wickline, Samuel A.

    2014-01-01

    Duchenne muscular dystrophy in boys progresses rapidly to severe impairment of muscle function and death in the second or third decade of life. Current supportive therapy with corticosteroids results in a modest increase in strength as a consequence of a general reduction in inflammation, albeit with potential untoward long-term side effects and ultimate failure of the agent to maintain strength. Here, we demonstrate that alternative approaches that rescue defective autophagy in mdx mice, a model of Duchenne muscular dystrophy, with the use of rapamycin-loaded nanoparticles induce a reproducible increase in both skeletal muscle strength and cardiac contractile performance that is not achievable with conventional oral rapamycin, even in pharmacological doses. This increase in physical performance occurs in both young and adult mice, and, surprisingly, even in aged wild-type mice, which sets the stage for consideration of systemic therapies to facilitate improved cell function by autophagic disposal of toxic byproducts of cell death and regeneration.—Bibee, K. P., Cheng, Y.-J., Ching, J. K., Marsh, J. N., Li, A. J., Keeling, R. M., Connolly, A. M., Golumbek, P. T., Myerson, J. W., Hu, G., Chen, J., Shannon, W. D., Lanza, G. M., Weihl, C. C., Wickline, S. A. Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function. PMID:24500923

  9. Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia.

    PubMed

    Hsu, Andrew R; Barnholt, Kimberly E; Grundmann, Nicolas K; Lin, Joseph H; McCallum, Stewart W; Friedlander, Anne L

    2006-06-01

    Sildenafil causes pulmonary vasodilation, thus potentially reducing impairments of hypoxia-induced pulmonary hypertension on exercise performance at altitude. The purpose of this study was to determine the effects of sildenafil during normoxic and hypoxic exercise. We hypothesized that 1) sildenafil would have no significant effects on normoxic exercise, and 2) sildenafil would improve cardiac output, arterial oxygen saturation (SaO2), and performance during hypoxic exercise. Ten trained men performed one practice and three experimental trials at sea level (SL) and simulated high altitude (HA) of 3,874 m. Each cycling test consisted of a set-work-rate portion (55% work capacity: 1 h SL, 30 min HA) followed immediately by a time trial (10 km SL, 6 km HA). Double-blinded capsules (placebo, 50, or 100 mg) were taken 1 h before exercise in a randomly counterbalanced order. For HA, subjects also began breathing hypoxic gas (12.8% oxygen) 1 h before exercise. At SL, sildenafil had no effects on any cardiovascular or performance measures. At HA, sildenafil increased stroke volume (measured by impedance cardiography), cardiac output, and SaO2 during set-work-rate exercise. Sildenafil lowered 6-km time-trial time by 15% (P<0.05). SaO2 was also higher during the time trial (P<0.05) in response to sildenafil, despite higher work rates. Post hoc analyses revealed two subject groups, sildenafil responders and nonresponders, who improved time-trial performance by 39% (P<0.05) and 1.0%, respectively. No dose-response effects were observed. During cycling exercise in acute hypoxia, sildenafil can greatly improve cardiovascular function, SaO2, and performance for certain individuals. PMID:16455814

  10. Trastuzumab Alters the Expression of Genes Essential for Cardiac Function and Induces Ultrastructural Changes of Cardiomyocytes in Mice

    PubMed Central

    ElZarrad, M. Khair; Mukhopadhyay, Partha; Mohan, Nishant; Hao, Enkui; Dokmanovic, Milos; Hirsch, Dianne S.; Shen, Yi; Pacher, Pal; Wu, Wen Jin

    2013-01-01

    Treatment with trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), very successfully improves outcomes for women with HER2-positive breast cancer. However, trastuzumab treatment was recently linked to potentially irreversible serious cardiotoxicity, the mechanisms of which are largely elusive. This study reports that trastuzumab significantly alters the expression of myocardial genes essential for DNA repair, cardiac and mitochondrial functions, which is associated with impaired left ventricular performance in mice coupled with significant ultrastructural alterations in cardiomyocytes revealed by electron microscopy. Furthermore, trastuzumab treatment also promotes oxidative stress and apoptosis in myocardium of mice, and elevates serum levels of cardiac troponin-I (cTnI) and cardiac myosin light chain-1 (cMLC1). The elevated serum levels of cMLC1 in mice treated with trastuzumab highlights the potential that cMLC1 could be a useful biomarker for trastuzumab-induced cardiotoxicity. PMID:24255707

  11. Estrogen-related receptor α (ERRα) and ERRγ are essential coordinators of cardiac metabolism and function.

    PubMed

    Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M; Patel, Vickas V; Pei, Liming

    2015-04-01

    Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor α (ERRα) and ERRγ are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERRα and ERRγ together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERRα and ERRγ influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

  12. Estrogen-Related Receptor α (ERRα) and ERRγ Are Essential Coordinators of Cardiac Metabolism and Function

    PubMed Central

    Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B.; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M.; Patel, Vickas V.

    2015-01-01

    Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor α (ERRα) and ERRγ are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERRα and ERRγ together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERRα and ERRγ influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

  13. Functional Relevance of Coronary Artery Disease by Cardiac Magnetic Resonance and Cardiac Computed Tomography: Myocardial Perfusion and Fractional Flow Reserve

    PubMed Central

    Andreini, Daniele; Bertella, Erika; Mushtaq, Saima; Guaricci, Andrea Igoren; Pepi, Mauro

    2015-01-01

    Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality and it is responsible for an increasing resource burden. The identification of patients at high risk for adverse events is crucial to select those who will receive the greatest benefit from revascularization. To this aim, several non-invasive functional imaging modalities are usually used as gatekeeper to invasive coronary angiography, but the diagnostic yield of elective invasive coronary angiography remains unfortunately low. Stress myocardial perfusion imaging by cardiac magnetic resonance (stress-CMR) has emerged as an accurate technique for diagnosis and prognostic stratification of the patients with known or suspected CAD thanks to high spatial and temporal resolution, absence of ionizing radiation, and the multiparametric value including the assessment of cardiac anatomy, function, and viability. On the other side, cardiac computed tomography (CCT) has emerged as unique technique providing coronary arteries anatomy and more recently, due to the introduction of stress-CCT and noninvasive fractional flow reserve (FFR-CT), functional relevance of CAD in a single shot scan. The current review evaluates the technical aspects and clinical experience of stress-CMR and CCT in the evaluation of functional relevance of CAD discussing the strength and weakness of each approach. PMID:25692133

  14. 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

  15. 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

  16. Targeting pleiotropic signaling pathways to control adult cardiac stem cell fate and function

    PubMed Central

    Pagliari, Stefania; Jelinek, Jakub; Grassi, Gabriele; Forte, Giancarlo

    2014-01-01

    The identification of different pools of cardiac progenitor cells resident in the adult mammalian heart opened a new era in heart regeneration as a means to restore the loss of functional cardiac tissue and overcome the limited availability of donor organs. Indeed, resident stem cells are believed to participate to tissue homeostasis and renewal in healthy and damaged myocardium although their actual contribution to these processes remain unclear. The poor outcome in terms of cardiac regeneration following tissue damage point out at the need for a deeper understanding of the molecular mechanisms controlling CPC behavior and fate determination before new therapeutic strategies can be developed. The regulation of cardiac resident stem cell fate and function is likely to result from the interplay between pleiotropic signaling pathways as well as tissue- and cell-specific regulators. Such a modular interaction—which has already been described in the nucleus of a number of different cells where transcriptional complexes form to activate specific gene programs—would account for the unique responses of cardiac progenitors to general and tissue-specific stimuli. The study of the molecular determinants involved in cardiac stem/progenitor cell regulatory mechanisms may shed light on the processes of cardiac homeostasis in health and disease and thus provide clues on the actual feasibility of cardiac cell therapy through tissue-specific progenitors. PMID:25071583

  17. Functional Outcomes: One Year after a Cardiac Arrest

    PubMed Central

    Raina, Ketki D.; Rittenberger, Jon C.; Holm, Margo B.; Callaway, Clifton W.

    2015-01-01

    Objective. The study aim was to characterize the time-course of recovery in impairments, activity limitations, participation restrictions, disability, and quality of life during the first year after cardiac arrest. Secondarily, the study described the associations between the instruments used to measure each of these domains. Methods. Measures of global disability (Cerebral Performance Category, CPC, Modified Rankin Scale, mRS), quality of life, activity limitations, participation restrictions, and affective and cognitive impairments were administered to 29 participants 1, 6, and 12 months after cardiac arrest. Results. Global measures of disability indicated recovery between one month and one year after cardiac arrest (mean CPC: 2.1 versus 1.69,  P < 0.05; mean mRS: 2.55 versus 1.83, P < 0.05). While global measures of disability were moderately associated with participation, they were poorly associated with other measures. The cohort endorsed depressive symptomatology throughout the year but did not have detectable cognitive impairment. Conclusions. Recovery from cardiac arrest is multifaceted and recovery continues for months depending upon the measures being used. Measures of global disability, reintegration into the community, and quality of life yield different information. Future clinical trials should include a combination of measures to yield the most complete representation of recovery after cardiac arrest. PMID:26421282

  18. 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

  19. 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.

  20. [Progress in research on function and mechanism of cardiac vascular system of taurine].

    PubMed

    Hua, Hao-ming; Ito, Takashi; Qiu, Zhi-gang; Azuma, Junichi

    2005-05-01

    The function for cardiac vascular system of taurine is extensive, and the mechanism is complicated. Taurine protects the cells from the cell injury caused by ischemia etc. Through repressing apoptosis, prevents endothelial dysfunction caused by hyperglycemia, hypercholesterolemia, smoking and homocysteine; suppresses the proliferation and calcification in vascular smooth muscle cells, promotes metabolization and excretion of cholesterol in the animal models of hyperlipemia, and confers the resistance to an oxidant, hypochlorous acid, produced by neutrophil on cells, and taurine chrolamine to inhibit activation of NF-kappaB, which might be associated with anti-atherosclerotic effect. Taurine mainly acts inside the cell. However, taurine transport system becomes aberrant in pathological myocardial and vascular tissue. In addition, taurine improves cardiovascular function in fructose-induced hypertension and an iron-overload murine animal models. PMID:16075725

  1. 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

    2015-01-01

    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. PMID:26113184

  2. Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving.

    PubMed

    Shiels, H A; Galli, G L J; Block, B A

    2015-02-01

    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 Ca(2+) 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

  3. 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

  4. Evidence for improved cardiac performance after beta-blockade in patients with coronary artery disease.

    PubMed

    Reale, A; Nigri, A; Gioffrè, P A

    1976-01-01

    The study was undertaken to investigate the acute haemodynamic effects of bunitrolol (0-2-hydroxy-3-(tert.butylamino)-propoxy)-bity. Right and left heart catheterization was performed in eleven patients with documented coronary artery disease. After bunitrolol (10 mg i.v.), there was a statistically significant decrease in left ventricular and aortic systolic pressures left ventricular end-diastolic pressure, aortic diastolic and mean pressures, pressure-rate product and compliance index (delta P/delta V). Left ventricular dp/dt, left ventricular dp/dt over isovolumic pressure, systemic resistance and heart rate tended to decrease, stroke volume and left ventricular stroke work index tended to increase, without statistical significance. Cardiac index showed individual variations, the mean values for the group being unchanged. Correlation of left ventricular end-diastolic pressure and left ventricular stroke work index showed a shift toward improved ventricular function curve in most cases, deterioration in no instance. Supine exercise was performed in ten patients. Angina occurred in nine patients; in five only before and in four before and after beta-blockade. Post-drug exercise heart rate, pressure-rate product and left ventricular end-diastolic pressure were significantly lower, the latter also in the four patients who still presented exercise angina. It is concluded that certain beta-blockers can improve cardiac performance at rest and during exercise in patients with coronary artery disease. This is explainable on the basis of a more favourable balance between oxygen supply and demand, together with a less marked negative inotropic effect due to the partial agonist activity of the agent used in the study. PMID:18374

  5. Plasma haemostatic markers, endothelial function and ambulatory blood pressure changes with home versus hospital cardiac rehabilitation: the Birmingham Rehabilitation Uptake Maximisation Study

    PubMed Central

    Lee, K W; Blann, A D; Jolly, K; Lip, G Y H

    2006-01-01

    Background Cardiac rehabilitation is an accepted therapeutic intervention in patients after myocardial infarction or coronary revascularisation. The effects of cardiac rehabilitation programmes, whether home based or hospital based, on haemostatic indices (as reflected by fibrinogen, plasma viscosity, fibrin D‐dimer (an index of thrombogenesis), von Willebrand factor (vWf, an index of endothelial damage/dysfunction), soluble P‐selectin (an index of platelet activation)), vasomotor function (using flow‐mediated dilatation (FMD)) and ambulatory blood pressure (ABP) in patients with coronary heart disease are unknown. Methods 81 patients (66 men, mean (SD) 59 (11) years) after myocardial infarction or coronary revascularisation were randomised to comprehensive hospital‐based (n = 40) or home‐based (n = 41) cardiac rehabilitation. Plasma levels of vWf, D‐dimer, fibrinogen, soluble P‐selectin and plasma viscosity, as well as FMD and 24‐h ABP, were measured at baseline and after 3 months of cardiac rehabilitation. Results In patients who completed cardiac rehabilitation, levels of vWf, fibrinogen and D‐dimer were significantly lower and FMD improved (all p⩽0.001), whereas levels were unchanged in controls. Significant reductions were also observed in 24‐h mean systolic blood pressure, diastolic blood pressure and mean aortic pressure after completion of cardiac rehabilitation (all p<0.05). No significant differences were observed between the hospital‐based and home‐based cardiac rehabilitation programmes on these indices. Conclusions Cardiac rehabilitation improves haemostasis, endothelial function and ABP in patients with coronary heart disease, with no significant differences between home‐based and hospital‐based cardiac rehabilitation programmes. These effects may contribute to the beneficial effects of cardiac rehabilitation programmes on CV outcomes. PMID:16807272

  6. 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

  7. Effect of Yoga on migraine: A comprehensive study using clinical profile and cardiac autonomic functions

    PubMed Central

    Kisan, Ravikiran; Sujan, MU; Adoor, Meghana; Rao, Raghavendra; Nalini, A; Kutty, Bindu M; Chindanda Murthy, BT; Raju, TR; Sathyaprabha, TN

    2014-01-01

    Context and Aims: Migraine is an episodic disabling headache requiring long-term management. Migraine management through Yoga therapy would reduce the medication cost with positive health benefits. Yoga has shown to improve the quality of life, reduce the episode of headache and medication. The aim of the present study was to evaluate the efficacy of Yoga as an adjuvant therapy in migraine patients by assessing clinical outcome and autonomic functions tests. Subjects and Methods: Migraine patients were randomly given either conventional care (n = 30) or Yoga with conventional care (n = 30). Yoga group received Yoga practice session for 5 days a week for 6 weeks along with conventional care. Clinical assessment (frequency, intensity of headache and headache impact) and autonomic function test were done at baseline and at the end of the intervention. Results: Yoga with conventional care and convention care groups showed significant improvement in clinical variables, but it was better with Yoga therapy. Improvement in the vagal tone along with reduced sympathetic activity was observed in patients with migraine receiving Yoga as adjuvant therapy. Conclusions: Intervention showed significant clinical improvement in both groups. Headache frequency and intensity were reduced more in Yoga with conventional care than the conventional care group alone. Furthermore, Yoga therapy enhanced the vagal tone and decreased the sympathetic drive, hence improving the cardiac autonomic balance. Thus, Yoga therapy can be effectively incorporated as an adjuvant therapy in migraine patients. PMID:25035622

  8. Myocardial injection of apelin-overexpressing bone marrow cells improves cardiac repair via upregulation of Sirt3 after myocardial infarction.

    PubMed

    Li, Lanfang; Zeng, Heng; Hou, Xuwei; He, Xiaochen; Chen, Jian-Xiong

    2013-01-01

    Our previous study shows that treatment with apelin increases bone marrow cells (BMCs) recruitment and promotes cardiac repair after myocardial infarction (MI). The objective of this study was to investigate whether overexpression of apelin in BMCs improved cell therapy and accelerated cardiac repair and functional recovery in post-MI mice. Mouse myocardial infarction was achieved by coronary artery ligation and BMCs overexpressing apelin (apelin-BMCs) or GFP (GFP-BMCs) were injected into ischemic area immediately after surgery. In vitro, exposure of cultured BMCs to apelin led to a gradual increase in SDF-1á and CXCR4 expression. Intramyocardial delivery of apelin-BMCs in post-MI mice resulted in a significant increase number of APJ⁺/c-kit⁺/Sca1⁺ cells in the injected area compared to GFP-BMCs treated post-MI mice. Treatment with apelin-BMCs increased expression of VEGF, Ang-1 and Tie-2 in post-MI mice. Apelin-BMCs treatment also significantly increased angiogenesis and attenuated cardiac fibrosis formation in post-MI mice. Most importantly, treatment with apelin-BMCs significantly improved left ventricular (LV) systolic function in post-MI mice. Mechanistically, Apelin-BMCs treatment led to a significant increase in Sirtuin3 (Sirt3) expression and reduction of reactive oxygen species (ROS) formation. Treatment of cultured BMCs with apelin also increased Notch3 expression and Akt phosphorylation. Apelin treatment further attenuated stress-induced apoptosis whereas knockout of Sirt3 abolished anti-apoptotic effect of apelin in cultured BMCs. Moreover, knockout of Sirt3 significantly attenuated apelin-BMCs-induced VEGF expression and angiogenesis in post-MI mice. Knockout of Sirt3 further blunted apelin-BMCs-mediated improvement of cardiac repair and systolic functional recovery in post-MI mice. These data suggest that apelin improves BMCs therapy on cardiac repair and systolic function in post-MI mice. Upregulation of Sirt3 may contribute to the protective

  9. Myocardial Injection of Apelin-Overexpressing Bone Marrow Cells Improves Cardiac Repair via Upregulation of Sirt3 after Myocardial Infarction

    PubMed Central

    Hou, Xuwei; He, Xiaochen; Chen, Jian-Xiong

    2013-01-01

    Our previous study shows that treatment with apelin increases bone marrow cells (BMCs) recruitment and promotes cardiac repair after myocardial infarction (MI). The objective of this study was to investigate whether overexpression of apelin in BMCs improved cell therapy and accelerated cardiac repair and functional recovery in post-MI mice. Mouse myocardial infarction was achieved by coronary artery ligation and BMCs overexpressing apelin (apelin-BMCs) or GFP (GFP-BMCs) were injected into ischemic area immediately after surgery. In vitro, exposure of cultured BMCs to apelin led to a gradual increase in SDF-1á and CXCR4 expression. Intramyocardial delivery of apelin-BMCs in post-MI mice resulted in a significant increase number of APJ+/c-kit+/Sca1+ cells in the injected area compared to GFP-BMCs treated post-MI mice. Treatment with apelin-BMCs increased expression of VEGF, Ang-1 and Tie-2 in post-MI mice. Apelin-BMCs treatment also significantly increased angiogenesis and attenuated cardiac fibrosis formation in post-MI mice. Most importantly, treatment with apelin-BMCs significantly improved left ventricular (LV) systolic function in post-MI mice. Mechanistically, Apelin-BMCs treatment led to a significant increase in Sirtuin3 (Sirt3) expression and reduction of reactive oxygen species (ROS) formation. Treatment of cultured BMCs with apelin also increased Notch3 expression and Akt phosphorylation. Apelin treatment further attenuated stress-induced apoptosis whereas knockout of Sirt3 abolished anti-apoptotic effect of apelin in cultured BMCs. Moreover, knockout of Sirt3 significantly attenuated apelin-BMCs-induced VEGF expression and angiogenesis in post-MI mice. Knockout of Sirt3 further blunted apelin-BMCs-mediated improvement of cardiac repair and systolic functional recovery in post-MI mice. These data suggest that apelin improves BMCs therapy on cardiac repair and systolic function in post-MI mice. Upregulation of Sirt3 may contribute to the protective effect

  10. Interoception across Modalities: On the Relationship between Cardiac Awareness and the Sensitivity for Gastric Functions

    PubMed Central

    Herbert, Beate M.; Muth, Eric R.; Pollatos, Olga; Herbert, Cornelia

    2012-01-01

    The individual sensitivity for ones internal bodily signals (“interoceptive awareness”) has been shown to be of relevance for a broad range of cognitive and affective functions. Interoceptive awareness has been primarily assessed via measuring the sensitivity for ones cardiac signals (“cardiac awareness”) which can be non-invasively measured by heartbeat perception tasks. It is an open question whether cardiac awareness is related to the sensitivity for other bodily, visceral functions. This study investigated the relationship between cardiac awareness and the sensitivity for gastric functions in healthy female persons by using non-invasive methods. Heartbeat perception as a measure for cardiac awareness was assessed by a heartbeat tracking task and gastric sensitivity was assessed by a water load test. Gastric myoelectrical activity was measured by electrogastrography (EGG) and subjective feelings of fullness, valence, arousal and nausea were assessed. The results show that cardiac awareness was inversely correlated with ingested water volume and with normogastric activity after water load. However, persons with good and poor cardiac awareness did not differ in their subjective ratings of fullness, nausea and affective feelings after drinking. This suggests that good heartbeat perceivers ingested less water because they subjectively felt more intense signals of fullness during this lower amount of water intake compared to poor heartbeat perceivers who ingested more water until feeling the same signs of fullness. These findings demonstrate that cardiac awareness is related to greater sensitivity for gastric functions, suggesting that there is a general sensitivity for interoceptive processes across the gastric and cardiac modality. PMID:22606278

  11. 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.

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

    PubMed

    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 Ca(2+) signal. Promisingly, our smartly formulated Ca(2+)-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

  13. 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

  14. 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.

  15. Efficacy of cardiac resynchronization with defibrillator insertion in patients undergone coronary artery bypass graft: A cohort study of cardiac function

    PubMed Central

    Karbasi-Afshar, Reza; Ramezani-Binabaj, Mahdi; Rezaee-Zavareh, Mohammad Saeid; Saburi, Amin; Ajudani, Reza

    2015-01-01

    Introduction: Cardiac resynchronization therapy (CRT) is a proven therapeutic method in selected patients with heart failure and systolic dysfunction which increases left ventricular function and patient survival. We designed a study that included patients undergoing coronary artery bypass graft (CABG), with and without CRT-defibrillator (CRT-D) inserting and then measured its effects on these two groups. Patients and Methods: Between 2010 and 2013, we conducted a prospective cohort study on 100 coronary artery disease patients where candidate for CABG. Then based on the receiving CRT-D, the patients were categorized in two groups; Group 1 (n = 48, with CRT-D insertion before CABG) and Group 2 (n = 52 without receiving CRT-D). Thereafter both of these groups were followed-up at 1–3 months after CABG for mortality, hospitalization, atrial fibrillation (AF), echocardiographic assessment, and New York Heart Association (NYHA) class level. Results: The mean age of participants in Group 1 (48 male) and in Group 2 (52 male) was 58 ± 13 and 57 ± 12 respectively. Difference between Groups 1 and 2 in cases of mean left ventricular ejection fraction (LVEF) changes and NYHA class level was significant (P > 0.05). Hospitalization (P = 0.008), mortality rate (P = 0.007), and AF were significantly different between these two groups. Conclusions: The results showed that the increase in LVEF and patient's improvement according to NYHA-class was significant in the first group, and readmission, mortality rate and AF was increased significantly in the second group. PMID:25566709

  16. 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

  17. Functional Analysis of the Engineered Cardiac Tissue Grown on Recombinant Spidroin Fiber Meshes

    PubMed Central

    Teplenin, Alexander; Krasheninnikova, Anna; Agladze, Nadezhda; Sidoruk, Konstantin; Agapova, Olga; Agapov, Igor; Bogush, Vladimir; Agladze, Konstantin

    2015-01-01

    In the present study, we examined the ability of the recombinant spidroin to serve as a substrate for the cardiac tissue engineering. For this purpose, isolated neonatal rat cardiomyocytes were seeded on the electrospun spidroin fiber matrices and cultured to form the confluent cardiac monolayers. Besides the adhesion assay and immunostaining analysis, we tested the ability of the cultured cardiomyocytes to form a functional cardiac syncytium by studying excitation propagation in the cultured tissue with the aid of optical mapping. It was demonstrated that recombinant spidroin fiber meshes are directly suitable for the adherence and growth of the cardiomyocytes without additional coating with the attachment factors, such as fibronectin. PMID:25799394

  18. Systematic Characterization of the Murine Mitochondrial Proteome Using Functionally Validated Cardiac Mitochondria

    PubMed Central

    Zhang, Jun; Li, Xiaohai; Mueller, Michael; Wang, Yueju; Zong, Chenggong; Deng, Ning; Vondriska, Thomas M.; Liem, David A.; Yang, Jeong-In; Korge, Paavo; Honda, Henry; Weiss, James N.; Apweiler, Rolf; Ping, Peipei

    2009-01-01

    Mitochondria play essential roles in cardiac pathophysiology and the murine model has been extensively used to investigate cardiovascular diseases. In the present study, we characterized murine cardiac mitochondria using an LC/MS/MS approach. We extracted and purified cardiac mitochondria; validated their functionality to ensure the final preparation contains necessary components to sustain their normal function; and subjected these validated organelles to LC/MS/MS-based protein identification. A total of 940 distinct proteins were identified from murine cardiac mitochondria, among which, 480 proteins were not previously identified by major proteomic profiling studies. The 940 proteins consist of functional clusters known to support oxidative phosphorylation, metabolism and biogenesis. In addition, there are several other clusters--including proteolysis, protein folding, and reduction/oxidation signaling-which ostensibly represent previously under-appreciated tasks of cardiac mitochondria. Moreover, many identified proteins were found to occupy other subcellular locations, including cytoplasm, ER, and golgi, in addition to their presence in the mitochondria. These results provide a comprehensive picture of the murine cardiac mitochondrial proteome and underscore tissue- and species-specification. Moreover, the use of functionally intact mitochondria insures that the proteomic observations in this organelle are relevant to its normal biology and facilitates decoding the interplay between mitochondria and other organelles. PMID:18348319

  19. miR-300 mediates Bmi1 function and regulates differentiation in primitive cardiac progenitors

    PubMed Central

    Cruz, F M; Tomé, M; Bernal, J A; Bernad, A

    2015-01-01

    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. PMID:26512961

  20. miR-300 mediates Bmi1 function and regulates differentiation in primitive cardiac progenitors.

    PubMed

    Cruz, F M; Tomé, M; Bernal, J A; Bernad, A

    2015-01-01

    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. PMID:26512961

  1. 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. PMID:26679609

  2. Nitrite reductase function of deoxymyoglobin: oxygen sensor and regulator of cardiac energetics and function.

    PubMed

    Rassaf, Tienush; Flögel, Ulrich; Drexhage, Christine; Hendgen-Cotta, Ulrike; Kelm, Malte; Schrader, Jürgen

    2007-06-22

    Although the primary function of myoglobin (Mb) has been considered to be cellular oxygen storage and supply, recent studies have suggested to classify Mb as a multifunctional allosteric enzyme. In the heart, Mb acts as a potent scavenger of nitric oxide (NO) and contributes to the attenuation of oxidative damage. Here we report that a dynamic cycle exists in which a decrease in tissue oxygen tension drives the conversion of Mb from being an NO scavenger in normoxia to an NO producer in hypoxia. The NO generated by reaction of deoxygenated Mb with nitrite is functionally relevant and leads to a downregulation of cardiac energy status, which was not observed in mice lacking Mb. As a consequence, myocardial oxygen consumption is reduced and cardiac contractility is dampened in wild-type mice. We propose that this pathway represents a novel homeostatic mechanism by which a mismatch between oxygen supply and demand in muscle is translated into the fractional increase of deoxygenated Mb exhibiting enhanced nitrite reductase activity. Thus, Mb may act as an oxygen sensor which through NO can adjust muscle energetics to limited oxygen supply. PMID:17495223

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

    PubMed

    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. PMID:26974408

  4. Cardiac function and rejection following transplantation of the heart

    SciTech Connect

    Schober, O.; Schuler, S.; Gratz, K.; Warnecke, H.; Lang, W.; Hetzer, R.; Creutzig, H.

    1985-05-01

    It was the purpose of the study to evaluate the noninvasive detection of rejection following cardiac transplantation. Multigated cardiac blood pool imaging (MUGA) at rest with assessment of ejection fraction (EF) and regional wall motion was determined prospectively in 14 patients with 180 studies (follow up 5.1 +- 3.2 months) following orthotopic cardiac transplantation. The results were compared with histological examination of a percutaneous endocardial biopsy specimen (EMB) from the right ventricle. Diagnosis of rejection by EF measurement was defined by a decrease of 10% if EF < 70%, and 15% if EF > 70%. In 152 studies a normal MUGA study correlated with none rejection as defined by EMB. In 14 of 22 studies with moderate or severe rejection decrease of EF followed the rejection with a delay of 5 days. Septal wall motion abnormalities were typical. In 6 studies an abnormal temporal course of EF was not related to a similar finding in EMB. A sensitivity of 69% and a specifity of 96% can be estimated in the investigated group, in which all patients survived during the period of the study. It is concluded that rejection can be excluded by noninvasive MUGA (specifity 96%) and that MUGA is predictive of rejection (sensitivity 67%) mostly with a delay of 5 days.

  5. Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation.

    PubMed

    Cagavi, Esra; Bartulos, Oscar; Suh, Carol Y; Sun, Baonan; Yue, Zhichao; Jiang, Zhengxin; Yue, Lixia; Qyang, Yibing

    2014-01-01

    As heart failure due to myocardial infarction remains a leading cause of morbidity worldwide, cell-based cardiac regenerative therapy using cardiac progenitor cells (CPCs) could provide a potential treatment for the repair of injured myocardium. As adult CPCs may have limitations regarding tissue accessibility and proliferative ability, CPCs derived from embryonic stem cells (ESCs) could serve as an unlimited source of cells with high proliferative ability. As one of the CPCs that can be derived from embryonic stem cells, Isl1 expressing cardiac progenitor cells (Isl1-CPCs) may serve as a valuable source of cells for cardiac repair due to their high cardiac differentiation potential and authentic cardiac origin. In order to generate an unlimited number of Isl1-CPCs, we used a previously established an ESC line that allows for isolation of Isl1-CPCs by green fluorescent protein (GFP) expression that is directed by the mef2c gene, specifically expressed in the Isl1 domain of the anterior heart field. To improve the efficiency of cardiac differentiation of Isl1-CPCs, we studied the role of Bmp4 in cardiogenesis of Isl1-CPCs. We show an inductive role of Bmp directly on cardiac progenitors and its enhancement on early cardiac differentiation of CPCs. Upon induction of Bmp4 to Isl1-CPCs during differentiation, the cTnT+ cardiomyocyte population was enhanced 2.8±0.4 fold for Bmp4 treated CPC cultures compared to that detected for vehicle treated cultures. Both Bmp4 treated and untreated cardiomyocytes exhibit proper electrophysiological and calcium signaling properties. In addition, we observed a significant increase in Tbx5 and Tbx20 expression in differentiation cultures treated with Bmp4 compared to the untreated control, suggesting a link between Bmp4 and Tbx genes which may contribute to the enhanced cardiac differentiation in Bmp4 treated cultures. Collectively these findings suggest a cardiomyogenic role for Bmp4 directly on a pure population of Isl1 expressing

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

    PubMed

    Loiselle, Denis S; Han, June-Chiew; Goo, Eden; Chapman, Brian; Barclay, Christopher J; Hickey, Anthony J R; Taberner, Andrew J

    2016-09-01

    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

  7. Effect of Depression and Sertraline Treatment on Cardiac Function in Female Nonhuman Primates

    PubMed Central

    Groban, Leanne; Kitzman, Dalane W.; Register, Thomas C.; Shively, Carol A.

    2014-01-01

    Objective Depression is a proposed risk factor for heart failure based largely on epidemiological data; little experimental data is available addressing this hypothesis. Methods Depression was evaluated in relation to cardiac structural and functional phenotypes assessed by transthoracic echocardiography in 42 adult female cynomolgus monkeys that consumed a Western-like diet for 3 years. Half of the monkeys were treated with the SSRI sertraline HCl for 18 months and depressive behavior was assessed for 12 months prior to echocardiography. Results Depressed monkeys (the 19/42 with depressive behavior rates above the mean rate) had higher HRs (171±4.1 vs 152±6.1), and smaller BSA (0.13±0.003 vs 0.15±0.004). Cardiac measures showed lower LV end systolic dimension (0.75±0.05 vs 0.89±0.04), LV systolic (0.76±0.08 vs 1.2±0.11) and diastolic (2.4±0.23 vs 3.4±0.26) volumes, and left atrial volumes (1.15±0.14 vs 1.75±0.12) in depressed versus nondepressed monkeys (p’s <0.05). Doppler profiles of depressed monkeys indicated greater myocardial relaxation (higher e′ and higher e′/a′ ratio) and lower filling pressures (lower E/e′) compared to nondepressed monkeys (p’s<0.05). Although treatment with sertraline reduced HR (150±5.8 vs 171±4.8) and modestly increased chamber dimensions (left ventricular end systolic dimension: 0.91±0.05 vs 0.74±0.03; left ventricular end diastolic dimension, BSA adjusted 1.69±0.05 vs 1.47±0.06) (p’s<0.05), it did not overtly affect systolic or diastolic function (p’s >0.10). Conclusions These data suggest that behavioral depression in female primates is accompanied by differences in cardiac function, although not in ways classically associated with subclinical heart failure. SSRIs show promise in supporting heart function by reducing HR and perhaps improving LV filling, however further investigation is needed to confirm this hypothesis. PMID:24470133

  8. Does quality of life improve in octogenarians following cardiac surgery? A systematic review

    PubMed Central

    Abah, Udo; Dunne, Mike; Cook, Andrew; Hoole, Stephen; Brayne, Carol; Vale, Luke; Large, Stephen

    2015-01-01

    Objectives Current outcome measures in cardiac surgery are largely described in terms of mortality. Given the changing demographic profiles and increasingly aged populations referred for cardiac surgery this may not be the most appropriate measure. Postoperative quality of life is an outcome of importance to all ages, but perhaps particularly so for those whose absolute life expectancy is limited by virtue of age. We undertook a systematic review of the literature to clarify and summarise the existing evidence regarding postoperative quality of life of older people following cardiac surgery. For the purpose of this review we defined our population as people aged 80 years of age or over. Methods A systematic review of MEDLINE, EMBASE, Cochrane Library, trial registers and conference abstracts was undertaken to identify studies addressing quality of life following cardiac surgery in patients 80 or over. Results Forty-four studies were identified that addressed this topic, of these nine were prospective therefore overall conclusions are drawn from largely retrospective observational studies. No randomised controlled data were identified. Conclusions Overall there appears to be an improvement in quality of life in the majority of elderly patients following cardiac surgery, however there was a minority in whom quality of life declined (8–19%). There is an urgent need to validate these data and if correct to develop a robust prediction tool to identify these patients before surgery. Such a tool could guide informed consent, policy development and resource allocation. PMID:25922099

  9. Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter.

    PubMed

    Holmström, Kira M; Pan, Xin; Liu, Julia C; Menazza, Sara; Liu, Jie; Nguyen, Tiffany T; Pan, Haihui; Parks, Randi J; Anderson, Stasia; Noguchi, Audrey; Springer, Danielle; Murphy, Elizabeth; Finkel, Toren

    2015-08-01

    Mitochondrial calcium is thought to play an important role in the regulation of cardiac bioenergetics and function. The entry of calcium into the mitochondrial matrix requires that the divalent cation pass through the inner mitochondrial membrane via a specialized pore known as the mitochondrial calcium uniporter (MCU). Here, we use mice deficient of MCU expression to rigorously assess the role of mitochondrial calcium in cardiac function. Mitochondria isolated from MCU(-/-) mice have reduced matrix calcium levels, impaired calcium uptake and a defect in calcium-stimulated respiration. Nonetheless, we find that the absence of MCU expression does not affect basal cardiac function at either 12 or 20months of age. Moreover, the physiological response of MCU(-/-) mice to isoproterenol challenge or transverse aortic constriction appears similar to control mice. Thus, while mitochondria derived from MCU(-/-) mice have markedly impaired mitochondrial calcium handling, the hearts of these animals surprisingly appear to function relatively normally under basal conditions and during stress. PMID:26057074

  10. 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%.

  11. 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

  12. Functional phosphorylation sites in cardiac myofilament proteins are evolutionarily conserved in skeletal myofilament proteins.

    PubMed

    Gross, Sean M; Lehman, Steven L

    2016-06-01

    Protein phosphorylation plays an important role in regulating cardiac contractile function, but phosphorylation is not thought to play a regulatory role in skeletal muscle. To examine how myofilament phosphorylation arose in the human heart, we analyzed the amino acid sequences of 25 cardiac phosphorylation sites in animals ranging from fruit flies to humans. These analyses indicated that of the 25 human phosphorylation sites examined, 11 have been conserved across vertebrates and four have been sporadically present in vertebrates. Furthermore, all 11 of the cardiac sites found across vertebrates were present in skeletal muscle isoforms, along with three sites that were sporadically present. Based on the conservation of amino acid sequences between cardiac and skeletal contractile proteins, we tested for phosphorylation in mammalian skeletal muscle using several biochemical techniques and found evidence that multiple myofilament proteins were phosphorylated. Several of these phosphorylation sites were validated using mass spectrometry, including one site that is present in slow- and fast-twitch troponin I (TnI), but was lost in cardiac TnI. Thus, several myofilament phosphorylation sites present in the human heart likely arose in invertebrate muscle, have been evolutionarily conserved in skeletal muscle, and potentially have functional effects in both skeletal and cardiac muscle. PMID:26993364

  13. 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. PMID:26519029

  14. Uterine-derived progenitor cells are immunoprivileged and effectively improve cardiac regeneration when used for cell therapy.

    PubMed

    Ludke, Ana; Wu, Jun; Nazari, Mansoreh; Hatta, Kota; Shao, Zhengbo; Li, Shu-Hong; Song, Huifang; Ni, Nathan C; Weisel, Richard D; Li, Ren-Ke

    2015-07-01

    Cell therapy to prevent cardiac dysfunction after myocardial infarction (MI) is less effective in aged patients because aged cells have decreased regenerative capacity. Allogeneic transplanted stem cells (SCs) from young donors are usually rejected. Maintaining transplanted SC immunoprivilege may dramatically improve regenerative outcomes. The uterus has distinct immune characteristics, and we showed that reparative uterine SCs home to the myocardium post-MI. Here, we identify immunoprivileged uterine SCs and assess their effects on cardiac regeneration after allogeneic transplantation. We found more than 20% of cells in the mouse uterus have undetectable MHC I expression by flow cytometry. Uterine MHC I((neg)) and MHC I((pos)) cells were separated by magnetic cell sorting. The MHC I((neg)) population expressed the SC markers CD34, Sca-1 and CD90, but did not express MHC II or c-kit. In vitro, MHC I((neg)) and ((pos)) SCs show colony formation and endothelial differentiation capacity. In mixed leukocyte co-culture, MHC I((neg)) cells showed reduced cell death and leukocyte proliferation compared to MHC I((pos)) cells. MHC I((neg)) and ((pos)) cells had significantly greater angiogenic capacity than mesenchymal stem cells. The benefits of intramyocardial injection of allogeneic MHC I((neg)) cells after MI were comparable to syngeneic bone marrow cell transplantation, with engraftment in cardiac tissue and limited recruitment of CD4 and CD8 cells up to 21 days post-MI. MHC I((neg)) cells preserved cardiac function, decreased infarct size and improved regeneration post-MI. This new source of immunoprivileged cells can induce neovascularization and could be used as allogeneic cell therapy for regenerative medicine. PMID:25939780

  15. Acceleration of crossbridge kinetics by protein kinase A phosphorylation of cardiac myosin binding protein C modulates cardiac function.

    PubMed

    Tong, Carl W; Stelzer, Julian E; Greaser, Marion L; Powers, Patricia A; Moss, Richard L

    2008-10-24

    Normal cardiac function requires dynamic modulation of contraction. beta1-adrenergic-induced protein kinase (PK)A phosphorylation of cardiac myosin binding protein (cMyBP)-C may regulate crossbridge kinetics to modulate contraction. We tested this idea with mechanical measurements and echocardiography in a mouse model lacking 3 PKA sites on cMyBP-C, ie, cMyBP-C(t3SA). We developed the model by transgenic expression of mutant cMyBP-C with Ser-to-Ala mutations on the cMyBP-C knockout background. Western blots, immunofluorescence, and in vitro phosphorylation combined to show that non-PKA-phosphorylatable cMyBP-C expressed at 74% compared to normal wild-type (WT) and was correctly positioned in the sarcomeres. Similar expression of WT cMyBP-C at 72% served as control, ie, cMyBP-C(tWT). Skinned myocardium responded to stretch with an immediate increase in force, followed by a transient relaxation of force and finally a delayed development of force, ie, stretch activation. The rate constants of relaxation, k(rel) (s-1), and delayed force development, k(df) (s-1), in the stretch activation response are indicators of crossbridge cycling kinetics. cMyBP-C(t3SA) myocardium had baseline k(rel) and k(df) similar to WT myocardium, but, unlike WT, k(rel) and k(df) were not accelerated by PKA treatment. Reduced dobutamine augmentation of systolic function in cMyBP-C(t3SA) hearts during echocardiography corroborated the stretch activation findings. Furthermore, cMyBP-C(t3SA) hearts exhibited basal echocardiographic findings of systolic dysfunction, diastolic dysfunction, and hypertrophy. Conversely, cMyBP-C(tWT) hearts performed similar to WT. Thus, PKA phosphorylation of cMyBP-C accelerates crossbridge kinetics and loss of this regulation leads to cardiac dysfunction. PMID:18802026

  16. Functional interaction between charged nanoparticles and cardiac tissue: a new paradigm for cardiac arrhythmia?

    PubMed Central

    Ruenraroengsak, Pakatip; Shevchuk, Andrew I; Korchev, Yuri E; Lab, Max J; Tetley, Teresa D; Gorelik, Julia

    2016-01-01

    Aim To investigate the effect of surface charge of therapeutic nanoparticles on sarcolemmal ionic homeostasis and the initiation of arrhythmias. Materials & methods Cultured neonatal rat myocytes were exposed to 50 nm-charged polystyrene latex nanoparticles and examined using a combination of hopping probe scanning ion conductance microscopy, optical recording of action potential characteristics and patch clamp. Results Positively charged, amine-modified polystyrene latex nanoparticles showed cytotoxic effects and induced large-scale damage to cardiomyocyte membranes leading to calcium alternans and cell death. By contrast, negatively charged, carboxyl-modified polystyrene latex nanoparticles (NegNPs) were not overtly cytotoxic but triggered formation of 50–250-nm nanopores in the membrane. Cells exposed to NegNPs revealed pro-arrhythmic events, such as delayed afterdepolarizations, reduction in conduction velocity and pathological increment of action potential duration together with an increase in ionic current throughout the membrane, carried by the nanopores. Conclusion The utilization of charged nanoparticles is a novel concept for targeting cardiac excitability. However, this unique nanoscopic investigation reveals an altered electrophysiological substrate, which sensitized the heart cells towards arrhythmias. PMID:23140503

  17. Cardiac Biomarkers: a Focus on Cardiac Regeneration

    PubMed Central

    Forough, Reza; Scarcello, Catherine; Perkins, Matthew

    2011-01-01

    Historically, biomarkers have been used in two major ways to maintain and improve better health status: first, for diagnostic purposes, and second, as specific targets to treat various diseases. A new era in treatment and even cure for the some diseases using reprograming of somatic cells is about to be born. In this approach, scientists are successfully taking human skin cells (previously considered terminally-differentiated cells) and re-programming them into functional cardiac myocytes and other cell types in vitro. A cell reprograming approach for treatment of cardiovascular diseases will revolutionize the field of medicine and significantly expand the human lifetime. Availability of a comprehensive catalogue for cardiac biomarkers is necessary for developing cell reprograming modalities to treat cardiac diseases, as well as for determining the progress of reprogrammed cells as they become cardiac cells. In this review, we present a comprehensive survey of the cardiac biomarkers currently known. PMID:23074366

  18. Effects of heme oxygenase-1 upregulation on blood pressure and cardiac function in an animal model of hypertensive myocardial infarction.

    PubMed

    Chen, Tian-Meng; Li, Jian; Liu, Lin; Fan, Li; Li, Xiao-Ying; Wang, Yu-Tang; Abraham, Nader G; Cao, Jian

    2013-01-01

    In this study, we evaluate the effect of HO-1 upregulation on blood pressure and cardiac function in the new model of infarct spontaneous hypertensive rats (ISHR). Male spontaneous hypertensive rats (SHR) at 13 weeks (n = 40) and age-matched male Wistar (WT) rats (n = 20) were divided into six groups: WT (sham + normal saline (NS)), WT (sham + Co(III) Protoporphyrin IX Chloride (CoPP)), SHR (myocardial infarction (MI) + NS), SHR (MI + CoPP), SHR (MI + CoPP + Tin Mesoporphyrin IX Dichloride (SnMP)), SHR (sham + NS); CoPP 4.5 mg/kg, SnMP 15 mg/kg, for six weeks, one/week, i.p., n = 10/group. At the sixth week, echocardiography (UCG) and hemodynamics were performed. Then, blood samples and heart tissue were collected. Copp treatment in the SHR (MI + CoPP) group lowered blood pressure, decreased infarcted area, restored cardiac function (left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), +dp/dt(max), (-dp/dt(max))/left ventricular systolic pressure (LVSP)), inhibited cardiac hypertrophy and ventricular enlargement (downregulating left ventricular end-systolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and heart weight/body weight (HW/BW)), lowered serum CRP, IL-6 and Glu levels and increased serum TB, NO and PGI2 levels. Western blot and immunohistochemistry showed that HO-1 expression was elevated in the SHR (MI + CoPP) group, while co-administration with SnMP suppressed the benefit functions mentioned above. In conclusion, HO-1 upregulation can lower blood pressure and improve post-infarct cardiac function in the ISHR model. These functions may be involved in the inhibition of inflammation and the ventricular remodeling process and in the amelioration of glucose metabolism and endothelial dysfunction. PMID:23358254

  19. Effect of Obesity on Cardiac Function in Children and Adolescents: A Review

    PubMed Central

    Rowland, Thomas W.

    2007-01-01

    Increases in cardiac mass, ventricular dimensions, and stroke volume are typically observed in obese adults, accompanied by evidence of diminished ventricular systolic and diastolic function. Given sufficient severity and duration of excessive body fat, signs of overt congestive heart failure may ensue (cardiomyopathy of obesity). This review of cardiac findings in obese children and adolescents indicates similar anatomic features as well as early subclinical findings of ventricular dysfunction. However, cardiac functional reserve (cardiovascular fitness) appears to be preserved even in those with morbid levels of obesity. Key pointsExcessive body fat increases the work output of the heart.Longstanding increases in heart work result in abnormalities of heart function.Early findings of such changes can be observed in adolescents with severe obesity. PMID:24149418

  20. RoY peptide-modified chitosan-based hydrogel to improve angiogenesis and cardiac repair under hypoxia.

    PubMed

    Shu, Yao; Hao, Tong; Yao, Fanglian; Qian, Yufeng; Wang, Yan; Yang, Boguang; Li, Junjie; Wang, Changyong

    2015-04-01

    Myocardial infarction (MI) still represents the "Number One Killer" in the world. The lack of functional vasculature of the infracted myocardium under hypoxia is one of the main problems for cardiac repair. In this study, a thermosensitive chitosan chloride-RoY (CSCl-RoY) hydrogel was developed to improve angiogenesis under hypoxia after MI. First, RoY peptides were conjugated onto the CSCl chain via amide linkages, and our data show that the conjugation of RoY peptide to CSCl does not interfere with the temperature sensitivity. Then, the effect of CSCl-RoY hydrogels on vascularization in vitro under hypoxia was investigated using human umbilical vein endothelial cells (HUVECs). Results show that CSCl-RoY hydrogels can promote the survival, proliferation, migration and tube formation of HUVECs under hypoxia compared with CSCl hydrogel. Further investigations suggest that CSCl-RoY hydrogels can modulate the expression of membrane surface GRP78 receptor of HUVECs under hypoxia and then activate Akt and ERK1/2 signaling pathways related to cell survival/proliferation, thereby enhancing angiogenic activity of HUVECs under hypoxia. To assess its therapeutic properties in vivo, a MI model was induced in rats by the left anterior descending artery ligation. CSCl or CSCl-RoY hydrogels were injected into the border of infracted hearts. The results demonstrate that the introduction of RoY peptide can not only improve angiogenesis at MI region but also improve the cardiac functions. Overall, we conclude that the CSCl-RoY may represent an ideal scaffold material for injectable cardiac tissue engineering. PMID:25756853

  1. Cardiac autonomic function during sleep: effects of alcohol dependence and evidence of partial recovery with abstinence

    PubMed Central

    de Zambotti, Massimiliano; Willoughby, Adrian R.; Baker, Fiona C.; Sugarbaker, David S.; Colrain, Ian M.

    2015-01-01

    Chronic alcoholism is associated with the development of cardiac and peripheral autonomic nervous system (ANS) pathology. The aim of the present study was to evaluate the extent to which recovery in ANS function could be demonstrated over the first 4 months of abstinence. Fifteen alcoholics (7 women) were studied on three occasions: within a month of detoxification, at approximately 2 months post-detox, and at 4 months post-detox. Thirteen control subjects (6 women) were also studied on three occasions with inter-study intervals matching those of the alcoholics. Six alcoholics relapsed, 48.7 ± 27.9 days following the initial PSG session. ANS function was assessed in the first part of stable non-rapid eye movement sleep. Frequency-domain power spectral analysis of heart rate variability (HRV) produced variables including: heart rate (HR), total power (TP; an index representing total HR variability), High Frequency power (HFa; an index reflecting cardiac vagal modulation), HF proportion of total power (HFprop sympathovagal balance), and HF peak frequency (HFpf; an index reflecting respiration rate). Overall, high total and high frequency variability and low sympathovagal balance and myocardial contractility are considered as desired conditions to promote cardiovascular health. At initial assessment, alcoholics had a higher HR (p < 0.001) and respiratory rate (p < 0.01), and lower vagal activity (HFa; p < 0.01) than controls. Alcoholics showed evidence of recovery in HR (p = 0.039) and HFa (p = 0.031) with 4 months of abstinence. Alcoholics with higher TP at the initial visit showed a greater improvement in TP from the initial to the 4-month follow-up session (r = 0.75, p < 0.05). Alcoholics showed substantial recovery in HR and vagal modulation of HRV with 4 months of abstinence, with evidence that the extent of recovery in HRV may be partially determined by the extent of alcohol dependence-related insult to the cardiac ANS system. These data support other studies

  2. Cardiac autonomic function during sleep: effects of alcohol dependence and evidence of partial recovery with abstinence.

    PubMed

    de Zambotti, Massimiliano; Willoughby, Adrian R; Baker, Fiona C; Sugarbaker, David S; Colrain, Ian M

    2015-06-01

    Chronic alcoholism is associated with the development of cardiac and peripheral autonomic nervous system (ANS) pathology. The aim of the present study was to evaluate the extent to which recovery in ANS function could be demonstrated over the first 4 months of abstinence. Fifteen alcoholics (7 women) were studied on three occasions: within a month of detoxification, at approximately 2 months post-detox, and at 4 months post-detox. Thirteen control subjects (6 women) were also studied on three occasions with inter-study intervals matching those of the alcoholics. Six alcoholics relapsed, 48.7 ± 27.9 days following the initial PSG session. ANS function was assessed in the first part of stable non-rapid eye movement sleep. Frequency-domain power spectral analysis of heart rate variability (HRV) produced variables including: heart rate (HR), total power (TP; an index representing total HR variability), High Frequency power (HFa; an index reflecting cardiac vagal modulation), HF proportion of total power (HFprop sympathovagal balance), and HF peak frequency (HFpf; an index reflecting respiration rate). Overall, high total and high frequency variability and low sympathovagal balance and myocardial contractility are considered as desired conditions to promote cardiovascular health. At initial assessment, alcoholics had a higher HR (p < 0.001) and respiratory rate (p < 0.01), and lower vagal activity (HFa; p < 0.01) than controls. Alcoholics showed evidence of recovery in HR (p = 0.039) and HFa (p = 0.031) with 4 months of abstinence. Alcoholics with higher TP at the initial visit showed a greater improvement in TP from the initial to the 4 month follow-up session (r = 0.75, p < 0.05). Alcoholics showed substantial recovery in HR and vagal modulation of HRV with 4 months of abstinence, with evidence that the extent of recovery in HRV may be partially determined by the extent of alcohol dependence-related insult to the cardiac ANS system. These data support other studies

  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. Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload.

    PubMed

    Shimano, Masayuki; Ouchi, Noriyuki; Nakamura, Kazuto; van Wijk, Bram; Ohashi, Koji; Asaumi, Yasuhide; Higuchi, Akiko; Pimentel, David R; Sam, Flora; Murohara, Toyoaki; van den Hoff, Maurice J B; Walsh, Kenneth

    2011-10-25

    Factors secreted by the heart, referred to as "cardiokines," have diverse actions in the maintenance of cardiac homeostasis and remodeling. Follistatin-like 1 (Fstl1) is a secreted glycoprotein expressed in the adult heart and is induced in response to injurious conditions that promote myocardial hypertrophy and heart failure. The aim of this study was to investigate the role of cardiac Fstl1 in the remodeling response to pressure overload. Cardiac myocyte-specific Fstl1-KO mice were constructed and subjected to pressure overload induced by transverse aortic constriction (TAC). Although Fstl1-KO mice displayed no detectable baseline phenotype, TAC led to enhanced cardiac hypertrophic growth and a pronounced loss in ventricular performance by 4 wk compared with control mice. Conversely, mice that acutely or chronically overexpressed Fstl1 were resistant to pressure overload-induced hypertrophy and cardiac failure. Fstl1-deficient mice displayed a reduction in TAC-induced AMP-activated protein kinase (AMPK) activation in heart, whereas Fstl1 overexpression led to increased myocardial AMPK activation under these conditions. In cultured neonatal cardiomyocytes, administration of Fstl1 promoted AMPK activation and antagonized phenylephrine-induced hypertrophy. Inhibition of AMPK attenuated the antihypertrophic effect of Fstl1 treatment. These results document that cardiac Fstl1 functions as an autocrine/paracrine regulatory factor that antagonizes myocyte hypertrophic growth and the loss of ventricular performance in response to pressure overload, possibly through a mechanism involving the activation of the AMPK signaling axis. PMID:21987816

  5. 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.

  6. Galnt1 Is Required for Normal Heart Valve Development and Cardiac Function

    PubMed Central

    Tian, E; Stevens, Sharon R.; Guan, Yu; Springer, Danielle A.; Anderson, Stasia A.; Starost, Matthew F.; Patel, Vyomesh; Ten Hagen, Kelly G.; Tabak, Lawrence A.

    2015-01-01

    Congenital heart valve defects in humans occur in approximately 2% of live births and are a major source of compromised cardiac function. In this study we demonstrate that normal heart valve development and cardiac function are dependent upon Galnt1, the gene that encodes a member of the family of glycosyltransferases (GalNAc-Ts) responsible for the initiation of mucin-type O-glycosylation. In the adult mouse, compromised cardiac function that mimics human congenital heart disease, including aortic and pulmonary valve stenosis and regurgitation; altered ejection fraction; and cardiac dilation, was observed in Galnt1 null animals. The underlying phenotype is aberrant valve formation caused by increased cell proliferation within the outflow tract cushion of developing hearts, which is first detected at developmental stage E11.5. Developing valves from Galnt1 deficient animals displayed reduced levels of the proteases ADAMTS1 and ADAMTS5, decreased cleavage of the proteoglycan versican and increased levels of other extracellular matrix proteins. We also observed increased BMP and MAPK signaling. Taken together, the ablation of Galnt1 appears to disrupt the formation/remodeling of the extracellular matrix and alters conserved signaling pathways that regulate cell proliferation. Our study provides insight into the role of this conserved protein modification in cardiac valve development and may represent a new model for idiopathic valve disease. PMID:25615642

  7. The Effects of a Rapid Response Team on Decreasing Cardiac Arrest Rates and Improving Outcomes for Cardiac Arrests Outside Critical Care Areas.

    PubMed

    Angel, Melissa; Ghneim, Mira; Song, Juhee; Brocker, Jason; Tipton, Phyllis Hart; Davis, Matthew

    2016-01-01

    A retrospective study was conducted to determine the effects of a well-functioning rapid response team (RRT) within one facility. A well-functioning RRT was associated with fewer cardiac arrests outside critical care settings and decreased critical care length of stay. PMID:27522841

  8. Cardiac resynchronization therapy and AV optimization increase myocardial oxygen consumption, but increase cardiac function more than proportionally☆

    PubMed Central

    Kyriacou, Andreas; Pabari, Punam A.; Mayet, Jamil; Peters, Nicholas S.; Davies, D. Wyn; Lim, P. Boon; Lefroy, David; Hughes, Alun D.; Kanagaratnam, Prapa; Francis, Darrel P.; I.Whinnett, Zachary

    2014-01-01

    Background The mechanoenergetic effects of atrioventricular delay optimization during biventricular pacing (“cardiac resynchronization therapy”, CRT) are unknown. Methods Eleven patients with heart failure and left bundle branch block (LBBB) underwent invasive measurements of left ventricular (LV) developed pressure, aortic flow velocity-time-integral (VTI) and myocardial oxygen consumption (MVO2) at 4 pacing states: biventricular pacing (with VV 0 ms) at AVD 40 ms (AV-40), AVD 120 ms (AV-120, a common nominal AV delay), at their pre-identified individualised haemodynamic optimum (AV-Opt); and intrinsic conduction (LBBB). Results AV-120, relative to LBBB, increased LV developed pressure by a mean of 11(SEM 2)%, p = 0.001, and aortic VTI by 11(SEM 3)%, p = 0.002, but also increased MVO2 by 11(SEM 5)%, p = 0.04. AV-Opt further increased LV developed pressure by a mean of 2(SEM 1)%, p = 0.035 and aortic VTI by 4(SEM 1)%, p = 0.017. MVO2 trended further up by 7(SEM 5)%, p = 0.22. Mechanoenergetics at AV-40 were no different from LBBB. The 4 states lay on a straight line for Δexternal work (ΔLV developed pressure × Δaortic VTI) against ΔMVO2, with slope 1.80, significantly > 1 (p = 0.02). Conclusions Biventricular pacing and atrioventricular delay optimization increased external cardiac work done but also myocardial oxygen consumption. Nevertheless, the increase in cardiac work was ~ 80% greater than the increase in oxygen consumption, signifying an improvement in cardiac mechanoenergetics. Finally, the incremental effect of optimization on external work was approximately one-third beyond that of nominal AV pacing, along the same favourable efficiency trajectory, suggesting that AV delay dominates the biventricular pacing effect — which may therefore not be mainly “resynchronization”. PMID:24332598

  9. 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

  10. Human Cardiac Function Simulator for the Optimal Design of a Novel Annuloplasty Ring with a Sub-valvular Element for Correction of Ischemic Mitral Regurgitation.

    PubMed

    Baillargeon, Brian; Costa, Ivan; Leach, Joseph R; Lee, Lik Chuan; Genet, Martin; Toutain, Arnaud; Wenk, Jonathan F; Rausch, Manuel K; Rebelo, Nuno; Acevedo-Bolton, Gabriel; Kuhl, Ellen; Navia, Jose L; Guccione, Julius M

    2015-06-01

    Ischemic mitral regurgitation is associated with substantial risk of death. We sought to: (1) detail significant recent improvements to the Dassault Systèmes human cardiac function simulator (HCFS); (2) use the HCFS to simulate normal cardiac function as well as pathologic function in the setting of posterior left ventricular (LV) papillary muscle infarction; and (3) debut our novel device for correction of ischemic mitral regurgitation. We synthesized two recent studies of human myocardial mechanics. The first study presented the robust and integrative finite element HCFS. Its primary limitation was its poor diastolic performance with an LV ejection fraction below 20% caused by overly stiff ex vivo porcine tissue parameters. The second study derived improved diastolic myocardial material parameters using in vivo MRI data from five normal human subjects. We combined these models to simulate ischemic mitral regurgitation by computationally infarcting an LV region including the posterior papillary muscle. Contact between our novel device and the mitral valve apparatus was simulated using Dassault Systèmes SIMULIA software. Incorporating improved cardiac geometry and diastolic myocardial material properties in the HCFS resulted in a realistic LV ejection fraction of 55%. Simulating infarction of posterior papillary muscle caused regurgitant mitral valve mechanics. Implementation of our novel device corrected valve dysfunction. Improvements in the current study to the HCFS permit increasingly accurate study of myocardial mechanics. The first application of this simulator to abnormal human cardiac function suggests that our novel annuloplasty ring with a sub-valvular element will correct ischemic mitral regurgitation. PMID:25984248

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

    PubMed Central

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

    2013-01-01

    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. PMID:24271490

  12. 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. PMID:24271490

  13. A review of heart chamber segmentation for structural and functional analysis using cardiac magnetic resonance imaging.

    PubMed

    Peng, Peng; Lekadir, Karim; Gooya, Ali; Shao, Ling; Petersen, Steffen E; Frangi, Alejandro F

    2016-04-01

    Cardiovascular magnetic resonance (CMR) has become a key imaging modality in clinical cardiology practice due to its unique capabilities for non-invasive imaging of the cardiac chambers and great vessels. A wide range of CMR sequences have been developed to assess various aspects of cardiac structure and function, and significant advances have also been made in terms of imaging quality and acquisition times. A lot of research has been dedicated to the development of global and regional quantitative CMR indices that help the distinction between health and pathology. The goal of this review paper is to discuss the structural and functional CMR indices that have been proposed thus far for clinical assessment of the cardiac chambers. We include indices definitions, the requirements for the calculations, exemplar applications in cardiovascular diseases, and the corresponding normal ranges. Furthermore, we review the most recent state-of-the art techniques for the automatic segmentation of the cardiac boundaries, which are necessary for the calculation of the CMR indices. Finally, we provide a detailed discussion of the existing literature and of the future challenges that need to be addressed to enable a more robust and comprehensive assessment of the cardiac chambers in clinical practice. PMID:26811173

  14. 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. PMID:26700795

  15. 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

  16. Effects of Modified Parvalbumin EF-Hand Motifs on Cardiac Myocyte Contractile Function.

    PubMed

    Asp, Michelle L; Sjaastad, Frances V; Siddiqui, Jalal K; Davis, Jonathan P; Metzger, Joseph M

    2016-05-10

    Cardiac gene delivery of parvalbumin (Parv), an EF-hand Ca(2+) buffer, has been studied as a therapeutic strategy for diastolic heart failure, in which slow Ca(2+) reuptake is an important contributor. A limitation of wild-type (WT) Parv is the significant trade-off between faster relaxation and blunted contraction amplitude, occurring because WT-Parv sequesters Ca(2+) too early in the cardiac cycle and prematurely truncates sarcomere shortening in the facilitation of rapid relaxation. We recently demonstrated that an E → Q substitution (ParvE101Q) at amino acid 12 of the EF-hand Ca(2+)/Mg(2+) binding loop disrupts bidentate Ca(2+) binding, reducing Ca(2+) affinity by 99-fold and increasing Mg(2+) affinity twofold. ParvE101Q caused faster relaxation and not only preserved contractility, but unexpectedly increased it above untreated myocytes. To gain mechanistic insight into the increased contractility, we focused here on amino acid 12 of the EF-hand motif. We introduced an E → D substitution (ParvE101D) at this site, which converts bidentate Ca(2+) coordination to monodentate coordination. ParvE101D decreased Ca(2+) affinity by 114-fold and increased Mg(2+) affinity 28-fold compared to WT-Parv. ParvE101D increased contraction amplitude compared to both untreated myocytes and myocytes with ParvE101Q, with limited improvement in relaxation. Additionally, ParvE101D increased spontaneous contractions after pacing stress. ParvE101D also increased Ca(2+) transient peak height and was diffusely localized around the Z-line of the sarcomere, suggesting a Ca(2+)-dependent mechanism of enhanced contractility. Sarcoplasmic reticulum Ca(2+) load was not changed with ParvE101D, but postpacing Ca(2+) waves were increased. Together, these data show that inverted Ca(2+)/Mg(2+) binding affinities of ParvE101D increase myocyte contractility through a Ca(2+)-dependent mechanism without altering sarcoplasmic reticulum Ca(2+) load and by increasing unstimulated contractions and Ca(2

  17. Plasminogen regulates cardiac repair after myocardial infarction through its non-canonical function in stem cell homing to the infarcted heart

    PubMed Central

    Gong, Yanqing; Zhao, Yujing; Li, Ying; Fan, Yi; Hoover-Plow, Jane

    2014-01-01

    Objective The purpose of this study was to investigate the role of Plasminogen (Plg) in stem cell-mediated cardiac repair and regeneration after myocardial infarction (MI) Background MI induces irreversible tissue damage, eventually leading to heart failure. Bone marrow (BM)-derived stem cells promote tissue repair and regeneration after MI. Thrombolytic treatment with Plg activators significantly improves the clinical outcome in MI by restoring cardiac perfusion. However, the role of Plg in stem cell-mediated cardiac repair remains unclear. Methods MI was induced in Plg deficient (Plg−/−) and wild-type (Plg+/+) mice by ligation of left anterior descending coronary artery (LAD). Stem cells were visualized by in vivo tracking of GFP-expressing BM cells after BM transplantation. Cardiac function, stem cell homing, signaling pathways downstream of Plg were examined. Results G-CSF, a stem cell mobilizer, significantly promoted BM-derived stem cells (GFP+c-kit+ cells) recruitment into infarcted heart and stem cell-meidated cardiac repair in Plg+/+ mice. However, Plg deficiency markedly inhibited stem cell homing and cardiac repair, suggesting that Plg is critical for stem cell-mediated cardiac repair. Moreover, Plg regulated CXCR4 expression in stem cells in vivo and in vitro through MMP-9. Lentiviral reconstitution of CXCR4 expression in BM cells rescued stem cell homing to the infarcted heart in Plg-deficient mice, indicating that a critical role of CXCR4 in Plg-mediated stem cell homing after MI. Conclusions These findings have identified a novel role of Plg in stem cell-mediated cardiac repair after MI. Thus, targeting Plg may offer a new therapeutic strategy for stem cell-mediated cardiac repair after MI. PMID:24681141

  18. 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

  19. Engineering a growth factor embedded nanofiber matrix niche to promote vascularization for functional cardiac regeneration.

    PubMed

    Lakshmanan, Rajesh; Kumaraswamy, Priyadharshini; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2016-08-01

    The major loss of tissue extracellular matrix (ECM) after myocardial ischemia is a serious burden that gradually leads to heart failure. Due to lack of available treatment methods to restore the cardiac function, various research strategies have come up to treat the ischemic myocardium. However these have met with limited success due to the complexity of the cardiac tissue, which exhibits a nanofibrous collagenous matrix with spatio-temporal localization of a combination of growth factors. To mimic the topographical and chemical cues of the natural cardiac tissue, we have fabricated a growth factor embedded nanofibrous scaffold through electrospinning. In our previous work, we have reported a nanofibrous matrix made of PLCL and PEOz with an average diameter of 500 nm. The scaffold properties were specifically characterized in vitro for cardio-compatibility. In the present study, we have loaded dual growth factors VEGF and bFGF in the nanofiber matrix and investigated its suitability for cardiac tissue engineering. The encapsulation and release of dual growth factors from the matrix were studied using XPS and ELISA. Bioactivity of the loaded growth factors towards proliferation and migration of endothelial cells (HUVECs) was evaluated through MTS and Boyden chamber assays respectively. The efficiency of growth factors on the nanofibrous matrix to activate signaling molecules was studied in HUVECs through gene expression analysis. Preclinical evaluation of the growth factor embedded nanofibrous patch in a rabbit acute myocardial infarction (AMI) model was studied and cardiac function assessment was made through ECG and echocardiography. The evidence for angiogenesis in the patch secured regions was analyzed through histopathology and immunohistochemistry. Our results confirm the effectiveness of growth factor embedded nanofiber matrix in restoration of cardiac function after ischemia when compared to conventional patch material thereby exhibiting promise as a

  20. 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,…

  1. In utero dimethadione exposure causes postnatal disruption in cardiac structure and function in the rat.

    PubMed

    Aasa, Kristiina L; Purssell, Elizabeth; Adams, Michael A; Ozolinš, Terence R S

    2014-12-01

    In utero exposure of rat embryos to dimethadione (DMO), the N-demethylated teratogenic metabolite of the anticonvulsant trimethadione, induces a high incidence of cardiac heart defects including ventricular septal defects (VSDs). The same exposure regimen also leads to in utero cardiac functional deficits, including bradycardia, dysrhythmia, and a reduction in cardiac output (CO) and ejection fraction that persist until parturition (10 days after the final dose). Despite a high rate of spontaneous postnatal VSD closure, we hypothesize that functional sequelae will persist into adulthood. Pregnant Sprague Dawley rats were administered six 300 mg/kg doses of DMO, one every 12 h in mid-pregnancy beginning on the evening of gestation day 8. Postnatal cardiac function was assessed in control (CTL) and DMO-exposed offspring using radiotelemetry and ultrasound at 3 and 11 months of age, respectively. Adult rats exposed to DMO in utero had an increased incidence of arrhythmia, elevated blood pressure and CO, greater left ventricular volume and elevated locomotor activity versus CTL. The mean arterial pressure of DMO-exposed rats was more sensitive to changes in dietary salt load compared with CTL. Importantly, most treated rats had functional deficits in the absence of a persistent structural defect. It was concluded that in utero DMO exposure causes cardiovascular deficits that persist into postnatal life in the rat, despite absence of visible structural anomalies. We speculate this is not unique to DMO, suggesting possible health implications for infants with unrecognized gestational chemical exposures. PMID:25239635

  2. EFFECTS OF PRENATAL NITROFEN EXPOSURE ON CARDIAC STRUCTURE AND FUNCTION IN THE RAT

    EPA Science Inventory

    The herbicide nitrofen was administered to pregnant Fischer-344 and Sprague-Dawley rats on days 10-13 of gestation (po., 20 or 40 mg/kg daily) and its effects on cardiac structure and function were investigated in the offspring. In the 21-day fetuses, nitrofen did not influence i...

  3. An innovative approach to evaluate a cardiac function based on surface measurement.

    PubMed

    Uematsu, M; Shiraishi, Y; Sekine, K; Yambe, T; Saijo, Y; Park, Y; Ando, H; Matsumoto, T; Takeda, S; Iwasaki, K; Umezu, M

    2005-01-01

    Major function of the heart is to pump blood flow up to all tissues or organs in the body, and it is generally recognized that cardiac function under various diseased conditions are mainly represented by a relationship between blood flow and pressure inside of the heart. In this report, an original proposal of evaluation method on cardiac function is introduced through a simultaneous measurement of various points of cardiac muscular surface. An optical three-dimensional location sensor was employed to measure a displacement change of anatomically specific points on heart surface. Then, changes in strain in each regional surface area were quantitatively obtained. This result indicated similar tendency obtained from echocardiogram. It was also indicated that there was a difference in displacements and phrases between control and arrhythmia. Moreover, strain change in regional area was coincident with a contraction of natural heart. It was found that an attempt to superimpose the data of strain change onto the video images of natural heart was extremely helpful to understand a cardiac function visually. PMID:17282050

  4. Functionally conservative substitutions at cardiac troponin I S43/45.

    PubMed

    Lang, Sarah E; Stevenson, Tamara K; Xu, Dongyang; O'Connell, Ryan; Westfall, Margaret V

    2016-07-01

    A phospho-null Ala substitution at protein kinase C (PKC)-targeted cardiac troponin I (cTnI) S43/45 reduces myocyte and cardiac contractile function. The goal of the current study was to test whether cTnIS43/45N is an alternative, functionally conservative substitution in cardiac myocytes. Partial and more extensive endogenous cTnI replacement was similar at 2 and 4 days after gene transfer, respectively, for epitope-tagged cTnI and cTnIS43/45N. This replacement did not significantly change thin filament stoichiometry. In functional studies, there were no significant changes in the amplitude and/or rates of contractile shortening and re-lengthening after this partial (2 days) and extensive (4 days) replacement with cTnIS43/45N. The cTnIS43/45N substitution also was not associated with adaptive changes in the myocyte Ca(2+) transient or in phosphorylation of the protein kinase A and C-targeted cTnIS23/24 site. These results provide evidence that cTnIS43/45N is a functionally conservative substitution, and may be appropriate for use as a phospho-null in rodent models designed for studies on PKC modulation of cardiac performance. PMID:26869200

  5. Parametric shape representation by a deformable NURBS model for cardiac functional measurements.

    PubMed

    Chen, Sheng Yong; Guan, Qiu

    2011-03-01

    This paper proposes a method of parametric representation and functional measurement of 3-D cardiac shapes in a deformable nonuniform rational B-splines (NURBS) model. This representation makes it very easy to automatically evaluate the functional parameters and myocardial kinetics of the heart, since quantitative analysis can be followed in a simple way. In the model, local deformation and motion on the cardiac shape are expressed in adjustable parameters. Especially, an effective integral algorithm is used for volumetric measurement of a NURBS shape since the volume is the most basic parameter in cardiac functional analysis. This method promises the numerical computation to be very convenient, efficient, and accurate, in comparison with traditional methods. Practical experiments are carried out, and results show that the algorithm can get satisfactory measurement accuracy and efficiency. The parametric NURBS model in cylindrical coordinates is not only very suitable to fit the anatomical surfaces of a cardiac shape, but also easy for geometric transformation and nonrigid registration, and able to represent local dynamics and kinetics, and thus, can easily be applied for quantitative and functional analysis of the heart. PMID:20952325

  6. 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…

  7. Analysis of 2-d ultrasound cardiac strain imaging using joint probability density functions.

    PubMed

    Ma, Chi; Varghese, Tomy

    2014-06-01

    Ultrasound frame rates play a key role for accurate cardiac deformation tracking. Insufficient frame rates lead to an increase in signal de-correlation artifacts resulting in erroneous displacement and strain estimation. Joint probability density distributions generated from estimated axial strain and its associated signal-to-noise ratio provide a useful approach to assess the minimum frame rate requirements. Previous reports have demonstrated that bi-modal distributions in the joint probability density indicate inaccurate strain estimation over a cardiac cycle. In this study, we utilize similar analysis to evaluate a 2-D multi-level displacement tracking and strain estimation algorithm for cardiac strain imaging. The effect of different frame rates, final kernel dimensions and a comparison of radio frequency and envelope based processing are evaluated using echo signals derived from a 3-D finite element cardiac model and five healthy volunteers. Cardiac simulation model analysis demonstrates that the minimum frame rates required to obtain accurate joint probability distributions for the signal-to-noise ratio and strain, for a final kernel dimension of 1 λ by 3 A-lines, was around 42 Hz for radio frequency signals. On the other hand, even a frame rate of 250 Hz with envelope signals did not replicate the ideal joint probability distribution. For the volunteer study, clinical data was acquired only at a 34 Hz frame rate, which appears to be sufficient for radio frequency analysis. We also show that an increase in the final kernel dimensions significantly affect the strain probability distribution and joint probability density function generated, with a smaller effect on the variation in the accumulated mean strain estimated over a cardiac cycle. Our results demonstrate that radio frequency frame rates currently achievable on clinical cardiac ultrasound systems are sufficient for accurate analysis of the strain probability distribution, when a multi-level 2-D

  8. Molecular Modulation of Actomyosin Function by Cardiac Myosin-Binding Protein C

    PubMed Central

    Previs, Michael J.; Michalek, Arthur J.; Warshaw, David M.

    2014-01-01

    Cardiac myosin-binding protein C is a key regulator of cardiac contractility and is capable of both activating the thin filament to initiate actomyosin motion generation and governing maximal sliding velocities. While MyBP-C’s C-terminus localizes the molecule within the sarcomere the N-terminus appears to confer regulatory function by binding to the myosin motor domain and/or actin. Literature pertaining to how MyBP-C binding to the myosin motor domain and or actin leads to MyBP-C’s dual modulatory roles that can impact actomyosin interactions are discussed. PMID:24407948

  9. Changes in right ventricular structure and function assessed using cardiac magnetic resonance imaging in bosentan-treated patients with pulmonary arterial hypertension.

    PubMed

    Chin, Kelly M; Kingman, Martha; de Lemos, James A; Warner, John J; Reimold, Sharon; Peshock, Ron; Torres, Fernando

    2008-06-01

    Patients with pulmonary arterial hypertension (PAH) usually show improvements in symptoms, exercise capacity, and hemodynamics after treatment with approved medical therapies. This study sought to determine whether improvement in right-sided cardiac function measured using cardiac magnetic resonance imaging would also be seen and whether these changes would correlate with improvement in exercise capacity. Sixteen patients with PAH underwent evaluation at baseline and after 12 months of treatment with bosentan. After treatment, cardiac index, pulmonary vascular resistance, and 6-minute walk distance improved, and there was a trend toward improvement in right ventricular (RV) stroke volume (70 +/- 27 to 81 +/- 30 ml; p = 0.08), but no change in RV ejection fraction (RVEF) or RV end-diastolic volume. Six-minute walk distance improved by 59 m (p <0.05) in the overall cohort and improved more in patients in whom RVEF increased compared with those with stable or decreased RVEF (+98 vs -37 m, respectively; p = 0.01). Three patients died during follow-up, and these patients had significantly lower RVEF and left ventricular end-diastolic volume indexes than surviving patients. In conclusion, these results suggest that cardiac magnetic resonance imaging may have value in determining response to therapy and prognosis in patients with PAH. PMID:18489949

  10. 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

  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. Age-related changes in tissue macrophages precede cardiac functional impairment.

    PubMed

    Pinto, Alexander R; Godwin, James W; Chandran, Anjana; Hersey, Lucy; Ilinykh, Alexei; Debuque, Ryan; Wang, Lina; Rosenthal, Nadia A

    2014-05-01

    Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent to which the cTM phenotype changes with age is unknown. This study characterizes aging-dependent phenotypic changes in cTM subsets. Using theCx3cr1(GFP/+) mouse reporter line where GFP marks cTMs, and the tissue macrophage marker Mrc1, we show that two major cardiac tissue macrophage subsets, Mrc1-GFP(hi) and Mrc1+GFP(hi) cTMs, are present in the young (<10 week old) mouse heart, and a third subset, Mrc1+GFP(lo), comprises ~50% of total Mrc1+ cTMs from 30 weeks of age. Immunostaining and functional assays show that Mrc1+ cTMs are the principal myeloid sentinels in the mouse heart and that they retain proliferative capacity throughout life. Gene expression profiles of the two Mrc1+ subsets also reveal that Mrc1+GFP(lo) cTMs have a decreased number of immune response genes (Cx3cr1, Lpar6, CD9, Cxcr4, Itga6 and Tgfβr1), and an increased number of fibrogenic genes (Ltc4s, Retnla, Fgfr1, Mmp9 and Ccl24), consistent with a potential role for cTMs in cardiac fibrosis. These findings identify early age-dependent gene expression changes in cTMs, with significant implications for cardiac tissue injury responses and aging-associated cardiac fibrosis. PMID:24861132

  13. 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. PMID:26578113

  14. [Anesthetic management for laparoscopic sigmoidectomy in a patient with impaired ventricular function caused by cardiac sarcoidosis].

    PubMed

    Nagata, Hirofumi; Sato, Yoshiharu; Oouchi, Sueko; Wakimoto, Masahiro; Ishikawa, Ko; Suzuki, Kenji

    2012-08-01

    It has been demonstrated that laparoscopic surgery can reduce surgical trauma and postoperative pain, allowing earlier recovery and hospital discharge. However, because patients with severe cardiac depression may not tolerate the adverse respiratory and cardiovascular effects of pneumoperitoneum with a head-up or head-down tilt position, laparoscopic surgery has been avoided in these patients. The present case with low ventricular function (ejection fraction=23-27%) due to cardiac sarcoidosis could successfully undergo laparoscopic sigmoidectomy by using pulmonary artery catheterization. Therefore, laparoscopic surgery can be performed in patients with cardiac dysfunction if the cardiopulmonary responses caused by pneumoperitoneum with a head-up or head-down tilt are sufficiently considered and adverse hemodynamic responses appropriately detected and treated through invasive monitoring techniques such as pulmonary artery catheterization and/or transesophageal echocardiography. PMID:22991812

  15. Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial

    PubMed Central

    2014-01-01

    vasoactive therapy, respiratory support, renal or liver function tests, duration of ICU and hospital stay or 28- and 90-day mortality. Conclusions Infusion of half-molar sodium lactate improved cardiac performance and led to metabolic alkalosis in AHF patients without any detrimental effects on organ function. Trial registration Clinicaltrials.gov NCT01981655. Registered 13 August 2013. PMID:24666826

  16. Statin Treatment Increases Lifespan and Improves Cardiac Health in Drosophila by Decreasing Specific Protein Prenylation

    PubMed Central

    Spindler, Stephen R.; Li, Rui; Dhahbi, Joseph M.; Yamakawa, Amy; Mote, Patricia; Bodmer, Rolf; Ocorr, Karen; Williams, Renee T.; Wang, Yinsheng; Ablao, Kenneth P.

    2012-01-01

    Statins such as simvastatin are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and standard therapy for the prevention and treatment of cardiovascular diseases in mammals. Here we show that simvastatin significantly increased the mean and maximum lifespan of Drosophila melanogaster (Drosophila) and enhanced cardiac function in aging flies by significantly reducing heart arrhythmias and increasing the contraction proportion of the contraction/relaxation cycle. These results appeared independent of internal changes in ubiquinone or juvenile hormone levels. Rather, they appeared to involve decreased protein prenylation. Simvastatin decreased the membrane association (prenylation) of specific small Ras GTPases in mice. Both farnesyl (L744832) and type 1 geranylgeranyl transferase (GGTI-298) inhibitors increased Drosophila lifespan. These data are the most direct evidence to date that decreased protein prenylation can increase cardiac health and lifespan in any metazoan species, and may explain the pleiotropic (non-cholesterol related) health effects of statins. PMID:22737247

  17. 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

  18. 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

  19. [Research of Left Ventricle Function Analysis Using Real-time Cardiac Magnetic Resonance Imaging].

    PubMed

    Yang, Fan; He, Yan; Zhang, Jie; Wu, Yin

    2015-12-01

    Real-time free breathing cardiac cine imaging is a reproducible method with shorter acquisition time and without breath-hold for cardiac magnetic resonance imaging. However, the detection of end-diastole and end-systole frames of real-time free breathing cardiac cine imaging for left ventricle function analysis is commonly completed by visual identification, which is time-consuming and laborious. In order to save processing time, we propose a method for semi-automatic identification of end-diastole and end-systole frames. The method fits respiratory motion signal and acquires the expiration phase, end-diastole and end-systole frames by cross correlation coefficient. The procedure successfully worked on ten healthy volunteers and validated by the analysis of left ventricle function compared to the standard breath-hold steady-state free precession cardiac cine imaging without any significant statistical differences. The results demonstrated that the present method could correctly detect end-diastole and end-systole frames. In the future, this technique may be used for rapid left ventricle function analysis in clinic. PMID:27079101

  20. 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. PMID:26116573

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

    PubMed Central

    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

    2015-01-01

    ABSTRACT 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. PMID:26116573

  2. 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

  3. Rapid D-Affine Biventricular Cardiac Function with Polar Prediction

    PubMed Central

    Gilbert, Kathleen; Cowan, Brett; Suinesiaputra, Avan; Occleshaw, Christopher; Young, Alistair

    2014-01-01

    Although many solutions have been proposed for left ventricular functional analysis of the heart, right and left (bi-) ventricular function has been problematic due to the complex geometry and large motions. Biventricular function is particularly important in congenital heart disease, the most common type of birth defects. We describe a rapid interactive analysis tool for biventricular function which incorporates 1) a 3D+ time finite element model of biventricular geometry, 2) a fast prediction step which estimates an initial geometry in a polar coordinate system, and 3) a Cartesian update which penalizes deviations from affine transformations (D-Affine) from a prior. Solution times were very rapid, enabling interaction in real time using guide point modeling. The method was applied to 13 patients with congenital heart disease and compared with the clinical gold standard of manual tracing. Results between the methods showed good correlation (R2 > 0.9) and good precision (volume<17ml; mass<11g) for both chambers. PMID:25485422

  4. Cardiac Ultrasonography in the critical care setting: a practical approach to asses cardiac function and preload for the "non-cardiologist".

    PubMed

    Vermeiren, Guy L J; Malbrain, Manu L N G; Walpot, Jeroen M J B

    2015-01-01

    Cardiac ultrasonography has become an indispensible tool in the management of hemodynamically unstable critically ill patients. Some consider it as the modern stethoscope. Echocardiography is non-invasive and safe while the modern portable devices allow to be used at the bedside in order to provide fast, specific and vital information regarding the hemodynamic status, as well as the function, structure and anatomy of the heart. In this review, we will give an overview of cardiac function in general followed by an assessment of left ventricular function using echocardiography with calculation of cardiac output, left ventricular ejection fraction (EF), fractional shortening, fractional area contraction, M mode EF, 2D planimetry and 3D volumetry. We will briefly discuss mitral annulus post systolic excursion (MAPSE), calculation of dP/dt, speckle tracking or eyeballing to estimate EF for the experienced user. In a following section, we will discuss how to assess cardiac preload and diastolic function in 4 simple steps. The first step is the assessment of systolic function. The next step assesses the left atrium. The third step evaluates the diastolic flow patterns and E/e' ratio. The final step integrates the information of the previous steps. Echocardiography is also the perfect tool to evaluate right ventricular function with tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging, together with inferior vena cava dimensions and systolic pulmonary artery pressure and right ventricular systolic pressure measurement. Finally, methods to assess fluid responsiveness with echocardiography are discussed with the inferior vena cava collapsibility index and the variation on left ventricle outflow tract peak velocity and velocity time integral. Cardiac ultrasonography is an indispensible tool for the critical care physician to assess cardiac preload, afterload and contractile function in hemodynamically unstable patients in order to fine-tune treatment

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

    PubMed

    French, Kristin M; Maxwell, Joshua T; Bhutani, Srishti; Ghosh-Choudhary, Shohini; Fierro, Marcos J; Johnson, Todd D; Christman, Karen L; Taylor, W Robert; Davis, Michael E

    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

  6. 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

  7. Enhanced Effect of Human Cardiac Stem Cells and Bone Marrow Mesenchymal Stem Cells to Reduce Infarct Size and Restore Cardiac Function after Myocardial Infarction

    PubMed Central

    Williams, Adam R.; Hatzistergos, Konstantinos E.; Addicott, Benjamin; McCall, Fred; Carvalho, Decio; Suncion, Viky; Morales, Azorides R.; Silva, Jose Da; Sussman, Mark A.; Heldman, Alan W.; Hare, Joshua M.

    2013-01-01

    Background As mesenchymal stem cells (MSCs) induce proliferation and differentiation of c-kit+ cardiac stem cells (CSCs) in vivo and in vitro, we hypothesized that combining human (h)MSCs with c-kit+ hCSCs produces greater infarct size reduction compared to either cell administered alone after MI. Methods and Results Yorkshire swine underwent balloon occlusion of the LAD coronary artery followed by reperfusion, and were immunosuppressed after MI with cyclosporine and methylprednisolone. Intramyocardial injection of either: combination hCSCs/hMSCs (1M/200M, n=5), hCSCs alone (1M, n=5), hMSCs alone (200M, n=5), or placebo (PBS, n=5) was administered to the infarct border zones at 14 days post-MI. Phenotypic response to cell therapy was assessed by cardiac MRI and micromanometer conductance catheterization hemodynamics. While each cell therapy group had reduced MI size relative to placebo (p<0.05), the MI size reduction was 2-fold greater in combination vs. either cell therapy alone (p<0.05). Accompanying enhanced MI size reduction was substantial improvement in LV chamber compliance (end-diastolic pressure volume relationship, p<0.01) and contractility (preload recruitable stroke work and dP/dtmax, p<0.05) in combination treated swine. EF was restored to baseline in cell treated pigs, while placebo pigs had persistently depressed LV function (p<0.05). Immunohistochemistry showed 7-fold enhanced engraftment of stem cells in the combination therapy group vs. either cell type alone (P<0.001). Conclusions Combining hMSCs and hCSCs as a cell therapeutic enhances scar size reduction, and restores diastolic and systolic function toward normal after MI. Taken together these findings illustrate important biological interactions between c-kit+ CSCs and MSCs that enhance cell-based therapeutic responses. PMID:23224061

  8. Interparental Relationship Dynamics and Cardiac Vagal Functioning in Infancy

    PubMed Central

    Graham, Alice M.; Ablow, Jennifer C.; Measelle, Jeffrey R.

    2010-01-01

    This study examined associations between interparental relationship dynamics and vagus system functioning in infancy. The functioning of the vagus system, part of the parasympathetic nervous system, indexes emotional reactivity and regulation. Interparental avoidance and dyadic adjustment constitute the focus of this study in order to bring attention to relationship dynamics not subsumed under overt conflict. Infants’ baseline vagal tone and change in vagal tone in response to a novel toy were assessed at five months in a sample of high-risk mother-infant dyads (n = 77). Maternal report of interparental avoidance demonstrated an association with infants’ baseline vagal tone, while interparental dyadic adjustment was associated with change in infants’ vagal tone from baseline to the novel toy. Infant gender moderated these associations. Maternal sensitivity did not mediate interparental relationship dynamics and infants’ vagal functioning. Results are discussed in the context of emotional security theory. PMID:20727595

  9. Glucosamine administration during resuscitation improves organ function after trauma hemorrhage.

    PubMed

    Yang, Shaolong; Zou, Lu-Yun; Bounelis, Pam; Chaudry, Irshad; Chatham, John C; Marchase, Richard B

    2006-06-01

    Stress-induced hyperglycemia is necessary for maximal rates of survival after severe hemorrhage; however, the responsible mechanisms are not clear. One consequence of hyperglycemia is an increase in hexosamine biosynthesis, which leads to increases in levels of O-linked attachment of N-acetyl-glucosamine (O-GlcNAc) on nuclear and cytoplasmic proteins. This modification has been shown to lead to improved survival of isolated cells after stress. In view of this, we hypothesized that glucosamine (GlcNH2), which more selectively increases the levels of O-GlcNAc administration after shock, will have salutary effects on organ function after trauma hemorrhage (TH). Fasted male rats that underwent midline laparotomy were bled to a mean arterial blood pressure of 40 mmHg for 90 min and then resuscitated with Ringer lactate (four times the shed blood volume). Administration of 2.5 mL of 150 mmol L GlcNH2 midway during resuscitation improved cardiac output 2-fold compared with controls that received 2.5 mL of 150 mmol L NaCl. GlcNH2 also improved perfusion of various organs systems, including kidney and brain, and attenuated the TH-induced increase in serum levels of IL-6 (902+/-224 vs. 585+/-103 pg mL) and TNF-alpha (540+/-81 vs. 345+/-110 pg mL) (values are mean+/-SD). GlcNH2 administration resulted in significant increase in protein-associated O-GlcNAc in the heart and brain after TH. Thus, GlcNH2 administered during resuscitation improves recovery from TH, as assessed by cardiac function, organ perfusion, and levels of circulating inflammatory cytokines. This protection correlates with enhanced levels of nucleocytoplasmic protein O-GlcNAcylation and suggests that increased O-GlcNAc could be the mechanism that links stress-induced hyperglycemia to improved outcomes. PMID:16721268

  10. 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. PMID:26847740

  11. LRRC10 is required to maintain cardiac function in response to pressure overload.

    PubMed

    Brody, Matthew J; Feng, Li; Grimes, Adrian C; Hacker, Timothy A; Olson, Timothy M; Kamp, Timothy J; Balijepalli, Ravi C; Lee, Youngsook

    2016-01-15

    We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10(-/-)) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10(-/-) mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10(-/-) mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10(-/-) cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His(150) of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis. PMID:26608339

  12. Renal Perfusion Index Reflects Cardiac Systolic Function in Chronic Cardio-Renal Syndrome

    PubMed Central

    Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

    2015-01-01

    Background Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Material/Methods Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2–4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. Results In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=−0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Conclusions Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation. PMID:25881555

  13. A multi-parameter in vitro screen in human stem cell-derived cardiomyocytes identifies ponatinib-induced structural and functional cardiac toxicity.

    PubMed

    Talbert, Dominique R; Doherty, Kimberly R; Trusk, Patricia B; Moran, Diarmuid M; Shell, Scott A; Bacus, Sarah

    2015-01-01

    Ponatinib, a multi-targeted TKI and potent pan-ABL inhibitor, approved for the treatment of Ph + ALL and CML, was temporarily withdrawn from the U.S. market due to severe vascular adverse events. Cardiac-specific toxicities including myocardial infarction, severe congestive heart failure, and cardiac arrhythmias have also been shown with ponatinib. Targeted oncology agents such as ponatinib have transformed cancer treatment but often induce toxicity due to inhibition of survival pathways shared by both cancer and cardiac cells. These toxicities are often missed by the standard preclinical toxicity assessment methods, which include human Ether-à-go-go-related gene (hERG) and animal toxicity testing. In this study, we show that a multiparameter in vitro toxicity screening approach using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) accurately predicted the cardiac toxicity potential of ponatinib. This in vitro model evaluated ponatinib's effect on the overall cell health, mitochondrial stress, and function of hiPSC-CM and also provided mechanistic insight into the signaling pathways and cellular structures altered with treatment. We show here that ponatinib rapidly inhibits prosurvival signaling pathways, induces structural cardiac toxicity (as shown by actin cytoskeleton damage, mitochondrial stress, cell death, and troponin secretion), and disrupts cardiac cell beating. Most of these effects occurred at doses between 10× and 50× ponatinib's Cmax, a dose range shown to be relevant for accurate prediction of in vivo toxicity. Together these studies show that a comprehensive in vitro screening tool in a more relevant human cardiac cell model can improve the detection of cardiac toxicity with targeted oncology agents such as ponatinib. PMID:25304212

  14. Effects of bone marrow mesenchymal stem cells on the cardiac function and immune system of mice with endotoxemia.

    PubMed

    Wu, Yuanfan; Zhou, Jing; Bi, Liqing; Huang, Min; Han, Yi; Zhang, Qian; Zhu, Dongmei; Zhou, Suming

    2016-06-01

    The present study aimed to investigate the effects of bone marrow mesenchymal stem cells (MSCs) on the cardiac function and immune system of mice with endotoxemia. The mice were divided into the following groups: Control group, endotoxemia group, lipopolysaccharide (LPS) treatment group, LPS and MSC treatment group (LPS + MSC group) and MSC group. Following treatment with LPS, the cardiac function of the mice was examined at after 2, 6 and 24 h, and on day 7. An enzyme‑linked immunofluorescent assay was used to analyze the serum and the levels of cytokines in the myocardium, and western blotting was used to investigate any changes in the levels of signaling proteins associated with the myocardium. A 3‑(4,5‑dimethyl‑2‑thiazolyl)‑2,5‑diphenyl‑2H‑tetrazolium bromide assay was used to investigate the growth rate of the splenic cells at after 24 h and on day 7, and the humoral immune function and phagocytosis of the macrophages in the mice were also examined. The cardiac function of the mice with endotoxemia declined, although this impairment was circumvented following treatment with MSCs. The levels of interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α and IL‑10 in the serum and the myocardium increased following stimulation by LPS, although these declined as a result of MSC treatment. The expression levels of Toll‑like receptor 4, p65‑nuclear factor‑κB and phosphorylated p38 in the mouse myocardium were enhanced following stimulation by LPS, which subsequently decreased as a result of MSC treatment. Compared with the control group, the growth rate of the splenic cells, humoral immune function and the level of phagocytosis of macrophages were all increased, although these parameters declined following treatment with MSCs. Taken together, the present study revealed that the MSCs inhibited the inflammatory reaction in the mice with endotoxemia, and improved cardiac function. By contrast, the cellular and humoral immunity were

  15. Effect of cardiac resynchronization therapy on pulmonary function in patients with heart failure.

    PubMed

    Cundrle, Ivan; Johnson, Bruce D; Somers, Virend K; Scott, Christopher G; Rea, Robert F; Olson, Lyle J

    2013-09-15

    Pulmonary congestion due to heart failure causes abnormal lung function. Cardiac resynchronization therapy (CRT) is a proven effective treatment for heart failure. The aim of this study was to test the hypothesis that CRT promotes increased lung volumes, bronchial conductance, and gas diffusion. Forty-four consecutive patients with heart failure were prospectively investigated before and after CRT. Spirometry, gas diffusion (diffusing capacity for carbon monoxide), cardiopulmonary exercise testing, New York Heart Association class, brain natriuretic peptide, the left ventricular ejection fraction, left atrial volume, and right ventricular systolic pressure were assessed before and 4 to 6 months after CRT. Pre- and post-CRT measures were compared using either paired Student's t tests or Wilcoxon's matched-pair test; p values <0.05 were considered significant. Improved New York Heart Association class, left ventricular ejection fraction, left atrial volume, right ventricular systolic pressure, and brain natriuretic peptide were observed after CRT (p <0.05 for all). Spirometry after CRT demonstrated increased percentage predicted total lung capacity (90 ± 17% vs 96 ± 15%, p <0.01) and percentage predicted forced vital capacity (80 ± 19% vs 90 ± 19%, p <0.01). Increased percentage predicted total lung capacity was significantly correlated with increased peak exercise end-tidal carbon dioxide (r = 0.43, p = 0.05). Increased percentage predicted forced vital capacity was significantly correlated with decreased right ventricular systolic pressure (r = -0.30, p = 0.05), body mass index (r = -0.35, p = 0.02) and creatinine (r = -0.49, p = 0.02), consistent with an association of improved bronchial conductance and decreased congestion. Diffusing capacity for carbon monoxide did not significantly change. In conclusion, increased lung volumes and bronchial conductance due to decreased pulmonary congestion and increased intrathoracic space contribute to an improved

  16. 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

  17. Chloroquine improves left ventricle diastolic function in streptozotocin-induced diabetic mice.

    PubMed

    Yuan, Xun; Xiao, Yi-Chuan; Zhang, Gui-Ping; Hou, Ning; Wu, Xiao-Qian; Chen, Wen-Liang; Luo, Jian-Dong; Zhang, Gen-Shui

    2016-01-01

    Diabetes is a potent risk factor for heart failure with preserved ejection fraction (HFpEF). Autophagy can be activated under pathological conditions, including diabetic cardiomyopathy. The therapeutic effects of chloroquine (CQ), an autophagy inhibitor, on left ventricle function in streptozotocin (STZ)-induced diabetic mice were investigated. The cardiac function, light chain 3 (LC3)-II/LC3-I ratio, p62, beclin 1, reactive oxygen species, apoptosis, and fibrosis were measured 14 days after CQ (ip 60 mg/kg/d) administration. In STZ-induced mice, cardiac diastolic function was decreased significantly with normal ejection fraction. CQ significantly ameliorated cardiac diastolic function in diabetic mice with HFpEF. In addition, CQ decreased the autophagolysosomes, cardiomyocyte apoptosis, and cardiac fibrosis but increased LC3-II and p62 expressions. These results suggested that CQ improved the cardiac diastolic function by inhibiting autophagy in STZ-induced HFpEF mice. Autophagic inhibitor CQ might be a potential therapeutic agent for HFpEF. PMID:27621594

  18. Chloroquine improves left ventricle diastolic function in streptozotocin-induced diabetic mice

    PubMed Central

    Yuan, Xun; Xiao, Yi-Chuan; Zhang, Gui-Ping; Hou, Ning; Wu, Xiao-Qian; Chen, Wen-Liang; Luo, Jian-Dong; Zhang, Gen-Shui

    2016-01-01

    Diabetes is a potent risk factor for heart failure with preserved ejection fraction (HFpEF). Autophagy can be activated under pathological conditions, including diabetic cardiomyopathy. The therapeutic effects of chloroquine (CQ), an autophagy inhibitor, on left ventricle function in streptozotocin (STZ)-induced diabetic mice were investigated. The cardiac function, light chain 3 (LC3)-II/LC3-I ratio, p62, beclin 1, reactive oxygen species, apoptosis, and fibrosis were measured 14 days after CQ (ip 60 mg/kg/d) administration. In STZ-induced mice, cardiac diastolic function was decreased significantly with normal ejection fraction. CQ significantly ameliorated cardiac diastolic function in diabetic mice with HFpEF. In addition, CQ decreased the autophagolysosomes, cardiomyocyte apoptosis, and cardiac fibrosis but increased LC3-II and p62 expressions. These results suggested that CQ improved the cardiac diastolic function by inhibiting autophagy in STZ-induced HFpEF mice. Autophagic inhibitor CQ might be a potential therapeutic agent for HFpEF. PMID:27621594

  19. Improving Ascertainment of Sudden Cardiac Death in Patients with End Stage Renal Disease

    PubMed Central

    Pun, Patrick H.; Herzog, Charles A.; Middleton, John P.

    2012-01-01

    Summary Background and objectives Data collected by the US Renal Data System (USRDS) identify sudden cardiac death (SCD) as the leading cause of death among hemodialysis patients. However, evidence suggests that clinical events captured on the USRDS death notification form may be inaccurate. A new method for classifying SCD was recently developed to enhance the accuracy of SCD classification. This study examined the performance characteristics of this refined definition using a cohort of hemodialysis patients who experienced a witnessed SCD as the reference standard. Design, setting, participants, & measurements This is a retrospective cohort study of 363 patients who experienced a witnessed SCD in US Gambro (DaVita) outpatient dialysis clinics. Sensitivity of SCD defined by death notification forms and SCD defined using additional administrative sources was compared. Clinical data recorded near time of death were also examined. Results Existing USRDS death notification forms reported 70.8% of witnessed SCD as “cardiac arrest/cause unknown” or “arrhythmia.” The refined definition significantly improved identification to 83.8% of witnessed SCD events (P<0.001). Verified SCD cases that were not identified by either definition were more likely to be reported on the death notification form as death due to myocardial infarction, hyperkalemia, sepsis, malignancy, or unknown cause. Conclusions Compared with the death notification form alone, the refined SCD definition significantly improves the sensitivity of reporting of witnessed SCD occurring within outpatient hemodialysis clinics. More accurate reporting of cardiac events by clinicians and refinements to existing death notification forms may further improve recognition and understanding of SCD. PMID:22076878

  20. 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.

  1. 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

  2. Functional 3-D cardiac co-culture model using bioactive chitosan nanofiber scaffolds.

    PubMed

    Hussain, Ali; Collins, George; Yip, Derek; Cho, Cheul H

    2013-02-01

    The in vitro generation of a three-dimensional (3-D) myocardial tissue-like construct employing cells, biomaterials, and biomolecules is a promising strategy in cardiac tissue regeneration, drug testing, and tissue engineering applications. Despite significant progress in this field, current cardiac tissue models are not yet able to stably maintain functional characteristics of cardiomyocytes for long-term culture and therapeutic purposes. The objective of this study was to fabricate bioactive 3-D chitosan nanofiber scaffolds using an electrospinning technique and exploring its potential for long-term cardiac function in the 3-D co-culture model. Chitosan is a natural polysaccharide biomaterial that is biocompatible, biodegradable, non-toxic, and cost effective. Electrospun chitosan was utilized to provide structural scaffolding characterized by scale and architectural resemblance to the extracellular matrix (ECM) in vivo. The chitosan fibers were coated with fibronectin via adsorption in order to enhance cellular adhesion to the fibers and migration into the interfibrous milieu. Ventricular cardiomyocytes were harvested from neonatal rats and studied in various culture conditions (i.e., mono- and co-cultures) for their viability and function. Cellular morphology and functionality were examined using immunofluorescent staining for alpha-sarcomeric actin (SM-actin) and gap junction protein, Connexin-43 (Cx43). Scanning electron microscopy (SEM) and light microscopy were used to investigate cellular morphology, spatial organization, and contractions. Calcium indicator was used to monitor calcium ion flux of beating cardiomyocytes. The results demonstrate that the chitosan nanofibers retained their cylindrical morphology in long-term cell cultures and exhibited good cellular attachment and spreading in the presence of adhesion molecule, fibronectin. Cardiomyocyte mono-cultures resulted in loss of cardiomyocyte polarity and islands of non-coherent contractions. However

  3. 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.

  4. Comparison of 4D-microSPECT and microCT for murine cardiac function

    PubMed Central

    Befera, Nicholas T.; Badea, Cristian T.; Johnson, G. Allan

    2014-01-01

    Purpose The objective of this study was to compare a new generation of four-dimensional (4D) microSPECT with microCT for quantitative in vivo assessment of murine cardiac function. Procedures 4D isotropic cardiac images were acquired from normal C57BL/6 mice with either microSPECT at 350-micron resolution (n=6) or microCT at 88-micron resolution (n=6). One additional mouse with myocardial infarction (MI) was scanned with both modalities. Prior to imaging, mice were injected with either 99mTc -tetrofosmin for microSPECT, or a liposomal blood pool contrast agent for microCT. Segmentation of the left ventricle (LV) was performed using Vitrea (Vital Images) software, to derive global and regional function. Results Measures of global LV function between microSPECT and microCT groups were comparable (e.g. ejection fraction=71±6%-microSPECT and 68±4%-microCT). Regional functional indices (wall motion, wall thickening, regional ejection fraction) were also similar for the two modalities. In the mouse with MI, microSPECT identified a large perfusion defect that was not evident with microCT. Conclusions Despite lower spatial resolution, microSPECT was comparable to microCT in the quantitative evaluation of cardiac function. MicroSPECT offers an advantage over microCT in the ability to evaluate myocardial perfusion radiotracer distribution and function simultaneously. MicroSPECT should be considered as an alternative to microCT and MR for preclinical cardiac imaging in the mouse. PMID:24037175

  5. Feasibility of Cognitive Functional Assessment in Cardiac Arrest Survivors Using an Abbreviated Laptop-Based Neurocognitive Battery

    PubMed Central

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

    2014-01-01

    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. PMID:25010524

  6. Human umbilical cord perivascular cells exhibit enhanced cardiomyocyte reprogramming and cardiac function after experimental acute myocardial infarction.

    PubMed

    Yannarelli, Gustavo; Dayan, Victor; Pacienza, Natalia; Lee, Chyan-Jang; Medin, Jeffrey; Keating, Armand

    2013-01-01

    We were interested in evaluating the ability of the mesenchymal stromal cell (MSC) population, human umbilical cord perivascular cells (HUCPVCs), to undergo cardiomyocyte reprogramming in an established coculture system with rat embryonic cardiomyocytes. Results were compared with human bone marrow-derived (BM) MSCs. The transcription factors GATA4 and Mef 2c were expressed in HUCPVCs but not BM-MSCs at baseline and, at 7 days, increased 7.6- and 3.5-fold, respectively, compared with BM-MSCs. Although cardiac-specific gene expression increased in both cell types in coculture, upregulation was more significant in HUCPVCs, consistent with Mef 2c-GATA4 synergism. Using a lentivector with eGFP transcribed from the α-myosin heavy chain (α-MHC) promoter, we found that cardiac gene expression was greater in HUCPVCs than BM-MSCs after 14 days coculture (52±17% vs. 29±6%, respectively). A higher frequency of HUCPVCs expressed α-MHC protein compared with BM-MSCs (11.6±0.9% vs. 5.3±0.3%); however, both cell types retained MSC-associated determinants. We also assessed the ability of the MSC types to mediate cardiac regeneration in a NOD/SCID γ mouse model of acute myocardial infarction (AMI). Fourteen days after AMI, cardiac function was significantly better in cell-treated mice compared with control animals and HUCPVCs exhibited greater improvement. Although human cells persisted in the infarct area, the frequency of α-MHC expression was low. Our results indicate that HUCPVCs exhibit a greater degree of cardiomyocyte reprogramming but that differentiation for both cell types is partial. We conclude that HUCPVCs may be preferable to BM-MSCs in the cell therapy of AMI. PMID:23043977

  7. The second phase in creating the cardiac center for the next generation: beyond structure to process improvement.

    PubMed

    Woods, J

    2001-01-01

    The third generation cardiac institute will build on the successes of the past in structuring the service line, re-organizing to assimilate specialist interests, and re-positioning to expand cardiac services into cardiovascular services. To meet the challenges of an increasingly competitive marketplace and complex delivery system, the focus for this new model will shift away from improved structures, and toward improved processes. This shift will require a sound methodology for statistically measuring and sustaining process changes related to the optimization of cardiovascular care. In recent years, GE Medical Systems has successfully applied Six Sigma methodologies to enable cardiac centers to control key clinical and market development processes through its DMADV, DMAIC and Change Acceleration processes. Data indicates Six Sigma is having a positive impact within organizations across the United States, and when appropriately implemented, this approach can serve as a solid foundation for building the next generation cardiac institute. PMID:11765624

  8. Pre-treatment of synthetic elastomeric scaffolds by cardiac fibroblasts improves engineered heart tissue.

    PubMed

    Radisic, Milica; Park, Hyoungshin; Martens, Timothy P; Salazar-Lazaro, Johanna E; Geng, Wenliang; Wang, Yadong; Langer, Robert; Freed, Lisa E; Vunjak-Novakovic, Gordana

    2008-09-01

    Native myocardium consists of several cell types, of which approximately one-third are myocytes and most of the nonmyocytes are fibroblasts. By analogy with monolayer culture in which fibroblasts were removed to prevent overgrowth, early attempts to engineer myocardium utilized cell populations enriched for cardiac myocytes (CMs; approximately 80-90% of total cells). We hypothesized that the pre-treatment of synthetic elastomeric scaffolds with cardiac fibroblasts (CFs) will enhance the functional assembly of the engineered cardiac constructs by creating an environment supportive of cardiomyocyte attachment and function. Cells isolated from neonatal rat ventricles were prepared to form three distinct populations: rapidly plating cells identified as CFs, slowly plating cells identified as CMs, and unseparated initial population of cells (US). The cell fractions (3 x 10(6) cells total) were seeded into poly(glycerol sebacate) scaffolds (highly porous discs, 5 mm in diameter x 2-mm thick) using Matrigeltrade mark, either separately (CM or CF), concurrently (US), or sequentially (CF pre-treatment followed by CM culture, CF + CM), and cultured in spinner flasks. The CF + CM group had the highest amplitude of contraction and the lowest excitation threshold, superior DNA content, and higher glucose consumption rate. The CF + CM group exhibited compact 100- to 200-mum thick layers of elongated myocytes aligned in parallel over layers of collagen-producing fibroblasts, while US and CM groups exhibited scattered and poorly elongated myocytes. The sequential co-culture of CF and CM on a synthetic elastomer scaffold thus created an environment supportive of cardiomyocyte attachment, differentiation, and contractile function, presumably due to scaffold conditioning by cultured fibroblasts. When implanted over the infarcted myocardium in a nude rat model, cell-free poly(glycerol sebacate) remained at the ventricular wall after 2 weeks of in vivo, and was vascularized. PMID

  9. 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

    2016-02-01

    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

  10. Functional TRPV2 and TRPV4 channels in human cardiac c-kit(+) progenitor cells.

    PubMed

    Che, Hui; Xiao, Guo-Sheng; Sun, Hai-Ying; Wang, Yan; Li, Gui-Rong

    2016-06-01

    The cellular physiology and biology of human cardiac c-kit(+) progenitor cells has not been extensively characterized and remains an area of active research. This study investigates the functional expression of transient receptor potential vanilloid (TRPV) and possible roles for this ion channel in regulating proliferation and migration of human cardiac c-kit(+) progenitor cells. We found that genes coding for TRPV2 and TRPV4 channels and their proteins are significantly expressed in human c-kit(+) cardiac stem cells. Probenecid, an activator of TRPV2, induced an increase in intracellular Ca(2+) (Ca(2+) i ), an effect that may be attenuated or abolished by the TRPV2 blocker ruthenium red. The TRPV4 channel activator 4α-phorbol 12-13-dicaprinate induced Ca(2+) i oscillations, which can be inhibited by the TRPV4 blocker RN-1734. The alteration of Ca(2+) i by probenecid or 4α-phorbol 12-13-dicprinate was dramatically inhibited in cells infected with TRPV2 short hairpin RNA (shRNA) or TRPV4 shRNA. Silencing TRPV2, but not TRPV4, significantly reduced cell proliferation by arresting cells at the G0/G1 boundary of the cell cycle. Cell migration was reduced by silencing TRPV2 or TRPV4. Western blot revealed that silencing TRPV2 decreased expression of cyclin D1, cyclin E, pERK1/2 and pAkt, whereas silencing TRPV4 only reduced pAkt expression. Our results demonstrate for the first time that functional TRPV2 and TRPV4 channels are abundantly expressed in human cardiac c-kit(+) progenitor cells. TRPV2 channels, but not TRPV4 channels, participate in regulating cell cycle progression; moreover, both TRPV2 and TRPV4 are involved in migration of human cardiac c-kit(+) progenitor cells. PMID:26865051

  11. Effect on the cardiac function of repeated LBNP during a 1-month head down tilt

    NASA Astrophysics Data System (ADS)

    Arbeille, Ph.; Lebouard, D.; Massabuau, M.; Pottier, J. M.; Patat, F.; Pourcelot, L.; Guell, A.

    Cardiovascular assessment by ultrasound methods was performed during two long duration (1 month) Head Down Tilt (HDT) on 6 healthy volunteers. On a first 1 month HDT session, 3 of the 6 subjects (A, B, C) had daily several lower body negative pressure tests (LBNP), whereas the 3 subjects remaining (D, E, F) rested without LBNP. On a second 1 month HDT session subjects D, E, and F had daily LBNP tests and the A, B and C subjects did not. The cardiac function was assessed by Echocardiography (B mode, TM mode). On all the "6 non LBNP" subjects the left ventricule diastolic volume (LVDV), the stroke volume (SV) and the cardiac output (CO) increase (+10%, -15%) after HDT then decrease and remain inferior (-5%, -5%) or equal to the basal value during the HDT. Immediately after the end of the HDT the heart rate (HR) increase (+10%, +30%) whereas the cardiac parameters decrease weakly (-5%, -10%) and normalize after 3 days of recovery. On the "6 LBNP" subjects the LVDV, SV and CO increase (+10%, +15%) after 1 h HDT as in the previous group then decrease but remain superior (+5%, +15%) or equal to the basal value. After the HDT session, the HR is markedly increased (+20%, +40%) the LVDV and SV decrease (-15%, -20%) whereas the CO increases or decreases depending on the amplitude of the HR variations. These parameters do not completely normalize after 3 days recovery. Repeated LBNP sessions have a significant effect on the cardiovascular function as it maintains all cardiac parameters above the basal value. The LBNP manoeuvre can be considered as an efficient countermeasure to prevent cardiac disadaptation induced by HDT position and probably microgravity.

  12. 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.

  13. 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.

  14. 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.

  15. Improved Fat Water Separation with Water Selective Inversion Pulse for Inversion Recovery Imaging in Cardiac MRI

    PubMed Central

    Havla, Lukas; Basha, Tamer; Rayatzadeh, Hussein; Shaw, Jaime L.; Manning, Warren J.; Reeder, Scott B.; Kozerke, Sebastian; Nezafat, Reza

    2012-01-01

    Purpose To develop an improved chemical shift-based water-fat separation sequence using a water-selective inversion pulse for inversion-recovery 3D contrast-enhanced cardiac MR. Materials and Methods In inversion-recovery sequences, the fat signal is substantially reduced due to the application of a non-selective inversion pulse. Therefore, for simultaneous visualization of water, fat, and myocardial enhancement in inversion-recovery based sequences such as late Gadolinium enhancement imaging, two separate scans are used. To overcome this, the non-selective inversion pulse is replaced with a water-selective inversion pulse. Imaging was performed in phantoms, 9 healthy subjects and 9 patients with suspected arrhythmogenic right ventricular cardiomyopathy plus 1 patient for tumor/mass imaging. In patients, images with conventional turbo-spin echo (TSE) with and without fat saturation were acquired prior to contrast injection for fat assessment. Subjective image scores (1=poor, 4=excellent) were used for image assessment. Results Phantom experiments showed a fat SNR increase between 1.7 to 5.9 times for inversion times of 150 and 300ms, respectively. The water-selective inversion pulse retains the fat signal in contrast-enhanced cardiac MR, allowing improved visualization of fat in the water-fat separated images of healthy subjects with a score of 3.7 ± 0.6. Patient images acquired with the proposed sequence were scored higher when compared with TSE sequence (3.5 ± 0.7 vs. 2.2 ± 0.5, p<0.05). Conclusion The water-selective inversion pulse retains the fat signal in inversion-recovery based contrast-enhanced cardiac MR, allowing simultaneous visualization of water and fat. PMID:22927327

  16. Simple RF design for human functional and morphological cardiac imaging at 7 tesla

    NASA Astrophysics Data System (ADS)

    Versluis, M. J.; Tsekos, N.; Smith, N. B.; Webb, A. G.

    2009-09-01

    Morphological and functional cardiac MRI can potentially benefit greatly from the recent advent of commercial high-field (7 tesla and above) MRI systems. However, conventional hardware configurations at lower field using a body-coil for homogeneous transmission are not available at these field strengths. Sophisticated multiple-transmit-channel systems have been shown to be able to image the human heart at 7 tesla but such systems are currently not widely available. In this paper, we empirically optimize the design of a simple quadrature coil for cardiac imaging at 7 tesla. The size, geometry, and position have been chosen to produce a B1 field with no tissue-induced signal voids within the heart. Standard navigator echoes for gating were adapted for operation at the heart/lung interface, directly along the head-foot direction. Using this setup, conventional and high-resolution cine functional imaging have been successfully performed, as has morphological imaging of the right coronary artery.

  17. The structure and function of cardiac t-tubules in health and disease.

    PubMed

    Ibrahim, Michael; Gorelik, Julia; Yacoub, Magdi H; Terracciano, Cesare M

    2011-09-22

    The transverse tubules (t-tubules) are invaginations of the cell membrane rich in several ion channels and other proteins devoted to the critical task of excitation-contraction coupling in cardiac muscle cells (cardiomyocytes). They are thought to promote the synchronous activation of the whole depth of the cell despite the fact that the signal to contract is relayed across the external membrane. However, recent work has shown that t-tubule structure and function are complex and tightly regulated in healthy cardiomyocytes. In this review, we outline the rapidly accumulating knowledge of its novel roles and discuss the emerging evidence of t-tubule dysfunction in cardiac disease, especially heart failure. Controversy surrounds the t-tubules' regulatory elements, and we draw attention to work that is defining these elements from the genetic and the physiological levels. More generally, this field illustrates the challenges in the dissection of the complex relationship between cellular structure and function. PMID:21697171

  18. Functional characterization of CaVα2δ mutations associated with sudden cardiac death.

    PubMed

    Bourdin, Benoîte; Shakeri, Behzad; Tétreault, Marie-Philippe; Sauvé, Rémy; Lesage, Sylvie; Parent, Lucie

    2015-01-30

    L-type Ca(2+) channels play a critical role in cardiac rhythmicity. These ion channels are oligomeric complexes formed by the pore-forming CaVα1 with the auxiliary CaVβ and CaVα2δ subunits. CaVα2δ increases the peak current density and improves the voltage-dependent activation gating of CaV1.2 channels without increasing the surface expression of the CaVα1 subunit. The functional impact of genetic variants of CACNA2D1 (the gene encoding for CaVα2δ), associated with shorter repolarization QT intervals (the time interval between the Q and the T waves on the cardiac electrocardiogram), was investigated after recombinant expression of the full complement of L-type CaV1.2 subunits in human embryonic kidney 293 cells. By performing side-by-side high resolution flow cytometry assays and whole-cell patch clamp recordings, we revealed that the surface density of the CaVα2δ wild-type protein correlates with the peak current density. Furthermore, the cell surface density of CaVα2δ mutants S755T, Q917H, and S956T was not significantly different from the cell surface density of the CaVα2δ wild-type protein expressed under the same conditions. In contrast, the cell surface expression of CaVα2δ D550Y, CaVα2δ S709N, and the double mutant D550Y/Q917H was reduced, respectively, by ≈30-33% for the single mutants and by 60% for the latter. The cell surface density of D550Y/Q917H was more significantly impaired than protein stability, suggesting that surface trafficking of CaVα2δ was disrupted by the double mutation. Co-expression with D550Y/Q917H significantly decreased CaV1.2 currents as compared with results obtained with CaVα2δ wild type. It is concluded that D550Y/Q917H reduced inward Ca(2+) currents through a defect in the cell surface trafficking of CaVα2δ. Altogether, our results provide novel insight in the molecular mechanism underlying the modulation of CaV1.2 currents by CaVα2δ. PMID:25527503

  19. 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. PMID:25882843

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

    PubMed Central

    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.

    2015-01-01

    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. PMID:25882843

  1. Cardiac function in muscular dystrophy associates with abdominal muscle pathology

    PubMed Central

    Gardner, Brandon B.; Swaggart, Kayleigh A.; Kim, Gene; Watson, Sydeaka; McNally, Elizabeth M.

    2015-01-01

    Background The muscular dystrophies target muscle groups differentially. In mouse models of muscular dystrophy, notably the mdx model of Duchenne Muscular Dystrophy, the diaphragm muscle shows marked fibrosis and at an earlier age than other muscle groups, more reflective of the histopathology seen in human muscular dystrophy. Methods Using a mouse model of limb girdle muscular dystrophy, the Sgcg mouse, we compared muscle pathology across different muscle groups and heart. A cohort of nearly 200 Sgcg mice were studied using multiple measures of pathology including echocardiography, Evans blue dye uptake and hydroxyproline content in multiple muscle groups. Spearman rank correlations were determined among echocardiographic and pathological parameters. Findings The abdominal muscles were found to have more fibrosis than other muscle groups, including the diaphragm muscle. The abdominal muscles also had more Evans blue dye uptake than other muscle groups. The amount of diaphragm fibrosis was found to correlate positively with fibrosis in the left ventricle, and abdominal muscle fibrosis correlated with impaired left ventricular function. Fibrosis in the abdominal muscles negatively correlated with fibrosis in the diaphragm and right ventricles. Together these data reflect the recruitment of abdominal muscles as respiratory muscles in muscular dystrophy, a finding consistent with data from human patients. PMID:26029630

  2. 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

  3. MicroRNA-133a engineered mesenchymal stem cells augment cardiac function and cell survival in the infarct heart

    PubMed Central

    Dakhlallah, Duaa; Zhang, Jianying; Yu, Lianbo; Marsh, Clay B.; Angelos, Mark G.; Khan, Mahmood

    2015-01-01

    Cardiovascular disease is the number one cause of morbidity and mortality in the United States. The most common manifestation of cardiovascular disease is myocardial infarction (MI), which can ultimately lead to congestive heart failure (CHF). Cell therap (cardiomyoplasty) is a new potential therapeutic treatment alternative for the damaged heart. Recent preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) are a promising cell type for cardiomyoplasty applications. However, a major limitation is the poor survival rate of transplanted stem cells in the infarcted heart. miR-133a is an abundantly expressed microRNA in the cardiac muscle and is down-regulated in patients with MI. We hypothesized that reprogramming MSCs using microRNA-mimics (double-stranded oligonucleotides) will improve survival of stem cells in the damaged heart. MSCs were transfected with miR-133a mimic and antagomirs and the levels of miR-133a were measured by qRT-PCR. Rat hearts were subjected to MI and MSCs transfected with miR-133a mimic or antagomir were implanted in the ischemic heart. Four weeks after MI, cardiac function, cardiac fibrosis, miR-133a levels and apoptosis related genes (Apaf-1, Capase-9 and Caspase-3) were measured in the heart. We found that transfecting MSCs with miR-133a mimic improves survival of MSCs as determined by the MTT assay. Similarly, transplantation of miR-133a mimic transfected MSCs in rat hearts subjected to MI led to a significant increase in cell engraftment, cardiac function and decreased fibrosis when compared with MSCs only or MI groups. At the molecular level, qRT-PCR data demonstrated a significant decrease in expression of the pro-apoptotic genes; Apaf-1, caspase-9 and caspase-3 in the miR-133a mimic transplanted group. Further, luciferase reporter assay confirmed that miR- 133a is a direct target for Apaf-1. Overall, bioengineering of stem cells through miRNAs manipulation could potentially improve the therapeutic outcome of

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

    PubMed Central

    Chen, Jie; Cai, Qingqing; Wang, Jingfeng; Huang, Hui

    2015-01-01

    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. PMID:26322503

  5. 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. PMID:26322503

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

    PubMed

    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

  7. 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

  8. Effects of real and simulated weightlessness on the cardiac and peripheral vascular functions of humans: A review.

    PubMed

    Zhu, Hui; Wang, Hanqing; Liu, Zhiqiang

    2015-01-01

    Weightlessness is an extreme environment that can cause a series of adaptive changes in the human body. Findings from real and simulated weightlessness indicate altered cardiovascular functions, such as reduction in left ventricular (LV) mass, cardiac arrhythmia, reduced vascular tone and so on. These alterations induced by weightlessness are detrimental to the health, safety and working performance of the astronauts, therefore it is important to study the effects of weightlessness on the cardiovascular functions of humans. The cardiovascular functional alterations caused by weightlessness (including long-term spaceflight and simulated weightlessness) are briefly reviewed in terms of the cardiac and peripheral vascular functions. The alterations include: changes of shape and mass of the heart; cardiac function alterations; the cardiac arrhythmia; lower body vascular regulation and upper body vascular regulation. A series of conclusions are reported, some of which are analyzed, and a few potential directions are presented. PMID:26224491

  9. Resorcylidene aminoguanidine (RAG) improves cardiac mitochondrial bioenergetics impaired by hyperglycaemia in a model of experimental diabetes.

    PubMed

    Labieniec-Watala, Magdalena; Siewiera, Karolina; Jozwiak, Zofia

    2011-01-01

    Diabetes is associated with a mitochondrial dysfunction. Hyperglycaemia is also clearly recognized as the primary culprit in the pathogenesis of cardiac complications. In response to glycation and oxidative stress, cardiac mitochondria undergo cumulative alterations, often leading to heart deterioration. There is a continuous search for innovative treatment strategies for protecting the heart mitochondria from the destructive impact of diabetes. Aminoguanidine derivatives have been successfully used in animal model studies on the treatment of experimental diabetes, as well as the diabetes-driven dysfunctions of peripheral tissues and cells. Considerable attention has been paid particularly to β-resorcylidene aminoguanidine (RAG), often shown as the efficient anti-glycation and anti-oxidant agent in both animal studies and in vitro experiments. The aim of the present study was to test the hypothesis that RAG improves oxidative phosphorylation and electron transport capacity in mitochondria impaired by hyperglycaemia. Diabetes mellitus was induced in Wistar rats by a single intraperitoneal injection of streptozotocin (70 mg/kg body weight). Heart mitochondria were isolated from healthy rats and rats with streptozotocin-diabetes. Mitochondrial respiratory capacity was measured by high resolution respirometry with the OROBOROS Oxygraph-2k according to experimental protocol including respiratory substrates and inhibitors. The results revealed that RAG protects the heart against diabetes-associated injury by improving the mitochondrial bioenergetics, thus suggesting a possible novel pharmacological strategy for cardioprotection. PMID:22174647

  10. 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

  11. 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. PMID:25724498

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

    PubMed Central

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

    2015-01-01

    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. PMID:25724498

  13. 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

  14. Cardiac function during breath-hold diving in humans: an echocardiographic study.

    PubMed

    Marabotti, C; Belardinelli, A; L'Abbate, A; Scalzini, A; Chiesa, F; Cialoni, D; Passera, M; Bedini, R

    2008-01-01

    Breath-hold diving induces, in marine mammals, a reduction of cardiac output due to a decrease of both heart rate and stroke volume. Cardiovascular changes in humans during breath-hold diving are only partially known due to the technical difficulty of studying fully immersed subjects. Recently, a submersible echocardiograph has been developed, allowing a feasible assessment of cardiac anatomy and function of subjects during diving. Aim of the study was to evaluate, by Doppler-echocardiography, the cardiovascular changes inducedby breath-hold diving in humans. Ten male subjects were studied by Doppler echocardiography in dry conditions and during breath-hold diving at 3 m depth. In addition 14 male subjects were studied, using the same protocol, before and during breath-hold diving at 10 m depth. At 3 m depth significant reductions in heart rate (-17%), stroke volume (-17%), cardiac output (-29%), left atrial dimensions, and deceleration time of early diastolic transmitral flow (DTE) were observed. At 10 m depth similar but more pronounced changes occurred. In particular, increase in early transmitral flow velocity became significant (+33%), while DTE decreased by 34%. At both depths dimensions of right cardiac chambers remained unchanged. Breath-hold diving at shallow depth induced, in humans, cardiovascular changes qualitatively similar to those observed in natural divers such as seals. The reduced dimensions of left atrium associated to a left ventricular diastolic pattern resembling that of restrictive/constrictive heart disease, suggest that the hemodynamic effects of diving could be explained, at least in part, by a constriction exerted on the heart by the reduced chest volume and the increased blood content of the lungs. Finally, the absence of dimensional changes in the right chambers suggests that most of the pulmonary blood shift occurred before cardiac imaging. PMID:18500072

  15. Isolation and expansion of functionally-competent cardiac progenitor cells directly from heart biopsies

    PubMed Central

    Davis, Darryl R; Kizana, Eddy; Terrovitis, John; Barth, Andreas S.; Zhang, Yiqiang; Smith, Rachel Ruckdeschel; Miake, Junichiro; Marbán, Eduardo

    2010-01-01

    The adult heart contains reservoirs of progenitor cells that express embryonic and stem cell-related antigens. While these antigenically-purified cells are promising candidates for autologous cell therapy, clinical application is hampered by their limited abundance and tedious isolation methods. Methods that involve an intermediate cardiosphere-forming step have proven successful and are being tested clinically, but it is unclear whether the cardiosphere step is necessary. Accordingly, we investigated the molecular profile and functional benefit of cells that spontaneously emigrate from cardiac tissue in primary culture. Adult Wistar-Kyoto rat hearts were minced, digested and cultured as separate anatomical regions. Loosely-adherent cells that surround the plated tissue were harvested weekly for a total of five harvests. Genetic lineage tracing demonstrated that a small proportion of the direct outgrowth from cardiac samples originates from myocardial cells. This outgrowth contains sub-populations of cells expressing embryonic (SSEA-1) and stem cell-related antigens (c-Kit, abcg2) that varied with time in culture but not with the cardiac chamber of origin. This direct outgrowth, and its expanded progeny, underwent marked in vitro angiogenic/cardiogenic differentiation and cytokine secretion (IGF-1, VGEF). In vivo effects included long-term functional benefits as gauged by MRI following cell injection in a rat model of myocardial infarction. Outgrowth cells afforded equivalent functional benefits to cardiosphere-derived cells, which require more processing steps to manufacture. These results provide the basis for a simplified and efficient process to generate autologous cardiac progenitor cells (and mesenchymal supporting cells) to augment clinically-relevant approaches for myocardial repair. PMID:20211627

  16. Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

    PubMed Central

    McDermott-Roe, Chris; Ye, Junmei; Ahmed, Rizwan; Sun, Xi-Ming; Serafín, Anna; Ware, James; Bottolo, Leonardo; Muckett, Phil; Cañas, Xavier; Zhang, Jisheng; Rowe, Glenn C.; Buchan, Rachel; Lu, Han; Braithwaite, Adam; Mancini, Massimiliano; Hauton, David; Martí, Ramon; García-Arumí, Elena; Hubner, Norbert; Jacob, Howard; Serikawa, Tadao; Zidek, Vaclav; Papousek, Frantisek; Kolar, Frantisek; Cardona, Maria; Ruiz-Meana, Marisol; García-Dorado, David; Comella, Joan X; Felkin, Leanne E; Barton, Paul JR; Arany, Zoltan; Pravenec, Michal; Petretto, Enrico; Sanchis, Daniel; Cook, Stuart A.

    2011-01-01

    Left ventricular mass (LVM) is a highly heritable trait1 and an independent risk factor for all-cause mortality2. To date, genome-wide association studies (GWASs) have not identified the genetic factors underlying LVM variation3 and the regulatory mechanisms for blood pressure (BP)-independent cardiac hypertrophy remain poorly understood4,5. Unbiased systems-genetics approaches in the rat6,7 now provide a powerful complementary tool to GWAS and we applied integrative genomics to dissect a highly replicated, BP-independent LVM locus on rat chromosome 3p. We identified endonuclease G (Endog), previously implicated in apoptosis8 but not hypertrophy, as the gene at the locus and demonstrated loss-of-function mutation in Endog associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly inferred ENDOG in fundamental mitochondrial processes unrelated to apoptosis. We showed direct regulation of ENDOG by ERRα and PGC1α, master regulators of mitochondrial and cardiac function9,10,11, interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, Endog deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated reactive oxygen species (ROS), which was associated with enlarged and steatotic cardiomyocytes. Our studies establish further the link between mitochondrial dysfunction, ROS and heart disease and demonstrate a new role for Endog in maladaptive cardiac hypertrophy. PMID:21979051

  17. The influence of isotonic exercise on cardiac hypertrophy in arterial hypertension: impact on cardiac function and on the capacity for aerobic work.

    PubMed

    Moreno Júnior, H; Cezareti, M L; Piçarro, I C; Barros Neto, T L; Kasinski, N; Martinez Filho, E E; Saragoça, M A

    1995-10-01

    Intense physical training through isotonic exercises has controversial effects in individuals with moderate to severe hypertension. In this study, normotensive Wistar rats and rats with renovascular hypertension (Goldblatt II) were subjected to intense physical exercise involving two 50-min swimming sessions per day for a period of 12 weeks. At the end of the study, we evaluated the effect of training on arterial pressure, the capacity for aerobic work and cardiac function. Our results demonstrate that intense physical training has no effect on the arterial blood pressure of normotensive rats or of animals with moderate renovascular hypertension. Hypertensive animals with cardiac hypertrophy require a greater period of training in order to attain the same capacity for aerobic work as normotensive rats. This difference may result from an inability of the former animals to increase cardiac compliance, thereby impeding more extensive usage of the Frank-Starling mechanism to subsequently increase the systolic cardiac performance. Cardiac hypertrophy induced by exercise did not summate with that induced by arterial hypertension. Physical exercise normalized the end-diastolic left ventricular pressure in hypertensive animals without any corresponding increase in the compliance of the chamber. The first derivative of left ventricular pulse pressure (+/- dP/dt) was greater in the hypertensive trained group than in the hypertensive sedentary rats. These observations suggest that a systolic dysfunction of the left ventricle involving an elevated residual volume secondary to arterial hypertension may be corrected by physical exercise such as swimming. PMID:7584822

  18. Preoperative Steroid Treatment Does Not Improve Markers of Inflammation Following Cardiac Surgery in Neonates: Results from a Randomized Trial

    PubMed Central

    Graham, Eric M.; Atz, Andrew M.; McHugh, Kimberly E.; Butts, Ryan J.; Baker, Nathaniel L.; Stroud, Robert E.; Reeves, Scott T.; Bradley, Scott M.; McGowan, Francis X.; Spinale, Francis G.

    2013-01-01

    Objective Neonatal cardiac surgery requiring cardiopulmonary bypass results in a heightened inflammatory response. Perioperative glucocorticoid administration is commonly utilized in attempt to reduce the inflammatory cascade, although characterization of the cytokine response to steroids in neonatal cardiac surgery remains elusive due to highly variable approaches in administration. This randomized trial was designed to prospectively evaluate the effect of specific glucocorticoid dosing protocols on inflammatory markers in neonatal cardiac surgery requiring cardiopulmonary bypass. Methods Neonates scheduled for cardiac surgery were randomly assigned to receive either two-dose (8 hours preoperatively and operatively, n=36) or single dose (operatively, n=32) methylprednisolone at 30mg/kg/dose in a prospective double-blind trial. The primary outcome was the effect of these steroid regimens on markers of inflammation. Secondary analyses evaluated the association of specific cytokine profiles with postoperative clinical outcomes. Results Patient demographics, perioperative variables and preoperative indices of inflammation were similar between the single and two-dose groups. Preoperative cytokine response after the two-dose methylprednisolone protocol was consistent with an anti-inflammatory effect, although this did not persist into the postoperative period. Pre-medication baseline levels of interleukin-6, interleukin-8, interleukin-10 and tumor necrosis factor alpha were predictive of postoperative intensive care unit and hospital length of stay. Only interleukin-8 demonstrated a postoperative response associated with duration of intensive care unit and hospital stay. Conclusions The addition of a preoperative dose of methylprednisolone to a standard intraoperative methylprednisolone dose does not improve markers of inflammation following neonatal cardiac surgery. The routine administration of preoperative glucocorticoids in neonatal cardiac surgery should be

  19. 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. PMID:26211431

  20. Impact of aortocaval shunt flow on cardiac and renal function in unilateral nephrectomized rats.

    PubMed

    Wu, Jie; Cheng, Zhong; Zhang, Mingjing; Zhu, Pengfei; Gu, Ye

    2016-01-01

    We previously reported significantly enhanced cardiac remodeling post aortocaval fistula (AV) in unilateral nephrectomized (UNX) rats. However, the relationship between the size of the AV and the cardiorenal effects in UNX rats remains unknown. In the present study, AV was induced by 20, 18 and 16 gauge needles in UNX rats to see if larger shunt would definitely induce heavier cardiac and renal damage in UNX rats. Our results demonstrated that bigger shunt size is linked with proportional more significant cardiorenal remodeling and dysfunction in UNX rats. Expression of inflammatory biomarkers including CRP, TNF-α, IL-6, IL-1β, TGF-β and MCP-1 in left kidney and heart was significantly increased in all UNX + AV groups compared to Sham rats. Inflammation might thus participate in the worsening cardiorenal functions and remodeling processes in this model. PMID:27279232

  1. Impact of aortocaval shunt flow on cardiac and renal function in unilateral nephrectomized rats

    PubMed Central

    Wu, Jie; Cheng, Zhong; Zhang, Mingjing; Zhu, Pengfei; Gu, Ye

    2016-01-01

    We previously reported significantly enhanced cardiac remodeling post aortocaval fistula (AV) in unilateral nephrectomized (UNX) rats. However, the relationship between the size of the AV and the cardiorenal effects in UNX rats remains unknown. In the present study, AV was induced by 20, 18 and 16 gauge needles in UNX rats to see if larger shunt would definitely induce heavier cardiac and renal damage in UNX rats. Our results demonstrated that bigger shunt size is linked with proportional more significant cardiorenal remodeling and dysfunction in UNX rats. Expression of inflammatory biomarkers including CRP, TNF-α, IL-6, IL-1β, TGF-β and MCP-1 in left kidney and heart was significantly increased in all UNX + AV groups compared to Sham rats. Inflammation might thus participate in the worsening cardiorenal functions and remodeling processes in this model. PMID:27279232

  2. Intravital imaging of cardiac function at the single-cell level

    PubMed Central

    Aguirre, Aaron D.; Vinegoni, Claudio; Sebas, Matt; Weissleder, Ralph

    2014-01-01

    Knowledge of cardiomyocyte biology is limited by the lack of methods to interrogate single-cell physiology in vivo. Here we show that contracting myocytes can indeed be imaged with optical microscopy at high temporal and spatial resolution in the beating murine heart, allowing visualization of individual sarcomeres and measurement of the single cardiomyocyte contractile cycle. Collectively, this has been enabled by efficient tissue stabilization, a prospective real-time cardiac gating approach, an image processing algorithm for motion-artifact-free imaging throughout the cardiac cycle, and a fluorescent membrane staining protocol. Quantification of cardiomyocyte contractile function in vivo opens many possibilities for investigating myocardial disease and therapeutic intervention at the cellular level. PMID:25053815

  3. 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

  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. Cardiac autonomic function measured by heart rate variability and turbulence in pre-hypertensive subjects.

    PubMed

    Erdem, Alim; Uenishi, Masahiro; Küçükdurmaz, Zekeriya; Matsumoto, Kazuo; Kato, Ritsushi; Hara, Motoki; Yazıcı, Mehmet

    2013-01-01

    Non-dipping blood pressure pattern was shown to be associated with increased cardiovascular events. In addition, cardiac autonomic dysfunction was found to be associated with non-dipper phenomenon. In this study, we aimed to evaluate the cardiac autonomic functions in dipper and non-dipper pre-hypertensive subjects. A total of 65 pre-hypertensive subjects were enrolled in this study. They were divided into two groups as non-dippers (40 subjects, 52% female) and dippers (25 subjects, 52.5% female). Cardiac autonomic functions of the two groups were compared with the aid of heart rate variability, heart rate turbulence (HRT), atrial premature contractions (APCs), ventricular premature contractions (VPCs), and mean heart rate (MHR). There was no significant difference between non-dippers and dippers in basal characteristics. The two parameters of HRT, turbulence onset and turbulence slope, were found to be significantly abnormal in non-dippers than in dippers (P < .011 and P < .002, respectively). Heart rate variability parameters, including SDNN, SDANN, RMSSD, and pNN50, were found to be similar in dipper and non-dipper pre-hypertensive subjects (P < .998, P < .453, P < .205, and P < .788, respectively). APCs, VPCs, and MHR were compared, and there were statistical differences between the groups (APCs 5.80 ± 4.55, 9.14 ± 7.33, P < .024; VPCs 8.48 ± 8.83, 13.23 ± 9.68, P < .044; and MHR 70.16 ± 11.08, 76.26 ± 11.31, P < .035; respectively). This study demonstrated a possible cardiac autonomic dysfunction in pre-hypertensive subjects with non-dipper pattern. This may be a basis for future studies related to pre-hypertension and non-dipping BP pattern. PMID:22676318

  6. 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

  7. Assessment of phase based dose modulation for improved dose efficiency in cardiac CT on an anthropomorphic motion phantom

    NASA Astrophysics Data System (ADS)

    Budde, Adam; Nilsen, Roy; Nett, Brian

    2014-03-01

    State of the art automatic exposure control modulates the tube current across view angle and Z based on patient anatomy for use in axial full scan reconstructions. Cardiac CT, however, uses a fundamentally different image reconstruction that applies a temporal weighting to reduce motion artifacts. This paper describes a phase based mA modulation that goes beyond axial and ECG modulation; it uses knowledge of the temporal view weighting applied within the reconstruction algorithm to improve dose efficiency in cardiac CT scanning. Using physical phantoms and synthetic noise emulation, we measure how knowledge of sinogram temporal weighting and the prescribed cardiac phase can be used to improve dose efficiency. First, we validated that a synthetic CT noise emulation method produced realistic image noise. Next, we used the CT noise emulation method to simulate mA modulation on scans of a physical anthropomorphic phantom where a motion profile corresponding to a heart rate of 60 beats per minute was used. The CT noise emulation method matched noise to lower dose scans across the image within 1.5% relative error. Using this noise emulation method to simulate modulating the mA while keeping the total dose constant, the image variance was reduced by an average of 11.9% on a scan with 50 msec padding, demonstrating improved dose efficiency. Radiation dose reduction in cardiac CT can be achieved while maintaining the same level of image noise through phase based dose modulation that incorporates knowledge of the cardiac reconstruction algorithm.

  8. Assessment of Cardiac Autonomic Functions in Medical Students With Type D Personality

    PubMed Central

    Panwar, R. Abhilasha Singh

    2016-01-01

    Introduction Type D personality experiences joint occurrence of Negative Affectivity and Social Inhibition. It is an emerging risk factor for cardiovascular disease, with prevalence being 18-53% among cardiac patients. Type D personality people have exaggerated cardiovascular activity mediated by increased sympathetic drive and decreased vagal control of the heart which leads to enhanced risk of hypertension and is an independent risk factor for coronary heart disease. Aim To compare the cardiac autonomic function of Type D and non-Type D students. To compare cardiac autonomic functions among male and female students and students with and without family history of hypertension and coronary artery disease among Type D. To find the most affected test among Type D students. Materials and Methods Thirty Type D and 30 non- Type D medical students were identified by DS14. The Parasympathetic cardiac autonomic tests done assessed Heart Rate response to valsalva manoeuvre, immediate heart rate response to standing and heart rate variation during deep breathing. Sympathetic tests assessed BP response to standing and Sustained Hand Grip. The heart rate and R-R interval measurement were got from lead II of ECG recordings on Polyrite D. Statistical analysis was done using SPSS software. Unpaired student’s t-test was used and p-value <0.05 was considered to be statistically significant. Results Type D students showed slightly decreased parasympathetic activity and increased sympathetic activity when compared to non-Type D students even though there was no statistically significant difference between them. There is a statistically significant decrease in valsalva ratio among females (p<0.01) when compared to males. There is a statistically significant decrease in 30:15 ratio and BP response to handgrip (p<0.05) among students with family history of hypertension and coronary artery disease when compared with students with no family history of coronary artery disease. Valsalva

  9. 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

  10. 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. PMID:24463621

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

    PubMed Central

    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

    2014-01-01

    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. PMID:24463621

  12. Human G109E-inhibitor-1 impairs cardiac function and promotes arrhythmias.

    PubMed

    Haghighi, Kobra; Pritchard, Tracy J; Liu, Guan-Sheng; Singh, Vivek P; Bidwell, Philip; Lam, Chi Keung; Vafiadaki, Elizabeth; Das, Parthib; Ma, Jianyong; Kunduri, Swati; Sanoudou, Despina; Florea, Stela; Vanderbilt, Erica; Wang, Hong-Shang; Rubinstein, Jack; Hajjar, Roger J; Kranias, Evangelia G

    2015-12-01

    A hallmark of human and experimental heart failure is deficient sarcoplasmic reticulum (SR) Ca-uptake reflecting impaired contractile function. This is at least partially attributed to dephosphorylation of phospholamban by increased protein phosphatase 1 (PP1) activity. Indeed inhibition of PP1 by transgenic overexpression or gene-transfer of constitutively active inhibitor-1 improved Ca-cycling, preserved function and decreased fibrosis in small and large animal models of heart failure, suggesting that inhibitor-1 may represent a potential therapeutic target. We recently identified a novel human polymorphism (G109E) in the inhibitor-1 gene with a frequency of 7% in either normal or heart failure patients. Transgenic mice, harboring cardiac-specific expression of G109E inhibitor-1, exhibited decreases in contractility, Ca-kinetics and SR Ca-load. These depressive effects were relieved by isoproterenol stimulation. Furthermore, stress conditions (2Hz +/- Iso) induced increases in Ca-sparks, Ca-waves (60% of G109E versus 20% in wild types) and after-contractions (76% of G109E versus 23% of wild types) in mutant cardiomyocytes. Similar findings were obtained by acute expression of the G109E variant in adult cardiomyocytes in the absence or presence of endogenous inhibitor-1. The underlying mechanisms included reduced binding of mutant inhibitor-1 to PP1, increased PP1 activity, and dephosphorylation of phospholamban at Ser16 and Thr17. However, phosphorylation of the ryanodine receptor at Ser2808 was not altered while phosphorylation at Ser2814 was increased, consistent with increased activation of Ca/calmodulin-dependent protein kinase II (CaMKII), promoting aberrant SR Ca-release. Parallel in vivo studies revealed that mutant mice developed ventricular ectopy and complex ventricular arrhythmias (including bigeminy, trigeminy and ventricular tachycardia), when challenged with isoproterenol. Inhibition of CaMKII activity by KN-93 prevented the increased propensity to

  13. Ways to improve your correlation functions

    NASA Technical Reports Server (NTRS)

    Hamilton, A. J. S.

    1993-01-01

    This paper describes a number of ways to improve on the standard method for measuring the two-point correlation function of large scale structure in the Universe. Issues addressed are: (1) the problem of the mean density, and how to solve it; (2) how to estimate the uncertainty in a measured correlation function; (3) minimum variance pair weighting; (4) unbiased estimation of the selection function when magnitudes are discrete; and (5) analytic computation of angular integrals in background pair counts.

  14. Impact of aging on mitochondrial function in cardiac and skeletal muscle.

    PubMed

    Hepple, R T

    2016-09-01

    Both skeletal muscle and cardiac muscle are subject to marked structural and functional impairment with aging and these changes contribute to the reduced capacity for exercise as we age. Since mitochondria are involved in multiple aspects of cellular homeostasis including energetics, reactive oxygen species signaling, and regulation of intrinsic apoptotic pathways, defects in this organelle are frequently implicated in the deterioration of skeletal and cardiac muscle with aging. On this basis, the purpose of this review is to evaluate the evidence that aging causes dysfunction in mitochondria in striated muscle with a view towards drawing conclusions about the potential of these changes to contribute to the deterioration seen in striated muscle with aging. As will be shown, impairment in respiration and reactive oxygen species emission with aging are highly variable between studies and seem to be largely a consequence of physical inactivity. On the other hand, both skeletal and cardiac muscle mitochondria are more susceptible to permeability transition and this seems a likely cause of the increased recruitment of mitochondrial-mediated pathways of apoptosis seen in striated muscle. The review concludes by examining the role of degeneration of mitochondrial DNA versus impaired mitochondrial quality control mechanisms in the accumulation of mitochondria that are sensitized to permeability transition, whereby the latter mechanism is favored as the most likely cause. PMID:27033952

  15. 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.

  16. E2F3 plays an essential role in cardiac development and function

    PubMed Central

    King, Jennifer C.; Moskowitz, Ivan P. G.; Burgon, Patrick G.; Ahmad, Ferhaan; Stone, James R.; Seidman, Jonathan G.; Lees, Jacqueline A.

    2009-01-01

    The E2F transcription factors are key downstream targets of the retinoblastoma protein tumor suppressor. They are known to regulate the expression of genes that control fundamental biological processes including cellular proliferation, apoptosis and differentiation. However, considerable questions remain about the precise roles of the individual E2F family members. This study shows that E2F3 is essential for normal cardiac development. E2F3-loss impairs the proliferative capacity of the embryonic myocardium and most E2f3−/− mice die in utero or perinatally with hypoplastic ventricular walls and/or severe atrial and ventricular septal defects. A small fraction of the E2f3−/− neonates have hearts that appear grossly normal and they initially survive. However, these animals develop ultrastructural defects in the cardiac muscle and ultimately die as a result of congestive heart failure. These data demonstrate a clear link between E2F3’s role in the proliferative capacity of the myocardium and cardiac function during both development and adulthood. PMID:19029823

  17. Effects of chronic hypoxia on cardiac function measured by pressure-volume catheter in fetal chickens

    PubMed Central

    Giraud, George D.; Espinoza, Herbert M.; Davis, Erica N.; Crossley, Dane A.

    2015-01-01

    Hypoxia is a common component of many developmental insults and has been studied in early-stage chicken development. However, its impact on cardiac function and arterial-ventricular coupling in late-stage chickens is relatively unknown. To test the hypothesis that hypoxic incubation would reduce baseline cardiac function but protect the heart during acute hypoxia in late-stage chickens, white Leghorn eggs were incubated at 21% O2 or 15% O2. At 90% of incubation (19 days), hypoxic incubation caused growth restriction (−20%) and increased the LV-to-body ratio (+41%). Left ventricular (LV) pressure-volume loops were measured in anesthetized chickens in normoxia and acute hypoxia (10% O2). Hypoxic incubation lowered the maximal rate of pressure generation (ΔP/ΔtMax; −22%) and output (−57%), whereas increasing end-systolic elastance (ELV; +31%) and arterial elastance (EA; +122%) at similar heart rates to normoxic incubation. Both hypoxic incubation and acute hypoxia lengthened the half-time of relaxation (τ; +24%). Acute hypoxia reduced heart rate (−8%) and increased end-diastolic pressure (+35%). Hearts were collected for mRNA analysis. Hypoxic incubation was marked by decreased mRNA expression of sarco(endo)plasmic reticulum Ca2+-ATPase 2, Na+/Ca2+ exchanger 1, phospholamban, and ryanodine receptor. In summary, hypoxic incubation reduces LV function in the late-stage chicken by slowing pressure generation and relaxation, which may be driven by altered intracellular excitation-contraction coupling. Cardiac efficiency is greatly reduced after hypoxic incubation. In both incubation groups acute hypoxia reduced diastolic function. PMID:25652537

  18. Microvascular function, metabolic syndrome, and novel risk factor status in women with cardiac syndrome X.

    PubMed

    Jadhav, Sachin T; Ferrell, William R; Petrie, John R; Scherbakova, Olga; Greer, Ian A; Cobbe, Stuart M; Sattar, Naveed

    2006-06-15

    To characterize microvascular function, candidate risk pathways, and metabolic syndrome prevalence in women with cardiac syndrome X, 52 nondiabetic women with angiographically normal epicardial arteries but >1 mm of planar ST depression during exercise testing (patients) and 24 healthy controls of similar age were recruited. In addition to fasting blood samples and anthropometric measurements, forearm cutaneous microvascular function after iontophoresis of acetylcholine and sodium nitroprusside was assessed by laser Doppler imaging. Despite body mass index correction and a larger proportion on statin therapy, patients had high levels of insulin (p=0.016), triglycerides (p=0.018), intercellular adhesion molecule-1 (p=0.021), von Willebrand factor (p=0.005), and leptin (p=0.005) and lower levels of high-density lipoprotein cholesterol (p=0.042) compared with controls. Consistent with these data, 30% of patients but only 8% of controls fulfilled criteria for the metabolic syndrome as defined by the National Cholesterol Education Program (p=0.015). Endothelium-dependent and -independent microvascular functions were markedly impaired in patients (p<0.001), and the odds ratio for cardiac syndrome X was 7.38 (95% confidence interval 2.2 to 24.7) if the acetylcholine response was <8,710 flux units. In conclusion, women with cardiac syndrome X more commonly have metabolic syndrome and related adiposity, metabolic, and inflammatory derangements. They also have significantly impaired skin microvascular function as assessed by laser Doppler imaging, consistent with generalized vascular dysfunction, a finding with potential diagnostic implications. PMID:16765122

  19. Effect of Actual and Simulated Microgravity on Cardiac Mass and Function in the Rat

    NASA Technical Reports Server (NTRS)

    Ray, Chester H.; Vasques, Marilyn; Miller, Todd H.; Wilkerson, M. Keith; Delp, Michael D.; Dalton, Bonnie (Technical Monitor)

    2001-01-01

    The purpose of this study was to test the hypothesis that exposure to actual or simulated microgravity induces cardiac atrophy in male Sprague-Dawley rats. For the microgravity study, rats were subdivided into four groups: Preflight (PF, n = 12); Flight (FL, n = 7); Flight Cage Simulation (SIM, n = 6), and Vivarium Control (VIV, n = 7). Animals in the FL group were exposed to 7 days of microgravity during the Spacelab 3 mission. Animals in the simulated microgravity study were subdivided into three groups: Control (CON, n = 20); 7 day hindlimb unloaded (7HU, n = 10); and 28 day unloaded (28HU, n = 19). In a subset of CON (n = 7) and 28HU (n = 6) rats, a catheter was advanced into the left ventricle to measure the rate of rise in ventricular pressure (+dP/dt) during standing as an estimate of cardiac contractility. After completion of their respective treatments, hearts were removed and weighed. Animals in the PF group were sacrificed 24 hr prior to launch while the FL group was sacrificed 11- 17 hr after landing. The SM and VIV groups were sacrificed 48 and 96 hr after the FL group, respectively. Heart mass was unchanged in adult animals exposed to 7 days of actual microgravity (PF 1.33 +/- .03 g; FL 1.32 +/- 0.02 g; SIM 1.28 +/- 0.04 g; VIV 1.35 +/- 0.04 g). Similarly, heart mass was unaltered with hinlimb unloading (CON 1.40 +/- 0.04 g; 7HU 1.35 +/- 0.06 g; 28HU 1.42 +/- 0.03 g). Hindlimb unloading also had no effect on myocardial contractility (CON 8055 +/- 385 mmHg/sec; 28HU 8545 +/- 755 mmHg/sec). These data suggest that cardiac atrophy does not occur following short-term exposure to microgravity, and that neither short- nor long-term simulated microgravity alter cardiac mass or function.

  20. Impaired heart rate regulation and depression of cardiac chronotropic and dromotropic function in polymicrobial sepsis

    PubMed Central

    Hoover, Donald B.; Ozment, Tammy R.; Wondergem, Robert; Li, Chuanfu; Williams, David L.

    2014-01-01

    The scope of cardiac pathophysiology in sepsis has not been fully defined. Accordingly, we evaluated the effects of sepsis on heart rate (HR), HR variability, and conduction parameters in a murine model of sepsis. Electrocardiograms were recorded non-invasively from conscious mice before and after cecal ligation and puncture (CLP) or sham surgery. Responses of isolated atria to tyramine and isoproterenol were quantified to assess the functional state of sympathetic nerves and postjunctional sensitivity to adrenergic stimulation. CLP mice had lower HR compared to sham at 16-18 h post-surgery (Sham: 741±7 beats per min, CLP: 557±31 beats per min, n=6/group, P<0.001), and there was significant prolongation of the PR, QRS and QTc intervals. Slowing of HR and conduction developed within 4-6 h after CLP and were preceded by a decrease in HR variability. Treatment of CLP mice with isoproterenol (5 mg/kg, i.p.) at 25 h post-surgery failed to increase HR or decrease conduction intervals. The lack of in vivo response to isoproterenol cannot be attributed to hypothermia since robust chronotropic and inotropic responses to isoproterenol were evoked from isolated atria at 25 and 30° C. These findings demonstrate that impaired regulation of HR (i.e, reduced HR variability) develops before the onset of overt cardiac rate and conduction changes in septic mice. Subsequent time-dependent decreases in HR and cardiac conduction can be attributed to hypothermia and would contribute to decreased cardiac output and organ perfusion. Since isolated atria from septic mice showed normal responsiveness to adrenergic stimulation, we conclude that impaired effectiveness of isoproterenol in vivo can be attributed to reversible effects of systemic factors on adrenergic receptors and/or post-receptor signaling. PMID:25271380

  1. 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

  2. Suppression of Induced microRNA-15b Prevents Rapid Loss of Cardiac Function in a Dicer Depleted Model of Cardiac Dysfunction

    PubMed Central

    Gnyawali, Surya C.; Khanna, Savita; He, Guanglong; Pfeiffer, Douglas; Zweier, Jay L.; Sen, Chandan K.

    2013-01-01

    Background Dicer endonuclease, critical for maturation of miRNAs, is depleted in certain forms of cardiomyopathy which results in differential expression of certain microRNAs. We sought to elucidate the mechanisms underlying the rapid loss of cardiac function following cardiac-specific Dicer depletion in adult mice. Results Conditional Dicer deletion in the adult murine myocardium demonstrated compromised heart function, mitochondrial dysfunction and oxidant stress. Elevated miR-15b was observed as an early response to Dicer depletion and was found to silence Pim-1 kinase, a protein responsible for maintaining mitochondrial integrity and function. Anti-miRNA based suppression of induced miRNA-15b rescued the function of Dicer-depleted adult heart and attenuated hypertrophy. Conclusions Anti-miRNA based suppression of inducible miRNA-15b can prevent rapid loss of cardiac function in a Dicer-depleted adult heart and can be a key approach worthy of therapeutic consideration. PMID:23840532

  3. 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.

  4. Acute Hemodynamic Efficacy of a 32-ml Subcutaneous Counterpulsation Device in a Calf Model of Diminished Cardiac Function

    PubMed Central

    Koenig, Steven C.; Litwak, Kenneth N.; Giridharan, Guruprasad A.; Pantalos, George M.; Dowling, Robert D.; Prabhu, Sumanth D.; Slaughter, Mark S.; Sobieski, Michael A.; Spence, Paul A.

    2010-01-01

    The acute hemodynamic efficacy of an implantable counter-pulsation device (CPD) was evaluated. The CPD is a valveless single port, 32-ml stroke volume blood chamber designed to be connected to the human axillary artery using a simple surface surgical procedure. Blood is drawn into the pump during systole and ejected during diastole. The acute hemodynamic effects of the 32-ml CPD were compared to a standard clinical 40-ml intra-aortic balloon pump (IABP) in calves (80 kg, n = 10). The calves were treated by a single oral dose of Monensin to produce a model of diminished cardiac function (DCF). The CPD and IABP produced similar increases in cardiac output (6% CPD vs. 5% IABP, p > 0.5) and reduction in left ventricular external work (14% CPD vs. 13% IABP, p > 0.5) compared to DCF (p < 0.05). However, the ratio of diastolic coronary artery flow to left ventricular external work increase from DCF baseline (p < 0.05) was greater with the CPD compared to the IABP (15% vs. 4%, p < 0.05). The CPD also produced a greater reduction in left ventricular myocardial oxygen consumption from DCF baseline (p < 0.05) compared to the IABP (13% vs. 9%, p < 0.05) despite each device providing similar improvements in cardiac output. There was no early indication of hemolysis, thrombus formation, or vascular injury. The CPD provides hemodynamic efficacy equivalent to an IABP and may become a therapeutic option for patients who may benefit from prolonged counterpulsation. PMID:19033769

  5. Acute hemodynamic efficacy of a 32-ml subcutaneous counterpulsation device in a calf model of diminished cardiac function.

    PubMed

    Koenig, Steven C; Litwak, Kenneth N; Giridharan, Guruprasad A; Pantalos, George M; Dowling, Robert D; Prabhu, Sumanth D; Slaughter, Mark S; Sobieski, Michael A; Spence, Paul A

    2008-01-01

    The acute hemodynamic efficacy of an implantable counterpulsation device (CPD) was evaluated. The CPD is a valveless single port, 32-ml stroke volume blood chamber designed to be connected to the human axillary artery using a simple surface surgical procedure. Blood is drawn into the pump during systole and ejected during diastole. The acute hemodynamic effects of the 32-ml CPD were compared to a standard clinical 40-ml intra-aortic balloon pump (IABP) in calves (80 kg, n = 10). The calves were treated by a single oral dose of Monensin to produce a model of diminished cardiac function (DCF). The CPD and IABP produced similar increases in cardiac output (6% CPD vs. 5% IABP, p > 0.5) and reduction in left ventricular external work (14% CPD vs. 13% IABP, p > 0.5) compared to DCF (p < 0.05). However, the ratio of diastolic coronary artery flow to left ventricular external work increase from DCF baseline (p < 0.05) was greater with the CPD compared to the IABP (15% vs. 4%, p < 0.05). The CPD also produced a greater reduction in left ventricular myocardial oxygen consumption from DCF baseline (p < 0.05) compared to the IABP (13% vs. 9%, p < 0.05) despite each device providing similar improvements in cardiac output. There was no early indication of hemolysis, thrombus formation, or vascular injury. The CPD provides hemodynamic efficacy equivalent to an IABP and may become a therapeutic option for patients who may benefit from prolonged counterpulsation. PMID:19033769

  6. Dual transcriptional activator and repressor roles of TBX20 regulate adult cardiac structure and function

    PubMed Central

    Sakabe, Noboru J.; Aneas, Ivy; Shen, Tao; Shokri, Leila; Park, Soo-Young; Bulyk, Martha L.; Evans, Sylvia M.; Nobrega, Marcelo A.

    2012-01-01

    The ongoing requirement in adult heart for transcription factors with key roles in cardiac development is not well understood. We recently demonstrated that TBX20, a transcriptional regulator required for cardiac development, has key roles in the maintenance of functional and structural phenotypes in adult mouse heart. Conditional ablation of Tbx20 in adult cardiomyocytes leads to a rapid onset and progression of heart failure, with prominent conduction and contractility phenotypes that lead to death. Here we describe a more comprehensive molecular characterization of the functions of TBX20 in adult mouse heart. Coupling genome-wide chromatin immunoprecipitation and transcriptome analyses (RNA-Seq), we identified a subset of genes that change expression in Tbx20 adult cardiomyocyte-specific knockout hearts which are direct downstream targets of TBX20. This analysis revealed a dual role for TBX20 as both a transcriptional activator and a repressor, and that each of these functions regulates genes with very specialized and distinct molecular roles. We also show how TBX20 binds to its targets genome-wide in a context-dependent manner, using various cohorts of co-factors to either promote or repress distinct genetic programs within adult heart. Our integrative approach has uncovered several novel aspects of TBX20 and T-box protein function within adult heart. Sequencing data accession number (http://www.ncbi.nlm.nih.gov/geo): GSE30943. PMID:22328084

  7. Palmitoyl acyltransferase Aph2 in cardiac function and the development of cardiomyopathy

    PubMed Central

    Zhou, Tielin; Li, Jing; Zhao, Peiquan; Liu, Huijuan; Jia, Deyong; Jia, Hao; He, Lin; Cang, Yong; Boast, Sharon; Chen, Yi-Han; Thibault, Hélène; Scherrer-Crosbie, Marielle; Goff, Stephen P.; Li, Baojie

    2015-01-01

    Protein palmitoylation regulates many aspects of cell function and is carried out by acyl transferases that contain zf-DHHC motifs. The in vivo physiological function of protein palmitoylation is largely unknown. Here we generated mice deficient in the acyl transferase Aph2 (Ablphilin 2 or zf-DHHC16) and demonstrated an essential role for Aph2 in embryonic/postnatal survival, eye development, and heart development. Aph2−/− embryos and pups showed cardiomyopathy and cardiac defects including bradycardia. We identified phospholamban, a protein often associated with human cardiomyopathy, as an interacting partner and a substrate of Aph2. Aph2-mediated palmitoylation of phospholamban on cysteine 36 differentially alters its interaction with PKA and protein phosphatase 1 α, augmenting serine 16 phosphorylation, and regulates phospholamban pentamer formation. Aph2 deficiency results in phospholamban hypophosphorylation, a hyperinhibitory form. Ablation of phospholamban in Aph2−/− mice histologically and functionally alleviated the heart defects. These findings establish Aph2 as a critical in vivo regulator of cardiac function and reveal roles for protein palmitoylation in the development of other organs including eyes. PMID:26644582

  8. Palmitoyl acyltransferase Aph2 in cardiac function and the development of cardiomyopathy.

    PubMed

    Zhou, Tielin; Li, Jing; Zhao, Peiquan; Liu, Huijuan; Jia, Deyong; Jia, Hao; He, Lin; Cang, Yong; Boast, Sharon; Chen, Yi-Han; Thibault, Hélène; Scherrer-Crosbie, Marielle; Goff, Stephen P; Li, Baojie

    2015-12-22

    Protein palmitoylation regulates many aspects of cell function and is carried out by acyl transferases that contain zf-DHHC motifs. The in vivo physiological function of protein palmitoylation is largely unknown. Here we generated mice deficient in the acyl transferase Aph2 (Ablphilin 2 or zf-DHHC16) and demonstrated an essential role for Aph2 in embryonic/postnatal survival, eye development, and heart development. Aph2(-/-) embryos and pups showed cardiomyopathy and cardiac defects including bradycardia. We identified phospholamban, a protein often associated with human cardiomyopathy, as an interacting partner and a substrate of Aph2. Aph2-mediated palmitoylation of phospholamban on cysteine 36 differentially alters its interaction with PKA and protein phosphatase 1 α, augmenting serine 16 phosphorylation, and regulates phospholamban pentamer formation. Aph2 deficiency results in phospholamban hypophosphorylation, a hyperinhibitory form. Ablation of phospholamban in Aph2(-/-) mice histologically and functionally alleviated the heart defects. These findings establish Aph2 as a critical in vivo regulator of cardiac function and reveal roles for protein palmitoylation in the development of other organs including eyes. PMID:26644582

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

    DOE PAGESBeta

    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 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

  10. 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.

  11. 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. PMID:26608937

  12. Oxygen supply and nitric oxide scavenging by myoglobin contribute to exercise endurance and cardiac function.

    PubMed

    Merx, Marc W; Gödecke, Axel; Flögel, Ulrich; Schrader, Jürgen

    2005-06-01

    Recent studies of myoglobin (Mb) knockout (myo-/-) mice have extended our understanding of Mb's diverse functions and have demonstrated a complex array of compensatory mechanisms. The present study was aimed at detailed analysis of cardiac function and exercise endurance in myo-/- mice and at providing evidence for Mb's functional relevance. Myo-/- isolated working hearts display decreased contractility (dP/dtmax 3883+/-351 vs. 4618+/-268 mmHg/sec, myo-/- vs. WT, P<0.005). Due to a shift in sympathetic/parasympathetic tone, heart rate is reduced in conscious myo mice-/- (615+/-33 vs. 645+/-27 bpm, myo-/- vs. WT, P<0.001). Oxygen consumption (VO2) under resting conditions (3082+/-413 vs. 4452+/-552 ml x kg(-1) x h(-1), myo-/- vs. WT, P<0.001) and exercise endurance, as determined by spiroergometry, are decreased (466+/-113 vs. 585+/-153 m, myo-/- vs. WT, P<0.01). Conscious myo-/- mice evaluated by echocardiography display lowered cardiac output (0.64+/-0.06 vs. 0.75+/-0.09 ml x min(-1) x g(-1), myo-/- vs. WT, P<0.001), impaired systolic shortening (60+/-3.5 vs. 65+/-4%, myo-/- vs. WT, P<0.001) and fail to respond to beta1-stimulation. Strikingly, the latter cardiac effects of Mb deficiency can be partially attenuated by NOS inhibition. Loss of Mb results in a distinct phenotype, even under resting conditions, and the importance of oxygen supply and nitric oxide scavenging by Mb is clearly demonstrated at the conscious animal level. PMID:15817640

  13. 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

  14. 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

  15. Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction

    PubMed Central

    Muthu, Priya; Wang, Li; Yuan, Chen-Ching; Kazmierczak, Katarzyna; Huang, Wenrui; Hernandez, Olga M.; Kawai, Masataka; Irving, Thomas C.; Szczesna-Cordary, Danuta

    2011-01-01

    The myosin essential light chain (ELC) is a structural component of the actomyosin cross-bridge, but its function is poorly understood, especially the role of the cardiac specific N-terminal extension in modulating actomyosin interaction. Here, we generated transgenic (Tg) mice expressing the A57G (alanine to glycine) mutation in the cardiac ELC known to cause familial hypertrophic cardiomyopathy (FHC). The function of the ELC N-terminal extension was investigated with the Tg-Δ43 mouse model, whose myocardium expresses a truncated ELC. Low-angle X-ray diffraction studies on papillary muscle fibers in rigor revealed a decreased interfilament spacing (∼1.5 nm) and no alterations in cross-bridge mass distribution in Tg-A57G mice compared to Tg-WT, expressing the full-length nonmutated ELC. The truncation mutation showed a 1.3-fold increase in I1,1/I1,0, indicating a shift of cross-bridge mass from the thick filament backbone toward the thin filaments. Mechanical studies demonstrated increased stiffness in Tg-A57G muscle fibers compared to Tg-WT or Tg-Δ43. The equilibrium constant for the cross-bridge force generation step was smallest in Tg-Δ43. These results support an important role for the N-terminal ELC extension in prepositioning the cross-bridge for optimal force production. Subtle changes in the ELC sequence were sufficient to alter cross-bridge properties and lead to pathological phenotypes.—Muthu, P., Wang, L., Yuan, C.-C., Kazmierczak, K., Huang, W., Hernandez, O. M., Kawai, M., Irving, T. C., Szczesna-Cordary, D. Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction. PMID:21885653

  16. [Research on Cardiac Structure and Function in the Overweight and Obese population and Influence Factors].

    PubMed

    Zhang, Yanmei; Han, Lina; Huang, He; Yu, Yerong; Li, Jiangbo; Liu, Xiaoqin

    2016-02-01

    In this study we performed Tissue Doppler Imaging (TDI), two-dimensional speckle tracking imaging (2D- STI) and three-dimensional speckle tracking imaging (3D-STI) on enrolled healthy, overweight and obese groups (34 subjects in each group), respectively, to analyze cardiac structure and its function. Compared with healthy group, global longitudinal strain (GLS), global circumferential strain (GCS), global area strain(GAS) and global radial strain (GRS) decreased progressively (P < 0.05). The ratio of early diastolic mitral inflow velocity to global early diastolic strain rate of left ventricle (E/e'sr) (r = 0.466, P < 0.001), GLS (r = 0.502, P < 0. 001), GCS (r = 0.426, P < 0.001), GAS (r = 0.535, P < 0.001) and GRS (r = -0.554, P < 0.001) were correlated with body mass index (BMI). E/e'sr (r = 0.37, P = 0.003), GLS (r = 0.455, P < 0.001), GCS (r = 0.282, P = 0.02), GAS (r = 0.412, P < 0.001) and GRS (r = -0.471, P < 0.001) were correlated with free fatty acid (FFA). Stepwise multiple linear regression revealed that BMI was independently correlated with E/e'sr, GLS, GCS, GAS and GRS. Waist to hip ratio (WHR) was independently correlated with GLS, GCS, GAS and GRS. FFA was independently correlated with E/e'sr (P < 0.05). The study showed that cardiac structure changed and impaired left ventricular global systolic and diastolic function in overweight and obes population. Moreover, BMI, WHR and FFA may be independent influence factors of cardiac function in overweight and obese population. PMID:27382752

  17. 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

  18. Simple Measures of Function and Symptoms in Hospitalized Heart Failure Patients Predict Short-Term Cardiac Event-Free Survival

    PubMed Central

    Cataldo, Janine; Mackin, Lynda

    2014-01-01

    Background. Heart failure (HF) is a prevalent chronic condition where patients experience numerous uncomfortable symptoms, low functional status, and high mortality rates. Objective. To determine whether function and/or symptoms predict cardiac event-free survival in hospitalized HF patients within 90 days of hospital discharge. Methods. Inpatients (N = 32) had HF symptoms assessed with 4 yes/no questions. Function was determined with NYHA Classification, Katz Index of Activities of Daily Living (ADLs), and directly with the short physical performance battery (SPPB). Survival was analyzed with time to the first postdischarge cardiac event with events defined as cardiac rehospitalization, heart transplantation, or death. Results. Mean age was 58.2 ± 13.6 years. Patient reported ADL function was nearly independent (5.6 ± 1.1) while direct measure (SPPB) showed moderate functional limitation (6.4 ± 3.1). Within 90 days, 40.6% patients had a cardiac event. At discharge, each increase in NYHA Classification was associated with a 3.4-fold higher risk of cardiac events (95% CI 1.4–8.5). Patients reporting symptoms of dyspnea, fatigue, and orthopnea before discharge had a 4.0-fold, 9.7-fold, and 12.8-fold, respectively, greater risk of cardiac events (95% CI 1.2–13.2; 1.2–75.1; 1.7–99.7). Conclusions. Simple assessments of function and symptoms easily performed at discharge may predict short-term cardiac outcomes in hospitalized HF patients. PMID:24672717

  19. Functional molecular markers for crop improvement.

    PubMed

    Kage, Udaykumar; Kumar, Arun; Dhokane, Dhananjay; Karre, Shailesh; Kushalappa, Ajjamada C

    2016-10-01

    A tremendous decline in cultivable land and resources and a huge increase in food demand calls for immediate attention to crop improvement. Though molecular plant breeding serves as a viable solution and is considered as "foundation for twenty-first century crop improvement", a major stumbling block for crop improvement is the availability of a limited functional gene pool for cereal crops. Advancement in the next generation sequencing (NGS) technologies integrated with tools like metabolomics, proteomics and association mapping studies have facilitated the identification of candidate genes, their allelic variants and opened new avenues to accelerate crop improvement through development and use of functional molecular markers (FMMs). The FMMs are developed from the sequence polymorphisms present within functional gene(s) which are associated with phenotypic trait variations. Since FMMs obviate the problems associated with random DNA markers, these are considered as "the holy grail" of plant breeders who employ targeted marker assisted selections (MAS) for crop improvement. This review article attempts to consider the current resources and novel methods such as metabolomics, proteomics and association studies for the identification of candidate genes and their validation through virus-induced gene silencing (VIGS) for the development of FMMs. A number of examples where the FMMs have been developed and used for the improvement of cereal crops for agronomic, food quality, disease resistance and abiotic stress tolerance traits have been considered. PMID:26171816

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

    PubMed Central

    SAENGKLUB, Nakkawee; LIMPRASUTR, Vudhiporn; SAWANGKOON, Suwanakiet; BURANAKARL, Chollada; HAMLIN, Robert L.; KIJTAWORNRAT, Anusak

    2015-01-01

    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. PMID:26346474

  1. 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

    2016-03-01

    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. PMID:26346474

  2. Bimodal biophotonic imaging of the structure-function relationship in cardiac tissue

    PubMed Central

    Hucker, William J.; Ripplinger, Crystal M.; Fleming, Christine P.; Fedorov, Vadim V.; Rollins, Andrew M.; Efimov, Igor R.

    2009-01-01

    The development of systems physiology is hampered by the limited ability to relate tissue structure and function in intact organs in vivo or in vitro. Here, we show the application of a bimodal biophotonic imaging approach that employs optical coherence tomography and fluorescent imaging to investigate the structure-function relationship at the tissue level in the heart. Reconstruction of cardiac excitation and structure was limited by the depth penetration of bimodal imaging to ∼2 mm in atrial tissue, and ∼1 mm in ventricular myocardium. The subcellular resolution of optical coherence tomography clearly demonstrated that microscopic fiber orientation governs the pattern of wave propagation in functionally characterized rabbit sinoatrial and atrioventricular nodal preparations and revealed structural heterogeneities contributing to ventricular arrhythmias. The combination of this bimodal biophotonic imaging approach with histology and/or immunohistochemistry can span multiple scales of resolution for the investigation of the molecular and structural determinants of intact tissue physiology. PMID:19021392

  3. Hyperinsulinemia improves ischemic LV function in insulin resistant subjects

    PubMed Central

    2010-01-01

    Background Glucose is a more efficient substrate for ATP production than free fatty acid (FFA). Insulin resistance (IR) results in higher FFA concentrations and impaired myocardial glucose use, potentially worsening ischemia. We hypothesized that metabolic manipulation with a hyperinsulinemic euglycemic clamp (HEC) would affect a greater improvement in left ventricular (LV) performance during dobutamine stress echo (DSE) in subjects with IR. Methods 24 subjects with normal LV function and coronary disease (CAD) awaiting revascularization underwent 2 DSEs. Prior to one DSEs they underwent an HEC, where a primed infusion of insulin (rate 43 mU/m 2/min) was co-administered with 20% dextrose at variable rates to maintain euglycemia. At steady-state the DSE was performed and images of the LV were acquired with tissue Doppler at each stage for offline analysis. Segmental peak systolic velocities (Vs) were recorded, as well as LV ejection fraction (EF). Subjects were then divided into two groups based on their insulin sensitivity during the HEC. Results HEC changed the metabolic environment, suppressing FFAs and thereby increasing glucose use. This resulted in improved LV performance at peak stress, measured by EF (IS group mean difference 5.3 (95% CI 2.5-8) %, p = 0.002; IR group mean difference 8.7 (95% CI 5.8-11.6) %, p < 0.0001) and peak V s in ischemic segments (IS group mean improvement 0.7(95% CI 0.07-1.58) cm/s, p = 0.07; IR group mean improvement 1.0 (95% CI 0.54-1.5) cm/s, p < 0.0001) , that was greater in the subjects with IR. Conclusions Increased myocardial glucose use induced by HEC improves LV function under stress in subjects with CAD and IR. Cardiac metabolic manipulation in subjects with IR is a promising target for future therapy. PMID:20576156

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

    PubMed Central

    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. PMID:23638213

  5. Effects of experimental cardiac volume loading on left atrial phasic function in healthy dogs.

    PubMed

    Osuga, Tatsuyuki; Nakamura, Kensuke; Morita, Tomoya; Nisa, Khoirun; Yokoyama, Nozomu; Sasaki, Noboru; Morishita, Keitaro; Ohta, Hiroshi; Takiguchi, Mitsuyoshi

    2016-09-01

    OBJECTIVE To elucidate the relationship between acute volume overload and left atrial phasic function in healthy dogs. ANIMALS 6 healthy Beagles. PROCEDURES Dogs were anesthetized. A Swan-Ganz catheter was placed to measure mean pulmonary capillary wedge pressure (PCWP). Cardiac preload was increased by IV infusion with lactated Ringer solution at 150 mL/kg/h for 90 minutes. Transthoracic echocardiography was performed before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after volume loading began. At each echocardiographic assessment point, apical 4-chamber images were recorded and analyzed to derive time-left atrial area curves. Left atrial total (for reservoir function), passive (for conduit function), and active (for booster-pump function) fractional area changes were calculated from the curves. RESULTS Volume overload resulted in a significant increase from baseline in PCWP from 15 to 90 minutes after volume loading began. All fractional area changes at 15 to 90 minutes were significantly increased from baseline. In multiple regression analysis, quadratic regression models were better fitted to the relationships between PCWP and each of the total and active fractional area changes than were linear regression models. A linear regression model was better fitted to the relationship between PCWP and passive fractional area change. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that left atrial phasic function assessed on the basis of left atrial phasic areas was enhanced during experimental cardiac volume loading in healthy dogs. The effect of volume load should be considered when evaluating left atrial phasic function by indices derived from left atrial phasic sizes. PMID:27580106

  6. 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.

  7. 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. PMID:26371171

  8. 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-da