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Sample records for factors cardiac function

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

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    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

  2. Cleavage of serum response factor mediated by enteroviral protease 2A contributes to impaired cardiac function

    Institute of Scientific and Technical Information of China (English)

    Jerry Wong; Jingchun Zhang; Bobby Yanagawa; Zongshu Luo; Xiangsheng Yang; Jiang Chang; Bruce McManus; Honglin Luo

    2012-01-01

    Enteroviral infection can lead to dilated cardiomyopathy (DCM),which is a major cause of cardiovascular mortality worldwide.However,the pathogenetic mechanisms have not been fully elucidated.Serum response factor (SRF) is a cardiac-enriched transcription regulator controlling the expression of a variety of target genes,including those involved in the contractile apparatus and immediate early response,as well as microRNAs that silence the expression of cardiac regulatory factors.Knockout of SRF in the heart results in downregulation of cardiac contractile gene expression and development of DCM.The goal of this study is to understand the role of SRF in enterovirus-induced cardiac dysfunction and progression to DCM.Here we report that SRF is cleaved following enteroviral infection of mouse heart and cultured cardiomyocytes.This cleavage is accompanied by impaired cardiac function and downregulation of cardiac-specific contractile and regulatory genes.Further investigation by antibody epitope mapping and site-directed mutagenesis demonstrates that SRF cleavage occurs at the region of its transactivation domain through the action of virus-encoded protease 2A.Moreover,we demonstrate that cleavage of SRF dissociates its transactivation domain from DNA-binding domain,resulting in the disruption of SRF-mediated gene transactivation.In addition to loss of functional SRF,finally we report that the N-terminal fragment of SRF cleavage products can also act as a dominant-negative transcription factor,which likely competes with the native SRF for DNA binding.Our results suggest a mechanism by which virus infection impairs heart function and may offer a new therapeutic strategy to ameliorate myocardial damage and progression to DCM.

  3. Stem cell factor gene transfer improves cardiac function after myocardial infarction in swine.

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    Ishikawa, Kiyotake; Fish, Kenneth; Aguero, Jaume; Yaniz-Galende, Elisa; Jeong, Dongtak; Kho, Changwon; Tilemann, Lisa; Fish, Lauren; Liang, Lifan; Eltoukhy, Ahmed A; Anderson, Daniel G; Zsebo, Krisztina; Costa, Kevin D; Hajjar, Roger J

    2015-01-01

    Stem cell factor (SCF), a ligand of the c-kit receptor, is a critical cytokine, which contributes to cell migration, proliferation, and survival. It has been shown that SCF expression increases after myocardial infarction (MI) and may be involved in cardiac repair. The aim of this study was to determine whether gene transfer of membrane-bound human SCF improves cardiac function in a large animal model of MI. A transmural MI was created by implanting an embolic coil in the left anterior descending artery in Yorkshire pigs. One week after the MI, the pigs received direct intramyocardial injections of either a recombinant adenovirus encoding for SCF (Ad.SCF, n=9) or β-gal (Ad.β-gal, n=6) into the infarct border area. At 3 months post-MI, ejection fraction increased by 12% relative to baseline after Ad.SCF therapy, whereas it decreased by 4.2% (P=0.004) in pigs treated with Ad.β-gal. Preload-recruitable stroke work was significantly higher in pigs after SCF treatment (Ad.SCF, 55.5±11.6 mm Hg versus Ad.β-gal, 31.6±12.6 mm Hg, P=0.005), indicating enhanced cardiac function. Histological analyses confirmed the recruitment of c-kit(+) cells as well as a reduced degree of apoptosis 1 week after Ad.SCF injection. In addition, increased capillary density compared with pigs treated with Ad.β-gal was found at 3 months and suggests an angiogenic role of SCF. Local overexpression of SCF post-MI induces the recruitment of c-kit(+) cells at the infarct border area acutely. In the chronic stages, SCF gene transfer was associated with improved cardiac function in a preclinical model of ischemic cardiomyopathy. © 2014 American Heart Association, Inc.

  4. Interferon Regulatory Factor 7 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

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    Jiang, Ding-Sheng; Liu, Yu; Zhou, Heng; Zhang, Yan; Zhang, Xiao-Dong; Zhang, Xiao-Fei; Chen, Ke; Gao, Lu; Peng, Juan; Gong, Hui; Chen, Yingjie; Yang, Qinglin; Liu, Peter P.; Fan, Guo-Chang; Zou, Yunzeng; Li, Hongliang

    2017-01-01

    Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding–induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload–induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II–induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBαS32A/S36A super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-βS177E/S181E (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy. PMID:24396025

  5. Interferon regulatory factor 7 functions as a novel negative regulator of pathological cardiac hypertrophy.

    Science.gov (United States)

    Jiang, Ding-Sheng; Liu, Yu; Zhou, Heng; Zhang, Yan; Zhang, Xiao-Dong; Zhang, Xiao-Fei; Chen, Ke; Gao, Lu; Peng, Juan; Gong, Hui; Chen, Yingjie; Yang, Qinglin; Liu, Peter P; Fan, Guo-Chang; Zou, Yunzeng; Li, Hongliang

    2014-04-01

    Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding-induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II-induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBα(S32A/S36A) super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-β(S177E/S181E) (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy.

  6. Granulocyte-macrophage colony stimulating factor improves cardiac function in rabbits following myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    董安平; 马爱群; 韩克; 杨春; 蔡平; 蒋文慧

    2003-01-01

    Objective: To investigate the therapeutic potency of recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in a rabbit myocardial infarction model. Methods: A myocardial infarction was created by the ligation of the major ventricular branch of the left coronary artery in rabbits. After myocardial infarction, the animals were randomly assigned to GM-CSF treatment group, untreated groups and sham-operated group. The rabbits of the treated group were injected into GM-CSF by subcutaneous administration, 10 μg/kg/day, once a day for 5 days. The untreated and sham-operated group received a equal saline in the same manner as treated group. Six weeks later echocardiography and haemodynamic assessment were undertaken to assesse cardiac function. The size of the infarct region of the heart were also studied. Results: The untreated group exhibited significant higher left ventricle end-diastolic pressure, higher central venous pressure, and with significant lower mean blood pressure, lower peak first derivative of left ventricle pressure (dP/dt) than the sham group. Also, Rabbits in untreated group display significant systolic dysfunction shown by the decreased ejection fraction, diastolic dysfunction shown by increasing in the ratio of E wave to A wave (E/A), and display left ventricle enlargement. However, GS-CSF singnificantly prevented heart dysfunction, left ventricle enlargement, and reduced infarct size in treatment group. Conclusion: Administration GM-CSF after cardiac infarction can improve heart function. These findings indicate the technique may be a novel and simple therapeutic method for ischemic myocardium.

  7. Assessment of Cardiac Functional Alterations of Ankylosing Spondylitis Patients without Cardiovascular Risk Factors

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    Alper Kepez

    2013-08-01

    Full Text Available Introduction: The aim of this study is to evaluate cardiac functional alterations of ankylosing spondylitis patients without any cardiovascular risk factors.Patients and Methods: Thirty seven consecutive akylosing spondylitis patients without any cardiovascular risk factors constituted our study patient population (age: 41.4 ± 11.1 years, 28 male. Electrocardiographs (ECG of all patients were obtained and all patients underwent comprehensive transthoracic echocardiographic examination. QRS durations, p wave dispersion and corrected QT dispersion (QTcd values were calculated from 12-lead ECG’s. Data reflecting left ventricular systolic and diastolic functions were obtained from echocardiographic examinations. Data of patients were compared with the data of 28 age-and gender matched healthy control subjects (age: 40.1 ± 10.5 years, 19 male.Results: There were no significant differences between patients and controls regarding QRS durations, p wave dispersion and QTcd values. There were also no significant differences between patients and controls regarding parameters reflecting left ventricular systolic and diastolic functions. Annular velocities at mitral and tricuspid annulus levels evaluated with pulsed-wave tissue Doppler imaging were also similar as well. Two (7.2% subjects in the control group and 2 (5.4% patients in the akylosing spondylitis group had minimal aortic regurgitation (p= 0.51. Conclusion: We could not demonstrate any electrocardiographic or echocardiographic evidence of structural myocardial alterations in a small sample of akylosing spondylitis patients free of cardiovascular risk factors. Effects of frequently encountered co-existent cardiovascular risk factors of ankylosing spondylitis patients might have contributed to the conflicting literature data related with this topic.

  8. The Function of the MEF2 Family of Transcription Factors in Cardiac Development, Cardiogenomics, and Direct Reprogramming

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    Cody A. Desjardins

    2016-08-01

    Full Text Available Proper formation of the mammalian heart requires precise spatiotemporal transcriptional regulation of gene programs in cardiomyocytes. Sophisticated regulatory networks have evolved to not only integrate the activities of distinct transcription factors to control tissue-specific gene programs but also, in many instances, to incorporate multiple members within these transcription factor families to ensure accuracy and specificity in the system. Unsurprisingly, perturbations in this elaborate transcriptional circuitry can lead to severe cardiac abnormalities. Myocyte enhancer factor–2 (MEF2 transcription factor belongs to the evolutionarily conserved cardiac gene regulatory network. Given its central role in muscle gene regulation and its evolutionary conservation, MEF2 is considered one of only a few core cardiac transcription factors. In addition to its firmly established role as a differentiation factor, MEF2 regulates wide variety of, sometimes antagonistic, cellular processes such as cell survival and death. Vertebrate genomes encode multiple MEF2 family members thereby expanding the transcriptional potential of this core transcription factor in the heart. This review highlights the requirement of the MEF2 family and their orthologs in cardiac development in diverse animal model systems. Furthermore, we describe the recently characterized role of MEF2 in direct reprogramming and genome-wide cardiomyocyte gene regulation. A thorough understanding of the regulatory functions of the MEF2 family in cardiac development and cardiogenomics is required in order to develop effective therapeutic strategies to repair the diseased heart.

  9. N-ethylmaleimide-sensitive factor siRNA improves cardiac function following myocardial infarction in rats.

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    Zhou, Y; Liu, Y; Yang, S X; Wang, Z

    2015-08-14

    This study examined the effects of N-ethylmaleimide-sensitive factor (NSF) small interfering RNA (siRNA) on cardiac function following myocardial infarction (MI) in rats. Thirty-six adult Sprague Dawley rats were randomly divided into three equivalent groups. An acute MI model was established by ligating the anterior descending branch of the left coronary artery and confirmed by electrocardiogram. Recombinant NSF-siRNA adenovirus (experimental), negative adenovirus (control), and normal saline were injected near the infarcted area of the left ventricle in each respective group. The left ventricular ejection fraction (LVEF) was measured with a noninvasive ultrasonic cardiogram. Left ventricular end-diastolic pressure (LVEDP) and the maximum rate of rise in left ventricular pressure (+dp/dt max) were measured using the BL-420 Biological Functional Experimental System. Hearts were sectioned and stained with 2,3,5,-triphenyl tetrazolium chloride (TTC) to observe the MI area. Two weeks after surgery, LVEF in the experimental group (46.0 ± 7.5%) was higher than control (34.0 ± 6.0%) and saline (37.5 ± 4.5%) group LVEFs (P function two weeks after MI, but had no impact on the MI area.

  10. Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Lipsic, Erik; van der Meer, Peter; van der Harst, Pirn; Oeseburg, Hisko; Sarvaas, Gideon J. Du Marchie; Koster, Johan; Voors, Adriaan A.; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Schoemaker, Regien G.

    2007-01-01

    Aims Erythropoietin (EPO) improves cardiac function and induces neovascutarization in chronic heart failure (CHF), although the exact mechanism has not been elucidated. We studied the effects of EPO on homing and incorporation of endothelial progenitor cells (EPC) into the myocardial microvasculatur

  11. Cardiac structure and function in relation to cardiovascular risk factors in Chinese

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    Zhang Yi

    2012-10-01

    Full Text Available Abstract Background Cardiac structure and function are well-studied in Western countries. However, epidemiological data is still scarce in China. Methods Our study was conducted in the framework of cardiovascular health examinations for the current and retired employees of a factory and their family members. According to the American Society of Echocardiography recommendations, we performed echocardiography to evaluate cardiac structure and function, including left atrial volume, left ventricular hypertrophy and diastolic dysfunction. Results The 843 participants (43.0 years included 288 (34.2% women, and 191 (22.7% hypertensive patients, of whom 82 (42.9% took antihypertensive drugs. The prevalence of left atrial enlargement, left ventricular hypertrophy and concentric remodeling was 2.4%, 5.0% and 12.7%, respectively. The prevalence of mild and moderate-to-severe left ventricular diastolic dysfunction was 14.2% and 3.3%, respectively. The prevalence of these cardiac abnormalities significantly (P ≤ 0.002 increased with age, except for the moderate-to-severe left ventricular diastolic dysfunction. After adjustment for age, gender, body height and body weight, left atrial enlargement was associated with plasma glucose (P = 0.009, and left ventricular hypertrophy and diastolic dysfunction were significantly associated with systolic and diastolic blood pressure (P ≤ 0.03, respectively. Conclusions The prevalence of cardiac structural and functional abnormalities increased with age in this Chinese population. Current drinking and plasma glucose had an impact on left atrial enlargement, whereas systolic and diastolic blood pressures were major correlates for left ventricular hypertrophy and diastolic dysfunction, respectively.

  12. Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Ruifrok, Willem-Peter T.; Voors, Adriaan A.; Tilton, Ronald G.; van Veldhuisen, Dirk J.; Schoemaker, Regien G.; van Gilst, Wiek H.; de Boer, Rudolf A.

    2010-01-01

    We intended to delineate the mechanisms of erythropoietin (EPO)-induced cardiac vascular endothelial growth factor (VEGF) production and to establish if VEGF is crucial for EPO-induced improvement of cardiac performance. The effects of EPO on VEGF expression were studied in cultured cardiac cells an

  13. Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Ruifrok, Willem-Peter T.; Voors, Adriaan A.; Tilton, Ronald G.; van Veldhuisen, Dirk J.; Schoemaker, Regien G.; van Gilst, Wiek H.; de Boer, Rudolf A.

    2010-01-01

    We intended to delineate the mechanisms of erythropoietin (EPO)-induced cardiac vascular endothelial growth factor (VEGF) production and to establish if VEGF is crucial for EPO-induced improvement of cardiac performance. The effects of EPO on VEGF expression were studied in cultured cardiac cells an

  14. Localized Delivery of Mechano-Growth Factor E-domain Peptide via Polymeric Microstructures Improves Cardiac Function following Myocardial Infarction

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    Peña, James R.; Pinney, James; Ayala, Perla; Desai, Tejal; Goldspink, Paul H.

    2015-01-01

    The Insulin like growth factor-I isoform mechano-growth factor (MGF), is expressed in the heart following myocardial infarction and encodes a unique E-domain region. To examine E-domain function, we delivered a synthetic peptide corresponding to the unique E-domain region of the human MGF (IGF-1Ec) via peptide eluting polymeric microstructures to the heart. The microstructures were made of poly (ethylene glycol) dimethacrylate hydrogel and bioengineered to be the same size as an adult cardiac myocyte (100×15×15 μm) and with a stiffness of 20 kPa. Peptide eluting microrods and empty microrods were delivered via intramuscular injection following coronary artery ligation in mice. To examine the physiologic consequences, we assessed the impact of peptide delivery on cardiac function and cardiovascular hemodynamics using pressure-volume loops and gene expression by quantitative RT-PCR. A significant decline in both systolic and diastolic function accompanied by pathologic hypertrophy occurred by 2 weeks which decompensated further by 10 weeks post-infarct in the untreated groups. Delivery of the E-domain peptide eluting microrods decreased mortality, ameliorated the decline in hemodynamics, and delayed decompensation. This was associated with the inhibition of pathologic hypertrophy despite increasing vascular impedance. Delivery of the empty microrods had limited effects on hemodynamics and while pathologic hypertrophy persisted there was a decrease in ventricular stiffness. Our data show that cardiac restricted administration of the MGF E-domain peptide using polymeric microstructures may be used to prevent adverse remodeling of the heart and improve function following myocardial infarction. PMID:25678113

  15. Combined treatment with erythropoietin and granulocyte colony-stimulating factor enhances neovascularization and improves cardiac function after myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Xue Jingyi; Du Guoqing; Shi Jing; Li Yue; Masahiro Yasutake; Liu Lei; Li Jianqiang

    2014-01-01

    Background Erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) are both potential novel therapeutics for use after myocardial infarction (MI).However,their underlying mechanisms remain unclear and the efficacy of monotherapy with EPO or G-CSF is also controversial.Therefore,we investigated the effects of combined treatment with EPO and G-CSF on neovascularization and cardiac function in post-infarction rats and explored the potential mechanisms.Methods Four groups of rats were used:control (saline injection after MI,i.h.),EPO (a single dose of 5 000 IU/kg after MI,i.h.),G-CSF (a dose of 50 μg· kg-1· d-1 for 5 days after MI,i.h.),and both EPO and G-CSF (EPO+G-CSF,using the same regiment as above).Cardiac function was assessed by echocardiography before and 1 day,7 days,14 days and 21 days after MI.CD34+/Flk-1+ cells in the peripheral blood were evaluated by flow cytometry before and 3 days,5 days and 7 days after MI.The infarct area and angiogenesis in the peri-infarct area were analyzed.The mRNA and protein expression of vascular endothelial growth factor (VEGF) and stromal-derived factor-1α (SDF-1α) in the peri-infarct area were detected by real-time quantitative RT-PCR and Western blotting.Results Compared with the control and monotherapy groups,the EPO+G-CSF group had significantly increased CD34+/ Flk-1+ endothelial progenitor calls (EPCs)in the peripheral blood (P <0.05),up-regulated VEGF and SDF-1α levels in the peri-infarct region (P <0.05),enhanced capillary density (P <0.05),reduced infarct size (P <0.05) and improved cardiac structure and function (P <0.05).G-CSF alone did not dramatically increase EPCs in the peripheral blood,enhance capillary density in the peri-infarct area or reduce infarct size compared with the control group.Conclusions Combined treatment with EPO and G-CSF increased EPCs mobilization,up-regulated VEGF and SDF-1α levels in the post-infarction microenvironment,subsequently enhanced

  16. Improvement of cardiac function by hepatocyte growth factor via intracoronary transfection in the swine myocardial infarction model

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    Wei Wang; Wenzhu Ma; Zhijian Yang; Dongchao Ma; Shunlin Xu; Yourong Zhang; Yuqing Zhang; Liansheng Wang; Bo Chen; Kejiang Cao

    2006-01-01

    Objective: To study the amelioration effect of Adenovirus5-mediated human hepatocyte growth factor (Ad5-HGF) on postinfarction heart failure in the swine myocardial infarction model. Methods: Twelve SuZhong young swine were randomly divided into 2 groups with 6 swine in each group: Ad5-HGF-treated group and null-Ad5 group. Four weeks after ligation at left anterior descending coronary artery in swine hearts, Ad5-HGF was transferred to the swine myocardium. Simultaneously,Gated myocardial perfusion imaging was performed to evaluate cardiac perfusion and heart function. After three weeks, Gated myocardial perfusion imaging was performed again, then the hearts were harvested and sectioned to examine the expression of HGF through ELISA. Results: High expression of human HGF was observed in the myocardium of Ad5-HGF-treated group. From 4 weeks to 7 weeks after operation, Left ventricular ejection fraction was increased in Ad5-HGF-treated group. The improvement in LVEF was greater in Ad5-HGF-treated group than that in null-Ad5 group at 7 weeks after operation. Cardiac perfusion was significantly improved in the Ad5-HGF-treated group. Conclusion: High expression of human HGF was observed in the myocardium through intracoronary transfection, which suggests that HGF can ameliorate heart function in swine with postinfarction heart failure.

  17. Effect of Roux-en-Y gastric bypass surgery on ventricular function and cardiac risk factors in obese patients: a systematic review

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    Alireza Abdollahi Moghaddam

    2016-03-01

    Full Text Available Introduction: Weight gain and obesity are two important public health problems, which are associated with many diseases such as cardiovascular disorders. Various policies such as bariatric surgery have been proposed for the treatment of morbid obesity. Methods: PubMed and Scopus were searched thoroughly with the following search terms (roux-en-y gastric bypass surgery AND (ventricular function, OR cardiac risk factors OR heart AND (BMI OR body mass index to find the articles in which the effect of roux-en-Y gastric bypass (RYGB surgery had been evaluated in severely obese patients.Result: Out of 120 articles which were found in PubMed, and 28 records which were found in Scopus, only 18 articles fully met the inclusion criteria. Out of 2740 participants in the included studied, 1706 were patients with body mass index (BMI over 40 kg/m2 who had undergone RYGB surgery, and 1034 were control participants. Results of the studies showed that RYGB surgery could reduce BMI, and cardiac risk factors, and improve diastolic function, systolic and diastolic blood pressures, and aortic function, postoperatively.Discussion: Obesity is associated with increased risk of cardiovascular diseases, impaired cardiac function, and hypertension. It is shown that RYGB surgery reduces the serum level of biochemical markers of cardiac diseases. Cardiac structure, parasympathetic indices of autonomic function, coronary circulatory function, hypertension, epicardial fat thickness, and ventricular performance improve after bariatric surgery.Conclusions: It is concluded that RYGB surgery is an effective strategy to improve ventricular function and cardiac risk factors in morbid obese patients.

  18. Administration of granulocyte-colony stimulating factor accompanied with a balanced diet improves cardiac function alterations induced by high fat diet in mice.

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    Daltro, Pâmela Santana; Alves, Paula Santana; Castro, Murilo Fagundes; Azevedo, Carine M; Vasconcelos, Juliana Fraga; Allahdadi, Kyan James; de Freitas, Luiz Antônio Rodrigues; de Freitas Souza, Bruno Solano; Dos Santos, Ricardo Ribeiro; Soares, Milena Botelho Pereira; Macambira, Simone Garcia

    2015-12-03

    High fat diet (HFD) is a major contributor to the development of obesity and cardiovascular diseases due to the induction of cardiac structural and hemodynamic abnormalities. We used a model of diabetic cardiomyopathy in C57Bl/6 mice fed with a HFD to investigate the effects of granulocyte-colony stimulating factor (G-CSF), a cytokine known for its beneficial effects in the heart, on cardiac anatomical and functional abnormalities associated with obesity and type 2 diabetes. Groups of C57Bl/6 mice were fed with standard diet (n = 8) or HFD (n = 16). After 36 weeks, HFD animals were divided into a group treated with G-CSF + standard diet (n = 8) and a vehicle control group + standard diet (n = 8). Cardiac structure and function were assessed by electrocardiography, echocardiography and treadmill tests, in addition to the evaluation of body weight, fasting glicemia, insulin and glucose tolerance at different time points. Histological analyses were performed in the heart tissue. HFD consumption induced metabolic alterations characteristic of type 2 diabetes and obesity, as well as cardiac fibrosis and reduced exercise capacity. Upon returning to a standard diet, obese mice body weight returned to non-obese levels. G-CSF administration accelerated the reduction in of body weight in obese mice. Additionally, G-CSF treatment reduced insulin levels, diminished heart fibrosis, increased exercise capacity and reversed cardiac alterations, including bradycardia, elevated QRS amplitude, augmented P amplitude, increased septal wall thickness, left ventricular posterior thickening and cardiac output reduction. Our results indicate that G-CSF administration caused beneficial effects on obesity-associated cardiac impairment.

  19. Influence of granulocyte colony-stimulating factor on cardiac function in patients with acute myocardial infarction and leukopenia after revascularization

    Institute of Scientific and Technical Information of China (English)

    GUO Shi-zun; WANG Ning-fu; ZHOU Liang; YE Xian-hua; PAN Hao; TONG Guo-xin; YANG Jian-min; XU Jian

    2010-01-01

    Background Granulocyte colony-stimulating factor (G-CSF) seems to improve cardiac function and perfusion when used systemically through mobilization of stem cells into peripheral blood, but results of previous clinical trials remain controversial. This study was designed to investigate safety and efficacy of subcutaneous injection of G-CSF on left ventricular function in patients with impaired left ventricular function after ST-segment elevation myocardial infarction (STEMI).Methods Thirty-three patients (22 men; age, (68.5±6.1) years) with STEMI and with comorbidity of leukopenia were included after successful primary percutaneous coronary intervention within 12 hours after symptom onset. Patients were randomized into G-CSF group who received G-CSF (10 μg/kg of body weight, daily) for continuous 7 days and control group. Results of blood analyses, echocardiography and angiography were documented as well as possibly occurred adverse events.Results No severe adverse events occurred in both groups. Mean segmental wall thickening in infract segments increased significantly at 6-month follow up compared with baseline in both groups, but the longitudinal variation between two groups had no significant difference (P >0.05). The same change could also be found in longitudinal variation of wall motion score index of infarct segments (P >0.05). At 6-month follow-up, left ventricular end-diastolic volume of both groups increased to a greater extent, but there were no significant differences between the two groups when comparing the longitudinal variations (P >0.05). In both groups, left ventricular ejection fraction measured by echocardiography ameliorated significantly at 6-month follow-up (P 0.05). When pay attention to left ventricular ejection fraction measured by angiocardiography,difference of the longitudinal variation between groups was significant (P=0.046). Early diastolic mitral flow velocity deceleration time changed significantly at 6-month follow-up in both

  20. Effect of Thermal Stress on Cardiac Function

    OpenAIRE

    Wilson, Thad E.; Crandall, Craig G.

    2011-01-01

    Whole-body heating decreases pulmonary capillary wedge pressure and cerebral vascular conductance, and causes an inotropic shift in the Frank-Starling curve. Whole-body cooling increases pulmonary capillary wedge pressure and cerebral vascular conductance without changing systolic function. These and other data indicate factors affecting cardiac function may mechanistically contribute to syncope during heat stress and improvements in orthostatic tolerance during cold stress.

  1. Angiogenesis and cardiac hypertrophy: maintenance of cardiac function and causative roles in heart failure.

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    Oka, Toru; Akazawa, Hiroshi; Naito, Atsuhiko T; Komuro, Issei

    2014-01-31

    Cardiac hypertrophy is an adaptive response to physiological and pathological overload. In response to the overload, individual cardiac myocytes become mechanically stretched and activate intracellular hypertrophic signaling pathways to re-use embryonic transcription factors and to increase the synthesis of various proteins, such as structural and contractile proteins. These hypertrophic responses increase oxygen demand and promote myocardial angiogenesis to dissolve the hypoxic situation and to maintain cardiac contractile function; thus, these responses suggest crosstalk between cardiac myocytes and microvasculature. However, sustained pathological overload induces maladaptation and cardiac remodeling, resulting in heart failure. In recent years, specific understanding has increased with regard to the molecular processes and cell-cell interactions that coordinate myocardial growth and angiogenesis. In this review, we summarize recent advances in understanding the regulatory mechanisms of coordinated myocardial growth and angiogenesis in the pathophysiology of cardiac hypertrophy and heart failure.

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

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

    2014-02-01

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

  3. Motivational factors of adherence to cardiac rehabilitation.

    Science.gov (United States)

    Shahsavari, Hooman; Shahriari, Mohsen; Alimohammadi, Nasrollah

    2012-05-01

    Main suggested theories about patients' adherence to treatment regimens recognize the importance of motivation in positive changes in behaviors. Since cardiac diseases are chronic and common, cardiac rehabilitation as an effective prevention program is crucial in management of these diseases. There is always concern about the patients' adherence to cardiac rehabilitation. The aim of this study was to describe the motivational factors affecting the patients' participation and compliance to cardiac rehabilitation by recognizing and understanding the nature of patients' experiences. The participants were selected among the patients with cardiac diseases who were referred to cardiac rehabilitation in Isfahan Cardiovascular Research Center, Iran. The purposive sampling method was used and data saturation achieved after 8 semi-structured interviews. The three main concepts obtained from this study are "beliefs", "supporters" and "group cohesion". In cardiac rehabilitation programs, emphasis on motivational factors affects the patient's adherence. It is suggested that in cardiac rehabilitation programs more attention should be paid to patients' beliefs, the role of patients' supporters and the role of group-based rehabilitation.

  4. Embryonic lethality in mice lacking the nuclear factor of activated T cells 5 protein due to impaired cardiac development and function.

    Directory of Open Access Journals (Sweden)

    Man Chi Mak

    Full Text Available Nuclear factor of activated T cells 5 protein (NFAT5 is thought to be important for cellular adaptation to osmotic stress by regulating the transcription of genes responsible for the synthesis or transport of organic osmolytes. It is also thought to play a role in immune function, myogenesis and cancer invasion. To better understand the function of NFAT5, we developed NFAT5 gene knockout mice. Homozygous NFAT5 null (NFAT5(-/- mouse embryos failed to develop normally and died after 14.5 days of embryonic development (E14.5. The embryos showed peripheral edema, and abnormal heart development as indicated by thinner ventricular wall and reduced cell density at the compact and trabecular areas of myocardium. This is associated with reduced level of proliferating cell nuclear antigen and increased caspase-3 in these tissues. Cardiomyocytes from E14.5 NFAT5(-/- embryos showed a significant reduction of beating rate and abnormal Ca(2+ signaling profile as a consequence of reduced sarco(endoplasmic reticulum Ca(2+-ATPase (SERCA and ryanodine receptor (RyR expressions. Expression of NFAT5 target genes, such as HSP 70 and SMIT were reduced in NFAT5(-/- cardiomyocytes. Our findings demonstrated an essential role of NFAT5 in cardiac development and Ca(2+ signaling. Cardiac failure is most likely responsible for the peripheral edema and death of NFAT5(-/- embryos at E14.5 days.

  5. Risk factors of cardiac allograft vasculopathy.

    Science.gov (United States)

    Szyguła-Jurkiewicz, Bożena; Szczurek, Wioletta; Gąsior, Mariusz; Zembala, Marian

    2015-12-01

    Despite advances in prevention and treatment of heart transplant rejection, development of cardiac allograft vasculopathy (CAV) remains the leading factor limiting long-term survival of the graft. Cardiac allograft vasculopathy etiopathogenesis is not fully understood, but a significant role is attributed to endothelial cell damage, caused by immunological and non-immunological mechanisms. Immunological factors include the differences between the recipient's and the donor's HLA systems, the presence of alloreactive antibodies and episodes of acute rejection. Among the non-immunological factors the most important are the age of the donor, ischemia-reperfusion injury and cytomegalovirus infection. The classical cardiovascular risk factors (diabetes, hypertension, obesity and hyperlipidemia) are also important. This study presents an up-to-date overview of current knowledge on the vasculopathy etiopathogenesis and the role played by endothelium and inflammatory processes in CAV, and it also investigates the factors which may serve as risk markers of cardiac allograft vasculopathy.

  6. Effects of Lifestyle Modification Programs on Cardiac Risk Factors

    Science.gov (United States)

    Razavi, Moaven; Fournier, Stephen; Shepard, Donald S.; Ritter, Grant; Strickler, Gail K.; Stason, William B.

    2014-01-01

    Medicare conducted a payment demonstration to evaluate the effectiveness of two intensive lifestyle modification programs in patients with symptomatic coronary artery disease: the Dr. Dean Ornish Program for Reversing Heart Disease (Ornish) and Cardiac Wellness Program of the Benson-Henry Mind Body Institute. This report describes the changes in cardiac risk factors achieved by each program during the active intervention year and subsequent year of follow-up. The demonstration enrolled 580 participants who had had an acute myocardial infarction, had undergone coronary artery bypass graft surgery or percutaneous coronary intervention within 12 months, or had documented stable angina pectoris. Of these, 98% completed the intense 3-month intervention, 71% the 12-month intervention, and 56% an additional follow-up year. Most cardiac risk factors improved significantly during the intense intervention period in both programs. Favorable changes in cardiac risk factors and functional cardiac capacity were maintained or improved further at 12 and 24 months in participants with active follow-up. Multivariable regressions found that risk-factor improvements were positively associated with abnormal baseline values, Ornish program participation for body mass index and systolic blood pressure, and with coronary artery bypass graft surgery. Expressed levels of motivation to lose weight and maintain weight loss were significant independent predictors of sustained weight loss (p = 0.006). Both lifestyle modification programs achieved well-sustained reductions in cardiac risk factors. PMID:25490202

  7. Effects of lifestyle modification programs on cardiac risk factors.

    Directory of Open Access Journals (Sweden)

    Moaven Razavi

    Full Text Available Medicare conducted a payment demonstration to evaluate the effectiveness of two intensive lifestyle modification programs in patients with symptomatic coronary artery disease: the Dr. Dean Ornish Program for Reversing Heart Disease (Ornish and Cardiac Wellness Program of the Benson-Henry Mind Body Institute. This report describes the changes in cardiac risk factors achieved by each program during the active intervention year and subsequent year of follow-up. The demonstration enrolled 580 participants who had had an acute myocardial infarction, had undergone coronary artery bypass graft surgery or percutaneous coronary intervention within 12 months, or had documented stable angina pectoris. Of these, 98% completed the intense 3-month intervention, 71% the 12-month intervention, and 56% an additional follow-up year. Most cardiac risk factors improved significantly during the intense intervention period in both programs. Favorable changes in cardiac risk factors and functional cardiac capacity were maintained or improved further at 12 and 24 months in participants with active follow-up. Multivariable regressions found that risk-factor improvements were positively associated with abnormal baseline values, Ornish program participation for body mass index and systolic blood pressure, and with coronary artery bypass graft surgery. Expressed levels of motivation to lose weight and maintain weight loss were significant independent predictors of sustained weight loss (p = 0.006. Both lifestyle modification programs achieved well-sustained reductions in cardiac risk factors.

  8. Echocardiographic assessment of cardiac morphology and function in Xenopus.

    Science.gov (United States)

    Bartlett, Heather L; Escalera, Robert B; Patel, Sonali S; Wedemeyer, Elesa W; Volk, Kenneth A; Lohr, Jamie L; Reinking, Benjamin E

    2010-04-01

    Advances using Xenopus as a model permit valuable inquiries into cardiac development from embryo to adult. Noninvasive methods are needed to study cardiac function longitudinally. The objective of this study was to evaluate the feasibility of echocardiographic studies in Xenopus and establish normative data of adult cardiac structure and function. Doppler and 2D echocardiograms and electrocardiograms were acquired from adult Xenopus laevis and X. tropicalis. Frogs were exposed to either isoflurane or tricaine to discern the effect of sedating agents on cardiac function. Cardiac dimensions, morphology, flow velocities, and electrophysiologic intervals were measured and evaluated by using bivariate and regression analyses. Normal cardiac dimensions relative to body weight and species were established by echocardiography. Normal conduction intervals were determined by electrocardiography and did not vary by body weight or species. Anesthetic agent did not affect ejection fraction or flow velocity but did alter the QRS duration and QT interval. Echocardiographic and electrocardiographic studies in Xenopus provide information about cardiac anatomy and physiology and can readily be used for longitudinal analyses of developmental inquiries. Body weight, species, and anesthetic agent are factors that should be considered in experimental design and analyses.

  9. Ultrasound assessment of fetal cardiac function

    Science.gov (United States)

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

    2015-01-01

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

  10. Cardiac hypertrophy: a risk factor for QT-prolongation and cardiac sudden death.

    Science.gov (United States)

    Kang, Y James

    2006-01-01

    Cardiac hypertrophy was viewed as a compensatory response to hemodynamic stress. However, cumulative evidence obtained from studies using more advanced technologies in human patients and animal models suggests that cardiac hypertrophy is a maladaptive process of the heart in response to intrinsic and extrinsic stimuli. Although hypertrophy can normalize wall tension, it is a risk factor for QT-prolongation and cardiac sudden death. Studies using molecular biology techniques such as transgenic and knockout mice have revealed many important molecules that are involved in the development of heart hypertrophy and have demonstrated signaling pathways leading to the pathogenesis. With the same approach, the consequence of heart hypertrophy has been examined. The significance of hypertrophy in the development of overt heart failure has been demonstrated and several critical molecular pathways involved in the process were revealed. A comprehensive understanding of the threats of heart hypertrophy to patients has helped to develop novel treatment strategies. The recognition of hypertrophy as a major risk factor for QT-prolongation and cardiac sudden death is an important advance in cardiac medicine. Cellular and molecular mechanisms of this risk aspect are currently under extensively exploring. These studies would lead to more comprehensive approaches to prevention of potential life threatening arrhythmia and cardiac sudden death. The adaptation of new approaches such as functional genomics and proteomics will further advance our knowledge of heart hypertrophy.

  11. Fibroblast growth factor homologous factors in the heart: a potential locus for cardiac arrhythmias.

    Science.gov (United States)

    Wei, Eric Q; Barnett, Adam S; Pitt, Geoffrey S; Hennessey, Jessica A

    2011-10-01

    The four fibroblast growth factor homologous factors (FHFs; FGF11-FGF14) are intracellular proteins that bind and modulate voltage-gated sodium channels (VGSCs). Although FHFs have been well studied in neurons and implicated in neurologic disease, their role in cardiomyocytes was unclear until recently. This review discusses the expression profile and function of FHFs in mouse and rat ventricular cardiomyocytes. Recent data show that FGF13 is the predominant FHF in the murine heart, directly binds the cardiac VGSC α subunit, and is essential for normal cardiac conduction. FHF loss-of-function mutations may be unrecognized causes of cardiac arrhythmias, such as long QT and Brugada syndromes.

  12. Phosphate excretion is decreased in older cardiac patients with normal kidney function: an emerging dietary risk factor?

    Science.gov (United States)

    Jozefacki, Alexis; White, Christine A; Shobeiri, Navid S; Hopman, Wilma M; Johri, Amer M; Adams, Michael A; Holden, Rachel M

    2016-04-01

    Serum phosphate independently predicts cardiovascular events and mortality. Sixteen healthy adults and 9 adults with cardiovascular disease (CVD) ingested 500 mg of sodium phosphate after an over-night fast. In control subjects, the urine phosphate/creatinine ratio was significantly higher at 2 h (3.12 ± 1.02) than at baseline (1.98 ± 0.58, p phosphate could accelerate vascular calcification and may be an under-recognized risk factor for CVD.

  13. Fibroblast Growth Factors and Vascular Endothelial Growth Factor Promote Cardiac Reprogramming under Defined Conditions

    Directory of Open Access Journals (Sweden)

    Hiroyuki Yamakawa

    2015-12-01

    Full Text Available Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs by overexpression of cardiac transcription factors, including Gata4, Mef2c, and Tbx5; however, this process is inefficient under serum-based culture conditions, in which conversion of partially reprogrammed cells into fully reprogrammed functional iCMs has been a major hurdle. Here, we report that a combination of fibroblast growth factor (FGF 2, FGF10, and vascular endothelial growth factor (VEGF, termed FFV, promoted cardiac reprogramming under defined serum-free conditions, increasing spontaneously beating iCMs by 100-fold compared with those under conventional serum-based conditions. Mechanistically, FFV activated multiple cardiac transcriptional regulators and converted partially reprogrammed cells into functional iCMs through the p38 mitogen-activated protein kinase and phosphoinositol 3-kinase/AKT pathways. Moreover, FFV enabled cardiac reprogramming with only Mef2c and Tbx5 through the induction of cardiac reprogramming factors, including Gata4. Thus, defined culture conditions promoted the quality of cardiac reprogramming, and this finding provides new insight into the mechanism of cardiac reprogramming.

  14. Factors influencing the cardiac MIBG accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Takatsu, Hisato; Fujiwara, Hisayoshi [Gifu Univ. (Japan). School of Medicine

    1997-02-01

    Following factors possibly influencing the cardiac MIBG accumulation were examined mainly in mice. 1. The specific activity of the MIBG (meta-iodo-benzyl guanidine) on the neuronal and non-neuronal fractions. 2. Motor restriction stress on MIBG accumulation and washout. 3. Loading and restriction of sodium chloride on the accumulation and effect of suppression of renin-angiotensin system. 4. Examinations in Dahl rats. 125I- or 131I-MIBG was intravenously administered to mice at 74 kBq. At 30 min or 4 hr after administration, mice were sacrificed and their left ventricles were dissected out for measurement of radioactivity in a liquid scintillation counter. Salt-sensitive and -resistant Dahl rats were given with 37 MBq of 123I-MIBG and cardiac radioactivity was measured externally for calculation of washout. Factors examined were found highly correlated with the accumulation of MIBG and measurement of its washout was considered useful for evaluating sympathetic activity. (K.H.)

  15. Risk factors and the effect of cardiac resynchronization therapy on cardiac and non-cardiac mortality in MADIT-CRT

    DEFF Research Database (Denmark)

    Perkiomaki, Juha S; Ruwald, Anne-Christine; Kutyifa, Valentina;

    2015-01-01

    causes, 108 (63.9%) deemed cardiac, and 61 (36.1%) non-cardiac. In multivariate analysis, increased baseline creatinine was significantly associated with both cardiac and non-cardiac deaths [hazard ratio (HR) 2.97, P ...AIMS: To understand modes of death and factors associated with the risk for cardiac and non-cardiac deaths in patients with cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) vs. implantable cardioverter-defibrillator (ICD) therapy, which may help clarify...... the action and limitations of cardiac resynchronization therapy (CRT) in relieving myocardial dysfunction. METHODS AND RESULTS: In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), during 4 years of follow-up, 169 (9.3%) of 1820 patients died of known...

  16. Cardiac mitochondria exhibit dynamic functional clustering

    Directory of Open Access Journals (Sweden)

    Felix Tobias Kurz

    2014-09-01

    Full Text Available Multi-oscillatory behavior of mitochondrial inner membrane potential ΔΨm in self-organized cardiac mitochondrial networks can be triggered by metabolic or oxidative stress. Spatio-temporal analyses of cardiac mitochondrial networks have shown that mitochondria are heterogeneously organized in synchronously oscillating clusters in which the mean cluster frequency and size are inversely correlated, thus suggesting a modulation of cluster frequency through local inter-mitochondrial coupling. In this study, we propose a method to examine the mitochondrial network's topology through quantification of its dynamic local clustering coefficients. Individual mitochondrial ΔΨm oscillation signals were identified for each cardiac myocyte and cross-correlated with all network mitochondria using previously described methods (Kurz et al., 2010. Time-varying inter-mitochondrial connectivity, defined for mitochondria in the whole network whose signals are at least 90% correlated at any given time point, allowed considering functional local clustering coefficients. It is shown that mitochondrial clustering in isolated cardiac myocytes changes dynamically and is significantly higher than for random mitochondrial networks that are constructed using the Erdös-Rényi model based on the same sets of vertices. The network's time-averaged clustering coefficient for cardiac myocytes was found to be 0.500 ± 0.051 (N=9 versus 0.061 ± 0.020 for random networks, respectively. Our results demonstrate that cardiac mitochondria constitute a network with dynamically connected constituents whose topological organization is prone to clustering. Cluster partitioning in networks of coupled oscillators has been observed in scale-free and chaotic systems and is therefore in good agreement with previous models of cardiac mitochondrial networks (Aon et al., 2008.

  17. Cardiac Regeneration using Growth Factors: Advances and Challenges

    Science.gov (United States)

    Rebouças, Juliana de Souza; Santos-Magalhães, Nereide Stela; Formiga, Fabio Rocha

    2016-01-01

    Myocardial infarction is the most significant manifestation of ischemic heart disease and is associated with high morbidity and mortality. Novel strategies targeting at regenerating the injured myocardium have been investigated, including gene therapy, cell therapy, and the use of growth factors. Growth factor therapy has aroused interest in cardiovascular medicine because of the regeneration mechanisms induced by these biomolecules, including angiogenesis, extracellular matrix remodeling, cardiomyocyte proliferation, stem-cell recruitment, and others. Together, these mechanisms promote myocardial repair and improvement of the cardiac function. This review aims to address the strategic role of growth factor therapy in cardiac regeneration, considering its innovative and multifactorial character in myocardial repair after ischemic injury. Different issues will be discussed, with emphasis on the regeneration mechanisms as a potential therapeutic resource mediated by growth factors, and the challenges to make these proteins therapeutically viable in the field of cardiology and regenerative medicine. PMID:27355588

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

    Science.gov (United States)

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

    2016-01-01

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

  19. Excess pressure integral predicts cardiovascular events independent of other risk factors in the conduit artery functional evaluation substudy of Anglo-Scandinavian Cardiac Outcomes Trial.

    Science.gov (United States)

    Davies, Justin E; Lacy, Peter; Tillin, Therese; Collier, David; Cruickshank, J Kennedy; Francis, Darrel P; Malaweera, Anura; Mayet, Jamil; Stanton, Alice; Williams, Bryan; Parker, Kim H; McG Thom, Simon A; Hughes, Alun D

    2014-07-01

    Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular events and target organ damage in treated hypertensive individuals. Radial blood pressure waveforms were acquired by tonometry in 2069 individuals (aged, 63±8 years) in the Conduit Artery Functional Evaluation (CAFE) substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Measurements of left ventricular mass index (n=862) and common carotid artery intima media thickness (n=923) were also performed. XSPI and the integral of reservoir pressure were lower in people treated with amlodipine±perindopril than in those treated with atenolol±bendroflumethiazide, although brachial systolic blood pressure was similar. A total of 134 cardiovascular events accrued during a median 3.4 years of follow-up; XSPI was a significant predictor of cardiovascular events after adjustment for age and sex, and this relationship was unaffected by adjustment for conventional cardiovascular risk factors or Framingham risk score. XSPI, central systolic blood pressure, central augmentation pressure, central pulse pressure, and integral of reservoir pressure were correlated with left ventricular mass index, but only XSPI, augmentation pressure, and central pulse pressure were associated positively with carotid artery intima media thickness. Associations between left ventricular mass index, XSPI, and integral of reservoir pressure and carotid artery intima media thickness and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of cardiovascular dysfunction and independently predicts cardiovascular events and targets organ damage in a prospective clinical trial.

  20. Reviewing EKGs in Thalassemia Patients to Evaluate Their Cardiac Function

    Directory of Open Access Journals (Sweden)

    Abdolhamid Bagheri

    2016-03-01

    Full Text Available Introduction: There are more than 18000 thalassemia patients in Iran. In a current study, a high rate of mortality in these patients due to heart failure, is shown. Main factors for evaluating this disorder in thalassemia patients were their electrocardiograms (EKGs and Serum Ferritin Levels (SFLs.Methods: We studied the cardiac function in 91 patients (73 major and 18 intermediate thalassemia patients treated in Zafar Thalassemia Center, of whom 35 (38.45% were male and 56 (61.55% were female. The Factors in this study contains: EKGs, mean annual serum ferritin (at least, three SFL had been recorded in each patient treatment file in 2009, mean annual hemoglobin (Hb levels and mean annual hematocrit (Hct levels (average, 12 recorded hematocrit levels during 2009.Results: Our findings have shown that Q-T interval did not correlate with ferritin (r = 0.05, P > 0.05. In both patients with LVH and without LVH, there was no significant difference in SFL (P > 0.05. Although, the mean rate among the thalassemia patients was 85.34 ± 12.91, it did not correlate significantly with QRS duration and P-R Interval (r = -0.08, P > 0.05. In addition, ferritin did not correlate significantly with QRS duration and P-R Interval (r = 0.1, r = 0.05 and P > 0.05, P > 0.05. Furthermore, there was no difference in SFL in patients with normal cardiac axis and those with cardiac axis deviation.Conclusion: There is no correlation between SFL and variations in EKG. Although EKG is an available method for checking cardiac function in thalassemic patients, especially in developing countries, physicians cannot rely on it for diagnosis or prognosis of cardiac failure in thalassemia patients. Therefore, other methods such as MRIT2* and Echocardiography are suggested to be used periodically in order to check the cardiac function in thalassemia patients.

  1. EPAC expression and function in cardiac fibroblasts and myofibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Olmedo, Ivonne; Muñoz, Claudia; Guzmán, Nancy; Catalán, Mabel; Vivar, Raúl; Ayala, Pedro; Humeres, Claudio; Aránguiz, Pablo [Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); García, Lorena [Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Velarde, Victoria [Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile (Chile); Díaz-Araya, Guillermo, E-mail: gadiaz@ciq.uchile.cl [Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile)

    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

  2. Interplay between cardiac function and heart development.

    Science.gov (United States)

    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.

  3. Gene transfer strategies for augmenting cardiac function.

    Science.gov (United States)

    Peppel, K; Koch, W J; Lefkowitz, R J

    1997-07-01

    Recent transgenic as well as gene-targeted animal models have greatly increased our understanding of the molecular mechanisms of normal and compromised heart function. These studies have raised the possibility of using somatic gene transfer as a means for improving cardiac function. DNA transfer to a significant portion of the myocardium has thus far been difficult to accomplish. This review describes current efforts to achieve myocardial gene transfer in several model systems, with particular emphasis placed on adenovirus-mediated gene delivery, its possibilities, and current limitations. (Trend Cardiovasc Med 1997;7:145-150). © 1997, Elsevier Science Inc.

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Cardiac function and cognition in older community-dwelling cardiac patients.

    Science.gov (United States)

    Eggermont, Laura H P; Aly, Mohamed F A; Vuijk, Pieter J; de Boer, Karin; Kamp, Otto; van Rossum, Albert C; Scherder, Erik J A

    2017-04-17

    Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown. An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification. During a home visit, a neuropsychological assessment was performed within 7.1 ± 3.8 months after echocardiographic assessment; the neuropsychological assessment included three subtests of a word-learning test (encoding, recall, recognition) to examine one memory function domain and three executive function tests, including digit span backwards, Trail Making Test B minus A, and the Stroop colour-word test. Regression analyses showed no significant linear or quadratic associations between any of the echocardiographic functions and the cognitive function measures. None of the echocardiographic measures as representative of cardiac function was correlated with memory or executive function in this group of community-dwelling older cardiac patients. These findings contrast with those of previous studies. © 2017 Japanese Psychogeriatric Society.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Peter Moritz Becher

    2017-01-01

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

  8. Identification and functional characterization of cardiac pacemaker cells in zebrafish.

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    Federico Tessadori

    Full Text Available In the mammalian heart a conduction system of nodes and conducting cells generates and transduces the electrical signals evoking myocardial contractions. Specialized pacemaker cells initiating and controlling cardiac contraction rhythmicity are localized in an anatomically identifiable structure of myocardial origin, the sinus node. We previously showed that in mammalian embryos sinus node cells originate from cardiac progenitors expressing the transcription factors T-box transcription factor 3 (Tbx3 and Islet-1 (Isl1. Although cardiac development and function are strikingly conserved amongst animal classes, in lower vertebrates neither structural nor molecular distinguishable components of a conduction system have been identified, questioning its evolutionary origin. Here we show that zebrafish embryos lacking the LIM/homeodomain-containing transcription factor Isl1 display heart rate defects related to pacemaker dysfunction. Moreover, 3D reconstructions of gene expression patterns in the embryonic and adult zebrafish heart led us to uncover a previously unidentified, Isl1-positive and Tbx2b-positive region in the myocardium at the junction of the sinus venosus and atrium. Through their long interconnecting cellular protrusions the identified Isl1-positive cells form a ring-shaped structure. In vivo labeling of the Isl1-positive cells by transgenic technology allowed their isolation and electrophysiological characterization, revealing their unique pacemaker activity. In conclusion we demonstrate that Isl1-expressing cells, organized as a ring-shaped structure around the venous pole, hold the pacemaker function in the adult zebrafish heart. We have thereby identified an evolutionary conserved, structural and molecular distinguishable component of the cardiac conduction system in a lower vertebrate.

  9. Functional cardiac imaging by random access microscopy

    Directory of Open Access Journals (Sweden)

    Claudia eCrocini

    2014-10-01

    Full Text Available 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.

  10. Evaluation of cardiac blood blow, metabolism and sympathetic nerve function in patients with cardiac failure using PET and SPECT. Prognostic diagnosis based on the analysis of aggravating factors of the disease

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Yoshio; Shimozu, Junko; Yasumura, Yoshio; Nagatani, Kenzo; Miyatake, Kunio [National Cardiovascular Center, Suita, Osaka (Japan)

    1998-02-01

    Focusing on the failure of energy metabolism, which is assumed to be attributed to the cardiac muscle disorder of a patient with cardiac failure, the characteristics and diagnostic significance of the metabolic disorders of cadiac muscles were investigated in those patients. The diagnostic efficacy of {beta}-methyl iodophenyl pentadecanoic acid (BMIPP) which is a imaging agent for lipid metabolism in the cardiac muscle was assessed in the clinical states of cardiac failure due to pulmonary hypertension. Even if there was a considerable increase in the mean pulmonary arterial pressure (mPAP), the initial accumulation of BMIPP linearly increased, similarly to the increase in the accumulation of MIBI, a blood flow agent. The initial accumulation of BMIPP was thought to reflect a thicken cardiac muscle and/or increased blood flow. Also, its washing-out rate was suggested to be usable as an clinical indicator to estimate the loading of ventricular pressure. (M.N.)

  11. Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats

    Institute of Scientific and Technical Information of China (English)

    TANG Cheng-chun; MA Gan-shan; CHEN Ji-yuan

    2010-01-01

    Background Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. AIIogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.Methods Primary cardiac fibroblasts from neonatal rats were treated with 5-azacytidine (10 μmol/L) or control.Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and β-myosin heavy chain (β-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0x106) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion.Results By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and β-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the

  12. Relationship between cardiac function and resting cerebral blood flow

    DEFF Research Database (Denmark)

    Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja;

    2014-01-01

    Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF...... and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1......) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P...

  13. Evaluation of cardiomuscular blood flow, metabolism and sympathetic functions in patients with cardiac failure by PET and SPECT. Estimation of its prognosis by analysis of aggravating factors for cardiac failure

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Yoshio; Sasaki, Tatsuya; Yasumura, Yoshio; Komamura, Kazuo; Miyatake, Kunio [National Cardiovascular Center, Suita, Osaka (Japan)

    1997-02-01

    In efficacy of I-123 metaiodobenzylguanidine (I-123MIBG), which is an agent for nuclear medical imaging was investigated by evaluating the degree of cardiac failure and estimating the therapeutic effects on the patients with idiopathic diastolic cardiomyopathy (DCM). In these patients, NE levels have an tendency to increase in the blood and decrease in the cardiac muscle with the progress of cardiac failure and I-123MIBG can provide the image showing the distribution of cardiac NE. The washing-out rate of I-123MIBG was significantly correlated to the ejection fraction of left ventricle and the blood NE level. And in most patients complicated with tachycardia, {sup 201}Tl-accumulation/MIBG deletion typed mismatch region was found in their cardiac muscles, suggesting the significance of the detection of local MIBG deletion for the estimation of the risk for tachycardia. In addition, marked decrease in MIBG accumulation was thought to be usable for predicting a case of which cardiac failure might be aggravated by {beta}-blocker therapy. (M.N.)

  14. Evaluation of platelet function in dogs with cardiac disease using the PFA-100 platelet function analyzer.

    Science.gov (United States)

    Clancey, Noel; Burton, Shelley; Horney, Barbara; Mackenzie, Allan; Nicastro, Andrea; Côté, Etienne

    2009-09-01

    Cardiac disease has the potential to alter platelet function in dogs. Evaluation of platelet function using the PFA-100 analyzer in dogs of multiple breeds and with a broad range of cardiac conditions would help clarify the effect of cardiac disease on platelets. The objective of this study was to assess differences in closure time (CT) in dogs with cardiac disease associated with murmurs, when compared with that of healthy dogs. Thirty-nine dogs with cardiac murmurs and turbulent blood flow as determined echocardiographically were included in the study. The dogs represented 23 different breeds. Dogs with murmurs were further divided into those with atrioventricular valvular insufficiency (n=23) and subaortic stenosis (n=9). Fifty-eight clinically healthy dogs were used as controls. CTs were determined in duplicate on a PFA-100 analyzer using collagen/ADP cartridges. Compared with CTs in the control group (mean+/-SD, 57.6+/-5.9 seconds; median, 56.5 seconds; reference interval, 48.0-77.0 seconds), dogs with valvular insufficiency (mean+/-SD, 81.9+/-26.3 seconds; median, 78.0 seconds; range, 52.5-187 seconds), subaortic stenosis (71.4+/-16.5 seconds; median, 66.0 seconds; range, 51.5-95.0 seconds), and all dogs with murmurs combined (79.6+/-24.1 seconds; median, 74.0 seconds; range, 48.0-187 seconds) had significantly prolonged CTs (P<.01). The PFA-100 analyzer is useful in detecting platelet function defects in dogs with cardiac murmurs, most notably those caused by mitral and/or tricuspid valvular insufficiency or subaortic stenosis. The form of turbulent blood flow does not appear to be an important factor in platelet hypofunction in these forms of cardiac disease.

  15. Prevalence of risk factors for sudden cardiac death in competitive ...

    African Journals Online (AJOL)

    Prevalence of risk factors for sudden cardiac death in competitive South African student ... personal and family history, physical examination (including blood pressure, ... Significant correlations were found between gender and family history of ...

  16. Cardiac function in trisomy 21 fetuses

    NARCIS (Netherlands)

    Clur, S. A. B.; Rengerink, K. Oude; Ottenkamp, J.; Bilardo, C. M.

    2011-01-01

    Objectives Trisomy 21 is associated with an increased nuchal translucency thickness (NT), abnormal ductus venosus (DV) flow at 11-14 weeks' gestation and congenital heart defects (CHD), and cardiac dysfunction has been hypothesized as the link between them. We therefore aimed to investigate whether

  17. Cardiac function in trisomy 21 fetuses

    NARCIS (Netherlands)

    Clur, S. A. B.; Rengerink, K. Oude; Ottenkamp, J.; Bilardo, C. M.

    2011-01-01

    Objectives Trisomy 21 is associated with an increased nuchal translucency thickness (NT), abnormal ductus venosus (DV) flow at 11-14 weeks' gestation and congenital heart defects (CHD), and cardiac dysfunction has been hypothesized as the link between them. We therefore aimed to investigate whether

  18. Inhibition of neutrophil activity improves cardiac function after cardiopulmonary bypass

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    Grünwald Frank

    2007-10-01

    Full Text Available Abstract Background The arterial in line application of the leukocyte inhibition module (LIM in the cardiopulmonary bypass (CPB limits overshooting leukocyte activity during cardiac surgery. We studied in a porcine model whether LIM may have beneficial effects on cardiac function after CPB. Methods German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min reperfusion without (group I; n = 6 or with LIM (group II; n = 6. The cardiac indices (CI and cardiac function were analyzed pre and post CPB with a Swan-Ganz catheter and the cardiac function analyzer. Neutrophil labeling with technetium, scintigraphy, and histological analyses were done to track activated neutrophils within the organs. Results LIM prevented CPB-associated increase of neutrophil counts in peripheral blood. In group I, the CI significantly declined post CPB (post: 3.26 ± 0.31; pre: 4.05 ± 0.45 l/min/m2; p 2; p = 0.23. Post CPB, the intergroup difference showed significantly higher CI values in the LIM group (p Conclusion Our data provides strong evidence that LIM improves perioperative hemodynamics and cardiac function after CPB by limiting neutrophil activity and inducing accelerated sequestration of neutrophils in the spleen.

  19. Effects of Lead on Systolic and Diastolic Cardiac Functions

    Institute of Scientific and Technical Information of China (English)

    ZOUHE-JIAN; DINGYUE; 等

    1995-01-01

    In this paper,both systolic and diastolic cardiac functions were evaluated in 54 lead exposed and 24 non-exposed workers by Doppler echocardiography.With regard to systolic cardiac function,the results suggested that cardiac systolic function increased in exposed groups as a compensatory response for the effect of lead on myocardium.To study left ventricular diastolic function,2.5MHz pulsed Doppler analyses of transmitral flow velocity were performed from apical four-chamber view.The results showed that timerelated parameters were comparable among all groups,but blood flow velocity through the mitral valve and Doppler area fractions changed significantly in lead-exposed groups as evidenced by increased value A,decreased value E and E/A ratio.The decrease of diastolic cardiac function was more significant in lead intoxication group.It was also observed in this study that the activity in serum of the MB isoenzyme of creatine phosphokinase(CPK-MB),one of the indices of myocardial damage,was significantly higher in exposed group than that in control(P<0.05),and a positive correlation was found between CPK-MB activity and Pb-B.It denoted that the increasing of lead burden leads to more relase of CPK-MB from the myocardial cells and suggested the existence of slight myocardial damage,which conceivably,might cause harm to diastolic cardiac function.

  20. Cardiac Regeneration using Growth Factors: Advances and Challenges.

    Science.gov (United States)

    Rebouças, Juliana de Souza; Santos-Magalhães, Nereide Stela; Formiga, Fabio Rocha

    2016-09-01

    Myocardial infarction is the most significant manifestation of ischemic heart disease and is associated with high morbidity and mortality. Novel strategies targeting at regenerating the injured myocardium have been investigated, including gene therapy, cell therapy, and the use of growth factors. Growth factor therapy has aroused interest in cardiovascular medicine because of the regeneration mechanisms induced by these biomolecules, including angiogenesis, extracellular matrix remodeling, cardiomyocyte proliferation, stem-cell recruitment, and others. Together, these mechanisms promote myocardial repair and improvement of the cardiac function. This review aims to address the strategic role of growth factor therapy in cardiac regeneration, considering its innovative and multifactorial character in myocardial repair after ischemic injury. Different issues will be discussed, with emphasis on the regeneration mechanisms as a potential therapeutic resource mediated by growth factors, and the challenges to make these proteins therapeutically viable in the field of cardiology and regenerative medicine. Resumo O infarto do miocárdio representa a manifestação mais significativa da cardiopatia isquêmica e está associado a elevada morbimortalidade. Novas estratégias vêm sendo investigadas com o intuito de regenerar o miocárdio lesionado, incluindo a terapia gênica, a terapia celular e a utilização de fatores de crescimento. A terapia com fatores de crescimento despertou interesse em medicina cardiovascular, devido aos mecanismos de regeneração induzidos por essas biomoléculas, incluindo angiogênese, remodelamento da matriz extracelular, proliferação de cardiomiócitos e recrutamento de células-tronco, dentre outros. Em conjunto, tais mecanismos promovem a reparação do miocárdio e a melhora da função cardíaca. Esta revisão pretende abordar o papel estratégico da terapia, com fatores de crescimento, para a regeneração cardíaca, considerando seu car

  1. Regulation of cardiac microRNAs by serum response factor

    Directory of Open Access Journals (Sweden)

    Wei Jeanne Y

    2011-02-01

    Full Text Available Abstract Serum response factor (SRF regulates certain microRNAs that play a role in cardiac and skeletal muscle development. However, the role of SRF in the regulation of microRNA expression and microRNA biogenesis in cardiac hypertrophy has not been well established. In this report, we employed two distinct transgenic mouse models to study the impact of SRF on cardiac microRNA expression and microRNA biogenesis. Cardiac-specific overexpression of SRF (SRF-Tg led to altered expression of a number of microRNAs. Interestingly, downregulation of miR-1, miR-133a and upregulation of miR-21 occurred by 7 days of age in these mice, long before the onset of cardiac hypertrophy, suggesting that SRF overexpression impacted the expression of microRNAs which contribute to cardiac hypertrophy. Reducing cardiac SRF level using the antisense-SRF transgenic approach (Anti-SRF-Tg resulted in the expression of miR-1, miR-133a and miR-21 in the opposite direction. Furthermore, we observed that SRF regulates microRNA biogenesis, specifically the transcription of pri-microRNA, thereby affecting the mature microRNA level. The mir-21 promoter sequence is conserved among mouse, rat and human; one SRF binding site was found to be in the mir-21 proximal promoter region of all three species. The mir-21 gene is regulated by SRF and its cofactors, including myocardin and p49/Strap. Our study demonstrates that the downregulation of miR-1, miR-133a, and upregulation of miR-21 can be reversed by one single upstream regulator, SRF. These results may help to develop novel therapeutic interventions targeting microRNA biogenesis.

  2. Functional Alterations of Ion Channels From Cardiac Fibroblasts in Heart Diseases

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    Gracious R. Ross

    2016-11-01

    Full Text Available In an aged population, cardiovascular disease is the leading cause of fatality and morbidity. Age-related fibrotic remodeling of the heart contributes to progressive myocardial dysfunction. Cardiac fibroblasts (CF, responsible for the maintenance of extracellular matrix and fibrosis process, play an important role in cardiac health and disease. CFs influence myocardial function by their chemical, electrical and mechanical interactions with cardiomyocytes through extracellular matrix deposition or secretion of cytokines and growth factors. These, in turn, are modulated by ion channels, macromolecular pores in the plasma membrane that allow selective ionic fluxes of major ions like K+, Ca2+, Na+ or Cl-, which affect membrane potential and cellular signal transduction. The importance of ion channels in modulating various functions of CFs, including proliferation, differentiation, secretion and apoptosis, is being recognized from recent studies of CFs from animal models and tissue from patients with various cardiac pathologies. Understanding the role of ion channels in CFs under physiological conditions and their alterations in age-related cardiac diseases may help facilitate development of novel therapeutic strategies to limit cardiac fibrosis and its adverse effect on myocardial function. This narrative review summarizes the knowledge gained thus far on ion channels in CFs and their relationship with cardiac diseases in human and experimental animal models.

  3. Functional Status, Anxiety, Cardiac Self-Efficacy, and Health Beliefs of Patients with Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Hamid Allahverdipour

    2013-12-01

    Full Text Available Background: Beliefs and emotions could effect on functional status, quality of life, and mortality amongst patients who are suffering coronary heart disease (CHD. Current study examined the role of anxiety: trait/ state, self-efficacy, health beliefs, and functional status among patient with history of CHD. Method: In this correlational study, 105 hospitalized and outpatients patients suffering CHD in Tehran Heart Center Hospital participated by using convenience sampling method in 2012. Cardiac self-efficacy, Seattle Angina, and research- designed health beliefs questionnaires were used to gather data. Results: The functional status in CHD patients showed significant relationships with gender, job, and type of medical insurance of the participants (All ps<0.05. In addition , perceived vulnerability to face again cardiac attack in the future, perceived severity of next cardiac attack, anxiety, state anxiety and trait anxiety (All ps<0.05 had significant and negative relationships with functional status. Conversely, the cardiac self-efficacy had a positive and significant relationship (P<0.001 with functional status. Conclusion: Psychological factors have important role in functional status and quality of life of patients who suffering CHD. Therefore, it is necessary to emphasize on supportive and complementary programs to promote Cardiac Rehabilitation Programs.

  4. The ET axis mediates arrhythmogenesis and compromised cardiac function in two cardiomyopathy models

    Institute of Scientific and Technical Information of China (English)

    YuFENG; De-zaiDAI; YuanZHANG; Hai-boHE; Min-youQI; YinDAI; FengYU

    2005-01-01

    AIM Endothelin 1(ET-1), a potent vasoconstrictor peptide, is also regarded as an important etiological factor involved in many cardiac diseases like heart failure and cardiac hypertrophy. It mediates pathologic changes by forming an """"ET axis"""" at the upstream to ion channels, such as stimulating oxidant stress, eliciting cardiac remodeling by proliferation of cardiomyocytes, inducing apoptosis, affecting signal transduction pathway, and modulating intranuclear gene transcription. The purpose of this study was to investigate the pivotal role by ET axis in worsening arrhythmias and cardiac function in experimental hypertrophic cardiomyopathy (HCM) and heart failure (HF) models. METHODS The rat HCM model was induced by s.c L-thyroxin (L-thy, 0.2mg/Kg/d) for 10d,

  5. Cardiac sympathetic nerve terminal function in congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    Chang-seng LIANG

    2007-01-01

    Increased cardiac release of norepinephrine (NE) and depleted cardiac stores of NE are two salient features of the human failing heart. Researches from my labo-ratory have shown that these changes are accompanied by a functional defect of NE uptake in the cardiac sympathetic nerve terminals. Our studies have shown that the decrease of NE uptake is caused by reduction of NE transporter density in the sympathetic nerve endings, and this change is responsible, at least in part, for the increased myocardial interstitial NE, decreased myocardial adrenoceptor density, and increased myocyte apoptosis in experimental cardiomyopathies. We have also provided evidence in both intact animals and cultured PC12 cells that the decrease of NE transporter is induced by the actions of oxidative metabolites of exogenous NE, involving endoplasmic reticulum stress and impaired N-glycosylation of the NE transporter. This change in the cardiac sympathetic NE uptake function, as demonstrated by [123I] metaiodobenzylguanidine in human studies, may not only serve as an important prognostic variable in patients with congestive heart failure, but also be used as a surrogate for the efficacies of various therapeutic interventions for heart failure. Finally, increasing evidence suggests and further studies are needed to show that the cardiac sympathetic nerve terminal function may be a direct target for pharmacologic treatment of congestive heart failure.

  6. Systolic and diastolic cardiac function in acromegaly. An echocardiographic study.

    Science.gov (United States)

    Galanti, G; Cappelli, B; Diricatti, G; Mininni, S; Vono, M C; Gensini, G F

    1996-01-01

    The aim of this study was to establish the existence of primary acromegalic cardiomyopathy different from the cardiovascular complications often associated with acromegaly. Thirty-four acromegalic patients, referred to our non-invasive laboratory and divided into two groups on the basis of the presence of hypertension, underwent echocardiographic studies. A control group of 34 subjects individually matched with the patients for age, sex, and blood pressure values was also studied. To evaluate cardiac function during exercise, the normotensive acromegalics, the control group, and a group of 9 athletes with left ventricular mass comparable to that of the acromegalic subjects underwent a handgrip test. Cardiac mass was increased in all patients; hypertensive patients had a greater increase than normotensive patients (144.9 +/- 38 vs 120.9 +/- 20.8 g/m, p cardiac hypertrophy caused by GH hyperincretion does not improve acromegalic heart activity: diastolic function, although normal at rest, appears deficient during isometric exercise.

  7. Cardiac Function in Long-Term Survivors of Childhood Lymphoma

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    Mark K. Friedberg

    2011-01-01

    Full Text Available Objectives. We studied long-term effects of therapy for childhood lymphoma on cardiac function. Design and patients. We prospectively evaluated 45 survivors of childhood lymphoma, using clinical parameters, electrocardiography and echocardiography. Further comparisons were made between lymphoma subgroups and between males and females. Results. Mean age at diagnosis was 9.1 years. Mean followup duration was 10.9 years. The NYHA functional class was I in 43 patients and II in 2 patients. A prolonged QTc interval (>0.44 msec was found in 8 patients. Left ventricular (LV systolic function and compliance were normal (LV shortening fraction 40±5.6%; cardiac index 2.84±1.13 L/min/m2; E/A wave ratio 2.5±1.3; mean ± S.D., LV mass was normal (97±40 grams/m2, mean ± S.D.. Mitral regurgitation was observed in 7/45 patients (16%. Asymptomatic pericardial effusions were found in 3/45 (7% patients. Conclusions. Long-term follow-up shows that most parameters of cardiac function are normal in survivors of childhood lymphoma. This is likely due to relatively low doses of anthracyclines in modern protocol modalities. Abnormalities in mitral valve flow, QTc prolongation and in a small proportion of survivors, and functional capacity necessitate long-term cardiac follow-up of these patients.

  8. EXCESS PRESSURE INTEGRAL PREDICTS CARDIOVASCULAR EVENTS INDEPENDENT OF OTHER RISK FACTORS IN THE CONDUIT ARTERY FUNCTIONAL EVALUATION (CAFE) SUB-STUDY OF ANGLO-SCANDINAVIAN CARDIAC OUTCOMES TRIAL (ASCOT)

    Science.gov (United States)

    Davies, Justin E; Lacy, Peter; Tillin, Therese; Collier, David; Cruickshank, J Kennedy; Francis, Darrel P; Malaweera, Anura; Mayet, Jamil; Stanton, Alice; Williams, Bryan; Parker, Kim H; McG Thom, Simon A; Hughes, Alun D

    2014-01-01

    Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure (BP) waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular (CV) events and target organ damage in treated hypertensive individuals. Radial BP waveforms were acquired by tonometry in 2069 individuals (63±8y) in the Conduit Artery Functional Evaluation sub-study of the Anglo-Scandinavian Cardiac Outcomes trial. Measurements of left ventricular mass index (LVMI; n = 862) and common carotid artery intima media thickness (cIMT; n = 923) were also performed. XSPI and the integral of reservoir pressure (PRI) were lower in people treated with amlodipine ± perindopril than atenolol ± bendroflumethiazide, although brachial systolic BP was similar. A total of 134 CV events accrued over a median 3.4 years of follow-up; XSPI was a significant predictor of CV events after adjustment for age and sex and this relationship was unaffected by adjustment for conventional CV risk factors or Framingham risk score. XSPI, central systolic BP, central augmentation pressure (AP), central pulse pressure (cPP) and PRI were correlated with LVMI, but only XSPI, AP and cPP were positively associated with cIMT. Associations between LVMI and XSPI and PRI, and cIMT and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of CV dysfunction and independently predicts CV events and target organ damage in a prospective clinical trial. PMID:24821941

  9. Acupuncture Effects on Cardiac Functions Measured by Cardiac Magnetic Resonance Imaging in a Feline Model

    Directory of Open Access Journals (Sweden)

    Jen-Hsou Lin

    2010-01-01

    Full Text Available 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.

  10. Physician-Related Factors Affecting Cardiac Rehabilitation Referral

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    Bahieh Moradi

    2011-12-01

    Full Text Available Background: Despite the positive impact of cardiac rehabilitation (CR on quality of life and mortality, the majority of people who could benefit from this program fail to participate in it. The lack of referral from the physician is a common reason that patients give for not seeking CR. The objective of this study was to compare factors affecting CR referral by cardiologists. Methods: A cross-sectional survey of 122 cardiologists, including 89 general cardiac specialists and 33 fellows in cardiology from 11 major cardiology training centers in Iran, was done in 2010. They responded to the 14- item investigator-generated survey, examining the physician’s attitudinal and knowledge factors affecting CR referral. Results: 47.9% of the subjects reported having available CR centers but only 6.6% reported continuous medical education on the topic. 90.7% of the physicians reported that less than 15% of patients are referred to CR centers. The main factor affecting the low referral rate was limited general knowledge about CR programs (79.5% such as program attributes and benefits, methods of reimbursement. Lack of insurance coverage, unavailability of CR centers in the community and low physicians’ fee were other factors reported by the physicians. Conclusion: Cardiologists’ inadequate general knowledge of and attitude toward CR programs seem to be a potential threat for cardiac prevention and rehabilitation in some societies.

  11. Effects of Obstructive Sleep Apnea on Cardiac Function and Clinical Outcomes in Chinese Patients with ST-Elevation Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Baoxin Liu

    2014-01-01

    Full Text Available Aim. The objective of this study was to investigate the influence of OSA on cardiac function in Chinese patients with ST-elevation myocardial infarction (STEMI and determine the prognostic impact of OSA among these patients. Methods. In this retrospective study, 198 STEMI patients were enrolled. Doppler echocardiography was performed to detect the effect of OSA on cardiac function. Major adverse cardiac events (MACE and cardiac mortality were analyzed to determine whether OSA was a clinical prognostic factor; its prognostic impact was then assessed adjusting for other covariates. Results. The echocardiographic results showed that the myocardium of STEMI patients with OSA appeared to be more hypertrophic and with a poorer cardiac function compared with non-OSA STEMI patients. A Kaplan-Meier survival analysis revealed significantly higher cumulative incidence of MACE and cardiac mortality in the OSA group compared with that in the non-OSA group during a mean follow-up of 24 months. Multivariate Cox regression analysis revealed that OSA was an independent risk factor for MACE and cardiac mortality. Conclusion. These results indicate that the OSA is a powerful predictor of decreased survival and exerts negative prognostic impact on cardiac function in STEMI patients.

  12. Cardiac function and hypertension in patients with obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Bertolami A

    2014-08-01

    Full Text Available Adriana Bertolami, Carolina Gonzaga, Celso AmodeoSleep Laboratory of Dante Pazzanese Institute of Cardiology, Sao Paulo, BrazilAbstract: Cardiovascular disease is one of the major causes of death worldwide. Among its risk factors, obstructive sleep apnea (OSA is a common but still underestimated condition. OSA often coexists and interacts with obesity, sharing multiple pathophysiological mechanisms and subsequent cardiovascular risk factors, such as type 2 diabetes, dyslipidemia, systemic inflammation, and in particular hypertension. There is also evidence suggesting an increased risk of arrhythmia, heart failure, renal failure, acute myocardial infarction, stroke, and death. OSA is characterized by recurrent episodes of partial (hypopnea or complete interruption (apnea of breathing during sleep due to airway collapse in the pharyngeal region. The main mechanisms linking OSA to impaired cardiovascular function are secondary to hypoxemia and reoxygenation, arousals, and negative intrathoracic pressure. Consequently, the sympathetic nervous and the renin-angiotensin-aldosterone systems may be overestimulated, and blood pressure increased. Resistance to treatment for hypertension represents a growing issue, and given that OSA has been recognized as the major secondary cause of resistant hypertension, clinical investigation for apnea is mandatory in this population. Standard diagnosis includes polysomnography, and treatment for OSA should include control of risk factors for cardiovascular disease, including obesity. So far, continuous positive airway pressure is the treatment of choice for OSA, impacting positively on blood pressure goals; however, the impact on long-term follow-up and on cardiovascular disease should be better assessed.Keywords: obstructive sleep apnea, hypertension, cardiac function

  13. Visualization and analysis of functional cardiac MRI data

    Science.gov (United States)

    McVeigh, Elliot R.; Guttman, Michael A.; Poon, Eric; Pisupati, Chandrasekhar; Moore, Christopher C.; Zerhouni, Elias A.; Solaiyappan, Meiyappan; Heng, PhengAnn

    1994-05-01

    Rapid analysis of large multi-dimensional data sets is critical for the successful implementation of a comprehensive MR cardiac exam. We have developed a software package for the analysis and visualization of cardiac MR data. The program allows interactive visualization of time and space stacks of MRI data, automatic segmentation of myocardial borders and myocardial tagging patterns, and visualization of functional parameters such a motion, strain, and blood flow, mapped as colors in an interactive dynamic 3D volume rendering of the beating heart.

  14. Radionuclide assessment of left ventricular function following cardiac surgery

    Energy Technology Data Exchange (ETDEWEB)

    Howe, W.R.; Jones, R.H.; Sabiston, D.C. Jr.

    1976-01-01

    Use of a high count-rate gamma scintillation camera permits the noninvasive assessment of left ventricular function by nuclear angiocardiography. Counts recorded from the region of the left ventricle at 50- or 100-msec intervals during the first transit of an intravenously administered bolus of radioisotope produce a high-fidelity indicator-dilution curve. Count fluctuations reflect left ventricular volume changes during the cardiac cycle and permit measurement of dv/dt, ejection fraction, mean transit time, and wall motion of this chamber. The present study evaluates (1) the accuracy of this technique compared to standard biplane cineangiography and (2) its usefulness in evaluating patients after cardiac surgery.

  15. Risk factors and risk index of cardiac events in pregnant women with heart disease

    Institute of Scientific and Technical Information of China (English)

    LIU Hua; HUANG Tao-tao; LIN Jian-hua

    2012-01-01

    Background Pregnant women with heart disease are at high risk.Studies of risk factors of these patients are of great significance to improve maternal and fetal outcomes.In this paper,we try to discuss the main risk factors of cardiac events in pregnant women with heart disease and to establish a risk assessment system.Methods A retrospective analysis was carried out for pregnancies in 1741 women with heart disease who delivered in Shanghai Obstetrical Cardiology Intensive Care Center between January 1993 and September 2010.A Logistic regression model was used to identify independent risk factors of cardiac events and calculate the risk index in pregnant women with heart disease.Results The composition of heart disease in pregnant women was arrhythmia (n=662,38.00%),congenital heart disease (CHD; n=529,30.40%),cardiomyopathy (n=327,18.80%),rheumatic heart disease (RHD; n=151,8.70%),and cardiopathy induced by pre-eclampsia (n=53,3.00%).Main cardiac events were heart failure (n=110,6.32%),symptomatic arrhythmia needing medication (n=43,2.47%),cardiac arrest (n=2,0.11%),syncope (n=3,0.17%),and maternal death (n=10,0.57%).Six independent risk factors to predict cardiac events in pregnant women with heart disease were cardiac events before pregnancy (heart failure,severe arrhythmia,cardiac shock,etc.,P=0.000),New York Heart Association (NYHA) class >ll (P=0.000),oxygen saturation <90% (P=0.018),pulmonary artery hypertention (PAH)>50 mmHg (P=0.025),cyanotic heart disease without surgical correction (P=0.015),and reduced left ventricular systolic function (ejection fraction <40%,P=0.003).Every risk factor was calculated as 1 score.The incidence of cardiac events in patients with scores 0,1,2,3,and ≥4 was 2.10%,31.61%,61.25%,68.97%,and 100.00% respectively.Conclusions Pregnancy with heart disease could lead to undesirable pregnancy outcomes.The risk of cardiac events in pregnant women with heart disease could be assessed by risk

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

    Science.gov (United States)

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

    2013-07-01

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

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

    Science.gov (United States)

    Vega, Rick B; Kelly, Daniel P

    2017-04-03

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

  18. Tumor necrosis factor receptor-associated factor 3 is a positive regulator of pathological cardiac hypertrophy.

    Science.gov (United States)

    Jiang, Xi; Deng, Ke-Qiong; Luo, Yuxuan; Jiang, Ding-Sheng; Gao, Lu; Zhang, Xiao-Fei; Zhang, Peng; Zhao, Guang-Nian; Zhu, Xueyong; Li, Hongliang

    2015-08-01

    Cardiac hypertrophy, a common early symptom of heart failure, is regulated by numerous signaling pathways. Here, we identified tumor necrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein in tumor necrosis factor-related signaling cascades, as a key regulator of cardiac hypertrophy in response to pressure overload. TRAF3 expression was upregulated in hypertrophied mice hearts and failing human hearts. Four weeks after aortic banding, cardiac-specific conditional TRAF3-knockout mice exhibited significantly reduced cardiac hypertrophy, fibrosis, and dysfunction. Conversely, transgenic mice overexpressing TRAF3 in the heart developed exaggerated cardiac hypertrophy in response to pressure overload. TRAF3 also promoted an angiotensin II- or phenylephrine-induced hypertrophic response in isolated cardiomyocytes. Mechanistically, TRAF3 directly bound to TANK-binding kinase 1 (TBK1), causing increased TBK1 phosphorylation in response to hypertrophic stimuli. This interaction between TRAF3 and TBK1 further activated AKT signaling, which ultimately promoted the development of cardiac hypertrophy. Our findings not only reveal a key role of TRAF3 in regulating the hypertrophic response but also uncover TRAF3-TBK1-AKT as a novel signaling pathway in the development of cardiac hypertrophy and heart failure. This pathway may represent a potential therapeutic target for this pathological process.

  19. A new predisposing factor for trigemino-cardiac reflex during subdural empyema drainage: a case report

    Directory of Open Access Journals (Sweden)

    Arasho Belachew

    2010-11-01

    Full Text Available Abstract Introduction The trigemino-cardiac reflex is defined as the sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea, or gastric hypermotility during stimulation of any of the sensory branches of the trigeminal nerve. Clinically, trigemino-cardiac reflex has been reported to occur during neurosurgical skull-base surgery. Apart from the few clinical reports, the physiological function of this brainstem reflex has not yet been fully explored. Little is known regarding any predisposing factors related to the intraoperative occurrence of this reflex. Case presentation We report the case of a 70-year-old Caucasian man who demonstrated a clearly expressed form of trigemino-cardiac reflex with severe bradycardia requiring intervention that was recorded during surgical removal of a large subdural empyema. Conclusion To the best of our knowledge, this is the first report of an intracranial infection leading to perioperative trigemino-cardiac reflex. We therefore add a new predisposing factor for trigemino-cardiac reflex to the existing literature. Possible mechanisms are discussed in the light of the relevant literature.

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

    DEFF Research Database (Denmark)

    Hesse, B.; Lindhardt, T.B.; Acampa, W.;

    2008-01-01

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

  1. Functional role of anion channels in cardiac diseases

    Institute of Scientific and Technical Information of China (English)

    Da-yue DUAN; Luis LH LIU; Nathan BOZEAT; Z Maggie HUANG; Sunny Y XIANG; Guan-lei WANG; Linda YE; Joseph R HUME

    2005-01-01

    In comparison to cation (K+, Na+, and Ca2+) channels, much less is currently known about the functional role of anion (Cl-) channels in cardiovascular physiology and pathophysiology. Over the past 15 years, various types of Cl- currents have been recorded in cardiac cells from different species including humans. All cardiac Cl- channels described to date may be encoded by five different Cl- channel genes: the PKA- and PKC-activated cystic fibrosis tansmembrane conductance regulator (CFTR), the volume-regulated ClC-2 and ClC-3, and the Ca2+-activated CLCA or Bestrophin. Recent studies using multiple approaches to examine the functional role of Cl- channels in the context of health and disease have demonstrated that Cl- channels might contribute to: 1) arrhythmogenesis in myocardial injury; 2) cardiac ischemic preconditioning; and 3) the adaptive remodeling of the heart during myocardial hypertrophy and heart failure. Therefore,anion channels represent very attractive novel targets for therapeutic approaches to the treatment of heart diseases. Recent evidence suggests that Cl- channels,like cation channels, might function as a multiprotein complex or functional module.In the post-genome era, the emergence of functional proteomics has necessitated a new paradigm shift to the structural and functional assessment of integrated Cl- channel multiprotein complexes in the heart, which could provide new insight into our understanding of the underlying mechanisms responsible for heart disease and protection.

  2. Autoimmune Response Confers Decreased Cardiac Function in ...

    African Journals Online (AJOL)

    ... interleukin-6 (IL-6), high –sensitivity C-reactive protein (hs-CRP) and echocardiographic indices of heart function in the two .... patients were classified as NYHA class II, fifteen as class III, and ... group were excluded if they had a history of.

  3. Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

    NARCIS (Netherlands)

    Wild, Philipp S.; Felix, Janine F.; Schillert, Arne; Teumer, Alexander; Chen, Ming-Huei; Leening, Maarten J. G.; Voelker, Uwe; Grossmann, Vera; Brody, Jennifer A.; Irvin, Marguerite R.; Shah, Sanjiv J.; Pramana, Setia; Lieb, Wolfgang; Schmidt, Reinhold; Stanton, Alice V.; Malzahn, Doerthe; Smith, Albert Vernon; Sundstrom, Johan; Minelli, Cosetta; Ruggiero, Daniela; Lyytikainen, Leo-Pekka; Tiller, Daniel; Smith, J. Gustav; Monnereau, Claire; Di Tullio, Marco R.; Musani, Solomon K.; Morrison, Alanna C.; Pers, Tune H.; Morley, Michael; Kleber, Marcus E.; Aragam, Jayashri; Benjamin, Emelia J.; Bis, Joshua C.; Bisping, Egbert; Broeckel, Ulrich; Cheng, Susan; Deckers, Jaap W.; Del Greco, Fabiola; Edelmann, Frank; Fornage, Myriam; Franke, Lude; Friedrich, Nele; Harris, Tamara B.; Hofer, Edith; Hofman, Albert; Huang, Jie; Hughes, Alun D.; Kahonen, Mika; Kruppa, Jochen; Lackner, Karl J.; Lannfelt, Lars; Laskowski, Rafael; Launer, Lenore J.; Leosdottir, Margret; Lin, Honghuang; Lindgren, Cecilia M.; Loley, Christina; MacRae, Calum A.; Mascalzoni, Deborah; Mayet, Jamil; Medenwald, Daniel; Morris, Andrew P.; Mueller, Christian; Mueller-Nurasyid, Martina; Nappo, Stefania; Nilsson, Peter M.; Nuding, Sebastian; Nutile, Teresa; Peters, Annette; Pfeufer, Arne; Pietzner, Diana; Pramstaller, Peter P.; Raitakari, Olli T.; Rice, Kenneth M.; Rivadeneira, Fernando; Rotter, Jerome I.; Ruohonen, Saku T.; Sacco, Ralph L.; Samdarshi, Tandaw E.; Schmidt, Helena; Sharp, Andrew S. P.; Shields, Denis C.; Sorice, Rossella; Sotoodehnia, Nona; Stricker, Bruno H.; Surendran, Praveen; Thom, Simon; Toeglhofer, Anna M.; Uitterlinden, Andre G.; Wachter, Rolf; Voelzke, Henry; Ziegler, Andreas; Muenzel, Thomas; Maerz, Winfried; Cappola, Thomas P.; Hirschhorn, Joel N.; Mitchell, Gary F.; Smith, Nicholas L.; Fox, Ervin R.; Dueker, Nicole D.; Jaddoe, Vincent W. V.; Melander, Olle; Russ, Martin; Lehtimaki, Terho; Ciullo, Marina; Hicks, Andrew A.; Lind, Lars; Gudnason, Vilmundur; Pieske, Burkert; Barron, Anthony J.; Zweiker, Robert; Schunkert, Heribert; Ingelsson, Erik; Liu, Kiang; Arnett, Donna K.; Psaty, Bruce M.; Blankenberg, Stefan; Larson, Martin G.; Felix, Stephan B.; Franco, Oscar H.; Zeller, Tanja; Vasan, Ramachandran S.; Doerr, Marcus

    2017-01-01

    BACKGROUND. Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS. A GWAS

  4. Improved cardiac function and exercise capacity following correction of pectus excavatum

    DEFF Research Database (Denmark)

    Sørensen, Marie Maagaard; Heiberg, Johan

    2016-01-01

    no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions......, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac function should be integrated in the clinical assessment of patients with PE....

  5. Small molecule cardiogenol C upregulates cardiac markers and induces cardiac functional properties in lineage-committed progenitor cells.

    Science.gov (United States)

    Mike, Agnes K; Koenig, Xaver; Koley, Moumita; Heher, Philipp; Wahl, Gerald; Rubi, Lena; Schnürch, Michael; Mihovilovic, Marko D; Weitzer, Georg; Hilber, Karlheinz

    2014-01-01

    Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited transdifferentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules. Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC), and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays. Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies. CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy.

  6. Paracrine Engineering of Human Explant-Derived Cardiac Stem Cells to Over-Express Stromal-Cell Derived Factor 1α Enhances Myocardial Repair.

    Science.gov (United States)

    Tilokee, Everad L; Latham, Nicholas; Jackson, Robyn; Mayfield, Audrey E; Ye, Bin; Mount, Seth; Lam, Buu-Khanh; Suuronen, Erik J; Ruel, Marc; Stewart, Duncan J; Davis, Darryl R

    2016-07-01

    First generation cardiac stem cell products provide indirect cardiac repair but variably produce key cardioprotective cytokines, such as stromal-cell derived factor 1α, which opens the prospect of maximizing up-front paracrine-mediated repair. The mesenchymal subpopulation within explant derived human cardiac stem cells underwent lentiviral mediated gene transfer of stromal-cell derived factor 1α. Unlike previous unsuccessful attempts to increase efficacy by boosting the paracrine signature of cardiac stem cells, cytokine profiling revealed that stromal-cell derived factor 1α over-expression prevented lv-mediated "loss of cytokines" through autocrine stimulation of CXCR4+ cardiac stem cells. Stromal-cell derived factor 1α enhanced angiogenesis and stem cell recruitment while priming cardiac stem cells to readily adopt a cardiac identity. As compared to injection with unmodified cardiac stem cells, transplant of stromal-cell derived factor 1α enhanced cells into immunodeficient mice improved myocardial function and angiogenesis while reducing scarring. Increases in myocardial stromal-cell derived factor 1α content paralleled reductions in myocyte apoptosis but did not influence long-term engraftment or the fate of transplanted cells. Transplantation of stromal-cell derived factor 1α transduced cardiac stem cells increased the generation of new myocytes, recruitment of bone marrow cells, new myocyte/vessel formation and the salvage of reversibly damaged myocardium to enhance cardiac repair after experimental infarction. Stem Cells 2016;34:1826-1835.

  7. Improvement of cardiac function after kidney transplantation with dilated cardiomyopathy and long dialysis vintage.

    Science.gov (United States)

    Mimura, Imari; Kawarazaki, Hiroo; Momose, Toshimitsu; Shibagaki, Yugo; Fujita, Toshiro

    2009-12-01

    Patients with long dialysis vintage have low cardiac output for various reasons. Although kidney transplantation is known to improve cardiac mortality, patients are sometimes evaluated as contraindicated for transplantation because of cardiac risk. We successfully performed kidney transplantation for a patient with a long dialysis vintage and dilated cardiomyopathy. Sequential (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy suggested that amelioration of uraemia improved cardiac function. Kidney transplantation for patients with severely impaired cardiac function is safe and effective under careful perioperative monitoring irrespective of dialysis vintage. Sequential (123)I-MIBG scintigraphy can be used as an evaluation tool for the improvement in cardiac function.

  8. Osteoprotegerin Levels Change During STEMI and Reflect Cardiac Function

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan S; Hoffmann, Søren

    2014-01-01

    of OPG levels during STEMI treated with percutaneous coronary intervention (PCI) and additionally, the effect of OPG levels on cardiac function. METHODS: We prospectively included 42 patients with STEMI treated with primary PCI. Four consecutive blood samples were obtained before and after PCI treatment......BACKGROUND: High levels of circulating osteoprotegerin (OPG) predicts long-term outcome in patients with ST-elevation myocardial infarction (STEMI), possibly because of increased vascular inflammation resulting in myocardial damage. In the present study we aimed at elucidating the dynamic progress....... Plasma OPG levels were determined using an in-house immunoassay. Cardiac function was increased according to echocardiography, estimating left ventricular ejection fraction (LVEF) 1-3 days after STEMI. RESULTS: During STEMI, OPG levels peaked after PCI and then decreased; mean concentrations (95...

  9. Effect of Mixed Anesthesia on Cardiac Function by Phonocardiogram

    Institute of Scientific and Technical Information of China (English)

    Fei Han; Hong-Mei Yan; Xin-Chuan Wei; Qing Yan

    2008-01-01

    Objective of this investigation is to further analyze the cardiac function status change by phonocar diogram during mixed anesthesia which is conducted by midazolam, skelaxin, fentanyi and propofoL The results show that blood pressure, heart rate, amplitude of R wave and T wave, amplitude of first heart sound (Si) and second heart sound (52) about 37 subjects after anesthesia decrease compared with baseline, while the. ratio of first heart sound and second heart sound (Si/S2) and the ratio of diastole duration and systole duration (DIS) increase. Our study demonstrates that phonocardiogram as a noninvasive, high benefit/cost ratio, objective, repeatable and portable method can be used for the monitoring and evaluation of cardiac function status during anesthesia and operations.

  10. Overhydration, Cardiac Function and Survival in Hemodialysis Patients

    OpenAIRE

    Mihai Onofriescu; Dimitrie Siriopol; Luminita Voroneanu; Simona Hogas; Ionut Nistor; Mugurel Apetrii; Laura Florea; Gabriel Veisa; Irina Mititiuc; Mehmet Kanbay; Radu Sascau; Adrian Covic

    2015-01-01

    RESEARCH ARTICLE Overhydration, Cardiac Function and Survival in Hemodialysis Patients Mihai Onofriescu1☯, Dimitrie Siriopol1☯, Luminita Voroneanu1, Simona Hogas1, Ionut Nistor1, Mugurel Apetrii1, Laura Florea1, Gabriel Veisa1, Irina Mititiuc1, Mehmet Kanbay3, Radu Sascau2, Adrian Covic1* 1 Department of Nephrology, University of Medicine and Pharmacy “Gr. T. Popa”, Iasi, Romania, 2 Department of Cardiology, University of Medicine and Pharmacy “Gr. T. Popa”, Iasi, Romania...

  11. STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.

    Directory of Open Access Journals (Sweden)

    Nelson W Chong

    Full Text Available BACKGROUND: STARS (STriated muscle Activator of Rho Signaling is a sarcomeric protein expressed early in cardiac development that acts as an acute stress sensor for pathological remodeling. However the role of STARS in cardiac development and function is incompletely understood. Here, we investigated the role of STARS in heart development and function in the zebrafish model and in vitro. METHODOLOGY AND PRINCIPAL FINDINGS: Expression of zebrafish STARS (zSTARS first occurs in the somites by the 16 somite stage [17 hours post fertilization (hpf]. zSTARS is expressed in both chambers of the heart by 48 hpf, and also in the developing brain, jaw structures and pectoral fins. Morpholino-induced knockdown of zSTARS alters atrial and ventricular dimensions and decreases ventricular fractional shortening (measured by high-speed video microscopy, with pericardial edema and decreased or absent circulation [abnormal cardiac phenotypes in 126/164 (77% of morpholino-injected embryos vs. 0/152 (0% of control morpholino embryos]. Co-injection of zsrf (serum response factor mRNA rescues the cardiac phenotype of zSTARS knockdown, resulting in improved fractional shortening and ventricular end-diastolic dimensions. Ectopic over-expression of STARS in vitro activates the STARS proximal promoter, which contains a conserved SRF site. Chromatin immunoprecipitation demonstrates that SRF binds to this site in vivo and the SRF inhibitor CCG-1423 completely blocks STARS proximal reporter activity in H9c2 cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates for the first time that STARS deficiency severely disrupts cardiac development and function in vivo and revealed a novel STARS-SRF feed-forward autoregulatory loop that could play an essential role in STARS regulation and cardiac function.

  12. Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    2015-06-01

    Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.

  13. Sexual activity and cardiac risk: is depression a contributing factor?

    Science.gov (United States)

    Roose, S P; Seidman, S N

    2000-07-20

    There is a well-documented association between depression, ischemic heart disease, and cardiovascular mortality. This association has a number of dimensions including: (1) depressed patients have a higher than expected rate of sudden cardiovascular death; (2) over the course of a lifetime, patients with depression develop symptomatic and fatal ischemic heart disease at a higher rate compared with a nondepressed group; and (3) depression after myocardial infarction (MI) is associated with increased cardiac mortality. Depression is also associated with sexual dysfunction, particularly erectile dysfunction. If depression is the primary illness, then erectile dysfunction can be considered a symptom of the depressive illness. However, if the erectile dysfunction is primary, men may develop a depressive syndrome in reaction to the loss of sexual function. Regardless of whether erectile dysfunction is a symptom of depression or depression is a consequence of erectile dysfunction, these conditions are frequently comorbid. Thus, the patient with ischemic heart disease who is depressed is more likely to have erectile difficulties. An attempt by this patient to engage in sexual activity is therefore more likely to be unsuccessful and, given the increase in cardiac mortality associated with depression, it may result in a serious cardiac event.

  14. Exercise improves cardiac function and attenuates insulin resistance in Dahl salt-sensitive rats.

    Science.gov (United States)

    Stevens, An L M; Ferferieva, Vesselina; Bito, Virginie; Wens, Inez; Verboven, Kenneth; Deluyker, Dorien; Voet, Annemie; Vanhoof, Joke; Dendale, Paul; Eijnde, Bert O

    2015-01-01

    The development of heart failure (HF) secondary to hypertension is a complex process related to a series of physiological and molecular factors including glucose dysregulation. The overall objective of this study was to investigate whether exercise training could improve cardiac function and insulin resistance in a rat model of hypertensive HF. Seven week old Dahl salt-sensitive rats received either 8% NaCl (n = 30) or 0.3% NaCl (n = 18) diet. After a 5-week diet, animals were randomly assigned to exercise training (treadmill running at 18 m/min, 5% inclination for 60 min, 5 days/week) or kept sedentary for 6 additional weeks. 2D echocardiography was used to calculate left ventricular (LV) dimensions, volumes and global functional parameters. LV global deformation parameters were measured with speckle tracking echocardiography. Insulin resistance was assessed using 1h oral glucose tolerance testing. High salt diet led to cardiac hypertrophy and HF, characterized by increased wall thicknesses and LV volumes as well as reduced deformation parameters. In addition, high salt diet was associated with the development of insulin resistance. Exercise training improved cardiac function, reduced the extent of interstitial fibrosis and reduced insulin levels 60 min post-glucose administration. Even if not fully reversed, exercise training in HF animals improved cardiac function and insulin resistance. Adjusted modalities of exercise training might offer new insights not only as a preventive strategy, but also as a treatment for HF patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Health-Related Quality of Life, Functional Status, and Cardiac Event-Free Survival in Patients With Heart Failure.

    Science.gov (United States)

    Wu, Jia-Rong; Lennie, Terry A; Frazier, Susan K; Moser, Debra K

    2016-01-01

    Health-related quality of life (HRQOL), functional status, and cardiac event-free survival are outcomes used to assess the effectiveness of interventions in patients with heart failure (HF). However, the nature of the relationships among HRQOL, functional status, and cardiac event-free survival remains unclear. The purpose of this study is to examine the nature of the relationships among HRQOL, functional status, and cardiac event-free survival in patients with HF. This was a prospective, observational study of 313 patients with HF that was a secondary analysis from a registry. At baseline, patient demographic and clinical data were collected. Health-related quality of life was assessed using the Minnesota Living With Heart Failure Questionnaire and functional status was measured using the Duke Activity Status Index. Cardiac event-free survival data were obtained by patient interview, hospital database, and death certificate review. Multiple linear and Cox regressions were used to explore the relationships among HRQOL, functional status, and cardiac event-free survival while adjusting for demographic and clinical factors. Participants (n = 313) were men (69%), white (79%), and aged 62 ± 11 years. Mean left ventricular ejection fraction was 35% ± 14%. The mean HRQOL score of 32.3 ± 20.6 indicated poor HRQOL. The mean Duke Activity Status Index score of 16.2 ± 12.9 indicated poor functional status. Cardiac event-free survival was significantly worse in patients who had worse HRQOL or poorer functional status. Patients who had better functional status had better HRQOL (P quality of life was not a significant predictor of cardiac event-free survival after entering functional status in the model (P = .54), demonstrating that it was a mediator of the relationship between HRQOL and outcome. Functional status was a mediator between HRQOL and cardiac event-free survival. These data suggest that intervention studies to improve functional status are needed.

  16. Through thick and thin: A circulating growth factor inhibits age-related cardiac hypertrophy

    OpenAIRE

    McPherron, Alexandra C.

    2013-01-01

    In an intriguing new study, Loffredo et al., report that joining the circulation of old mice with that of young mice reduces age-related cardiac hypertrophy. They also found that the growth factor GDF11 is a circulating negative regulator of cardiac hypertrophy which suggests that raising GDF11 levels may be useful to treat cardiac hypertrophy associated with aging.

  17. Renal function changes after elective cardiac surgery with cardiopulmonary bypass.

    Science.gov (United States)

    de Moraes Lobo, E M; Burdmann, E A; Abdulkader, R C

    2000-01-01

    Cardiac surgery can either induce acute renal failure or improve GFR by improving the cardiac performance. In order to study renal function changes after elective cardiac surgery (CS) with cardiopulmonary bypass (CPBP), 21 patients undergoing valvular CS (VCS) or coronary artery bypass (CAB) were prospectively evaluated in three time periods: before, 24 hours after surgery and 48 hours after surgery. Patients were divided in 2 groups according to the GFR percent change in comparison to the baseline value found 24 hours after CS (deltaGFR24): Group 1, deltaGFR24 decrease higher than 20% (n = 11) and Group 2, deltaGFR24 decrease UpH) in both groups. The deltaGFR24 showed positive correlation with baseline FENa (r = 0.44 p = 0.04) and negative correlation with volume balance during the first 24h after CS (r = -0.63, p = 0.007). More patients in Group 1 required nitroprusside than in Group 2 (66% vs. 14%, p = 0.04). Anesthesia time was shorter in Group 1 as compared to Group 2: 323+/-21 vs. 395+/-26 min, p = 0.04. No significant hemolysis occurred during CS in either group. There were no differences in age, gender, CPBP time, need for dopamine and/or dobutamine between the two groups. In conclusion, patients who presented GFR decrease after CS underwent VCS more frequently, had more prevalence of previous CS, presented lower baseline FENa, required more volume infusion and more nitroprusside use. On the other hand, no tubular dysfunction was detected in the early follow-up of CS. These results suggest that the observed renal function changes should be the result of an appropriated renal response to a low effective blood volume. In fact, a low baseline FENa anticipated a GFR decrease in these patients. Consistently, CAB patients that usually improve their cardiac output after surgery showed a clear GFR improvement.

  18. The role of sirtuins in mitochondrial function and doxorubicin-induced cardiac dysfunction.

    Science.gov (United States)

    Dolinsky, Vernon W

    2017-08-28

    Anthracycline chemotherapeutics such as doxorubicin continue to be important treatments for many cancers. Through improved screening and therapy, more patients are surviving and living longer after the diagnosis of their cancer. However, anthracyclines are associated with both short- and long-term cardiotoxic effects. Doxorubicin-induced mitochondrial dysfunction is a central mechanism in the cardiotoxic effects of doxorubicin that contributes to impaired cardiac energy levels, increased reactive oxygen species production, cardiomyocyte apoptosis and the decline in cardiac function. Sirtuins are protein deacetylases that are activated by low energy levels and stimulate energy production through their activation of transcription factors and enzymatic regulators of cardiac energy metabolism. In addition, sirtuins activate oxidative stress resistance pathways. SIRT1 and SIRT3 are expressed at high levels in the cardiomyocyte. This review examines the function of sirtuins in the regulation of cardiac mitochondrial function, with a focus on their role in heart failure and an emphasis on their effects on doxorubicin-induced cardiotoxicity. We discuss the potential for sirtuin activation in combination with anthracycline chemotherapy in order to mitigate its cardiotoxic side-effects without reducing the antineoplastic activity of anthracyclines.

  19. Nebivolol: impact on cardiac and endothelial function and clinical utility

    Directory of Open Access Journals (Sweden)

    Toblli JE

    2012-03-01

    Full Text Available Jorge Eduardo Toblli1, Federico DiGennaro1, Jorge Fernando Giani2, Fernando Pablo Dominici21Hospital Aleman, 2Instituto de Química y Fisicoquímica Biológicas (IQUIFIB, Facultad de Farmacia y Bioquímica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaAbstract: Endothelial dysfunction is a systemic pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as disarrangement in vascular wall metabolism and function. One of the key factors in endothelial dysfunction is overproduction of reactive oxygen species which participate in the development of hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke. Because impaired endothelial activity is believed to have a major causal role in the pathophysiology of vascular disease, hypertension, and heart failure, therapeutic agents which modify this condition are of clinical interest. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenergic receptors and causes vasodilation by interaction with the endothelial L-arginine/nitric oxide pathway. This dual mechanism of action underscores several hemodynamic qualities of nebivolol, which include reductions in heart rate and blood pressure and improvements in systolic and diastolic function. Although nebivolol reduces blood pressure to a degree similar to that of conventional β-blockers and other types of antihypertensive drugs, it may have advantages in populations with difficult-to-treat hypertension, such as patients with heart failure along with other comorbidities, like diabetes and obesity, and elderly patients in whom nitric oxide-mediated endothelial dysfunction may be more pronounced. Furthermore, recent data indicate that nebivolol appears to be a cost-effective treatment for elderly patients with

  20. Playing with cardiac "redox switches": the "HNO way" to modulate cardiac function.

    Science.gov (United States)

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

    2011-05-01

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

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

    Science.gov (United States)

    Wu, Mingming; Sato, Thomas N

    2008-01-01

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

  2. Risk Factors for Sudden Cardiac Death : Risk Factors for Sudden Cardiac Death

    NARCIS (Netherlands)

    M.N. Niemeijer (Maartje)

    2016-01-01

    markdownabstractSCD is a common cause of death, with around four to five million cases annually worldwide. Determining which persons are at high risk for SCD remains difficult, due to lack of knowledge on individual risk factors and because in the majority of cases, SCD is the first manifestation of

  3. Exendin-4 improves cardiac function in mice overexpressing monocyte chemoattractant protein-1 in cardiomyocytes.

    Science.gov (United States)

    Younce, Craig W; Niu, Jianli; Ayala, Jennifer; Burmeister, Melissa A; Smith, Layton H; Kolattukudy, Pappachan; Ayala, Julio E

    2014-11-01

    The incretin hormone glucagon-like peptide-1 (Glp1) is cardioprotective in models of ischemia-reperfusion injury, myocardial infarction and gluco/lipotoxicity. Inflammation is a factor in these models, yet it is unknown whether Glp1 receptor (Glp1r) agonists are protective against cardiac inflammation. We tested the hypothesis that the Glp1r agonist Exendin-4 (Ex4) is cardioprotective in mice with cardiac-specific monocyte chemoattractant protein-1 overexpression. These MHC-MCP1 mice exhibit increased cardiac monocyte infiltration, endoplasmic reticulum (ER) stress, apoptosis, fibrosis and left ventricular dysfunction. Ex4 treatment for 8 weeks improved cardiac function and reduced monocyte infiltration, fibrosis and apoptosis in MHC-MCP1 mice. Ex4 enhanced expression of the ER chaperone glucose-regulated protein-78 (GRP78), decreased expression of the pro-apoptotic ER stress marker CCAAT/-enhancer-binding protein homologous protein (CHOP) and increased expression of the ER calcium regulator Sarco/Endoplasmic Reticulum Calcium ATPase-2a (SERCA2a). These findings suggest that the Glp1r is a viable target for treating cardiomyopathies associated with stimulation of pro-inflammatory factors.

  4. Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures.

    Directory of Open Access Journals (Sweden)

    Hong Jin

    Full Text Available The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ~50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.

  5. Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures.

    Science.gov (United States)

    Jin, Hong; Stojnic, Robert; Adryan, Boris; Ozdemir, Anil; Stathopoulos, Angelike; Frasch, Manfred

    2013-01-01

    The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP) from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ~50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.

  6. Chronic Intermittent Hypobaric Hypoxia Improves Cardiac Function through Inhibition of Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Yuan, Fang; Zhang, Li; Li, Yan-Qing; Teng, Xu; Tian, Si-Yu; Wang, Xiao-Ran; Zhang, Yi

    2017-08-11

    We investigated the role of endoplasmic reticulum stress (ERS) in chronic intermittent hypobaric hypoxia (CIHH)-induced cardiac protection. Adult male Sprague-Dawley rats were exposed to CIHH treatment simulating 5000 m altitude for 28 days, 6 hours per day. The heart was isolated and perfused with Langendorff apparatus and subjected to 30-min ischemia followed by 60-min reperfusion. Cardiac function, infarct size, and lactate dehydrogenase (LDH) activity were assessed. Expression of ERS molecular chaperones (GRP78, CHOP and caspase-12) was assayed by western blot analysis. CIHH treatment improved the recovery of left ventricular function and decreased cardiac infarct size and activity of LDH after I/R compared to control rats. Furthermore, CIHH treatment inhibited over-expression of ERS-related factors including GRP78, CHOP and caspase-12. CIHH-induced cardioprotection and inhibition of ERS were eliminated by application of dithiothreitol, an ERS inducer, and chelerythrine, a protein kinase C (PKC) inhibitor. In conclusion CIHH treatment exerts cardiac protection against I/R injury through inhibition of ERS via PKC signaling pathway.

  7. Genetic and environmental factors in cardiac sodium channel disease

    NARCIS (Netherlands)

    Mizusawa, Y.

    2016-01-01

    Cardiac sodium channelopathies, such as long QT syndrome type3 (LQT3), Brugada syndrome (BrS) and cardiac conduction disease (CCD), are heritable diseases associated with mutations in the SCN5A gene and sudden cardiac death. They were classically thought to be a monogenic disease. However, while LQT

  8. Genetic and environmental factors in cardiac sodium channel disease

    NARCIS (Netherlands)

    Mizusawa, Y.

    2016-01-01

    Cardiac sodium channelopathies, such as long QT syndrome type3 (LQT3), Brugada syndrome (BrS) and cardiac conduction disease (CCD), are heritable diseases associated with mutations in the SCN5A gene and sudden cardiac death. They were classically thought to be a monogenic disease. However, while LQT

  9. Fibroblast growth factor 21 as a possible endogenous factor inhibits apoptosis in cardiac endothelial cells

    Institute of Scientific and Technical Information of China (English)

    L(U) Yun; ZHANG Ying-chuan; LIU Jing-hua; ZHANG Li-ke; DU Jie; ZENG Xiang-jun; HAO Gang; HUANG Ji; ZHAO Dong-hui; WANG Guo-zhong

    2010-01-01

    Background Fibroblast growth factor 21 (FGF21) is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection factor.Methods The present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein (ox-LDL), and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells (CMECs) were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMFCs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 levels.Results The secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 μmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis (P <0.05).Conclusions FGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.

  10. Functional Maximum Autocorrelation Factors

    DEFF Research Database (Denmark)

    Larsen, Rasmus; Nielsen, Allan Aasbjerg

    2005-01-01

    Purpose. We aim at data where samples of an underlying function are observed in a spatial or temporal layout. Examples of underlying functions are reflectance spectra and biological shapes. We apply functional models based on smoothing splines and generalize the functional PCA in\\verb+~+\\$\\backsl......Purpose. We aim at data where samples of an underlying function are observed in a spatial or temporal layout. Examples of underlying functions are reflectance spectra and biological shapes. We apply functional models based on smoothing splines and generalize the functional PCA in...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Maagaard, Marie; Heiberg, Johan

    2016-09-01

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

  14. Protective effects of garlic extract on cardiac function, heart rate variability, and cardiac mitochondria in obese insulin-resistant rats.

    Science.gov (United States)

    Supakul, Luerat; Pintana, Hiranya; Apaijai, Nattayaporn; Chattipakorn, Siriporn; Shinlapawittayatorn, Krekwit; Chattipakorn, Nipon

    2014-04-01

    Garlic has been shown to exhibit antioxidant effects and cardioprotective properties. However, the effects of garlic extract on the heart in insulin resistance induced by long-term high-fat-diet consumption are not well defined. Therefore, we sought to determine the effects of garlic extract in the obese insulin-resistant rats. Male Wistar rats (180-200 g) were divided into two groups: normal-diet or high-fat-diet (n = 24/group) fed for 12 weeks. Rats in each groups were divided into three subgroups (n = 8 each): vehicle or garlic extract (250 or 500 mg/kg/day, respectively) treated for 28 days. At the end of the treatment, the metabolic parameters, heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined. Rats that received a high-fat-diet for 12 weeks had increased body weight, visceral fat, plasma insulin levels, total cholesterol, oxidative stress levels, depressed HRV, and cardiac mitochondrial dysfunction. Garlic extract at both concentrations significantly decreased the plasma insulin, total cholesterol, homeostasis model assessment index, and oxidative stress levels. Furthermore, garlic extract at both doses restored the HRV, cardiac function, and cardiac mitochondrial function. We concluded that garlic extract at both concentrations exerted cardioprotective effects against cardiac dysfunction and mitochondrial dysfunction in obese insulin-resistant rats.

  15. Cardiac Autonomic Function Is Associated With the Coronary Microcirculatory Function in Patients With Type 2 Diabetes

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Hansen, Christian Stevns; Hasbak, Philip

    2016-01-01

    Cardiac autonomic dysfunction and cardiac microvascular dysfunction are diabetic complications associated with increased mortality, but the association between these has been difficult to assess. We applied new and sensitive methods to assess this in patients with type 2 diabetes mellitus (T2DM...... (123)I-metaiodobenzylguanidine scintigraphy was conducted in a subgroup of 29 patients and 14 control subjects and evaluated as the late heart-to-mediastinum ratio and washout rate. Impaired function of all the cardiac autonomic measures (except the washout rate) was associated with reduced CFR....... A heart rate variability index, reflecting sympathetic and parasympathetic function (low-frequency power), and the late heart-to-mediastinum ratio, reflecting the function of adrenergic receptors and sympathetic activity, were positively correlated with CFR after adjustment for age and heart rate...

  16. Longstanding hyperthyroidism is associated with normal or enhanced intrinsic cardiomyocyte function despite decline in global cardiac function.

    Directory of Open Access Journals (Sweden)

    Nathan Y Weltman

    Full Text Available Thyroid hormones (THs play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH. LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function.

  17. Longstanding Hyperthyroidism Is Associated with Normal or Enhanced Intrinsic Cardiomyocyte Function despite Decline in Global Cardiac Function

    Science.gov (United States)

    Redetzke, Rebecca A.; Gerdes, A. Martin

    2012-01-01

    Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function. PMID:23056390

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

    Science.gov (United States)

    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 football practice presented enhanced physical fitness and autonomic function, by increasing vagal tone at rest. PMID:26448848

  19. Altering Cardiac Function via Transgenesis A Nuts and Bolts Approach.

    Science.gov (United States)

    Robbins, J

    1997-08-01

    Transgenesis provides a means to modify the mammalian genome. By directing expression of a engineered protein to the heart, one now is able to remodel effectively the cardiac protein profile and study the consequences of a single genetic manipulation at the molecular, biochemical, cytological, and physiologic levels. Often, a particular pathology or even a global remodeling process such as hypertrophy is accompanied by the upregulation or downregulation of a gene or set(s) of genes. What is not known is whether these changes represent a beneficial compensatory response or contribute to the continued degeneration of normal heart function. The ability to perform genetic manipulations on cardiac gene expression via transgenesis offers one a rapid and effective means of extending the correlations noted to the mechanistic level. Now, one can, in theory, express a candidate protein at a particular developmental time and determine the direct consequences of its appearance. Similarly, one can explore structure-function relationships, both between different forms of a protein family and in terms of active domains within a protein, by expressing a transgene that encodes a suitable mutation or ectopic protein isoform. This review explores the practical considerations of the transgenic approach in terms of what is important for a successful experiment from the necessary animal husbandry to designing constructs that will express at appropriate levels in the heart. (Trends Cardiovasc Med 1997;7:185-191). © 1997, Elsevier Science Inc.

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

    OpenAIRE

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

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1...

  1. Skeletal myoblasts for heart regeneration and repair: state of the art and perspectives on the mechanisms for functional cardiac benefits.

    Science.gov (United States)

    Formigli, L; Zecchi-Orlandini, S; Meacci, E; Bani, D

    2010-01-01

    Until recently, skeletal myoblasts (SkMBs) have been the most widely used cells in basic research and clinical trials of cell based therapy for cardiac repair and regeneration. Although SkMB engraftment into the post-infarcted heart has been consistently found to improve cardiac contractile function, the underlying therapeutic mechanisms remain still a matter of controversy and debate. This is basically because SkMBs do not attain a cardiac-like phenotype once homed into the diseased heart nor they form a contractile tissue functionally coupled with the surrounding viable myocardium. This issue of concern has generated the idea that the cardiotropic action of SkMBs may depend on the release of paracrine factors. However, the paracrine hypothesis still remains ill-defined, particularly concerning the identification of the whole spectrum of cell-derived soluble factors and details on their cardiac effects. In this context, the possibility to genetically engineering SkMBs to potentate their paracrine attitudes appears particularly attractive and is actually raising great expectation. Aim of the present review is not to cover all the aspects of cell-based therapy with SkMBs, as this has been the object of previous exhaustive reviews in this field. Rather, we focused on novel aspects underlying the interactions between SkMBs and the host cardiac tissues which may be relevant for directing the future basic and applied research on SkMB transplantation for post ischemic cardiac dysfunction.

  2. Risk factor paradox in the occurrence of cardiac arrest in acute coronary syndrome patients

    Science.gov (United States)

    Rosa, Silvia Aguiar; Timóteo, Ana Teresa; Nogueira, Marta Afonso; Belo, Adriana; Ferreira, Rui Cruz

    2016-01-01

    Objective To compare patients without previously diagnosed cardiovascular risk factors) and patients with one or more risk factors admitted with acute coronary syndrome. Methods This was a retrospective analysis of patients admitted with first episode of acute coronary syndrome without previous heart disease, who were included in a national acute coronary syndrome registry. The patients were divided according to the number of risk factors, as follows: 0 risk factor (G0), 1 or 2 risk factors (G1 - 2) and 3 or more risk factors (G ≥ 3). Comparative analysis was performed between the three groups, and independent predictors of cardiac arrest and death were studied. Results A total of 5,518 patients were studied, of which 72.2% were male and the mean age was 64 ± 14 years. G0 had a greater incidence of ST-segment elevation myocardial infarction, with the left anterior descending artery being the most frequently involved vessel, and a lower prevalence of multivessel disease. Even though G0 had a lower Killip class (96% in Killip I; p < 0.001) and higher ejection fraction (G0 56 ± 10% versus G1 - 2 and G ≥ 3 53 ± 12%; p = 0.024) on admission, there was a significant higher incidence of cardiac arrest. Multivariate analysis identified the absence of risk factors as an independent predictor of cardiac arrest (OR 2.78; p = 0.019). Hospital mortality was slightly higher in G0, although this difference was not significant. By Cox regression analysis, the number of risk factors was found not to be associated with mortality. Predictors of death at 1 year follow up included age (OR 1.05; p < 0.001), ST-segment elevation myocardial infarction (OR 1.94; p = 0.003) and ejection fraction < 50% (OR 2.34; p < 0.001). Conclusion Even though the group without risk factors was composed of younger patients with fewer comorbidities, better left ventricular function and less extensive coronary disease, the absence of risk factors was an independent predictor of cardiac arrest. PMID

  3. Critical role of bicarbonate and bicarbonate transporters in cardiac function

    Institute of Scientific and Technical Information of China (English)

    Hong-Sheng; Wang; Yamei; Chen; Kanimozhi; Vairamani; Gary; E; Shull

    2014-01-01

    Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2 O, either spontaneously or via the catalytic activity of carbonic anhydrase. It serves as a component of the major buffer system, thereby playing a critical role in pH homeostasis. Bicarbonate can also be utilized by a variety of ion transporters, often working in coupled systems, to transport other ions and organic substrates across cell membranes. The functions of HCO3- and HCO3--transporters in epithelial tissues have been studied extensively, but their functions in heart are less well understood. Here we review studies of the identities and physiological functions of Cl-/HCO3- exchangers and Na+/HCO3-cotransporters of the SLC4 A and SLC26 A families in heart. We also present RNA Seq analysis of their cardiac mRNA expression levels. These studies indicate that slc4a3(AE3) is the major Cl-/HCO3- exchanger and plays a protective role in heart failure, and that Slc4a4(NBCe1) is the major Na+/HCO3- cotransporter and affects action potential duration. In addition, previous studies show that HCO3- has a positive inotropic effect in the perfused heart that is largely independent of effects on intracellular Ca2+. The importance of HCO3- in the regulation of contractility is supported by experiments showing that isolated cardiomyocytes exhibit sharply enhanced contractility, with no change in Ca2+ transients, when switched from Hepes-buffered to HCO3-- buffered solutions. These studies demonstrate that HCO3- and HCO3--handling proteins play important roles in the regulation of cardiac function.

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

    Science.gov (United States)

    Nelson, O Lynne; Robbins, Charles T

    2010-03-01

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

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

    OpenAIRE

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

    2016-01-01

    Abstract Introduction: Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. Objective: To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. Methods: This is a clinical randomized controlled tri...

  6. Protection of Coronary Endothelial Function during Cardiac Surgery: Potential of Targeting Endothelial Ion Channels in Cardioprotection

    Directory of Open Access Journals (Sweden)

    Qin Yang

    2014-01-01

    Full Text Available Vascular endothelium plays a critical role in the control of blood flow by producing vasoactive factors to regulate vascular tone. Ion channels, in particular, K+ channels and Ca2+-permeable channels in endothelial cells, are essential to the production and function of endothelium-derived vasoactive factors. Impairment of coronary endothelial function occurs in open heart surgery that may result in reduction of coronary blood flow and thus in an inadequate myocardial perfusion. Hyperkalemic exposure and concurrent ischemia-reperfusion during cardioplegic intervention compromise NO and EDHF-mediated function and the impairment involves alterations of K+ channels, that is, KATP and KCa, and Ca2+-permeable TRP channels in endothelial cells. Pharmacological modulation of these channels during ischemia-reperfusion and hyperkalemic exposure show promising results on the preservation of NO and EDHF-mediated endothelial function, which suggests the potential of targeting endothelial K+ and TRP channels for myocardial protection during cardiac surgery.

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

    Science.gov (United States)

    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.

  8. Small Molecule Cardiogenol C Upregulates Cardiac Markers and Induces Cardiac Functional Properties in Lineage-Committed Progenitor Cells

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    Agnes K. Mike

    2014-01-01

    Full Text Available Background/Aims: Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited transdifferentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules. Methods: Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC, and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays. Results: Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies. Conclusion: CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy.

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

    Science.gov (United States)

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

    2017-01-01

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

  10. Risk Factors for post-Cardiac Surgery Diaphragmatic Paralysis in Children with Congenital Heart Disease

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    Parvin Akbariasbagh

    2015-12-01

    Full Text Available Background: Injured phrenic nerve secondary to cardiac surgeries is the most common cause of diaphragmatic paralysis (DP in infants. The aim of this study was to determine the risk factors for DP caused by congenital heart defect corrective surgeries in pediatrics.Methods: This cross-sectional study, conducted in a 2-year period (2006–2008, included 451 children with congenital heart diseases admitted to the Pediatric Cardiac Surgery Ward of Imam Khomeini Hospital. The diaphragmatic function was examined via fluoroscopy, and the frequency of DP and its relevant parameters were evaluated.Results: Of the 451 patients, comprising 268 males and 183 females at an age range of 3 days to 204 months (28.2 ± 33.4 months, 25 (5.5% infants (60% male and 40% female, age range = 15 days to 132 months, 41.2 ± 28.1 months had DP as follows: 48% unilateral right-sided and 36% unilateral left-sided. Additionally, 68% had cyanotic congenital heart disease and 84% had DP following total correction surgery.  The highest prevalence rates of DP resulting in phrenic hemiparesis were observed after arterial switch operation, Fontan procedure, and Blalock–Taussig shunt surgery, respectively. Thirteen (52% of the 25 DP patients underwent surgical diaphragmatic plication because of severe respiratory distress and dependency on mechanical ventilation, and most of the cases of plication underwent arterial switch operation. The rate of mortality was 24% (6 patients.Conclusion: DP with a prevalence of 5.5% was one of the most common complications secondary to cardiac surgeries in the infants included in the present study. Effective factors were age, weight, cyanotic congenital heart defects, and previous cardiac surgery. Diaphragmatic plication improved prognosis in severe cases.

  11. Risk factors for lead complications in cardiac pacing

    DEFF Research Database (Denmark)

    Kirkfeldt, Rikke Esberg; Johansen, Jens Brock; Nøhr, Ellen Aagaard;

    2011-01-01

    Lead complications are the main reason for reoperation after implantation of pacemakers (PM) or cardiac resynchronization therapy (CRT-P) devices.......Lead complications are the main reason for reoperation after implantation of pacemakers (PM) or cardiac resynchronization therapy (CRT-P) devices....

  12. Pharmacological and Biological Risk Factors for Cardiac Arrhythmias

    NARCIS (Netherlands)

    C. van Noord (Charlotte)

    2009-01-01

    textabstractSudden death is among the most common causes of death in developed countries. Sudden death from cardiac causes accounts for approximately 50% of all deaths from cardiovascular diseases and 20% of all deaths. The majority (80-85%) of sudden cardiac deaths are caused by acute ventricular a

  13. Restoration of Circulating MFGE8 (Milk Fat Globule-EGF Factor 8) Attenuates Cardiac Hypertrophy Through Inhibition of Akt Pathway.

    Science.gov (United States)

    Deng, Ke-Qiong; Li, Jing; She, Zhi-Gang; Gong, Jun; Cheng, Wen-Lin; Gong, Fu-Han; Zhu, Xue-Yong; Zhang, Yan; Wang, Zhihua; Li, Hongliang

    2017-10-01

    Cardiac hypertrophy occurs in response to numerous stimuli like neurohumoral stress, pressure overload, infection, and injury, and leads to heart failure. Mfge8 (milk fat globule-EGF factor 8) is a secreted protein involved in various human diseases, but its regulation and function during cardiac hypertrophy remain unexplored. Here, we found that circulating MFGE8 levels declined significantly in failing hearts from patients with dilated cardiomyopathy. Correlation analyses revealed that circulating MFGE8 levels were negatively correlated with the severity of cardiac dysfunction and remodeling in affected patients. Deleting Mfge8 in mice maintained normal heart function at basal level but substantially exacerbated the hypertrophic enlargement of cardiomyocytes, reprogramming of pathological genes, contractile dysfunction, and myocardial fibrosis after aortic banding surgery. In contrast, cardiac-specific Mfge8 overexpression in transgenic mice significantly blunted aortic banding-induced cardiac hypertrophy. Whereas MAPK (mitogen-activated protein kinase) pathways were unaffected in either Mfge8-knockout or Mfge8-overexpressing mice, the activated Akt/PKB (protein kinase B)-Gsk-3β (glycogen synthase kinase-3β)/mTOR (mammalian target of rapamycin) pathway after aortic banding was significantly potentiated by Mfge8 deficiency but suppressed by Mfge8 overexpression. Inhibition of Akt with MK-2206 blocked the prohypertrophic effects of Mfge8 deficiency in angiotensin II-treated neonatal rat cardiomyocytes. Finally, administering a recombinant human MFGE8 in mice in vivo alleviated cardiac hypertrophy induced by aortic banding. Our findings indicate that Mfge8 is an endogenous negative regulator of pathological cardiac hypertrophy and may, thus, have potential both as a novel biomarker and as a therapeutic target for treatment of cardiac hypertrophy. © 2017 American Heart Association, Inc.

  14. Comparison of Cardiac Autonomic Functions in Glucometabolic Disturbances

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    Seda Elçim Yıldırım

    2016-12-01

    Full Text Available INTRODUCTION: Autonomic neuropathy is a common complication of diabetes mellitus. The aim of the present study was to compare heart rate recovery time and heart rate variation among the indicators of cardiac autonomic function between patients with glucometabolic abnormalities in various levels and normal glucose homeostasis. METHODS: A total of 90 patients were enrolled in the study. The patients were divided into four groups: impaired fasting glucose (IFG (n=18, impaired glucose tolerance (IGT (n=25, type 2 diabetes mellitus (DM (n=21, and the control group (n=26. Cardiac autonomic neuropathy (CAN was evaluated by the maximum exercise stress test and Holter electrocardiography. RESULTS: The baseline heart rate in the DM group was higher than the IFG, IGT, and control groups, but the difference was not statistically significant (93.5±15.5, 87.8±9.4, 84.3±10.8, and 84.3±14.2, respectively; p=0.06. In multiple regression analysis FPG level was an independent variable, increased baseline heart rate was correlated with an elevated FPG level (constant: 71.35, p: 0.004. The metabolic equivalent of task (MET value was lower in the DM group compared to the IFG, IGT, and control groups (9.9±1.2, 9.0±1.6, 9.78±1.46, 8.77±1.74 p=0.06. DISCUSSION AND CONCLUSION: When compared to patients with normal glucose homeostasis heart rate at rest was higher in the IGT, IFG, and DM groups. Elevated fasting glucose levels were correlated with an increased baseline heart rate. A negative correlation was found between HbA1c levels and HRRT, and HR index. These finding indicate autonomic functions are impaired in patients with DM, IGT and IFG groups.

  15. X indening oral liquid improves cardiac function of rats with chronic cardiac failure via TGF-ß1/Smad3 and p38 MAPK pathway.

    Science.gov (United States)

    Wei, Yunliang; Guo, Changsheng; Zhao, Jingsheng; Yang, Jun; Yi, Weiguo; Liu, Hong; Lin, Xinwei; Zhang, Zhengchen

    2017-05-01

    Xindening oral liquid (Xin) is a widely used traditional Chinese medicine for the treatment of chronic heart failure (CHF). However, the exact mechanisms related to its therapeutic effects against CHF remain unclear. In the present study, we investigate the effects of Xin on cardiac function in CHF rats and the possible mechanisms involved. Transverse aortic constriction (TAC) was conducted to induce a CHF rat model in this study. Sixty male Wistar rats were randomly assigned to six groups 28 days after TAC: sham; CHF model; Xin at concentrations of 5 ml/kg, 10 mL/kg, and 20 mL/kg; and QiLi 0.6 g/kg. After four weeks, the rats were treated with Xin (5, 10, or 20 mL/kg/d) for six weeks consecutively. At the end of the study, the cardiac function, heart weight index (HWI) and left ventricular mass index (LVMI), serum level of LDH, B-type natriuretic peptide (BNP), cTnI and CK-MB, and collagen volume fraction were studied. The expression of transforming growth factor-ß1 (TGF-ß1), drosophila mothers against decapentaplegic protein 3 (Smad3), and p38 mitogen activated protein kinase (p38 MAPK) were detected. The results showed that Xin treatment significantly improved cardiac function but decreased the serum level of LDH, BNP, cTnI, and CKMB of CHF rats. In addition, it reduced the HWI, LVMI, and collagen volume fraction compared with the model group. Xin treatment significantly improved cardiac function and attenuated cardiac fibrosis by suppressing the p38 MAPK and TGF-ß1/Smad3 signaling pathway in CHF rats. These results suggested that Xin might be a promising complementary treatment for CHF. More detailed experimental studies will be carried out in our subsequent research.

  16. (Prorenin receptor triggers distinct angiotensin II-independent extracellular matrix remodeling and deterioration of cardiac function.

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    Anne-Mari Moilanen

    Full Text Available BACKGROUND: Activation of the renin-angiotensin-system (RAS plays a key pathophysiological role in heart failure in patients with hypertension and myocardial infarction. However, the function of (prorenin receptor ((PRR is not yet solved. We determined here the direct functional and structural effects of (PRR in the heart. METHODOLOGY/PRINCIPAL FINDINGS: (PRR was overexpressed by using adenovirus-mediated gene delivery in normal adult rat hearts up to 2 weeks. (PRR gene delivery into the anterior wall of the left ventricle decreased ejection fraction (P<0.01, fractional shortening (P<0.01, and intraventricular septum diastolic and systolic thickness, associated with approximately 2-fold increase in left ventricular (PRR protein levels at 2 weeks. To test whether the worsening of cardiac function and structure by (PRR gene overexpression was mediated by angiotensin II (Ang II, we infused an AT(1 receptor blocker losartan via osmotic minipumps. Remarkably, cardiac function deteriorated in losartan-treated (PRR overexpressing animals as well. Intramyocardial (PRR gene delivery also resulted in Ang II-independent activation of extracellular-signal-regulated kinase1/2 phosphorylation and myocardial fibrosis, and the expression of transforming growth factor-β1 and connective tissue growth factor genes. In contrast, activation of heat shock protein 27 phosphorylation and apoptotic cell death by (PRR gene delivery was Ang II-dependent. Finally, (PRR overexpression significantly increased direct protein-protein interaction between (PRR and promyelocytic zinc-finger protein. CONCLUSIONS/SIGNIFICANCE: These results indicate for the first time that (PRR triggers distinct Ang II-independent myocardial fibrosis and deterioration of cardiac function in normal adult heart and identify (PRR as a novel therapeutic target to optimize RAS blockade in failing hearts.

  17. PPARα augments heart function and cardiac fatty acid oxidation in early experimental polymicrobial sepsis.

    Science.gov (United States)

    Standage, Stephen W; Bennion, Brock G; Knowles, Taft O; Ledee, Dolena R; Portman, Michael A; McGuire, John K; Liles, W Conrad; Olson, Aaron K

    2017-02-01

    Children with sepsis and multisystem organ failure have downregulated leukocyte gene expression of peroxisome proliferator-activated receptor-α (PPARα), a nuclear hormone receptor transcription factor that regulates inflammation and lipid metabolism. Mouse models of sepsis have likewise demonstrated that the absence of PPARα is associated with decreased survival and organ injury, specifically of the heart. Using a clinically relevant mouse model of early sepsis, we found that heart function increases in wild-type (WT) mice over the first 24 h of sepsis, but that mice lacking PPARα (Ppara(-/-)) cannot sustain the elevated heart function necessary to compensate for sepsis pathophysiology. Left ventricular shortening fraction, measured 24 h after initiation of sepsis by echocardiography, was higher in WT mice than in Ppara(-/-) mice. Ex vivo working heart studies demonstrated greater developed pressure, contractility, and aortic outflow in WT compared with Ppara(-/-) mice. Furthermore, cardiac fatty acid oxidation was increased in WT but not in Ppara(-/-) mice. Regulatory pathways controlling pyruvate incorporation into the citric acid cycle were inhibited by sepsis in both genotypes, but the regulatory state of enzymes controlling fatty acid oxidation appeared to be permissive in WT mice only. Mitochondrial ultrastructure was not altered in either genotype indicating that severe mitochondrial dysfunction is unlikely at this stage of sepsis. These data suggest that PPARα expression supports the hyperdynamic cardiac response early in the course of sepsis and that increased fatty acid oxidation may prevent morbidity and mortality. In contrast to previous studies in septic shock using experimental mouse models, we are the first to demonstrate that heart function increases early in sepsis with an associated augmentation of cardiac fatty acid oxidation. Absence of peroxisome proliferator-activated receptor-α (PPARα) results in reduced cardiac performance and fatty

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fabricio Furtado Vieira

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

  1. 67. Do prenatal intracardiac echogenic foci affect postnatal cardiac function?

    Directory of Open Access Journals (Sweden)

    R. Bader

    2016-07-01

    Full Text Available Echogenic foci in the prenatal hear is not an uncommon finding. To determine whether prenatally diagnosed intracardiac echogenic foci are associated with neonatal cardiac dysfunction and persistence. Fetuses in which intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center from (September 2009 to December 2013 underwent postnatal echocardiography at ages 1 month to1 year. A single pediatric cardiologist assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid valve regurgitation was also sought. Prenatally 60 fetuses had intracardiac echogenic foci mean age ± SD at diagnosis (23 ± 3.1. 53 (88.3% had left ventricular intracardiac echogenic foci, and 7 (11.6% had right ventricular intracardiac echogenic foci. 12 preganant ladies were lost for follow up (2 fetuses of 7 (28.5% with right ventricular intracardiac echogenic foci., and 10 fetuses of 53 (18.8% with LV intracardiac echogenic foci %. Post natally, those infants, 32 (66.6% males and 16 (33.3% females were examined. At a mean age ± SD of 7.4 ± 3.1 months. Prenatally, all infants had a normal left ventricular shortening fraction. The overall mean left ventricular myocardial performance index (reference value, 0.36 ± 0.06, was normal for both infants with left ventricular intracardiac echogenic foci (0.32 ± 0.01 and those with right ventricular intracardiac echogenic foci (0.33 ± 0.05. Trace tricuspid valve regurgitation were noted in 15 (31% of the infants. Left ventricular intracardiac echogenic foci persisted in 15 infants (34.8%, whereas right ventricular intracardiac echogenic foci persisted in 1 infant (20%. Prenatally diagnosed intracardiac echogenic foci can be persistent but is not associated with myocardial dysfunction in the first year of life.

  2. The Beneficial Effects of Cardiac Rehabilitation on the Function and Levels of Endothelial Progenitor Cells.

    Science.gov (United States)

    Guo, Yuan; Ledesma, Robert Andre; Peng, Ran; Liu, Qiong; Xu, Danyan

    2017-01-01

    Cardiac rehabilitation (CR) is a comprehensive program, which mainly focusses on exercise training, disease evaluation, cardiovascular risk factors control, medication therapy, psychosocial intervention, and patient education. Although the beneficial properties of CR have been widely evidenced, its mechanism is still not completely clarified. To date, endothelial progenitor cells (EPCs) have been explored by emerging studies, and evidence has suggested that CR, especially exercise training, significantly increases the function and levels of EPCs, which is likely to elucidate the profiting mechanism of CR. Thus, this review summarises the potential relationship between CR and EPCs with an aim of providing novel directions for future CR research. Copyright © 2016. Published by Elsevier B.V.

  3. Etiologic factors of gastric cardiac adenocarcinoma among men in Taiwan

    Institute of Scientific and Technical Information of China (English)

    Mei-Ju Chen; Deng-Chyang Wu; Jia-Ming Lin; Ming-Tsang Wu; Fung-Chang Sung

    2009-01-01

    AIM: To elucidate etiologic associations between Helicobacter pylori ( H pylori), lifestyle, environmental factors and gastric cardiac adenocarcinoma (GCA) among men.METHODS: A hospital-based case-control study was conducted in Taiwan from 2000 to 2009.All cases were newly confirmed as primary GCA.Five controls were selected matching with age, sex, and admission date to each case.Participants were informed of potential risk factors with a structured questionnaire by trained interviewers during hospitalization and provided a blood sample for the determination of H pylori infection.Odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate risk, and a multivariate conditional logistic regression model was performed.RESULTS: All participants recruited for this study were men, consisting of 41 cases and 205 controls.Results of the univariate analysis showed that significant factors associated with the etiology of GCA included H pylori (OR = 2.69, 95% CI = 1.30-5.53), cigarette smoking (OR = 2.28, 95% CI = 1.05-4.96), working or exercising after meals (OR = 3.26, 95% CI = 1.31-8.11), salted food (OR = 2.51, 95%CI = 1.08-6.11), fresh vegetables (OR = 0.28, 95% CI = 0.09-0.80), fruits (OR = 0.19, 95% CI = 0.04-0.89), and rice as principal food (OR = 0.53, 95% CI = 0.30-0.85).Multivariate conditional logistic regression models indicated that a significantly elevated risk of contracting GCA was associated with working or exercising after meals (OR = 3.18, 95% CI = 1.23-9.36) and H pylori infection (OR = 2.93, 95% CI = 1.42-6.01).In contrast, the consumption of fresh vegetables (OR = 0.22, 95% CI = 0.06-0.83), fruits (OR = 0.28, 95% CI = 0.09-0.79) and rice as principal food (OR = 0.48, 95% CI = 0.24-0.93) remained as significant beneficial factor associated with GCA.CONCLUSION: Working or exercising after meals and H pylori infection increase the risk of GCA, but higher intakes of rice, fresh vegetables and fruits reduce the risk.

  4. Interoception across modalities: on the relationship between cardiac awareness and the sensitivity for gastric functions.

    Directory of Open Access Journals (Sweden)

    Beate M Herbert

    Full Text Available 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.

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

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    Fernandes

    2015-09-01

    Full Text Available 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.

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

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    Leela K Lella

    Full Text Available 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.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 30 days outcomes included, cardiac re-hospitalization, worsening congestive heart failure and mortality. Mean clinical follow up was 14 months.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.Abnormal RVEF is a stronger predictor for long-term cardiac re-hospitalization than abnormal LVEF in patients undergoing isolated CABG and valve procedures.

  7. Sodium Channel (Dys)Function and Cardiac Arrhythmias

    NARCIS (Netherlands)

    C.A. Remme; C.R. Bezzina

    2010-01-01

    P>Cardiac voltage-gated sodium channels are transmembrane proteins located in the cell membrane of cardiomyocytes. Influx of sodium ions through these ion channels is responsible for the initial fast upstroke of the cardiac action potential. This inward sodium current thus triggers the initiation an

  8. Renal replacement therapy after cardiac surgery; renal function recovers

    DEFF Research Database (Denmark)

    Steinthorsdottir, Kristin Julia; Kandler, Kristian; Agerlin Windeløv, Nis

    2013-01-01

    To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy.......To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy....

  9. Human Induced Pluripotent Stem Cell-Derived Cardiac Progenitor Cells in Phenotypic Screening: A Transforming Growth Factor-β Type 1 Receptor Kinase Inhibitor Induces Efficient Cardiac Differentiation.

    Science.gov (United States)

    Drowley, Lauren; Koonce, Chad; Peel, Samantha; Jonebring, Anna; Plowright, Alleyn T; Kattman, Steven J; Andersson, Henrik; Anson, Blake; Swanson, Bradley J; Wang, Qing-Dong; Brolen, Gabriella

    2016-02-01

    Several progenitor cell populations have been reported to exist in hearts that play a role in cardiac turnover and/or repair. Despite the presence of cardiac stem and progenitor cells within the myocardium, functional repair of the heart after injury is inadequate. Identification of the signaling pathways involved in the expansion and differentiation of cardiac progenitor cells (CPCs) will broaden insight into the fundamental mechanisms playing a role in cardiac homeostasis and disease and might provide strategies for in vivo regenerative therapies. To understand and exploit cardiac ontogeny for drug discovery efforts, we developed an in vitro human induced pluripotent stem cell-derived CPC model system using a highly enriched population of KDR(pos)/CKIT(neg)/NKX2.5(pos) CPCs. Using this model system, these CPCs were capable of generating highly enriched cultures of cardiomyocytes under directed differentiation conditions. In order to facilitate the identification of pathways and targets involved in proliferation and differentiation of resident CPCs, we developed phenotypic screening assays. Screening paradigms for therapeutic applications require a robust, scalable, and consistent methodology. In the present study, we have demonstrated the suitability of these cells for medium to high-throughput screens to assess both proliferation and multilineage differentiation. Using this CPC model system and a small directed compound set, we identified activin-like kinase 5 (transforming growth factor-β type 1 receptor kinase) inhibitors as novel and potent inducers of human CPC differentiation to cardiomyocytes. Significance: Cardiac disease is a leading cause of morbidity and mortality, with no treatment available that can result in functional repair. This study demonstrates how differentiation of induced pluripotent stem cells can be used to identify and isolate cell populations of interest that can translate to the adult human heart. Two separate examples of phenotypic

  10. Growth Factors in Synaptic Function

    Directory of Open Access Journals (Sweden)

    Vivian Yi Nuo Poon

    2013-09-01

    Full Text Available Synapses are increasingly recognized as key structures that malfunction in disorders like schizophrenia, mental retardation, and neurodegenerative diseases. The importance and complexity of the synapse has fuelled research into the molecular mechanisms underlying synaptogenesis, synaptic transmission, and plasticity. In this regard, neurotrophic factors such as netrin, Wnt, transforming growth factor-beta (TGF-beta, tumor necrosis factor-α (TNF-α, and others have gained prominence for their ability to regulate synaptic function. Several of these factors were first implicated in neuroprotection, neuronal growth, and axon guidance. However, their roles in synaptic development and function have become increasingly clear, and the downstream signaling pathways employed by these factors have begun to be elucidated. In this review, we will address the role of these factors and their downstream effectors in synaptic function in vivo and in cultured neurons.

  11. Measurement of Cardiac Angiotensin II by Immunoassays, HPLC-Chip/Mass Spectrometry, and Functional Assays.

    Science.gov (United States)

    De Mello, Walmor C; Gerena, Yamil

    2017-01-01

    The molecular mechanisms related to the effect of angiotensin II, its level on cardiac tissues, as well as its overexpression represent an important aspect of cardiovascular pharmacology and pathology. Severe alterations of cardiac functions are induced by hypertension including activation of circulating and local cardiac renin angiotensin systems. In this chapter, we are providing the methods and materials necessary for further investigation of this important topic.

  12. Antiarrhythmic effect of growth factor-supplemented cardiac progenitor cells in chronic infarcted heart.

    Science.gov (United States)

    Savi, Monia; Bocchi, Leonardo; Rossi, Stefano; Frati, Caterina; Graiani, Gallia; Lagrasta, Costanza; Miragoli, Michele; Di Pasquale, Elisa; Stirparo, Giuliano G; Mastrototaro, Giuseppina; Urbanek, Konrad; De Angelis, Antonella; Macchi, Emilio; Stilli, Donatella; Quaini, Federico; Musso, Ezio

    2016-06-01

    c-Kit(pos) cardiac progenitor cells (CPCs) represent a successful approach in healing the infarcted heart and rescuing its mechanical function, but electrophysiological consequences are uncertain. CPC mobilization promoted by hepatocyte growth factor (HGF) and IGF-1 improved electrogenesis in myocardial infarction (MI). We hypothesized that locally delivered CPCs supplemented with HGF + IGF-1 (GFs) can concur in ameliorating electrical stability of the regenerated heart. Adult male Wistar rats (139 rats) with 4-wk-old MI or sham conditions were randomized to receive intramyocardial injection of GFs, CPCs, CPCs + GFs, or vehicle (V). Enhanced green fluorescent protein-tagged CPCs were used for cell tracking. Vulnerability to stress-induced arrhythmia was assessed by telemetry-ECG. Basic cardiac electrophysiological properties were examined by epicardial multiple-lead recording. Hemodynamic function was measured invasively. Hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. Compared with V and at variance with individual CPCs, CPCs + GFs approximately halved arrhythmias in all animals, restoring cardiac anisotropy toward sham values. GFs alone reduced arrhythmias by less than CPCs + GFs, prolonging ventricular refractoriness without affecting conduction velocity. Concomitantly, CPCs + GFs reactivated the expression levels of Connexin-43 and Connexin-40 as well as channel proteins of key depolarizing and repolarizing ion currents differently than sole GFs. Mechanical function and anatomical remodeling were equally improved by all regenerative treatments, thus exhibiting a divergent behavior relative to electrical aspects. Conclusively, we provided evidence of distinctive antiarrhythmic action of locally injected GF-supplemented CPCs, likely attributable to retrieval of Connexin-43, Connexin-40, and Cav1.2 expression, favoring intercellular coupling and spread of excitation in mended heart.

  13. Molecular Mechanisms for Exercise Training-Induced Changes in Vascular Structure and Function: Skeletal Muscle, Cardiac Muscle, and the Brain.

    Science.gov (United States)

    Olver, T Dylan; Ferguson, Brian S; Laughlin, M Harold

    2015-01-01

    Compared with resting conditions, during incremental exercise, cardiac output in humans is elevated from ~5 to 25 L min(-1). In conjunction with this increase, the proportion of cardiac output directed toward skeletal muscle increases from ~20% to 85%, while blood flow to cardiac muscle increases 500% and blood flow to specific brain structures increases nearly 200%. Based on existing evidence, researchers believe that blood flow in these tissues is matched to the increases in metabolic rate during exercise. This phenomenon, the matching of blood flow to metabolic requirement, is often referred to as functional hyperemia. This chapter summarizes mechanical and metabolic factors that regulate functional hyperemia as well as other exercise-induced signals, which are also potent stimuli for chronic adaptations in vascular biology. Repeated exposure to exercise-induced increases in shear stress and the induction of angiogenic factors alter vascular cell gene expression and mediate changes in vascular volume and blood flow control. The magnitude and regulation of this coordinated response appear to be tissue specific and coupled to other factors such as hypertrophy and hyperplasia. The cumulative effects of these adaptations contribute to increased exercise capacity, reduced relative challenge of a given submaximal exercise bout and ameliorated vascular outcomes in patient populations with pathological conditions. In the subsequent discussion, this chapter explores exercise as a regulator of vascular biology and summarizes the molecular mechanisms responsible for exercise training-induced changes in vascular structure and function in skeletal and cardiac muscle as well as the brain.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    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

  16. Neurohormones as markers of right- and left-sided cardiac dimensions and function in patients with untreated chronic heart failure

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Hildebrandt, Per; Appel, Jon;

    2005-01-01

    BACKGROUND: It is now well accepted that neuroendocrine activation is of pathophysiological and prognostic importance in patients with chronic heart failure (CHF). We hypothesized that the different neuroendocrine factors reflect different aspects of the cardiac dysfunction in CHF patients...... and that neuroendocrine profiling could be of value. In order to study this, we investigated the relationship between hormones and cardiac dimensions and function of both the right and left ventricle. METHODS: Twenty-three patients with newly diagnosed, untreated CHF were included. Right (RVEF) and left ventricular...

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

    Science.gov (United States)

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

    2016-01-01

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

  18. Evaluation of cardiac functions in patients with thalassemia major

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    Kucuk, N.O.; Aras, G.; Sipahi, T.; Ibis, E.; Akar, N.; Soylu, A.; Erbay, G. [Ankara Univ. (Turkey). Medical School

    1999-06-01

    It is known that a blood transfusion is necessary for survival in patients with thalassemia, but it may cause myocardial dysfunction due to myocardial siderosis as in other organs. The aim of this study was to evaluate myocardial perfusion by means of stress thallium scanning (MPS) and left ventricular functions by rest radionuclide ventriculography (RNV). Twenty-one patients at ages 9-16 (mean 12.1{+-}3.2) who have been diagnosed with thalassemia for 4-15 years mean 12.7{+-}4.8) were included in the study. They had blood transfusion 78-318 times (mean 162.1{+-}71). MPS and RNV was performed within two days after the any transfusion. MPS showed ischemia in 3 patients and normal perfusion in 18 patients. RNV revealed normal systolic parameters (wall motion, EF, PER, TPE) but diminished diastolic parameters (TPF, PFR) compared with normal values (p<0.05). We conclude that ischemia or fixed defects may be seen in stress MPS as results of cardiac involvement in patients with thalassemia. But, RNV is an important and preferable test for the early detection of subclinic cardiomyopathy. RNV may therefore show diastolic abnormalities before the systolic abnormalities show up. (author)

  19. Cardiac Function in 7-8-Year-Old Offspring of Women with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Maarten Rijpert

    2011-01-01

    Full Text Available Offspring of type 1 diabetic mothers (ODMs are at risk of short-term and long-term complications, such as neonatal macrosomia (birth weight >90th percentile, hypertrophic cardiomyopathy, and cardiovascular morbidity in later life. However, no studies have been performed regarding cardiac outcome. In this study, we investigated cardiac dimensions and function in 30 ODMs at 7-8 years of age in relation to neonatal macrosomia and maternal glycemic control during pregnancy and compared these with those in a control group of 30 children of nondiabetic women. We found that cardiac dimensions and systolic and diastolic function parameters in ODMs were comparable with those in controls. Neonatal macrosomia and poorer maternal glycemic control during pregnancy were not related to worse cardiac outcome in ODM. We conclude that cardiac function at 7-8 years of age in offspring of women with type 1 diabetes is reassuring and comparable with that in controls.

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

    Science.gov (United States)

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

    2016-12-01

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

  1. Functional and Hemodynamic Cardiac Determinants of Exercise Capacity in Patients With Systolic Heart Failure

    NARCIS (Netherlands)

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

    2012-01-01

    Decreased exercise capacity is the main symptom in patients with heart failure (HF). We assessed the association among noninvasively determined maximal cardiac output at exercise, systolic and diastolic cardiac functions at rest, and peak oxygen uptake (pVO(2)) exercise capacity in patients with con

  2. 24-Hour motor activity and autonomic cardiac functioning in major depressive disorder

    NARCIS (Netherlands)

    A.C. Volkers (Anita)

    2002-01-01

    textabstractThe studies of this thesis concern the spontaneous pattern of motor activity and autonomic cardiac functioning in major depressive disorder. The main purpose of the studies was to obtain insight in the psychomotor and autonomic cardiac dysfunction in depression by investigating the 24-ho

  3. Olmesartan attenuates cardiac hypertrophy and improves cardiac diastolic function in spontaneously hypertensive rats through inhibition of calcineurin pathway.

    Science.gov (United States)

    Fu, Mingqiang; Zhou, Jingmin; Xu, Jianfeng; Zhu, Hongmin; Liao, Jianquan; Cui, Xiaotong; Sun, Aijun; Fu, Michael; Zou, Yunzeng; Hu, Kai; Ge, Junbo

    2014-03-01

    To test whether olmesartan ameliorates cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs) through calcineurin pathway. Twenty-four male SHRs of 6 months were divided into saline- (n = 12) and olmesartan-treated (n = 12) groups. Age-matched WKY (n = 12) rats served as controls. Saline (10 mL·kg·d) or the same volume of olmesartan liquor (2.5 mg·kg·d) was administered by gavage for 3 months. Heart rate, systolic blood pressure, cardiac structure, and function and histological studies were determined. Expression of calcineurin and downstream NFAT3 were also detected. Compared with age-matched Wistar Kyoto rats, SHRs of 6 months exhibited evident cardiac hypertrophy and diastolic dysfunction as demonstrated by elevated systolic blood pressure and E/E', decreased E/A and E'/A', while F, left ventricular ejection fraction and fractional shortening remained unimpaired. Treatment with olmesartan significantly decreased systolic blood pressure and ventricular hypertrophy, attenuated fibrosis, and improved diastolic function (all P olmesartan group compared with the other 2 groups (both P olmesartan on cardiac structure and diastolic dysfunction, and it may be mediated through calcineurin pathway. This indicates a new therapeutic target for diastolic dysfunction.

  4. Critical role of transcription factor cyclic AMP response element modulator in beta1-adrenoceptor-mediated cardiac dysfunction.

    Science.gov (United States)

    Lewin, Geertje; Matus, Marek; Basu, Abhijit; Frebel, Karin; Rohsbach, Sebastian Pius; Safronenko, Andrej; Seidl, Matthias Dodo; Stümpel, Frank; Buchwalow, Igor; König, Simone; Engelhardt, Stefan; Lohse, Martin J; Schmitz, Wilhelm; Müller, Frank Ulrich

    2009-01-06

    Chronic stimulation of the beta(1)-adrenoceptor (beta(1)AR) plays a crucial role in the pathogenesis of heart failure; however, underlying mechanisms remain to be elucidated. The regulation by transcription factors cAMP response element-binding protein (CREB) and cyclic AMP response element modulator (CREM) represents a fundamental mechanism of cyclic AMP-dependent gene control possibly implicated in beta(1)AR-mediated cardiac deterioration. We studied the role of CREM in beta(1)AR-mediated cardiac effects, comparing transgenic mice with heart-directed expression of beta(1)AR in the absence and presence of functional CREM. CREM inactivation protected from cardiomyocyte hypertrophy, fibrosis, and left ventricular dysfunction in beta(1)AR-overexpressing mice. Transcriptome and proteome analysis revealed a set of predicted CREB/CREM target genes including the cardiac ryanodine receptor, tropomyosin 1alpha, and cardiac alpha-actin as altered on the mRNA or protein level along with the improved phenotype in CREM-deficient beta(1)AR-transgenic hearts. The results imply the regulation of genes by CREM as an important mechanism of beta(1)AR-induced cardiac damage in mice.

  5. Cardiac regeneration by pharmacologically active microcarriers releasing growth factors and/or transporting adipose-derived stem cells

    Directory of Open Access Journals (Sweden)

    Monia Savi

    2014-01-01

    Full Text Available We tested the hypothesis that cardiac regeneration through local delivery of adipose-derived stem cells (ASCs, activation of resident cardiac stem cells via growth factors (GFs [hepatocyte growth factor (HGF and insulin-like growth factor 1 (IGF-1:GFs] or both, are improved by pharmacologically active microcarriers (PAMs interacting with cells/molecules conveyed on their surface. Rats with one-month old myocardial infarction were treated with ASCs, ASCs+PAMs, GF-releasing PAMs, ASCs+GF-releasing PAMs or vehicle. Two weeks later, hemodynamic function and inducibility of ventricular arrhythmias (VAs were assessed. Eventually, the hearts were subjected to anatomical and immunohistochemical analyses. A significant ASCs engraftment and the largest improvement in cardiac mechanics occurred in ASC+GF-releasing PAM rats which by contrast were more vulnerable to VAs. Thus, PAMs may improve cell/GF-based cardiac regeneration although caution should be paid on the electrophysiological impact of their physical interaction with the myocardium.

  6. Pulmonary function and adverse cardiovascular outcomes: Can cardiac function explain the link?

    Science.gov (United States)

    Burroughs Peña, Melissa S; Dunning, Allison; Schulte, Phillip J; Durheim, Michael T; Kussin, Peter; Checkley, William; Velazquez, Eric J

    2016-12-01

    The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization. A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97). In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Risk Factors for Postoperative Encephalopathies in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    A. N. Shepelyuk

    2012-01-01

    Full Text Available Objective: to reveal risk factors for postoperative neurological complications (PONC during surgery under extracorporeal circulation (EC. Subjects and methods. Five hundred and forty-eight patients were operated on under EC. Multimodality monitoring was performed in all the patients. Pre-, intra-, and postoperative data were analyzed. Results. Two patient groups were identified. These were 1 59 patients with PONC and 2 489 patients without PONC. The patients with PONC were older than those without PONC (61.95±1.15 and 59±0.4 years and had a smaller body surface area (1.87±0.02 and 1.97±0.01 m2; in the PONC group, there were more women (37.3±6.4 and 22.1±1.9%. In Group 1, comorbidity was a significantly more common indication for surgery (33.9±6.22 and 9.2±1.29%. In this group, cerebral oxygenation (CO was significantly lower (64±1.41 and 69.9±0.38%. In the preoperative period, there were group differences in hemoglobin (Hb, total protein, creatinine, and urea (135±2.03; 142±0.71 g/l, 73±0.93; 74.9±0.3 mmol/l, 104.7±3.3; 96.3±1.06 mmol/l, 7.5±0.4; 6.5±0.1 mmol/l, respectively. The PONC group more frequently exhibited more than 50% internal carotid artery (ICA stenosis (28.8±5.95; 15.3± 1.63%; р<0.05, dyscirculatory encephalopathies (DEP (38.9±6.4 and 19.4±1.8%; р<0.05, CO, Hb, hematocrit, and oxygen delivery were lower in Group 1 at all stages. In the preperfusion period, cardiac index was lower in Group 1 (2.3±0.1 and 2.5±0.03 l/min/m2; р<0.01. In the postper-fusion period, blood pressure was lower in Group 1 (72.3±1.4 and 76.4±0.47 mm Hg; р=0.007 and higher rate was higher (92.65±1.5 and 88.16±0.49 min-1; р=0.007. Lower PCO2a was noted in Group 1. In this group, the patients were given epinephrine more frequently (33.9±6.2 and 20.5±1.8%; р<0.05 and in larger dosages (0.02±0.001 and 0.01±0.003 ^g/kg/min; р<0.05. Conclusion. The preoperative risk factors of CONC is female gender, lower body surface area

  8. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

    Directory of Open Access Journals (Sweden)

    Vinicius S Carreira

    Full Text Available The Developmental Origins of Health and Disease (DOHaD Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR, either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

  9. Factors influencing Neurodevelopment after Cardiac Surgery during Infancy

    Directory of Open Access Journals (Sweden)

    Hedwig Hubertine Hövels-Gürich

    2016-12-01

    function in adolescents have been found correlated with cognitive, motor and executive dysfunctions. Finally, family and environmental factors independently moderate against ND outcomes. In conclusion, the different mediating factors may exert independent effects on ND as well as interactive influences. Implications for the future comprise modifying clinical risk factors such as perioperative cerebral oxygen delivery, conducting brain MRI studies in correlation to ND outcomes, and extending psychosocial interventions leading to adequate resilience.

  10. Factors Influencing Neurodevelopment after Cardiac Surgery during Infancy

    Science.gov (United States)

    Hövels-Gürich, Hedwig Hubertine

    2016-01-01

    function in adolescents have been found correlated with cognitive, motor, and executive dysfunctions. Finally, family and environmental factors independently moderate against ND outcomes. In conclusion, the different mediating factors may exert independent effects on ND and interactive influences. Implications for the future comprise modifying clinical risk factors, such as perioperative cerebral oxygen delivery, conducting brain MRI studies in correlation to ND outcomes, and extending psychosocial interventions leading to adequate resilience. PMID:28018896

  11. Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression.

    Science.gov (United States)

    Byrne, Nikole J; Levasseur, Jody; Sung, Miranda M; Masson, Grant; Boisvenue, Jamie; Young, Martin E; Dyck, Jason R B

    2016-05-15

    Impaired cardiac substrate metabolism plays an important role in heart failure (HF) pathogenesis. Since many of these metabolic changes occur at the transcriptional level of metabolic enzymes, it is possible that this loss of metabolic flexibility is permanent and thus contributes to worsening cardiac function and/or prevents the full regression of HF upon treatment. However, despite the importance of cardiac energetics in HF, it remains unclear whether these metabolic changes can be normalized. In the current study, we investigated whether a reversal of an elevated aortic afterload in mice with severe HF would result in the recovery of cardiac function, substrate metabolism, and transcriptional reprogramming as well as determined the temporal relationship of these changes. Male C57Bl/6 mice were subjected to either Sham or transverse aortic constriction (TAC) surgery to induce HF. After HF development, mice with severe HF (% ejection fraction hypertrophy/HF were returned to values observed in healthy controls. Interestingly, pressure-overload-induced left ventricular hypertrophy (LVH) and cardiac substrate metabolism were restored at 1-week post-DB, which preceded functional recovery. The regression of severe HF is associated with early and dramatic improvements in cardiac energy metabolism and LVH normalization that precede restored cardiac function, suggesting that metabolic and structural improvements may be critical determinants for functional recovery. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Gianluca Pontone

    2015-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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. Connecting teratogen-induced congenital heart defects to neural crest cells and their effect on cardiac function.

    Science.gov (United States)

    Karunamuni, Ganga H; Ma, Pei; Gu, Shi; Rollins, Andrew M; Jenkins, Michael W; Watanabe, Michiko

    2014-09-01

    Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies.

  15. Hypertension is a conditional factor for the development of cardiac hypertrophy in type 2 diabetic mice.

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    Marc van Bilsen

    Full Text Available BACKGROUND: Type 2 diabetes is frequently associated with co-morbidities, including hypertension. Here we investigated if hypertension is a critical factor in myocardial remodeling and the development of cardiac dysfunction in type 2 diabetic db/db mice. METHODS: Thereto, 14-wks-old male db/db mice and non-diabetic db/+ mice received vehicle or angiotensin II (AngII for 4 wks to induce mild hypertension (n = 9-10 per group. Left ventricular (LV function was assessed by serial echocardiography and during a dobutamine stress test. LV tissue was subjected to molecular and (immunohistochemical analysis to assess effects on hypertrophy, fibrosis and inflammation. RESULTS: Vehicle-treated diabetic mice neither displayed marked myocardial structural remodeling nor cardiac dysfunction. AngII-treatment did not affect body weight and fasting glucose levels, and induced a comparable increase in blood pressure in diabetic and control mice. Nonetheless, AngII-induced LV hypertrophy was significantly more pronounced in diabetic than in control mice as assessed by LV mass (increase +51% and +34%, respectively, p<0.01 and cardiomyocyte size (+53% and +31%, p<0.001. This was associated with enhanced LV mRNA expression of markers of hypertrophy and fibrosis and reduced activation of AMP-activated protein kinase (AMPK, while accumulation of Advanced Glycation End products (AGEs and the expression levels of markers of inflammation were not altered. Moreover, AngII-treatment reduced LV fractional shortening and contractility in diabetic mice, but not in control mice. CONCLUSIONS: Collectively, the present findings indicate that type 2 diabetes in its early stage is not yet associated with adverse cardiac structural changes, but already renders the heart more susceptible to hypertension-induced hypertrophic remodeling.

  16. Stem cell factor gene transfer promotes cardiac repair after myocardial infarction via in situ recruitment and expansion of c-kit+ cells.

    Science.gov (United States)

    Yaniz-Galende, Elisa; Chen, Jiqiu; Chemaly, Elie; Liang, Lifan; Hulot, Jean-Sebastien; McCollum, LaTronya; Arias, Teresa; Fuster, Valentin; Zsebo, Krisztina M; Hajjar, Roger J

    2012-11-09

    There is growing evidence that the myocardium responds to injury by recruiting c-kit(+) cardiac progenitor cells to the damage tissue. Even though the ability of exogenously introducing c-kit(+) cells to injured myocardium has been established, the capability of recruiting these cells through modulation of local signaling pathways by gene transfer has not been tested. To determine whether stem cell factor gene transfer mediates cardiac regeneration in a rat myocardial infarction model, through survival and recruitment of c-kit(+) progenitors and cell-cycle activation in cardiomyocytes, and explore the mechanisms involved. Infarct size, cardiac function, cardiac progenitor cells recruitment, fibrosis, and cardiomyocyte cell-cycle activation were measured at different time points in controls (n=10) and upon stem cell factor gene transfer (n=13) after myocardial infarction. We found a regenerative response because of stem cell factor overexpression characterized by an enhancement in cardiac hemodynamic function: an improvement in survival; a reduction in fibrosis, infarct size and apoptosis; an increase in cardiac c-kit(+) progenitor cells recruitment to the injured area; an increase in cardiomyocyte cell-cycle activation; and Wnt/β-catenin pathway induction. Stem cell factor gene transfer induces c-kit(+) stem/progenitor cell expansion in situ and cardiomyocyte proliferation, which may represent a new therapeutic strategy to reverse adverse remodeling after myocardial infarction.

  17. Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Jarfelt, Marianne; Andersen, Niels Holmark; Glosli, Heidi

    2015-01-01

    OBJECTIVES: We report cardiac function of patients treated for Childhood acute myeloid leukemia with chemotherapy only according to three consecutive Nordic protocols. METHODS: Ninety-eight of 138 eligible patients accepted examination with standardized echocardiography. Results were compared...

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

    NARCIS (Netherlands)

    Aengevaeren, V.L.; Claassen, J.A.H.R.; Levine, B.D.; Zhang, R.

    2013-01-01

    Cerebral blood flow (CBF) is stably maintained through the combined effects of blood pressure (BP) regulation and cerebral autoregulation. Previous studies suggest that aerobic exercise training improves cardiac baroreflex function and beneficially affects BP regulation, but may negatively affect ce

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

    Science.gov (United States)

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

    2016-06-01

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

  20. Amitraz and its metabolite modulate honey bee cardiac function and tolerance to viral infection.

    Science.gov (United States)

    O'Neal, Scott T; Brewster, Carlyle C; Bloomquist, Jeffrey R; Anderson, Troy D

    2017-10-01

    The health and survival of managed honey bee (Apis mellifera) colonies are affected by multiple factors, one of the most important being the interaction between viral pathogens and infestations of the ectoparasitic mite Varroa destructor. Currently, the only effective strategy available for mitigating the impact of viral infections is the chemical control of mite populations. Unfortunately, the use of in-hive acaricides comes at a price, as they can produce sublethal effects that are difficult to quantify, but may ultimately be as damaging as the mites they are used to treat. The goal of this study was to investigate the physiological and immunological effects of the formamidine acaricide amitraz and its primary metabolite in honey bees. Using flock house virus as a model for viral infection, this study found that exposure to a formamidine acaricide may have a negative impact on the ability of honey bees to tolerate viral infection. Furthermore, this work has demonstrated that amitraz and its metabolite significantly alter honey bee cardiac function, most likely through interaction with octopamine receptors. The results suggest a potential drawback to the in-hive use of amitraz and raise intriguing questions about the relationship between insect cardiac function and disease tolerance. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-12-17

    BACKGROUND This study aimed to decrease leukocytes counts by hydroxyurea (Hu) in an acute myocardial infarction (AMI) rat model and examine its effect on the inflammatory response of myocardial infarction and cardiac functions. MATERIAL AND METHODS AMI was successfully caused in 36 rats, and 12 control rats received sham operation. Rats in the AMI group were then randomly divided into Hu and vehicle group with 18 rats each. Rats in the Hu AMI group received Hu (200 mg/kg) intragastrically while vehicle AMI group received saline. Leukocytes counts, cardiac functions, myocardial tissue morphology, and levels of soluble intercellular adhesion molecule-1 (sICAM), P-selectin and platelet activating factor (PAF) were measured and compared among the three groups four weeks after AMI induction. RESULTS Leukocytes, neutrophils, and leukomonocyte counts in vehicle AMI rats were significantly higher than that of the normal control group (pEchocardiography analysis showed that Hu treatment increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) compared to that of vehicle AMI group (prats.

  2. EFFECT OF OBESITY ON CARDIAC FUNCTION IN CHILDREN AND ADOLESCENTS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Thomas W. Rowland

    2007-09-01

    Full Text Available 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

  3. Action potential duration heterogeneity of cardiac tissue can be evaluated from cell properties using Gaussian Green's function approach.

    Directory of Open Access Journals (Sweden)

    Arne Defauw

    Full Text Available Action potential duration (APD heterogeneity of cardiac tissue is one of the most important factors underlying initiation of deadly cardiac arrhythmias. In many cases such heterogeneity can be measured at tissue level only, while it originates from differences between the individual cardiac cells. The extent of heterogeneity at tissue and single cell level can differ substantially and in many cases it is important to know the relation between them. Here we study effects from cell coupling on APD heterogeneity in cardiac tissue in numerical simulations using the ionic TP06 model for human cardiac tissue. We show that the effect of cell coupling on APD heterogeneity can be described mathematically using a Gaussian Green's function approach. This relates the problem of electrotonic interactions to a wide range of classical problems in physics, chemistry and biology, for which robust methods exist. We show that, both for determining effects of tissue heterogeneity from cell heterogeneity (forward problem as well as for determining cell properties from tissue level measurements (inverse problem, this approach is promising. We illustrate the solution of the forward and inverse problem on several examples of 1D and 2D systems.

  4. Effects of Long-term Right Ventricular Apical Pacing on Left Ventricular Remodeling and Cardiac Function

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective: To investigate the impacts of long-term right ventricular apical pacing on the ventricular remodeling and cardiac functions of patients with high-grade and third-degree atrioventricular blockage with normal heart structures and cardiac functions. In addition, we provide many evidences for choosing an optimal electrode implantation site.Methods: Study participants included patients who were admitted for pacemaker replacements and revisited for examinations of implanted pacemakers at outpatient. Pa...

  5. Echocardiographic Evaluation of Cardiac Function in Ischemic Rats: Value of M-Mode Echocardiography

    OpenAIRE

    Darbandi Azar, Amir; Tavakoli, Fatemeh; Moladoust, Hassan; Zare, Asghar; Sadeghpour, Anita

    2014-01-01

    Background: Echocardiography is a well-established diagnostic tool for a safe, reproducible and accurate evaluation of cardiac anatomy, hemodynamics and function in clinical practice. Objectives: We sought to demonstrate the efficacy and feasibility of M-mode echocardiography to evaluate cardiac structure and function in normal and MI-induced adult rats. Materials and Methods: All animal procedures were approved by the ethics committee of Tehran University of Medical Sciences and the investig...

  6. Erythropoietin protects myocardin-expressing cardiac stem cells against cytotoxicity of tumor necrosis factor-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Madonna, Rosalinda [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); Institute of Cardiology, and Center of Excellence on Aging, ' G. d' Annunzio' University, Chieti (Italy); Shelat, Harnath; Xue, Qun; Willerson, James T. [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); The Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, Texas (United States); De Caterina, Raffaele [Institute of Cardiology, and Center of Excellence on Aging, ' G. d' Annunzio' University, Chieti (Italy); Geng, Yong-Jian, E-mail: yong-jian.geng@uth.tmc.edu [The Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Texas (United States); The Texas Heart Institute at St. Luke' s Episcopal Hospital, Houston, Texas (United States)

    2009-10-15

    Cardiac stem cells are vulnerable to inflammation caused by infarction or ischemic injury. The growth factor, erythropoietin (Epo), ameliorates the inflammatory response of the myocardium to ischemic injury. This study was designed to assess the role of Epo in regulation of expression and activation of the cell death-associated intracellular signaling components in cardiac myoblasts stimulated with the proinflammatory cytokine tumor necrosis factor (TNF)-{alpha}. Cardiac myoblasts isolated from canine embryonic hearts characterized by expression of myocardin A, a promyogenic transcription factor for cardiovascular muscle development were pretreated with Epo and then exposed to TNF-{alpha}. Compared to untreated cells, the Epo-treated cardiac myoblasts exhibited better morphology and viability. Immunoblotting revealed lower levels of active caspase-3 and reductions in iNOS expression and NO production in Epo-treated cells. Furthermore, Epo pretreatment reduced nuclear translocation of NF-{kappa}B and inhibited phosphorylation of inhibitor of kappa B (I{kappa}B) in TNF-{alpha}-stimulated cardiac myoblasts. Thus, Epo protects cardiac myocyte progenitors or myoblasts against the cytotoxic effects of TNF-{alpha} by inhibiting NF-{kappa}B-mediated iNOS expression and NO production and by preventing caspase-3 activation.

  7. Risk factors for decreased cardiac output after coronary artery bypass grafting: a prospective cohort study.

    Science.gov (United States)

    Dos Santos, Eduarda Ribeiro; Lopes, Camila Takao; Maria, Vera Lucia Regina; de Barros, Alba Lucia Bottura Leite

    2017-04-01

    No previous study has investigated the predictive risk factors of the nursing diagnosis of risk for decreased cardiac output after coronary artery bypass grafting (CABG). This study aimed to identify the predictive risk factors of the nursing diagnosis of risk for decreased cardiac output after CABG. This was a prospective cohort study performed at a cardiac university hospital in São Paulo, Brazil and 257 adult patients undergoing CABG were included. Potential risk factors for low cardiac output in the immediate post-operative period were investigated using the patients' medical records. Univariate analysis and logistic regression were used to identify the predictive risk factors of decreased cardiac output. The area under the receiver operating characteristic curve was calculated as a measure of accuracy. The variables that could not be analysed through logistic regression were analysed through Fisher's exact test. One hundred and ninety-five patients had low cardiac output in the immediate post-operative period. The predictive risk factors included age ⩾60 years, decreased left ventricle ejection fraction, not using the radial artery graft, positive fluid balance and post-operative arrhythmia that differed from the pre-operative arrhythmia. This model predicted the outcome with a sensitivity of 62.9%, a specificity of 87.2% and an accuracy of 81.5%. The variables analysed through Fisher's exact test included heart failure, re-exploration and bleeding-related re-exploration. The predictive risk factors for the nursing diagnosis of risk for decreased cardiac output after CABG were found. These results can be used to direct nurses in patient monitoring, staff training and nursing team staffing.

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

    Science.gov (United States)

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

    2015-01-01

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

  9. Comparative Toxicity of Different Crude Oils on the Cardiac Function of Marine Medaka (Oryzias melastigma Embryo

    Directory of Open Access Journals (Sweden)

    Zhendong Zhang

    2014-12-01

    Full Text Available The acute toxic effect of different crude oils (heavy crude oil and bonny light crude oil on embryos of marine medaka Oryzias melastigma was measured and evaluated by exposure to the water-accommodated fraction (WAF in the present study. The cardiac function of medaka embryos was used as target organ of ecotoxicological effect induced by oil exposure. Results showed that the developing marine medaka heart was a sensitive target organ to crude oil exposure the heavy crude oil WAF was more toxic to cardiac function of medaka embryos than bonny light cured oil one. Cardiac function of medaka embryos was clearly affected by exposure to heavy crude oil WAF after 24 hours exposure and showed a dose-dependent slowing of heart rate. Furthermore, swelled and enlarged heart morphology, lowered blood circulation and accumulation of blood cells around the heart area were found. However, the toxic effect of bonny light crude oil on cardiac function of medaka embryos was comparatively low. Statistical results showed that the cardiac function was only affected by highest bonny light crude oil WAF (9.8 mg/L exposure treatment. These findings indicated that cardiac function of marine medaka embryo was a good toxicity model for oil pollution and could be used to compare and evaluate the toxicity of different crude oils. The heart rate was an appropriate endpoint in the acute toxicity test.

  10. Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia inducible factor-lα in rats.

    Science.gov (United States)

    Zhu, Zeng-Yan; Gao, Tian; Huang, Yan; Xue, Jie; Xie, Mei-Lin

    2016-04-01

    Apigenin is a natural flavonoid compound that can inhibit hypoxia-inducible factor (HIF)-1α expression in cultured tumor cells under hypoxic conditions. Hypertension-induced cardiac hypertrophy is always accompanied by abnormal myocardial glucolipid metabolism due to an increase of HIF-1α. However, whether or not apigenin may ameliorate the cardiac hypertrophy and abnormal myocardial glucolipid metabolism remains unknown. This study aimed to examine the effects of apigenin. Rats with cardiac hypertrophy induced by renovascular hypertension were treated with apigenin 50-100 mg kg(-1) (the doses can be achieved by pharmacological or dietary supplementation for an adult person) by gavage for 4 weeks. The results showed that after treatment with apigenin, the blood pressure, heart weight, heart weight index, cardiomyocyte cross-sectional area, serum angiotensin II, and serum and myocardial free fatty acids were reduced. It is important to note that apigenin decreased the expression level of myocardial HIF-1α protein. Moreover, apigenin simultaneously increased the expression levels of myocardial peroxisome proliferator-activated receptor (PPAR) α, carnitine palmitoyltransferase (CPT)-1, and pyruvate dehydrogenase kinase (PDK)-4 proteins and decreased the expression levels of myocardial PPARγ, glycerol-3-phosphate acyltransferase genes (GPAT), and glucose transporter (GLUT)-4 proteins. These findings demonstrated that apigenin could improve hypertensive cardiac hypertrophy and abnormal myocardial glucolipid metabolism in rats, and its mechanisms might be associated with the down-regulation of myocardial HIF-1α expression and, subsequently increasing the expressions of myocardial PPARα and its target genes CPT-1 and PDK-4, and decreasing the expressions of myocardial PPARγ and its target genes GPAT and GLUT-4.

  11. Evaluation of Resting Cardiac Power Output as a Prognostic Factor in Patients with Advanced Heart Failure.

    Science.gov (United States)

    Yildiz, Omer; Aslan, Gamze; Demirozu, Zumrut T; Yenigun, Cemal Deniz; Yazicioglu, Nuran

    2017-09-15

    If the heart is represented by a hydraulic pump, cardiac power represents the hydraulic function of the heart. Cardiac pump function is frequently determined through left ventricular ejection fraction using imaging. This study aims to validate resting cardiac power output (CPO) as a predictive biomarker in patients with advanced heart failure (HF). One hundred and seventy-two patients with HF severe enough to warrant cardiac transplantation were retrospectively reviewed at a single tertiary care institution between September 2010 and July 2013. Patients were initially evaluated with simultaneous right-sided and left-sided cardiac catheter-based hemodynamic measurements, followed by longitudinal follow-up (median of 52 months) for adverse events (cardiac mortality, cardiac transplantation, or ventricular assist device placement). Median resting CPO was 0.54 W (long rank chi-square = 33.6; p < 0.0001). Decreased resting CPO (<0.54 W) predicted increased risk for adverse outcomes. Fifty cardiac deaths, 10 cardiac transplants, and 12 ventricular assist device placements were documented. The prognostic relevance of resting CPO remained significant after adjustment for age, gender, left ventricular ejection fraction, mean arterial pressure, pulmonary vascular resistance, right atrial pressure, and estimated glomerular filtration rate (HR, 3.53; 95% confidence interval, 1.66 to 6.77; p = 0.0007). In conclusion, lower resting CPO supplies independent prediction of adverse outcomes. Thus, it could be effectively used for risk stratification in patients with advanced HF. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Near death experiences, cognitive function and psychological outcomes of surviving cardiac arrest.

    Science.gov (United States)

    Parnia, S; Spearpoint, K; Fenwick, P B

    2007-08-01

    Cardiac arrest is associated with a number of cognitive processes as well as long term psychological outcomes. Recent studies have indicated that approximately 10-20% of cardiac arrest survivors report cognitive processes, including the ability to recall specific details of their resuscitation from the period of cardiac arrest. In addition it has been demonstrated that these cognitive processes are consistent with the previously described near death experience and that those who have these experiences are left with long term positive life enhancing effects. There have also been numerous studies that have indicated that although the quality of life for cardiac arrest survivors is generally good, some are left with long term cognitive impairments as well as psychological sequelae such as post-traumatic stress disorder. This paper will review near death experiences, cognitive function and psychological outcomes in survivors of cardiac arrest.

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

    Science.gov (United States)

    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.

  14. FOXO3a regulates BNIP3 and modulates mitochondrial calcium, dynamics, and function in cardiac stress.

    Science.gov (United States)

    Chaanine, Antoine H; Kohlbrenner, Erik; Gamb, Scott I; Guenzel, Adam J; Klaus, Katherine; Fayyaz, Ahmed U; Nair, K Sreekumaran; Hajjar, Roger J; Redfield, Margaret M

    2016-12-01

    The forkhead box O3a (FOXO3a) transcription factor has been shown to regulate glucose metabolism, muscle atrophy, and cell death in postmitotic cells. Its role in regulation of mitochondrial and myocardial function is not well studied. Based on previous work, we hypothesized that FOXO3a, through BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3), modulates mitochondrial morphology and function in heart failure (HF). We modulated the FOXO3a-BNIP3 pathway in normal and phenylephrine (PE)-stressed adult cardiomyocytes (ACM) in vitro and developed a cardiotropic adeno-associated virus serotype 9 encoding dominant-negative FOXO3a (AAV9.dn-FX3a) for gene delivery in a rat model of HF with preserved ejection fraction (HFpEF). We found that FOXO3a upregulates BNIP3 expression in normal and PE-stressed ACM, with subsequent increases in mitochondrial Ca(2+), leading to decreased mitochondrial membrane potential, mitochondrial fragmentation, and apoptosis. Whereas dn-FX3a attenuated the increase in BNIP3 expression and its consequences in PE-stressed ACM, AAV9.dn-FX3a delivery in an experimental model of HFpEF decreased BNIP3 expression, reversed adverse left ventricular remodeling, and improved left ventricular systolic and, particularly, diastolic function, with improvements in mitochondrial structure and function. Moreover, AAV9.dn-FX3a restored phospholamban phosphorylation at S16 and enhanced dynamin-related protein 1 phosphorylation at S637. Furthermore, FOXO3a upregulates maladaptive genes involved in mitochondrial apoptosis, autophagy, and cardiac atrophy. We conclude that FOXO3a activation in cardiac stress is maladaptive, in that it modulates Ca(2+) cycling, Ca(2+) homeostasis, and mitochondrial dynamics and function. Our results suggest an important role of FOXO3a in HF, making it an attractive potential therapeutic target. Copyright © 2016 the American Physiological Society.

  15. 青年急性心肌梗死患者危险因素、冠脉造影及心功能特点分析%Analysis of characteristics of risk factors, coronary angiography and car-diac functions in young patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    颜翠萍; 宿海峰

    2015-01-01

    Objective To investigate the characteristics of risk factors, coronary angiography (CAG) and cardiac func tions in young patients with acute myocardial infarction (AMI). Methods A total of 37 cases of young patients with acute myocardial infarction were chosen, and 41 cases of middle-aged and aged patients with acute myocardial infarction who were admitted in our hospital in the same period were chosen. The differences of risk factors, infarction position, coro-nary angiography infarction and heart functions between the youth group and the middle-aged and aged group were analyzed. Results Males accounted for 92.1%in the young group. Smoking, family history of coronary heart disease and high triglycerides (TG) were independent risk factors for the youth group. Coronary artery disease of the youth group compared with that of the middle-aged and aged group was mainly characterized by a single branch disease (55.3%), and that of the middle-aged and aged group was mainly characterized by triple vessel lesions (43.9%). And infarct-re lated artery anterior in the youth group occurred mainly in the descending branch (71.7%). It was found that cardiac functions of the middle-aged and aged group were better than those of the youth group by cardiac angiography (P<0.05). Conclusion Acute myocardial infarction in youth group mainly occurs in men with several risk factors and coronary an-giography single vessel disease is more common by coronary angiography with no significant change in cardiac structure and functions. Strengthening the MI education, early detection and intervention may improve prognosis.%目的:探讨青年急性心肌梗死(AMI)患者的危险因素、冠脉造影(CAG)、心功能特点。方法选取青年急性心肌梗死患者37例,同期入院的中老年急性心肌梗死41例,分析青年组危险因素、梗死部位、冠脉造影、心功能情况与老年组的差异。结果青年组以男性为主(92.1%),吸烟、冠心病家族史、高

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

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    Guo, Hai-dong [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Cui, Guo-hong; Yang, Jia-jun [Department of Neurology, Shanghai No. 6 People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233 (China); Wang, Cun [Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 (China); Zhu, Jing; Zhang, Li-sheng; Jiang, Jun [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Shao, Shui-jin, E-mail: shaoshuijin@163.com [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China)

    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.

  17. Kruppel-like factor 2 is required for normal mouse cardiac development.

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    Aditi R Chiplunkar

    Full Text Available Krüppel-like factor 2 (KLF2 is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5 in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2-/- embryos die earlier, by E11.5. E9.5 FVB/N KLF2-/- hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By E10.5, traditional and endothelial-specific FVB/N KLF2-/- AV cushions are hypocellular, suggesting that the cells accumulating at the AV canal have a defect in endothelial to mesenchymal transformation (EMT. E10.5 FVB/N KLF2-/- hearts have reduced glycosaminoglycans in the cardiac jelly, correlating with the reduced EMT. However, the number of mesenchymal cells migrating from FVB/N KLF2-/- AV explants into a collagen matrix is reduced considerably compared to wild-type, suggesting that the EMT defect is not due solely to abnormal cardiac jelly. Echocardiography of E10.5 FVB/N KLF2-/- embryos indicates that they have abnormal heart function compared to wild-type. E10.5 C57BL/6 KLF2-/- hearts have largely normal AV cushions. However, E10.5 FVB/N and C57BL/6 KLF2-/- embryos have a delay in the formation of the atrial septum that is not observed in a defined mixed background. KLF2 ablation results in reduced Sox9, UDP-glucose dehydrogenase (Ugdh, Gata4 and Tbx5 mRNA in FVB/N AV canals. KLF2 binds to the Gata4, Tbx5 and Ugdh promoters in chromatin immunoprecipitation assays, indicating that KLF2 could directly regulate these genes. In conclusion, KLF2-/- heart phenotypes are genetic background-dependent. KLF2 plays a role in EMT through its regulation of important cardiovascular genes.

  18. Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

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    Mihai Onofriescu

    .67, 95%CI = 2.29-5.89 for RFO >17.4% and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4% Cox regression analysis.The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

  19. Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice

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    Zuheng Liu

    2017-09-01

    Full Text Available Physical exercise is commonly regarded as protective against cardiovascular disease (CVD. Recent studies have reported that exercise alters the gut microbiota and that modification of the gut microbiota can influence cardiac function. Here, we focused on the relationships among exercise, the gut microbiota and cardiac function after myocardial infarction (MI. Four-week-old C57BL/6J mice were exercised on a treadmill for 4 weeks before undergoing left coronary artery ligation. Cardiac function was assessed using echocardiography. Gut microbiomes were evaluated post-exercise and post-MI using 16S rRNA gene sequencing on an Illumina HiSeq platform. Exercise training inhibited declines in cardiac output and stroke volume in post-MI mice. In addition, physical exercise and MI led to alterations in gut microbial composition. Exercise training increased the relative abundance of Butyricimonas and Akkermansia. Additionally, key operational taxonomic units were identified, including 24 lineages (mainly from Bacteroidetes, Barnesiella, Helicobacter, Parabacteroides, Porphyromonadaceae, Ruminococcaceae, and Ureaplasma that were closely related to exercise and cardiac function. These results suggested that exercise training improved cardiac function to some extent in addition to altering the gut microbiota; therefore, they could provide new insights into the use of exercise training for the treatment of CVD.

  20. Exogenous nerve growth factor supplementation elevates myocardial immunoreactivity and attenuates cardiac remodeling in pressure-overload rats

    Institute of Scientific and Technical Information of China (English)

    Bing He; and Yuming Li; Fan Ye; Xin Zhou; He Li; Xiaoqing Xun; Xiaoqing Ma; Xudong Liu; Zhihong Wang; Pengxiao Xu

    2012-01-01

    It is postulated that supplementation of exogenous nerve growth factor (NGF) might mediate improvement of the cardiac sympathetic nerve function in heart failure (HF).Local intramuscular injection of NGF near the cardiac sympathetic ganglia could influence the innervation pattern,norepinephrine transporter (NET) gene expression,and improve the cardiac remodeling in experimental HF animals.In this study,we injected NGF into the scalenus medius muscles of Sprague-Dawley rats with abdominal aortic constriction (AC).The nerve innervated pattern,left ventricular morphology,and function following injection in rats with AC were investigated respectively by immunohistochemistry and echocardiography.Levels of mRNA expression of NET,growth associated protein 43 (GAP 43),NGF and its receptors TrkA and p75NTR,and brain natriuretic peptide (BNP) were measured by realtime polymerase chain reaction.The results showed that myocardial NGF mRNA levels were comparable in rats with AC.Short-term supplementation of exogenous NGF raised the myocardial NGF immunoreactivity,but did not cause hyperinnervation and NET mRNA upregulation in the AC rats.Furthermore,myocardial TrkA mRNA was found to be remarkably decreased and p75NTR mRNA was increased.Myocardial TrkA downregulation may play a beneficial effect for avoiding the hyperinnervation,and it is reasonable to postulate that p75NTR can function as an NGF receptor in the absence of TrkA.Interestingly,local NGF administration into the neck muscles near the ganglia could attenuate cardiac remodeling and downregulate BNP mRNA.These results suggest that exogenous NGF can reach the target tissue along the axons anterogradely,and improve the cardiac remodeling.

  1. Acute improvement of cardiac function with intravenous L-propionylcarnitine in humans.

    Science.gov (United States)

    Bartels, G L; Remme, W J; Pillay, M; Schönfeld, D H; Cox, P H; Kruijssen, H A; Knufman, N M

    1992-07-01

    As the myocardial carnitine content, a key control factor in myocardial oxidative metabolism and energy transfer, is reduced in heart failure, administration of L-propionylcarnitine (LPC), a potent analogue of L-carnitine, potentially may improve cardiac function, possibly through a positive inotropic effect. As its hemodynamic profile is unknown in humans, 32 fasting normotensive patients with coronary artery disease received either 15 mg/kg of LPC (n = 16) or vehicle (mannitol/acetate, n = 16) infused over 5 min. Hemodynamic, radionuclide [peak ejection and filling rates (PER and PFR, respectively)], and metabolic variables (myocardial O2, lactate, and carnitine uptake) were studied at baseline and 1, 3, 5, 10, 15, and 45 min postdrug. The baseline ejection fraction was depressed in LPC patients (40 +/- 3% vs. 48 +/- 4% in the vehicle group, p less than 0.05) as a result of a significant high incidence of previous infarctions. Immediately following LPC, the cardiac total carnitine uptake changed from 102 +/- 181 to 5,335 +/- 1,761 mumol/L (p less than 0.05). In both groups, left ventricular systolic and end-diastolic pressures increased significantly by 5 and 20%, respectively, during the first 5 min. In the vehicle group, contractility decreased by 5%, accompanied by a significant 11% fall in the stroke volume. In contrast, following LPC, isovolumetric contractility indices remained unaltered. Instead, both the PER and PFR improved by 16% at 45 min. Moreover, the cardiac output increased by 8%. LPC did not affect systemic or coronary hemodynamics. Lactate uptake increased by 42%, but myocardial O2 consumption did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Type III Transforming Growth Factor-β Receptor Drives Cardiac Hypertrophy Through β-Arrestin2-Dependent Activation of Calmodulin-Dependent Protein Kinase II.

    Science.gov (United States)

    Lou, Jie; Zhao, Dan; Zhang, Ling-Ling; Song, Shu-Ying; Li, Yan-Chao; Sun, Fei; Ding, Xiao-Qing; Yu, Chang-Jiang; Li, Yuan-Yuan; Liu, Mei-Tong; Dong, Chang-Jiang; Ji, Yong; Li, Hongliang; Chu, Wenfeng; Zhang, Zhi-Ren

    2016-09-01

    The role of type III transforming growth factor-β receptor (TβRIII) in the pathogenesis of heart diseases remains largely unclear. Here, we investigated the functional role and molecular mechanisms of TβRIII in the development of myocardial hypertrophy. Western blot and quantitative real time-polymerase chain reaction analyses revealed that the expression of TβRIII was significantly elevated in human cardiac hypertrophic samples. Consistently, TβRIII expression was substantially increased in transverse aortic constriction (TAC)- and isoproterenol-induced mouse cardiac hypertrophy in vivo and in isoproterenol-induced cardiomyocyte hypertrophy in vitro. Overexpression of TβRIII resulted in cardiomyocyte hypertrophy, whereas isoproterenol-induced cardiomyocyte hypertrophy was greatly attenuated by knockdown of TβRIII in vitro. Cardiac-specific transgenic expression of TβRIII independently led to cardiac hypertrophy in mice, which was further aggravated by isoproterenol and TAC treatment. Cardiac contractile function of the mice was not altered in TβRIII transgenic mice; however, TAC led to significantly decreased cardiac contractile function in TβRIII transgenic mice compared with control mice. Conversely, isoproterenol- and TAC-induced cardiac hypertrophy and TAC-induced cardiac contractile function impairment were partially reversed by suppression of TβRIII in vivo. Our data suggest that TβRIII mediates stress-induced cardiac hypertrophy through activation of Ca(2+)/calmodulin-dependent protein kinase II, which requires a physical interaction of β-arrestin2 with both TβRIII and calmodulin-dependent protein kinase II. Our findings indicate that stress-induced increase in TβRIII expression results in cardiac hypertrophy through β-arrestin2-dependent activation of calmodulin-dependent protein kinase II and that transforming growth factor-β and β-adrenergic receptor signaling are not involved in spontaneous cardiac hypertrophy in cardiac

  3. Risk factors for transient dysfunction of gas exchange after cardiac surgery

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    Cristiane Delgado Alves Rodrigues

    2015-02-01

    Full Text Available Objective: A retrospective cohort study was preformed aiming to verify the presence of transient dysfunction of gas exchange in the postoperative period of cardiac surgery and determine if this disorder is linked to cardiorespiratory events. Methods: We included 942 consecutive patients undergoing cardiac surgery and cardiac procedures who were referred to the Intensive Care Unit between June 2007 and November 2011. Results: Fifteen patients had acute respiratory distress syndrome (2%, 199 (27.75% had mild transient dysfunction of gas exchange, 402 (56.1% had moderate transient dysfunction of gas exchange, and 39 (5.4% had severe transient dysfunction of gas exchange. Hypertension and cardiogenic shock were associated with the emergence of moderate transient dysfunction of gas exchange postoperatively (P=0.02 and P=0.019, respectively and were risk factors for this dysfunction (P=0.0023 and P=0.0017, respectively. Diabetes mellitus was also a risk factor for transient dysfunction of gas exchange (P=0.03. Pneumonia was present in 8.9% of cases and correlated with the presence of moderate transient dysfunction of gas exchange (P=0.001. Severe transient dysfunction of gas exchange was associated with patients who had renal replacement therapy (P=0.0005, hemotherapy (P=0.0001, enteral nutrition (P=0.0012, or cardiac arrhythmia (P=0.0451. Conclusion: Preoperative hypertension and cardiogenic shock were associated with the occurrence of postoperative transient dysfunction of gas exchange. The preoperative risk factors included hypertension, cardiogenic shock, and diabetes. Postoperatively, pneumonia, ventilator-associated pneumonia, renal replacement therapy, hemotherapy, and cardiac arrhythmia were associated with the appearance of some degree of transient dysfunction of gas exchange, which was a risk factor for reintubation, pneumonia, ventilator-associated pneumonia, and renal replacement therapy in the postoperative period of cardiac surgery and

  4. Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction.

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    Kazuaki Nakajima

    Full Text Available Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×10(6 or 1x10(6 cells were transplanted with GH (10 mg/ml to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS, only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×10(6 CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05, only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05. Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01 and angiogenesis was significantly enhanced (p<0.05 in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05. Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH

  5. Endurance training prevents negative effects of the hypoxia mimetic dimethyloxalylglycine on cardiac and skeletal muscle function.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  7. Cardiac function and rejection following transplantation of the heart

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Cardiac deficiency of single cytochrome oxidase assembly factor scox induces p53-dependent apoptosis in a Drosophila cardiomyopathy model

    Science.gov (United States)

    Martínez-Morentin, Leticia; Martínez, Lidia; Piloto, Sarah; Yang, Hua; Schon, Eric A.; Garesse, Rafael; Bodmer, Rolf; Ocorr, Karen; Cervera, Margarita; Arredondo, Juan J.

    2015-01-01

    The heart is a muscle with high energy demands. Hence, most patients with mitochondrial disease produced by defects in the oxidative phosphorylation (OXPHOS) system are susceptible to cardiac involvement. The presentation of mitochondrial cardiomyopathy includes hypertrophic, dilated and left ventricular noncompaction, but the molecular mechanisms involved in cardiac impairment are unknown. One of the most frequent OXPHOS defects in humans frequently associated with cardiomyopathy is cytochrome c oxidase (COX) deficiency caused by mutations in COX assembly factors such as Sco1 and Sco2. To investigate the molecular mechanisms that underlie the cardiomyopathy associated with Sco deficiency, we have heart specifically interfered scox expression, the single Drosophila Sco orthologue. Cardiac-specific knockdown of scox reduces fly lifespan, and it severely compromises heart function and structure, producing dilated cardiomyopathy. Cardiomyocytes with low levels of scox have a significant reduction in COX activity and they undergo a metabolic switch from OXPHOS to glycolysis, mimicking the clinical features found in patients harbouring Sco mutations. The major cardiac defects observed are produced by a significant increase in apoptosis, which is dp53-dependent. Genetic and molecular evidence strongly suggest that dp53 is directly involved in the development of the cardiomyopathy induced by scox deficiency. Remarkably, apoptosis is enhanced in the muscle and liver of Sco2 knock-out mice, clearly suggesting that cell death is a key feature of the COX deficiencies produced by mutations in Sco genes in humans. PMID:25792727

  9. Tissue Factor Structure and Function

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    Saulius Butenas

    2012-01-01

    Full Text Available Tissue factor (TF is an integral membrane protein that is essential to life. It is a component of the factor VIIa-TF complex enzyme and plays a primary role in both normal hemostasis and thrombosis. With a vascular injury, TF becomes exposed to blood and binds plasma factor VIIa, and the resulting complex initiates a series of enzymatic reactions leading to clot formation and vascular sealing. Many cells, both healthy, and tumor cells, produce detectable amounts of TF, especially when they are stimulated by various agents. Despite the relative simplicity and small size of TF, there are numerous contradictory reports about the synthesis and presentation of TF on blood cells and circulation in normal blood either on microparticles or as a soluble protein. Another subject of controversy is related to the structure/function of TF. It has been almost commonly accepted that cell-surface-associated TF has low (if any activity, that is, is “encrypted” and requires specific conditions/reagents to become active, that is, “decrypted.” However there is a lack of agreement related to the mechanism and processes leading to alterations in TF function. In this paper TF structure, presentation, and function, and controversies concerning these features are discussed.

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

    Science.gov (United States)

    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.

  11. Transcutaneous cervical vagal nerve stimulation modulates cardiac vagal tone and tumor necrosis factor-alpha.

    Science.gov (United States)

    Brock, C; Brock, B; Aziz, Q; Møller, H J; Pfeiffer Jensen, M; Drewes, A M; Farmer, A D

    2016-12-12

    The vagus nerve is a central component of cholinergic anti-inflammatory pathways. We sought to evaluate the effect of bilateral transcutaneous cervical vagal nerve stimulation (t-VNS) on validated parameters of autonomic tone and cytokines in 20 healthy subjects. 24 hours after t-VNS, there was an increase in cardiac vagal tone and a reduction in tumor necrosis factor-α in comparison to baseline. No change was seen in blood pressure, cardiac sympathetic index or other cytokines. These preliminary data suggest that t-VNS exerts an autonomic and a subtle antitumor necrosis factor-α effect, which warrants further evaluation in larger controlled studies.

  12. Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function.

    Directory of Open Access Journals (Sweden)

    Armand O Brown

    2014-09-01

    Full Text Available Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1β was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD.

  13. Factors affecting survival in pediatric cardiac tamponade caused by central venous catheters.

    Science.gov (United States)

    Kayashima, Kenji

    2015-12-01

    Pediatric central venous catheter (CVC) placement is useful but associated with complications such as cardiac tamponade. We aimed to identify risk factors for death in cardiac tamponade. Published articles on pediatric CVC-associated cardiac tamponade were obtained by searching PubMed and Google and retrospectively reviewed to analyze risk factors for death. Factors examined for their effect on mortality risk included patient age, weight, CVC size, days from CVC insertion to tamponade occurrence, substances administered, insertion site, treatment, CVC material, and initial CVC tip position. Of 110 patients reported in 62 articles, 69 survived and 41 died. Among survivors, 55 of 69 patients were treated; among deaths, only 7 of 38 (OR 537.9, 95% CI 29.3-9,877, p tamponade survival. Past studies have mainly discussed how to avoid pediatric cardiac tamponade; by contrast, the present study focused on how to avoid deaths. The findings of this review suggest that cardiac tamponade survival is better when tamponade is detected early and treated promptly and might be affected by initial CVC tip position.

  14. Qiliqiangxin Enhances Cardiac Glucose Metabolism and Improves Diastolic Function in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Jingfeng Wang

    2017-01-01

    Full Text Available Cardiac diastolic dysfunction has emerged as a growing type of heart failure. The present study aims to explore whether Qiliqiangxin (QL can benefit cardiac diastolic function in spontaneously hypertensive rat (SHR through enhancement of cardiac glucose metabolism. Fifteen 12-month-old male SHRs were randomly divided into QL-treated, olmesartan-treated, and saline-treated groups. Age-matched WKY rats served as normal controls. Echocardiography and histological analysis were performed. Myocardial glucose uptake was determined by 18F-FDG using small-animal PET imaging. Expressions of several crucial proteins and key enzymes related to glucose metabolism were also evaluated. As a result, QL improved cardiac diastolic function in SHRs, as evidenced by increased E′/A′and decreased E/E′ (P<0.01. Meanwhile, QL alleviated myocardial hypertrophy, collagen deposits, and apoptosis (P<0.01. An even higher myocardial glucose uptake was illustrated in QL-treated SHR group (P<0.01. Moreover, an increased CS activity and ATP production was observed in QL-treated SHRs (P<0.05. QL enhanced cardiac glucose utilization and oxidative phosphorylation in SHRs by upregulating AMPK/PGC-1α axis, promoting GLUT-4 expression, and regulating key enzymes related to glucose aerobic oxidation such as HK2, PDK4, and CS (P<0.01. Our data suggests that QL improves cardiac diastolic function in SHRs, which may be associated with enhancement of myocardial glucose metabolism.

  15. The effect of marine n-3 polyunsaturated fatty acids on cardiac autonomic and hemodynamic function in patients with psoriatic arthritis

    DEFF Research Database (Denmark)

    Kristensen, Salome; Schmidt, Erik Berg; Schlemmer, Annette;

    2016-01-01

    The aim of this study was to investigate the effect of marine n-3 polyunsaturated fatty acids (PUFA) on cardiac autonomic function and vascular function in patients with psoriatic arthritis.......The aim of this study was to investigate the effect of marine n-3 polyunsaturated fatty acids (PUFA) on cardiac autonomic function and vascular function in patients with psoriatic arthritis....

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

    Directory of Open Access Journals (Sweden)

    Viveka P Jyotsna

    2013-01-01

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

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

    Science.gov (United States)

    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.

  18. ICF-based approach to evaluating functionality in cardiac rehabilitation patients after heart surgery.

    Science.gov (United States)

    Racca, V; Di Rienzo, M; Mazzini, P; Ripamonti, V; Gasti, G; Spezzaferri, R; Modica, M; Ferratini, M

    2015-08-01

    Heart surgery is a frequent reason for admission to in-patient cardiac rehabilitation programmes. ICF approach has never been used to evaluate cardiac patients after major heart surgery. The aim was to evaluate and measure functionality in cardiac patients who have undergone heart surgery, using for the first time the ICF-based approach and to assess whether such approach can be feasible and useful in cardiac rehabilitation. Observational study. In-patients cardiac Rehabilitation Unit in Milan. Fifty consecutively admitted patients who had undergone heart surgery (34 males, 16 females; mean age 65.7±12.5 years). We prepared a ICF-core set short enough to be feasible and practical. Patients were individually interviewed by different healthcare professionals (randomly selected from a group of two physicians, two physiotherapists and two psychologists) at the beginning (T1) and end of cardiac rehabilitation (T2) RESULTS: The sum of the scores of each ICF body function, body structure, activity and participation code significantly decreased between T1 and T2 (PICF body function scores and Barthel's index (ρ=0.381; P=0.006), NYHA class (ρ=0.404; P=0.004) and plasma Cr-P levels (r=0.31; P=0.03), between the ICF body structure codes and the Conley scale (ρ=0.306; P=0.02), and between the activity/participation codes and SpO2 (ρ=0.319; P=0.04). There were no correlations between the ICF environmental codes and clinical parameters. The ICF-based data provided functional information that was consistent with the patients' clinical course. The core set used allowed to quantify important body functions and activities, including some areas that are generally insufficiently considered by healthcare professionals during cardiac rehabilitation, and document their improvement.

  19. Endothelial Function as a Possible Significant Determinant of Cardiac Function during Exercise in Patients with Structural Heart Disease

    Directory of Open Access Journals (Sweden)

    Bonpei Takase

    2009-01-01

    Full Text Available This study was investigated the role that endothelial function and systemic vascular resistance (SVR play in determining cardiac function reserve during exercise by a new ambulatory radionuclide monitoring system (VEST in patients with heart disease. The study population consisted of 32 patients. The patients had cardiopulmonary stress testing using the treadmill Ramp protocol and the VEST. The anaerobic threshold (AT was autodetermined using the V-slope method. The SVR was calculated by determining the mean blood pressure/cardiac output. Flow-mediated vasodilation (FMD was measured in the brachial artery to evaluate endotheilial function. FMD and the percent change f'rom rest to AT in SVR correlated with those from rest to AT in ejection fraction and peak ejection ratio by VEST, respectively. Our findings suggest that FMD in the brachial artery and the SVR determined by VEST in patients with heart disease can possibly reflect cardiac function reserve during aerobic exercise.

  20. False dyssynchrony: problem with image-based cardiac functional analysis using x-ray computed tomography

    Science.gov (United States)

    Kidoh, Masafumi; Shen, Zeyang; Suzuki, Yuki; Ciuffo, Luisa; Ashikaga, Hiroshi; Fung, George S. K.; Otake, Yoshito; Zimmerman, Stefan L.; Lima, Joao A. C.; Higuchi, Takahiro; Lee, Okkyun; Sato, Yoshinobu; Becker, Lewis C.; Fishman, Elliot K.; Taguchi, Katsuyuki

    2017-03-01

    We have developed a digitally synthesized patient which we call "Zach" (Zero millisecond Adjustable Clinical Heart) phantom, which allows for an access to the ground truth and assessment of image-based cardiac functional analysis (CFA) using CT images with clinically realistic settings. The study using Zach phantom revealed a major problem with image-based CFA: "False dyssynchrony." Even though the true motion of wall segments is in synchrony, it may appear to be dyssynchrony with the reconstructed cardiac CT images. It is attributed to how cardiac images are reconstructed and how wall locations are updated over cardiac phases. The presence and the degree of false dyssynchrony may vary from scan-to-scan, which could degrade the accuracy and the repeatability (or precision) of image-based CT-CFA exams.

  1. A Psychological Factor Affecting a Cardiac Condition in a Psychotherapist

    Directory of Open Access Journals (Sweden)

    R Waxman

    2009-03-01

    Full Text Available It has been established that intense emotions can affect the development and course of cardiac arrhythmias. This study sought to convey that a lack of expression of emotion can also have an effect on arrhythmias. A psychotherapist with Idiopathic Ventricular Fibrillation and an Implantable Cardioverter Defibrillator measured his rate of Premature Ventricular Contractions using a Holter monitor during three separate six-week periods and in three domains: A work days vs. off days, B a 27 hour work week vs. 22 hour work week, and C in 5 different modalities including 1 Meeting with department head 2 Individual psychotherapy with patients 3 Group therapy with patients 4 Supervision of residents 5 Personal psychoanalysis. The results showed more than a 3-fold increase of arrhythmogenic activity during the 27-hour work week vs. 22 and a 5-fold increase in arrhythmogenic activity on work days compared to days off. Department Head meetings were found to be most arrhythmogenic and personal psychoanalysis was least. The data suggest that the psychiatrist’s lack of emotional expression in his clinical work has been demonstrated to markedly worsen his arrhythmia. The results also point to the potential ameliorating effects of the therapist’s own psychotherapy.

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

    Science.gov (United States)

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

    2017-01-01

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

  3. Cardiac Structure and Function in Weight Trainers Runners, and Runner/Weight Trainers.

    Science.gov (United States)

    Elias, Barbara A.; And Others

    1991-01-01

    Study compared cardiac structure and function in adult male weight trainers, runners, and those who did both. Results indicate men who run or weight train and run have similar heart structural and functional characteristics and greater relative internal diameter and left ventricular wall thickness than men who only weight train. (SM)

  4. SHEAR-INDUCED PATHWAY OF PLATELET-FUNCTION IN CARDIAC-SURGERY

    NARCIS (Netherlands)

    TABUCHI, N; TIGCHELAAR, [No Value; VANOEVEREN, W

    1995-01-01

    The contribution of platelet dysfunction to the impaired hemostasis after cardiac surgery remains to be established, because there is no sensitive method to assess platelet function. Measurement of the shear-induced pathway of platelet function, an important mechanism in inducing hemostasis, became

  5. SHEAR-INDUCED PATHWAY OF PLATELET-FUNCTION IN CARDIAC-SURGERY

    NARCIS (Netherlands)

    TABUCHI, N; TIGCHELAAR, [No Value; VANOEVEREN, W

    1995-01-01

    The contribution of platelet dysfunction to the impaired hemostasis after cardiac surgery remains to be established, because there is no sensitive method to assess platelet function. Measurement of the shear-induced pathway of platelet function, an important mechanism in inducing hemostasis, became

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

    Science.gov (United States)

    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…

  7. Velvet antler peptide prevents pressure overload-induced cardiac fibrosis via transforming growth factor (TGF)-β1 pathway inhibition.

    Science.gov (United States)

    Zhao, Lihong; Mi, Yang; Guan, Hongya; Xu, Yan; Mei, Yingwu

    2016-07-15

    Velvet antlers (VAs) are commonly used in traditional Chinese medicine and invigorant and contain many functional components for health promotion. The velvet antler peptide sVAP32 is one of active components in VAs; based on structural study, the sVAP32 interacts with TGF-β1 receptors and disrupts the TGF-β1 pathway. We hypothesized that sVAP32 prevents cardiac fibrosis from pressure overload by blocking TGF-β1 signaling. Sprague-Dawley rats underwent transverse aortic constriction (TAC) or a sham operation. After one month, rats received either sVAP32 (15mg/kg/day) or vehicle for an additional one month. TAC surgery induced significant cardiac dysfunction, fibroblast activation and fibrosis; these effects were improved by treatment with sVAP32. In the heart tissue, TAC remarkably increased the expression of TGF-β1 and connective tissue growth factor (CTGF), reactive oxygen species levels, and the phosphorylation levels of Smad2/3 and extracellular signal-regulated kinases 1/2 (ERK1/2). SVAP32 inhibited the increases in reactive oxygen species levels, CTGF expression and the phosphorylation of Smad2/3 and ERK1/2, but not TGF-β1 expression. In cultured cardiac fibroblasts, angiotensin II (Ang II) had similar effects compared to TAC surgery, such as increases in α-SMA-positive cardiac fibroblasts and collagen synthesis. SVAP32 eliminated these effects by disrupting TGF-β1 binding to its receptors and blocking Ang II/TGF-β1 downstream signaling. These results demonstrated that sVAP32 has anti-fibrotic effects by blocking the TGF-β1 pathway in cardiac fibroblasts.

  8. L-propionylcarnitine effects on cardiac carnitine content and function in secondary carnitine deficiency.

    Science.gov (United States)

    Broderick, T L; DiDomenico, D; Shug, A L; Paulson, D J

    1995-04-01

    Long-term treatment with sodium pivalate, a compound conjugated to carnitine and excreted in the urine, results in carnitine deficiency and cardiac dysfunction. Since L-propionylcarnitine (LPC) is generally of benefit to cardiac function, it was of interest to determine whether it is effective in preventing the reductions in both heart carnitine content and function from occurring in carnitine deficiency. Secondary carnitine deficiency was induced in male Sprague-Dawley rats by supplementing the drinking water with 20 mM sodium pivalate for 26 weeks. Control animals received an equimolar concentration of sodium bicarbonate. At 13 weeks into treatment, a subgroup of control and sodium pivalate animals were given 80 mg/kg of LPC in their drinking water. Following treatment, isolated working hearts were perfused with buffer containing 11 mM glucose and 0.4 mM palmitate. Hearts from sodium pivalate treated animals demonstrated a severe reduction in tissue carnitine. When mechanical function was measured in these hearts, heart rate, rate-pressure product, and aortic flow were significantly depressed. Treatment with LPC, however, prevented the depletion in cardiac carnitine content and improved these cardiac parameters. Our results demonstrate that LPC treatment is beneficial in preventing the depression in cardiac function from occurring in this model of secondary carnitine deficiency.

  9. American Heart Association's Life's Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function.

    Science.gov (United States)

    Folsom, Aaron R; Shah, Amil M; Lutsey, Pamela L; Roetker, Nicholas S; Alonso, Alvaro; Avery, Christy L; Miedema, Michael D; Konety, Suma; Chang, Patricia P; Solomon, Scott D

    2015-09-01

    Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association's Life's Simple 7 guidelines—on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose—is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults ages 45-64 years in 1987-1989. From the 1987-1989 risk factor measurements, we created a Life's Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4855 participants free of clinical cardiovascular disease in 2011-2013, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. One in four participants (25.5%) developed heart failure through age 85 years. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life's Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life's Simple 7 score, compared with an inadequate score. Greater achievement of American Heart Association's Life's Simple 7 in middle age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. PET measures of pre- and post-synaptic cardiac beta adrenergic function

    Energy Technology Data Exchange (ETDEWEB)

    Link, Jeanne M.; Stratton, John R.; Levy, Wayne; Poole, Jeanne E.; Shoner, Steven C.; Stuetzle, Werner; Caldwell, James H. E-mail: jcald@u.washington.edu

    2003-11-01

    Positron Emission Tomography was used to measure global and regional cardiac {beta}-adrenergic function in 19 normal subjects and 9 congestive heart failure patients. [{sup 11}C]-meta-hydroxyephedrine was used to image norepinephrine transporter function as an indicator of pre-synaptic function and [{sup 11}C]-CGP12177 was used to measure cell surface {beta}-receptor density as an indicator of post-synaptic function. Pre-synaptic, but not post-synaptic, function was significantly different between normals and CHF patients. Pre-synaptic function was well matched to post-synaptic function in the normal hearts but significantly different and poorly matched in the CHF patients studied. This imaging technique can help us understand regional sympathetic function in cardiac disease.

  11. Evaluation of cardiac structures and function in hypertrophic cardiomyopathy with magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To assess the capability of magnetic resonance imaging(MRI)in evaluating the cardiac structures and function in the hypertrophic cardiomyopathy(HCM).Methods:Fourteen healthy volunteers and eighteen cases with HCM verified by history,clinical presentation,electrocardiogram and echocardiography(ECG)were performed with MRI.The myocardial thickness of interventricular septum at the basal segment and that of posterolateral free wall of the left ventricle(LV)were measured.Some indexes for evaluating cardiac function were measured using ARGUS auto-quantitative program.Resuits:The myocardial thickness of septum at the basal segment had significant difference between the HCM patients and the healthy volunteers.There was no significant difference between MRI and ECG in examining end-diastolic volume,ejection fraction of the LV.Conclusion:MRI can fully provide more information on the abnormalities of cardiac anatomy and function;thus,it is of great value in clinical application.

  12. Functionally significant, rare transcription factor variants in tetralogy of Fallot.

    Directory of Open Access Journals (Sweden)

    Ana Töpf

    Full Text Available Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF.We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1 in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network.This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.

  13. Functionally significant, rare transcription factor variants in tetralogy of Fallot.

    Science.gov (United States)

    Töpf, Ana; Griffin, Helen R; Glen, Elise; Soemedi, Rachel; Brown, Danielle L; Hall, Darroch; Rahman, Thahira J; Eloranta, Jyrki J; Jüngst, Christoph; Stuart, A Graham; O'Sullivan, John; Keavney, Bernard D; Goodship, Judith A

    2014-01-01

    Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF). We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1) in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network. This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.

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

    Science.gov (United States)

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

    2017-03-01

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

  15. Assembly of a functional 3D primary cardiac construct using magnetic levitation

    Directory of Open Access Journals (Sweden)

    Glauco Souza

    2016-07-01

    Full Text Available Easily assembled organotypic co-cultures have long been sought in medical research. In vitro tissue constructs with faithful representation of in vivo tissue characteristics are highly desirable for screening and characteristic assessment of a variety of tissue types. Cardiac tissue analogs are particularly sought after due to the phenotypic degradation and difficulty of culture of primary cardiac myocytes. This study utilized magnetic nanoparticles and primary cardiac myocytes in order to levitate and culture multicellular cardiac aggregates (MCAs. Cells were isolated from 2 day old Sprague Dawley rat hearts and subsequently two groups were incubated with either C1: 33 µL nanoshell/million cells or C2: 50 µL nanoshell/million cells. Varying numbers of cells for each concentration were cultured in a magnetic field in a 24 well plate and observed over a period of 12 days. Constructs generally formed spherical structures. Masson’s trichrome staining of a construct shows the presence of extracellular matrix protein, indicating the presence of functional fibroblasts. Many constructs exhibited noticeable contraction after 4 days of culture and continued contracting noticeably past day 9 of culture. Noticeable contractility indicates the presence of functional primary cardiac myocytes in culture. Phenotypic conservation of cardiac cells was ascertained using IHC staining by α-actinin and collagen. CD31 and fibrinogen were probed in order to assess localization of fibroblasts and endothelial cells. The study verifies a protocol for the use of magnetic levitation in order to rapidly assemble 3D cardiac like tissue with phenotypic and functional stability.

  16. Galnt1 is required for normal heart valve development and cardiac function.

    Directory of Open Access Journals (Sweden)

    E Tian

    Full Text Available 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.

  17. Preserved recovery of cardiac function following ischemia-reperfusion in mice lacking SIRT3.

    Science.gov (United States)

    Koentges, Christoph; Pfeil, Katharina; Meyer-Steenbuck, Maximilian; Lother, Achim; Hoffmann, Michael M; Odening, Katja E; Hein, Lutz; Bode, Christoph; Bugger, Heiko

    2016-01-01

    Lack of the mitochondrial deacetylase sirtuin 3 (SIRT3) impairs mitochondrial function and increases the susceptibility to induction of the mitochondrial permeability transition pore. Because these alterations contribute to myocardial ischemia-reperfusion (IR) injury, we hypothesized that SIRT3 deficiency may increase cardiac injury following myocardial IR. Hearts of 10-week-old mice were perfused in the isolated working mode and subjected to 17.5 min of global no-flow ischemia, followed by 30 min of reperfusion. Measurements before ischemia revealed a decrease in cardiac power (-20%) and rate pressure product (-15%) in SIRT3(-/-) mice. Mitochondrial state 3 respiration (-15%), ATP synthesis (-39%), and ATP/O ratios (-29%) were decreased in hearts of SIRT3(-/-) mice. However, percent recovery of cardiac power (WT 94% ± 9%; SIRT3(-/-) 89% ± 9%) and rate pressure product (WT 89% ± 16%; SIRT3(-/-) 96% ± 3%) following IR was similar in both groups. Myocardial infarct size was not increased in SIRT3(-/-) mice following permanent ligation of the left anterior descending coronary artery (LAD). Left ventricular pressure and dP/dtmax, and mitochondrial respiration and ATP synthesis were not different between groups following LAD ligation. Thus, despite pre-existing defects in cardiac function and mitochondrial respiratory capacity in SIRT3(-/-) mice, SIRT3 deficiency does not additionally impair cardiac function following IR or following myocardial infarction.

  18. CHIP Enhances Angiogenesis and Restores Cardiac Function After Infarction in Transgenic Mice

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    Cheng-Wei Xu

    2013-02-01

    Full Text Available Background: Carboxyl terminus of Hsp70-interacting protein (CHIP is a chaperone/ubiquitin ligase that plays an important role in stress-induced apoptosis. However, the effect of CHIP on angiogenesis, cardiac function and survival 4 weeks after myocardial infarction (MI remain to be explored. Methods: Wild-type (WT and transgenic mice (TG with cardiac-specific overexpression of CHIP were used for coronary artery ligation. The cardiac function, cardiomyocyte apoptosis, inflammation and angiogenesis were examined by echocardiography, histological analysis, real-time PCR and Western blot analysis. Results: At 4 weeks of after coronary artery ligation, echocardiography demonstrated that cardiac remodeling and dysfunction were prevented in TG mice compared with WT mice. The infarct size, cardiomyocyte apoptosis and inflammation were significantly reduced in TG mice than in WT mice. The survival rate after MI in TG mice was higher than that of WT mice. Furthermore, the levels of p53 protein was markedly decreased, but the expression of HIF-1α and VEGF, and the formation of capillary and arteriole after MI were significantly enhanced in TG mice compared with WT mice. Conclusion: We report the first in vivo evidence that CHIP enhances angiogenesis, inhibits inflammation, restores cardiac function, and improves survival at 4 weeks after MI. The present study expands on previous results and defines a novel mechanism. Thus, increased CHIP level may provide a novel therapeutic approach for left ventricular dysfunction after MI.

  19. Effects of a single terlipressin administration on cardiac function and perfusion in cirrhosis

    DEFF Research Database (Denmark)

    Krag, Aleksander; Bendtsen, Flemming; Mortensen, Christian

    2010-01-01

    BACKGROUND: The vasoconstrictor terlipressin is widely used in the treatment of the hepatorenal syndrome and variceal bleeding. However, terlipressin may compromise cardiac function and induce ischemia. AIM: Therefore, we aimed to assess the effects of terlipressin on cardiac function and perfusion...... with nonrefractory ascites, both at baseline and after terlipressin treatment. The decrease in the left ventricular wall thickening and wall motion correlated with the Child--Pugh score, r=-0.59, P=0.005 and r=-0.48, P=0.03. CONCLUSION: In advanced cirrhosis, the increase in afterload and EDV after terlipressin...

  20. Influence of transposed stomach on cardiac function in patients with resected esophageal cancer.

    Science.gov (United States)

    Coral, R P; Constant-Neto, M; Silva, I S; Barros, S; Jawetz, J

    2004-01-01

    Although the use of the posterior mediastinum and the stomach as a reconstruction option after esophagectomy has wide acceptance, there are concerns about the potential cardiac impairment it could cause. We prospectively studied 27 patients regarding the function and the systolic diameter, diastolic diameter, shortening fraction, ejection fraction and the presence of extrinsic compression. The patients were studied preoperatively and between the 45th and 60th postoperative days. The parameters were still within normal clinical ranges. We concluded that this type of reconstruction does not harm the patients in terms of their cardiac function.

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

    Science.gov (United States)

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

    2017-01-01

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

  2. Assessment of factors that influence weaning from long-term mechanical ventilation after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Emília Nozawa

    2003-03-01

    Full Text Available OBJECTIVE: To analyze parameters of respiratory system mechanics and oxygenation and cardiovascular alterations involved in weaning tracheostomized patients from long-term mechanical ventilation after cardiac surgery. METHODS: We studied 45 patients in their postoperative period of cardiac surgery, who required long-term mechanical ventilation for more than 10 days and had to undergo tracheostomy due to unsuccessful weaning from mechanical ventilation. The parameters of respiratory system mechanics, oxigenation and the following factors were analyzed: type of surgical procedure, presence of cardiac dysfunction, time of extracorporeal circulation, and presence of neurologic lesions. RESULTS: Of the 45 patients studied, successful weaning from mechanical ventilation was achieved in 22 patients, while the procedure was unsuccessful in 23 patients. No statistically significant difference was observed between the groups in regard to static pulmonary compliance (p=0.23, airway resistance (p=0.21, and the dead space/tidal volume ratio (p=0.54. No difference was also observed in regard to the variables PaO2/FiO2 ratio (p=0.86, rapid and superficial respiration index (p=0.48, and carbon dioxide arterial pressure (p=0.86. Cardiac dysfunction and time of extracorporeal circulation showed a significant difference. CONCLUSION: Data on respiratory system mechanics and oxygenation were not parameters for assessing the success or failure. Cardiac dysfunction and time of cardiopulmonary bypass, however, significantly interfered with the success in weaning patients from mechanical ventilation.

  3. Cardiac fibroblasts are predisposed to convert into myocyte phenotype: Specific effect of transforming growth factor. beta

    Energy Technology Data Exchange (ETDEWEB)

    Eghbali, M.; Tomek, R.; Woods, C.; Bhambi, B. (Univ. of Chicago, IL (United States))

    1991-02-01

    Cardiac fibroblasts are mainly responsible for the synthesis of major extracellular matrix proteins in the heart, including fibrillar collagen types I and III and fibronectin. In this report we show that these cells, when stimulated by transforming growth factor {beta}{sub 1} (TGF-{beta}{sub 1}), acquire certain myocyte-specific properties. Cultured cardiac fibroblasts from adult rabbit heart were treated with TGF-{beta}{sub 1}, (10-15 ng/ml) for different periods of time. Northern hybridization analysis of total RNA showed that cells treated with TGF-{beta}{sub 1} became stained with a monoclonal antibody to muscle-specific actin. After treatment of quiescent cells with TGF-{beta}{sub 1}, cell proliferation (as measured by ({sup 3}H)thymidine incorporation) was moderately increased. Cultured cardiac fibroblasts at the subconfluent stage, when exposed to TGF-{beta}{sub 1} in the presence of 10% fetal bovine serum, gave rise to a second generation of slowly growing cells that expressed muscle-specific actin filaments. The findings demonstrate that cardiac fibroblasts can be made to differentiate into cells that display many characteristics of cardiac myocytes. TGF-{beta}{sub 1} seems to be a specific inducer of such conversion.

  4. Risk factors for biliary complications after liver transplantation from donation after cardiac death

    Directory of Open Access Journals (Sweden)

    LYU Guoyue

    2015-12-01

    Full Text Available Liver transplantation has become the effective therapeutic method for end-stage liver disease, but the incidence of biliary complications after liver transplantation remains high. With an increasing number of liver transplantation procedures from donation after cardiac death (DCD, it is necessary to investigate the risk factors for biliary complications after liver transplantation from DCD and enhance our understanding of such risk factors in order to reduce biliary complications after liver transplantation from DCD.

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

    Science.gov (United States)

    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, premodeling.

  6. Creatinine clearance versus serum creatinine as a risk factor in cardiac surgery.

    Science.gov (United States)

    Walter, Jörg; Mortasawi, Amir; Arnrich, Bert; Albert, Alexander; Frerichs, Inez; Rosendahl, Ulrich; Ennker, Jürgen

    2003-06-17

    Renal impairment is one of the predictors of mortality in cardiac surgery. Usually a binarized value of serum creatinine is used to assess the renal function in risk models. Creatinine clearance can be easily estimated by the Cockcroft and Gault equation from serum creatinine, gender, age and body weight. In this work we examine whether this estimation of the glomerular filtration rate can advantageously replace the serum creatinine in the EuroSCORE preoperative risk assessment. In a group of 8138 patients out of a total of 11878 patients, who underwent cardiac surgery in our hospital between January 1996 and July 2002, the 18 standard EuroSCORE parameters could retrospectively be determined and logistic regression analysis performed. In all patients scored, creatinine clearance was calculated according to Cockcroft and Gault. The relationship between the predicted and observed 30-days mortality was evaluated in systematically selected intervals of creatinine clearance and significance values computed by employing Monte Carlo methods. Afterwards, risk scoring was performed using a continuous or a categorical value of creatinine clearance instead of serum creatinine. The predictive ability of several risk score models and the individual contribution of their predictor variables were studied using ROC curve analysis. The comparison between the expected and observed 30-days mortalities, which were determined in different intervals of creatinine clearance, revealed the best threshold value of 55 ml/min. A significantly higher 30-days mortality was observed below this threshold and vice versa (both with p Differential ROC analysis revealed that CC is superior to SC in providing predictive power within the logistic regression. Variable rank comparison identified CC as the best single variable predictor, even better than the variable age, former number 1, and SC, previously number 9 in the standard set of EuroSCORE variables. The renal function is an important determinant

  7. [Progress of studies on mechanisms of acupuncture underlying regulation of cardiac function via autonomic nervous system].

    Science.gov (United States)

    Wang, Ya-Li; Yu, Zhi; Xu, Bin

    2014-02-01

    Acupuncture therapy has been confirmed to be effective in treating cardiovascular diseases in clinical practice. Acupuncture-induced balance of the autonomic nervous system activities is one of its key mechanisms. In the present paper, the authors review progress of studies on acupuncture treatment of cardiovascular diseases from 1) regulating cardiac sympathetic-beta-adrenergic receptor activity and myocardial intracellular GTP-binding protein (Gs)-adenylylcyclase (AC)-cyclic adenosine monophosphate (cAMP)-protein kinase (PKA) signaling, and 2) balancing cardiac sympathetic and vagal nerve activities. Due to limited experimental conditions, in-depth studies about the mechanisms of acupuncture intervention underlying improvement of cardiovascular functions are relatively fewer up to now. Along with the further development of modern biology, the mechanism of acupuncture intervention underlying regulation of cardiac function via autonomic nerve system will be revealed in detail.

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

    Science.gov (United States)

    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.

  9. Effects of interval and continuous exercise training on autonomic cardiac function in COPD patients.

    Science.gov (United States)

    Rodríguez, Diego A; Arbillaga, Ane; Barberan-Garcia, Anael; Ramirez-Sarmiento, Alba; Torralba, Yolanda; Vilaró, Jordi; Gimeno-Santos, Elena; Gea, Joaquim; Orozco-Levi, Mauricio; Roca, Josep; Marco, Ester

    2016-01-01

    Both interval (IT) and continuous (CT) exercise training results in an improvement of aerobic capacity in patients with chronic obstructive pulmonary disease (COPD); however, their effects on cardiac autonomic function remains unclear. The aim of our study was to evaluate the effect of a supervised CT vs IT on autonomic cardiac function in COPD patients. COPD patients were divided into two different groups according to training modality (IT or CT). Autonomic cardiac dysfunction (ACD) was defined as a heart rate recovery lower than 12 bpm heart rate after the first minute of maximal exercise (HRR1 ) and an abnormal chronotropic response (CR) to exercise (exercise training improve heart rate recovery and CR in COPD patients. These benefits could help to individualize exercise training. © 2014 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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.

  11. Cardiac mass and function decrease in bronchiolitis obliterans syndrome after lung transplantation: relationship to physical activity?

    Directory of Open Access Journals (Sweden)

    Jan B Hinrichs

    Full Text Available RATIONALE: There is a need to expand knowledge on cardio-pulmonary pathophysiology of bronchiolitis obliterans syndrome (BOS following lung transplantation (LTx. OBJECTIVES: The purpose of this study was to assess MRI-derived biventricular cardiac mass and function parameters as well as flow hemodynamics in patients with and without BOS after LTx. METHODS: Using 1.5T cardiac MRI, measurements of myocardial structure and function as well as measurements of flow in the main pulmonary artery and ascending aorta were performed in 56 lung transplant patients. The patients were dichotomized into two gender matched groups of comparable age range: one with BOS (BOS stages 1-3 and one without BOS (BOS 0/0p. MEASUREMENTS AND MAIN RESULTS: Significantly lower biventricular cardiac mass, right and left ventricular end-diastolic volume, biventricular stroke volume, flow hemodynamics and significant higher heart rate but preserved cardiac output were observed in patients with BOS 1-3 compared to the BOS 0/0p group (p < 0.05. In a stepwise logistic regression analysis global cardiac mass (p = 0.046 and days after LTx (p = 0.0001 remained independent parameters to predict BOS. In a second model an indicator for the physical fitness level - walking number of stairs - was added to the logistic regression model. In this second model, time after LTx (p = 0.005 and physical fitness (p = 0.01 remained independent predictors for BOS. CONCLUSION: The observed changes in biventricular cardiac mass and function as well as changes in hemodynamic flow parameters in the pulmonary trunk and ascending aorta are likely attributed to the physical fitness level of patients after lung transplantation, which in turn is strongly related to lung function.

  12. Changes to both cardiac metabolism and performance accompany acute reductions in functional capillary supply.

    Science.gov (United States)

    Hauton, David; Winter, James; Al-Shammari, Abdullah A; Gaffney, Eamonn A; Evans, Rhys D; Egginton, Stuart

    2015-04-01

    The relative importance of arteriole supply or ability to switch between substrates to preserve cardiac performance is currently unclear, but may be critically important in conditions such as diabetes. Metabolism of substrates was measured before and after infusion of polystyrene microspheres in the perfused working heart to mimic random capillary loss due to microvascular disease. The effect of acute loss of functional capillary supply on palmitate and glucose metabolism together with function was quantified, and theoretical tissue oxygen distribution calculated from histological samples and ventricular VO(2) estimated. Microsphere infusion led to a dose-dependent decrease in rate-pressure product (RPP) and oxygen consumption (Ppatent capillaries (P<0.001) and correspondingly increased the average capillary supply area by 40% (P<0.01). Calculated rates of oxygen consumption declined from 16.6±7.2 ml/100 ml/min to 12.4±9 ml/100 ml/min following arteriole occlusion, coupled with increases in size of regions of myocardial hypoxia (Control=22.0% vs. Microspheres=42.2%). Cardiac mechanical performance is very sensitive to arteriolar blockade, but metabolite switching from fatty acid to glucose utilisation may also support cardiac function in regions of declining PO(2). Preserving functional capillary supply may be critical for maintenance of cardiac function when metabolic flexibility is lost, as in diabetes. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-01

    Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes. PMID:28408970

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Christian Luck

    2017-01-01

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

  16. Attenuated muscle metaboreflex-induced increases in cardiac function in hypertension.

    Science.gov (United States)

    Sala-Mercado, Javier A; Spranger, Marty D; Abu-Hamdah, Rania; Kaur, Jasdeep; Coutsos, Matthew; Stayer, Douglas; Augustyniak, Robert A; O'Leary, Donal S

    2013-11-15

    Sympathoactivation may be excessive during exercise in subjects with hypertension, leading to increased susceptibility to adverse cardiovascular events, including arrhythmias, infarction, stroke, and sudden cardiac death. The muscle metaboreflex is a powerful cardiovascular reflex capable of eliciting marked increases in sympathetic activity during exercise. We used conscious, chronically instrumented dogs trained to run on a motor-driven treadmill to investigate the effects of hypertension on the mechanisms of the muscle metaboreflex. Experiments were performed before and 30.9 ± 4.2 days after induction of hypertension, which was induced via partial, unilateral renal artery occlusion. After induction of hypertension, resting mean arterial pressure was significantly elevated from 98.2 ± 2.6 to 141.9 ± 7.4 mmHg. The hypertension was caused by elevated total peripheral resistance. Although cardiac output was not significantly different at rest or during exercise after induction of hypertension, the rise in cardiac output with muscle metaboreflex activation was significantly reduced in hypertension. Metaboreflex-induced increases in left ventricular function were also depressed. These attenuated cardiac responses caused a smaller metaboreflex-induced rise in mean arterial pressure. We conclude that the ability of the muscle metaboreflex to elicit increases in cardiac function is impaired in hypertension, which may contribute to exercise intolerance.

  17. The alpha1-adrenergic receptors in cardiac hypertrophy: signaling mechanisms and functional implications.

    Science.gov (United States)

    Cotecchia, Susanna; Del Vescovo, Cosmo Damiano; Colella, Matilde; Caso, Stefania; Diviani, Dario

    2015-10-01

    Cardiac hypertrophy is a complex remodeling process of the heart induced by physiological or pathological stimuli resulting in increased cardiomyocyte size and myocardial mass. Whereas cardiac hypertrophy can be an adaptive mechanism to stressful conditions of the heart, prolonged hypertrophy can lead to heart failure which represents the primary cause of human morbidity and mortality. Among G protein-coupled receptors, the α1-adrenergic receptors (α1-ARs) play an important role in the development of cardiac hypertrophy as demonstrated by numerous studies in the past decades, both in primary cardiomyocyte cultures and genetically modified mice. The results of these studies have provided evidence of a large variety of α1-AR-induced signaling events contributing to the defining molecular and cellular features of cardiac hypertrophy. Recently, novel signaling mechanisms have been identified and new hypotheses have emerged concerning the functional role of the α1-adrenergic receptors in the heart. This review will summarize the main signaling pathways activated by the α1-AR in the heart and their functional implications in cardiac hypertrophy. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. ASSESSMENT OF SELECTED CARDIAC FUNCTIONS OF SPORTSPERSON OF VADODARA CITY

    Directory of Open Access Journals (Sweden)

    Rachit Joshi

    2012-02-01

    Full Text Available Aims and objective: Sports activity had always been an epitome of physical fitness activities. Multiple studies have shown that people, who maintain appropriate body fitness, using judicious regimens of exercise and weight control, have the additional benefit of prolonged life. The aim of this study was to find out and confirm the fact that regular exercise or sports activity have a beneficial effect on the various system of our body especially the cardiovascular system. Methodology: A comparative study was carried out at IPCL sports complex of Vadodara city in between the sportsperson and control persons using unpaired ‘t’ test for resting heart rate and blood pressure. They were subjected to hopping test: following which the maximum heart rate achieved and time taken for recovery to resting heart rate was measured. Results: As a result of our study we came to know that sportsperson have a significantly lower resting heart rate; lower maximum heart rate achieved and a reduced recovery time after hopping test than sedentary individuals. Conclusion: Our study reaffirms the fact that regular physical activity in any form slows the rate of decline with age of most of the physiological parameters that we associate with health and fitness especially by decline in basal heart rate and increased cardiac reserves. [National J of Med Res 2012; 2(1.000: 47-50

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

    CERN Document Server

    Arntz, Y; Dumitresco, B; Eclancher, B; Prat, V

    1999-01-01

    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 5x5x2 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) wh...

  20. Relationship between serum cardiac troponin T level and cardiopulmonary function in stable chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Hattori K

    2015-02-01

    Full Text Available Kumiko Hattori, Takeo Ishii, Takashi Motegi, Yuji Kusunoki, Akihiko Gemma, Kozui Kida Department of Pulmonary Medicine and Oncology; Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan Background: High-sensitivity cardiac troponin T (hs-cTnT in serum is a useful marker of acute myocardial injury, yet information is limited in patients with chronic obstructive pulmonary disease. We aimed to explore the association between hs-cTnT levels and cardiac and pulmonary dysfunction in patients with stable chronic obstructive pulmonary disease and at-risk individuals. Methods: We examined community-dwelling adults with/without chronic obstructive pulmonary disease, with a life-long smoking history, current symptoms of dyspnea during exertion, prolonged coughing, and/or sputum. Serum hs-cTnT concentrations were measured, and subjects underwent pulmonary function tests, high-resolution computed tomography of the chest, an echocardiogram, and a 6-minute walking test. Results: Eighty-six stable patients were identified (mean age 65.5 years; predicted forced expiratory volume in 1 second [FEV1% predicted] 75.0%. Their overall mean hs-cTnT level was 0.008 ng/mL. Logarithmically transformed hs-cTnT levels significantly and positively correlated with age, smoking index, serum high-sensitivity C-reactive protein levels, right ventricle systolic pressure, low attenuation area percentage, and brain natriuretic peptide levels (range r=0.231–0.534, P=0.000 to P=0.042. Further, logarithmically transformed hs-cTnT values significantly and negatively correlated with forced vital capacity, FEV1% predicted, diffusion capacity, arterial oxygen tension, and 6-minute walking distance (range r= -0.482 to -0.377, P=0.000 to P=0.002. Multivariate analyses showed that hs-cTnT values varied independently according to the following three parameters: high-sensitivity C-reactive protein levels (B=0.157, ß=0.450, t=3.571, P=0.001, age (B=0.008, ß=0.352, t=2.789, P=0

  1. Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Laila Elsherif

    Full Text Available Mice expressing the tetracycline transactivator (tTA transcription factor driven by the rat α-myosin heavy chain promoter (α-MHC-tTA are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these α-MHC-tTA mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury in both in vitro and in vivo models in the absence of associated cardiac hypertrophy or remodeling. Cardiac function, as assessed by echocardiography, did not differ between α-MHC-tTA and control animals, and there were no noticeable differences observed between the two groups in HW/TL ratio or LV end-diastolic and end-systolic dimensions. Protection against ischemia/reperfusion injury was assessed using isolated perfused hearts where α-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, α-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that α-MHC-tTA transgenic mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury similar to cardiac pre- and post-conditioning effects. However, in contrast to classical pre- and post-conditioning, the α-MHC-tTA phenotype is not inhibited by the classic preconditioning inhibitor LY294002 suggesting involvement of a non-PI3K-AKT signaling pathway in this phenotype. Thus, further study of the α-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury.

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

    Science.gov (United States)

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

    2016-05-26

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

  3. Norepinephrine-induced nerve growth factor depletion causes cardiac sympathetic denervation in severe heart failure.

    Science.gov (United States)

    Kimura, Kensuke; Kanazawa, Hideaki; Ieda, Masaki; Kawaguchi-Manabe, Haruko; Miyake, Yoshiko; Yagi, Takashi; Arai, Takahide; Sano, Motoaki; Fukuda, Keiichi

    2010-08-25

    In severe congestive heart failure (CHF), sympathetic overactivity correlates with the exacerbation of cardiac performance. To test the hypothesis that the cardiac sympathetic nerve density dramatically changes with the acceleration of circulating norepinephrine (NE) concentration, we investigated the temporal association of nerve growth factor (NGF) expression in the heart and cardiac sympathetic nerve density during the development of CHF in the continuous NE-infused rats. The animals were analyzed at 0-, 1-, 3-, 7-, 14-, and 28-day after implantation of osmotic pump at a rate of 0.05 mg/kg/hr. The cardiac performance was temporally facilitated in NE-exposed rats at 3-day in accordance with the sympathetic hyper-innervation induced by the augmentation of NGF mRNA expression in the heart. In NE-treated rats, left ventricular end-diastolic pressure was significantly increased after 7-day and marked left ventricular hypertrophy and systemic fluid retention were observed at 28-day. CHF-induced sympathetic overactivity further increased plasma NE concentration in NE-treated rats and finally reached to 16.1+/-5.6 ng/ml at 28-day (control level was 0.39+/-0.1 ng/ml, pcardiac performance. The cardiac sympathetic fiber loss was also confirmed in NE-exposed DBH (dopamine beta-hydroxylase)-Cre/Floxed-EGFP (enhanced green fluorescent protein) mice with severe CHF, in which sympathetic nerve could be traced by EGFP. Our results suggest that the cardiac sympathetic nerve density is strictly regulated by the NGF expression in the heart and long-exposure of high plasma NE concentration caused myocardial NGF reduction, following sympathetic fiber loss in severe CHF animals.

  4. Cardiac CT: are we underestimating the dose? A radiation dose study utilizing the 2007 ICRP tissue weighting factors and a cardiac specific scan volume

    Energy Technology Data Exchange (ETDEWEB)

    Gosling, O., E-mail: Oliver.gosling@pms.ac.u [Plymouth Hospitals NHS Trust, Derriford Hospital, Plymouth, Devon (United Kingdom); Loader, R.; Venables, P.; Rowles, N.; Morgan-Hughes, G. [Plymouth Hospitals NHS Trust, Derriford Hospital, Plymouth, Devon (United Kingdom); Roobottom, C. [Peninsula College of Medicine and Dentistry, University of Plymouth, Devon (United Kingdom)

    2010-12-15

    Aim: To calculate the effective dose from cardiac multidetector computed tomography (MDCT) using a computer-based model utilizing the latest International Commission on Radiation Protection (ICRP) 103 tissue-weighting factors (2007), to compare this dose with those calculated with previously published chest conversion factors and to produce a conversion factor specific for cardiac MDCT. Materials and methods: An observational study of 152 patients attending for cardiac MDCT as part of their usual clinical care in a university teaching hospital. The dose for each examination was calculated using the computer-based anthropomorphic ImPACT model (the imaging performance assessment of CT scanners) and this was compared with the dose derived from the dose-length product (DLP) and a chest conversion factor. Results: The median effective dose calculated using the ImPACT calculator (4.5 mSv) was significantly higher than the doses calculated with the chest conversion factors (2.2-3 mSv). Conclusion: The use of chest conversion factors significantly underestimates the effective dose when compared to the dose calculated using the ImPACT calculator. A conversion factor of 0.028 would give a better estimation of the effective dose from prospectively gated cardiac MDCT.

  5. Cardiac Autonomic Function in Patients With Ankylosing Spondylitis: A Case-Control Study.

    Science.gov (United States)

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

    2016-05-01

    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.

  6. Risk factors for systemic inflammatory response after congenital cardiac surgery.

    Science.gov (United States)

    Güvener, Murat; Korun, Oktay; Demirtürk, Orhan Saim

    2015-01-01

    This study aims to assess the frequency of systemic inflammatory response syndrome (SIRS) following congenital heart surgery and risk factors associated with this clinical syndrome. Charts of all patients undergoing surgery for congenital heart disease in a single institution over a five-year period were analyzed retrospectively. The presence of SIRS was evaluated based on the criteria of the International Pediatric Sepsis Consensus Conference. Of the 246 patients included in the study 22 (8.9%) had clinical parameters indicating SIRS. The patients in the SIRS group had significantly longer cardiopulmonary bypass time (105.14 ± 27.27 vs. 66.86 ± 26.64 min; p SIRS group. Binary logistic regression revealed cardiopulmonary bypass time (OR: 1.05, p SIRS. SIRS was also found to be a strong independent predictor of mortality (OR: 10.13, p SIRS after congenital heart surgery is associated with increased mortality. Independent risk factors for SIRS in the patient population of the study were cardiopulmonary bypass time, body weight below 10 kg and preoperative diagnosis of right to left shunt congenital heart disease. © 2014 Wiley Periodicals, Inc.

  7. Exercise and Type 2 Diabetes Mellitus : Changes in Tissue-specific Fat Distribution and Cardiac Function

    NARCIS (Netherlands)

    Jonker, Jacqueline T.; de Mol, Pieter; de Vries, Suzanna T.; Widya, Ralph L.; Hammer, Sebastiaan; van Schinkel, Linda D.; van der Meer, Rutger W.; Gans, Rijk O. B.; Webb, Andrew G.; Kan, Hermien E.; de Koning, Eelco J. P.; Bilo, Henk J. G.; Lamb, Hildo J.

    2013-01-01

    Purpose: To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Materials and Methods: Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics

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

    NARCIS (Netherlands)

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

    2011-01-01

    Yin M, van der Horst IC, van Melle JP, Qian C, van Gilst WH, Sillje HH, de Boer RA. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol 301: H459-H468, 2011. First published May 13, 2011; doi:10.1152/ajpheart.00054.2011.-Metformin

  9. Sinus node function after cardiac surgery : is impairment specific for the maze procedure?

    NARCIS (Netherlands)

    Tuinenburg, AE; Van Gelder, IC; Van Den Berg, MP; Grandjean, JG; Tieleman, RG; Smit, AJ; Huet, RCG; Van Der Maaten, JMAA; Volkers, CP; Ebels, T; Crijns, HJGM

    2004-01-01

    Background: Maze surgery is a final solution for intractable atrial fibrillation (AF), but an adverse effect on postoperative sinus node function has been reported. Whether this also applies to other types of cardiac surgery is unclear. Methods: We assessed postoperative rhythm by means of repeated

  10. Early association of electrocardiogram alteration with infarct size and cardiac function after myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    陶则伟; 黄元伟; 夏强; 傅军; 赵志宏; 陆贤; BRUCEI.C.

    2004-01-01

    Objective:Myocardial infarction (MI) is the main cause of heart failure, but the relationship between the extent of MI and cardiac function has not been clearly determined.The present study was undertaken to investigate early changes in the electrocardiogram associated with infarct size and cardiac function after MI. Methods: MI was induced by ligating the left anterior descending coronary artery in rats. Electrocardiograms, echocardiographs and hemodynamic parameters were assessed and myocardial infarct size was measured from mid-transverse sections stained with Masson's trichrome. Results:The sum of pathological Q wave amplitudes was strongly correlated with myocardial infarct size (r=0.920, P<0.0001), left ventricular ejection fraction (r=-0.868, P<0.0001) and left ventricular end diastolic pressure (r=0.835, P<0.0004).Furthermore, there was close relationship between MI size and cardiac function as assessed by left ventricular ejection fraction (r=-0.913, P<0.0001) and left ventricular end diastolic pressure (r=0.893, P<0.0001).Conclusion: The sum of pathological Q wave amplitudes after MI can be used to estimate the extent of MI as well as cardiac function.

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

    Directory of Open Access Journals (Sweden)

    André Luiz Lisboa Cordeiro

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    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,…

  14. An Exploratory Study of Functional Status in Post Cardiac Arrest Survivors Discharged To Home

    Science.gov (United States)

    2005-08-01

    arrest. The physical functioning (PF) and mental health (MH) scales were relatively wholesome, being specific to medical or psychiatric disorders ...cardiac rehabilitation post myocardial infarction. Exclusion criteria for this sample included 1. The existence of cognitive inability, delusional ...illness, and monitor response to treatment. The MMSE has also been used as a research tool to screen for cognitive disorders in epidemiological studies

  15. Early association of electrocardiogram alteration with infarct size and cardiac function after myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    TAO Ze-wei (陶则伟); HUANG Yuan-wei (黄元伟); XIA Qiang (夏强); FU Jun (傅军); ZHAO Zhi-hong (赵志宏); LU Xian (陆贤); BRUCE I.C.

    2004-01-01

    Objective: Myocardial infarction (MI) is the main cause of heart failure, but the relationship between the extent of MI and cardiac function has not been clearly determined. The present study was undertaken to investigate early changes in the electrocardiogram associated with infarct size and cardiac function after MI. Methods: MI was induced by ligating the left anterior descending coronary artery in rats. Electrocardiograms, echocardiographs and hemodynamic parameters were assessed and myocardial infarct size was measured from mid-transverse sections stained with Masson's trichrome. Results: The sum of pathological Q wave amplitudes was strongly correlated with myocardial infarct size (r = 0.920, P < 0.0001), left ventricular ejection fraction (r = (0.868, P < 0.0001) and left ventricular end diastolic pressure (r = 0.835, P < 0.0004). Furthermore, there was close relationship between MI size and cardiac function as assessed by left ventricular ejection fraction (r = (0.913, P < 0.0001) and left ventricular end diastolic pressure (r = 0.893, P < 0.0001). Conclusion: The sum of pathological Q wave amplitudes after MI can be used to estimate the extent of MI as well as cardiac function.

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

    Science.gov (United States)

    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.

  17. Value of plasma ADMA in predicting cardiac structure and function of patients with chronic kidney diseases

    Institute of Scientific and Technical Information of China (English)

    叶建华

    2012-01-01

    Objective To explore the predicting value of plasma asymmetric dimethylarginine (ADMA) in cardiac structure and function of patients with chronic kidney diseases(CKD). Methods A total of 100 CKD patients were enrolled in this cross-sectional study. According to staging of the

  18. Multimodality Cardiac Imaging for the Assessment of Left Atrial Function and the Association With Atrial Arrhythmias

    DEFF Research Database (Denmark)

    Olsen, Flemming Javier; Bertelsen, Litten; de Knegt, Martina Chantal

    2016-01-01

    an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing...

  19. Novel Measures of Volume Status and Cardiac Function in Traumatic Shock

    Science.gov (United States)

    2016-06-01

    Focused rapid echocardiographic evaluation versus vascular catheter-based assessment of cardiac output and function in critically ill trauma ...adequacy of resuscitation in patients with traumatic shock and (2) to determine the incidence, time course, and clinical relevance of trauma ...evaluation serially over time in a civilian model of military trauma . Upon closure of the study, only six patients were enrolled, so no association

  20. Effects of interleukin-1 on cardiac fibroblast function: relevance to post-myocardial infarction remodelling.

    Science.gov (United States)

    Turner, Neil A

    2014-01-01

    The cardiac fibroblast (CF) is a multifunctional and heterogeneous cell type that plays an essential role in regulating cardiac development, structure and function. Following myocardial infarction (MI), the myocardium undergoes complex structural remodelling in an attempt to repair the damaged tissue and overcome the loss of function induced by ischemia/reperfusion injury. Evidence is emerging that CF play critical roles in all stages of post-MI remodelling, including the initial inflammatory phase that is triggered in response to myocardial damage. CF are particularly responsive to the proinflammatory cytokine interleukin-1 (IL-1) whose levels are rapidly induced in the myocardium after MI. Studies from our laboratory in recent years have sought to evaluate the functional effects of IL-1 on human CF function and to determine the underlying molecular mechanisms. This review summarises these data and sets it in the context of post-MI cardiac remodelling, identifying the fibroblast as a potential therapeutic target for reducing adverse cardiac remodelling and its devastating consequences. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Effect of weight support exercise therapy on the cardiac function in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    Dong-Dong Jiao; Wen-Yu Zhang; Jing Xu; Guang-Jian Zhu; Jia Chen

    2016-01-01

    Objective:To explore the effect of weight support exercise therapy on the cardiac function and living quality in patients with chronic heart failure.Methods: A total of 75 patients with CHF were included in the study and randomized into the observation group (n=38) and the control group (n=37). the patients in the control group were given routine drug therapy. on the above basis, the patients in the observation group were given weight support exercise therapy for rehabilitation. six-month treatment was regarded as one course. the plasma BNP and aldosterone levels before and after treatment in the two groups were detected. the related cardiac function indicators in the two groups were compared. 6mwt and MHL were used to evaluate the exercise tolerance and living quality, respectively.Results:The comparison of plasma BNP and aldosterone levels, various cardiac function indicators, 6 min walking distance, and MHL score before treatment between the two groups was not statistically significant. BNP and aldosterone levels after treatment in the two groups were significantly reduced, and the reduced degree in the observation group was significantly greater than that in the control group. after treatment, HR, LVEDD, and MHL score were significantly reduced, LVEF, FS, and 6 min walking distance were significantly increased, and the comparison between the two groups was statistically significant.Conclusions:Weight support exercise therapy can significantly reduce the plasma BNP and aldosterone levels in CHF patients, improve the cardiac function, and enhance the exercise tolerance and living quality.

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

    Science.gov (United States)

    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,…

  3. Association of renal function with cardiac calcifications in older adults : the cardiovascular health study

    NARCIS (Netherlands)

    Asselbergs, Folkert W.; Mozaffarian, Dariush; Katz, Ronit; Kestenbaum, Bryan; Fried, Linda F.; Gottdiener, John S.; Shlipak, Michael G.; Siscovick, David S.

    2009-01-01

    Background. Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are highly prevalent in patients with end-stage renal disease. It is less well established whether milder kidney disease is associated with cardiac calcifications. We evaluated the relationships between renal function an

  4. Tei index in determination of fetal cardiac function in pregnant women with gestational diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Guo-Dong Li; Jia-Yuan Yi; Shu-Yu Gao; Hong-Ping Liang; Yan-Qing Liu

    2016-01-01

    Objective:To explore the application value of Tei index in determination of fetal cardiac function in pregnant women with gestational diabetes mellitus (GDM).Methods: A total of 60 gestational diabetes mellitus pregnant women with single birth were included in the study and served as GDM group, while 60 healthy pregnant women with single birth were served as the control group. The fetal echocardiography was performed. The cardiac structure, function, and other related indicators were detected and compared.Results:IVSs, LVWT, RVWT, LVEF, LVFS, and RVFS in GDM group were significantly greater than those in the control group (P<0.05). E/A MV and E/A TV in GDM group were significantly lower than those in the control group (P<0.05). The left and right ventricular Tei index in GDM group was significantly higher than that in the control group (P<0.05).Conclusions:The fetal cardiac structure and function in GDM pregnant women can cause damage to a different degree. Tei index is an important indicator to evaluate the fetal cardiac function in GDM pregnant women, and can be applied in the early diagnosis and treatment; therefore, it deserved to be widely recommended in the clinic.

  5. The impact of therapeutic hypothermia on neurological function and quality of life after cardiac arrest

    DEFF Research Database (Denmark)

    Bro-Jeppesen, John; Kjaergaard, Jesper; Horsted, Tina I;

    2008-01-01

    AIMS: To assess the impact of therapeutic hypothermia on cognitive function and quality of life in comatose survivors of out of Hospital Cardiac arrest (OHCA). METHODS: We prospectively studied comatose survivors of OHCA consecutively admitted in a 4-year period. Therapeutic hypothermia was imple...

  6. Effect of contractile protein alterations on cardiac myofilament function in human heart failure

    NARCIS (Netherlands)

    Narolska, N.A.

    2006-01-01

    The main objective of this thesis was to elucidate the effect of translational and post-translational alterations in contractile proteins occurring during heart failure on contractile function in human cardiac tissue. Isometric force and ATPase activity measurements were performed in skinned human

  7. The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children

    NARCIS (Netherlands)

    Chockalingam, Priya; Clur, Sally-Ann B.; Breur, Johannes M. P. J.; Kriebel, Thomas; Paul, Thomas; Rammeloo, Lukas A.; Wilde, Arthur A. M.; Blom, Nico A.

    2012-01-01

    BACKGROUND Loss-of-function sodium channelopathies manifest as a spectrum of diseases including Brugada syndrome (BrS) and cardiac conduction disease. OBJECTIVE To analyze the diagnostic and therapeutic aspects of these disorders in children. METHODS Patients aged 98th percentile for age). RESULTS:

  8. Cardiac and pulmonary function variability in Duchenne/Becker muscular dystrophy: an initial report.

    Science.gov (United States)

    Birnkrant, David J; Ashwath, Mahi Lakshmi; Noritz, Garey H; Merrill, Michelle C; Shah, Tushar A; Crowe, Carol A; Bahler, Robert C

    2010-09-01

    The Duchenne and Becker forms of muscular dystrophy are associated with dilated cardiomyopathy and are diseases in which pulmonary function peaks and then progressively declines. In this report, the authors quantify cardiopulmonary function variability among brothers. Brothers in 3 of 7 eligible sibships had discordant pulmonary function, with significant differences between the brothers' peak forced vital capacities and their vital capacities at last comparable age. There was no relationship between pulmonary and cardiac function among the siblings. The authors concluded that despite identical genetic mutations, cardiac and pulmonary function variability was common among brothers in their clinic with Duchenne or Becker muscular dystrophy. If confirmed by larger studies, these results have negative implications for the use of genetic testing to predict cardiopulmonary course and response to therapies in Duchenne or Becker muscular dystrophy.

  9. Performance of automated software in the assessment of segmental left ventricular function in cardiac CT: Comparison with cardiac magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Rui [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Capital Medical University, Department of Radiology, Beijing Anzhen Hospital, Beijing (China); Meinel, Felix G. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Ludwig-Maximilians-University Hospital, Institute for Clinical Radiology, Munich (Germany); Schoepf, U.J. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Medical University of South Carolina, Division of Cardiology, Department of Medicine, Charleston, SC (United States); Canstein, Christian [Siemens Medical Solutions USA, Malvern, PA (United States); Spearman, James V. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); De Cecco, Carlo N. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); University of Rome ' ' Sapienza' ' , Departments of Radiological Sciences, Oncology and Pathology, Latina (Italy)

    2015-12-15

    To evaluate the accuracy, reliability and time saving potential of a novel cardiac CT (CCT)-based, automated software for the assessment of segmental left ventricular function compared to visual and manual quantitative assessment of CCT and cardiac magnetic resonance (CMR). Forty-seven patients with suspected or known coronary artery disease (CAD) were enrolled in the study. Wall thickening was calculated. Segmental LV wall motion was automatically calculated and shown as a colour-coded polar map. Processing time for each method was recorded. Mean wall thickness in both systolic and diastolic phases on polar map, CCT, and CMR was 9.2 ± 0.1 mm and 14.9 ± 0.2 mm, 8.9 ± 0.1 mm and 14.5 ± 0.1 mm, 8.3 ± 0.1 mm and 13.6 ± 0.1 mm, respectively. Mean wall thickening was 68.4 ± 1.5 %, 64.8 ± 1.4 % and 67.1 ± 1.4 %, respectively. Agreement for the assessment of LV wall motion between CCT, CMR and polar maps was good. Bland-Altman plots and ICC indicated good agreement between CCT, CMR and automated polar maps of the diastolic and systolic segmental wall thickness and thickening. The processing time using polar map was significantly decreased compared with CCT and CMR. Automated evaluation of segmental LV function with polar maps provides similar measurements to manual CCT and CMR evaluation, albeit with substantially reduced analysis time. (orig.)

  10. Healthy aging does not compromise the augmentation of cardiac function during heat stress.

    Science.gov (United States)

    Gagnon, Daniel; Romero, Steven A; Ngo, Hai; Sarma, Satyam; Cornwell, William K; Poh, Paula Y S; Stoller, Douglas; Levine, Benjamin D; Crandall, Craig G

    2016-10-01

    During heat stress, stroke volume is maintained in young adults despite reductions in cardiac filling pressures. This is achieved by a general augmentation of cardiac function, highlighted by a left and upward shift of the Frank-Starling relation. In contrast, healthy aged adults are unable to maintain stroke volume during heat stress. We hypothesized that this would be associated with a lack of shift in the Frank-Starling relation. Frank-Starling relations were examined in 11 aged [69 ± 4 (SD) yr, 4 men/7 women] and 12 young (26 ± 5 yr, 6 men/6 women) adults during normothermic and heat stress (1.5°C increase in core temperature) conditions. During heat stress, increases in cardiac output were attenuated in aged adults (+2.5 ± 0.3 (95% CI) vs. young: +4.5 ± 0.5 l/min, P < 0.01) because of an attenuated chronotropic response (+30 ± 4 vs. young: +42 ± 5 beats/min, P < 0.01). In contrast to our hypothesis, a leftward shift of the Frank-Starling relation maintained stroke volume during heat stress in aged adults (76 ± 8 vs. normothermic: 74 ± 8 ml, P = 0.38) despite reductions in cardiac filling pressure (6.6 ± 1.0 vs. normothermic: 8.9 ± 1.1 mmHg, P < 0.01). In a subset of participants, volume loading was used to return cardiac filling pressure during heat stress to normothermic values, which resulted in a greater stroke volume for a given cardiac filling pressure in both groups. These results demonstrate that the Frank-Starling relation shifts during heat stress in healthy young and aged adults, thereby preserving stroke volume despite reductions in cardiac filling pressures. Copyright © 2016 the American Physiological Society.

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

    Science.gov (United States)

    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

  12. Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis.

    Science.gov (United States)

    Perlini, Stefano; Salinaro, Francesco; Musca, Francesco; Mussinelli, Roberta; Boldrini, Michele; Raimondi, Ambra; Milani, Paolo; Foli, Andrea; Cappelli, Francesco; Perfetto, Federico; Palladini, Giovanni; Rapezzi, Claudio; Merlini, Giampaolo

    2014-05-01

    Cardiac amyloidosis represents an archetypal form of restrictive heart disease, characterized by profound diastolic dysfunction. As ejection fraction is preserved until the late stage of the disease, the majority of patients do fulfill the definition of diastolic heart failure, that is, heart failure with preserved ejection fraction (HFpEF). In another clinical model of HFpEF, that is, pressure-overload hypertrophy, depressed midwall fractional shortening (mFS) has been shown to be a powerful prognostic factor. To assess the potential prognostic role of mFS in cardiac light-chain amyloidosis with preserved ejection fraction, we enrolled 221 consecutive untreated patients, in whom a first diagnosis of cardiac light-chain amyloidosis was concluded between 2008 and 2010. HFpEF was present in 181 patients. Patients in whom cardiac involvement was excluded served as controls (n = 121). Prognosis was assessed after a median follow-up of 561 days. When compared with light-chain amyloidosis patients without myocardial involvement, cardiac light-chain amyloidosis was characterized by increased wall thickness (P chain amyloidosis with normal ejection fraction, depressed circumferential mFS, a marker of myocardial contractile dysfunction, is a powerful predictor of survival.

  13. Influence of enteral nutrition duration in treatment of cardiac function and inflammatory factors in patients with elderly chronic pulmonary heart failure%肠内营养不同治疗时限对老年肺心病心衰患者炎性因子及心功能的影响

    Institute of Scientific and Technical Information of China (English)

    王瑞萍; 杨莉; 王俊; 王煜; 李轶炜

    2012-01-01

    目的 探讨肠内营养不同治疗时限对老年肺心病心衰患者血清炎性因子及心功能的影响.方法 以90例老年肺心病心衰患者为研究对象,将患者随机分为三组,三组在常规治疗心衰同时,A组给予自由饮食,B组给予肠内营养治疗1月,C组给予肠内营养治疗6月.各组治疗前后均检测各营养指标,用放免发测TNF-α、IL-6,用心脏超声检测左室射血分数LVEF.结果 肠内营养组患者在治疗后各营养指标均有改善,炎性因子水平均有降低,心功能均有所改善,治疗前后比较有统计学意义(P<0.05),尤其在C组中改善更为明显(P<0.01).自由饮食组中,治疗后各营养指标无改善,血清炎性因子水平及心功能有所改善,但治疗前后比较无统计学意义(P>0.05).结论 老年肺心病心衰患者,在常规治疗心衰同时重视肠内营养治疗,可以改善患者营养状况从而改善免疫功能,调节炎性因子水平,进一步改善患者心功能,并且治疗时限越长心功能及炎性因子水平改善越明显.%Objectives To investigate the influence of enteral nutrition duration in treatment of cardiac function and inflammatory factors in patients with elderly chronic pulmonary heart failure. Methods The patients were randomly divided into three groups for the study ,90 cases of senile pulmonary heart disease in patients with heart failure. Three groups in the conventional treatment of heart failure at the same time, group A given free diet, group B enteral nutrition in the treatment for one month,group C enteral nutrition therapy for 6 months. Various nutrition indicators in each group before and after treatment to detect the nutritional index, measured by RIA hair TNF - α, IL - 6, with a heart ultrasonic testing of left ventricular ejection fraction LVEF. Results Enteral nutrition in patients after treatment were significantly decreased, inflammatory cytokines were reduced,heart function improved after treatment

  14. Fusion of structural and functional cardiac magnetic resonance imaging data for studying ventricular fibrillation.

    Science.gov (United States)

    Magtibay, K; Beheshti, M; Foomany, F H; Balasundaram, K; Masse, S; Lai, P; Asta, J; Zamiri, N; Jaffray, D A; Nanthakumar, K; Krishnan, S; Umapathy, K

    2014-01-01

    Magnetic Resonance Imaging (MRI) techniques such as Current Density Imaging (CDI) and Diffusion Tensor Imaging (DTI) provide a complementing set of imaging data that can describe both the functional and structural states of biological tissues. This paper presents a Joint Independent Component Analysis (jICA) based fusion approach which can be utilized to fuse CDI and DTI data to quantify the differences between two cardiac states: Ventricular Fibrillation (VF) and Asystolic/Normal (AS/NM). Such an approach could lead to a better insight on the mechanism of VF. Fusing CDI and DTI data from 8 data sets from 6 beating porcine hearts, in effect, detects the differences between two cardiac states, qualitatively and quantitatively. This initial study demonstrates the applicability of MRI-based imaging techniques and jICA-based fusion approach in studying cardiac arrhythmias.

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

    Science.gov (United States)

    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.

  16. Protective function of tocilizumab in human cardiac myocytes ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Hai-Feng Cheng; Yan Feng; Da-Ming Jiang; Kai-Yu Tao; Min-Jian Kong

    2015-01-01

    Objective:To investigate the protective function of tocilizumab in human cardiac myocytes ischemia-reperfusion injury.Methods:The human cardiac myocytes were treated by tocilizumab with different concentrations(1.0 mg/mL, 3.0 mg/mL, 5.0 mg/mL) for 24 h,then cells were cultured in ischemia environment for 24 h and reperfusion environment for 1 h. The MTT and flow cytometry were used to detect the proliferation and apoptosis of human cardiac myocytes, respectively. The mRNA and protein expressions of Bcl-2 and Bax were measured by qRT-PCR and western blot, respectively.Results:Compared to the negative group, pretreated by tocilizumab could significantly enhance the proliferation viability and suppress apoptosis of human cardiac myocytes after suffering ischemia reperfusion injury(P<0.05).The expression of Bcl-2 in tocilizumab treated group were higher thanNC group(P<0.05), while theBax expression were lower(P<0.05).Conclusions:Tocilizumab could significantly inhibit apoptosis and keep the proliferation viability of human cardiac myocytes after suffering ischemia reperfusion injury. Tocilizumab may obtain a widely application in the protection of ischemia reperfusion injury.

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

    Science.gov (United States)

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

    2012-05-01

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

  18. Endogenous muscle atrophy F-box mediates pressure overload-induced cardiac hypertrophy through regulation of nuclear factor-kappaB.

    Science.gov (United States)

    Usui, Soichiro; Maejima, Yasuhiro; Pain, Jayashree; Hong, Chull; Cho, Jaeyeaon; Park, Ji Yeon; Zablocki, Daniela; Tian, Bin; Glass, David J; Sadoshima, Junichi

    2011-07-08

    Overexpression of muscle atrophy F-box (MAFbx/atrogin-1), an E3 ubiquitin ligase, induces proteasomal degradation in cardiomyocytes. The role of endogenous MAFbx in regulating cardiac hypertrophy and failure remains unclear. We investigated the role of MAFbx in regulating cardiac hypertrophy and function in response to pressure overload. Transverse aortic constriction (TAC) was applied to MAFbx knockout (KO) and wild-type (WT) mice. Expression of MAFbx in WT mice was significantly increased by TAC. TAC-induced increases in cardiac hypertrophy were significantly smaller in MAFbx KO than in WT mice. There was significantly less lung congestion and interstitial fibrosis in MAFbx KO than in WT mice. MAFbx KO also inhibited β-adrenergic cardiac hypertrophy. DNA microarray analysis revealed that activation of genes associated with the transcription factor binding site for the nuclear factor-κB family were inhibited in MAFbx KO mice compared with WT mice after TAC. Although the levels of IκB-α were significantly decreased after TAC in WT mice, they were increased in MAFbx KO mice. MAFbx regulates ubiquitination and proteasomal degradation of IκB-α in cardiomyocytes. In primary cultured rat cardiomyocytes, phenylephrine-induced activation of nuclear factor-κB and hypertrophy were significantly suppressed by MAFbx knockdown but were partially rescued by overexpression of nuclear factor-κB p65. MAFbx plays an essential role in mediating cardiac hypertrophy in response to pressure overload. Downregulation of MAFbx inhibits cardiac hypertrophy in part through stabilization of IκB-α and inactivation of nuclear factor-κB. Taken together, inhibition of MAFbx attenuates pathological hypertrophy, thereby protecting the heart from progression into heart failure.

  19. Improvement of cardiac contractile function by peptide-based inhibition of NF-κB in the utrophin/dystrophin-deficient murine model of muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Guttridge Denis C

    2011-05-01

    Full Text Available Abstract Background Duchenne muscular dystrophy (DMD is an inherited and progressive disease causing striated muscle deterioration. Patients in their twenties generally die from either respiratory or cardiac failure. In order to improve the lifespan and quality of life of DMD patients, it is important to prevent or reverse the progressive loss of contractile function of the heart. Recent studies by our labs have shown that the peptide NBD (Nemo Binding Domain, targeted at blunting Nuclear Factor κB (NF-κB signaling, reduces inflammation, enhances myofiber regeneration, and improves contractile deficits in the diaphragm in dystrophin-deficient mdx mice. Methods To assess whether cardiac function in addition to diaphragm function can be improved, we investigated physiological and histological parameters of cardiac muscle in mice deficient for both dystrophin and its homolog utrophin (double knockout = dko mice treated with NBD peptide. These dko mice show classic pathophysiological hallmarks of heart failure, including myocyte degeneration, an impaired force-frequency response and a severely blunted β-adrenergic response. Cardiac contractile function at baseline and frequencies and pre-loads throughout the in vivo range as well as β-adrenergic reserve was measured in isolated cardiac muscle preparations. In addition, we studied histopathological and inflammatory markers in these mice. Results At baseline conditions, active force development in cardiac muscles from NBD treated dko mice was more than double that of vehicle-treated dko mice. NBD treatment also significantly improved frequency-dependent behavior of the muscles. The increase in force in NBD-treated dko muscles to β-adrenergic stimulation was robustly restored compared to vehicle-treated mice. However, histological features, including collagen content and inflammatory markers were not significantly different between NBD-treated and vehicle-treated dko mice. Conclusions We conclude

  20. Hypoxic preconditioning improves survival of cardiac progenitor cells: role of stromal cell derived factor-1α-CXCR4 axis.

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    Fengdi Yan

    Full Text Available BACKGROUND: Cardiac progenitor cells (CPCs have been shown to be suitable in stem cell therapy for resurrecting damaged myocardium, but poor retention of transplanted cells in the ischemic myocardium causes ineffective cell therapy. Hypoxic preconditioning of cells can increase the expression of CXCR4 and pro-survival genes to promote better cell survival; however, it is unknown whether hypoxia preconditioning will influence the survival and retention of CPCs via the SDF-1α/CXCR4 axis. METHODS AND RESULTS: CPCs were isolated from adult mouse hearts and purified by magnetic activated cell sorting using c-kit magnetic beads. These cells were cultured at various times in either normoxic or hypoxic conditions, and cell survival was analyzed using flow cytometry and the expression of hypoxia-inducible factor-1α (HIF-1α, CXCR4, phosphorylated Akt and Bcl-2 were measured by Western blot. Results showed that the expression of pro-survival genes significantly increased after hypoxia treatment, especially in cells cultured in hypoxic conditions for six hours. Upon completion of hypoxia preconditioning from c-kit+ CPCs for six hours, the anti-apoptosis, migration and cardiac repair potential were evaluated. Results showed a significant enhancement in anti-apoptosis and migration in vitro, and better survival and cardiac function after being transplanted into acute myocardial infarction (MI mice in vivo. The beneficial effects induced by hypoxia preconditioning of c-kit+ CPCs could largely be blocked by the addition of CXCR4 selective antagonist AMD3100. CONCLUSIONS: Hypoxic preconditioning may improve the survival and retention of c-kit+ CPCs in the ischemic heart tissue through activating the SDF-1α/CXCR4 axis and the downstream anti-apoptosis pathway. Strategies targeting this aspect may enhance the effectiveness of cell-based cardiac regenerative therapy.

  1. Insulin-like growth factor 1 treatment of MSCs attenuates inflammation and cardiac dysfunction following MI.

    Science.gov (United States)

    Guo, Jun; Zheng, Dong; Li, Wen-feng; Li, Hai-rui; Zhang, Ai-dong; Li, Zi-cheng

    2014-12-01

    It has been reported that insulin-like growth factor 1 (IGF-1) promoted migration of endothelial cells and cardiac resident progenitor cells. In the previous study, we found the time-dependent and dose-dependent effects of IGF-1 treatment on the CXCR4 expression in MSCs in vitro, but it is still not clear whether IGF-1 pretreatment of MSCs may play anti-apoptotic and anti-inflammation role in myocardial infarction. In this study, we demonstrated that IGF-1-treated MSCs' transplantation attenuate cardiac dysfunction, increase the survival of engrafted cells in the ischemic heart, decrease myocardium cells apoptosis, and inhibit protein production and gene expression of inflammation cytokines tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6. IGF-1 pretreatment of MSCs may play anti-apoptotic and anti-inflammation roles in post-myocardial infarction.

  2. Altered activities of transcription factors and their related gene expression in cardiac tissues of diabetic rats.

    Science.gov (United States)

    Nishio, Y; Kashiwagi, A; Taki, H; Shinozaki, K; Maeno, Y; Kojima, H; Maegawa, H; Haneda, M; Hidaka, H; Yasuda, H; Horiike, K; Kikkawa, R

    1998-08-01

    Gene regulation in the cardiovascular tissues of diabetic subjects has been reported to be altered. To examine abnormal activities in transcription factors as a possible cause of this altered gene regulation, we studied the activity of two redox-sensitive transcription factors--nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1)--and the change in the mRNA content of heme oxygenase-1, which is regulated by these transcription factors in the cardiac tissues of rats with streptozotocin-induced diabetes. Increased activity of NF-kappaB and AP-1 but not nuclear transcription-activating factor, as determined by an electrophoretic mobility shift assay, was found in the hearts of 4-week diabetic rats. Glycemic control by a subcutaneous injection of insulin prevented these diabetes-induced changes in transcription factor activity. In accordance with these changes, the mRNA content of heme oxygenase-1 was increased fourfold in 4-week diabetic rats and threefold in 24-week diabetic rats as compared with control rats (P oxidative stress is involved in the activation of the transcription factors NF-kappaB and AP-1 in the cardiac tissues of diabetic rats, and that these abnormal activities of transcription factors could be associated with the altered gene regulation observed in the cardiovascular tissues of diabetic rats.

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

    Science.gov (United States)

    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.

  4. Out-of-hospital cardiac arrest: determinant factors for immediate survival after cardiopulmonary resuscitation1

    Science.gov (United States)

    Morais, Daniela Aparecida; Carvalho, Daclé Vilma; Correa, Allana dos Reis

    2014-01-01

    OBJECTIVE: to analyze determinant factors for the immediate survival of persons who receive cardiopulmonary resuscitation from the advanced support units of the Mobile Emergency Medical Services (SAMU) of Belo Horizonte. METHOD: this is a retrospective, epidemiological study which analyzed 1,165 assistance forms, from the period 2008 - 2010. The collected data followed the Utstein style, being submitted to descriptive and analytical statistics with tests with levels of significance of 5%. RESULTS: the majority were male, the median age was 64 years, and the ambulance response time, nine minutes. Immediate survival was observed in 239 persons. An association was ascertained of this outcome with "cardiac arrest witnessed by persons trained in basic life support" (OR=3.49; p<0.05; CI 95%), "cardiac arrest witnessed by Mobile Emergency Medical Services teams" (OR=2.99; p<0.05; CI95%), "only the carry out of basic life support" (OR=0.142; p<0.05; CI95%), and "initial cardiac rhythm of asystole" (OR=0.33; p<0.05; CI 95%). CONCLUSION: early access to cardiopulmonary resuscitation was related to a favorable outcome, and the non-undertaking of advanced support, and asystole, were associated with worse outcomes. Basic and advanced life support techniques can alter survival in the event of cardiac arrest. PMID:25296138

  5. Out-of-hospital cardiac arrest: determinant factors for immediate survival after cardiopulmonary resuscitation

    Directory of Open Access Journals (Sweden)

    Daniela Aparecida Morais

    2014-08-01

    Full Text Available OBJECTIVE: to analyze determinant factors for the immediate survival of persons who receive cardiopulmonary resuscitation from the advanced support units of the Mobile Emergency Medical Services (SAMU of Belo Horizonte.METHOD: this is a retrospective, epidemiological study which analyzed 1,165 assistance forms, from the period 2008 - 2010. The collected data followed the Utstein style, being submitted to descriptive and analytical statistics with tests with levels of significance of 5%.RESULTS: the majority were male, the median age was 64 years, and the ambulance response time, nine minutes. Immediate survival was observed in 239 persons. An association was ascertained of this outcome with "cardiac arrest witnessed by persons trained in basic life support" (OR=3.49; p<0.05; CI 95%, "cardiac arrest witnessed by Mobile Emergency Medical Services teams" (OR=2.99; p<0.05; CI95%, "only the carry out of basic life support" (OR=0.142; p<0.05; CI95%, and "initial cardiac rhythm of asystole" (OR=0.33; p<0.05; CI 95%.CONCLUSION: early access to cardiopulmonary resuscitation was related to a favorable outcome, and the non-undertaking of advanced support, and asystole, were associated with worse outcomes. Basic and advanced life support techniques can alter survival in the event of cardiac arrest.

  6. 59. Urinary tract infection in children after cardiac surgery: Incidence, risk factors and outcome

    Directory of Open Access Journals (Sweden)

    Rehana Shafi

    2015-10-01

    Conclusions: Foley catheter duration, presence of syndrome and prolonged PCICU and hospital stay were the main risk factors for CAUTI in postoperative pediatric cardiac patients. Resistant Gram-negative were the main cause for BSI with one third of CAUTI cases caused by MDRO or ESBL organisms. The cases with CAUTI were generally sicker and with more morbidity. The study will establish a baseline clinical indicator for monitoring quality improvement and the future measures to minimize CAUTI incidence, and its co-morbidity.

  7. Predictive factors for bleeding-related re-exploration after cardiac surgery: A prospective cohort study.

    Science.gov (United States)

    Lopes, Camila T; Brunori, Evelise H Fadini Reis; Santos, Vinicius Batista; Moorhead, Sue A; Lopes, Juliana de Lima; de Barros, Alba L Bottura Leite

    2016-04-01

    Bleeding-related re-exploration is a life-threatening complication after cardiac surgery. Nurses must be aware of important risk factors for this complication so that their assessment, monitoring and evaluation activities can be prioritized, focused and anticipated. To identify the predictive factors for bleeding-related re-exploration after cardiac surgery and to describe the sources of postoperative bleeding. This is a prospective cohort study at a tertiary cardiac school-hospital in São Paulo/SP, Brazil. Adult patients (n=323) submitted to surgical correction of acquired cardiac diseases were included. Potential risk factors for bleeding-related re-exploration within the 24 hours following admission to the intensive care unit were investigated in the patients' charts. A univariate analysis and a multiple analysis through logistic regression were conducted to identify the outcome predictors. The area under the receiver-operating characteristic curve was calculated as a measure of accuracy considering the cut-off points with the highest sensitivity and specificity. The univariate factors significantly associated with bleeding-related re-exploration were a lower preoperative platelet count, a lower number of bypasses in coronary artery bypass surgery and postoperatively, a lower body temperature, infusion of lower intravenous volume, a higher positive end-expiratory pressure during mechanical ventilation and transfusion of blood products. The independent predictors of bleeding-related re-exploration included postoperative red blood cell transfusion, and transfusion of fresh frozen plasma, platelet or cryoprecipitate units. These predictors had a sensitivity of 87.5%, a specificity of 99.28% and an accuracy of 97.93%. Blood product transfusion postoperatively is an independent predictor of bleeding-related re-exploration. Surgical errors prevailed as sources of bleeding. © The European Society of Cardiology 2015.

  8. TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui; Wang, Lin; Song, Li; Zhang, Yan-Wan; Ye, Jue; Xu, Rui-Xia; Shi, Na; Meng, Xian-Min [Core Laboratory, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

    2013-02-01

    The phosphorylation of cardiac troponin I (cTnI) plays an important role in the contractile dysfunction associated with heart failure. Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. The purpose of this study was to investigate whether TNNI3K can phosphorylate cTnI at specific sites and to examine whether the phosphorylation of cTnI caused by TNNI3K can regulate cardiac myofilament contractile function. Co-immunoprecipitation was performed to confirm that TNNI3K could interact with cTnI. Kinase assays further indicated that TNNI3K did not phosphorylate cTnI at Ser23/24 and Ser44, but directly phosphorylated Ser43 and Thr143 in vitro. The results obtained for adult rat cardiomyocytes also indicated that enhanced phosphorylation of cTnI at Ser43 and Thr143 correlated with rTNNI3K (rat TNNI3K) overexpression, and phosphorylation was reduced when rTNNI3K was knocked down. To determine the contractile function modulated by TNNI3K-mediated phosphorylation of cTnI, cardiomyocyte contraction was studied in adult rat ventricular myocytes. The contraction of cardiomyocytes increased with rTNNI3K overexpression and decreased with rTNNI3K knockdown. We conclude that TNNI3K may be a novel mediator of cTnI phosphorylation and contribute to the regulation of cardiac myofilament contraction function.

  9. Delayed xenograft rejection of pig-to-baboon cardiac transplants after cobra venom factor therapy.

    Science.gov (United States)

    Kobayashi, T; Taniguchi, S; Neethling, F A; Rose, A G; Hancock, W W; Ye, Y; Niekrasz, M; Kosanke, S; Wright, L J; White, D J; Cooper, D K

    1997-11-15

    This study sought to (i) investigate the efficacy of cobra venom factor (CVF) in preventing hyperacute rejection (HAR) after pig-to-baboon heart transplantation, (ii) examine the effect of additional splenectomy (Spx) and pharmacologic immunosuppression (IS), and (iii) study delayed graft rejection when HAR is avoided by complement depletion. Eleven recipient baboons received heterotopic pig heart transplants. Three received either no therapy or IS (cyclosporine + methylprednisolone +/- cyclophosphamide +/- methotrexate) at clinically well-tolerated doses, with graft survival for only 40, 32, and 15 min, respectively. Two received CVF+/-Spx, which extended survival to 5 and 6 days, respectively. Six underwent Spx + CVF therapy + IS; graft survival was 3 hr (technical complication), 6 days (death from sepsis), 10, 12, and 22 days (vascular rejection), and <25 days (euthanized for viral pneumonia with a functioning graft that showed histopathologic features of vascular rejection). Dense deposition of IgM and, to a lesser extent, IgG and IgA were seen on the endothelial cells within 1 hr of transplantation, but only trace levels of complement deposition were present in CVF-treated recipients. Within approximately 5-12 days, cardiac xenografts showed progressive infiltration by mononuclear cells, consisting primarily of activated macrophages producing tumor necrosis factor-alpha and small numbers of natural killer cells; T and B cells were absent. We conclude that (i) CVF prevents HAR, (ii) the addition of Spx + IS delays rejection, but (iii) the early deposition of antibody leads to progressive graft injury, resulting in (iv) delayed vascular rejection. Our findings indicate that the features of delayed xenograft rejection described in small animal models also occur in the pig-to-baboon model, and that rejection may occur in a complement-independent manner from the effects of antibody and/or host macrophages.

  10. Postoperative delirium and factors related in a cardiac surgery unit care

    Directory of Open Access Journals (Sweden)

    Julia de las Pozas Abril

    2011-07-01

    Full Text Available Objective: Describe the incidence of postoperative delirium and related risk factors associated with this complication in patients undergoing cardiac surgery. Method: Cohort study conducted for 3 months in a sample of 105 patients undergoing cardiac surgery in a hospital in Madrid. The emergence of delirium with scale ICDSC (Intensive Care Delirium Screening Checklist was measured during the first five days of postoperative and collected data on preoperative, intra-operative and post-operative factors to relate to the emergence of delirium. Results: 95 Patients studied, 15 of them developed delirium, which means an incidence of 15.7%. We found that there was a significant relationship between delirium appearance and age of the patients, the presence of atrial fibrillation, intubation orotraqueal time and the administration of adrenaline during the immediate post-operative management. The multivariable model showed the duration of orotraqueal intubation to be independently associated with delirium. Conclusions: The incidence of delirium found in this study as well as the identification of the time of orotraqueal intubation as independent risk factor supposes a new contribution to the knowledge of this postoperative complication and allow us to begin to evaluate its importance in the unit of cardiac surgery.

  11. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

    Science.gov (United States)

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T; Komorowski, Richard; Fish, Brian L; Migrino, Raymond Q; Harmann, Leanne; Hopewell, John W; Kronenberg, Amy; Patel, Shailendra; Moulder, John E; Baker, John E

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

  12. Effect of Different Styles of Coronary Heart Disease and Its Risk Factors on Cardiac Remodeling and Dysfunction

    Institute of Scientific and Technical Information of China (English)

    Wang Xuelihong; Guo Xuewei; Ma Yushan; Su Shuangshan; Guo Xiangyu

    2006-01-01

    Objectives To evaluate the effect of different styles of coronary heart disease (CHD),different regions of acute myocardial infarction (AMI),its risk factors and branches of coronary stenosis on left ventricular remodeling and dysfunction by applying echocardiography. Methods 251 patients with CHD and 96 patients without CHD (NoCHD) were verified by selective coronary angiography. CHD patients were divided into stable angina pectoris(SAP) 26, unstable angina pectoris(UAP) 53, acute myocardial infarction (AMI) 140 and old myocardial infarction (OMI) 30 based on clinical situation, cTnT, cardiac enzyme and ECG. AMI patients were further divided into subgroups including acute anterior myocardial infarct (Aa,n =53), acute inferior myocardial infarction(Ai, n=54)and Aa+Ai(n=33) based on ECG. Cardiac parameters:end-diastolic interventricular septum thickness (IVSd),end-diastolic left ventricular internal diameter(LVd ),left ventricular mass (LM), end-diastolic left ventricular volume (EDV), end-systolic left ventricular volume (ESV) and left ventricular ejection fraction(LVEF) were measured by ACUSON 128XP/10 echocardiography.Multiples linear regression analyses were performed to test statistical associations between LVEF and the involved branches of coronary stenosis, blood pressure, lipids, glucose and etc after onset of myocardial infarction. Results EDV and ESV were increased and LVEF decreased on patients with AMI,OMI and UAP (P<0.05-0.0001). LM was mainly increased in patients with OMI (P<0.01) and LVd was mainly enlarged in patients with AMI. EF was significantly decreased and EDV, ESV, LM and LVd were remarkably increased in AMI patients with Aa and Aa+Ai. With the multiple linear regression analyses by SPSS software, we found that LVEF was negatively correlated to the involved branches of coronary stenosis as well as to systolic blood pressure after onset of myocardial infarction while there was no significant correlation between LVEF and other factors. LVEF

  13. Fast, reproducible measurement of the vascular input function in mice using constrained reconstruction and cardiac sampling.

    Science.gov (United States)

    Ragan, Dustin K; Lai, Stephen Y; Bankson, James A

    2011-05-01

    Dynamic contrast-enhanced MRI is often used to assess the response to therapy in small animal models of cancer. Rigorous quantification of dynamic contrast-enhanced MRI data using common pharmacokinetic models requires dynamic determination of the concentration of contrast in tumor tissue and in blood. Measurement of the blood concentration, or vascular input function (VIF), requires high temporal resolution and is prone to distortion as a result of flow and partial volume artifacts when measured in local blood vessels. We have developed a strategy for the robust measurement of VIF in mice that uses a constrained reconstruction algorithm to enable sampling from the left ventricle of the heart. The feasibility of the algorithm and its resistance to cardiac motion are demonstrated in vivo and through numerical simulations. VIF sampling is interleaved with slices dedicated to tumor coverage to yield a fast VIF sampling period (81 ms) that is decoupled from the temporal resolution of tumor data (3.9 s). The algorithm provides results that agree with fully encoded measurements in the slowly varying component of VIF to within a 4% root-mean-square signal difference. Analysis of a parametric representation of VIFs measured in a population of mice showed a significant reduction in variations observed within subjects (5%-58% over four parameters; p model of anaplastic thyroid cancer revealed a decrease in the variation of pharmacokinetic parameters between mice by a factor of two. Copyright © 2010 John Wiley & Sons, Ltd.

  14. Chronic Endurance Exercise Impairs Cardiac Structure and Function in Middle-Aged Mice with Impaired Nrf2 Signaling

    Directory of Open Access Journals (Sweden)

    Gobinath Shanmugam

    2017-05-01

    Full Text Available Nuclear factor erythroid 2 related factor 2 (Nrf2 signaling maintains the redox homeostasis and its activation is shown to suppress cardiac maladaptation. Earlier we reported that acute endurance exercise (2 days evoked antioxidant cytoprotection in young WT animals but not in aged WT animals. However, the effect of repeated endurance exercise during biologic aging (WT characterized by an inherent deterioration in Nrf2 signaling and pathological aging (pronounced oxidative susceptibility—Nrf2 absence in the myocardium remains elusive. Thus, the purpose of our study was to determine the effect of chronic endurance exercise-induced cardiac adaptation in aged mice with and without Nrf2. Age-matched WT and Nrf2-null mice (Nrf2−/− (>22 months were subjected to 6 weeks chronic endurance exercise (25 meter/min, 12% grade. The myocardial redox status was assessed by expression of antioxidant defense genes and proteins along with immunochemical detection of DMPO-radical adduct, GSH-NEM, and total ubiquitination. Cardiac functions were assessed by echocardiography and electrocardiogram. At sedentary state, loss of Nrf2 resulted in significant downregulation of antioxidant gene expression (Nqo1, Ho1, Gclm, Cat, and Gst-α with decreased GSH-NEM immuno-fluorescence signals. While Nrf2−/− mice subjected to CEE showed an either similar or more pronounced reduction in the transcript levels of Gclc, Nqo1, Gsr, and Gst-α in relation to WT littermates. In addition, the hearts of Nrf2−/− on CEE showed a substantial reduction in specific antioxidant proteins, G6PD and CAT along with decreased GSH, a pronounced increase in DMPO-adduct and the total ubiquitination levels. Further, CEE resulted in a significant upregulation of hypertrophy genes (Anf, Bnf, and β-Mhc (p < 0.05 in the Nrf2−/− hearts in relation to WT mice. Moreover, the aged Nrf2−/− mice exhibited a higher degree of cardiac remodeling in association with a significant decrease in

  15. A retrospective study of echocardiographic cardiac function and structure in adolescents with congenital scoliosis

    Institute of Scientific and Technical Information of China (English)

    LIANG Jin-qian; QIU Gui-xing; SHEN Jian-xiong; LEE Chia-I; WANG Yi-peng; ZHANG Jian-guo; ZHAO Hong

    2009-01-01

    Background Patients with congenital scoliosis often also have intraspinaJ abnormalities and other organ defects, and few studies of the effects of congenital scoliosis on cardiac function and structure have been published.Methods A total of 215 adolescent patients with congenital scoliosis (average age, 13.58 years) underwent preoperative echocardiography and were then assigned to subgroups according to apex vertebral rotation, side of convexity, curvature severity in the coronal and sagittal planes, type of deformity, and sex. Differences between the subgroups were compared by independent-samples ttest or a one-factor analysis of variance.Results We observed statistically significant differences between patients with right-sided scoliosis curvature and those with left-sided scoliosis curvature, respectively, in left ventricular inner diameter at end-diastole ((39.39±4.66)mm vs (41.74±4.90)mm), left ventricular inner diameter at end-systole ((24.8±3.45)mm vs (25.92±3.07)mm), interventricular septum thickness at end-diastole ((5.66±0.98)mm vs (5.98±1.03)mm), and posterior wail of left ventricle at end-diastole ((5.61±0.98)mm vs (6.06±1.20)mm). When the patients were evaluated by coronal plane Cobb angle, significant differences were found between those with Cobb angle of 40Ω-80Ω and of >80Ω in left ventricular inner diameter at end-diastole ((40.97±5.06)mm vs (38.98±4.45)mm) and left ventricular inner diameter at end-systole ((25.53±3.39)mm vs (24.36±3.14)mm), respectively. When the patients were evaluated by sagittal plane Cobb angle (40Ω, group 3), significant differences were found in right ventricular diameter between those with Cobb angle of 40Ω ((23.83±3.39)mm vs (24.90±3.30)mm), respectively. No significant differences were found in ejection fraction and fractional shortening between patients according to apex vertebral rotation, side of convexity, coronal plane and sagittal plane Cobb angles, type of deformity, or sex

  16. Cardiac Function Evaluation Analyzing Spectral Components due to the Consumption of Energy Drinks

    Directory of Open Access Journals (Sweden)

    Md. Bashir Uddin

    2014-05-01

    Full Text Available The aim of this study is to investigate the effect of energy drinks consumption on cardiac function of human being by analyzing the spectral components of pulse and ECG of several healthy people. Using pulse transducer connected with MP36 (Biopac, USA data acquisition unit, pulse recordings were performed. With electrode lead set connected to the same MP36 data acquisition unit, ECG recordings were also performed. At before and after the consumption of energy drinks available in Bangladesh, pulse and ECG recordings as well as analysis were performed with Biopac software. After having energy drinks, the spectral components such as power of spectral density and amplitude of fast Fourier transform of pulse signal decreased about 47.5 and 37%, respectively. In case of ECG signal, the spectral components such as power of spectral density and amplitude of fast Fourier transform increased about 17 and 7.5% within a short interval about 0-20 min, then effective decrements about 10 and 18.5%, respectively started for long duration. Analyzing spectral parameters, the findings highlight the adverse impacts on cardiac function which may cause cardiac abnormality as well as severe cardiac disease due to the regular consumption of energy drinks.

  17. Docetaxel does not impair cardiac autonomic function in breast cancer patients previously treated with anthracyclines.

    Science.gov (United States)

    Ekholm, Eeva; Rantanen, Virpi; Syvänen, Kari; Jalonen, Jarmo; Antila, Kari; Salminen, Eeva

    2002-04-01

    The effects of docetaxel treatment on autonomic cardiac function was studied with 24-h ECG recordings in breast cancer patients pretreated with anthracyclines. Twenty-four women were evaluated before docetaxel treatment and after 3-4 courses of docetaxel 100 mg/m(2). The heart rate, cardiac extrasystoles and heart rate variability (HRV) in both the time and frequency domain were assessed from 24-h ECG recordings. The acute effects of docetaxel were calculated from 1-h recordings immediately prior to, during and after infusion. Long-term effects were evaluated from 24-h recordings performed before treatment and after 3-4 courses of docetaxel. There was no increase in the number of cardiac extrasystoles during docetaxel infusion. The number of ventricular extrasystoles decreased from 14 (23) to 7 (14) during and 5 (10) after the first infusion (p=0.02). The heart rate, HRV and extrasystoles were similar before and after 3-4 courses of docetaxel. The treatment did not abolish circadian variability of the heart rate. Docetaxel did not deteriorate autonomic cardiac function. In conclusion, our findings suggest that docetaxel does not have harmful cumulative effects on autonomic control of the heart and is therefore unlikely to be cardiotoxic.

  18. A VEGF delivery system targeting MI improves angiogenesis and cardiac function based on the tropism of MSCs and layer-by-layer self-assembly.

    Science.gov (United States)

    Liu, Ge; Li, Li; Huo, Da; Li, Yanzhao; Wu, Yangxiao; Zeng, Lingqing; Cheng, Panke; Xing, Malcolm; Zeng, Wen; Zhu, Chuhong

    2017-05-01

    Myocardial infarction (MI) is a serious ischemic condition affecting many individuals around the world. Vascular endothelial growth factor (VEGF) is considered a promising factor for enhancing cardiac function by promoting angiogenesis. However, the lack of a suitable method of VEGF delivery to the MI area is a serious challenge. In this study, we screened a suitable delivery carrier with favorable biocompatibility that targeted the MI area using the strategy of an inherent structure derived from the body and that was based on characteristics of the MI. Mesenchymal stem cells (MSCs) are important infiltrating cells that are derived from blood and have an inherent tropism for the MI zone. We hypothesized that VEGF-encapsulated MSCs targeting MI tissue could improve cardiac function by angiogenesis based on the tropism of the MSCs to the MI area. We first developed VEGF-encapsulated MSCs using self-assembled gelatin and alginate polyelectrolytes to improve angiogenesis and cardiac function. In vitro, the results showed that VEGF-encapsulated MSCs had a sustained release of VEGF and tropism to SDF-1. In vivo, VEGF-encapsulated MSCs migrated to the MI area, enhanced cardiac function, perfused the infarcted area and promoted angiogenesis. These preclinical findings suggest that VEGF-loaded layer-by-layer self-assembled encapsulated MSCs may be a promising and minimally invasive therapy for treating MI. Furthermore, other drugs loaded to layer-by-layer self-assembled encapsulated MSCs may be promising therapies for treating other diseases.

  19. Cardiac contraction and calcium transport function aftersevere burn injury in rats

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To examine the function change of myocardial calcium transports and determined what role the change plays in cardiac dysfunction after severe burn injury in rats. Methods: The contraction and relaxation properties of the left ventricle (LV) were studied in the isolated hearts preparations of Wistar rats at 3, 8, and 24 h after a 30%TBSA (total body surface area) full-thickness burn. The calcium transport function of the sarcoplasmic reticulum (SR) was measured by the millipore filtration technique. Results: The maximal rate of LV pressure (± dp/dtmax) of the burn group was significantly lower than that of the control group (P < 0.01). In addition, the calciumdependent ATPase activity and the coupling ratio of SR were also markedly depressed. Conclusions: It indicates that the decrease in the SR calcium transport function is one of the important mechanisms for the cardiac contractile dysfunction after severe burn injury.

  20. The diagnostic and therapeutic aspects of loss-of-function cardiac sodium channelopathies in children.

    Science.gov (United States)

    Chockalingam, Priya; Clur, Sally-Ann B; Breur, Johannes M P J; Kriebel, Thomas; Paul, Thomas; Rammeloo, Lukas A; Wilde, Arthur A M; Blom, Nico A

    2012-12-01

    Loss-of-function sodium channelopathies manifest as a spectrum of diseases including Brugada syndrome (BrS) and cardiac conduction disease. To analyze the diagnostic and therapeutic aspects of these disorders in children. Patients aged ≤ 16 years with genetically confirmed loss-of-function sodium channelopathies (SCN5A mutation), presenting with cardiac symptoms, positive family history, and/or abnormal electrocardiogram (ECG), were included. Abnormal ECG consisted of type 1 BrS ECG and/or prolonged conduction intervals (PR interval/QRS duration > 98th percentile for age). Among the cohort (n = 33, age 6 ± 5 years, 58% male subjects, 30% probands), 14 (42%) patients were symptomatic, presenting with syncope (n = 5), palpitations (n = 1), supraventricular arrhythmias (n = 3), aborted cardiac arrest (n = 3), and sudden cardiac death (n = 2). Heart rate was 91 ± 26 beats/min, PR interval 168 ± 35 ms, QRS duration 112 ± 20 ms, and heart-rate corrected QT interval 409 ± 26 ms. Conduction intervals were prolonged in 28 (85%) patients; 6 of these patients also had spontaneous type 1 BrS ECG. Eight fever-associated events occurred in 6 patients; 2 of these were vaccination-related fever episodes. Treatment included aggressive antipyretics during fever in all patients; antiarrhythmic treatment included implantable cardioverter-defibrillator (n = 4), pacemaker (n = 2), and beta-blockers, either alone (n = 3) or in combination with device (n = 2). During follow-up (4 ± 4 years), 2 previously symptomatic patients had monomorphic ventricular tachycardia; there were no deaths. Diagnosis of loss-of-function sodium channelopathies in children relies on cardiac symptoms, family history, and ECG. Fever and vaccination are potential arrhythmia triggers; conduction delay is the commonest finding on ECG. Beta-blockers have a role in preventing tachycardia-induced arrhythmias; implantable cardioverter-defibrillator should probably be reserved for severe cases. Copyright © 2012

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

    Science.gov (United States)

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

    2016-06-01

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

  2. Assessment of inflammatory factors and cardiac troponin T in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Falaknazi Kianoosh

    2009-01-01

    Full Text Available Hemodialysis (HD patients suffer from chronic inflammations which make them at increased risk of cardiovascular diseases. The purpose of this study was to see if there is a significant association between inflammatory factors such as ferritin and C-reactive protein (CRP as well as troponin T in patients on HD. We assessed these serum factors as well as other known cardiac risk factors in 53 patients on HD. The serum ferritin and CRP levels were measured by chemiluminescence′s immune assay while troponin T levels were measured by electrochemist luminescence immune assay. We found that serum concentrations of CRP and ferritin were not significantly higher in patients on HD with known cardiac risk factors (compared with the control group (p< 0.05. However, the serum troponin T levels in HD patients with cardiovascular risk factors were significantly higher than the control group. Our study suggests that elevated serum troponin T levels can play an important role as a predictor of cardiovascular disease in HD patients. Also, inflammatory factors such as CRP and ferritin may be influenced by chronic inflammation or nutritional status of these patients.

  3. Subject specific BOLD fMRI respiratory and cardiac response functions obtained from global signal.

    Science.gov (United States)

    Falahpour, Maryam; Refai, Hazem; Bodurka, Jerzy

    2013-05-15

    Subtle changes in either breathing pattern or cardiac pulse rate alter blood oxygen level dependent functional magnetic resonance imaging signal (BOLD fMRI). This is problematic because such fluctuations could possibly not be related to underlying neuronal activations of interest but instead the source of physiological noise. Several methods have been proposed to eliminate physiological noise in BOLD fMRI data. One such method is to derive a template based on average multi-subject data for respiratory response function (RRF) and cardiac response function (CRF) by simultaneously utilizing an external recording of cardiac and respiratory waveforms with the fMRI. Standard templates can then be used to model, map, and remove respiration and cardiac fluctuations from fMRI data. Utilizing these does not, however, account for intra-subject variations in physiological response. Thus, performing a more individualized approach for single subject physiological noise correction becomes more desirable, especially for clinical purposes. Here we propose a novel approach that employs subject-specific RRF and CRF response functions obtained from the whole brain or brain tissue-specific global signals (GS). Averaging multiple voxels in global signal computation ensures physiological noise dominance over thermal and system noise in even high-spatial-resolution fMRI data, making the GS suitable for deriving robust estimations of both RRF and CRF for individual subjects. Using these individualized response functions instead of standard templates based on multi-subject averages judiciously removes physiological noise from the data, assuming that there is minimal neuronal contribution in the derived individualized filters. Subject-specific physiological response functions obtained from the GS better maps individuals' physiological characteristics.

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

    Science.gov (United States)

    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

  5. Ultrasonographic and histological evaluation of the effects of long-term carotid catheterization on cardiac function in NMRI mice

    DEFF Research Database (Denmark)

    Teilmann, Anne C; Thomsen, Morten B; Ihms, Elizabeth A

    2017-01-01

    weights were compared between groups. No effects on echocardiography parameters, histology, body weights or cardiac weights could be found between groups. In the present study, implantation of a carotid catheter with catheter tip placement in the proximal brachiocephalic trunk had minimal influence...... to the small body size of the mouse, a catheter tends to occupy a great part of even the larger vessel lumens, and this may increase vascular resistance with potential pathophysiological impacts on the heart. The present study compared cardiac function of catheterized mice, with catheter tip placement...... on cardiac and aortic physiology and did not induce significant cardiac changes....

  6. Impairment of diastolic function in adult patients affected by osteogenesis imperfecta clinically asymptomatic for cardiac disease: casuality or causality?

    Science.gov (United States)

    Migliaccio, Silvia; Barbaro, Giuseppe; Fornari, Rachele; Di Lorenzo, Gabriella; Celli, Mauro; Lubrano, Carla; Falcone, Stefania; Fabbrini, Elisa; Greco, Emanuela; Zambrano, Anna; Brama, Marina; Prossomariti, Giancarlo; Marzano, Sara; Marini, Mario; Conti, Francesco; D'Eufemia, Patrizia; Spera, Giovanni

    2009-01-09

    Osteogenesis imperfecta (OI) is a rare inherited connective disorder causing increased bone fragility and low bone mass. OI includes severe bone fragility, impaired dentinogenesis, with less common alterations in the joints, blood vessels, heart valves, skin. Interestingly, description of left ventricular rupture, aortic dissection and heart valves incompetence has been previously described. Death may occur in OI patients for cardiac disease in asyntomatic subjects. Aim of our study has been to evaluate the presence of potential subclinical cardiac disorders and to characterize cardiac functional parameters by echocardiography in adults with OI in absence of cardiac symptoms. Forty patients (21 females and 19 males) affected by type I, III, IV OI and 40 control subjects (20 females and 20 males) were evaluated in the study. Patients and controls underwent clinical examination, screening for endocrine and metabolic disorders, 12-lead electrocardiogram and echocardiogram. In particular, all subjects were evaluated by two-dimensional echocardiography with continuous- and pulse-wave Doppler. Patients and controls belonged to NYHA class I and no significant electrocardiographic alteration was documented in both groups. Thirty-eight patients (95%) showed valvular regurgitation compared to one control subject (2.5%; Prelaxation time (IRT) was increased by 47% (95% CI: 26% to 53%; Pmetabolic alterations. These diastolic echocardiographic parameters might worsen over time, especially if other cardiovascular risk factors (e.g., smoking, hypertension, metabolic and endocrine alterations) are not carefully checked, monitored and treated. In the context of a multidisciplinary evaluation of OI patients, our data suggest that a careful cardiological evaluation of these patients is indicated beside skeletal evaluation and therapeutical skeletal options.

  7. Clinical characteristics and vital and functional prognosis of out-of-hospital cardiac arrest survivors admitted to five cardiac intensive care units.

    Science.gov (United States)

    Loma-Osorio, Pablo; Aboal, Jaime; Sanz, Maria; Caballero, Ángel; Vila, Montserrat; Lorente, Victoria; Sánchez-Salado, José Carlos; Sionis, Alessandro; Curós, Antoni; Lidón, Rosa-Maria

    2013-08-01

    Survivors of out-of-hospital cardiac arrest constitute an increasing patient population in cardiac intensive care units. Our aim was to characterize these patients and determine their vital and functional prognosis in accordance with the latest evidence. A multicenter, prospective register was constructed with information from patients admitted to 5 cardiac intensive care units from January 2010 through January 2012 with a diagnosis of resuscitated out-of-hospital cardiac arrest. The information included clinical status, cardiac arrest characteristics, in-hospital course, and vital and neurologic status at discharge and at 6 months. A total of 204 patients were included. In 64% of cases, a first shockable rhythm was identified. The time to return of spontaneous circulation was 29 (18) min. An etiologic diagnosis was made in 86% of patients; 44% were discharged with no neurologic sequelae; 40% died in the hospital. At 6 months, 79% of survivors at discharge were still alive and neurologically intact with minimal sequelae. Short resuscitation time, first recorded rhythm, pH on admission >7.1, absence of shock, and use of hypothermia were the independent variables associated with a good neurologic prognosis. Half the patients who recovered from out-of-hospital cardiac arrest had good neurologic prognosis at discharge, and 79% of survivors were alive and neurologically intact after 6 months of follow-up. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  8. [Sudden Cardiac Death of Young Persons: Risk Factors, Causes, Morphological Equivalents].

    Science.gov (United States)

    Shilova, M A; Mamedov, M N

    2015-01-01

    The article contains literature review on the problem of causes of sudden cardiac death (SCD) among young people as well as results of author's own retrospective study of deaths of persons before 39 years based on forensic autopsies performed during 10 year period. The study of structure and dynamics of causes of death, its risk factors and the role of connective tissue dysplasia in development of terminal symptomocomlexes allowed to establish that main mechanism of SCD in young people was arrhythmogenic developing as a response to provoking factors--physical effort, psychoemotional stress, consumption of light alcoholic beverages.

  9. Adenylyl cyclase type 6 overexpression selectively enhances beta-adrenergic and prostacyclin receptor-mediated inhibition of cardiac fibroblast function because of colocalization in lipid rafts.

    Science.gov (United States)

    Liu, Xiaoqiu; Thangavel, Muthusamy; Sun, Shu Qiang; Kaminsky, Joseph; Mahautmr, Penden; Stitham, Jeremiah; Hwa, John; Ostrom, Rennolds S

    2008-06-01

    Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Fibroblasts are activated by factors such as transforming growth factor beta and inhibited by agents that elevate 3',5'-cyclic adenosine monophosphate (cAMP) levels. cAMP signal generation and response is known to be compartmentalized in many cell types in part through the colocalization of receptors and specific adenylyl cyclase isoforms in lipid rafts and caveolae. The present study sought to define the localization of key G protein-coupled receptors with adenylyl cyclase type 6 (AC6) in lipid rafts of rat cardiac fibroblasts and to determine if this colocalization was functionally relevant. We found that cardiac fibroblasts produce cAMP in response to agonists for beta-adrenergic (isoproterenol), prostaglandin EP2 (butaprost), adenosine (adenosine-5'-N-ethylcarboxamide, NECA), and prostacyclin (beraprost) receptors. Overexpression of AC6 increased cAMP production stimulated by isoproterenol and beraprost but not by butaprost or NECA. A key function of fibroblasts is the production of collagen. Isoproterenol- and beraprostmediated inhibition of collagen synthesis was also enhanced by AC6 overexpression, while inhibition by butaprost and NECA were unaltered. Lipid raft fractions from cardiac fibroblasts contain the preponderance of beta-adrenergic receptors and AC6 but exclude EP2 receptors. While we could not determine the localization of native prostacyclin receptors, we were able to determine that epitope-tagged prostanoid IP receptors (IPR) expressed in COS7 cells did localize, in part, in lipid raft fractions. These findings indicate that IP receptors are expressed in lipid rafts and can activate raft-localized AC isoforms. AC6 is completely compartmentized in lipid raft domains where it is activated solely by coresident G protein-coupled receptors to regulate cardiac fibroblast function.

  10. Efficacy of Atorvastatin combined with adipose-derived mesenchymal stem cell transplantation on cardiac function in rats with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Anping Cai; Jian Kuang; Gang Dai; Weiyi Mai; Dongdan Zheng; Yugang Dong; Ruofeng Qiu; Yuli Huang; Yuanbin Song; Zhigao Jiang; Shaoqi Rao; Xinxue Liao

    2011-01-01

    Mesenchymal stem cells (MSCs) have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction (AMI).However,the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates.Therefore,the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI.In this paper,MSCs isolated from rat inguinal fat tissues were termed as adiposederived mesenchymal stem cells (ASCs),and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs.Fourteen days later,GATA-4 (a transcription factor) and cardiac troponin-Ⅰ were detected by cellular immunofluorescence.Atorvastatin (Ator group) or vehicle (control group) was administrated for the first 24 h after AMI production in rats.Fourteen days later,inflammatory parameters and cardiac function were evaluated.The other surviving rats were injected with a total of 1 × 106 co-ASCs/100 μ1 phosphate-buffered saline (PBS),1 × 106 ASCs/100 μl PBS,or 100 μl PBS.Twenty-eight days after cell injection,survival and differentiated rates of transplanted cells and cardiac function were evaluated.The percentage of GATA-4 expression in co-ASCs was 28.5% ± 5.6% and of cardiac troponin-Ⅰ was 22.8% ±3.2%.Compared with the control group,the number of infiltrating inflammatory cells,myeloperoxidase activity,inflammatory cytokines (VCAM-1, TNF-α, Hs-CRP)mRNA expression,and Bax protein expression were significantly reduced in the three Ator groups,accompanied by a significant improvement of Bcl-2 protein expression and cardiac function (P<0.05).Compared with the Ator2 + ASCs group and Con + co-ASCs group,the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I-positive transplanted cells,concomitant with cardiac function,were improved most prominently in the Ator3 + co-ASCs group (P<0

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

    Science.gov (United States)

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

    2017-01-01

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

  12. Leptin as a cardiac pro-hypertrophic factor and its potential role in the development of heart failure.

    Science.gov (United States)

    Karmazyn, Morris; Rajapurohitam, Venkatesh

    2014-01-01

    The identification of the adipocyte as a source of production of biologically-active peptides has materialized into an active area of research related to the role of these peptides in physiology and pathophysiology. Moreover, this research has resulted in the identification of the adipocyte as an endocrine organ producing potent bioactive compounds. An increasing number of these adipokines are being identified, the first of which was leptin, a product of the obesity gene whose primary function is to act as a satiety factor but which is now known to exert a myriad of effects. It is now recognized that virtually all adipokines produce effects on numerous organ systems including the heart and many of these, including leptin, are produced by cardiac tissue. Here we focus primarily on the diverse effects of leptin on the heart especially as it pertains to hypertrophy and discuss the potential cell signaling mechanisms underlying their actions. Current evidence suggests that leptin is a cardiac hypertrophic factor and from clinical studies there is evidence that hyperleptinemia is associated with cardiovascular risk especially as it pertains to heart failure. While more substantial research needs to be carried out, leptin may represent a potential link between obesity, which is associated with hyperleptinemia, and increased cardiovascular risk.

  13. APACHE II score, rather than cardiac function, may predict poor prognosis in patients with stress-induced cardiomyopathy.

    Science.gov (United States)

    Joe, Byung-Hyun; Jo, Uk; Kim, Hyun-Soo; Park, Chang-Bum; Hwang, Hui-Jeong; Sohn, Il-Suk; Jin, Eun-Sun; Cho, Jin-Man; Park, Jeong-Hwan; Kim, Chong-Jin

    2012-01-01

    While the disease course of stress-induced cardiomyopathy (SIC) is usually benign, it can be fatal. The prognostic factors to predict poorer outcome are not well established, however. We analyzed the Acute Physiology And Chronic Health Evaluation (APACHE) II score to assess its value for predicting poor prognosis in patients with SIC. Thirty-seven consecutive patients with SIC were followed prospectively during their hospitalization. Clinical factors, including APACHE II score, coronary angiogram, echocardiography and cardiac enzymes at presentation were analyzed. Of the 37 patients, 27 patients (73%) were women. The mean age was 66.1 ± 15.6 yr, and the most common presentation was chest pain (38%). Initial echocardiographic left ventricular ejection fraction (EF) was 42.5% ± 9.3%, and the wall motion score index (WMSI) was 1.9 ± 0.3. Six patients (16%) expired during the follow-up period of hospitalization. Based on the analysis of characteristics and clinical factors, the only predictable variable in prognosis was APACHE II score. The patients with APACHE II score greater than 20 had tendency to expire than the others (P = 0.001). Based on present study, APACHE II score more than 20, rather than cardiac function, is associated with mortality in patients with SIC.

  14. Preserved cardiac function despite marked impairment of cAMP generation.

    Directory of Open Access Journals (Sweden)

    Mei Hua Gao

    Full Text Available OBJECTIVES: So many clinical trials of positive inotropes have failed, that it is now axiomatic that agents that increase cAMP are deleterious to the failing heart. An alternative strategy is to alter myocardial Ca(2+ handling or myofilament response to Ca(2+ using agents that do not affect cAMP. Although left ventricular (LV function is tightly linked to adenylyl cyclase (AC activity, the beneficial effects of AC may be independent of cAMP and instead stem from effects on Ca(2+ handling. Here we ask whether an AC mutant molecule that reduces LV cAMP production would have favorable effects on LV function through its effects on Ca(2+ handling alone. METHODS AND RESULTS: We generated transgenic mice with cardiac-directed expression of an AC6 mutant (AC6mut. Cardiac myocytes showed impaired cAMP production in response to isoproterenol (74% reduction; p<0.001, but LV size and function were normal. Isolated hearts showed preserved LV function in response to isoproterenol stimulation. AC6mut expression was associated with increased sarcoplasmic reticulum Ca(2+ uptake and the EC50 for SERCA2a activation was reduced. Cardiac myocytes isolated from AC6mut mice showed increased amplitude of Ca(2+ transients in response to isoproterenol (p = 0.0001. AC6mut expression also was associated with increased expression of LV S100A1 (p = 0.03 and reduced expression of phospholamban protein (p = 0.01. CONCLUSION: LV AC mutant expression is associated with normal cardiac function despite impaired cAMP generation. The mechanism appears to be through effects on Ca(2+ handling - effects that occur despite diminished cAMP.

  15. Haemodynamics and cardiac function during robotic-assisted laparoscopic prostatectomy in steep Trendelenburg position.

    Science.gov (United States)

    Haas, Sebastian; Haese, Alexander; Goetz, Alwin E; Kubitz, Jens C

    2011-12-01

    Robotic-assisted laparoscopic prostatectomy (RALP) is usually performed in steep Trendelenburg position, which can be associated with cardiac impairment due to positioning and capnoperitoneum. This study investigated haemodynamic consequences and cardiac function in this type of surgery and evaluated the hypothesis that steep Trendelenburg position and capnoperitoneum results in haemodynamic and ventricular impairment. 10 patients (ASA I-III) scheduled for RALP in steep Trendelenburg position with capnoperitoneum were prospectively studied. Heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP) were recorded. Stroke volume variation (SVV) and cardiac output (CO) were measured using pulse-contour analysis. Further, cardiac function was assessed using trans-oesophageal echocardiography before positioning (T1) and 10 min (T2) and 60 min (T3) after implementation of steep Trendelenburg position and capnoperitoneum. HR did not change statistically. MAP (T1, 69.7 ± 1.55; T2, 82.9 ± 3.05; T3, 79.4 ± 2.18 mmHg), CVP (T1, 7.7 ± 1.3; T2, 17.3 ± 2.01; T3, 16.9 ± 1.66 mmHg) and CO (T1, 4.0 ± 0.15; T2, 4.9 ± 0.26; T3, 4.9 ± 0.36 l/min) increased significantly at T2 and T3. Echocardiography showed no deterioration of left or right ventricular function. In one patient with pre-existing mitral valve insufficiency (I°) an aggravation of the insufficiency (III°) was observed. No other valve dysfunctions were observed. The steep Trendelenburg position may improve haemodynamic function and does not deteriorate left or right ventricular function during RALP. However, mitral valve insufficiency may be aggravated by positioning and capnoperitoneum. Copyright © 2011 John Wiley & Sons, Ltd.

  16. Factorized molecular wave functions: Analysis of the nuclear factor

    Energy Technology Data Exchange (ETDEWEB)

    Lefebvre, R., E-mail: roland.lefebvre@u-psud.fr [Institut des Sciences Moléculaires d’ Orsay, Bâtiment 350, UMR8214, CNRS- Université. Paris-Sud, 91405 Orsay, France and Sorbonne Universités, UPMC Univ Paris 06, UFR925, F-75005 Paris (France)

    2015-06-07

    The exact factorization of molecular wave functions leads to nuclear factors which should be nodeless functions. We reconsider the case of vibrational perturbations in a diatomic species, a situation usually treated by combining Born-Oppenheimer products. It was shown [R. Lefebvre, J. Chem. Phys. 142, 074106 (2015)] that it is possible to derive, from the solutions of coupled equations, the form of the factorized function. By increasing artificially the interstate coupling in the usual approach, the adiabatic regime can be reached, whereby the wave function can be reduced to a single product. The nuclear factor of this product is determined by the lowest of the two potentials obtained by diagonalization of the potential matrix. By comparison with the nuclear wave function of the factorized scheme, it is shown that by a simple rectification, an agreement is obtained between the modified nodeless function and that of the adiabatic scheme.

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

    Science.gov (United States)

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

    2016-02-07

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

  18. Altered right ventricular contractile pattern after cardiac surgery: monitoring of septal function is essential.

    Science.gov (United States)

    Nguyen, Tin; Cao, Long; Movahed, Assad

    2014-10-01

    Assessment of right ventricular (RV) function is important in the management of various forms of cardiovascular disease. Accurately assessing RV volume and systolic function is a challenge in day-to-day clinical practice due to its complex geometry. Tricuspid annular plane systolic excursion (TAPSE) and systolic excursion velocity (S') have been reviewed to further assess their suitability and objectivity in evaluating RV function. Multiple studies have validated their diagnostic and prognostic values in numerous pathologic conditions. Diminished longitudinal contraction after cardiothoracic surgery is a well-known phenomenon, but it is not well validated. Despite significant reduction in RV performance along the long-axis assessed by TAPSE and S' after cardiac surgery, RV ejection fractions did not change as well as the left ventricular parameters and exercise capacity. RV contractile patterns were markedly altered with decreased longitudinal shortening and increased transverse shortening, which are likely resulted from the septal damage during cardiac surgery. The septum is essential for RV performance due to its oblique fiber orientation. This allows ventricular twisting, which is a vital mechanism against increased pulmonary vascular resistance. The septum function along with TAPSE and S' should be adequately assessed during cardiac surgery, and evidence of septal dysfunction should lead to reevaluation of myocardial protection methods.

  19. Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ohkusu, Yasuo; Takahashi, Nobukazu; Ishikawa, Toshiyuki [Yokohama City Univ. (Japan). School of Medicine] [and others

    2002-11-01

    We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6{+-}10.0 yrs) and 15 with DCM (45.3{+-}8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac {sup 123}I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. Left ventricular ejection fraction (LVEF) was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21{+-}0.44 vs. 2.10{+-}0.42, 35.3{+-}13.1 vs. 36.0{+-}10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41{+-}0.34 vs. 0.08{+-}0.20, 20.5{+-}14.4 vs. -2.1{+-}9.6%, p<0.01). In TC, heart failure improved after a shorter duration of treatment (p<0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM. (author)

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

    Science.gov (United States)

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

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

  1. Structural and functional cardiac changes in myotonic dystrophy type 1: a cardiovascular magnetic resonance study

    Directory of Open Access Journals (Sweden)

    Hermans Mieke CE

    2012-07-01

    Full Text Available Abstract Background Myotonic dystrophy type 1 (MD1 is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death. Considering the importance of cardiomyopathy as a predictor of prognosis, we aimed to systematically evaluate and describe structural and functional cardiac alterations in patients with MD1. Methods Eighty MD1 patients underwent physical examination, electrocardiography (ECG, echocardiography and cardiovascular magnetic resonance (CMR. Blood samples were taken for determination of NT-proBNP plasma levels and CTG repeat length. Results Functional and structural abnormalities were detected in 35 patients (44%. Left ventricular systolic dysfunction was found in 20 cases, left ventricular dilatation in 7 patients, and left ventricular hypertrophy in 6 patients. Myocardial fibrosis was seen in 10 patients (12.5%. In general, patients had low left ventricular mass indexes. Right ventricular involvement was uncommon and only seen together with left ventricular abnormalities. Functional or structural cardiac involvement was associated with age (p = 0.04, male gender (p Conclusions CMR can be useful to detect early structural and functional myocardial abnormalities in patients with MD1. Myocardial involvement is strongly associated with conduction abnormalities, but a normal ECG does not exclude myocardial alterations. These findings lend support to the hypothesis that MD1 patients have a complex cardiac phenotype, including both myocardial and conduction system alteration.

  2. Functional and morphological cardiac magnetic resonance imaging of mice using a cryogenic quadrature radiofrequency coil.

    Directory of Open Access Journals (Sweden)

    Babette Wagenhaus

    Full Text Available 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.

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

    Science.gov (United States)

    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

  4. The cycle of form and function in cardiac valvulogenesis

    Directory of Open Access Journals (Sweden)

    Stephanie E. Lindsey

    2011-12-01

    Full Text Available The formation and remodeling of the embryonic valves is a complex and dynamic process that occurs within a constantly changing hemodynamic environment. Defects in embryonic and fetal valve remodeling are the leading cause of congenital heart defects, yet very little is known about how fibrous leaflet tissue is created from amorphous gelatinous masses called cushions. Microenvironmental cues such as mechanical forces and extracellular matrix composition play major roles in cell differentiation, but almost all research efforts in valvulogenesis center around genetics and molecular approaches. This review summarizes what is known about the dynamic mechanical and extracellular matrix microenvironment of the atrioventricular and semilunar valves during embryonic development and their possible guidance roles. A variety of new computational tools and sophisticated experimental techniques are progressing that enable precise microenvironmental alterations that are critical to complement genetic gain and loss of function approaches. Studies at the interface of mechanical and genetic signaling in embryonic valvulogenesis will likely pay significant dividends, not only in terms of increasing our mechanistic understanding, but also lead to the development of novel therapeutic strategies for patients with congenital valve abnormalities.

  5. EFFECTS OF EPCs OR b-FGF INTRAMYOCARDIAL INFUSION ON CARDIAC FUNCTION AND NEOVASCULARIZATION FOR DILATED CARDIOMYOPATHY RATS

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin; WEI Meng; YAN Xiao-yu

    2008-01-01

    Objective To compare the different effects of endothelia progenitor cells (EPCs) or basic fibroblast growth factor (b-FGF) intromyocardial infusion on cardiac function and neovascularization for dilated cardiomyopathy(DCM)rats.Methods Fifty adult female rats received inguinal subcutaneous injections of isoproterenol (ISO, 250 mg/kg) for induction of DCM. Four weeks later, the model rats were randomly divided into EPCs group, b-FGF group and control group. The 2×106 EPCs (resolved in 100 μL PBS), 100 μL b-FGF (100 μg/mL) and 100 μL PBS were evenly transplanted into the myocardium of EPCs group, b-FGF group and control group, respectively. Three months later, echocardiographic examination and regional myocardial blood flow (RMBF)measurement were performed. EPCs were traced by fluorescence in situ hybridization (FISH). The protein and mRNA expression of b-FGF in each group was measured by ELISA assay and reverse transcription-polymerase chain reaction (RT-PCR).Results Three months after transplantation, sry positive cells were detected only in EPCs group. The cardiac function as well as RMBF was significantly improved in EPCs group compared with b-FGF group or control group. There was higher capillary density in EPCs group. The protein and mRNA expression of b-FGF was stronger than b-FGF group and control group.Conclusion Transplantation of EPCs can improve cardiac function, induce neovascularization and increase RMBF for DCM rats. The treatment with EPCs has better effect than administration of b-FGF alone.

  6. Natural aminoacyl tRNA synthetase fragment enhances cardiac function after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Margaret E McCormick

    Full Text Available A naturally-occurring fragment of tyrosyl-tRNA synthetase (TyrRS has been shown in higher eukaryotes to 'moonlight' as a pro-angiogenic cytokine in addition to its primary role in protein translation. Pro-angiogenic cytokines have previously been proposed to be promising therapeutic mechanisms for the treatment of myocardial infarction. Here, we show that systemic delivery of the natural fragment of TyRS, mini-TyrRS, improves heart function in mice after myocardial infarction. This improvement is associated with reduced formation of scar tissue, increased angiogenesis of cardiac capillaries, recruitment of c-kitpos cells and proliferation of myocardial fibroblasts. This work demonstrates that mini-TyrRS has beneficial effects on cardiac repair and regeneration and offers support for the notion that elucidation of the ever expanding repertoire of noncanonical functions of aminoacyl tRNA synthetases offers unique opportunities for development of novel therapeutics.

  7. CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

    Directory of Open Access Journals (Sweden)

    A. O. Shevchenko

    2015-01-01

    Full Text Available Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts. Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD pts without decompensated heart failure were included. Along with resistive index (Ri, pulsative index (Pi, and CCW intima-media thickness (IMT, CCW rigidity index (iRIG was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7% and 17 (18.3% cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec2, respectively, p = 0.001. Area under ROC for iRIG was 0.90 ± 0.03 units2. Analysis showed that iRIG values above estimated treshold 7172 cm/sec2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9 sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84

  8. Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

    Energy Technology Data Exchange (ETDEWEB)

    Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil); Mostarda, Cristiano [Departamento de Educação Física, Universidade Federal do Maranhão (UFMA), São Luís, MA (Brazil); Figueroa, Diego Mendrot [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Angelis, Kátia De [Laboratório de Fisiologia Translacional, Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Irigoyen, Maria Cláudia [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Rodrigues, Bruno, E-mail: bruno.rodrigues@incor.usp.br [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil)

    2014-07-15

    Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

  9. Hypertensive Disorders of Pregnancy and Offspring Cardiac Structure and Function in Adolescence

    OpenAIRE

    Timpka, Simon; Macdonald-Wallis, Corrie; Hughes, Alun D.; Chaturvedi, Nish; Franks, Paul; Lawlor, Debbie; Fraser, Abigail

    2016-01-01

    BACKGROUND: Fetal exposure to preeclampsia is associated with higher blood pressure and later risk of stroke. We aimed to investigate the associations of maternal preeclampsia, gestational hypertension, and maternal blood pressure change in pregnancy with offspring cardiac structure and function in adolescence. METHODS AND RESULTS: Using data from a prospective birth cohort study, we included offspring who underwent echocardiography (mean age, 17.7 years; SD, 0.3; N=1592). We examined whether...

  10. Doxorubicin Cardiotoxicity and Cardiac Function Improvement After Stem Cell Therapy Diagnosed by Strain Echocardiography

    OpenAIRE

    Oliveira, Maira S.; Melo, Marcos B; Carvalho, Juliana L; Melo, Isabela M; Lavor, Mario SL; Gomes, Dawidson A.; Goes, Alfredo M.; Melo, Marilia M

    2013-01-01

    Doxorubicin (Dox) is one of the most effective chemotherapeutic agents; however, it causes dose-dependent cardiotoxicity. Evaluation of left ventricular function relies on measurements based on M-mode echocardiography. A new technique based on quantification of myocardial motion and deformation, strain echocardiography, has been showed promising profile for early detection of cardiac dysfunction. Different therapy strategies, such as flavonoid plant extracts and stem cells, have been investig...

  11. Effects of right atrial and ventricular DDD pacing on cardiac function and ventricular contraction synchrony

    Institute of Scientific and Technical Information of China (English)

    支力大; 华伟; 张澍; 史蓉芳; 王方正; 陈新

    2004-01-01

    Background Right ventricular apical pacing has been reported to reduce cardiac performance. But there are few reports on the effects of dual chamber (DDD) pacing on cardiac function compared to sinus rhythm. In this study, we evaluated the effects of right atrial and ventricular DDD pacing on cardiac function and ventricular contraction synchrony using equilibrium radionuclide angiography.Methods Ten patients implanted with a right atrial and ventricular DDD pacemaker underwent equilibrium radionuclide angiography. The scintigraphic data were obtained during sinus rhythm and pacing rhythm. Cardiac function parameters were obtained semimanually. Phase analysis was used to study the ventricular activation sequence and ventricular synchrony.Results The left ventricular 1/3 ejection fraction decreased significantly during pacing compared with that during sinus rhythm[(23.4 ±6.1)% vs(27.7 ±4.5)%, P =0.01]. Regional ejection fraction also decreased during pacing, although the difference was not statistically significant. Phase analysis showed that the right ventricle was activated earlier than the left ventricle during pacing, and that the phase shift was significantly greater during pacing than that during sinus rhythm[64.13°±16.80° vs 52.88°± 9.26°, P =0.007]. The activation of both ventricles occurred simultaneously during sinus rhythm, with the activation sequence from proximal septum or base of left ventricle to apex. The earliest activation during pacing occurred at the right ventricular apex, and subsequently spread to the base and left ventricle.Conclusion Right atrial and ventricular DDD pacing impairs left ventricular systolic function and ventricular synchrony.

  12. Muscarinic 2 Receptors Modulate Cardiac Proteasome Function in a Protein Kinase G-dependent Manner

    OpenAIRE

    Ranek, Mark J.; Kost, Curtis K.; Hu, Chengjun; Martin, Douglas S.; Wang, Xuejun

    2014-01-01

    Proteasome function insufficiency and inadequate protein quality control are strongly implicated in a large subset of cardiovascular disease and may play an important role in their pathogenesis. Protein degradation by the ubiquitin proteasome system can be physiologically regulated. Cardiac muscarinic 2 (M2) receptors were pharmacologically interrogated in intact mice and cultured neonatal rat ventricular myocytes (NRVMs). Proteasome-mediated proteolysis was measured with a surrogate misfolde...

  13. Ameliorated stress related proteins are associated with improved cardiac function by sarcoplasmic reticulum calcium ATPase gene transfer in heart failure

    Institute of Scientific and Technical Information of China (English)

    Zhi-Qing Fu; Xiao-Ying Li; Xiao-Chun Lu; Ya-Fei Mi; Tao Liu; Wei-Hua Ye

    2012-01-01

    Background Previous studies showed that overexpression of sarco-endoplasmic reticulum calcium ATPase (SERCA2a) in a variety of heart failure (HF) models was associated with greatly enhanced cardiac performance. However, it still undefined the effect of SERCA2a overexpression on the systemic inflammatory response and neuro-hormonal factors. Methods A rapid right ventricular pacing model of experimental HF was used in beagles. Then the animals underwent recombinant adeno-associated virus 1 (rAAV1) mediated gene transfection by direct intra-myocardium injection. HF animals were randomized to receive the SERCA2a gene, enhanced green fluorescent protein (control) gene, or equivalent phosphate buffered saline. Thirty days after gene delivery, the cardiac function was evaluated by echocardiographic testing. The protein level of SERCA2a was measured by western blotting. The proteomic analysis of left ventricular (LV) sample was determined using two-dimensional (2-D) gel electrophoresis and MALDI-TOF-MS. The serum levels of the systemic inflammatory and neuro-hormonal factors were assayed using radioimmunoassay kits. Results The cardiac function improved after SERCA- 2a gene transfer due to the significantly increased SERCA2a protein level. Beagles treated with SERCA2a had significantly decreased serum levels of the inflammatory markers (interleukin-6 and tumor necrosis factor-α) and neuro-hormonal factors (brain natriuretic peptide, endothelin-1 and angiotensin Ⅱ) compared with HF animals. The myocardial proteomic analysis showed that haptoglobin heavy chain, heat shock protein (alpha-crystallin-related, B6) were down-regulated, and galectin-1 was up-regulated in SERCA2a group compared with HF group, companied by up-regulated contractile proteins and NADH dehydrogenase. Conclusions These findings demonstrate that regional intramyocardial injections of rAAV1-SERCA2a vectors may improve global LV function, correlating with reverse activation of the systemic inflammatory

  14. [Successful mitral valve replacement in a patient with functional mitral regurgitation induced by cardiac sarcoidosis;report of a case].

    Science.gov (United States)

    Sato, Ken; Takazawa, Ippei; Aizawa, Kei; Misawa, Yoshio

    2015-03-01

    We report a case of cardiac sarcoidosis associated with mitral valve regurgitation. A 62-year-old woman with cardiac sarcoidosis was admitted for the treatment of an intractable mitral regurgitation. She had been treated for cardiac sarcoidosis with prednisolone, and she had undergone pacemaker implantation because of advanced complete A-V block 5 years before. However, her hemodynamics deteriorated, and echocardiography revealed severe functional mitral regurgitation, thinning of the ventricular septum, and left ventricular dysfunction. The patient underwent mitral valve replacement with a mechanical prosthetic valve, and her postoperative course was uneventful. She is currently well without exacerbation of heart failure at 2 years after operation. Functional mitral regurgitation is a relatively common complication in patients with cardiac sarcoidosis. Mitral valve replacement should be considered in patients with medically intractable mitral valve dysfunction due to cardiac sarcoidosis.

  15. Influence of fluvastatin on cardiac function and baroreflex sensitivity in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Fang XIE; Chao SUN; Li-hua SUN; Jing-yuan LI; Xin CHEN; Hui CHE; Guan-yi LU; Bao-feng YANG; Jing AI

    2011-01-01

    Aim: To investigate whether fluvastatin is able to ameliorate the impaired cardiac function or baroreflex sensitivity (BRS) in rats with type 1 diabetes.Methods: Type 1 diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) and then administered fluvastatin (1.5,cardiac function and BRS were measured in diabetic rats after fluvastatin treatment for 30 d.Results: The polydipsia, polyphagia and abnormal biochemical indexes of blood were significantly ameliorated by the the 3.0- and 6.0-mg doses of fluvastatin in STZ-induced diabetic rats. FBG was decreased in diabetic rats after fluvastatin treatment for 30 d. The left ventricular systolic pressure (LVSP) and the maximum rate of change of left ventricular pressure in the isovolumic contraction and relaxation period (±dp/dtmax) were elevated, and left ventricular diastolic pressure (LVEDP) was decreased by fluvastatin. The attenuated heart rate responses to arterial blood pressure (ABP) increase induced by phenylephrine (PE) and ABP decrease induced by sodium nitroprusside (SNP) were reversed by the 3.0-mg dose of fluvastatin.Conclusion: Fluvastatin regulates blood lipid levels and decreases the FBG level in diabetic rats. These responses can protect the diabetic heart from complications by improving cardiac function and BRS.

  16. Usefulness of true FISP cine MR imaging in patients with poor cardiac function

    Energy Technology Data Exchange (ETDEWEB)

    Sakuma, Toshiharu; Yamada, Naoaki; Motooka, Makoto; Enomoto, Naoyuki; Maeshima, Isamu; Matsuda, Kazuhide; Urayama, Shinichi; Ikeo, Miki [National Cardiovascular Center, Suita, Osaka (Japan)

    2002-01-01

    This study was done to assess the value of True FISP cine in patients with poor cardiac function. True FISP cine and FLASH cine imaging were performed on a 1.5 T machine. Both short axis and horizontal long axis imaging sections were used. The imaging sections used a Matrix (120 x 128), FOV (24 x 32 cm), and had a slice thickness of 8 mm. The imaging time for True FISP cine was 8 heart beats and 17 heart beats for FLASH cine. The contrast-to-noise ratio between the blood and myocardium (CNR) was measured at enddiastole and endsystole. The subjects in the study were 10 healty volunteers (average age 26.5{+-}3.2 years) and 12 patients with hypofunction (average age 53.9{+-}13.2 years). In the volunteers, the CNR of the short axis imaging was similar in both True FISP (24.6{+-}3.7) and FLASH (23.4{+-}5.9). In the patients with poor cardiac function however, the CNR of True FISP was larger than FLASH in both the short and long axis. In the short axis (22.7{+-}6.1 vs. 17.9{+-}5.3, P<0.01) and in the long axis (17.4{+-}4.3 vs. 9.3{+-}4.0, P<0.01). We conclude that True FISP cine has a higher contrast in a shorter imaging time than FLASH cine. True FISP cine is especially useful in patients with poor cardiac function. (author)

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

    Science.gov (United States)

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

    2015-04-21

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

  18. Exercise training and cardiac autonomic function in type 2 diabetes mellitus: A systematic review.

    Science.gov (United States)

    Bhati, Pooja; Shenoy, Shweta; Hussain, M Ejaz

    2017-09-06

    Cardiac autonomic neuropathy (CAN) is a common complication of type 2 diabetes mellitus (T2DM). It has been found to independently predict all cause and cardiovascular disease (CVD) mortality. It remains unclear whether exercise training could improve autonomic control in T2DM patients. The purpose of this study was to systematically review the effects of exercise training on cardiac autonomic function in T2DM patients. Electronic databases (MEDLINE, CENTRAL, PEDro, Scopus and Web of science) were systematically searched to retrieve relevant evidence. Clinical trials administering exercise training for at least 4 weeks and examining either heart rate variability (HRV), baroreflex sensitivity (BRS), heart rate recovery (HRR) as outcome measures were eligible. Eighteen articles were found to be relevant and were then assessed for characteristics and quality. Fifteen studies out of 18 found that exercise training leads to positive improvements in autonomic function of T2DM patients. Exercise participation enhances cardiac autonomic function of type 2 diabetics and therefore should be implemented in their management programs. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  20. Echocardiographic evaluation of female centrifuge subjects for chronic changes in cardiac function.

    Science.gov (United States)

    Albery, W B

    1999-06-01

    High sustained G exposure as experienced in flying high performance aircraft can affect cardiac function. Numerous studies, mostly on male pilots, have evaluated the chronic effects of exposure to high G. To date, none of these studies has revealed significant positive findings in cardiac function as a result of long-term high G exposure. A longitudinal study was conducted on six female centrifuge panel members who did not have a history of significant high +Gz exposure. Baseline echocardiographic studies were conducted prior to any +Gz exposure on the Dynamic Environment Simulator (DES) centrifuge. The echocardiograms were repeated after each panel member completed approximately 100 3-min high G (up to 9 G) exposures over the period of 7 mo. These follow-up echos were performed after all six subjects had been exposed to at least 6 h (cumulative) of sustained acceleration > 3 G. The women were protected with the COMBAT EDGE positive pressure breathing G protection ensemble. Each subject served as her own control. All studies were evaluated independently by a cardiologist who was blinded to the order in which the echos were performed. Although complete echocardiographic studies were performed, only the parameters identified as significant in prior studies were evaluated. No significant differences were found between the initial and follow-up echo parameters. We found no significant differences in cardiac function after at least 6 and up to 17 h (cumulative) of exposure to G > 3 in women. These subjects will be monitored during a longitudinal study throughout their centrifuge subject career.

  1. Treatment with hESC-Derived Myocardial Precursors Improves Cardiac Function after a Myocardial Infarction.

    Directory of Open Access Journals (Sweden)

    Jianqin Ye

    Full Text Available We previously reported the generation of a reporter line of human embryonic stem cells (hESCs with enhanced green fluorescent protein (eGFP expression driven by the α-myosin heavy chain (αMHC promoter. The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs in vitro. In this study, we evaluated the therapeutic effects of GFP+/αMHC+ cells isolated from the reporter line in a mouse model of myocardial infarction (MI.MI was generated in immunodeficient mice. hMPs were injected into murine infarcted hearts under ultrasound guidance at 3 days post-MI. Human fetal skin fibroblasts (hFFs were injected as control. Cardiac function was evaluated by echocardiography. Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining.Compared with control, hMPs resulted in improvement of cardiac function post-MI with smaller infarct size, induced endogenous angiogenesis, and reduced apoptosis of host cardiomyocytes at the peri-infarct zone at 28 days post-MI.Intramyocardial injection of hMPs improved cardiac function post-MI. The engraftment rate of these cells in the myocardium post-MI was low, suggesting that the majority of effect occurs via paracrine mechanisms.

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

    Science.gov (United States)

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

    2012-06-15

    To better understand the mechanisms contributing to improved exercise capacity with cardiac resynchronization therapy (CRT), we studied the effects of 6 mo of CRT on pulmonary O(2) uptake (Vo(2)) kinetics, exercise left ventricular (LV) function, and peak Vo(2) in 12 subjects (age: 56 ± 15 yr, peak Vo(2): 12.9 ± 3.2 ml·kg(-1)·min(-1), ejection fraction: 18 ± 3%) with heart failure. We hypothesized that CRT would speed Vo(2) kinetics due to an increase in stroke volume secondary to a reduction in LV end-systolic volume (ESV) and that the increase in peak Vo(2) would be related to an increase in cardiac output reserve. We found that Vo(2) kinetics were faster during the transition to moderate-intensity exercise after CRT (pre-CRT: 69 ± 21 s vs. post-CRT: 54 ± 17 s, P exercise, LV ESV reserve (exercise - resting) increased 9 ± 7 ml (vs. a 3 ± 9-ml decrease pre-CRT, P increased (pre-CRT: 42 ± 8 ml vs. post-CRT: 61 ± 12 ml, P exercise post-CRT (P > 0.05). CRT improved heart rate, measured as a lower resting and steady-state exercise heart rate and as faster heart rate kinetics after CRT (pre-CRT: 89 ± 12 s vs. post-CRT: 69 ± 21 s, P exercise, cardiac output reserve increased significantly post-CRT and was 22% higher at peak exercise post-CRT (both P increase in cardiac output was due to both a significant increase in peak and reserve stroke volume and to a nonsignificant increase in heart rate reserve. Similar patterns in LV volumes as moderate-intensity exercise were observed at peak exercise. Cardiac output reserve was related to peak Vo(2) (r = 0.48, P increase in peak Vo(2) in clinically stable heart failure patients.

  3. Fibroblast Growth Factor-23 in Obese, Normotensive Adolescents is Associated with Adverse Cardiac Structure

    Science.gov (United States)

    Ali, Farah N.; Falkner, Bonita; Gidding, Samuel S.; Price, Heather E.; Keith, Scott W.; Langman, Craig B.

    2014-01-01

    Objectives Fibroblast growth factor-23 (FGF23) is a biomarker for cardiovascular (CV) disease. Obesity may promote FGF23 production in the absence of chronic kidney disease (CKD). We sought to determine among normotensive African American adolescents, whether FGF23 levels are higher in obese compared with normal weight African American adolescents; and to determine the relationship of FGF23 with markers of cardiac structure and insulin resistance. Study design Cross-sectional data were obtained from a cohort of 130 normotensive, African American adolescents aged 13-18 years old without CKD; 74 were obese; 56 were normal weight. Plasma C-terminal FGF23, fasting glucose and insulin, and hsCRP were measured; participants underwent M-mode echocardiography. Results FGF23 was skewed and approximately normally distributed after natural log transformation (logFGF23). FGF23 levels were higher in obese versus normal weight participants (geometric mean 43 vs. 23 RU/mL, p<0.01). FGF23 values were significantly higher in participants with eccentric or concentric cardiac hypertrophy compared with those without hypertrophy (p<0.01). LogFGF23 directly correlated with BMI, BMI z-score, waist circumference, fasting insulin levels, and HOMA scores. Regression models adjusted for age, sex, and hsCRP suggest that each 10% increase in FGF23 is associated with 1.31 unit increase in LVM (p<0.01), 0.29 unit increase in LVMI (p<0.01), and 0.01 unit increase in left atrial dimension indexed to height (p=0.02). Conclusions In this sample of obese African American adolescents, FGF23 blood levels were associated with abnormal cardiac structure. We postulate that FGF23 may be an early marker of cardiac injury in obese but otherwise healthy African American adolescents. PMID:25063724

  4. Factors influencing the outcome of paediatric cardiac surgical patients during extracorporeal circulatory support

    Directory of Open Access Journals (Sweden)

    Peek Giles J

    2007-01-01

    Full Text Available Abstract Background Veno-arterial extracorporeal membrane oxygenation (ECMO is a common modality of circulatory assist device used in children. We assessed the outcome of children who had ECMO following repair of congenital cardiac defects (CCD and identified the risk factors associated with hospital mortality. Methods From April 1990 to December 2003, 53 patients required ECMO following surgical correction of CCD. Retrospectively collected data was analyzed with univariate and multivariate logistic regression analysis. Results Median age and weight of the patients were 150 days and 5.4 kgs respectively. The indications for ECMO were low cardiac output in 16, failure to wean cardiopulmonary bypass in 13, cardiac arrest in 10 and cardio-respiratory failure in 14 patients. The mean duration of ECMO was 143 hours. Weaning off from ECMO was successful in 66% and of these 83% were survival to hospital-discharge. 37.7% of patients were alive for the mean follow-up period of 75 months. On univariate analysis, arrhythmias, ECMO duration >168 hours, bleeding complications, renal replacement therapy on ECMO, arrhythmias and cardiac arrest after ECMO were associated with hospital mortality. On multivariate analysis, abnormal neurology, bleeding complications and arrhythmias after ECMO were associated with hospital mortality. Extra and intra-thoracic cannulations were used in 79% and 21% of patients respectively and extra-thoracic cannulation had significantly less bleeding complications (p = 0.031. Conclusion ECMO provides an effective circulatory support following surgical repair of CCD in children. Extra-thoracic cannulation is associated with less bleeding complications. Abnormal neurology, bleeding complications on ECMO and arrhythmias after ECMO are poor prognostic indicators for hospital survival.

  5. Randomised controlled trial of a 12 week yoga intervention on negative affective states, cardiovascular and cognitive function in post-cardiac rehabilitation patients.

    Science.gov (United States)

    Yeung, Alan; Kiat, Hosen; Denniss, A Robert; Cheema, Birinder S; Bensoussan, Alan; Machliss, Bianca; Colagiuri, Ben; Chang, Dennis

    2014-10-24

    Negative affective states such as anxiety, depression and stress are significant risk factors for cardiovascular disease, particularly in cardiac and post-cardiac rehabilitation populations.Yoga is a balanced practice of physical exercise, breathing control and meditation that can reduce psychosocial symptoms as well as improve cardiovascular and cognitive function. It has the potential to positively affect multiple disease pathways and may prove to be a practical adjunct to cardiac rehabilitation in further reducing cardiac risk factors as well as improving self-efficacy and post-cardiac rehabilitation adherence to healthy lifestyle behaviours. This is a parallel arm, multi-centre, randomised controlled trial that will assess the outcomes of post- phase 2 cardiac rehabilitation patients assigned to a yoga intervention in comparison to a no-treatment wait-list control group. Participants randomised to the yoga group will engage in a 12 week yoga program comprising of two group based sessions and one self-administered home session each week. Group based sessions will be led by an experienced yoga instructor. This will involve teaching beginner students a hatha yoga sequence that incorporates asana (poses and postures), pranayama (breathing control) and meditation. The primary outcomes of this study are negative affective states of anxiety, depression and stress assessed using the Depression Anxiety Stress Scale. Secondary outcomes include measures of quality of life, and cardiovascular and cognitive function. The cardiovascular outcomes will include blood pressure, heart rate, heart rate variability, pulse wave velocity, carotid intima media thickness measurements, lipid/glucose profiles and C-reactive protein assays. Assessments will be conducted prior to (week 0), mid-way through (week 6) and following the intervention period (week 12) as well as at a four week follow-up (week 16). This study will determine the effect of yoga practice on negative affective states

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

    Science.gov (United States)

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

    2003-12-01

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

  7. [The immunologic function and role of allograft inflammatory factor-1].

    Science.gov (United States)

    Yamamoto, Aihiro; Kawahito, Yutaka

    2014-01-01

    Allograft inflammatory factor-1 is the protein that expressed in the macrophages around the coronary arteries in rat ectopic cardiac allograft model. AIF-1 is produced mainly by macrophages and regulated by interferon-gamma (IFN-γ). There are various splicing valiants in AIF-1, and the functions are different. AIF-1 has Ca-binding EF-hand motif that induces cell proliferation and migration by structural features. Besides cell proliferation and migration, AIF-1 contributes to secretion of inflammatory cytokines and chemokines such as IL-6, IL-10, IL-12, and transforming growth factor-beta (TGF-β), insulin resistance by downregulation of GLUT4 or IRS-1, and fibrosis process by upregulation of collagen production. It has been elucidated that AIF-1 is responsible for the onset of various diseases such as rheumatoid arthritis and systemic sclerosis, atherosclerotic disease, diabetes mellitus. AIF-1 may have the therapeutic potential for chronic inflammatory diseases by elucidation of the mechanism.

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

    Science.gov (United States)

    Akhter, Shirin; Jin, J-P

    2015-01-01

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

  9. Prognostic Factors for Outcomes of In-Flight Sudden Cardiac Arrest on Commercial Airlines.

    Science.gov (United States)

    Alves, Paulo M; DeJohn, Charles A; Ricaurte, Eduard M; Mills, William D

    In-flight cardiac arrest (IFCA) is a relatively rare but challenging event. Outcomes and prognostic factors are not entirely understood for victims of IFCAs in commercial aviation. This was a retrospective cohort study of airline passengers who experienced IFCA. Demographic and operational variables were studied to identify association in a multivariate logistic regression model with the outcome of survival-to-hospital. In-flight medical emergencies were processed by a ground-based medical center. Subsequent comparisons were made between reported shockable-rhythm (RSR) and reported non-shockable-rhythm (RNSR) groups. Logistic regression was also used to identify predictors for shock advised and flight diversions using a case control study design. Significant predictors for survival-to-hospital were RSR and remaining flight time to destination. The percentage of RSR cases was 24.6%. The survival to hospital admission was 22.7% (22/97) for passengers in RSR compared with 2.4% (7/297) in the RNSR group. The adjusted odds ratio for survival-to-hospital for the RSR group compared to the RNSR group was 13.6 (5.5-33.5). The model showed odds for survival to hospital decreased with longer scheduled remaining flight duration with adjusted OR = 0.701 (0.535-0.920) per hour increase. No correlation between diversions and survival for RSR cases was found. Survival-to-hospital from IFCAs is best when an RSR is present. The percentage of RSR cases was lower than in other out-of-hospital cardiac arrest (OHCA) settings, which suggests delayed discovery. Flight diversions did not significantly affect resuscitation outcome. We emphasize good quality cardio-pulmonary resuscitation (CPR) and early defibrillation as key factors for IFCA survival. Alves PM, DeJohn CA, Ricaurte EM, Mills WD. Prognostic factors for outcomes of in-flight sudden cardiac arrest on commercial airlines. Aerosp Med Hum Perform. 2016; 87(10):862-868.

  10. Post-Traumatic Stress Disorder among Cardiac Patients: Prevalence, Risk Factors, and Considerations for Assessment and Treatment

    Directory of Open Access Journals (Sweden)

    Heather Tulloch

    2014-12-01

    Full Text Available There is increasing awareness of the impact of post-traumatic stress disorder (PTSD on physical health, particularly cardiovascular disease. We review the literature on the role of trauma in the development of cardiovascular risk factors and disease, aftermath of a cardiac event, and risk for recurrence in cardiac patients. We explore possible mechanisms to explain these relationships, as well as appropriate assessment and treatment strategies for this population. Our main conclusion is that screening and referral for appropriate treatments are important given the high prevalence rates of PTSD in cardiac populations and the associated impact on morbidity and mortality.

  11. Age-specific associations between cardiac vagal activity and functional somatic symptoms : a population-based study

    NARCIS (Netherlands)

    Tak, Lineke M.; Janssens, Karin A. M.; Dietrich, Andrea; Slaets, Joris P. J.; Rosmalen, Judith G. M.

    2010-01-01

    BACKGROUND: Functional somatic symptoms (FSS) are symptoms not explained by underlying organic pathology. It has frequently been suggested that dysfunction of the autonomic nervous system (ANS) contributes to the development of FSS. We hypothesized that decreased cardiac vagal activity is

  12. Cardiac surgery-associated acute kidney injury in a developing country: Prevalence, risk factors and outcome

    OpenAIRE

    2015-01-01

    Little is known about cardiac surgery-associated acute kidney injury (CS-AKI) in children in developing regions of the world. The study aimed to determine the prevalence of CSAKI, associated factors and its impact on mortality and utilization of hospital services. The hospital records of children aged 0-17 years who underwent CS at an Indian hospital were reviewed. CS-AKI was defined as a rise in serum creatinine of ≥0.3 mg/dL in any 48 h and or by urine output

  13. Factors predisposing to wound infection in cardiac surgery. A prospective study of 517 patients.

    Science.gov (United States)

    Wilson, A P; Livesey, S A; Treasure, T; Grüneberg, R N; Sturridge, M F

    1987-01-01

    Postoperative wound infection can greatly prolong hospital stay after cardiac surgery, so the identification of predisposing factors may help in prevention or early institution of treatment. Transfer of organisms from the leg to the sternum during coronary artery surgery has been proposed as a major additional cause of sepsis. The definition of wound infection is not standardised and therefore makes comparison between centres difficult. In a prospective study of 517 patients, a wound scoring method (ASEPSIS) has been used to register all abnormal wounds to maximise the chances of identifying factors predisposing to infection. Abnormal healing was noted in 99 (19%) sternal wounds and 29 (8%) leg wounds. Obesity was the principal risk factor (P less than 0.005). Diabetes, reoperation, length of preoperative hospital stay, age, sex, or previous cardiac surgery had little effect on wound healing. The range of bacteria isolated from chest wounds after coronary artery surgery was similar to that after valvular surgery, but the rate of isolation was significantly greater. With careful attention to technique, leg wound infection rarely presented a clinical problem and did not appear to be a source of bacteria infecting the chest wound.

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

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    Antônio Carlos Cicogna

    1999-04-01

    Full Text Available OBJECTIVE: To assess the effect of food restriction (FR on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR. METHODS: Isolated papillary muscle preparations of the left ventricle (LV of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1 reduction in the body weight and LV weight of SHR and WKY rats; 2 increase in the time to peak shortening and the time to peak developed tension (DT in the hypertrophied myocardium of the SHR; 3 diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

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

    Directory of Open Access Journals (Sweden)

    Ehécatl M. A. García-Trejo

    2016-01-01

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

  17. Relationship between myocardial T2* values and cardiac volumetric and functional parameters in β-thalassemia patients evaluated by cardiac magnetic resonance in association with serum ferritin levels

    Energy Technology Data Exchange (ETDEWEB)

    Liguori, Carlo, E-mail: c.liguori@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Pitocco, Francesca, E-mail: f.pitocco@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Di Giampietro, Ilenia, E-mail: i.digiampietro@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Vivo, Aldo Eros de, E-mail: devivoeros@gmail.com [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Schena, Emiliano, E-mail: e.schena@unicampus.it [Unit of Measurements and Biomedical Instrumentation, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Cianciulli, Paolo, E-mail: CIANCIULLI.PAOLO@aslrmc.it [Thalassemia Unit, Ospedale Sant Eugenio, Piazzale dell’Umanesimo 10, 00143 Rome (Italy); Zobel, Bruno Beomonte, E-mail: b.zobel@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy)

    2013-09-15

    Purpose: Myocardial T2* cardiovascular magnetic resonance provides a rapid and reproducible assessment of cardiac iron load in thalassemia patients. Although cardiac involvement is mainly characterized by left ventricular dysfunction caused by iron overload, little is known about right ventricular function. The aim of this study was to assess the relationship between T2* value in myocardium and left–right ventricular volumetric and functional parameters and to evaluate the existing associations between left–right ventricles volumetric and functional parameter, myocardial T2* values and blood ferritin levels. Materials and methods: A retrospective analysis of 208 patients with β-thalassemia major and thalassemia intermedia was performed (109 males and 99 females; mean age 37.7 ± 13 years; 143 thalassemia major, 65 thalassemia intermedia). Myocardial iron load was assessed by T2* measurements, and volumetric functions were analyzed using the steady state free precession sequence. Results: A significant correlation was observed between EFLV and T2* (p = 0.0001), EFRV and T2* (p = 0.0279). An inverse correlation was present between DVLV and T2* (p = 0.0468), SVLV and T2* (p = 0.0003), SVRV and T2* (p = 0.0001). There was no significant correlation between cardiac T2* and LV–RV mass indices. A significant correlation was observed between T2* and serum ferritin levels (p < 0.001) and between EFLV and serum ferritin (p < 0.05). Conclusion: Myocardial iron load assessed by T2* cardiac magnetic resonance is associated with deterioration in left–right ventricular function; this is more evident when T2* values fall below 14 ms. CMR appears to be a promising approach for cardiac risk evaluation in TM patients.

  18. Cardiac denervation in the calf using cryoablation: functional evidence and regional tissue catecholamine content.

    Science.gov (United States)

    Gaer, J A; Wharton, J; Gordon, L; Swift, R I; Munsch, C; Inglis, G C; Polak, J M; Taylor, K M

    1992-01-01

    Twenty-six calves were subjected to a technique of cryoablation in order to establish an animal model of complete cardiac denervation. All 26 survived the procedure, and 20 were alive to be re-evaluated 2-4 weeks later. Mean heart rate in the denervated animals rose from 77 +/- 7.8 beats/min to 102 +/- 16.4 (P less than 0.01). Cryoablation abolished the heart rate responses to electrical stimulation of the vagus nerve and thoracic sympathetic trunk. The reduction in myocardial noradrenaline concentrations averaged 99% in the right atrium, 90% in the left atrium, 85% in the right ventricle and 90% in the left ventricle, when compared with tissue obtained from control animals. Cryoablation is a relatively simple means of accomplishing complete functional cardiac denervation in the calf. On the basis of the observed change in heart rate, the calf model appears to be more comparable with human heart transplant recipients than the dog.

  19. Assessment of cardiac functions using tissue Doppler imaging in children with familial Mediterranean fever.

    Science.gov (United States)

    Ozdemir, Osman; Agras, Pinar Isik; Aydin, Yusuf; Abaci, Ayhan; Hizli, Samil; Akkus, Halil Ibrahim; Fidan, Cihan

    2012-04-01

    Familial Mediterranean fever may carry a potential for cardiovascular disorders because of sustained inflammation during its course; however, there has been a limited number of studies investigating the cardiac functions in children. The aim of this study was to assess both ventricular diastolic functions using conventional echocardiography and tissue Doppler imaging in children with familial Mediterranean fever. The study population included 25 patients with familial Mediterranean fever - mean age was 11.8 plus or minus 5.30 years - and 23 healthy patients as controls - mean age was 9.88 plus or minus 3.69 years. Both ventricular functions were measured using echocardiography comprising standard M-mode and conventional Doppler and tissue Doppler imaging during an attack-free period. The conventional echocardiographic parameters with myocardial performance index were in normal ranges and similar in patients with familial Mediterranean fever and controls, with a p-value more than 0.05. However, right ventricular diastolic dysfunction was observed in patients with familial Mediterranean fever documented by tissue Doppler imaging, with a p-value less than 0.05 for E't and A't wave ratio. Using tissue Doppler imaging, we have demonstrated that although left ventricular functions were comparable in the patients and healthy children, right ventricular diastolic function indices were impaired in patients with familial Mediterranean fever during childhood. Impaired right ventricular diastolic function may be an early manifestation of cardiac involvement in children with familial Mediterranean fever.

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

    Science.gov (United States)

    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 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.

  1. Transplantation of autologous adipose-derived stem cells ameliorates cardiac function in rabbits with myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    ZHANG Duan-zhen; GAI Lu-yue; LIU Hong-wei; JIN Qin-hua; HUANG Jian-hua; ZHU Xian-yang

    2007-01-01

    Background Adipose-derived stem cells (ADSCs) are capable of differentiating into cardiomyogenic and endothelial cells in vitro. We tested the hypothesis that transplantation of ADSCs into myocardial scar may regenerate infracted myocardium and restore cardiac function.Methods ADSCs were isolated from the fatty tissue of New Zealand white rabbits and cultured in Iscove's modified dulbecco's medium. Three weeks after ligation of left anterior descending coronary artery of rabbits, either a graft of untreated ADSCs (UASCs, n=14), 5-azacytidine-pretreated ADSCs (AASCs, n=13), or phosphate buffer saline (n=13)were injected into the infarct region. Transmural scar size, cardiac function, and immunohistochemistry were performed 5 weeks after cell transplantation.Results ADSCs in culture demonstrated a fibroblast-like appearance and expressed CD29, CD44 and CD105. Five weeks after cell transplantation, transmural scar size in AASC-implanted hearts was smaller than that of the other hearts.Many ADSCs were differentiated into cardiomyocytes. The AASCs in the prescar appeared more myotube-like. AASCs in the middle of the scar and UASCs, in contrast, were poorly differentiated. Some ADSCs were differentiated into endothelial cells and participate in vessel-like structures formation. All the ADSC-implanted hearts had a greater capillary density in the infarct region than did the control hearts. Statistical analyses revealed significant improvement in left ventricular ejection fraction, myocardial performance index, end-diastolic pressure, and peak +dP/dt, in two groups of ADSC-implanted hearts relative to the control hearts. AASC-implanted hearts had higher peak -dP/dt values than did control, higher ejection fraction and peak +dP/dtvalues than did UASC-implanted hearts.Conclusions ADSCs transplanted into the myocardial scar tissue formed cardiac islands and vessel-like structures,induced angiogenesis and improved cardiac function. 5-Azacytidine pretreatment before

  2. Effects of Short-term Renovascular Hypertension and Type 2 Diabetes on Cardiac Functions in Rats

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    Ali Akbar Nekooeian

    2014-01-01

    Full Text Available Background: The cardiac effects simultaneously occurring during experimental hypertension and diabetes have rarely been investigated. This study aimed at examining the effects of short-term renovascular hypertension and type 2 diabetes on cardiac functions. Methods: Five groups (7 each of male Sprague-Dawley rats, including a control group, a diabetes (induced by Streptozocin and Nicotinamide group, a renovascular hypertensive (induced by placing Plexiglas clips on the left renal arteries group, a sham group, and a simultaneously hypertensive-diabetic group, were used. The animals’ hearts were used for isolated heart studies, and the indices of cardiac functions and coronary effluent creatine kinase MB were measured. The results were analyzed using One-way Analysis of Variance, followed by the Duncan Multiple Range test. Results: The diabetic group had a significantly lower rate of rise (-29.5% and decrease (-36.18% in ventricular pressure, left ventricular developed pressure (-28.8%, and rate pressure product (-35%, and significantly higher creatine kinase MB (+166% and infarct size (+36.2% than those of the control group. The hypertensive group had a significantly higher rate of rise (+12.17% and decrease (+16.2% in ventricular pressure, left ventricular developed pressure (+16%, and rate pressure product (+24%, and significantly lower creatine kinase MB (-30% and infarct size (-27% than those of the sham group. Simultaneously, the diabetic and hypertensive rats had a significantly higher rate of rise (+32% and decrease (+30.2% in ventricular pressure, left ventricular developed pressure (+17.2%, and rate pressure product (+22.2%, and significantly lower creatine kinase MB (-24% and infarct size (-16.2% than those of the diabetic group. Conclusion: The findings indicated that the simultaneity of hypertension with type 2 diabetes attenuated diabetes-induced cardiac impairment.

  3. Effect of exercise on cardiac autonomic function in females with rheumatoid arthritis.

    Science.gov (United States)

    Janse van Rensburg, Dina C; Ker, James A; Grant, Catharina C; Fletcher, Lizelle

    2012-08-01

    The objective of this study is to evaluate the effect of exercise on cardiac autonomic function as measured by short-term heart rate variability (HRV) in females suffering from rheumatoid arthritis (RA). Females with confirmed RA were randomly assigned to an exercise group (RAE) and a sedentary group (RAC). RAE was required to train under supervision two to three times per week, for 3 months. Three techniques (time domain, frequency domain and Poincaré plot analyses) were used to measure HRV at baseline and study completion. At baseline, RAC (n = 18) had a significantly higher variability compared to RAE (n = 19) for most HRV indicators. At study completion, the variables showing significant changes (p = 0.01 to 0.05) favoured RAE in all instances. Wilcoxon signed rank tests were performed to assess changes within groups from start to end. RAE showed significant improvement for most of the standing variables, including measurements of combined autonomic influence, e.g. SDRR (p = 0.002) and variables indicating only vagal influence, e.g. pNN50 (p = 0.014). RAC mostly deteriorated with emphasis on variables measuring vagal influence (RMSSD, pNN50, SD1 and HF (ms(2)). Study results indicated that 12 weeks of exercise intervention had a positive effect on cardiac autonomic function as measured by short-term HRV, in females with RA. Several of the standing variables indicated improved vagal influence on the heart rate. Exercise can thus potentially be used as an instrument to improve cardiac health in a patient group known for increased cardiac morbidity.

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

    Science.gov (United States)

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

    2017-04-01

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

  5. Cardiomyocyte-specific expression of lamin a improves cardiac function in Lmna-/- mice.

    Directory of Open Access Journals (Sweden)

    Richard L Frock

    Full Text Available Lmna(-/- mice display multiple tissue defects and die by 6-8 weeks of age reportedly from dilated cardiomyopathy with associated conduction defects. We sought to determine whether restoration of lamin A in cardiomyocytes improves cardiac function and extends the survival of Lmna(-/- mice. We observed increased total desmin protein levels and disorganization of the cytoplasmic desmin network in ~20% of Lmna(-/- ventricular myocytes, rescued in a cell-autonomous manner in Lmna(-/- mice expressing a cardiac-specific lamin A transgene (Lmna(-/-; Tg. Lmna(-/-; Tg mice displayed significantly increased contractility and preservation of myocardial performance compared to Lmna(-/- mice. Lmna(-/-; Tg mice attenuated ERK1/2 phosphorylation relative to Lmna(-/- mice, potentially underlying the improved localization of connexin43 to the intercalated disc. Electrocardiographic recordings from Lmna(-/- mice revealed arrhythmic events and increased frequency of PR interval prolongation, which is partially rescued in Lmna(-/-; Tg mice. These findings support our observation that Lmna(-/-; Tg mice have a 12% median extension in lifespan compared to Lmna(-/- mice. While significant, Lmna(-/-; Tg mice only have modest improvement in cardiac function and survival likely stemming from the observation that only 40% of Lmna(-/-; Tg cardiomyocytes have detectable lamin A expression. Cardiomyocyte-specific restoration of lamin A in Lmna(-/- mice improves heart-specific pathology and extends lifespan, demonstrating that the cardiac pathology of Lmna(-/- mice limits survival. The expression of lamin A is sufficient to rescue certain cellular defects associated with loss of A-type lamins in cardiomyocytes in a cell-autonomous fashion.

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

    Directory of Open Access Journals (Sweden)

    Reza Karbasi Afshar

    2015-01-01

    Full Text Available 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.

  7. The PKD inhibitor CID755673 enhances cardiac function in diabetic db/db mice.

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    Kylie Venardos

    Full Text Available The development of diabetic cardiomyopathy is a key contributor to heart failure and mortality in obesity and type 2 diabetes (T2D. Current therapeutic interventions for T2D have limited impact on the development of diabetic cardiomyopathy. Clearly, new therapies are urgently needed. A potential therapeutic target is protein kinase D (PKD, which is activated by metabolic insults and implicated in the regulation of cardiac metabolism, contractility and hypertrophy. We therefore hypothesised that PKD inhibition would enhance cardiac function in T2D mice. We first validated the obese and T2D db/db mouse as a model of early stage diabetic cardiomyopathy, which was characterised by both diastolic and systolic dysfunction, without overt alterations in left ventricular morphology. These functional characteristics were also associated with increased PKD2 phosphorylation in the fed state and a gene expression signature characteristic of PKD activation. Acute administration of the PKD inhibitor CID755673 to normal mice reduced both PKD1 and 2 phosphorylation in a time and dose-dependent manner. Chronic CID755673 administration to T2D db/db mice for two weeks reduced expression of the gene expression signature of PKD activation, enhanced indices of both diastolic and systolic left ventricular function and was associated with reduced heart weight. These alterations in cardiac function were independent of changes in glucose homeostasis, insulin action and body composition. These findings suggest that PKD inhibition could be an effective strategy to enhance heart function in obese and diabetic patients and provide an impetus for further mechanistic investigations into the role of PKD in diabetic cardiomyopathy.

  8. Chronic mitral regurgitation detected on cardiac MDCT: differentiation between functional and valvular aetiologies.

    LENUS (Irish Health Repository)

    Killeen, Ronan P

    2012-02-01

    OBJECTIVE: To determine whether cardiac computed tomography (MDCT) can differentiate between functional and valvular aetiologies of chronic mitral regurgitation (MR) compared with echocardiography (TTE). METHODS: Twenty-seven patients with functional or valvular MR diagnosed by TTE and 19 controls prospectively underwent cardiac MDCT. The morphological appearance of the mitral valve (MV) leaflets, MV geometry, MV leaflet angle, left ventricular (LV) sphericity and global\\/regional wall motion were analysed. The coronary arteries were evaluated for obstructive atherosclerosis. RESULTS: All control and MR cases were correctly identified by MDCT. Significant differences were detected between valvular and control groups for anterior leaflet length (30 +\\/- 7 mm vs. 22 +\\/- 4 mm, P < 0.02) and thickness (3.0 +\\/- 1 mm vs. 2.2 +\\/- 1 mm, P < 0.01). High-grade coronary stenosis was detected in all patients with functional MR compared with no controls (P < 0.001). Significant differences in those with\\/without MV prolapse were detected in MV tent area (-1.0 +\\/- 0.6 mm vs. 1.3 +\\/- 0.9 mm, P < 0.0001) and MV tent height (-0.7 +\\/- 0.3 mm vs. 0.8 +\\/- 0.8 mm, P < 0.0001). Posterior leaflet angle was significantly greater for functional MR (37.9 +\\/- 19.1 degrees vs. 22.9 +\\/- 14 degrees , P < 0.018) and less for valvular MR (0.6 +\\/- 35.5 degrees vs. 22.9 +\\/- 14 degrees, P < 0.017). Sensitivity, specificity, and positive and negative predictive values of MDCT were 100%, 95%, 96% and 100%. CONCLUSION: Cardiac MDCT allows the differentiation between functional and valvular causes of MR.

  9. Effect of endothelial progenitor cell treated by ranulocyte colony stimulating factor on cardiac function in patients with heart failure after myocardial infarction%粒细胞集落刺激因子动员血管内皮祖细胞对心肌梗死后心力衰竭患者心肌能量消耗的影响

    Institute of Scientific and Technical Information of China (English)

    赵子粼; 郭志刚; 吴平生; 沈安娜; 许顶立

    2011-01-01

    死后心力衰竭患者,可有效改善心功能,减轻心室重构,降低心肌能量消耗.%Objectives To study the changes of cardiac function and myocardial energy expenditure in patients with heart failure after myocardial infarction treated with granulocyte colony stimulating factor (G-CSF). Methods Thirty-eight patients with heart failure after myocardial infarction were randomized divided into treatment group and control group. All patients received conventional treatment (medication and interventional therapy), patients in treatment group were given additional G-CSF mobilization injection (600 μg/d), continuous for 7 d. Plasma concentration of brain-type natriuretic peptide ( BNP ) and the number of endothelial progenitor cell (EPC) in peripheral blood were detected pre-treatment and 7 d. 4 months post-treatment. Cardiac function [ejection fraction (EF) , shortening fraction (FS). Left ventricular internal diameter at end-systole (LVIDs), posterior wall thickniss (PWTs) , end diastolic volume (EDV), stroke volume (SV ), ejection time(ET)] was evaluated by ultrasonic imaging at pre-treatment and 2 weeks, 4 months post-treatment. Myocardium energy expenditure(MEE) and left ventricular circumferential end systolic wall stress (cESS) were calculated by the formula. Results The number of EPC in treatment group increased more than that in control group, especially at 7 d post-treatment (78.2±7.6 vs. 50.4±5.3 ,P<0.01 ), The BNP concentration of the two groups decreased and returned to normal level after treatment (P<0.01). The level of cardiac function increased in all patients at 2 weeks, 4 months post-treatment, and the value were statistically different between two groups(P<0.05),especially at 2 weeks post-treatment the value of the the MEE , cESS decreased significantly compared with control group [ (251.3± 29.5)xl0-2N/cm2vs. ( 277.6±28.7) xl0-2N/cm2, P<0.01; (1.35±0.36) cal/systole vs. (1.46+0.41) cal/systole, P< 0.01]. At 4 months post-treatment, the

  10. Cardiac function improved by sarcoplasmic reticulum Ca2+-ATPase overexpression in a heart failure model induced by chronic myocardial ischemia

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    Wei XIN

    2011-04-01

    Full Text Available Objective Chronic myocardial ischemia(CMI has become an important cause of heart failure(HF.The aim of present study was to examine the effects of Sarco-endoplasmic reticulum calcium ATPase(SERCA2a gene transfer in HF model in large animal induced by CMI.Methods HF was reproduced in minipigs by ligating the initial segment of proximal left anterior descending(LAD coronary artery with an ameroid constrictor to produce progressive vessel occlusion and ischemia.After confirmation of myocardial perfusion defect and cardiac function impairment by SPECT and echocardiography in the model,animals were divided into 4 groups: HF group;HF+enhanced green fluorescent protein(EGFP group;HF+SERCA2a group;and sham operation group as control.rAAV1-EGFP and rAAV1-SERCA2a(1×1012 vg for each animal were directly and intramyocardially injected to the animals of HF+EGFP and HF+SERCA2a groups.Sixty days after the gene transfer,the expression of SERCA2a at the protein level was examined by Western blotting and immunohistochemistry,the changes in cardiac function were determined by echocardiographic and hemodynamic analysis,and the changes in serum inflammatory and neuro-hormonal factors(including BNP,TNF-a,IL-6,ET-1 and Ang II were determined by radioimmunoassay.Results Sixty days after gene transfer,LVEF,Ev/Av and ±dp/dtmax increased significantly(P < 0.05,along with an increase of SERCA2a protein expression in the ischemic myocardium(PP < 0.05,accompanied by a significant decrease of inflammatory and neural-hormonal factors(PP < 0.05 in HF+SERCA2a group as compared with HF/HF+EGFP group.Conclusions Overexpression of SERCA2a may significantly improve the cardiac function of the ischemic myocardium of HF model induced by CMI and reverse the activation of neural-hormonal factors,implying that it has a potential therapeutic significance in CMI related heart failure.

  11. Methotrexate carried in lipid core nanoparticles reduces myocardial infarction size and improves cardiac function in rats.

    Science.gov (United States)

    Maranhão, Raul C; Guido, Maria C; de Lima, Aline D; Tavares, Elaine R; Marques, Alyne F; Tavares de Melo, Marcelo D; Nicolau, Jose C; Salemi, Vera Mc; Kalil-Filho, Roberto

    2017-01-01

    Acute myocardial infarction (MI) is accompanied by myocardial inflammation, fibrosis, and ventricular remodeling that, when excessive or not properly regulated, may lead to heart failure. Previously, lipid core nanoparticles (LDE) used as carriers of the anti-inflammatory drug methotrexate (MTX) produced an 80-fold increase in the cell uptake of MTX. LDE-MTX treatment reduced vessel inflammation and atheromatous lesions induced in rabbits by cholesterol feeding. The aim of the study was to investigate the effects of LDE-MTX on rats with MI, compared with commercial MTX treatment. Thirty-eight Wistar rats underwent left coronary artery ligation and were treated with LDE-MTX, or with MTX (1 mg/kg intraperitoneally, once/week, starting 24 hours after surgery) or with LDE without drug (MI-controls). A sham-surgery group (n=12) was also included. Echocardiography was performed 24 hours and 6 weeks after surgery. The animals were euthanized and their hearts were analyzed for morphometry, protein expression, and confocal microscopy. LDE-MTX treatment achieved a 40% improvement in left ventricular (LV) systolic function and reduced cardiac dilation and LV mass, as shown by echocardiography. LDE-MTX reduced the infarction size, myocyte hypertrophy and necrosis, number of inflammatory cells, and myocardial fibrosis, as shown by morphometric analysis. LDE-MTX increased antioxidant enzymes; decreased apoptosis, macrophages, reactive oxygen species production; and tissue hypoxia in non-infarcted myocardium. LDE-MTX increased adenosine bioavailability in the LV by increasing adenosine receptors and modulating adenosine catabolic enzymes. LDE-MTX increased the expression of myocardial vascular endothelium growth factor (VEGF) associated with adenosine release; this correlated not only with an increase in angiogenesis, but also with other parameters improved by LDE-MTX, suggesting that VEGF increase played an important role in the beneficial effects of LDE-MTX. Overall effects of

  12. Postoperative Arrhythmias after Cardiac Surgery: Incidence, Risk Factors, and Therapeutic Management

    Directory of Open Access Journals (Sweden)

    Giovanni Peretto

    2014-01-01

    Full Text Available Arrhythmias are a known complication after cardiac surgery and represent a major cause of morbidity, increased length of hospital stay, and economic costs. However, little is known about incidence, risk factors, and treatment of early postoperative arrhythmias. Both tachyarrhythmias and bradyarrhythmias can present in the postoperative period. In this setting, atrial fibrillation is the most common heart rhythm disorder. Postoperative atrial fibrillation is often self-limiting, but it may require anticoagulation therapy and either a rate or rhythm control strategy. However, ventricular arrhythmias and conduction disturbances can also occur. Sustained ventricular arrhythmias in the recovery period after cardiac surgery may warrant acute treatment and long-term preventive strategy in the absence of reversible causes. Transient bradyarrhythmias may be managed with temporary pacing wires placed at surgery, but significant and persistent atrioventricular block or sinus node dysfunction can occur with the need for permanent pacing. We provide a complete and updated review about mechanisms, risk factors, and treatment strategies for the main postoperative arrhythmias.

  13. Experiments in cardiac xenotransplantation. Response to intrathymic xenogeneic cells and intravenous cobra venom factor.

    Science.gov (United States)

    Mohiuddin, M; Kline, G; Shen, Z; Ruggiero, V; Rostami, S; DiSesa, V J

    1993-10-01

    Permanent tolerance to an experimental cardiac allograft can be achieved by pretransplantation intrathymic inoculation of donor-specific lymphoid cells. We studied the effects of intrathymic inoculation of xenogeneic cells and intravenous cobra venom factor in a rodent model of cardiac xenotransplantation. Lewis rats underwent intraabdominal heterotopic heart transplantation with Syrian hamster donors. In untreated animals, mean graft survival time was 3 days. Five rats had 1 ml of antilymphocyte serum administered intraperitoneally. One day later, 2.5 x 10(7) hamster spleen cells were inoculated into the thymus under direct vision. Twenty-one days after antilymphocyte serum was given, heterotopic heart transplantation with a hamster donor was carried out. In all cases, rejection was accelerated and occurred between 20 minutes and 1 day after transplantation. Mean graft survival time was 5.2 hours (p cobra venom factor, a complement antagonist, administered intravenously 3 hours before transplantation and every other day thereafter. Mean graft survival was 3 days, which was not different from the response of naive animals. Animals treated with antilymphocyte serum only had no prolongation of graft survival (mean survival time 3 days, p = not significant). Animals treated with cobra venom factor alone (n = 5) before transplantation and on alternate days subsequently had mild graft prolongation with a mean survival time of 4 days (p = 0.0133). In contrast to experimental allograft models, intrathymic inoculation of xenogeneic cells produces hyperacute rejection in these naturally concordant species. The administration of cobra venom factor abrogates the hyperacute response, but the combination of cobra venom factor and intrathymic inoculation does not produce long-term graft survival.

  14. Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor.

    Science.gov (United States)

    Singh, Sanjay; Sayers, Scott; Walter, James S; Thomas, Donald; Dieter, Robert S; Nee, Lisa M; Wurster, Robert D

    2013-08-19

    Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm(2); Phypertrophy of neurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.

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

    Science.gov (United States)

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

    2014-06-01

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

  16. Cardiac autonomic and ventricular mechanical functions in asymptomatic chronic chagasic cardiomyopathy.

    Science.gov (United States)

    Vasconcelos, Daniel França; Junqueira, Luiz Fernando

    2012-02-01

    The association of variably altered cardiac autonomic and ventricular systolic and diastolic functions is still controversial and little explored in chronic Chagas' disease. To evaluate the extent to which cardiac autonomic and mechanical ventricular functions are altered and whether they are associated in asymptomatic chagasic cardiomyopathy. A total of 13 patients with asymptomatic chagasic cardiomyopathy and 15 normal subjects (control group) were evaluated and the autonomic modulation of heart rate variability for five minutes, in the temporal and spectral domains, in the supine and orthostatic positions, as well as ventricular function based on morphological-functional variables obtained by Doppler echocardiography were correlated. Statistical analysis used the Mann-Whitney test and Spearman's correlation. In both positions, the temporal index (p = 0.0004 to 0.01) and total (p = 0.0007-0.005) and absolute spectral areas, of low and high frequencies (p = 0.0001 to 0.002), were lower in the chagasic group. The vagal-sympathetic balance was similar in both positions (p = 0.43 to 0.89). The echocardiographic variables did not differ between groups (p = 0.13 to 0.82), except the left ventricular end-systolic diameter, which was larger (p = 0.04) and correlated directly with reduced rates of global (p = 0.01 to 0.04) and parasympathetic (p = 0.002 to 0.01) autonomic modulation in patients with Chagas disease in the orthostatic position. The sympathetic and parasympathetic depressions with preserved balance were associated with only one ventricular dysfunction indicator. This suggests that cardiac autonomic dysfunction may precede and be independently more severe than ventricular dysfunction, with no causal association between both disorders in chronic chagasic cardiomyopathy.

  17. Cardiac autonomic function and high-intensity interval training in middle-age men.

    Science.gov (United States)

    Kiviniemi, Antti M; Tulppo, Mikko P; Eskelinen, Joonas J; Savolainen, Anna M; Kapanen, Jukka; Heinonen, Ilkka H A; Huikuri, Heikki V; Hannukainen, Jarna C; Kalliokoski, Kari K

    2014-10-01

    The effects of short-term high-intensity interval training (HIT) on cardiac autonomic function are unclear. The present study assessed cardiac autonomic adaptations to short-term HIT in comparison with aerobic endurance training (AET). Twenty-six healthy middle-age sedentary men were randomized into HIT (n = 13, 4-6 × 30 s of all-out cycling efforts with 4-min recovery) and AET (n = 13, 40-60 min at 60% of peak workload) groups, performing six sessions within 2 wk. The participants underwent a 24-h ECG recording before and after the intervention and, additionally, recorded R-R interval data in supine position (5 min) at home every morning during the intervention. Mean HR and low-frequency (LF) and high-frequency (HF) power of R-R interval oscillation were analyzed from these recordings. Peak oxygen consumption (V˙O2peak) increased in both groups (P training, most probably by inducing larger increases in cardiac vagal activity. The acute autonomic responses to the single HIT session were not modified by short-term training.

  18. Cardiac Myocyte De Novo DNA Methyltransferases 3a/3b Are Dispensable for Cardiac Function and Remodeling after Chronic Pressure Overload in Mice.

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    Thomas G Nührenberg

    Full Text Available Recent studies reported altered DNA methylation in failing human hearts. This may suggest a role for de novo DNA methylation in the development of heart failure. Here, we tested whether cardiomyocyte-specific loss of de novo DNA methyltransferases Dnmt3a and Dnmt3b altered cardiac function and remodeling after chronic left ventricular pressure overload.Mice with specific ablation of Dnmt3a and Dnmt3b expression in cardiomyocytes were generated by crossing floxed Dnmt3afl and Dnmt3bfl alleles with mice expressing Cre recombinase under control of the atrial myosin light chain gene promoter. The efficacy of combined Dnmt3a/3b ablation (DKO was characterized on cardiomyocyte-specific genomic DNA and mRNA levels. Cardiac phenotyping was carried out without (sham or with left ventricular pressure overload induced by transverse aortic constriction (TAC. Under similar conditions, cardiac genome-wide transcriptional profiling was performed and DNA methylation levels of promoters of differentially regulated genes were assessed by pyrosequencing.DKO cardiomyocytes showed virtual absence of targeted Dnmt3a and Dnmt3b mRNA transcripts. Cardiac phenotyping revealed no significant differences between DKO and control mice under sham and TAC conditions. Transcriptome analyses identified upregulation of 44 and downregulation of 9 genes in DKO as compared with control sham mice. TAC mice showed similar changes with substantial overlap of regulated genes compared to sham. Promoters of upregulated genes were largely unmethylated in DKO compared to control mice.The absence of cardiac pathology in the presence of the predicted molecular phenotype suggests that de novo DNA methylation in cardiomyocytes is dispensable for adaptive mechanisms after chronic cardiac pressure overload.

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

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    Polizzi Clara

    2010-11-01

    Full Text Available Abstract 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.

  20. Decoding the Long Noncoding RNA During Cardiac Maturation: A Roadmap for Functional Discovery.

    Science.gov (United States)

    Touma, Marlin; Kang, Xuedong; Zhao, Yan; Cass, Ashley A; Gao, Fuying; Biniwale, Reshma; Coppola, Giovanni; Xiao, Xinshu; Reemtsen, Brian; Wang, Yibin

    2016-10-01

    Cardiac maturation during perinatal transition of heart is critical for functional adaptation to hemodynamic load and nutrient environment. Perturbation in this process has major implications in congenital heart defects. Transcriptome programming during perinatal stages is an important information but incomplete in current literature, particularly, the expression profiles of the long noncoding RNAs (lncRNAs) are not fully elucidated. From comprehensive analysis of transcriptomes derived from neonatal mouse heart left and right ventricles, a total of 45 167 unique transcripts were identified, including 21 916 known and 2033 novel lncRNAs. Among these lncRNAs, 196 exhibited significant dynamic regulation along maturation process. By implementing parallel weighted gene co-expression network analysis of mRNA and lncRNA data sets, several lncRNA modules coordinately expressed in a developmental manner similar to protein coding genes, while few lncRNAs revealed chamber-specific patterns. Out of 2262 lncRNAs located within 50 kb of protein coding genes, 5% significantly correlate with the expression of their neighboring genes. The impact of Ppp1r1b-lncRNA on the corresponding partner gene Tcap was validated in cultured myoblasts. This concordant regulation was also conserved in human infantile hearts. Furthermore, the Ppp1r1b-lncRNA/Tcap expression ratio was identified as a molecular signature that differentiated congenital heart defect phenotypes. The study provides the first high-resolution landscape on neonatal cardiac lncRNAs and reveals their potential interaction with mRNA transcriptome during cardiac maturation. Ppp1r1b-lncRNA was identified as a regulator of Tcap expression, with dynamic interaction in postnatal cardiac development and congenital heart defects. © 2016 American Heart Association, Inc.

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

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    Ballinger Michelle R

    2008-01-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

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

    2014-07-01

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

  3. Structural and functional cardiac adaptations to 6 months of football training in untrained hypertensive men

    DEFF Research Database (Denmark)

    Andersen, L. J.; Randers, M. B.; Hansen, P. R.

    2014-01-01

    We investigated the effects of 3 and 6 months of regular football training on cardiac structure and function in hypertensive men. Thirty-one untrained males with mild-to-moderate hypertension were randomized 2:1 to a football training group (n = 20) and a control group receiving traditional...... recommendations on healthy lifestyle (n = 11). Cardiac measures were evaluated by echocardiography. The football group exhibited significant (P function after just 3 months: Left ventricular (LV) end-diastolic volume increased from 104 ± 25 to 117 ± 29 mL. LV diastolic...... function improved measured as E/A ratio (1.15 ± 0.32 to 1.54 ± 0.38), early diastolic velocity, E' (11.0 ± 2.5 to 11.9 ± 2.6 cm/s), and isovolumetric relaxation time (74 ± 13 to 62 ± 13 ms). LV systolic function improved measured as longitudinal displacement (10.7 ± 2.1 to 12.1 ± 2.3 mm). Right ventricular...

  4. Pancreatic cellular injury after cardiac surgery with cardiopulmonary bypass: frequency, time course and risk factors.

    Science.gov (United States)

    Nys, Monique; Venneman, Ingrid; Deby-Dupont, Ginette; Preiser, Jean-Charles; Vanbelle, Sophie; Albert, Adelin; Camus, Gérard; Damas, Pierre; Larbuisson, Robert; Lamy, Maurice

    2007-05-01

    Although often clinically silent, pancreatic cellular injury (PCI) is relatively frequent after cardiac surgery with cardiopulmonary bypass; and its etiology and time course are largely unknown. We defined PCI as the simultaneous presence of abnormal values of pancreatic isoamylase and immunoreactive trypsin (IRT). The frequency and time evolution of PCI were assessed in this condition using assays for specific exocrine pancreatic enzymes. Correlations with inflammatory markers were searched for preoperative risk factors. One hundred ninety-three patients submitted to cardiac surgery were enrolled prospectively. Blood IRT, amylase, pancreatic isoamylase, lipase, and markers of inflammation (alpha1-protease inhibitor, alpha2-macroglobulin, myeloperoxidase) were measured preoperatively and postoperatively until day 8. The postoperative increase in plasma levels of pancreatic enzymes and urinary IRT was biphasic in all patients: early after surgery and later (from day 4 to 8 after surgery). One hundred thirty-three patients (69%) experienced PCI, with mean IRT, isoamylase, and alpha1-protease inhibitor values higher for each sample than that in patients without PCI. By multiple regression analysis, we found preoperative values of plasma IRT >or=40 ng/mL, amylase >or=42 IU/mL, and pancreatic isoamylase >or=20 IU/L associated with a higher incidence of postsurgery PCI (P < 0.005). In the PCI patients, a significant correlation was found between the 4 pancreatic enzymes and urinary IRT, total calcium, myeloperoxidase, alpha1-protease inhibitor, and alpha2-macroglobulin. These data support a high prevalence of postoperative PCI after cardiac surgery with cardiopulmonary bypass, typically biphasic and clinically silent, especially when pancreatic enzymes were elevated preoperatively.

  5. Protein kinase G1 α overexpression increases stem cell survival and cardiac function after myocardial infarction.

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    Linlin Wang

    Full Text Available BACKGROUND: We hypothesized that overexpression of cGMP-dependent protein kinase type 1α (PKG1α could mimic the effect of tadalafil on the survival of bone marrow derived mesenchymal stem cells (MSCs contributing to regeneration of the ischemic heart. METHODS AND RESULTS: MSCs from male rats were transduced with adenoviral vector encoding for PKG1α ((PKG1αMSCs.Controls included native MSCs ((NatMSCs and MSCs transduced with an empty vector ((NullMSCs. PKG1α activity was increased approximately 20, 5 and 16 fold respectively in (PKG1αMSCs. (PKG1αMSCs showed improved survival under oxygen and glucose deprivation (OGD which was evidenced by lower LDH release, caspase-3/7 activity and number of positive TUNEL cells. Anti-apoptotic proteins pAkt, pGSK3β, and Bcl-2 were significantly increased in (PKG1αMSCs compared to (NatMSCs and (NullMSCs. Higher release of multiple prosurvival and angiogenic factors such as HGF, bFGF, SDF-1 and Ang-1 was observed in (PKG1αMSCs before and after OGD. In a female rat model of acute myocardial infarction, (PKG1αMSCs group showed higher survival compared with (NullMSCs group at 3 and 7 days after transplantation as determined by TUNEL staining and sry-gene quantitation by real-time PCR. Increased anti-apoptotic proteins and paracrine factors in vitro were also identified. Immunostaining for cardiac troponin I combined with GFP showed increased myogenic differentiation of (PKG1αMSCs. At 4 weeks after transplantation, compared to DMEM group and (NullMSCs group, (PKG1αMSCs group showed increased blood vessel density in infarct and peri-infarct areas (62.5±7.7; 68.8±7.3 per microscopic view, p<0.05 and attenuated infarct size (27.2±2.5%, p<0.01. Heart function indices including ejection fraction (52.1±2.2%, p<0.01 and fractional shortening (24.8%±1.3%, p<0.01 were improved significantly in (PKG1αMSCs group. CONCLUSION: Overexpression of PKG1α transgene could be a powerful approach to improve MSCs

  6. The effects of cardiopulmonary bypass on pulmonary function during robotic cardiac surgery.

    Science.gov (United States)

    Wang, G; Xiao, S; Gao, C

    2015-04-01

    We aimed to investigate the effects of cardiopulmonary bypass (CPB) on pulmonary function under the conditions of one-lung ventilation (OLV) and carbon dioxide pneumothorax in robotic cardiac surgery. Ninety-eight patients underwent robotic cardiac surgery using the da Vinci Surgical System, including 58 on-pump surgeries and 40 off-pump surgeries. Respiratory parameters and arterial blood gases were assessed at the following time points: 25 min after the induction of anesthesia under two-lung ventilation (T1), 25 min after OLV (T2), 25 min after the termination of CPB under OLV in the on-pump group or 25 min after the main surgery intervention in the off-pump group (T3) and 20 min before the end of surgery (T4). Dynamic lung compliance (Cdyn), alveolar-arterial PO2 difference (PA-aDO2), oxygenation index (OI) and artery-alveolar O2 pressure ratio (a/A) were calculated. No significant differences in pulmonary function parameters between T2 and T3 were observed in the off-pump group. However, in the on-pump group, compared with those at T2, PETCO2, Ppeak, PaCO2 and PA-aDO2 at T3 were higher, whereas SpO2, Cdyn, PaO2, OI and a/A were lower (probotic cardiac surgery under the conditions of OLV and carbon dioxide pneumothorax, CPB worsened pulmonary function and tolerance to OLV and carbon dioxide pneumothorax. © The Author(s) 2014.

  7. Cell functional enviromics: Unravelling the function of environmental factors

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    Alves Paula M

    2011-06-01

    Full Text Available Abstract Background While functional genomics, focused on gene functions and gene-gene interactions, has become a very active field of research in molecular biology, equivalent methodologies embracing the environment and gene-environment interactions are relatively less developed. Understanding the function of environmental factors is, however, of paramount importance given the complex, interactive nature of environmental and genetic factors across multiple time scales. Results Here, we propose a systems biology framework, where the function of environmental factors is set at its core. We set forth a "reverse" functional analysis approach, whereby cellular functions are reconstructed from the analysis of dynamic envirome data. Our results show these data sets can be mapped to less than 20 core cellular functions in a typical mammalian cell culture, while explaining over 90% of flux data variance. A functional enviromics map can be created, which provides a template for manipulating the environmental factors to induce a desired phenotypic trait. Conclusion Our results support the feasibility of cellular function reconstruction guided by the analysis and manipulation of dynamic envirome data.

  8. [Left ventricular functions in patients with cardiac syndrome X: a tissue Doppler study].

    Science.gov (United States)

    Yazici, Hüseyin Uğur; Sen, Nihat; Tavil, Yusuf; Hizal, Fatma; Turfan, Murat; Poyraz, Fatih; Boyaci, Bülent; Cengel, Atiye

    2009-12-01

    The aim of the study was to compare diagnostic accuracy of tissue Doppler imaging (TDI) and conventional Doppler echocardiography in diagnosis of left ventricular diastolic dysfunction in patients with cardiac syndrome X. Our study was designed as cross-sectional study. In our study, we compared 35 patients with cardiac syndrome X (19 female, mean age 47.2+/- 7.3 years) with 33 healthy persons as control group (18 female, mean age 49.5+/- 7.1 years) with no coronary artery disease and having no ischemic complaints or findings at exercise test. Left ventricular systolic function was found by considering mean values of modified Simpson method for left ventricular ejection fraction and TDI assessment of systolic wave peak velocity. The diastolic function of left ventricle was assessed with conventional echocardiography and TDI. Unpaired t test for independent samples or Mann-Whitney U test were used for comparison of continuous variables, Chi square test - for comparison of categorical variables. To define the capability of predicting diastolic dysfunction for conventional Doppler echocardiography and tissue Doppler imaging ROC curve analysis was applied. Left ventricular ejection fraction and systolic wave peak velocity were similar for both groups. Conventional Doppler echocardiographic measurements for left ventricular diastolic functions delineated the more frequent presence of diastolic dysfunction in cardiac syndrome X group As compared with controls (48% vs 18%; p<0.01). When both methods used for assessing diastolic dysfunction, it was found more apparent (66% vs 24%; p<0.01). When ROC curve was drawn for conventional Doppler echocardiography the AUC was 0.623, the sensitivity and the specificity were 49% and 76%, respectively. When the same was done for TDI the values were AUC=0.669, the sensitivity - 66% and the specificity - 68%. Our study revealed the deterioration of left ventricular diastolic function in patients with cardiac syndrome X. We found TDI

  9. Hyperpolarized Metabolic MR in the Study of Cardiac Function and Disease

    DEFF Research Database (Denmark)

    Lauritzen, M H; Sogaard, L V; Madsen, P L

    2014-01-01

    Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR...... literature on hyperpolarized pyruvate that has been used to characterize cardiac disease in various in vivo models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and heart failure. The technical aspects of the technique are presented as well as the challenges of translating...

  10. Hyperpolarized metabolic MR in the study of cardiac function and disease

    DEFF Research Database (Denmark)

    Lauritzen, M. H.; Søgaard, L. V.; Madsen, Pia Lisbeth

    2014-01-01

    Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR...... literature on hyperpolarized pyruvate that has been used to characterize cardiac disease in various in vivo models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and heart failure. The technical aspects of the technique are presented as well as the challenges of translating...

  11. Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury.

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    Jianqin Ye

    Full Text Available BACKGROUND: Endogenous cardiac progenitor cells are a promising option for cell-therapy for myocardial infarction (MI. However, obtaining adequate numbers of cardiac progenitors after MI remains a challenge. Cardiospheres (CSs have been proposed to have cardiac regenerative properties; however, their cellular composition and how they may be influenced by the tissue milieu remains unclear. METHODOLOGY/PRINCIPAL FINDING: Using "middle aged" mice as CSs donors, we found that acute MI induced a dramatic increase in the number of CSs in a mouse model of MI, and this increase was attenuated back to baseline over time. We also observed that CSs from post-MI hearts engrafted in ischemic myocardium induced angiogenesis and restored cardiac function. To determine the role of Sca-1(+CD45(- cells within CSs, we cloned these from single cell isolates. Expression of Islet-1 (Isl1 in Sca-1(+CD45(- cells from CSs was 3-fold higher than in whole CSs. Cloned Sca-1(+CD45(- cells had the ability to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. We also observed that cloned cells engrafted in ischemic myocardium induced angiogenesis, differentiated into endothelial and smooth muscle cells and improved cardiac function in post-MI hearts. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate that cloned Sca-1(+CD45(- cells derived from CSs from infarcted "middle aged" hearts are enriched for second heart field (i.e., Isl-1(+ precursors that give rise to both myocardial and vascular tissues, and may be an appropriate source of progenitor cells for autologous cell-therapy post-MI.

  12. Epigenetic regulation in cardiac fibrosis

    Institute of Scientific and Technical Information of China (English)

    Li-Ming; Yu; Yong; Xu

    2015-01-01

    Cardiac fibrosis represents an adoptive response in the heart exposed to various stress cues. While resolution of the fibrogenic response heralds normalization of heart function, persistent fibrogenesis is usually associated with progressive loss of heart function and eventually heart failure. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix proteins, a process the epigenetic machinery plays a pivotal role. In this minireview, we summarize recent advances regarding the epigenetic regulation of cardiac fibrosis focusing on the role of histone and DNA modifications and non-coding RNAs.

  13. Cardiac function in total anomalous pulmonary venous return before and after surgery.

    Science.gov (United States)

    Mathew, R; Thilenius, O G; Replogle, R L; Arcilla, R A

    1977-02-01

    Cardiac performance was evaluated in 12 infants with isolated total anomalous pulmonary venous return. Four had significant pulmonary venous obstruction and severe pulmonary hypertension (group A). Eight had no obvious venous obstruction, and the pulmonary pressures were lower (group B). In all subjects, right ventricular end-diastolic volume was increased (197% of predicted normal) and its ejection fraction was normal. Left ventricular volume was, generally speaking, still in the normal range (87% of predicted normal); however, its ejection fraction was reduced (0.57 vs normal of 0.73) and left ventricular output was low (3.08 L/min/m2 vs normal of 3.98). Left atrial volume was consistently small (53% of predicted normal) with an appendage of normal size. The infants in group A had smaller chamber volumes/m2 BSA than those in group B. Left atrial function was abnormal, characterized by reduced reservoir function and a greater role as "conduit" from right atrium to left ventricle. Left atrial size was not found to be critical in the surgical repair of TAPVR. Cardiac function is restored to normal following surgery.

  14. Effect of Losartan on the Cardiac and Renal Function in Patients With Chronic Heart Failure

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    To explore the effect of losartan on cardiac and renal function in patients with chronic heart failure (CI-IF). Methods Sixty-five patients with CHF were divided into two groups using a randomized, control and single blind method: losartan group ( n = 30) and convention group ( n = 35 ), with a treatment course of 8 weeks for both groups. The concentrations of cystatin C (cys C) in serum, microamount albumin (MA) in urine were measured by immunoturbidimetry. The concentration of aquaporin-2 (AQP-2) was determined by enzyme-linked-immunosorbent assay (ELISA) and the heart contractile function was measured by echocardiography before and after treatment respectively. Results Comparing with routine treatment group, left ventricular end-diastolic dimension (LVEDd) decreased significantly, while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening ( LVFS ) increased significantly in losartan group. The levels of cys C in serum and MA, AQP-2 in urine were significantly lower in losartan group than in routine treatment group. Conclusion Losartan can improve cardiac and renal function in patients with CHF.

  15. Traditional Chinese Medicine Tongxinluo Improves Cardiac Function of Rats with Dilated Cardiomyopathy

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    Fang-Fang Shen

    2014-01-01

    Full Text Available The study aimed at testing the hypothesis that tongxinluo capsule might exert its cardioprotective effect by preventing ventricular remodeling and improving coronary microvascular function in a rat model of doxorubicin-induced dilated cardiomyopathy (DCM. Rats that survived DCM induction were randomly divided into three groups to be given 1.5 g·kg−1·day−1 (TXL-H, n=9 or 0.15 g·kg−1·day−1 (TXL-L, n=10 of tongxinluo, or normal saline at the same volume (DCM-C, n=10 intragastrically. Age matched normal rats treated with normal saline were used as normal controls (NOR-C, n=9. After four weeks of treatment, the DCM-C, TXL-H, and TXL-L groups exhibited significant cardiac dysfunction, left ventricular remodeling, and coronary microvascular dysfunction, compared with the NOR-C rats. However, myocardial functional parameters were significantly improved and microvascular density (MVD increased in the TXL-H group compared with the DCM-C group (all P<0.01. Left ventricular remodeling was prevented. There were close linear relationships between CVF and LVEF (r=-0.683, P<0.05, MVD and LVEF (r=0.895, P<0.05, and MVD and CVF (r=-0.798, P<0.05. It was indicated that high-dose tongxinluo effectively improved cardiac function in rat model of DCM.

  16. Beneficial effects of schisandrin B on the cardiac function in mice model of myocardial infarction.

    Science.gov (United States)

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

    2013-01-01

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

  17. Beneficial effects of schisandrin B on the cardiac function in mice model of myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Pengsheng Chen

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

  18. Impaired cardiac response to exercise in post-menopausal women: relationship with peripheral vascular function.

    Science.gov (United States)

    Yoshioka, J; Node, K; Hasegawa, S; Paul, A K; Mu, X; Maruyama, K; Nakatani, D; Kitakaze, M; Hori, M; Nishimura, T

    2003-04-01

    Endothelial dysfunction has been demonstrated in post-menopausal women. To assess the relationship between peripheral vascular reserve and cardiac function during exercise in post-menopausal women, 91 subjects, who had no ischaemic findings on myocardial SPECT, were assigned to four groups: pre-menopausal women (n=13), post-menopausal women (n=33), younger men aged 50 years (n=35). First-pass radionuclide angiography was performed before and during bicycle exercise to calculate ejection fraction (EF) and peripheral vascular resistance (VR). There were no differences in haemodynamic variables among the groups at baseline. The per cent increase in EF=(exercise EF - resting EF)x100/resting EF, and the per cent decrease in VR=(resting VR - exercise VR)x100/resting VR were depressed in the post-menopausal women (0.4+/-2% and 35+/-3%, respectively) compared to the pre-menopausal women (10+/-3% and 47+/-3%, respectively; PPost-menopausal women exhibited depressed cardiac function during exercise, which may be related to the impairment of peripheral vascular function after menopause.

  19. Effects of glycine supplementation on myocardial damage and cardiac function after severe burn.

    Science.gov (United States)

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

    2013-06-01

    Glycine has been shown to participate in protection from hypoxia/reoxygenation injury. However, the cardioprotective effect of glycine after burn remains unclear. This study aimed to explore the protective effect of glycine on myocardial damage in severely burned rats. Seventy-two Wistar rats were randomly divided into three groups: normal controls (C), burned controls (B), and glycine-treated (G). Groups B and G were given a 30% total body surface area full-thickness burn. Group G was administered 1.5 g/(kg d) glycine and group B was given the same dose of alanine via intragastric administration for 3d. Serum creatine kinase (CK), lactate dehydrogenase (LDH), aspartate transaminase (AST), and blood lactate, as well as myocardial ATP and glutathione (GSH) content, were measured. Cardiac contractile function and histopathological changes were analyzed at 12, 24, 48, and 72 hours. Serum CK, LDH, AST, and blood lactate increased, while myocardial ATP and GSH content decreased in both burned groups. Compared with group B, the levels of CK, LDH, and AST significantly decreased, whereas blood lactate as well as myocardial ATP and GSH content increased in group G. Moreover, cardiac contractile function inhibition and myocardial histopathological damage in group G significantly decreased compared with group B. Myocardial histological structure and function were damaged significantly after burn. Glycine is beneficial to myocardial preservation by improving cardiomyocyte energy metabolism and increasing ATP and GSH abundance. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  20. Effect of exercise combined with glucagon-like peptide-1 receptor agonist treatment on cardiac function

    DEFF Research Database (Denmark)

    Jørgensen, Peter G; Jensen, Magnus T; Mensberg, Pernille

    2017-01-01

    groups, P  = .03). We found no significant differences in heart rate, left ventricular (LV) structure or function within or between the groups. In conclusion, the addition of liraglutide to exercise in sedentary patients with dysregulated type 2 diabetes may blunt the suggested beneficial effect......In patients with type 2 diabetes, both supervised exercise and treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) liraglutide may improve cardiac function. We evaluated cardiac function before and after 16 weeks of treatment with the GLP-1RA liraglutide or placebo......, combined with supervised exercise, in 33 dysregulated patients with type 2 diabetes on diet and/or metformin. Early diastolic myocardial tissue velocity was improved by exercise in the placebo group (mean ± standard deviation [s.d.] -7.1 ± 1.6 to -7.7 ± 1.8 cm/s, P  = .01), but not in the liraglutide group...

  1. Echocardiographic evaluation of cardiac functions in newborns of mildly preeclamptic pregnant women within postnatal 24-48 hours.

    Science.gov (United States)

    Mutlu, Kadir; Karadas, Ulas; Yozgat, Yilmaz; Meşe, Timur; Demirol, Mustafa; Coban, Senay; Karadeniz, Cem; Özdemir, Rahmi; Orbatu, Dilek; Karaarslan, Utku; Tavli, Vedide

    2017-06-20

    The aim of this study is to detect preeclampsia-related cardiac dysfunction within 24-48 hours of delivery in newborns born from preeclamptic mothers. Forty newborns from mildly preeclamptic mothers formed the study group and the control group was formed by 40 healthy newborns. Cardiac function for the groups were evaluated using conventional echocardiography and myocardial performance index (MPI) within the first 24-48 hours of their lifetime and the results of both groups were compared. A significant difference between the groups was observed especially in the PW Doppler MPI measurements (the left ventricle MPI 0.37 ± 0.09 and 0.26 ± 0.11, p functions to determine preeclampsia-related cardiac injury in newborns from preeclamptic mothers within the first 24-48 hours of their lifetime. Impact statement Today, the methods which may detect cardiac injury earlier than conventional echocardiographic methods are used for evaluating cardiac functions. Among them, myocardial performance index (MPI) measurement with PW Doppler is the most common ones. While studies are available in the literature evaluating foetal cardiac functions with MPI in foetuses of preeclamptic women, studies evaluating cardiac functions with MPI index within the first 24-48 hours in postnatal period are not available. This is the first study to detect cardiac injury by measuring cardiac functions of the newborns of preeclamptic babies using conventional echocardiography (EF, SF, mitral and tricuspid E/A) and myocardial performance index within the first 24-48 hours of life and compare these values with those of a control group composed of healthy newborns with similar demographic characteristics. According to the results of the study, elongation in right and left ventricle MPI was detected to be more significant compared to systolic and diastolic functions for determining preeclampsia-related cardiac injury in newborns of preeclamptic mothers within 24-48 hours of delivery

  2. Prospective randomized controlled intervention trial: Comprehensive Yogic Breathing Improves Cardiac autonomic functions and Quality of life in Diabetes

    Directory of Open Access Journals (Sweden)

    V P Jyotsna

    2012-01-01

    Full Text Available Aims and Objectives: To assess the effect of Comprehensive Yogic Breathing Program on glycemic control, quality of life, and cardiac autonomic functions in diabetes. Material and Methods: This is a prospective randomized controlled intervention trial. Cardiac autonomic functions were assessed in 120 diabetics. Patients were randomized into two groups, one group receiving standard therapy for diabetes (n = 56 and the other group receiving standard therapy for diabetes and comprehensive yogic breathing program (n = 64. Standard therapy included advice on diet, walk, and oral antidiabetic drugs. Comprehensive yogic breathing program was an interactive session in which Sudarshan kriya yoga, a rhythmic cyclical breathing, preceded by Pranayam was taught under guidance of a certified teacher. Change in fasting, post prandial blood sugars, glycated hemoglobin, and quality of life were assessed. Cardiac autonomic function tests were done before and six months after intervention. Results: There was significant improvement in psychological (P = 0.006 and social domains (P = 0.04 and total quality of life (P = 0.02 in the group practicing comprehensive yogic breathing program as compared to the group following standard therapy alone. In the group following breathing program, the improvement in sympathetic cardiac autonomic functions was statistically significant (P = 0.01, while the change in the standard group was not significant (P = 0.17. When both parasympathetic and sympathetic cardiac autonomic functions were considered, there was a trend toward improvement in patients following comprehensive yogic breathing program (P = 0.07. In the standard therapy group, no change in cardiac autonomic functions was noted (P = 0.76. The parameters of glycemic control were comparable in both groups. Conclusion: There was significant improvement in quality of life and cardiac autonomic functions in the diabetes patients practicing comprehensive yogic breathing

  3. Maternal-engineered nanomaterial exposure disrupts progeny cardiac function and bioenergetics.

    Science.gov (United States)

    Hathaway, Quincy A; Nichols, Cody E; Shepherd, Danielle L; Stapleton, Phoebe A; McLaughlin, Sarah L; Stricker, Janelle C; Rellick, Stephanie L; Pinti, Mark V; Abukabda, Alaeddin B; McBride, Carroll R; Yi, Jinghai; Stine, Seth M; Nurkiewicz, Timothy R; Hollander, John M

    2017-03-01

    Nanomaterial production is expanding as new industrial and consumer applications are introduced. Nevertheless, the impacts of exposure to these compounds are not fully realized. The present study was designed to determine whether gestational nano-sized titanium dioxide exposure impacts cardiac and metabolic function of developing progeny. Pregnant Sprague-Dawley rats were exposed to nano-aerosols (~10 mg/m(3), 130- to 150-nm count median aerodynamic diameter) for 7-8 nonconsecutive days, beginning at gestational day 5-6 Physiological and bioenergetic effects on heart function and cardiomyocytes across three time points, fetal (gestational day 20), neonatal (4-10 days), and young adult (6-12 wk), were evaluated. Functional analysis utilizing echocardiography, speckle-tracking based strain, and cardiomyocyte contractility, coupled with mitochondrial energetics, revealed effects of nano-exposure. Maternal exposed progeny demonstrated a decrease in E- and A-wave velocities, with a 15% higher E-to-A ratio than controls. Myocytes isolated from exposed animals exhibited ~30% decrease in total contractility, departure velocity, and area of contraction. Bioenergetic analysis revealed a significant increase in proton leak across all ages, accompanied by decreases in metabolic function, including basal respiration, maximal respiration, and spare capacity. Finally, electron transport chain complex I and IV activities were negatively impacted in the exposed group, which may be linked to a metabolic shift. Molecular data suggest that an increase in fatty acid metabolism, uncoupling, and cellular stress proteins may be associated with functional deficits of the heart. In conclusion, gestational nano-exposure significantly impairs the functional capabilities of the heart through cardiomyocyte impairment, which is associated with mitochondrial dysfunction.NEW & NOTEWORTHY Cardiac function is evaluated, for the first time, in progeny following maternal nanomaterial inhalation. The

  4. Manual hyperinflation partly prevents reductions of functional residual capacity in cardiac surgical patients - a randomized controlled trial

    OpenAIRE

    Paulus, Frederique; Veelo, Denise P; Selma B. de Nijs; Beenen, Ludo FM; Bresser, Paul; de Mol, Bas AJM; Binnekade, Jan M; Schultz, Marcus J

    2011-01-01

    Introduction Cardiac surgery is associated with post-operative reductions of functional residual capacity (FRC). Manual hyperinflation (MH) aims to prevent airway plugging, and as such could prevent the reduction of FRC after surgery. The main purpose of this study was to determine the effect of MH on post-operative FRC of cardiac surgical patients. Methods This was a randomized controlled trial of patients after elective coronary artery bypass graft and/or valve surgery admitted to the inten...

  5. Complex SUMO-1 regulation of cardiac transcription factor Nkx2-5.

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    Mauro W Costa

    Full Text Available Reversible post-translational protein modifications such as SUMOylation add complexity to cardiac transcriptional regulation. The homeodomain transcription factor Nkx2-5/Csx is essential for heart specification and morphogenesis. It has been previously suggested that SUMOylation of lysine 51 (K51 of Nkx2-5 is essential for its DNA binding and transcriptional activation. Here, we confirm that SUMOylation strongly enhances Nkx2-5 transcriptional activity and that residue K51 of Nkx2-5 is a SUMOylation target. However, in a range of cultured cell lines we find that a point mutation of K51 to arginine (K51R does not affect Nkx2-5 activity or DNA binding, suggesting the existence of additional Nkx2-5 SUMOylated residues. Using biochemical assays, we demonstrate that Nkx2-5 is SUMOylated on at least one additional site, and this is the predominant site in cardiac cells. The second site is either non-canonical or a "shifting" site, as mutation of predicted consensus sites and indeed every individual lysine in the context of the K51R mutation failed to impair Nkx2-5 transcriptional synergism with SUMO, or its nuclear localization and DNA binding. We also observe SUMOylation of Nkx2-5 cofactors, which may be critical to Nkx2-5 regulation. Our data reveal highly complex regulatory mechanisms driven by SUMOylation to modulate Nkx2-5 activity.

  6. Functional high-resolution time-course expression analysis of human embryonic stem cells undergoing cardiac induction

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    Ilaria Piccini

    2016-12-01

    Full Text Available Cardiac induction of human embryonic stem cells (hESCs is a process bearing increasing medical relevance, yet it is poorly understood from a developmental biology perspective. Anticipated technological progress in deriving stably expandable cardiac precursor cells or in advancing cardiac subtype specification protocols will likely require deeper insights into this fascinating system. Recent improvements in controlling hESC differentiation now enable a near-homogeneous induction of the cardiac lineage. This is based on an optimized initial stimulation of mesoderm-inducing signaling pathways such as Activin and/or FGF, BMP, and WNT, followed by WNT inhibition as a secondary requirement. Here, we describe a comprehensive data set based on varying hESC differentiation conditions in a systematic manner and recording high-resolution differentiation time-courses analyzed by genome-wide expression profiling (GEO accession number GSE67154. As a baseline, hESCs were differentiated into cardiomyocytes under optimal conditions. Moreover, in additional time-series, individual signaling factors were withdrawn from the initial stimulation cocktail to reveal their specific roles via comparison to the standard condition. Hence, this data set presents a rich resource for hypothesis generation in studying human cardiac induction, as we reveal numbers of known as well as uncharacterized genes prominently marking distinct intermediate stages in the process. These data will also be useful for identifying putative cardiac master regulators in the human system as well as for characterizing expandable cardiac stem cells.

  7. Impact of thoracic surgery on cardiac morphology and function in small animal models of heart disease: a cardiac MRI study in rats.

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    Peter Nordbeck

    Full Text Available BACKGROUND: Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies. METHODS: Female Wistar rats (n = 6 per group were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition. RESULTS: Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05 and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05 after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw, such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05, or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05. Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass, but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease. CONCLUSION: Cardio-thoracic surgical procedures in experimental myocardial infarction

  8. Impact of type 2 diabetes and duration of type 2 diabetes on cardiac structure and function

    DEFF Research Database (Denmark)

    Jørgensen, Peter G; Jensen, Magnus T; Mogelvang, Rasmus;

    2016-01-01

    BACKGROUND: Contemporary treatment of type 2 diabetes (T2D) has improved patient outcome and may also have affected myocardial structure and function. We aimed to describe the effect of T2D and T2D duration on cardiac structure and function in a large outpatient population. METHODS: We performed...... dysfunction persisted after multivariable adjustment (P=0.013). CONCLUSIONS: In patients with T2D, LV structural and functional alterations persist and are accentuated with increasing diabetes duration despite reductions in overall risk of cardiovascular disease in this patient population....... comprehensive echocardiography on a representative sample of 1004 persons including a representative sample of 770 patients with T2D without known heart disease and 234 age- and sex-matched controls. RESULTS: T2D was associated with increased left ventricular (LV) wall thicknesses and decreased LV internal...

  9. Tissue Doppler echocardiography reveals impaired cardiac function in patients with reversible ischaemia

    DEFF Research Database (Denmark)

    Hoffmann, Søren; Mogelvang, Rasmus; Sogaard, Peter

    2011-01-01

    AIMS: To determine if echocardiographic tissue Doppler imaging (TDI) performed at rest detects reduced myocardial function in patients with reversible ischaemia. METHODS AND RESULTS: Eighty-four patients with angina pectoris, no previous history of ischaemic heart disease and normal left ventricu......AIMS: To determine if echocardiographic tissue Doppler imaging (TDI) performed at rest detects reduced myocardial function in patients with reversible ischaemia. METHODS AND RESULTS: Eighty-four patients with angina pectoris, no previous history of ischaemic heart disease and normal left...... velocities could be demonstrated in patients with a false-positive SPECT compared with controls. CONCLUSION: In patients with stable angina pectoris, preserved ejection fraction, and reversible ischaemia assessed by SPECT, echocardiographic colour TDI performed at rest reveals impaired cardiac function...

  10. Thalamic nuclear abnormalities as a contributory factor in sudden cardiac deaths among patients with schizophrenia

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    Fulvio A. Scorza

    2010-01-01

    Full Text Available Patients with schizophrenia have a two- to three-fold increased risk of premature death as compared to patients without this disease. It has been established that patients with schizophrenia are at a high risk of developing cardiovascular disease. Moreover, an important issue that has not yet been explored is a possible existence of a "cerebral" focus that could trigger sudden cardiac death in patients with schizophrenia. Along these lines, several structural and functional alterations in the thalamic complex are evident in patients with schizophrenia and have been correlated with the symptoms manifested by these patients. With regard to abnormalities on the cellular and molecular level, previous studies have shown that schizophrenic patients have fewer neuronal projections from the thalamus to the prefrontal cortex as well as a reduced number of neurons, a reduced volume of either the entire thalamus or its subnuclei, and abnormal glutamate signaling. According to the glutamate hypothesis of schizophrenia, hypofunctional corticostriatal and striatothalamic projections are directly involved in the pathophysiology of the disease. Animal and post-mortem studies have provided a large amount of evidence that links the sudden unexpected death in epilepsy (SUDEP that occurs in patients with schizophrenia and epilepsy to thalamic changes. Based on the results of these prior studies, it is clear that further research regarding the relationship between the thalamus and sudden cardiac death is of vital importance.

  11. The extracytoplasmic function (ECF) sigma factors.

    Science.gov (United States)

    Helmann, John D

    2002-01-01

    Bacterial sigma (sigma) factors are an essential component of RNA polymerase and determine promoter selectivity. The substitution of one sigma factor for another can redirect some or all of the RNA polymerase in a cell to activate the transcription of genes that would otherwise be silent. As a class, alternative sigma factors play key roles in coordinating gene transcription during various stress responses and during morphological development. The extracytoplasmic function (ECF) sigma factors are small regulatory proteins that are quite divergent in sequence relative to most other sigma factors. Many bacteria, particularly those with more complex genomes, contain multiple ECF sigma factors and these regulators often outnumber all other types of sigma factor combined. Examples include Bacillus subtilis (7 ECF sigma factors), Mycobacterium tuberculosis (10), Caulobacter crescentus (13), Pseudomonas aeruginosa (approximately 19), and Streptomyces coelicolor (approximately 50). The roles and mechanisms of regulation for these various ECF sigma factors are largely unknown, but significant progress has been made in selected systems. As a general trend, most ECF sigma factors are cotranscribed with one or more negative regulators. Often, these include a transmembrane protein functioning as an anti-sigma factor that binds, and inhibits, the cognate sigma factor. Upon receiving a stimulus from the environment, the sigma factor is released and can bind to RNA polymerase to stimulate transcription. In many ways, these anti-sigma:sigma pairs are analogous to the more familiar two-component regulatory systems consisting of a transmembrane histidine protein kinase and a DNA-binding response regulator. Both are mechanisms of coordinating a cytoplasmic transcriptional response to signals perceived by protein domains external to the cell membrane. Here, I review current knowledge of some of the better characterized ECF sigma factors, discuss the variety of experimental approaches

  12. Caffeine acts via A1 adenosine receptors to disrupt embryonic cardiac function.

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    Daniela L Buscariollo

    Full Text Available BACKGROUND: Evidence suggests that adenosine acts via cardiac A1 adenosine receptors (A1ARs to protect embryos against hypoxia. During embryogenesis, A1ARs are the dominant regulator of heart rate, and A1AR activation reduces heart rate. Adenosine action is inhibited by caffeine, which is widely consumed during pregnancy. In this study, we tested the hypothesis that caffeine influences developing embryos by altering cardiac function. METHODOLOGY/PRINCIPAL FINDINGS: Effects of caffeine and adenosine receptor-selective antagonists on heart rate were studied in vitro using whole murine embryos at E9.5 and isolated hearts at E12.5. Embryos were examined in room air (21% O(2 or hypoxic (2% O(2 conditions. Hypoxia decreased heart rates of E9.5 embryos by 15.8% and in E12.5 isolated hearts by 27.1%. In room air, caffeine (200 µM had no effect on E9.5 heart rates; however, caffeine increased heart rates at E12.5 by 37.7%. Caffeine abolished hypoxia-mediated bradycardia at E9.5 and blunted hypoxia-mediated bradycardia at E12.5. Real-time PCR analysis of RNA from isolated E9.5 and E12.5 hearts showed that A1AR and A2aAR genes were expressed at both ages. Treatment with adenosine receptor-selective antagonists revealed that SCH-58261 (A2aAR-specific antagonist had no affects on heart function, whereas DPCPX (A1AR-specific antagonist had effects similar to caffeine treatment at E9.5 and E12.5. At E12.5, embryonic hearts lacking A1AR expression (A1AR-/- had elevated heart rates compared to A1AR+/- littermates, A1AR-/- heart rates failed to decrease to levels comparable to those of controls. Caffeine did not significantly affect heart rates of A1AR-/- embryos. CONCLUSIONS/SIGNIFICANCE: These data show that caffeine alters embryonic cardiac function and disrupts the normal cardiac response to hypoxia through blockade of A1AR action. Our results raise concern for caffeine exposure during embryogenesis, particularly in pregnancies with increased risk of

  13. Evolution from increased cardiac mechanical function towards cardiomyopathy in the obese rat due to unbalanced high fat and abundant equilibrated diets

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    Mourmoura Evangelia

    2015-07-01

    Full Text Available The aim of our study was to know whether high dietary energy intake (HDEI with equilibrated and unbalanced diets in term of lipid composition modify the fatty acid profile of cardiac phospholipids and function of various cardiac cells and to know if the changes in membrane lipid composition can explain the modifications of cellular activity. Wistar rats were fed either a control or high-fat (HF diet for 12 weeks and Zucker diabetic fatty (ZDF rats as well as their lean littermate (ZL a control diet between week 7 to 11 of their life. Energy intake and abdominal obesity was increased in HF-fed and ZDF rats. Circulating lipids were also augmented in both strains although hyperglycemia was noticed only in ZDF rats. HDEI induced a decrease in linoleate and increase in arachidonate in membrane phospholipids which was more pronounced in the ZDF rats compared to the HF-fed rats. In vivo cardiac function (CF was improved in HF-fed rats whereas ex vivo cardiac function was unchanged, suggesting that environmental factors such as catecholamines stimulated the in vivo CF. The unchanged ex vivo CF was associated with an increased cardiac mass which indicated development of fibrosis and/or hypertrophy. The increased in vivo CF was sustained by an augmented coronary reserve which was related to the cyclooxygenase pathway and accumulation of arachidonate in membrane phospholipids. In conclusion, before triggering a diabetic cardiomyopathy, HDEI stimulated the CF. The development of cardiomyopathy seems to result from fibrosis and/or hypertrophy which augments myocardial stiffness and decreases contractility.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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; Whinnett, Zachary I

    2014-02-01

    The mechanoenergetic effects of atrioventricular delay optimization during biventricular pacing ("cardiac resynchronization therapy", CRT) are unknown. 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). 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). 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". © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

  16. Hydrogen sulfide suppresses transforming growth factor-β1-induced differentiation of human cardiac fibroblasts into myofibroblasts.

    Science.gov (United States)

    Zhang, YouEn; Wang, JiaNing; Li, Hua; Yuan, LiangJun; Wang, Lei; Wu, Bing; Ge, JunBo

    2015-11-01

    In heart disease, transforming growth factor-β1 (TGF-β1) converts fibroblasts into myofibroblasts, which synthesize and secrete fibrillar type I and III collagens. The purpose of the present study was to investigate how hydrogen sulfide (H2S) suppresses TGF-β1-induced differentiation of human cardiac fibroblasts to myofibroblasts. Human cardiac fibroblasts were serum-starved in fibroblast medium for 16 h before exposure to TGF-β1 (10 ng mL(-1)) for 24 h with or without sodium hydrosulfide (NaHS, 100 µmol L(-1), 30 min pretreatment) treatment. NaHS, an exogenous H2S donor, potently inhibited the proliferation and migration of TGF-β1-induced human cardiac fibroblasts and regulated their cell cycle progression. Furthermore, NaHS treatment led to suppression of fibroblast differentiation into myofibroblasts, and reduced the levels of collagen, TGF-β1, and activated Smad3 in TGF-β1-induced human cardiac fibroblasts in vitro. We therefore conclude that H2S suppresses TGF-β1-stimulated conversion of fibroblasts to myofibroblasts by inhibiting the TGF-β1/Smad3 signaling pathway, as well as by inhibiting the proliferation, migration, and cell cycle progression of human cardiac myofibroblasts. These effects of H2S may play significant roles in cardiac remodeling associated with heart failure.

  17. MicroRNA-125b Prevents Cardiac Dysfunction in Polymicrobial Sepsis by Targeting TRAF6-Mediated Nuclear Factor κB Activation and p53-Mediated Apoptotic Signaling.

    Science.gov (United States)

    Ma, He; Wang, Xiaohui; Ha, Tuanzhu; Gao, Ming; Liu, Li; Wang, Ruitao; Yu, Kaijiang; Kalbfleisch, John H; Kao, Race L; Williams, David L; Li, Chuanfu

    2016-12-01

     This study examined the effect of microRNA-125b (miR-125b) on sepsis-induced cardiac dysfunction.  Mouse hearts were transfected with lentivirus expressing miR-125b (LmiR-125b) 7 days before cecal ligation and puncture (CLP)-induced sepsis. Cardiac function was examined by echocardiography before and 6 hours after CLP (n = 6/group). Survival was monitored following CLP-induced sepsis (n = 12/group).  LmiR-125b transfection significantly attenuated cardiac dysfunction due to CLP-induced sepsis. Fractional shortening and ejection fraction values were significantly (P sepsis. Transfection of LmiR-125b into the heart significantly suppressed the expression of ICAM-1 and VCAM-1, decreased the accumulation of macrophages and neutrophils in the myocardium, and decreased serum levels of tumor necrosis factor α and interleukin 1β by targeting tumor necrosis factor receptor-associated factor 6 (TRAF6)-mediated nuclear factor κB (NF-κB) activation. In addition, sepsis-induced myocardial apoptosis was markedly attenuated by LmiR-125b transfection through suppression of p53, Bax, and Bak1 expression. In vitro transfection of endothelial cells with miR-125b mimics attenuate LPS-induced ICAM-1 and VCAM-1 expression by suppressing TRAF6 and NF-κB activation.  Increased myocardial miR-125b expression attenuates sepsis-induced cardiac dysfunction and improves survival. miR-125b may be a target for septic cardiomyopathy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  18. Endothelium-Derived Hyperpolarizing Factor and Vascular Function

    Directory of Open Access Journals (Sweden)

    Muhiddin A. Ozkor

    2011-01-01

    Full Text Available Endothelial function refers to a multitude of physiological processes that maintain healthy homeostasis of the vascular wall. Exposure of the endothelium to cardiac risk factors results in endothelial dysfunction and is associated with an alteration in the balance of vasoactive substances produced by endothelial cells. These include a reduction in nitric oxide (NO, an increase in generation of potential vasoconstrictor substances and a potential compensatory increase in other mediators of vasodilation. The latter has been surmised from data demonstrating persistent endothelium-dependent vasodilatation despite complete inhibition of NO and prostaglandins. This remaining non-NO, non-prostaglandin mediated endothelium-dependent vasodilator response has been attributed to endothelium-derived hyperpolarizing factor/s (EDHF. Endothelial hyperpolarization is likely due to several factors that appear to be site and species specific. Experimental studies suggest that the contribution of the EDHFs increase as the vessel size decreases, with a predominance of EDHF activity in the resistance vessels, and a compensatory up-regulation of hyperpolarization in states characterized by reduced NO availability. Since endothelial dysfunction is a precursor for atherosclerosis development and its magnitude is a reflection of future risk, then the mechanisms underlying endothelial dysfunction need to be fully understood, so that adequate therapeutic interventions can be designed.

  19. A Meta-Analysis of Renal Function After Adult Cardiac Surgery With Pulsatile Perfusion.

    Science.gov (United States)

    Nam, Myung Ji; Lim, Choon Hak; Kim, Hyun-Jung; Kim, Yong Hwi; Choi, Hyuk; Son, Ho Sung; Lim, Hae Ja; Sun, Kyung

    2015-09-01

    The aim of this meta-analysis was to determine whether pulsatile perfusion during cardiac surgery has a lesser effect on renal dysfunction than nonpulsatile perfusion after cardiac surgery in randomized controlled trials. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were used to identify available articles published before April 25, 2014. Meta-analysis was conducted to determine the effects of pulsatile perfusion on postoperative renal functions, as determined by creatinine clearance (CrCl), serum creatinine (Cr), urinary neutrophil gelatinase-associated lipocalin (NGAL), and the incidences of acute renal insufficiency (ARI) and acute renal failure (ARF). Nine studies involving 674 patients that received pulsatile perfusion and 698 patients that received nonpulsatile perfusion during cardiopulmonary bypass (CPB) were considered in the meta-analysis. Stratified analysis was performed according to effective pulsatility or unclear pulsatility of the pulsatile perfusion method in the presence of heterogeneity. NGAL levels were not significantly different between the pulsatile and nonpulsatile groups. However, patients in the pulsatile group had a significantly higher CrCl and lower Cr levels when the analysis was restricted to studies on effective pulsatile flow (P < 0.00001, respectively). The incidence of ARI was significantly lower in the pulsatile group (P < 0.00001), but incidences of ARF were similar. In conclusion, the meta-analysis suggests that the use of pulsatile flow during CPB results in better postoperative renal function.

  20. Morphological and functional evaluation of quadricuspid aortic valves using cardiac computed tomography

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    Song, In Young; Park, Jung Ah; Choi, Bo Hwa; Ko, Sung Min; Shin, Je Kyoun; Chee, Hyun Keun; KIm, Jun Seok [Konkuk University Medical Center, Konkuk University School of Medicine, Seoul (Korea, Republic of)

    2016-07-15

    The aim of this study was to identify the morphological and functional characteristics of quadricuspid aortic valves (QAV) on cardiac computed tomography (CCT). We retrospectively enrolled 11 patients with QAV. All patients underwent CCT and transthoracic echocardiography (TTE), and 7 patients underwent cardiovascular magnetic resonance (CMR). The presence and classification of QAV assessed by CCT was compared with that of TTE and intraoperative findings. The regurgitant orifice area (ROA) measured by CCT was compared with