WorldWideScience

Sample records for human cardiac failure

  1. Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

    Directory of Open Access Journals (Sweden)

    McIver Lauren J

    2009-12-01

    Full Text Available Abstract Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level.

  2. Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

    OpenAIRE

    Singh, Sanjay; Sayers, Scott; Walter, James S.; Thomas, Donald; Dieter, Robert S.; Nee, Lisa M.; Wurster, Robert D.

    2013-01-01

    Background 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 hyper...

  3. Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure.

    Science.gov (United States)

    Meana, Clara; Rubín, José Manuel; Bordallo, Carmen; Suárez, Lorena; Bordallo, Javier; Sánchez, Manuel

    2016-02-01

    Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N(1)-acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO-N(1) -acetylspermine (r = -0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N(1)-acetylspermidine (r = -0.554, P = 0.032; r = -0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = -0.835, P = 0.001) and with cAMP/ODC (r = -0.794, P = 0.011), cAMP/spermidine (r = -0.813, P = 0.001) and cAMP/spermine (r = -0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N(1) -acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = -0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of

  4. 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); Phearts (767.80±18.37 versus 650.23±9.84 μm(2); Pneurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm(2); Pneurons 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.

  5. [Acute cardiac failure in pheochromocytoma.

    DEFF Research Database (Denmark)

    Jønler, Morten; Munk, Kim

    2008-01-01

    Pheochromocytoma (P) is an endocrine catecholamine-secreting tumor. Classical symptoms like hypertension, attacks of sweating, palpitations, headache and palor are related to catecholamine discharge. We provide a case of P in a 71 year-old man presenting with acute cardiac failure, severe reduction...

  6. Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure.

    Science.gov (United States)

    Marques, Francine Z; Prestes, Priscilla R; Byars, Sean G; Ritchie, Scott C; Würtz, Peter; Patel, Sheila K; Booth, Scott A; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P; Curl, Claire L; Bell, James R; Wai, Bryan; Srivastava, Piyush M; Kangas, Antti J; Soininen, Pasi; Ruohonen, Saku; Kähönen, Mika; Lehtimäki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E; Lewandowski, Paul A; Delbridge, Lea M; Burrell, Louise M; Inouye, Michael; Harrap, Stephen B; Charchar, Fadi J

    2017-06-14

    Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2 -knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2 -knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis -eQTL for LCN2 expression. Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  7. Acute cardiac failure in neuroleptic malignant syndrome.

    LENUS (Irish Health Repository)

    Sparrow, Patrick

    2012-02-03

    We present a case of rapid onset acute cardiac failure developing as part of neuroleptic malignant syndrome in a 35-year-old woman following treatment with thioridazine and lithium. Post mortem histology of cardiac and skeletal muscle showed similar changes of focal cellular necrosis and vacuolation suggesting a common disease process.

  8. Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure.

    Science.gov (United States)

    Morine, Kevin J; Qiao, Xiaoying; York, Sam; Natov, Peter S; Paruchuri, Vikram; Zhang, Yali; Aronovitz, Mark J; Karas, Richard H; Kapur, Navin K

    2018-02-27

    Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity. Methods -We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We utilized the thoracic aortic constriction (TAC) induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results -BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates Type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and an siRNA approach. In BMP9 -/- mice subjected to TAC, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to TAC with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 compared to vehicle treated controls. Since endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to TAC induced heart failure limits collagen production, increases BMP9 protein levels, and increases

  9. Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, X.Q. [Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei (China); Hong, H.S. [Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Lin, X.H. [Department of Emergency Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Chen, L.L. [Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian (China); Li, Y.H. [Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei (China)

    2014-07-11

    The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

  10. Giant cardiac fibroma: an unusual cause of failure to thrive.

    Science.gov (United States)

    Navarini, Susanne; Latzin, Philipp; Kadner, Alexander; Carrel, Thierry; Hutter, Damian

    2013-06-01

    Cardiac fibromas are extremely rare in the general pediatric population and may present with a wide spectrum of clinical signs, including life-threatening arrhythmias and sudden death. We report a 14-month-old boy who presented with failure to thrive as the only symptom. Echocardiography showed a large cardiac fibroma in the right ventricle. Cardiac magnetic resonance imaging confirmed the diagnosis. After complete surgical tumor resection, the boy showed normal catch-up growth. This case underlines the diversity of clinical features of cardiac tumors, which implies that they should be considered early in the differential diagnosis of infants with failure to thrive.

  11. Macrophage microRNA-155 promotes cardiac hypertrophy and failure

    NARCIS (Netherlands)

    Heymans, Stephane; Corsten, Maarten F.; Verhesen, Wouter; Carai, Paolo; van Leeuwen, Rick E. W.; Custers, Kevin; Peters, Tim; Hazebroek, Mark; Stöger, Lauran; Wijnands, Erwin; Janssen, Ben J.; Creemers, Esther E.; Pinto, Yigal M.; Grimm, Dirk; Schürmann, Nina; Vigorito, Elena; Thum, Thomas; Stassen, Frank; Yin, Xiaoke; Mayr, Manuel; de Windt, Leon J.; Lutgens, Esther; Wouters, Kristiaan; de Winther, Menno P. J.; Zacchigna, Serena; Giacca, Mauro; van Bilsen, Marc; Papageorgiou, Anna-Pia; Schroen, Blanche

    2013-01-01

    Cardiac hypertrophy and subsequent heart failure triggered by chronic hypertension represent major challenges for cardiovascular research. Beyond neurohormonal and myocyte signaling pathways, growing evidence suggests inflammatory signaling pathways as therapeutically targetable contributors to this

  12. Cardiac Arrythmias in Acute and Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Ali A. Handjani

    1966-01-01

    Full Text Available Cardiac arrythmias are frequent complications in acute and chronic renal failure and they may well account for sudden unexplained death in these patients. Based upon our recent study, we strongly believe that among other causative factors, focal degeneration of myocardium is the commonest and the most potentially dangerous cause of cardiac arrythmias. We suggest in emergency instances, ouabain to be used instead of digitalis which appears to be quite safe with dramatic results in cardiac arrythmias of these group.

  13. Intrinsic cardiac nervous system in tachycardia induced heart failure.

    Science.gov (United States)

    Arora, Rakesh C; Cardinal, Rene; Smith, Frank M; Ardell, Jeffrey L; Dell'Italia, Louis J; Armour, J Andrew

    2003-11-01

    The purpose of this study was to test the hypothesis that early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiac function. After 2 wk of rapid ventricular pacing in nine anesthetized canines, cardiac and right atrial neuronal function were evaluated in situ in response to enhanced cardiac sensory inputs, stimulation of extracardiac autonomic efferent neuronal inputs, and close coronary arterial administration of neurochemicals that included nicotine. Right atrial neuronal intracellular electrophysiological properties were then evaluated in vitro in response to synaptic activation and nicotine. Intrinsic cardiac nicotine-sensitive, neuronally induced cardiac responses were also evaluated in eight sham-operated, unpaced animals. Two weeks of rapid ventricular pacing reduced the cardiac index by 54%. Intrinsic cardiac neurons of paced hearts maintained their cardiac mechano- and chemosensory transduction properties in vivo. They also responded normally to sympathetic and parasympathetic preganglionic efferent neuronal inputs, as well as to locally administered alpha-or beta-adrenergic agonists or angiotensin II. The dose of nicotine needed to modify intrinsic cardiac neurons was 50 times greater in failure compared with normal preparations. That dose failed to alter monitored cardiovascular indexes in failing preparations. Phasic and accommodating neurons identified in vitro displayed altered intracellular membrane properties compared with control, including decreased membrane resistance, indicative of reduced excitability. Early-stage heart failure differentially affects the intrinsic cardiac nervous system's capacity to regulate cardiodynamics. While maintaining its capacity to transduce cardiac mechano- and chemosensory inputs, as well as inputs from extracardiac autonomic efferent neurons, intrinsic cardiac nicotine-sensitive, local-circuit neurons differentially remodel such that their capacity to

  14. Exercise training restores cardiac protein quality control in heart failure.

    Directory of Open Access Journals (Sweden)

    Juliane C Campos

    Full Text Available Exercise training is a well-known coadjuvant in heart failure treatment; however, the molecular mechanisms underlying its beneficial effects remain elusive. Despite the primary cause, heart failure is often preceded by two distinct phenomena: mitochondria dysfunction and cytosolic protein quality control disruption. The objective of the study was to determine the contribution of exercise training in regulating cardiac mitochondria metabolism and cytosolic protein quality control in a post-myocardial infarction-induced heart failure (MI-HF animal model. Our data demonstrated that isolated cardiac mitochondria from MI-HF rats displayed decreased oxygen consumption, reduced maximum calcium uptake and elevated H₂O₂ release. These changes were accompanied by exacerbated cardiac oxidative stress and proteasomal insufficiency. Declined proteasomal activity contributes to cardiac protein quality control disruption in our MI-HF model. Using cultured neonatal cardiomyocytes, we showed that either antimycin A or H₂O₂ resulted in inactivation of proteasomal peptidase activity, accumulation of oxidized proteins and cell death, recapitulating our in vivo model. Of interest, eight weeks of exercise training improved cardiac function, peak oxygen uptake and exercise tolerance in MI-HF rats. Moreover, exercise training restored mitochondrial oxygen consumption, increased Ca²⁺-induced permeability transition and reduced H₂O₂ release in MI-HF rats. These changes were followed by reduced oxidative stress and better cardiac protein quality control. Taken together, our findings uncover the potential contribution of mitochondrial dysfunction and cytosolic protein quality control disruption to heart failure and highlight the positive effects of exercise training in re-establishing cardiac mitochondrial physiology and protein quality control, reinforcing the importance of this intervention as a non-pharmacological tool for heart failure therapy.

  15. Practolol in Hyperthyroid Cardiac Failure | Epstein | South African ...

    African Journals Online (AJOL)

    Practolol (Eraldint), a recently developed beta-adrenergic blocking agent, has been found useful in conjunction with digitalis and diuretics in 6 patients with thyrocardiac disease who had been refractory to therapy. In all cases cardiac failure improved dramatically, suggesting better myocardial efficiency and a return of ...

  16. Congestive Cardiac Failure in a patient with Systemic Sclerosis ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    disease(ILD) and cardiac function ... failure symptoms, in order to avoid a ... were a few blood vessels with thickened wall .... mean left atrial diameter, a smaller LV ejection ... resistance to flow is at the level of the ... 8The finding of mitral valve.

  17. Home-based cardiac rehabilitation for people with heart failure

    DEFF Research Database (Denmark)

    Zwisler, Ann Dorthe Olsen; Norten, RJ; Dean, SG

    2016-01-01

    AIMS: To assess the effectiveness of home-based cardiac rehabilitation (CR) for heart failure compared to either usual medical care (i.e. no CR) or centre-based CR on mortality, morbidity, exercise capacity, health-related quality of life, drop out, adherence rates, and costs. METHODS: Randomised...

  18. Exercise on-transition uncoupling of ventilatory, gas exchange and cardiac hemodynamic kinetics accompany pulmonary oxygen stores depletion to impact exercise intolerance in human heart failure.

    Science.gov (United States)

    Van Iterson, E H; Smith, J R; Olson, T P

    2018-03-25

    In contrast to knowledge that heart failure (HF) patients demonstrate peak exercise uncoupling across ventilation, gas exchange and cardiac haemodynamics, whether this dyssynchrony follows that at the exercise on-transition is unclear. This study tested whether exercise on-transition temporal lag for ventilation relative to gas exchange and oxygen pulse (O 2 pulse) couples with effects from abnormal pulmonary gaseous oxygen store (O 2store ) contributions to V˙O 2 to interdependently precipitate persistently elevated ventilatory demand and low oxidative metabolic capacity in HF. Beat-to-beat HR and breath-to-breath ventilation and gas exchange were continuously acquired in HF (N = 9, ejection fraction = 30 ± 9%) and matched controls (N = 10) during square-wave ergometry at 60% V˙O 2peak (46 ± 14 vs 125 ± 54-W, P < .001). Temporal responses across V˙ E , V˙O 2 and O 2 pulse were assessed for the exercise on-transition using single exponential model Phase II on-kinetic time constants (τ = time to reach 63% steady-state rise). Breath-to-breath gas fractions and respiratory flows were used to determine O 2stores . HF vs controls: τ for V˙ E (137 ± 93 vs 74 ± 40-seconds, P = .03), V˙O 2 (60 ± 40 vs 23 ± 5-seconds, P = .03) and O 2 pulse (28 ± 18 vs 23 ± 15-seconds, P = .59). Within HF, τ for V˙ E differed from O 2 pulse (P < .02), but not V˙O 2 . Exercise V˙ E rise (workload indexed) differed in HF vs controls (545 ± 139 vs 309 ± 88-mL min -1 W -1 , P < .001). Exercise on-transition O 2store depletion in HF exceeded controls, generally persisting to end-exercise. These data suggest HF demonstrated exercise on-transition O 2store depletion (high O 2store contribution to V˙O 2 ) coupled with dyssynchronous V˙ E , V˙O 2 and O 2 pulse kinetics-not attributable to prolonged cardiac haemodynamics. Persistent high ventilatory demand and low oxidative metabolic capacity in HF may be precipitated by physiological uncoupling occurring within the exercise

  19. Cardiac overexpression of Mammalian enabled (Mena) exacerbates heart failure in mice.

    Science.gov (United States)

    Belmonte, Stephen L; Ram, Rashmi; Mickelsen, Deanne M; Gertler, Frank B; Blaxall, Burns C

    2013-09-15

    Mammalian enabled (Mena) is a key regulator of cytoskeletal actin dynamics, which has been implicated in heart failure (HF). We have previously demonstrated that cardiac Mena deletion produced cardiac dysfunction with conduction abnormalities and hypertrophy. Moreover, elevated Mena expression correlates with HF in human and animal models, yet the precise role of Mena in cardiac pathophysiology is unclear. In these studies, we evaluated mice with cardiac myocyte-specific Mena overexpression (TTA/TgTetMena) comparable to that observed in cardiac pathology. We found that the hearts of TTA/TgTetMena mice were functionally and morphologically comparable to wild-type littermates, except for mildly increased heart mass in the transgenic mice. Interestingly, TTA/TgTetMena mice were particularly susceptible to cardiac injury, as these animals experienced pronounced decreases in ejection fraction and fractional shortening as well as heart dilatation and hypertrophy after transverse aortic constriction (TAC). By "turning off" Mena overexpression in TTA/TgTetMena mice either immediately prior to or immediately after TAC surgery, we discovered that normalizing Mena levels eliminated cardiac hypertrophy in TTA/TgTetMena animals but did not preclude post-TAC cardiac functional deterioration. These findings indicate that hearts with increased levels of Mena fare worse when subjected to cardiac injury and suggest that Mena contributes to HF pathophysiology.

  20. Cardiac retransplantation is an efficacious therapy for primary cardiac allograft failure

    Directory of Open Access Journals (Sweden)

    Acker Michael A

    2008-05-01

    Full Text Available Abstract Background Although orthotopic heart transplantation has been an effective treatment for end-stage heart failure, the incidence of allograft failure has increased, necessitating treatment options. Cardiac retransplantation remains the only viable long-term solution for end-stage cardiac allograft failure. Given the limited number of available donor hearts, the long term results of this treatment option need to be evaluated. Methods 709 heart transplants were performed over a 20 year period at our institution. Repeat cardiac transplantation was performed in 15 patients (2.1%. A retrospective analysis was performed to determine the efficacy of cardiac retransplantation. Variables investigated included: 1 yr and 5 yr survival, length of hospitalization, post-operative complications, allograft failure, recipient and donor demographics, renal function, allograft ischemic time, UNOS listing status, blood group, allograft rejection, and hemodynamic function. Results Etiology of primary graft failure included transplant arteriopathy (n = 10, acute rejection (n = 3, hyperacute rejection (n = 1, and a post-transplant diagnosis of metastatic melanoma in the donor (n = 1. Mean age at retransplantation was 45.5 ± 9.7 years. 1 and 5 year survival for retransplantation were 86.6% and 71.4% respectively, as compared to 90.9% and 79.1% for primary transplantation. Mean ejection fraction was 67.3 ± 12.2% at a mean follow-up of 32.6 ± 18.5 mos post-retransplant; follow-up biopsy demonstrated either ISHLT grade 1A or 0 rejection (77.5 ± 95.7 mos post-transplant. Conclusion Cardiac retransplantation is an efficacious treatment strategy for cardiac allograft failure.

  1. Deranged Cardiac Metabolism and the Pathogenesis of Heart Failure

    Science.gov (United States)

    2016-01-01

    Activation of the neuro-hormonal system is a pathophysiological consequence of heart failure. Neuro-hormonal activation promotes metabolic changes, such as insulin resistance, and determines an increased use of non-carbohydrate substrates for energy production. Fasting blood ketone bodies as well as fat oxidation are increased in patients with heart failure, yielding a state of metabolic inefficiency. The net result is additional depletion of myocardial adenosine triphosphate, phosphocreatine and creatine kinase levels with further decreased efficiency of mechanical work. In this context, manipulation of cardiac energy metabolism by modification of substrate use by the failing heart has produced positive clinical results. The results of current research support the concept that shifting the energy substrate preference away from fatty acid metabolism and towards glucose metabolism could be an effective adjunctive treatment in patients with heart failure. The additional use of drugs able to partially inhibit fatty acids oxidation in patients with heart failure may therefore yield a significant protective effect for clinical symptoms and cardiac function improvement, and simultaneously ameliorate left ventricular remodelling. Certainly, to clarify the exact therapeutic role of metabolic therapy in heart failure, a large multicentre, randomised controlled trial should be performed. PMID:28785448

  2. Frequency and echocardiographic study of dilated cardiomyopathy in children presenting with cardiac failure

    International Nuclear Information System (INIS)

    Khan, M.A.; Mohammad, J.; Hussain, M.

    2004-01-01

    Objective: To evaluate the role of echocardiography in diagnosis of dilated cardiomyopathy as a cause of cardiac failure in children. Design: This was descriptive study. Children presenting with cardiac failure from indoor patients were selected and echocardiography along with chest X- ray, ECG, cardiac enzymes and ASO titre was performed in all patients. Subject: Fifty hospitalized patients with congestive heart failure were selected consecutively from hospitalized patients. Main Outcome: Role of echocardiography in the diagnosis of dilated cardiomyopathy in children presenting with cardiac failure. Results: Out of fifty patients admitted with cardiac failure 27 (54%) cases were found to be dilated cardiomyopathy while congenital heart disease, myocarditis and rheumatic heart disease were found in 12 (24%), 8 (16%) and 3 (6%) cases respectively. Conclusion: Dilated cardiomyopathy is an important cause of cardiac failure in children and echocardiography is an important tool to diagnose and differentiate dilated cardiomyopathy from other causes of cardiac failure. (author)

  3. Hemorrhagic Stroke Associated with Pulmonary Edema and Catastrophic Cardiac Failure

    Directory of Open Access Journals (Sweden)

    Jiun-Chang Lee

    2008-06-01

    Full Text Available Cerebral arteriovenous fistula (AVF is a vascular malformation that is rare in the pediatric population. Older children with cerebral AVF tend to present with neurologic problems related to intracranial venous hypertension or intracranial hemorrhage. Cardiac and pulmonary complications following acute neurologic injury such as subarachnoid hemorrhage are common in adults, but are rarely reported in children. However, complications have been reported in cases of enterovirus 71 rhombencephalitis in infants and children and can cause high morbidity and mortality. Here, we report a 14-year-old boy who presented with cardiac failure associated with pulmonary edema following cerebral hemorrhagic stroke due to AVF. After aggressive investigation and management, we intervened before significant hypoxia and hypotension developed, potentially reducing the risk of long-term adverse neurologic consequences in this patient.

  4. Human technology after cardiac epigenesis. Artificial heart versus cardiac transplantation.

    Science.gov (United States)

    Losman, J G

    1977-09-24

    Cardiovascular disease is the chief cause of death in technologically advanced countries and accounts for more than 50% of all deaths in the USA. For a patient with end-stage cardiac failure the only treatment presently available is organ replacement, either by transplantation or by the use of a mechanical heart. Transplantation has demonstrated its value: survival of more than 8 years and restoration of a normal quality of life to patients who were in end-stage cardiac decompensation. However, the prospect of routine clinical application of an artificial heart remains distant. The development of a totally implantable artificial heart still presents a series of challenging engineering problems with regard to strict constraints of size, weight, blood-material compatibility, adaptability of output to demand, efficiency and reliability of the power supply, and safety if nuclear fuel is used. The totally artificial heart is presently not an alternative to the cardiac allograft, but could provide short-term support for patients awaiting cardiac transplantation.

  5. Chronic Cardiac-Targeted RNA Interference for the Treatment of Heart Failure Restores Cardiac Function and Reduces Pathological Hypertrophy

    Science.gov (United States)

    Suckau, Lennart; Fechner, Henry; Chemaly, Elie; Krohn, Stefanie; Hadri, Lahouaria; Kockskämper, Jens; Westermann, Dirk; Bisping, Egbert; Ly, Hung; Wang, Xiaomin; Kawase, Yoshiaki; Chen, Jiqiu; Liang, Lifan; Sipo, Isaac; Vetter, Roland; Weger, Stefan; Kurreck, Jens; Erdmann, Volker; Tschope, Carsten; Pieske, Burkert; Lebeche, Djamel; Schultheiss, Heinz-Peter; Hajjar, Roger J.; Poller, Wolfgang Ch.

    2009-01-01

    Background RNA interference (RNAi) has the potential to be a novel therapeutic strategy in diverse areas of medicine. We report on targeted RNAi for the treatment of heart failure (HF), an important disorder in humans resulting from multiple etiologies. Successful treatment of HF is demonstrated in a rat model of transaortic banding by RNAi targeting of phospholamban (PLB), a key regulator of cardiac Ca2+ homeostasis. Whereas gene therapy rests on recombinant protein expression as its basic principle, RNAi therapy employs regulatory RNAs to achieve its effect. Methods and Results We describe structural requirements to obtain high RNAi activity from adenoviral (AdV) and adeno-associated virus (AAV9) vectors and show that an AdV short hairpin RNA vector (AdV-shRNA) silenced PLB in cardiomyocytes (NRCMs) and improved hemodynamics in HF rats 1 month after aortic root injection. For simplified long-term therapy we developed a dimeric cardiotropic AAV vector (rAAV9-shPLB) delivering RNAi activity to the heart via intravenous injection. Cardiac PLB protein was reduced to 25% and SERCA2a suppression in the HF groups was rescued. In contrast to traditional vectors rAAV9 shows high affinity for myocardium, but low affinity for liver and other organs. rAAV9-shPLB therapy restored diastolic (LVEDP, dp/dtmin, Tau) and systolic (fractional shortening) functional parameters to normal range. The massive cardiac dilation was normalized and the cardiac hypertrophy, cardiomyocyte diameter and cardiac fibrosis significantly reduced. Importantly, there was no evidence of microRNA deregulation or hepatotoxicity during these RNAi therapies. Conclusion Our data show, for the first time, high efficacy of an RNAi therapeutic strategy in a cardiac disease. PMID:19237664

  6. Detection of intra-cardiac thrombi and congestive heart failure in cats using computed tomographic angiography.

    Science.gov (United States)

    Vititoe, Kyle P; Fries, Ryan C; Joslyn, Stephen; Selmic, Laura E; Howes, Mark; Vitt, Jordan P; O'Brien, Robert T

    2018-04-16

    Arterial thromboembolism is a life-threatening condition in cats most commonly secondary to cardiac disease. Echocardiography is the reference standard to evaluate for presence of a thrombus. In humans, computed tomographic (CT) angiography is becoming widely used to detect left atrial thrombi precluding the use of sedation. The purpose of this prospective, controlled, methods comparison pilot study was threefold: (1) describe new CT angiography protocol used in awake cats with cardiac disease and congestive heart failure; (2) determine accuracy of continuous and dynamic acquisition CT angiography to identify and characterize cardiac thrombi from spontaneous echocardiographic contrast using transthoracic echocardiography as our reference standard; (3) identify known negative prognostic factors and comorbidities of the thorax that CT angiography may provide that complement or supersede echocardiographic examination. Fourteen cats with heart disease were recruited; 7 with thrombi and 7 with spontaneous echocardiographic contrast. Echocardiography and awake CT angiography were performed using a microdose of contrast. Six of 7 thrombi were identified on CT angiography as filling defects by at least one reviewer within the left auricle (n = 6) and right heart (n = 1). Highest sensitivity (71.4%) was in continuous phase and highest specificity (85.7%) was in dynamic studies with fair to moderate interobserver agreement (0.38 and 0.44). CT angiography identified prognostic cardiac information (left atrial enlargement, congestive heart failure, arterial thromboembolism) and comorbidities (suspected idiopathic pulmonary fibrosis, asthma). This study indicates CT angiography can readily identify cardiac thrombi, important prognostic information and comorbidities, and can be safely performed in cats with cardiac disease and congestive heart failure. © 2018 American College of Veterinary Radiology.

  7. Cardiac Depression Scale: Mokken scaling in heart failure patients

    Directory of Open Access Journals (Sweden)

    Ski Chantal F

    2012-11-01

    Full Text Available Abstract Background There is a high prevalence of depression in patients with heart failure (HF that is associated with worsening prognosis. The value of using a reliable and valid instrument to measure depression in this population is therefore essential. We validated the Cardiac Depression Scale (CDS in heart failure patients using a model of ordinal unidimensional measurement known as Mokken scaling. Findings We administered in face-to-face interviews the CDS to 603 patients with HF. Data were analysed using Mokken scale analysis. Items of the CDS formed a statistically significant unidimensional Mokken scale of low strength (H0.8. Conclusions The CDS has a hierarchy of items which can be interpreted in terms of the increasingly serious effects of depression occurring as a result of HF. Identifying an appropriate instrument to measure depression in patients with HF allows for early identification and better medical management.

  8. Paradoxical euthyroid hormone profile in a case of Graves' disease with cardiac failure

    Directory of Open Access Journals (Sweden)

    Kapoor Aditya

    2011-07-01

    Full Text Available Abstract Cardiac failure is an uncommon complication of juvenile hyperthyroidism. We describe an adolescent boy with Graves' disease who developed manifestations of heart failure while on antithyroid medications. There was no evidence of any underlying cardiac disease. He had paradoxical euthyroid hormone profile which rose to hyperthyroid range when the manifestations of the cardiac failure subsided. The case highlights several unusual features of Graves' disease.

  9. Brain renin angiotensin system in cardiac hypertrophy and failure

    Directory of Open Access Journals (Sweden)

    Luciana eCampos

    2012-01-01

    Full Text Available Brain renin-angiotensin system (RAS is significantly involved in the roles of the endocrine RAS in cardiovascular regulation. Our studies indicate that the brain RAS participates in the development of cardiac hypertrophy and fibrosis through sympathetic activation. Inhibition of sympathetic hyperactivity after myocardial infarction through suppression of the brain RAS appears beneficial. The brain RAS is involved in the modulation of circadian rhythms of arterial pressure, contributing to nondipping hypertension. We conclude that the brain RAS in pathophysiological states interacts synergistically with the chronically overactive RAS through a positive biofeedback in order to maintain a state of alert diseased conditions, such as cardiac hypertrophy and failure. Therefore, targeting brain RAS with drugs such as angiotensin converting inhibitors or receptor blockers having increased brain penetrability could be of advantage. These RAS-targeting drugs are first-line therapy for all heart failure patients. Since the RAS has both endocrine and local tissue components, RAS drugs are being developed to attain increased tissue penetrability and volume of distribution and consequently an efficient inhibition of both RAS components.

  10. Human failure evolution process and prevention

    International Nuclear Information System (INIS)

    Chen Zhenwen

    2006-01-01

    The human failure in the nuclear power plant is analyzed. According to the staff career development and professional qualification 3 stages of the human failure evolution, viz, cognition, logics and emotion are defined. Some human failure prevention measures are brought forward from both the microcosmic and macrocosmic point of view. (author)

  11. Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

    NARCIS (Netherlands)

    Homburger, J.R. (Julian R.); Green, E.M. (Eric M.); Caleshu, C. (Colleen); Sunitha, M.S. (Margaret S.); Taylor, R.E. (Rebecca E.); Ruppel, K.M. (Kathleen M.); Metpally, R.P.R. (Raghu Prasad Rao); S.D. Colan (Steven); M. Michels (Michelle); Day, S.M. (Sharlene M.); I. Olivotto (Iacopo); Bustamante, C.D. (Carlos D.); Dewey, F.E. (Frederick E.); Ho, C.Y. (Carolyn Y.); Spudich, J.A. (James A.); Ashley, E.A. (Euan A.)

    2016-01-01

    textabstractMyosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac

  12. Acute Cardiac Failure in a Pregnant Woman due to Thyrotoxic Crisis

    Directory of Open Access Journals (Sweden)

    Nao Okuda

    2012-01-01

    Full Text Available Introduction. Cardiac failure during pregnancy is usually related to preeclampsia/eclampsia, rarely to hyperthyroidism. While hyperthyroidism can easily lead to hypertensive cardiac failure and may harm the fetus, it is sometimes difficult to distinguish hyperthyroidism from normal pregnancy. Case Presentation. We encountered a case of 41-year-old pregnant woman with hypertensive cardiac failure. Because we initially diagnosed as pre-eclampsia/eclampsia, Caesarian section was performed. However, her symptoms still persisted after delivery. After thyroid function test results taken on the day of admission were obtained on the fourth day, we could diagnose that her cardiac failure was caused by thyrotoxic crisis. Conclusions. Hypertensive cardiac failure due to hyperthyroidism during pregnancy is rare and difficult to diagnose because of similar presentation of normal pregnancy. However, physicians should be aware of the risks posed by hyperthyroidism during pregnancy.

  13. High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure.

    Science.gov (United States)

    Rosa-Garrido, Manuel; Chapski, Douglas J; Schmitt, Anthony D; Kimball, Todd H; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J; Ren, Shuxun; Wang, Yibin; Ren, Bing; Vondriska, Thomas M

    2017-10-24

    Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. © 2017 The Authors.

  14. Cardiac rehabilitation in patients with ST-segment elevation myocardial infarction: can its failure be predicted?

    Science.gov (United States)

    Irzmański, Robert; Kapusta, Joanna; Obrębska-Stefaniak, Agnieszka; Urzędowicz, Beata; Kowalski, Jan

    2017-07-01

    The prognosis in patients after acute coronary syndromes (ACS) is significantly burdened by coexisting anaemia, leukocytosis and low glomerular filtration rate (GFR). Hyperglycaemia in the early stages of ACS is a strong predictor of death and heart failure in non-diabetic subjects. This study aimed to evaluate the effect of hyperglycaemia, anaemia, leukocytosis, thrombocytopaenia and decreased GFR on the risk of the failure of cardiac rehabilitation (phase II at the hospital) in post-ST-segment elevation myocardial infarction (STEMI) patients. The study included 136 post-STEMI patients, 96 men and 40 women, aged 60.1 ± 11.8 years, admitted for cardiac rehabilitation (phase II) to the Department of Internal Medicine and Cardiac Rehabilitation, WAM University Hospital in Lodz, Poland. On admission fasting blood cell count was performed and serum glucose and creatinine level was determined (GFR assessment). The following results were considered abnormal: glucose ⩾ 100 mg/dl, GFR 10 × 103/μl; platelets (PLTs) failure of cardiac rehabilitation. This risk has been defined on the basis of the patient's inability to tolerate workload increment >5 Watt in spite of the applied program of cardiac rehabilitation. As a result of building a logistic regression model, the most statistically significant risk factors were selected, on the basis of which cardiac rehabilitation failure index was determined. leukocytosis and reduced GFR determined most significantly the risk of failure of cardiac rehabilitation (respectively OR = 6.42 and OR = 3.29, p = 0.007). These parameters were subsequently utilized to construct a rehabilitation failure index. Peripheral blood cell count and GFR are important in assessing the prognosis of cardiac rehabilitation effects. leukocytosis and decreased GFR determine to the highest degree the risk of cardiac rehabilitation failure. Cardiac rehabilitation failure index may be useful in classifying patients into an appropriate model of

  15. High-output cardiac failure secondary to multiple vascular malformations in the liver: case report

    International Nuclear Information System (INIS)

    Spaner, S.; Demeter, S.; Lien, D.; Shapiro, J.; McCarthy, M.; Raymond, G.

    2001-01-01

    High-output cardiac failure is associated with several systemic illnesses, including hyperthyroidism, thiamine deficiency, severe anemia, multiple myeloma, Paget's disease of bone and Osler-Weber-Rendu syndrome. We present an unusual case of a woman with high-output cardiac failure as a result of multiple arteriovenous fistulas in the liver, most likely representing an unusual variant of Osler-Weber-Rendu syndrome (i.e., no other telangiectasias or a family history of vascular malformations was demonstrated). (author)

  16. Influence of the timing of cardiac catheterization and amount of contrast media on acute renal failure after cardiac surgery.

    Science.gov (United States)

    Sadeghi, Mohsen Mirmohammad; Gharipour, Mojgan; Nilforoush, Peiman; Shamsolkotabi, Hamid; Sadeghi, Hamid Mirmohammad; Kiani, Amjad; Sadeghi, Pouya Mirmohammad; Farahmand, Niloufar

    2011-04-01

    There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF). Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated. Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression. The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05). Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57%) and 6 (52.17%) after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002), followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482-32.032 and p = 0.009) and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031). Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have this protective effect.

  17. Pathophysiology of cardiac hypertrophy and heart failure: signaling pathways and novel therapeutic targets.

    Science.gov (United States)

    Tham, Yow Keat; Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; McMullen, Julie R

    2015-09-01

    The onset of heart failure is typically preceded by cardiac hypertrophy, a response of the heart to increased workload, a cardiac insult such as a heart attack or genetic mutation. Cardiac hypertrophy is usually characterized by an increase in cardiomyocyte size and thickening of ventricular walls. Initially, such growth is an adaptive response to maintain cardiac function; however, in settings of sustained stress and as time progresses, these changes become maladaptive and the heart ultimately fails. In this review, we discuss the key features of pathological cardiac hypertrophy and the numerous mediators that have been found to be involved in the pathogenesis of cardiac hypertrophy affecting gene transcription, calcium handling, protein synthesis, metabolism, autophagy, oxidative stress and inflammation. We also discuss new mediators including signaling proteins, microRNAs, long noncoding RNAs and new findings related to the role of calcineurin and calcium-/calmodulin-dependent protein kinases. We also highlight mediators and processes which contribute to the transition from adaptive cardiac remodeling to maladaptive remodeling and heart failure. Treatment strategies for heart failure commonly include diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers and β-blockers; however, mortality rates remain high. Here, we discuss new therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, small molecules) either entering clinical trials or in preclinical development. Finally, we address the challenges that remain in translating these discoveries to new and approved therapies for heart failure.

  18. Impact of KChIP2 on Cardiac Electrophysiology and the Progression of Heart Failure

    DEFF Research Database (Denmark)

    Grubb, Søren; Callø, Kirstine; Thomsen, Morten B

    2012-01-01

    Electrophysiological remodeling of cardiac potassium ion channels is important in the progression of heart failure. A reduction of the transient outward potassium current (I(to)) in mammalian heart failure is consistent with a reduced expression of potassium channel interacting protein 2 (KChIP2...

  19. An endogenously produced fragment of cardiac myosin-binding protein C is pathogenic and can lead to heart failure.

    Science.gov (United States)

    Razzaque, Md Abdur; Gupta, Manish; Osinska, Hanna; Gulick, James; Blaxall, Burns C; Robbins, Jeffrey

    2013-08-16

    A stable 40-kDa fragment is produced from cardiac myosin-binding protein C when the heart is stressed using a stimulus, such as ischemia-reperfusion injury. Elevated levels of the fragment can be detected in the diseased mouse and human heart, but its ability to interfere with normal cardiac function in the intact animal is unexplored. To understand the potential pathogenicity of the 40-kDa fragment in vivo and to investigate the molecular pathways that could be targeted for potential therapeutic intervention. We generated cardiac myocyte-specific transgenic mice using a Tet-Off inducible system to permit controlled expression of the 40-kDa fragment in cardiomyocytes. When expression of the 40-kDa protein is induced by crossing the responder animals with tetracycline transactivator mice under conditions in which substantial quantities approximating those observed in diseased hearts are reached, the double-transgenic mice subsequently experience development of sarcomere dysgenesis and altered cardiac geometry, and the heart fails between 12 and 17 weeks of age. The induced double-transgenic mice had development of cardiac hypertrophy with myofibrillar disarray and fibrosis, in addition to activation of pathogenic MEK-ERK pathways. Inhibition of MEK-ERK signaling was achieved by injection of the mitogen-activated protein kinase (MAPK)/ERK inhibitor U0126. The drug effectively improved cardiac function, normalized heart size, and increased probability of survival. These results suggest that the 40-kDa cardiac myosin-binding protein C fragment, which is produced at elevated levels during human cardiac disease, is a pathogenic fragment that is sufficient to cause hypertrophic cardiomyopathy and heart failure.

  20. Impaired cardiac uptake of meta-[123I]iodobenzylguanidine in Parkinson's disease with autonomic failure

    International Nuclear Information System (INIS)

    Braune, S.; Luecking, C.H.; Reinhardt, M.; Bathmann, J.; Krause, T.; Lehmann, M.

    1998-01-01

    Objective - To selectively investigate postganglionic sympathetic cardiac neurons in patients with Parkinson's disease and autonomic failure. Material and methods - Metaiodobenzylguanidine (MIBG) is a pharmacologically inactive analogue of noradrenaline, which is similarly metabolized in noradrenergic neurons. Therefore the uptake of radiolabelled MIBG represents not only the localization of postganglionic sympathetic neurons but also their functional integrity. Ten patients with Parkinson's disease and autonomic failure underwent standardized autonomic testing, assessment of catecholamine plasma levels and scintigraphy with [ 123 I]MIGB. Results - The cardiac uptake of MIBG, as demonstrated by the heart/mediastinum ratio, was significantly lower in patients in comparison with controls. Scintigraphy with MIBG allowed the selective in-vivo investigation of postganglionic sympathetic cardiac efferent in patients with autonomic failure, a procedure which was previously confined to post-mortem examination. Conclusion - These findings point to a relevant postganglionic pattern of involvement of the autonomic nervous system (ANS) in Parkinson's disease and autonomic failure. (au)

  1. Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure-Prone Rats

    Science.gov (United States)

    Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance...

  2. Contribution of cardiac and extra-cardiac disease burden to risk of cardiovascular outcomes varies by ejection fraction in heart failure

    DEFF Research Database (Denmark)

    Wolsk, Emil; Claggett, Brian; Køber, Lars

    2018-01-01

    AIMS: Patients with heart failure (HF) often have multiple co-morbidities that contribute to the risk of adverse cardiovascular (CV) and non-CV outcomes. We assessed the relative contribution of cardiac and extra-cardiac disease burden and demographic factors to CV outcomes in HF patients...... Association class, systolic blood pressure, time since HF diagnosis, HF medication use), extra-cardiac (body mass index, creatinine, diabetes mellitus, chronic obstructive pulmonary disease, smoker), and demographic (age, gender) categories, and calculated subscores for each patient representing the burden......EF patients (PAR: 76% cardiac disease vs. 58% extra-cardiac disease, P vs. 49% extra-cardiac disease, P

  3. Cardiac failure due to arteriovenous fistula with brachiocephalic stenosis: a gated heart case study

    International Nuclear Information System (INIS)

    Abel, G.; Irish, A.; Henderson, A.; Lenzo, N.

    2003-01-01

    Full text: There are numerous causes of cardiac failure of which the commonest in our community include ischaemic cardiomyopathy, post-viral cardiomyopathy, alcohol-induced cardiomyopathy and drug-induced cardiomyopathy. All these entities cause low output cardiac failure however high output cardiac failure is also well recognised. This includes heart failure related to such conditions as hyperthyroidism, anaemia, pregnancy, beri-beri, and Paget's disease. A rare cause of high output cardiac failure is an arteriovenous fistula. We present an unusual case of a patient with end-stage renal failure on haemodialysis who developed extensive dilatation of their left arm arteriovenous fistula secondary to bachiocephalic vein stenosis. The labelled red blood cell gated heart blood pool study demonstrated decreased left ventricular function and extensive pooling of blood within the tortuous dilated left arm vessels. A follow-up study post-ligation of the arteriovenous fistula showed improvement of the left ventricular ejection fraction. The associated contrast venography findings are also demonstrated. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc

  4. Increased in vivo mitochondrial oxygenation with right ventricular failure induced by pulmonary arterial hypertension: Mitochondrial inhibition as driver of cardiac failure?

    NARCIS (Netherlands)

    G. Balestra (Gianmarco); E.G. Mik (Egbert); O. Eerbeek (Otto); P. Specht (Patricia); W.J. van der Laarse (Willem J.); C.J. Zuurbier (Coert J.)

    2015-01-01

    textabstractBackground: The leading cause of mortality due to pulmonary arterial hypertension (PAH) is failure of the cardiac right ventricle. It has long been hypothesized that during the development of chronic cardiac failure the heart becomes energy deprived, possibly due to shortage of oxygen at

  5. Cardiac Resynchronization Therapy Defibrillator Treatment in a Child with Heart Failure and Ventricular Arrhythmia

    Directory of Open Access Journals (Sweden)

    Hak Ju Kim

    2016-08-01

    Full Text Available Cardiac resynchronization therapy (CRT is a new treatment for refractory heart failure. However, most patients with heart failure treated with CRT are adults, middle-aged or older with idiopathic or ischemic dilated cardiomyopathy. We treated a 12-year-old boy, who was transferred after cardiac arrest, with dilated cardiomyopathy, left bundle-branch block, and ventricular tachycardia. We performed cardiac resynchronization therapy with a defibrillator (CRT-D. After CRT-D, left ventricular ejection fraction improved from 22% to 4 4% a ssessed by e chocardiog ram 1 year p ostoperatively. On e lectrocardiog ram, Q RS d uration was shortened from 206 to 144 ms. The patient’s clinical symptoms also improved. For pediatric patients with refractory heart failure and ventricular arrhythmia, CRT-D could be indicated as an effective therapeutic option.

  6. Systemic arteriovenous malformations as a cause of cardiac failure: Treatment with embolization

    International Nuclear Information System (INIS)

    Smith, E.J.; Hemingway, A.P.; Allison, D.J.

    1987-01-01

    Massive cogenital systemic arteriovenous malformations (AVMs) present considerable management problems for clinicians. Their size, position, and vascularity make successful surgical reaction impossible. Attempts at resection produce only temporary relief of symptoms and cause further disfigurement. Large AVMs give rise to pain, swelling, and distal ischaemia, can erode bone, and give rise to life-threatening hemorrhage, and a massive left or right shunt causes high-output cardiac failure and death. Ten patients (age range, 5-50 years; mean 26 years) have massive AVMs giving rise to high-output cardiac failure (26-28 liters). These patients (seven male, three female), have undergone a total of 43 embolization procedures. The advent of nonionic contrast media, digital subtraction angiography, steel coils, and balloons allows us to successfully treat these patients who until recently were condemned to die in high-output cardiac failure

  7. Influence of the timing of cardiac catheterization and amount of contrast media on acute renal failure after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Mohsen Mirmohammad Sadeghi

    2011-01-01

    Full Text Available Background: There is limited data about the influence of timing of cardiac surgery in relation to diagnostic angiography and/or the impact of the amount of contrast media used during angiography on the occurance of acute renal failure (ARF. Therefore, in the present study the effect of the time interval between diagnostic angiography and cardiac surgery and also the amount of contrast media used during the diagnostic procedure on the incidence of ARF after cardiac surgery was investigated. Methods: Data of 1177 patients who underwent different types of cardiac surgeries after cardiac catheterization were prospectively examined. The influence of time interval between cardiac catheterization and surgery as well as the amount of contrast agent on postoperative ARF were assessed using multivariable logistic regression. Results: The patients who progressed to ARF were more likely to have received a higher dose of contrast agent compared to the mean dose. However, the time interval between cardiac surgery and last catheterization was not significantly different between the patients with and without ARF (p = 0.05. Overall, postoperative peak creatinine was highest on day 0, then decreased and remained significantly unchanged after this period. Overall prevalence of acute renal failure during follow-up period had a changeable trend and had the highest rates in days 1 (53.57% and 6 (52.17% after surgery. Combined coronary bypass and valve surgery were the strongest predictor of postoperative ARF (OR: 4.976, CI = 1.613-15.355 and p = 0.002, followed by intra-aortic balloon pump insertion (OR: 6.890, CI = 1.482-32.032 and p = 0.009 and usage of higher doses of contrast media agent (OR: 1.446, CI = 1.033-2.025 and p = 0.031. Conclusions: Minimizing the amount of contrast agent has a potential role in reducing the incidence of postoperative ARF in patients undergoing cardiac surgery, but delaying cardiac surgery after exposure to these agents might not have

  8. Riboflavin alleviates cardiac failure in Type I diabetic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Xue Zhao

    2011-09-01

    Full Text Available Heart failure (HF is a common and serious comorbidity of diabetes. Oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. Riboflavin constitutes an essential nutrient for humans and animals and it is an important food additive. Riboflavin, a precursor of flavin mononucleotide (FMN and flavin adenine dinucleotide (FAD, enhances the oxidative folding and subsequent secretion of proteins. The objective of this study was to investigate the cardioprotective effect of riboflavin in diabetic rats. Diabetes was induced in 30 rats by a single injection of streptozotocin (STZ (70 mg /kg. Riboflavin (20 mg/kg was orally administered to animals immediately after induction of diabetes and was continued for eight weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV remadynamic function. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD, the level of malondialdehyde (MDA as well as heme oxygenase-1 (HO-1 protein level. Myocardial connective tissue growth factor (CTGF level was measured by Western blot in all rats at the end of the study. In the untreated diabetic rats, left ventricular systolic pressure (LVSP rate of pressure rose (+dp/dt, and rate of pressure decay (−dp/dt were depressed while left ventricular enddiastolic pressure (LVEDP was increased, which indicated the reduced left ventricular contractility and slowing of left ventricular relaxation. The level of SOD decreased, CTGF and HO-1 protein expression and MDA content rose. Riboflavin treatment significantly improved left ventricular systolic and diastolic function in diabetic rats, there were persistent increases in significant activation of SOD and the level of HO-1 protein, and a decrease in the level of CTGF. These results suggest

  9. Imaging cardiac activation sequence during ventricular tachycardia in a canine model of nonischemic heart failure.

    Science.gov (United States)

    Han, Chengzong; Pogwizd, Steven M; Yu, Long; Zhou, Zhaoye; Killingsworth, Cheryl R; He, Bin

    2015-01-15

    Noninvasive cardiac activation imaging of ventricular tachycardia (VT) is important in the clinical diagnosis and treatment of arrhythmias in heart failure (HF) patients. This study investigated the ability of the three-dimensional cardiac electrical imaging (3DCEI) technique for characterizing the activation patterns of spontaneously occurring and norepinephrine (NE)-induced VTs in a newly developed arrhythmogenic canine model of nonischemic HF. HF was induced by aortic insufficiency followed by aortic constriction in three canines. Up to 128 body-surface ECGs were measured simultaneously with bipolar recordings from up to 232 intramural sites in a closed-chest condition. Data analysis was performed on the spontaneously occurring VTs (n=4) and the NE-induced nonsustained VTs (n=8) in HF canines. Both spontaneously occurring and NE-induced nonsustained VTs initiated by a focal mechanism primarily from the subendocardium, but occasionally from the subepicardium of left ventricle. Most focal initiation sites were located at apex, right ventricular outflow tract, and left lateral wall. The NE-induced VTs were longer, more rapid, and had more focal sites than the spontaneously occurring VTs. Good correlation was obtained between imaged activation sequence and direct measurements (averaged correlation coefficient of ∼0.70 over 135 VT beats). The reconstructed initiation sites were ∼10 mm from measured initiation sites, suggesting good localization in such a large animal model with cardiac size similar to a human. Both spontaneously occurring and NE-induced nonsustained VTs had focal initiation in this canine model of nonischemic HF. 3DCEI is feasible to image the activation sequence and help define arrhythmia mechanism of nonischemic HF-associated VTs. Copyright © 2015 the American Physiological Society.

  10. Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis

    Directory of Open Access Journals (Sweden)

    Ralph Lohner

    2013-01-01

    Full Text Available Background. Aim was to elucidate the role of toll-like receptor 9 (TLR9 in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis. Methods. Sepsis was induced via colon ascendens stent peritonitis (CASP in C57BL/6 wild-type (WT and TLR9-deficient (TLR9-D mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitored in vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria. Results. CASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice. Conclusions. In polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure.

  11. A different management of saphenous vein graft failure related to cardiac tamponade following coronary surgery

    Directory of Open Access Journals (Sweden)

    Hamit Serdar Başbuğ

    2016-03-01

    Full Text Available Cardiac tamponade is a state of constriction of the heart with an excessive fluid or hematoma resulted from various conditions. Postoperative tamponade can occur after coronary bypass surgery. Despite it is uncommon, its results may have a high risk of mortality and morbidity. Acute postoperative cardiac tamponade reveals a vast spectrum of symptoms. Moreover, a compression over the saphenous vein graft is the worst complication that should be managed without delay. We report a rare case of saphenous vein graft failure due to the cardiac tamponade following a coronary surgery and its management with a practical measure.

  12. Cardiac magnetic resonance imaging in heart failure: where the alphabet begins!

    Science.gov (United States)

    Aljizeeri, Ahmed; Sulaiman, Abdulbaset; Alhulaimi, Naji; Alsaileek, Ahmed; Al-Mallah, Mouaz H

    2017-07-01

    Cardiac Magnetic Resonance Imaging has become a cornerstone in the evaluation of heart failure. It provides a comprehensive evaluation by answering all the pertinent clinical questions across the full pathological spectrum of heart failure. Nowadays, CMR is considered the gold standard in evaluation of ventricular volumes, wall motion and systolic function. Through its unique ability of tissue characterization, it provides incremental diagnostic and prognostic information and thus has emerged as a comprehensive imaging modality in heart failure. This review outlines the role of main conventional CMR sequences in the evaluation of heart failure and their impact in the management and prognosis.

  13. Is human failure a stochastic process?

    International Nuclear Information System (INIS)

    Dougherty, Ed M.

    1997-01-01

    Human performance results in failure events that occur with a risk-significant frequency. System analysts have taken for granted the random (stochastic) nature of these events in engineering assessments such as risk assessment. However, cognitive scientists and error technologists, at least those who have interest in human reliability, have, over the recent years, claimed that human error does not need this stochastic framework. Yet they still use the language appropriate to stochastic processes. This paper examines the potential for the stochastic nature of human failure production as the basis for human reliability analysis. It distinguishes and leaves to others, however, the epistemic uncertainties over the possible probability models for the real variability of human performance

  14. Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting

    Science.gov (United States)

    Breitbart, Astrid; Auger-Messier, Mannix; Molkentin, Jeffery D.

    2011-01-01

    A significant proportion of heart failure patients develop skeletal muscle wasting and cardiac cachexia, which is associated with a very poor prognosis. Recently, myostatin, a cytokine from the transforming growth factor-β (TGF-β) family and a known strong inhibitor of skeletal muscle growth, has been identified as a direct mediator of skeletal muscle atrophy in mice with heart failure. Myostatin is mainly expressed in skeletal muscle, although basal expression is also detectable in heart and adipose tissue. During pathological loading of the heart, the myocardium produces and secretes myostatin into the circulation where it inhibits skeletal muscle growth. Thus, genetic elimination of myostatin from the heart reduces skeletal muscle atrophy in mice with heart failure, whereas transgenic overexpression of myostatin in the heart is capable of inducing muscle wasting. In addition to its endocrine action on skeletal muscle, cardiac myostatin production also modestly inhibits cardiomyocyte growth under certain circumstances, as well as induces cardiac fibrosis and alterations in ventricular function. Interestingly, heart failure patients show elevated myostatin levels in their serum. To therapeutically influence skeletal muscle wasting, direct inhibition of myostatin was shown to positively impact skeletal muscle mass in heart failure, suggesting a promising strategy for the treatment of cardiac cachexia in the future. PMID:21421824

  15. Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies

    Directory of Open Access Journals (Sweden)

    Georges N. Kanaan

    2018-04-01

    Full Text Available Glutaredoxin 2 (GRX2, a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies. Keywords: Human heart, Mitochondria, Oxidative stress, Redox, Cardiac metabolism, Cardiac hypertrophy

  16. Cardiac Auscultation for Noncardiologists: Application in Cardiac Rehabilitation Programs: PART I: PATIENTS AFTER ACUTE CORONARY SYNDROMES AND HEART FAILURE.

    Science.gov (United States)

    Compostella, Leonida; Compostella, Caterina; Russo, Nicola; Setzu, Tiziana; Iliceto, Sabino; Bellotto, Fabio

    2017-09-01

    During outpatient cardiac rehabilitation after an acute coronary syndrome or after an episode of congestive heart failure, a careful, periodic evaluation of patients' clinical and hemodynamic status is essential. Simple and traditional cardiac auscultation could play a role in providing useful prognostic information.Reduced intensity of the first heart sound (S1), especially when associated with prolonged apical impulse and the appearance of added sounds, may help identify left ventricular (LV) dysfunction or conduction disturbances, sometimes associated with transient myocardial ischemia. If both S1 and second heart sound (S2) are reduced in intensity, a pericardial effusion may be suspected, whereas an increased intensity of S2 may indicate increased pulmonary artery pressure. The persistence of a protodiastolic sound (S3) after an acute coronary syndrome is an indicator of severe LV dysfunction and a poor prognosis. In patients with congestive heart failure, the association of an S3 and elevated heart rate may indicate impending decompensation. A presystolic sound (S4) is often associated with S3 in patients with LV failure, although it could also be present in hypertensive patients and in patients with an LV aneurysm. Careful evaluation of apical systolic murmurs could help identifying possible LV dysfunction or mitral valve pathology, and differentiate them from a ruptured papillary muscle or ventricular septal rupture. Friction rubs after an acute myocardial infarction, due to reactive pericarditis or Dressler syndrome, are often associated with a complicated clinical course.During cardiac rehabilitation, periodic cardiac auscultation may provide useful information about the clinical-hemodynamic status of patients and allow timely detection of signs, heralding possible complications in an efficient and low-cost manner.

  17. Acromegaly Presenting as Cardiac Failure - A Case Report

    Directory of Open Access Journals (Sweden)

    Shohael Mahmud Arafat

    2011-09-01

    Full Text Available Acromegaly is characterized by chronic hypersecretion of growth hormone (GH and is associated with increased mortality rate because of the potential complications such as cardiovascular disease, respiratory disease, or malignancy, which are probably caused by the long-term exposure of tissues to excess GH, for at least 10 years, before diagnosis and treatment. Here we are reporting a case of acromegaly who initially presented with features of left ventricular failure for which she got herself admitted in CCU and was treated conservatively. Later on, after clinical examination and investigations she was diagnosed as a case of mitral regurgitation due to cardiomyopathy caused by acromegaly. After the successful transsphenoidal resection of the pituitary microadenoma, the level of GH was normalized and heart failure improved. Key words: acromegaly; heart failure; Pituitary microadenoma. DOI: http://dx.doi.org/10.3329/bsmmuj.v4i2.8644 BSMMU J 2011; 4(2:122-124

  18. Cardiac index and pulmonary arterial blood pressure during exercise in cases of suspected latent heart failure

    International Nuclear Information System (INIS)

    Agapov, A.A.; Berzak, N.V.; Vladimirov, S.S.

    1987-01-01

    The results studying hemodynamics during maximum physical load (veloeriometry when sitting) for 24 patients examined to avoid heart failure are presented. 19 patients were subjected to coronaroangiography and contrast ventriculography, and 12 patients - to myocardium scintigraphy with 99m Tc-pyrophosphate. It is shown that registration of diaslotic pressure in a pulmonary artery and in a cardiac index permits to diagnose failure in the miocardic function of patients with different heart diseases

  19. Aberrant Glycosylation in the Left Ventricle and Plasma of Rats with Cardiac Hypertrophy and Heart Failure.

    Directory of Open Access Journals (Sweden)

    Chiaki Nagai-Okatani

    Full Text Available Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases.

  20. The clinical value of cardiac sympathetic imaging in heart failure

    DEFF Research Database (Denmark)

    Christensen, Thomas Emil; Kjaer, Andreas; Hasbak, Philip

    2014-01-01

    The autonomic nervous system plays an important role in the pathology of heart failure. The single-photon emission computed tomography tracer iodine-123-metaiodobenzylguanidine ((123) I-MIBG) can be used to investigate the activity of the predominant neurotransmitter of the sympathetic nervous...

  1. Type D personality and cardiac mortality in patients with chronic heart failure

    DEFF Research Database (Denmark)

    Schiffer, Angélique A; Smith, Otto R F; Pedersen, Susanne S.

    2010-01-01

    Clinical predictors of cardiac mortality in chronic heart failure (CHF) are established, but less is known about chronic psychological predictors. Therefore, we examined the prognostic value of Type D personality (tendency to experience negative feelings and inhibit self-expression) in CHF patients....

  2. Exercise-based cardiac rehabilitation in patients with chronic heart failure: a Dutch practice guideline

    NARCIS (Netherlands)

    Achttien, R.J.; Staal, J.B.; Voort, S. van der; Kemps, H.M.; Koers, H.; Jongert, M.W.; Hendriks, E.J.

    2015-01-01

    RATIONALE: To improve the quality of exercise-based cardiac rehabilitation (CR) in patients with chronic heart failure (CHF) a practice guideline from the Dutch Royal Society for Physiotherapy (KNGF) has been developed. GUIDELINE DEVELOPMENT: A systematic literature search was performed to formulate

  3. Exercise-based cardiac rehabilitation in patients with chronic heart failure: a Dutch practice guideline

    NARCIS (Netherlands)

    Achttien, R. J.; Staal, J. B.; van der Voort, S.; Kemps, H. M.; Koers, H.; Jongert, M. W. A.; Hendriks, E. J. M.

    2015-01-01

    To improve the quality of exercise-based cardiac rehabilitation (CR) in patients with chronic heart failure (CHF) a practice guideline from the Dutch Royal Society for Physiotherapy (KNGF) has been developed. A systematic literature search was performed to formulate conclusions on the efficacy of

  4. Impact of Ejection Fraction on the Clinical Response to Cardiac Resynchronization Therapy in Mild Heart Failure

    DEFF Research Database (Denmark)

    Linde, Cecilia; Daubert, Claude; Abraham, William T

    2013-01-01

    Current guidelines recommend cardiac resynchronization therapy (CRT) in mild heart failure (HF) patients with QRS prolongation and ejection fraction (EF) ≤30%. To assess the effect of CRT in less severe systolic dysfunction, outcomes in the REsynchronization reVErses Remodeling in Systolic left v...

  5. Cardiac dysfunction in heart failure: the cardiologist's love affair with time.

    Science.gov (United States)

    Brutsaert, Dirk L

    2006-01-01

    Translating research into clinical practice has been a challenge throughout medical history. From the present review, it should be clear that this is particularly the case for heart failure. As a consequence, public awareness of this disease has been disillusionedly low, despite its prognosis being worse than that of most cancers and many other chronic diseases. We explore how over the past 150 years since Ludwig and Marey concepts about the evaluation of cardiac performance in patients with heart failure have emerged. From this historical-physiologic perspective, we have seen how 3 increasingly reductionist approaches or schools of thought have evolved in parallel, that is, an input-output approach, a hemodynamic pump approach, and a muscular pump approach. Each one of these has provided complementary insights into the pathophysiology of heart failure and has resulted in measurements or derived indices, some of which still being in use in present-day cardiology. From the third, most reductionist muscular pump approach, we have learned that myocardial and ventricular relaxation properties as well as temporal and spatial nonuniformities have been largely overlooked in the 2 other, input-output and hemodynamic pump, approaches. A key message from the present review is that relaxation and nonuniformities can be fully understood only from within the time-space continuum of cardiac pumping. As cyclicity and rhythm are, in some way, the most basic aspects of cardiac function, considerations of time should dominate over any measurement of cardiac performance as a muscular pump. Any measurement that is blind for the arrow of cardiac time should therefore be interpreted with caution. We have seen how the escape from the time domain-as with the calculation of LV ejection fraction-fascinating though as it may be, has undoubtedly served to hinder a rational scientific debate on the recent, so-called systolic-diastolic heart failure controversy. Lacking appreciation of early

  6. Early dystrophin loss is coincident with the transition of compensated cardiac hypertrophy to heart failure.

    Directory of Open Access Journals (Sweden)

    Fernanda P Prado

    Full Text Available Hypertension causes cardiac hypertrophy, one of the most important risk factors for heart failure (HF. Despite the importance of cardiac hypertrophy as a risk factor for the development of HF, not all hypertrophied hearts will ultimately fail. Alterations of cytoskeletal and sarcolemma-associated proteins are considered markers cardiac remodeling during HF. Dystrophin provides mechanical stability to the plasma membrane through its interactions with the actin cytoskeleton and, indirectly, to extracellular matrix proteins. This study was undertaken to evaluate dystrophin and calpain-1 in the transition from compensated cardiac hypertrophy to HF. Wistar rats were subjected to abdominal aorta constriction and killed at 30, 60 and 90 days post surgery (dps. Cardiac function and blood pressure were evaluated. The hearts were collected and Western blotting and immunofluorescence performed for dystrophin, calpain-1, alpha-fodrin and calpastatin. Statistical analyses were performed and considered significant when p<0.05. After 90 dps, 70% of the animals showed hypertrophic hearts (HH and 30% hypertrophic+dilated hearts (HD. Systolic and diastolic functions were preserved at 30 and 60 dps, however, decreased in the HD group. Blood pressure, cardiomyocyte diameter and collagen content were increased at all time points. Dystrophin expression was lightly increased at 30 and 60 dps and HH group. HD group showed decreased expression of dystrophin and calpastatin and increased expression of calpain-1 and alpha-fodrin fragments. The first signals of dystrophin reduction were observed as early as 60 dps. In conclusion, some hearts present a distinct molecular pattern at an early stage of the disease; this pattern could provide an opportunity to identify these failure-prone hearts during the development of the cardiac disease. We showed that decreased expression of dystrophin and increased expression of calpains are coincident and could work as possible

  7. Novel protective role of endogenous cardiac myocyte P2X4 receptors in heart failure.

    Science.gov (United States)

    Yang, Tiehong; Shen, Jian-bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberly; Grady, James; Jacobson, Kenneth A; Liang, Bruce T

    2014-05-01

    Heart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload. Mice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation-induced postinfarct or transverse aorta constriction-induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N(5)-(1-iminoethyl)ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout. This study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection. © 2014 American Heart Association, Inc.

  8. Polymer microfiber meshes facilitate cardiac differentiation of c-kit{sup +} human cardiac stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Kan, Lijuan [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States); Thayer, Patrick [Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); Fan, Huimin [Research Institute of Heart Failure, Shanghai East Hospital of Tongji University, Shanghai (China); Ledford, Benjamin; Chen, Miao [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States); Goldstein, Aaron [Department of Chemical Engineering, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); Cao, Guohua [School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA (United States); He, Jia-Qiang, E-mail: jiahe@vt.edu [Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA (United States)

    2016-09-10

    Electrospun microfiber meshes have been shown to support the proliferation and differentiation of many types of stem cells, but the phenotypic fate of c-kit{sup +} human cardiac stem cells (hCSCs) have not been explored. To this end, we utilized thin (~5 µm) elastomeric meshes consisting of aligned 1.7 µm diameter poly (ester-urethane urea) microfibers as substrates to examine their effect on hCSC viability, morphology, proliferation, and differentiation relative to cells cultured on tissue culture polystyrene (TCPS). The results showed that cells on microfiber meshes displayed an elongated morphology aligned in the direction of fiber orientation, lower proliferation rates, but increased expressions of genes and proteins majorly associated with cardiomyocyte phenotype. The early (NK2 homeobox 5, Nkx2.5) and late (cardiac troponin I, cTnI) cardiomyocyte genes were significantly increased on meshes (Nkx=2.5 56.2±13.0, cTnl=2.9±0.56,) over TCPS (Nkx2.5=4.2±0.9, cTnl=1.6±0.5, n=9, p<0.05 for both groups) after differentiation. In contrast, expressions of smooth muscle markers, Gata6 and myosin heavy chain (SM-MHC), were decreased on meshes. Immunocytochemical analysis with cardiac antibody exhibited the similar pattern of above cardiac differentiation. We conclude that aligned microfiber meshes are suitable for guiding cardiac differentiation of hCSCs and may facilitate stem cell-based therapies for treatment of cardiac diseases. - Highlights: • First study to characterize c-kit{sup +} human cardiac stem cells on microfiber meshes. • Microfiber meshes seem reducing cell proliferation, but no effect on cell viability. • Microfiber meshes facilitate the elongation of human cardiac stem cells in culture. • Cardiac but not smooth muscle differentiation were enhanced on microfiber meshes. • Microfiber meshes may be used as cardiac patches in cell-based cardiac therapy.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. Estimating changes in cardiac output using an implanted hemodynamic monitor in heart failure patients

    DEFF Research Database (Denmark)

    Ståhlberg, Marcus; Damgaard, Morten; Ersgård, David

    2010-01-01

    OBJECTIVES: The aim of this study was to evaluate an algorithm that estimates changes in cardiac output (CO) from right ventricular (RV) pressure waveforms derived from an implantable hemodynamic monitor (IHM) in heart failure patients. DESIGN: Twelve heart failure patients (NYHA II-III, EF 32......%) with an implantable hemodynamic monitor (Chronicle) were included in this study. Changes in cardiac output were provoked by body position change at rest (left lateral supine, horizontal supine, sitting, and standing) and a steady state bicycle exercise at 20 watts. Estimated CO derived from the IHM (CO...... was -0.39 L/min (11%). Limits of agreement were +/-1.56 L/min and relative error was 21%. CONCLUSIONS: A simple algorithm based on RV pressure wave form characteristics derived from an IHM can be used to estimate changes in CO in heart failure patients. These findings encourage further research aiming...

  11. Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure.

    Science.gov (United States)

    Hanft, Laurin M; Emter, Craig A; McDonald, Kerry S

    2017-07-01

    Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca 2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faster loaded shortening, and greater power output; however, with progression to overt heart failure, we predicted marked depression in these contractile properties. We assessed contractile properties in skinned cardiac myocyte preparations from left ventricles of Wistar-Kyoto control rats and spontaneous hypertensive heart failure (SHHF) rats at ~3, ~12, and >20 mo of age to evaluate the time course of myofilament properties associated with normal aging processes compared with myofilaments from rats with a predisposition to heart failure. In control rats, the myofilament contractile properties were virtually unchanged throughout the aging process. Conversely, in SHHF rats, the rate of force development, loaded shortening velocity, and power all increased at ~12 mo and then significantly fell at the >20-mo time point, which coincided with a decrease in left ventricular fractional shortening. Furthermore, these changes occurred independent of changes in β-myosin heavy chain but were associated with depressed phosphorylation of myofibrillar proteins, and the fall in loaded shortening and peak power output corresponded with the onset of clinical signs of heart failure. NEW & NOTEWORTHY This novel study systematically examined the power-generating capacity of cardiac myofilaments during the progression from hypertension to heart disease. Previously

  12. Epigenome-Wide Association Study Identifies Cardiac Gene Patterning and a Novel Class of Biomarkers for Heart Failure.

    Science.gov (United States)

    Meder, Benjamin; Haas, Jan; Sedaghat-Hamedani, Farbod; Kayvanpour, Elham; Frese, Karen; Lai, Alan; Nietsch, Rouven; Scheiner, Christina; Mester, Stefan; Bordalo, Diana Martins; Amr, Ali; Dietrich, Carsten; Pils, Dietmar; Siede, Dominik; Hund, Hauke; Bauer, Andrea; Holzer, Daniel Benjamin; Ruhparwar, Arjang; Mueller-Hennessen, Matthias; Weichenhan, Dieter; Plass, Christoph; Weis, Tanja; Backs, Johannes; Wuerstle, Maximilian; Keller, Andreas; Katus, Hugo A; Posch, Andreas E

    2017-10-17

    Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with dilated cardiomyopathy and controls. Infinium human methylation 450 was used for high-density epigenome-wide mapping of DNA methylation in left-ventricular biopsies and whole peripheral blood of living probands. RNA deep sequencing was performed on the same samples in parallel. Whole-genome sequencing of all patients allowed exclusion of promiscuous genotype-induced methylation calls. In the screening stage, we detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy (false discovery corrected P ≤0.05), with 3 of them reaching epigenome-wide significance at P ≤5×10 -8 . Twenty-seven (46%) of these loci could be replicated in independent cohorts, underlining the role of epigenetic regulation of key cardiac transcription regulators. Using a staged multi-omics study design, we link a subset of 517 epigenetic loci with dilated cardiomyopathy and cardiac gene expression. Furthermore, we identified distinct epigenetic methylation patterns that are conserved across tissues, rendering these CpGs novel epigenetic biomarkers for heart failure. The present study provides to our knowledge the first epigenome-wide association study in living patients with heart failure using a multi-omics approach. © 2017 American Heart Association, Inc.

  13. Cardiac glycosides induce cell death in human cells by inhibiting general protein synthesis.

    Directory of Open Access Journals (Sweden)

    Andrea Perne

    2009-12-01

    Full Text Available Cardiac glycosides are Na(+/K(+-pump inhibitors widely used to treat heart failure. They are also highly cytotoxic, and studies have suggested specific anti-tumor activity leading to current clinical trials in cancer patients. However, a definitive demonstration of this putative anti-cancer activity and the underlying molecular mechanism has remained elusive.Using an unbiased transcriptomics approach, we found that cardiac glycosides inhibit general protein synthesis. Protein synthesis inhibition and cytotoxicity were not specific for cancer cells as they were observed in both primary and cancer cell lines. These effects were dependent on the Na(+/K(+-pump as they were rescued by expression of a cardiac glycoside-resistant Na(+/K(+-pump. Unlike human cells, rodent cells are largely resistant to cardiac glycosides in vitro and mice were found to tolerate extremely high levels.The physiological difference between human and mouse explains the previously observed sensitivity of human cancer cells in mouse xenograft experiments. Thus, published mouse xenograft models used to support anti-tumor activity for these drugs require reevaluation. Our finding that cardiac glycosides inhibit protein synthesis provides a mechanism for the cytotoxicity of CGs and raises concerns about ongoing clinical trials to test CGs as anti-cancer agents in humans.

  14. Clinical research on correlation between BNP and left cardiac function in patients with heart failure

    International Nuclear Information System (INIS)

    Yin Xin; Xu Dandan; Wu Chunxu

    2005-01-01

    To investigate the correlation between brain natriuretic peptide (BNP) and the cardiac function in patients with heart failure(HF), the plasma level of BNP was determined by IRMA and the left cardiac function parameters were measured on echocardiogram in patients with different grade of HF. The results showed that the plasma level of BNP elevated with the worsening of heart failure (NYHA classification). The plasma levels of BNP were negatively correlated with left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVDd). The plasma level of BNP increases significantly along with the severity of HF classified by NYHA, and might be a biochemical parameter for evaluating the left ventricular function. (authors)

  15. Hereditary Hemorrhagic Telangiectasia Presenting as High Output Cardiac Failure during Pregnancy

    Directory of Open Access Journals (Sweden)

    Tareq Goussous

    2009-01-01

    Full Text Available High-output cardiac failure secondary to hepatic involvement is a rare complication of hereditary hemorrhagic telangiectasia (HHT. Here we report a 43-year-old woman who presented at 29 weeks gestation of her second pregnancy with complications of right-sided heart failure and preterm labor. After delivery via cesarean section, the patient was found to have intrahepatic arteriovenous malformations through non-invasive imaging. Subsequently, a family history of vascular malformations and epistaxis was elucidated and a diagnosis of HHT was made. This case is presented, along with a review of the literature and discussion of hepatic involvement in HHT with particular focus on the pregnant patient.

  16. Usefulness of cardiac 123I-MIBG imaging for the evaluation of diastolic heart failure

    International Nuclear Information System (INIS)

    Tanaka, Haruki; Kozai, Toshiyuki; Urabe, Yoshitoshi

    2007-01-01

    Significance of 123 I-MIBG (metaiodobenzylguanidine) scintigraphy in diagnosis of cardiac sympathetic nerve function is not yet elucidated in chronic heart failure derived from left ventricular diastolic defect despite its established importance in evaluation of severity and prognosis of chronic systolic heart failure. This study was performed to elucidate the usefulness of the imaging for chronic diastolic heart failure. Comparison was made of 47 hospitalized patients with chronic diastolic heart failure (D-group; left ejection fraction, 50% or more), 45 with chronic systolic failure (S-group; the fraction 123 I-MIBG with 2-detector gamma camera (Toshiba E.CAM), of which images were analyzed by Toshiba GMS-7000. Cardiac sympathetic nerve function in D-group was found stimulated to be impaired, in a similar extent to that in S-group; severity in NYHA classification was significantly correlated with late H/M ratio and WR; WR in cases with atrial fibrillation complication showed a significant correlation with plasma BNP level; and 123 I-MIBG scintigraphic evaluation of the nerve function in D-group was concluded to be useful for severity assessment. (T.I.)

  17. Successful treatment of 54 patients with acute renal failure after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Lei CHEN

    2015-06-01

    Full Text Available Objectives To evaluate the result of treatment of acute renal failure (ARF in patients after cardiac surgery. Methods The clinical data of 54 cases admitted to the hospital from Jan. 2004 to Jan. 2014 and suffered from ARF after cardiac surgery were retrospectively analyzed. Among 54 cases, there were 35 males and 19 females, aged from one month to 79 years with a median of 52 years. The surgical procedures included coronary artery bypass grafting (CABG, 10 cases, valve surgery (22 cases, combined CABG and valve surgery (4 cases, operation on aorta (14 case, and radical correction of Fallot tetralogy (4 cases. After the operations mentioned above, 50 patients received continuous renal replacement therapy (CRRT, and 4 patients received peritoneal dialysis. Results Nine patients died, the mortality rate was 16.7%. Exploratory hemostasis by thoracotomy was performed in 8 patients, and extubation failure occurred in 4 cases. Of the 9 non-survivors, 6 died from multiple organ failure (MOF, 2 died from cerebral hemorrhage, and one died from acute respiratory failure. Serum creatinine (SCr and blood urea nitrogen (BUN levels declined obviously after CRRT and peritoneal dialysis (P<0.05, and all the patients were shown to have stable hemodynamics in the course of treatment, and no hemorrhage or embolism occurred. Conclusions ARF after cardiac surgery should be detected early and treated in time. CRRT and peritoneal dialysis are safe, convenient and effective procedures, and may decrease the mortality rate in patients with ARF after cardiac surgery. DOI: 10.11855/j.issn.0557-7402.2015.04.13

  18. Raised cardiac enzymes in sepsis with renal failure: An encompassing umbrella or a masquerader?

    Directory of Open Access Journals (Sweden)

    Dilip Gude

    2014-01-01

    Full Text Available Elevation of cardiac enzymes and troponins particularly in settings of sepsis and renal failure may cloud the diagnostic picture of acute coronary syndrome in many cases. Interpretation of such elevated enzymes thus warrants caution. It necessitates adequate awareness amongst clinicians, of conditions with such elevation in the absence of myocardial ischemia/infarction as well as those that harbinger false positives. We discuss one such case that posed a diagnostic dilemma and review the pertinent literature.

  19. Renal function in patients with hypertension associated congestive cardiac failure seen in a tertiary hospital.

    Science.gov (United States)

    Osuji, C U; Nwaneli, C U; Onwubere, B J; Onwubuya, E I; Ahaneku, G I

    2012-01-01

    Background. Chronic kidney disease is frequently seen in patients with congestive cardiac failure and is an independent risk factor for morbidity and mortality. The aim of this study was to determine the prevalence of chronic kidney disease in patients with hypertension associated congestive cardiac failure. Method. One hundred and fifty patients with hypertension associated congestive cardiac failure were recruited consecutively from the medical outpatient department and the medical wards of the Nnamdi Azikiwe University Teaching Hospital Nnewi over a one year period, January to December 2010. Patients' biodata and medical history were obtained, detailed physical examination done and each patient had a chest X-ray, 12 lead ECG, urinalysis, serum urea and creatinine assay done. Ethical clearance was obtained from the Ethical Review Board of our institution and data analysed using SPSS-version 16. Results. There were 86 males and 64 females with mean age 62.7 ± 12.5 years. The mean blood pressures were systolic 152.8 ± 28.5 mmHg and diastolic 94.3 ± 18 mmHg. 84.7% had blood pressure ≥140/90 mmHg on presentation. The mean GFR was 70.1 ± 31.3 mls/min. 76% of subjects had GFR <90 mls/min and no statistical significant difference between males and females, P = 0.344. The mean serum urea was 7.2 ± 51 mmol/L while the mean serum creatinine was 194 ± 416.2 mmol/L. Conclusions. This study has demonstrated that majority of patients presenting with hypertension associated congestive cardiac failure have some degree of chronic kidney disease.

  20. Prevention of liver cancer cachexia-induced cardiac wasting and heart failure

    Science.gov (United States)

    Springer, Jochen; Tschirner, Anika; Haghikia, Arash; von Haehling, Stephan; Lal, Hind; Grzesiak, Aleksandra; Kaschina, Elena; Palus, Sandra; Pötsch, Mareike; von Websky, Karoline; Hocher, Berthold; Latouche, Celine; Jaisser, Frederic; Morawietz, Lars; Coats, Andrew J.S.; Beadle, John; Argiles, Josep M.; Thum, Thomas; Földes, Gabor; Doehner, Wolfram; Hilfiker-Kleiner, Denise; Force, Thomas; Anker, Stefan D.

    2014-01-01

    Aims Symptoms of cancer cachexia (CC) include fatigue, shortness of breath, and impaired exercise capacity, which are also hallmark symptoms of heart failure (HF). Herein, we evaluate the effects of drugs commonly used to treat HF (bisoprolol, imidapril, spironolactone) on development of cardiac wasting, HF, and death in the rat hepatoma CC model (AH-130). Methods and results Tumour-bearing rats showed a progressive loss of body weight and left-ventricular (LV) mass that was associated with a progressive deterioration in cardiac function. Strikingly, bisoprolol and spironolactone significantly reduced wasting of LV mass, attenuated cardiac dysfunction, and improved survival. In contrast, imidapril had no beneficial effect. Several key anabolic and catabolic pathways were dysregulated in the cachectic hearts and, in addition, we found enhanced fibrosis that was corrected by treatment with spironolactone. Finally, we found cardiac wasting and fibrotic remodelling in patients who died as a result of CC. In living cancer patients, with and without cachexia, serum levels of brain natriuretic peptide and aldosterone were elevated. Conclusion Systemic effects of tumours lead not only to CC but also to cardiac wasting, associated with LV-dysfunction, fibrotic remodelling, and increased mortality. These adverse effects of the tumour on the heart and on survival can be mitigated by treatment with either the β-blocker bisoprolol or the aldosterone antagonist spironolactone. We suggest that clinical trials employing these agents be considered to attempt to limit this devastating complication of cancer. PMID:23990596

  1. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.

    Directory of Open Access Journals (Sweden)

    Jessica Jen-Chu Wang

    2016-07-01

    Full Text Available We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls.

  2. Plasma urocortin in human systolic heart failure.

    Science.gov (United States)

    Ng, Leong L; Loke, Ian W; O'Brien, Russell J; Squire, Iain B; Davies, Joan E

    2004-04-01

    Urocortin (UCN), a member of the corticotrophin-releasing factor family, is expressed in heart, brain and gut. UCN has potent cardiostimulatory, cardioprotective, vasodilator and diuretic/natriuretic effects, and cardiac UCN expression is increased in heart failure (HF). In the present study, we investigated plasma levels of UCN in 119 patients with HF and 212 age- and gender-matched controls to clarify its relationship with gender and disease severity. UCN was elevated in HF [normal males, 19.5 (3.9-68.8) pmol/l and HF males, 50.2 (6.9-108.2) pmol/l, P fall in UCN levels with increasing NYHA class was reinforced by a significant correlation between UCN and ejection fraction ( r(s) = 0.45, P < 0.0005) in HF patients. Although receiver operating characteristic (ROC) curves for diagnosis of all HF cases yielded an area under the curve (AUC) of 0.76, ROC AUCs for patients with early HF (NYHA class I and II) were better (0.91). ROC AUCs for logistic models incorporating N-terminal probrain natriuretic peptide (N-BNP) and UCN were better than either peptide alone. In conclusion, plasma UCN is elevated in HF, especially in its early stages. Its decline with increasing HF severity may expedite disease progression due to diminished cardioprotective/anti-inflammatory effects. UCN measurement may also complement N-BNP in the diagnosis of early HF.

  3. Peripheral vasodilatation determines cardiac output in exercising humans

    DEFF Research Database (Denmark)

    Bada, A A; Svendsen, J H; Secher, N H

    2012-01-01

    In dogs, manipulation of heart rate has no effect on the exercise-induced increase in cardiac output. Whether these findings apply to humans remain uncertain, because of the large differences in cardiovascular anatomy and regulation. To investigate the role of heart rate and peripheral...... arterial ATP infusion at rest. Exercise and ATP infusion increased cardiac output, leg blood flow and vascular conductance (P heart rate by up to 54 beats min(−1), cardiac output did not change in any of the three...... demonstrate that the elevated cardiac output during steady-state exercise is regulated by the increase in skeletal muscle blood flow and venous return to the heart, whereas the increase in heart rate appears to be secondary to the regulation of cardiac output....

  4. A review of economic evaluation models for cardiac resynchronization therapy with implantable cardioverter defibrillators in patients with heart failure

    NARCIS (Netherlands)

    Tomini, F.; van Asselt, A. D.

    OBJECTIVES: Cardiac resynchronization therapy with biventricular pacemaker (CRT-P) is considered an effective treatment for heart failure (HF). Adding implantable cardioverter defibrillators (CRT-D) may further reduce the risk of sudden cardiac death (SCD). However, economic evaluations have shown

  5. A review of economic evaluation models for cardiac resynchronization therapy with implantable cardioverter defibrillators in patients with heart failure

    NARCIS (Netherlands)

    Tomini, F.; van Asselt, A. D.

    2012-01-01

    OBJECTIVES: Cardiac resynchronization therapy with biventricular pacemaker (CRT-P) is considered an effective treatment for heart failure (HF). Adding implantable cardioverter defibrillators (CRT-D) may further reduce the risk of sudden cardiac death (SCD). However, economic evaluations have shown

  6. State-of-the-art implantable cardiac assist device therapy for heart failure: bridge to transplant and destination therapy.

    Science.gov (United States)

    Park, S J; Kushwaha, S S; McGregor, C G A

    2012-01-01

    Congestive heart failure is associated with poor quality of life (QoL) and low survival rates. The development of state-of-the-art cardiac devices holds promise for improved therapy in patients with heart failure. The field of implantable cardiac assist devices is changing rapidly with the emergence of continuous-flow pumps (CFPs). The important developments in this field, including pertinent clinical trials, registry reports, innovative research, and potential future directions are discussed in this paper.

  7. The benefits of the Atlas of Human Cardiac Anatomy website for the design of cardiac devices.

    Science.gov (United States)

    Spencer, Julianne H; Quill, Jason L; Bateman, Michael G; Eggen, Michael D; Howard, Stephen A; Goff, Ryan P; Howard, Brian T; Quallich, Stephen G; Iaizzo, Paul A

    2013-11-01

    This paper describes how the Atlas of Human Cardiac Anatomy website can be used to improve cardiac device design throughout the process of development. The Atlas is a free-access website featuring novel images of both functional and fixed human cardiac anatomy from over 250 human heart specimens. This website provides numerous educational tutorials on anatomy, physiology and various imaging modalities. For instance, the 'device tutorial' provides examples of devices that were either present at the time of in vitro reanimation or were subsequently delivered, including leads, catheters, valves, annuloplasty rings and stents. Another section of the website displays 3D models of the vasculature, blood volumes and/or tissue volumes reconstructed from computed tomography and magnetic resonance images of various heart specimens. The website shares library images, video clips and computed tomography and MRI DICOM files in honor of the generous gifts received from donors and their families.

  8. PET imaging of human cardiac opioid receptors

    Energy Technology Data Exchange (ETDEWEB)

    Villemagne, Patricia S.R.; Dannals, Robert F. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ravert, Hayden T. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Frost, James J. [Department of Radiology, The Johns Hopkins University School of Medicine, 605 N Caroline St., Baltimore, Maryland (United States); Department of Environmental Health Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2002-10-01

    The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image {mu} and {delta} opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65{+-}8 years old) underwent PET scanning of the chest with [{sup 11}C]carfentanil ([{sup 11}C]CFN) and [{sup 11}C]-N-methyl-naltrindole ([{sup 11}C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [{sup 11}C]CFN or [{sup 11}C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [{sup 11}C]CFN and [{sup 11}C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37{+-}0.91 with [{sup 11}C]CFN and 3.86{+-}0.60 with [{sup 11}C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [{sup 11}C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [{sup 11}C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function. (orig.)

  9. Techniques for Identification of Left Ventricular Asynchrony for Cardiac Resynchronization Therapy in Heart Failure

    Directory of Open Access Journals (Sweden)

    Peter Schuster

    2005-07-01

    Full Text Available The most recent treatment option of medically refractory heart failure includes cardiac resynchronization therapy (CRT by biventricular pacing in selected patients in NYHA functional class III or IV heart failure. The widely used marker to indicate left ventricular (LV asynchrony has been the surface ECG, but seems not to be a sufficient marker of the mechanical events within the LV and prediction of clinical response. This review presents an overview of techniques for identification of left ventricular intra- and interventricular asynchrony. Both manuscripts for electrical and mechanical asynchrony are reviewed, partly predicting response to CRT. In summary there is still no gold standard for assessment of LV asynchrony for CRT, but both traditional and new echocardiographic methods have shown asynchronous LV contraction in heart failure patients, and resynchronized LV contraction during CRT and should be implemented as additional methods for selecting patients to CRT.

  10. Evaluation of long-term prognosis in patients with heart failure. Is cardiac imaging with iodine-123 metaiodobenzylguanidine useful?

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi

    1998-01-01

    The effect of cardiac sympathetic activity on long-term prognosis in patients with heart failure was evaluated by cardiac imaging with 123 I-MIBG in 46 patients admitted for the first episode of heart failure. Cardiac imaging was performed with 123 I-MIBG and 201 Tl at rest on separate days before discharge. Using whole body imaging, the ratio of cardiac uptake of the isotope to total injected dose was calculated (percentage uptake). The cardiac uptake ratio of 123 I-MIBG (percentage uptake of 123 I-MIBG divided by percentage uptake of 201 Tl) and percentage washout of 123 I-MIBG from the heart over 3 hours were calculated as scintigraphic parameters. Cardiac events were defined as cardiac death or deterioration of heart failure requiring readmission. Scintigraphic parameters, clinical parameters, left ventricular function obtained by echocardiography and neurohumoral parameters were compared between the event group and event-free group. During the follow-up period, cardiac events developed in 14 patients (30%). Univariate analysis showed uptake ratio and washout rate of 123 I-MIBG, percentage uptake of 201 Tl, New York Heart Association class at discharge, fractional shortening of the left ventricle, serum norepinephrine and atrial natriuretic peptide levels differed significantly between the two groups. Cox proportional-hazard analysis showed that the uptake ratio was an independent predictor of cardiac events. When a cut-off point in the uptake ratio equal to or less than 0.50 and age equal to or more than 65 years old were included in the Cox proportional-hazard analysis instead of actual numbers, relative risks of cardiac events by each index were 31.2 and 4.2, respectively. These data suggest that cardiac uptake of 123 I-MIBG is a strong and independent predictor of long-term prognosis in patients with heart failure. (K.H.)

  11. Evaluation of long-term prognosis in patients with heart failure. Is cardiac imaging with iodine-123 metaiodobenzylguanidine useful?

    Energy Technology Data Exchange (ETDEWEB)

    Narita, Michihiro; Kurihara, Tadashi [Sumitomo Hospital, Osaka (Japan)

    1998-06-01

    The effect of cardiac sympathetic activity on long-term prognosis in patients with heart failure was evaluated by cardiac imaging with {sup 123}I-MIBG in 46 patients admitted for the first episode of heart failure. Cardiac imaging was performed with {sup 123}I-MIBG and {sup 201}Tl at rest on separate days before discharge. Using whole body imaging, the ratio of cardiac uptake of the isotope to total injected dose was calculated (percentage uptake). The cardiac uptake ratio of {sup 123}I-MIBG (percentage uptake of {sup 123}I-MIBG divided by percentage uptake of {sup 201}Tl) and percentage washout of {sup 123}I-MIBG from the heart over 3 hours were calculated as scintigraphic parameters. Cardiac events were defined as cardiac death or deterioration of heart failure requiring readmission. Scintigraphic parameters, clinical parameters, left ventricular function obtained by echocardiography and neurohumoral parameters were compared between the event group and event-free group. During the follow-up period, cardiac events developed in 14 patients (30%). Univariate analysis showed uptake ratio and washout rate of {sup 123}I-MIBG, percentage uptake of {sup 201}Tl, New York Heart Association class at discharge, fractional shortening of the left ventricle, serum norepinephrine and atrial natriuretic peptide levels differed significantly between the two groups. Cox proportional-hazard analysis showed that the uptake ratio was an independent predictor of cardiac events. When a cut-off point in the uptake ratio equal to or less than 0.50 and age equal to or more than 65 years old were included in the Cox proportional-hazard analysis instead of actual numbers, relative risks of cardiac events by each index were 31.2 and 4.2, respectively. These data suggest that cardiac uptake of {sup 123}I-MIBG is a strong and independent predictor of long-term prognosis in patients with heart failure. (K.H.)

  12. 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.

  13. Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons.

    Science.gov (United States)

    Hasan, Wohaib; Smith, Peter G

    2014-04-01

    Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine's role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1h of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24h. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Radioimmunoassay of human cardiac tropomyosin in acute myocardial infarction

    International Nuclear Information System (INIS)

    Cummins, P.; McGurk, B.; Littler, W.A.

    1981-01-01

    Tropomyosin was prepared from fresh human myocardium and antisera raised in rabbits. A sensitive radioimmunoassay was developed for the detection of human cardiac 125 I-labelled tropomyosin in human sera down to levels of 1 ng/ml. Values for human cardiac tropomyosin in normal patients ranged from less than 1 to 3 ng/ml. In 18 patients with acute myocardial infarction all had elevated tropomyosin levels ranging from 41 to above 200 ng/ml with a mean peak level of 101 ng/ml. In this study there were no false positive or false negative results. In the initial stages of infarction the time course of appearance and peak levels of cardiac tropomyosin, total creatine kinase and creatine kinase MB isoenzyme were similar. Although total creatine kinase and creatine kinase MB isoenzyme levels were normal after 72 h in patients with single, uncomplicated infarction, cardiac tropomyosin levels were still significantly elevated above normal after this time, being 30-60% of peak values. Radioimmunoassay of human cardiac tropomyosin may prove useful in the diagnosis and in the management of patients with acute myocardial infarction, particularly in the long-term postinfarction period. (author)

  15. Therapeutic drug monitoring of digoxin in cardiac heart failure outpatients: comparisons of two analytical methods

    Directory of Open Access Journals (Sweden)

    Isabel Cristina Medeiros Barros

    2014-01-01

    Full Text Available Objective: To compare two analytical techniques used in the determination of plasma digoxin (LC-MS/MS and immunoassay and to verify which one better answer the need of the clinical monitoring routine of patients with cardiac heart failure. Method: The clinical findings in 15 cardiac heart failure (CHF outpatients of the Cardiac Heart Service of the Goias Federal University Clinical Hospital were investigated. Blood samples of the patients were collected and analysed by Immunoassay and by Liquid Chromatography coupled to Mass Spectrometry (LC-MS/MS. Results: The results of the statistic test (Student p = 0,05 showed a significant difference between the analytical methods: immunoassay concentrations were higher than the concentrations determined by LCMS/ MS. The explanation may be because immunoassay method measures digoxin plus other metabolites and endogenous substances, while the LC-MS/MS method measures only the digoxin molecule. None of the patients, showed relevant clinical data suggestive of digitalis intoxication, even several drugs with potential interaction were associated with treatment. Conclusion: It was concluded, therefore, that LC-MS/MS me thod is safer, more selective and specific than immunoassay, being an option for therapeutic drug monitoring of digoxin, since the reference values would be obtain for digoxinemia by LC-MS/MS.

  16. EVALUATION CARDIAC RESYNCHRONIZATION THERAPY IN PATIENTS WITH CHRONIC ISCHEMIC HEART FAILURE

    Directory of Open Access Journals (Sweden)

    A. J. Fishman

    2011-01-01

    Full Text Available Objective — studying dyssynchrony characteristics and evaluation correction effectiveness in patients with chronic heart failure (CHF of ischemic origin.Materials and methods. The study included 125 patients with chronic heart failure of ischemic etiology, 28 of them — with coronary heart disease (CHD who had undergone aorto-and / or mammarokoronary bypass and / or percutaneous coronary intervention, 42 — with coronary artery disease and postinfarction cardiosclerosis, 32 — with arrhythmic variant of coronary artery disease, 23 — with stable angina without evidence of arrhythmia. Among included patients, biventricular pacemakers were implanted for 17 patients. All patients underwent echocardiography with determination of the parameters of dyssynchrony.Results and conclusion. Among patients with CHF ischemic symptoms dyssynchrony was diagnosed in 36 (28.8 % cases. Statistically significant association between patients with cardiac arrhythmias and dyssynchrony was determined. At the same time the incidence of dyssynchrony was not associated with various forms of ischemic heart disease, and did not depend on the anamnesis of cardiac surgery. Dependence of the frequency of occurrence of dyssynchrony on the severity of CHF was revealed. Patients selected for implantation of biventricular pacemakers, especially in view of echocardiographic signs of dyssynchrony had significant improvement after providing cardiac resynchronization therapy. Effect of the treatment does not depend on the atrial fibrillation rhythm presence.

  17. The Role of Nrf2-Mediated Pathway in Cardiac Remodeling and Heart Failure

    Directory of Open Access Journals (Sweden)

    Shanshan Zhou

    2014-01-01

    Full Text Available Heart failure (HF is frequently the consequence of sustained, abnormal neurohormonal, and mechanical stress and remains a leading cause of death worldwide. The key pathophysiological process leading to HF is cardiac remodeling, a term referring to maladaptation to cardiac stress at the molecular, cellular, tissue, and organ levels. HF and many of the conditions that predispose one to HF are associated with oxidative stress. Increased generation of reactive oxygen species (ROS in the heart can directly lead to increased necrosis and apoptosis of cardiomyocytes which subsequently induce cardiac remodeling and dysfunction. Nuclear factor-erythroid-2- (NF-E2- related factor 2 (Nrf2 is a transcription factor that controls the basal and inducible expression of a battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes that are ubiquitously expressed in the cardiovascular system. Emerging evidence has revealed that Nrf2 and its target genes are critical regulators of cardiovascular homeostasis via the suppression of oxidative stress, which is the key player in the development and progression of HF. The purpose of this review is to summarize evidence that activation of Nrf2 enhances endogenous antioxidant defenses and counteracts oxidative stress-associated cardiac remodeling and HF.

  18. ELABELA-APJ axis protects from pressure overload heart failure and angiotensin II-induced cardiac damage.

    Science.gov (United States)

    Sato, Teruki; Sato, Chitose; Kadowaki, Ayumi; Watanabe, Hiroyuki; Ho, Lena; Ishida, Junji; Yamaguchi, Tomokazu; Kimura, Akinori; Fukamizu, Akiyoshi; Penninger, Josef M; Reversade, Bruno; Ito, Hiroshi; Imai, Yumiko; Kuba, Keiji

    2017-06-01

    Elabela/Toddler/Apela (ELA) has been identified as a novel endogenous peptide ligand for APJ/Apelin receptor/Aplnr. ELA plays a crucial role in early cardiac development of zebrafish as well as in maintenance of self-renewal of human embryonic stem cells. Apelin was the first identified APJ ligand, and exerts positive inotropic heart effects and regulates the renin-angiotensin system. The aim of this study was to investigate the biological effects of ELA in the cardiovascular system. Continuous infusion of ELA peptide significantly suppressed pressure overload-induced cardiac hypertrophy, fibrosis and impaired contractility in mice. ELA treatment reduced mRNA expression levels of genes associated with heart failure and fibrosis. The cardioprotective effects of ELA were diminished in APJ knockout mice, indicating that APJ is the key receptor for ELA in the adult heart. Mechanistically, ELA downregulated angiotensin-converting enzyme (ACE) expression in the stressed hearts, whereas it showed little effects on angiotensin-converting enzyme 2 (ACE2) expression, which are distinct from the effects of Apelin. FoxM1 transcription factor, which induces ACE expression in the stressed hearts, was downregulated by ELA but not by Apelin. ELA antagonized angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. The ELA-APJ axis protects from pressure overload-induced heart failure possibly via suppression of ACE expression and pathogenic angiotensin II signalling. The different effects of ELA and Apelin on the expression of ACE and ACE2 implicate fine-tuned mechanisms for a ligand-induced APJ activation and downstream signalling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

  19. [Reliability of nursing outcomes classification label "Knowledge: cardiac disease management (1830)" in outpatients with heart failure].

    Science.gov (United States)

    Cañón-Montañez, Wilson; Oróstegui-Arenas, Myriam

    2015-01-01

    To determine the reliability (internal consistency, inter-rater reproducibility and level of agreement) of nursing outcome: "Knowledge: cardiac disease management (1830)" of the version published in Spanish, in outpatients with heart failure. A reliability study was conducted on 116 outpatients with heart failure. Six indicators of nursing outcome were operationalized. All participants were assessed simultaneously by two evaluators. Three evaluation periods were defined: initial (at baseline), final (a month later), and follow-up (two months later). Internal consistency by Cronbach alpha coefficient, inter-rater reproducibility with intraclass correlation coefficient of reproducibility or agreement and level agreement using the 95% limits of Bland and Altman. Cronbach's alpha was 0.83 (95% CI: 0.77 - 0.89) in the final evaluation, and follow-up values of 0.85 (95% CI: 0.82-0.89) and 0.83 (95% CI: 0.78 - 0.88) were found for the first and second evaluator, respectively. The intraclass correlation coefficient showed values greater 0.9 in the three evaluation periods in both the random and mixed model. The Bland-Altman 95% limits of agreement were close to zero in the three evaluations performed. The questionnaire operationalized to assess the nursing outcome: "Knowledge: cardiac disease management (1830)" in its Spanish version, is a reliable method to measure skills and knowledge in outpatients with heart failure in the Colombian context. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  20. Personal and social factors regarding medical non-compliance in cardiac failure patients

    International Nuclear Information System (INIS)

    Mujtaba, S.F.; Masood, T.; Khalid, D.

    2011-01-01

    Objective: To determine the frequency and association of various personal and social factors with medical non-compliance in cardiac failure patients. Study Design: Cross-sectional, observational study. Place and Duration of Study: National Institute of Cardiovascular Diseases (NICVD), Karachi from January to August 2010. Methodology: Patients admitted in the medical wards of NICVD, who were being treated for cardiac failure, were included. Information regarding basic demographics, education level, self engagement in therapy and status of compliance was obtained by questionnaire. Statistical analysis was carried out by using Fisher's exact test and chi-square. Level of significance was < 0.05. Data was analyzed using SPSS V-15. Out of 267 patients, 73 (27.3%) were compliant while 194 (72.7%) were non-compliant. Educated, self caring patient, and those who knew names of their medications were more compliant than the rest. Conclusion: Medical non-compliance is very common in heart failure patients. Illiteracy and no self engagement in therapy are associated with non-compliance. (author)

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

    Science.gov (United States)

    Duncker, D; Veltmann, C

    2018-05-09

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

  2. [The Relationship Between Quality of Life and Psychological and Behavioral Factors in Patients With Heart Failure Following Cardiac Resynchronization Therapy].

    Science.gov (United States)

    Huang, Jing; Fang, Jin-Bo; Zhao, Yi-Heng

    2018-06-01

    While cardiac resynchronization therapy improves the quality of life of patients with heart failure, some psychological and behavioral factors still affect the quality of life of these patients. However, information on the factors that affect the quality of life of these patients is limited. To describe the quality of life and investigate the relationship between quality of life and behavioral and psychological factors such as depression, smoking, drinking, water and sodium restrictions, exercise, and adherence in patients with chronic heart failure following cardiac resynchronization therapy. This cross-sectional study was conducted using the Morisky Medication Adherence Scale, Minnesota Living With Heart Failure Questionnaire, and Cardiac Depression Scale. A convenience sample of 141 patients with heart failure following cardiac resynchronization therapy were recruited from a tertiary academic hospital in Chengdu. The mean overall score of the Minnesota Living With Heart Failure Questionnaire was 30.89 (out of a total possible score of 105). Water restrictions, sodium restrictions, depression, and exercise were all shown to significantly predict quality of life among the participants. This paper describes the quality of life and defines the behavioral factors that affect the quality of life of patients with heart failure following cardiac resynchronization therapy. The findings suggest that nurses should manage and conduct health education for patients in order to improve their quality of life.

  3. Ongoing myocardial damage relates to cardiac sympathetic nervous disintegrity in patients with heart failure

    International Nuclear Information System (INIS)

    Arimoto, Takanori; Takeishi, Yasuchika; Niizeki, Takeshi

    2005-01-01

    Iodine-123-metaiodobenzylguanidine ( 123 I-MIBG) has been used to assess the integrity and function of the cardiac sympathetic nervous system in patients with heart failure. Heart-type fatty acid binding protein (H-FABP) is released into the circulation when the myocardium is injured, and H-FABP has been recently used as a novel marker for the diagnosis of ongoing myocardial damage. The aim of the present study was to compare cardiac sympathetic nervous activity assessed by 123 I-MIBG imaging with serum levels of H-FABP in patients with heart failure. Fifty patients with chronic heart failure were studied. 123 I-MIBG imaging was carried out at 30 min (early) and 240 min (delayed) after the tracer injection. We measured serum levels of H-FABP using a sandwich enzyme linked immunosorbent assay. Heart to mediastinum (H/M) ratios of 123 I-MIBG decreased and washout rate increased with higher New York Heart Association (NYHA) functional class. H-FABP, norepinephrine and brain natriuretic peptide (BNP) levels increased as the severity of NYHA class advanced. Delayed H/M ratio was significantly correlated with H-FABP (r=-0.296, p=0.029) and BNP (r=-0.335, p=0.0213). Myocardial washout rate of 123 I-MIBG was also correlated with H-FABP (r=0.469, p 123 I-MIBG imaging is an appropriate approach to evaluate non-invasively not only cardiac sympathetic nervous activity, but also latent ongoing myocardial damage in the failing heart. (author)

  4. [11C]-Acetoacetate PET imaging: a potential early marker for cardiac heart failure

    International Nuclear Information System (INIS)

    Croteau, Etienne; Tremblay, Sébastien; Gascon, Suzanne; Dumulon-Perreault, Véronique; Labbé, Sébastien M.; Rousseau, Jacques A.; Cunnane, Stephen C.; Carpentier, André C.; Bénard, François; Lecomte, Roger

    2014-01-01

    The ketone body acetoacetate could be used as an alternate nutrient for the heart, and it also has the potential to improve cardiac function in an ischemic–reperfusion model or reduce the mitochondrial production of oxidative stress involved in cardiotoxicity. In this study, [ 11 C]-acetoacetate was investigated as an early marker of intracellular damage in heart failure. Methods: A rat cardiotoxicity heart failure model was induced by doxorubicin, Dox(+). [ 14 C]-Acetoacetate, a non-positron (β −) emitting radiotracer, was used to characterize the arterial blood input function and myocardial mitochondrial uptake. Afterward, [ 11 C]-acetoacetate (β +) myocardial PET images were obtained for kinetic analysis and heart function assessment in control Dox(−) (n = 15) and treated Dox(+) (n = 6) rats. The uptake rate (K 1 ) and myocardial clearance rate (k 2 or k mono ) were extracted. Results: [ 14 C]-Acetoacetate in the blood was increased in Dox(+), from 2 min post-injection until the last withdrawal point when the heart was harvested, as well as the uptake in the heart and myocardial mitochondria (unpaired t-test, p < 0.05). PET kinetic analysis of [ 11 C]-acetoacetate showed that rate constants K 1 , k 2 and k mono were decreased in Dox(+) (p < 0.05) combined with a reduction of 24% of the left ventricular ejection fraction (p < 0.001). Conclusion: Radioactive acetoacetate ex vivo analysis [ 14 C], and in vivo kinetic [ 11 C] studies provided evidence that [ 11 C]-acetoacetate can assess heart failure Dox(+). Contrary to myocardial flow reserve (rest–stress protocol), [ 11 C]-acetoacetate can be used to assess reduced kinetic rate constants without requirement of hyperemic stress response. The proposed [ 11 C]-acetoacetate cardiac radiotracer in the investigation of heart disease is novel and paves the way to a potential role for [ 11 C]-acetoacetate in cardiac pathophysiology

  5. MicroRNAs in Heart Failure, Cardiac Transplantation, and Myocardial Recovery: Biomarkers with Therapeutic Potential.

    Science.gov (United States)

    Shah, Palak; Bristow, Michael R; Port, J David

    2017-12-01

    Heart failure is increasing in prevalence with a lack of recently developed therapies that produce major beneficial effects on its associated mortality. MicroRNAs are small non-coding RNA molecules that regulate gene expression, are differentially regulated in heart failure, and are found in the circulation serving as a biomarker of heart failure. Data suggests that microRNAs may be used to detect allograft rejection in cardiac transplantation and may predict the degree of myocardial recovery in patients with a left ventricular assist device or treated with beta-blocker therapy. Given their role in regulating cellular function, microRNAs are an intriguing target for oligonucleotide therapeutics, designed to mimic or antagonize (antagomir) their biological effects. We review the current state of microRNAs as biomarkers of heart failure and associated conditions, the mechanisms by which microRNAs control cellular function, and how specific microRNAs may be targeted with novel therapeutics designed to treat heart failure.

  6. Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure

    Directory of Open Access Journals (Sweden)

    Gabriele G. Schiattarella

    2018-05-01

    Full Text Available Left ventricular hypertrophy (LVH is a major contributor to the development of heart failure (HF. Alterations in cyclic adenosine monophosphate (cAMP-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA anchor proteins (AKAPs, tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 (Akap1-/-, Akap1 heterozygous (Akap1+/-, and their wild-type (wt littermates underwent transverse aortic constriction (TAC or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1-/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 (Siah2 knockout mice (Siah2-/-. Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

  7. Caffeoylxanthiazonoside exerts cardioprotective effects during chronic heart failure via inhibition of inflammatory responses in cardiac cells.

    Science.gov (United States)

    Yang, Bin; Wang, Fei; Cao, Huili; Liu, Guifang; Zhang, Yuean; Yan, Ping; Li, Bao

    2017-11-01

    Caffeoylxanthiazonoside (CYT) is an active constituent isolated from the fruit of the Xanthium strumarium L plant. The aim of the present study was to investigate the cardioprotective effects of oral administration of CYT on chronic heart failure (CHF) and its underlying mechanisms. A rat model of CHF was first established, and cardiac function indices, including the heart/body weight index, left heart/body weight index, fractional shortening (FS), ejection fraction (EF), cardiac output (CO) and heart rate (HR), were subsequently determined by cardiac ultrasound. Serum levels of lactate dehydrogenase (LDH) and creatine kinase (CK), and the levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in heart tissues and cardiac microvascular endothelial cells (CMECs) were determined using ELISA. In addition, the protein expression levels of nuclear factor-κB (NF-κB) signaling pathway members were determined by western blotting in CMECs. The results demonstrated that oral administration of 10, 20, 40 mg/kg CYT significantly reduced cardiac hypertrophy and reversed FS, EF, CO and HR when compared with CHF model rats. In addition, CYT administration significantly decreased the levels of TNF-α, IL-6 and IL-1β in heart tissues, as well as serum LDH and CK levels. Furthermore, exposure of CMECs to 20, 40 and 80 µg/ml CYT significantly decreased the production of TNF-α, IL-1β and IL-6. The protein expression levels of cytoplasmic NF-κB p65 and IκB were upregulated, while nuclear NF-κB p65 was downregulated following treatment of CMECs with 20, 40 and 80 µg/ml CYT when compared with untreated CHF model controls. In conclusion, the results of the current study suggest that CYT demonstrates cardioprotective effects in CHF model rats by suppressing the expression of pro-inflammatory cytokines and the NF-κB signaling pathway.

  8. FIASCO II failure to achieve a satisfactory cardiac outcome study: the elimination of system errors.

    Science.gov (United States)

    Farid, Shakil; Page, Aravinda; Jenkins, David; Jones, Mark T; Freed, Darren; Nashef, Samer A M

    2013-07-01

    Death in low-risk cardiac surgical patients provides a simple and accessible method by which modifiable causes of death can be identified. In the first FIASCO study published in 2009, local potentially modifiable causes of preventable death in low-risk patients with a logistic EuroSCORE of 0-2 undergoing cardiac surgery were inadequate myocardial protection and lack of clarity in the chain of responsibility. As a result, myocardial protection was improved, and a formalized system introduced to ensure clarity of the chain of responsibility in the care of all cardiac surgical patients. The purpose of the current study was to re-audit outcomes in low-risk patients to see if improvements have been achieved. Patients with a logistic EuroSCORE of 0-2 who had cardiac surgery from January 2006 to August 2012 were included. Data were prospectively collected and retrospectively analysed. The case notes of patients who died in hospital were subject to internal and external review and classified according to preventability. Two thousand five hundred and forty-nine patients with a logistic EuroSCORE of 0-2 underwent cardiac surgery during the study period. Seven deaths occurred in truly low-risk patients, giving a mortality of 0.27%. Of the seven, three were considered preventable and four non-preventable. Mortality was marginally lower than in our previous study (0.37%), and no death occurred as a result of inadequate myocardial protection or communication failures. We postulate that the regular study of such events in all institutions may unmask systemic errors that can be remedied to prevent or reduce future occurrences. We encourage all units to use this methodology to detect any similarly modifiable factors in their practice.

  9. Loss of Akap1 Exacerbates Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure.

    Science.gov (United States)

    Schiattarella, Gabriele G; Boccella, Nicola; Paolillo, Roberta; Cattaneo, Fabio; Trimarco, Valentina; Franzone, Anna; D'Apice, Stefania; Giugliano, Giuseppe; Rinaldi, Laura; Borzacchiello, Domenica; Gentile, Alessandra; Lombardi, Assunta; Feliciello, Antonio; Esposito, Giovanni; Perrino, Cinzia

    2018-01-01

    Left ventricular hypertrophy (LVH) is a major contributor to the development of heart failure (HF). Alterations in cyclic adenosine monophosphate (cAMP)-dependent signaling pathways participate in cardiomyocyte hypertrophy and mitochondrial dysfunction occurring in LVH and HF. cAMP signals are received and integrated by a family of cAMP-dependent protein kinase A (PKA) anchor proteins (AKAPs), tethering PKA to discrete cellular locations. AKAPs encoded by the Akap1 gene (mitoAKAPs) promote PKA mitochondrial targeting, regulating mitochondrial structure and function, reactive oxygen species production, and cell survival. To determine the role of mitoAKAPs in LVH development, in the present investigation, mice with global genetic deletion of Akap1 ( Akap1 -/- ), Akap1 heterozygous ( Akap1 +/- ), and their wild-type ( wt ) littermates underwent transverse aortic constriction (TAC) or SHAM procedure for 1 week. In wt mice, pressure overload induced the downregulation of AKAP121, the major cardiac mitoAKAP. Compared to wt, Akap1 -/- mice did not display basal alterations in cardiac structure or function and cardiomyocyte size or fibrosis. However, loss of Akap1 exacerbated LVH and cardiomyocyte hypertrophy induced by pressure overload and accelerated the progression toward HF in TAC mice, and these changes were not observed upon prevention of AKAP121 degradation in seven in absentia homolog 2 ( Siah2 ) knockout mice ( Siah2 -/- ). Loss of Akap1 was also associated to a significant increase in cardiac apoptosis as well as lack of activation of Akt signaling after pressure overload. Taken together, these results demonstrate that in vivo genetic deletion of Akap1 enhances LVH development and accelerates pressure overload-induced cardiac dysfunction, pointing at Akap1 as a novel repressor of pathological LVH. These results confirm and extend the important role of mitoAKAPs in cardiac response to stress.

  10. Human failure and industrial safety. The human factor in technology and organisation

    International Nuclear Information System (INIS)

    Semmer, N.

    1999-01-01

    Human failure is not the opposite of successful human action gut follows the same principles. The manner in which humans acquire and process information is influenced by cognitive, social and motivational aspects. Further, human failure generally means a failure of the whole system man/technology/organisation. If serious consequences are to be avoided, the logic of failures must be analyzed in the context of this system, and human staff should be trained in managing failures and not just avoiding them [de

  11. Renal and cardiac function during alpha1-beta-blockade in congestive heart failure

    DEFF Research Database (Denmark)

    Heitmann, M; Davidsen, U; Stokholm, K H

    2002-01-01

    The kidney and the neurohormonal systems are essential in the pathogenesis of congestive heart failure (CHF) and the physiologic response. Routine treatment of moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE) inhibition and beta-blockade. The need for control...... of renal function during initiation of ACE-inhibition in patients with CHF is well known. The aim of this study was to investigate whether supplementation by a combined alpha1-beta-blockade to diuretics and ACE-inhibition might improve cardiac function without reducing renal function....

  12. Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure

    Science.gov (United States)

    Finosh, G.T.; Jayabalan, Muthu

    2012-01-01

    Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed. PMID:23507781

  13. Team-Based Care for Managing Cardiac Comorbidities in Heart Failure.

    Science.gov (United States)

    Bellam, Naveen; Kelkar, Anita A; Whellan, David J

    2015-07-01

    The need for HF management is predicted to increase as the HF population ages. Balancing HF and the multiple cardiac comorbidities remains difficult for any single provider, but becomes Fig. 6. Five-year rates of death or urgent heart transplantation by deciles of total cholesterol in heart failure. (From Horwich TB, Fonarow GC, Hamilton MA, et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002;8(4):222; with permission.) easier with the involvement of a team. Collaboration between physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other health care workers reduces the burden of care coordination and simultaneously improves delivery of care. Team-based approaches increase cost-effectiveness, reduce hospitalization rates, and equally important, give patients more resources and support, which research shows may ultimately improve compliance and outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Angiotensin-converting enzyme inhibition improves cardiac fatty acid metabolism in patients with congestive heart failure.

    Science.gov (United States)

    Yamauchi, S; Takeishi, Y; Minamihaba, O; Arimoto, T; Hirono, O; Takahashi, H; Miyamoto, T; Nitobe, J; Nozaki, N; Tachibana, H; Watanabe, T; Fukui, A; Kubota, I

    2003-08-01

    This study aimed to examine whether angiotensin-converting enzyme (ACE) inhibition improved cardiac fatty acid metabolism in patients with congestive heart failure (CHF). Myocardial 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging was performed in 25 patients with CHF and in 10 control subjects. Myocardial 123I-BMIPP images were obtained 30 min and 4 h after tracer injection. The heart-to-mediastinum (H/M) ratio of 123I-BMIPP uptake and the washout rate of 123I-BMIPP from the myocardium were calculated. Patients were given enalapril for 6 months, and 123I-BMIPP imaging was repeated. H/M ratios on early and delayed images were lower in CHF patients than in normal controls (Pacid metabolism by ACE inhibition may represent a new mechanism for the beneficial effect of this therapy in heart failure.

  15. Analysis and prevention of human failure in nuclear power plants

    International Nuclear Information System (INIS)

    Liu Xinshuan

    2001-01-01

    Based on the performances in Daya Bay Nuclear Power Plant and the common experience from the world nuclear industry, the features and usual kinds of human failures in nuclear power plants are highlighted and the prominent factors on the personal, external and decision problems which might cause the human failures are analyzed. Effective preventive measures have been proposed respectively. Some successful human-failure-prevention practices applied in the Daya Bay Nuclear Power Plant are illustrated specifically

  16. Pig models for the human heart failure syndrome

    DEFF Research Database (Denmark)

    Hunter, Ingrid; Terzic, Dijana; Zois, Nora Elisabeth

    2014-01-01

    Human heart failure remains a challenging illness despite advances in the diagnosis and treatment of heart failure patients. There is a need for further improvement of our understanding of the failing myocardium and its molecular deterioration. Porcine models provide an important research tool...... in this respect as molecular changes can be examined in detail, which is simply not feasible in human patients. However, the human heart failure syndrome is based on symptoms and signs, where pig models mostly mimic the myocardial damage, but without decisive data on clinical presentation and, therefore, a heart...... to elucidate the human heart failure syndrome....

  17. Cardiac Progenitor Cell Extraction from Human Auricles

    KAUST Repository

    Di Nardo, Paolo

    2017-02-22

    For many years, myocardial tissue has been considered terminally differentiated and, thus, incapable of regenerating. Recent studies have shown, instead, that cardiomyocytes, at least in part, are slowly substituted by new cells originating by precursor cells mostly embedded into the heart apex and in the atria. We have shown that an elective region of progenitor cell embedding is represented by the auricles, non-contractile atria appendages that can be easily sampled without harming the patient. The protocol here reported describes how from auricles a population of multipotent, cardiogenic cells can be isolated, cultured, and differentiated. Further studies are needed to fully exploit this cell population, but, sampling auricles, it could be possible to treat cardiac patients using their own cells circumventing rejection or organ shortage limitations.

  18. Human cardiac-derived adherent proliferating cells reduce murine acute Coxsackievirus B3-induced myocarditis.

    Directory of Open Access Journals (Sweden)

    Kapka Miteva

    Full Text Available BACKGROUND: Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs. They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3-induced myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression. CONCLUSIONS: We conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

  19. Human initiated cascading failures in societal infrastructures.

    Directory of Open Access Journals (Sweden)

    Chris Barrett

    Full Text Available In this paper, we conduct a systematic study of human-initiated cascading failures in three critical inter-dependent societal infrastructures due to behavioral adaptations in response to a crisis. We focus on three closely coupled socio-technical networks here: (i cellular and mesh networks, (ii transportation networks and (iii mobile call networks. In crises, changes in individual behaviors lead to altered travel, activity and calling patterns, which influence the transport network and the loads on wireless networks. The interaction between these systems and their co-evolution poses significant technical challenges for representing and reasoning about these systems. In contrast to system dynamics models for studying these interacting infrastructures, we develop interaction-based models in which individuals and infrastructure elements are represented in detail and are placed in a common geographic coordinate system. Using the detailed representation, we study the impact of a chemical plume that has been released in a densely populated urban region. Authorities order evacuation of the affected area, and this leads to individual behavioral adaptation wherein individuals drop their scheduled activities and drive to home or pre-specified evacuation shelters as appropriate. They also revise their calling behavior to communicate and coordinate among family members. These two behavioral adaptations cause flash-congestion in the urban transport network and the wireless network. The problem is exacerbated with a few, already occurring, road closures. We analyze how extended periods of unanticipated road congestion can result in failure of infrastructures, starting with the servicing base stations in the congested area. A sensitivity analysis on the compliance rate of evacuees shows non-intuitive effect on the spatial distribution of people and on the loading of the base stations. For example, an evacuation compliance rate of 70% results in higher number

  20. Extracorporeal membrane oxygenation in near-drowning patients with cardiac or pulmonary failure.

    Science.gov (United States)

    Kim, Kun Il; Lee, Won Yong; Kim, Hyoung Soo; Jeong, Jae Han; Ko, Ho Hyun

    2014-12-12

    The aim of this study was to determine the early outcomes of using extracorporeal membrane oxygenation (ECMO) in near-drowning patients with cardiac or pulmonary failure. This study was based on data from 9 patients including 2 children (mean age 33; 8 males, 1 female) who received ECMO after near-drowning between 2008 and 2013. Veno-arterial or veno-arteriovenous ECMO was used in 2 patients with sustained cardiac arrest and veno-venous ECMO was used in 7 patients with severe acute respiratory distress syndrome (ARDS). The means of the partial arterial oxygen pressure (PaO2), Murray score, sequential organ failure assessment (SOFA) score, and simplified acute physiology score II (SAPS-II) prior to ECMO were 59.7 ± 9.9 mmHg on 100% oxygen, 3.5 ± 0.6, 11.4 ± 1.9, and 73.0 ± 9.2, respectively. The PaO2 mean improved to 182 ± 152 mmHg within 2 h post-ECMO. The mean of SOFA score and SAPS-II decreased significantly to 8.6 ± 3.2 (p = 0.013) and 46.4 ± 5.1 (p = 0.008), respectively, at 24 h post-ECMO with mean flow rate of 3.9 ± 0.8 l/min. ECMO was weaned at a mean duration of 188 (range, 43-672) h in all patients. Seven patients were discharged home without neurological sequelae, while 2 patients who had hypoxic brain damage died after further referral. The overall survival with favourable neurological outcomes at 3 months was 77.8%. There were no complications related to ECMO. ECMO was safe and effective for patients with ongoing cardiac arrest or ARDS after a near-drowning incident and can be used as a resuscitative strategy in near-drowning patients with cardiac or pulmonary failure resistant to conventional ventilator therapy.

  1. [Sodium hydrosulfide improves cardiac functions and structures in rats with chronic heart failure].

    Science.gov (United States)

    Li, Xiao-hui; Zhang, Chao-ying; Zhang, Ting

    2011-11-22

    To explore the effects of sodium hydrosulfide (NaHS), a hydrogen sulphide (H(2)S) donor, on cardiac functions and structures in rats with chronic heart failure induced by volume overload and examine its influence on cardiac remodelling. A total of 47 SD rats (120 - 140 g) were randomly divided into 5 groups:shunt group (n = 11), sham group (n = 8), shunt + NaHS group (n = 10), sham + NaHS group (n = 8) and shunt + phentolamine group (n = 10). The rat model of chronic heart failure was induced by abdominal aorta-inferior vena cava puncture. At Week 8 post-operation, hemodynamic parameters, microstructures and ultrastructures of myocardial tissues were analyzed. Extracellular collagen content in myocardial tissues was analyzed after Sirius red staining. Right ventricular hydroxyproline concentration was determined and compared. At Week 8 post-operation, compared with the sham operation and shunt + NaHS groups, the shunt group showed significantly increased right ventricular systolic pressure (RVSP) and right ventricular end diastolic pressure (RVEDP) (mm Hg: 35.2 ± 3.9 vs 21.4 ± 3.7 and 28.1 ± 2.7, 32 ± 5 vs 21 ± 4 and 26 ± 4, all P vs 2336 ± 185 and 1835 ± 132, 1331 ± 107 vs 2213 ± 212 and 1768 ± 116, all P non-uniformly in the shunt group, some fiber mitochondria were highly swollen and contained vacuoles. And sarcoplasmic reticulum appeared slightly dilated. Polarized microscopy indicated that, collagen content (particularly type-I collagen) increased in the shunt group compared with the sham operation group. Additionally, compared with the shunt group, the shunt and NaHS treatment groups showed an amelioration of myocardial damage, an alleviation of myocardial fiber changes and a decrease in myocardial collagen content (particularly type-I collagen). Compared with the sham operation and shunt + NaHS groups, the shunt group displayed increased right ventricular hydroxyproline (mg×g(-1)·pro: 1.32 ± 0.25 vs 0.89 ± 0.18 and 0.83 ± 0.19, all P < 0

  2. Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging

    International Nuclear Information System (INIS)

    Karasawa, Kensuke; Ayusawa, Mamoru; Noto, Nobutaka; Sumitomo, Naokata; Okada, Tomoo; Harada, Kensuke

    2000-01-01

    Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5±6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33±0.22 in chronic heart failure class I, 2.50±0.34 in class II, 1.95±0.61 in class III, and 1.39±0.29 in class IV (p<0.05). %WR was 24.8±12.8% in chronic heart failure class I, 23.3±10.2% in class II, 49.2±24.5% in class III, and 66.3±26.5% in class IV (p<0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and mortality in children with chronic heart failure. (author)

  3. Assessment of cardiac sympathetic nerve activity in children with chronic heart failure using quantitative iodine-123 metaiodobenzylguanidine imaging

    Energy Technology Data Exchange (ETDEWEB)

    Karasawa, Kensuke; Ayusawa, Mamoru; Noto, Nobutaka; Sumitomo, Naokata; Okada, Tomoo; Harada, Kensuke [Nihon Univ., Tokyo (Japan). School of Medicine

    2000-12-01

    Cardiac sympathetic nerve activity in children with chronic heart failure was examined by quantitative iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging in 33 patients aged 7.5{+-}6.1 years (range 0-18 years), including 8 with cardiomyopathy, 15 with congenital heart disease, 3 with anthracycrine cardiotoxicity, 3 with myocarditis, 3 with primary pulmonary hypertension and 1 with Pompe's disease. Anterior planar images were obtained 15 min and 3 hr after the injection of iodine-123 MIBG. The cardiac iodine-123 MIBG uptake was assessed as the heart to upper mediastinum uptake activity ratio of the delayed image (H/M) and the cardiac percentage washout rate (%WR). The severity of chronic heart failure was class I (no medication) in 8 patients, class II (no symptom with medication) in 9, class III (symptom even with medication) in 10 and class IV (late cardiac death) in 6. H/M was 2.33{+-}0.22 in chronic heart failure class I, 2.50{+-}0.34 in class II, 1.95{+-}0.61 in class III, and 1.39{+-}0.29 in class IV (p<0.05). %WR was 24.8{+-}12.8% in chronic heart failure class I, 23.3{+-}10.2% in class II, 49.2{+-}24.5% in class III, and 66.3{+-}26.5% in class IV (p<0.05). The low H/M and high %WR were proportionate to the severity of chronic heart failure. Cardiac iodine-123 MIBG showed cardiac adrenergic neuronal dysfunction in children with severe chronic heart failure. Quantitative iodine-123 MIBG myocardial imaging is clinically useful as a predictor of therapeutic outcome and mortality in children with chronic heart failure. (author)

  4. Radioimmunoassay of human cardiac tropomyosin in acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Cummins, P; McGurk, B; Littler, W A [Queen Elizabeth Hospital, Birmingham (UK)

    1981-03-01

    Tropomyosin was prepared from fresh human myocardium and antisera raised in rabbits. A sensitive radioimmunoassay was developed for the detection of human cardiac /sup 125/I-labelled tropomyosin in human sera down to levels of 1 ng/ml. Values for human cardiac tropomyosin in normal patients ranged from less than 1 to 3 ng/ml. In 18 patients with acute myocardial infarction all had elevated tropomyosin levels ranging from 41 to above 200 ng/ml with a mean peak level of 101 ng/ml. In this study there were no false positive or false negative results. In the initial stages of infarction the time course of appearance and peak levels of cardiac tropomyosin, total creatine kinase and creatine kinase MB isoenzyme were similar. Although total creatine kinase and creatine kinase MB isoenzyme levels were normal after 72 h in patients with single, uncomplicated infarction, cardiac tropomyosin levels were still significantly elevated above normal after this time, being 30-60% of peak valuctional hourly rate of absorption and the plasma /sup 32/P radioactivity at 60 min corrected for extracellular fluid volume provided the best app elements, the characteristics of which are determined by employing the Lagrange multiplier concept. Unknowns of the resulting simultaneous equation consist of usual nodal displacements of the whole stru element codes. Therefore, FAST should be useful in several areas for which all other codes are too unwieldy and expensivnt makers was established, in which the investigations and studies have started.

  5. Extracellular high-mobility group box 1 mediates pressure overload-induced cardiac hypertrophy and heart failure.

    Science.gov (United States)

    Zhang, Lei; Liu, Ming; Jiang, Hong; Yu, Ying; Yu, Peng; Tong, Rui; Wu, Jian; Zhang, Shuning; Yao, Kang; Zou, Yunzeng; Ge, Junbo

    2016-03-01

    Inflammation plays a key role in pressure overload-induced cardiac hypertrophy and heart failure, but the mechanisms have not been fully elucidated. High-mobility group box 1 (HMGB1), which is increased in myocardium under pressure overload, may be involved in pressure overload-induced cardiac injury. The objectives of this study are to determine the role of HMGB1 in cardiac hypertrophy and cardiac dysfunction under pressure overload. Pressure overload was imposed on the heart of male wild-type mice by transverse aortic constriction (TAC), while recombinant HMGB1, HMGB1 box A (a competitive antagonist of HMGB1) or PBS was injected into the LV wall. Moreover, cardiac myocytes were cultured and given sustained mechanical stress. Transthoracic echocardiography was performed after the operation and sections for histological analyses were generated from paraffin-embedded hearts. Relevant proteins and genes were detected. Cardiac HMGB1 expression was increased after TAC, which was accompanied by its translocation from nucleus to both cytoplasm and intercellular space. Exogenous HMGB1 aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction, as demonstrated by echocardiographic analyses, histological analyses and foetal cardiac genes detection. Nevertheless, the aforementioned pathological change induced by TAC could partially be reversed by HMGB1 inhibition. Consistent with the in vivo observations, mechanical stress evoked the release and synthesis of HMGB1 in cultured cardiac myocytes. This study indicates that the activated and up-regulated HMGB1 in myocardium, which might partially be derived from cardiac myocytes under pressure overload, may be of crucial importance in pressure overload-induced cardiac hypertrophy and cardiac dysfunction. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. Human torso phantom for imaging of heart with realistic modes of cardiac and respiratory motion

    Science.gov (United States)

    Boutchko, Rostyslav; Balakrishnan, Karthikayan; Gullberg, Grant T; O& #x27; Neil, James P

    2013-09-17

    A human torso phantom and its construction, wherein the phantom mimics respiratory and cardiac cycles in a human allowing acquisition of medical imaging data under conditions simulating patient cardiac and respiratory motion.

  7. Insulin resistance is associated with impaired cardiac sympathetic innervation in patients with heart failure.

    Science.gov (United States)

    Paolillo, S; Rengo, G; Pellegrino, T; Formisano, R; Pagano, G; Gargiulo, P; Savarese, G; Carotenuto, R; Petraglia, L; Rapacciuolo, A; Perrino, C; Piscitelli, S; Attena, E; Del Guercio, L; Leosco, D; Trimarco, B; Cuocolo, A; Perrone-Filardi, P

    2015-10-01

    Insulin resistance (IR) represents, at the same time, cause and consequence of heart failure (HF) and affects prognosis in HF patients, but pathophysiological mechanisms remain unclear. Hyperinsulinemia, which characterizes IR, enhances sympathetic drive, and it can be hypothesized that IR is associated with impaired cardiac sympathetic innervation in HF. Yet, this hypothesis has never been investigated. Aim of the present observational study was to assess the relationship between IR and cardiac sympathetic innervation in non-diabetic HF patients. One hundred and fifteen patients (87% males; 65 ± 11.3 years) with severe-to-moderate HF (ejection fraction 32.5 ± 9.1%) underwent iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) myocardial scintigraphy to assess sympathetic innervation and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) evaluation to determine the presence of IR. From (123)I-MIBG imaging, early and late heart to mediastinum (H/M) ratios and washout rate were calculated. Seventy-two (63%) patients showed IR and 43 (37%) were non-IR. Early [1.68 (IQR 1.53-1.85) vs. 1.79 (IQR 1.66-1.95); P = 0.05] and late H/M ratio [1.50 (IQR 1.35-1.69) vs. 1.65 (IQR 1.40-1.85); P = 0.020] were significantly reduced in IR compared with non-IR patients. Early and late H/M ratio showed significant inverse correlation with fasting insulinemia and HOMA-IR. Cardiac sympathetic innervation is more impaired in patients with IR and HF compared with matched non-IR patients. These findings shed light on the relationship among IR, HF, and cardiac sympathetic nervous system. Additional studies are needed to clarify the pathogenetic relationship between IR and HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  8. Subclinical Atherosclerosis, Cardiac and Kidney Function, Heart Failure, and Dementia in the Very Elderly.

    Science.gov (United States)

    Kuller, Lewis H; Lopez, Oscar L; Gottdiener, John S; Kitzman, Dalane W; Becker, James T; Chang, Yuefang; Newman, Anne B

    2017-07-22

    Heart failure (HF) and dementia are major causes of disability and death among older individuals. Risk factors and biomarkers of HF may be determinants of dementia in the elderly. We evaluated the relationship between biomarkers of cardiovascular disease and HF and risk of dementia and death. Three hypotheses were tested: (1) higher levels of high-sensitivity cardiac troponin T, N-terminal of prohormone brain natriuretic peptide, and cystatin C predict risk of death, cardiovascular disease, HF, and dementia; (2) higher levels of cardiovascular disease biomarkers are associated with increased risk of HF and then secondary increased risk of dementia; and (3) risk of dementia is lower among participants with a combination of lower coronary artery calcium, atherosclerosis, and lower high-sensitivity cardiac troponin T (myocardial injury). The Cardiovascular Health Study Cognition Study was a continuation of the Cardiovascular Health Study limited to the Pittsburgh, PA, center from 1998-1999 to 2014. In 1992-1994, 924 participants underwent magnetic resonance imaging of the brain. There were 199 deaths and 116 developed dementia before 1998-1999. Of the 609 participants eligible for the Pittsburgh Cardiovascular Health Study Cognition Study, 87.5% (n=532) were included in the study. There were 120 incident HF cases and 72% had dementia. In 80 of 87, dementia preceded HF. A combination of low coronary artery calcium score and low high-sensitivity cardiac troponin T was significantly associated with reduced risk of dementia and HF. Most participants with HF had dementia but with onset before HF. Lower high-sensitivity cardiac troponin T and coronary artery calcium was associated with low risk of dementia based on a small number of events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  9. Associations between cardiac pathology and clinical, echocardiographic and electrocardiographic findings in dogs with chronic congestive heart failure

    DEFF Research Database (Denmark)

    Falk, Bo Torkel; Jönsson, Lennart; Olsen, Lisbeth Høier

    2010-01-01

    The objective of this study was to correlate defined pathological features with clinical findings in dogs with naturally occurring congestive heart failure (CHF). Fifty-eight dogs with CHF were examined clinically and using echocardiography and electrocardiography. Detailed cardiac post...... such as MMVD, myocardial atrophy and fibrosis, and by arteriosclerosis. Further, more extensive research will be required to establish cause-effect relationships between these cardiac lesions and the pathophysiology of CHF in dogs....

  10. A risk score for predicting 30-day mortality in heart failure patients undergoing non-cardiac surgery

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Gislason, Gunnar H; Hlatky, Mark A

    2014-01-01

    BACKGROUND: Heart failure is an established risk factor for poor outcomes in patients undergoing non-cardiac surgery, yet risk stratification remains a clinical challenge. We developed an index for 30-day mortality risk prediction in this particular group. METHODS AND RESULTS: All individuals...... with heart failure undergoing non-cardiac surgery between October 23 2004 and October 31 2011 were included from Danish administrative registers (n = 16 827). In total, 1787 (10.6%) died within 30 days. In a simple risk score based on the variables from the revised cardiac risk index, plus age, gender, acute...... by bootstrapping (1000 re-samples) provided c-statistic of 0.79. A more complex risk score based on stepwise logistic regression including 24 variables at P heart failure, this simple...

  11. Cardiac I123-MIBG Correlates Better than Ejection Fraction with Symptoms Severity in Systolic Heart Failure

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, Sandra M.; Moscavitch, Samuel D.; Carestiato, Larissa R. [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Felix, Renata M. [Departamento de Medicina Nuclear, Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil); Rodrigues, Ronaldo C.; Messias, Leandro R. [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Azevedo, Jader C. [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Departamento de Medicina Nuclear, Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil); Nóbrega, Antonio Cláudio L.; Mesquita, Evandro Tinoco [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Mesquita, Claudio Tinoco, E-mail: ctinocom@cardiol.br [Programa de Pós-Graduação em Ciências Cardiovasculares, Hospital Universitário Antonio Pedro, Universidade Federal Fluminense, Rio de Janeiro, RJ (Brazil); Departamento de Medicina Nuclear, Hospital Pró-Cardíaco, Rio de Janeiro, RJ (Brazil)

    2013-07-15

    The association of autonomic activation, left ventricular ejection fraction (LVEF) and heart failure functional class is poorly understood. Our aim was to correlate symptom severity with cardiac sympathetic activity, through iodine-123-metaiodobenzylguanidine ({sup 123}I-MIBG) scintigraphy and with LVEF in systolic heart failure (HF) patients without previous beta-blocker treatment. Thirty-one patients with systolic HF, class I to IV of the New York Heart Association (NYHA), without previous beta-blocker treatment, were enrolled and submitted to {sup 123}I-MIBG scintigraphy and to radionuclide ventriculography for LVEF determination. The early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) were performed. According with symptom severity, patients were divided into group A, 13 patients in NYHA class I/II, and group B, 18 patients in NYHA class III/IV. Compared with group B patients, group A had a significantly higher LVEF (25% ± 12% in group B vs. 32% ± 7% in group A, p = 0.04). Group B early and delayed H/M ratios were lower than group A ratios (early H/M 1.49 ± 0.15 vs. 1.64 ± 0.14, p = 0.02; delayed H/M 1.39 ± 0.13 vs. 1.58 ± 0.16, p = 0.001, respectively). WR was significantly higher in group B (36% ± 17% vs. 30% ± 12%, p= 0.04). The variable that showed the best correlation with NYHA class was the delayed H/M ratio (r= -0.585; p=0.001), adjusted for age and sex. This study showed that cardiac {sup 123}I-MIBG correlates better than ejection fraction with symptom severity in systolic heart failure patients without previous beta-blocker treatment.

  12. Emerging role of liver X receptors in cardiac pathophysiology and heart failure.

    Science.gov (United States)

    Cannon, Megan V; van Gilst, Wiek H; de Boer, Rudolf A

    2016-01-01

    Liver X receptors (LXRs) are master regulators of metabolism and have been studied for their pharmacological potential in vascular and metabolic disease. Besides their established role in metabolic homeostasis and disease, there is mounting evidence to suggest that LXRs may exert direct beneficial effects in the heart. Here, we aim to provide a conceptual framework to explain the broad mode of action of LXRs and how LXR signaling may be an important local and systemic target for the treatment of heart failure. We discuss the potential role of LXRs in systemic conditions associated with heart failure, such as hypertension, diabetes, and renal and vascular disease. Further, we expound on recent data that implicate a direct role for LXR activation in the heart, for its impact on cardiomyocyte damage and loss due to ischemia, and effects on cardiac hypertrophy, fibrosis, and myocardial metabolism. Taken together, the accumulating evidence supports the notion that LXRs may represent a novel therapeutic target for the treatment of heart failure.

  13. Influence of water immersion, water gymnastics and swimming on cardiac output in patients with heart failure.

    Science.gov (United States)

    Schmid, Jean-Paul; Noveanu, Markus; Morger, Cyrill; Gaillet, Raymond; Capoferri, Mauro; Anderegg, Matthias; Saner, Hugo

    2007-06-01

    Whole-body water immersion leads to a significant shift of blood from the periphery to the intrathoracic circulation, followed by an increase in central venous pressure and heart volume. In patients with severely reduced left ventricular function, this hydrostatically induced volume shift might overstrain the cardiovascular adaptive mechanisms and lead to cardiac decompensation. To assess the haemodynamic response to water immersion, gymnastics and swimming in patients with chronic heart failure (CHF). 10 patients with compensated CHF (62.9 (6.3) years, ejection fraction 31.5% (4.1%), peak oxygen consumption (Vo(2)) 19.4 (2.8) ml/kg/min), 10 patients with coronary artery disease (CAD) but preserved left ventricular function (57.2 (5.6) years, ejection fraction 63.9% (5.5%), peak Vo(2) 28 (6.3) ml/kg/min), and 10 healthy controls (32.8 (7.2) years, peak Vo(2) 45.6 (6) ml/kg/min) were examined. Haemodynamic response to thermoneutral (32 degrees C) water immersion and exercise was measured using a non-invasive foreign gas rebreathing method during stepwise water immersion, water gymnastics and swimming. Water immersion up to the chest increased cardiac index by 19% in controls, by 21% in patients with CAD and by 16% in patients with CHF. Although some patients with CHF showed a decrease of stroke volume during immersion, all subjects were able to increase cardiac index (by 87% in healthy subjects, by 77% in patients with CAD and by 53% in patients with CHF). Vo(2) during swimming was 9.7 (3.3) ml/kg/min in patients with CHF, 12.4 (3.5) ml/kg/min in patients with CAD and 13.9 (4) ml/kg/min in controls. Patients with severely reduced left ventricular function but stable clinical conditions and a minimal peak Vo(2) of at least 15 ml/kg/min during a symptom-limited exercise stress test tolerate water immersion and swimming in thermoneutral water well. Although cardiac index and Vo(2) are lower than in patients with CAD with preserved left ventricular function and controls

  14. Adaptive servo ventilation improves Cheyne-Stokes respiration, cardiac function, and prognosis in chronic heart failure patients with cardiac resynchronization therapy.

    Science.gov (United States)

    Miyata, Makiko; Yoshihisa, Akiomi; Suzuki, Satoshi; Yamada, Shinya; Kamioka, Masashi; Kamiyama, Yoshiyuki; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

    2012-09-01

    Cheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT. Twenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group. ASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  15. Hemodynamic changes during weaning: can we assess and predict cardiac-related weaning failure by transthoracic echocardiography?

    Science.gov (United States)

    Voga, Gorazd

    2010-01-01

    Cardiac-related failure of weaning from mechanical ventilation is an important reason for prolonged mechanical ventilation, intensive care unit treatment, and increased morbidity and mortality. When transthoracic echocardiography (TTE) is routinely performed before a weaning trial, patients at high risk of cardiac-related failure can be detected by low left ventricular (LV) ejection fraction, diastolic dysfunction, and elevated LV filling pressure. During the weaning trial, a further increase of LV filling pressure and progression of diastolic failure can be observed by repeated TTE. Owing to certain limitations concerning patients and methodology, TTE cannot be employed in every patient and invasive hemodynamic monitoring is still mandatory in selected patients with repetitive weaning failure.

  16. Exploration of flexible phenylpropylurea scaffold as novel cardiac myosin activators for the treatment of systolic heart failure.

    Science.gov (United States)

    Manickam, Manoj; Jalani, Hitesh B; Pillaiyar, Thanigaimalai; Sharma, Niti; Boggu, Pulla Reddy; Venkateswararao, Eeda; Lee, You-Jung; Jeon, Eun-Seok; Jung, Sang-Hun

    2017-07-07

    A series of flexible urea derivatives have been synthesized and demonstrated as selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3-phenylpropyl)urea (1, cardiac myosin ATPase activation at 10 μM = 51.1%; FS = 18.90; EF = 12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase activation = 53.3%; FS = 30.04; EF = 18.27) showed significant activity in vitro and in vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1-(3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin ATPase activation = 81.4%; FS = 20.50; EF = 13.10), and morpholine moiety viz., 1-(2-morpholinoethyl)-3-(3-phenylpropyl)urea (21, cardiac myosin ATPase activation = 44.0%; FS = 24.79; EF = 15.65), proved to be efficient to activate the cardiac myosin. The potent compounds 1, 9, 14 and 21 were found to be selective for cardiac myosin over skeletal and smooth myosins. Thus, these urea derivatives are potent scaffold to develop as a newer cardiac myosin activator for the treatment of systolic heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Cardiac Failure as an Unusual Presentation in a Patient with History of Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Mohammad Hasan Namazi

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most well-known form of motor neuron diseases in which both upper and lower motor neurons are involved in this disease. We presented an unusual case of ALS whom had presented with chief complaint of dyspnea. Cardiac failure was diagnosed at the final stage of the ALS disease. The pathogenetic mechanism leading to an elevated occurrence of cardiomyopathy in ALS is not comprehensible. Dilated cardiomyopathy has been explained in some previous studies. Based on the collected data, it was hypothesized that cardiomyopathy is underdiagnosed in the ALS population, probably because symptoms are masqueraded as a result of the patients’ disability. It was suggested that in all motor neuron diseases a serial cardiological evaluation should be executed, including annual echocardiography.

  18. Association of hypothyroidism with adverse events in patients with heart failure receiving cardiac resynchronization therapy.

    Science.gov (United States)

    Sharma, Ajay K; Vegh, Eszter; Orencole, Mary; Miller, Alexandra; Blendea, Dan; Moore, Stephanie; Lewis, Gregory D; Singh, Jagmeet P; Parks, Kimberly A; Heist, E Kevin

    2015-05-01

    Hypothyroidism is associated with an adverse prognosis in cardiac patients in general and in particular in patients with heart failure (HF). The aim of this study was to evaluate the impact of hypothyroidism on patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of level of control of hypothyroidism on risk of adverse events after CRT implantation was also evaluated. We included consecutive patients in whom a CRT device was implanted from April 2004 to April 2010 at our institution with sufficient follow-up data available for analysis; 511 patients were included (age 68.5±12.4 years, women 20.4%); 84 patients with a clinical history of hypothyroidism, on treatment with thyroid hormone repletion or serum thyroid-stimulating hormone level≥5.00 μU/ml, were included in the hypothyroid group. The patients were followed for up to 3 years after implant for a composite end point of hospitalization for HF, left ventricular assist device placement, or heart transplant and cardiac death; 215 composite end point events were noted in this period. In a multivariate model, hypothyroidism (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.027 to 2.085, p=0.035), female gender (HR 0.64, 95% CI 0.428 to 0.963, p=0.032), and creatinine (HR 1.26, 95% CI 1.145 to 1.382, phypothyroidism at baseline developed the composite end point compared with 39.8% of those with euthyroidism (p=0.02). In conclusion, hypothyroidism is associated with a worse prognosis after CRT implantation. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. [Cardiac resynchronization therapy for heart failure - from experimental pacing to evidence-based therapy].

    Science.gov (United States)

    Götze, S; Butter, C; Fleck, E

    2006-01-01

    Within the last decade, cardiac resynchronization therapy (CRT) has become an evidence-based cornerstone for a subset of patients with chronic heart failure. For those, who suffer from ischemic or non-ischemic cardiomyopathies at NYHA III or IV, have sinus rhythm, a left bundle branch block and a left ventricular ejection fraction below 35%, CRT has evolved as an important treatment option with promising results. Numerous studies have shown that in these patients pacemaker-mediated correction of intra- and interventicular conduction disturbances can improve not only clinical symptoms, exercise tolerance and the frequency of hospitalizations, but even more important the overall mortality. These clinical results are due to several functional aspects. In the failing heart characteristic intra- and interventricular alterations in electrical conduction result in mechanical asynchrony that leads to an abnormal contraction of the left ventricle with delayed activation of the lateral wall, a paradoxical septal movement, a reduced diastolic filling and a mitral regurgitation due to dyssynchrony of papillary muscle activation. It is conceivable that these functional changes have fatal consequences for the failing heart. AV-optimized left- or biventricular stimulation by modern pacemakers can correct the pathological dyssynchrony, thereby improving cardiac function and clinical outcome in these patients. Although tremendous progress in cardiac resynchronization therapy has been made during the last decade, a couple of questions still need to be resolved. Critical issues are the identification of patients, who will predictably benefit from CRT, the value of CRT-pacemakers versus CRT-ICDs, and the usefullness of CRT in patients with atrial fibrillation.

  20. Noninvasive pulse contour analysis for determination of cardiac output in patients with chronic heart failure.

    Science.gov (United States)

    Roth, Sebastian; Fox, Henrik; Fuchs, Uwe; Schulz, Uwe; Costard-Jäckle, Angelika; Gummert, Jan F; Horstkotte, Dieter; Oldenburg, Olaf; Bitter, Thomas

    2018-05-01

    Determination of cardiac output (CO) is essential in diagnosis and management of heart failure (HF). The gold standard to obtain CO is invasive assessment via thermodilution (TD). Noninvasive pulse contour analysis (NPCA) is supposed as a new method of CO determination. However, a validation of this method in HF is pending and performed in the present study. Patients with chronic-stable HF and reduced left ventricular ejection fraction (LVEF ≤ 45%; HF-REF) underwent right heart catheterization including TD. NPCA using the CNAP Monitor (V5.2.14, CNSystems Medizintechnik AG) was performed simultaneously. Three standardized TD measurements were compared with simultaneous auto-calibrated NPCA CO measurements. In total, 84 consecutive HF-REF patients were enrolled prospectively in this study. In 4 patients (5%), TD was not successful and for 22 patients (26%, 18 with left ventricular assist device), no NPCA signal could be obtained. For the remaining 58 patients, Bland-Altman analysis revealed a mean bias of + 1.92 L/min (limits of agreement ± 2.28 L/min, percentage error 47.4%) for CO. With decreasing cardiac index, as determined by the gold standard of TD, there was an increasing gap between CO values obtained by TD and NPCA (r = - 0.75, p TD-CI classified 52 (90%) patients to have a reduced CI (REF patients, auto-calibrated NPCA systematically overestimates CO with decrease in cardiac function. Therefore, to date, NPCA cannot be recommended in this cohort.

  1. Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats.

    Science.gov (United States)

    Bozi, Luiz H M; Jannig, Paulo R; Rolim, Natale; Voltarelli, Vanessa A; Dourado, Paulo M M; Wisløff, Ulrik; Brum, Patricia C

    2016-11-01

    Cardiac endoplasmic reticulum (ER) stress through accumulation of misfolded proteins plays a pivotal role in cardiovascular diseases. In an attempt to reestablish ER homoeostasis, the unfolded protein response (UPR) is activated. However, if ER stress persists, sustained UPR activation leads to apoptosis. There is no available therapy for ER stress relief. Considering that aerobic exercise training (AET) attenuates oxidative stress, mitochondrial dysfunction and calcium imbalance, it may be a potential strategy to reestablish cardiac ER homoeostasis. We test the hypothesis that AET would attenuate impaired cardiac ER stress after myocardial infarction (MI). Wistar rats underwent to either MI or sham surgeries. Four weeks later, rats underwent to 8 weeks of moderate-intensity AET. Myocardial infarction rats displayed cardiac dysfunction and lung oedema, suggesting heart failure. Cardiac dysfunction in MI rats was paralleled by increased protein levels of UPR markers (GRP78, DERLIN-1 and CHOP), accumulation of misfolded and polyubiquitinated proteins, and reduced chymotrypsin-like proteasome activity. These results suggest an impaired cardiac protein quality control. Aerobic exercise training improved exercise capacity and cardiac function of MI animals. Interestingly, AET blunted MI-induced ER stress by reducing protein levels of UPR markers, and accumulation of both misfolded and polyubiquinated proteins, which was associated with restored proteasome activity. Taken together, our study provide evidence for AET attenuation of ER stress through the reestablishment of cardiac protein quality control, which contributes to better cardiac function in post-MI heart failure rats. These results reinforce the importance of AET as primary non-pharmacological therapy to cardiovascular disease. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. Medical Image of the Week: Cardiac Magnetic Resonance Imaging Findings of Severe RV Failure

    Directory of Open Access Journals (Sweden)

    Wickstrom K

    2018-05-01

    Full Text Available No abstract available. Article truncated at 150 words. A 56-year-old man with history a of alcohol abuse presents with progressive shortness of breath on exertion, bilateral lower extremity swelling and 12-pound weight gain over two weeks. His transthoracic echocardiography (Figure 1 demonstrated severely increased global right ventricle (RV size, severely dilated right atrium (RA, severe pulmonary artery (PA dilation, moderate tricuspid regurgitation (TR and right ventricular systolic pressure (RVSP estimated at 85 + central venous pressure (CVP in the context of severely reduced RV systolic function. Right heart catheterization (RHC showed PA pressure (systolic/diastolic, mean of 94/28, 51 mmHg with a PA occlusion pressure of 12 mmHg. After extensive evaluation, our patient’s presentation of right heart failure seemed to be a manifestation of idiopathic pulmonary arterial hypertension. Our patient subsequently had cardiac MRI (cMRI with findings shown above (Figure 2. CMRI is a valuable, three-dimensional imaging modality that provides detailed morphology of the cardiac chambers along with accurate …

  3. Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in patients with chronic heart failure.

    Science.gov (United States)

    Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Funayama, Akira; Kinoshita, Daisuke; Yokoyama, Miyuki; Takahashi, Tetsuya; Nishiyama, Satoshi; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

    2016-02-01

    Renal tubular damage (RTD) and hypoalbuminemia are risks for poor prognosis in patients with chronic heart failure (CHF). Renal tubules play a pivotal role in amino acid and albumin reabsorption, which maintain serum albumin levels. The aims of the present study were to (1) examine the association of RTD with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD and hypoalbuminemia in patients with CHF. We measured N-acetyl-β-D-glucosamidase (NAG) levels and the urinary β2-microglobulin to creatinine ratio (UBCR) in 456 patients with CHF. RTD was defined as UBCR ≥ 300 μg/g or NAG ≥ 14.2 U/g. There were moderate correlations between RTD markers and serum albumin (NAG, r = -0.428, P < 0.0001; UBCR, r = -0.399, P < 0.0001). Multivariate logistic analysis showed that RTD was significantly related to hypoalbuminemia in patients with CHF. There were 134 cardiac events during a median period of 808 days. The comorbidity of RTD and hypoalbuminemia was increased with advancing New York Heart Association functional class. Multivariate Cox proportional hazard regression analysis showed that the presence of RTD and hypoalbuminemia was associated with cardiac events. The net reclassification index was significantly improved by adding RTD and hypoalbuminemia to the basic risk factors. Comorbid RTD and hypoalbuminemia are frequently observed and increase the risk for extremely poor outcome in patients with CHF.

  4. Association of cardiac cachexia and atrial fibrillation in heart failure patients.

    Science.gov (United States)

    Arámbula-Garza, Estefanía; Castillo-Martínez, Lilia; González-Islas, Dulce; Orea-Tejeda, Arturo; Santellano-Juárez, Brenda; Keirns-Davies, Candace; Peláez-Hernández, Viridiana; Sánchez-Santillán, Rocío; Pineda-Juárez, Juan; Cintora-Martínez, Carlos; Pablo-Santiago, Ruth

    2016-11-15

    Cachexia is a common complication in patients with advanced heart failure (HF) associated with inflammatory response activation. Atrial fibrillation (AF) is the most frequent arrhythmia (26%), probably both exacerbate the cardiac cachexia (CC). Evaluate the association of cardiac cachexia and atrial fibrillation in heart failure patients. In a case control study, CC was diagnosed by electrical bioimpedance with vectorial analysis (BIVA). Subjects with congenital heart disease, cancer, HIV, drug use and other causes than HF were excluded. Of the 359 subjects analyzed (men: 52.9%) median age 65years (55-74). Those with CC were older [72 (61-67)] vs. without [62 (52-70) years old, p<0.01]. During follow-up 47.8% of subjects developed CC and 17.27% AF, this was significantly more frequent in cachectic patients CC (23% vs 12.11%, OR: 2.17, 95% CI: 1.19-4.01, p=0.006). Subjects, with AF had lower left ventricular ejection fraction (25.49±12.96 vs. 32.01±15.02, p=0.08), lower posterior wall thickness (10.03±2.12 vs. 11.00±2.47, p=0.007), larger diameter of the left atrium (49.87±9.84 vs. 42.66±7.56, p<0.001), and a higher prevalence of CC (85.42% vs. 69.77%, p=0.028). The 50.58% of was in NYHA class I. In NYHA III, 22.95% were in AF vs. 12.10% with not AF (p=0.027). The frequent coexistence of CC and AF as HF complications indicate greater severity of HF, regardless of its type of HF. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Study on the relationship between plasma BNP levels and left cardiac function in patients with heart failure

    International Nuclear Information System (INIS)

    Yin Xin; Xu Dandan; Wu Chunxu

    2005-01-01

    Objective: To investigate the relationship between plasma brain natriuretic peptide (BNP) levels and cardiac function in patients with heart failure. Methods: Plasma levels of BNP (with IRMA) and left cardiac function parameters (examined with echocardiogram) were obtained in 80 patients with heart failure at admission and repeatedly examined in 43 of them later after 2w treatment a swell as in 30 controls. Results: The plasma BNP levels increased along with the deterioration of cardiac function, with significant differences among the patients with different cardiac function grades (P<0.01). After 2w treatment, the plasma BNP levels were significantly lower than those before (P<0.01). The plasma levels of BNP were negatively correlated with left ventricular ejection fraction (LVEF) and left ventricle fraction shortening, but positively correlated with left ventricular end-systolic diameter (LVSd) and left ventricular end-diastolic diameter (LVDd). Conclusion: Plasma levels of BNP were closely related to the severity of heart failure and could serve as a biochemical marker for assessing the left cardiac function. (authors)

  6. Impact of exercise rehabilitation on cardiac neuronal function in heart failure. An iodine-123 metaiodobenzylguanidine scintigraphy study

    Energy Technology Data Exchange (ETDEWEB)

    Agostini, D.; Bouvard, G. [Service de Medecine Nucleaire, CHU Cote de Nacre, Caen (France); Lecluse, E.; Grollier, G.; Potier, J.C. [Service de Cardiologie, CHU Cote de Nacre, Caen (France); Belin, A. [Service de Readaptation Cardiaque, CHU Cote de Nacre, Caen (France); Babatasi, G. [Service de Chirurgie Cardio-Thoracique, CHU Cote de Nacre, Caen (France); Amar, M.H. [Centre Francois Baclesse, Caen (France). Service de Recherche Clinique

    1998-03-01

    Exercise training can induce important haemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examined the impact of exercise rehabilitation on cardiac neuronal function using iodine-123 metaiobodenzylguanidine (MIBG) scintigraphy. Fourteen patients (11 men, 3 women; mean age 48 years; range: 36-66 years) with stable chronic heart failure of NYHA class II-III and an initial resting radionuclide left ventricular ejection fraction (LVEF) <50% were enrolled in the study. Patients underwent progressive, supervised endurance training (treadmill test, Bruce protocol) during a 6-month period (60 sessions, 3 sessions per week) at a cardiac rehabilitation referral centre in order to measure exercise parameters. Planar {sup 123}I-MIBG scintigraphy provided measurements of cardiac neuronal uptake (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of exercise training. Workload (801{+-}428 vs 1229{+-}245 kpm.min{sup -1}, P=0.001), exercise duration (504{+-}190 vs 649{+-}125 s, P=0.02), and myocardial MIBG uptake (135%{+-}19% vs 156%{+-}25%, P=0.02) increased significantly after rehabilitation. However, LVEF did not change significantly (23%{+-}9% vs 21%{+-}10%, p=NS). It is concluded that exercise rehabilitation induces improvement of cardiac neuronal function without having negative effects on cardiac contractility in patients with stable chronic heart failure. (orig.)

  7. Red Cell Distribution Width and Serum BNP Level Correlation in Diabetic Patients with Cardiac Failure: A Cross - Sectional Study.

    Science.gov (United States)

    A R, Subhashree

    2014-06-01

    Red cell distribution width (RDW) is a red cell measurement given by fully automated hematology analyzers. It is a measure of heterogeneity in the size of circulating erythrocytes. Studies have shown that it is a prognostic marker in non - anemic diabetic patients with symptomatic cardiovascular disease but its correlation with cardiac failure in diabetics has not been studied so far. Moreover, studies have also shown that a higher RDW may reflect an underlying inflammatory state. Since Diabetes is a pro inflammatory state there is a possibility that it might have an influence on the RDW values even when there is no cardiac failure, but research data on this aspect is lacking. B-type natriuretic peptide (BNP) is a proven marker for cardiac failure whose values are comparable with echo cardio graphic findings in assessing the left ventricular dysfunction. This study aimed to find out the correlation between RDW% and serum BNP levels in Diabetics with heart failure (cases) when compared to those without failure (controls). Further, we compared the RDW % values of the cases with controls. Settings and Design : The study was approved by institutional ethical and research committee. A cross-sectional study was conducted with patients attending the Diabetes clinic of a tertiary care hospital in Chennai, India, during the period of October to December 2013. Hundred known cases of type II Diabetes mellitus attending Diabetes centre of the Hospital, with clinical and Echo cardio graphic features of cardiac failure were included as cases. Hundred age and gender matched diabetics with negative history of cardiovascular disease and with normal Echo cardio graphic features were included as controls. Informed consent was obtained from all the cases and controls. Demographic data and clinical history were gathered from all the cases and controls by using a standardized self - administered questionnaire. Biochemical and hematological parameters which included Fasting and

  8. Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes : The ADVANCE Trial

    NARCIS (Netherlands)

    Ohkuma, Toshiaki; Jun, Min; Woodward, Mark; Zoungas, Sophia; Cooper, Mark E; Grobbee, Diederick E; Hamet, Pavel; Mancia, Giuseppe; Williams, Bryan; Welsh, Paul; Sattar, Naveed; Shaw, Jonathan E.; Rahimi, Kazem; Chalmers, John

    OBJECTIVE: This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and hs-CRP on the prediction of heart failure incidence or progression in patients with type 2 diabetes.

  9. Constant infusion transpulmonary thermodilution for the assessment of cardiac output in exercising humans

    DEFF Research Database (Denmark)

    Calbet, J A L; Mortensen, Stefan; Munch, G D W

    2016-01-01

    To determine the accuracy and precision of constant infusion transpulmonary thermodilution cardiac output (CITT-Q) assessment during exercise in humans, using indocyanine green (ICG) dilution and bolus transpulmonary thermodilution (BTD) as reference methods, cardiac output (Q) was determined......: 6.1-11.1%). In conclusion, cardiac output can be precisely and accurately determined with constant infusion transpulmonary thermodilution in exercising humans....

  10. Kinin B1 receptor blockade and ACE inhibition attenuate cardiac postinfarction remodeling and heart failure in rats

    International Nuclear Information System (INIS)

    Lin, Xinchun; Bernloehr, Christian; Hildebrandt, Tobias; Stadler, Florian J.; Doods, Henri; Wu, Dongmei

    2016-01-01

    Introduction: The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats. Methods and results: Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6 weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, and improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (± dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls. Conclusion: The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor. - Highlights: • We examined the role of kinin B1 receptors in the development of heart failure. • Kinin B1 receptor blockade attenuates post-infarction cardiac remodeling. • Kinin B1 receptor blockade improves dysfunction, and prevented heart failure. • B1 receptor blockade does not affect the cardio-protection of an ACE inhibitor.

  11. Kinin B1 receptor blockade and ACE inhibition attenuate cardiac postinfarction remodeling and heart failure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Xinchun [Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140 (United States); Bernloehr, Christian; Hildebrandt, Tobias [Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach (Germany); Stadler, Florian J., E-mail: fjstadler@szu.edu.cn [Shenzhen Engineering Laboratory for Advanced Technology of Ceramics, Shenzhen 518060 (China); Doods, Henri [Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach (Germany); Wu, Dongmei, E-mail: dongmeiwu@bellsouth.net [Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140 (United States); Department of BIN Convergence Technology, Chonbuk National University (Korea, Republic of)

    2016-08-15

    Introduction: The aim of the present study was to evaluate the effects of the novel kinin B1 receptor antagonist BI113823 on postinfarction cardiac remodeling and heart failure, and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin 1 converting enzyme (ACE) inhibitor in rats. Methods and results: Sprague Dawley rats were subjected to permanent occlusion of the left coronary artery. Cardiovascular function was determined at 6 weeks postinfarction. Treatment with either B1 receptor antagonist (BI113823) or an ACE inhibitor (lisinopril) alone or in combination significantly reduced the heart weight-to-body weight and lung weight-to-body weight ratios, and improved postinfarction cardiac function as evidenced by greater cardiac output, the maximum rate of left ventricular pressure rise (± dP/dtmax), left ventricle ejection fraction, fractional shorting, better wall motion, and attenuation of elevated left ventricular end diastolic pressure (LVEDP). Furthermore, all three treatment groups exhibited significant reduction in cardiac interstitial fibrosis, collagen deposition, CD68 positive macrophages, neutrophils, and proinflammatory cytokine production (TNF-α and IL-1β), compared to vehicle controls. Conclusion: The present study shows that treatment with the novel kinin B1 receptor antagonist, BI113823, reduces postinfarction cardiac remodeling and heart failure, and does not influence the cardiovascular effects of the ACE inhibitor. - Highlights: • We examined the role of kinin B1 receptors in the development of heart failure. • Kinin B1 receptor blockade attenuates post-infarction cardiac remodeling. • Kinin B1 receptor blockade improves dysfunction, and prevented heart failure. • B1 receptor blockade does not affect the cardio-protection of an ACE inhibitor.

  12. Characterization of human cardiac myosin heavy chain genes

    International Nuclear Information System (INIS)

    Yamauchi-Takihara, K.; Sole, M.J.; Liew, J.; Ing, D.; Liew, C.C.

    1989-01-01

    The authors have isolated and analyzed the structure of the genes coding for the α and β forms of the human cardiac myosin heavy chain (MYHC). Detailed analysis of four overlapping MYHC genomic clones shows that the α-MYHC and β-MYHC genes constitute a total length of 51 kilobases and are tandemly linked. The β-MYHC-encoding gene, predominantly expressed in the normal human ventricle and also in slow-twitch skeletal muscle, is located 4.5 kilobases upstream of the α-MYHC-encoding gene, which is predominantly expressed in normal human atrium. The authors have determined the nucleotide sequences of the β form of the MYHC gene, which is 100% homologous to the cardiac MYHC cDNA clone (pHMC3). It is unlikely that the divergence of a few nucleotide sequences from the cardiac β-MYHC cDNA clone (pHMC3) reported in a MYHC cDNA clone (PSMHCZ) from skeletal muscle is due to a splicing mechanism. This finding suggests that the same β form of the cardiac MYHC gene is expressed in both ventricular and slow-twitch skeletal muscle. The promoter regions of both α- and β-MYHC genes, as well as the first four coding regions in the respective genes, have also been sequenced. The sequences in the 5'-flanking region of the α- and β-MYHC-encoding genes diverge extensively from one another, suggesting that expression of the α- and β-MYHC genes is independently regulated

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

    Science.gov (United States)

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

    2015-09-22

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

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

    Science.gov (United States)

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

    2015-01-01

    Cardiac remodeling is one of the most common cardiac abnormalities and associated with a high mortality in chronic renal failure (CRF) patients. Apocynin, a nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been showed cardio-protective effects. However, whether apocynin can improve cardiac remodeling in CRF and what is the underlying mechanism are unclear. In the present study, we enrolled 94 participants. In addition, we used 5/6 nephrectomized rats to mimic cardiac remodeling in CRF. Serum levels of epoxyeicosatrienoic acids (EETs) and its mainly metabolic enzyme-soluble epoxide hydrolase (sEH) were measured. The results showed that the serum levels of EETs were significantly decreased in renocardiac syndrome participants (P < 0.05). In 5/6 nephrectomized CRF model, the ratio of left ventricular weight /body weight, left ventricular posterior wall thickness, and cardiac interstitial fibrosis were significantly increased while ejection fraction significantly decreased (P < 0.05). All these effects could partly be reversed by apocynin. Meanwhile, we found during the process of cardiac remodeling in CRF, apocynin significantly increased the reduced serum levels of EETs and decreased the mRNA and protein expressions of sEH in the heart (P < 0.05). Our findings indicated that the protective effect of apocynin on cardiac remodeling in CRF was associated with the up-regulation of EETs. EETs may be a new mediator for the injury of kidney-heart interactions. PMID:26322503

  15. Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish.

    Science.gov (United States)

    Mishra, Shikha; Guan, Jian; Plovie, Eva; Seldin, David C; Connors, Lawreen H; Merlini, Giampaolo; Falk, Rodney H; MacRae, Calum A; Liao, Ronglih

    2013-07-01

    Systemic amyloid light-chain (AL) amyloidosis is associated with rapidly progressive and fatal cardiomyopathy resulting from the direct cardiotoxic effects of circulating AL light chain (AL-LC) proteins and the indirect effects of AL fibril tissue infiltration. Cardiac amyloidosis is resistant to standard heart failure therapies, and, to date, there are limited treatment options for these patients. The mechanisms underlying the development of cardiac amyloidosis and AL-LC cardiotoxicity are largely unknown, and their study has been limited by the lack of a suitable in vivo model system. Here, we establish an in vivo zebrafish model of human AL-LC-induced cardiotoxicity. AL-LC isolated from AL cardiomyopathy patients or control nonamyloidogenic LC protein isolated from multiple myeloma patients (Con-LC) was directly injected into the circulation of zebrafish at 48 h postfertilization. AL-LC injection resulted in impaired cardiac function, pericardial edema, and increased cell death relative to Con-LC, culminating in compromised survival with 100% mortality within 2 wk, independent of AL fibril deposition. Prior work has implicated noncanonical p38 MAPK activation in the pathogenesis of AL-LC-induced cardiotoxicity, and p38 MAPK inhibition via SB-203580 rescued AL-LC-induced cardiac dysfunction and cell death and attenuated mortality in zebrafish. This in vivo zebrafish model of AL-LC cardiotoxicity demonstrates that antagonism of p38 MAPK within the AL-LC cardiotoxic signaling response may serve to improve cardiac function and mortality in AL cardiomyopathy. Furthermore, this in vivo model system will allow for further study of the molecular underpinnings of AL cardiotoxicity and identification of novel therapeutic strategies.

  16. Impact of exercise rehabilitation on cardiac neuronal function in heart failure. An iodine-123 metaiodobenzylguanidine scintigraphy study

    International Nuclear Information System (INIS)

    Agostini, D.; Bouvard, G.; Lecluse, E.; Grollier, G.; Potier, J.C.; Belin, A.; Babatasi, G.; Amar, M.H.

    1998-01-01

    Exercise training can induce important haemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examined the impact of exercise rehabilitation on cardiac neuronal function using iodine-123 metaiobodenzylguanidine (MIBG) scintigraphy. Fourteen patients (11 men, 3 women; mean age 48 years; range: 36-66 years) with stable chronic heart failure of NYHA class II-III and an initial resting radionuclide left ventricular ejection fraction (LVEF) 123 I-MIBG scintigraphy provided measurements of cardiac neuronal uptake (heart-mediastinum ratio activity, 4 h after intravenous injection of 185 MBq of MIBG). Radionuclide LVEF was also assessed at the outset and after 6 months of exercise training. Workload (801±428 vs 1229±245 kpm.min -1 , P=0.001), exercise duration (504±190 vs 649±125 s, P=0.02), and myocardial MIBG uptake (135%±19% vs 156%±25%, P=0.02) increased significantly after rehabilitation. However, LVEF did not change significantly (23%±9% vs 21%±10%, p=NS). It is concluded that exercise rehabilitation induces improvement of cardiac neuronal function without having negative effects on cardiac contractility in patients with stable chronic heart failure. (orig.)

  17. Nutritional leucine supplementation attenuates cardiac failure in tumour-bearing cachectic animals.

    Science.gov (United States)

    Toneto, Aline Tatiane; Ferreira Ramos, Luiz Alberto; Salomão, Emilianne Miguel; Tomasin, Rebeka; Aereas, Miguel Arcanjo; Gomes-Marcondes, Maria Cristina Cintra

    2016-12-01

    The condition known as cachexia presents in most patients with malignant tumours, leading to a poor quality of life and premature death. Although the cancer-cachexia state primarily affects skeletal muscle, possible damage in the cardiac muscle remains to be better characterized and elucidated. Leucine, which is a branched chain amino acid, is very useful for preserving lean body mass. Thus, this amino acid has been studied as a coadjuvant therapy in cachectic cancer patients, but whether this treatment attenuates the effects of cachexia and improves cardiac function remains poorly understood. Therefore, using an experimental cancer-cachexia model, we evaluated whether leucine supplementation ameliorates cachexia in the heart. Male Wistar rats were fed either a leucine-rich or a normoprotein diet and implanted or not with subcutaneous Walker-256 carcinoma. During the cachectic stage (approximately 21 days after tumour implantation), when the tumour mass was greater than 10% of body weight, the rats were subjected to an electrocardiogram analysis to evaluate the heart rate, QT-c, and T wave amplitude. The myocardial tissues were assayed for proteolytic enzymes (chymotrypsin, alkaline phosphatase, cathepsin, and calpain), cardiomyopathy biomarkers (myeloperoxidase, tissue inhibitor of metalloproteinases, and total plasminogen activator inhibitor 1), and caspase-8, -9, -3, and -7 activity. Both groups of tumour-bearing rats, especially the untreated group, had electrocardiography alterations that were suggestive of ischemia, dilated cardiomyopathy, and sudden death risk. Additionally, the rats in the untreated tumour-bearing group but not their leucine-supplemented littermates exhibited remarkable increases in chymotrypsin activity and all three heart failure biomarkers analysed, including an increase in caspase-3 and -7 activity. Our data suggest that a leucine-rich diet could modulate heart damage, cardiomyocyte proteolysis, and apoptosis driven by cancer

  18. Cardiac Organ Damage and Arterial Stiffness in Autonomic Failure: Comparison With Essential Hypertension.

    Science.gov (United States)

    Milazzo, Valeria; Maule, Simona; Di Stefano, Cristina; Tosello, Francesco; Totaro, Silvia; Veglio, Franco; Milan, Alberto

    2015-12-01

    Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m(2), P=0.59) and carotid-femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (Phypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four-hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability. © 2015 American Heart Association, Inc.

  19. Cardiac regeneration therapy: connections to cardiac physiology.

    Science.gov (United States)

    Takehara, Naofumi; Matsubara, Hiroaki

    2011-12-01

    Without heart transplantation, a large number of patients with failing hearts worldwide face poor outcomes. By means of cardiomyocyte regeneration, cardiac regeneration therapy is emerging with great promise as a means for restoring loss of cardiac function. However, the limited success of clinical trials using bone marrow-derived cells and myoblasts with heterogeneous constituents, transplanted at a wide range of cell doses, has led to disagreement on the efficacy of cell therapy. It is therefore essential to reevaluate the evidence for the efficacy of cell-based cardiac regeneration therapy, focusing on targets, materials, and methodologies. Meanwhile, the revolutionary innovation of cardiac regeneration therapy is sorely needed to help the millions of people who suffer heart failure from acquired loss of cardiomyocytes. Cardiac regeneration has been used only in limited species or as a developing process in the rodent heart; now, the possibility of cardiomyocyte turnover in the human heart is being revisited. In the pursuit of this concept, the use of cardiac stem/progenitor stem cells in the cardiac niche must be focused to usher in a second era of cardiac regeneration therapy for the severely injured heart. In addition, tissue engineering and cellular reprogramming will advance the next era of treatment that will enable current cell-based therapy to progress to "real" cardiac regeneration therapy. Although many barriers remain, the prevention of refractory heart failure through cardiac regeneration is now becoming a realistic possibility.

  20. Identifying potential functional impact of mutations and polymorphisms: Linking heart failure, increased risk of arrhythmias and sudden cardiac death.

    Directory of Open Access Journals (Sweden)

    BENOIT eJAGU

    2013-09-01

    Full Text Available Researchers and clinicians have discovered several important concepts regarding the mechanisms responsible for increased risk of arrhythmias, heart failure and sudden cardiac death. One major step in defining the molecular basis of normal and abnormal cardiac electrical behaviour has been the identification of single mutations that greatly increase the risk for arrhythmias and sudden cardiac death by changing channel-gating characteristics. Indeed, mutations in several genes encoding ion channels, such as SCN5A, which encodes the major cardiac Na+ channel, have emerged as the basis for a variety of inherited cardiac arrhythmias such as long QT syndrome, Brugada syndrome, progressive cardiac conduction disorder, sinus node dysfunction or sudden infant death syndrome. In addition, genes encoding ion channel accessory proteins, like anchoring or chaperone proteins, which modify the expression, the regulation of endocytosis and the degradation of ion channel α-subunits have also been reported as susceptibility genes for arrhythmic syndromes. The regulation of ion channel protein expression also depends on a fine-tuned balance among different other mechanisms, such as gene transcription, RNA processing, post-transcriptional control of gene expression by miRNA, protein synthesis, assembly and post-translational modification and trafficking.

  1. Relationship between quantitative cardiac neuronal imaging with {sup 123}I-meta-iodobenzylguanidine and hospitalization in patients with heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Parker, Matthew W.; Sood, Nitesh [University of Connecticut, School of Medicine Department of Medicine, Farmington, CT (United States); Hartford Hospital, Division of Cardiology, Hartford, CT (United States); Ahlberg, Alan W. [Hartford Hospital, Division of Cardiology, Hartford, CT (United States); Jacobson, Arnold F. [GE Healthcare, Princeton, NJ (United States); Heller, Gary V. [The Intersocietal Accreditation Commission, Ellicott City, MD (United States); Lundbye, Justin B. [University of Connecticut, School of Medicine Department of Medicine, Farmington, CT (United States); The Hospital of Central Connecticut, Division of Cardiology, New Britain, CT (United States)

    2014-09-15

    Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by {sup 123}I-meta-iodobenzylguanidine ({sup 123}I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between {sup 123}I-mIBG imaging findings and hospitalization. Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using {sup 123}I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression. During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than subjects with higher H/M ratios (log-rank p = 0.003). After adjusting for elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 - 2.0; p = 0.02). The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships. (orig.)

  2. Relationship between quantitative cardiac neuronal imaging with 123I-meta-iodobenzylguanidine and hospitalization in patients with heart failure

    International Nuclear Information System (INIS)

    Parker, Matthew W.; Sood, Nitesh; Ahlberg, Alan W.; Jacobson, Arnold F.; Heller, Gary V.; Lundbye, Justin B.

    2014-01-01

    Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by 123 I-meta-iodobenzylguanidine ( 123 I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between 123 I-mIBG imaging findings and hospitalization. Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using 123 I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression. During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than subjects with higher H/M ratios (log-rank p = 0.003). After adjusting for elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 - 2.0; p = 0.02). The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships. (orig.)

  3. Human embryonic stem cell derived mesenchymal progenitors express cardiac markers but do not form contractile cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Christophe M Raynaud

    Full Text Available Mesenchymal progenitors or stromal cells have shown promise as a therapeutic strategy for a range of diseases including heart failure. In this context, we explored the growth and differentiation potential of mesenchymal progenitors (MPs derived in vitro from human embryonic stem cells (hESCs. Similar to MPs isolated from bone marrow, hESC derived MPs (hESC-MPs efficiently differentiated into archetypical mesenchymal derivatives such as chondrocytes and adipocytes. Upon treatment with 5-Azacytidine or TGF-β1, hESC-MPs modified their morphology and up-regulated expression of key cardiac transcription factors such as NKX2-5, MEF2C, HAND2 and MYOCD. Nevertheless, NKX2-5+ hESC-MP derivatives did not form contractile cardiomyocytes, raising questions concerning the suitability of these cells as a platform for cardiomyocyte replacement therapy. Gene profiling experiments revealed that, although hESC-MP derived cells expressed a suite of cardiac related genes, they lacked the complete repertoire of genes associated with bona fide cardiomyocytes. Our results suggest that whilst agents such as TGF-β1 and 5-Azacytidine can induce expression of cardiac related genes, but treated cells retain a mesenchymal like phenotype.

  4. Baseline Hemodynamics and Response to Contrast Media During Diagnostic Cardiac Catheterization Predict Adverse Events in Heart Failure Patients.

    Science.gov (United States)

    Denardo, Scott J; Vock, David M; Schmalfuss, Carsten M; Young, Gregory D; Tcheng, James E; O'Connor, Christopher M

    2016-07-01

    Contrast media administered during cardiac catheterization can affect hemodynamic variables. However, little is documented about the effects of contrast on hemodynamics in heart failure patients or the prognostic value of baseline and changes in hemodynamics for predicting subsequent adverse events. In this prospective study of 150 heart failure patients, we measured hemodynamics at baseline and after administration of iodixanol or iopamidol contrast. One-year Kaplan-Meier estimates of adverse event-free survival (death, heart failure hospitalization, and rehospitalization) were generated, grouping patients by baseline measures of pulmonary capillary wedge pressure (PCWP) and cardiac index (CI), and by changes in those measures after contrast administration. We used Cox proportional hazards modeling to assess sequentially adding baseline PCWP and change in CI to 5 validated risk models (Seattle Heart Failure Score, ESCAPE [Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness], CHARM [Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity], CORONA [Controlled Rosuvastatin Multinational Trial in Heart Failure], and MAGGIC [Meta-Analysis Global Group in Chronic Heart Failure]). Median contrast volume was 109 mL. Both contrast media caused similarly small but statistically significant changes in most hemodynamic variables. There were 39 adverse events (26.0%). Adverse event rates increased using the composite metric of baseline PCWP and change in CI (Pcontrast correlated with the poorest prognosis. Adding both baseline PCWP and change in CI to the 5 risk models universally improved their predictive value (P≤0.02). In heart failure patients, the administration of contrast causes small but significant changes in hemodynamics. Calculating baseline PCWP with change in CI after contrast predicts adverse events and increases the predictive value of existing models. Patients with elevated baseline PCWP and

  5. 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

    International Nuclear Information System (INIS)

    Ishida, Yoshio; Shimozu, Junko; Yasumura, Yoshio; Nagatani, Kenzo; Miyatake, Kunio

    1998-01-01

    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 β-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.)

  6. 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.)

  7. High intensity interval and endurance training have opposing effects on markers of heart failure and cardiac remodeling in hypertensive rats.

    Science.gov (United States)

    Holloway, Tanya M; Bloemberg, Darin; da Silva, Mayne L; Simpson, Jeremy A; Quadrilatero, Joe; Spriet, Lawrence L

    2015-01-01

    There has been re-emerging interest and significant work dedicated to investigating the metabolic effects of high intensity interval training (HIIT) in recent years. HIIT is considered to be a time efficient alternative to classic endurance training (ET) that elicits similar metabolic responses in skeletal muscle. However, there is a lack of information on the impact of HIIT on cardiac muscle in disease. Therefore, we determined the efficacy of ET and HIIT to alter cardiac muscle characteristics involved in the development of diastolic dysfunction, such as ventricular hypertrophy, fibrosis and angiogenesis, in a well-established rodent model of hypertension-induced heart failure before the development of overt heart failure. ET decreased left ventricle fibrosis by ~40% (P hypertension. However, HIIT promoted a pathological adaptation in the left ventricle in the presence of hypertension, highlighting the need for further research on the widespread effects of HIIT in the presence of disease.

  8. Successful treatment of thyroid storm presenting as recurrent cardiac arrest and subsequent multiorgan failure by continuous renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Han Soo Park

    2017-03-01

    Full Text Available Thyroid storm is a rare and potentially life-threatening medical emergency. We experienced a case of thyroid storm associated with sepsis caused by pneumonia, which had a catastrophic course including recurrent cardiac arrest and subsequent multiple organ failure (MOF. A 22-year-old female patient with a 10-year history of Graves’ disease was transferred to our emergency department (ED. She had a cardiac arrest at her home and a second cardiac arrest at the ED. Her heart recovered after 20 min of cardiac resuscitation. She was diagnosed with thyroid storm associated with hyperthyroidism complicated by pneumonia and sepsis. Although full conventional medical treatment was given, she had progressive MOF and hemodynamic instability consisting of hyperthermia, tachycardia and hypotension. Because of hepatic and renal failure with refractory hypotension, we reduced the patient’s dose of beta-blocker and antithyroid drug, and she was started on continuous veno-venous renal replacement therapy (CRRT with intravenous albumin and plasma supplementation. Subsequently, her body temperature and pulse rate began to stabilize within 1 h, and her blood pressure reached 120/60 mmHg after 6 h. We discontinued antithyroid drug 3 days after admission because of aggravated hyperbilirubinemia. The patient exhibited progressive improvement in thyroid function even after cessation of antithyroid drug, and she successfully recovered from thyroid storm and MOF. This is the first case of thyroid storm successfully treated by CRRT in a patient considered unfit for antithyroid drug treatment.

  9. The quantitative failure of human reliability analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, C.T.

    1995-07-01

    This philosophical treatise argues the merits of Human Reliability Analysis (HRA) in the context of the nuclear power industry. Actually, the author attacks historic and current HRA as having failed in informing policy makers who make decisions based on risk that humans contribute to systems performance. He argues for an HRA based on Bayesian (fact-based) inferential statistics, which advocates a systems analysis process that employs cogent heuristics when using opinion, and tempers itself with a rational debate over the weight given subjective and empirical probabilities.

  10. Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats.

    Science.gov (United States)

    Razavi Tousi, Seyed Mohammad Taghi; Faghihi, Mahdieh; Nobakht, Maliheh; Molazem, Mohammad; Kalantari, Elham; Darbandi Azar, Amir; Aboutaleb, Nahid

    2016-07-06

    Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs) in rats with heart failure (HF). Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each) as 1- Control 2- Heart Failure (HF) 3- Sham 4- Culture media 5- Stem Cell Transplantation (SCT). Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×10 6 cells in 150 µl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done. Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 ± 9% to 81/25 ± 6/05% in SCT group (p value < 0.001). Fraction shortening in HF group was increased from 27/53 ± 8/58% into 45/55 ± 6/91% in SCT group (p value < 0.001). Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value < 0.001) compared with the animals in the HF group. Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters.

  11. Competing Risk of Cardiac Status and Renal Function During Hospitalization for Acute Decompensated Heart Failure.

    Science.gov (United States)

    Salah, Khibar; Kok, Wouter E; Eurlings, Luc W; Bettencourt, Paulo; Pimenta, Joana M; Metra, Marco; Verdiani, Valerio; Tijssen, Jan G; Pinto, Yigal M

    2015-10-01

    The aim of this study was to analyze the dynamic changes in renal function in combination with dynamic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients hospitalized for acute decompensated heart failure (ADHF). Treatment of ADHF improves cardiac parameters, as reflected by lower levels of NT-proBNP. However this often comes at the cost of worsening renal parameters (e.g., serum creatinine, estimated glomerular filtration rate [eGFR], or serum urea). Both the cardiac and renal markers are validated indicators of prognosis, but it is not yet clear whether the benefits of lowering NT-proBNP are outweighed by the concomitant worsening of renal parameters. This study was an individual patient data analysis assembled from 6 prospective cohorts consisting of 1,232 patients hospitalized for ADHF. Endpoints were all-cause mortality and the composite of all-cause mortality and/or readmission for a cardiovascular reason within 180 days after discharge. A significant reduction in NT-proBNP was not associated with worsening of renal function (WRF) or severe WRF (sWRF). A reduction of NT-proBNP of more than 30% during hospitalization determined prognosis (all-cause mortality hazard ratio [HR]: 1.81; 95% confidence Interval [CI]: 1.32 to 2.50; composite endpoint: HR: 1.36, 95% CI: 1.13 to 1.64), regardless of changes in renal function and other clinical variables. When we defined prognosis, NT-proBNP changes during hospitalization for treatment of ADHF prevailed over parameters for worsening renal function. Severe WRF is a measure of prognosis, but is of lesser value than, and independent of the prognostic changes induced by adequate NT-proBNP reduction. This suggests that in ADHF patients it may be warranted to strive for an optimal decrease in NT-proBNP, even if this induces WRF. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  12. Interpolation of vector fields from human cardiac DT-MRI

    International Nuclear Information System (INIS)

    Yang, F; Zhu, Y M; Rapacchi, S; Robini, M; Croisille, P; Luo, J H

    2011-01-01

    There has recently been increased interest in developing tensor data processing methods for the new medical imaging modality referred to as diffusion tensor magnetic resonance imaging (DT-MRI). This paper proposes a method for interpolating the primary vector fields from human cardiac DT-MRI, with the particularity of achieving interpolation and denoising simultaneously. The method consists of localizing the noise-corrupted vectors using the local statistical properties of vector fields, removing the noise-corrupted vectors and reconstructing them by using the thin plate spline (TPS) model, and finally applying global TPS interpolation to increase the resolution in the spatial domain. Experiments on 17 human hearts show that the proposed method allows us to obtain higher resolution while reducing noise, preserving details and improving direction coherence (DC) of vector fields as well as fiber tracking. Moreover, the proposed method perfectly reconstructs azimuth and elevation angle maps.

  13. Empagliflozin Prevents Worsening of Cardiac Function in an Experimental Model of Pressure Overload-Induced Heart Failure

    Directory of Open Access Journals (Sweden)

    Nikole J. Byrne, BSc

    2017-08-01

    Full Text Available This study sought to determine whether the sodium/glucose cotransporter 2 (SGLT2 inhibitor empagliflozin improved heart failure (HF outcomes in nondiabetic mice. The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients trial demonstrated that empagliflozin markedly prevented HF and cardiovascular death in subjects with diabetes. However, despite ongoing clinical trials in HF patients without type 2 diabetes, there are no objective and translational data to support an effect of SGLT2 inhibitors on cardiac structure and function, particularly in the absence of diabetes and in the setting of established HF. Male C57Bl/6 mice were subjected to either sham or transverse aortic constriction surgery to induce HF. Following surgery, mice that progressed to HF received either vehicle or empagliflozin for 2 weeks. Cardiac function was then assessed in vivo using echocardiography and ex vivo using isolated working hearts. Although vehicle-treated HF mice experienced a progressive worsening of cardiac function over the 2-week treatment period, this decline was blunted in empagliflozin-treated HF mice. Treatment allocation to empagliflozin resulted in an improvement in cardiac systolic function, with no significant changes in cardiac remodeling or diastolic dysfunction. Moreover, isolated hearts from HF mice treated with empagliflozin displayed significantly improved ex vivo cardiac function compared to those in vehicle-treated controls. Empagliflozin treatment of nondiabetic mice with established HF blunts the decline in cardiac function both in vivo and ex vivo, independent of diabetes. These data provide important basic and translational clues to support the evaluation of SGLT2 inhibitors as a treatment strategy in a broad range of patients with established HF.

  14. Alterations of left ventricular deformation and cardiac sympathetic derangement in patients with systolic heart failure: a 3D speckle tracking echocardiography and cardiac {sup 123}I-MIBG study

    Energy Technology Data Exchange (ETDEWEB)

    Leosco, Dario; Parisi, Valentina; Pagano, Gennaro; Femminella, Grazia Daniela; Bevilacqua, Agnese; Formisano, Roberto; Ferro, Gaetana; De Lucia, Claudio; Ferrara, Nicola [University Federico II, Department of Translational Medical Science, Naples (Italy); Pellegrino, Teresa [Italian National Research Council (CNR), Institute of Biostructure and Bioimaging, Naples (Italy); University Federico II, Department of Advanced Biomedical Science, Naples (Italy); Paolillo, Stefania [University Federico II, Department of Advanced Biomedical Science, Naples (Italy); SDN Foundation, Institute of Diagnostic and Nuclear Development, Naples (Italy); Prastaro, Maria; Filardi, Pasquale Perrone; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Science, Naples (Italy); Rengo, Giuseppe [University Federico II, Department of Translational Medical Science, Naples (Italy); Salvatore Maugeri Foundation, IRCCS, Istituto di Telese, Benevento, BN (Italy)

    2015-09-15

    Myocardial contractile function is under the control of cardiac sympathetic activity. Three-dimensional speckle tracking echocardiography (3D-STE) and cardiac imaging with {sup 123}I-metaiodobenzylguanidine ({sup 123}I-MIBG) are two sophisticated techniques for the assessment of left ventricular (LV) deformation and sympathetic innervation, respectively, which offer important prognostic information in patients with heart failure (HF). The purpose of this investigation was to explore, in patients with systolic HF, the relationship between LV deformation assessed by 3D-STE and cardiac sympathetic derangement evaluated by {sup 123}I-MIBG imaging. We prospectively studied 75 patients with systolic HF. All patients underwent a 3D-STE study (longitudinal, circumferential, area and radial) and {sup 123}I-MIBG planar and SPECT cardiac imaging. 3D-STE longitudinal, circumferential and area strain values were correlated with {sup 123}I-MIBG late heart to mediastinum (H/M) ratio and late SPECT total defect score. After stratification of the patients according to ischaemic or nonischaemic HF aetiology, we observed a good correlation of all 3D-STE measurements with late H/M ratio and SPECT data in the ischaemic group, but in patients with HF of nonischaemic aetiology, no correlation was found between LV deformation and cardiac sympathetic activity. At the regional level, the strongest correlation between LV deformation and adrenergic innervation was found for the left anterior descending coronary artery distribution territory for all four 3D-STE values. In multivariate linear regression analyses, including age, gender, LV ejection fraction, NYHA class, body mass index, heart rate and HF aetiology, only 3D-STE area and radial strain values significantly predicted cardiac sympathetic derangement on {sup 123}I-MIBG late SPECT. This study indicated that 3D-STE measurements are correlated with {sup 123}I-MIBG planar and SPECT data. Furthermore, 3D-STE area and radial strain values

  15. A New Face of Cardiac Emergencies: Human Immunodeficiency Virus-Related Cardiac Disease.

    Science.gov (United States)

    Tsabedze, Nqoba; Vachiat, Ahmed; Zachariah, Don; Manga, Pravin

    2018-02-01

    The human immunodeficiency virus epidemic is a major health challenge of the twenty-first century as the transition from infectious complications to noncommunicable disease becomes more evident. These patients may present to the emergency department with a variety of cardiovascular diseases, such as acute coronary syndromes, heart failure, pericardial disease, infective endocarditis, venothromboembolism, and other conditions. Increased awareness is needed among health care professionals to enhance adequate identification and promote prompt management of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons

    OpenAIRE

    Hasan, Wohaib; Smith, Peter G

    2013-01-01

    Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is a...

  17. Positive predictive value and impact of misdiagnosis of a heart failure diagnosis in administrative registers among patients admitted to a University Hospital cardiac care unit

    DEFF Research Database (Denmark)

    Mard, Shan; Nielsen, Finn Erland

    2010-01-01

    To evaluate the positive predictive value (PPV) of a diagnosis of heart failure (HF) in the Danish National Registry of Patients (NRP) among patients admitted to a University Hospital cardiac care unit, and to evaluate the impact of misdiagnosing HF.......To evaluate the positive predictive value (PPV) of a diagnosis of heart failure (HF) in the Danish National Registry of Patients (NRP) among patients admitted to a University Hospital cardiac care unit, and to evaluate the impact of misdiagnosing HF....

  18. Reduced capacity of cardiac efferent sympathetic neurons to release noradrenaline and modify cardiac function in tachycardia-induced canine heart failure.

    Science.gov (United States)

    Cardinal, R; Nadeau, R; Laurent, C; Boudreau, G; Armour, J A

    1996-09-01

    To investigate the capacity of efferent sympathetic neurons to modulate the failing heart, stellate ganglion stimulation was performed in dogs with biventricular heart failure induced by rapid ventricular pacing (240 beats/min) for 4-6 weeks. Less noradrenaline was released from cardiac myoneural junctions into coronary sinus blood in response to left stellate ganglion stimulation in anesthetized failing heart preparations (582 pg/mL, lower and upper 95% confidence intervals of 288 and 1174 pg/mL, n = 19) compared with healthy heart preparations (6391 pg/mL, 95% confidence intervals of 4180 and 9770 pg/mL, n = 14; p < 0.001). There was substantial adrenaline extraction by failing hearts (49 +/- 6%), although it was slightly lower than in healthy heart preparations (65 +/- 9%, p = 0.055). In contrast with healthy heart preparations, no net release of adrenaline occurred during stellate ganglion stimulation in any of the failing heart preparations, and ventricular tissue levels of adrenaline fell below the sensitivity limit of the HPLC technique. In failing heart preparations, maximal electrical stimulation of right or left stellate ganglia resulted in minimal augmentation of left ventricular intramyocardial (17%) and chamber (12%) systolic pressures. These indices were augmented by 145 and 97%, respectively, following exogenous noradrenaline administration. Thus, the cardiac efferent sympathetic neurons' reduced capacity to release noradrenaline and modify cardiac function can contribute to reduction of sympathetic support to the failing heart.

  19. Heterogeneous response of cardiac sympathetic function to cardiac resynchronization therapy in heart failure documented by 11[C]-hydroxy-ephedrine and PET/CT

    International Nuclear Information System (INIS)

    Capitanio, Selene; Nanni, Cristina; Marini, Cecilia; Bonfiglioli, Rachele; Martignani, Cristian; Dib, Bassam; Fuccio, Chiara; Boriani, Giuseppe; Picori, Lorena; Boschi, Stefano; Morbelli, Silvia

    2015-01-01

    Introduction: Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III–IV) after CRT using 11 C-hydroxyephedrine (HED) PET/CT. Methods: Ten IHF patients (mean age = 68; range = 55–81; average left ventricular ejection fraction 26 ± 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps. Results: At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 ± 5%. This variable markedly decreased after three months CRT (12 ± 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with “impaired innervation” (SUV 2.61 ± 0.92 at PET1 and 3.05 ± 1.67 at three months, p < 0.01). Conclusion: As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. Advances in Knowledge: These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation

  20. Cardiac rehabilitation

    Science.gov (United States)

    ... rehab; Heart failure - cardiac rehab References Anderson L, Taylor RS. Cardiac rehabilitation for people with heart disease: ... of Medicine, Division of Cardiology, Harborview Medical Center, University of Washington Medical School, Seattle, WA. Also reviewed ...

  1. Detection of cardiac activity changes from human speech

    Science.gov (United States)

    Tovarek, Jaromir; Partila, Pavol; Voznak, Miroslav; Mikulec, Martin; Mehic, Miralem

    2015-05-01

    Impact of changes in blood pressure and pulse from human speech is disclosed in this article. The symptoms of increased physical activity are pulse, systolic and diastolic pressure. There are many methods of measuring and indicating these parameters. The measurements must be carried out using devices which are not used in everyday life. In most cases, the measurement of blood pressure and pulse following health problems or other adverse feelings. Nowadays, research teams are trying to design and implement modern methods in ordinary human activities. The main objective of the proposal is to reduce the delay between detecting the adverse pressure and to the mentioned warning signs and feelings. Common and frequent activity of man is speaking, while it is known that the function of the vocal tract can be affected by the change in heart activity. Therefore, it can be a useful parameter for detecting physiological changes. A method for detecting human physiological changes by speech processing and artificial neural network classification is described in this article. The pulse and blood pressure changes was induced by physical exercises in this experiment. The set of measured subjects was formed by ten healthy volunteers of both sexes. None of the subjects was a professional athlete. The process of the experiment was divided into phases before, during and after physical training. Pulse, systolic, diastolic pressure was measured and voice activity was recorded after each of them. The results of this experiment describe a method for detecting increased cardiac activity from human speech using artificial neural network.

  2. Cardiac spheroids as promising in vitro models to study the human heart microenvironment

    DEFF Research Database (Denmark)

    Polonchuk, Liudmila; Chabria, Mamta; Badi, Laura

    2017-01-01

    Three-dimensional in vitro cell systems are a promising alternative to animals to study cardiac biology and disease. We have generated three-dimensional in vitro models of the human heart ("cardiac spheroids", CSs) by co-culturing human primary or iPSC-derived cardiomyocytes, endothelial cells an...

  3. 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.

    2015-01-01

    BACKGROUND 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. METHODS We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults aged 45-64 years in 1987-89. From the 1987-89 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 2,218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4,855 participants free of clinical cardiovascular disease in 2011-13, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. RESULTS One in four participants (25.5%) developed heart failure through age 85. 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. CONCLUSIONS 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. PMID:25908393

  4. Quantitative 1H MR spectroscopy of the brain in patients with congestive heart failure before and after cardiac transplantation

    International Nuclear Information System (INIS)

    Lim, Soo Mee; Lee, Ho Kyu; Choi, Choong Gon; Lim, Tae Hwan; Lee, Jung Hee

    1999-01-01

    To evaluate the effects of cardiac transplantation on the brain in patients with congestive heart failure (CHF), using quantitative 1 H MR spectroscopy ( 1 H-MRS). Ten patients with CHF underwent MRI and quantitative 1 H-MRS before and 1-2 and 4-9 months after cardiac transplantation. MR spectra were obtained from parietal white matter (PWM) and occipital gray matter (OGM) using PROBE (PROton Brain Exam). Changes in MR signal intensity were evaluated, and the cerebral metabolic concentrations in PWM and OGM were compared. For comparative purposes, 20 normal volunteers were included. No abnormal MR signal intensity was seen in the brain before or after cardiac transplantation. Changes in cerebral metabolic concentrations were observed on 1 H-MRS; concentrations of creatine (Cr) in PWM, and of N-acetylacepartate (NAA), Cr and myo-Inositol(mI) in OGM were significantly lower before transplantation. After successful transplantation, Cr levels returned to their normal range in PWM and OGM, while a slightly increase choline (Cho) level was observed in PWM. Cerebral hypoperfusion in CHF can be evaluated using 1 H-MRS. MRS may play a substantial role in monitoring the effect of cardiac transplantation

  5. Higher dietary lycopene intake is associated with longer cardiac event-free survival in patients with heart failure.

    Science.gov (United States)

    Biddle, Martha; Moser, Debra; Song, Eun Kyeung; Heo, Seongkum; Payne-Emerson, Heather; Dunbar, Sandra B; Pressler, Susan; Lennie, Terry

    2013-08-01

    The antioxidant lycopene may be beneficial for patients with heart failure (HF). Processed tomato products are a major source of lycopene, although they are also high in sodium. Increased sodium intake may counter the positive antioxidant effect of lycopene. This was a prospective study of 212 patients with HF. Dietary intake of lycopene and sodium was obtained from weighted 4-day food diaries. Patients were grouped by the median split of lycopene of 2471 µg/day and stratified by daily sodium levels above and below 3 g/day. Patients were followed for 1 year to collect survival and hospitalization data. Cox proportional hazards modeling was used to compare cardiac event-free survival between lycopene groups within each stratum of sodium intake. Higher lycopene intake was associated with longer cardiac event-free survival compared with lower lycopene intake (p = 0.003). The worst cardiac event-free survival was observed in the low lycopene intake group regardless of sodium intake (> 3 g/day HR = 3.01; p = 0.027 and ≤ 3 g/day HR= 3.34; p = 0.023). These findings suggest that increased lycopene intake has the potential to improve cardiac event-free survival in patients with HF independent of sodium intake.

  6. Quantitative {sup 1}H MR spectroscopy of the brain in patients with congestive heart failure before and after cardiac transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Soo Mee; Lee, Ho Kyu; Choi, Choong Gon; Lim, Tae Hwan [Asan Medical Center, Ulsan Univ. College of Medicine, Ulsan (Korea, Republic of); Lee, Jung Hee [Asan Institute for Life Sciences, Seoul (Korea, Republic of)

    1999-12-01

    To evaluate the effects of cardiac transplantation on the brain in patients with congestive heart failure (CHF), using quantitative {sup 1}H MR spectroscopy ({sup 1}H-MRS). Ten patients with CHF underwent MRI and quantitative {sup 1}H-MRS before and 1-2 and 4-9 months after cardiac transplantation. MR spectra were obtained from parietal white matter (PWM) and occipital gray matter (OGM) using PROBE (PROton Brain Exam). Changes in MR signal intensity were evaluated, and the cerebral metabolic concentrations in PWM and OGM were compared. For comparative purposes, 20 normal volunteers were included. No abnormal MR signal intensity was seen in the brain before or after cardiac transplantation. Changes in cerebral metabolic concentrations were observed on {sup 1}H-MRS; concentrations of creatine (Cr) in PWM, and of N-acetylacepartate (NAA), Cr and myo-Inositol(mI) in OGM were significantly lower before transplantation. After successful transplantation, Cr levels returned to their normal range in PWM and OGM, while a slightly increase choline (Cho) level was observed in PWM. Cerebral hypoperfusion in CHF can be evaluated using {sup 1}H-MRS. MRS may play a substantial role in monitoring the effect of cardiac transplantation.

  7. Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation.

    Science.gov (United States)

    Meyer-Roxlau, Stefanie; Lämmle, Simon; Opitz, Annett; Künzel, Stephan; Joos, Julius P; Neef, Stefan; Sekeres, Karolina; Sossalla, Samuel; Schöndube, Friedrich; Alexiou, Konstantin; Maier, Lars S; Dobrev, Dobromir; Guan, Kaomei; Weber, Silvio; El-Armouche, Ali

    2017-07-01

    Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression. Using western blot analysis, we found greater abundance of PP1 isoforms α and γ but unaltered PP1β levels in left ventricular myocardial tissues from HF patients as compared to non-failing controls. However, expression of all three PP1 isoforms was higher in atrial appendages from patients with AF compared to patients with sinus rhythm. Moreover, we found that in human failing ventricles, beta-blocker therapy was associated with lower PP1α abundance and activity, as indicated by higher phosphorylation of the PP1α-specific substrate eIF2α. Greater eIF2α phosphorylation is a known repressor of protein translation, and accordingly, we found lower levels of the endoplasmic reticulum (ER) stress marker Grp78 in the very same samples. We propose that isoform-specific targeting of PP1α activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions.

  8. Fluorescent Reporters in Human Pluripotent Stem Cells: Contributions to Cardiac Differentiation and Their Applications in Cardiac Disease and Toxicity

    NARCIS (Netherlands)

    den Hartogh, Sabine C.; Passier, Petrus Christianus Johannes Josephus

    2016-01-01

    In the last decade, since the first report of induced pluripotent stem cells, the stem cell field has made remarkable progress in the differentiation to specialized cell-types of various tissues and organs, including the heart. Cardiac lineage- and tissue-specific human pluripotent stem cell (hPSC)

  9. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.

    Directory of Open Access Journals (Sweden)

    Francesca Oltolina

    Full Text Available A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM. We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol.

  10. Defining the molecular signatures of human right heart failure.

    Science.gov (United States)

    Williams, Jordan L; Cavus, Omer; Loccoh, Emefah C; Adelman, Sara; Daugherty, John C; Smith, Sakima A; Canan, Benjamin; Janssen, Paul M L; Koenig, Sara; Kline, Crystal F; Mohler, Peter J; Bradley, Elisa A

    2018-03-01

    Right ventricular failure (RVF) varies significantly from the more common left ventricular failure (LVF). This study was undertaken to determine potential molecular pathways that are important in human right ventricular (RV) function and may mediate RVF. We analyzed mRNA of human non-failing LV and RV samples and RVF samples from patients with pulmonary arterial hypertension (PAH), and post-LVAD implantation. We then performed transcript analysis to determine differential expression of genes in the human heart samples. Immunoblot quantification was performed followed by analysis of non-failing and failing phenotypes. Inflammatory pathways were more commonly dysregulated in RV tissue (both non-failing and failing phenotypes). In non-failing human RV tissue we found important differences in expression of FIGF, TRAPPAC, and CTGF suggesting that regulation of normal RV and LV function are not the same. In failing RV tissue, FBN2, CTGF, SMOC2, and TRAPP6AC were differentially expressed, and are potential targets for further study. This work provides some of the first analyses of the molecular heterogeneity between human RV and LV tissue, as well as key differences in human disease (RVF secondary to pulmonary hypertension and LVAD mediated RVF). Our transcriptional data indicated that inflammatory pathways may be more important in RV tissue, and changes in FIGF and CTGF supported this hypothesis. In PAH RV failure samples, upregulation of FBN2 and CTGF further reinforced the potential significance that altered remodeling and inflammation play in normal RV function and failure. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  12. Heart failure-induced changes of voltage-gated Ca2+ channels and cell excitability in rat cardiac postganglionic neurons.

    Science.gov (United States)

    Tu, Huiyin; Liu, Jinxu; Zhang, Dongze; Zheng, Hong; Patel, Kaushik P; Cornish, Kurtis G; Wang, Wei-Zhong; Muelleman, Robert L; Li, Yu-Long

    2014-01-15

    Chronic heart failure (CHF) is characterized by decreased cardiac parasympathetic and increased cardiac sympathetic nerve activity. This autonomic imbalance increases the risk of arrhythmias and sudden death in patients with CHF. We hypothesized that the molecular and cellular alterations of cardiac postganglionic parasympathetic (CPP) neurons located in the intracardiac ganglia and sympathetic (CPS) neurons located in the stellate ganglia (SG) possibly link to the cardiac autonomic imbalance in CHF. Rat CHF was induced by left coronary artery ligation. Single-cell real-time PCR and immunofluorescent data showed that L (Ca(v)1.2 and Ca(v)1.3), P/Q (Ca(v)2.1), N (Ca(v)2.2), and R (Ca(v)2.3) types of Ca2+ channels were expressed in CPP and CPS neurons, but CHF decreased the mRNA and protein expression of only the N-type Ca2+ channels in CPP neurons, and it did not affect mRNA and protein expression of all Ca2+ channel subtypes in the CPS neurons. Patch-clamp recording confirmed that CHF reduced N-type Ca2+ currents and cell excitability in the CPP neurons and enhanced N-type Ca2+ currents and cell excitability in the CPS neurons. N-type Ca2+ channel blocker (1 μM ω-conotoxin GVIA) lowered Ca2+ currents and cell excitability in the CPP and CPS neurons from sham-operated and CHF rats. These results suggest that CHF reduces the N-type Ca2+ channel currents and cell excitability in the CPP neurons and enhances the N-type Ca2+ currents and cell excitability in the CPS neurons, which may contribute to the cardiac autonomic imbalance in CHF.

  13. Serial measurements of high sensitive cardiac troponin I in patients with acutely decompensated heart failure treated with carperitide or nitrates.

    Science.gov (United States)

    Sato, Yukihito; Nishi, Kiyoto; Saijo, Sayaka; Tanada, Yohei; Goto, Taisuke; Takahashi, Naoki; Yamamoto, Erika; Fukuhara, Rei; Miyamoto, Tadashi; Taniguchi, Ryoji; Fujiwara, Hisayoshi; Takatsu, Yoshiki

    2010-07-01

    In patients with acutely decompensated heart failure (ADHF), elevated serum concentration of cardiac troponin is an independent predictor of adverse cardiac events. In ADHF with a preserved systolic blood pressure, treatment with intravenous vasodilator is recommended. However, the effect of vasodilators on troponin concentrations has not been elucidated well. Serial high sensitive cardiac troponin I (hs-TnI) was measured in 36 patients presenting with ADHF and preserved systolic blood pressure, of whom 20 were treated with atrial natriuretic peptide (ANP) and 16 with nitrates. The concentrations of hs-TnI ranged from 0.069+/-0.114ng/ml at baseline to 0.076+/-0.121ng/ml at 5h, 0.062+/-0.106ng/ml at 1 day, and 0.056+/-0.089ng/ml at day 7 (n=36,ns). The relative change in hs-TnI between baseline and at 5h, day 1 and day 7 were 1.13+/-0.43, 0.95+/-0.44 and 0.93+/-0.64 in patients treated with ANP, and 1.02+/-0.19, 0.95+/-0.31 and 1.19+/-1.38 in patients treated with nitrates (ns; ANP versus nitrates). On day 7, a hs-TnI change, >20% decrease from baseline, was observed in 55% patients with ANP versus 56% patients with nitrates (ns). The cardiac event rates were similar in both groups. In ADHF patients with preserved systolic blood pressure, the administration of intravenous vasodilators did not decrease hs-TnI over the first 7 days. Treatments with ANP and nitrates were associated with similar short-term decreases in hs-TnI and long-term adverse cardiac events. Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  14. Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

    Science.gov (United States)

    Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.

    2016-01-01

    Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

  15. Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure: new developments and challenges.

    Science.gov (United States)

    Finosh, G T; Jayabalan, Muthu

    2012-01-01

    Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed.

  16. Cardiac MRI and Transthoracic Echocardiography of Left Ventricular Myocardial Noncompaction in A Patient with Congestive Heart Failure: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Eui Min; Byun, Joo Nam [Chosun University Hospital College of Medicine, Gwangju (Korea, Republic of); Kim, Dong Hun [Soonchunhyang University Hospital Bucheon College of Medicine, Bucheon (Korea, Republic of)

    2010-11-15

    We report a case of a 38-year-old male presenting with new-onset dyspnea, that was diagnosed as left ventricular noncompaction by transthoracic echocardiographic and cardiac MR. The tests revealed left ventricular systolic dysfunction with prominent trabeculations associated with deep intertrabecular recesses and an enddiastolic noncompacted to compacted ratio of 2.5 in the whole apical wall and mid-ventricular anterolateral and inferolateral walls. Delayed gadolinium contrast-enhanced MRI revealed subepicardial mid-wall hyperenhancement of the midventricular anteroseptal and inferoseptal walls, which suggested myocardial fibrosis. We review the pathophysiology, clinical characteristics, and diagnostic approach of the left ventricular noncompaction associated with congestive heart failure

  17. Human atrial natriuretic peptide treatment for acute heart failure: a systematic review of efficacy and mortality.

    Science.gov (United States)

    Kobayashi, Daiki; Yamaguchi, Norihiro; Takahashi, Osamu; Deshpande, Gautam A; Fukui, Tsuguya

    2012-01-01

    The objectives of this study were to assess the effect of human atrial natriuretic peptide (hANP) treatment on physiological parameters and mortality in acute heart failure. The MEDLINE (1966-2009), EMBASE (1980-2009), Cochrane Central Register of Controlled Trials (1991-2009), American College of Physicians Journal Club (1991), Ichushi (Japana Centra Revuo Medicina) (1983-2009), Cinni (NII Scholarly and Academic Information Navigator) (1959-2009), National Diet Library Online Public Access Catalog (1969-2009), Webcat Plus (Japanese National Institute of Informatics) (1986-2009), Medical Online (1947-2009), and JST China (1981-2009) databases were searched for studies that compared the efficacy of hANP and the mortality in patients with acute heart failure with placebo controls. Only randomized controlled trials (RCTs) were included in the study. Out of 347 articles, a total of 4 studies involving 220 patients with acute heart failure fulfilled the predefined inclusion criteria. There were significant differences in the hemodynamic parameters between the hANP and placebo groups, especially in the pulmonary capillary wedge pressure (PCWP) reduction (standard mean difference [SMD] 2.07; 95% confidence interval [CI], 0.34-3.81) and the cardiac index (SMD 1.79; 95% CI, 0.12-3.47). No statistically significant differences in mortality rates were found (relative risk 1.03; 95% CI, 0.27-3.92). In a limited number of studies, hANP appears to improve several hemodynamic parameters, including pulmonary capillary wedge pressure and cardiac index, but not mortality. Further high-quality studies are needed to corroborate these results. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  18. Mechanical stretch up-regulates the B-type natriuretic peptide system in human cardiac fibroblasts: a possible defense against transforming growth factor-ß mediated fibrosis

    LENUS (Irish Health Repository)

    Watson, Chris J

    2012-07-07

    AbstractBackgroundMechanical overload of the heart is associated with excessive deposition of extracellular matrix proteins and the development of cardiac fibrosis. This can result in reduced ventricular compliance, diastolic dysfunction, and heart failure. Extracellular matrix synthesis is regulated primarily by cardiac fibroblasts, more specifically, the active myofibroblast. The influence of mechanical stretch on human cardiac fibroblasts’ response to pro-fibrotic stimuli, such as transforming growth factor beta (TGFβ), is unknown as is the impact of stretch on B-type natriuretic peptide (BNP) and natriuretic peptide receptor A (NPRA) expression. BNP, acting via NPRA, has been shown to play a role in modulation of cardiac fibrosis.Methods and resultsThe effect of cyclical mechanical stretch on TGFβ induction of myofibroblast differentiation in primary human cardiac fibroblasts and whether differences in response to stretch were associated with changes in the natriuretic peptide system were investigated. Cyclical mechanical stretch attenuated the effectiveness of TGFβ in inducing myofibroblast differentiation. This finding was associated with a novel observation that mechanical stretch can increase BNP and NPRA expression in human cardiac fibroblasts, which could have important implications in modulating myocardial fibrosis. Exogenous BNP treatment further reduced the potency of TGFβ on mechanically stretched fibroblasts.ConclusionWe postulate that stretch induced up-regulation of the natriuretic peptide system may contribute to the observed reduction in myofibroblast differentiation.

  19. The diagnosis of anthracycline-induced cardiac damage and heart failure

    Directory of Open Access Journals (Sweden)

    Jarosław Dudka

    2009-05-01

    Full Text Available Routine examinations during chemotherapy containing anthracyclines evaluate heart function before treatment and monitor cardiotoxic effects during and after therapy. A number of methods are useful in cardiac assessment, including electrocardiography, radiology techniques (RTG, CT, MRI, PET-CT, PET-MRI, echocardiography, radioisotope imaging techniques (scyntygraphy, MUGA, PET, and ultra-structure evaluation in biopsy samples. Nevertheless, there is a continuous need for new methods to predict future damage at the initial stages of cardiac changes. In recent years the therapeutic usefulness of biochemical blood parameters in anthracycline-treated patients has been assessed. The levels of cardiac troponines (cTnI, cTnT, natriuretic peptides (ANP, BNP, and endothelin 1 have been included in the studies. Heart-type fatty acid binding protein (H-FABP is another promising factor showing cardiomyocytic impairment. However, the clinical use of biochemical parameters in diagnosing anthracycline-related cardiotoxicity is still a controversial issue.

  20. Effects of valsartan combined with atorvastatin on cardiac function, myocardial enzymes and thyroxine levels in patients with chronic heart failure

    Directory of Open Access Journals (Sweden)

    Xiao-Gang Wang1

    2017-04-01

    Full Text Available Objective: To observe the effects of valsartan combined with atorvastatin on cardiac function, myocardial enzymes and thyroxine levels in patients with chronic heart failure (CHF. Methods: 90 cases of CHF cases were divided into observation group and control group according to the order of single and double number, 45 cases each. In the control group, atorvastatin was given on the basis of conventional therapy, and the observation group was given valsartan on the basis of the control group. After 6 months, the differences of cardiac function indexes (LVEF, LVEDD, LVESD, E/A, myocardial enzymes (LDH, AST, CK, CKMB and thyroxine (TT3, TT4, FT3, FT4, TSH in the two groups were observed. Results: After treatment, LVEF and E/A in both groups increased significantly (P0.05, the observation group TT3 and FT3 were respectively (1.37±0.33 mol/L and (2.61±0.69 pmol/L , higher than the control group, the difference was statistically significant (P<0.05. Conclusion: valsartan combined with atorvastatin in the treatment of CHF, can improve cardiac function and myocardial protection effect, and can effectively promote the recovery of thyroid hormone levels, better than the single use of atorvastatin.

  1. Effects of cardiac energy efficiency in diastolic heart failure. Assessment with positron emission tomography with 11C-acetate

    International Nuclear Information System (INIS)

    Hasegawa, Shinji; Yamamoto, Kazuhiro; Sakata, Yasushi; Takeda, Yasuharu; Kajimoto, Katsufumi; Kanai, Yasukazu; Hori, Masatsugu; Hatazawa, Jun

    2008-01-01

    Diastolic heart failure (DHF) has become a high social burden, and its major underlying cardiovascular disease is hypertensive heart disease. However, the pathogenesis of DHF remains to be clarified. This study aimed to assess the effects of cardiac energy efficiency in DHF patients. 11 C-Acetate positron emission tomography and echocardiography were conducted in 11 DHF Japanese patients and 10 normal volunteers. The myocardial clearance rate of radiolabeled 11 C-acetate was measured to calculate the work metabolic index (WMI), an index of cardiac efficiency. The ratio of peak mitral E wave velocity to peak early diastolic septal myocardial velocity (E/e') was calculated to assess left ventricular (LV) filling pressure. The LV mass index was greater and the mean age was higher in the DHF patients than in the normal volunteers. There was no difference in WMI between the two groups. However, WMI varied widely among the DHF patients and was inversely correlated with E/e' (r=-0.699, p=0.017). In contrast, there was no correlation in the normal volunteers. In conclusion, the inefficiency of energy utilization is not a primary cause of diastolic dysfunction or DHF, and cardiac efficiency may not affect diastolic function in normal hearts. However, the energy-wasting state may induce the elevation of LV filling pressure in DHF patients, which was considered to principally result from the progressive diastolic dysfunction. (author)

  2. Predictors of response to cardiac resynchronization therapy in chronic heart failure patients

    Directory of Open Access Journals (Sweden)

    Mohamed Loutfi

    2016-12-01

    Full Text Available Cardiac resynchronization therapy (CRT is established in the management patients with moderate to severe symptoms due to left ventricular systolic dysfunction who present with signs of electrical dyssynchrony. There is wide variability in the clinical response and improvement in LVEF with CRT. Prediction of response to CRT is an important goal in order to tailor this therapy to patients most apt to derive benefit. Aim: The aim of the study was to assess and identify the best predictors of CRT response. Patients and methods: The study included 170 consecutive heart failure (HF patients in New York Heart Association (NYHA functional class III or IV and LVEF ⩽ 35%. Routine device and clinical follow-up, as well as CRT optimization, were performed at baseline and at 3-month intervals. Responders were defined as having an absolute reduction in left ventricular end-systolic diameter >15% and an improvement in LVEF >10%. Results: 170 patients were included [71.1% men; mean age 68.8 ± 9.7 years; 159 patients NYHA class III, 11 patients ambulatory NYHA class IV; 91 patients had non-ischemic cardiomyopathy (ICM – 79 patients had ICM; 55.3% of patients had LBBB; mean QRS duration 145 ± 25 ms; left ventricular ejection fraction 28.38 ± 7.2]. CRT-P was implanted in 65 patients and CRT-D was implanted in 105 patients. CRT response was achieved in 114 patients (67.1%. Mean LVEF improved from 28.38 ± 7.2% to 35.46 ± 9.3% (p = 0.001, mean LV end-diastolic diameter reduced from 67.91 ± 8.7 to 64.95 ± 8.9 mm (p 150 ms, non-ICM, TAPSE >15 mm, sinus rhythm, the absence of COPD and the absence of renal disease were the independent predictors of CRT response. We generated a new CRT score to predict responders to CRT. The score consists of maximum 9 points. The CRT response rate has been markedly different according to the CRT score: CRT response rate was 97.5% patients with CRT score >6 vs 40.7% if CRT score <6, p < 0

  3. Failure to diagnose cardiac treatment rejection with Tc99m-PYP images

    International Nuclear Information System (INIS)

    McKillop, J.H.; McDougall, I.R.; Goris, M.L.; Mason, J.W.; Reitz, B.A.

    1981-01-01

    The possibility of diagnosing transplant rejection using Tc-99m-PYP imaging was examined in 12 cardiac transplant recipients. Two patients were studied on two occasions. The presence or absence of active rejection was established by endomyocardial biopsy. The intensity and pattern of myocardial uptake of the tracer did not differ significantly in the two patients studied at the time of rejection compared to the remainder. It is concluded that a single Tc-99m-PYP study cannot be used to diagnose cardiac transplant rejection

  4. Positive pressure ventilation in the management of acute and chronic cardiac failure: a systematic review and meta-analysis.

    Science.gov (United States)

    Nadar, Sunil; Prasad, Neeraj; Taylor, Rod S; Lip, Gregory Y H

    2005-03-18

    Chronic heart failure (CHF) is a common condition and is associated with excess morbidity and mortality, in spite of the many advances in its treatment. Chronic stable heart failure is also associated with an increased incidence of sleep-related breathing disorders, such as central sleep apnoea (CSA) and Cheyne Stokes respiration (CSR). Continuous positive airways pressure (CPAP) has been shown to alleviate the symptoms of CHF, improve left ventricular function and oxygenation. To a certain extent, CPAP also abolishes sleep-related breathing disorders in patients with chronic heart failure. In patients with acute pulmonary oedema, the use of positive pressure ventilation improves cardiac haemodynamic indices, as well as symptoms and oxygenation, and is associated with a lower need for intubation. However, some studies have cast doubts about its safety and suggest a higher rate of myocardial infarction associated with its use. In our opinion, non-invasive positive pressure ventilation and CPAP offers an adjunctive mode of therapy in patients with acute pulmonary oedema and chronic heart failure, who may not be suitable for intubation and in those not responsive to conventional therapies. Non-invasive ventilation also helps to improve oxygenation in those patients with exhaustion and respiratory acidosis. Many trials are still ongoing and the results of these studies would throw more light on the present role of non-invasive ventilation in the management of CHF.

  5. Cardiac Ablation of Rheb1 Induces Impaired Heart Growth, Endoplasmic Reticulum-Associated Apoptosis and Heart Failure in Infant Mice

    Science.gov (United States)

    Cao, Yunshan; Tao, Lichan; Shen, Shutong; Xiao, Junjie; Wu, Hang; Li, Beibei; Wu, Xiangqi; Luo, Wen; Xiao, Qi; Hu, Xiaoshan; Liu, Hailang; Nie, Junwei; Lu, Shuangshuang; Yuan, Baiyin; Han, Zhonglin; Xiao, Bo; Yang, Zhongzhou; Li, Xinli

    2013-01-01

    Ras homologue enriched in brain 1 (Rheb1) plays an important role in a variety of cellular processes. In this study, we investigate the role of Rheb1 in the post-natal heart. We found that deletion of the gene responsible for production of Rheb1 from cardiomyocytes of post-natal mice resulted in malignant arrhythmias, heart failure, and premature death of these mice. In addition, heart growth impairment, aberrant metabolism relative gene expression, and increased cardiomyocyte apoptosis were observed in Rheb1-knockout mice prior to the development of heart failure and arrhythmias. Also, protein kinase B (PKB/Akt) signaling was enhanced in Rheb1-knockout mice, and removal of phosphatase and tensin homolog (Pten) significantly prolonged the survival of Rheb1-knockouts. Furthermore, signaling via the mammalian target of rapamycin complex 1 (mTORC1) was abolished and C/EBP homologous protein (CHOP) and phosphorylation levels of c-Jun N-terminal kinase (JNK) were increased in Rheb1 mutant mice. In conclusion, this study demonstrates that Rheb1 is important for maintaining cardiac function in post-natal mice via regulation of mTORC1 activity and stress on the endoplasmic reticulum. Moreover, activation of Akt signaling helps to improve the survival of mice with advanced heart failure. Thus, this study provides direct evidence that Rheb1 performs multiple important functions in the heart of the post-natal mouse. Enhancing Akt activity improves the survival of infant mice with advanced heart failure. PMID:24351823

  6. High Intensity Interval and Endurance Training Have Opposing Effects on Markers of Heart Failure and Cardiac Remodeling in Hypertensive Rats

    Science.gov (United States)

    Holloway, Tanya M.; Bloemberg, Darin; da Silva, Mayne L.; Simpson, Jeremy A.; Quadrilatero, Joe; Spriet, Lawrence L.

    2015-01-01

    There has been re-emerging interest and significant work dedicated to investigating the metabolic effects of high intensity interval training (HIIT) in recent years. HIIT is considered to be a time efficient alternative to classic endurance training (ET) that elicits similar metabolic responses in skeletal muscle. However, there is a lack of information on the impact of HIIT on cardiac muscle in disease. Therefore, we determined the efficacy of ET and HIIT to alter cardiac muscle characteristics involved in the development of diastolic dysfunction, such as ventricular hypertrophy, fibrosis and angiogenesis, in a well-established rodent model of hypertension-induced heart failure before the development of overt heart failure. ET decreased left ventricle fibrosis by ~40% (P HIIT did not decrease existing fibrosis, and HIIT animals displayed a 20% increase in left ventricular mass (PHIIT also increased brain natriuretic peptide by 50% (PHIIT promoted a pathological adaptation in the left ventricle in the presence of hypertension, highlighting the need for further research on the widespread effects of HIIT in the presence of disease. PMID:25803693

  7. Reduced peripheral arterial blood flow with preserved cardiac output during submaximal bicycle exercise in elderly heart failure

    Directory of Open Access Journals (Sweden)

    Leng Xiaoyan

    2009-11-01

    Full Text Available Abstract Background Older heart failure (HF patients exhibit exercise intolerance during activities of daily living. We hypothesized that reduced lower extremity blood flow (LBF due to reduced forward cardiac output would contribute to submaximal exercise intolerance in older HF patients. Methods and Results Twelve HF patients both with preserved and reduced left ventricular ejection fraction (LVEF (aged 68 ± 10 years without large (aorta or medium sized (iliac or femoral artery vessel atherosclerosis, and 13 age and gender matched healthy volunteers underwent a sophisticated battery of assessments including a peak exercise oxygen consumption (peak VO2, b physical function, c cardiovascular magnetic resonance (CMR submaximal exercise measures of aortic and femoral arterial blood flow, and d determination of thigh muscle area. Peak VO2 was reduced in HF subjects (14 ± 3 ml/kg/min compared to healthy elderly subjects (20 ± 6 ml/kg/min (p = 0.01. Four-meter walk speed was 1.35 ± 0.24 m/sec in healthy elderly verses 0.98 ± 0.15 m/sec in HF subjects (p p ≤ 0.03. Conclusion During CMR submaximal bike exercise in the elderly with heart failure, mechanisms other than low cardiac output are responsible for reduced lower extremity blood flow.

  8. Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

    Science.gov (United States)

    Luo, Da; Hu, Huihui; Qin, Zhiliang; Liu, Shan; Yu, Xiaomei; Ma, Ruisong; He, Wenbo; Xie, Jing; Lu, Zhibing; He, Bo; Jiang, Hong

    2017-12-01

    Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. High intensity interval and endurance training have opposing effects on markers of heart failure and cardiac remodeling in hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Tanya M Holloway

    Full Text Available There has been re-emerging interest and significant work dedicated to investigating the metabolic effects of high intensity interval training (HIIT in recent years. HIIT is considered to be a time efficient alternative to classic endurance training (ET that elicits similar metabolic responses in skeletal muscle. However, there is a lack of information on the impact of HIIT on cardiac muscle in disease. Therefore, we determined the efficacy of ET and HIIT to alter cardiac muscle characteristics involved in the development of diastolic dysfunction, such as ventricular hypertrophy, fibrosis and angiogenesis, in a well-established rodent model of hypertension-induced heart failure before the development of overt heart failure. ET decreased left ventricle fibrosis by ~40% (P < 0.05, and promoted a 20% (P<0.05 increase in the left ventricular capillary/fibre ratio, an increase in endothelial nitric oxide synthase protein (P<0.05, and a decrease in hypoxia inducible factor 1 alpha protein content (P<0.05. In contrast, HIIT did not decrease existing fibrosis, and HIIT animals displayed a 20% increase in left ventricular mass (P<0.05 and a 20% decrease in cross sectional area (P<0.05. HIIT also increased brain natriuretic peptide by 50% (P<0.05, in the absence of concomitant angiogenesis, strongly suggesting pathological cardiac remodeling. The current data support the longstanding belief in the effectiveness of ET in hypertension. However, HIIT promoted a pathological adaptation in the left ventricle in the presence of hypertension, highlighting the need for further research on the widespread effects of HIIT in the presence of disease.

  10. Identification of failure sequences sensitive to human error

    International Nuclear Information System (INIS)

    1987-06-01

    This report prepared by the participants of the technical committee meeting on ''Identification of Failure Sequences Sensitive to Human Error'' addresses the subjects discussed during the meeting and the conclusions reached by the committee. Chapter 1 reviews the INSAG recommendations and the main elements of the IAEA Programme in the area of human element. In Chapter 2 the role of human actions in nuclear power plants safety from insights of operational experience is reviewed. Chapter 3 is concerned with the relationship between probabilistic safety assessment and human performance associated with severe accident sequences. Chapter 4 addresses the role of simulators in view of training for accident conditions. Chapter 5 presents the conclusions and future trends. The seven papers presented by members of this technical committee are also included in this technical document. A separate abstract was prepared for each of these papers

  11. Neurohormonal activation and diagnostic value of cardiac peptides in patients with suspected mild heart failure

    DEFF Research Database (Denmark)

    Mikkelsen, Kirsten V.; Bie, Peter; Møller, Jacob E.

    2006-01-01

    accuracy of cardiac peptides to detect any left ventricular dysfunction (LVD) in patients referred from primary care with suspected HF before institution of medical therapy. METHODS: Of 166 referred patients 150 were consecutively included (14 were excluded and two refused consent). Echocardiography...

  12. Diabetes Mellitus, Microalbuminuria, and Subclinical Cardiac Disease: Identification and Monitoring of Individuals at Risk of Heart Failure.

    Science.gov (United States)

    Swoboda, Peter P; McDiarmid, Adam K; Erhayiem, Bara; Ripley, David P; Dobson, Laura E; Garg, Pankaj; Musa, Tarique A; Witte, Klaus K; Kearney, Mark T; Barth, Julian H; Ajjan, Ramzi; Greenwood, John P; Plein, Sven

    2017-07-17

    Patients with type 2 diabetes mellitus and elevated urinary albumin:creatinine ratio (ACR) have increased risk of heart failure. We hypothesized this was because of cardiac tissue changes rather than silent coronary artery disease. In a case-controlled observational study 130 subjects including 50 ACR+ve diabetes mellitus patients with persistent microalbuminuria (ACR >2.5 mg/mol in males and >3.5 mg/mol in females, ≥2 measurements, no previous renin-angiotensin-aldosterone therapy, 50 ACR-ve diabetes mellitus patients and 30 controls underwent cardiovascular magnetic resonance for investigation of myocardial fibrosis, ischemia and infarction, and echocardiography. Thirty ACR+ve patients underwent further testing after 1-year treatment with renin-angiotensin-aldosterone blockade. Cardiac extracellular volume fraction, a measure of diffuse fibrosis, was higher in diabetes mellitus patients than controls (26.1±3.4% and 23.3±3.0% P =0.0002) and in ACR+ve than ACR-ve diabetes mellitus patients (27.2±4.1% versus 25.1±2.9%, P =0.004). ACR+ve patients also had lower E' measured by echocardiography (8.2±1.9 cm/s versus 8.9±1.9 cm/s, P =0.04) and elevated high-sensitivity cardiac troponin T 18% versus 4% ≥14 ng/L ( P =0.05). Rate of silent myocardial ischemia or infarction were not influenced by ACR status. Renin-angiotensin-aldosterone blockade was associated with increased left ventricular ejection fraction (59.3±7.8 to 61.5±8.7%, P =0.03) and decreased extracellular volume fraction (26.5±3.6 to 25.2±3.1, P =0.01) but no changes in diastolic function or high-sensitivity cardiac troponin T levels. Asymptomatic diabetes mellitus patients with persistent microalbuminuria have markers of diffuse cardiac fibrosis including elevated extracellular volume fraction, high-sensitivity cardiac troponin T, and diastolic dysfunction, which may in part be reversible by renin-angiotensin-aldosterone blockade. Increased risk in these patients may be mediated by

  13. Isolated Non-Compaction of the Left Ventricle in a Patient with New-Onset Heart Failure: Morphologic and Functional Evaluation with Cardiac Multidetector Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Heon [Soonchuhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Kim, Seok Yeon [Seoul Medical Center, Seoul (Korea, Republic of); Schoepf, U. Joseph [Medical University of South Carolina, SC (United States)

    2012-03-15

    We describe a case of new-onset heart failure in a patient in whom cardiac CT enabled the non-invasive diagnosis of isolated non-compaction and associated functional abnormalities of the left ventricle with the concomitant evaluation of coronary arteries. This case highlights the utility of cardiac CT for the morphological and functional evaluation of the heart as a single imaging modality.

  14. De Novo Human Cardiac Myocytes for Medical Research: Promises and Challenges

    Directory of Open Access Journals (Sweden)

    Veronique Hamel

    2017-01-01

    Full Text Available The advent of cellular reprogramming technology has revolutionized biomedical research. De novo human cardiac myocytes can now be obtained from direct reprogramming of somatic cells (such as fibroblasts, from induced pluripotent stem cells (iPSCs, which are reprogrammed from somatic cells, and from human embryonic stem cells (hESCs. Such de novo human cardiac myocytes hold great promise for in vitro disease modeling and drug screening and in vivo cell therapy of heart disease. Here, we review the technique advancements for generating de novo human cardiac myocytes. We also discuss several challenges for the use of such cells in research and regenerative medicine, such as the immature phenotype and heterogeneity of de novo cardiac myocytes obtained with existing protocols. We focus on the recent advancements in addressing such challenges.

  15. Effect of milrinone on the cardiac function and N-terminal pro-brain natriuretic peptide levels in patients with senile refractory heart failure

    Directory of Open Access Journals (Sweden)

    Jiao-Na Wei1

    2017-06-01

    Full Text Available Objective: To study the effect of milrinone on the cardiac function and N-terminal probrain natriuretic peptide (NT-proBNP levels in patients with senile refractory heart failure. Methods: 90 patients with senile refractory heart failure who were treated in our hospital between August 2013 and August 2016 were collected and divided into control group (n=45 and observation group (n=45 according to the random number table. The control group received regular clinical treatment, and the observation group received regular + milrinone treatment. The cardiac function and serum NT-proBN contents were compared between two groups of patients before and after treatment. Results: Before treatment, the differences in ultrasound and serum cardiac function indexes and serum NT-proBN levels were not statistically significant between two groups of patients. After treatment, ultrasound serum cardiac function parameter LVEDD level in observation group was lower than that in control group while CI and SV levels were higher than those in control group; serum cardiac function indexes Cys-C, GDF-15, sST2 and H-FABP contents were lower than those in control group; serum NT-proBNP content was lower than that in control group. Conclusion: Milrinone therapy can optimize the cardiac function and reduce the serum NT-proBN levels in patients with senile refractory heart failure.

  16. Cardiac-Derived Extracellular Matrix Enhances Cardiogenic Properties of Human Cardiac Progenitor Cells

    NARCIS (Netherlands)

    Gaetani, Roberto; Yin, Christopher; Srikumar, Neha; Braden, Rebecca; Doevendans, Pieter A; Sluijter, Joost P G; Christman, Karen L

    2016-01-01

    The use of biomaterials has been demonstrated as a viable strategy to promote cell survival and cardiac repair. However, limitations on combinational cell-biomaterial therapies exist, as cellular behavior is influenced by the microenvironment and physical characteristics of the material. Among the

  17. Impact of etiology on the outcomes in heart failure patients treated with cardiac resynchronization therapy: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yanmei Chen

    Full Text Available BACKGROUND: Cardiac resynchronization therapy (CRT has been extensively demonstrated to benefit heart failure patients, but the role of underlying heart failure etiology in the outcomes was not consistently proven. This meta-analysis aimed to determine whether efficacy and effectiveness of CRT is affected by underlying heart failure etiology. METHODS AND RESULTS: Searches of MEDLINE, EMBASE and Cochrane databases were conducted to identify RCTs and observational studies that reported clinical and functional outcomes of CRT in ischemic cardiomyopathy (ICM and non-ischemic cardiomyopathy (NICM patients. Efficacy of CRT was assessed in 7 randomized controlled trials (RCTs with 7072 patients and effectiveness of CRT was evaluated in 14 observational studies with 3463 patients In the pooled analysis of RCTs, we found that CRT decreased mortality or heart failure hospitalization by 29% in ICM patients (95% confidence interval [CI], 21% to 35%, and by 28% (95% CI, 18% to 37% in NICM patients. No significant difference was observed between the 2 etiology groups (P = 0.55. In the pooled analysis of observational studies, however, we found that ICM patients had a 54% greater risk for mortality or HF hospitalization than NICM patients (relative risk: 1.54; 95% CI: 1.30-1.83; P<0.001. Both RCTs and observational studies demonstrated that NICM patients had greater echocardiographic improvements in the left ventricular ejection fraction and end-systolic volume, as compared with ICM patients (both P<0.001. CONCLUSION: CRT might reduce mortality or heart failure hospitalization in both ICM and NICM patients similarly. The improvement of the left ventricular function and remodeling is greater in NICM patients.

  18. Molecular and cellular characterization of cardiac overload-induced hypertrophy and failure

    NARCIS (Netherlands)

    Umar, Soban

    2009-01-01

    In neonatal rat ventricular cardiomyocytes (NRVCs), we activated integrins by RGD to test whether integrin stimulation produced hypertrophy. Effect of RGD was compared with pro-hypertrophic effects of phenylephrine (chapter 2). Ventricular failure is associated with disturbed collagen turnover.

  19. The cognitive basis of effective team performance: features of failure and success in simulated cardiac resuscitation.

    Science.gov (United States)

    Shetty, Pallavi; Cohen, Trevor; Patel, Bhavesh; Patel, Vimla L

    2009-11-14

    Despite a body of research on teams in other fields relatively little is known about measuring teamwork in healthcare. The aim of this study is to characterize the qualitative dimensions of team performance during cardiac resuscitation that results in good and bad outcomes. We studied each team's adherence to Advanced Cardiac Life Support (ACLS) protocol for ventricular fibrillation/tachycardia and identified team behaviors during simulated critical events that affected their performance. The process was captured by a developed task checklist and a validated team work coding system. Results suggest that deviation from the sequence suggested by the ACLS protocol had no impact on the outcome as the successful team deviated more from this sequence than the unsuccessful team. It isn't the deviation from the protocol per se that appears to be important, but how the leadership flexibly adapts to the situational changes with deviations is the crucial factor in team competency.

  20. Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects

    Science.gov (United States)

    Koh, J.; Brown, T. E.; Beightol, L. A.; Ha, C. Y.; Eckberg, D. L.

    1994-01-01

    1. We studied eight young men (age range: 20-37 years) with chronic, clinically complete high cervical spinal cord injuries and ten age-matched healthy men to determine how interruption of connections between the central nervous system and spinal sympathetic motoneurones affects autonomic cardiovascular control. 2. Baseline diastolic pressures and R-R intervals (heart periods) were similar in the two groups. Slopes of R-R interval responses to brief neck pressure changes were significantly lower in tetraplegic than in healthy subjects, but slopes of R-R interval responses to steady-state arterial pressure reductions and increases were comparable. Plasma noradrenaline levels did not change significantly during steady-state arterial pressure reductions in tetraplegic patients, but rose sharply in healthy subjects. The range of arterial pressure and R-R interval responses to vasoactive drugs (nitroprusside and phenylephrine) was significantly greater in tetraplegic than healthy subjects. 3. Resting R-R interval spectral power at respiratory and low frequencies was similar in the two groups. During infusions of vasoactive drugs, low-frequency R-R interval spectral power was directly proportional to arterial pressure in tetraplegic patients, but was unrelated to arterial pressure in healthy subjects. Vagolytic doses of atropine nearly abolished both low- and respiratory-frequency R-R interval spectral power in both groups. 4. Our conclusions are as follows. First, since tetraplegic patients have significant levels of low-frequency arterial pressure and R-R interval spectral power, human Mayer arterial pressure waves may result from mechanisms that do not involve stimulation of spinal sympathetic motoneurones by brainstem neurones. Second, since in tetraplegic patients, low-frequency R-R interval spectral power is proportional to arterial pressure, it is likely to be mediated by a baroreflex mechanism. Third, since low-frequency R-R interval rhythms were nearly abolished

  1. High-sensitivity cardiac troponin I and risk of heart failure in patients with suspected acute coronary syndrome: a cohort study.

    Science.gov (United States)

    Stelzle, Dominik; Shah, Anoop S V; Anand, Atul; Strachan, Fiona E; Chapman, Andrew R; Denvir, Martin A; Mills, Nicholas L; McAllister, David A

    2018-01-01

    Heart failure may occur following acute myocardial infarction, but with the use of high-sensitivity cardiac troponin assays we increasingly diagnose patients with minor myocardial injury. Whether troponin concentrations remain a useful predictor of heart failure in patients with acute coronary syndrome is uncertain. We identified all consecutive patients (n = 4748) with suspected acute coronary syndrome (61 ± 16 years, 57% male) presenting to three secondary and tertiary care hospitals. Cox-regression models were used to evaluate the association between high-sensitivity cardiac troponin I concentration and subsequent heart failure hospitalization. C-statistics were estimated to evaluate the predictive value of troponin for heart failure hospitalization. Over 2071 years of follow-up there were 83 heart failure hospitalizations. Patients with troponin concentrations above the upper reference limit (URL) were more likely to be hospitalized with heart failure than patients below the URL (118/1000 vs. 17/1000 person years, adjusted hazard ratio: 7.0). Among patients with troponin concentrations acute coronary syndrome. The strongest associations were observed in patients with troponin concentrations in the normal reference range, in whom high-sensitivity cardiac troponin assays identify those at increased risk of heart failure who may benefit from further investigation and treatment. © The Author 2017. Published on behalf of the European Society of Cardiology

  2. Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model

    Science.gov (United States)

    Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo

    2017-01-01

    Background Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. Methods The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. Results The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. Conclusion The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients. PMID:29020031

  3. Relationship between quantitative cardiac neuronal imaging with ¹²³I-meta-iodobenzylguanidine and hospitalization in patients with heart failure.

    Science.gov (United States)

    Parker, Matthew W; Sood, Nitesh; Ahlberg, Alan W; Jacobson, Arnold F; Heller, Gary V; Lundbye, Justin B

    2014-09-01

    Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by (123)I-meta-iodobenzylguanidine ((123)I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between (123)I-mIBG imaging findings and hospitalization. Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using (123)I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression. During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 - 2.0; p = 0.02). The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships.

  4. Contribution of two-pore K+ channels to cardiac ventricular action potential revealed using human iPSC-derived cardiomyocytes.

    Science.gov (United States)

    Chai, Sam; Wan, Xiaoping; Nassal, Drew M; Liu, Haiyan; Moravec, Christine S; Ramirez-Navarro, Angelina; Deschênes, Isabelle

    2017-06-01

    Two-pore K + (K 2p ) channels have been described in modulating background conductance as leak channels in different physiological systems. In the heart, the expression of K 2p channels is heterogeneous with equivocation regarding their functional role. Our objective was to determine the K 2p expression profile and their physiological and pathophysiological contribution to cardiac electrophysiology. Induced pluripotent stem cells (iPSCs) generated from humans were differentiated into cardiomyocytes (iPSC-CMs). mRNA was isolated from these cells, commercial iPSC-CM (iCells), control human heart ventricular tissue (cHVT), and ischemic (iHF) and nonischemic heart failure tissues (niHF). We detected 10 K 2p channels in the heart. Comparing quantitative PCR expression of K 2p channels between human heart tissue and iPSC-CMs revealed K 2p 1.1, K 2p 2.1, K 2p 5.1, and K 2p 17.1 to be higher expressed in cHVT, whereas K 2p 3.1 and K 2p 13.1 were higher in iPSC-CMs. Notably, K 2p 17.1 was significantly lower in niHF tissues compared with cHVT. Action potential recordings in iCells after K 2p small interfering RNA knockdown revealed prolongations in action potential depolarization at 90% repolarization for K 2p 2.1, K 2p 3.1, K 2p 6.1, and K 2p 17.1. Here, we report the expression level of 10 human K 2p channels in iPSC-CMs and how they compared with cHVT. Importantly, our functional electrophysiological data in human iPSC-CMs revealed a prominent role in cardiac ventricular repolarization for four of these channels. Finally, we also identified K 2p 17.1 as significantly reduced in niHF tissues and K 2p 4.1 as reduced in niHF compared with iHF. Thus, we advance the notion that K 2p channels are emerging as novel players in cardiac ventricular electrophysiology that could also be remodeled in cardiac pathology and therefore contribute to arrhythmias. NEW & NOTEWORTHY Two-pore K + (K 2p ) channels are traditionally regarded as merely background leak channels in myriad

  5. Regional and ethnic differences among patients with heart failure in Asia: the Asian sudden cardiac death in heart failure registry.

    Science.gov (United States)

    Lam, Carolyn S P; Teng, Tiew-Hwa Katherine; Tay, Wan Ting; Anand, Inder; Zhang, Shu; Shimizu, Wataru; Narasimhan, Calambur; Park, Sang Weon; Yu, Cheuk-Man; Ngarmukos, Tachapong; Omar, Razali; Reyes, Eugene B; Siswanto, Bambang B; Hung, Chung-Lieh; Ling, Lieng H; Yap, Jonathan; MacDonald, Michael; Richards, A Mark

    2016-11-01

    To characterize regional and ethnic differences in heart failure (HF) across Asia. We prospectively studied 5276 patients with stable HF and reduced ejection fraction (≤40%) from 11 Asian regions (China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan, and Thailand). Mean age was 59.6 ± 13.1 years, 78.2% were men, and mean body mass index was 24.9 ± 5.1 kg/m 2 . Majority (64%) of patients had two or more comorbid conditions such as hypertension (51.9%), coronary artery disease (CAD, 50.2%), or diabetes (40.4%). The prevalence of CAD was highest in Southeast Asians (58.8 vs. 38.2% in Northeast Asians). Compared with Chinese ethnicity, Malays (adjusted odds ratio [OR] 1.97, 95% CI 1.63-2.38) and Indians (OR 1.44, 95% CI 1.24-1.68) had higher odds of CAD, whereas Koreans (OR 0.38, 95% CI 0.29-0.50) and Japanese (OR 0.44, 95% CI 0.36-0.55) had lower odds. The prevalence of hypertension and diabetes was highest in Southeast Asians (64.2 and 49.3%, respectively) and high-income regions (59.7 and 46.2%, respectively). There was significant interaction between ethnicity and region, where the adjusted odds were 3.95 (95% CI 2.51-6.21) for hypertension and 4.91 (95% CI 3.07-7.87) for diabetes among Indians from high- vs. low-income regions; and 2.60 (95% CI 1.66-4.06) for hypertension and 2.62 (95% CI 1.73-3.97) for diabetes among Malays from high- vs. low-income regions. These first prospective multi-national data from Asia highlight the significant heterogeneity among Asian patients with stable HF, and the important influence of both ethnicity and regional income level on patient characteristics. NCT01633398. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  6. Mechanisms of initial endplate failure in the human vertebral body.

    Science.gov (United States)

    Fields, Aaron J; Lee, Gideon L; Keaveny, Tony M

    2010-12-01

    Endplate failure occurs frequently in osteoporotic vertebral fractures and may be related to the development of high tensile strain. To determine whether the highest tensile strains in the vertebra occur in the endplates, and whether such high tensile strains are associated with the material behavior of the intervertebral disc, we used micro-CT-based finite element analysis to assess tissue-level strains in 22 elderly human vertebrae (81.5 ± 9.6 years) that were compressed through simulated intervertebral discs. In each vertebra, we compared the highest tensile and compressive strains across the different compartments: endplates, cortical shell, and trabecular bone. The influence of Poisson-type expansion of the disc on the results was determined by compressing the vertebrae a second time in which we suppressed the Poisson expansion. We found that the highest tensile strains occurred within the endplates whereas the highest compressive strains occurred within the trabecular bone. The ratio of strain to assumed tissue-level yield strain was the highest for the endplates, indicating that the endplates had the greatest risk of initial failure. Suppressing the Poisson expansion of the disc decreased the amount of highly tensile-strained tissue in the endplates by 79.4 ± 11.3%. These results indicate that the endplates are at the greatest risk of initial failure due to the development of high tensile strains, and that such high tensile strains are associated with the Poisson expansion of the disc. We conclude that initial failure of the vertebra is associated with high tensile strains in the endplates, which in turn are influenced by the material behavior of the disc. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Possible genetic implications in the response to cardiac resynchronisation therapy in a patient affected by heart failure

    Directory of Open Access Journals (Sweden)

    Natalia Pezzali

    2011-06-01

    Full Text Available This report presents a case of a patient with idiopathic dilated cardiomyopathy and severe left ventricular systolic dysfunction who underwent cardiac resynchronisation therapy (CRT. During the follow-up a progressive increase in left ventricular ejection fraction was observed, as well as clinical improvement. No cardiovascular events occurred during the follow-up, except for appropriate Implantable Cardioverter Defibrillator (ICD bursts for fast ventricular tachycardia. Genotyping for adrenoceptor gene polymorphisms detected that the patient was Glu27Glu homozygous carrier. There’s a large interindividual variability in response to CRT. Despite attempts to identify factors having an impact on this therapy, only QRS duration is accepted according to guidelines. Beta-adrenoceptors polymorphisms, modulating sympathetic drive in heart failure and left ventricular remodelling, may have a role in identifying patients with a better response to CRT, in order to target and individualise the patients’ treatment.

  8. Why did high-dose rosuvastatin not improve cardiac remodeling in chronic heart failure? Mechanistic insights from the UNIVERSE study.

    Science.gov (United States)

    Ashton, Emma; Windebank, Emma; Skiba, Marina; Reid, Christopher; Schneider, Hans; Rosenfeldt, Franklin; Tonkin, Andrew; Krum, Henry

    2011-02-03

    Statins are often prescribed for prevention of atherosclerotic outcomes in patients who have chronic heart failure (CHF), if this has an ischaemic etiology. These agents may also possess additional properties, independent of effects on blood lipid levels, which may have an effect on cardiac remodeling. However, beneficial effects were not observed in the recent UNIVERSE trial. We prospectively planned a sub-study of UNIVERSE to explore relevant mechanistic effects of rosuvastatin, including effects on collagen turnover and plasma coenzyme Q10 (CoQ) levels. Additionally, CoQ levels in CHF patients receiving chronic statin therapy were measured. CoQ levels were significantly reduced after 26 weeks of rosuvastatin statin therapy (n = 32), compared to placebo (n = 37) in CHF patients in UNIVERSE trial. Patients with CHF (n = 56) matched for age, gender and severity of disease who had been taking statins for 12 months or longer had CoQ levels of 847 ± 344 nmol/L, significantly lower than 1065.4 ± 394 nmol/L in UNIVERSE patients at baseline (p = 0.0001). Serum types I and III N-terminal procollagen peptide (PINP and PIIINP), measures of collagen turnover which can contribute to cardiac fibrosis were significantly increased in the rosuvastatin group compared to baseline in UNIVERSE patients (PINP: p = 0.03, PIIINP: p = 0.001). In conclusion putative beneficial effects of statin therapy on cardiac remodeling in UNIVERSE may have been negated by increases in collagen turnover markers as well as a reduction in plasma CoQ levels in these patients with CHF. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

    Science.gov (United States)

    Kiuchi, Shunsuke; Hisatake, Shinji; Kabuki, Takayuki; Oka, Takashi; Dobashi, Shintaro; Fujii, Takahiro; Ikeda, Takanori

    2018-01-27

    Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and 123 I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

  10. Effects of percutaneous renal sympathetic denervation on cardiac function and exercise tolerance in patients with chronic heart failure.

    Science.gov (United States)

    Gao, Jun-Qing; Xie, Yun; Yang, Wei; Zheng, Jian-Pu; Liu, Zong-Jun

    2017-01-01

    Sympathetic hyperactivity, a vital factor in the genesis and development of heart failure (HF), has been reported to be effectively reduced by percutaneous renal denervation (RDN), which may play an important role in HF treatment. To determine the effects of percutaneous RDN on cardiac function in patients with chronic HF (CHF). Fourteen patients (mean age 69.6 years; ejection fraction [EF] <45%) with CHF received bilateral RDN. Adverse cardiac events, blood pressure (BP), and biochemical parameters were assessed before and six months after percutaneous operation. Patients also underwent echocardiographic assessment of cardiac function and 6-min walk test before and at six months after percutaneous operation. The distance achieved by the 14 patients in the 6-min walk test increased significantly from 152.9±38.0 m before RDN to 334.3±94.4 m at six months after RDN (p<0.001), while EF increased from 36.0±4.1% to 43.8±7.9% (p=0.003) on echocardiography. No RDN-related complications were observed during the follow-up period. In 6-month follow-up, systolic BP decreased from 138.6±22.1 mmHg to 123.2±10.5 mmHg (p=0.026) and diastolic BP from 81.1±11.3 mmHg to 72.9±7.5 mmHg (p=0.032). Creatinine levels did not change significantly (1.3±0.65 mg/dl to 1.2±0.5 mg/dl, p=0.8856). RDN is potentially an effective technique for the treatment of severe HF that can significantly increase EF and improve exercise tolerance. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. A prediction model for 5-year cardiac mortality in patients with chronic heart failure using {sup 123}I-metaiodobenzylguanidine imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Kenichi; Matsuo, Shinro [Kanazawa University Hospital, Department of Nuclear Medicine, Kanazawa (Japan); Nakata, Tomoaki [Sapporo Medical University School of Medicine, Second Department of Internal Medicine (Cardiology), Sapporo (Japan); Hakodate-Goryoukaku Hospital, Department of Cardiology, Hakodate (Japan); Yamada, Takahisa [Osaka Prefectural General Medical Center, Department of Cardiology, Osaka (Japan); Yamashina, Shohei [Toho University Omori Medical Center, Department of Cardiovascular Medicine, Tokyo (Japan); Momose, Mitsuru [Tokyo Women' s Medical University, Department of Nuclear Medicine, Tokyo (Japan); Kasama, Shu [Cardiovascular Hospital of Central Japan, Department of Cardiology, Shibukawa (Japan); Matsui, Toshiki [Social Insurance Shiga General Hospital, Department of Cardiology, Otsu (Japan); Travin, Mark I. [Albert Einstein Medical College, Department of Cardiology and Nuclear Medicine, Montefiore Medical Center, Bronx, NY (United States); Jacobson, Arnold F. [GE Healthcare, Medical Diagnostics, Princeton, NJ (United States)

    2014-09-15

    Prediction of mortality risk is important in the management of chronic heart failure (CHF). The aim of this study was to create a prediction model for 5-year cardiac death including assessment of cardiac sympathetic innervation using data from a multicenter cohort study in Japan. The original pooled database consisted of cohort studies from six sites in Japan. A total of 933 CHF patients who underwent {sup 123}I-metaiodobenzylguanidine (MIBG) imaging and whose 5-year outcomes were known were selected from this database. The late MIBG heart-to-mediastinum ratio (HMR) was used for quantification of cardiac uptake. Cox proportional hazard and logistic regression analyses were used to select appropriate variables for predicting 5-year cardiac mortality. The formula for predicting 5-year mortality was created using a logistic regression model. During the 5-year follow-up, 205 patients (22 %) died of a cardiac event including heart failure death, sudden cardiac death and fatal acute myocardial infarction (64 %, 30 % and 6 %, respectively). Multivariate logistic analysis selected four parameters, including New York Heart Association (NYHA) functional class, age, gender and left ventricular ejection fraction, without HMR (model 1) and five parameters with the addition of HMR (model 2). The net reclassification improvement analysis for all subjects was 13.8 % (p < 0.0001) by including HMR and its inclusion was most effective in the downward reclassification of low-risk patients. Nomograms for predicting 5-year cardiac mortality were created from the five-parameter regression model. Cardiac MIBG imaging had a significant additive value for predicting cardiac mortality. The prediction formula and nomograms can be used for risk stratifying in patients with CHF. (orig.)

  12. TVP1022 attenuates cardiac remodeling and kidney dysfunction in experimental volume overload-induced congestive heart failure.

    Science.gov (United States)

    Abassi, Zaid A; Barac, Yaron D; Kostin, Sawa; Roguin, Ariel; Ovcharenko, Elena; Awad, Hoda; Blank, Ayelet; Bar-Am, Orit; Amit, Tamar; Schaper, Jutta; Youdim, Moussa; Binah, Ofer

    2011-07-01

    Despite the availability of many pharmacological and mechanical therapies, the mortality rate among patients with congestive heart failure (CHF) remains high. We tested the hypothesis that TVP1022 (the S-isomer of rasagiline; Azilect), a neuroprotective and cytoprotective molecule, is also cardioprotective in the settings of experimental CHF in rats. In rats with volume overload-induced CHF, we investigated the therapeutic efficacy of TVP1022 (7.5 mg/kg) on cardiac function, structure, biomarkers, and kidney function. Treatment with TVP1022 for 7 days before CHF induction prevented the increase in left ventricular end-diastolic area and end-systolic area, and the decrease in fractional shortening measured 14 days after CHF induction. Additionally, TVP1022 pretreatment attenuated CHF-induced cardiomyocyte hypertrophy, fibrosis, plasma and ventricular B-type natriuretic peptide levels, and reactive oxygen species expression. Further, in CHF rats, TVP1022 decreased cytochrome c and caspase 3 expression, thereby contributing to the cardioprotective efficacy of the drug. TVP1022 also enhanced the urinary Na(+) excretion and improved the glomerular filtration rate. Similar cardioprotective effects were obtained when TVP1022 was given to rats after CHF induction. TVP1022 attenuated the adverse functional, structural, and molecular alterations in CHF, rendering this drug a promising candidate for improving cardiac and renal function in this disease state.

  13. Distinct trajectories of disease-specific health status in heart failure patients undergoing cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H.; Pedersen, Susanne S.; Meine, Mathias

    2016-01-01

    of beta-blockers, use of psychotropic medication, anxiety, depression, and type D personality were found to be associated with poorer health status in unadjusted analyses. Interestingly, subgroups of patients (12-20 %) who experienced poor health status at baseline improved to stable good health status....... The timely identification of CRT-D patients who present with poor disease-specific health status (i.e., KCCQ score anxiety, depression, and/or type D personality) is paramount, as they may benefit from cardiac rehabilitation in combination...

  14. Collaborative care model improves self-care ability, quality of life and cardiac function of patients with chronic heart failure

    Directory of Open Access Journals (Sweden)

    C.Y. Hua

    2017-09-01

    Full Text Available Chronic heart failure (CHF is a common chronic disease that requires much care. This study aimed to explore the effects of collaborative care model (CCM on patients with CHF. A total of 114 CHF patients were enrolled in this study, and were randomly and equally divided into two groups: control and experimental. Patients in the two groups received either usual care or CCM for 3 continuous months. The impacts of CCM on the self-care ability and quality of life were assessed using self-care of heart failure index and short form health survey 12, respectively. Further, cardiac function was assessed by measuring left ventricular ejection fraction (LVEF and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP, and by the 6-min walking test. Clinical and demographic characteristics of patients in the control and CCM groups were statistically equivalent. Compared with usual care, CCM significantly enhanced self-care abilities of patients with CHF, including self-care maintenance, self-care management and self-care confidence (all P<0.05. The physical and mental quality of life was also significantly improved by CCM (P<0.01 or P<0.05. Compared with usual care, CCM significantly increased the LVEF (P<0.01, decreased the NT-proBNP level (P<0.01, and enhanced exercise capacity (P<0.001. In conclusion, CCM improved the self-care, quality of life and cardiac function of patients with CHF compared with usual care.

  15. NATO Symposium on Human Detection and Diagnosis of System Failures

    CERN Document Server

    Rouse, William

    1981-01-01

    This book includes all of the papers presented at the NATO Symposium on Human Detection and Diagnosis of System Failures held at Roskilde, Denmark on August 4-8, 1980. The Symposium was sponsored by the Scientific Affairs Division of NATO and the Rise National Laboratory of Denmark. The goal of the Symposium was to continue the tradition initiated by the NATO Symposium on Monitoring Behavior and Supervisory Control held in Berchtesgaden, F .R. Germany in 1976 and the NATO Symposium on Theory and Measurement of Mental Workload held in Mati, Greece in 1977. To this end, a group of 85 psychologists and engineers coming from industry, government, and academia convened to discuss, and to generate a "state-of-the-art" consensus of the problems and solutions associated with the human IS ability to cope with the increasing scale of consequences of failures within complex technical systems. The Introduction of this volume reviews their findings. The Symposium was organized to include brief formal presentations of pape...

  16. Heart failure in pregnant women with cardiac disease: Data from the ROPAC

    NARCIS (Netherlands)

    T.P.E. Ruys (Titia); J.W. Roos-Hesselink (Jolien); R. Hall (Ruth); M.T. Subirana-Domèlnech (Maria); J. Grando-Ting (Jennifer); M. Estensen (Mette); R. Crepaz (Roberto); V. Fesslova (Vlasta); M. Gurvitz (Michelle); J. de Backer (Julie); M.R. Johnson (Mark); P.G. Pieper (Petronella)

    2014-01-01

    textabstractObjective Heart failure (HF) is one of the most important complications in pregnant women with heart disease, causing maternal and fetal mortality and morbidity. Methods This is an international observational registry of patients with structural heart disease during pregnancy. Sixty

  17. Heart failure in pregnant women with cardiac disease : data from the ROPAC

    NARCIS (Netherlands)

    Ruys, Titia P. E.; Roos-Hesselink, Jolien W.; Hall, Roger; Subirana-Domenech, Maria T.; Grando-Ting, Jennifer; Estensen, Mette; Crepaz, Roberto; Fesslova, Vlasta; Gurvitz, Michelle; De Backer, Julie; Johnson, Mark R.; Pieper, Petronella G.

    2014-01-01

    Objective Heart failure (HF) is one of the most important complications in pregnant women with heart disease, causing maternal and fetal mortality and morbidity. Methods This is an international observational registry of patients with structural heart disease during pregnancy. Sixty hospitals in 28

  18. Salt-induced changes in cardiac phosphoproteome in a rat model of chronic renal failure.

    Directory of Open Access Journals (Sweden)

    Zhengxiu Su

    Full Text Available Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model or sham operation were treated for 2 weeks with a normal-(0.4% NaCl, or high-salt (4% NaCl diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54% phosphopeptides upregulated and 76 (46% phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49% phosphopeptides and downregulation of 88 (51% phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.

  19. Preparation of human cardiac anti-myosin: a review

    International Nuclear Information System (INIS)

    Okada, H.; Souza, I.T.T.

    1990-01-01

    The present communication is a review of the physicochemical characterization and immunological properties of myosin isolated from the cardiac muscle, the production of monoclonal antibody anti-myosin, the radiolabeling of this antibody and its applications as radiopharmaceuticals to imaging myocardial infarcts. The classical example of radioimmunologic diagnosis of non malignant tissues is the detection of myocardial infarction by radiolabeled antibodies to myosin. (author)

  20. Cardiac function improved by sarcoplasmic reticulum Ca2+-ATPase overexpression in a heart failure model induced by chronic myocardial ischemia

    Directory of Open Access Journals (Sweden)

    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.

  1. TNF-α receptor 1 knockdown in the subfornical organ ameliorates sympathetic excitation and cardiac hemodynamics in heart failure rats.

    Science.gov (United States)

    Yu, Yang; Wei, Shun-Guang; Weiss, Robert M; Felder, Robert B

    2017-10-01

    In systolic heart failure (HF), circulating proinflammatory cytokines upregulate inflammation and renin-angiotensin system (RAS) activity in cardiovascular regions of the brain, contributing to sympathetic excitation and cardiac dysfunction. Important among these is the subfornical organ (SFO), a forebrain circumventricular organ that lacks an effective blood-brain barrier and senses circulating humors. We hypothesized that the tumor necrosis factor-α (TNF-α) receptor 1 (TNFR1) in the SFO contributes to sympathetic excitation and cardiac dysfunction in HF rats. Rats received SFO microinjections of a TNFR1 shRNA or a scrambled shRNA lentiviral vector carrying green fluorescent protein, or vehicle. One week later, some rats were euthanized to confirm the accuracy of the SFO microinjections and the transfection potential of the lentiviral vector. Other rats underwent coronary artery ligation (CL) to induce HF or a sham operation. Four weeks after CL, vehicle- and scrambled shRNA-treated HF rats had significant increases in TNFR1 mRNA and protein, NF-κB activity, and mRNA for inflammatory mediators, RAS components and c-Fos protein in the SFO and downstream in the hypothalamic paraventricular nucleus, along with increased plasma norepinephrine levels and impaired cardiac function, compared with vehicle-treated sham-operated rats. In HF rats treated with TNFR1 shRNA, TNFR1 was reduced in the SFO but not paraventricular nucleus, and the central and peripheral manifestations of HF were ameliorated. In sham-operated rats treated with TNFR1 shRNA, TNFR1 expression was also reduced in the SFO but there were no other effects. These results suggest a key role for TNFR1 in the SFO in the pathophysiology of systolic HF. NEW & NOTEWORTHY Activation of TNF-α receptor 1 in the subfornical organ (SFO) contributes to sympathetic excitation in heart failure rats by increasing inflammation and renin-angiotensin system activity in the SFO and downstream in the hypothalamic

  2. Effect of the adjuvant milrinone therapy on cardiac function, myocardial remodeling and RAAS system activity in patients with chronic heart failure

    Directory of Open Access Journals (Sweden)

    Jing Chen

    2017-09-01

    Full Text Available Objective: To explore the effect of the adjuvant milrinone therapy on cardiac function, myocardial remodeling and RAAS system activity in patients with chronic heart failure. Methods: A total of 110 patients with chronic heart failure who were treated in the hospital between January 2015 and January 2017 were divided into control group (n=55 and observation group (n=55 by random number table method. Control group received conventional therapy for chronic heart failure, and the observation group received milrinone on the basis of conventional therapy. The differences in ultrasound cardiac function and myocardial remodeling index levels as well as serum RAAS index contents were compared between the two groups before and after treatment. Results: Before treatment, the differences in ultrasound cardiac function and myocardial remodeling index levels as well as serum RAAS index contents were not statistically significant between the two groups. After treatment, CO and SV levels of both groups of patients were significantly higher than those before treatment while LADd, LVEDd, LVPWT, IVST and LVMI levels as well as serum PRA, AngⅡ and ALD contents were significantly lower than those before treatment, and CO and SV levels of observation group were significantly higher than those of control group while LADd, LVEDd, LVPWT, IVST and LVMI levels as well as serum PRA, AngⅡ and ALD contents were significantly lower than those of control group. Conclusion: Adjuvant milrinone therapy can effectively enhance the cardiac function, inhibit the myocardial remodeling and decrease the RAAS system activity in patients with chronic heart failure.

  3. Positive predictive value and impact of misdiagnosis of a heart failure diagnosis in administrative registers among patients admitted to a University Hospital cardiac care unit

    DEFF Research Database (Denmark)

    Mard, Shan; Nielsen, Finn Erland

    2010-01-01

    OBJECTIVE: To evaluate the positive predictive value (PPV) of a diagnosis of heart failure (HF) in the Danish National Registry of Patients (NRP) among patients admitted to a University Hospital cardiac care unit, and to evaluate the impact of misdiagnosing HF. DESIGN: The NRP was used to identify...

  4. Effect of cardiac resynchronization therapy-defibrillator implantation on health status in patients with mild versus moderate symptoms of heart failure

    DEFF Research Database (Denmark)

    Versteeg, Henneke; van den Broek, Krista C; Theuns, Dominic A M J

    2011-01-01

    Indications for cardiac resynchronization therapy (CRT) have expanded to include patients with mild congestive heart failure (CHF) symptoms (New York Heart Association [NYHA] functional class II) because of a demonstrated morbidity reduction in this subset of patients. However, little is known...

  5. Influence of the definition of acute renal failure post-cardiac surgery on incidence, patient identification, and identification of risk factors

    NARCIS (Netherlands)

    Noyez, L.

    2011-01-01

    OBJECTIVE: Acute renal failure post-cardiac surgery (RF) is a major complication and is associated with increased postoperative morbidity and mortality. Early recognition and identification of risk factors for RF is therefore important. However, several definitions of RF are used. The intention of

  6. Long Non-Coding RNA Malat-1 Is Dispensable during Pressure Overload-Induced Cardiac Remodeling and Failure in Mice.

    Directory of Open Access Journals (Sweden)

    Tim Peters

    Full Text Available Long non-coding RNAs (lncRNAs are a class of RNA molecules with diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases and in particular heart failure is still in its infancy. The exceptionally well conserved nuclear lncRNA Metastasis associated in lung adenocarcinoma transcript 1 (Malat-1 is a regulator of mRNA splicing and highly expressed in the heart. Malat-1 modulates hypoxia-induced vessel growth, activates ERK/MAPK signaling, and scavenges the anti-hypertrophic microRNA-133. We therefore hypothesized that Malat-1 may act as regulator of cardiac hypertrophy and failure during cardiac pressure overload induced by thoracic aortic constriction (TAC in mice.Absence of Malat-1 did not affect cardiac hypertrophy upon pressure overload: Heart weight to tibia length ratio significantly increased in WT mice (sham: 5.78±0.55, TAC 9.79±1.82 g/mm; p<0.001 but to a similar extend also in Malat-1 knockout (KO mice (sham: 6.21±1.12, TAC 8.91±1.74 g/mm; p<0.01 with no significant difference between genotypes. As expected, TAC significantly reduced left ventricular fractional shortening in WT (sham: 38.81±6.53%, TAC: 23.14±11.99%; p<0.01 but to a comparable degree also in KO mice (sham: 37.01±4.19%, TAC: 25.98±9.75%; p<0.05. Histological hallmarks of myocardial remodeling, such as cardiomyocyte hypertrophy, increased interstitial fibrosis, reduced capillary density, and immune cell infiltration, did not differ significantly between WT and KO mice after TAC. In line, the absence of Malat-1 did not significantly affect angiotensin II-induced cardiac hypertrophy, dysfunction, and overall remodeling. Above that, pressure overload by TAC significantly induced mRNA levels of the hypertrophy marker genes Nppa, Nppb and Acta1, to a similar extend in both genotypes. Alternative splicing of Ndrg2 after TAC was apparent in WT (isoform ratio

  7. Cardiac Rotational Mechanics As a Predictor of Myocardial Recovery in Heart Failure Patients Undergoing Chronic Mechanical Circulatory Support: A Pilot Study.

    Science.gov (United States)

    Bonios, Michael J; Koliopoulou, Antigone; Wever-Pinzon, Omar; Taleb, Iosif; Stehlik, Josef; Xu, Weining; Wever-Pinzon, James; Catino, Anna; Kfoury, Abdallah G; Horne, Benjamin D; Nativi-Nicolau, Jose; Adamopoulos, Stamatis N; Fang, James C; Selzman, Craig H; Bax, Jeroen J; Drakos, Stavros G

    2018-04-01

    Impaired qualitative and quantitative left ventricular (LV) rotational mechanics predict cardiac remodeling progression and prognosis after myocardial infarction. We investigated whether cardiac rotational mechanics can predict cardiac recovery in chronic advanced cardiomyopathy patients. Sixty-three patients with advanced and chronic dilated cardiomyopathy undergoing implantation of LV assist device (LVAD) were prospectively investigated using speckle tracking echocardiography. Acute heart failure patients were prospectively excluded. We evaluated LV rotational mechanics (apical and basal LV twist, LV torsion) and deformational mechanics (circumferential and longitudinal strain) before LVAD implantation. Cardiac recovery post-LVAD implantation was defined as (1) final resulting LV ejection fraction ≥40%, (2) relative LV ejection fraction increase ≥50%, (iii) relative LV end-systolic volume decrease ≥50% (all 3 required). Twelve patients fulfilled the criteria for cardiac recovery (Rec Group). The Rec Group had significantly less impaired pre-LVAD peak LV torsion compared with the Non-Rec Group. Notably, both groups had similarly reduced pre-LVAD LV ejection fraction. By receiver operating characteristic curve analysis, pre-LVAD peak LV torsion of 0.35 degrees/cm had a 92% sensitivity and a 73% specificity in predicting cardiac recovery. Peak LV torsion before LVAD implantation was found to be an independent predictor of cardiac recovery after LVAD implantation (odds ratio, 0.65 per 0.1 degrees/cm [0.49-0.87]; P =0.014). LV rotational mechanics seem to be useful in selecting patients prone to cardiac recovery after mechanical unloading induced by LVADs. Future studies should investigate the utility of these markers in predicting durable cardiac recovery after the explantation of the cardiac assist device. © 2018 American Heart Association, Inc.

  8. Identification of genetic markers for treatment success in heart failure patients: insight from cardiac resynchronization therapy.

    Science.gov (United States)

    Schmitz, Boris; De Maria, Renata; Gatsios, Dimitris; Chrysanthakopoulou, Theodora; Landolina, Maurizio; Gasparini, Maurizio; Campolo, Jonica; Parolini, Marina; Sanzo, Antonio; Galimberti, Paola; Bianchi, Michele; Lenders, Malte; Brand, Eva; Parodi, Oberdan; Lunati, Maurizio; Brand, Stefan-Martin

    2014-12-01

    Cardiac resynchronization therapy (CRT) can improve ventricular size, shape, and mass and reduce mitral regurgitation by reverse remodeling of the failing ventricle. About 30% of patients do not respond to this therapy for unknown reasons. In this study, we aimed at the identification and classification of CRT responder by the use of genetic variants and clinical parameters. Of 1421 CRT patients, 207 subjects were consecutively selected, and CRT responder and nonresponder were matched for their baseline parameters before CRT. Treatment success of CRT was defined as a decrease in left ventricular end-systolic volume >15% at follow-up echocardiography compared with left ventricular end-systolic volume at baseline. All other changes classified the patient as CRT nonresponder. A genetic association study was performed, which identified 4 genetic variants to be associated with the CRT responder phenotype at the allelic (Passociated with remodeling of the failing ventricle. © 2014 American Heart Association, Inc.

  9. Gαq protein carboxyl terminus imitation polypeptide GCIP-27 improves cardiac function in chronic heart failure rats.

    Directory of Open Access Journals (Sweden)

    Xiao Lan Lu

    Full Text Available Gαq protein carboxyl terminus imitation polypeptide (GCIP-27 has been shown to alleviate pathological cardiomyocyte hypertrophy induced by various factors. Pathological cardiac hypertrophy increases the morbidity and mortality of cardiovascular diseases while it compensates for poor heart function. This study was designed to investigate the effects of GCIP-27 on heart function in rats with heart failure induced by doxorubicin.Forty-eight rats were randomly divided into the following six groups receiving vehicle (control, doxorubicin (Dox, losartan (6 mg/kg, i.g. and three doses of GCIP-27 (10, 30, 90 μg/kg; i.p., bid, respectively. Heart failure was induced by Dox, which was administered at a 20 mg/kg cumulative dose. After 10 weeks of treatment, we observed that GCIP-27 (30, 90 μg/kg significantly increased ejection fraction, fraction shortening, stroke volume and sarcoplasmic reticulum Ca2+ ATPase activity of Dox-treated hearts. Additionally, GCIP-27 decreased myocardial injury, heart weight index and left ventricular weight index, fibrosis and serum cardiac troponin-I concentration in Dox-treated mice. Immunohistochemistry, western blotting and real-time PCR experiments indicated that GCIP-27 (10-90 μg/kg could markedly upregulate the protein expression of myocardial α-myosin heavy chain (MHC, Bcl-2, protein kinase C (PKC ε and phosphorylated extracellular signal-regulated kinase (p-ERK 1/2 as well as the mRNA expression of α-MHC, but downregulated the expression of β-MHC, Bax and PKC βII, and the mRNA expression levels of β-MHC in Dox-treated mice. It was also found that GCIP-27 (30, 90 μg/L decreased cell size and protein content of cardiomyocytes significantly in vitro by comparison of Dox group.GCIP-27 could effectively ameliorate heart failure development induced by Dox. PKC-ERK1/2 signaling might represent the underlying mechanism of the beneficial effects of GCIP-27.

  10. Inspiration from heart development: Biomimetic development of functional human cardiac organoids.

    Science.gov (United States)

    Richards, Dylan J; Coyle, Robert C; Tan, Yu; Jia, Jia; Wong, Kerri; Toomer, Katelynn; Menick, Donald R; Mei, Ying

    2017-10-01

    Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Understanding and Resolving Failures in Human-Robot Interaction: Literature Review and Model Development

    Directory of Open Access Journals (Sweden)

    Shanee Honig

    2018-06-01

    Full Text Available While substantial effort has been invested in making robots more reliable, experience demonstrates that robots operating in unstructured environments are often challenged by frequent failures. Despite this, robots have not yet reached a level of design that allows effective management of faulty or unexpected behavior by untrained users. To understand why this may be the case, an in-depth literature review was done to explore when people perceive and resolve robot failures, how robots communicate failure, how failures influence people's perceptions and feelings toward robots, and how these effects can be mitigated. Fifty-two studies were identified relating to communicating failures and their causes, the influence of failures on human-robot interaction (HRI, and mitigating failures. Since little research has been done on these topics within the HRI community, insights from the fields of human computer interaction (HCI, human factors engineering, cognitive engineering and experimental psychology are presented and discussed. Based on the literature, we developed a model of information processing for robotic failures (Robot Failure Human Information Processing, RF-HIP, that guides the discussion of our findings. The model describes the way people perceive, process, and act on failures in human robot interaction. The model includes three main parts: (1 communicating failures, (2 perception and comprehension of failures, and (3 solving failures. Each part contains several stages, all influenced by contextual considerations and mitigation strategies. Several gaps in the literature have become evident as a result of this evaluation. More focus has been given to technical failures than interaction failures. Few studies focused on human errors, on communicating failures, or the cognitive, psychological, and social determinants that impact the design of mitigation strategies. By providing the stages of human information processing, RF-HIP can be used as a

  12. Predictive value of cardiac autonomic indexes and MIBG washout in ICD recipients with mild to moderate heart failure

    International Nuclear Information System (INIS)

    Koutelou, M.; Katsikis, A.; Livanis, E.; Georgiadis, M.; Voudris, V.; Flevari, P.; Kremastinos, D.; Theodorakis, G.

    2009-01-01

    We aimed at evaluating the combined use of heart rate variability (HRV), baroreflex sensitivity (BRS), and metaiodobenzylguanidine (MIBG) imaging in the risk stratification for sudden cardiac death (SCD) of patients with mild to moderate heart failure. Twenty-five patients (17 male and 8 female, mean age 63±5 years, mean left ventricular ejection fraction (LVEF) 36±3%) with a recently implanted cardioverter-defibrillator (ICD) and mild (NYHA I-II) heart failure due to either ischemic (n=15) or dilated (n=10) cardiomyopathy were studied. One week after ICD implantation they underwent baroreflex sensitivity (BRS) evaluation to bolus phenylephrine by the Oxford method, 24-h heart rate variability (HRV) assessment, and MIBG imaging. The mean patient follow-up was 32±10 months. Simple correlation and stepwise multiple regression analysis was performed to evaluate if the number of sustained ventricular tachycardia (cycle length <330 ms) or fibrillation episodes per month is related to one or more of MIBG, BRS, and HRV indexes and if MIBG % washout is related to HRV and/or BRS. The frequency of fast ventricular arrhythmic episodes (FVAE) demonstrated an inverse relation to BRS (p<0.0001), rMSSD (p=0.001), and pNN50 (p=0.0034), while it was positively related to low frequency (LF) (p<0.0001) and MIBG % washout (p=0.001). BRS, LF, rMSSD, and MIBG washout were also independent predictors of FVAE. MIBG washout was related to only one HRV marker (SDNN-I, p<0.0001), while no correlation was observed with BRS. In ICD recipients with well-compensated heart failure, autonomic markers derived from BRS, HRV, and MIBG studies are related to FVAE. These markers have limited inter-dependency and constitute useful means for SCD risk stratification in this subgroup of patients. (author)

  13. Cardiac Stress and Inflammatory Markers as Predictors of Heart Failure in Patients With Type 2 Diabetes: The ADVANCE Trial.

    Science.gov (United States)

    Ohkuma, Toshiaki; Jun, Min; Woodward, Mark; Zoungas, Sophia; Cooper, Mark E; Grobbee, Diederick E; Hamet, Pavel; Mancia, Giuseppe; Williams, Bryan; Welsh, Paul; Sattar, Naveed; Shaw, Jonathan E; Rahimi, Kazem; Chalmers, John

    2017-09-01

    This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and hs-CRP on the prediction of heart failure incidence or progression in patients with type 2 diabetes. A nested case-cohort study was conducted in 3,098 participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. A higher value of each biomarker was significantly associated with a higher risk of heart failure incidence or progression, after adjustment for major risk factors. The hazard ratios per 1-SD increase were 3.06 (95% CI 2.37, 3.96) for NT-proBNP, 1.50 (1.27, 1.77) for hs-cTnT, 1.48 (1.27, 1.72) for IL-6, and 1.32 (1.12, 1.55) for hs-CRP. The addition of NT-proBNP to the model including conventional risk factors meaningfully improved 5-year risk-predictive performance (C statistic 0.8162 to 0.8800; continuous net reclassification improvement [NRI] 73.1%; categorical NRI [10% 5-year risk] 24.2%). In contrast, the addition of hs-cTnT, IL-6, or hs-CRP did not improve the prediction metrics consistently in combination or when added to NT-proBNP. Only NT-proBNP strongly and consistently improved the prediction of heart failure in patients with type 2 diabetes beyond a wide range of clinical risk factors and biomarkers. © 2017 by the American Diabetes Association.

  14. ATPase activity and contraction in porcine and human cardiac muscle

    Czech Academy of Sciences Publication Activity Database

    Griffiths, P. J.; Isackson, H.; Redwood, C.; Marston, S.; Pelc, Radek; Funari, S.; Watkins, H.; Ashley, C. C.

    2008-01-01

    Roč. 29, 6-8 (2008), s. 277-277 ISSN 0142-4319. [European Muscle Conference of the European Society for Muscle Research /37./. 13.09.2008-16.09.2008, Oxford] R&D Projects: GA MŠk(CZ) LC06063 Grant - others:EC(XE) RII3-CT-2004-506008 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * ATP-asa * cardiac muscle * molecular motor Subject RIV: ED - Physiology

  15. Top-down and bottom-up definitions of human failure events in human reliability analysis

    International Nuclear Information System (INIS)

    Boring, Ronald Laurids

    2014-01-01

    In the probabilistic risk assessments (PRAs) used in the nuclear industry, human failure events (HFEs) are determined as a subset of hardware failures, namely those hardware failures that could be triggered by human action or inaction. This approach is top-down, starting with hardware faults and deducing human contributions to those faults. Elsewhere, more traditionally human factors driven approaches would tend to look at opportunities for human errors first in a task analysis and then identify which of those errors is risk significant. The intersection of top-down and bottom-up approaches to defining HFEs has not been carefully studied. Ideally, both approaches should arrive at the same set of HFEs. This question is crucial, however, as human reliability analysis (HRA) methods are generalized to new domains like oil and gas. The HFEs used in nuclear PRAs tend to be top-down - defined as a subset of the PRA - whereas the HFEs used in petroleum quantitative risk assessments (QRAs) often tend to be bottom-up - derived from a task analysis conducted by human factors experts. The marriage of these approaches is necessary in order to ensure that HRA methods developed for top-down HFEs are also sufficient for bottom-up applications.

  16. Biotechnological approaches to cardiac differentiation of human induced pluripotent stem cells

    OpenAIRE

    Di Guglielmo, Claudia

    2016-01-01

    [eng] The heart can be considered the most important organ of our body, as it supplies nutrients to all the cells. When affected from injuries or diseases, the heart function is hampered, as the damaged area is substituted by a fibrotic scar instead of functional tissue. Understanding the mechanisms leading to heart failure and finding a cure for cardiac diseases represents a major challenge of modern medicine, since they are the leading cause of death and disability in Western world. Being ...

  17. Electrical Stimulation Promotes Cardiac Differentiation of Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Damián Hernández

    2016-01-01

    Full Text Available Background. Human induced pluripotent stem cells (iPSCs are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin-2 cell line, brief electrical stimulation at 65 mV/mm or 200 mV/mm for 5 min significantly increased the percentage of beating EBs present by day 14 after plating. Acute electrical stimulation also significantly increased the cardiac gene expression of ACTC1, TNNT2, MYH7, and MYL7. However, the cardiogenic effect of electrical stimulation was not reproducible in another iPS cell line, CERA007c6. Beating EBs from control and electrically stimulated groups expressed various cardiac-specific transcription factors and contractile muscle markers. Beating EBs were also shown to cycle calcium and were responsive to the chronotropic agents, isoproterenol and carbamylcholine, in a concentration-dependent manner. Conclusions. Our results demonstrate that brief electrical stimulation can promote cardiac differentiation of human iPS cells. The cardiogenic effect of brief electrical stimulation is dependent on the cell line used.

  18. Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E.; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Liao, Mei-Ling Chang; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D.; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W.; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A.; Unger, Andreas; Linke, Wolfgang A.; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C.; Zimmermann, Wolfram-Hubertus

    2017-01-01

    Background Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards an adult phenotype under defined conditions. Methods We systematically investigated cell composition, matrix and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We employed morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M-bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency-response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β1- and β2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and NT-proBNP release; all are classical hallmarks of heart failure. Additionally, we demonstrate scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions We provide proof-of-concept for a universally applicable technology for the engineering of macro-scale human myocardium for disease modelling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. PMID:28167635

  19. Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

    Science.gov (United States)

    Tiburcy, Malte; Hudson, James E; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Chang Liao, Mei-Ling; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A; Unger, Andreas; Linke, Wolfgang A; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C; Zimmermann, Wolfram-Hubertus

    2017-05-09

    Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1 - and β 2 -adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. © 2017 American Heart Association, Inc.

  20. Genetic and Epigenetic Regulation of Human Cardiac Reprogramming and Differentiation in Regenerative Medicine.

    Science.gov (United States)

    Burridge, Paul W; Sharma, Arun; Wu, Joseph C

    2015-01-01

    Regeneration or replacement of lost cardiomyocytes within the heart has the potential to revolutionize cardiovascular medicine. Numerous methodologies have been used to achieve this aim, including the engraftment of bone marrow- and heart-derived cells as well as the identification of modulators of adult cardiomyocyte proliferation. Recently, the conversion of human somatic cells into induced pluripotent stem cells and induced cardiomyocyte-like cells has transformed potential approaches toward this goal, and the engraftment of cardiac progenitors derived from human embryonic stem cells into patients is now feasible. Here we review recent advances in our understanding of the genetic and epigenetic control of human cardiogenesis, cardiac differentiation, and the induced reprogramming of somatic cells to cardiomyocytes. We also cover genetic programs for inducing the proliferation of endogenous cardiomyocytes and discuss the genetic state of cells used in cardiac regenerative medicine.

  1. Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure

    DEFF Research Database (Denmark)

    St John Sutton, Martin; Ghio, Stefano; Plappert, Ted

    2009-01-01

    BACKGROUND: Cardiac resynchronization therapy (CRT) improves LV structure, function, and clinical outcomes in New York Heart Association class III/IV heart failure with prolonged QRS. It is not known whether patients with New York Heart Association class I/II systolic heart failure exhibit left...... ventricular (LV) reverse remodeling with CRT or whether reverse remodeling is modified by the cause of heart failure. METHODS AND RESULTS: Six hundred ten patients with New York Heart Association class I/II heart failure, QRS duration > or =120 ms, LV end-diastolic dimension > or =55 mm, and LV ejection...... reduction in LV end-diastolic and end-systolic volume indexes and a 3-fold greater increase in LV ejection fraction in patients with nonischemic causes of heart failure. CONCLUSIONS: CRT in patients with New York Heart Association I/II resulted in major structural and functional reverse remodeling at 1 year...

  2. A New Transgenic Mouse Model of Heart Failure and Cardiac Cachexia Raised by Sustained Activation of Met Tyrosine Kinase in the Heart

    Directory of Open Access Journals (Sweden)

    Valentina Sala

    2016-01-01

    Full Text Available Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level.

  3. Image-guided left ventricular lead placement in cardiac resynchronization therapy for patients with heart failure: a meta-analysis.

    Science.gov (United States)

    Jin, Yan; Zhang, Qi; Mao, Jia-Liang; He, Ben

    2015-05-10

    Heart failure (HF) is a debilitating condition that affects millions of people worldwide. One means of treating HF is cardiac resynchronization therapy (CRT). Recently, several studies have examined the use of echocardiography (ECHO) in the optimization of left ventricular (LV) lead placement to increase the response to CRT. The objective of this study was to synthesize the available data on the comparative efficacy of image-guided and standard CRT. We searched the PubMed, Cochrane, Embase, and ISI Web of Knowledge databases through April 2014 with the following combinations of search terms: left ventricular lead placement, cardiac resynchronization therapy, image-guided, and echocardiography-guided. Studies meeting all of the inclusion criteria and none of the exclusion criteria were eligible for inclusion. The primary outcome measures were CRT response rate, change in LV ejection fraction (LVEF), and change in LV end systolic volume (LVESV). Secondary outcomes included the rates of all-cause mortality and HF-related hospitalization. Our search identified 103 articles, 3 of which were included in the analysis. In total, 270 patients were randomized to the image-guided CRT and 241, to the standard CRT. The pooled estimates showed a significant benefit for image-guided CRT (CRT response: OR, 2.098, 95 % CI, 1.432-3.072; LVEF: difference in means, 3.457, 95 % CI, 1.910-5.005; LVESV: difference in means, -20.36, 95 % CI, -27.819 - -12.902). Image-guided CRT produced significantly better clinical outcomes than the standard CRT. Additional trials are warranted to validate the use of imaging in the prospective optimization of CRT.

  4. Factors influencing change in walking ability in patients with heart failure undergoing exercise-based cardiac rehabilitation.

    Science.gov (United States)

    Sutherland, Natasha; Harrison, Alexander; Doherty, Patrick

    2018-05-17

    Exercise-based cardiac rehabilitation (CR) is an effective intervention for patients with heart failure (HF), in which one of the main targets is to increase physical capacity. In the HF population this is traditionally assessed using distance covered during a walking test. This study aims to establish the extent to which change in walking ability, in HF patients attending CR, is determined by patient characteristics and service provision. The study utilised routine clinical data from the National Audit of Cardiac Rehabilitation to perform a robust analysis. Change, in metres, between pre- and post-CR six-minute walk tests was calculated. Multivariate linear regression models were used to explore the relationship between patient characteristics, service-level variables, and change in metres walked. Complete and valid data from 633 patients was analysed, and a mean change of 51.30 m was calculated. Female gender (-34.13 m, p = 0.007), being retired (-36.41 m, p = 0.001) and being married/in a relationship (-32.54 m, p = 0.023) were all significant negative predictors of change. There was an additional negative relationship with body mass index (BMI) whereby for every unit increase in BMI, predicted change reduces by 2.48 m (p = 0.006). This study identified significant patient-level characteristics strongly associated with limited improvement in walking ability following CR. Improving physical capacity is a core component of CR, therefore services should aim to account for baseline characteristics identified in this study as part of tailoring the CR intervention around the individual. Pre- and post-CR physical capacity assessments, which constitute minimum standards for CR, are worryingly low and should be given high priority. Copyright © 2017. Published by Elsevier B.V.

  5. The Visible Heart® project and free-access website 'Atlas of Human Cardiac Anatomy'.

    Science.gov (United States)

    Iaizzo, Paul A

    2016-12-01

    Pre- and post-evaluations of implantable cardiac devices require innovative and critical testing in all phases of the design process. The Visible Heart ® Project was successfully launched in 1997 and 3 years later the Atlas of Human Cardiac Anatomy website was online. The Visible Heart ® methodologies and Atlas website can be used to better understand human cardiac anatomy, disease states and/or to improve cardiac device design throughout the development process. To date, Visible ® Heart methodologies have been used to reanimate 75 human hearts, all considered non-viable for transplantation. The Atlas is a unique free-access website featuring novel images of functional and fixed human cardiac anatomies from >400 human heart specimens. Furthermore, this website includes education tutorials on anatomy, physiology, congenital heart disease and various imaging modalities. For instance, the Device Tutorial provides examples of commonly deployed devices that were present at the time of in vitro reanimation or were subsequently delivered, including: leads, catheters, valves, annuloplasty rings, leadless pacemakers and stents. Another section of the website displays 3D models of vasculature, blood volumes, and/or tissue volumes reconstructed from computed tomography (CT) and magnetic resonance images (MRI) of various heart specimens. A new section allows the user to interact with various heart models. Visible Heart ® methodologies have enabled our laboratory to reanimate 75 human hearts and visualize functional cardiac anatomies and device/tissue interfaces. The website freely shares all images, video clips and CT/MRI DICOM files in honour of the generous gifts received from donors and their families. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

  6. Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Nakata, Tomoaki; Wakabayashi, Takeru; Kyuma, Michifumi; Takahashi, Toru; Tsuchihashi, Kazufumi; Shimamoto, Kazuaki [Sapporo Medical University School of Medicine, Second Department of Internal Medicine (Cardiology), Sapporo (Japan)

    2005-02-01

    Although the benefits of treatment with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well known, no method has as yet been established to predict the efficacy of drug therapy. This study tested whether cardiac{sup 123}I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and can predict the improvement in heart failure patients resulting from treatment with ACE inhibitors and/or beta-blockers. Following quantification of the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart failure who were treated with ACE inhibitors and/or beta-blockers (treated group) and 79 patients with heart failure who were treated conventionally without the aforementioned agents, and who served as controls, were followed up for 43 months with a primary endpoint of cardiac death. The treated group had a significantly lower prevalence of cardiac death and a significantly lower mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%, p<0.05, respectively). Multivariate analysis revealed that significant predictors were HMR, age, nitrate use and ventricular tachycardia for the treated group, and HMR, nitrate use and NYHA class for the control group. The drug treatment significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality within 5 years in patients without a severe MIBG defect (67%) was twice that in patients with such a defect (32%) (p<0.05). The reduction in mortality risk achieved by using ACE inhibitors and/or beta-blockers is associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG activity can consequently be of long-term prognostic value in predicting the effectiveness of such treatment in patients with heart failure. (orig.)

  7. Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure

    International Nuclear Information System (INIS)

    Nakata, Tomoaki; Wakabayashi, Takeru; Kyuma, Michifumi; Takahashi, Toru; Tsuchihashi, Kazufumi; Shimamoto, Kazuaki

    2005-01-01

    Although the benefits of treatment with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well known, no method has as yet been established to predict the efficacy of drug therapy. This study tested whether cardiac 123 I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and can predict the improvement in heart failure patients resulting from treatment with ACE inhibitors and/or beta-blockers. Following quantification of the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart failure who were treated with ACE inhibitors and/or beta-blockers (treated group) and 79 patients with heart failure who were treated conventionally without the aforementioned agents, and who served as controls, were followed up for 43 months with a primary endpoint of cardiac death. The treated group had a significantly lower prevalence of cardiac death and a significantly lower mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%, p<0.05, respectively). Multivariate analysis revealed that significant predictors were HMR, age, nitrate use and ventricular tachycardia for the treated group, and HMR, nitrate use and NYHA class for the control group. The drug treatment significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality within 5 years in patients without a severe MIBG defect (67%) was twice that in patients with such a defect (32%) (p<0.05). The reduction in mortality risk achieved by using ACE inhibitors and/or beta-blockers is associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG activity can consequently be of long-term prognostic value in predicting the effectiveness of such treatment in patients with heart failure. (orig.)

  8. Anesthetic-Induced Myocardial Preconditioning and Some Biochemical Markers for Cardiac and Coronary Failures after Aortocoronary Bypass Surgery

    Directory of Open Access Journals (Sweden)

    V. V. Moroz

    2013-01-01

    Full Text Available Objective: to provide a rationale for the efficiency of sevoflurane-induced cardiac preconditioning (CPC, by assessing the pattern of recovery of heart rate and by estimating troponin I levels and changes in NT-proBNP concentrations in patients undergoing aortocoronary bypass surgery (ACBS under extracorporeal circulation (EC. Subjects and methods. Sixty patients aged 60.6±8 years (M±& were examined after elective ACBS using EC and divided into two groups of 30 patients each: 1 inhalation induction and maintenance of anesthesia (IIMA with sevoflurane and fentanyl, with CPC being simulated; 2 total intravenous anesthesia (TIA with propofol and fentanyl. Inhalation induction of sevoflurane anesthesia was performed in the IIMA group. Ten minutes before aortic ligation, the dose of the anesthetic was increased up to 2 MAC for CPC. Inhaled anesthetics were not used in the TIA group. The authors assessed the pattern of cardiac performance recovery and estimated the level of NT-proBNP 24 and 48 hours after tracheal intubation and that of troponin I following 24 hours of the intubation. Results. Defibrillation was required in one patient from the TIA group who developed ventricular fibrillation. The baseline levels of NT-proBNP were comparable in both groups. Following 24 hours, its level was more than thrice higher in the TIA group than that in the IIMA one (p<0.05. By the end of 2 days, the concentration of NT-proBNP continued to rise (up to 480% of the baseline level in the TIA group and returned to the preoperative values in the IIMA group (p=0.05. Twenty-four hours after tracheal intubation the level of troponin I was insignificantly higher in the TIA group than that in the IIMA group (p=0.1. Conclusion. Sevoflurane has cardioprotective properties in preventing and/or reducing the degree of heart failure after ACBS using EC. There is a need to continue the study in increased cohort to provide evidence that sevoflurane-induced CPC can lower

  9. A Dynamic Approach to Modeling Dependence Between Human Failure Events

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald Laurids [Idaho National Laboratory

    2015-09-01

    In practice, most HRA methods use direct dependence from THERP—the notion that error be- gets error, and one human failure event (HFE) may increase the likelihood of subsequent HFEs. In this paper, we approach dependence from a simulation perspective in which the effects of human errors are dynamically modeled. There are three key concepts that play into this modeling: (1) Errors are driven by performance shaping factors (PSFs). In this context, the error propagation is not a result of the presence of an HFE yielding overall increases in subsequent HFEs. Rather, it is shared PSFs that cause dependence. (2) PSFs have qualities of lag and latency. These two qualities are not currently considered in HRA methods that use PSFs. Yet, to model the effects of PSFs, it is not simply a matter of identifying the discrete effects of a particular PSF on performance. The effects of PSFs must be considered temporally, as the PSFs will have a range of effects across the event sequence. (3) Finally, there is the concept of error spilling. When PSFs are activated, they not only have temporal effects but also lateral effects on other PSFs, leading to emergent errors. This paper presents the framework for tying together these dynamic dependence concepts.

  10. Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

    Science.gov (United States)

    Grassi, Bruno; Majerczak, Joanna; Bardi, Eleonora; Buso, Alessia; Comelli, Marina; Chlopicki, Stefan; Guzik, Magdalena; Mavelli, Irene; Nieckarz, Zenon; Salvadego, Desy; Tyrankiewicz, Urszula; Skórka, Tomasz; Bottinelli, Roberto; Zoladz, Jerzy A; Pellegrino, Maria Antonietta

    2017-08-01

    Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα q *44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgα q *44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgα q *44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance. NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration

  11. Regulation of cardiac remodeling by cardiac Na/K-ATPase isoforms

    Directory of Open Access Journals (Sweden)

    Lijun Catherine Liu

    2016-09-01

    Full Text Available Cardiac remodeling occurs after cardiac pressure/volume overload or myocardial injury during the development of heart failure and is a determinant of heart failure. Preventing or reversing remodeling is a goal of heart failure therapy. Human cardiomyocyte Na+/K+-ATPase has multiple α isoforms (1-3. The expression of the α subunit of the Na+/K+-ATPase is often altered in hypertrophic and failing hearts. The mechanisms are unclear. There are limited data from human cardiomyocytes. Abundant evidences from rodents show that Na+/K+-ATPase regulates cardiac contractility, cell signaling, hypertrophy and fibrosis. The α1 isoform of the Na+/K+-ATPase is the ubiquitous isoform and possesses both pumping and signaling functions. The α2 isoform of the Na+/K+-ATPase regulates intracellular Ca2+ signaling, contractility and pathological hypertrophy. The α3 isoform of the Na+/K+-ATPase may also be a target for cardiac hypertrophy. Restoration of cardiac Na+/K+-ATPase expression may be an effective approach for prevention of cardiac remodeling. In this article, we will overview: (1 the distribution and function of isoform specific Na+/K+-ATPase in the cardiomyocytes. (2 the role of cardiac Na+/K+-ATPase in the regulation of cell signaling, contractility, cardiac hypertrophy and fibrosis in vitro and in vivo. Selective targeting of cardiac Na+/K+-ATPase isoform may offer a new target for the prevention of cardiac remodeling.

  12. The China Patient-centered Evaluative Assessment of Cardiac Events (China PEACE) retrospective heart failure study design.

    Science.gov (United States)

    Yu, Yuan; Zhang, Hongzhao; Li, Xi; Lu, Yuan; Masoudi, Frederick A; Krumholz, Harlan M; Li, Jing

    2018-05-10

    Heart failure (HF) is a leading cause of hospitalisation in China, which is experiencing a rapid increase in cardiovascular disease prevalence. Yet, little is known about current burden of disease, quality of care and treatment outcomes of HF in China. The objective of this paper is to describe the study methodology, data collection and abstraction, and progress to date of the China Patient-centered Evaluative Assessment of Cardiac Events 5 Retrospective Heart Failure Study (China PEACE 5r-HF). The China PEACE 5r-HF Study will examine a nationally representative sample of more than 10 000 patient records hospitalised for HF in 2015 in China. The study is a retrospective cohort study. Patients have been selected using a two-stage sampling design stratified by economic-geographical regions. We will collect patient characteristics, diagnostic testing, treatments and in-hospital outcomes, including death and complications, and charges of hospitalisation. Data quality will be monitored by a central coordinating centre and will address case ascertainment, data abstraction and data management. As of October 2017, we have sampled 15 538 medical records from 189 hospitals, and have received 15 057 (96.9%) of these for data collection, and completed data abstraction and quality control on 7971. The Central Ethics Committee at the Chinese National Center for Cardiovascular Diseases approved the study. All collaborating hospitals accepted central ethics committee approval with the exception of 15 hospitals, which obtained local approval by internal ethics committees. Findings will be disseminated in future peer-reviewed papers and will serve as a foundation for improving the care for HF in China. NCT02877914. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. Genetically Modified Mouse Models Used for Studying the Role of the AT2 Receptor in Cardiac Hypertrophy and Heart Failure

    Directory of Open Access Journals (Sweden)

    Maria D. Avila

    2011-01-01

    Full Text Available The actions of Angiotensin II have been implicated in many cardiovascular conditions. It is widely accepted that the cardiovascular effects of Angiotensin II are mediated by different subtypes of receptors: AT1 and AT2. These membrane-bound receptors share a part of their nucleic acid but seem to have different distribution and pathophysiological actions. AT1 mediates most of the Angiotensin II actions since it is ubiquitously expressed in the cardiovascular system of the normal adult. Moreover AT2 is highly expressed in the developing fetus but its expression in the cardiovascular system is low and declines after birth. However the expression of AT2 appears to be modulated by pathological states such as hypertension, myocardial infarction or any pathology associated to tissue remodeling or inflammation. The specific role of this receptor is still unclear and different studies involving in vivo and in vitro experiments have shown conflicting data. It is essential to clarify the role of the AT2 receptor in the different pathological states as it is a potential site for an effective therapeutic regimen that targets the Angiotensin II system. We will review the different genetically modified mouse models used to study the AT2 receptor and its association with cardiac hypertrophy and heart failure.

  14. Ruling out cardiac failure: Cost-benefit analysis of a sequential testing strategy with NT-proBNP before echocardiography

    Science.gov (United States)

    Ferrandis, Maria-José; Ryden, Ingvar; Lindahl, Tomas L.

    2013-01-01

    Objectives To estimate the possible economic benefit of a sequential testing strategy with NT-proBNP to reduce the number of echocardiographies. Methods Retrospective study in a third-party payer perspective. The costs were calculated from three Swedish counties: Blekinge, Östergötland, and Uppland. Two cut-off levels of NT-proBNP were used: 400 and 300 pg/mL. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for echocardiographies. Results The estimated costs for NT-proBNP tests and echocardiographies per county were reduced by 33%–36% with the 400 pg/mL cut-off and by 28%–29% with the 300 pg/mL cut-off. This corresponded to a yearly cost reduction of approximately €2–5 million per million inhabitants in these counties. Conclusion The use of NT-proBNP as a screening test could substantially reduce the number of echocardiographies in the diagnostic work-up of patients with suspected cardiac failure, as well as the associated costs. PMID:23230860

  15. Concise Review: Pluripotent Stem Cell-Derived Cardiac Cells, A Promising Cell Source for Therapy of Heart Failure: Where Do We Stand?

    Science.gov (United States)

    Gouadon, Elodie; Moore-Morris, Thomas; Smit, Nicoline W; Chatenoud, Lucienne; Coronel, Ruben; Harding, Sian E; Jourdon, Philippe; Lambert, Virginie; Rucker-Martin, Catherine; Pucéat, Michel

    2016-01-01

    Heart failure is still a major cause of hospitalization and mortality in developed countries. Many clinical trials have tested the use of multipotent stem cells as a cardiac regenerative medicine. The benefit for the patients of this therapeutic intervention has remained limited. Herein, we review the pluripotent stem cells as a cell source for cardiac regeneration. We more specifically address the various challenges of this cell therapy approach. We question the cell delivery systems, the immune tolerance of allogenic cells, the potential proarrhythmic effects, various drug mediated interventions to facilitate cell grafting and, finally, we describe the pathological conditions that may benefit from such an innovative approach. As members of a transatlantic consortium of excellence of basic science researchers and clinicians, we propose some guidelines to be applied to cell types and modes of delivery in order to translate pluripotent stem cell cardiac derivatives into safe and effective clinical trials. © 2015 AlphaMed Press.

  16. Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.

    Science.gov (United States)

    Yamada, Yuko; Kinoshita, Hideyuki; Kuwahara, Koichiro; Nakagawa, Yasuaki; Kuwabara, Yoshihiro; Minami, Takeya; Yamada, Chinatsu; Shibata, Junko; Nakao, Kazuhiro; Cho, Kosai; Arai, Yuji; Yasuno, Shinji; Nishikimi, Toshio; Ueshima, Kenji; Kamakura, Shiro; Nishida, Motohiro; Kiyonaka, Shigeki; Mori, Yasuo; Kimura, Takeshi; Kangawa, Kenji; Nakao, Kazuwa

    2014-10-01

    Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca(2+) channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure. We compared the effects of cilnidipine, a dual N- and L-type Ca(2+) channel blocker, with those of nitrendipine, a selective L-type Ca(2+) channel blocker, in transgenic mice expressing a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). In this mouse model of dilated cardiomyopathy leading to sudden arrhythmic death, cardiac structure and function did not significantly differ among the control, cilnidipine, and nitrendipine groups. However, cilnidipine dramatically reduced arrhythmias in dnNRSF-Tg mice, significantly improving their survival rate and correcting the imbalance between cardiac sympathetic and parasympathetic nervous system activity. A β-blocker, bisoprolol, showed similar effects in these mice. Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B, which encodes the α1 subunit of NCCs, improved the survival rate. With restoration of cardiac autonomic balance, dnNRSF-Tg;CACNA1B(+/-) mice showed fewer malignant arrhythmias than dnNRSF-Tg;CACNA1B(+/+) mice. Both pharmacological blockade of NCCs and their genetic titration improved cardiac autonomic balance and prevented lethal arrhythmias in a mouse model of dilated cardiomyopathy and sudden arrhythmic death. Our findings suggest that NCC blockade is a potentially useful approach to preventing sudden death in patients with heart failure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  17. A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

    Science.gov (United States)

    Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

  18. A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy and Heart Failure

    DEFF Research Database (Denmark)

    Aubdool, Aisah A; Thakore, Pratish; Argunhan, Fulye

    2017-01-01

    cardiovascular disease in two distinct murine models of hypertension and heart failure in vivoMethods -The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin using a CGRP receptor antagonist. The effect of the αAnalogue on Angiotensin II (AngII)-induced hypertension......, Western blot and histology. Results -The AngII-induced hypertension was attenuated by co-treatment with the αAnalogue (50nmol/kg/day, s.c., at a dose selected for lack of long term hypotensive effects at baseline). The αAnalogue protected against vascular, renal and cardiac dysfunction, characterised...... failure. It preserved heart function, assessed by echocardiography, whilst protecting against adverse cardiac remodelling and apoptosis. Moreover, treatment with the αAnalogue was well-tolerated with neither signs of desensitisation nor behavioural changes. Conclusions -These findings, in two distinct...

  19. Cardiac influence on mechanical ventilation time and mortality in exacerbated chronic respiratory failure patients. The role of echocardiographic parameters

    Directory of Open Access Journals (Sweden)

    Paulo Marcelino

    2006-03-01

    Full Text Available Objective: To study the influence of cardiac status on the length of mechanical ventilation, outcome and disease severity in patients admitted to an Intensive Care Unit (ICU with exacerbation of chronic respiratory failure. Design and setting: A 30-month prospective study in a 14 bed ICU Patients and methods: Fifty nine patients were enrolled, with a mean age 74.7 +/- 9.7 years, mean length of ventilator support 10.8 +/- 12.6 days, and mean APACHE II score 23 +/- 8.3. Within the first 24 hours of admittance, cardiac chamber dimensions, inferior vena cava (IVC, and mitral transvalvular Doppler were evaluated using transthoracic echocardiography; the cardiac rhythm was recorded (presence of sinus rhythm or atrial fibrillation. Blood gases were evaluated at discharge. Results: Greater length of ventilation was observed in patients presenting atrial fibrillation (p = 0.027, particularly when a dilated IVC was also present (>20 mm, p = 0.004. A high level of serum bicarbonate (>35 mEq/l, was also related with longer ventilation (p = 0. 04. Twelve patients died. Mortality was related to the presence of a dilated right ventricle (p = 0.03 and a ratio between right and left ventricle > 0. 6 (p = 0.04. Conclusion: Patients submitted to mechanical ventilation due to exacerbation of chronic respiratory failure which present atrial fibrillation require a longer ventilation period, particularly if a dilated IVC is also present. Patients with dilated right cardiac chambers are at an increased risk of a fatal outcome. Resumo: Objectivo: estudar determinantes cardiovasculares condicionantes do tempo de ventilação, mortalidade e gravidade de doença em doentes admitidos numa unidade de cuidados intensivos para ventilação mecânica por exacerbação de insuficiência respiratória crónica. Desenho e local: Estudo prospectivo, com duração de 30 meses numa unidade de cuidados intensivos médico-cirúrgica com 14 camas. Material e m

  20. Cardiac Amyloidosis and its New Clinical Phenotype: Heart Failure with Preserved Ejection Fraction.

    Science.gov (United States)

    Mesquita, Evandro Tinoco; Jorge, Antonio José Lagoeiro; Souza, Celso Vale; Andrade, Thais Ribeiro de

    2017-07-01

    Heart failure with preserved ejection fraction (HFpEF) is now an emerging cardiovascular epidemic, being identified as the main phenotype observed in clinical practice. It is more associated with female gender, advanced age and comorbidities such as hypertension, diabetes, obesity and chronic kidney disease. Amyloidosis is a clinical disorder characterized by the deposition of aggregates of insoluble fibrils originating from proteins that exhibit anomalous folding. Recently, pictures of senile amyloidosis have been described in patients with HFpEF, demonstrating the need for clinical cardiologists to investigate this etiology in suspect cases. The clinical suspicion of amyloidosis should be increased in cases of HFPS where the cardio imaging methods are compatible with infiltrative cardiomyopathy. Advances in cardio imaging methods combined with the possibility of performing genetic tests and identification of the type of amyloid material allow the diagnosis to be made. The management of the diagnosed patients can be done in partnership with centers specialized in the study of amyloidosis, which, together with the new technologies, investigate the possibility of organ or bone marrow transplantation and also the involvement of patients in clinical studies that evaluate the action of the new emerging drugs. Resumo A insuficiência cardíaca com fração de ejeção preservada (ICFEP) é hoje uma epidemia cardiovascular emergente, sendo identificada como o principal fenótipo observado na prática clínica. Está mais associado ao sexo feminino, idade avançada e a comorbidades como hipertensão arterial, diabetes, obesidade e doença renal crônica. A amiloidose é uma desordem clínica caracterizada pelo depósito de agregados de fibrilas insolúveis originadas de proteínas que apresentam dobramento anômalo. Recentemente, têm sido descritos quadros de amiloidose senil em pacientes com ICFEP, demonstrando a necessidade de os cardiologistas clínicos investigarem

  1. Chronic activation of hypothalamic oxytocin neurons improves cardiac function during left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Garrott, Kara; Dyavanapalli, Jhansi; Cauley, Edmund; Dwyer, Mary Kate; Kuzmiak-Glancy, Sarah; Wang, Xin; Mendelowitz, David; Kay, Matthew W

    2017-09-01

    A distinctive hallmark of heart failure (HF) is autonomic imbalance, consisting of increased sympathetic activity, and decreased parasympathetic tone. Recent work suggests that activation of hypothalamic oxytocin (OXT) neurons could improve autonomic balance during HF. We hypothesized that a novel method of chronic selective activation of hypothalamic OXT neurons will improve cardiac function and reduce inflammation and fibrosis in a rat model of HF. Two groups of male Sprague-Dawley rats underwent trans-ascending aortic constriction (TAC) to induce left ventricular (LV) hypertrophy that progresses to HF. In one TAC group, OXT neurons in the paraventricular nucleus of the hypothalamus were chronically activated by selective expression and activation of excitatory DREADDs receptors with daily injections of clozapine N-oxide (CNO) (TAC + OXT). Two additional age-matched groups received either saline injections (Control) or CNO injections for excitatory DREADDs activation (OXT NORM). Heart rate (HR), LV developed pressure (LVDP), and coronary flow rate were measured in isolated heart experiments. Isoproterenol (0.01 nM-1.0 µM) was administered to evaluate β-adrenergic sensitivity. We found that increases in cellular hypertrophy and myocardial collagen density in TAC were blunted in TAC + OXT animals. Inflammatory cytokine IL-1β expression was more than twice higher in TAC than all other hearts. LVDP, rate pressure product (RPP), contractility, and relaxation were depressed in TAC compared with all other groups. The response of TAC and TAC + OXT hearts to isoproterenol was blunted, with no significant increase in RPP, contractility, or relaxation. However, HR in TAC + OXT animals increased to match Control at higher doses of isoproterenol. Activation of hypothalamic OXT neurons to elevate parasympathetic tone reduced cellular hypertrophy, levels of IL-1β, and fibrosis during TAC-induced HF in rats. Cardiac contractility parameters were

  2. Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.

    Science.gov (United States)

    Yamanushi, Tomoko T; Kabuto, Hideaki; Hirakawa, Eiichiro; Janjua, Najma; Takayama, Fusako; Mankura, Mitsumasa

    2014-04-01

    This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

  3. Cardiac-specific inducible overexpression of human plasma membrane Ca2+ ATPase 4b is cardioprotective and improves survival in mice following ischemic injury.

    Science.gov (United States)

    Sadi, Al Muktafi; Afroze, Talat; Siraj, M Ahsan; Momen, Abdul; White-Dzuro, Colin; Zarrin-Khat, Dorrin; Handa, Shivalika; Ban, Kiwon; Kabir, M Golam; Trivieri, Maria G; Gros, Robert; Backx, Peter; Husain, Mansoor

    2018-03-30

    Background: Heart failure (HF) is associated with reduced expression of plasma membrane Ca 2+ -ATPase 4 (PMCA4). Cardiac-specific overexpression of human PMCA4b in mice inhibited nNOS activity and reduced cardiac hypertrophy by inhibiting calcineurin. Here we examine temporally regulated cardiac-specific overexpression of hPMCA4b in mouse models of myocardial ischemia reperfusion injury (IRI) ex vivo , and HF following experimental myocardial infarction (MI) in vivo Methods and results: Doxycycline-regulated cardiomyocyte-specific overexpression and activity of hPMCA4b produced adaptive changes in expression levels of Ca 2+ -regulatory genes, and induced hypertrophy without significant differences in Ca 2+ transients or diastolic Ca 2+ concentrations. Total cardiac NOS and nNOS-specific activities were reduced in mice with cardiac overexpression of hPMCA4b while nNOS, eNOS and iNOS protein levels did not differ. hMPCA4b-overexpressing mice also exhibited elevated systolic blood pressure vs. controls, with increased contractility and lusitropy in vivo In isolated hearts undergoing IRI, hPMCA4b overexpression was cardioprotective. NO donor-treated hearts overexpressing hPMCA4b showed reduced LVDP and larger infarct size versus vehicle-treated hearts undergoing IRI, demonstrating that the cardioprotective benefits of hPMCA4b-repressed nNOS are lost by restoring NO availability. Finally, both pre-existing and post-MI induction of hPMCA4b overexpression reduced infarct expansion and improved survival from HF. Conclusions: Cardiac PMCA4b regulates nNOS activity, cardiac mass and contractility, such that PMCA4b overexpression preserves cardiac function following IRI, heightens cardiac performance and limits infarct progression, cardiac hypertrophy and HF, even when induced late post-MI. These data identify PMCA4b as a novel therapeutic target for IRI and HF. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  4. An analysis of human maintenance failures of a nuclear power plant

    International Nuclear Information System (INIS)

    Pyy, P.

    2000-01-01

    In the report, a study of faults caused by maintenance activities is presented. The objective of the study was to draw conclusions on the unplanned effects of maintenance on nuclear power plant safety and system availability. More than 4400 maintenance history reports from the years 1992-1994 of Olkiluoto BWR nuclear power plant (NPP) were analysed together with the maintenance personnel. The human action induced faults were classified, e.g., according to their multiplicity and effects. This paper presents and discusses the results of a statistical analysis of the data. Instrumentation and electrical components appeared to be especially prone to human failures. Many human failures were found in safety related systems. Several failures also remained latent from outages to power operation. However, the safety significance of failures was generally small. Modifications were an important source of multiple human failures. Plant maintenance data is a good source of human reliability data and it should be used more in the future. (orig.)

  5. Cardiac complication after experimental human malaria infection: a case report

    Directory of Open Access Journals (Sweden)

    Druilhe Pierre

    2009-12-01

    Full Text Available Abstract A 20 year-old healthy female volunteer participated in a clinical Phase I and IIa safety and efficacy trial with candidate malaria vaccine PfLSA-3-rec adjuvanted with aluminium hydroxide. Eleven weeks after the third and last immunization she was experimentally infected by bites of Plasmodium falciparum-infected mosquitoes. When the thick blood smear became positive, at day 11, she was treated with artemether/lumefantrine according to protocol. On day 16 post-infection i.e. two days after completion of treatment, she woke up with retrosternal chest pain. She was diagnosed as acute coronary syndrome and treated accordingly. She recovered quickly and her follow-up was uneventful. Whether the event was related to the study procedures such as the preceding vaccinations, malaria infection or antimalarial drugs remains elusive. However, the relation in time with the experimental malaria infection and apparent absence of an underlying condition makes the infection the most probable trigger. This is in striking contrast, however, with the millions of malaria cases each year and the fact that such complication has never been reported in the literature. The rare occurrence of cardiac events with any of the preceding study procedures may even support a coincidental finding. Apart from acute coronary syndrome, myocarditis can be considered as a final diagnosis, but the true nature and patho-physiological explanation of the event remain unclear.

  6. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation.

    Science.gov (United States)

    Bernardo, Bianca C; Sapra, Geeta; Patterson, Natalie L; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A; McMullen, Julie R

    2015-01-01

    Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions.

  7. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation.

    Directory of Open Access Journals (Sweden)

    Bianca C Bernardo

    Full Text Available Previous animal studies had shown that increasing heat shock protein 70 (Hsp70 using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF. AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC. Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions.

  8. Denoising human cardiac diffusion tensor magnetic resonance images using sparse representation combined with segmentation

    International Nuclear Information System (INIS)

    Bao, L J; Zhu, Y M; Liu, W Y; Pu, Z B; Magnin, I E; Croisille, P; Robini, M

    2009-01-01

    Cardiac diffusion tensor magnetic resonance imaging (DT-MRI) is noise sensitive, and the noise can induce numerous systematic errors in subsequent parameter calculations. This paper proposes a sparse representation-based method for denoising cardiac DT-MRI images. The method first generates a dictionary of multiple bases according to the features of the observed image. A segmentation algorithm based on nonstationary degree detector is then introduced to make the selection of atoms in the dictionary adapted to the image's features. The denoising is achieved by gradually approximating the underlying image using the atoms selected from the generated dictionary. The results on both simulated image and real cardiac DT-MRI images from ex vivo human hearts show that the proposed denoising method performs better than conventional denoising techniques by preserving image contrast and fine structures.

  9. Human cardiac telocytes: 3D imaging by FIB-SEM tomography.

    Science.gov (United States)

    Cretoiu, D; Hummel, E; Zimmermann, H; Gherghiceanu, M; Popescu, L M

    2014-11-01

    Telocyte (TC) is a newly identified type of cell in the cardiac interstitium (www.telocytes.com). TCs are described by classical transmission electron microscopy as cells with very thin and long telopodes (Tps; cellular prolongations) having podoms (dilations) and podomers (very thin segments). TCs' three-dimensional (3D) morphology is still unknown. Cardiac TCs seem to be particularly involved in long and short distance intercellular signalling and, therefore, their 3D architecture is important for understanding their spatial connections. Using focused ion beam scanning electron microscopy (FIB-SEM) we show, for the first time, the whole ultrastructural anatomy of cardiac TCs. 3D reconstruction of cardiac TCs by FIB-SEM tomography confirms that they have long, narrow but flattened (ribbon-like) telopodes, with humps generated by the podoms. FIB-SEM tomography also confirms the network made by TCs in the cardiac interstitium through adherens junctions. This study provides the first FIB-SEM tomography of a human cell type. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  10. Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity

    Directory of Open Access Journals (Sweden)

    Ashraf H. ElGhandour

    2009-04-01

    Full Text Available Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin’s lymphoma (NHL may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP, not exceeding the total allowed dose of doxorubicin (500 mg/m2. Ten healthy controls were included in our study. Human heart-type fatty acid binding protein (H-FABP was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.

  11. Risk stratification in patients with advanced heart failure requiring biventricular assist device support as a bridge to cardiac transplantation.

    Science.gov (United States)

    Cheng, Richard K; Deng, Mario C; Tseng, Chi-hong; Shemin, Richard J; Kubak, Bernard M; MacLellan, W Robb

    2012-08-01

    Prior studies have identified risk factors for survival in patients with end-stage heart failure (HF) requiring left ventricular assist device (LVAD) support. However, patients with biventricular HF may represent a unique cohort. We retrospectively evaluated a consecutive cohort of 113 adult, end-stage HF patients at University of California Los Angeles Medical Center who required BIVAD support between 2000 and 2009. Survival to transplant was 66.4%, with 1-year actuarial survival of 62.8%. All patients were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Level 1 or 2 and received Thoratec (Pleasanton, CA) paracorporeal BIVAD as a bridge to transplant. Univariate analyses showed dialysis use, ventilator use, extracorporal membrane oxygenation use, low cardiac output, preserved LV ejection fraction (restrictive physiology), normal-to-high sodium, low platelet count, low total cholesterol, low high-density and high-density lipoprotein, low albumin, and elevated aspartate aminotransferase were associated with increased risk of death. We generated a scoring system for survival to transplant. Our final model, with age, sex, dialysis, cholesterol, ventilator, and albumin, gave a C-statistic of 0.870. A simplified system preserved a C-statistic of 0.844. Patients were divided into high-risk or highest-risk groups (median respective survival, 367 and 17 days), with strong discrimination between groups for death. We have generated a scoring system that offers high prognostic ability for patients requiring BIVAD support and hope that it may assist in clinical decision making. Further studies are needed to prospectively validate our scoring system. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Protocol-driven remote monitoring of cardiac resynchronization therapy as part of a heart failure disease management strategy.

    Science.gov (United States)

    Smeets, Christophe J P; Verbrugge, Frederik H; Vranken, Julie; Van der Auwera, Jo; Mullens, Wilfried; Dupont, Matthias; Grieten, Lars; De Cannière, Hélène; Lanssens, Dorien; Vandenberk, Thijs; Storms, Valerie; Thijs, Inge M; Vandervoort, Pieter

    2017-08-14

    Cardiac resynchronisation therapy (CRT) is an established treatment for heart failure (HF) with reduced ejection fraction. CRT devices are equipped with remote monitoring functions, which are pivotal in the detection of device problems, but may also facilitate disease management. The aim of this study was to provide a comprehensive overview of the clinical interventions taken based on remote monitoring. This is a single centre observational study of consecutive CRT patients (n = 192) participating in protocol-driven remote follow-up. Incoming technical- and disease-related alerts were analysed together with subsequently triggered interventions. During 34 ± 13 months of follow-up, 1372 alert-containing notifications were received (2.53 per patient-year of follow-up), comprising 1696 unique alerts (3.12 per patient-year of follow-up). In 60%, notifications resulted in a phone contact. Technical alerts constituted 8% of incoming alerts (0.23 per patient-year of follow-up). Rhythm (1.43 per patient-year of follow-up) and bioimpedance alerts (0.98 per patient-year of follow-up) were the most frequent disease-related alerts. Notifications included a rhythm alert in 39%, which triggered referral to the emergency room (4%), outpatient cardiology clinic (36%) or general practitioner (7%), or resulted in medication changes (13%). Sole bioimpedance notifications resulted in a telephone contact in 91%, which triggered outpatient evaluation in 8% versus medication changes in 10%. Clinical outcome was excellent with 97% 1-year survival. Remote CRT follow-up resulted in 0.23 technical- versus 2.64 disease-related alerts annually. Rhythm and bioimpedance notifications constituted the majority of incoming notifications which triggered an actual intervention in 22% and 15% of cases, respectively.

  13. Deadline pressure and human error: a study of human failures on a particle accelerator at Brookhaven National Laboratory

    International Nuclear Information System (INIS)

    Tiagha, E.A.

    1982-01-01

    The decline in industrial efficiency may be linked to decreased reliability of complex automatic systems. This decline threatens the viability of complex organizations in industrialized economies. Industrial engineering techniques that minimize system failure by increasing the reliability of systems hardware are well developed in comparison with those available to reduce human operator errors. The problem of system reliability and the associated costs of breakdown can be reduced if we understand how highly skilled technical personnel function in complex operations and systems. The purpose of this research is to investigate how human errors are affected by deadline pressures, technical communication and other socio-dynamic factors. Through the analysis of a technologically complex particle accelerator prototype at Brookhaven National Laboratory, two failure mechanisms: (1) physical defects in the production process and (2) human operator errors were identified. Two instruments were used to collect information on human failures: objective laboratory data and a human failure questionnaire. The results of human failures from the objective data were used to test for the deadline hypothesis and also to validate the human failure questionnaire. To explain why the human failures occurred, data were collected from a four-part, closed choice questionnaire administered to two groups of scientists, engineers, and technicians, working together against a deadline to produce an engineering prototype of a particle accelerator

  14. Clinical value of iodine-123 beta-methyliodophenyl pentadecanoic acid (BMIPP) myocardial single photon emission computed tomography for predicting cardiac death among patients with chronic heart failure

    International Nuclear Information System (INIS)

    Sasaki, Ryu; Usui, Takashi; Mitani, Isao

    2003-01-01

    In the present study, the effectiveness of 123 I-β-methyliodophenyl pentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) for predicting cardiac death of patients with chronic heart failure was evaluated. Abnormalities of fatty acid metabolism are found in patients with chronic heart failure and BMIPP was developed as a tracer for scintigraphic assessment of myocardial fatty acid utilization. The study group comprised 74 patients with chronic heart failure with a left ventricular ejection fraction (LVEF) 201 Tl SPECT and BMIPP SPECT. The uptake of tracer was scored semiquantitatively from 0 (normal) to 4 (defect) in 20 segments and a total defect score (TDS) for all 20 segments was calculated. On planar images the mediastinum to heart count ratio (H/M) was calculated for the BMIPP and Tl studies, and the H/M BMIPP :H/M Tl (H/M BMIPP divided by H/M Tl ) was also calculated. The mean follow-up period was 660 days and there were 17 cases of cardiac death. Multivariate analysis identified H/M BMIPP :H/M Tl (p BMIPP :H/M Tl was situated to the left relative to LVEF. Analysis of the myocardial metabolism by BMIPP SPECT can predict the high-risk patients with chronic heart failure. (author)

  15. In silico prediction of sex-based differences in human susceptibility to cardiac ventricular tachyarrhythmias

    Directory of Open Access Journals (Sweden)

    Pei-Chi eYang

    2012-09-01

    Full Text Available Sex-based differences in human susceptibility to cardiac ventricular tachyarrhythmias likely result from the emergent effects of multiple intersecting processes that fundamentally differ in male and female hearts. Included are measured differences in the genes encoding key cardiac ion channels and effects of sex steroid hormones to acutely modify electrical activity. At the genome scale, human females have recently been shown to have lower expression of genes encoding key cardiac repolarizing potassium currents and connexin43, the primary ventricular gap junction subunit. Human males and females also have distinct sex steroid hormones. Here, we developed mathematical models for male and female ventricular human heart cells by incorporating experimentally determined genomic differences and effects of sex steroid hormones into the O’Hara-Rudy model. These male and female model cells and tissues then were used to predict how various sex-based differences underlie arrhythmia risk. Genomic-based differences in ion channel expression were alone sufficient to determine longer female cardiac action potential durations (APD in both epicardial and endocardial cells compared to males. Subsequent addition of sex steroid hormones exacerbated these differences, as testosterone further shortened APDs, while estrogen and progesterone application resulted in disparate effects on APDs. Our results indicate that incorporation of experimentally determined genomic differences from human hearts in conjunction with sex steroid hormones are consistent with clinically observed differences in QT interval, T-wave shape and morphology, and critically, in the higher vulnerability of adult human females to Torsades de Pointes type arrhythmias. The model suggests that female susceptibility to alternans stems from longer female action potentials, while reentrant arrhythmia derives largely from sex-based differences in conduction play an important role in arrhythmia

  16. Differential gene expression of cardiac ion channels in human dilated cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Maria Micaela Molina-Navarro

    Full Text Available BACKGROUND: Dilated cardiomyopathy (DCM is characterized by idiopathic dilation and systolic contractile dysfunction of the cardiac chambers. The present work aimed to study the alterations in gene expression of ion channels involved in cardiomyocyte function. METHODS AND RESULTS: Microarray profiling using the Affymetrix Human Gene® 1.0 ST array was performed using 17 RNA samples, 12 from DCM patients undergoing cardiac transplantation and 5 control donors (CNT. The analysis focused on 7 cardiac ion channel genes, since this category has not been previously studied in human DCM. SCN2B was upregulated, while KCNJ5, KCNJ8, CLIC2, CLCN3, CACNB2, and CACNA1C were downregulated. The RT-qPCR (21 DCM and 8 CNT samples validated the gene expression of SCN2B (p < 0.0001, KCNJ5 (p < 0.05, KCNJ8 (p < 0.05, CLIC2 (p < 0.05, and CACNB2 (p < 0.05. Furthermore, we performed an IPA analysis and we found a functional relationship between the different ion channels studied in this work. CONCLUSION: This study shows a differential expression of ion channel genes involved in cardiac contraction in DCM that might partly underlie the changes in left ventricular function observed in these patients. These results could be the basis for new genetic therapeutic approaches.

  17. Impact of aging on cardiac sympathetic innervation measured by {sup 123}I-mIBG imaging in patients with systolic heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Rengo, Giuseppe; Ferrara, Nicola [Scientific Institute of Telese Terme, Salvatore Maugeri Foundation, IRCCS, Telese Terme (Italy); University of Naples Federico II, Division of Geriatrics, Department of Translational Medical Sciences, Naples (Italy); Pagano, Gennaro; Formisano, Roberto; Komici, Klara; Petraglia, Laura; Parisi, Valentina; Femminella, Grazia Daniela; De Lucia, Claudio; Cannavo, Alessandro; Memmi, Alessia; Leosco, Dario [University of Naples Federico II, Division of Geriatrics, Department of Translational Medical Sciences, Naples (Italy); Vitale, Dino Franco [Scientific Institute of Telese Terme, Salvatore Maugeri Foundation, IRCCS, Telese Terme (Italy); Paolillo, Stefania [Institute of Diagnostic and Nuclear Development, SDN Foundation, Naples (Italy); Attena, Emilio [Fatebenefratelli Hospital, Department of Cardiology, Naples (Italy); Pellegrino, Teresa [Institute of Biostructures and Bioimages of the National Council of Research, Naples (Italy); Federico II University of Naples, Division of Imaging, Radiotherapy, Neuroradiology, and Medical Physics, Department of Advanced Biomedical Sciences, Naples (Italy); Dellegrottaglie, Santo [Ospedale Medico-Chirurgico Accreditato Villa dei Fiori, Division of Cardiology, Acerra, Naples (Italy); Trimarco, Bruno; Filardi, Pasquale Perrone [Federico II University of Naples, Division of Cardiology, Department of Advanced Biomedical Sciences, Naples (Italy); Cuocolo, Alberto [Institute of Diagnostic and Nuclear Development, SDN Foundation, Naples (Italy); Federico II University of Naples, Division of Imaging, Radiotherapy, Neuroradiology, and Medical Physics, Department of Advanced Biomedical Sciences, Naples (Italy)

    2016-12-15

    Sympathetic nervous system (SNS) hyperactivity is a salient characteristic of chronic heart failure (HF) and contributes to the progression of the disease. Iodine-123 meta-iodobenzylguanidine ({sup 123}I-mIBG) imaging has been successfully used to assess cardiac SNS activity in HF patients and to predict prognosis. Importantly, SNS hyperactivity characterizes also physiological ageing, and there is conflicting evidence on cardiac {sup 123}I-mIBG uptake in healthy elderly subjects compared to adults. However, little data are available on the impact of ageing on cardiac sympathetic nerve activity assessed by {sup 123}I-mIBG scintigraphy, in patients with HF. We studied 180 HF patients (age = 66.1 ± 10.5 years [yrs]), left ventricular ejection fraction (LVEF = 30.6 ± 6.3 %) undergoing cardiac {sup 123}I-mIBG imaging. Early and late heart to mediastinum (H/M) ratios and washout rate were calculated in all patients. Demographic, clinical, and echocardiographic data were also collected. Our study population consisted of 53 patients aged >75 years (age = 77.7 ± 4.0 year), 67 patients aged 62-72 years (age = 67.9 ± 3.2 years) and 60 patients aged ≤61 year (age = 53.9 ± 5.6 years). In elderly patients, both early and late H/M ratios were significantly lower compared to younger patients (p < 0.05). By multivariate analysis, H/M ratios (both early and late) and washout rate were significantly correlated with LVEF and age. Our data indicate that, in a population of HF patients, there is an independent age-related effect on cardiac SNS innervation assessed by {sup 123}I-mIBG imaging. This finding suggests that cardiac {sup 123}I-mIBG uptake in patients with HF might be affected by patient age. (orig.)

  18. Occurrence, aetiology and challenges in the management of congestive heart failure in sub-saharan Africa: experience of the Cardiac Centre in Shisong, Cameroon

    Directory of Open Access Journals (Sweden)

    Tantchou Tchoumi Jacques Cabral

    2011-02-01

    Full Text Available INTRODUCTION: The aim of the study was to investigate the occurrence, the aetiology and the management of congestive heart failure in the cardiac centre of the St. Elizabeth catholic general hospital Shisong in Cameroon. METHODS: Between November 2002 and November 2008, a population of 8121 patients was consulted in the referral cardiac centre of St. Elizabeth Catholic General Hospital. Of these patients, 462 were diagnosed with congestive heart failure according to the modified Framingham criteria for the diagnosis of heart failure. Complementary investigations used to confirm and establish the aetiology of the disease were the chest X-ray, electrocardiography, bi-dimensional Doppler echocardiography. RESULTS: The results showed that the occurrence of congestive heart failure in our centre was 5,7%. Congestive heart failure was diagnosed in 198 females and 264 males, aged between 8 and 86 years old (42.5, plus or minus 18 years old. Post rheumatic valvulopathies (14.6% and congenital heart diseases (1.9% were the first aetiologic factor of congestive heart failure in the young, meanwhile cardiomyopathies (8,3% in elderly followed by hypertensive cardiomyopathy (4.4%. Congestive heart failure was also seen in adults with congenital heart diseases in 0.01%. In this zone of Cameroon, we discovered that HIV cardiomyopathy (1.6% and Cor pulmonale (8% were represented, aetiological factors not mentioned in previous studies conducted in urban areas of Cameroon. The mean duration of hospital stay for the compensation treatment was thirteen days, ranging between 7 and 21 days, the mortality being 9.2%. All the medications recommended for the treatment of congestive heart failure are available in our centre but many patients are not compliant to the therapy or cannot afford them. Financial limitation is causing the exacerbation of the disease and premature death. CONCLUSION: Our data show a high incidence of congestive heart failure mainly due to post

  19. Heart failure and sudden cardiac death in heritable thoracic aortic disease caused by pathogenic variants in the SMAD3 gene.

    Science.gov (United States)

    Backer, Julie De; Braverman, Alan C

    2018-05-01

    Predominant cardiovascular manifestations in the spectrum of Heritable Thoracic Aortic Disease include by default aortic root aneurysms- and dissections, which may be associated with aortic valve disease. Mitral- and tricuspid valve prolapse are other commonly recognized features. Myocardial disease, characterized by heart failure and/or malignant arrhythmias has been reported in humans and in animal models harboring pathogenic variants in the Fibrillin1 gene. Description of clinical history of three cases from one family in Ghent (Belgium) and one family in St. Louis (US). We report on three cases from two families presenting end-stage heart failure (in two) and lethal arrhythmias associated with moderate left ventricular dilatation (in one). All three cases harbor a pathogenic variant in the SMAD3 gene, known to cause aneurysm osteoarthritis syndrome, Loeys-Dietz syndrome type 3 or isolated Heritable Thoracic Aortic Disease. These unusual presentations warrant awareness for myocardial disease in patients harboring pathogenic variants in genes causing Heritable Thoracic Aortic Disease and indicate the need for prospective studies in larger cohorts. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  20. The importance of daily physical activity for improved exercise tolerance in heart failure patients with limited access to centre-based cardiac rehabilitation.

    Science.gov (United States)

    Sato, Noriaki; Origuchi, Hideki; Yamamoto, Umpei; Takanaga, Yasuhiro; Mohri, Masahiro

    2012-09-01

    Supervised cardiac rehabilitation provided at dedicated centres ameliorates exercise intolerance in patients with chronic heart failure. To correlate the amount of physical activity outside the hospital with improved exercise tolerance in patients with limited access to centre-based programs. Forty patients (median age 69 years) with stable heart failure due to systolic left ventricular dysfunction participated in cardiac rehabilitation once per week for five months. Using a validated single-axial accelerometer, the number of steps and physical activity-related energy expenditures on nonrehabilitation days were determined. Median (interquartile range) peak oxygen consumption was increased from 14.4 mL/kg/min (range 12.9 mL/kg/min to 17.8 mL/kg/min) to 16.4 mL/kg/min (range 13.9 mL/kg/min to 19.1 mL/kg/min); Pdaily number of steps (Pexercise time per day and time spent for light (≤3 metabolic equivalents) exercise, but not with time spent for moderate/vigorous (>3 metabolic equivalents) exercise. The number of steps and energy expenditures outside the hospital were correlated with improved exercise capacity. An accelerometer may be useful for guiding home-based cardiac rehabilitation.

  1. The common mode failures analysis of the redundent system with dependent human error

    International Nuclear Information System (INIS)

    Kim, M.K.; Chang, S.H.

    1983-01-01

    Common mode failures (CMFs) have been a serious concern in the nuclear power plant. Thereis a broad category of the failure mechanisms that can cause common mode failures. This paper is a theoretical investigation of the CMFs on the unavailability of the redundent system. It is assumed that the total CMFs consist of the potential CMFs and the dependent human error CMFs. As the human error dependency is higher, the total CMFs are more effected by the dependent human error. If the human error dependence is lower, the system unavailability strongly depends on the potential CMFs, rather than the mechanical failure or the dependent human error. And it is shown that the total CMFs are dominant factor to the unavailability of the redundent system. (Author)

  2. Multiple sequential failure model: A probabilistic approach to quantifying human error dependency

    International Nuclear Information System (INIS)

    Samanta

    1985-01-01

    This paper rpesents a probabilistic approach to quantifying human error dependency when multiple tasks are performed. Dependent human failures are dominant contributors to risks from nuclear power plants. An overview of the Multiple Sequential Failure (MSF) model developed and its use in probabilistic risk assessments (PRAs) depending on the available data are discussed. A small-scale psychological experiment was conducted on the nature of human dependency and the interpretation of the experimental data by the MSF model show remarkable accommodation of the dependent failure data. The model, which provides an unique method for quantification of dependent failures in human reliability analysis, can be used in conjunction with any of the general methods currently used for performing the human reliability aspect in PRAs

  3. Statistical analysis of human maintenance failures of a nuclear power plant

    International Nuclear Information System (INIS)

    Pyy, P.

    2000-01-01

    In this paper, a statistical study of faults caused by maintenance activities is presented. The objective of the study was to draw conclusions on the unplanned effects of maintenance on nuclear power plant safety and system availability. More than 4400 maintenance history reports from the years 1992-1994 of Olkiluoto BWR nuclear power plant (NPP) were analysed together with the maintenance personnel. The human action induced faults were classified, e.g., according to their multiplicity and effects. This paper presents and discusses the results of a statistical analysis of the data. Instrumentation and electrical components are especially prone to human failures. Many human failures were found in safety related systems. Similarly, several failures remained latent from outages to power operation. The safety significance was generally small. Modifications are an important source of multiple human failures. Plant maintenance data is a good source of human reliability data and it should be used more, in future. (orig.)

  4. Human induced pluripotent stem cell-derived beating cardiac tissues on paper.

    Science.gov (United States)

    Wang, Li; Xu, Cong; Zhu, Yujuan; Yu, Yue; Sun, Ning; Zhang, Xiaoqing; Feng, Ke; Qin, Jianhua

    2015-11-21

    There is a growing interest in using paper as a biomaterial scaffold for cell-based applications. In this study, we made the first attempt to fabricate a paper-based array for the culture, proliferation, and direct differentiation of human induced pluripotent stem cells (hiPSCs) into functional beating cardiac tissues and create "a beating heart on paper." This array was simply constructed by binding a cured multi-well polydimethylsiloxane (PDMS) mold with common, commercially available paper substrates. Three types of paper material (print paper, chromatography paper and nitrocellulose membrane) were tested for adhesion, proliferation and differentiation of human-derived iPSCs. We found that hiPSCs grew well on these paper substrates, presenting a three-dimensional (3D)-like morphology with a pluripotent property. The direct differentiation of human iPSCs into functional cardiac tissues on paper was also achieved using our modified differentiation approach. The cardiac tissue retained its functional activities on the coated print paper and chromatography paper with a beating frequency of 40-70 beats per min for up to three months. Interestingly, human iPSCs could be differentiated into retinal pigment epithelium on nitrocellulose membrane under the conditions of cardiac-specific induction, indicating the potential roles of material properties and mechanical cues that are involved in regulating stem cell differentiation. Taken together, these results suggest that different grades of paper could offer great opportunities as bioactive, low-cost, and 3D in vitro platforms for stem cell-based high-throughput drug testing at the tissue/organ level and for tissue engineering applications.

  5. Identification of cellular targets involved in cardiac failure caused by PKI in oncology: an approach combining pharmacovigilance and pharmacodynamics.

    Science.gov (United States)

    Patras de Campaigno, Emilie; Bondon-Guitton, Emmanuelle; Laurent, Guy; Montastruc, Francois; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse; Despas, Fabien

    2017-07-01

    The aims of the present study were to evaluate the risk of cardiac failure (CF) associated with 15 anticancer protein kinase inhibitors (PKIs) through a case/noncase analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. In order to evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the World Health Organization safety report database (VigiBase®). We realised a literature review to identify 21 protein kinases (PKs) that were possibly involved in CF caused by PKIs. Pearson correlation coefficients (r) between aRORs and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely to be involved in PKI-induced CF. A total of 141 601 individual case safety reports (ICSRs) were extracted from VigiBase® for the following PKIs: afatinib, axitinib, bosutinib, crizotinib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, pazopanib, ruxolitinib, sorafenib, sunitinib and vandetanib. Among them, 2594 ICSRs concerned CF. The disproportionality analysis revealed that, for dasatinib, imatinib, bosutinib, sunitinib and nilotinib, disproportionality for CF was significantly higher than for other PKIs, with aRORs of 2.52 [95% CI 2.26, 2.82], 1.79 (95% CI 1.57, 2.03), 1.73 (95% CI 1.18, 2.54), 1.67 (95% CI 1.51, 1.84) and 1.38 (95% CI 1.18, 1.61), respectively. Significant values for correlation coefficients between the product of dissociation constant (pKd) and aROR were observed for two non-receptor protein kinases: ABL1 (non-phosphorylated and phosphorylated forms) and ABL2 protein kinases, with values of r = 0.83 (P = 0.0001), r = 0.75 (P = 0.0014) and r = 0.78 (P = 0.0006), respectively. We observed a higher disproportionality for CF with dasatinib, imatinib, bosutinib, sunitinib and nilotinib than with other PKIs. In addition, the study highlighted the role of ABL tyrosine kinases in CF caused by anticancer PKIs. © 2017 The British

  6. Effects of perindopril on cardiac sympathetic nerve activity in patients with congestive heart failure: comparison with enalapril

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Suzuki, Tadashi; Kurabayashi, Masahiko [Gunma University School of Medicine, Department of Cardiovascular Medicine, Maebashi, Gunma (Japan); Kumakura, Hisao; Takayama, Yoshiaki; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan, Department of Internal Medicine, Gunma (Japan)

    2005-08-01

    The production of aldosterone in the heart is suppressed by the angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with congestive heart failure (CHF). Moreover, perindopril has been reported to have more cardioprotective effects than enalapril. Forty patients with CHF [left ventricular ejection fraction (LVEF) <45%; mean 33{+-}7%] were randomly assigned to perindopril (2 mg/day; n=20) or enalapril (5 mg/day; n=20). All patients were also treated with diuretics. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS) and washout rate (WR) were determined from {sup 123}I-meta-iodobenzylguanidine (MIBG) images, and plasma brain natriuretic peptide (BNP) concentrations were measured before and 6 months after treatment. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and LVEF were also determined by echocardiography. After treatment, in patients receiving perindopril, TDS decreased from 39{+-}10 to 34{+-}9 (P<0.01), H/M ratios increased from 1.62{+-}0.27 to 1.76{+-}0.29 (P<0.01), WR decreased from 50{+-}14% to 42{+-}14% (P<0.05) and plasma BNP concentrations decreased from 226{+-}155 to 141{+-}90 pg/ml (P<0.0005). In addition, the LVEDV decreased from 180{+-}30 to 161{+-}30 ml (P<0.05) and the LVESV decreased from 122{+-}35 to 105{+-}36 ml (P<0.05). Although the LVEF tended to increase, the change was not statistically significant (from 33{+-}8% to 36{+-}12%; P=NS). On the other hand, there were no significant changes in these parameters in patients receiving enalapril. Plasma BNP concentrations, {sup 123}I-MIBG scintigraphic and echocardiographic parameters improved after 6 months of perindopril treatment. These findings indicate that perindopril treatment can ameliorate the cardiac sympathetic nerve activity and the left ventricular performance in patients with CHF. (orig.)

  7. Reproducibility of the acute rejection diagnosis in human cardiac allografts. The Stanford Classification and the International Grading System

    DEFF Research Database (Denmark)

    Nielsen, H; Sørensen, Flemming Brandt; Nielsen, B

    1993-01-01

    Transplantation has become an accepted treatment of many cardiac end-stage diseases. Acute cellular rejection accounts for 15% to 20% of all graft failures. The first grading system of acute cellular rejection, the Stanford Classification, was introduced in 1979, and since then many other grading...

  8. Utility of heart rate turbulence and T-Wave alternans to assess risk for Re-admission and cardiac death in hospitalized heart failure patients.

    Science.gov (United States)

    Yamada, Shinya; Yoshihisa, Akiomi; Sato, Yu; Sato, Takamasa; Kamioka, Masashi; Kaneshiro, Takashi; Oikawa, Masayoshi; Kobayashi, Atsushi; Suzuki, Hitoshi; Ishida, Takafumi; Takeishi, Yasuchika

    2018-05-18

    Heart failure (HF) patients have a higher risk of recurrent HF and cardiac death, and electrical remodeling is considered to be an important factor for HF progression. The present study aimed to validate the utility of electrocardiogram and Holter monitoring for the risk stratification of HF patients. Our study comprised 215 patients (144 males, mean age 62 years) who had been hospitalized due to acute decompensated HF. Electrocardiogram (QRS duration and QTc interval) and 24-hour Holter monitoring (heart rate variability, heart rate turbulence and T-wave alternans [TWA]) were performed in stable condition before discharge. The clinical characteristics and outcomes were then investigated. During a median follow-up period of 2.7 years, there were 83 (38.6%) cardiac events (re-hospitalization due to worsening HF [n = 51] or cardiac death [n = 32]). The patients with cardiac events had a lower turbulence slope (TS) and higher TWA compared to those without cardiac events (TS, 3.0±5.5 ms/RR vs. 5.3±5.6 ms/RR, P = 0.001; TWA, 66.1±19.6 μV vs. 54.7±15.1 μV, P < 0.001). Univariable analysis showed that TS, TWA, QRS duration, and QTc interval were associated with cardiac events (P = 0.004, P < 0.001, P = 0.037 and P = 0.024, respectively), while the multivariable analysis after the adjustment of multiple confounders showed that TS and TWA were independent predictive factors of cardiac events with a hazard ratio of 0.936 and 1.015 (95% confidence interval [CI]: 0.860-0.974, P = 0.006; and 95% CI: 1.003-1.027, p = 0.016), respectively. The measurement of TS and TWA is useful for assessing risk for re-hospitalization and cardiac death in HF patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  9. An exploratory study on the efficacy and safety of a BCAA preparation used in combination with cardiac rehabilitation for patients with chronic heart failure.

    Science.gov (United States)

    Takata, Munenori; Amiya, Eisuke; Watanabe, Masafumi; Hosoya, Yumiko; Nakayama, Atsuko; Fujiwara, Takayuki; Taya, Masanobu; Oguri, Gaku; Hyodo, Kanako; Takayama, Naoko; Takano, Nami; Mashiko, Tomoe; Uemura, Yukari; Komuro, Issei

    2017-07-27

    Sarcopenia is generally complicated with patients with chronic heart failure (CHF) and its presence negatively affects the course of heart failure, however effective nutritional intervention had not been elucidated yet. The primary objective of this study is to explore whether the addition of a branched-chain amino acid (BCAA) preparation for cardiac rehabilitation (CR) of patients with CHF further improves cardiopulmonary functions, skeletal muscle functions, and metabolism in comparison with conventional CR. This is a randomized, parallel-group comparative study. The elderly patients that were participated in CR and complicated with left ventricular systolic or diastolic dysfunction are randomized into two groups, CR + BCAA and CR. 20 weeks later, the second randomization is performed, which divide subjects into two groups with and without BCAA intervention without CR. Primary outcome measure is the rate of change of the anaerobic threshold workload from baseline to post-intervention. Secondary outcome include parameters of exercise capacity, cardiac function and psychological status. In the current study the effect of a promising new intervention, BCAA, will be assessed to determine whether its addition to CR improve exercise capacity in patients with heart failure, who are generally complicated with sarcopenia. This clinical trial was registered with the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR; JPRN-UMIN R000022440 ).

  10. Effect of granulocyte colony stimulating EPC on cardiac function and myocardial energy expenditure in patients with heart failure after myocardial infarction.

    Science.gov (United States)

    Zhao, Zilin; Luo, Jianchun; Ma, Lixian; Luo, Xia; Huang, Liangyan

    2015-01-01

    To study the changes of cardiac function and myocardial energy expenditure following treatment with granulocyte colony stimulating factor (G-CSF) in patients with heart failure after myocardial infarction. Thirty-eight patients with heart failure after myocardial infarction were randomized into G-CSF treatment group and control group. All the patients received conventional treatment (medication and interventional therapy), and the patients in treatment group were given additional G-CSF (600 μg/day) for 7 consecutive days. The plasma level of brain-type natriuretic peptide (BNP) and the number of endothelial progenitor cells (EPC) in the peripheral blood were detected before and at 7 days and 4 months after the treatment. The cardiac functions (LVEF, FS, LVIDs, PWTs, EDV, SV, ET) was evaluated by ultrasonic imaging before and at 2 weeks and 4 months after the treatment. The MEE and circumferential end-systolic wall stress (cESS) were calculated by correlation formula. The number of EPC was significantly higher in the treatment group than in the control group after the treatment especially at 7 days (Pexpenditure were improved in all the patients at 2 weeks and 4 months after the treatment, and the improvement was more obvious in the treatment group (Pexpenditure in patients with heart failure after myocardial infarction.

  11. Metabolic determinants of electrical failure in ex-vivo canine model of cardiac arrest: evidence for the protective role of inorganic pyrophosphate.

    Directory of Open Access Journals (Sweden)

    Junko Shibayama

    Full Text Available Deterioration of ventricular fibrillation (VF into asystole or severe bradycardia (electrical failure heralds a fatal outcome of cardiac arrest. The role of metabolism in the timing of electrical failure remains unknown.To determine metabolic factors of early electrical failure in an ex-vivo canine model of cardiac arrest (VF+global ischemia.Metabolomic screening was performed in left ventricular biopsies collected before and after 0.3, 2, 5, 10 and 20 min of VF and global ischemia. Electrical activity was monitored via plunge needle electrodes and pseudo-ECG. Four out of nine hearts exhibited electrical failure at 10.1±0.9 min (early-asys, while 5/9 hearts maintained VF for at least 19.7 min (late-asys. As compared to late-asys, early-asys hearts had more ADP, less phosphocreatine, and higher levels of lactate at some time points during VF/ischemia (all comparisons p<0.05. Pre-ischemic samples from late-asys hearts contained ∼25 times more inorganic pyrophosphate (PPi than early-asys hearts. A mechanistic role of PPi in cardioprotection was then tested by monitoring mitochondrial membrane potential (ΔΨ during 20 min of simulated-demand ischemia using potentiometric probe TMRM in rabbit adult ventricular myocytes incubated with PPi versus control group. Untreated myocytes experienced significant loss of ΔΨ while in the PPi-treated myocytes ΔΨ was relatively maintained throughout 20 min of simulated-demand ischemia as compared to control (p<0.05.High tissue level of PPi may prevent ΔΨm loss and electrical failure at the early phase of ischemic stress. The link between the two protective effects may involve decreased rates of mitochondrial ATP hydrolysis and lactate accumulation.

  12. Evaluating Failures and near Misses in Human Spaceflight History for Lessons for Future Human Spaceflight

    Science.gov (United States)

    Barr, Stephanie

    2010-01-01

    Studies done in the past have drawn on lessons learned with regard to human loss-of-life events. However, an examination of near-fatal accidents can be equally useful, not only in detecting causes, both proximate and systemic, but also for determining what factors averted disaster, what design decisions and/or operator actions prevented catastrophe. Binary pass/fail launch history is often used for risk, but this also has limitations. A program with a number of near misses can look more reliable than a consistently healthy program with a single out-of-family failure. Augmenting reliability evaluations with this near miss data can provide insight and expand on the limitations of a strictly pass/fail evaluation. This paper intends to show how near-miss lessons learned can provide crucial data for any new human spaceflight programs that are interested in sending man into space

  13. Oral treatment with herbal formula B307 alleviates cardiac failure in aging R6/2 mice with Huntington’s disease via suppressing oxidative stress, inflammation, and apoptosis

    Directory of Open Access Journals (Sweden)

    Lin CL

    2015-07-01

    Full Text Available Ching-Lung Lin,1 Sheue-Er Wang,2 Chih-Hsiang Hsu,1 Shuenn-Jyi Sheu,3 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, Taipei, 2Department of Pathological Inspection, Soeurs de Saint Paul de Chartres Medical Corporate Body, Taoyuan City, 3Brion Research Institute of Taiwan, New Taipei City, Taiwan Abstract: Cardiac failure is often observed in aging patients with Huntington’s disease (HD. However, conventional pharmacological treatments for cardiac failure in HD patients have rarely been studied. Chinese herbal medicines, especially combined herbal formulas, have been widely used to treat cardiac dysfunctions over the centuries. Thus, we assess whether oral treatment with herbal formula B307 can alleviate cardiac failure in transgenic mice with HD. After oral B307 or vehicle treatment for 2 weeks, cardiac function and cardiomyocytes in 12-week-old male R6/2 HD mice and their wild-type littermate controls (WT were examined and then compared via echocardiography, immunohistochemistry, and Western blotting. We found that cardiac performance in aging R6/2 HD mice had significantly deteriorated in comparison with their WT (P<0.01. Cardiac expressions of superoxide dismutase 2 (SOD2 and B-cell lymphoma 2 (Bcl-2 in aging R6/2 HD mice were significantly lower than their WT (P<0.01, but cardiac expressions of tumor necrosis factor alpha (TNF-α, neurotrophin-3 (3-NT, 4-hydroxynonenal (4-HNE, Bcl-2-associated X protein (Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly higher than their WT (P<0.05. Furthermore, we found that cardiac performance in aging R6/2 HD mice had significantly improved under oral B307 treatment (P<0.05. Cardiac expressions of SOD2 and Bcl-2 of aging R6/2 HD mice were significantly higher under oral B307 treatment (P<0.01, but cardiac expressions of TNF-α, 3-NT, 4-HNE, Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly

  14. Rigid microenvironments promote cardiac differentiation of mouse and human embryonic stem cells

    Science.gov (United States)

    Arshi, Armin; Nakashima, Yasuhiro; Nakano, Haruko; Eaimkhong, Sarayoot; Evseenko, Denis; Reed, Jason; Stieg, Adam Z.; Gimzewski, James K.; Nakano, Atsushi

    2013-04-01

    While adult heart muscle is the least regenerative of tissues, embryonic cardiomyocytes are proliferative, with embryonic stem (ES) cells providing an endless reservoir. In addition to secreted factors and cell-cell interactions, the extracellular microenvironment has been shown to play an important role in stem cell lineage specification, and understanding how scaffold elasticity influences cardiac differentiation is crucial to cardiac tissue engineering. Though previous studies have analyzed the role of matrix elasticity on the function of differentiated cardiomyocytes, whether it affects the induction of cardiomyocytes from pluripotent stem cells is poorly understood. Here, we examine the role of matrix rigidity on cardiac differentiation using mouse and human ES cells. Culture on polydimethylsiloxane (PDMS) substrates of varied monomer-to-crosslinker ratios revealed that rigid extracellular matrices promote a higher yield of de novo cardiomyocytes from undifferentiated ES cells. Using a genetically modified ES system that allows us to purify differentiated cardiomyocytes by drug selection, we demonstrate that rigid environments induce higher cardiac troponin T expression, beating rate of foci, and expression ratio of adult α- to fetal β- myosin heavy chain in a purified cardiac population. M-mode and mechanical interferometry image analyses demonstrate that these ES-derived cardiomyocytes display functional maturity and synchronization of beating when co-cultured with neonatal cardiomyocytes harvested from a developing embryo. Together, these data identify matrix stiffness as an independent factor that instructs not only the maturation of already differentiated cardiomyocytes but also the induction and proliferation of cardiomyocytes from undifferentiated progenitors. Manipulation of the stiffness will help direct the production of functional cardiomyocytes en masse from stem cells for regenerative medicine purposes.

  15. A universal system for highly efficient cardiac differentiation of human induced pluripotent stem cells that eliminates interline variability.

    Directory of Open Access Journals (Sweden)

    Paul W Burridge

    2011-04-01

    Full Text Available The production of cardiomyocytes from human induced pluripotent stem cells (hiPSC holds great promise for patient-specific cardiotoxicity drug testing, disease modeling, and cardiac regeneration. However, existing protocols for the differentiation of hiPSC to the cardiac lineage are inefficient and highly variable. We describe a highly efficient system for differentiation of human embryonic stem cells (hESC and hiPSC to the cardiac lineage. This system eliminated the variability in cardiac differentiation capacity of a variety of human pluripotent stem cells (hPSC, including hiPSC generated from CD34(+ cord blood using non-viral, non-integrating methods.We systematically and rigorously optimized >45 experimental variables to develop a universal cardiac differentiation system that produced contracting human embryoid bodies (hEB with an improved efficiency of 94.7±2.4% in an accelerated nine days from four hESC and seven hiPSC lines tested, including hiPSC derived from neonatal CD34(+ cord blood and adult fibroblasts using non-integrating episomal plasmids. This cost-effective differentiation method employed forced aggregation hEB formation in a chemically defined medium, along with staged exposure to physiological (5% oxygen, and optimized concentrations of mesodermal morphogens BMP4 and FGF2, polyvinyl alcohol, serum, and insulin. The contracting hEB derived using these methods were composed of high percentages (64-89% of cardiac troponin I(+ cells that displayed ultrastructural properties of functional cardiomyocytes and uniform electrophysiological profiles responsive to cardioactive drugs.This efficient and cost-effective universal system for cardiac differentiation of hiPSC allows a potentially unlimited production of functional cardiomyocytes suitable for application to hPSC-based drug development, cardiac disease modeling, and the future generation of clinically-safe nonviral human cardiac cells for regenerative medicine.

  16. Significance of change in serum bilirubin in predicting left ventricular reverse remodeling and outcomes in heart failure patients with cardiac resynchronization therapy.

    Science.gov (United States)

    Hosoda, Junya; Ishikawa, Toshiyuki; Matsumoto, Katsumi; Iguchi, Kohei; Matsushita, Hirooki; Ogino, Yutaka; Taguchi, Yuka; Sugano, Teruyasu; Ishigami, Tomoaki; Kimura, Kazuo; Tamura, Kouichi

    2017-11-01

    Research on the correlation of serum bilirubin level with cardiac function as well as outcomes in heart failure patients with cardiac resynchronization therapy (CRT) has not yet been reported. The aim of this study was to analyze the relationship between change in serum bilirubin level and left ventricular reverse remodeling, and also to clarify the impact of bilirubin change on clinical outcomes in CRT patients. We evaluated 105 consecutive patients who underwent CRT. Patients who had no serum total-bilirubin data at both baseline and 3-9 months' follow-up or had died less than 3 months after CRT implantation were excluded. Accordingly, a total of 69 patients were included in the present analysis. The patients were divided into two groups: decreased bilirubin group (serum total-bilirubin level at follow-up≤that at baseline; n=48) and increased bilirubin group (serum total-bilirubin level at follow-up>that at baseline; n=21). Mean follow-up period was 39.3 months. In the decreased bilirubin group, mean left ventricular end-systolic diameter decreased from 54.5mm to 50.2mm (p=0.001) and mean left ventricular ejection fraction increased significantly from 29.8% to 37.0% (p=0.001). In the increased bilirubin group, there was no significant change in echocardiographic parameters from baseline to follow-up. In Kaplan-Meyer analysis, cardiac mortality combined with heart failure hospitalization in the increased bilirubin group was significantly higher than that in the decreased bilirubin group (log-rank p=0.018). Multivariate Cox regression analysis revealed that increased bilirubin was an independent predictor of cardiac mortality combined with heart failure hospitalization (OR=2.66, p=0.023). The change in serum bilirubin is useful for assessment of left ventricular reverse remodeling and prediction of outcomes in heart failure patients with CRT. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  17. A quantitative impact analysis of sensor failures on human operator's decision making in nuclear power plants

    International Nuclear Information System (INIS)

    Seong, Poong Hyun

    2004-01-01

    In emergency or accident situations in nuclear power plants, human operators take important roles in generating appropriate control signals to mitigate accident situation. In human reliability analysis (HRA) in the framework of probabilistic safety assessment (PSA), the failure probabilities of such appropriate actions are estimated and used for the safety analysis of nuclear power plants. Even though understanding the status of the plant is basically the process of information seeking and processing by human operators, it seems that conventional HRA methods such as THERP, HCR, and ASEP does not pay a lot of attention to the possibilities of providing wrong information to human operators. In this paper, a quantitative impact analysis of providing wrong information to human operators due to instrument faults or sensor failures is performed. The quantitative impact analysis is performed based on a quantitative situation assessment model. By comparing the situation in which there are sensor failures and the situation in which there are not sensor failures, the impact of sensor failures can be evaluated quantitatively. It is concluded that the impact of sensor failures are quite significant at the initial stages, but the impact is gradually reduced as human operators make more and more observations. Even though the impact analysis is highly dependent on the situation assessment model, it is expected that the conclusions made based on other situation assessment models with be consistent with the conclusion made in this paper. (author)

  18. Environmental Toxin Screening Using Human-Derived 3D Bioengineered Liver and Cardiac Organoids

    Directory of Open Access Journals (Sweden)

    Steven D. Forsythe

    2018-04-01

    Full Text Available IntroductionEnvironmental toxins, such as lead and other heavy metals, pesticides, and other compounds, represent a significant health concern within the USA and around the world. Even in the twenty-first century, a plethora of cities and towns in the U.S. have suffered from exposures to lead in drinking water or other heavy metals in food or the earth, while there is a high possibility of further places to suffer such exposures in the near future.MethodsWe employed bioengineered 3D human liver and cardiac organoids to screen a panel of environmental toxins (lead, mercury, thallium, and glyphosate, and charted the response of the organoids to these compounds. Liver and cardiac organoids were exposed to lead (10 µM–10 mM, mercury (200 nM–200 µM, thallium (10 nM–10 µM, or glyphosate (25 µM–25 mM for a duration of 48 h. The impacts of toxin exposure were then assessed by LIVE/DEAD viability and cytotoxicity staining, measuring ATP activity and determining IC50 values, and determining changes in cardiac organoid beating activity.ResultsAs expected, all of the toxins induced toxicity in the organoids. Both ATP and LIVE/DEAD assays showed toxicity in both liver and cardiac organoids. In particular, thallium was the most toxic, with IC50 values of 13.5 and 1.35 µM in liver and cardiac organoids, respectively. Conversely, glyphosate was the least toxic of the four compounds, with IC50 values of 10.53 and 10.85 mM in liver and cardiac organoids, respectively. Additionally, toxins had a negative influence on cardiac organoid beating activity as well. Thallium resulting in the most significant decreases in beating rate, followed by mercury, then glyphosate, and finally, lead. These results suggest that the 3D organoids have significant utility to be deployed in additional toxicity screening applications, and future development of treatments to mitigate exposures.Conclusion3D organoids have significant utility to be

  19. Human error recovery failure probability when using soft controls in computerized control rooms

    International Nuclear Information System (INIS)

    Jang, Inseok; Kim, Ar Ryum; Seong, Poong Hyun; Jung, Wondea

    2014-01-01

    Many literatures categorized recovery process into three phases; detection of problem situation, explanation of problem causes or countermeasures against problem, and end of recovery. Although the focus of recovery promotion has been on categorizing recovery phases and modeling recovery process, research related to human recovery failure probabilities has not been perform actively. On the other hand, a few study regarding recovery failure probabilities were implemented empirically. Summarizing, researches that have performed so far have several problems in terms of use in human reliability analysis (HRA). By adopting new human-system interfaces that are based on computer-based technologies, the operation environment of MCRs in NPPs has changed from conventional MCRs to advanced MCRs. Because of the different interfaces between conventional and advanced MCRs, different recovery failure probabilities should be considered in the HRA for advanced MCRs. Therefore, this study carries out an empirical analysis of human error recovery probabilities under an advanced MCR mockup called compact nuclear simulator (CNS). The aim of this work is not only to compile a recovery failure probability database using the simulator for advanced MCRs but also to collect recovery failure probability according to defined human error modes to compare that which human error mode has highest recovery failure probability. The results show that recovery failure probability regarding wrong screen selection was lowest among human error modes, which means that most of human error related to wrong screen selection can be recovered. On the other hand, recovery failure probabilities of operation selection omission and delayed operation were 1.0. These results imply that once subject omitted one task in the procedure, they have difficulties finding and recovering their errors without supervisor's assistance. Also, wrong screen selection had an effect on delayed operation. That is, wrong screen

  20. Metabolic activity and mRNA levels of human cardiac CYP450s involved in drug metabolism.

    Directory of Open Access Journals (Sweden)

    Veronique Michaud

    2010-12-01

    Full Text Available Tissue-specific expression of CYP450s can regulate the intracellular concentration of drugs and explain inter-subject variability in drug action. The overall objective of our study was to determine in a large cohort of samples, mRNA levels and CYP450 activity expressed in the human heart.CYP450 mRNA levels were determined by RTPCR in left ventricular samples (n = 68 of explanted hearts from patients with end-stage heart failure. Samples were obtained from ischemic and non-ischemic hearts. In some instances (n = 7, samples were available from both the left and right ventricles. A technique for the preparation of microsomes from human heart tissue was developed and CYP450-dependent activity was determined using verapamil enantiomers as probe-drug substrates.Our results show that CYP2J2 mRNA was the most abundant isoform in all human heart left ventricular samples tested. Other CYP450 mRNAs of importance were CYP4A11, CYP2E1, CYP1A1 and CYP2C8 mRNAs while CYP2B6 and CYP2C9 mRNAs were present at low levels in only some of the hearts analyzed. CYP450 mRNAs did not differ between ischemic and non-ischemic hearts and appeared to be present at similar levels in the left and right ventricles. Incubation of verapamil with heart microsomes led to the formation of nine CYP450-dependent metabolites: a major finding was the observation that stereoselectivity was reversed compared to human liver microsomes, in which the R-enantiomer is metabolized to a greater extent.This study determined cardiac mRNA levels of various CYP450 isozymes involved in drug metabolism and demonstrated the prevalent expression of CYP2J2 mRNA. It revealed that cardiomyocytes can efficiently metabolize drugs and that cardiac CYP450s are highly relevant with regard to clearance of drugs in the heart. Our results support the claim that drug metabolism in the vicinity of a drug effector site can modulate drug effects.

  1. Beneficial effect of perindopril on cardiac sympathetic nerve activity and brain natriuretic peptide in patients with chronic heart failure. Comparison with enalapril

    International Nuclear Information System (INIS)

    Tsutamoto, Takayoshi; Tanaka, Toshinari; Sakai, Hiroshi

    2008-01-01

    In patients with chronic heart failure (CHF), it remains unclear whether perindopril is more cardioprotective than enalapril. Forty-five stable CHF outpatients undergoing conventional therapy including enalapril therapy were randomized to 2 groups [group I (n=24): continuous enalapril treatment; group II (n=21): enalapril was changed to perindopril]. Cardiac sympathetic nerve activity was evaluated using cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and 6 months after treatment. There was no difference in baseline characteristics between the 2 groups. In group I, there were no changes in MIBG parameters, left ventricular ejection fraction (LVEF) or plasma level of brain natriuretic peptide (BNP). In contrast, in group II delayed heart/mediastinum count ratio was significantly increased (2.0±0.07 vs 2.15±0.07, p=0.013) and the washout rate was significantly decreased (33.0±1.4 vs 30.5±1.2, p=0.030) after 6 months compared with the baseline value. In addition, LVEF was significantly increased and the plasma BNP level was significantly decreased. These findings suggest that for the treatment of CHF, perindopril is superior to enalapril with respect of cardiac sympathetic nerve activity and BNP. (author)

  2. Cytokine-induced oxidative stress in cardiac inflammation and heart failure – how the ubiquitin proteasome system targets this vicious cycle

    Directory of Open Access Journals (Sweden)

    Antje eVoigt

    2013-03-01

    Full Text Available The ubiquitin proteasome system (UPS is critical for the regulation of many intracellular processes necessary for cell function and survival. The absolute requirement of the UPS for the maintenance of protein homeostasis and thereby for the regulation of protein quality control is reflected by the fact that deviation of proteasome function from the norm was reported in cardiovascular pathologies. Inflammation is a major factor contributing to cardiac pathology. Herein, cytokines induce protein translation and the production of free radicals, thereby challenging the cellular protein equilibrium. Here, we discuss current knowledge on the mechanisms of UPS-functional adaptation in response to oxidative stress in cardiac inflammation. The increasing pool of oxidant-damaged degradation-prone proteins in cardiac pathology accounts for the need for enhanced protein turnover by the UPS. This process is accomplished by an up-regulation of the ubiquitylation machinery and the induction of immunoproteasomes. Thereby, the inflamed heart muscle is cleared from accumulating misfolded proteins. Current advances on immunoproteasome-specific inhibitors in this field question the impact of the proteasome as a therapeutic target in heart failure.

  3. Evaluation of a self-management patient education program for patients with chronic heart failure undergoing inpatient cardiac rehabilitation: study protocol of a cluster randomized controlled trial.

    Science.gov (United States)

    Meng, Karin; Musekamp, Gunda; Seekatz, Bettina; Glatz, Johannes; Karger, Gabriele; Kiwus, Ulrich; Knoglinger, Ernst; Schubmann, Rainer; Westphal, Ronja; Faller, Hermann

    2013-08-23

    Chronic heart failure requires a complex treatment regimen on a life-long basis. Therefore, self-care/self-management is an essential part of successful treatment and comprehensive patient education is warranted. However, specific information on program features and educational strategies enhancing treatment success is lacking. This trial aims to evaluate a patient-oriented and theory-based self-management educational group program as compared to usual care education during inpatient cardiac rehabilitation in Germany. The study is a multicenter cluster randomized controlled trial in four cardiac rehabilitation clinics. Clusters are patient education groups that comprise HF patients recruited within 2 weeks after commencement of inpatient cardiac rehabilitation. Cluster randomization was chosen for pragmatic reasons, i.e. to ensure a sufficient number of eligible patients to build large-enough educational groups and to prevent contamination by interaction of patients from different treatment allocations during rehabilitation. Rehabilitants with chronic systolic heart failure (n = 540) will be consecutively recruited for the study at the beginning of inpatient rehabilitation. Data will be assessed at admission, at discharge and after 6 and 12 months using patient questionnaires. In the intervention condition, patients receive the new patient-oriented self-management educational program, whereas in the control condition, patients receive a short lecture-based educational program (usual care). The primary outcome is patients' self-reported self-management competence. Secondary outcomes include behavioral determinants and self-management health behavior (symptom monitoring, physical activity, medication adherence), health-related quality of life, and treatment satisfaction. Treatment effects will be evaluated separately for each follow-up time point using multilevel regression analysis, and adjusting for baseline values. This study evaluates the effectiveness of a

  4. Is cardiac resynchronization therapy an option in heart failure patients with preserved ejection fraction? Justification for the ongoing KaRen project.

    Science.gov (United States)

    Donal, Erwan; Lund, Lars; Linde, Cecilia; Daubert, Jean-Claude

    2010-01-01

    The relevance of electrical and mechanical dyssynchrony has been demonstrated in heart failure with reduced ejection fraction. Preserved ejection fraction is present in as many as 50% of patients with chronic heart failure. Recent small studies suggest that both electrical and mechanical left ventricular dyssynchrony are sometimes present in patients with heart failure and preserved ejection fraction (HFPEF). These data remain controversial and a robust validation of this hypothesis has to be achieved. In the present paper, we review in detail the concepts and try to justify the ongoing KaRen registry. This is a prospective, multicentre, international, observational study to characterize the prevalence of electrical or mechanical dyssynchrony in HFPEF and the resultant effect on prognosis. Patients are enrolled currently at the time of an acute congestive episode. The diagnosis of HFPEF is made according to clinical data, natriuretic peptides and echocardiography for the measurement of ejection fraction. Once stabilized, patients return for a hospital check-up. They undergo clinical and biological evaluation, electrocardiography and Doppler echocardiography. Thereafter, patients are followed every six months, for at least 18 months for mortality, and heart failure-related and non-cardiovascular hospitalizations. KaRen aims to characterize electrical and mechanical dyssynchrony and to assess its prognostic impact in HFPEF. The results may improve our understanding of HFPEF and generate answers to the question of whether or not dyssynchrony could be a target for cardiac resynchronization therapy in HFPEF. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  5. Effect of adjuvant noninvasive positive pressure ventilation on blood gas parameters, cardiac function and inflammatory state in patients with COPD and type II respiratory failure

    Directory of Open Access Journals (Sweden)

    You-Ming Zhu1

    2017-03-01

    Full Text Available Objective: T o analyze the effect of adjuvant noninvasive positive pressure ventilation on blood gas parameters, cardiac function and inflammatory state in patients with chronic obstructive pulmonary disease (COPD and type II respiratory failure. Methods: 90 patients with COPD and type II respiratory failure were randomly divided into observation group and control group (n=45. Control group received conventional therapy, observation group received conventional therapy + adjuvant noninvasive positive pressure ventilation, and differences in blood gas parameters, cardiac function, inflammatory state, etc., were compared between two groups of patients 2 weeks after treatment. Results: Arterial blood gas parameters pH and alveolar-arterial partial pressure of oxygen [P(A-aO2] levels of observation group were higher than those of control group while, potassium ion (K+, chloride ion (Cl﹣ and carbon dioxide combining power (CO2CP levels were lower than those of control group 2 weeks after treatment; echocardiography parameters Doppler-derived tricuspid lateral annular systolic velocity (DTIS and pulmonary arterial velocity (PAV levels were lower than those of control group (P<0.05 while pulmonary artery accelerating time (PAACT, left ventricular enddiastolic dimension (LVDd and right atrioventricular tricuspid annular plane systolic excursion (TAPSE levels were higher than those of control group (P<0.05; serum cardiac function indexes adiponectin (APN, Copeptin, N-terminal pro-B-type natriuretic peptide (NT-proBNP, cystatin C (CysC, growth differentiation factor-15 (GDF-15 and heart type fatty acid binding protein (H-FABP content were lower than those of control group (P<0.05; serum inflammatory factors hypersensitive C-reactive protein (hs-CRP, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, IL-8, IL-10, and transforming growth factor-β1 (TGF-β1 content were lower than those of control group (P<0.05. Conclusions: Adjuvant

  6. Pharmacokinetic/pharmacodynamic modeling of cardiac toxicity in human acute overdoses: utility and limitations.

    Science.gov (United States)

    Mégarbane, Bruno; Aslani, Arsia Amir; Deye, Nicolas; Baud, Frédéric J

    2008-05-01

    Hypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings. To review the utility and limits of PK/PD studies of cardiac toxicity. Discussion of various models, mainly those obtained in digitalis, cyanide, venlafaxine and citalopram poisonings. A sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.

  7. Identification of the human factors contributing to maintenance failures in a petroleum operation.

    Science.gov (United States)

    Antonovsky, Ari; Pollock, Clare; Straker, Leon

    2014-03-01

    This research aimed to identify the most frequently occurring human factors contributing to maintenance-related failures within a petroleum industry organization. Commonality between failures will assist in understanding reliability in maintenance processes, thereby preventing accidents in high-hazard domains. Methods exist for understanding the human factors contributing to accidents. Their application in a maintenance context mainly has been advanced in aviation and nuclear power. Maintenance in the petroleum industry provides a different context for investigating the role that human factors play in influencing outcomes. It is therefore worth investigating the contributing human factors to improve our understanding of both human factors in reliability and the factors specific to this domain. Detailed analyses were conducted of maintenance-related failures (N = 38) in a petroleum company using structured interviews with maintenance technicians. The interview structure was based on the Human Factor Investigation Tool (HFIT), which in turn was based on Rasmussen's model of human malfunction. A mean of 9.5 factors per incident was identified across the cases investigated.The three most frequent human factors contributing to the maintenance failures were found to be assumption (79% of cases), design and maintenance (71%), and communication (66%). HFIT proved to be a useful instrument for identifying the pattern of human factors that recurred most frequently in maintenance-related failures. The high frequency of failures attributed to assumptions and communication demonstrated the importance of problem-solving abilities and organizational communication in a domain where maintenance personnel have a high degree of autonomy and a wide geographical distribution.

  8. Hazards caused by human failure and measures to reduce them

    International Nuclear Information System (INIS)

    Hartmann, W.; Hartmann, L.

    1985-01-01

    The safety engineer's method of thinking is discussed especially in the context of a nuclear power plant. The importance of human and medical factors in safety is stressed. A comparison with safety measures in the chemical industry is given

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

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Y. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China); Liu, B. [Department of Pathology, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei (China); Wang, H.P. [Department of Histology and Embryology, Hebei North University, Zhangjiakou, Hebei (China); Zhang, L. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China)

    2016-05-31

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  11. 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

  12. Atorvastatin improves cardiac function and remodeling in chronic non-ischemic heart failure: A clinical and pre-clinical study

    Directory of Open Access Journals (Sweden)

    Ibrahim Elmadbouh

    2015-12-01

    Conclusions: Atorvastatin with standard CHF therapy improved cardiac function and remodeling. Cardio-protective “pleiotropic” actions of atorvastatin are anti-inflammatory, anti-fibrotic and anti-oxidative. Thus, atorvastatin has a potential therapeutic value in the management of CHF patients.

  13. High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure

    NARCIS (Netherlands)

    M. Rosa-Garrido (Manuel); Chapski, D.J. (Douglas J.); Schmitt, A.D. (Anthony D.); Kimball, T.H. (Todd H.); Karbassi, E. (Elaheh); Monte, E. (Emma); Balderas, E. (Enrique); Pellegrini, M. (Matteo); Shih, T.-T. (Tsai-Ting); Soehalim, E. (Elizabeth); D.A. Liem (David); Ping, P. (Peipei); N.J. Galjart (Niels); Ren, S. (Shuxun); Wang, Y. (Yibin); Ren, B. (Bing); Vondriska, T.M. (Thomas M.)

    2017-01-01

    textabstractBACKGROUND: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined.METHODS: To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation

  14. Expression of a novel cardiac-specific tropomyosin isoform in humans

    International Nuclear Information System (INIS)

    Denz, Christopher R.; Narshi, Aruna; Zajdel, Robert W.; Dube, Dipak K.

    2004-01-01

    Tropomyosins are a family of actin binding proteins encoded by a group of highly conserved genes. Humans have four tropomyosin-encoding genes: TPM1, TPM2, TPM3, and TPM4, each of which is known to generate multiple isoforms by alternative splicing, promoters, and 3 ' end processing. TPM1 is the most versatile and encodes a variety of tissue specific isoforms. The TPM1 isoform specific to striated muscle, designated TPM1α, consists of 10 exons: 1a, 2b, 3, 4, 5, 6b, 7, 8, and 9a/b. In this study, using RT-PCR with adult and fetal human RNAs, we present evidence for the expression of a novel isoform of the TPM1 gene that is specifically expressed in cardiac tissues. The new isoform is designated TPM1κ and contains exon 2a instead of 2b. Ectopic expression of human GFP.TPM1κ fusion protein can promote myofibrillogenesis in cardiac mutant axolotl hearts that are lacking in tropomyosin

  15. Diabetic db/db mice do not develop heart failure upon pressure overload: a longitudinal in vivo PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations.

    Science.gov (United States)

    Abdurrachim, Desiree; Nabben, Miranda; Hoerr, Verena; Kuhlmann, Michael T; Bovenkamp, Philipp; Ciapaite, Jolita; Geraets, Ilvy M E; Coumans, Will; Luiken, Joost J F P; Glatz, Jan F C; Schäfers, Michael; Nicolay, Klaas; Faber, Cornelius; Hermann, Sven; Prompers, Jeanine J

    2017-08-01

    Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. Transverse aortic constriction (TAC) was performed in non-diabetic (db/+) and diabetic (db/db) mice to induce pressure overload. Magnetic resonance imaging, 31P magnetic resonance spectroscopy (MRS), 1H MRS, and 18F-fluorodeoxyglucose-positron emission tomography (PET) were applied to measure cardiac function, energy status, lipid content, and glucose uptake, respectively. In vivo measurements were complemented with ex vivo techniques of high-resolution respirometry, proteomics, and western blotting to elucidate the underlying molecular pathways. In non-diabetic mice, TAC induced progressive cardiac hypertrophy and dysfunction, which correlated with increased protein kinase D-1 (PKD1) phosphorylation and increased glucose uptake. These changes in glucose utilization preceded a reduction in cardiac energy status. At baseline, compared with non-diabetic mice, diabetic mice showed normal cardiac function, higher lipid content and mitochondrial capacity for fatty acid oxidation, and lower PKD1 phosphorylation, glucose uptake, and energetics. Interestingly, TAC affected cardiac function only mildly in diabetic mice, which was accompanied by normalization of phosphorylated PKD1, glucose uptake, and cardiac energy status. The cardiac metabolic adaptations in diabetic mice seem to prevent the heart from failing upon pressure overload, suggesting that restoring the balance between glucose and fatty acid utilization is beneficial for cardiac function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions

  16. Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs) Cultured on an Aligned-Nanofiber Cardiac Patch.

    Science.gov (United States)

    Khan, Mahmood; Xu, Yanyi; Hua, Serena; Johnson, Jed; Belevych, Andriy; Janssen, Paul M L; Gyorke, Sandor; Guan, Jianjun; Angelos, Mark G

    2015-01-01

    Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates. hiPSC-CMs were cultured on; 1) a highly aligned polylactide-co-glycolide (PLGA) nanofiber scaffold (~50 microns thick) and 2) on a standard flat culture plate. Scanning electron microscopy (SEM) was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43) was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes. SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro. Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic environment

  17. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    Science.gov (United States)

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  18. Concise Review: Fluorescent Reporters in Human Pluripotent Stem Cells: Contributions to Cardiac Differentiation and Their Applications in Cardiac Disease and Toxicity.

    Science.gov (United States)

    Den Hartogh, Sabine C; Passier, Robert

    2016-01-01

    In the last decade, since the first report of induced pluripotent stem cells, the stem cell field has made remarkable progress in the differentiation to specialized cell-types of various tissues and organs, including the heart. Cardiac lineage- and tissue-specific human pluripotent stem cell (hPSC) reporter lines have been valuable for the identification, selection, and expansion of cardiac progenitor cells and their derivatives, and for our current understanding of the underlying molecular mechanisms. In order to further advance the use of hPSCs in the fields of regenerative medicine, disease modeling, and preclinical drug development in cardiovascular research, it is crucial to identify functionally distinct cardiac subtypes and to study their biological signaling events and functional aspects in healthy and diseased conditions. In this review, we discuss the various strategies that have been followed to generate and study fluorescent reporter lines in hPSCs and provide insights how these reporter lines contribute to a better understanding and improvement of cell-based therapies and preclinical drug and toxicity screenings in the cardiac field. © AlphaMed Press.

  19. From human error to organizational failure: a historical perspective

    International Nuclear Information System (INIS)

    Guarnieri, F.; Cambon, J.; Boissieres, I.

    2008-01-01

    This article hinges around three main parts.The first part goes back over the foundations of the human factor approach. It introduces the basic assumptions as well as some of the methods which have been developed. The second part accounts for the reasons why organizational factors have drawn our attention at the first place underlying two major points: the limits of the human factor approach but also the original contribution and the innovative aspect of sociology. At last, the third part describes the keystone principles and hypotheses on which lay the foundations of the organizational factor approach and draws a brief overview of the methods which have lately been implanted within the industrial world. (authors)

  20. Cost-Effectiveness of Adding Cardiac Resynchronization Therapy to an Implantable Cardioverter-Defibrillator Among Patients With Mild Heart Failure

    DEFF Research Database (Denmark)

    Woo, Christopher Y; Strandberg, Erika J; Schmiegelow, Michelle D

    2015-01-01

    -defibrillator (ICD) alone among patients with left ventricular systolic dysfunction, prolonged intraventricular conduction, and mild heart failure. DESIGN: Markov decision model. DATA SOURCES: Clinical trials, clinical registries, claims data from Centers for Medicare & Medicaid Services, and Centers for Disease...

  1. Characterization of exercise limitations by evaluating individual cardiac output patterns : A prospective cohort study in patients with chronic heart failure

    NARCIS (Netherlands)

    Spee, R.F.; Niemeijer, V.M.; Wessels, B.; Jansen, J.P.; Wijn, P.F.F.; Doevendans, P.A.F.M.; Kemps, H.M.C.

    2015-01-01

    Background: Patients with chronic heart failure (CHF) suffer from exercise intolerance due to impaired central hemodynamics and subsequent alterations in peripheral skeletal muscle function and structure. The relative contribution of central versus peripheral factors in the reduced exercise capacity

  2. Characterization of exercise limitations by evaluating individual cardiac output patterns: a prospective cohort study in patients with chronic heart failure

    NARCIS (Netherlands)

    Spee, Ruud F.; Niemeijer, Victor M.; Wessels, Bart; Jansen, Jasper P.; Wijn, Pieter F. F.; Doevendans, Pieter A. F. M.; Kemps, Hareld M. C.

    2015-01-01

    Patients with chronic heart failure (CHF) suffer from exercise intolerance due to impaired central hemodynamics and subsequent alterations in peripheral skeletal muscle function and structure. The relative contribution of central versus peripheral factors in the reduced exercise capacity is still

  3. Changes in cardiac glycoside receptor sites /sup 86/ rubidium uptake and intracellular sodium concentrations in the erythrocytes of patients receiving digoxin during the early phases of treatment of cardiac failure in regular rhythm and of atrial fibrillation

    Energy Technology Data Exchange (ETDEWEB)

    Ford, A R; Aronson, J K; Grahame-Smith, D G; Carver, J G [Medical Research Council, Oxford (UK)

    1979-08-01

    Measurements of the binding of 12-..cap alpha..-(/sup 3/H)-digoxin to the membranes of intact erythrocytes, erythrocytic /sup 86/Rb uptake and intraerythrocytic sodium concentrations have been made in the red cells of patients receiving digoxin in the short-term for atrial fibrillation or cardiac failure in regular rhythm. During the first few days of treatment (/sup 3/H)-digoxin binding and /sup 86/Rb uptake fall and intraerythrocytic sodium concentrations rise. Subsequently parallel fluctuations occur in (/sup 3/H)-digoxin binding and /sup 86/Rb uptake but not in intraerythrocytic sodium concentrations and the significance of the fluctuations is discussed. The values of all three measurements correlate significantly with the response of the heart in sinus rhythm as measured by QS/sub 2/I. Plasma digoxin concentrations do not correlate with QS/sub 2/I.

  4. The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses α Myosin Heavy-Chain Gene Expression

    Science.gov (United States)

    Sucharov, Carmen C.; Helmke, Steve M.; Langer, Stephen J.; Perryman, M. Benjamin; Bristow, Michael; Leinwand, Leslie

    2004-01-01

    Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure. PMID:15367688

  5. Ebola virus glycoprotein-mediated anoikis of primary human cardiac microvascular endothelial cells

    International Nuclear Information System (INIS)

    Ray, Ratna B.; Basu, Arnab; Steele, Robert; Beyene, Aster; McHowat, Jane; Meyer, Keith; Ghosh, Asish K.; Ray, Ranjit

    2004-01-01

    Ebola virus glycoprotein (EGP) has been implicated for the induction of cytotoxicity and injury in vascular cells. On the other hand, EGP has also been suggested to induce massive cell rounding and detachment from the plastic surface by downregulating cell adhesion molecules without causing cytotoxicity. In this study, we have examined the cytotoxic role of EGP in primary endothelial cells by transduction with a replication-deficient recombinant adenovirus expressing EGP (Ad-EGP). Primary human cardiac microvascular endothelial cells (HCMECs) transduced with Ad-EGP displayed loss of cell adhesion from the plastic surface followed by cell death. Transfer of conditioned medium from EGP-transduced HCMEC into naive cells did not induce loss of adhesion or cell death, suggesting that EGP needs to be expressed intracellularly to exert its cytotoxic effect. Subsequent studies suggested that HCMEC death occurred through apoptosis. Results from this study shed light on the EGP-induced anoikis in primary human cardiac endothelial cells, which may have significant pathological consequences

  6. Computational study of ‘HUB’ microRNA in human cardiac diseases

    Science.gov (United States)

    Krishnan, Remya; Nair, Achuthsankar S.; Dhar, Pawan K.

    2017-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs ~22 nucleotides long that do not encode for proteins but have been reported to influence gene expression in normal and abnormal health conditions. Though a large body of scientific literature on miRNAs exists, their network level profile linking molecules with their corresponding phenotypes, is less explored. Here, we studied a network of 191 human miRNAs reported to play a role in 30 human cardiac diseases. Our aim was to study miRNA network properties like hubness and preferred associations, using data mining, network graph theory and statistical analysis. A total of 16 miRNAs were found to have a disease node connectivity of >5 edges (i.e., they were linked to more than 5 diseases) and were considered hubs in the miRNAcardiac disease network. Alternatively, when diseases were considered as hubs, >10 of miRNAs showed up on each ‘disease hub node’. Of all the miRNAs associated with diseases, 19 miRNAs (19/24= 79.1% of upregulated events) were found to be upregulated in atherosclerosis. The data suggest micro RNAs as early stage biological markers in cardiac conditions with potential towards microRNA based therapeutics. PMID:28479745

  7. Human failure event analysis and precautionary methods and their application to reactor system

    International Nuclear Information System (INIS)

    Zhang Li; Huang Shudong; Wang Yiqun; Gao Wenyu; Zhang Jin

    2003-01-01

    Making use of human factor engineering, control science and safety science and adopting the method of systemically collection and doing research work factually, the authors analyze the problem and tendency of human factor science, the classification system, the formation, the quantitative appraisal, data collection and data bank, the effect and influence of organization management, the root cause analysis technology, and human error failure mode and effect and criticality analysis, the method and strategy of defense-in-depth for preventing human-initiated accident. The human factor accidents theory and mechanism are constructed. All of the above was successfully applied to Daya Bay Nuclear Power Station and Lingao Nuclear Power Station. (authors)

  8. I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: insights from a retrospective European multicenter study

    Energy Technology Data Exchange (ETDEWEB)

    Agostini, Denis [CHU Cote de Nacre, Caen (France); Verberne, Hein J. [Academic Medical Centre, Amsterdam (Netherlands); Burchert, Wolfgang [Ruhr University Bochum, Institute of Radiology, Nuclear Medicine and Molecular Imaging, Heart and Diabetes Center NRW, Bad Oeyenhausen (Germany); Knuuti, Juhani [Turku University Central Hospital, Turku (Finland); Povinec, Pavol [Comenius University School of Medicine, Bratislava (Slovakia); Sambuceti, Gianmario [University of Genova, Genova (Italy); Unlu, Mustafa [Gazi University, Ankara (Turkey); Estorch, Montserrat [Hospital Sant Pau, Barcelona (Spain); Banerjee, Gopa; Jacobson, Arnold F. [GE Healthcare, Princeton, NJ (United States)

    2008-03-15

    Single-center experiences have shown that myocardial meta-iodobenzylguanidine (mIBG) uptake has prognostic value in heart failure (HF) patients. To verify these observations using a rigorous clinical trial methodology, a retrospective review and prospective quantitative reanalysis was performed on a series of cardiac {sup 123}I-mIBG scans acquired during a 10-year period at six centers in Europe. {sup 123}I-mIBG scans obtained on 290 HF patients [(262 with left ventricular ejection fraction (LVEF) < 50%)] from 1993 to 2002 were reanalyzed using a standardized methodology to determine the heart-to-mediastinum ratio (H/M) on delayed planar images. All image results were verified by three independent reviewers. Major cardiac events [MCEs; cardiac death, cardiac transplant, potentially fatal arrhythmia (including implantable cardioverter-defibrillator discharge)] during 24-month follow-up were confirmed by an adjudication committee. MCEs occurred in 67 patients (26%): mean H/M ratio was 1.51 {+-} 0.30 for the MCE group and 1.97 {+-} 0.54 for the non-MCE group (p < 0.001). Two-year event-free survival using an optimum H/M ratio threshold of 1.75 was 62% for H/M ratio less than 1.75, 95% for H/M ratio greater than or equal to 1.75 (p < 0.0001). Logistic regression showed H/M ratio and LVEF as the only significant predictors of MCE. Using the lower and upper H/M quartiles of 1.45 and 2.17 as high- and very low-risk thresholds, 2-year event-free survival rates were 52% and 98%, respectively. Among patients with LVEF {<=} 35% and H/M {>=} 1.75 (n = 73), there were nine MCEs because of progressive HF and only one because of an arrhythmia. Application of a clinical trial methodology via the retrospective reanalysis of {sup 123}I-mIBG images confirms the previously reported prognostic value of this method in HF patients, including potential identification of a quantitative threshold for low risk for cardiac mortality and potentially fatal ventricular arrhythmias. (orig.)

  9. On the development of life prediction methodologies for the failure of human teeth

    Energy Technology Data Exchange (ETDEWEB)

    Nalla, R.K.; Imbeni, V.; Kinney, J.H.; Marshall, S.J.; Ritchie, R.O.

    2002-09-18

    Human dentin is known to be susceptible to failure under cyclic loading. Surprisingly, there are few reports that quantify the effect of such loading, considering the fact that a typical tooth experiences a million or so loading cycles annually. In the present study, a systematic investigation is described of the effects of prolonged cyclic loading on human dentin in a simulated physiological environment. In vitro stress-life (S/N) data are discussed in the context of possible mechanisms of fatigue damage and failure.

  10. 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

  11. Human and equine cardiovascular endocrinology

    DEFF Research Database (Denmark)

    Vekens, Nicky Van Der; Hunter, Ingrid; Gøtze, Jens Peter

    2013-01-01

    Cardiac biomarkers such as troponins and natriuretic peptides are routinely used in human medicine for the evaluation of myocardial damage and heart failure. Recently, these markers have also been introduced in veterinary medicine. Comparison between human and equine cardiac biomarker studies sho...

  12. Reference values for total blood volume and cardiac output in humans

    Energy Technology Data Exchange (ETDEWEB)

    Williams, L.R. [Indiana Univ., South Bend, IN (United States). Division of Liberal Arts and Sciences

    1994-09-01

    Much research has been devoted to measurement of total blood volume (TBV) and cardiac output (CO) in humans but not enough effort has been devoted to collection and reduction of results for the purpose of deriving typical or {open_quotes}reference{close_quotes} values. Identification of normal values for TBV and CO is needed not only for clinical evaluations but also for the development of biokinetic models for ultra-short-lived radionuclides used in nuclear medicine (Leggett and Williams 1989). The purpose of this report is to offer reference values for TBV and CO, along with estimates of the associated uncertainties that arise from intra- and inter-subject variation, errors in measurement techniques, and other sources. Reference values are derived for basal supine CO and TBV in reference adult humans, and differences associated with age, sex, body size, body position, exercise, and other circumstances are discussed.

  13. A mid-layer model for human reliability analysis: understanding the cognitive causes of human failure events

    International Nuclear Information System (INIS)

    Shen, Song-Hua; Chang, James Y.H.; Boring, Ronald L.; Whaley, April M.; Lois, Erasmia; Langfitt Hendrickson, Stacey M.; Oxstrand, Johanna H.; Forester, John Alan; Kelly, Dana L.; Mosleh, Ali

    2010-01-01

    The Office of Nuclear Regulatory Research (RES) at the US Nuclear Regulatory Commission (USNRC) is sponsoring work in response to a Staff Requirements Memorandum (SRM) directing an effort to establish a single human reliability analysis (HRA) method for the agency or guidance for the use of multiple methods. As part of this effort an attempt to develop a comprehensive HRA qualitative approach is being pursued. This paper presents a draft of the method's middle layer, a part of the qualitative analysis phase that links failure mechanisms to performance shaping factors. Starting with a Crew Response Tree (CRT) that has identified human failure events, analysts identify potential failure mechanisms using the mid-layer model. The mid-layer model presented in this paper traces the identification of the failure mechanisms using the Information-Diagnosis/Decision-Action (IDA) model and cognitive models from the psychological literature. Each failure mechanism is grouped according to a phase of IDA. Under each phase of IDA, the cognitive models help identify the relevant performance shaping factors for the failure mechanism. The use of IDA and cognitive models can be traced through fault trees, which provide a detailed complement to the CRT.

  14. A Mid-Layer Model for Human Reliability Analysis: Understanding the Cognitive Causes of Human Failure Events

    Energy Technology Data Exchange (ETDEWEB)

    Stacey M. L. Hendrickson; April M. Whaley; Ronald L. Boring; James Y. H. Chang; Song-Hua Shen; Ali Mosleh; Johanna H. Oxstrand; John A. Forester; Dana L. Kelly; Erasmia L. Lois

    2010-06-01

    The Office of Nuclear Regulatory Research (RES) is sponsoring work in response to a Staff Requirements Memorandum (SRM) directing an effort to establish a single human reliability analysis (HRA) method for the agency or guidance for the use of multiple methods. As part of this effort an attempt to develop a comprehensive HRA qualitative approach is being pursued. This paper presents a draft of the method’s middle layer, a part of the qualitative analysis phase that links failure mechanisms to performance shaping factors. Starting with a Crew Response Tree (CRT) that has identified human failure events, analysts identify potential failure mechanisms using the mid-layer model. The mid-layer model presented in this paper traces the identification of the failure mechanisms using the Information-Diagnosis/Decision-Action (IDA) model and cognitive models from the psychological literature. Each failure mechanism is grouped according to a phase of IDA. Under each phase of IDA, the cognitive models help identify the relevant performance shaping factors for the failure mechanism. The use of IDA and cognitive models can be traced through fault trees, which provide a detailed complement to the CRT.

  15. Thallium-201 myocardial scintigraphy and cardiac pool scintigraphy with technetium-99m labelled human serum albumin of complicated anomalous heart

    International Nuclear Information System (INIS)

    Tanaka, Minoru; Watanabe, Takashi; Murase, Mitsuya; Shimizu, Ken; Abe, Toshio

    1979-01-01

    Nuclear cardiology has been used in the diagnosis of congenital heart disease, but these studies have not shown the dramatic increase that has occurred in their use in coronary heart disease. In this report, thallium-201 myocardial scintigraphy and cardiac pool scintigraphy with technetium-99m labelled human serum albumin of 13 patients with complicated congenital heart disease were compared with contrast angiography. The application of these scanning methods to visualization of the size and shape of ventricle and interventricular septum was very useful. At times these methods give us the more accurate information about cardiac shape, especially of complicated anomalous heart, than contrast angiography. Of course these methods will never replace cardiac catheterization and contrast angiography. But these studies are non-invasive. So it was concluded that these scanning methods had better be applied in patients with complicated cardiac anomaly before invasive contrast angiography. (author)

  16. The effect of intermittent atrial tachyarrhythmia on heart failure or death in cardiac resynchronization therapy with defibrillator versus implantable cardioverter-defibrillator patients

    DEFF Research Database (Denmark)

    Ruwald, Anne-Christine; Pietrasik, Grzegorz; Goldenberg, Ilan

    2014-01-01

    OBJECTIVES: This study aimed to investigate the effect of both history of intermittent atrial tachyarrhythmias (IAT) and in-trial IAT on the risk of heart failure (HF) or death comparing cardiac resynchronization therapy with defibrillator (CRT-D) to implantable cardioverter-defibrillator (ICD......) treatment in mildly symptomatic HF patients with left bundle branch block (LBBB). BACKGROUND: Limited data exist regarding the benefit of CRT-D in patients with IAT. METHODS: The benefit of CRT-D in reducing the risk of HF/death was evaluated using multivariate Cox models incorporating the presence of......-D versus ICD on the risk of HF/death was not significantly different between LBBB patients with or without history of IAT (HR: 0.50, p = 0.028, and HR: 0.46, p

  17. High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

    DEFF Research Database (Denmark)

    Kashioulis, Pavlos; Hammarsten, Ola; Marcussen, Niels

    2016-01-01

    AIMS: To examine the effects of 2 weeks of high-NaCl diet on left ventricular (LV) morphology and serum levels of cardiac troponin T (cTnT) in rats with adenine-induced chronic renal failure (ACRF). METHODS: Male Sprague-Dawley rats either received chow containing adenine or were pair......-fed an identical diet without adenine [controls (C)]. Approximately 10 weeks after the beginning of the study, the rats were randomized to either remain on a normal NaCl diet (NNa; 0.6%) or to be switched to high-NaCl chow (HNa; 4%) for 2 weeks, after which acute experiments were performed. RESULTS: Rats with ACRF...... showed statistically significant increases (p rats (p

  18. Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals.

    Science.gov (United States)

    Byrne, M J; Power, J M; Preovolos, A; Mariani, J A; Hajjar, R J; Kaye, D M

    2008-12-01

    Abnormal excitation-contraction coupling is a key pathophysiologic component of heart failure (HF), and at a molecular level reduced expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA2a) is a major contributor. Previous studies in small animals have suggested that restoration of SERCA function is beneficial in HF. Despite this promise, the means by which this information might be translated into potential clinical application remains uncertain. Using a recently established cardiac-directed recirculating method of gene delivery, we administered adeno-associated virus 2 (AAV2)/1SERCA2a to sheep with pacing-induced HF. We explored the effects of differing doses of AAV2/1SERCA2a (low 1 x 10(10) d.r.p.; medium 1 x 10(12) d.r.p. and high 1 x 10(13) d.r.p.) in conjunction with an intra-coronary delivery group (2.5 x 10(13) d.r.p.). At the end of the study, haemodynamic, echocardiographic, histopathologic and molecular biologic assessments were performed. Cardiac recirculation delivery of AAV2/1SERCA2a elicited a dose-dependent improvement in cardiac performance determined by left ventricular pressure analysis, (+d P/d t(max); low dose -220+/-70, P>0.05; medium dose 125+/-53, P0.05; medium dose 1+/-2, P>0.05; high dose 6.5+/-3.9, Preversal of the HF molecular phenotype. In contrast, direct intra-coronary infusion did not elicit any effect on ventricular function. As such, AAV2/1SERCA2a elicits favourable functional and molecular actions when delivered in a mechanically targeted manner in an experimental model of HF. These observations lay a platform for potential clinical translation.

  19. Low-dose β-blocker in combination with milrinone safely improves cardiac function and eliminates pulsus alternans in patients with acute decompensated heart failure.

    Science.gov (United States)

    Kobayashi, Shigeki; Susa, Takehisa; Tanaka, Takeo; Murakami, Wakako; Fukuta, Seiko; Okuda, Shinichi; Doi, Masahiro; Wada, Yasuaki; Nao, Tomoko; Yamada, Jutaro; Okamura, Takayuki; Yano, Masafumi; Matsuzaki, Masunori

    2012-01-01

    The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia. Twenty ADHF patients (New York Heart Association classification III, n=1, and IV, n=19; heart rate [HR], 107±12 beats/min; left ventricular ejection fraction, 24±7%; cardiac index [CI], 2.2±0.6 L·min(-1)·m(-2); pulmonary capillary wedge pressure [PCWP], 26±8 mmHg) were enrolled in this study. The patients first underwent conventional therapy with milrinone, vasodilators and diuretics; landiolol (1.5-6.0 µg·kg(-1)·min(-1); i.v.), which is an ultra-short-acting β(1)-selective blocker, was then added to the treatment regimen to study its effect on hemodynamics. Low-dose landiolol (1.5 µg·kg(-1)·min(-1)) significantly reduced HR by 11% without changing blood pressure (BP) and CI, whereas higher doses (≥3.0 µg·kg(-1)·min(-1)) tended to decrease BP and CI while increasing PCWP and systemic vascular resistance. After treatment with landiolol (1.5 µg·kg(-1)·min(-1)), hemodynamic parameters such as PCWP, stroke volume index, SvO(2), rate pressure product, filling time/RR, E/e', and Tei index were significantly improved. A low-dose β-blocker in combination with milrinone improved cardiac function in ADHF patients with tachycardia; therefore, it may be considered as an adjunct therapy for use when standard therapy with milrinone is not effective at slowing HR.

  20. A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

    Science.gov (United States)

    Chen, Yu-Yang; Shu, Xiao-Rong; Su, Zi-Zhuo; Lin, Rong-Jie; Zhang, Hai-Feng; Yuan, Wo-Liang; Wang, Jing-Feng; Xie, Shuang-Lun

    2017-12-12

    Thyroid dysfunction is prevalent in patients with heart failure (HF) and hypothyroidism is related to the adverse prognosis of HF subjects receiving cardiac resynchronization therapy (CRT). We aim to investigate whether low-normal free triiodothyronine (fT3) level is related to CRT response and the prognosis of euthyroid patients with HF after CRT implantation.One hundred and thirteen euthyroid patients who received CRT therapy without previous thyroid disease and any treatment affecting thyroid hormones were enrolled. All of patients were evaluated for cardiac function and thyroid hormones (serum levels of fT3, free thyroxine [fT4] and thyroid-stimulating hormone [TSH]). The end points were overall mortality and hospitalization for HF worsening. During a follow-up period of 39 ± 3 weeks, 36 patients (31.9%) died and 45 patients (39.8%) had hospitalization for HF exacerbation. A higher rate of NYHA III/IV class and a lower fT3 level were both observed in death group and HF event group. Multivariate Cox regression analyses disclosed that a lower-normal fT3 level (HR = 0.648, P = 0.009) and CRT response (HR = 0.441, P = 0.001) were both independent predictors of overall mortality. In addition, they were also both related to HF re-hospitalization event (P < 0.01 for both). Patients with fT3 < 3.00 pmol/L had a significantly higher overall mortality than those with fT3 ≥ 3.00 pmol/L (P = 0.027). Meanwhile, a higher HF hospitalization event rate was also found in patients with fT3 < 3.00 pmol/L (P < 0.001).A lower-normal fT3 level is correlated with a worse cardiac function an adverse prognosis in euthyroid patients with HF after CRT implantation.

  1. Effects of Statin Treatment on Inflammation and Cardiac Function in Heart Failure: An Adjusted Indirect Comparison Meta-Analysis of Randomized Trials.

    Science.gov (United States)

    Bonsu, Kwadwo Osei; Reidpath, Daniel Diamond; Kadirvelu, Amudha

    2015-12-01

    Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF. The current meta-analysis was performed to compare the treatment effects of lipophilic and hydrophilic statins on inflammation and cardiac function in HF. Outcomes were indicators of cardiac function [changes in left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP)] and inflammation [changes in highly sensitive C-reactive protein (hsCRP) and interluekin-6 (IL-6)]. We conducted a search of PubMed, EMBASE, and the Cochrane databases until December 31, 2014 for randomized control trials (RCTs) of statin versus placebo in patients with HF. RCTs with their respective extracted information were dichotomized into statin type evaluated and analyzed separately. Outcomes were pooled with random effect approach, producing standardized mean differences (SMD) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons for each outcome. Data from 6214 patients from 19 trials were analyzed. Lipophilic statin was superior to hydrophilic statin treatment regarding follow-up LVEF (SMD, 4.54; 95% CI, 4.16-4.91; P statin produces greater treatment effects on cardiac function and inflammation compared with hydrophilic statin in patients with HF. Until data from adequately powered head-to-head trial of the statin types are available, our meta-analysis brings clinicians and researchers a step closer to the quest on which statin--lipophilic or hydrophilic--is associated with better outcomes in HF. © 2015 John Wiley & Sons Ltd.

  2. Human based roots of failures in nuclear events investigations

    Energy Technology Data Exchange (ETDEWEB)

    Ziedelis, Stanislovas; Noel, Marc; Strucic, Miodrag [Commission of the European Communities, Petten (Netherlands). European Clearinghouse on Operational Experience Feedback for Nuclear Power Plants

    2012-10-15

    This paper aims for improvement of quality of the event investigations in the nuclear industry through analysis of the existing practices, identifying and removing the existing Human and Organizational Factors (HOF) and management related barriers. It presents the essential results of several studies performed by the European Clearinghouse on Operational Experience. Outcomes of studies are based on survey of currently existing event investigation practices typical for nuclear industry of 12 European countries, as well as on insights from analysis of numerous event investigation reports. System of operational experience feedback from information based on event investigation results is not enough effective to prevent and even to decrease frequency of recurring events due to existing methodological, HOF-related and/or knowledge management related constraints. Besides that, several latent root causes of unsuccessful event investigation are related to weaknesses in safety culture of personnel and managers. These weaknesses include focus on costs or schedule, political manipulation, arrogance, ignorance, entitlement and/or autocracy. Upgrades in safety culture of organization's personnel and its senior management especially seem to be an effective way to improvement. Increasing of competencies, capabilities and level of independency of event investigation teams, elaboration of comprehensive software, ensuring of positive approach, adequate support and impartiality of management could also facilitate for improvement of quality of the event investigations. (orig.)

  3. Human based roots of failures in nuclear events investigations

    International Nuclear Information System (INIS)

    Ziedelis, Stanislovas; Noel, Marc; Strucic, Miodrag

    2012-01-01

    This paper aims for improvement of quality of the event investigations in the nuclear industry through analysis of the existing practices, identifying and removing the existing Human and Organizational Factors (HOF) and management related barriers. It presents the essential results of several studies performed by the European Clearinghouse on Operational Experience. Outcomes of studies are based on survey of currently existing event investigation practices typical for nuclear industry of 12 European countries, as well as on insights from analysis of numerous event investigation reports. System of operational experience feedback from information based on event investigation results is not enough effective to prevent and even to decrease frequency of recurring events due to existing methodological, HOF-related and/or knowledge management related constraints. Besides that, several latent root causes of unsuccessful event investigation are related to weaknesses in safety culture of personnel and managers. These weaknesses include focus on costs or schedule, political manipulation, arrogance, ignorance, entitlement and/or autocracy. Upgrades in safety culture of organization's personnel and its senior management especially seem to be an effective way to improvement. Increasing of competencies, capabilities and level of independency of event investigation teams, elaboration of comprehensive software, ensuring of positive approach, adequate support and impartiality of management could also facilitate for improvement of quality of the event investigations. (orig.)

  4. Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure.

    Science.gov (United States)

    Mielczarek, Ewelina; Blaszkowska, Joanna

    2016-08-01

    Trichomonas vaginalis, which colonizes the genitourinary tract of men and women, is a sexually transmitted parasite causing symptomatic or asymptomatic trichomoniasis. The host-parasite relationship is very complex, and clinical symptoms cannot likely be attributed to a single pathogenic effect. Among the many factors responsible for interactions between T. vaginalis and host tissues, contact-dependent and contact-independent mechanisms are important in pathogenicity, as is the immune response. This review focuses on the potential virulence properties of T. vaginalis and its role in female and male infertility. It highlights the association between T. vaginalis infection and serious adverse health consequences experienced by women, including infertility, preterm birth and low-birth-weight infants. Long-term clinical observations and results of in vitro experimental studies indicate that in men, trichomoniasis has been also associated with infertility through inflammatory damage to the genitourinary tract or interference with sperm function. These results contribute significantly to improving our knowledge of the role of parasitic virulence factors in the development of infection and its role in human infertility.

  5. Influence of the definition of acute renal failure post-cardiac surgery on incidence, patient identification, and identification of risk factors.

    Science.gov (United States)

    Noyez, Luc

    2011-03-01

    Acute renal failure post-cardiac surgery (RF) is a major complication and is associated with increased postoperative morbidity and mortality. Early recognition and identification of risk factors for RF is therefore important. However, several definitions of RF are used. The intention of this study is to evaluate if the used definitions influence the incidence and the identification of risk factors for RF. We identified, after exclusion of 13 patients with preoperative dialysis, 995 consecutive patients undergoing cardiac surgery at the UMC St. Radboud Medical Center between January 2009 and 15 February 2010 as our study cohort. Apart from the definition used by the Society of Thoracic Surgeons, we selected five major international studies concerning RF, each using a different RF definition. These six definitions were used to evaluate the incidence of and identification of risk factors for RF in our study cohort. There is not only a statistically significant difference in incidence (range 4.94-38.1%) of RF between the definitions (p definition several common but also several different risk variables. Multivariate analysis identified also different independent predictors, with different odds ratios for RF for each definition. This study shows that the used definition of RF influences not only the incidence of RF, but also patient identification and the identification of risk variables. Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

  6. The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure

    International Nuclear Information System (INIS)

    Goliasch, Georg; Khorsand, Aliasghar; Sochor, Heinz; Schmidinger, Herwig; Graf, Senta; Schuetz, Matthias; Karanikas, Georgios; Khazen, Cesar; Wolzt, Michael

    2012-01-01

    Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO 2 ) in patients with chronic heart failure using 11 C-acetate positron emission tomography (PET). We prospectively enrolled 21 patients with severe heart failure. 11 C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. Under resting conditions, the values of myocardial blood flow (MBF), MVO 2 and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 ± 0.18 ml min -1 g -1 with the device off and 0.80 ± 0.15 ml min -1 g -1 with the device on (p = 0.818), MVO 2 was 6.81 ± 1.69 ml/min/100 g with the device off and 7.15 ± 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 ± 1.14 mmHg ml/m 2 with the device off and 5.21 ± 1.36 mmHg ml/m 2 with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO 2 and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. These results indicate that CCM does not induce increased MVO 2 , even under stress conditions. (orig.)

  7. Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide

    International Nuclear Information System (INIS)

    Kasama, Shu; Toyama, Takuji; Kurabayashi, Masahiko; Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi; Matsumoto, Naoya; Nakata, Tomoaki

    2014-01-01

    Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. 123 I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP. (orig.)

  8. Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Nakata, Tomoaki [Sapporo Medical University School of Medicine, Second (Cardiology) Department of Internal Medicine, Sapporo, Hokkaido (Japan)

    2014-09-15

    Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. {sup 123}I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP. (orig.)

  9. The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Goliasch, Georg; Khorsand, Aliasghar; Sochor, Heinz; Schmidinger, Herwig; Graf, Senta [Vienna General Hospital/Medical University of Vienna, Department of Cardiology, Vienna (Austria); Schuetz, Matthias; Karanikas, Georgios [Vienna General Hospital/Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Khazen, Cesar [Vienna General Hospital/ Medical University of Vienna, Department of Cardiothoracic Surgery, Vienna (Austria); Wolzt, Michael [Vienna General Hospital/Medical University of Vienna, Department of Cardiology, Vienna (Austria); Vienna General Hospital/ Medical University of Vienna, Department of Clinical Pharmacology, Vienna (Austria)

    2012-03-15

    Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO{sub 2}) in patients with chronic heart failure using {sup 11}C-acetate positron emission tomography (PET). We prospectively enrolled 21 patients with severe heart failure. {sup 11}C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. Under resting conditions, the values of myocardial blood flow (MBF), MVO{sub 2} and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 {+-} 0.18 ml min{sup -1} g{sup -1} with the device off and 0.80 {+-} 0.15 ml min{sup -1} g{sup -1} with the device on (p = 0.818), MVO{sub 2} was 6.81 {+-} 1.69 ml/min/100 g with the device off and 7.15 {+-} 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 {+-} 1.14 mmHg ml/m{sup 2} with the device off and 5.21 {+-} 1.36 mmHg ml/m{sup 2} with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO{sub 2} and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. These results indicate that CCM does not induce increased MVO{sub 2}, even under stress conditions. (orig.)

  10. Human pluripotent stem cell models of cardiac disease: from mechanisms to therapies

    Directory of Open Access Journals (Sweden)

    Karina O. Brandão

    2017-09-01

    Full Text Available It is now a decade since human induced pluripotent stem cells (hiPSCs were first described. The reprogramming of adult somatic cells to a pluripotent state has become a robust technology that has revolutionised our ability to study human diseases. Crucially, these cells capture all the genetic aspects of the patient from which they were derived. Combined with advances in generating the different cell types present in the human heart, this has opened up new avenues to study cardiac disease in humans and investigate novel therapeutic approaches to treat these pathologies. Here, we provide an overview of the current state of the field regarding the generation of cardiomyocytes from human pluripotent stem cells and methods to assess them functionally, an essential requirement when investigating disease and therapeutic outcomes. We critically evaluate whether treatments suggested by these in vitro models could be translated to clinical practice. Finally, we consider current shortcomings of these models and propose methods by which they could be further improved.

  11. In vitro cultured progenitors and precursors of cardiac cell lineages from human normal and post-ischemic hearts

    Directory of Open Access Journals (Sweden)

    F Di Meglio

    2009-08-01

    Full Text Available The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR. The amount of proteins characteristic for cardiac cells (a-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively inclines toward an increase in both a-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart.

  12. Human-induced pluripotent stem cell-derived cardiomyocytes from cardiac progenitor cells: effects of selective ion channel blockade.

    Science.gov (United States)

    Altomare, Claudia; Pianezzi, Enea; Cervio, Elisabetta; Bolis, Sara; Biemmi, Vanessa; Benzoni, Patrizia; Camici, Giovanni G; Moccetti, Tiziano; Barile, Lucio; Vassalli, Giuseppe

    2016-12-01

    Human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes are likely to revolutionize electrophysiological approaches to arrhythmias. Recent evidence suggests the somatic cell origin of hiPSCs may influence their differentiation potential. Owing to their cardiomyogenic potential, cardiac-stromal progenitor cells (CPCs) are an interesting cellular source for generation of hiPSC-derived cardiomyocytes. The effect of ionic current blockade in hiPSC-derived cardiomyocytes generated from CPCs has not been characterized yet. Human-induced pluripotent stem cell-derived cardiomyocytes were generated from adult CPCs and skin fibroblasts from the same individuals. The effect of selective ionic current blockade on spontaneously beating hiPSC-derived cardiomyocytes was assessed using multi-electrode arrays. Cardiac-stromal progenitor cells could be reprogrammed into hiPSCs, then differentiated into hiPSC-derived cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes of cardiac origin showed higher upregulation of cardiac-specific genes compared with those of fibroblastic origin. Human-induced pluripotent stem cell-derived cardiomyocytes of both somatic cell origins exhibited sensitivity to tetrodotoxin, a blocker of Na +  current (I Na ), nifedipine, a blocker of L-type Ca 2+  current (I CaL ), and E4031, a blocker of the rapid component of delayed rectifier K +  current (I Kr ). Human-induced pluripotent stem cell-derived cardiomyocytes of cardiac origin exhibited sensitivity to JNJ303, a blocker of the slow component of delayed rectifier K +  current (I Ks ). In hiPSC-derived cardiomyocytes of cardiac origin, I Na , I CaL , I Kr , and I Ks were present as tetrodotoxin-, nifedipine-, E4031-, and JNJ303-sensitive currents, respectively. Although cardiac differentiation efficiency was improved in hiPSCs of cardiac vs. non-cardiac origin, no major functional differences were observed between hiPSC-derived cardiomyocytes of different somatic

  13. Quantification of human error and common-mode failures in man-machine systems

    International Nuclear Information System (INIS)

    Lisboa, J.J.

    1988-01-01

    Quantification of human performance, particularly the determination of human error, is essential for realistic assessment of overall system performance of man-machine systems. This paper presents an analysis of human errors in nuclear power plant systems when measured against common-mode failures (CMF). Human errors evaluated are improper testing, inadequate maintenance strategy, and miscalibration. The methodology presented in the paper represents a positive contribution to power plant systems availability by identifying sources of common-mode failure when operational functions are involved. It is also applicable to other complex systems such as chemical plants, aircraft and motor industries; in fact, any large man-created, man-machine system could be included

  14. Effects of alagebrium, an advanced glycation endproduct breaker, on exercise tolerance and cardiac function in patients with chronic heart failure

    NARCIS (Netherlands)

    Hartog, Jasper W. L.; Willemsen, Suzan; van Veldhuisen, Dirk J.; Posma, Jan L.; van Wijk, Leen M.; Hummel, Yoran M.; Hillege, Hans L.; Voors, Adriaan A.

    Aims Advanced glycation endproducts (AGEs) have been associated with the development and progression of chronic heart failure (CHF). Advanced glycation endproducts-crosslink breakers might be of benefit in HF, but only small-scale and uncontrolled data are available. Our aim was to conduct a

  15. Phenotyping of left and right ventricular function in mouse models of compensated hypertrophy and heart failure with cardiac MRI

    NARCIS (Netherlands)

    van Nierop, Bastiaan J.; van Assen, Hans C.; van Deel, Elza D.; Niesen, Leonie B. P.; Duncker, Dirk J.; Strijkers, Gustav J.; Nicolay, Klaas

    2013-01-01

    Left ventricular (LV) and right ventricular (RV) function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding mouse model.

  16. Phenotyping of left and right ventricular function in mouse models of compensated hypertrophy and heart failure with cardiac MRI

    NARCIS (Netherlands)

    Nierop, van B.J.; Assen, van H.C.; Deel, van E.D.; Niesen, L.B.P.; Duncker, D.J.; Strijkers, G.J.; Nicolay, K.

    2013-01-01

    Background: Left ventricular (LV) and right ventricular (RV) function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding

  17. Non-invasive measurement of cardiac output in heart failure patients using a new foreign gas rebreathing technique

    DEFF Research Database (Denmark)

    Gabrielsen, Anders; Videbaek, Regitze; Schou, Morten

    2002-01-01

    (FICK)) and thermodilution (CO(TD)) methods in patients with heart failure or pulmonary hypertension. In 11 patients, of which three had shunt flow through areas without significant gas exchange, the mean difference (bias) and limits of agreement (+/- 2 S.D.) were 0.6 +/- 1.2 litre x min(-1) when comparing CO(FICK) and Q...

  18. The failure of retrograde autologous priming of the cardiopulmonary bypass circuit to reduce blood use after cardiac surgical procedures.

    Science.gov (United States)

    Murphy, Glenn S; Szokol, Joseph W; Nitsun, Martin; Alspach, David A; Avram, Michael J; Vender, Jeffery S; Votapka, Timothy V; Rosengart, Todd K

    2004-05-01

    Hemodilution during cardiopulmonary bypass (CPB) is a primary risk factor for blood transfusion in cardiac surgical patients. Priming of the CPB circuit with the patients' own blood (retrograde autologous priming, RAP) is a technique used to limit hemodilution and reduce transfusion requirements. We designed this study to examine the impact of RAP on perioperative blood product use. Using a retrospective cohort study design, the medical records of all patients undergoing CPB (excluding circulatory arrest cases) by a single surgeon were examined. Data were collected over a 24-mo period when RAP was routinely used as a blood conservation strategy (RAP group, n = 257). This group was compared with a cohort of patients during the 24 mo immediately preceding the introduction of RAP into clinical practice (no RAP group, n = 288). A small, statistically insignificant reduction in the percentage of patients receiving packed red blood cells was observed in the RAP group (44% versus 51% no RAP, P = 0.083). No differences were found between the groups in the number of units of packed red blood cells, platelets, or fresh frozen plasma transfused throughout the perioperative period. These results suggest that overall, RAP does not offer a clinically important benefit as a blood conservation technique. Priming of the cardiopulmonary bypass circuit with the patients' own blood (retrograde autologous priming) resulted in insignificant reductions in blood use in a large, unselected group of patients undergoing cardiac surgical procedures.

  19. Model-based imaging of cardiac electrical function in human atria

    Science.gov (United States)

    Modre, Robert; Tilg, Bernhard; Fischer, Gerald; Hanser, Friedrich; Messnarz, Bernd; Schocke, Michael F. H.; Kremser, Christian; Hintringer, Florian; Roithinger, Franz

    2003-05-01

    Noninvasive imaging of electrical function in the human atria is attained by the combination of data from electrocardiographic (ECG) mapping and magnetic resonance imaging (MRI). An anatomical computer model of the individual patient is the basis for our computer-aided diagnosis of cardiac arrhythmias. Three patients suffering from Wolff-Parkinson-White syndrome, from paroxymal atrial fibrillation, and from atrial flutter underwent an electrophysiological study. After successful treatment of the cardiac arrhythmia with invasive catheter technique, pacing protocols with stimuli at several anatomical sites (coronary sinus, left and right pulmonary vein, posterior site of the right atrium, right atrial appendage) were performed. Reconstructed activation time (AT) maps were validated with catheter-based electroanatomical data, with invasively determined pacing sites, and with pacing at anatomical markers. The individual complex anatomical model of the atria of each patient in combination with a high-quality mesh optimization enables accurate AT imaging, resulting in a localization error for the estimated pacing sites within 1 cm. Our findings may have implications for imaging of atrial activity in patients with focal arrhythmias.

  20. Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes.

    Science.gov (United States)

    Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B Cicero; Zarzoso, Manuel; Ramirez, Rafael J; Sener, Michelle F; Mundada, Lakshmi V; Klos, Matthew; Devaney, Eric J; Vikstrom, Karen L; Herron, Todd J; Jalife, José

    2013-11-01

    Applications of human induced pluripotent stem cell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricular myocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. © 2013.

  1. Do anabolic nutritional supplements stimulate human growth hormone secretion in elderly women with heart failure?

    NARCIS (Netherlands)

    Smeets, Ellen T.H.C.; Schutzler, Scott E.; Wei, Jeanne Y.; Azhar, Gohar; Wolfe, Robert R.

    2017-01-01

    Growth hormone treatment has gained attention over the past decade as a treatment for heart failure. Human growth hormone (HGH) must be administered by injections (usually daily), so there is considerable advantage to stimulation of endogenous secretion by amino acid-based nutritional

  2. Prediction of drug-related cardiac adverse effects in humans--B: use of QSAR programs for early detection of drug-induced cardiac toxicities.

    Science.gov (United States)

    Frid, Anna A; Matthews, Edwin J

    2010-04-01

    This report describes the use of three quantitative structure-activity relationship (QSAR) programs to predict drug-related cardiac adverse effects (AEs), BioEpisteme, MC4PC, and Leadscope Predictive Data Miner. QSAR models were constructed for 9 cardiac AE clusters affecting Purkinje nerve fibers (arrhythmia, bradycardia, conduction disorder, electrocardiogram, palpitations, QT prolongation, rate rhythm composite, tachycardia, and Torsades de pointes) and 5 clusters affecting the heart muscle (coronary artery disorders, heart failure, myocardial disorders, myocardial infarction, and valve disorders). The models were based on a database of post-marketing AEs linked to 1632 chemical structures, and identical training data sets were configured for three QSAR programs. Model performance was optimized and shown to be affected by the ratio of the number of active to inactive drugs. Results revealed that the three programs were complementary and predictive performances using any single positive, consensus two positives, or consensus three positives were as follows, respectively: 70.7%, 91.7%, and 98.0% specificity; 74.7%, 47.2%, and 21.0% sensitivity; and 138.2, 206.3, and 144.2 chi(2). In addition, a prospective study using AE data from the U.S. Food and Drug Administration's (FDA's) MedWatch Program showed 82.4% specificity and 94.3% sensitivity. Furthermore, an external validation study of 18 drugs with serious cardiotoxicity not considered in the models had 88.9% sensitivity. Published by Elsevier Inc.

  3. Establishment of a PRKAG2 cardiac syndrome disease model and mechanism study using human induced pluripotent stem cells.

    Science.gov (United States)

    Zhan, Yongkun; Sun, Xiaolei; Li, Bin; Cai, Huanhuan; Xu, Chen; Liang, Qianqian; Lu, Chao; Qian, Ruizhe; Chen, Sifeng; Yin, Lianhua; Sheng, Wei; Huang, Guoying; Sun, Aijun; Ge, Junbo; Sun, Ning

    2018-04-01

    PRKAG2 cardiac syndrome is a distinct form of human cardiomyopathy characterized by cardiac hypertrophy, ventricular pre-excitation and progressive cardiac conduction disorder. However, it remains unclear how mutations in the PRKAG2 gene give rise to such a complicated disease. To investigate the underlying molecular mechanisms, we generated disease-specific hiPSC-derived cardiomyocytes from two brothers both carrying a heterozygous missense mutation c.905G>A (R302Q) in the PRKAG2 gene and further corrected the R302Q mutation with CRISPR-Cas9 mediated genome editing. Disease-specific hiPSC-cardiomyocytes recapitulated many phenotypes of PRKAG2 cardiac syndrome including cellular enlargement, electrophysiological irregularities and glycogen storage. In addition, we found that the PRKAG2-R302Q mutation led to increased AMPK activities, resulting in extensive glycogen deposition and cardiomyocyte hypertrophy. Finally we confirmed that disrupted phenotypes of PRKAG2 cardiac syndrome caused by the specific PRKAG2-R302Q mutation can be alleviated by small molecules inhibiting AMPK activity and be rescued with CRISPR-Cas9 mediated genome correction. Our results showed that disease-specific hiPSC-CMs and genetically-corrected hiPSC-cardiomyocytes would be a very useful platform for understanding the pathogenesis of, and testing autologous cell-based therapies for, PRKAG2 cardiac syndrome. Copyright © 2018. Published by Elsevier Ltd.

  4. Expression of androgen-binding protein (ABP) in human cardiac myocytes.

    Science.gov (United States)

    Schock, H W; Herbert, Z; Sigusch, H; Figulla, H R; Jirikowski, G F; Lotze, U

    2006-04-01

    Cardiomyocytes are known to be androgen targets. Changing systemic steroid levels are thought to be linked to various cardiac ailments, including dilated cardiomyopathy (DCM). The mode of action of gonadal steroid hormones on the human heart is unknown to date. In the present study, we used high-resolution immunocytochemistry on semithin sections (1 microm thick), IN SITU hybridization, and mass spectrometry to investigate the expression of androgen-binding protein (ABP) in human myocardial biopsies taken from male patients with DCM. We observed distinct cytoplasmic ABP immunoreactivity in a fraction of the myocytes. IN SITU hybridization with synthetic oligonucleotide probes revealed specific hybridization signals in these cells. A portion of the ABP-positive cells contained immunostaining for androgen receptor. With SELDI TOF mass spectrometry of affinity purified tissue extracts of human myocardium, we confirmed the presence of a 50 kDa protein similar to ABP. Our observations provide evidence of an intrinsic expression of ABP in human heart. ABP may be secreted from myocytes in a paracrine manner perhaps to influence the bioavailabity of gonadal steroids in myocardium.

  5. Effects of national culture on human failures in container shipping: the moderating role of Confucian dynamism.

    Science.gov (United States)

    Lu, Chin-Shan; Lai, Kee-hung; Lun, Y H Venus; Cheng, T C E

    2012-11-01

    Recent reports on work safety in container shipping operations highlight high frequencies of human failures. In this study, we empirically examine the effects of seafarers' perceptions of national culture on the occurrence of human failures affecting work safety in shipping operations. We develop a model adopting Hofstede's national culture construct, which comprises five dimensions, namely power distance, collectivism/individualism, uncertainty avoidance, masculinity/femininity, and Confucian dynamism. We then formulate research hypotheses from theory and test the hypotheses using survey data collected from 608 seafarers who work on global container carriers. Using a point scale for evaluating seafarers' perception of the five national culture dimensions, we find that Filipino seafarers score highest on collectivism, whereas Chinese and Taiwanese seafarers score highest on Confucian dynamism, followed by collectivism, masculinity, power distance, and uncertainty avoidance. The results also indicate that Taiwanese seafarers have a propensity for uncertainty avoidance and masculinity, whereas Filipino seafarers lean more towards power distance, masculinity, and collectivism, which are consistent with the findings of Hofstede and Bond (1988). The results suggest that there will be fewer human failures in container shipping operations when power distance is low, and collectivism and uncertainty avoidance are high. Specifically, this study finds that Confucian dynamism plays an important moderating role as it affects the strength of associations between some national culture dimensions and human failures. Finally, we discuss our findings' contribution to the development of national culture theory and their managerial implications for reducing the occurrence of human failures in shipping operations. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

    Directory of Open Access Journals (Sweden)

    Olivia Chen

    2015-01-01

    Full Text Available Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate both in vitro and in vivo. Several experiments show functional improvements in mouse models of myocardial infarction following in situ generation of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming.

  7. Atomic force microscope observation of branching in single transcript molecules derived from human cardiac muscle

    International Nuclear Information System (INIS)

    Reed, Jason; Hsueh, Carlin; Gimzewski, James K; Mishra, Bud

    2008-01-01

    We have used an atomic force microscope to examine a clinically derived sample of single-molecule gene transcripts, in the form of double-stranded cDNA, (c: complementary) obtained from human cardiac muscle without the use of polymerase chain reaction (PCR) amplification. We observed a log-normal distribution of transcript sizes, with most molecules being in the range of 0.4-7.0 kilobase pairs (kb) or 130-2300 nm in contour length, in accordance with the expected distribution of mRNA (m: messenger) sizes in mammalian cells. We observed novel branching structures not previously known to exist in cDNA, and which could have profound negative effects on traditional analysis of cDNA samples through cloning, PCR and DNA sequencing

  8. Cardiac development in zebrafish and human embryonic stem cells is inhibited by exposure to tobacco cigarettes and e-cigarettes.

    Directory of Open Access Journals (Sweden)

    Nathan J Palpant

    Full Text Available Maternal smoking is a risk factor for low birth weight and other adverse developmental outcomes.We sought to determine the impact of standard tobacco cigarettes and e-cigarettes on heart development in vitro and in vivo.Zebrafish (Danio rerio were used to assess developmental effects in vivo and cardiac differentiation of human embryonic stem cells (hESCs was used as a model for in vitro cardiac development.In zebrafish, exposure to both types of cigarettes results in broad, dose-dependent developmental defects coupled with severe heart malformation, pericardial edema and reduced heart function. Tobacco cigarettes are more toxic than e-cigarettes at comparable nicotine concentrations. During cardiac differentiation of hESCs, tobacco smoke exposure results in a delayed transition through mesoderm. Both types of cigarettes decrease expression of cardiac transcription factors in cardiac progenitor cells, suggesting a persistent delay in differentiation. In definitive human cardiomyocytes, both e-cigarette- and tobacco cigarette-treated samples showed reduced expression of sarcomeric genes such as MLC2v and MYL6. Furthermore, tobacco cigarette-treated samples had delayed onset of beating and showed low levels and aberrant localization of N-cadherin, reduced myofilament content with significantly reduced sarcomere length, and increased expression of the immature cardiac marker smooth muscle alpha-actin.These data indicate a negative effect of both tobacco cigarettes and e-cigarettes on heart development in vitro and in vivo. Tobacco cigarettes are more toxic than E-cigarettes and exhibit a broader spectrum of cardiac developmental defects.

  9. Cardiac pacing in heart failure patients with left bundle branch block: impact of pacing site for optimizing left ventricular resynchronization.

    Science.gov (United States)

    Pappone, C; Rosanio, S; Oreto, G; Tocchi, M; Gulletta, S; Salvati, A; Dicandia, C; Santinelli, V; Mazzone, P; Veglia, F; Ding, J; Sallusti, L; Spinelli, J; Vicedomini, G

    2000-07-01

    Acute left ventricular pacing has been associated with hemodynamic improvement in patients with congestive heart failure and wide QRS complex. We hypothesized that pacing two left ventricular sites simultaneously would produce faster activation and better systolic function than single-site pacing. We selected 14 heart failure patients (NYHA functional class III or IV) in normal sinus rhythm with left bundle branch block and QRS > 150 ms. An 8F dual micromanometer catheter was placed in the aorta for measuring +dP/dt (mmHg/s), aortic pulse pressure (mmHg), and end-diastolic pressure (mmHg). Pacing leads were positioned via coronary veins at the posterior base and lateral wall. Patients were acutely paced VDD at the posterior base, lateral wall, and both sites (dual-site) with 5 atrioventricular delays (from 8 ms to PR -30 ms). Pacing sequences were executed in randomized order using a custom external computer (FlexStim, Guidant CRM). Dual-site pacing increased peak +dP/dt significantly more than posterior base and lateral wall pacing. Dual-site and posterior base pacing raised aortic pulse pressure significantly more than lateral wall pacing. Dual-site pacing shortened QRS duration by 22 %, whereas posterior base and lateral wall pacing increased it by 2 and 12%, respectively (p = 0.006). In heart failure patients with left bundle branch block, dual-site pacing improves systolic function more than single-site stimulation. Improved ventricular activation synchrony, expressed by paced QRS narrowing, may account for the additional benefit of dual- vs single-site pacing in enhancing contractility. This novel approach deserves consideration for future heart failure pacing studies.

  10. 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

    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...... was normal in all subjects as well as right ventricular volumes. Likewise, on average, the lung transit time (LTT) was normal. Brain natriuretic peptide (BNP) significantly correlated with LVEF, left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-systolic volume index (LVESVI...... ejection fractions (LVEF) and volumes were measured by means of first-pass and equilibrium radionuclide ventriculography. RESULTS: LVEF was 0.29 (range: 0.11-0.55). Two-thirds of the patients had dilated left ventricles with volumes above upper reference limit. Right ventricular ejection fraction...

  11. SIMULATED HUMAN ERROR PROBABILITY AND ITS APPLICATION TO DYNAMIC HUMAN FAILURE EVENTS

    Energy Technology Data Exchange (ETDEWEB)

    Herberger, Sarah M.; Boring, Ronald L.

    2016-10-01

    Abstract Objectives: Human reliability analysis (HRA) methods typically analyze human failure events (HFEs) at the overall task level. For dynamic HRA, it is important to model human activities at the subtask level. There exists a disconnect between dynamic subtask level and static task level that presents issues when modeling dynamic scenarios. For example, the SPAR-H method is typically used to calculate the human error probability (HEP) at the task level. As demonstrated in this paper, quantification in SPAR-H does not translate to the subtask level. Methods: Two different discrete distributions were generated for each SPAR-H Performance Shaping Factor (PSF) to define the frequency of PSF levels. The first distribution was a uniform, or uninformed distribution that assumed the frequency of each PSF level was equally likely. The second non-continuous distribution took the frequency of PSF level as identified from an assessment of the HERA database. These two different approaches were created to identify the resulting distribution of the HEP. The resulting HEP that appears closer to the known distribution, a log-normal centered on 1E-3, is the more desirable. Each approach then has median, average and maximum HFE calculations applied. To calculate these three values, three events, A, B and C are generated from the PSF level frequencies comprised of subtasks. The median HFE selects the median PSF level from each PSF and calculates HEP. The average HFE takes the mean PSF level, and the maximum takes the maximum PSF level. The same data set of subtask HEPs yields starkly different HEPs when aggregated to the HFE level in SPAR-H. Results: Assuming that each PSF level in each HFE is equally likely creates an unrealistic distribution of the HEP that is centered at 1. Next the observed frequency of PSF levels was applied with the resulting HEP behaving log-normally with a majority of the values under 2.5% HEP. The median, average and maximum HFE calculations did yield

  12. Immunosuppression in cardiac graft rejection: A human in vitro model to study the potential use of new immunomodulatory drugs

    International Nuclear Information System (INIS)

    Crescioli, Clara; Squecco, Roberta; Cosmi, Lorenzo; Sottili, Mariangela; Gelmini, Stefania; Borgogni, Elisa; Sarchielli, Erica; Scolletta, Sabino; Francini, Fabio; Annunziato, Francesco; Vannelli, Gabriella Barbara; Serio, Mario

    2008-01-01

    CXCL10-CXCR3 axis plays a pivotal role in cardiac allograft rejection, so that targeting CXCL10 without inducing generalized immunosuppression may be of therapeutic significance in allotransplantation. Since the role of resident cells in cardiac rejection is still unclear, we aimed to establish reliable human cardiomyocyte cultures to investigate Th1 cytokine-mediated response in allograft rejection. We used human fetal cardiomyocytes (Hfcm) isolated from fetal hearts, obtained after legal abortions. Hfcm expressed specific cardiac lineage markers, specific cardiac structural proteins, typical cardiac currents and generated ventricular action potentials. Thus, Hfcm represent a reliable in vitro tool for allograft rejection research, since they resemble the features of mature cells. Hfcm secreted CXCL10 in response to IFNγ and TNFαα; this effect was magnified by cytokine combination. Cytokine synergy was associated to a significant TNFα-induced up-regulation of IFNγR. The response of Hfcm to some currently used immunosuppressive drugs compared to rosiglitazone, a peroxisome proliferator-activated receptor γ agonist and Th1-mediated response inhibitor, was also evaluated. Only micophenolic acid and rosiglitazone halved CXCL10 secretion by Hfcm. Given the pivotal role of IFNγ-induced chemokines in Th1-mediated allograft rejection, these preliminary results suggest that the combined effects of immunosuppressive agents and rosiglitazone could be potentially beneficial to patients receiving heart transplants

  13. A Transcriptomic and Epigenomic Comparison of Fetal and Adult Human Cardiac Fibroblasts Reveals Novel Key Transcription Factors in Adult Cardiac Fibroblasts

    Directory of Open Access Journals (Sweden)

    Malin K.B. Jonsson, PhD

    2016-12-01

    Full Text Available Cardiovascular disease remains the number one global cause of death and presents as multiple phenotypes in which the interplay between cardiomyocytes and cardiac fibroblasts (CFs has become increasingly highlighted. Fetal and adult CFs influence neighboring cardiomyocytes in different ways. Thus far, a detailed comparison between the two is lacking. Using a genome-wide approach, we identified and validated 2 crucial players for maintaining the adult primary human CF phenotype. Knockdown of these factors induced significant phenotypical changes, including senescence and reduced collagen gene expression. These may now represent novel therapeutic targets against deleterious functions of CFs in adult cardiovascular disease.

  14. Harmonic Force Spectroscopy Reveals a Force-Velocity Curve from a Single Human Beta Cardiac Myosin Motor

    DEFF Research Database (Denmark)

    Sung, Jongmin; Nag, Suman; Vestergaard, Christian L.

    2014-01-01

    human beta cardiac myosin S1. We also compare load-velocity curves for wild-type motors with load-velocity curves of mutant forms that cause hypertrophic or dilated-cardiomyopathy (HCM or DCM), in order to understand the effects of mutations on the contractile cycle at the single molecule level....

  15. Cardiac ankyrin repeat protein (CARP) expression in human and murine atherosclerotic lesions - Activin induces carp in smooth muscle cells

    NARCIS (Netherlands)

    de Waard, Vivian; van Achterberg, Tanja A. E.; Beauchamp, Nicholas J.; Pannekoek, Hans; de Vries, Carlie J. M.

    2003-01-01

    Objective-Cardiac ankyrin repeat protein (CARP) is a transcription factor-related protein that has been studied most extensively in the heart. In the present study, we investigated the expression and the potential function of CARP in human and murine atherosclerosis. Methods and Results-CARP

  16. Embryonic cardiac morphometry in Carnegie stages 15-23, from the Complutense University of Madrid Institute of Embryology Human Embryo Collection.

    Science.gov (United States)

    Arráez-Aybar, L A; Turrero-Nogués, A; Marantos-Gamarra, D G

    2008-01-01

    We performed a morphometric study of cardiac development on human embryos to complement the scarce data on human embryonic cardiac morphometry and to attempt to establish, from these, algorithms describing cardiac growth during the second month of gestation. Thirty human embryos from Carnegie stages 15-23 were included in the study. Shrinkage and compression effects from fixation and inclusion in paraffin were considered in our calculations. Growth of the cardiac (whole heart) volume and volume of ventricular myocardium through the Carnegie stages were analysed by ANOVA. Linear correlation was used to describe the relationship between the ventricular myocardium and cardiac volumes. Comparisons of models were carried out through the R2 statistic. The relationship volume of ventricular myocardium versus cardiac volume is expressed by the equation: cardiac volume = 0.6266 + 2.4778 volume of ventricular myocardium. The relationship cardiac volume versus crown-rump length is expressed by the equation: cardiac volume = 1.3 e(0.126 CR length), where e is the base of natural logarithms. At a clinical level, these results can contribute towards the establishment of a normogram for cardiac development, useful for the design of strategies for early diagnosis of congenital heart disease. They can also help in the study of embryogenesis, for example in the discussion of ventricular trabeculation. Copyright 2007 S. Karger AG, Basel.

  17. [Effect of benazepril on cardiac function in Chinese patients with chronic heart failure: a meta-analysis of randomized controlled trials].

    Science.gov (United States)

    Yan, Xiaowei; Xu, Dingli; Huang, Jun

    2014-10-14

    To evaluate the efficacy and tolerability of benazepril in Chinese patients with chronic systolic heart failure. We searched the databases of Cochrane, PubMed, EMbase, CBM and CNKI from January 1989 to November 2010 for the relevant studies. Two investigators identified randomized controlled trials (RCTs) independently according to the predefined inclusion and exclusion criteria. Statistical data analysis was performed with the Stata 11 software. A total of 15 studies with 1 355 Chinese patients of chronic systolic heart failure fulfilled the inclusion criteria. Among them, 546 received benazepril monotherapy. The dose range of benazepril was 5 to 40 mg daily. And it was similar to angiotensin II receptor blockers (ARBs) in improving left ventricular ejection fraction (LVEF)(P = 0.674), reducing LVEDD (P = 0.511) and improving cardiac output (P = 0.363). The combination therapy of benazepril and ARB was superior to ARB monotherapy in reducing left ventricular end-diastolic diameter (LVEDD) (P = 0.001). However, LVEF was comparable between patients with ACEI/ARB combination therapy and those with ARB monotherapy (P = 0.105). Compared with blank control, benazepril treatment was associated with a significant improvement in LVEF from baseline to follow-up (WMD = 6.5%; 95% CI: 0.9%, 12.0%; P = 0.022). Compared with baseline, benazepril treatment significantly increased LVEF (WMD = 10.4%; 95% confidence interval [CI]:7.1%, 13.8%; P benazepril group. As the most common side effect after benazepril treatment, cough had a prevalence of 11.6%. Other side effects were rare. Benazepril is both efficacious and safe in the management of Chinese patients with chronic heart failure.

  18. A crucial role of activin A-mediated growth hormone suppression in mouse and human heart failure.

    Directory of Open Access Journals (Sweden)

    Noritoshi Fukushima

    Full Text Available Infusion of bone marrow-derived mononuclear cells (BMMNC has been reported to ameliorate cardiac dysfunction after acute myocardial infarction. In this study, we investigated whether infusion of BMMNC is also effective for non-ischemic heart failure model mice and the underlying mechanisms. Intravenous infusion of BMMNC showed transient cardioprotective effects on animal models with dilated cardiomyopathy (DCM without their engraftment in heart, suggesting that BMMNC infusion improves cardiac function via humoral factors rather than their differentiation into cardiomyocytes. Using conditioned media from sorted BMMNC, we found that the cardioprotective effects were mediated by growth hormone (GH secreted from myeloid (Gr-1(+ cells and the effects was partially mediated by signal transducer and activator of transcription 3 in cardiomyocytes. On the other hand, the GH expression in Gr-1(+ cells was significantly downregulated in DCM mice compared with that in healthy control, suggesting that the environmental cue in heart failure might suppress the Gr-1(+ cells function. Activin A was upregulated in the serum of DCM models and induced downregulation of GH levels in Gr-1(+ cells and serum. Furthermore, humoral factors upregulated in heart failure including angiotensin II upregulated activin A in peripheral blood mononuclear cells (PBMNC via activation of NFκB. Similarly, serum activin A levels were also significantly higher in DCM patients with heart failure than in healthy subjects and the GH levels in conditioned medium from PBMNC of DCM patients were lower than that in healthy subjects. Inhibition of activin A increased serum GH levels and improved cardiac function of DCM model mice. These results suggest that activin A causes heart failure by suppressing GH activity and that inhibition of activin A might become a novel strategy for the treatment of heart failure.

  19. Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats

    Czech Academy of Sciences Publication Activity Database

    Beneš, J.; Kazdová, L.; Drahota, Zdeněk; Houštěk, Josef; Medříková, Daša; Kopecký, Jan; Kovářová, Nikola; Vrbacký, Marek; Sedmera, David; Strnad, Hynek; Kolář, Michal; Petrák, J.; Benada, Oldřich; Škaroupková, P.; Červenka, L.; Melenovský, V.

    2011-01-01

    Roč. 121, č. 1 (2011), s. 29-41 ISSN 0143-5221 R&D Projects: GA MŠk(CZ) 1M0510; GA MZd(CZ) NS9757; GA MŠk(CZ) 1M0520 Grant - others:GA MZd(CZ) NS10497; GA ČR(CZ) GA305/09/1390 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50520514; CEZ:AV0Z50200510 Keywords : AMP-activated protein kinase * energy metabolism * heart failure * metformin * survival * volume overload Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.317, year: 2011

  20. One Size Does Not Fit All: Human Failure Event Decomposition and Task Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ronald Laurids Boring, PhD

    2014-09-01

    In the probabilistic safety assessments (PSAs) used in the nuclear industry, human failure events (HFEs) are determined as a subset of hardware failures, namely those hardware failures that could be triggered or exacerbated by human action or inaction. This approach is top-down, starting with hardware faults and deducing human contributions to those faults. Elsewhere, more traditionally human factors driven approaches would tend to look at opportunities for human errors first in a task analysis and then identify which of those errors is risk significant. The intersection of top-down and bottom-up approaches to defining HFEs has not been carefully studied. Ideally, both approaches should arrive at the same set of HFEs. This question remains central as human reliability analysis (HRA) methods are generalized to new domains like oil and gas. The HFEs used in nuclear PSAs tend to be top-down—defined as a subset of the PSA—whereas the HFEs used in petroleum quantitative risk assessments (QRAs) are more likely to be bottom-up—derived from a task analysis conducted by human factors experts. The marriage of these approaches is necessary in order to ensure that HRA methods developed for top-down HFEs are also sufficient for bottom-up applications. In this paper, I first review top-down and bottom-up approaches for defining HFEs and then present a seven-step guideline to ensure a task analysis completed as part of human error identification decomposes to a level suitable for use as HFEs. This guideline illustrates an effective way to bridge the bottom-up approach with top-down requirements.

  1. Elimination of remaining undifferentiated induced pluripotent stem cells in the process of human cardiac cell sheet fabrication using a methionine-free culture condition.

    Science.gov (United States)

    Matsuura, Katsuhisa; Kodama, Fumiko; Sugiyama, Kasumi; Shimizu, Tatsuya; Hagiwara, Nobuhisa; Okano, Teruo

    2015-03-01

    Cardiac tissue engineering is a promising method for regenerative medicine. Although we have developed human cardiac cell sheets by integration of cell sheet-based tissue engineering and scalable bioreactor culture, the risk of contamination by induced pluripotent stem (iPS) cells in cardiac cell sheets remains unresolved. In the present study, we established a novel culture method to fabricate human cardiac cell sheets with a decreased risk of iPS cell contamination while maintaining viabilities of iPS cell-derived cells, including cardiomyocytes and fibroblasts, using a methionine-free culture condition. When cultured in the methionine-free condition, human iPS cells did not survive without feeder cells and could not proliferate or form colonies on feeder cells or in coculture with cells for cardiac cell sheet fabrication. When iPS cell-derived cells after the cardiac differentiation were transiently cultured in the methionine-free condition, gene expression of OCT3/4 and NANOG was downregulated significantly compared with that in the standard culture condition. Furthermore, in fabricated cardiac cell sheets, spontaneous and synchronous beating was observed in the whole area while maintaining or upregulating the expression of various cardiac and extracellular matrix genes. These findings suggest that human iPS cells are methionine dependent and a methionine-free culture condition for cardiac cell sheet fabrication might reduce the risk of iPS cell contamination.

  2. In vitro epigenetic reprogramming of human cardiac mesenchymal stromal cells into functionally competent cardiovascular precursors.

    Directory of Open Access Journals (Sweden)

    Matteo Vecellio

    Full Text Available Adult human cardiac mesenchymal-like stromal cells (CStC represent a relatively accessible cell type useful for therapy. In this light, their conversion into cardiovascular precursors represents a potential successful strategy for cardiac repair. The aim of the present work was to reprogram CStC into functionally competent cardiovascular precursors using epigenetically active small molecules. CStC were exposed to low serum (5% FBS in the presence of 5 µM all-trans Retinoic Acid (ATRA, 5 µM Phenyl Butyrate (PB, and 200 µM diethylenetriamine/nitric oxide (DETA/NO, to create a novel epigenetically active cocktail (EpiC. Upon treatment the expression of markers typical of cardiac resident stem cells such as c-Kit and MDR-1 were up-regulated, together with the expression of a number of cardiovascular-associated genes including KDR, GATA6, Nkx2.5, GATA4, HCN4, NaV1.5, and α-MHC. In addition, profiling analysis revealed that a significant number of microRNA involved in cardiomyocyte biology and cell differentiation/proliferation, including miR 133a, 210 and 34a, were up-regulated. Remarkably, almost 45% of EpiC-treated cells exhibited a TTX-sensitive sodium current and, to a lower extent in a few cells, also the pacemaker I(f current. Mechanistically, the exposure to EpiC treatment introduced global histone modifications, characterized by increased levels of H3K4Me3 and H4K16Ac, as well as reduced H4K20Me3 and H3s10P, a pattern compatible with reduced proliferation and chromatin relaxation. Consistently, ChIP experiments performed with H3K4me3 or H3s10P histone modifications revealed the presence of a specific EpiC-dependent pattern in c-Kit, MDR-1, and Nkx2.5 promoter regions, possibly contributing to their modified expression. Taken together, these data indicate that CStC may be epigenetically reprogrammed to acquire molecular and biological properties associated with competent cardiovascular precursors.

  3. Dual-Energy Computed Tomography Gemstone Spectral Imaging: A Novel Technique to Determine Human Cardiac Calculus Composition.

    Science.gov (United States)

    Cheng, Ching-Li; Chang, Hsiao-Huang; Ko, Shih-Chi; Huang, Pei-Jung; Lin, Shan-Yang

    2016-01-01

    Understanding the chemical composition of any calculus in different human organs is essential for choosing the best treatment strategy for patients. The purpose of this study was to assess the capability of determining the chemical composition of a human cardiac calculus using gemstone spectral imaging (GSI) mode on a single-source dual-energy computed tomography (DECT) in vitro. The cardiac calculus was directly scanned on the Discovery CT750 HD FREEdom Edition using GSI mode, in vitro. A portable fiber-optic Raman spectroscopy was also applied to verify the quantitative accuracy of the DECT measurements. The results of spectral DECT measurements indicate that effective Z values in 3 designated positions located in this calculus were 15.02 to 15.47, which are close to values of 15.74 to 15.86, corresponding to the effective Z values of calcium apatite and hydroxyapatite. The Raman spectral data were also reflected by the predominant Raman peak at 960 cm for hydroxyapatite and the minor peak at 875 cm for calcium apatite. A potential single-source DECT with GSI mode was first used to examine the morphological characteristics and chemical compositions of a giant human cardiac calculus, in vitro. The CT results were consistent with the Raman spectral data, suggesting that spectral CT imaging techniques could be accurately used to diagnose and characterize the compositional materials in the cardiac calculus.

  4. Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells

    Directory of Open Access Journals (Sweden)

    Agneta Månsson-Broberg

    2016-04-01

    Full Text Available The intrinsic regenerative capacity of human fetal cardiac mesenchymal stromal cells (MSCs has not been fully characterized. Here we demonstrate that we can expand cells with characteristics of cardiovascular progenitor cells from the MSC population of human fetal hearts. Cells cultured on cardiac muscle laminin (LN-based substrata in combination with stimulation of the canonical Wnt/β-catenin pathway showed increased gene expression of ISL1, OCT4, KDR, and NKX2.5. The majority of cells stained positive for PDGFR-α, ISL1, and NKX2.5, and subpopulations also expressed the progenitor markers TBX18, KDR, c-KIT, and SSEA-1. Upon culture of the cardiac MSCs in differentiation media and on relevant LNs, portions of the cells differentiated into spontaneously beating cardiomyocytes, and endothelial and smooth muscle-like cells. Our protocol for large-scale culture of human fetal cardiac MSCs enables future exploration of the regenerative functions of these cells in the context of myocardial injury in vitro and in vivo.

  5. Adherence to 2016 European Society of Cardiology guidelines predicts outcome in a large real-world population of heart failure patients requiring cardiac resynchronization therapy.

    Science.gov (United States)

    Stabile, Giuseppe; Pepi, Patrizia; Palmisano, Pietro; D'Onofrio, Antonio; De Simone, Antonio; Caico, Salvatore Ivan; Pecora, Domenico; Rapacciuolo, Antonio; Arena, Giuseppe; Marini, Massimiliano; Pieragnoli, Paolo; Badolati, Sandra; Savarese, Gianluca; Maglia, Gianpiero; Iuliano, Assunta; Botto, Giovanni Luca; Malacrida, Maurizio; Bertaglia, Emanuele

    2018-04-14

    Professional guidelines are based on the best available evidence. However, patients treated in clinical practice may differ from those included in reference trials. The aim of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in a large population of patients implanted with a CRT device stratified in accordance with the 2016 European heart failure (HF) guidelines. We collected data on 930 consecutive patients from the Cardiac Resynchronization Therapy MOdular REgistry. The primary end point was a composite of death and HF hospitalization. Five hundred sixty-three (60.5%) patients met class I indications, 145 (15.6%) class IIa, 108 (11.6%) class IIb, and 114 (12.3%) class III. After a median follow-up of 1001 days, 120 patients who had an indication for CRT implantation had died and 71 had been hospitalized for HF. The time to the end point was longer in patients with a class I indication (hazard ratio 0.55; 95% confidence interval 0.39-0.76; P = .0001). After 12 months, left ventricular (LV) end-systolic volume had decreased by ≥15% in 61.5% of patients whereas in 57.5% of patients the absolute LV ejection fraction improvement was ≥5%. Adherence to class I was also associated with an absolute LV ejection fraction increase of >5% (P = .0142) and an LV end-systolic volume decrease of ≥15% (P = .0055). In our population, ∼60% of patients underwent implantation according to the 2016 European HF guidelines class I indication. Adherence to class I was associated with a lower death and HF hospitalization rate and better LV reverse remodeling. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  6. Effect of long-term non-invasive ventilation on quality of life and cardiac function of children's neuromuscular disorders with chronic respiratory failure: a clinical trial

    Directory of Open Access Journals (Sweden)

    Saeed Sadr

    2018-04-01

    Full Text Available Background: Use of long-term non-invasive positive pressure ventilation is increasing greatly worldwide in children with chronic respiratory failure (CRF of all ages. This treatment requires delivery of ventilation through a non-invasive interface. Cardiac function in majority of these children is impaired. The aim of this study was to assess the effect of institution of non-invasive ventilation (NIV on quality of life (QOL and cardiac function in children with CRF related to neuromuscular disorders. Methods: Information obtained from all of the children under 16 years old with CRF due to neuromuscular disorders who were on NIV for at least six months and that were referred to Mofid children's hospital, Tehran, Iran between September 1, 2013, to September 1, 2017.Based on previous studies they were assessed from the year prior to starting NIV and annually thereafter. Data obtained included diagnosis, pulmonary function test, echocardiographic data, length of hospitalizations, and health care costs. Patients and parents completed questionnaires assessing QOL with NIV and recalling QOL one year before commencing NIV. All results were recorded in information forms and data were analyzed with chi square and entered in SPSS 21. Results: Follow-up ranged from 6 to 36 months (median 18. Before and after NIV hospitalization rates (P<0.001, PICU admission (P<0.001 and health care costs decreased respectively. QOL remained stable after NIV despite disease progression (P<0.001. Systolic pulmonary arterial pressure (P=0.009 is diminished. Symptoms of daytime sleepiness (P<0.001 and headache (P<0.001 improved after initiation of NIV. Conclusions: This study revealed that use of NIV results in a reduction in PAH without adverse effects on quality of life and pulmonary function.

  7. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment

    International Nuclear Information System (INIS)

    Iso, Yoshitaka; Spees, Jeffrey L.; Serrano, Claudia; Bakondi, Benjamin; Pochampally, Radhika; Song, Yao-Hua; Sobel, Burton E.; Delafontaine, Patrick; Prockop, Darwin J.

    2007-01-01

    The aim of this study was to determine whether intravenously administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group were significantly improved compared with controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion

  8. Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial.

    Science.gov (United States)

    Zuchinali, Priccila; Souza, Gabriela C; Pimentel, Maurício; Chemello, Diego; Zimerman, André; Giaretta, Vanessa; Salamoni, Joyce; Fracasso, Bianca; Zimerman, Leandro I; Rohde, Luis E

    2016-12-01

    The presumed proarrhythmic action of caffeine is controversial. Few studies have assessed the effect of high doses of caffeine in patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias. To compare the effect of high-dose caffeine or placebo on the frequency of supraventricular and ventricular arrhythmias, both at rest and during a symptom-limited exercise test. Double-blinded randomized clinical trial with a crossover design conducted at the heart failure and cardiac transplant clinic of a tertiary-care university hospital. The trial included patients with chronic heart failure with moderate-to-severe systolic dysfunction (left ventricular ejection fraction capsules, in addition to 5 doses of 100 mL decaffeinated coffee at 1-hour intervals, for a total of 500 mg of caffeine or placebo during a 5-hour protocol. After a 1-week washout period, the protocol was repeated. Number and percentage of ventricular and supraventricular premature beats assessed by continuous electrocardiographic monitoring. We enrolled 51 patients (37 [74%] male; mean [SD] age, 60.6 [10.9] years) with predominantly moderate-to-severe left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 29% [7%]); 31 [61%] had an implantable cardioverter-defibrillator device. No significant differences between the caffeine and placebo groups were observed in the number of ventricular (185 vs 239 beats, respectively; P = .47) and supraventricular premature beats (6 vs 6 beats, respectively; P = .44), as well as in couplets, bigeminal cycles, or nonsustained tachycardia during continuous electrocardiographic monitoring. Exercise test-derived variables, such as ventricular and supraventricular premature beats, duration of exercise, estimated peak oxygen consumption, and heart rate, were not influenced by caffeine ingestion. We observed no increases in ventricular premature beats (91 vs 223 vs 207 beats, respectively

  9. Do I Dare to Be Human? The Perverse Failure to Mourn, to Think, and to Love.

    Science.gov (United States)

    Shoshani, Michael; Shoshani, Batya

    2016-06-01

    The authors discuss the relation between perverse psychic formations and the ability to develop a mind of one's own. The authors characterize the formation of perversity in terms of failure to develop the key capacities of thinking, mourning, and loving. These failures result in the abolishment of thinking and the repudiation of separateness and lead to the creation of different kinds of twisted coalitions, which shape the transference-counter-transference matrix. Persons with perverse psychic organizations have difficulties developing their own minds due to their refusal to acknowledge human limitations and their inability to accept the fundamental differences of human existence: self-other, child-adult, male-female. These characterizations are illustrated by clinical material, including a detailed analytic session, demonstrating the perverse aggresivization and sexualization of the analytic relationship. The role of the analyst is to detoxify the violence and destruction and to translate the language of perversion into the language of love.

  10. The NUCLARR databank: Human reliability and hardware failure data for the nuclear power industry

    International Nuclear Information System (INIS)

    Reece, W.J.

    1993-01-01

    Under the sponsorship of the US Nuclear Regulatory Commission (NRC), the Nuclear Computerized Library for Assessing Reactor Reliability (NUCLARR) was developed to provide human reliability and hardware failure data to analysts in the nuclear power industry. This IBM-compatible databank is contained on a set of floppy diskettes which include data files and a menu-driven system for locating, reviewing, sorting, and retrieving the data. NUCLARR contains over 2500 individual data records, drawn from more, than 60 sources. The system is upgraded annually, to include additional human error and hardware component failure data and programming enhancements (i.e., increased user-friendliness). NUCLARR is available from the NRC through project staff at the INEL

  11. Cardiac neuronal imaging with 123I-meta-iodobenzylguanidine in heart failure: implications of endpoint selection and quantitative analysis on clinical decisions

    International Nuclear Information System (INIS)

    Petretta, Mario; Pellegrino, Teresa; Cuocolo, Alberto

    2014-01-01

    There are a number of radiopharmaceuticals that can be used to investigate autonomic neuronal functions. Among these, the norepinephrine analogue meta-iodobenzylguanidine (MIBG) labelled with 123 I has been widely used and validated as a marker of adrenergic neuron function. The first study addressing the prognostic value of 123 I-MIBG imaging in heart failure (HF) was that of Merlet et al. in 90 patients suffering from either ischaemic or idiopathic cardiomyopathy. After publication of this study, more recent studies have indicated that patients with HF and decreased late heart-to-mediastinum (H/M) ratio or increased myocardial MIBG washout have a worse prognosis than those with normal quantitative myocardial MIBG parameters. However, MIBG scintigraphy has still to reach widespread clinical application mainly because of the value of other cheaper variables such as left ventricular (LV) ejection fraction and brain natriuretic peptide (BNP) plasma levels. The possibility that the detection of mechanical dyssynchrony by innervation imaging might identify patients who would benefit from resynchronization pacing is another area of research interest. In 2010, the landmark AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study was published. This trial consisted of two identical open-label phase III studies enrolling patients in 96 sites in North America and Europe to provide prospective validation of the prognostic role of quantitation of sympathetic cardiac innervation using MIBG. The primary endpoint was the relationship between late HIM ratio and time-to-occurrence of the first event among a combination of HF progression, potentially life-threatening arrhythmic event, and cardiac death. The authors found that a HIM ratio <1.6 provided prognostic information beyond LV ejection fraction, BNP, and New York Heart Association (NYHA) functional class at the time of enrolment. In a recent article in this journal, Parker et al. present the results

  12. Cardiac neuronal imaging with {sup 123}I-meta-iodobenzylguanidine in heart failure: implications of endpoint selection and quantitative analysis on clinical decisions

    Energy Technology Data Exchange (ETDEWEB)

    Petretta, Mario [University Federico II, Department of Translational Medicine, Naples (Italy); Pellegrino, Teresa [National Council of Research, Institute of Biostructure and Bioimaging, Naples (Italy); Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy)

    2014-09-15

    There are a number of radiopharmaceuticals that can be used to investigate autonomic neuronal functions. Among these, the norepinephrine analogue meta-iodobenzylguanidine (MIBG) labelled with {sup 123}I has been widely used and validated as a marker of adrenergic neuron function. The first study addressing the prognostic value of {sup 123}I-MIBG imaging in heart failure (HF) was that of Merlet et al. in 90 patients suffering from either ischaemic or idiopathic cardiomyopathy. After publication of this study, more recent studies have indicated that patients with HF and decreased late heart-to-mediastinum (H/M) ratio or increased myocardial MIBG washout have a worse prognosis than those with normal quantitative myocardial MIBG parameters. However, MIBG scintigraphy has still to reach widespread clinical application mainly because of the value of other cheaper variables such as left ventricular (LV) ejection fraction and brain natriuretic peptide (BNP) plasma levels. The possibility that the detection of mechanical dyssynchrony by innervation imaging might identify patients who would benefit from resynchronization pacing is another area of research interest. In 2010, the landmark AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) study was published. This trial consisted of two identical open-label phase III studies enrolling patients in 96 sites in North America and Europe to provide prospective validation of the prognostic role of quantitation of sympathetic cardiac innervation using MIBG. The primary endpoint was the relationship between late HIM ratio and time-to-occurrence of the first event among a combination of HF progression, potentially life-threatening arrhythmic event, and cardiac death. The authors found that a HIM ratio <1.6 provided prognostic information beyond LV ejection fraction, BNP, and New York Heart Association (NYHA) functional class at the time of enrolment. In a recent article in this journal, Parker et al. present

  13. Cardiac-specific overexpression of aldehyde dehydrogenase 2 exacerbates cardiac remodeling in response to pressure overload

    Directory of Open Access Journals (Sweden)

    Sujith Dassanayaka

    2018-07-01

    Full Text Available Pathological cardiac remodeling during heart failure is associated with higher levels of lipid peroxidation products and lower abundance of several aldehyde detoxification enzymes, including aldehyde dehydrogenase 2 (ALDH2. An emerging idea that could explain these findings concerns the role of electrophilic species in redox signaling, which may be important for adaptive responses to stress or injury. The purpose of this study was to determine whether genetically increasing ALDH2 activity affects pressure overload-induced cardiac dysfunction. Mice subjected to transverse aortic constriction (TAC for 12 weeks developed myocardial hypertrophy and cardiac dysfunction, which were associated with diminished ALDH2 expression and activity. Cardiac-specific expression of the human ALDH2 gene in mice augmented myocardial ALDH2 activity but did not improve cardiac function in response to pressure overload. After 12 weeks of TAC, ALDH2 transgenic mice had larger hearts than their wild-type littermates and lower capillary density. These findings show that overexpression of ALDH2 augments the hypertrophic response to pressure overload and imply that downregulation of ALDH2 may be an adaptive response to certain forms of cardiac pathology. Keywords: Heart failure, Hypertrophy, Oxidative stress, Aldehydes, Cardiac remodeling, Hormesis

  14. The cardiac glycoside oleandrin induces apoptosis in human colon cancer cells via the mitochondrial pathway.

    Science.gov (United States)

    Pan, Li; Zhang, Yuming; Zhao, Wanlu; Zhou, Xia; Wang, Chunxia; Deng, Fan

    2017-07-01

    Evidence indicates that the cardiac glycoside oleandrin exhibits cytotoxic activity against several different types of cancer. However, the specific mechanisms underlying oleandrin-induced anti-tumor effects remain largely unknown. The present study examined the anti-cancer effect and underlying mechanism of oleandrin on human colon cancer cells. The cytotoxicity and IC50 of five small molecule compounds (oleandrin, neriifolin, strophanthidin, gitoxigenin, and convallatoxin) in human colon cancer cell line SW480 cells and normal human colon cell line NCM460 cells were determined by cell counting and MTT assays, respectively. Apoptosis was determined by staining cells with annexin V-FITC and propidium iodide, followed by flow cytometry. Intracellular Ca 2+ was determined using Fluo-3 AM,glutathione (GSH) levels were measured using a GSH detection kit,and the activity of caspase-3, -9 was measured using a peptide substrate. BAX, pro-caspase-3, -9, cytochrome C and BCL-2 expression were determined by Western blotting. Oleandrin significantly decreased cell viabilities in SW480, HCT116 and RKO cells. The IC50 for SW480 cells was 0.02 µM, whereas for NCM460 cells 0.56 µM. More interestingly, the results of flow cytometry showed that oleandrin potently induced apoptosis in SW480 and RKO cells. Oleandrin downregulated protein expression of pro-caspase-3, -9, but enhanced caspase-3, -9 activities. These effects were accompanied by upregulation of protein expression of cytochrome C and BAX, and downregulation of BCL-2 protein expression in a concentration-dependent manner. Furthermore, oleandrin increased intracellular Ca 2+ concentration, but decreased GSH concentration in the cells. The present results suggest that oleandrin induces apoptosis in human colorectal cancer cells via the mitochondrial pathway. Our findings provide new insight into the mechanism of anti-cancer property of oleandrin.

  15. Comparison of Methods for Dependency Determination between Human Failure Events within Human Reliability Analysis

    International Nuclear Information System (INIS)

    Cepin, M.

    2008-01-01

    The human reliability analysis (HRA) is a highly subjective evaluation of human performance, which is an input for probabilistic safety assessment, which deals with many parameters of high uncertainty. The objective of this paper is to show that subjectivism can have a large impact on human reliability results and consequently on probabilistic safety assessment results and applications. The objective is to identify the key features, which may decrease subjectivity of human reliability analysis. Human reliability methods are compared with focus on dependency comparison between Institute Jozef Stefan human reliability analysis (IJS-HRA) and standardized plant analysis risk human reliability analysis (SPAR-H). Results show large differences in the calculated human error probabilities for the same events within the same probabilistic safety assessment, which are the consequence of subjectivity. The subjectivity can be reduced by development of more detailed guidelines for human reliability analysis with many practical examples for all steps of the process of evaluation of human performance

  16. Comparison of methods for dependency determination between human failure events within human reliability analysis

    International Nuclear Information System (INIS)

    Cepis, M.

    2007-01-01

    The Human Reliability Analysis (HRA) is a highly subjective evaluation of human performance, which is an input for probabilistic safety assessment, which deals with many parameters of high uncertainty. The objective of this paper is to show that subjectivism can have a large impact on human reliability results and consequently on probabilistic safety assessment results and applications. The objective is to identify the key features, which may decrease of subjectivity of human reliability analysis. Human reliability methods are compared with focus on dependency comparison between Institute Jozef Stefan - Human Reliability Analysis (IJS-HRA) and Standardized Plant Analysis Risk Human Reliability Analysis (SPAR-H). Results show large differences in the calculated human error probabilities for the same events within the same probabilistic safety assessment, which are the consequence of subjectivity. The subjectivity can be reduced by development of more detailed guidelines for human reliability analysis with many practical examples for all steps of the process of evaluation of human performance. (author)

  17. Three-Dimensional Human Cardiac Tissue Engineered by Centrifugation of Stacked Cell Sheets and Cross-Sectional Observation of Its Synchronous Beatings by Optical Coherence Tomography.

    Science.gov (United States)

    Haraguchi, Yuji; Hasegawa, Akiyuki; Matsuura, Katsuhisa; Kobayashi, Mari; Iwana, Shin-Ichi; Kabetani, Yasuhiro; Shimizu, Tatsuya

    2017-01-01

    Three-dimensional (3D) tissues are engineered by stacking cell sheets, and these tissues have been applied in clinical regenerative therapies. The optimal fabrication technique of 3D human tissues and the real-time observation system for these tissues are important in tissue engineering, regenerative medicine, cardiac physiology, and the safety testing of candidate chemicals. In this study, for aiming the clinical application, 3D human cardiac tissues were rapidly fabricated by human induced pluripotent stem (iPS) cell-derived cardiac cell sheets with centrifugation, and the structures and beatings in the cardiac tissues were observed cross-sectionally and noninvasively by two optical coherence tomography (OCT) systems. The fabrication time was reduced to approximately one-quarter by centrifugation. The cross-sectional observation showed that multilayered cardiac cell sheets adhered tightly just after centrifugation. Additionally, the cross-sectional transmissions of beatings within multilayered human cardiac tissues were clearly detected by OCT. The observation showed the synchronous beatings of the thicker 3D human cardiac tissues, which were fabricated rapidly by cell sheet technology and centrifugation. The rapid tissue-fabrication technique and OCT technology will show a powerful potential in cardiac tissue engineering, regenerative medicine, and drug discovery research.

  18. Insomnia Self-Management in Heart Failure

    Science.gov (United States)

    2018-01-05

    Cardiac Failure; Heart Failure; Congestive Heart Failure; Heart Failure, Congestive; Sleep Initiation and Maintenance Disorders; Chronic Insomnia; Disorders of Initiating and Maintaining Sleep; Fatigue; Pain; Depressive Symptoms; Sleep Disorders; Anxiety

  19. Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

    Science.gov (United States)

    Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

    2016-11-25

    In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

  20. An Autonomic Link Between Inhaled Diesel Exhaust and Impaired Cardiac Performance: Insight From Treadmill and Doubutamine Challenges in Heart Failure-Prone Rats

    Science.gov (United States)

    Background: Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) is an ubiquitous air pollutant believed to provoke cardiac events partly through imbalance of the sympathetic and parasympathetic branches of the autonomic nervo...

  1. An empirical study on the human error recovery failure probability when using soft controls in NPP advanced MCRs

    International Nuclear Information System (INIS)

    Jang, Inseok; Kim, Ar Ryum; Jung, Wondea; Seong, Poong Hyun

    2014-01-01

    Highlights: • Many researchers have tried to understand human recovery process or step. • Modeling human recovery process is not sufficient to be applied to HRA. • The operation environment of MCRs in NPPs has changed by adopting new HSIs. • Recovery failure probability in a soft control operation environment is investigated. • Recovery failure probability here would be important evidence for expert judgment. - Abstract: It is well known that probabilistic safety assessments (PSAs) today consider not just hardware failures and environmental events that can impact upon risk, but also human error contributions. Consequently, the focus on reliability and performance management has been on the prevention of human errors and failures rather than the recovery of human errors. However, the recovery of human errors is as important as the prevention of human errors and failures for the safe operation of nuclear power plants (NPPs). For this reason, many researchers have tried to find a human recovery process or step. However, modeling the human recovery process is not sufficient enough to be applied to human reliability analysis (HRA), which requires human error and recovery probabilities. In this study, therefore, human error recovery failure probabilities based on predefined human error modes were investigated by conducting experiments in the operation mockup of advanced/digital main control rooms (MCRs) in NPPs. To this end, 48 subjects majoring in nuclear engineering participated in the experiments. In the experiments, using the developed accident scenario based on tasks from the standard post trip action (SPTA), the steam generator tube rupture (SGTR), and predominant soft control tasks, which are derived from the loss of coolant accident (LOCA) and the excess steam demand event (ESDE), all error detection and recovery data based on human error modes were checked with the performance sheet and the statistical analysis of error recovery/detection was then

  2. Electrical remodeling of cardiac myocytes from mice with heart failure due to the overexpression of tumor necrosis factor-alpha.

    Science.gov (United States)

    Petkova-Kirova, Polina S; Gursoy, Erdal; Mehdi, Haider; McTiernan, Charles F; London, Barry; Salama, Guy

    2006-05-01

    Mice that overexpress the inflammatory cytokine tumor necrosis factor-alpha in the heart (TNF mice) develop heart failure characterized by atrial and ventricular dilatation, decreased ejection fraction, atrial and ventricular arrhythmias, and increased mortality (males > females). Abnormalities in Ca2+ handling, prolonged action potential duration (APD), calcium alternans, and reentrant atrial and ventricular arrhythmias were previously observed with the use of optical mapping of perfused hearts from TNF mice. We therefore tested whether altered voltage-gated outward K+ and/or inward Ca2+ currents contribute to the altered action potential characteristics and the increased vulnerability to arrhythmias. Whole cell voltage-clamp recordings of K+ currents from left ventricular myocytes of TNF mice revealed an approximately 50% decrease in the rapidly activating, rapidly inactivating transient outward K+ current Ito and in the rapidly activating, slowly inactivating delayed rectifier current IK,slow1, an approximately 25% decrease in the rapidly activating, slowly inactivating delayed rectifier current IK,slow2, and no significant change in the steady-state current Iss compared with controls. Peak amplitudes and inactivation kinetics of the L-type Ca2+ current ICa,L were not altered. Western blot analyses revealed a reduction in the proteins underlying Kv4.2, Kv4.3, and Kv1.5. Thus decreased K+ channel expression is largely responsible for the prolonged APD in the TNF mice and may, along with abnormalities in Ca2+ handling, contribute to arrhythmias.

  3. Intermittent Hypoxia Causes Inflammation and Injury to Human Adult Cardiac Myocytes.

    Science.gov (United States)

    Wu, Jing; Stefaniak, Joanna; Hafner, Christina; Schramel, Johannes Peter; Kaun, Christoph; Wojta, Johann; Ullrich, Roman; Tretter, Verena Eva; Markstaller, Klaus; Klein, Klaus Ulrich

    2016-02-01

    Intermittent hypoxia may occur in a number of clinical scenarios, including interruption of myocardial blood flow or breathing disorders such as obstructive sleep apnea. Although intermittent hypoxia has been linked to cardiovascular and cerebrovascular disease, the effect of intermittent hypoxia on the human heart is not fully understood. Therefore, in the present study, we compared the cellular responses of cultured human adult cardiac myocytes (HACMs) exposed to intermittent hypoxia and different conditions of continuous hypoxia and normoxia. HACMs were exposed to intermittent hypoxia (0%-21% O2), constant mild hypoxia (10% O2), constant severe hypoxia (0% O2), or constant normoxia (21% O2), using a novel cell culture bioreactor with gas-permeable membranes. Cell proliferation, lactate dehydrogenase release, vascular endothelial growth factor release, and cytokine (interleukin [IL] and macrophage migration inhibitory factor) release were assessed at baseline and after 8, 24, and 72 hours of exposure. A signal transduction pathway finder array was performed to determine the changes in gene expression. In comparison with constant normoxia and constant mild hypoxia, intermittent hypoxia induced earlier and greater inflammatory response and extent of cell injury as evidenced by lower cell numbers and higher lactate dehydrogenase, vascular endothelial growth factor, and proinflammatory cytokine (IL-1β, IL-6, IL-8, and macrophage migration inhibitory factor) release. Constant severe hypoxia showed more detrimental effects on HACMs at later time points. Pathway analysis demonstrated that intermittent hypoxia primarily altered gene expression in oxidative stress, Wnt, Notch, and hypoxia pathways. Intermittent and constant severe hypoxia, but not constant mild hypoxia or normoxia, induced inflammation and cell injury in HACMs. Cell injury occurred earliest and was greatest after intermittent hypoxia exposure. Our in vitro findings suggest that intermittent hypoxia

  4. Plasma Amino Acid Abnormalities in Chronic Heart Failure. Mechanisms, Potential Risks and Targets in Human Myocardium Metabolism

    Directory of Open Access Journals (Sweden)

    Roberto Aquilani

    2017-11-01

    Full Text Available The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF, and relate them to left ventricular function and disease severity. Amino acids (AAs play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA class II to IV were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (KcalI, protein-, fat-, carbohydrate-intake, resting energy expenditure (REE, total daily energy expenditure (REE × 1.3, and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001 and cardiac index (r = 0.4243; p = 0.0028. The value of arterial aspartic acid (µmol/L multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076. All NYHA groups had adequate protein intake (≥1.1 g/kg/day and inadequate calorie intake (KcalI < REE × 1.3 was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction.

  5. Mediterranean Diet and Other Dietary Patterns in Primary Prevention of Heart Failure and Changes in Cardiac Function Markers: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Karina Sanches Machado d’Almeida

    2018-01-01

    Full Text Available Background: Heart failure (HF is a complex syndrome and is recognized as the ultimate pathway of cardiovascular disease (CVD. Studies using nutritional strategies based on dietary patterns have proved to be effective for the prevention and treatment of CVD. Although there are studies that support the protective effect of these diets, their effects on the prevention of HF are not clear yet. Methods: We searched the Medline, Embase, and Cochrane databases for studies that examined dietary patterns, such as dietary approaches to stop hypertension (DASH diet, paleolithic, vegetarian, low-carb and low-fat diets and prevention of HF. No limitations were used during the search in the databases. Results: A total of 1119 studies were identified, 14 met the inclusion criteria. Studies regarding the Mediterranean, DASH, vegetarian, and Paleolithic diets were found. The Mediterranean and DASH diets showed a protective effect on the incidence of HF and/or worsening of cardiac function parameters, with a significant difference in relation to patients who did not adhere to these dietary patterns. Conclusions: It is observed that the adoption of Mediterranean or DASH-type dietary patterns may contribute to the prevention of HF, but these results need to be analyzed with caution due to the low quality of evidence.

  6. The effects of test environment and cyclic stretching on the failure properties of human patellar tendons

    International Nuclear Information System (INIS)

    Haut, R.C.; Powlison, A.C.

    1990-01-01

    There is a need to document the mechanical properties of patellar tendon allografts used for reconstructive surgery of the damaged anterior cruciate ligament, especially the effects of irradiation sterilization. The purpose of this study was to investigate the influences of in vitro test environment and low-level cyclic stretching prior to failure tests on nonirradiated and irradiated human graft tissues. Bilateral patellar tendons were split and each half processed accordingly. Some graft tissues were stretched cyclically at 2.5 mm deformation before failure. Experiments were performed in a 37 degrees C saline bath or with tissues moistened with a drip of the same. The irradiated grafts relaxed less and generated less slack length in the drip environment than the nonirradiated controls. Cyclic stretching did not alter failure characteristics of either graft tissue. While no significant differences in the tensile responses or failure characteristics were noted for irradiated and nonirradiated grafts in the drip, in the bath environment the nonirradiated tissues had greater strength and modulus. This resulted in there being a significant difference between irradiated and nonirradiated tissue responses in a heated saline bath environment. These experimental results exemplify the need to control in vitro test environments in the evaluation of various sterilization and preservation protocols for soft tissue allografts

  7. Fucoidan promotes early step of cardiac differentiation from human embryonic stem cells and long-term maintenance of beating areas.

    Science.gov (United States)

    Hamidi, Sofiane; Letourneur, Didier; Aid-Launais, Rachida; Di Stefano, Antonio; Vainchenker, William; Norol, Françoise; Le Visage, Catherine

    2014-04-01

    Somatic stem cells require specific niches and three-dimensional scaffolds provide ways to mimic this microenvironment. Here, we studied a scaffold based on Fucoidan, a sulfated polysaccharide known to influence morphogen gradients during embryonic development, to support human embryonic stem cells (hESCs) differentiation toward the cardiac lineage. A macroporous (pore 200 μm) Fucoidan scaffold was selected to support hESCs attachment and proliferation. Using a protocol based on the cardiogenic morphogen bone morphogenic protein 2 (BMP2) and transforming growth factor (TGFβ) followed by tumor necrosis factor (TNFα), an effector of cardiopoietic priming, we examined the cardiac differentiation in the scaffold compared to culture dishes and embryoid bodies (EBs). At day 8, Fucoidan scaffolds supported a significantly higher expression of the 3 genes encoding for transcription factors marking the early step of embryonic cardiac differentiation NKX2.5 (prelease TGFβ and TNFα was confirmed by Luminex technology. We also found that Fucoidan scaffolds supported the late stage of embryonic cardiac differentiation marked by a significantly higher atrial natriuretic factor (ANF) expression (pstress in the soft hydrogel impaired sarcomere formation, as confirmed by molecular analysis of the cardiac muscle myosin MYH6 and immunohistological staining of sarcomeric α-actinin. Nevertheless, Fucoidan scaffolds contributed to the development of thin filaments connecting beating areas through promotion of smooth muscle cells, thus enabling maintenance of beating areas for up to 6 months. In conclusion, Fucoidan scaffolds appear as a very promising biomaterial to control cardiac differentiation from hESCs that could be further combined with mechanical stress to promote sarcomere formation at terminal stages of differentiation.

  8. Simple suspension culture system of human iPS cells maintaining their pluripotency for cardiac cell sheet engineering.

    Science.gov (United States)

    Haraguchi, Yuji; Matsuura, Katsuhisa; Shimizu, Tatsuya; Yamato, Masayuki; Okano, Teruo

    2015-12-01

    In this study, a simple three-dimensional (3D) suspension culture method for the expansion and cardiac differentiation of human induced pluripotent stem cells (hiPSCs) is reported. The culture methods were easily adapted from two-dimensional (2D) to 3D culture without any additional manipulations. When hiPSCs were directly applied to 3D culture from 2D in a single-cell suspension, only a few aggregated cells were observed. However, after 3 days, culture of the small hiPSC aggregates in a spinner flask at the optimal agitation rate created aggregates which were capable of cell passages from the single-cell suspension. Cell numbers increased to approximately 10-fold after 12 days of culture. The undifferentiated state of expanded hiPSCs was confirmed by flow cytometry, immunocytochemistry and quantitative RT-PCR, and the hiPSCs differentiated into three germ layers. When the hiPSCs were subsequently cultured in a flask using cardiac differentiation medium, expression of cardiac cell-specific genes and beating cardiomyocytes were observed. Furthermore, the culture of hiPSCs on Matrigel-coated dishes with serum-free medium containing activin A, BMP4 and FGF-2 enabled it to generate robust spontaneous beating cardiomyocytes and these cells expressed several cardiac cell-related genes, including HCN4, MLC-2a and MLC-2v. This suggests that the expanded hiPSCs might maintain the potential to differentiate into several types of cardiomyocytes, including pacemakers. Moreover, when cardiac cell sheets were fabricated using differentiated cardiomyocytes, they beat spontaneously and synchronously, indicating electrically communicative tissue. This simple culture system might enable the generation of sufficient amounts of beating cardiomyocytes for use in cardiac regenerative medicine and tissue engineering. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines.

    Science.gov (United States)

    van Nimwegen, Frederika A; Ntentas, Georgios; Darby, Sarah C; Schaapveld, Michael; Hauptmann, Michael; Lugtenburg, Pieternella J; Janus, Cecile P M; Daniels, Laurien; van Leeuwen, Flora E; Cutter, David J; Aleman, Berthe M P

    2017-04-20

    Hodgkin lymphoma (HL) survivors treated with radiotherapy and/or chemotherapy are known to have increased risks of heart failure (HF), but a radiation dose-response relationship has not previously been derived. A case-control study, nested in a cohort of 2617 five-year survivors of HL diagnosed before age 51 years during 1965 to 1995, was conducted. Cases (n = 91) had moderate or severe HF as their first cardiovascular diagnosis. Controls (n = 278) were matched to cases on age, sex, and HL diagnosis date. Treatment and follow-up information were abstracted from medical records. Mean heart doses and mean left ventricular doses (MLVD) were estimated by reconstruction of individual treatments on representative computed tomography datasets. Average MLVD was 16.7 Gy for cases and 13.8 Gy for controls ( P difference = .003). HF rate increased with MLVD: relative to 0 Gy, HF rates following MVLD of 1-15, 16-20, 21-25, and ≥26 Gy were 1.27, 1.65, 3.84, and 4.39, respectively ( P trend < .001). Anthracycline-containing chemotherapy increased HF rate by a factor of 2.83 (95% CI: 1.43-5.59), and there was no significant interaction with MLVD ( P interaction = .09). Twenty-five-year cumulative risks of HF following MLVDs of 0-15 Gy, 16-20 Gy, and ≥21 Gy were 4.4%, 6.2%, and 13.3%, respectively, in patients treated without anthracycline-containing chemotherapy, and 11.2%, 15.9%, and 32.9%, respectively, in patients treated with anthracyclines. We have derived quantitative estimates of HF risk in patients treated for HL following radiotherapy with or without anthracycline-containing chemotherapy. Our results enable estimation of HF risk for patients before treatment, during radiotherapy planning, and during follow-up. © 2017 by The American Society of Hematology.

  10. Cardiac support device (ASD) delivers bone marrow stem cells repetitively to epicardium has promising curative effects in advanced heart failure.

    Science.gov (United States)

    Yue, Shizhong; Naveed, Muhammad; Gang, Wang; Chen, Dingding; Wang, Zhijie; Yu, Feng; Zhou, Xiaohui

    2018-05-12

    Ventricular restraint therapy is a non-transplant surgical option for the management of advanced heart failure (HF). To augment the therapeutic applications, it is hypothesized that ASD shows remarkable capabilities not only in delivering stem cells but also in dilated ventricles. Male SD rats were divided into four groups (n = 6): normal, HF, HF + ASD, and HF + ASD-BMSCs respectively. HF was developed by left anterior descending (LAD) coronary artery ligation in all groups except normal group. Post-infarcted electrocardiography (ECG) and brain natriuretic peptide (BNP) showed abnormal heart function in all model groups and HF + ASD-BMSCs group showed significant improvement as compared to other HF, HF + ASD groups on day 30. Masson's trichrome staining was used to study the histology, and a large blue fibrotic area has been observed in HF and HF + ASD groups and quantification of fibrosis was assessed. ASD-treated rats showed normal heart rhythm, demonstrated by smooth -ST and asymmetrical T-wave. The mechanical function of the heart such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate was brought to normal when treated with ASD-BMSCs. This effect was more prominent than that of ASD therapy alone. In comparison to HF group, the SD rats in HF + ASD-BMBCs group showed a significant decline in BNP levels. So ASD can deliver BMSCs to the cardiomyocytes successfully and broaden the therapeutic efficacy, in comparison to the restraint device alone. An effective methodology to manage the end-stage HF has been proved.

  11. Raf-mediated cardiac hypertrophy in adult Drosophila

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2013-07-01

    In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERKD334N, which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for Raf

  12. Development of a scalable suspension culture for cardiac differentiation from human pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Vincent C. Chen

    2015-09-01

    Full Text Available To meet the need of a large quantity of hPSC-derived cardiomyocytes (CM for pre-clinical and clinical studies, a robust and scalable differentiation system for CM production is essential. With a human pluripotent stem cells (hPSC aggregate suspension culture system we established previously, we developed a matrix-free, scalable, and GMP-compliant process for directing hPSC differentiation to CM in suspension culture by modulating Wnt pathways with small molecules. By optimizing critical process parameters including: cell aggregate size, small molecule concentrations, induction timing, and agitation rate, we were able to consistently differentiate hPSCs to >90% CM purity with an average yield of 1.5 to 2 × 109 CM/L at scales up to 1 L spinner flasks. CM generated from the suspension culture displayed typical genetic, morphological, and electrophysiological cardiac cell characteristics. This suspension culture system allows seamless transition from hPSC expansion to CM differentiation in a continuous suspension culture. It not only provides a cost and labor effective scalable process for large scale CM production, but also provides a bioreactor prototype for automation of cell manufacturing, which will accelerate the advance of hPSC research towards therapeutic applications.

  13. Effect of global cardiac ischemia on human ventricular fibrillation: insights from a multi-scale mechanistic model of the human heart.

    Directory of Open Access Journals (Sweden)

    Ivan V Kazbanov

    2014-11-01

    Full Text Available Acute regional ischemia in the heart can lead to cardiac arrhythmias such as ventricular fibrillation (VF, which in turn compromise cardiac output and result in secondary global cardiac ischemia. The secondary ischemia may influence the underlying arrhythmia mechanism. A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global ischemia the dominant frequency of activation decreased, while after reperfusion it increased rapidly. At the same time the complexity of epicardial excitation, measured as the number of epicardical phase singularity points, remained approximately constant during ischemia. Here we perform numerical studies based on these clinical data and propose explanations for the observed dynamics of the period and complexity of activation patterns. In particular, we study the effects on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an anatomically accurate model of human heart ventricles. We demonstrate that the fall of dominant frequency in VF during secondary ischemia can be explained by an increase in extracellular potassium, while the increase during reperfusion is consistent with washout of potassium and continued activation of the ATP-dependent potassium channels. We also suggest that memory effects are responsible for the observed complexity dynamics. In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements.

  14. Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy.

    Science.gov (United States)

    Matsumoto, Tadashi; Miyakoshi, Kei; Saisho, Yoshifumi; Ishii, Tomohiro; Ikenoue, Satoru; Kasuga, Yoshifumi; Kadohira, Ikuko; Sato, Seiji; Momotani, Naoko; Minegishi, Kazuhiro; Yoshimura, Yasunori

    2013-01-01

    High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

  15. Quantification of a cardiac biomarker in human serum using extraordinary optical transmission (EOT.

    Directory of Open Access Journals (Sweden)

    Tao Ding

    Full Text Available Nanoimprinting lithography (NIL is a manufacturing process that can produce macroscale surface areas with nanoscale features. In this paper, this technique is used to solve three fundamental issues for the application of localized surface plasmonic resonance (LSPR in practical clinical measurements: assay sensitivity, chip-to-chip variance, and the ability to perform assays in human serum. Using NIL, arrays of 140 nm square features were fabricated on a sensing area of 1.5 mm x 1.5 mm with low cost. The high reproducibility of NIL allowed for the use of a one-chip, one-measurement approach with 12 individually manufactured surfaces with minimal chip-to-chip variations. To better approximate a real world setting, all chips were modified with a biocompatible, multi-component monolayer and inter-chip variability was assessed by measuring a bioanalyte standard (2.5-75 ng/ml in the presence of a complex biofluid, human serum. In this setting, nanoimprinted LSPR chips were able to provide sufficient characteristics for a 'low-tech' approach to laboratory-based bioanalyte measurement, including: 1 sufficient size to interface with a common laboratory light source and detector without the need for a microscope, 2 high sensitivity in serum with a cardiac troponin limit of detection of 0.55 ng/ml, and 3 very low variability in chip manufacturing to produce a figure of merit (FOM of 10.5. These findings drive LSPR closer to technical comparability with ELISA-based assays while preserving the unique particularities of a LSPR based sensor, suitability for multiplexing and miniaturization, and point-of-care detections.

  16. Chronic heart failure

    OpenAIRE

    Hopper, Ingrid; Easton, Kellie

    2017-01-01

    1. The common symptoms and signs of chronic heart failure are dyspnoea, ankle swelling, raised jugular venous pressure and basal crepitations. Other conditions may be confused with chronic heart failure, including dependent oedema or oedema due to renal or hepatic disease. Shortness of breath may be due to respiratory disease or severe anaemia. Heart failure secondary to lung disease (cor pulmonale) should be distinguished from congestive cardiac failure. Heart failure may also present with l...

  17. Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3β signaling

    International Nuclear Information System (INIS)

    Tateishi, Kento; Ashihara, Eishi; Honsho, Shoken; Takehara, Naofumi; Nomura, Tetsuya; Takahashi, Tomosaburo; Ueyama, Tomomi; Yamagishi, Masaaki; Yaku, Hitoshi; Matsubara, Hiroaki; Oh, Hidemasa

    2007-01-01

    Recent evidence suggested that human cardiac stem cells (hCSCs) may have the clinical application for cardiac repair; however, their characteristics and the regulatory mechanisms of their growth have not been fully investigated. Here, we show the novel property of hCSCs with respect to their origin and tissue distribution in human heart, and demonstrate the signaling pathway that regulates their growth and survival. Telomerase-active hCSCs were predominantly present in the right atrium and outflow tract of the heart (infant > adult) and had a mesenchymal cell-like phenotype. These hCSCs expressed the embryonic stem cell markers and differentiated into cardiomyocytes to support cardiac function when transplanted them into ischemic myocardium. Inhibition of Akt pathway impaired the hCSC proliferation and induced apoptosis, whereas inhibition of glycogen synthase kinase-3 (GSK-3) enhanced their growth and survival. We conclude that hCSCs exhibit mesenchymal features and that Akt/GSK-3β may be crucial modulators for hCSC maintenance in human heart

  18. [Cardiac cachexia].

    Science.gov (United States)

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

    2006-05-01

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

  19. Neural mechanisms underlying catastrophic failure in human-machine interaction during aerial navigation

    Science.gov (United States)

    Saproo, Sameer; Shih, Victor; Jangraw, David C.; Sajda, Paul

    2016-12-01

    Objective. We investigated the neural correlates of workload buildup in a fine visuomotor task called the boundary avoidance task (BAT). The BAT has been known to induce naturally occurring failures of human-machine coupling in high performance aircraft that can potentially lead to a crash—these failures are termed pilot induced oscillations (PIOs). Approach. We recorded EEG and pupillometry data from human subjects engaged in a flight BAT simulated within a virtual 3D environment. Main results. We find that workload buildup in a BAT can be successfully decoded from oscillatory features in the electroencephalogram (EEG). Information in delta, theta, alpha, beta, and gamma spectral bands of the EEG all contribute to successful decoding, however gamma band activity with a lateralized somatosensory topography has the highest contribution, while theta band activity with a fronto-central topography has the most robust contribution in terms of real-world usability. We show that the output of the spectral decoder can be used to predict PIO susceptibility. We also find that workload buildup in the task induces pupil dilation, the magnitude of which is significantly correlated with the magnitude of the decoded EEG signals. These results suggest that PIOs may result from the dysregulation of cortical networks such as the locus coeruleus (LC)—anterior cingulate cortex (ACC) circuit. Significance. Our findings may generalize to similar control failures in other cases of tight man-machine coupling where gains and latencies in the control system must be inferred and compensated for by the human operators. A closed-loop intervention using neurophysiological decoding of workload buildup that targets the LC-ACC circuit may positively impact operator performance in such situations.

  20. Rationale and design of a multicenter echocardiographic study to assess the relationship between cardiac structure and function and heart failure risk in a biracial cohort of community-dwelling elderly persons: the Atherosclerosis Risk in Communities study.

    Science.gov (United States)

    Shah, Amil M; Cheng, Susan; Skali, Hicham; Wu, Justina; Mangion, Judy R; Kitzman, Dalane; Matsushita, Kunihiro; Konety, Suma; Butler, Kenneth R; Fox, Ervin R; Cook, Nakela; Ni, Hanyu; Coresh, Josef; Mosley, Thomas H; Heiss, Gerardo; Folsom, Aaron R; Solomon, Scott D

    2014-01-01

    Heart failure is an important public health concern, particularly among persons>65 years of age. Women and blacks are critically understudied populations that carry a sizeable portion of the heart failure burden. Limited normative and prognostic data exist on measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community. The Atherosclerosis Risk in Communities (ARIC) study is a large, predominantly biracial, National Heart, Lung, and Blood Institute-sponsored epidemiological cohort study. Between 2011 and 2013, ≈6000 surviving participants, now in their seventh to ninth decade of life, are expected to return for a fifth study visit during which comprehensive 2-dimensional, Doppler, tissue Doppler, and speckle-tracking echocardiography will be performed uniformly in all cohort clinic visit participants. The following objectives will be addressed: (1) to characterize cardiac structural and functional abnormalities among the elderly and to determine how they differ by sex and race/ethnicity, (2) to determine the relationship between ventricular and vascular abnormalities, and (3) to prospectively examine the extent to which these noninvasive measures associate with incident heart failure. We describe the design, imaging acquisition and analysis methods, and quality assurance metrics for echocardiography in visit 5 of the ARIC cohort. A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen our understanding of the pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies.

  1. Tire aging: a human factors analysis of failure to warn and inform.

    Science.gov (United States)

    Wogalter, Michael S; Laughery, Kenneth R

    2012-01-01

    A scenario of an automotive accident caused by tire failure is given followed by a human factors analysis of the information available to consumers on tire aging. Consumers have not been told that the age of the tire is a safety concern. It is not easy to decode the date of manufacture on tires. More publicity and prominent warnings are needed to communicate the dangers of older tires. Also, better ways to present the date of manufacture so that consumers can more easily and accurately assess tire age are needed.

  2. Human Factors Predicting Failure and Success in Hospital Information System Implementations in Sub-Saharan Africa.

    Science.gov (United States)

    Verbeke, Frank; Karara, Gustave; Nyssen, Marc

    2015-01-01

    From 2007 through 2014, the authors participated in the implementation of open source hospital information systems (HIS) in 19 hospitals in Rwanda, Burundi, DR Congo, Congo-Brazzaville, Gab