Mathematical Models of Cardiac Pacemaking Function

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Pan eLi

2013-10-01

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

Autoimmune Response Confers Decreased Cardiac Function in ...

African Journals Online (AJOL)

inflammatory response; rather, autoimmune response would keep affecting decreased heart function in. RHD patients who ... untreated children. Nearly 30 - 45 % of the affected children could ..... Technology Department of Anhui Province (PR.

Functional cardiac imaging: positron emission tomography

International Nuclear Information System (INIS)

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

1984-01-01

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

Cardiac function studies

International Nuclear Information System (INIS)

Horn, H.J.

1986-01-01

A total of 27 patients were subjected tointramyocardial sequential scintiscanning (first pass) using 99m-Tc human serum albumin. A refined method is described that is suitable to analyse clinically relevant parameters like blood volume, cardiac output, ejection fraction, stroke volume, enddiastolic and endsystolic volumes as well as pulmonal transition time and uses a complete camaracomputer system adapted to the requirements of a routine procedure. Unless there is special hardware available, the method does not yet appear mature enough to be put into general practice. Its importance recently appeared in a new light due to the advent of particularly shortlived isotopes. For the time being, however, ECG-triggered equilibrium studies are to be preferred for cardiac function tests. (TRV) [de

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

Meta-Analysis of the Relation of Baseline Right Ventricular Function to Response to Cardiac Resynchronization Therapy.

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Sharma, Abhishek; Bax, Jerome J; Vallakati, Ajay; Goel, Sunny; Lavie, Carl J; Kassotis, John; Mukherjee, Debabrata; Einstein, Andrew; Warrier, Nikhil; Lazar, Jason M

2016-04-15

Right ventricular (RV) dysfunction has been associated with adverse clinical outcomes in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves left ventricular (LV) size and function in patients with markedly abnormal electrocardiogram QRS duration. However, relation of baseline RV function with response to CRT has not been well described. In this study, we aim to investigate the relation of baseline RV function with response to CRT as assessed by change in LV ejection fraction (EF). A systematic search of studies published from 1966 to May 31, 2015 was conducted using PubMed, CINAHL, Cochrane CENTRAL, and the Web of Science databases. Studies were included if they have reported (1) parameters of baseline RV function (tricuspid annular plane systolic excursion [TAPSE] or RVEF or RV basal strain or RV fractional area change [FAC]) and (2) LVEF before and after CRT. Random-effects metaregression was used to evaluate the effect of baseline RV function parameters and change in LVEF. Sixteen studies (n = 1,764) were selected for final analysis. Random-effects metaregression analysis showed no significant association between the magnitude of the difference in EF before and after CRT with baseline TAPSE (β = 0.005, p = 0.989); baseline RVEF (β = 0.270, p = 0.493); baseline RVFAC (β = -0.367, p = 0.06); baseline basal strain (β = -0.342, p = 0.462) after a mean follow-up period of 10.5 months. In conclusion, baseline RV function as assessed by TAPSE, FAC, basal strain, or RVEF does not determine response to CRT as assessed by change in LVEF. Copyright © 2016 Elsevier Inc. All rights reserved.

Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates.

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Mitchell, Timothy; MacDonald, James W; Srinouanpranchanh, Sengkeo; Bammler, Theodor K; Merillat, Sean; Boldenow, Erica; Coleman, Michelle; Agnew, Kathy; Baldessari, Audrey; Stencel-Baerenwald, Jennifer E; Tisoncik-Go, Jennifer; Green, Richard R; Gale, Michael J; Rajagopal, Lakshmi; Adams Waldorf, Kristina M

2018-04-01

Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development. We obtained fetal cardiac tissue after necropsy from a well-described pregnant nonhuman primate model (pigtail macaque, Macaca nemestrina) of intrauterine infection (n=5) and controls (n=5). Cases with the fetal inflammatory response syndrome (fetal plasma interleukin-6 >11 pg/mL) were induced by either choriodecidual inoculation of a hypervirulent group B streptococcus strain (n=4) or intraamniotic inoculation of Escherichia coli (n=1). RNA and protein were extracted from fetal hearts and profiled by microarray and Luminex (Millipore, Billerica, MA) for cytokine analysis, respectively. Results were validated by quantitative reverse transcriptase polymerase chain reaction. Statistical and bioinformatics analyses included single gene analysis, gene set analysis, Ingenuity Pathway Analysis (Qiagen, Valencia, CA), and Wilcoxon rank sum. Severe fetal inflammation developed in the context of intraamniotic infection and a disseminated bacterial infection in the fetus. Interleukin-6 and -8 in fetal cardiac tissues were elevated significantly in fetal inflammatory response syndrome cases vs controls (P1.5-fold change, P<.05) in the fetal heart (analysis of variance). Altered expression of select genes was validated by quantitative reverse transcriptase polymerase chain reaction that included several with known functions in cardiac injury, morphogenesis

TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

Energy Technology Data Exchange (ETDEWEB)

Kurhanewicz, Nicole [Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599 (United States); McIntosh-Kastrinsky, Rachel [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599 (United States); Tong, Haiyan; Ledbetter, Allen; Walsh, Leon; Farraj, Aimen [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hazari, Mehdi, E-mail: hazari.mehdi@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

2017-06-01

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac

TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein

International Nuclear Information System (INIS)

Kurhanewicz, Nicole; McIntosh-Kastrinsky, Rachel; Tong, Haiyan; Ledbetter, Allen; Walsh, Leon; Farraj, Aimen; Hazari, Mehdi

2017-01-01

Short-term exposure to ambient air pollution is linked with adverse cardiovascular effects. While previous research focused primarily on particulate matter-induced responses, gaseous air pollutants also contribute to cause short-term cardiovascular effects. Mechanisms underlying such effects have not been adequately described, however the immediate nature of the response suggests involvement of irritant neural activation and downstream autonomic dysfunction. Thus, this study examines the role of TRPA1, an irritant sensory receptor found in the airways, in the cardiac response of mice to acrolein and ozone. Conscious unrestrained wild-type C57BL/6 (WT) and TRPA1 knockout (KO) mice implanted with radiotelemeters were exposed once to 3 ppm acrolein, 0.3 ppm ozone, or filtered air. Heart rate (HR) and electrocardiogram (ECG) were recorded continuously before, during and after exposure. Analysis of ECG morphology, incidence of arrhythmia and heart rate variability (HRV) were performed. Cardiac mechanical function was assessed using a Langendorff perfusion preparation 24 h post-exposure. Acrolein exposure increased HRV independent of HR, as well as incidence of arrhythmia. Acrolein also increased left ventricular developed pressure in WT mice at 24 h post-exposure. Ozone did not produce any changes in cardiac function. Neither gas produced ECG effects, changes in HRV, arrhythmogenesis, or mechanical function in KO mice. These data demonstrate that a single exposure to acrolein causes cardiac dysfunction through TRPA1 activation and autonomic imbalance characterized by a shift toward parasympathetic modulation. Furthermore, it is clear from the lack of ozone effects that although gaseous irritants are capable of eliciting immediate cardiac changes, gas concentration and properties play important roles. - Highlights: • Acute acrolein exposure causes autonomic imbalance and altered CV function in mice. • TRPA1 mediates acrolein-induced autonomic nervous system cardiac

Sodium Channel (Dys)Function and Cardiac Arrhythmias

NARCIS (Netherlands)

Remme, Carol Ann; Bezzina, Connie R.

2010-01-01

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

Sarcospan Regulates Cardiac Isoproterenol Response and Prevents Duchenne Muscular Dystrophy-Associated Cardiomyopathy.

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Parvatiyar, Michelle S; Marshall, Jamie L; Nguyen, Reginald T; Jordan, Maria C; Richardson, Vanitra A; Roos, Kenneth P; Crosbie-Watson, Rachelle H

2015-12-23

Duchenne muscular dystrophy is a fatal cardiac and skeletal muscle disease resulting from mutations in the dystrophin gene. We have previously demonstrated that a dystrophin-associated protein, sarcospan (SSPN), ameliorated Duchenne muscular dystrophy skeletal muscle degeneration by activating compensatory pathways that regulate muscle cell adhesion (laminin-binding) to the extracellular matrix. Conversely, loss of SSPN destabilized skeletal muscle adhesion, hampered muscle regeneration, and reduced force properties. Given the importance of SSPN to skeletal muscle, we investigated the consequences of SSPN ablation in cardiac muscle and determined whether overexpression of SSPN into mdx mice ameliorates cardiac disease symptoms associated with Duchenne muscular dystrophy cardiomyopathy. SSPN-null mice exhibited cardiac enlargement, exacerbated cardiomyocyte hypertrophy, and increased fibrosis in response to β-adrenergic challenge (isoproterenol; 0.8 mg/day per 2 weeks). Biochemical analysis of SSPN-null cardiac muscle revealed reduced sarcolemma localization of many proteins with a known role in cardiomyopathy pathogenesis: dystrophin, the sarcoglycans (α-, δ-, and γ-subunits), and β1D integrin. Transgenic overexpression of SSPN in Duchenne muscular dystrophy mice (mdx(TG)) improved cardiomyofiber cell adhesion, sarcolemma integrity, cardiac functional parameters, as well as increased expression of compensatory transmembrane proteins that mediate attachment to the extracellular matrix. SSPN regulates sarcolemmal expression of laminin-binding complexes that are critical to cardiac muscle function and protects against transient and chronic injury, including inherited cardiomyopathy. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

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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

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

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Redetzke, Rebecca A.; Gerdes, A. Martin

2012-01-01

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

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

Directory of Open Access Journals (Sweden)

Nathan Y Weltman

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

Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction

DEFF Research Database (Denmark)

González-Santamaría, José; Villalba, María; Busnadiego, Oscar

2016-01-01

arrhythmias, and sudden cardiac death. Cardiac fibrosis is characterized by extensive deposition of collagen and also by increased stiffness as a consequence of enhanced collagen cross-linking. Members of the lysyl oxidase (LOX) family of enzymes are responsible for the formation of collagen cross......-links. This study investigates the contribution of LOX family members to the heart response to MI. METHODS AND RESULTS: Experimental MI was induced in C57BL/6 mice by permanent ligation of the left anterior descending coronary artery. The expression of LOX isoforms (LOX and LOXL1-4) was strongly increased upon MI...... resulted in reduced ventricular dilatation and improved cardiac function. CONCLUSION: LOX family members contribute significantly to the detrimental effects of cardiac remodelling, highlighting LOX inhibition as a potential therapeutic strategy for post-infarction recovery....

Asymptomatic Changes in Cardiac Function Can Occur in DCIS Patients Following Treatment with HER-2/neu Pulsed Dendritic Cell Vaccines

Science.gov (United States)

Bahl, Susan; Roses, Robert; Sharma, Anupama; Koldovsky, Ursula; Xu, Shuwen; Weinstein, Susan; Nisenbaum, Harvey; Fox, Kevin; Pasha, Theresa; Zhang, Paul; Araujo, Louis; Carver, Joseph; Czerniecki, Brian J

2009-01-01

Background Targeting HER-2/neu with Trastuzumab has been associated with development of cardiac toxicity. Methods Twenty-seven patients with ductal carcinoma in situ (DCIS) of the breast completed an IRB approved clinical trial of a HER-2/neu targeted dendritic cell based vaccine. Four weekly vaccinations were administered prior to surgical resection. All subjects underwent pre- and post-vaccine cardiac monitoring by MUGA/ECHO scanning allowing for a comparison of cardiac function. Results In 3 of 27 vaccinated patients (11%) transient asymptomatic decrements in ejection fraction of greater than 15% were noted after vaccination. Notably, evidence of circulating anti-HER-2/neu antibody was found prior to vaccination in all three patients, but cardiac toxicity was not noted until induction of cellular mediated immune responses. Conclusions This is the first description of HER-2/neu targeted vaccination associated with an incidence of cardiac changes, and the induction of cellular immune responses combined with antibody may contribute to changes in cardiac function. PMID:19800453

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

Directory of Open Access Journals (Sweden)

Gianluca Pontone

2015-01-01

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

Myocardin-related transcription factors are required for cardiac development and function

OpenAIRE

Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

2015-01-01

Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the d...

The effect of childhood obesity on cardiac functions.

Science.gov (United States)

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

2014-03-01

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

The changes in beta-adrenoceptor-mediated cardiac function in experimental hypothyroidism: the possible contribution of cardiac beta3-adrenoceptors.

Science.gov (United States)

Arioglu, E; Guner, S; Ozakca, I; Altan, V M; Ozcelikay, A T

2010-02-01

Thyroid hormone deficiency has been reported to decrease expression and function of both beta(1)- and beta(2)-adrenoceptor in different tissues including heart. The purpose of this study was to examine the possible contribution of beta(3)-adrenoceptors to cardiac dysfunction in hypothyroidism. In addition, effect of this pathology on beta(1)- and beta(2)-adrenoceptor was investigated. Hypothyroidism was induced by adding methimazole (300 mg/l) to drinking water of rats for 8 weeks. Cardiac hemodynamic parameters were measured in anesthetised rats in vivo. Responses to beta-adrenoceptor agonists were examined in rat papillary muscle in vitro. We also studied the effect of hypotyroidism on mRNA expression of beta-adrenoceptors, Gialpha, GRK, and eNOS in rat heart. All of the hemodynamic parameters (systolic, diastolic and mean arterial pressure, left ventricular pressure, heart rate, +dp/dt, and -dp/dt) were significantly reduced by the methimazole treatment. The negative inotropic effect elicited by BRL 37344 (a beta(3)-adrenoceptor preferential agonist) and positive inotropic effects produced by isoprenaline and noradrenaline, respectively, were significantly decreased in papillary muscle of hypothyroid rats as compared to those of controls. On the other hand, hypothyroidism resulted in increased cardiac beta(2)- and beta(3)-adrenoceptor, Gialpha(2), Gialpha(3), GRK3, and eNOS mRNA expressions. However, beta(1)-adrenoceptor and GRK2 mRNA expressions were not changed significantly in this pathology. These results show that mRNA expression of beta(3)-adrenoceptors as well as the signalling pathway components mediated through beta(3)-adrenoceptors are significantly increased in hypothyroid rat heart. Since we could not correlate these alternates with the decreased negative inotropic response mediated by this receptor subtype, it is not clear whether these changes are important for hypothyroid induced reduction in cardiac function.

Cardiac structure and function in Cushing's syndrome: a cardiac magnetic resonance imaging study.

Science.gov (United States)

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

2014-11-01

Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2-12 mo) after the treatment of hypercortisolism. Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism.

Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment.

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Lyra-Leite, Davi M; Andres, Allen M; Petersen, Andrew P; Ariyasinghe, Nethika R; Cho, Nathan; Lee, Jezell A; Gottlieb, Roberta A; McCain, Megan L

2017-10-01

Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes. To test this, we developed a new procedure to transfer tunable polydimethylsiloxane disks microcontact-printed with fibronectin into cell culture microplates. We cultured Sprague-Dawley neonatal rat ventricular myocytes within the wells, which consistently formed tissues following the printed fibronectin, and measured oxygen consumption rate using a Seahorse extracellular flux analyzer. Our data indicate that parameters associated with baseline metabolism are predominantly regulated by ECM elasticity, whereas the ability of tissues to adapt to metabolic stress is regulated by both ECM elasticity and tissue alignment. Furthermore, bioenergetic health index, which reflects both the positive and negative aspects of oxygen consumption, was highest in aligned tissues on the most rigid substrate, suggesting that overall mitochondrial function is regulated by both ECM elasticity and tissue alignment. Our results demonstrate that mitochondrial function is regulated by both ECM elasticity and myofibril architecture in cardiac myocytes. This provides novel insight into how extracellular cues impact mitochondrial function in the context of cardiac development and disease. NEW & NOTEWORTHY A new methodology has been developed to measure O 2 consumption rates in engineered cardiac tissues with independent control over tissue alignment and matrix elasticity. This led to the findings that matrix

Influence of the low thyroid state in diabetes mellitus on cardiac function and inotropic responsiveness to alpha 1-adrenoceptor stimulation: comparison with the role of hypothyroidism alone.

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Beenen, O H; Pfaffendorf, M; van Zwieten, P A

1996-10-01

The hypothyroid state accompanying diabetes mellitus has been suggested to be partly responsible for the diabetes-induced metabolic, hemodynamic, and pharmacological cardiovascular changes. We assessed the effectivity of streptozotocin (STZ) to induce diabetes mellitus and a hypothyroid state. Furthermore, we investigated the influence of diabetes and hypothyrodism on cardiac function and the inotropic responsiveness to the alpha 1-adrenoceptor agonist cirazoline in isolated perfused hearts. Fasted or nonfasted Wistar rats were made diabetic with STZ 20, 40 or 60 mg/kg intravenously (i.v.). Another group was made hypothyroid by addition of 6-n-propyl-2-thiouracil (PTU) to their drinking water. Rats receiving PTU became hypothyroid, whereas rats receiving STZ became simultaneously diabetic and hypothyroid. Basal functional parameters obtained in isolated perfused hearts were not influenced by diabetes, whereas maximal contractility was reduced in hearts obtained from hypothyroid animals. Cardiac inotropic responses to cirazoline were increased in diabetic rats, whereas responses in hypothyroid rats were not different from those in hearts obtained from control animals. Although diabetes mellitus and hypothyroidism are associated with various similar metabolic and haemodynamic parameters, the increased inotropic response to alpha 1-adrenoceptor stimulation as observed in isolated perfused hearts of diabetic rats cannot be explained by the decrease in serum thyroxine levels.

Simultaneous determination of dynamic cardiac metabolism and function using PET/MRI.

Science.gov (United States)

Barton, Gregory P; Vildberg, Lauren; Goss, Kara; Aggarwal, Niti; Eldridge, Marlowe; McMillan, Alan B

2018-05-01

Cardiac metabolic changes in heart disease precede overt contractile dysfunction. However, metabolism and function are not typically assessed together in clinical practice. The purpose of this study was to develop a cardiac positron emission tomography/magnetic resonance (PET/MR) stress test to assess the dynamic relationship between contractile function and metabolism in a preclinical model. Following an overnight fast, healthy pigs (45-50 kg) were anesthetized and mechanically ventilated. 18 F-fluorodeoxyglucose ( 18 F-FDG) solution was administered intravenously at a constant rate of 0.01 mL/s for 60 minutes. A cardiac PET/MR stress test was performed using normoxic gas (F I O 2  = .209) and hypoxic gas (F I O 2  = .12). Simultaneous cardiac imaging was performed on an integrated 3T PET/MR scanner. Hypoxic stress induced a significant increase in heart rate, cardiac output, left ventricular (LV) ejection fraction (EF), and peak torsion. There was a significant decline in arterial SpO 2 , LV end-diastolic and end-systolic volumes in hypoxia. Increased LV systolic function was coupled with an increase in myocardial FDG uptake (Ki) during hypoxic stress. PET/MR with continuous FDG infusion captures dynamic changes in both cardiac metabolism and contractile function. This technique warrants evaluation in human cardiac disease for assessment of subtle functional and metabolic abnormalities.

Use of I-123 MIBG cardiac scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

International Nuclear Information System (INIS)

Maunoury, C.; Acar, P.; Sidi, D.

2006-01-01

I-123 MIBG cardiac scintigraphy is a useful tool to assess cardiac adrenergic neuronal function, which is impaired in children with dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function and on left ventricular function in seventeen patients (11 female, 6 male, mean age 39 ± 57 months, range 1 - 168 months) with DCM. All patients underwent I-123 MIBG cardiac scintigraphy and equilibrium radio-nuclide angiography before and after a 6 month period of carvedilol therapy. A static anterior view of the chest was acquired 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. Cardiac neuronal uptake of I-123 MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. There was no major cardiac events (death or transplantation) during the follow-up period. I-123 MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR 223 ± 49% vs 162 ± 26%, p < 0.0001 and LVEF = 43 ± 17% vs 26 ± 11%, p < 0.0001). Carvedilol can improve cardiac adrenergic neuronal function and left ventricular function in children with DCM. Further studies are needed to assess the relationship between improvement in I-123 MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (authors)

Cardiac telomere length in heart development, function, and disease.

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Booth, S A; Charchar, F J

2017-07-01

Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

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

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Liu, Zhenzhen; Du, Lupei; Li, Minyong

2012-01-01

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

Novel axolotl cardiac function analysis method using magnetic resonance imaging

NARCIS (Netherlands)

Sanches, Pedro Gomes; Op 't Veld, Roel C.; de Graaf, Wolter; Strijkers, Gustav J.; Grüll, Holger

2017-01-01

The salamander axolotl is capable of complete regeneration of amputated heart tissue. However, non-invasive imaging tools for assessing its cardiac function were so far not employed. In this study, cardiac magnetic resonance imaging is introduced as a non-invasive technique to image heart function

Novel axolotl cardiac function analysis method using magnetic resonance imaging

NARCIS (Netherlands)

Sanches, P.G.; Op ‘t Veld, R.C.; de Graaf, W.; Strijkers, G.J.; Grüll, H.

2017-01-01

The salamander axolotl is capable of complete regeneration of amputated heart tissue. However, non-invasive imaging tools for assessing its cardiac function were so far not employed. In this study, cardiac magnetic resonance imaging is introduced as a noninvasive technique to image heart function of

Cardiac molecular-acclimation mechanisms in response to swimming-induced exercise in Atlantic salmon.

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Vicente Castro

Full Text Available Cardiac muscle is a principal target organ for exercise-induced acclimation mechanisms in fish and mammals, given that sustained aerobic exercise training improves cardiac output. Yet, the molecular mechanisms underlying such cardiac acclimation have been scarcely investigated in teleosts. Consequently, we studied mechanisms related to cardiac growth, contractility, vascularization, energy metabolism and myokine production in Atlantic salmon pre-smolts resulting from 10 weeks exercise-training at three different swimming intensities: 0.32 (control, 0.65 (medium intensity and 1.31 (high intensity body lengths s(-1. Cardiac responses were characterized using growth, immunofluorescence and qPCR analysis of a large number of target genes encoding proteins with significant and well-characterized function. The overall stimulatory effect of exercise on cardiac muscle was dependent on training intensity, with changes elicited by high intensity training being of greater magnitude than either medium intensity or control. Higher protein levels of PCNA were indicative of cardiac growth being driven by cardiomyocyte hyperplasia, while elevated cardiac mRNA levels of MEF2C, GATA4 and ACTA1 suggested cardiomyocyte hypertrophy. In addition, up-regulation of EC coupling-related genes suggested that exercised hearts may have improved contractile function, while higher mRNA levels of EPO and VEGF were suggestive of a more efficient oxygen supply network. Furthermore, higher mRNA levels of PPARα, PGC1α and CPT1 all suggested a higher capacity for lipid oxidation, which along with a significant enlargement of mitochondrial size in cardiac myocytes of the compact layer of fish exercised at high intensity, suggested an enhanced energetic support system. Training also elevated transcription of a set of myokines and other gene products related to the inflammatory process, such as TNFα, NFκB, COX2, IL1RA and TNF decoy receptor. This study provides the first

Cardiac dimensions and function in female handball players.

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Malmgren, A; Dencker, M; Stagmo, M; Gudmundsson, P

2015-04-01

Long-term intensive endurance training leads to increased left ventricular mass and increased left ventricular end-diastolic and left atrial end-systolic diameters. Different types of sports tend to give rise to distinct morphological forms of the athlete's heart. However, the sport-specific aspects have not been fully investigated in female athletes. The purpose of the present study was to investigate differences in left and right cardiac dimensions, cardiac volumes, and systolic and diastolic function in elite female handball players compared to sedentary controls. A cross-sectional study of 33 elite female handball players was compared to 33 matched sedentary controls. Mean age was 21.5±2 years. The subjects underwent echocardiography examinations, both 2-dimensional (2DE) and 3-dimensional (3DE). Cardiac dimensions and volumes were quantified using M-mode, 2DE and 3DE. Systolic and diastolic left ventricular functions were also evaluated. All cardiac dimensions and volumes were adjusted for body surface area (BSA). Left atrium and left ventricle volumes were significantly (Phandball players compared with sedentary controls. Even right atrium area as well as right ventricular end-diastolic and end-systolic area were significantly (Phandball players. Significant differences were observed in three out of five systolic parameters. Most diastolic function parameters did not differ between the two groups. The findings from the present study suggest that similar cardiac remodeling takes place in elite female handball players as it does in athletes pursuing endurance or team game sports.

Sex-related differences in the normal cardiac response to upright exercise

International Nuclear Information System (INIS)

Higginbotham, M.B.; Morris, K.G.; Coleman, R.E.; Cobb, F.R.

1984-01-01

In previous studies from this laboratory, it was found that approximately 30% of women with chest pain and normal coronary arteries demonstrated either a decrease in or a failure to increase radionuclide ejection fraction during exercise. To examine the hypothesis that this apparent abnormality in left ventricular function represents a physiologic difference between men and women, a prospective study was made of central and peripheral cardiovascular responses to exercise in 31 age-matched healthy volunteers (16 women and 15 men). A combination of quantitative radionuclide (technetium) angiography and expired-gas analysis was used to measure ejection fraction and relative changes in end-diastolic counts, stroke counts, count output, and arteriovenous oxygen difference during symptom-limited upright bicycle exercise. Normal male and female volunteers demonstrated comparable baseline left ventricular function and similar aerobic capacity, as determined by weight-adjusted peak oxygen consumption. However, their cardiac responses to exercise were significantly different. The ejection fraction increased by 5 points or more in 14 of 15 men, but in only seven of the 16 women. End-diastolic counts increased by 30% in women, but was unchanged in men. Because decreases in ejection fraction were matched by increases in end-diastolic counts, relative increases in stroke counts and count output were the same for men and women. These data demonstrate a basic difference between men and women with respect to the mechanism by which they achieve a normal response of stroke volume to exercise; these differences must be taken into account when measurements of cardiac function during exercise stress are used for diagnostic purposes

Mechanisms Regulating the Cardiac Output Response to Cyanide Infusion, a Model of Hypoxia

Science.gov (United States)

Liang, Chang-seng; Huckabee, William E.

1973-01-01

When tissue metabolic changes like those of hypoxia were induced by intra-aortic infusion of cyanide in dogs, cardiac output began to increase after 3 to 5 min, reached a peak (220% of the control value) at 15 min, and returned to control in 40 min. This pattern of cardiac output rise was not altered by vagotomy with or without atropine pretreatment. However, this cardiac output response could be differentiated into three phases by pretreating the animals with agents that block specific activities of the sympatho-adrenal system. First, ganglionic blockade produced by mecamylamine or sympathetic nerve blockade by bretylium abolished the middle phase of the cardiac output seen in the untreated animal, but early and late phases still could be discerned. Second, beta-adrenergic receptor blockade produced by propranolol shortened the total duration of the cardiac output rise by abolishing the late phase. Third, when given together, propranolol and mecamylamine (or bretylium) prevented most of the cardiac output rise that follows the early phase. When cyanide was given to splenectomized dogs, the duration of the cardiac output response was not shortened, but the response became biphasic, resembling that seen after chemical sympathectomy. A similar biphasic response of the cardiac output also resulted from splenic denervation; sham operation or nephrectomy had no effect on the monophasic pattern of the normal response. Splenic venous blood obtained from cyanide-treated dogs, when infused intraportally, caused an increase in cardiac output in recipient dogs; similar infusion of arterial blood had no effects. These results suggest that the cardiac output response to cyanide infusion consists of three components: an early phase, related neither to the autonomic nervous system nor to circulating catecholamines; a middle phase, caused by a nonadrenergic humoral substance released from the spleen by sympathetic stimulation; and a late phase, dependent upon adrenergic receptors

Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

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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.

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....

The effects of balneotherapy on acute, process-related, and cumulative peripheral cardiac responses and pulmonary functions in patients with musculoskeletal disorders.

Science.gov (United States)

Şaş, Senem; Toprak Çelenay, Şeyda; Özer Kaya, Derya

2016-12-20

This study aimed to evaluate the effects of balneotherapy on acute, process-related, and cumulative peripheral cardiac responses and pulmonary functions in patients with musculoskeletal disorders. Ninety-eight patients with musculoskeletal disorders referred to physiotherapy with balneotherapy were recruited. The patients received balneotherapy for 20 min 5 times per week for 2 weeks. Blood pressure and pulse were measured at the 0th, 5th, 10th, 20th, and 30th minutes during the 1st and 10th sessions. All patients were subjected to pulmonary function testing before balneotherapy and after the 10th session. It was found that systolic blood pressure decreased between the 10th and 20th minutes of the 1st session and between the 10th and 20th minutes and the 20th and 30th minutes of the 10th session (P balneotherapy (P balneotherapy (P Balneotherapy may be effective for improving peripheral cardiopulmonary responses in patients with musculoskeletal disorders.

Pim-1 Kinase Phosphorylates Cardiac Troponin I and Regulates Cardiac Myofilament Function

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Ni Zhu

2018-03-01

Full Text Available Background/Aims: Pim-1 is a serine/threonine kinase that is highly expressed in the heart, and exerts potent cardiac protective effects through enhancing survival, proliferation, and regeneration of cardiomyocytes. Its myocardial specific substrates, however, remain unknown. In the present study, we aim to investigate whether Pim-1 modulates myofilament activity through phosphorylation of cardiac troponin I (cTnI, a key component in regulating myofilament function in the heart. Methods: Coimmunoprecipitation and immunofluorescent assays were employed to investigate the interaction of Pim-1 with cTnI in cardiomyocytes. Biochemical, site directed mutagenesis, and mass spectrometric analyses were utilized to identify the phosphorylation sites of Pim1 in cTnI. Myofilament functional assay using skinned cardiac fiber was used to assess the effect of Pim1-mediated phosphorylation on cardiac myofilament activity. Lastly, the functional significance of Pim1-mediated cTnI in heart disease was determined in diabetic mice. Results: We found that Pim-1 specifically interacts with cTnI in cardiomyocytes and this interaction leads to Pim1-mediated cTnI phosphorylation, predominantly at Ser23/24 and Ser150. Furthermore, our functional assay demonstrated that Pim-1 induces a robust phosphorylation of cTnI within the troponin complex, thus leading to a decreased Ca2+ sensitivity. Insulin-like growth factor 1 (IGF-1, a peptide growth factor that has been shown to stimulate myocardial contractility, markedly induces cTnI phosphorylation at Ser23/24 and Ser150 through increasing Pim-1 expression in cardiomyocytes. In a high-fat diabetic mice model, the expression of Pim1 in the heart is significantly decreased, which is accompanied by a decreased phosphorylation of cTnI at Ser23/24 and Ser150, further implicating the pathological significance of the Pim1/cTnI axis in the development of diabetic cardiomyopathy. Conclusion: Our results demonstrate that Pim-1 is a

Cardiac responsiveness to attention-demanding tasks in socially maladaptive children

NARCIS (Netherlands)

Althaus, M; Aarnoudse, CC; Minderaa, RB; Mulder, Gysbertus; Mulder, Lambertus

Cardiac responsiveness to attention-demanding tasks in socially maladaptive children A psychofysiological study of the cardiac adaptivity to attention-demanding reaction time tasks demonstrated that children with a lesser variant of the pervasive developmental disorder (DSM-IV: PDDNOS) exhibit less

Pregnancy as a cardiac stress model

Science.gov (United States)

Chung, Eunhee; Leinwand, Leslie A.

2014-01-01

Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women without any known cardiovascular disease. Peripartum cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy. To understand how pregnancy can cause heart disease, it is first important to understand cardiac adaptation during normal pregnancy. This review provides an overview of the cardiac consequences of pregnancy, including haemodynamic, functional, structural, and morphological adaptations, as well as molecular phenotypes. In addition, this review describes the signalling pathways responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also compare and contrast cardiac adaptation in response to disease, exercise, and pregnancy. The comparisons of these settings of cardiac hypertrophy provide insight into pregnancy-associated cardiac adaptation. PMID:24448313

The role of the anterodorsal thalami nuclei in the regulation of adrenal medullary function, beta-adrenergic cardiac receptors and anxiety responses in maternally deprived rats under stressful conditions.

Science.gov (United States)

Suárez, M M; Rivarola, M A; Molina, S M; Levin, G M; Enders, J; Paglini, P

2004-09-01

Maternal separation can interfere with growth and development of the brain and represents a significant risk factor for adult psychopathology. In rodents, prolonged separation from the mother affects the behavioral and endocrine responses to stress for the lifetime of the animal. Limbic structures such as the anterodorsal thalamic nuclei (ADTN) play an important role in the control of neuroendocrine and sympathetic-adrenal function. In view of these findings we hypothesized that the function of the ADTN may be affected in an animal model of maternal deprivation. To test this hypothesis female rats were isolated 4.5 h daily, during the first 3 weeks of life and tested as adults. We evaluated plasma epinephrine (E) and norepinephrine (NE), cardiac adrenoreceptors and anxiety responses after maternal deprivation and variable chronic stress (VCS) in ADTN-lesioned rats. Thirty days after ADTN lesion, in non-maternally deprived rats basal plasma NE concentration was greater and cardiac beta-adrenoreceptor density was lower than that in the sham-lesioned group. Maternal deprivation induced a significant increase in basal plasma NE concentration, which was greater in lesioned rats, and cardiac beta-adrenoreceptor density was decreased in lesioned rats. After VCS plasma catecholamine concentration was much greater in non-maternally deprived rats than in maternally-deprived rats; cardiac beta-adrenoreceptor density was decreased by VCS in both maternally-deprived and non-deprived rats, but more so in non-deprived rats, and further decreased by the ADTN lesion. In the plus maze test, the number of open arm entries was greater in the maternally deprived and in the stressed rats. Thus, sympathetic-adrenal medullary activation produced by VCS was much greater in non-deprived rats, and was linked to a down regulation of myocardial beta-adrenoceptors. The ADTN are not responsible for the reduced catecholamine responses to stress in maternally-deprived rats. Maternal deprivation or

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

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Darin J Falk

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

Sensitivity Analysis of Vagus Nerve Stimulation Parameters on Acute Cardiac Autonomic Responses: Chronotropic, Inotropic and Dromotropic Effects.

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David Ojeda

provoke significantly different cardiac responses, showing the feasibility of a parameter-based functional selectivity. These results are of primary importance for the optimal, subject-specific definition of VNS parameters for a given therapy and may lead to new closed-loop methods allowing for the optimal adaptation of VNS therapy through time.

The effects of malnutrition on cardiac function in African children.

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Silverman, Jonathan A; Chimalizeni, Yamikani; Hawes, Stephen E; Wolf, Elizabeth R; Batra, Maneesh; Khofi, Harriet; Molyneux, Elizabeth M

2016-02-01

Cardiac dysfunction may contribute to high mortality in severely malnourished children. Our objective was to assess the effect of malnutrition on cardiac function in hospitalised African children. Prospective cross-sectional study. Public referral hospital in Blantyre, Malawi. We enrolled 272 stable, hospitalised children ages 6-59 months, with and without WHO-defined severe acute malnutrition. Cardiac index, heart rate, mean arterial pressure, stroke volume index and systemic vascular resistance index were measured by the ultrasound cardiac output monitor (USCOM, New South Wales, Australia). We used linear regression with generalised estimating equations controlling for age, sex and anaemia. Our primary outcome, cardiac index, was similar between those with and without severe malnutrition: difference=0.22 L/min/m(2) (95% CI -0.08 to 0.51). No difference was found in heart rate or stroke volume index. However, mean arterial pressure and systemic vascular resistance index were lower in children with severe malnutrition: difference=-8.6 mm Hg (95% CI -12.7 to -4.6) and difference=-200 dyne s/cm(5)/m(2) (95% CI -320 to -80), respectively. In this largest study to date, we found no significant difference in cardiac function between hospitalised children with and without severe acute malnutrition. Further study is needed to determine if cardiac function is diminished in unstable malnourished children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

DEFF Research Database (Denmark)

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

2016-01-01

Cardiac autonomic dysfunction and cardiac microvascular dysfunction are diabetic complications associated with increased mortality, but the association between these has been difficult to assess. We applied new and sensitive methods to assess this in patients with type 2 diabetes mellitus (T2DM......). In a cross-sectional design, coronary flow reserve (CFR) assessed by cardiac (82)Rb-positron emission tomography/computed tomography, cardiac autonomic reflex tests, and heart rate variability indices were performed in 55 patients with T2DM, without cardiovascular disease, and in 28 control subjects. Cardiac....... A heart rate variability index, reflecting sympathetic and parasympathetic function (low-frequency power), and the late heart-to-mediastinum ratio, reflecting the function of adrenergic receptors and sympathetic activity, were positively correlated with CFR after adjustment for age and heart rate...

Cardiac β-adrenergic responsiveness of obese Zucker rats: The role of AMPK.

Science.gov (United States)

Bussey, Carol T; Thaung, Hp Aye; Hughes, Gillian; Bahn, Andrew; Lamberts, Regis R

2018-06-05

What is the central question of the study? What is the main finding and its importance? 1. Is the reduced signalling of AMPK, a key regulator of energy homeostasis in the heart, responsible for the reduced β-adrenergic responsiveness of the heart in obesity? 2. Inhibition of AMPK in isolated hearts prevented the reduced cardiac β-adrenergic responsiveness of obese rats, which was accompanied by reduced phosphorylation of AMPK, a proxy of AMPK activity. This suggests a direct functional link between β-adrenergic responsiveness and AMPK signalling in the heart, and that AMPK might be an important target to restore the β-adrenergic responsiveness in the heart in obesity. The obesity epidemic impacts heavily on cardiovascular health, in part due to changes in cardiac metabolism. AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis in the heart, and is regulated by β-adrenoceptors (AR) under normal conditions. In obesity, chronic sympathetic overactivation leads to impaired cardiac β-AR responsiveness, although it is unclear whether AMPK signalling, downstream of β-AR, contributes to this dysfunction. Therefore, we aimed to determine whether reduced AMPK signalling is responsible for the reduced β-AR responsiveness in obesity. In isolated hearts of lean and obese Zucker rats, we tested β-AR responsiveness to β 1 -AR agonist isoproterenol (ISO, 1 × 10 -10 - 5 × 10 -8  M) in the absence and presence of the AMPK inhibitor compound C (CC, 10 μM). β 1 -AR expression and AMPK phosphorylation were assessed by Western blot. β-Adrenergic responsiveness was reduced in the hearts of obese rats (LogEC50 of ISO-developed pressure dose-response curves: lean -8.53 ± 0.13 vs. obese -8.35 ± 0.10 10 x M; p  0.05, n = 6 per group). β 1 -AR expression and AMPK phosphorylation were reduced in hearts of obese rats (AMPK at Thr 172 : lean 1.73 ± 0.17 vs. lean CC 0.81 ± 0.13, and obese 1.18 ± 0.09 vs. obese CC 0.81 ± 0

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

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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.

Assessment of Cardiac Function in Fetuses of Gestational Diabetic Mothers During the Second Trimester.

Science.gov (United States)

Atiq, Mehnaz; Ikram, Anum; Hussain, Batool M; Saleem, Bakhtawar

2017-06-01

Fetuses of diabetic mothers may have structural or functional cardiac abnormalities which increase morbidity and mortality. Isolated functional abnormalities have been identified in the third trimester. The aim of the present study was to assess fetal cardiac function (systolic, diastolic, and global myocardial performance) in the second trimester in mothers with gestational diabetes, and also to relate cardiac function with glycemic control. Mothers with gestational diabetes mellitus referred for fetal cardiac evaluation in the second trimester (between 19 and 24 weeks) from March 2015 to February 2016 were enrolled as case subjects in this study. Non-diabetic mothers who had a fetal echocardiogram done between 19 and 24 weeks for other indications were enrolled as controls. Functional cardiac variables showed a statistically significant difference in isovolumetric relaxation and contraction times and the myocardial performance index and mitral E/A ratios in the gestational diabetic group (p = 0.003). Mitral annular plane systolic excursion was significantly less in the diabetic group (p = 0.01). The only functional cardiac variable found abnormal in mothers with poor glycemic control was the prolonged isovolumetric relaxation time. Functional cardiac abnormalities can be detected in the second trimester in fetuses of gestational diabetic mothers and timely intervention can improve postnatal outcomes.

Evaluation of left ventricular function by cardiac CT

International Nuclear Information System (INIS)

Naito, Hiroaki; Kozuka, Takahiro

1982-01-01

Left ventricular function was evaluated by CT, which was compared with the data of left ventriculography for various cardiac diseases. The end diastolic volume of the left ventricle can be readily computed from CT, with a satisfactory correlation with that of left ventriculography (r = 0.95). The left ventricular ejection fraction, calculated from the areal ratio of the left ventricular lumen in end-diastolic imaging to that in end-sytolic imaging, also roughly reflects left ventricular contractile function, but shows correlation with left ventriculography by only r = 0.79. Although the cardiac output is not sensitive for functional evaluation, it can be directly calculated by means of dynamic scanning and shows a satisfactory correlation with the ear piece pigment dilution (r = 0.85). Evaluation of left ventricular function by CT shows a high precision in comparison with left ventriculography, but still lacks temporal resolving power. (Chiba, N.)

Is applying the same exercise-based inpatient program to normal and reduced left ventricular function patients the best strategy after coronary surgery? A focus on autonomic cardiac response.

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Mendes, Renata Gonçalves; Simões, Rodrigo Polaquini; Costa, Fernando de Souza Melo; Pantoni, Camila Bianca Falasco; Di Thommazo-Luporini, Luciana; Luzzi, Sérgio; Amaral-Neto, Othon; Arena, Ross; Catai, Aparecida Maria; Borghi-Silva, Audrey

2014-01-01

To assess whether the same exercise-based inpatient program applied to patients with normal and reduced left ventricular function (LVF) evokes a similar cardiac autonomic response after coronary artery bypass graft (CABG). Forty-four patients post-CABG, subgrouped according to normal LVF [LVFN: n = 23; left ventricular ejection fraction (LVEF) ≥ 55%] and reduced LVF (LVFR: n = 21; LVEF 35-54%), were included. All initiated the exercise protocol on post-operative day 1 (PO1), following a whole progressive program until discharge. Cardiac autonomic response was assessed by the indices of heart rate variability (HRV) at rest and during exercise (extremity range of motion and ambulation). During ambulation, lower values of HRV indices were found in the LVFR group compared with the LVFN group [standard deviation of all RR (STDRR; 6.1 ± 2.7 versus 8.9 ± 4.7 ms), baseline width of the RR histogram (TINN; 30.6 ± 14.8 versus 45.8 ± 24.9 ms), SD2 (14.8 ± 8.0 versus 21.3 ± 9.0 ms), Shannon entropy (3.6 ± 0.5 versus 3.9 ± 0.4) and correlation dimension (0.08 ± 0.2 versus 0.2 ± 0.2)]. Also, when comparing the ambulation to rest change, lower values were observed in the LVFR group for linear (STDRR, TINN, RR TRI, rMSSD) and non-linear (SD2 and correlation dimension) HRV indices (p exercise (extremity range of motion), for mean intervals between heart beats and heart rate. For patients with LVFN, the same inpatient exercise protocol triggered a more attenuated autonomic response compared with patients with LVFR. These findings have implications as to how exercise should be prescribed according to LVF in the early stages following recovery from CABG. Implications for Rehabilitation Exercise-based inpatient program, performed by post-CABG patients who have normal left ventricular function, triggered a more attenuated cardiac autonomic response compared with patients with reduced left ventricular function. Volume of the inpatient exercises should be prescribed according

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

Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart.

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Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Ardell, Jeffrey L; Armour, J Andrew

2009-01-28

Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.

New aspects of HERG K⁺ channel function depending upon cardiac spatial heterogeneity.

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Pen Zhang

Full Text Available HERG K(+ channel, the genetic counterpart of rapid delayed rectifier K(+ current in cardiac cells, is responsible for many cases of inherited and drug-induced long QT syndromes. HERG has unusual biophysical properties distinct from those of other K(+ channels. While the conventional pulse protocols in patch-clamp studies have helped us elucidate these properties, their limitations in assessing HERG function have also been progressively noticed. We employed AP-clamp techniques using physiological action potential waveforms recorded from various regions of canine heart to study HERG function in HEK293 cells and identified several novel aspects of HERG function. We showed that under AP-clamp IHERG increased gradually with membrane repolarization, peaked at potentials around 20-30 mV more negative than revealed by pulse protocols and at action potential duration (APD to 60%-70% full repolarization, and fell rapidly at the terminal phase of repolarization. We found that the rising phase of IHERG was conferred by removal of inactivation and the decaying phase resulted from a fall in driving force, which were all determined by the rate of membrane repolarization. We identified regional heterogeneity and transmural gradient of IHERG when quantified with the area covered by IHERG trace. In addition, we observed regional and transmural differences of IHERG in response to dofetilide blockade. Finally, we characterized the influence of HERG function by selective inhibition of other ion currents. Based on our results, we conclude that the distinct biophysical properties of HERG reported by AP-clamp confer its unique function in cardiac repolarization thereby in antiarrhythmia and arrhythmogenesis.

Primary hemochromatosis: anatomic and physiologic characteristics of the cardiac ventricles and their response to phlebotomy

International Nuclear Information System (INIS)

Dabestani, A.; Child, J.S.; Henze, E.; Perloff, J.K.; Schon, H.; Figueroa, W.G.; Schelbert, H.R.; Thessomboon, S.

1984-01-01

M-mode and 2-dimensional echocardiography and gated equilibrium blood pool imaging (rest and exercise) were used in 10 patients with primary hemochromatosis to characterize the spectrum of pathophysiologic abnormalities of the cardiac ventricles and to determine the response to chronic therapeutic phlebotomy. Dilated and restrictive cardiomyopathic patterns were identified in 1 patient each, but our data do not permit conclusions on when in the natural history a given pattern becomes overt. On entry into study, 3 patients had normal ventricles and 7 had ventricular abnormalities on echocardiography and blood pool angiography. In 2 of the latter patients, biventricular dysfunction and increased left ventricular (LV) mass normalized after phlebotomy; 1 patient achieved a normal LV response to exercise. Of the 4 patients with isolated abnormal LV ejection fraction responses to exercise, the EF normalized in 2 after phlebotomy. In 1 patient, isolated right ventricular enlargement and dysfunction (echocardiographic and radionuclide imaging) normalized after phlebotomy. Thus, primary hemochromatosis can effect LV and RV size and function; clinically occult cardiac involvement can be identified by echocardiography and equilibrium blood pool imaging; therapeutic phlebotomy can ameliorate or reverse the deleterious effects of excess cardiac iron deposition which appears to exert its harm, at least in part, by a mechanism other than irreversible connective tissue replacement

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

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

2011-05-01

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

In vivo cardiac role of migfilin during experimental pressure overload.

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Haubner, Bernhard Johannes; Moik, Daniel; Schuetz, Thomas; Reiner, Martin F; Voelkl, Jakob G; Streil, Katrin; Bader, Kerstin; Zhao, Lei; Scheu, Claudia; Mair, Johannes; Pachinger, Otmar; Metzler, Bernhard

2015-06-01

Increased myocardial wall strain triggers the cardiac hypertrophic response by increasing cardiomyocyte size, reprogramming gene expression, and enhancing contractile protein synthesis. The LIM protein, migfilin, is a cytoskeleton-associated protein that was found to translocate in vitro into the nucleus in a Ca(2+)-dependent manner, where it co-activates the pivotal cardiac transcription factor Csx/Nkx2.5. However, the in vivo role of migfilin in cardiac function and stress response is unclear. To define the role of migfilin in cardiac hypertrophy, we induced hypertension by transverse aortic constriction (TAC) and compared cardiac morphology and function of migfilin knockout (KO) with wild-type (WT) hearts. Heart size and myocardial contractility were comparable in untreated migfilin KO and WT hearts, but migfilin-null hearts presented a reduced extent of hypertrophic remodelling in response to chronic hypertensile stress. Migfilin KO mice maintained their cardiac function for a longer time period compared with WT mice, which presented extensive fibrosis and death due to heart failure. Migfilin translocated into the nucleus of TAC-treated cardiomyocytes, and migfilin KO hearts showed reduced Akt activation during the early response to pressure overload. Our findings indicate an important role of migfilin in the regulation of cardiac hypertrophy upon experimental TAC. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

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

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

2003-11-01

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

Loss of stearoyl-CoA desaturase 1 rescues cardiac function in obese leptin-deficient mice.

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Dobrzyn, Pawel; Dobrzyn, Agnieszka; Miyazaki, Makoto; Ntambi, James M

2010-08-01

The heart of leptin-deficient ob/ob mice is characterized by pathologic left ventricular hypertrophy along with elevated triglyceride (TG) content, increased stearoyl-CoA desaturase (SCD) activity, and increased myocyte apoptosis. In the present study, using an ob/ob;SCD1(-/-) mouse model, we tested the hypothesis that lack of SCD1 could improve steatosis and left ventricle (LV) function in leptin deficiency. We show that disruption of the SCD1 gene improves cardiac function in ob/ob mice by correcting systolic and diastolic dysfunction without affecting levels of plasma TG and FFA. The improvement is associated with reduced expression of genes involved in FA transport and lipid synthesis in the heart, as well as reduction in cardiac FFA, diacylglycerol, TG, and ceramide levels. The rate of FA beta-oxidation is also significantly lower in the heart of ob/ob;SCD1(-/-) mice compared with ob/ob controls. Moreover, SCD1 deficiency reduces cardiac apoptosis in ob/ob mice due to increased expression of antiapoptotic factor Bcl-2 and inhibition of inducible nitric oxide synthase and caspase-3 activities. Reduction in myocardial lipid accumulation and inhibition of apoptosis appear to be one of the main mechanisms responsible for improved LV function in ob/ob mice caused by SCD1 deficiency.

Effects of plasma viscosity modulation on cardiac function during moderate hemodilution

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Chatpun Surapong

2010-01-01

Full Text Available Background : Previous studies have found that increasing plasma viscosity as whole blood viscosity decrease has beneficial effects in microvascular hemodynamics. As the heart couples with systemic vascular network, changes in plasma and blood viscosity during hemodilution determine vascular pressure drop and flow rate, which influence cardiac function. This study aimed to investigate how changes in plasma viscosity affect on cardiac function during acute isovolemic hemodilution. Materials and Methods: Plasma viscosity was modulated by hemodilution of 40% of blood volume with three different plasma expanders (PEs. Dextran 2000 kDa (Dx2M, 6.3 cP and dextran 70 kDa (Dx70, 3.0 cP were used as high and moderate viscogenic PEs, respectively. Polyethylene glycol conjugated with human serum albumin (PEG-HSA, 2.2 cP was used as low viscogenic PE. The cardiac function was assessed using a miniaturized pressure-volume conductance catheter. Results: After hemodilution, pressure dropped to 84%, 79%, and 78% of baseline for Dx2M, Dx70 and PEG-HSA, respectively. Cardiac output markedly increased for Dx2M and PEG-HSA. Dx2M significantly produced higher stroke work relative to baseline and compared to Dx70. Conclusion: Acute hemodilution with PEG-HSA without increasing plasma viscosity provided beneficial effects on cardiac function compared to Dx70, and similar to those measured with Dx2M. Potentially negative effects of increasing peripheral vascular resistance due to the increase in plasma viscosity were prevented.

CARDIAC STRUCTURAL AND FUNCTIONAL ABNORMALITIES IN FEMALES WITH UNTREATED HYPOPITUITARISM DUE TO SHEEHAN SYNDROME: RESPONSE TO HORMONE REPLACEMENT THERAPY.

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Laway, Bashir Ahmad; Ramzan, Mahroosa; Allai, Mohd Sultan; Wani, Arshad Iqbal; Misgar, Raiz Ahmad

2016-09-01

Data on cardiac abnormalities in females with untreated hypopituitarism are limited. We investigated echocardiographic abnormalities in females with untreated hypopituitarism and their response to treatment. Twenty-three females with treatment-naïve hypopituitarism and 30 matched healthy controls were evaluated for cardiac structure and function. Echocardiographic evaluation was done at presentation and after achieving a euthyroid and eucortisol state. Fourteen (61%) patients had mitral regurgitation, and 11 (48%) had pericardial effusion as against none among controls. Indices of left ventricular (LV) size like LV end diastolic dimension (LVEDD; 44.5 ± 3.5 mm in cases vs. 47.6 ± 3.8 mm in controls, P = .004), and LV diastolic volume (LVEDV; 91.8 ± 18.0 mL versus 106.5 ± 20.4 mL, P = .009) were significantly lower in the SS group compared with controls. LV mass (LVM) was 70.8 ± 19.2 g in cases and 108.0 ± 33.2 g in controls (P = .02). Similarly, indices of LV systolic function like stroke volume (SV; 59.1 ± 12.0 mL in cases and 74.4 ± 15.8 mL in controls; P = .000), ejection fraction (EF; 64.3 ± 6.2 % in cases against 69.9 ± 9.2 % in controls; P = .03), and fractional shortening (FS; 34.9 ± 4.7% versus 40.1 ± 4.4%, P = .000) were significantly decreased in patients compared with controls. Cardiac abnormalities normalized with restoration of a euthyroid and eucortisol state. Pericardial effusion, mitral regurgitation, and diminished LVM are common in females with untreated hypopituitarism. ACTH = adrenocorticotrophic hormone BMI = body mass index DT = deceleration time EDV = end-diastolic volume EF = ejection fraction FS = fractional shortening GH = growth hormone IGF-1 = insulin growth factor-1 ITT = insulin tolerance test IVSd = interventricular septal diameter LH = luteinizing hormone LV = left ventricular LVEDD = LV end diastolic dimension LVEDV = LV end diastolic volume LVM = LV mass MRI = magnetic resonance imaging MVP = mitral value prolapse PPH

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.

ABC of the cardiac magnetic resonance. Part 1: anatomy and function

International Nuclear Information System (INIS)

Loureiro, Ricardo; Rached, Heron; Castro, Claudio C.; Cerri, Giovanni G.; Favaro, Daniele; Baptista, Luciana; Andrade, Joalbo; Rochitte, Carlos E.; Parga Filho, Jose; Avila, Luiz F.; Piva, Rosa M.V.

2003-01-01

The objective of this work is to demonstrate the fundamental concepts, the basic sequences and the clinical and potential applications of cardiac magnetic resonance as a diagnostic technique in updated radiology and cardiology practices. In this first part, we present the basic planning of the cardiac image acquisition, the nomenclature and standardized myocardial segmentation, image synchronization principles for electrocardiogram and the heart functional and anatomical evaluation by cardiac magnetic resonance. (author)

Functions of PDE3 Isoforms in Cardiac Muscle

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Movsesian, Matthew; Ahmad, Faiyaz

2018-01-01

Isoforms in the PDE3 family of cyclic nucleotide phosphodiesterases have important roles in cyclic nucleotide-mediated signalling in cardiac myocytes. These enzymes are targeted by inhibitors used to increase contractility in patients with heart failure, with a combination of beneficial and adverse effects on clinical outcomes. This review covers relevant aspects of the molecular biology of the isoforms that have been identified in cardiac myocytes; the roles of these enzymes in modulating cAMP-mediated signalling and the processes mediated thereby; and the potential for targeting these enzymes to improve the profile of clinical responses. PMID:29415428

The cardiac patients' perceptions of their responsibilities in adherence to care: a qualitative interview study.

Science.gov (United States)

Kangasniemi, Mari; Hirjaba, Marina; Kohonen, Katja; Vellone, Ercole; Moilanen, Tanja; Pietilä, Anna-Maija

2017-09-01

To describe cardiac patients' perceptions of their responsibilities in adherence to care. The responsibilities of cardiac patients' adherence to care is a topical issue because of the increasing prevalence of noncommunicable diseases in Western countries, including cardiovascular disease (CVD). Responsibilities for cardiac patients' care have been studied, but little is described about patients' perspectives in this study. A qualitative, hermeneutic inquiry. We used face-to-face individual semistructured interviews with 21 cardiac patients (76% male) aged 58-86 in an urban area of Finland in winter 2013. The data were analysed hermeneutically with inductive content analysis. Based on our results, patients with cardiac disease understood that autonomy provided a basis for their responsibility in adherence to care. It included being able to make independent decisions, in collaboration with health professionals, or even to entrust that responsibility to healthcare professionals. Responsibilities were understood to be an expression of adherence, perceived to benefit the patient and included the duty to adopt a healthy lifestyle and care for their own medical condition. The main factors that influenced patients' responsibilities around adherence to care were their individual resources and motivation, relationships with healthcare professionals and the resources of the healthcare system. Autonomy is an inherent part of cardiac patients' adherence to care, but there has been little focus on their responsibilities in the literature. More attention needs to be paid to the healthcare providers' abilities to support patients' duties and responsibilities in clinical practice and to future research. © 2016 John Wiley & Sons Ltd.

Sexual counselling of cardiac patients : Nurses' perception of practice, responsibility and confidence

NARCIS (Netherlands)

Jaarsma, T.; Stromberg, A.; Fridlund, B.; De Geest, S.; Martensson, J.; Moons, P.; Norekval, T. M.; Smith, K.; Steinke, E.; Thompson, D. R.

Background: Cardiac patients may experience problems with sexual activity as a result of their disease, medications or anxiety and nurses play an important role in sexual counselling. We studied the practice, responsibility and confidence of cardiac nurses in the sexual counselling of these

The Role of Oxygen Sensors, Hydroxylases, and HIF in Cardiac Function and Disease

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W. H. Davin Townley-Tilson

2015-01-01

Full Text Available Ischemic heart disease is the leading cause of death worldwide. Oxygen-sensing proteins are critical components of the physiological response to hypoxia and reperfusion injury, but the role of oxygen and oxygen-mediated effects is complex in that they can be cardioprotective or deleterious to the cardiac tissue. Over 200 oxygen-sensing proteins mediate the effects of oxygen tension and use oxygen as a substrate for posttranslational modification of other proteins. Hydroxylases are an essential component of these oxygen-sensing proteins. While a major role of hydroxylases is regulating the transcription factor HIF, we investigate the increasing scope of hydroxylase substrates. This review discusses the importance of oxygen-mediated effects in the heart as well as how the field of oxygen-sensing proteins is expanding, providing a more complete picture into how these enzymes play a multifaceted role in cardiac function and disease. We also review how oxygen-sensing proteins and hydroxylase function could prove to be invaluable in drug design and therapeutic targets for heart disease.

Abnormal Cardiac Autonomic Regulation in Mice Lacking ASIC3

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Ching-Feng Cheng

2014-01-01

Full Text Available Integration of sympathetic and parasympathetic outflow is essential in maintaining normal cardiac autonomic function. Recent studies demonstrate that acid-sensing ion channel 3 (ASIC3 is a sensitive acid sensor for cardiac ischemia and prolonged mild acidification can open ASIC3 and evoke a sustained inward current that fires action potentials in cardiac sensory neurons. However, the physiological role of ASIC3 in cardiac autonomic regulation is not known. In this study, we elucidate the role of ASIC3 in cardiac autonomic function using Asic3−/− mice. Asic3−/− mice showed normal baseline heart rate and lower blood pressure as compared with their wild-type littermates. Heart rate variability analyses revealed imbalanced autonomic regulation, with decreased sympathetic function. Furthermore, Asic3−/− mice demonstrated a blunted response to isoproterenol-induced cardiac tachycardia and prolonged duration to recover to baseline heart rate. Moreover, quantitative RT-PCR analysis of gene expression in sensory ganglia and heart revealed that no gene compensation for muscarinic acetylcholines receptors and beta-adrenalin receptors were found in Asic3−/− mice. In summary, we unraveled an important role of ASIC3 in regulating cardiac autonomic function, whereby loss of ASIC3 alters the normal physiological response to ischemic stimuli, which reveals new implications for therapy in autonomic nervous system-related cardiovascular diseases.

Intrinsic cardiac nervous system in tachycardia induced heart failure.

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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

Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.

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Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja; Larsson, Henrik B W; Rostrup, Egill

2014-11-01

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Role of Nuclear Medicine in the cardiac resinchronization therapy

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Brandao, Simone Cristina Soares, E-mail: simonecordis@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Giorgi, Maria Clementina Pinto; D' Orio, Silvana Angelina; Meneghetti, Jose Claudio [Instituto do Coracao (InCor/FM/USP), Sao Paulo, SP (Brazil)

2011-10-15

Cardiac resynchronization therapy (CRT) emerged as one of the most promising approaches in the treatment of cardiac dyssynchrony in heart failure patients' refractory to medical treatment. However, despite very promising clinical and functional results, individual response analyses show that a significant number of patients do not respond to treatment. The role of nuclear medicine and molecular imaging in the selection of CRT candidates by the assessment of cardiac dyssynchrony, myocardial viability, myocardial perfusion and blood flow and sympathetic cardiac activity has been discussed in this review. The potential utilization of this tool to improve the comprehension of detrimental effects of dyssynchrony on cardiac function and the evaluation and monitoring of the response to CRT were also considered. Other molecular targets that characterize glucose and fatty acid metabolism, apoptosis, angiotensin converting enzyme activity and angiogenesis that can be evaluated with this technique were described. (author)

Role of Nuclear Medicine in the cardiac resinchronization therapy

Energy Technology Data Exchange (ETDEWEB)

Brandao, Simone Cristina Soares, E-mail: simonecordis@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Giorgi, Maria Clementina Pinto; D' Orio, Silvana Angelina; Meneghetti, Jose Claudio [Instituto do Coracao (InCor/FM/USP), Sao Paulo, SP (Brazil)

2011-10-15

Cardiac resynchronization therapy (CRT) emerged as one of the most promising approaches in the treatment of cardiac dyssynchrony in heart failure patients' refractory to medical treatment. However, despite very promising clinical and functional results, individual response analyses show that a significant number of patients do not respond to treatment. The role of nuclear medicine and molecular imaging in the selection of CRT candidates by the assessment of cardiac dyssynchrony, myocardial viability, myocardial perfusion and blood flow and sympathetic cardiac activity has been discussed in this review. The potential utilization of this tool to improve the comprehension of detrimental effects of dyssynchrony on cardiac function and the evaluation and monitoring of the response to CRT were also considered. Other molecular targets that characterize glucose and fatty acid metabolism, apoptosis, angiotensin converting enzyme activity and angiogenesis that can be evaluated with this technique were described. (author)

A high-sugar and high-fat diet impairs cardiac systolic and diastolic function in mice.

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Carbone, Salvatore; Mauro, Adolfo G; Mezzaroma, Eleonora; Kraskauskas, Donatas; Marchetti, Carlo; Buzzetti, Raffaella; Van Tassell, Benjamin W; Abbate, Antonio; Toldo, Stefano

2015-11-01

Heart failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, exercise intolerance and cardiac dysfunction. Unhealthy diet has been associated with increased risk of obesity and heart disease, but whether it directly affects cardiac function, and promotes the development and progression of HF is unknown. We fed 8-week old male or female CD-1 mice with a standard diet (SD) or a diet rich in saturated fat and sugar, resembling a "Western" diet (WD). Cardiac systolic and diastolic function was measured at baseline and 4 and 8 weeks by Doppler echocardiography, and left ventricular (LV) end-diastolic pressure (EDP) by cardiac catheterization prior to sacrifice. An additional group of mice received WD for 4 weeks followed by SD (wash-out) for 8 weeks. WD-fed mice experienced a significant decreased in LV ejection fraction (LVEF), reflecting impaired systolic function, and a significant increase in isovolumetric relaxation time (IRT), myocardial performance index (MPI), and LVEDP, showing impaired diastolic function, without any sex-related differences. Switching to a SD after 4 weeks of WD partially reversed the cardiac systolic and diastolic dysfunction. A diet rich in saturated fat and sugars (WD) impairs cardiac systolic and diastolic function in the mouse. Further studies are required to define the mechanism through which diet affects cardiac function, and whether dietary interventions can be used in patients with, or at risk for, HF. Published by Elsevier Ireland Ltd.

Coronary flow response to remote ischemic preconditioning is preserved in old cardiac patients.

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Santillo, Elpidio; Migale, Monica; Balestrini, Fabrizio; Postacchini, Demetrio; Bustacchini, Silvia; Lattanzio, Fabrizia; Antonelli-Incalzi, Raffaele

2017-10-20

The effect of remote ischemic preconditioning (RIPC) on coronary flow in elderly cardiac patients has not been investigated yet. Thus, we aimed to study the change of coronary flow subsequent to RIPC in old patients with heart diseases and to identify its main correlates. Ninety-five elderly patients (aged ≥ 65 years) accessing cardiac rehabilitation ward underwent transthoracic ultrasound evaluation of peak diastolic flow velocity of left anterior descending artery. Measurements of coronary flow velocity were performed on baseline and after an RIPC protocol (three cycles of 5 min ischemia of right arm alternating 5 min reperfusion). Differences between subjects with coronary flow velocity change over or equal the 75° percentile (high-responders) and subjects with a coronary flow velocity change under the 75° percentile (low-responders) were assessed. In enrolled elderly heart patients, coronary flow velocity significantly augmented from baseline after RIPC [0.23 m/s (0.18-0.28) vs 0.27 m/s (0.22-0.36); p < 0.001 by Wilcoxon test]. High-responders to RIPC were significantly younger and in better functional status than low-responders. Heart failure resulted as the main variable associated with impairment of RIPC responsiveness (R 2  = 0.202; p = 0.002)]. Our sample of old cardiac patients presented a significant median increment of coronary flow velocity after RIPC. The magnitude of the observed change of coronary flow velocity was comparable to that previously described in healthy subjects. The coronary response to RIPC was attenuated by heart failure. Further research should define whether such RIPC responsiveness is associated with cardioprotection and carries prognostic implications.

Cardiac structure and function predicts functional decline in the oldest old.

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Leibowitz, David; Jacobs, Jeremy M; Lande-Stessman, Irit; Gilon, Dan; Stessman, Jochanan

2018-02-01

Background This study examined the association between cardiac structure and function and the deterioration in activities of daily living (ADLs) in an age-homogenous, community-dwelling population of patients born in 1920-1921 over a five-year follow-up period. Design Longitudinal cohort study. Methods Patients were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920-1921. Patients underwent home echocardiography and were followed up for five years. Dependence was defined as needing assistance with one or more basic ADL. Standard echocardiographic assessment of cardiac structure and function, including systolic and diastolic function, was performed. Reassessment of ADLs was performed at the five-year follow-up. Results A total of 459 patients were included in the study. Of these, 362 (79%) showed a deterioration in at least one ADL at follow-up. Patients with functional deterioration had a significantly higher left ventricular mass index and left atrial volume with a lower ejection fraction. There was no significant difference between the diastolic parameters the groups in examined. When the data were examined categorically, a significantly larger percentage of patients with functional decline had an abnormal left ventricular ejection fraction and left ventricular hypertrophy. The association between left ventricular mass index and functional decline remained significant in all multivariate models. Conclusions In this cohort of the oldest old, an elevated left ventricular mass index, higher left atrial volumes and systolic, but not diastolic dysfunction, were predictive of functional disability.

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

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

2016-06-01

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

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

Science.gov (United States)

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

2016-01-01

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

A new function for ATP: activating cardiac sympathetic afferents during myocardial ischemia.

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Fu, Liang-Wu; Longhurst, John C

2010-12-01

Myocardial ischemia activates cardiac sympathetic afferents leading to chest pain and reflex cardiovascular responses. Brief myocardial ischemia leads to ATP release in the interstitial space. Furthermore, exogenous ATP and α,β-methylene ATP (α,β-meATP), a P2X receptor agonist, stimulate cutaneous group III and IV sensory nerve fibers. The present study tested the hypothesis that endogenous ATP excites cardiac afferents during ischemia through activation of P2 receptors. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicates (T(2)-T(5)) in anesthetized cats. Single fields of 45 afferents (conduction velocities = 0.25-4.92 m/s) were identified in the left ventricle with a stimulating electrode. Five minutes of myocardial ischemia stimulated 39 of 45 cardiac afferents (8 Aδ, 37 C fibers). Epicardial application of ATP (1-4 μmol) stimulated six ischemically sensitive cardiac afferents in a dose-dependent manner. Additionally, epicardial ATP (2 μmol), ADP (2 μmol), a P2Y agonist, and α,β-meATP (0.5 μmol) significantly activated eight other ischemically sensitive afferents. Third, pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid, a P2 receptor antagonist, abolished the responses of six afferents to epicardial ATP (2 μmol) and attenuated the ischemia-related increase in activity of seven other afferents by 37%. In the absence of P2 receptor blockade, cardiac afferents responded consistently to repeated application of ATP (n = 6) and to recurrent myocardial ischemia (n = 6). Finally, six ischemia-insensitive cardiac spinal afferents did not respond to epicardial ATP (2-4 μmol), although these afferents did respond to epicardial bradykinin. Taken together, these data indicate that, during ischemia, endogenously released ATP activates ischemia-sensitive, but not ischemia-insensitive, cardiac spinal afferents through stimulation of P2 receptors likely located on the cardiac sensory

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

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Maarten Rijpert

2011-01-01

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

Acute systemic inflammatory response after cardiac surgery in ...

African Journals Online (AJOL)

2017-09-03

Sep 3, 2017 ... valve(s) replacement were enrolled, from a single center hospital, after informed consent was obtained. C-reactive ... Cite as: Gojo MKE, Prakaschandra R. Acute systemic inflammatory response after cardiac surgery in patients infected with human im- ..... Arroyo-Espliguero R, Avanzas P, Cosín-Sales J, Al-.

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

DEFF Research Database (Denmark)

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

2016-01-01

Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the c......Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function...... atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered...... an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing...

Effects of a Structured Discharge Planning Program on Perceived Functional Status, Cardiac Self-efficacy, Patient Satisfaction, and Unexpected Hospital Revisits Among Filipino Cardiac Patients: A Randomized Controlled Study.

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Cajanding, Ruff Joseph

Cardiovascular diseases remain the leading cause of morbidity and mortality among Filipinos and are responsible for a very large number of hospital readmissions. Comprehensive discharge planning programs have demonstrated positive benefits among various populations of patients with cardiovascular disease, but the clinical and psychosocial effects of such intervention among Filipino patients with acute myocardial infarction (AMI) have not been studied. In this study we aimed to determine the effectiveness of a nurse-led structured discharge planning program on perceived functional status, cardiac self-efficacy, patient satisfaction, and unexpected hospital revisits among Filipino patients with AMI. A true experimental (randomized control) 2-group design with repeated measures and data collected before and after intervention and at 1-month follow-up was used in this study. Participants were assigned to either the control (n = 68) or the intervention group (n = 75). Intervention participants underwent a 3-day structured discharge planning program implemented by a cardiovascular nurse practitioner, which is comprised of a series of individualized lecture-discussion, provision of feedback, integrative problem solving, goal setting, and action planning. Control participants received standard routine care. Measures of functional status, cardiac self-efficacy, and patient satisfaction were measured at baseline; cardiac self-efficacy and patient satisfaction scores were measured prior to discharge, and perceived functional status and number of revisits were measured 1 month after discharge. Participants in the intervention group had significant improvement in functional status, cardiac self-efficacy, and patient satisfaction scores at baseline and at follow-up compared with the control participants. Furthermore, participants in the intervention group had significantly fewer hospital revisits compared with those who received only standard care. The results demonstrate that a

Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation.

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Emil D Bartels

Full Text Available Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and beta-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP; the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease.

Cardiac function associated with home ventilator care in Duchenne muscular dystrophy.

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Lee, Sangheun; Lee, Heeyoung; Eun, Lucy Youngmin; Gang, Seung Woong

2018-02-01

Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy because mechanically assisted lung ventilation and assisted coughing have helped resolve respiratory complications. To clarify cardiopulmonary function, we compared cardiac function between the home ventilator-assisted and non-ventilator-assisted groups. We retrospectively reviewed patients with Duchenne muscular dystrophy from January 2010 to March 2016 at Gangnam Severance Hospital. Demographic characteristics, pulmonary function, and echocardiography data were investigated. Fifty-four patients with Duchenne muscular dystrophy were divided into 2 groups: home ventilator-assisted and non-ventilator-assisted. The patients in the home ventilator group were older (16.25±1.85 years) than those in the nonventilator group (14.73±1.36 years) ( P =0.001). Height, weight, and body surface area did not differ significantly between groups. The home ventilator group had a lower seated functional vital capacity (1,038±620.41 mL) than the nonventilator group (1,455±603.12 mL). Mean left ventricular ejection fraction and fractional shortening were greater in the home ventilator group, but the data did not show any statistical difference. The early ventricular filling velocity/late ventricular filling velocity ratio (1.7±0.44) was lower in the home ventilator group than in the nonventilator group (2.02±0.62). The mitral valve annular systolic velocity was higher in the home ventilator group (estimated β, 1.06; standard error, 0.48). Patients with Duchenne muscular dystrophy on a ventilator may have better systolic and diastolic cardiac functions. Noninvasive ventilator assistance can help preserve cardiac function. Therefore, early utilization of noninvasive ventilation or oxygen may positively influence cardiac function in patients with Duchenne muscular dystrophy.

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

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Zuheng Liu

2017-09-01

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

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

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Beate M Herbert

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

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

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Guttridge Denis C

2011-05-01

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

Assessment of cardiac neuronal function with iodine-123 MIBG scintigraphy in children with idiopathic dilated cardiomyopathy

International Nuclear Information System (INIS)

Maunoury, Ch.; Sebahoun, St.; Hallaj, I.; Barritault, L.; Acar, Ph.; Sidi, D.; Kachaner, J.; Agostini, D.; Bouvard, G.

2000-01-01

The I-123 MIBG cardiac scintigraphy can assess norepinephrine uptake. It has been showed that cardiac adrenergic neuronal function was impaired in adults with dilated cardiomyopathy. The aim of this prospective study was to assess cardiac neuronal function in children with idiopathic dilated cardiomyopathy (DCM) and to compare cardiac uptake of I-123 MIBG with left ventricular ejection fraction (LVEF). We studied 26 consecutive patients with idiopathic DCM, aged 44 ± 50 months, and 12 controls, aged 49 ±65 months. A planar scintigraphy was performed in all children 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. A static anterior view was acquired for 10 minutes. Cardiac uptake of I-123 MIBG was expressed as the heart to mediastinum count ratio (HMR). Equilibrium radionuclide angiography was performed following a standard protocol. Cardiac uptake of I-123 MIBG was significantly decreased in patients with idiopathic DCM when compared with cardiac uptake in controls (172±34% vs 277±14%, P<0.0001. There was a good correlation between RCM and LVEF in patients with idiopathic DCM (y = 2.5 x +113.3, r = 0.80, P < 0.0001). In conclusion, cardiac neuronal function was impaired in children with idiopathic DCM and related to impairment of left ventricular function. (author)

[Structure and functional organization of integrated cardiac intensive care].

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Scherillo, Marino; Miceli, Domenico; Tubaro, Marco; Guiducci, Umberto

2007-05-01

The early invasive strategy for the treatment of acute coronary syndromes and the increasing number of older and sicker patients requiring prolonged and more complex intensive care have induced many changes in the function of the intensive care units. These changes include the statement that specially trained cardiologists and cardiac nurses who can manage patients with acute cardiac conditions should staff the intensive care units. This document indicates the structure of the units and specific recommendations for the number of beds, monitoring system, respirators, pacemaker/defibrillators and additional equipment.

The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function.

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Roe, Nathan D; Handzlik, Michal K; Li, Tao; Tian, Rong

2018-03-21

It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARα signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.

Cardiac Myosin Binding Protein-C Autoantibodies are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome.

Science.gov (United States)

Lynch, Thomas L; Kuster, Diederik W D; Gonzalez, Beverly; Balasubramanian, Neelam; Nair, Nandini; Day, Sharlene; Calvino, Jenna E; Tan, Yanli; Liebetrau, Christoph; Troidl, Christian; Hamm, Christian W; Güçlü, Ahmet; McDonough, Barbara; Marian, Ali J; van der Velden, Jolanda; Seidman, Christine E; Huggins, Gordon S; Sadayappan, Sakthivel

2017-04-01

The degradation and release of cardiac myosin binding protein-C (cMyBP-C) upon cardiac damage may stimulate an inflammatory response and autoantibody (AAb) production. We determined whether the presence of cMyBP-C-AAbs associated with adverse cardiac function in CVD patients. Importantly, cMyBP-C-AAbs were significantly detected in ACS patient sera upon arrival to the emergency department, particularly in STEMI patients. Patients positive for cMyBP-C-AAbs had a reduced LVEF and elevated levels of clinical biomarkers of MI. We conclude that cMyBP-C-AAbs may serve as early predictive indicators of deteriorating cardiac function and patient outcome in ACS patients prior to the infarction.

Regulation of cardiac microRNAs by serum response factor

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Wei Jeanne Y

2011-02-01

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

Exercise capacity and cardiac hemodynamic response in female ApoE/LDLR−/− mice: a paradox of preserved V’O2max and exercise capacity despite coronary atherosclerosis

Science.gov (United States)

Wojewoda, M.; Tyrankiewicz, U.; Gwozdz, P.; Skorka, T.; Jablonska, M.; Orzylowska, A.; Jasinski, K.; Jasztal, A.; Przyborowski, K.; Kostogrys, R. B.; Zoladz, J. A.; Chlopicki, S.

2016-01-01

We assessed exercise performance, coronary blood flow and cardiac reserve of female ApoE/LDLR−/− mice with advanced atherosclerosis compared with age-matched, wild-type C57BL6/J mice. Exercise capacity was assessed as whole body maximal oxygen consumption (V’O2max), maximum running velocity (vmax) and maximum distance (DISTmax) during treadmill exercise. Cardiac systolic and diastolic function in basal conditions and in response to dobutamine (mimicking exercise-induced cardiac stress) were assessed by Magnetic Resonance Imaging (MRI) in vivo. Function of coronary circulation was assessed in isolated perfused hearts. In female ApoE/LDLR−/− mice V’O2max, vmax and DISTmax were not impaired as compared with C57BL6/J mice. Cardiac function at rest and systolic and diastolic cardiac reserve were also preserved in female ApoE/LDLR−/− mice as evidenced by preserved fractional area change and similar fall in systolic and end diastolic area after dobutamine. Moreover, endothelium-dependent responses of coronary circulation induced by bradykinin (Bk) and acetylcholine (ACh) were preserved, while endothelium-independent responses induced by NO-donors were augmented in female ApoE/LDLR−/− mice. Basal COX-2-dependent production of 6-keto-PGF1α was increased. Concluding, we suggest that robust compensatory mechanisms in coronary circulation involving PGI2- and NO-pathways may efficiently counterbalance coronary atherosclerosis-induced impairment in V’O2max and exercise capacity. PMID:27108697

Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

Science.gov (United States)

Longhurst, John C.

2013-01-01

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the

Functional modulation of cardiac form through regionally confined cell shape changes.

Directory of Open Access Journals (Sweden)

Heidi J Auman

2007-03-01

Full Text Available Developing organs acquire a specific three-dimensional form that ensures their normal function. Cardiac function, for example, depends upon properly shaped chambers that emerge from a primitive heart tube. The cellular mechanisms that control chamber shape are not yet understood. Here, we demonstrate that chamber morphology develops via changes in cell morphology, and we determine key regulatory influences on this process. Focusing on the development of the ventricular chamber in zebrafish, we show that cardiomyocyte cell shape changes underlie the formation of characteristic chamber curvatures. In particular, cardiomyocyte elongation occurs within a confined area that forms the ventricular outer curvature. Because cardiac contractility and blood flow begin before chambers emerge, cardiac function has the potential to influence chamber curvature formation. Employing zebrafish mutants with functional deficiencies, we find that blood flow and contractility independently regulate cell shape changes in the emerging ventricle. Reduction of circulation limits the extent of cardiomyocyte elongation; in contrast, disruption of sarcomere formation releases limitations on cardiomyocyte dimensions. Thus, the acquisition of normal cardiomyocyte morphology requires a balance between extrinsic and intrinsic physical forces. Together, these data establish regionally confined cell shape change as a cellular mechanism for chamber emergence and as a link in the relationship between form and function during organ morphogenesis.

Effects of vildagliptin versus sitagliptin, on cardiac function, heart rate variability and mitochondrial function in obese insulin-resistant rats

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Apaijai, Nattayaporn; Pintana, Hiranya; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2013-01-01

Background and Purpose Long-term high-fat diet (HFD) consumption has been shown to cause insulin resistance, which is characterized by hyperinsulinaemia with metabolic inflexibility. Insulin resistance is associated with cardiac sympathovagal imbalance, cardiac dysfunction and cardiac mitochondrial dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors, vildagliptin and sitagliptin, are oral anti-diabetic drugs often prescribed in patients with cardiovascular disease. Therefore, in this study, we sought to determine the effects of vildagliptin and sitagliptin in a murine model of insulin resistance. Experimental Approach Male Wistar rats weighing 180–200 g, were fed either a normal diet (20% energy from fat) or a HFD (59% energy from fat) for 12 weeks. These rats were then divided into three subgroups to receive vildagliptin (3 mg·kg−1·day−1), sitagliptin (30 mg·kg−1·day−1) or vehicle for another 21 days. Metabolic parameters, oxidative stress, heart rate variability (HRV), cardiac function and cardiac mitochondrial function were determined. Key Results Rats that received HFD developed insulin resistance characterized by increased body weight, plasma insulin, total cholesterol and oxidative stress levels along with a decreased high-density lipoprotein (HDL) level. Moreover, cardiac dysfunction, depressed HRV, cardiac mitochondrial dysfunction and cardiac mitochondrial morphology changes were observed in HFD rats. Both vildagliptin and sitagliptin decreased plasma insulin, total cholesterol and oxidative stress as well as increased HDL level. Furthermore, vildagliptin and sitagliptin attenuated cardiac dysfunction, prevented cardiac mitochondrial dysfunction and completely restored HRV. Conclusions and Implications Both vildagliptin and sitagliptin share similar efficacy in cardioprotection in obese insulin-resistant rats. PMID:23488656

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

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Viveka P Jyotsna

2013-01-01

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

Physiologic stress interventions in cardiac imaging

International Nuclear Information System (INIS)

Buda, A.J.

1985-01-01

Physiologic stress interventions are designed to assess the reserve capability of coronary flow and myocardial function. In the normal individual, a sufficiently intense physiologic stress may increase coronary flow and cardiac output by 500% to 600%. However, in patients with cardiac disease, these reserve responses may be absent, or considerably blunted. Thus, physiologic stress testing has proved extremely helpful in detecting cardiac abnormalities when resting cardiac function appears normal. Although dynamic exercise remains the standard approach to physiologic stress testing, a number of other interventions have been used, including: (1) isometric exercise, (2) atrial pacing, (3) cold pressor testing, (4) postextrasystolic potentiation, (5) volume loading, and (6) negative intrathoracic pressure. Each of these may be considered an alternative physiologic intervention whenever dynamic exercise is not feasible. These alternative approaches are important since, in our experience, 20% to 30% of subjects are unable to perform dynamic exercise, or exercise inadequately to produce a sufficiently intense cardiac stress. This chapter reviews physiologic considerations, indications, contraindications, protocols, and results of these physiologic stress interventions when used in combination with cardiac radionuclide procedures

Psychosocial responses of children to cardiac pacemakers.

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Alpern, D; Uzark, K; Dick, M

1989-03-01

To examine the psychosocial responses of children and adolescents with a cardiac pacemaker and compare their responses to those of their peers, we evaluated 30 pediatric pacemaker patients, aged 7 to 19 years, and two age- and sex-matched comparison groups, including 30 patients with similar heart disease but without pacemakers and 30 physically healthy children, using standardized psychometric tests and a specific interview format. We postulated that children with pacemakers would experience greater stress in psychosocial adaptation. No significant differences on standardized measures of trait anxiety, self-competence, or self-esteem were found between the pacemaker group and the comparison groups. In contrast, pacemaker subjects were significantly (p less than 0.05) more external in their locus-of-control orientation than were healthy subjects, suggesting a diminished sense of personal control and less autonomy. Pacemaker subjects, particularly the older ones, had significantly (p less than 0.05) greater knowledge of pacemaker systems than did subjects in the other two groups, facilitating the use of intellectualization as a coping mechanism. The pacemaker patients were likely to be as fearful of social rejection as of potential pacemaker failure. All three groups identified potential negative peer reactions toward an individual with a pacemaker. The patients with cardiac disease but without pacemakers and the healthy subjects perceived significant (p less than 0.05) social and emotional differences between patients with pacemakers and their peers, but the pacemaker patients did not view themselves as different from their peers. This study demonstrates healthy psychosocial adaptation of children with cardiac pacemakers. Although these children appear to cope effectively with the stress of their life situation through the use of denial and intellectualization, they may experience problems both in the development of autonomy and in social isolation and rejection.

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

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Bonpei Takase

2009-01-01

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

Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs.

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Wang, Bo; Patnaik, Sourav S; Brazile, Bryn; Butler, J Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

2015-01-01

Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status.

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Léger, Thibault; Charrier, Alice; Moreau, Clarisse; Hininger-Favier, Isabelle; Mourmoura, Evangelia; Rigaudière, Jean-Paul; Pitois, Elodie; Bouvier, Damien; Sapin, Vincent; Pereira, Bruno; Azarnoush, Kasra; Demaison, Luc

2017-07-01

If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll-like receptor-9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF- α and IL-1 β In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham-operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF- α and gene expression of IL-1 β and TNF- α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF- α and IL-1 β on the cardiac function is known to occur at very high concentrations. The influence of low- to moderate-grade inflammation on the myocardial mechanical behavior must thus be revisited. © 2017 French National Institute of Agronomical Research (INRA). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Acute effect of Vagus nerve stimulation parameters on cardiac chronotropic, inotropic, and dromotropic responses

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Ojeda, David; Le Rolle, Virginie; Romero-Ugalde, Hector M.; Gallet, Clément; Bonnet, Jean-Luc; Henry, Christine; Bel, Alain; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I.

2017-11-01

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy and depression, and is considered as a potential therapy for other pathologies, including Heart Failure (HF) or inflammatory diseases. In the case of HF, several experimental studies on animals have shown an improvement in the cardiac function and a reverse remodeling of the cardiac cavity when VNS is applied. However, recent clinical trials have not been able to reproduce the same response in humans. One of the hypothesis to explain this lack of response is related to the way in which stimulation parameters are defined. The combined effect of VNS parameters is still poorly-known, especially in the case of VNS synchronously delivered with cardiac activity. In this paper, we propose a methodology to analyze the acute cardiovascular effects of VNS parameters individually, as well as their interactive effects. A Latin hypercube sampling method was applied to design a uniform experimental plan. Data gathered from this experimental plan was used to produce a Gaussian process regression (GPR) model in order to estimate unobserved VNS sequences. Finally, a Morris screening sensitivity analysis method was applied to each obtained GPR model. Results highlight dominant effects of pulse current, pulse width and number of pulses over frequency and delay and, more importantly, the degree of interactions between these parameters on the most important acute cardiovascular responses. In particular, high interacting effects between current and pulse width were found. Similar sensitivity profiles were observed for chronotropic, dromotropic and inotropic effects. These findings are of primary importance for the future development of closed-loop, personalized neuromodulator technologies.

Cortical Bone Stem Cell Therapy Preserves Cardiac Structure and Function After Myocardial Infarction.

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Sharp, Thomas E; Schena, Giana J; Hobby, Alexander R; Starosta, Timothy; Berretta, Remus M; Wallner, Markus; Borghetti, Giulia; Gross, Polina; Yu, Daohai; Johnson, Jaslyn; Feldsott, Eric; Trappanese, Danielle M; Toib, Amir; Rabinowitz, Joseph E; George, Jon C; Kubo, Hajime; Mohsin, Sadia; Houser, Steven R

2017-11-10

Cortical bone stem cells (CBSCs) have been shown to reduce ventricular remodeling and improve cardiac function in a murine myocardial infarction (MI) model. These effects were superior to other stem cell types that have been used in recent early-stage clinical trials. However, CBSC efficacy has not been tested in a preclinical large animal model using approaches that could be applied to patients. To determine whether post-MI transendocardial injection of allogeneic CBSCs reduces pathological structural and functional remodeling and prevents the development of heart failure in a swine MI model. Female Göttingen swine underwent left anterior descending coronary artery occlusion, followed by reperfusion (ischemia-reperfusion MI). Animals received, in a randomized, blinded manner, 1:1 ratio, CBSCs (n=9; 2×10 7 cells total) or placebo (vehicle; n=9) through NOGA-guided transendocardial injections. 5-ethynyl-2'deoxyuridine (EdU)-a thymidine analog-containing minipumps were inserted at the time of MI induction. At 72 hours (n=8), initial injury and cell retention were assessed. At 3 months post-MI, cardiac structure and function were evaluated by serial echocardiography and terminal invasive hemodynamics. CBSCs were present in the MI border zone and proliferating at 72 hours post-MI but had no effect on initial cardiac injury or structure. At 3 months, CBSC-treated hearts had significantly reduced scar size, smaller myocytes, and increased myocyte nuclear density. Noninvasive echocardiographic measurements showed that left ventricular volumes and ejection fraction were significantly more preserved in CBSC-treated hearts, and invasive hemodynamic measurements documented improved cardiac structure and functional reserve. The number of EdU + cardiac myocytes was increased in CBSC- versus vehicle- treated animals. CBSC administration into the MI border zone reduces pathological cardiac structural and functional remodeling and improves left ventricular functional reserve

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

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

2016-06-01

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

Age-related normal structural and functional ventricular values in cardiac function assessed by magnetic resonance

International Nuclear Information System (INIS)

Fiechter, Michael; Gaemperli, Oliver; Kaufmann, Philipp A; Fuchs, Tobias A; Gebhard, Catherine; Stehli, Julia; Klaeser, Bernd; Stähli, Barbara E; Manka, Robert; Manes, Costantina; Tanner, Felix C

2013-01-01

The heart is subject to structural and functional changes with advancing age. However, the magnitude of cardiac age-dependent transformation has not been conclusively elucidated. This retrospective cardiac magnetic resonance (CMR) study included 183 subjects with normal structural and functional ventricular values. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were obtained from the left and the right ventricle in breath-hold cine CMR. Patients were classified into four age groups (20–29, 30–49, 50–69, and ≥70 years) and cardiac measurements were compared using Pearson’s rank correlation over the four different groups. With advanced age a slight but significant decrease in ESV (r=−0.41 for both ventricles, P<0.001) and EDV (r=−0.39 for left ventricle, r=−0.35 for right ventricle, P<0.001) were observed associated with a significant increase in left (r=0.28, P<0.001) and right (r=0.27, P<0.01) ventricular EF reaching a maximal increase in EF of +8.4% (P<0.001) for the left and +6.1% (P<0.01) for the right ventricle in the oldest compared to the youngest patient group. Left ventricular myocardial mass significantly decreased over the four different age groups (P<0.05). The aging process is associated with significant changes in left and right ventricular EF, ESV and EDV in subjects with no cardiac functional and structural abnormalities. These findings underline the importance of using age adapted values as standard of reference when evaluating CMR studies

8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish

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Yan, Lifeng [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China); Zhou, Yong [Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Yu, Shanhe [Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025 (China); Ji, Guixiang [Nanjing Institute of Environmental Sciences/Key Laboratory of Pesticide Environmental Assessment and Pollution Control, Ministry of Environmental Protection, Nanjing 210042 (China); Wang, Lei [Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Liu, Wei [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China); Gu, Aihua, E-mail: aihuagu@njmu.edu.cn [State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029 (China)

2013-11-15

Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes and nkx2.5{sup +} cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits. - Highlights: • A key DNA repair enzyme ogg1 is expressed in the embryonic heart in zebrafish. • We found that ogg1 is essential for normal cardiac morphogenesis in zebrafish. • The production of embryonic cardiomyocytes requires appropriate ogg1 expression. • Ogg1 critically regulated proliferation of cardiac progenitor cells in zebrafish. • foxh1 is a partner of ogg1 in the cardiac development in response to DNA damage.

Methyl-CpG binding-protein 2 function in cholinergic neurons mediates cardiac arrhythmogenesis.

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Herrera, José A; Ward, Christopher S; Wehrens, Xander H T; Neul, Jeffrey L

2016-11-15

Sudden unexpected death occurs in one quarter of deaths in Rett Syndrome (RTT), a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). People with RTT show a variety of autonomic nervous system (ANS) abnormalities and mouse models show similar problems including QTc interval prolongation and hypothermia. To explore the role of cardiac problems in sudden death in RTT, we characterized cardiac rhythm in mice lacking Mecp2 function. Male and female mutant mice exhibited spontaneous cardiac rhythm abnormalities including bradycardic events, sinus pauses, atrioventricular block, premature ventricular contractions, non-sustained ventricular arrhythmias, and increased heart rate variability. Death was associated with spontaneous cardiac arrhythmias and complete conduction block. Atropine treatment reduced cardiac arrhythmias in mutant mice, implicating overactive parasympathetic tone. To explore the role of MeCP2 within the parasympathetic neurons, we selectively removed MeCP2 function from cholinergic neurons (MeCP2 ChAT KO), which recapitulated the cardiac rhythm abnormalities, hypothermia, and early death seen in RTT male mice. Conversely, restoring MeCP2 only in cholinergic neurons rescued these phenotypes. Thus, MeCP2 in cholinergic neurons is necessary and sufficient for autonomic cardiac control, thermoregulation, and survival, and targeting the overactive parasympathetic system may be a useful therapeutic strategy to prevent sudden unexpected death in RTT.

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

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Zhendong Zhang

2014-12-01

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

Exercise improves cardiac autonomic function in obesity and diabetes.

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

2013-05-01

Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

EANM/ESC guidelines for radionuclide imaging of cardiac function

DEFF Research Database (Denmark)

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

2008-01-01

radionuclide ventriculography, gated myocardial perfusion scintigraphy, gated PET, and studies with non-imaging devices for the evaluation of cardiac function. The items covered are presented in 11 sections: clinical indications, radiopharmaceuticals and dosimetry, study acquisition, RV EF, LV EF, LV volumes...

Novel axolotl cardiac function analysis method using magnetic resonance imaging.

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Pedro Gomes Sanches

Full Text Available The salamander axolotl is capable of complete regeneration of amputated heart tissue. However, non-invasive imaging tools for assessing its cardiac function were so far not employed. In this study, cardiac magnetic resonance imaging is introduced as a non-invasive technique to image heart function of axolotls. Three axolotls were imaged with magnetic resonance imaging using a retrospectively gated Fast Low Angle Shot cine sequence. Within one scanning session the axolotl heart was imaged three times in all planes, consecutively. Heart rate, ejection fraction, stroke volume and cardiac output were calculated using three techniques: (1 combined long-axis, (2 short-axis series, and (3 ultrasound (control for heart rate only. All values are presented as mean ± standard deviation. Heart rate (beats per minute among different animals was 32.2±6.0 (long axis, 30.4±5.5 (short axis and 32.7±4.9 (ultrasound and statistically similar regardless of the imaging method (p > 0.05. Ejection fraction (% was 59.6±10.8 (long axis and 48.1±11.3 (short axis and it differed significantly (p = 0.019. Stroke volume (μl/beat was 133.7±33.7 (long axis and 93.2±31.2 (short axis, also differed significantly (p = 0.015. Calculations were consistent among the animals and over three repeated measurements. The heart rate varied depending on depth of anaesthesia. We described a new method for defining and imaging the anatomical planes of the axolotl heart and propose one of our techniques (long axis analysis may prove useful in defining cardiac function in regenerating axolotl hearts.

Decreased Polycystin 2 Levels Result in Non-Renal Cardiac Dysfunction with Aging.

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Kuo, Ivana Y; Duong, Sophie L; Nguyen, Lily; Ehrlich, Barbara E

2016-01-01

Mutations in the gene for polycystin 2 (Pkd2) lead to polycystic kidney disease, however the main cause of mortality in humans is cardiac related. We previously showed that 5 month old Pkd2+/- mice have altered calcium-contractile activity in cardiomyocytes, but have preserved cardiac function. Here, we examined 1 and 9 month old Pkd2+/- mice to determine if decreased amounts of functional polycystin 2 leads to impaired cardiac function with aging. We observed changes in calcium handling proteins in 1 month old Pkd2+/- mice, and these changes were exacerbated in 9 month old Pkd2+/- mice. Anatomically, the 9 month old Pkd2+/- mice had thinner left ventricular walls, consistent with dilated cardiomyopathy, and the left ventricular ejection fraction was decreased. Intriguingly, in response to acute isoproterenol stimulation to examine β-adrenergic responses, the 9 month old Pkd2+/- mice exhibited a stronger contractile response, which also coincided with preserved localization of the β2 adrenergic receptor. Importantly, the Pkd2+/- mice did not have any renal impairment. We conclude that the cardiac-related impact of decreased polycystin 2 progresses over time towards cardiac dysfunction and altered adrenergic signaling. These results provide further evidence that polycystin 2 provides a critical function in the heart, independent of renal involvement.

Importance of circulating IGF-1 for normal cardiac morphology, function and post infarction remodeling.

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Scharin Täng, M; Redfors, B; Lindbom, M; Svensson, J; Ramunddal, T; Ohlsson, C; Shao, Y; Omerovic, E

2012-12-01

IGF-1 plays an important role in cardiovascular homeostasis, and plasma levels of IGF-1 correlate inversely with systolic function in heart failure. It is not known to what extent circulating IGF-1 secreted by the liver and local autocrine/paracrine IGF-1 expressed in the myocardium contribute to these beneficial effects on cardiac function and morphology. In the present study, we used a mouse model of liver-specific inducible deletion of the IGF-1 gene (LI-IGF-1 -/- mouse) in an attempt to evaluate the importance of circulating IGF-I on cardiac morphology and function under normal and pathological conditions, with an emphasis on its regulatory role in myocardial phosphocreatine metabolism. Echocardiography was performed in LI-IGF-1 -/- and control mice at rest and during dobutamine stress, both at baseline and post myocardial infarction (MI). High-energy phosphate metabolites were compared between LI-IGF-1 -/- and control mice at 4 weeks post MI. We found that LI-IGF-1 -/- mice had significantly greater left ventricular dimensions at baseline and showed a greater relative increase in cardiac dimensions, as well as deterioration of cardiac function, post MI. Myocardial creatine content was 17.9% lower in LI-IGF-1 -/- mice, whereas there was no detectable difference in high-energy nucleotides. These findings indicate an important role of circulating IGF-1 in preserving cardiac structure and function both in physiological settings and post MI. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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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.

Assessment of cardiac morphology and ventricular function in healthy Chinese individuals using MRI

International Nuclear Information System (INIS)

Lu Minjie; Zhao Shihua; Jiang Shiliang

2011-01-01

Objective: To investigate reproducibility of cardiac MRI for assessment of cardiac morphology and ventricular function in selected normal Chinese Han population. Methods: Two hundred and sixty-nine normal volunteers underwent cardiac MRI using a 1.5 T MR system. HASTE and steady state free precession imaging were performed with long and short axis images and cine mode through the ventricle with wireless vector cardiac gating. The images were reviewed by two independent observers. The dimensions of cardiac chambers and ventricular function including ejection fraction (EF), end diastolic volume (EDV) , end systolic volume (ESV) and myocardial mass were evaluated. The data between male and female were compared by using two-tailed unpaired t test. Results: Total imaging time was (15±3) min. The anteroposterior diameter of the left atrium was (2.87±0.77) cm, the right atrial diameter perpendicular to the atrial septum was (3.61±0.57) cm, the end diastolic diameter of the left ventricle was (4.97± 0.52) cm, the end diastolic diameter of the right ventricle was (2.65±0.48) cm. On the left ventricle, EF was (60.62±7.08)%, EDV was (115.37±26.71) ml, ESV was (46.02±15.72) ml and LV mass was (82.97±24.03) g. On the right ventricle, EF was (47.73±6.50)%, EDV was (128.27±32.16) ml, ESV was (67.7±21.07) ml and RV mass was (48.24±13.42) g. There were no statistically significant differences in LVESV (P=0.144), LVEDV index (P=0.714), LVESV index (P=0.113), LVCI (P=0.199), RVEF (P=0.296) and RV mass (P=0.093), and statistically significant differences in other cardiac parameters between male and female. Conclusion: Cardiac MRI can provide useful information about cardiac function and morphology with a high level of reproducibility in normal Chinese Han population. (authors)

Evaluating the cardiac function of duchenne muscular dystrophy with Doppler Tei index

International Nuclear Information System (INIS)

Yao Fengjuan; Zheng Ju; Lu Kun; Liu Donghong; Wu Miaoling; Lin Hong; Zhang Cheng; Yu Hongkui

2007-01-01

Objective: To evaluate the cardiac function of early Duchenne muscular dystrophy (DMD) by left ventricular ejection fraction (LVEF) and pulse Doppler Tei index. Methods: Twenty-eight DMD patients and fifteen normal people were studied. LVEF, E/A and Tei index were measured and calculated by M-mode and Pulse wave Doppler respectively. Results: Compared with control group, Tei index and IRT were significantly high, and there were not significant difference in LVEF(%) and E/A. Conclusion: Tei index was valuable in assessing cardiac function of early DMD. (authors)

[Cardiac Synchronization Function Estimation Based on ASM Level Set Segmentation Method].

Science.gov (United States)

Zhang, Yaonan; Gao, Yuan; Tang, Liang; He, Ying; Zhang, Huie

At present, there is no accurate and quantitative methods for the determination of cardiac mechanical synchronism, and quantitative determination of the synchronization function of the four cardiac cavities with medical images has a great clinical value. This paper uses the whole heart ultrasound image sequence, and segments the left & right atriums and left & right ventricles of each frame. After the segmentation, the number of pixels in each cavity and in each frame is recorded, and the areas of the four cavities of the image sequence are therefore obtained. The area change curves of the four cavities are further extracted, and the synchronous information of the four cavities is obtained. Because of the low SNR of Ultrasound images, the boundary lines of cardiac cavities are vague, so the extraction of cardiac contours is still a challenging problem. Therefore, the ASM model information is added to the traditional level set method to force the curve evolution process. According to the experimental results, the improved method improves the accuracy of the segmentation. Furthermore, based on the ventricular segmentation, the right and left ventricular systolic functions are evaluated, mainly according to the area changes. The synchronization of the four cavities of the heart is estimated based on the area changes and the volume changes.

Inhibition of miR-15 Protects Against Cardiac Ischemic Injury

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

2012-01-01

Rationale Myocardial infarction (MI) is a leading cause of death worldwide. Because endogenous cardiac repair mechanisms are not sufficient for meaningful tissue regeneration, MI results in loss of cardiac tissue and detrimental remodeling events. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression in a sequence dependent manner. Our previous data indicate that miRNAs are dysregulated in response to ischemic injury of the heart and actively contribute to cardiac remodeling after MI. Objective This study was designed to determine whether miRNAs are dysregulated on ischemic damage in porcine cardiac tissues and whether locked nucleic acid (LNA)-modified anti-miR chemistries can target cardiac expressed miRNAs to therapeutically inhibit miR-15 on ischemic injury. Methods and Results Our data indicate that the miR-15 family, which includes 6 closely related miRNAs, is regulated in the infarcted region of the heart in response to ischemia-reperfusion injury in mice and pigs. LNA-modified chemistries can effectively silence miR-15 family members in vitro and render cardiomyocytes resistant to hypoxia-induced cardiomyocyte cell death. Correspondingly, systemic delivery of miR-15 anti-miRs dose-dependently represses miR-15 in cardiac tissue of both mice and pigs, whereas therapeutic targeting of miR-15 in mice reduces infarct size and cardiac remodeling and enhances cardiac function in response to MI. Conclusions Oligonucleotide-based therapies using LNA-modified chemistries for modulating cardiac miRNAs in the setting of heart disease are efficacious and validate miR-15 as a potential therapeutic target for the manipulation of cardiac remodeling and function in the setting of ischemic injury. PMID:22052914

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

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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.

Importance of Heart Rate During Exercise for Response to Cardiac Resynchronization Therapy

NARCIS (Netherlands)

Maass, Alexander H.; Buck, Sandra; Nieuwland, Wybe; Bruegemann, Johan; Van Veldhuisen, Dirk J.; Van Gelder, Isabelle C.

Background: Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60-70% of patients. Objectives: To study exercise-related factors predicting response to CRT. Methods: We retrospectively

Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears.

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Nelson, O Lynne; Robbins, Charles T; Wu, Yiming; Granzier, Henk

2008-07-01

The hibernation phenomenon captures biological as well as clinical interests to understand how organs adapt. Here we studied how hibernating grizzly bears (Ursus arctos horribilis) tolerate extremely low heart rates without developing cardiac chamber dilation. We evaluated cardiac filling function in unanesthetized grizzly bears by echocardiography during the active and hibernating period. Because both collagen and titin are involved in altering diastolic function, we investigated both in the myocardium of active and hibernating grizzly bears. Heart rates were reduced from 84 beats/min in active bears to 19 beats/min in hibernating bears. Diastolic volume, stroke volume, and left ventricular ejection fraction were not different. However, left ventricular muscle mass was significantly lower (300 +/- 12 compared with 402 +/- 14 g; P = 0.003) in the hibernating bears, and as a result the diastolic volume-to-left ventricular muscle mass ratio was significantly greater. Early ventricular filling deceleration times (106.4 +/- 14 compared with 143.2 +/- 20 ms; P = 0.002) were shorter during hibernation, suggesting increased ventricular stiffness. Restrictive pulmonary venous flow patterns supported this conclusion. Collagen type I and III comparisons did not reveal differences between the two groups of bears. In contrast, the expression of titin was altered by a significant upregulation of the stiffer N2B isoform at the expense of the more compliant N2BA isoform. The mean ratio of N2BA to N2B titin was 0.73 +/- 0.07 in the active bears and decreased to 0.42 +/- 0.03 (P = 0.006) in the hibernating bears. The upregulation of stiff N2B cardiac titin is a likely explanation for the increased ventricular stiffness that was revealed by echocardiography, and we propose that it plays a role in preventing chamber dilation in hibernating grizzly bears. Thus our work identified changes in the alternative splicing of cardiac titin as a major adaptive response in hibernating grizzly

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

[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.

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

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Samer eAl-Samir

2016-05-01

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

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)

CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

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A. O. Shevchenko

2015-01-01

Full Text Available Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts. Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD pts without decompensated heart failure were included. Along with resistive index (Ri, pulsative index (Pi, and CCW intima-media thickness (IMT, CCW rigidity index (iRIG was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7% and 17 (18.3% cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec2, respectively, p = 0.001. Area under ROC for iRIG was 0.90 ± 0.03 units2. Analysis showed that iRIG values above estimated treshold 7172 cm/sec2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9 sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84

Targeting sodium channels in cardiac arrhythmia

NARCIS (Netherlands)

Remme, Carol Ann; Wilde, Arthur A. M.

2014-01-01

Cardiac voltage-gated sodium channels are responsible for proper electrical conduction in the heart. During acquired pathological conditions and inherited sodium channelopathies, altered sodium channel function causes conduction disturbances and ventricular arrhythmias. Although the clinical,

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

Science.gov (United States)

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

2013-02-01

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

Identification and functional characterization of cardiac pacemaker cells in zebrafish.

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Federico Tessadori

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

Children's expressions of negative emotions and adults' responses during routine cardiac consultations.

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Vatne, Torun M; Ruland, Cornelia M; Ørnes, Knut; Finset, Arnstein

2012-03-01

One function of expressing emotion is to receive support. The aim of this study was to assess how children with heart disease express negative emotions during routine consultations, and examine the interaction between children's expressions and adults' responses. Seventy children, aged 7-13 years, completed measures of anxiety and were videotaped during cardiology visits. Adult-child interactions were analyzed using the Verona Definitions of Emotional Sequences. Children expressed negative emotion, mainly in subtle ways; however, adults rarely recognized and responded to these expressions. The frequency of children's expressions and adults' responses were related to the child's age, level of anxiety, and verbal participation. Children do not openly express negative emotions frequently during routine cardiac consultations; they are more likely to provide subtle cues of negative emotion. When expression of negative emotions does occur, adults may consider using the opportunity to explore the child's emotional experiences.

Cognitive function in patients with stable coronary heart disease: Related cerebrovascular and cardiovascular responses.

Science.gov (United States)

Gayda, Mathieu; Gremeaux, Vincent; Bherer, Louis; Juneau, Martin; Drigny, Joffrey; Dupuy, Olivier; Lapierre, Gabriel; Labelle, Véronique; Fortier, Annik; Nigam, Anil

2017-01-01

Chronic exercise has been shown to prevent or slow age-related decline in cognitive functions in otherwise healthy, asymptomatic individuals. We sought to assess cognitive function in a stable coronary heart disease (CHD) sample and its relationship to cerebral oxygenation-perfusion, cardiac hemodynamic responses, and [Formula: see text] peak compared to age-matched and young healthy control subjects. Twenty-two young healthy controls (YHC), 20 age-matched old healthy controls (OHC) and 25 patients with stable CHD were recruited. Cognitive function assessment included short term-working memory, perceptual abilities, processing speed, cognitive inhibition and flexibility and long-term verbal memory. Maximal cardiopulmonary function (gas exchange analysis), cardiac hemodynamic (impedance cardiography) and left frontal cerebral oxygenation-perfusion (near-infra red spectroscopy) were measured during and after a maximal incremental ergocycle test. Compared to OHC and CHD, YHC had higher [Formula: see text] peak, maximal cardiac index (CI max), cerebral oxygenation-perfusion (ΔO2 Hb, ΔtHb: exercise and recovery) and cognitive function (for all items) (Pcognitive inhibition and flexibility and long-term verbal memory (Pcognitive function (Pcognitive function (Pcognitive function, a similar cerebral oxygenation/perfusion during exercise but reduced one during recovery vs. their aged-matched healthy counterparts. In the all sample, cognitive functions correlated with [Formula: see text] peak, CI max and cerebral oxygenation-perfusion.

Survivors of cardiac arrest with good neurological outcome show considerable impairments of memory functioning.

Science.gov (United States)

Sulzgruber, Patrick; Kliegel, Andreas; Wandaller, Cosima; Uray, Thomas; Losert, Heidrun; Laggner, Anton N; Sterz, Fritz; Kliegel, Matthias

2015-03-01

Deficits in cognitive function are a well-known dysfunction in survivors of cardiac arrest. However, data concerning memory function in this neurological vulnerable patient collective remain scarce and inconclusive. Therefore, we aimed to assess multiple aspects of retrospective and prospective memory performance in patients after cardiac arrest. We prospectively enrolled 33 survivors of cardiac arrest, with cerebral performance categories (CPC) 1 and 2 and a control-group (n=33) matched in sex, age and educational-level. To assess retrospective and prospective memory performance we administrated 4 weeks after cardiac arrest the "Rey Adult Learning Test" (RAVLT), the "Digit-Span-Backwards Test", the "Logic-Memory Test" and the "Red-Pencil Test". Results indicate an impairment in immediate and delayed free recall, but not in recognition. However, the overall impairment in immediate recall was qualified by analyzing RAVLT performance, showing that patients were only impaired in trials 4 and 5 of the learning sequence. Moreover, working and prospective memory as well as prose recall were worse in cardiac arrest survivors. Cranial computed tomography was available in 61% of all patients (n=20) but there was no specific neurological damage detectable that could be linked to this cognitive impairment. Episodic long-term memory functioning appears to be particularly impaired after cardiac arrest. In contrast, short-term memory storage, even tested via free-call, seems not to be affected. Based on cranial computed tomography we suggest that global brain ischemia rather than focal brain lesions appear to underlie these effects. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Detecting early cardiac dysfunction with radionuclide cardiac blood-pool imaging

International Nuclear Information System (INIS)

Wu Kegui; Chen Daguang; Lin Haoxue

1992-01-01

Cardiac function was measured by radionuclide cardiac blood-pool imaging in 15 normal persons, 19 cases of hypertension, 32 cases of coronary heart disease, 35 cases of coronary heart disease combined with hypertension and 44 cases of myocardial infarction. Significant differences have been found in indices of cardiac function between normal subjects and patients with coronary heart disease and coronary heart disease combined with hypertension, even though the patients were without any clinical sin of cardiac failure. Lowered regional EF and decreased ventricular was motion were found in 38.8% of patients, while 65.7%of patients revealed marked abnormality in MFR. The results indicate that latent cardiac dysfunction is common in patients with coronary heart disease. The earliest change is diastolic function abnormalities

Cardiac Myosin Binding Protein-C Autoantibodies Are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome

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Thomas L. Lynch, IVPhD

2017-04-01

Full Text Available Summary: The degradation and release of cardiac myosin binding protein-C (cMyBP-C upon cardiac damage may stimulate an inflammatory response and autoantibody (AAb production. We determined whether the presence of cMyBP-C-AAbs associated with adverse cardiac function in cardiovascular disease patients. Importantly, cMyBP-C-AAbs were significantly detected in acute coronary syndrome patient sera upon arrival to the emergency department, particularly in ST-segment elevation myocardial infarction patients. Patients positive for cMyBP-C-AAbs had reduced left ventricular ejection fraction and elevated levels of clinical biomarkers of myocardial infarction. We conclude that cMyBP-C-AAbs may serve as early predictive indicators of deteriorating cardiac function and patient outcome in acute coronary syndrome patients prior to the infarction. Key Words: acute myocardial infarction, autoantibodies, cardiac myosin binding protein-c, cardiomyopathy

Cardiac MRI in restrictive cardiomyopathy

Energy Technology Data Exchange (ETDEWEB)

Gupta, A. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Singh Gulati, G., E-mail: gulatigurpreet@rediffmail.com [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Seth, S. [Department of Cardiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Sharma, S. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India)

2012-02-15

Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury.

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Jianqin Ye

Full Text Available BACKGROUND: Endogenous cardiac progenitor cells are a promising option for cell-therapy for myocardial infarction (MI. However, obtaining adequate numbers of cardiac progenitors after MI remains a challenge. Cardiospheres (CSs have been proposed to have cardiac regenerative properties; however, their cellular composition and how they may be influenced by the tissue milieu remains unclear. METHODOLOGY/PRINCIPAL FINDING: Using "middle aged" mice as CSs donors, we found that acute MI induced a dramatic increase in the number of CSs in a mouse model of MI, and this increase was attenuated back to baseline over time. We also observed that CSs from post-MI hearts engrafted in ischemic myocardium induced angiogenesis and restored cardiac function. To determine the role of Sca-1(+CD45(- cells within CSs, we cloned these from single cell isolates. Expression of Islet-1 (Isl1 in Sca-1(+CD45(- cells from CSs was 3-fold higher than in whole CSs. Cloned Sca-1(+CD45(- cells had the ability to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. We also observed that cloned cells engrafted in ischemic myocardium induced angiogenesis, differentiated into endothelial and smooth muscle cells and improved cardiac function in post-MI hearts. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate that cloned Sca-1(+CD45(- cells derived from CSs from infarcted "middle aged" hearts are enriched for second heart field (i.e., Isl-1(+ precursors that give rise to both myocardial and vascular tissues, and may be an appropriate source of progenitor cells for autologous cell-therapy post-MI.

Graded Cycling Test Combined With the Talk Test Is Responsive in Cardiac Rehabilitation

DEFF Research Database (Denmark)

Nielsen, Susanne Grøn; Vinther, Anders

2016-01-01

PURPOSE: To evaluate clinical assessment outcome of cardiac rehabilitation, a simple and reliable submaximal exercise test, not based on heart rate, is warranted. The Talk Test (TT) has been found to correlate well with the ventilatory threshold, and excellent reliability was observed for TT...... combined with the Graded Cycling Test (GCT-TT) in cardiac patients. The purpose was to investigate responsiveness of GCT-TT in cardiac rehabilitation patients. METHODS: Patients (n = 93) referred to 8 weeks of cardiac rehabilitation were included. Pre- and posttests were performed using GCT-TT. Mean test...... changes in watts (W) were compared with the standard error of measurement (SEM95) for groups and the smallest real difference (SRD) for individuals. Minimal clinically important difference was assessed by comparing patient perceived changes in physical fitness with the test changes. RESULTS...

Combining computer modelling and cardiac imaging to understand right ventricular pump function.

Science.gov (United States)

Walmsley, John; van Everdingen, Wouter; Cramer, Maarten J; Prinzen, Frits W; Delhaas, Tammo; Lumens, Joost

2017-10-01

Right ventricular (RV) dysfunction is a strong predictor of outcome in heart failure and is a key determinant of exercise capacity. Despite these crucial findings, the RV remains understudied in the clinical, experimental, and computer modelling literature. This review outlines how recent advances in using computer modelling and cardiac imaging synergistically help to understand RV function in health and disease. We begin by highlighting the complexity of interactions that make modelling the RV both challenging and necessary, and then summarize the multiscale modelling approaches used to date to simulate RV pump function in the context of these interactions. We go on to demonstrate how these modelling approaches in combination with cardiac imaging have improved understanding of RV pump function in pulmonary arterial hypertension, arrhythmogenic right ventricular cardiomyopathy, dyssynchronous heart failure and cardiac resynchronization therapy, hypoplastic left heart syndrome, and repaired tetralogy of Fallot. We conclude with a perspective on key issues to be addressed by computational models of the RV in the near future. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

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

DEFF Research Database (Denmark)

Krag, Aleksander; Bendtsen, Flemming; Mortensen, Christian

2010-01-01

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

Effect of prolonged space flight on cardiac function and dimensions

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

1974-01-01

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

Restricted N-terminal truncation of cardiac troponin T: a novel mechanism for functional adaptation to energetic crisis.

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Feng, Han-Zhong; Biesiadecki, Brandon J; Yu, Zhi-Bin; Hossain, M Moazzem; Jin, J-P

2008-07-15

The N-terminal variable region of cardiac troponin T (TnT) is a regulatory structure that can be selectively removed during myocardial ischaemia reperfusion by mu-calpain proteolysis. Here we investigated the pathophysiological significance of this post-translational modification that removes amino acids 1-71 of cardiac TnT. Working heart preparations were employed to study rat acute myocardial infarction and transgenic mouse hearts over-expressing the N-terminal truncated cardiac TnT (cTnT-ND). Ex vivo myocardial infarction by ligation of the left anterior descending coronary artery induced heart failure and produced cTnT-ND not only in the infarct but also in remote zones, including the right ventricular free wall, indicating a whole organ response in the absence of systemic neurohumoral mechanisms. Left ventricular pressure overload in mouse working hearts produced increased cTnT-ND in both ventricles, suggesting a role of haemodynamic stress in triggering an acute whole organ proteolytic regulation. Transgenic mouse hearts in which the endogenous intact cardiac TnT was partially replaced by cTnT-ND showed lowered contractile velocity. When afterload increased from 55 mmHg to 90 mmHg, stroke volume decreased in the wild type but not in the transgenic mouse hearts. Correspondingly, the left ventricular rapid-ejection time of the transgenic mouse hearts was significantly longer than that of wild type hearts, especially at high afterload. The restricted deletion of the N-terminal variable region of cardiac troponin T demonstrates a novel mechanism by which the thin filament regulation adapts to sustain cardiac function under stress conditions.

Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus.

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Gonçalves, N; Gomes-Ferreira, C; Moura, C; Roncon-Albuquerque, R; Leite-Moreira, A F; Falcão-Pires, I

2016-08-15

Diabetic cardiomyopathy is characterized by cardiac structural and functional abnormalities. Additionally, chronic pressure overload conditions are highly prevalent amongst diabetic population and this association leads to a more severe myocardial impairment. The differences in myocardial pathophysiology between type 1 and type 2 diabetes mellitus (DM) still remain to be clarified. Thus, we aimed to investigate biventricular structural and functional changes promoted by the two types of DM and the impact of concomitant chronic pressure overload. Wistar rats were injected with streptozotocin (Type 1 DM, T1DM) or fed with a hypercaloric diet (Type 2 DM, T2DM). Pressure overload was imposed in DM animals by aortic constriction and after 5weeks of DM the cardiac function and structure were evaluated. Both types of DM promoted hypertrophy, increased fibrosis and advanced glycation end-products deposition, in the two ventricles. Interestingly, the induced myocardial alterations were distinct. While T1DM stimulated a pronounced hypertrophy and extracellular matrix remodeling, T2DM induced functional impairment. The negative impact of the association of DM with aortic constriction was more pronounced in T2DM, promoting impaired function and increased stiffness, particularly in the right ventricle. Our study demonstrated that the two types of diabetes induce distinct cardiac alterations per se or when combined with chronic pressure overload. T1DM promoted a more extensive remodeling in cardiac structure while T2DM significantly impaired ventricular function. The impact of pressure overload was more notorious in T2DM as observed by worse myocardial remodeling, suggesting a higher susceptibility to the deleterious effects of chronic pressure overload, namely hypertension, among this diabetic population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Impact of a Non-Functional Thyroid Receptor Beta upon Triiodotironine-Induced Cardiac Hypertrophy in Mice

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Güínever Eustáquio do Império

2015-08-01

Full Text Available Background/Aims: Thyroid hormone (TH signalling is critical for heart function. The heart expresses thyroid hormone receptors (THRs; THRα1 and THRβ1. We aimed to investigate the regulation mechanisms of the THRβ isoform, its association with gene expression changes and implications for cardiac function. Methods: The experiments were performed using adult male mice expressing TRβΔ337T, which contains the Δ337T mutation of the human THRB gene and impairs ligand binding. Cardiac function and RNA expression were studied after hypo-or hyperthyroidism inductions. T3-induced cardiac hypertrophy was not observed in TRβΔ337T mice, showing the fundamental role of THRβ in cardiac hypertrophy. Results: We identified a group of independently regulated THRβ genes, which includes Adrb2, Myh7 and Hcn2 that were normally regulated by T3 in the TRβΔ337T group. However, Adrb1, Myh6 and Atp2a2 were regulated via THRβ. The TRβΔ337T mice exhibited a contractile deficit, decreased ejection fraction and stroke volume, as assessed by echocardiography. In our model, miR-208a and miR-199a may contribute to THRβ-mediated cardiac hypertrophy, as indicated by the absence of T3-regulated ventricular expression in TRβΔ337T mice. Conclusion: THRβ has important role in the regulation of specific mRNA and miRNA in T3-induced cardiac hypertrophic growth and in the alteration of heart functions.

Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

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

2013-11-01

To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study. RSNA, 2013

Cardiac microvascular endothelial cells express a functional Ca+ -sensing receptor.

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Berra Romani, Roberto; Raqeeb, Abdul; Laforenza, Umberto; Scaffino, Manuela Federica; Moccia, Francesco; Avelino-Cruz, Josè Everardo; Oldani, Amanda; Coltrini, Daniela; Milesi, Veronica; Taglietti, Vanni; Tanzi, Franco

2009-01-01

The mechanism whereby extracellular Ca(2+) exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca(2+)-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca(2+)-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd(3+), La(3+) and neomycin, elicited a heterogeneous intracellular Ca(2+) signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP(3)) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na(+)/Ca(2+) exchanger upon substitution of extracellular Na(+) unmasked the Ca(2+) signal triggered by an increase in extracellular Ca(2+) levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca(2+) response to the CaSR agonist La(3+). These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca(2+) from intracellular InsP(3)-sensitive stores. Copyright 2008 S. Karger AG, Basel.

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

Science.gov (United States)

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

2014-08-05

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

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.

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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).

Abnormal autonomic cardiac response to transient hypoxia in sickle cell anemia

International Nuclear Information System (INIS)

Sangkatumvong, S; Khoo, M C K; Coates, T D

2008-01-01

The objective of this study was to non-invasively assess cardiac autonomic control in subjects with sickle cell anemia (SCA) by tracking the changes in heart rate variability (HRV) that occur following brief exposure to a hypoxic stimulus. Five African–American SCA patients and seven healthy control subjects were recruited to participate in this study. Each subject was exposed to a controlled hypoxic stimulus consisting of five breaths of nitrogen. Time-varying spectral analysis of HRV was applied to estimate the cardiac autonomic response to the transient episode of hypoxia. The confounding effects of changes in respiration on the HRV spectral indices were reduced by using a computational model. A significant decrease in the parameters related to parasympathetic control was detected in the post-hypoxic responses of the SCA subjects relative to normal controls. The spectral index related to sympathetic activity, on the other hand, showed a tendency to increase the following hypoxic stimulation, but the change was not significant. This study suggests that there is some degree of cardiovascular autonomic dysfunction in SCA that is revealed by the response to transient hypoxia

Effect of Low Amphetamine Doses on Cardiac Responses to Emotional Stress in Aged Rats

NARCIS (Netherlands)

Nyakas, Csaba; Buwalda, Bauke; Luiten, Paul G.M.; Bohus, Bela

1992-01-01

In young Wistar rats conditioned emotional stress can be characterized by a learned bradycardiac response to an inescapable footshock. In aged rats this bradycardiac response is attenuated and accompanied by suppressed behavioral arousal in response to novelty. In the present study, cardiac

Inhibition of cardiac inward rectifier currents by cationic amphiphilic drugs.

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van der Heyden, M A G; Stary-Weinzinger, A; Sanchez-Chapula, J A

2013-09-01

Cardiac inward rectifier channels belong to three different classes of the KIR channel protein family. The KIR2.x proteins generate the classical inward rectifier current, IK1, while KIR3 and KIR6 members are responsible for the acetylcholine responsive and ATP sensitive inward rectifier currents IKAch and IKATP, respectively. Aberrant function of these channels has been correlated with severe cardiac arrhythmias, indicating their significant contribution to normal cardiac electrophysiology. A common feature of inward rectifier channels is their dependence on the lipid phosphatidyl-4,5-bisphospate (PIP2) interaction for functional activity. Cationic amphiphilic drugs (CADs) are one of the largest classes of pharmaceutical compounds. Several widely used CADs have been associated with inward rectifier current disturbances, and recent evidence points to interference of the channel-PIP2 interaction as the underlying mechanism of action. Here, we will review how six of these well known drugs, used for treatment in various different conditions, interfere in cardiac inward rectifier functioning. In contrast, KIR channel inhibition by the anionic anesthetic thiopental is achieved by a different mechanism of channel-PIP2 interference. We will discuss the latest basic science insights of functional inward rectifier current characteristics, recently derived KIR channel structures and specific PIP2-receptor interactions at the molecular level and provide insight in how these drugs interfere in the structure-function relationships.

The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction.

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Mavrommatis, Evangelos; Shioura, Krystyna M; Los, Tamara; Goldspink, Paul H

2013-09-01

Insulin-like growth factor-1 (IGF-1) isoforms are expressed via alternative splicing. Expression of the minor isoform IGF-1Eb [also known as mechano-growth factor (MGF)] is responsive to cell stress. Since IGF-1 isoforms differ in their E-domain regions, we are interested in determining the biological function of the MGF E-domain. To do so, a synthetic peptide analog was used to gain mechanistic insight into the actions of the E-domain. Treatment of H9c2 cells indicated a rapid cellular uptake mechanism that did not involve IGF-1 receptor activation but resulted in a nuclear localization. Peptide treatment inhibited the intrinsic apoptotic pathway in H9c2 cells subjected to cell stress with sorbitol by preventing the collapse of the mitochondrial membrane potential and inhibition of caspase-3 activation. Therefore, we administered the peptide at the time of myocardial infarction (MI) in mice. At 2 weeks post-MI cardiac function, gene expression and cell death were assayed. A significant decline in both systolic and diastolic function was evident in untreated mice based on PV loop analysis. Delivery of the E-peptide ameliorated the decline in function and resulted in significant preservation of cardiac contractility. Associated with these changes were an inhibition of pathologic hypertrophy and significantly fewer apoptotic nuclei in the viable myocardium of E-peptide-treated mice post-MI. We conclude that administration of the MGF E-domain peptide may provide a means of modulating local tissue IGF-1 autocrine/paracrine actions to preserve cardiac function, prevent cell death, and pathologic remodeling in the heart.

Differential cardiac effects in rats exposed to atmospheric ...

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The results of this study demonstrate that atmospheric smog generated from both isoprene and toluene cause cardiac effects in rats. In addition, it appears that smog from toluene is more toxic in terms of cardiac arrhythmogenicity. Smog, which is a complex mixture of particulate matter and gaseous irritants (ozone, sulfur dioxide, reactive aldehydes), as well as components which react with sunlight to form secondary pollutants, has recently been linked to increased risk of adverse cardiac responses. The components, and therefore health effects, of atmospheric smog are determined by the fuel used to generate them. In this study we examined the difference between isoprene- and toluene-generated smog in causing cardiac effects in rats and hypothesized that both atmospheres would cause cardiac electrical and functional changes in rats. Male Wistar-Kyoto rats were exposed to either atmospheric smog generated by the USEPA’s mobile reaction chamber using either isoprene or toluene, or filtered air for four hours. One day later, rats were anesthetized and left ventricular functional responses to dobutamine were measured using a Millar probe and arrhythmia sensitivity to aconitine. Baseline left ventricular pressure (LVP) was lower in toluene-exposed animals but not isoprene when compared to air. Increases in LVP with increasing doses of dobutamine were impaired only in toluene-exposed rats. Both isoprene and toluene impaired the rate of ventri

Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus

NARCIS (Netherlands)

van der Meer, Rutger W.; Rijzewijk, Luuk J.; de Jong, Hugo W. A. M.; Lamb, Hildo J.; Lubberink, Mark; Romijn, Johannes A.; Bax, Jeroen J.; de Roos, Albert; Kamp, Otto; Paulus, Walter J.; Heine, Robert J.; Lammertsma, Adriaan A.; Smit, Johannes W. A.; Diamant, Michaela

2009-01-01

Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy

Cardiac damage in athlete's heart: When the "supernormal" heart fails!

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Carbone, Andreina; D'Andrea, Antonello; Riegler, Lucia; Scarafile, Raffaella; Pezzullo, Enrica; Martone, Francesca; America, Raffaella; Liccardo, Biagio; Galderisi, Maurizio; Bossone, Eduardo; Calabrò, Raffaele

2017-06-26

Intense exercise may cause heart remodeling to compensate increases in blood pressure or volume by increasing muscle mass. Cardiac changes do not involve only the left ventricle, but all heart chambers. Physiological cardiac modeling in athletes is associated with normal or enhanced cardiac function, but recent studies have documented decrements in left ventricular function during intense exercise and the release of cardiac markers of necrosis in athlete's blood of uncertain significance. Furthermore, cardiac remodeling may predispose athletes to heart disease and result in electrical remodeling, responsible for arrhythmias. Athlete's heart is a physiological condition and does not require a specific treatment. In some conditions, it is important to differentiate the physiological adaptations from pathological conditions, such as hypertrophic cardiomyopathy, arrhythmogenic dysplasia of the right ventricle, and non-compaction myocardium, for the greater risk of sudden cardiac death of these conditions. Moreover, some drugs and performance-enhancing drugs can cause structural alterations and arrhythmias, therefore, their use should be excluded.

Prospective randomized controlled intervention trial: Comprehensive Yogic Breathing Improves Cardiac autonomic functions and Quality of life in Diabetes

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V P Jyotsna

2012-01-01

Full Text Available Aims and Objectives: To assess the effect of Comprehensive Yogic Breathing Program on glycemic control, quality of life, and cardiac autonomic functions in diabetes. Material and Methods: This is a prospective randomized controlled intervention trial. Cardiac autonomic functions were assessed in 120 diabetics. Patients were randomized into two groups, one group receiving standard therapy for diabetes (n = 56 and the other group receiving standard therapy for diabetes and comprehensive yogic breathing program (n = 64. Standard therapy included advice on diet, walk, and oral antidiabetic drugs. Comprehensive yogic breathing program was an interactive session in which Sudarshan kriya yoga, a rhythmic cyclical breathing, preceded by Pranayam was taught under guidance of a certified teacher. Change in fasting, post prandial blood sugars, glycated hemoglobin, and quality of life were assessed. Cardiac autonomic function tests were done before and six months after intervention. Results: There was significant improvement in psychological (P = 0.006 and social domains (P = 0.04 and total quality of life (P = 0.02 in the group practicing comprehensive yogic breathing program as compared to the group following standard therapy alone. In the group following breathing program, the improvement in sympathetic cardiac autonomic functions was statistically significant (P = 0.01, while the change in the standard group was not significant (P = 0.17. When both parasympathetic and sympathetic cardiac autonomic functions were considered, there was a trend toward improvement in patients following comprehensive yogic breathing program (P = 0.07. In the standard therapy group, no change in cardiac autonomic functions was noted (P = 0.76. The parameters of glycemic control were comparable in both groups. Conclusion: There was significant improvement in quality of life and cardiac autonomic functions in the diabetes patients practicing comprehensive yogic breathing

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

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Hong Jin

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

Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection

Science.gov (United States)

See Hoe, Louise E.; Schilling, Jan M.; Tarbit, Emiri; Kiessling, Can J.; Busija, Anna R.; Niesman, Ingrid R.; Du Toit, Eugene; Ashton, Kevin J.; Roth, David M.; Headrick, John P.; Patel, Hemal H.

2014-01-01

Cholesterol-rich caveolar microdomains and associated caveolins influence sarcolemmal ion channel and receptor function and protective stress signaling. However, the importance of membrane cholesterol content to cardiovascular function and myocardial responses to ischemia-reperfusion (I/R) and cardioprotective stimuli are unclear. We assessed the effects of graded cholesterol depletion with methyl-β-cyclodextrin (MβCD) and lifelong knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on cardiac function, I/R tolerance, and opioid receptor (OR)-mediated protection. Langendorff-perfused hearts from young male C57Bl/6 mice were untreated or treated with 0.02–1.0 mM MβCD for 25 min to deplete membrane cholesterol and disrupt caveolae. Hearts were subjected to 25-min ischemia/45-min reperfusion, and the cardioprotective effects of morphine applied either acutely or chronically [sustained ligand-activated preconditioning (SLP)] were assessed. MβCD concentration dependently reduced normoxic contractile function and postischemic outcomes in association with graded (10–30%) reductions in sarcolemmal cholesterol. Cardioprotection with acute morphine was abolished with ≥20 μM MβCD, whereas SLP was more robust and only inhibited with ≥200 μM MβCD. Deletion of Cav-3 also reduced, whereas Cav-3 OE improved, myocardial I/R tolerance. Protection via SLP remained equally effective in Cav-3 KO mice and was additive with innate protection arising with Cav-3 OE. These data reveal the membrane cholesterol dependence of normoxic myocardial and coronary function, I/R tolerance, and OR-mediated cardioprotection in murine hearts (all declining with cholesterol depletion). In contrast, baseline function appears insensitive to Cav-3, whereas cardiac I/R tolerance parallels Cav-3 expression. Novel SLP appears unique, being less sensitive to cholesterol depletion than acute OR protection and arising independently of Cav-3 expression. PMID:25063791

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

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Guo-Dong Li

2016-09-01

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

Proangiogenic scaffolds as functional templates for cardiac tissue engineering

OpenAIRE

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

2010-01-01

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-s...

Titanium dioxide nanoparticle-induced dysfunction of cardiac hemodynamics is involved in cardiac inflammation in mice.

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Hong, Fashui; Wu, Nan; Zhao, Xiangyu; Tian, Yusheng; Zhou, Yingjun; Chen, Ting; Zhai, Yanyu; Ji, Li

2016-12-01

In the past two decades, titanium dioxide nanoparticles (TiO 2 NPs) have been extensively used in medicine, food industry and other daily life, while their possible interactions with the their influence and human body on human health remain not well understood. Thus, the study was designed to examine whether long-term exposure to TiO 2 NPs cause myocardial dysfunction which is involved in cardiac lesions and alter expression of genes and proteins involving inflammatory response in the mouse heart. The findings showed that intragastric feeding for nine consecutive months with TiO 2 NPs resulted in titanium accumulation, infiltration of inflammatory cells and apoptosis of heart, reductions in net increases of body weight, cardiac indices of function (LV systolic pressure, maximal rate of pressure increase over time, maximal rate of pressure decrease over time and coronary flow), and increases in heart indices, cardiac indices of function (LV end-diastolic pressure and heart rate) in mice. TiO 2 NPs also decreased ATP production in the hearts. Furthermore, TiO 2 NPs increased expression of nuclear factor-κB, interleukin-lβ and tumour necrosis factor-α, and reduced expression of anti-inflammatory cytokines including suppressor of cytokine signaling (SOCS) 1 and SOCS3 in the cardiac tissue. These results suggest that TiO 2 NPs may modulate the cardiac function and expression of inflammatory cytokines. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2917-2927, 2016. © 2016 Wiley Periodicals, Inc.

Evaluation of cardiac morphology and function in mitral stenosis using CT

Energy Technology Data Exchange (ETDEWEB)

Ohnishi, Masaki [Chiba Univ. (Japan). School of Medicine

1992-11-01

The purpose of this study was to evaluate cardiac morphology and function in patients with mitral stenosis (MS). The subjects consisted of 96 patients (23 males and 73 females) with MS who underwent plain and contrast-enhanced CT. Follow-up examinations were performed at least twice in 42 patients, including 18 who were examined before and after surgery. The volume of each cardiac chamber was calculated by Simpson's rule and was divided by body surface area (BSA). The average left atrial (LA) volume was 171[+-]80 cm[sup 3]/m[sup 2] BSA in the 96 MS patients, and 46[+-]10 cm[sup 3]/m[sup 2] BSA in normal control subjects. Atrial fibrillation (Af) was present in 61 patients (64%), and left atrial thrombi were detected in 15 (25%) of them. LA volume increased by 16% in 24 patients without surgery during a mean follow-up period of 4.1 years. The LA tended to enlarge more in the patients with a smaller mitral valve area, a larger LA volume at the first examination, or Af. In 18 patients, after open surgery or percutaneous transvenous mitral commissurotomy, pulmonary CT values decreased significantly as a result of the improvement of pulmonary congestion. LA and RA volume decreased significantly and LV volume increased after surgery. It was concluded that CT was useful for evaluating cardiac function and morphological changes, not only by detecting mitral valve calcification and LA thrombi but also by measuring cardiac volume and pulmonary CT values. (author).

Use of 123I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

International Nuclear Information System (INIS)

Maunoury, Christophe; Acar, Philippe; Sidi, Daniel

2003-01-01

Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using 123 I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39±57 months, range 1-168 months) with DCM and left ventricular dysfunction underwent 123 I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20-75 MBq of 123 I-MIBG. Cardiac neuronal uptake of 123 I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%±49% vs 162%±26%, P<0.0001, and LVEF=43%±17% vs 26%±11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (orig.)

Cardiovascular measurement and cardiac function analysis with electron beam computed tomography in health Chinese people (50 cases report)

International Nuclear Information System (INIS)

Lu Bin; Dai Ruping; Zhang Shaoxiong; Bai Hua; Jing Baolian; Cao Cheng; He Sha; Ren Li

1998-01-01

Purpose: To quantitatively measure cardiovascular diameters and function parameters by using electron beam computed tomography, EBCT. Methods: Men 50 health Chinese people accepted EBCT common transverse and short-axis enhanced movie scan (27 men, 23 women, average age 47.7 years.). The transverse scan was used to measure the diameters of the ascending aorta, descending aorta, pulmonary artery and left atrium. The movie study was used to measure the left ventricular myocardium thickness and analysis global, sectional and segmental function of the right and left ventricles. Results: The cardiovascular diameters and cardiac functional parameters were calculated. The diameters and most functional parameters (end syspoble volume, syspole volume, ejection fraction, cardiac-output, cardiac index) of normal Chinese men were greater than those of women (P>0.05). However, the EDV and MyM(myocardium mass) of both ventricles were significant (p<0.01). Conclusion: EBCT is a minimally invasive method for cardiovascular measurement and cardiac function evaluation

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

International Nuclear Information System (INIS)

Wang, Hui; Wang, Lin; Song, Li; Zhang, Yan-Wan; Ye, Jue; Xu, Rui-Xia; Shi, Na; Meng, Xian-Min

2013-01-01

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

The effects of levosimendan in cardiac surgery patients with poor left ventricular function

NARCIS (Netherlands)

de Hert, Stefan G.; Lorsomradee, Suraphong; Cromheecke, Stefanie; van der Linden, Philippe J.

2007-01-01

BACKGROUND: Patients with poor left ventricular function often require inotropic drug support immediately after cardiopulmonary bypass. Levosimendan improves cardiac function by a novel mechanism of action compared to currently available drugs. We hypothesized that, in patients with severely

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo.

Science.gov (United States)

Palpant, Nathan J; D'Alecy, Louis G; Metzger, Joseph M

2009-05-01

Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO(2) challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a beta-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any beta-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.

Image processing of x-ray left ventricular cineangiocardiograms and displays of cardiac functions

International Nuclear Information System (INIS)

Eiho, Shigeru; Yamada, Shigeru; Kuwahara, Michiyoshi

1980-01-01

Cineangiocardiography has been often used as one of the highly helpful techniques to examine the cardiac function. This paper deals with the method of tracing automatically the boundaries of the left ventricle on cineangiocardiograms, the method to evaluate and display various cardiac functions, the method to reconstruct the left ventricular cavity from biplane cineangiocardiograms and the method to display a 3-dimensional shape of the left ventricle reconstructed. Our algorithm of boundary tracing is based on a heuristic search for a local maximum of the changing rate in the gray level of cineangiocardiogram. The boundaries of endocardial margins of the left ventricle on 80 to 120 consecutive frames are automatically traced by our method. By using the detected boundaries of the left ventricle, a lot of quantitative information may be established on the cardiac function. The volume change, the wall motions and the %-shortening are displayed graphically. The motion of the boundary of the left ventricle is displayed on a CRT as a moving picture. The left ventricular cavity is reconstructed from the detected boundaries of the left ventricle on biplane cineangiocardiograms. A reconstructed image can be shown as superimposed lines or halftone planes to produce a 3-dimensional perspective. The %-shortening which shows the contractility of the regional myocardium is displayed on a silhouette of the left ventricle. We can easily recognize the abnormal area of contraction and the level and spread of abnormality from this displayed image. With the use of the system described in this paper, we can grasp the movement of the left ventricle exactly and evaluate the cardiac function quantitatively. (author)

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

Prediction of cardiac sympathetic nerve activity and cardiac functional outcome after treatment in patients with dilated cardiomyopathy. Examination using dobutamine gated blood pool scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Kasama, Shu; Toyama, Takuji; Iwasaki, Tsutomu; Suzuki, Tadashi [Gunma Univ., Maebashi (Japan). School of Medicine; Hoshizaki, Hiroshi; Oshima, Shigeru; Taniguchi, Koichi; Nagai, Ryozo

2000-07-01

This study evaluated whether dobutamine gated blood pool scintigraphy can predict improvement of cardiac sympathetic nerve activity and cardiac function. Sixteen patients (10 men and 6 women, mean age 59{+-}13 years) with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15 {mu}g/kg/min before treatment. Patients were divided into good responders (LVEF increase {>=}15%) 8 patients (GR Group) and poor responders (LVEF increase <15%) 8 patients (PR Group) after treatment with {beta}-blocker or amiodarone with a background treatment of digitalis, diuretics and angiotensin converting enzyme inhibitor. I-123 metaiodobenzylguanidine (MIBG) imaging to evaluate cardiac sympathetic nerve activity and echocardiography were performed before and at one year after treatment. MIBG imaging was obtained 4 hours after tracer injection, and the heart/mediastinum count ratio (H/M ratio) calculated from the anterior planar image and the total defect score (TDS) from the single photon emission computed tomography image. LVEF and left ventricular endo-diastolic dimension (LVDd) were measured by echocardiography and New York Heart Association (NYHA) functional class was evaluated. The GR Group showed TDS decreased from 28{+-}6 to 17{+-}12 (p<0.05), H/M ratio increased from 1.79{+-}0.26 to 2.07{+-}0.32 (p<0.05), LVEF increased from 29{+-}8% to 48{+-}10% (p<0.01), and LVDd decreased from 65{+-}4 mm to 58{+-}5 mm (p<0.05). In contrast, the PR group showed no significant changes in TDS. H/M ratio, LVEF and LVDd. NYHA functional class improved in both groups. The improvement was better in the GR Group than in the PR group. Dobutamine gated blood pool scintigraphy is useful to predict the improvement of the cardiac sympathetic nerve activity and cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy. (author)

Evaluation of cardiac motion and function by cine magnetic resonance imaging

International Nuclear Information System (INIS)

Kondo, Takeshi; Kurokawa, Hiroshi; Anno, Hirofumi

1992-01-01

Cardiac cine magnetic resonance imaging (MRI) was studied to evaluate the cardiac motion and function, and a water-stream phantom study was performed to clarify whether it was possible to quantitatively assess the valvular regurgitation flow by the size of the flow void. In normal subjects, the left ventricular (LV) epicardial apex swung up to the base only a few millimeters, and the mitral annulus ring moved about 14 mm as mean value toward the apex during systole. Those motions of mitral annulus ring may contribute to the left atrial filling. The LV longitudinal shortening and torsions were shown by the tagging method. This tagging method was the best method for estimating cardiac motions. Cardiac cine MRI using software including a modified Simpson's method program and a wall motion analysis program was useful for routine LV volumetry and wall motion analysis because it was a simple and reliable method. Our water-stream phantom studies demonstrated that it might be difficult to perform quantitative evaluation of valvular regurgitation flow by using only the size of the flow void without acquiring information relating to the orifice area. (author)

Toll‐Like Receptor‐2 Mediates Adaptive Cardiac Hypertrophy in Response to Pressure Overload Through Interleukin‐1β Upregulation via Nuclear Factor κB Activation

Science.gov (United States)

Higashikuni, Yasutomi; Tanaka, Kimie; Kato, Megumi; Nureki, Osamu; Hirata, Yasunobu; Nagai, Ryozo; Komuro, Issei; Sata, Masataka

2013-01-01

Background Inflammation is induced in the heart during the development of cardiac hypertrophy. The initiating mechanisms and the role of inflammation in cardiac hypertrophy, however, remain unclear. Toll‐like receptor‐2 (TLR2) recognizes endogenous molecules that induce noninfectious inflammation. Here, we examined the role of TLR2‐mediated inflammation in cardiac hypertrophy. Methods and Results At 2 weeks after transverse aortic constriction, Tlr2−/− mice showed reduced cardiac hypertrophy and fibrosis with greater left ventricular dilatation and impaired systolic function compared with wild‐type mice, which indicated impaired cardiac adaptation in Tlr2−/− mice. Bone marrow transplantation experiment revealed that TLR2 expressed in the heart, but not in bone marrow–derived cells, is important for cardiac adaptive response to pressure overload. In vitro experiments demonstrated that TLR2 signaling can induce cardiomyocyte hypertrophy and fibroblast and vascular endothelial cell proliferation through nuclear factor–κB activation and interleukin‐1β upregulation. Systemic administration of a nuclear factor–κB inhibitor or anti–interleukin‐1β antibodies to wild‐type mice resulted in impaired adaptive cardiac hypertrophy after transverse aortic constriction. We also found that heat shock protein 70, which was increased in murine plasma after transverse aortic constriction, can activate TLR2 signaling in vitro and in vivo. Systemic administration of anti–heat shock protein 70 antibodies to wild‐type mice impaired adaptive cardiac hypertrophy after transverse aortic constriction. Conclusions Our results demonstrate that TLR2‐mediated inflammation induced by extracellularly released heat shock protein 70 is essential for adaptive cardiac hypertrophy in response to pressure overload. Thus, modulation of TLR2 signaling in the heart may provide a novel strategy for treating heart failure due to inadequate adaptation to hemodynamic

Impact of titin strain on the cardiac slow force response.

Science.gov (United States)

Ait-Mou, Younss; Zhang, Mengjie; Martin, Jody L; Greaser, Marion L; de Tombe, Pieter P

2017-11-01

Stretch of myocardium, such as occurs upon increased filling of the cardiac chamber, induces two distinct responses: an immediate increase in twitch force followed by a slower increase in twitch force that develops over the course of several minutes. The immediate response is due, in part, to modulation of myofilament Ca 2+ sensitivity by sarcomere length (SL). The slowly developing force response, termed the Slow Force Response (SFR), is caused by a slowly developing increase in intracellular Ca 2+ upon sustained stretch. A blunted immediate force response was recently reported for myocardium isolated from homozygous giant titin mutant rats (HM) compared to muscle from wild-type littermates (WT). Here, we examined the impact of titin isoform on the SFR. Right ventricular trabeculae were isolated and mounted in an experimental chamber. SL was measured by laser diffraction. The SFR was recorded in response to a 0.2 μm SL stretch in the presence of [Ca 2+ ] o  = 0.4 mM, a bathing concentration reflecting ∼50% of maximum twitch force development at 25 °C. Presence of the giant titin isoform (HM) was associated with a significant reduction in diastolic passive force upon stretch, and ∼50% reduction of the magnitude of the SFR; the rate of SFR development was unaffected. The sustained SL stretch was identical in both muscle groups. Therefore, our data suggest that cytoskeletal strain may underlie directly the cellular mechanisms that lead to the increased intracellular [Ca 2+ ] i that causes the SFR, possibly by involving cardiac myocyte integrin signaling pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

Self-reported physical activity and lung function two months after cardiac surgery--a prospective cohort study.

Science.gov (United States)

Jonsson, Marcus; Urell, Charlotte; Emtner, Margareta; Westerdahl, Elisabeth

2014-03-28

Physical activity has well-established positive health-related effects. Sedentary behaviour has been associated with postoperative complications and mortality after cardiac surgery. Patients undergoing cardiac surgery often suffer from impaired lung function postoperatively. The association between physical activity and lung function in cardiac surgery patients has not previously been reported. Patients undergoing cardiac surgery were followed up two months postoperatively. Physical activity was assessed on a four-category scale (sedentary, moderate activity, moderate regular exercise, and regular activity and exercise), modified from the Swedish National Institute of Public Health's national survey. Formal lung function testing was performed preoperatively and two months postoperatively. The sample included 283 patients (82% male). Two months after surgery, the level of physical activity had increased (p < 0.001) in the whole sample. Patients who remained active or increased their level of physical activity had significantly better recovery of lung function than patients who remained sedentary or had decreased their level of activity postoperatively in terms of vital capacity (94 ± 11% of preoperative value vs. 91 ± 9%; p = 0.03), inspiratory capacity (94 ± 14% vs. 88 ± 19%; p = 0.008), and total lung capacity (96 ± 11% vs. 90 ± 11%; p = 0.01). An increased level of physical activity, compared to preoperative level, was reported as early as two months after surgery. Our data shows that there could be a significant association between physical activity and recovery of lung function after cardiac surgery. The relationship between objectively measured physical activity and postoperative pulmonary recovery needs to be further examined to verify these results.

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

Science.gov (United States)

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

2014-01-01

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

Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats.

Science.gov (United States)

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

2016-12-01

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

Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts.

Science.gov (United States)

Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; Patterson, Natalie L; McMullen, Julie R

2018-01-01

The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation. This includes cardiac excitation and contraction, mitochondrial adaptations, cellular stress responses to promote survival (heat shock response, ubiquitin-proteasome system, autophagy-lysosomal system, endoplasmic reticulum unfolded protein response, DNA damage response), extracellular matrix, inflammatory response, and organ-to-organ crosstalk. We summarize therapeutic strategies targeting known regulators of exercise-induced protection and the challenges translating findings from bench to bedside. We conclude that technological advancements that allow for in-depth profiling of the genome, transcriptome, proteome and metabolome, combined with animal and human studies, provide new opportunities for comprehensively defining the signaling and regulatory aspects of cell/organelle functions that underpin the protective properties of exercise. This is likely to lead to the identification of novel biomarkers and therapeutic targets for heart disease.

Cardiodynamicsgram: a novel tool for monitoring cardiac function in exercise training.

Science.gov (United States)

Wen, Xu; Guo, Bokai; Gong, Yinglan; Xia, Ling; Yu, Jie

2018-04-27

This study evaluated the feasibility of cardiodynamicsgram (CDG) for monitoring the cardiac functions of athletes and exercisers. CDG could provide an effective, simple, and economical tool for exercise training. Seventeen middle-distance race athletes aged 14-28 years old were recruited. CDG tests and blood test including creatine kinase (CK), CK-MB isoenzyme, and high-sensitivity troponin I (hsTnI) were performed before a high-intensity prolonged training, as well as 2 and 14 h after training, respectively. The CDG test result was unsatisfactory when the CK test result was used as standard. However, the accuracy of CDG test was about 80% when CK-MB and hsTnI were used as standards. Thus, CDG offers a noninvasive, simple, and economical approach for monitoring the cardiac function of athletes and exercisers during exercise training. Nonetheless, the applicability of CDG needs further investigation.

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

Directory of Open Access Journals (Sweden)

Leela K Lella

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

Immune function surveillance: association with rejection, infection and cardiac allograft vasculopathy.

Science.gov (United States)

Heikal, N M; Bader, F M; Martins, T B; Pavlov, I Y; Wilson, A R; Barakat, M; Stehlik, J; Kfoury, A G; Gilbert, E M; Delgado, J C; Hill, H R

2013-01-01

Rejection, cardiac allograft vasculopathy (CAV), and infection are significant causes of mortality in heart transplantation recipients. Assessing the immune status of a particular patient remains challenging. Although endomyocardial biopsy (EMB) and angiography are effective for the identification of rejection and CAV, respectively, these are expensive, invasive, and may have numerous complications. The aim of this study was to evaluate the immune function and assess its utility in predicting rejection, CAV, and infection in heart transplantation recipients. We prospectively obtained samples at the time of routine EMB and when clinically indicated for measurement of the ImmuKnow assay (IM), 12 cytokines and soluble CD30 (sCD30). EMB specimens were evaluated for acute cellular rejection, and antibody-mediated rejection (AMR). CAV was diagnosed by the development of angiographic coronary artery disease. Infectious episodes occurring during the next 30 days after testing were identified by the presence of positive bacterial or fungal cultures and/or viremia that prompted treatment with antimicrobials. We collected 162 samples from 56 cardiac transplant recipients. There were 31 infection episodes, 7 AMR, and 4 CAV cases. The average IM value was significantly lower during infection, (P = .04). Soluble CD30 concentrations showed significantly positive correlation with infection episodes, (P = .001). Significant positive correlation was observed between interleukin-5(IL-5) and AMR episodes (P = .008). Tumor necrosis factor-α and IL-8 showed significant positive correlation with CAV (P = .001). Immune function monitoring appears promising in predicting rejection, CAV, and infection in cardiac transplantation recipients. This approach may help in more individualized immunosuppression and it may also minimize unnecessary EMBs and cardiac angiographies. Published by Elsevier Inc.

Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat

International Nuclear Information System (INIS)

Benderitter, M.; Assem, M.; Maupoil, V.

1995-01-01

During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional response of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glustathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probable due to the production of free radical species associated with the development of inflammation. 49 refs., 8 figs., 1 tab

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

Energy Technology Data Exchange (ETDEWEB)

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

2002-11-01

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

Pulse wave velocity and cardiac autonomic function in type 2 diabetes mellitus.

Science.gov (United States)

Chorepsima, Stamatina; Eleftheriadou, Ioanna; Tentolouris, Anastasios; Moyssakis, Ioannis; Protogerou, Athanasios; Kokkinos, Alexandros; Sfikakis, Petros P; Tentolouris, Nikolaos

2017-05-19

Increased carotid-femoral pulse wave velocity (PWV) has been associated with incident cardiovascular disease, independently of traditional risk factors. Cardiac autonomic dysfunction is a common complication of diabetes and has been associated with reduced aortic distensibility. However, the association of cardiac autonomic dysfunction with PWV is not known. In this study we examined the association between cardiac autonomic function and PWV in subjects with type 2 diabetes mellitus. A total of 290 patients with type 2 diabetes were examined. PWV was measured at the carotid-femoral segment with applanation tonometry. Central mean arterial blood pressure (MBP) was determined by the same apparatus. Participants were classified as having normal (n = 193) or abnormal (n = 97) PWV values using age-corrected values. Cardiac autonomic nervous system activity was determined by measurement of parameters of heart rate variability (HRV). Subjects with abnormal PWV were older, had higher arterial blood pressure and higher heart rate than those with normal PWV. Most of the values of HRV were significantly lower in subjects with abnormal than in those with normal PWV. Multivariate analysis, after controlling for various confounding factors, demonstrated that abnormal PWV was associated independently only with peripheral MBP [odds ratio (OR) 1.049, 95% confidence intervals (CI) 1.015-1.085, P = 0.005], central MBP (OR 1.052, 95% CI 1.016-1.088, P = 0.004), log total power (OR 0.490, 95% CI 0.258-0.932, P = 0.030) and log high frequency power (OR 0.546, 95% CI 0.301-0.991, P = 0.047). In subjects with type 2 diabetes, arterial blood pressure and impaired cardiac autonomic function is associated independently with abnormal PWV.

Use of {sup 123}I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

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Maunoury, Christophe [Service de Medecine Nucleaire, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75743, Paris Cedex 15 (France); Acar, Philippe; Sidi, Daniel [Service de Cardiologie Pediatrique, Hopital Necker-Enfants Malades, Paris (France)

2003-12-01

Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using {sup 123}I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39{+-}57 months, range 1-168 months) with DCM and left ventricular dysfunction underwent {sup 123}I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20-75 MBq of {sup 123}I-MIBG. Cardiac neuronal uptake of {sup 123}I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%{+-}49% vs 162%{+-}26%, P<0.0001, and LVEF=43%{+-}17% vs 26%{+-}11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (orig.)

Heme oxygenase-1 induction improves cardiac function following myocardial ischemia by reducing oxidative stress.

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Yossi Issan

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

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

Science.gov (United States)

Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

2006-03-01

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

The relationship between the hypokalaemic response to adrenaline, beta-adrenoceptors, and Na(+)-K+ pumps in skeletal and cardiac muscle membranes in the rabbit

International Nuclear Information System (INIS)

Elfellah, M.S.; Reid, J.L.

1990-01-01

The hypokalaemic response to adrenaline and the involvement of beta-adrenoceptors and Na(+)-K+ pumps were investigated in control rabbits and animals chronically pretreated with adrenaline. The hypokalaemic response to acute intravenous infusion of adrenaline was significantly reduced when rabbits were chronically pretreated with adrenaline for 10 days. Chronic pretreatment of rabbits with adrenaline significantly reduced the densities for [125I]cyanopindolol and [3H]ouabain binding sites in skeletal muscle and heart. Furthermore, there was a strong positive correlation (r = 0.97, p less than 0.001) between the Bmax for ICYP and [3H]ouabain, in the rabbit heart. Ouabain-sensitive 86Rb uptake and the activity of 3-O-methylfluorescein phosphate phosphatase were used to assess the function of the Na(+)-K+ pump in skeletal and cardiac muscle. There was no significant difference in these functional indices of the Na(+)-K+ pump between the control and adrenaline-pretreated animals, in skeletal or cardiac muscle. Thus, downregulation of the [3H]ouabain binding sites did not appear to be accompanied by reduced function of the Na(+)-K+ pump. Additional investigations are required to confirm further the dissociation between the function of the pump and the ouabain binding sites

Persistence of normal cardiac function and myocardial perfusion in irradiated long-term survivors of Hodgkin's disease

International Nuclear Information System (INIS)

Constine, L.S.; Schwartz, R.G.; Savage, D.E.; King, V.; Muhs, A.; Rubin, P.

1996-01-01

Purpose: The risk of myocardial infarction and cardiac dysfunction following mantle irradiation (RT) for Hodgkin's disease is controversial. The relative risk of fatal myocardial infarction is 2.8 in our Hodgkin's patients, similar to other reports. Sensitive evaluations of cardiac function and myocardial perfusion might be expected to reveal pre-clinical abnormalities of potential significance. We hypothesized the presence of pre-clinical cardiac toxicity and progressive deterioration of left ventricular performance and myocardial ischemia over time in long-term survivors of Hodgkin's disease. The data reported herein extend our previous study in patient number (n=50) and follow-up duration (mean 16.5 years). Materials and Methods: Equilibrium radionuclide angiocardiography (ERNA) was used to quantify left ventricular (LV) systolic and diastolic function with LV ejection fraction (LVEF) and peak filling rate (PFR), respectively. Quantitative myocardial perfusion scintigraphy (MPS) and ECG stress testing with exercise or dipyridamole were used to assess myocardial perfusion and electrical function. Patients at least 1.0 year after RT were eligible if ≤ 50 years old at RT and without known Hodgkin's or cardiac disease. Fifty patients, ages 10-46 years (mean 26.0) at RT, were tested 1.1 to 29.1 years (mean 9.1) after RT. Seventeen patients were tested 2 - 3 times separated by 0.5 - 6.5 years (mean 3.3). The mean central cardiac RT dose was 35.1 Gy (range 18.5 - 47.5) in daily 1.5-2.0 Gy fractions. Twelve patients were additionally irradiated to the left ventricle (LVRT), usually through partial transmission left lung shields (range 14.3-21.3 Gy). Results: No patient had symptomatic cardiac disease at the time of evaluation. The mean LVEF (first test, n = 50) was 60 ± 6% (range 42-73%) [normal ≥ 50%], and PFR (first test, n=44) was 3.43 ± 0.83 end diastolic volume per second (range 1.5-5.2 EDV/sec) [normal ≥ 2.54 EDV/sec] with 2 and 7 patients below normal

Relationship between myocardial T2* values and cardiac volumetric and functional parameters in β-thalassemia patients evaluated by cardiac magnetic resonance in association with serum ferritin levels

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Liguori, Carlo, E-mail: c.liguori@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Pitocco, Francesca, E-mail: f.pitocco@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Di Giampietro, Ilenia, E-mail: i.digiampietro@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Vivo, Aldo Eros de, E-mail: devivoeros@gmail.com [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Schena, Emiliano, E-mail: e.schena@unicampus.it [Unit of Measurements and Biomedical Instrumentation, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy); Cianciulli, Paolo, E-mail: CIANCIULLI.PAOLO@aslrmc.it [Thalassemia Unit, Ospedale Sant Eugenio, Piazzale dell’Umanesimo 10, 00143 Rome (Italy); Zobel, Bruno Beomonte, E-mail: b.zobel@unicampus.it [Department of Diagnostic Imaging, Campus Bio Medico University, via Alvaro del Portillo 200, 00128 Rome (Italy)

2013-09-15

Purpose: Myocardial T2* cardiovascular magnetic resonance provides a rapid and reproducible assessment of cardiac iron load in thalassemia patients. Although cardiac involvement is mainly characterized by left ventricular dysfunction caused by iron overload, little is known about right ventricular function. The aim of this study was to assess the relationship between T2* value in myocardium and left–right ventricular volumetric and functional parameters and to evaluate the existing associations between left–right ventricles volumetric and functional parameter, myocardial T2* values and blood ferritin levels. Materials and methods: A retrospective analysis of 208 patients with β-thalassemia major and thalassemia intermedia was performed (109 males and 99 females; mean age 37.7 ± 13 years; 143 thalassemia major, 65 thalassemia intermedia). Myocardial iron load was assessed by T2* measurements, and volumetric functions were analyzed using the steady state free precession sequence. Results: A significant correlation was observed between EFLV and T2* (p = 0.0001), EFRV and T2* (p = 0.0279). An inverse correlation was present between DVLV and T2* (p = 0.0468), SVLV and T2* (p = 0.0003), SVRV and T2* (p = 0.0001). There was no significant correlation between cardiac T2* and LV–RV mass indices. A significant correlation was observed between T2* and serum ferritin levels (p < 0.001) and between EFLV and serum ferritin (p < 0.05). Conclusion: Myocardial iron load assessed by T2* cardiac magnetic resonance is associated with deterioration in left–right ventricular function; this is more evident when T2* values fall below 14 ms. CMR appears to be a promising approach for cardiac risk evaluation in TM patients.

Relationship between myocardial T2* values and cardiac volumetric and functional parameters in β-thalassemia patients evaluated by cardiac magnetic resonance in association with serum ferritin levels

International Nuclear Information System (INIS)

Liguori, Carlo; Pitocco, Francesca; Di Giampietro, Ilenia; Vivo, Aldo Eros de; Schena, Emiliano; Cianciulli, Paolo; Zobel, Bruno Beomonte

2013-01-01

Purpose: Myocardial T2* cardiovascular magnetic resonance provides a rapid and reproducible assessment of cardiac iron load in thalassemia patients. Although cardiac involvement is mainly characterized by left ventricular dysfunction caused by iron overload, little is known about right ventricular function. The aim of this study was to assess the relationship between T2* value in myocardium and left–right ventricular volumetric and functional parameters and to evaluate the existing associations between left–right ventricles volumetric and functional parameter, myocardial T2* values and blood ferritin levels. Materials and methods: A retrospective analysis of 208 patients with β-thalassemia major and thalassemia intermedia was performed (109 males and 99 females; mean age 37.7 ± 13 years; 143 thalassemia major, 65 thalassemia intermedia). Myocardial iron load was assessed by T2* measurements, and volumetric functions were analyzed using the steady state free precession sequence. Results: A significant correlation was observed between EFLV and T2* (p = 0.0001), EFRV and T2* (p = 0.0279). An inverse correlation was present between DVLV and T2* (p = 0.0468), SVLV and T2* (p = 0.0003), SVRV and T2* (p = 0.0001). There was no significant correlation between cardiac T2* and LV–RV mass indices. A significant correlation was observed between T2* and serum ferritin levels (p < 0.001) and between EFLV and serum ferritin (p < 0.05). Conclusion: Myocardial iron load assessed by T2* cardiac magnetic resonance is associated with deterioration in left–right ventricular function; this is more evident when T2* values fall below 14 ms. CMR appears to be a promising approach for cardiac risk evaluation in TM patients

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

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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.

Functional Assessment of Cardiac Responses of Adult Zebrafish (Danio rerio to Acute and Chronic Temperature Change Using High-Resolution Echocardiography.

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Ling Lee

Full Text Available The zebrafish (Danio rerio is an important organism as a model for understanding vertebrate cardiovascular development. However, little is known about adult ZF cardiac function and how contractile function changes to cope with fluctuations in ambient temperature. The goals of this study were to: 1 determine if high resolution echocardiography (HRE in the presence of reduced cardiodepressant anesthetics could be used to accurately investigate the structural and functional properties of the ZF heart and 2 if the effect of ambient temperature changes both acutely and chronically could be determined non-invasively using HRE in vivo. Heart rate (HR appears to be the critical factor in modifying cardiac output (CO with ambient temperature fluctuation as it increases from 78 ± 5.9 bpm at 18°C to 162 ± 9.7 bpm at 28°C regardless of acclimation state (cold acclimated CA- 18°C; warm acclimated WA- 28°C. Stroke volume (SV is highest when the ambient temperature matches the acclimation temperature, though this difference did not constitute a significant effect (CA 1.17 ± 0.15 μL at 18°C vs 1.06 ± 0.14 μl at 28°C; WA 1.10 ± 0.13 μL at 18°C vs 1.12 ± 0.12 μl at 28°C. The isovolumetric contraction time (IVCT was significantly shorter in CA fish at 18°C. The CA group showed improved systolic function at 18°C in comparison to the WA group with significant increases in both ejection fraction and fractional shortening and decreases in IVCT. The decreased early peak (E velocity and early peak velocity / atrial peak velocity (E/A ratio in the CA group are likely associated with increased reliance on atrial contraction for ventricular filling.

Distributed predictive control of spiral wave in cardiac excitable media

International Nuclear Information System (INIS)

Zheng-Ning, Gan; Xin-Ming, Cheng

2010-01-01

In this paper, we propose the distributed predictive control strategies of spiral wave in cardiac excitable media. The modified FitzHugh–Nagumo model was used to express the cardiac excitable media approximately. Based on the control-Lyapunov theory, we obtained the distributed control equation, which consists of a positive control-Lyapunov function and a positive cost function. Using the equation, we investigate two kinds of robust control strategies: the time-dependent distributed control strategy and the space-time dependent distributed control strategy. The feasibility of the strategies was demonstrated via an illustrative example, in which the spiral wave was prevented to occur, and the possibility for inducing ventricular fibrillation was eliminated. The strategies are helpful in designing various cardiac devices. Since the second strategy is more efficient and robust than the first one, and the response time in the second strategy is far less than that in the first one, the former is suitable for the quick-response control systems. In addition, our spatiotemporal control strategies, especially the second strategy, can be applied to other cardiac models, even to other reaction-diffusion systems. (general)

Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

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Haddad, Rami, E-mail: rami.haddad@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Kasneci, Amanda, E-mail: amanda.kasneci@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Mepham, Kathryn, E-mail: katherine.mepham@mail.mcgill.ca [Lady Davis Institute for Medical Research, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); Division of Experimental Medicine, Department of Medicine, McGill University, 850 Sherbrooke Street, Montréal, Québec, Canada H3A 1A2 (Canada); Sebag, Igal A., E-mail: igal.sebag@mcgill.ca [Division of Cardiology, Jewish General Hospital, 3755 chemin Cote Ste Catherine, Montréal, Québec, Canada H3T 1E2 (Canada); and others

2013-01-01

Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

Emotional Body Odors as Context: Effects on Cardiac and Subjective Responses.

Science.gov (United States)

Ferreira, Jacqueline; Parma, Valentina; Alho, Laura; Silva, Carlos F; Soares, Sandra C

2018-05-23

Many studies have indicated that the chemical cues from body odors (BOs) of donors experiencing negative emotions can influence the psychophysiological and behavioral response of the observers. However, these olfactory cues have been used mainly as contextual information for processing visual stimuli. Here, for the first time, we evaluate how emotional BO affects the emotional tone of a subsequent BO message. Axillary sweat samples were taken from 20 donors in 3 separate sessions while they watched fear, disgust, or neutral videos. In a double-blind experiment, we assessed the cardiac and subjective responses from 69 participants who were either exposed to negative emotional or neutral BOs. Our results showed a reduced cardiac parasympathetic activity (HF%)-indicating increased stress-when participants smelled the emotional BOs before the neutral BOs, compared to when they smelled neutral followed by emotional BOs. The intensity of the neutral odor also increased following the exposure to both negative BOs. These findings indicate that BOs contain an emotion-dependent chemical cue that affects the perceiver both at the physiological and subjective levels.

Functional significance of cardiac reinnervation in heart transplant recipients.

Science.gov (United States)

Schwaiblmair, M; von Scheidt, W; Uberfuhr, P; Ziegler, S; Schwaiger, M; Reichart, B; Vogelmeier, C

1999-09-01

There is accumulating evidence of structural sympathetic reinnervation after human cardiac transplantation. However, the functional significance of reinnervation in terms of exercise capacity has not been established as yet; we therefore investigated the influence of reinnervation on cardiopulmonary exercise testing. After orthotopic heart transplantation 35 patients (mean age, 49.1 +/- 8.4 years) underwent positron emission tomography with scintigraphically measured uptake of C11-hydroxyephedrine (HED), lung function testing, and cardiopulmonary exercise testing. Two groups were defined based on scintigraphic findings, indicating a denervated group (n = 15) with a HED uptake of 5.45%/min and a reinnervated group (n = 20) with a HED uptake of 10.59%/min. The two study groups did not show significant differences with regard to anthropometric data, number of rejection episodes, preoperative hemodynamics, and postoperative lung function data. The reinnervated group had a significant longer time interval from transplantation (1625 +/- 1069 versus 800 +/- 1316 days, p exercise (137 +/- 15 versus 120 +/- 20 beats/min, p = .012), peak oxygen uptake (21.0 +/- 4 versus 16.1 +/- 5 mL/min/kg, p = .006), peak oxygen pulse (12.4 +/- 2.9 versus 10.2 +/- 2.7 mL/min/beat, p = .031), and anaerobic threshold (11.2 +/- 1.8 versus 9.5 +/- 2.1 mL/min, p = .046) were significantly increased in comparison to denervated transplant recipients. Additionally, a decreased functional dead space ventilation (0.24 +/- 0.05 versus 0.30 +/- 0.05, p = .004) was observed in the reinnervated group. Our study results support the hypothesis that partial sympathetic reinnervation after cardiac transplantation is of functional significance. Sympathetic reinnervation enables an increased peak oxygen uptake. This is most probably due to partial restoration of the chronotropic and inotropic competence of the heart as well as an improved oxygen delivery to the exercising muscles and a reduced ventilation

Cardiac tumors: optimal cardiac MR sequences and spectrum of imaging appearances.

LENUS (Irish Health Repository)

O'Donnell, David H

2012-02-01

OBJECTIVE: This article reviews the optimal cardiac MRI sequences for and the spectrum of imaging appearances of cardiac tumors. CONCLUSION: Recent technologic advances in cardiac MRI have resulted in the rapid acquisition of images of the heart with high spatial and temporal resolution and excellent myocardial tissue characterization. Cardiac MRI provides optimal assessment of the location, functional characteristics, and soft-tissue features of cardiac tumors, allowing accurate differentiation of benign and malignant lesions.

Impact of thoracic surgery on cardiac morphology and function in small animal models of heart disease: a cardiac MRI study in rats.

Directory of Open Access Journals (Sweden)

Peter Nordbeck

Full Text Available BACKGROUND: Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies. METHODS: Female Wistar rats (n = 6 per group were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition. RESULTS: Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05 and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05 after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw, such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05, or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05. Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass, but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease. CONCLUSION: Cardio-thoracic surgical procedures in experimental myocardial infarction

Use of the cardiopulmonary flow index to evaluate cardiac function in thoroughbred horses

International Nuclear Information System (INIS)

Guthrie, A.J.; Killeen, V.M.; Grosskopf, J.F.W.

1991-01-01

The ratio of the cardiopulmonary blood volume to stroke volume is called the cardiopulmonary flow index (CPFI). The CPFI can be determined indirectly from the simultaneous recording of a radiocardiogram and an electrocardiogram. The CPFI and cardiac output were measured simultaneously in horses that were diagnosed as having cardiac disease. The results obtained from these subjects were compared with those from control animals and significant differences were found between the mean CPFI of the control horses and those with macroscopically visible myocardial fibrosis on post mortem examination. No significant differences were found between the means of the cardiac output measured in either of the groups of horses. The effect of pharmacological acceleration of the heart rate on the CPFI was also studied. Significant differences were found between the mean CPFI and the slopes of the regression lines of CPFI on heart rate of the control and principal groups of horses. These differences were greatest at heart rates near to the resting heart rates of the individuals. The CPFI was found to be a more sensitive measure of cardiac function than cardiac output, in the horses. 16 refs., 2 figs., 2 tabs

Hemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans

Science.gov (United States)

Convertino, V. A.; Thompson, C. A.; Benjamin, B. A.; Keil, L. C.; Savin, W. M.; Gordon, E. P.; Haskell, W. L.; Schroeder, J. S.; Sandler, H.

1990-01-01

Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in ten cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 deg head down tilt (HDT) followed by 20 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15, and 30 min of HDT, and 5, 15, and 30 min of seated recovery. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Resting plasma volume (PV) was measured by Evans blue dye and percent changes in PV during posture changes were calculated from changes in hematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. Results indicate that cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man.

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

NARCIS (Netherlands)

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

2011-01-01

Factors secreted by the heart, referred to as "cardiokines," have diverse actions in the maintenance of cardiac homeostasis and remodeling. Follistatin-like 1 (Fstl1) is a secreted glycoprotein expressed in the adult heart and is induced in response to injurious conditions that promote myocardial

Investigations of new cardiac functional imaging using Fourier analysis of gated blood-pool study

International Nuclear Information System (INIS)

Maeda, H.; Takeda, K.; Nakagawa, T.; Yamaguchi, N.; Taguchi, M.; Konishi, T.; Hamada, M.

1982-01-01

A new cardiac functional imaging, using temporal Fourier analysis of 28-frame gated cardiac blood-pool studies, was developed. A time-activity curve of each pixel was approximated by its Fourier series. Approximation by the sum for terms to the 3rd frequency of its Fourier series was considered to be most reasonable because of having the least aberration due to statistical fluctuation and close agreement between the global left ventricular curve and the regional fitted curves in normal subjects. To evaluate the ventricular systolic and diastolic performances, 9 parameters were analyzed from thus fitted curves on a pixel-by-pixel basis and displayed on a colour CRT in 64x64 matrix form. In patients with hypertrophic obstructive cardiomyopathy and other cardiac lesions, detailed information on the regional ventricular systolic and diastolic performances was clearly visualized by this method, which was difficult to obtain from the usual functional images of phase and amplitude at the fundamental frequency alone

Chronic mitral regurgitation detected on cardiac MDCT: differentiation between functional and valvular aetiologies.

LENUS (Irish Health Repository)

Killeen, Ronan P

2012-02-01

OBJECTIVE: To determine whether cardiac computed tomography (MDCT) can differentiate between functional and valvular aetiologies of chronic mitral regurgitation (MR) compared with echocardiography (TTE). METHODS: Twenty-seven patients with functional or valvular MR diagnosed by TTE and 19 controls prospectively underwent cardiac MDCT. The morphological appearance of the mitral valve (MV) leaflets, MV geometry, MV leaflet angle, left ventricular (LV) sphericity and global\\/regional wall motion were analysed. The coronary arteries were evaluated for obstructive atherosclerosis. RESULTS: All control and MR cases were correctly identified by MDCT. Significant differences were detected between valvular and control groups for anterior leaflet length (30 +\\/- 7 mm vs. 22 +\\/- 4 mm, P < 0.02) and thickness (3.0 +\\/- 1 mm vs. 2.2 +\\/- 1 mm, P < 0.01). High-grade coronary stenosis was detected in all patients with functional MR compared with no controls (P < 0.001). Significant differences in those with\\/without MV prolapse were detected in MV tent area (-1.0 +\\/- 0.6 mm vs. 1.3 +\\/- 0.9 mm, P < 0.0001) and MV tent height (-0.7 +\\/- 0.3 mm vs. 0.8 +\\/- 0.8 mm, P < 0.0001). Posterior leaflet angle was significantly greater for functional MR (37.9 +\\/- 19.1 degrees vs. 22.9 +\\/- 14 degrees , P < 0.018) and less for valvular MR (0.6 +\\/- 35.5 degrees vs. 22.9 +\\/- 14 degrees, P < 0.017). Sensitivity, specificity, and positive and negative predictive values of MDCT were 100%, 95%, 96% and 100%. CONCLUSION: Cardiac MDCT allows the differentiation between functional and valvular causes of MR.

Roles of PDE1 in Pathological Cardiac Remodeling and Dysfunction.

Science.gov (United States)

Chen, Si; Knight, Walter E; Yan, Chen

2018-04-23

Pathological cardiac hypertrophy and dysfunction is a response to various stress stimuli and can result in reduced cardiac output and heart failure. Cyclic nucleotide signaling regulates several cardiac functions including contractility, remodeling, and fibrosis. Cyclic nucleotide phosphodiesterases (PDEs), by catalyzing the hydrolysis of cyclic nucleotides, are critical in the homeostasis of intracellular cyclic nucleotide signaling and hold great therapeutic potential as drug targets. Recent studies have revealed that the inhibition of the PDE family member PDE1 plays a protective role in pathological cardiac remodeling and dysfunction by the modulation of distinct cyclic nucleotide signaling pathways. This review summarizes recent key findings regarding the roles of PDE1 in the cardiac system that can lead to a better understanding of its therapeutic potential.

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

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Camilla Figueiredo Grans

2014-07-01

Full Text Available Background: Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective: To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods: Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week. At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results: The maximum load test increased in groups trained control (+32% and trained infarcted (+46% in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%, myocardial performance index (-39% and systolic blood pressure (+6% improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%, as well as in the low frequency band of systolic blood pressure (-46% in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion: Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

International Nuclear Information System (INIS)

Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

2014-01-01

Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

Energy Technology Data Exchange (ETDEWEB)

Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil); Mostarda, Cristiano [Departamento de Educação Física, Universidade Federal do Maranhão (UFMA), São Luís, MA (Brazil); Figueroa, Diego Mendrot [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Angelis, Kátia De [Laboratório de Fisiologia Translacional, Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Irigoyen, Maria Cláudia [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Rodrigues, Bruno, E-mail: bruno.rodrigues@incor.usp.br [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil)

2014-07-15

Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

Science.gov (United States)

Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

2014-01-01

Background Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats. PMID:25014059

Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males.

Science.gov (United States)

Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

1997-12-01

Although studies have shown that testosterone receptor blockade with flutamide after hemorrhage restores the depressed immune function, it remains unknown whether administration of flutamide following trauma and hemorrhage and resuscitation has any salutary effects on the depressed cardiovascular and hepatocellular functions. To study this, male rats underwent a laparotomy (representing trauma) and were then bled and maintained at a mean arterial pressure (MAP) of 40 mmHg until the animals could not maintain this pressure. Ringer lactate was given to maintain a MAP of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. The rats were then resuscitated with four times the shed blood volume in the form of Ringer lactate over 60 min. Flutamide (25 mg/kg) or an equal volume of the vehicle propanediol was injected subcutaneously 15 min before the end of resuscitation. Various in vivo heart performance parameters (e.g., maximal rate of the pressure increase or decrease), cardiac output, and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 20 h after resuscitation. Additionally, hepatic microvascular blood flow (HMBF) was determined using a laser Doppler flowmeter. The results indicate that left ventricular performance, cardiac output, HMBF, and hepatocellular function decreased significantly at 20 h after the completion of trauma, hemorrhage, and resuscitation. Administration of the testosterone receptor blocker flutamide, however, significantly improved cardiac performance, HMBF, and hepatocellular function. Thus flutamide appears to be a novel and useful adjunct for improving cardiovascular and hepatocellular functions in males following trauma and hemorrhagic shock.

Hypothalamus-pituitary-thyroid axis activity and function of cardiac muscle in energy deficit

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Katarzyna Lachowicz

2017-12-01

Full Text Available Frequently repeated statement that energy restriction is a factor that improves cardiovascular system function seems to be not fully truth. Low energy intake modifies the hypothalamus-pituitary-thyroid axis activity and thyroid hormone peripheral metabolism. Thyroid hormones, as modulators of the expression and activity of many cardiomyocyte proteins, control heart function. Decreased thyroid hormone levels and their disturbanced conversion and action result in alternation of cardiac remodeling, disorder of calcium homeostasis and diminish myocardial contractility. This review provides a summary of the current state of knowledge about the mechanisms of energy restriction effects on thyroidal axis activity, thyroid hormone peripheral metabolism and action in target tissues, especially in cardiac myocytes. We also showed the existence of energy restriction-thyroid-heart pathway.

Postoperative Pulmonary Dysfunction and Mechanical Ventilation in Cardiac Surgery

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Rafael Badenes

2015-01-01

Full Text Available Postoperative pulmonary dysfunction (PPD is a frequent and significant complication after cardiac surgery. It contributes to morbidity and mortality and increases hospitalization stay and its associated costs. Its pathogenesis is not clear but it seems to be related to the development of a systemic inflammatory response with a subsequent pulmonary inflammation. Many factors have been described to contribute to this inflammatory response, including surgical procedure with sternotomy incision, effects of general anesthesia, topical cooling, and extracorporeal circulation (ECC and mechanical ventilation (VM. Protective ventilation strategies can reduce the incidence of atelectasis (which still remains one of the principal causes of PDD and pulmonary infections in surgical patients. In this way, the open lung approach (OLA, a protective ventilation strategy, has demonstrated attenuating the inflammatory response and improving gas exchange parameters and postoperative pulmonary functions with a better residual functional capacity (FRC when compared with a conventional ventilatory strategy. Additionally, maintaining low frequency ventilation during ECC was shown to decrease the incidence of PDD after cardiac surgery, preserving lung function.

Effects of protein-calorie restriction on mechanical function of hypertrophied cardiac muscle

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Antônio Carlos Cicogna

1999-04-01

Full Text Available OBJECTIVE: To assess the effect of food restriction (FR on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR. METHODS: Isolated papillary muscle preparations of the left ventricle (LV of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1 reduction in the body weight and LV weight of SHR and WKY rats; 2 increase in the time to peak shortening and the time to peak developed tension (DT in the hypertrophied myocardium of the SHR; 3 diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.

Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats

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Fabricio Furtado Vieira

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

Safety and efficacy of high-dose melphalan and auto-SCT in patients with AL amyloidosis and cardiac involvement.

Science.gov (United States)

Girnius, S; Seldin, D C; Meier-Ewert, H K; Sloan, J M; Quillen, K; Ruberg, F L; Berk, J L; Doros, G; Sanchorawala, V

2014-03-01

In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse prognosis and increased treatment-related complications. In this retrospective cohort study, we assessed survival, hematologic and cardiac responses to high-dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac involvement, stratified by cardiac biomarkers brain natriuretic peptide and Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent HDM/SCT based upon functional measures; six patients had modified cardiac stage I disease, seventeen had modified cardiac stage II disease and twenty-four had modified cardiac stage III disease. Treatment-related mortality was 4% for all patients and 8% for patients with stage III disease. Three-year survival was 88% and EFS was 47%; these did not differ by stage. By intention-to-treat analysis, 27% of patients achieved a hematologic complete response and 32% a very good partial response, of whom 70 and 45%, respectively, have not required additional therapy at 36 months. Cardiac response was achieved in 53% of patients. We conclude that with appropriate patient selection and a risk-adapted treatment approach, HDM/SCT is safe and effective in patients with AL amyloidosis and cardiac involvement.

Regular physical exercise improves cardiac autonomic and muscle vasodilatory responses to isometric exercise in healthy elderly

Science.gov (United States)

Sarmento, Adriana de Oliveira; Santos, Amilton da Cruz; Trombetta, Ivani Credidio; Dantas, Marciano Moacir; Oliveira Marques, Ana Cristina; do Nascimento, Leone Severino; Barbosa, Bruno Teixeira; Dos Santos, Marcelo Rodrigues; Andrade, Maria do Amparo; Jaguaribe-Lima, Anna Myrna; Brasileiro-Santos, Maria do Socorro

2017-01-01

The objective of this study was to evaluate cardiac autonomic control and muscle vasodilation response during isometric exercise in sedentary and physically active older adults. Twenty healthy participants, 10 sedentary and 10 physically active older adults, were evaluated and paired by gender, age, and body mass index. Sympathetic and parasympathetic cardiac activity (spectral and symbolic heart rate analysis) and muscle blood flow (venous occlusion plethysmography) were measured for 10 minutes at rest (baseline) and during 3 minutes of isometric handgrip exercise at 30% of the maximum voluntary contraction (sympathetic excitatory maneuver). Variables were analyzed at baseline and during 3 minutes of isometric exercise. Cardiac autonomic parameters were analyzed by Wilcoxon and Mann–Whitney tests. Muscle vasodilatory response was analyzed by repeated-measures analysis of variance followed by Tukey’s post hoc test. Sedentary older adults had higher cardiac sympathetic activity compared to physically active older adult subjects at baseline (63.13±3.31 vs 50.45±3.55 nu, P=0.02). The variance (heart rate variability index) was increased in active older adults (1,438.64±448.90 vs 1,402.92±385.14 ms, P=0.02), and cardiac sympathetic activity (symbolic analysis) was increased in sedentary older adults (5,660.91±1,626.72 vs 4,381.35±1,852.87, P=0.03) during isometric handgrip exercise. Sedentary older adults showed higher cardiac sympathetic activity (spectral analysis) (71.29±4.40 vs 58.30±3.50 nu, P=0.03) and lower parasympathetic modulation (28.79±4.37 vs 41.77±3.47 nu, P=0.03) compared to physically active older adult subjects during isometric handgrip exercise. Regarding muscle vasodilation response, there was an increase in the skeletal muscle blood flow in the second (4.1±0.5 vs 3.7±0.4 mL/min per 100 mL, P=0.01) and third minute (4.4±0.4 vs 3.9±0.3 mL/min per 100 mL, P=0.03) of handgrip exercise in active older adults. The results indicate that

The Role of Levosimendan in Patients with Decreased Left Ventricular Function Undergoing Cardiac Surgery

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Marija Bozhinovska

2016-06-01

Full Text Available The postoperative low cardiac output is one of the most important complications following cardiac surgery and is associated with increased morbidity and mortality. The condition requires inotropic support to achieve adequate hemodynamic status and tissue perfusion. While catecholamines are utilised as a standard therapy in cardiac surgery, their use is limited due to increased oxygen consumption. Levosimendan is calcium sensitising inodilatator expressing positive inotropic effect by binding with cardiac troponin C without increasing oxygen demand. Furthermore, the drug opens potassium ATP (KATP channels in cardiac mitochondria and in the vascular muscle cells, showing cardioprotective and vasodilator properties, respectively. In the past decade, levosimendan demonstrated promising results in treating patients with reduced left ventricular function when administered in peri- or post- operative settings. In addition, pre-operative use of levosimendan in patients with severely reduced left ventricular ejection fraction may reduce the requirements for postoperative inotropic support, mechanical support, duration of intensive care unit stay as well as hospital stay and a decrease in post-operative mortality. However, larger studies are needed to clarify clinical advantages of levosimendan versus conventional inotropes.

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

Science.gov (United States)

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

2007-05-01

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

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)

Structural and functional cardiac adaptations to 6 months of football training in untrained hypertensive men

DEFF Research Database (Denmark)

Andersen, L. J.; Randers, M. B.; Hansen, P. R.

2014-01-01

We investigated the effects of 3 and 6 months of regular football training on cardiac structure and function in hypertensive men. Thirty-one untrained males with mild-to-moderate hypertension were randomized 2:1 to a football training group (n = 20) and a control group receiving traditional...... training improves LV diastolic function in untrained men with mild-to-moderate arterial hypertension. Furthermore, it may improve longitudinal systolic function of both ventricles. The results suggest that football training has favorable effects on cardiac function in hypertensive men....... function improved with respect to tricuspid annular plane systolic excursion (21.8 ± 3.2 to 24.5 ± 3.7 mm). Arterial blood pressure decreased in both groups, but significantly more in the football training group. No significant changes were observed in the control group. In conclusion, short-term football...

An Echocardiographic Study of Left Ventricular Size and Cardiac Function in Adolescent Females with Anorexia Nervosa.

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Escudero, Carolina A; Potts, James E; Lam, Pei-Yoong; De Souza, Astrid M; Mugford, Gerald J; Sandor, George G S

2016-01-01

This retrospective case-control study investigated cardiac dimensions and ventricular function in female adolescents with anorexia nervosa (AN) compared with controls. Echocardiographic measurements of left ventricular (LV) dimensions, LV mass index, left atrial size and cardiac index were made. Detailed measures of systolic and diastolic ventricular function were made including tissue Doppler imaging. Patients were stratified by body mass index ≤10th percentile (AN ≤ 10th) and >10th percentile (AN > 10th). Ninety-five AN patients and 58 controls were included. AN and AN ≤ 10th groups had reduced LV dimensions, LV mass index, left atrial size and cardiac index compared with controls. There were no differences between groups in measures of systolic function. Measures of diastolic tissue Doppler imaging were decreased in AN and AN ≤ 10th. No differences in echocardiographic measurements existed between controls and AN > 10th. Female adolescents with AN have preserved systolic function and abnormalities of diastolic ventricular function. AN ≤ 10th may be a higher risk group. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

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

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Margaret E McCormick

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

Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery.

Science.gov (United States)

Newman, M F; Grocott, H P; Mathew, J P; White, W D; Landolfo, K; Reves, J G; Laskowitz, D T; Mark, D B; Blumenthal, J A

2001-12-01

The importance of perioperative cognitive decline has long been debated. We recently demonstrated a significant correlation between perioperative cognitive decline and long-term cognitive dysfunction. Despite this association, some still question the importance of these changes in cognitive function to the quality of life of patients and their families. The purpose of our investigation was to determine the association between cognitive dysfunction and long-term quality of life after cardiac surgery. After institutional review board approval and patient informed consent, 261 patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled and followed for 5 years. Cognitive function was measured with a battery of tests at baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life was assessed with well-validated, standardized assessments at the 5-year end point. Our results demonstrate significant correlations between cognitive function and quality of life in patients after cardiac surgery. Lower 5-year overall cognitive function scores were associated with lower general health and a less productive working status. Multivariable logistic and linear regression controlling for age, sex, education, and diabetes confirmed this strong association in the majority of areas of quality of life. Five years after cardiac surgery, there is a strong relationship between neurocognitive functioning and quality of life. This has important social and financial implications for preoperative evaluation and postoperative care of patients undergoing cardiac surgery.

Cardiac structure and functions in patients with asymptomatic primary hyperparathyroidism.

Science.gov (United States)

Aktas Yılmaz, B; Akyel, A; Kan, E; Ercin, U; Tavil, Y; Bilgihan, A; Cakır, N; Arslan, M; Balos Toruner, F

2013-11-01

The data about cardiovascular (CV) changes in patients with asymptomatic primary hyperparathyroidism (PHPT) are scarce. The aim of this study is to compare cardiac structure and functions in patients with asymptomatic PHPT and controls by using tissue Doppler echocardiography. Thirty-eight patients with asymptomatic PHPT and 31 sex- and age-matched controls with similar cardiac risk factors were evaluated. There was no significant difference in ejection fraction (EF) between the patients and the controls [64±5.95 vs 62±3.25% (p=0.094)]. Left ventricular mass index (LVMI) was significantly higher in patients than controls [105.96 (66.45-167.24) vs 93.79 (64.25- 139.25) g/m2, p=0.014]. There was a significant correlation between LVMI and serum calcium (Ca) (r=0.240, p<0.005). Myocardial performance index (MPI) was significantly higher in patients than controls [0.49 (0.35-0.60) vs 0.39 (0.33-0.62), p<0.001]. There was positive correlation between theMPI and serumCa levels (r=0.505, p<0.001), parathyroid hormone (PTH) levels (r=0.464, p<0.001) and LVMI (r=0.270, p<0.005). When the normotensive patients and controls were evaluated, the difference between the groups remained statistically significant considering LVMI and MPI [109 (66.45-167.24) g/m2 vs 94.17 (64.25-75.10) g/m2, p=0.03; and 0.49 (0.35-0.60) vs 0.39 (0.33-0.62), p<0.01, respectively]. There were significant correlations between MPI and Ca (r=0.566, p<0.001), and PTH (r=0.472, p<0.001). Our study results showed that cardiacmorphology and diastolic functions are altered in the patients with asymptomatic PHPT. High serum PTH and Ca levels may have an impact on these CV changes. Whether these subtle CV changes would affect cardiac systolic functions and mortality in patients with asymptomatic PHPT should be investigated in further prospective studies.

Is pancreatic polypeptide response to food ingestion a reliable index of vagal function in type 1 diabetes?

DEFF Research Database (Denmark)

Damholt, M B; Arlien-Soeborg, P; Hilsted, L

2006-01-01

The diagnosis of autonomic neuropathy in diabetic patients is based on cardiovascular reflex tests. Since cardiac function may be affected by arteriosclerosis and cardiomyopathy in type 1 diabetes mellitus, alternative tests reflecting vagal nerve function, in other organ systems, are needed....... In this study the pancreatic polypeptide (PP) response to a mixed meal was evaluated in healthy subjects and in recently diagnosed type 1 diabetic patients....

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

Science.gov (United States)

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

2016-04-01

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

Comparison of health-related quality of life and functional recovery measurement tools in out-of-hospital cardiac arrest survivors.

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Andrew, Emily; Nehme, Ziad; Bernard, Stephen; Smith, Karen

2016-10-01

Although a number of validated health-related quality of life (HR-QOL) instruments exist for critical care populations, a standardised approach to assessing the HR-QOL of out-of-hospital cardiac arrest (OHCA) survivors has not been developed. We sought to compare the responses of 12-month OHCA survivors to three HR-QOL and functional recovery instruments, and assess instrument validity. The Victorian Ambulance Cardiac Arrest Registry invited 12-month OHCA survivors to participate in telephone follow-up between January 2011 and December 2015. Responders provided answers to the 12 Item Short Form Health Survey (SF-12), Three-Level EuroQol-5D (EQ-5D-3L) and the Glasgow Outcome Scale-Extended (GOSE). The SF-12 was also used to derive the SF-6D. Responses were used to assess the interpretability and construct validity of the instruments. A total of 1188 patients and proxies responded. Large ceiling effects were observed for the EQ-5D-3L (patients=46%, proxies=23%). Substantial variability was also observed in SF-6D responses for patients who reported full health according to the EQ-5D-3L. For patient responders, the strongest correlations were observed between the EQ-5D-3L index score and SF-6D (ρ=0.65, pGOSE outcome and lower or upper good recovery (pGOSE suggest that these may be useful measures of HR-QOL and functional recovery in OHCA survivors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cardiac function and perfusion dynamics measured on a beat-by-beat basis in the live mouse using ultra-fast 4D optoacoustic imaging

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Ford, Steven J.; Deán-Ben, Xosé L.; Razansky, Daniel

2015-03-01

The fast heart rate (~7 Hz) of the mouse makes cardiac imaging and functional analysis difficult when studying mouse models of cardiovascular disease, and cannot be done truly in real-time and 3D using established imaging modalities. Optoacoustic imaging, on the other hand, provides ultra-fast imaging at up to 50 volumetric frames per second, allowing for acquisition of several frames per mouse cardiac cycle. In this study, we combined a recently-developed 3D optoacoustic imaging array with novel analytical techniques to assess cardiac function and perfusion dynamics of the mouse heart at high, 4D spatiotemporal resolution. In brief, the heart of an anesthetized mouse was imaged over a series of multiple volumetric frames. In another experiment, an intravenous bolus of indocyanine green (ICG) was injected and its distribution was subsequently imaged in the heart. Unique temporal features of the cardiac cycle and ICG distribution profiles were used to segment the heart from background and to assess cardiac function. The 3D nature of the experimental data allowed for determination of cardiac volumes at ~7-8 frames per mouse cardiac cycle, providing important cardiac function parameters (e.g., stroke volume, ejection fraction) on a beat-by-beat basis, which has been previously unachieved by any other cardiac imaging modality. Furthermore, ICG distribution dynamics allowed for the determination of pulmonary transit time and thus additional quantitative measures of cardiovascular function. This work demonstrates the potential for optoacoustic cardiac imaging and is expected to have a major contribution toward future preclinical studies of animal models of cardiovascular health and disease.

Cardiac diastolic function after recovery from pre-eclampsia.

Science.gov (United States)

Soma-Pillay, P; Louw, M C; Adeyemo, A O; Makin, J; Pattinson, R C

Pre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery. The objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk. This was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum. At one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks' gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11-10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not. Women who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.

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

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Kazuaki Nakajima

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

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

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

2013-01-01

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

Exercise capacity in diabetes mellitus is predicted by activity status and cardiac size rather than cardiac function: a case control study.

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Roberts, Timothy J; Burns, Andrew T; MacIsaac, Richard J; MacIsaac, Andrew I; Prior, David L; La Gerche, André

2018-03-23

The reasons for reduced exercise capacity in diabetes mellitus (DM) remains incompletely understood, although diastolic dysfunction and diabetic cardiomyopathy are often favored explanations. However, there is a paucity of literature detailing cardiac function and reserve during incremental exercise to evaluate its significance and contribution. We sought to determine associations between comprehensive measures of cardiac function during exercise and maximal oxygen consumption ([Formula: see text]peak), with the hypothesis that the reduction in exercise capacity and cardiac function would be associated with co-morbidities and sedentary behavior rather than diabetes itself. This case-control study involved 60 subjects [20 with type 1 DM (T1DM), 20 T2DM, and 10 healthy controls age/sex-matched to each diabetes subtype] performing cardiopulmonary exercise testing and bicycle ergometer echocardiography studies. Measures of biventricular function were assessed during incremental exercise to maximal intensity. T2DM subjects were middle-aged (52 ± 11 years) with a mean T2DM diagnosis of 12 ± 7 years and modest glycemic control (HbA 1c 57 ± 12 mmol/mol). T1DM participants were younger (35 ± 8 years), with a 19 ± 10 year history of T1DM and suboptimal glycemic control (HbA 1c 65 ± 16 mmol/mol). Participants with T2DM were heavier than their controls (body mass index 29.3 ± 3.4 kg/m 2 vs. 24.7 ± 2.9, P = 0.001), performed less exercise (10 ± 12 vs. 28 ± 30 MET hours/week, P = 0.031) and had lower exercise capacity ([Formula: see text]peak = 26 ± 6 vs. 38 ± 8 ml/min/kg, P accounting for age, sex and body surface area in a multivariate analysis, significant positive predictors of [Formula: see text]peak were cardiac size (LV end-diastolic volume, LVEDV) and estimated MET-hours, while T2DM was a negative predictor. These combined factors accounted for 80% of the variance in [Formula: see text

Homocyst(e)ine impairs endocardial endothelial function.

Science.gov (United States)

Tyagi, S C; Smiley, L M; Mujumdar, V S

1999-12-01

Homocyst(e)ine injured vascular endothelium and modulated endothelial-dependent vascular function. Endothelium plays an analogous role in both the vessel and the endocardium. Therefore, we hypothesized that homocyst(e)ine modulated endocardial endothelium (EE) dependent cardiac function. The ex vivo cardiac rings from normal male Wistar-Kyoto rats were prepared. The contractile responses of left and right ventricular rings were measured in an isometric myobath, using different concentrations of CaCl2. The response was higher in the left ventricle than right ventricle and was elevated in endocardium without endothelium. The half effective concentration (EC50) and maximum tension generated by homocyst(e)ine were 10(6) and 5-fold lower than endothelin (ET) and angiotensin II (AII), respectively. However, in endothelial-denuded endocardium, homocyst(e)ine response was significantly increased (pine, and endothelial nitric oxide in EE function, cardiac rings were pretreated with AII (10(-10) M) or ET (10(-13) M) and then treated with homocyst(e)ine (10(-8) M). Results suggested that at these concentrations AII, ET, or homocyst(e)ine alone had no effect on cardiac contraction. However, in the presence of 10(-10) M AII or 10(-13) M ET, the cardiac contraction to homocyst(e)ine (10(-8) M) was significantly enhanced (pine. These results suggested that homocyst(e)ine impaired EE-dependent cardiac function and acted synergistically with AII and ET in enhancing the cardiac contraction.

Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights From Simultaneous Cardioneural Mapping.

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Hamon, David; Rajendran, Pradeep S; Chui, Ray W; Ajijola, Olujimi A; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S; Armour, J Andrew; Ardell, Jeffrey L; Shivkumar, Kalyanam

2017-04-01

Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system, a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on intrinsic cardiac nervous system function in generating cardiac neuronal and electric instability using a novel cardioneural mapping approach. In a porcine model (n=8), neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli ( P <0.001). Compared with fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response ( P <0.05 versus short CI), particularly on convergent neurons ( P <0.05), as well as neurons receiving sympathetic ( P <0.05) and parasympathetic input ( P <0.05). The greatest cardiac electric instability was also observed after variable (short) CI PVCs. Variable CI PVCs affect critical populations of intrinsic cardiac nervous system neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling, leading to cardiomyopathy. © 2017 American Heart Association, Inc.

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

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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

The incidence and functional consequences of RT-associated cardiac perfusion defects

International Nuclear Information System (INIS)

Marks, Lawrence B.; Yu Xiaoli; Prosnitz, Robert G.; Zhou Sumin; Hardenbergh, Patricia H.; Blazing, Michael; Hollis, Donna; Lind, Pehr; Tisch, Andrea; Wong, Terence Z.; Borges-Neto, Salvador

2005-01-01

Purpose: Radiation therapy (RT) for left-sided breast cancer has been associated with cardiac dysfunction. We herein assess the temporal nature and volume dependence of RT-induced left ventricular perfusion defects and whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. Methods: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function after RT for left-sided breast cancer. Patients were imaged 30 to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT perfusion scans were compared with the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. Two-tailed Fisher's exact test and the Cochran-Armitage test for linear trends were used for statistical analysis. Results: The incidence of new perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%, respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of patients with less than 5%, and greater than 5%, of their left ventricle included within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall motion abnormalities in patients with and without perfusion defects were 12% to 40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the post-RT interval. Conclusions: Radiation therapy causes volume-dependent perfusion defects in approximately 40% of patients within 2 years of RT. These perfusion defects are associated with corresponding wall-motion abnormalities. Additional study is necessary to better define the long-term functional consequences of RT-induced perfusion defects

Right and left ventricular cardiac function in a developed world population with human immunodeficiency virus studied with radionuclide ventriculography

DEFF Research Database (Denmark)

Lebech, Anne-Mette; Gerstoft, Jan; Hesse, Birger

2004-01-01

. No correlations were found between reduced cardiac function and levels of the 3 peptides measured. CONCLUSIONS: No major dysfunction of the left ventricle is present in a developed world HIV population. However, a small but significant part of this population has modestly reduced right-sided systolic function.......-associated morbidity and mortality rates. Accordingly, the prevalence of HIV-associated cardiac dysfunction may also have changed. The aim of the study was to establish the prevalence of right- and left-sided cardiac dysfunction in a Danish HIV population, most of whom were undergoing HAART, with radionuclide...... ventricular ejection fraction and 6 (7%) had a reduced right ventricle ejection fraction (0.35-0.42) compared with reference values from the age- and sex-matched reference population. Patients with HIV and reduced cardiac function did not differ in the duration of HIV, CD4 count, CD4 nadir, or HIV RNA load...

Cardiac structure and function and dependency in the oldest old.

Science.gov (United States)

Leibowitz, David; Jacobs, Jeremy M; Stessman-Lande, Irit; Cohen, Aharon; Gilon, Dan; Ein-Mor, Eliana; Stessman, Jochanan

2011-08-01

To examine the association between cardiac function and activities of daily living (ADLs) in an age-homogenous, community-dwelling population born in 1920 and 1921. Cross-sectional analysis of a prospective cohort study. Community-dwelling elderly population. Participants were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920 and 1921. Four hundred eighty-nine of the participants (228 male, 261 female) from the most recent set of data collection in 2005 and 2006 underwent echocardiography at their place of residence in addition to structured interviews and physical examination. A home-based comprehensive assessment was performed to assess health and functional status, including performance of ADLs. Dependence was defined as needing assistance with one or more basic ADLs. Standard echocardiographic assessment of cardiac structure and function, including ejection fraction (EF) and diastolic function as assessed using early diastolic mitral annular tissue velocity measurements obtained using tissue Doppler, was performed. Of the participants with limitation in at least one ADL, significantly more had low EF (dependence in ADL had higher left ventricular mass index (LVMI) (129.3 vs 119.7 g/m²) and left atrial volume index (LAVI) (41.3 vs 36.7 mL/m²). There were no differences between the groups in percentage of participants with impaired diastolic function or average ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (11.5 vs 11.8; P=.64). In this age-homogenous cohort of the oldest old, high LVMI and LAVI and indices of systolic but not diastolic function as assessed according to Doppler were associated with limitations in ADLs. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

Nanotized PPARα Overexpression Targeted to Hypertrophied Myocardium Improves Cardiac Function by Attenuating the p53-GSK3β-Mediated Mitochondrial Death Pathway.

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Rana, Santanu; Datta, Ritwik; Chaudhuri, Ratul Datta; Chatterjee, Emeli; Chawla-Sarkar, Mamta; Sarkar, Sagartirtha

2018-05-09

Metabolic remodeling of cardiac muscles during pathological hypertrophy is characterized by downregulation of fatty acid oxidation (FAO) regulator, peroxisome proliferator-activated receptor alpha (PPARα). Thereby, we hypothesized that a cardiac-specific induction of PPARα might restore the FAO-related protein expression and resultant energy deficit. In the present study, consequences of PPARα augmentation were evaluated for amelioration of chronic oxidative stress, myocyte apoptosis, and cardiac function during pathological cardiac hypertrophy. Nanotized PPARα overexpression targeted to myocardium was done by a stearic acid-modified carboxymethyl-chitosan (CMC) conjugated to a 20-mer myocyte-targeted peptide (CMCP). Overexpression of PPARα ameliorated pathological hypertrophy and improved cardiac function. Augmented PPARα in hypertrophied myocytes revealed downregulated p53 acetylation (lys 382), leading to reduced apoptosis. Such cells showed increased binding of PPARα with p53 that in turn reduced interaction of p53 with glycogen synthase kinase-3β (GSK3β), which upregulated inactive phospho-GSK3β (serine [Ser]9) expression within mitochondrial protein fraction. Altogether, the altered molecular milieu in PPARα-overexpressed hypertrophy groups restored mitochondrial structure and function both in vitro and in vivo. Cardiomyocyte-targeted overexpression of a protein of interest (PPARα) by nanotized plasmid has been described for the first time in this study. Our data provide a novel insight towards regression of pathological hypertrophy by ameliorating mitochondrial oxidative stress in targeted PPARα-overexpressed myocardium. PPARα-overexpression during pathological hypertrophy showed substantial betterment of mitochondrial structure and function, along with downregulated apoptosis. Myocardium-targeted overexpression of PPARα during pathological cardiac hypertrophy led to an overall improvement of cardiac energy deficit and subsequent cardiac

Cognitive function in patients with stable coronary heart disease: Related cerebrovascular and cardiovascular responses.

Directory of Open Access Journals (Sweden)

Mathieu Gayda

Full Text Available Chronic exercise has been shown to prevent or slow age-related decline in cognitive functions in otherwise healthy, asymptomatic individuals. We sought to assess cognitive function in a stable coronary heart disease (CHD sample and its relationship to cerebral oxygenation-perfusion, cardiac hemodynamic responses, and [Formula: see text] peak compared to age-matched and young healthy control subjects. Twenty-two young healthy controls (YHC, 20 age-matched old healthy controls (OHC and 25 patients with stable CHD were recruited. Cognitive function assessment included short term-working memory, perceptual abilities, processing speed, cognitive inhibition and flexibility and long-term verbal memory. Maximal cardiopulmonary function (gas exchange analysis, cardiac hemodynamic (impedance cardiography and left frontal cerebral oxygenation-perfusion (near-infra red spectroscopy were measured during and after a maximal incremental ergocycle test. Compared to OHC and CHD, YHC had higher [Formula: see text] peak, maximal cardiac index (CI max, cerebral oxygenation-perfusion (ΔO2 Hb, ΔtHb: exercise and recovery and cognitive function (for all items (P<0.05. Compared to OHC, CHD patients had lower [Formula: see text] peak, CI max, cerebral oxygenation-perfusion (during recovery and short term-working memory, processing speed, cognitive inhibition and flexibility and long-term verbal memory (P<0.05. [Formula: see text] peak and CI max were related to exercise cerebral oxygenation-perfusion and cognitive function (P<0.005. Cerebral oxygenation-perfusion (exercise was related to cognitive function (P<0.005. Stable CHD patients have a worse cognitive function, a similar cerebral oxygenation/perfusion during exercise but reduced one during recovery vs. their aged-matched healthy counterparts. In the all sample, cognitive functions correlated with [Formula: see text] peak, CI max and cerebral oxygenation-perfusion.

Laughter as a social rejection cue: gelotophobia and transient cardiac responses to other persons' laughter and insult.

Science.gov (United States)

Papousek, Ilona; Aydin, Nilüfer; Lackner, Helmut K; Weiss, Elisabeth M; Bühner, Markus; Schulter, Günter; Charlesworth, Canice; Freudenthaler, H Harald

2014-11-01

Other persons' laughter, normally perceived as a signal that persons are friendly and inviting others to approach, can also be perceived as a cue of social rejection. In this study, prerecorded laughter was placed in a realistic and personally relevant context, and participants' responses were related to gelotophobia, a trait predisposing to perceiving laughter as a cue of social rejection. Individuals with gelotophobia showed marked heart rate deceleration in response to the laughter stimulus, possibly indicating a "freezing-like" response. Moreover, cardiac responses to anger provocation by overtly insulting statements indicated heightened aggressive anger in response to cumulated social threat. The study adds to recent research showing specific cardiac responses to social rejection and to the literature on social rejection sensitivity by demonstrating the value of using well interpretable physiological measures in this research context. Copyright © 2014 Society for Psychophysiological Research.

Nuclear cardiac

International Nuclear Information System (INIS)

Slutsky, R.; Ashburn, W.L.

1982-01-01

The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques

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.

Evaluation of Cardiac Mitochondrial Function by a Nuclear Imaging Technique using Technetium-99m-MIBI Uptake Kinetics

International Nuclear Information System (INIS)

Matsuo, Shinro; Nakajima, Kenichi; Kinuya, Seigo

2013-01-01

Mitochondria play an important role in energy production for the cell. The proper function of a myocardial cell largely depends on the functional capacity of the mitochondria. Therefore it is necessary to establish a novel and reliable method for a non-invasive assessment of mitochondrial function and metabolism in humans. Although originally designed for evaluating myocardial perfusion, 99m Tc-MIBI can be also used to evaluate cardiac mitochondrial function. In a clinical study on ischemic heart disease, reverse redistribution of 99m Tc-MIBI was evident after direct percutaneous transluminal coronary angioplasty. The presence of increased washout of 99m Tc-MIBI was associated with the infarct-related artery and preserved left ventricular function. In non-ischemic cardiomyopathy, an increased washout rate of 99m Tc-MIBI, which correlated inversely with left ventricular ejection fraction, was observed in patients with congestive heart failure. Increased 99m Tc-MIBI washout was also observed in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and in doxorubicin-induced cardiomyopathy. Noninvasive assessment of cardiac mitochondrial function could be greatly beneficial in monitoring possible cardiotoxic drug use and in the evaluation of cardiac damage in clinical medicine

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

Directory of Open Access Journals (Sweden)

Vinicius S Carreira

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

Association of Weight and Body Composition on Cardiac Structure and Function in the ARIC Study (Atherosclerosis Risk in Communities).

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Bello, Natalie A; Cheng, Susan; Claggett, Brian; Shah, Amil M; Ndumele, Chiadi E; Roca, Gabriela Querejeta; Santos, Angela B S; Gupta, Deepak; Vardeny, Orly; Aguilar, David; Folsom, Aaron R; Butler, Kenneth R; Kitzman, Dalane W; Coresh, Josef; Solomon, Scott D

2016-08-01

Obesity increases cardiovascular risk. However, the extent to which various measures of body composition are associated with abnormalities in cardiac structure and function, independent of comorbidities commonly affecting obese individuals, is not clear. This study sought to examine the relationship between body mass index, waist circumference, and percent body fat with conventional and advanced measures of cardiac structure and function. We studied 4343 participants of the ARIC study (Atherosclerosis Risk in Communities) who were aged 69 to 82 years, free of coronary heart disease and heart failure, and underwent comprehensive echocardiography. Increasing body mass index, waist circumference, and body fat were associated with greater left ventricular (LV) mass and left atrial volume indexed to height(2.7) in both men and women (Pheart disease or heart failure, obesity was associated with subclinical abnormalities in cardiac structure in both men and women and with adverse LV remodeling and impaired LV systolic function in women. These data highlight the association of obesity and subclinical abnormalities of cardiac structure and function, particularly in women. © 2016 American Heart Association, Inc.

Improvement in cardiac function and free fatty acid metabolism in a case of dilated cardiomyopathy with CD36 deficiency.

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Hirooka, K; Yasumura, Y; Ishida, Y; Komamura, K; Hanatani, A; Nakatani, S; Yamagishi, M; Miyatake, K

2000-09-01

A 27-year-old man diagnosed as having dilated cardiomyopathy (DCM) without myocardial accumulation of 123I-beta-methyl-iodophenylpentadecanoic acid, and he was found to have type I CD36 deficiency. This abnormality of cardiac free fatty acid metabolism was also confirmed by other methods: 18F-fluoro-2-deoxyglucose positron emission tomography, measurements of myocardial respiratory quotient and cardiac fatty acid uptake. Although the type I CD36 deficiency was reconfirmed after 3 months, the abnormal free fatty acid metabolism improved after carvedilol therapy and was accompanied by improved cardiac function. Apart from a cause-and-effect relationship, carvedilol can improve cardiac function and increase free fatty acid metabolism in patients with both DCM and CD36 deficiency.

ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

International Nuclear Information System (INIS)

Icli, Basak; Bharti, Ajit; Pentassuglia, Laura; Peng, Xuyang; Sawyer, Douglas B.

2012-01-01

Highlights: ► ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. ► Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. ► Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or γ-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants.

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Fernandes, T; Soci, U P R; Oliveira, E M

2011-09-01

Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin) are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1) receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs) have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

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T. Fernandes

2011-09-01

Full Text Available Among the molecular, biochemical and cellular processes that orchestrate the development of the different phenotypes of cardiac hypertrophy in response to physiological stimuli or pathological insults, the specific contribution of exercise training has recently become appreciated. Physiological cardiac hypertrophy involves complex cardiac remodeling that occurs as an adaptive response to static or dynamic chronic exercise, but the stimuli and molecular mechanisms underlying transduction of the hemodynamic overload into myocardial growth are poorly understood. This review summarizes the physiological stimuli that induce concentric and eccentric physiological hypertrophy, and discusses the molecular mechanisms, sarcomeric organization, and signaling pathway involved, also showing that the cardiac markers of pathological hypertrophy (atrial natriuretic factor, β-myosin heavy chain and α-skeletal actin are not increased. There is no fibrosis and no cardiac dysfunction in eccentric or concentric hypertrophy induced by exercise training. Therefore, the renin-angiotensin system has been implicated as one of the regulatory mechanisms for the control of cardiac function and structure. Here, we show that the angiotensin II type 1 (AT1 receptor is locally activated in pathological and physiological cardiac hypertrophy, although with exercise training it can be stimulated independently of the involvement of angiotensin II. Recently, microRNAs (miRs have been investigated as a possible therapeutic approach since they regulate the translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in relation to physiological hypertrophy have not been extensively investigated. We summarize here profiling studies that have examined miRs in pathological and physiological cardiac hypertrophy. An understanding of physiological cardiac remodeling may provide a strategy to improve ventricular function in cardiac dysfunction.

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

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

2011-01-01

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

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

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Alireza Abdollahi Moghaddam

2016-03-01

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

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

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

2015-01-01

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

Cardiac magnetic resonance imaging in Alström syndrome

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Carey Catherine M

2009-06-01

Full Text Available Abstract Background A case series of the cardiac magnetic resonance imaging findings in seven adult Alström patients. Methods Seven patients from the National Specialist Commissioning Group Centre for Alström Disease, Torbay, England, UK, completed the cardiac magnetic resonance imaging protocol to assess cardiac structure and function in Alström cardiomyopathy. Results All patients had some degree of left and right ventricular dysfunction. Patchy mid wall gadolinium delayed enhancement was demonstrated, suggesting an underlying fibrotic process. Some degree of cardiomyopathy was universal. No evidence of myocardial infarction or fatty infiltration was demonstrated, but coronary artery disease cannot be completely excluded. Repeat scanning after 18 months in one subject showed progression of fibrosis and decreased left ventricular function. Conclusion Adult Alström cardiomyopathy appears to be a fibrotic process causing impairment of both ventricles. Serial cardiac magnetic resonance scanning has helped clarify the underlying disease progression and responses to treatment. Confirmation of significant mutations in the ALMS1 gene should lead to advice to screen the subject for cardiomyopathy, and metabolic disorders.

Usefulness of true FISP cine MR imaging in patients with poor cardiac function

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Sakuma, Toshiharu; Yamada, Naoaki; Motooka, Makoto; Enomoto, Naoyuki; Maeshima, Isamu; Matsuda, Kazuhide; Urayama, Shinichi; Ikeo, Miki [National Cardiovascular Center, Suita, Osaka (Japan)

2002-01-01

This study was done to assess the value of True FISP cine in patients with poor cardiac function. True FISP cine and FLASH cine imaging were performed on a 1.5 T machine. Both short axis and horizontal long axis imaging sections were used. The imaging sections used a Matrix (120 x 128), FOV (24 x 32 cm), and had a slice thickness of 8 mm. The imaging time for True FISP cine was 8 heart beats and 17 heart beats for FLASH cine. The contrast-to-noise ratio between the blood and myocardium (CNR) was measured at enddiastole and endsystole. The subjects in the study were 10 healty volunteers (average age 26.5{+-}3.2 years) and 12 patients with hypofunction (average age 53.9{+-}13.2 years). In the volunteers, the CNR of the short axis imaging was similar in both True FISP (24.6{+-}3.7) and FLASH (23.4{+-}5.9). In the patients with poor cardiac function however, the CNR of True FISP was larger than FLASH in both the short and long axis. In the short axis (22.7{+-}6.1 vs. 17.9{+-}5.3, P<0.01) and in the long axis (17.4{+-}4.3 vs. 9.3{+-}4.0, P<0.01). We conclude that True FISP cine has a higher contrast in a shorter imaging time than FLASH cine. True FISP cine is especially useful in patients with poor cardiac function. (author)

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

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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.

Hyperpolarized metabolic MR in the study of cardiac function and disease

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Lauritzen, M. H.; Søgaard, L. V.; Madsen, Pia Lisbeth

2014-01-01

Several diseases of the heart have been linked to an insufficient ability to generate enough energy (ATP) to sustain proper heart function. Hyperpolarized magnetic resonance (MR) is a novel technique that can visualize and quantify myocardial energy metabolism. Hyperpolarization enhances the MR...... signal from a biological molecule of interest by more than 10,000 times, making it possible to measure its cellular uptake and conversion in specific enzymatic pathways in real time. We review the role of hyperpolarized MR in identifying changes in cardiac metabolism in vivo, and present the extensive...... literature on hyperpolarized pyruvate that has been used to characterize cardiac disease in various in vivo models, such as myocardial ischemia, hypertension, diabetes, hyperthyroidism and heart failure. The technical aspects of the technique are presented as well as the challenges of translating...

The importance of myocardial contractile reserve in predicting response to cardiac resynchronization therapy

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Kloosterman, Mariëlle; Damman, Kevin; Van Veldhuisen, Dirk J; Rienstra, Michiel; Maass, Alexander H

AimTo perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure. Methods and resultsWe searched MEDLINE/PubMed and Cochrane for all papers published up

Myocardial functional responses do not contribute to maximal exercise performance in the heat.

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Smith, Denise L; DeBlois, Jacob P; Wharton, Margaret; Rowland, Thomas

2015-01-01

Both the extent and means by which maximal oxygen uptake ([Formula: see text]) is depressed by elevated ambient temperature are uncertain. Particularly, information is currently unavailable regarding the possible influence of alterations in myocardial function on [Formula: see text] and performance during exercise in the heat. This study investigated the effects of environmental heat on [Formula: see text], peak work capacity, and myocardial function during a standard, progressive cycle test to exhaustion. Twelve euhydrated men (aged 20.7 ± 1.7 years) performed a maximal cycle test in an environmental chamber in both heat stress [35°C, 30% relative humidity (RH)] and temperate (20°C, 30% RH) conditions with measurement of standard gas exchange variables, core temperature, and echocardiographic measures of cardiac function. A small but statistically significant reduction of peak work capacity was observed in the heat stress versus temperate conditions (253 ± 30 and 259 ± 30 W, respectively, p = 0.02). Mean [Formula: see text] was not statistically different in the two conditions (p = 0.16) but values were 3.4% lower in the heat, and 9 of 12 participants demonstrated lower values in the heat stress trial. No differences in responses of heart rate, cardiac output, stroke volume, core temperature, hydration status, or myocardial systolic or diastolic function were observed between the two conditions, but perceived body temperature was higher in the heat. The small, negative impact of heat on exercise performance and [Formula: see text] could not be explained by disturbances in myocardial functional responses to exercise in young adult males.

Cognitive function in survivors of out-of-hospital cardiac arrest after target temperature management at 33°C versus 36°C

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Lilja, Gisela; Nielsen, Niklas; Friberg, Hans

2015-01-01

assessed with tests for memory (Rivermead Behavioural Memory Test), executive functions (Frontal Assessment Battery), and attention/mental speed (Symbol Digit Modalities Test). A control group of 119 matched patients hospitalized for acute ST-segment-elevation myocardial infarction without cardiac arrest...... was more affected among cardiac arrest patients, but results for memory and executive functioning were similar. CONCLUSIONS: Cognitive function was comparable in survivors of out-of-hospital cardiac arrest when a temperature of 33°C and 36°C was targeted. Cognitive impairment detected in cardiac arrest...... performed the same assessments. Half of the cardiac arrest survivors had cognitive impairment, which was mostly mild. Cognitive outcome did not differ (P>0.30) between the 2 temperature groups (33°C/36°C). Compared with control subjects with ST-segment-elevation myocardial infarction, attention/mental speed...

Locating AED Enabled Medical Drones to Enhance Cardiac Arrest Response Times.

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Pulver, Aaron; Wei, Ran; Mann, Clay

2016-01-01

Out-of-hospital cardiac arrest (OOHCA) is prevalent in the United States. Each year between 180,000 and 400,000 people die due to cardiac arrest. The automated external defibrillator (AED) has greatly enhanced survival rates for OOHCA. However, one of the important components of successful cardiac arrest treatment is emergency medical services (EMS) response time (i.e., the time from EMS "wheels rolling" until arrival at the OOHCA scene). Unmanned Aerial Vehicles (UAV) have regularly been used for remote sensing and aerial imagery collection, but there are new opportunities to use drones for medical emergencies. The purpose of this study is to develop a geographic approach to the placement of a network of medical drones, equipped with an automated external defibrillator, designed to minimize travel time to victims of out-of-hospital cardiac arrest. Our goal was to have one drone on scene within one minute for at least 90% of demand for AED shock therapy, while minimizing implementation costs. In our study, the current estimated travel times were evaluated in Salt Lake County using geographical information systems (GIS) and compared to the estimated travel times of a network of AED enabled medical drones. We employed a location model, the Maximum Coverage Location Problem (MCLP), to determine the best configuration of drones to increase service coverage within one minute. We found that, using traditional vehicles, only 4.3% of the demand can be reached (travel time) within one minute utilizing current EMS agency locations, while 96.4% of demand can be reached within five minutes using current EMS vehicles and facility locations. Analyses show that using existing EMS stations to launch drones resulted in 80.1% of cardiac arrest demand being reached within one minute Allowing new sites to launch drones resulted in 90.3% of demand being reached within one minute. Finally, using existing EMS and new sites resulted in 90.3% of demand being reached while greatly reducing

The Role of Exercise in Cardiac Aging: From Physiology to Molecular Mechanisms.

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Roh, Jason; Rhee, James; Chaudhari, Vinita; Rosenzweig, Anthony

2016-01-22

Aging induces structural and functional changes in the heart that are associated with increased risk of cardiovascular disease and impaired functional capacity in the elderly. Exercise is a diagnostic and therapeutic tool, with the potential to provide insights into clinical diagnosis and prognosis, as well as the molecular mechanisms by which aging influences cardiac physiology and function. In this review, we first provide an overview of how aging impacts the cardiac response to exercise, and the implications this has for functional capacity in older adults. We then review the underlying molecular mechanisms by which cardiac aging contributes to exercise intolerance, and conversely how exercise training can potentially modulate aging phenotypes in the heart. Finally, we highlight the potential use of these exercise models to complement models of disease in efforts to uncover new therapeutic targets to prevent or treat heart disease in the aging population. © 2016 American Heart Association, Inc.

Supplementary Administration of Everolimus Reduces Cardiac Systolic Function in Kidney Transplant Recipients.

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Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Abe, Masami; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

2017-05-26

BACKGROUND The effect of everolimus, one of the mammalian targets of rapamycin inhibitors, on cardiac function was evaluated in kidney transplant recipients. MATERIAL AND METHODS Seventy-six participants who underwent kidney transplant between March 2009 and May 2016 were retrospectively reviewed. To standardize everolimus administration, the following criteria were used: (1) the recipient did not have a donor-specific antigen before kidney transplantation; (2) the recipient did not have proteinuria and uncontrollable hyperlipidemia after kidney transplantation; and (3) acute rejection was not observed on protocol biopsy 3 months after kidney transplantation. According to these criteria, everolimus administration for maintenance immunosuppression after kidney transplantation was included. Cardiac function was compared between the treatment group (n=30) and non-treatment group (n=46). RESULTS The mean observation periods of the treatment and non-treatment groups were 41.3±12.6 and 43.9±19.8 months, respectively (p=0.573). The mean ejection fraction and fractional shortening of the treatment and non-treatment groups after kidney transplant were 66.5±7.9% vs. 69.6±5.5% (p=0.024) and 37.1±6.2% vs. 39.3±4.7% (p=0.045), respectively. In the treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation did not differ significantly (p=0.604 and 0.606, respectively). In the non-treatment group, the mean ejection fraction and fractional shortening before and after kidney transplantation differed significantly (p=0.004 and 0.006, respectively). CONCLUSIONS Supplementary administration of everolimus after kidney transplantation can reduce cardiac systolic function.

Relationship between cardiac function and resting cerebral blood flow

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

2014-01-01

) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P...... = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed...

Positron emission tomographic imaging of cardiac sympathetic innervation and function

International Nuclear Information System (INIS)

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

1990-01-01

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

Functional capacity and mental state of patients undergoing cardiac surgery

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Bruna Corrêa

Full Text Available Abstract Introduction: Cardiovascular diseases are a serious public health problem in Brazil. Myocardial revascularization surgery (MRS as well as cardiac valve replacement and repair are procedures indicated to treat them. Thus, extracorporeal circulation (ECC is still widely used in these surgeries, in which patients with long ECC times may have greater neurological deficits. Neurological damage resulting from MRS can have devastating consequences such as loss of independence and worsening of quality of life. Objective: To assess the effect of cardiac surgery on a patient’s mental state and functional capacity in both the pre- and postoperative periods. Methods: We conducted a cross-sectional study with convenience sampling of subjects undergoing MRS and valve replacement. Participants were administered the Mini-Mental State Exam (MMSE and the Duke Activity Status Index (DASI in the pre- and postoperative periods, as well as before their hospital discharge. Results: This study assessed nine patients (eight males aged 62.4 ± 6.3 years with a BMI of 29.5 ± 2.3 kg/m2. There was a significant decrease in DASI scores and VO2 from preoperative to postoperative status (p = 0.003 and p = 0.003, respectively. Conclusion: This study revealed a loss of cognitive and exercise capacity after cardiac surgery. A larger sample however is needed to consolidate these findings.

Ghrelin potentiates cardiac reactivity to stress by modulating sympathetic control and beta-adrenergic response.

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Camargo-Silva, Gabriel; Turones, Larissa Córdova; da Cruz, Kellen Rosa; Gomes, Karina Pereira; Mendonça, Michelle Mendanha; Nunes, Allancer; de Jesus, Itamar Guedes; Colugnati, Diego Basile; Pansani, Aline Priscila; Pobbe, Roger Luis Henschel; Santos, Robson; Fontes, Marco Antônio Peliky; Guatimosim, Silvia; de Castro, Carlos Henrique; Ianzer, Danielle; Ferreira, Reginaldo Nassar; Xavier, Carlos Henrique

2018-03-01

Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol. Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors. Copyright © 2018 Elsevier Inc. All rights reserved.

Highly-accelerated self-gated free-breathing 3D cardiac cine MRI: validation in assessment of left ventricular function.

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Liu, Jing; Feng, Li; Shen, Hsin-Wei; Zhu, Chengcheng; Wang, Yan; Mukai, Kanae; Brooks, Gabriel C; Ordovas, Karen; Saloner, David

2017-08-01

This work presents a highly-accelerated, self-gated, free-breathing 3D cardiac cine MRI method for cardiac function assessment. A golden-ratio profile based variable-density, pseudo-random, Cartesian undersampling scheme was implemented for continuous 3D data acquisition. Respiratory self-gating was achieved by deriving motion signal from the acquired MRI data. A multi-coil compressed sensing technique was employed to reconstruct 4D images (3D+time). 3D cardiac cine imaging with self-gating was compared to bellows gating and the clinical standard breath-held 2D cine imaging for evaluation of self-gating accuracy, image quality, and cardiac function in eight volunteers. Reproducibility of 3D imaging was assessed. Self-gated 3D imaging provided an image quality score of 3.4 ± 0.7 vs 4.0 ± 0 with the 2D method (p = 0.06). It determined left ventricular end-systolic volume as 42.4 ± 11.5 mL, end-diastolic volume as 111.1 ± 24.7 mL, and ejection fraction as 62.0 ± 3.1%, which were comparable to the 2D method, with bias ± 1.96 × SD of -0.8 ± 7.5 mL (p = 0.90), 2.6 ± 3.3 mL (p = 0.84) and 1.4 ± 6.4% (p = 0.45), respectively. The proposed 3D cardiac cine imaging method enables reliable respiratory self-gating performance with good reproducibility, and provides comparable image quality and functional measurements to 2D imaging, suggesting that self-gated, free-breathing 3D cardiac cine MRI framework is promising for improved patient comfort and cardiac MRI scan efficiency.

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

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Hermans Mieke CE

2012-07-01

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

Pulmonary function and health-related quality of life 1-year follow up after cardiac surgery.

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Westerdahl, Elisabeth; Jonsson, Marcus; Emtner, Margareta

2016-07-08

Pulmonary function is severely reduced in the early period after cardiac surgery, and impairments have been described up to 4-6 months after surgery. Evaluation of pulmonary function in a longer perspective is lacking. In this prospective study pulmonary function and health-related quality of life were investigated 1 year after cardiac surgery. Pulmonary function measurements, health-related quality of life (SF-36), dyspnoea, subjective breathing and coughing ability and pain were evaluated before and 1 year after surgery in 150 patients undergoing coronary artery bypass grafting, valve surgery or combined surgery. One year after surgery the forced vital capacity and forced expiratory volume in 1 s were significantly decreased (by 4-5 %) compared to preoperative values (p < 0.05). Saturation of peripheral oxygen was unchanged 1 year postoperatively compared to baseline. A significantly improved health-related quality of life was found 1 year after surgery, with improvements in all eight aspects of SF-36 (p < 0.001). Sternotomy-related pain was low 1 year postoperatively at rest (median 0 [min-max; 0-7]), while taking a deep breath (0 [0-4]) and while coughing (0 [0-8]). A more pronounced decrease in pulmonary function was associated with dyspnoea limitations and impaired subjective breathing and coughing ability. One year after cardiac surgery static and dynamic lung function measurements were slightly decreased, while health-related quality of life was improved in comparison to preoperative values. Measured levels of pain were low and saturation of peripheral oxygen was same as preoperatively.

Cardiac response to hypobaric hypoxia: persistent changes in cardiac mass, function, and energy metabolism after a trek to Mt. Everest Base Camp

NARCIS (Netherlands)

Holloway, Cameron J.; Montgomery, Hugh E.; Murray, Andrew J.; Cochlin, Lowri E.; Codreanu, Ion; Hopwood, Naomi; Johnson, Andrew W.; Rider, Oliver J.; Levett, Denny Z. H.; Tyler, Damian J.; Francis, Jane M.; Neubauer, Stefan; Grocott, Michael P. W.; Clarke, Kieran; Grocott, Mike; Montgomery, Hugh; Levett, Denny; Martin, Daniel; Wilson, Mark; Windsor, Jeremy; Luery, Helen; Murray, Andrew; Stroud, Mike; Khosravi, Maryam; Wandrag, Liesl; Holloway, Cameron; Edwards, Lindsay; Ince, Can; Mythen, Monty; Jonas, Max; Imray, Chris; Newman, Stan; Stygal, Jan; Doyle, Patrick; Rodway, George; Howard, David; McMorrow, Roger; Ahuja, Vijay; Aref-Adib, Golnar; Burnham, Richard Dick; Chisholm, Amber; Coates, David; Cook, Debbie; Dhillon, Sundeep; Dougall, Christina; Duncan, Polly; Edsell, Mark; Evans, Lynn; Gardiner, Paul Bugs; Gunning, Paul

2011-01-01

We postulated that changes in cardiac high-energy phosphate metabolism may underlie the myocardial dysfunction caused by hypobaric hypoxia. Healthy volunteers (n=14) were studied immediately before, and within 4 d of return from, a 17-d trek to Mt. Everest Base Camp (5300 m). (31)P magnetic

Changes of cardiac function in hyperthyroidism and hypothyroidism

International Nuclear Information System (INIS)

Morishita, Takeshi; Kawamura, Yasuaki; Yamazaki, Junichi; Okuzumi, Ichio; Muto, Toshinori; Wakakura, Manabu; Okamoto, Kiyoshi; Irie, Minoru; Inoue, Kazuko.

1988-01-01

Changes of cardiac parameters in patients with 21 hyperthyroidisms and 11 primary hypothyroidisms were studied administered by methimazole or 1-thyroxine using radionuclide method. In hyperthyroidisms, cardiac parameter (CI, EF, PEP/LVET, PEP) normalized 4 - 6 week delayed compared with hormonal level (T 3 , T 4 ) recovery period. On the other hand, in hypothyroidism PEP/LVET delayed about 2 weeks compared with hormonal level, however, other cardiac parameters were maintained within normal level, relatively. Correlation between T 3 and LVET was significant statistically (r = -0.59, p 3 and PEP was significant (r = -0.60, p < 0.01) in hypothyroidisms, respectively. (author)

Response to cardiac resynchronization therapy

DEFF Research Database (Denmark)

Versteeg, Henneke; Schiffer, Angélique A; Widdershoven, Jos W

2009-01-01

Cardiac resynchronization therapy (CRT) is a promising treatment for a subgroup of patients with advanced congestive heart failure and a prolonged QRS interval. Despite the majority of patients benefiting from CRT, 10-40% of patients do not respond to this treatment and are labeled as nonresponders...

Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function

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Xin Sun

2018-01-01

Full Text Available How chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example, Baf60c (Smarcd3 encodes a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex, but its role in heart development is not fully understood. We found that constitutive loss of Baf60c leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of Baf60c in cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function. Baf60c regulates a gene expression program that includes genes encoding contractile proteins, modulators of sarcomere function, and cardiac metabolic genes. Many of the genes deregulated in Baf60c null embryos are targets of the MEF2/SRF co-factor Myocardin (MYOCD. In a yeast two-hybrid screen, we identified MYOCD as a BAF60c interacting factor; we showed that BAF60c and MYOCD directly and functionally interact. We conclude that Baf60c is essential for coordinating a program of gene expression that regulates the fundamental functional properties of cardiomyocytes.

Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass

NARCIS (Netherlands)

Loef, BG; Henning, RH; Epema, AH; Rietman, GW; van Oeveren, W; Navis, GJ; Ebels, T

2004-01-01

Background. In cardiac surgery with cardiopulmonary bypass (CPB), corticosteroids are administered to attenuate the physiological changes caused by the systemic inflammatory response. The effects of corticosteroids on CPB-associated renal damage have not been documented. The purpose of this study

[Experimental therapy of cardiac remodeling with quercetin-containing drugs].

Science.gov (United States)

Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

2013-01-01

It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

Cardiac arrest during gamete release in chum salmon regulated by the parasympathetic nerve system.

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Yuya Makiguchi

Full Text Available Cardiac arrest caused by startling stimuli, such as visual and vibration stimuli, has been reported in some animals and could be considered as an extraordinary case of bradycardia and defined as reversible missed heart beats. Variability of the heart rate is established as a balance between an autonomic system, namely cholinergic vagus inhibition, and excitatory adrenergic stimulation of neural and hormonal action in teleost. However, the cardiac arrest and its regulating nervous mechanism remain poorly understood. We show, by using electrocardiogram (ECG data loggers, that cardiac arrest occurs in chum salmon (Oncorhynchus keta at the moment of gamete release for 7.39+/-1.61 s in females and for 5.20+/-0.97 s in males. The increase in heart rate during spawning behavior relative to the background rate during the resting period suggests that cardiac arrest is a characteristic physiological phenomenon of the extraordinarily high heart rate during spawning behavior. The ECG morphological analysis showed a peaked and tall T-wave adjacent to the cardiac arrest, indicating an increase in potassium permeability in cardiac muscle cells, which would function to retard the cardiac action potential. Pharmacological studies showed that the cardiac arrest was abolished by injection of atropine, a muscarinic receptor antagonist, revealing that the cardiac arrest is a reflex response of the parasympathetic nerve system, although injection of sotalol, a beta-adrenergic antagonist, did not affect the cardiac arrest. We conclude that cardiac arrest during gamete release in spawning release in spawning chum salmon is a physiological reflex response controlled by the parasympathetic nervous system. This cardiac arrest represents a response to the gaping behavior that occurs at the moment of gamete release.

Candida glabrata binds to glycosylated and lectinic receptors on the coronary endothelial luminal membrane and inhibits flow sense and cardiac responses to agonists.

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Torres-Tirado, David; Knabb, Maureen; Castaño, Irene; Patrón-Soberano, Araceli; De Las Peñas, Alejandro; Rubio, Rafael

2016-01-01

Candida glabrata (CG) is an opportunistic fungal pathogen that initiates infection by binding to host cells via specific lectin-like adhesin proteins. We have previously shown the importance of lectin-oligosaccharide binding in cardiac responses to flow and agonists. Because of the lectinic-oligosaccharide nature of CG binding, we tested the ability of CG to alter the agonist- and flow-induced changes in cardiac function in isolated perfused guinea pig hearts. Both transmission and scanning electron microscopy showed strong attachment of CG to the coronary endothelium, even after extensive washing. CG shifted the coronary flow vs. auricular-ventricular (AV) delay relationship upward, indicating that greater flow was required to achieve the same AV delay. This effect was completely reversed with mannose, partially reversed with galactose and N-acetylgalactosamine, but hyaluronan had no effect. Western blot analysis was used to determine binding of CG to isolated coronary endothelial luminal membrane (CELM) receptors, and the results indicate that flow-sensitive CELM receptors, ANG II type I, α-adrenergic 1A receptor, endothelin-2, and VCAM-1 bind to CG. In addition, CG inhibited agonist-induced effects of bradykinin, angiotensin, and phenylephrine on AV delay, coronary perfusion pressure, and left ventricular pressure. Mannose reversed the inhibitory effects of CG on the agonist responses. These results suggest that CG directly binds to flow-sensitive CELM receptors via lectinic-oligosaccharide interactions with mannose and disrupts the lectin-oligosaccharide binding necessary for flow-induced cardiac responses. Copyright © 2016 the American Physiological Society.

Usefulness of true FISP cine MR imaging in patients with poor cardiac function

International Nuclear Information System (INIS)

Sakuma, Toshiharu; Yamada, Naoaki; Motooka, Makoto; Enomoto, Naoyuki; Maeshima, Isamu; Matsuda, Kazuhide; Urayama, Shinichi; Ikeo, Miki

2002-01-01

This study was done to assess the value of True FISP cine in patients with poor cardiac function. True FISP cine and FLASH cine imaging were performed on a 1.5 T machine. Both short axis and horizontal long axis imaging sections were used. The imaging sections used a Matrix (120 x 128), FOV (24 x 32 cm), and had a slice thickness of 8 mm. The imaging time for True FISP cine was 8 heart beats and 17 heart beats for FLASH cine. The contrast-to-noise ratio between the blood and myocardium (CNR) was measured at enddiastole and endsystole. The subjects in the study were 10 healty volunteers (average age 26.5±3.2 years) and 12 patients with hypofunction (average age 53.9±13.2 years). In the volunteers, the CNR of the short axis imaging was similar in both True FISP (24.6±3.7) and FLASH (23.4±5.9). In the patients with poor cardiac function however, the CNR of True FISP was larger than FLASH in both the short and long axis. In the short axis (22.7±6.1 vs. 17.9±5.3, P<0.01) and in the long axis (17.4±4.3 vs. 9.3±4.0, P<0.01). We conclude that True FISP cine has a higher contrast in a shorter imaging time than FLASH cine. True FISP cine is especially useful in patients with poor cardiac function. (author)

Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing

Science.gov (United States)

Lind, Johan U.; Busbee, Travis A.; Valentine, Alexander D.; Pasqualini, Francesco S.; Yuan, Hongyan; Yadid, Moran; Park, Sung-Jin; Kotikian, Arda; Nesmith, Alexander P.; Campbell, Patrick H.; Vlassak, Joost J.; Lewis, Jennifer A.; Parker, Kevin K.

2017-03-01

Biomedical research has relied on animal studies and conventional cell cultures for decades. Recently, microphysiological systems (MPS), also known as organs-on-chips, that recapitulate the structure and function of native tissues in vitro, have emerged as a promising alternative. However, current MPS typically lack integrated sensors and their fabrication requires multi-step lithographic processes. Here, we introduce a facile route for fabricating a new class of instrumented cardiac microphysiological devices via multimaterial three-dimensional (3D) printing. Specifically, we designed six functional inks, based on piezo-resistive, high-conductance, and biocompatible soft materials that enable integration of soft strain gauge sensors within micro-architectures that guide the self-assembly of physio-mimetic laminar cardiac tissues. We validated that these embedded sensors provide non-invasive, electronic readouts of tissue contractile stresses inside cell incubator environments. We further applied these devices to study drug responses, as well as the contractile development of human stem cell-derived laminar cardiac tissues over four weeks.

Long-lasting functional disabilities in patients who recover from coma after cardiac operations.

Science.gov (United States)

Rodriguez, Rosendo A; Nair, Shona; Bussière, Miguel; Nathan, Howard J

2013-03-01

Uncertainty regarding the long-term functional outcome of patients who awaken from coma after cardiac operations is difficult for families and physicians and may delay rehabilitation. We studied the long-term functional status of these patients to determine if duration of coma predicted outcome. We followed 71 patients who underwent cardiac operations; recovered their ability to respond to verbal commands after coma associated with postoperative stroke, encephalopathy, and/or seizures; and were discharged from the hospital. The Glasgow Outcome Scale Extended (GOSE) was used to assess functional disability 2 to 4 years after discharge. Outcomes were classified as favorable (GOSE scores 7 and 8) and unfavorable (GOSE scores 1-6). Of 71 patients identified, 39 were interviewed, 15 died, 1 refused to be interviewed, and 16 were lost to follow-up. Of the 54 patients with completed GOSE evaluations, only 15 (28%) had favorable outcomes. Among patients with unfavorable outcomes, 15 (28%) died, 14 (26%) survived with moderate disabilities, and 10 (18%) had severe disabilities. Factors associated with unfavorable outcomes were increases in duration of coma (p = 0.007), time in intensive care (p = 0.006), length of hospitalization (p = 0.004), and postoperative serum creatine kinase levels (p = 0.006). Only duration of coma was an independent predictor of unfavorable outcome (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.008-1.537; p = 0.042). Patients with durations of coma greater than 4 days were more likely to have unfavorable outcomes (OR, 5.1; 95% CI, 1.3-21.3; p = 0.02). Two thirds of comatose patients who survived to discharge after cardiac operations had unfavorable long-term functional outcomes. A longer duration of unconsciousness is a predictor of unfavorable outcome. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma

International Nuclear Information System (INIS)

Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.; Steen, V.D.; Uretsky, B.F.; Owens, G.R.; Rodnan, G.P.

1984-01-01

To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thallium defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent, and 36 +/- 12 per cent vs. 47 +/- 7 per cent, respectively). The authors conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury

Evaluation of right cardiac function with sup(81m)Kr

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Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Kotsuka, Takahiro [National Cardiovascular Center, Suita, Osaka (Japan)

1982-10-01

Right cardiac function was evaluated by a first-pass method of repeated rapid injections of sup(81m)Kr, and by a multigated scanning of continuous injections using a scinticamera and a computer system. Right ventricular ejection fraction (RVEF) was rather low in the ascending course of time-activity curve and rather high in the descending course by the use of rapid injection. The RVEF estimated by the rapid injection method was relatively high in ischemic heart disease; but the figure was a little changed in tricuspid insufficiency, especially in the case with high reflux, showing no effect of rapid injection. There was a good correlation between the result of rapid injection and that of the sup(99m)Tc-first-pass method. Clinically, a little increase in RVEF due to exercise was observed in a group of right coronary artery obstruction, and in all the cases of tricuspid insufficiency changes in RVEF due to exercise was in good accordance with the result of classification of severity of the disease. Accuracy in RVEF estimated by the rapid injection method was correlated with that of multi-gated scanning. In continuous observation of right cardiac function by the continuous injection method, decreased RVEF following exercise was noted in cases of inferior wall infarction with atrial fibrillation, compared with the RVEF in cases of anterior wall infarction with normal right coronary arteries.

A model of survival following pre-hospital cardiac arrest based on the Victorian Ambulance Cardiac Arrest Register.

Science.gov (United States)

Fridman, Masha; Barnes, Vanessa; Whyman, Andrew; Currell, Alex; Bernard, Stephen; Walker, Tony; Smith, Karen L

2007-11-01

This study describes the epidemiology of sudden cardiac arrest patients in Victoria, Australia, as captured via the Victorian Ambulance Cardiac Arrest Register (VACAR). We used the VACAR data to construct a new model of out-of-hospital cardiac arrest (OHCA), which was specified in accordance with observed trends. All cases of cardiac arrest in Victoria that were attended by Victorian ambulance services during the period of 2002-2005. Overall survival to hospital discharge was 3.8% among 18,827 cases of OHCA. Survival was 15.7% among 1726 bystander witnessed, adult cardiac arrests of presumed cardiac aetiology, presenting in ventricular fibrillation or ventricular tachycardia (VF/VT), where resuscitation was attempted. In multivariate logistic regression analysis, bystander CPR, cardiac arrest (CA) location, response time, age and sex were predictors of VF/VT, which, in turn, was a strong predictor of survival. The same factors that affected VF/VT made an additional contribution to survival. However, for bystander CPR, CA location and response time this additional contribution was limited to VF/VT patients only. There was no detectable association between survival and age younger than 60 years or response time over 15min. The new model accounts for relationships among predictors of survival. These relationships indicate that interventions such as reduced response times and bystander CPR act in multiple ways to improve survival.

Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

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Ken Shinmura

2013-01-01

Full Text Available The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

Stable xenon CT measurement of cerebral blood flow in cardiac transplantation candidates: Correlation with cognitive function

International Nuclear Information System (INIS)

Bello, J.A.; Fink, M.E.; Hilal, S.K.; Rose, E.A.; Reemtsma, K.

1987-01-01

Thirteen consecutive unselected patients with NYHA class 4 cardiac failure referred for cardiac transplantation underwent neurologic examination and cerebral blood flow measurement (rCBF) using the stable xenon enhanced CT method on a GE9800 system. Eleven men and two women were studied (mean age = 43.8 +- 6.1). On neurological examination, six of the patients demonstrated normal mental function; the remaining seven patients demonstrated memory, language, or learning impairment. There was no difference in mean cardiac output between the groups (4.9 L/min +- 1.68 vs. 4.2L/min +- 1.57). rCBF was significantly reduced in the impaired group. Cognitive impairment in patients with cardiac failure can be correlated with cerebral ischemia. Stable xenon CT measurement of rCBF in transplant candidates may help identify patients requiring more rapid transplantation to prevent permanent cerebral injury

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

Science.gov (United States)

Nelson, O Lynne; Robbins, Charles T

2010-03-01

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

Adaptations to iron deficiency: cardiac functional responsiveness to norepinephrine, arterial remodeling, and the effect of beta-blockade on cardiac hypertrophy

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Walker LeeAnn

2002-01-01

Full Text Available Abstract Background Iron deficiency (ID results in ventricular hypertrophy, believed to involve sympathetic stimulation. We hypothesized that with ID 1 intravenous norepinephrine would alter heart rate (HR and contractility, 2 abdominal aorta would be larger and more distensible, and 3 the beta-blocker propanolol would reduce hypertrophy. Methods 1 30 CD rats were fed an ID or replete diet for 1 week or 1 month. Norepinephrine was infused via jugular vein; pressure was monitored at carotid artery. Saline infusions were used as a control. The pressure trace was analyzed for HR, contractility, systolic and diastolic pressures. 2 Abdominal aorta catheters inflated the aorta, while digital microscopic images were recorded at stepwise pressures to measure arterial diameter and distensibility. 3 An additional 10 rats (5 ID, 5 control were given a daily injection of propanolol or saline. After 1 month, the hearts were excised and weighed. Results Enhanced contractility, but not HR, was associated with ID hypertrophic hearts. Systolic and diastolic blood pressures were consistent with an increase in arterial diameter associated with ID. Aortic diameter at 100 mmHg and distensibility were increased with ID. Propanolol was associated with an increase in heart to body mass ratio. Conclusions ID cardiac hypertrophy results in an increased inotropic, but not chronotropic response to the sympathetic neurotransmitter, norepinephrine. Increased aortic diameter is consistent with a flow-dependent vascular remodeling; increased distensibility may reflect decreased vascular collagen content. The failure of propanolol to prevent hypertrophy suggests that ID hypertrophy is not mediated via beta-adrenergic neurotransmission.

Chronic resuscitation after trauma-hemorrhage and acute fluid replacement improves hepatocellular function and cardiac output.

Science.gov (United States)

Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

1998-01-01

To determine whether prolonged (chronic) resuscitation has any beneficial effects on cardiac output and hepatocellular function after trauma-hemorrhage and acute fluid replacement. Acute fluid resuscitation after trauma-hemorrhage restores but does not maintain the depressed hepatocellular function and cardiac output. Male Sprague-Dawley rats underwent a 5-cm laparotomy (i.e., trauma was induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleed-out volume was returned in the form of Ringer's lactate (RL). The animals were acutely resuscitated with RL using 4 times the volume of maximum bleed-out over 60 minutes, followed by chronic resuscitation of 0, 5, or 10 mL/kg/hr RL for 20 hours. Hepatocellular function was determined by an in vivo indocyanine green clearance technique. Hepatic microvascular blood flow was assessed by laser Doppler flowmetry. Plasma levels of interleukin-6 (IL-6) were determined by bioassay. Chronic resuscitation with 5 mL/kg/hr RL, but not with 0 or 10 mL/kg/hr RL, restored cardiac output, hepatocellular function, and hepatic microvascular blood flow at 20 hours after hemorrhage. The regimen above also reduced plasma IL-6 levels. Because chronic resuscitation with 5 mL/kg/hr RL after trauma-hemorrhage and acute fluid replacement restored hepatocellular function and hepatic microvascular blood flow and decreased plasma levels of IL-6, we propose that chronic fluid resuscitation in addition to acute fluid replacement should be routinely used in experimental studies of trauma-hemorrhage.

Cardiac output response to changes of the atrioventricular delay in different body positions and during exercise in patients receiving cardiac resynchronization therapy

DEFF Research Database (Denmark)

Ståhlberg, Marcus; Damgaard, Morten; Norsk, Peter

2009-01-01

AIMS: The aim of this study was to study the haemodynamic effect of atrioventricular delay (AVD) modifications within a narrow range in different body positions and during exercise in patients receiving cardiac resynchronization therapy (CRT). METHODS: The previously optimized AVD was shortened...... and prolonged by 40 ms in 27 CRT patients and 9 controls without heart failure. Cardiac output (CO) was measured by inert gas rebreathing (Innocor) as the average over different body positions (left-lateral, supine, sitting, standing, and exercise). In eight CRT patients with an implantable haemodynamic monitor......, the estimated pulmonary artery diastolic pressure (ePAD) was analysed. RESULTS: The magnitude of CO response to AVD changes was greater in CRT patients than in controls (0.25 vs. 0.20 L/min, Psize (r=0...

Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model.

Science.gov (United States)

Tveita, Torkjel; Sieck, Gary C

2012-08-01

Due to adverse effects of β-receptor agonists reported when applied during hypothermia, left ventricular (LV) cardiac effects of milrinone, a PDE3 inhibitor which mode of action is deprived the sarcolemmal β-receptor-G protein-PKA system, was tested during cooling to 15 °C. Sprague Dawley rats were instrumented to measure left ventricular (LV) pressure-volume changes using a Millar pressure-volume conductance catheter. Core temperature was reduced from 37 to 15 °C (60 min) using internal and external heat exchangers. Milrinone, or saline placebo, was given as continuous i.v. infusions for 30 min at 37 °C and during cooling. In normothermic controls continuous milrinone infusion for 90 min elevated cardiac output (CO) and stroke volume (SV) significantly. Significant differences in cardiac functional variables between the milrinone group and the saline control group during cooling to 15 °C were found: Compared to saline treated animals throughout cooling from 33 to 15 °CSV was significantly elevated in milrinone animals, the index of LV isovolumic relaxation, Tau, was significantly better preserved, and both HR and CO were significantly higher from 33 to 24 °C. Likewise, during cooling between 33 and 28 °C also LVdP/dt(max) was significantly higher in the milrinone group. Milrinone preserved LV systolic and diastolic function at a significantly higher level than in saline controls during cooling to 15 °C. In essential contrast to our previous results when using β-receptor agonists during hypothermia, the present experiment demonstrates the positive inotropic effects of milrinone on LV cardiac function during cooling to 15 °C. Copyright © 2012 Elsevier Inc. All rights reserved.

Searching for a job: Cardiac responses to acute stress and the mediating role of threat appraisal in young people.

Science.gov (United States)

Zandara, M; Garcia-Lluch, M; Villada, C; Hidalgo, V; Salvador, A

2018-02-01

Being unemployed and looking for a job has become a source of stress for many people in several European countries. However, little attention has been paid to the impact of this stressful situation on the individuals' psychophysiological stress responses. The aim of this study was to investigate the effect of being an unemployed job seeker on cognitive threat appraisal and cardiac responses to a psychosocial stressor. We exposed a group of unemployed job seekers (N = 42) and a matched group of unemployed non-job seekers (N = 40) to a standardized social stressor in form of job interview, the Trier Social Stress Test. Our results showed that unemployed job seekers manifest lower cardiac responses, along with a lower cognitive threat appraisal, compared to non-job seekers. Moreover, we observed a full mediating role of cognitive threat appraisal on the relationship between being an unemployed job seeker and cardiac responses to stress. These findings reveal that being unemployed and looking for a job has an effect on physiological responses to acute stress, as well as the importance of psychological process related to the situation. These responses might lead to negative health and motivational consequences. Theoretical and practical implications are discussed. Copyright © 2017 John Wiley & Sons, Ltd.

The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent.

Science.gov (United States)

Grimes, Kelly M; Barefield, David Y; Kumar, Mohit; McNamara, James W; Weintraub, Susan T; de Tombe, Pieter P; Sadayappan, Sakthivel; Buffenstein, Rochelle

2017-12-01

The long-lived, hypoxic-tolerant naked mole-rat well-maintains cardiac function over its three-decade-long lifespan and exhibits many cardiac features atypical of similar-sized laboratory rodents. For example, they exhibit low heart rates and resting cardiac contractility, yet have a large cardiac reserve. These traits are considered ecophysiological adaptations to their dank subterranean atmosphere of low oxygen and high carbon dioxide levels and may also contribute to negligible declines in cardiac function during aging. We asked if naked mole-rats had a different myofilament protein signature to that of similar-sized mice that commonly show both high heart rates and high basal cardiac contractility. Adult mouse ventricles predominantly expressed α-myosin heavy chain (97.9 ± 0.4%). In contrast, and more in keeping with humans, β myosin heavy chain was the dominant isoform (79.0 ± 2.0%) in naked mole-rat ventricles. Naked mole-rat ventricles diverged from those of both humans and mice, as they expressed both cardiac and slow skeletal isoforms of troponin I. This myofilament protein profile is more commonly observed in mice in utero and during cardiomyopathies. There were no species differences in phosphorylation of cardiac myosin binding protein-C or troponin I. Phosphorylation of both ventricular myosin light chain 2 and cardiac troponin T in naked mole-rats was approximately half that observed in mice. Myofilament function was also compared between the two species using permeabilized cardiomyocytes. Together, these data suggest a cardiac myofilament protein signature that may contribute to the naked mole-rat's suite of adaptations to its natural subterranean habitat.

The effects of pleural fluid drainage on respiratory function in mechanically ventilated patients after cardiac surgery.

Science.gov (United States)

Brims, Fraser J H; Davies, Michael G; Elia, Andy; Griffiths, Mark J D

2015-01-01

Pleural effusions occur commonly after cardiac surgery and the effects of drainage on gas exchange in this population are not well established. We examined pulmonary function indices following drainage of pleural effusions in cardiac surgery patients. We performed a retrospective study examining the effects of pleural fluid drainage on the lung function indices of patients recovering from cardiac surgery requiring mechanical ventilation for more than 7 days. We specifically analysed patients who had pleural fluid removed via an intercostal tube (ICT: drain group) compared with those of a control group (no effusion, no ICT). In the drain group, 52 ICTs were sited in 45 patients. The mean (SD) volume of fluid drained was 1180 (634) mL. Indices of oxygenation were significantly worse in the drain group compared with controls prior to drainage. The arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (P/F) ratio improved on day 1 after ICT placement (mean (SD), day 0: 31.01 (8.92) vs 37.18 (10.7); pdrain group patients were more likely to have an improved mode of ventilation on day 1 compared with controls (p=0.028). Pleural effusion after cardiac surgery may impair oxygenation. Drainage of pleural fluid is associated with a rapid and sustained improvement in oxygenation.

Raf-mediated cardiac hypertrophy in adult Drosophila

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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

Effects of cigarette smoking on cardiac autonomic function during dynamic exercise.

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

2011-06-01

The purpose of this study was to investigate the acute effect of cigarette smoking on cardiac autonomic function in young adult smokers during dynamic exercise. Fourteen healthy young smokers (21.4 ± 3.4 years) performed peak and submaximal exercise protocols under control and smoking conditions. Resting and submaximal beat-to-beat R-R series were recorded and spectrally decomposed using the fast Fourier transformation. Smoking resulted in a significant decrease in work time, VO(2peak) and peak O(2) pulse (P exercise after smoking (P smoking, both at rest and during exercise (P smoking (P smoking, but only at rest (P smoking is accompanied by acute changes in heart rate spectral components both at rest and during exercise. Therefore, the cardiac autonomic control is altered by smoking not only at rest, but also during exercise, resulting in reduced vagal modulation and increased sympathetic dominance.

Autonomic cardiac innervation

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Hasan, Wohaib

2013-01-01

Autonomic cardiac neurons have a common origin in the neural crest but undergo distinct developmental differentiation as they mature toward their adult phenotype. Progenitor cells respond to repulsive cues during migration, followed by differentiation cues from paracrine sources that promote neurochemistry and differentiation. When autonomic axons start to innervate cardiac tissue, neurotrophic factors from vascular tissue are essential for maintenance of neurons before they reach their targets, upon which target-derived trophic factors take over final maturation, synaptic strength and postnatal survival. Although target-derived neurotrophins have a central role to play in development, alternative sources of neurotrophins may also modulate innervation. Both developing and adult sympathetic neurons express proNGF, and adult parasympathetic cardiac ganglion neurons also synthesize and release NGF. The physiological function of these “non-classical” cardiac sources of neurotrophins remains to be determined, especially in relation to autocrine/paracrine sustenance during development.   Cardiac autonomic nerves are closely spatially associated in cardiac plexuses, ganglia and pacemaker regions and so are sensitive to release of neurotransmitter, neuropeptides and trophic factors from adjacent nerves. As such, in many cardiac pathologies, it is an imbalance within the two arms of the autonomic system that is critical for disease progression. Although this crosstalk between sympathetic and parasympathetic nerves has been well established for adult nerves, it is unclear whether a degree of paracrine regulation occurs across the autonomic limbs during development. Aberrant nerve remodeling is a common occurrence in many adult cardiovascular pathologies, and the mechanisms regulating outgrowth or denervation are disparate. However, autonomic neurons display considerable plasticity in this regard with neurotrophins and inflammatory cytokines having a central regulatory

Ultrasonographic assessment of maternal cardiac function and peripheral circulation during normal gestation in dogs.

Science.gov (United States)

Blanco, Paula G; Tórtora, Mariana; Rodríguez, Raúl; Arias, Daniel O; Gobello, Cristina

2011-10-01

The aim of this study was to describe changes in cardiac morphology, systolic function and some peripheral hemodynamic parameters during normal pregnancy in dogs. Twenty healthy bitches, 10 pregnant (PG) and 10 non-pregnant controls (CG), were evaluated every 10 days using echocardiography from day 0 of the estrus cycle to parturition or to day 65 for the PG and CG groups, respectively. Systolic blood pressure (SBP) and uterine artery resistance index (RI) were also assessed. Throughout the study, the shortening fraction and cardiac output increased up to 30% vs. 5% (Pdogs. Copyright © 2010 Elsevier Ltd. All rights reserved.

Optogenetic release of norepinephrine from cardiac sympathetic neurons alters mechanical and electrical function.

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Wengrowski, Anastasia M; Wang, Xin; Tapa, Srinivas; Posnack, Nikki Gillum; Mendelowitz, David; Kay, Matthew W

2015-02-01

Release of norepinephrine (NE) from sympathetic neurons enhances heart rate (HR) and developed force through activation of β-adrenergic receptors, and this sympathoexcitation is a key risk for the generation of cardiac arrhythmias. Studies of β-adrenergic modulation of cardiac function typically involve the administration of exogenous β-adrenergic receptor agonists to directly elicit global β-adrenergic receptor activation by bypassing the involvement of sympathetic nerve terminals. In this work, we use a novel method to activate sympathetic fibres within the myocardium of Langendorff-perfused hearts while measuring changes in electrical and mechanical function. The light-activated optogenetic protein channelrhodopsin-2 (ChR2) was expressed in murine catecholaminergic sympathetic neurons. Sympathetic fibres were then photoactivated to examine changes in contractile force, HR, and cardiac electrical activity. Incidence of arrhythmia was measured with and without exposure to photoactivation of sympathetic fibres, and hearts were optically mapped to detect changes in action potential durations and conduction velocities. Results demonstrate facilitation of both developed force and HR after photostimulated release of NE, with increases in contractile force and HR of 34.5 ± 5.5 and 25.0 ± 9.3%, respectively. Photostimulation of sympathetic fibres also made hearts more susceptible to arrhythmia, with greater incidence and severity. In addition, optically mapped action potentials displayed a small but significant shortening of the plateau phase (-5.5 ± 1.0 ms) after photostimulation. This study characterizes a powerful and clinically relevant new model for studies of cardiac arrhythmias generated by increasing the activity of sympathetic nerve terminals and the resulting activation of myocyte β-adrenergic receptors. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

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

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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

Cardiac autonomic responses induced by mental tasks and the influence of musical auditory stimulation.

Science.gov (United States)

Barbosa, Juliana Cristina; Guida, Heraldo L; Fontes, Anne M G; Antonio, Ana M S; de Abreu, Luiz Carlos; Barnabé, Viviani; Marcomini, Renata S; Vanderlei, Luiz Carlos M; da Silva, Meire L; Valenti, Vitor E

2014-08-01

We investigated the acute effects of musical auditory stimulation on cardiac autonomic responses to a mental task in 28 healthy men (18-22 years old). In the control protocol (no music), the volunteers remained at seated rest for 10 min and the test was applied for five minutes. After the end of test the subjects remained seated for five more minutes. In the music protocol, the volunteers remained at seated rest for 10 min, then were exposed to music for 10 min; the test was then applied over five minutes, and the subjects remained seated for five more minutes after the test. In the control and music protocols the time domain and frequency domain indices of heart rate variability remained unchanged before, during and after the test. We found that musical auditory stimulation with baroque music did not influence cardiac autonomic responses to the mental task. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.)

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.

Cardiac Response to Chronic Intermittent Hypoxia with a Transition from Adaptation to Maladaptation: The Role of Hydrogen Peroxide

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Xia Yin

2012-01-01

Full Text Available Obstructive sleep apnea (OSA is a highly prevalent respiratory disorder of sleep, and associated with chronic intermittent hypoxia (CIH. Experimental evidence indicates that CIH is a unique physiological state with potentially “adaptive” and “maladaptive” consequences for cardio-respiratory homeostasis. CIH is also a critical element accounting for most of cardiovascular complications of OSA. Cardiac response to CIH is time-dependent, showing a transition from cardiac compensative (such as hypertrophy to decompensating changes (such as failure. CIH-provoked mild and transient oxidative stress can induce adaptation, but severe and persistent oxidative stress may provoke maladaptation. Hydrogen peroxide as one of major reactive oxygen species plays an important role in the transition of adaptive to maladaptive response to OSA-associated CIH. This may account for the fact that although oxidative stress has been recognized as a driver of cardiac disease progression, clinical interventions with antioxidants have had little or no impact on heart disease and progression. Here we focus on the role of hydrogen peroxide in CIH and OSA, trying to outline the potential of antioxidative therapy in preventing CIH-induced cardiac damage.

Evaluation of the diagnostic accuracy of ultra-miniaturized pocket ultrasound device on cardiac function in critically ill patients

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Li WANG

2016-09-01

Full Text Available Objective 　To compare the diagnostic accuracy of a new ultra-miniaturized pocket ultrasound device (PUD (VscanTM, GE Healthcare, Wauwatosa, WI and conventional high-quality echocardiography system (Vivid qTM, GE Healthcare for a cardiac focused ultrasonography in critical patients. Methods 　The patients admitted to our hospital and receiving transthoracic echocardiography (TTE using a PUD and a conventional echocardiography system were included in this study during the 10 months from December 2013 to October 2014. Each examination was performed independently by an intensive care unit (ICU physician and an experienced ultrasound doctor, unaware of the results found by the alternative device. The following parameters were assessed: global cardiac systolic function, identification of ventricular size, whether or not accompanying enlargement or hypertrophy, assessment for the morphology of cardiac valves and its function, pericardial effusion and estimation of the inferior vena cava (IVC diameter. The time-consuming of each device were recorded. Results 　One hundred and twenty-eight patients were included in the study. Their left ventricular wall motion abnormalities, global left ventricular systolic dysfunction, pericardial effusion, IVC dilation were assessed by PUD and the assessment results were highly consistent with those by Vivid q (κ>0.84. The consistency was slightly lower in evaluating the left and right ventricular size. For evaluating the cardiac valves function, the agreement of two devices were relatively low (κ=0.69-0.84. Compared with Vivid q, PUD took less time (4.7±1.4min vs 6.3±2.6min; P<0.05. Conclusion 　PUD can provide fast, reliable cardiac examination, thus being an effective method for ICU physicians to assess the cardiac f unction in critical patients. DOI: 10.11855/j.issn.0577-7402.2016.08.10

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

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

2011-01-01

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

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

NARCIS (Netherlands)

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

2012-01-01

BACKGROUND Loss-of-function sodium channelopathies manifest as a spectrum of diseases including Brugada syndrome (BrS) and cardiac conduction disease. OBJECTIVE To analyze the diagnostic and therapeutic aspects of these disorders in children. METHODS Patients aged <= 16 years with genetically

Premature Ventricular Contraction Coupling Interval Variability Destabilizes Cardiac Neuronal and Electrophysiological Control: Insights from Simultaneous Cardio-Neural Mapping

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Hamon, David; Rajendran, Pradeep S.; Chui, Ray W.; Ajijola, Olujimi A.; Irie, Tadanobu; Talebi, Ramin; Salavatian, Siamak; Vaseghi, Marmar; Bradfield, Jason S.; Armour, J. Andrew; Ardell, Jeffrey L.; Shivkumar, Kalyanam

2017-01-01

Background Variability in premature ventricular contraction (PVC) coupling interval (CI) increases the risk of cardiomyopathy and sudden death. The autonomic nervous system regulates cardiac electrical and mechanical indices, and its dysregulation plays an important role in cardiac disease pathogenesis. The impact of PVCs on the intrinsic cardiac nervous system (ICNS), a neural network on the heart, remains unknown. The objective was to determine the effect of PVCs and CI on ICNS function in generating cardiac neuronal and electrical instability using a novel cardio-neural mapping approach. Methods and Results In a porcine model (n=8) neuronal activity was recorded from a ventricular ganglion using a microelectrode array, and cardiac electrophysiological mapping was performed. Neurons were functionally classified based on their response to afferent and efferent cardiovascular stimuli, with neurons that responded to both defined as convergent (local reflex processors). Dynamic changes in neuronal activity were then evaluated in response to right ventricular outflow tract PVCs with fixed short, fixed long, and variable CI. PVC delivery elicited a greater neuronal response than all other stimuli (P<0.001). Compared to fixed short and long CI, PVCs with variable CI had a greater impact on neuronal response (P<0.05 versus short CI), particularly on convergent neurons (P<0.05), as well as neurons receiving sympathetic (P<0.05) and parasympathetic input (P<0.05). The greatest cardiac electrical instability was also observed following variable (short) CI PVCs. Conclusions Variable CI PVCs affect critical populations of ICNS neurons and alter cardiac repolarization. These changes may be critical for arrhythmogenesis and remodeling leading to cardiomyopathy. PMID:28408652

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

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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...

Cardiac function and tadalafil used for treating fetal growth restriction in pregnant women without cardiovascular disease.

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Tanaka, Kayo; Tanaka, Hiroaki; Maki, Shintaro; Kubo, Michiko; Nii, Masafumi; Magawa, Shoichi; Hatano, Fumi; Tsuji, Makoto; Osato, Kazuhiro; Kamimoto, Yuki; Umekawa, Takashi; Ikeda, Tomoaki

2018-02-20

The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason. We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use. Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use. Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother's cardiac function.

Right-sided cardiac function in healthy volunteers measured by first-pass radionuclide ventriculography and gated blood-pool SPECT: comparison with cine MRI

DEFF Research Database (Denmark)

Kjaer, Andreas; Lebech, Anne-Mette; Hesse, Birger

2005-01-01

for evaluation of right-sided cardiac function. The aim of our study was to compare the agreement between these methods when measuring right-sided cardiac function. METHODS: Twenty-four healthy volunteers were included. Mean age was 44 years (range: 25-60) and 29% were females. All participants had FP, GBPS...

Gravity Reception and Cardiac Function in the Spider

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Finck, A.

1985-01-01

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

Cardiac fluid dynamics meets deformation imaging.

Science.gov (United States)

Dal Ferro, Matteo; Stolfo, Davide; De Paris, Valerio; Lesizza, Pierluigi; Korcova, Renata; Collia, Dario; Tonti, Giovanni; Sinagra, Gianfranco; Pedrizzetti, Gianni

2018-02-20

Cardiac function is about creating and sustaining blood in motion. This is achieved through a proper sequence of myocardial deformation whose final goal is that of creating flow. Deformation imaging provided valuable contributions to understanding cardiac mechanics; more recently, several studies evidenced the existence of an intimate relationship between cardiac function and intra-ventricular fluid dynamics. This paper summarizes the recent advances in cardiac flow evaluations, highlighting its relationship with heart wall mechanics assessed through the newest techniques of deformation imaging and finally providing an opinion of the most promising clinical perspectives of this emerging field. It will be shown how fluid dynamics can integrate volumetric and deformation assessments to provide a further level of knowledge of cardiac mechanics.

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.)

The effects of pleural fluid drainage on respiratory function in mechanically ventilated patients after cardiac surgery

Science.gov (United States)

Brims, Fraser J H; Davies, Michael G; Elia, Andy; Griffiths, Mark J D

2015-01-01

Background Pleural effusions occur commonly after cardiac surgery and the effects of drainage on gas exchange in this population are not well established. We examined pulmonary function indices following drainage of pleural effusions in cardiac surgery patients. Methods We performed a retrospective study examining the effects of pleural fluid drainage on the lung function indices of patients recovering from cardiac surgery requiring mechanical ventilation for more than 7 days. We specifically analysed patients who had pleural fluid removed via an intercostal tube (ICT: drain group) compared with those of a control group (no effusion, no ICT). Results In the drain group, 52 ICTs were sited in 45 patients. The mean (SD) volume of fluid drained was 1180 (634) mL. Indices of oxygenation were significantly worse in the drain group compared with controls prior to drainage. The arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (P/F) ratio improved on day 1 after ICT placement (mean (SD), day 0: 31.01 (8.92) vs 37.18 (10.7); pdrain group patients were more likely to have an improved mode of ventilation on day 1 compared with controls (p=0.028). Conclusions Pleural effusion after cardiac surgery may impair oxygenation. Drainage of pleural fluid is associated with a rapid and sustained improvement in oxygenation. PMID:26339492

Peptide Functionalized Gold Nanorods for the Sensitive Detection of a Cardiac Biomarker Using Plasmonic Paper Devices (Postprint)

Science.gov (United States)

2015-11-10

Albumin to saturate the non-specific binding sites on the paper substrate prior to troponin exposure. For testing the biosensor, troponin of various...AFRL-RX-WP-JA-2016-0191 PEPTIDE FUNCTIONALIZED GOLD NANORODS FOR THE SENSITIVE DETECTION OF A CARDIAC BIOMARKER USING PLASMONIC PAPER ...SENSITIVE DETECTION OF A CARDIAC BIOMARKER USING PLASMONIC PAPER DEVICES (POSTPRINT) 5a. CONTRACT NUMBER FA8650-15-D-5405-0001 5b. GRANT NUMBER 5c

Traditional Chinese Medicine Tongxinluo Improves Cardiac Function of Rats with Dilated Cardiomyopathy

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Fang-Fang Shen

2014-01-01

Full Text Available The study aimed at testing the hypothesis that tongxinluo capsule might exert its cardioprotective effect by preventing ventricular remodeling and improving coronary microvascular function in a rat model of doxorubicin-induced dilated cardiomyopathy (DCM. Rats that survived DCM induction were randomly divided into three groups to be given 1.5 g·kg−1·day−1 (TXL-H, n=9 or 0.15 g·kg−1·day−1 (TXL-L, n=10 of tongxinluo, or normal saline at the same volume (DCM-C, n=10 intragastrically. Age matched normal rats treated with normal saline were used as normal controls (NOR-C, n=9. After four weeks of treatment, the DCM-C, TXL-H, and TXL-L groups exhibited significant cardiac dysfunction, left ventricular remodeling, and coronary microvascular dysfunction, compared with the NOR-C rats. However, myocardial functional parameters were significantly improved and microvascular density (MVD increased in the TXL-H group compared with the DCM-C group (all P<0.01. Left ventricular remodeling was prevented. There were close linear relationships between CVF and LVEF (r=-0.683, P<0.05, MVD and LVEF (r=0.895, P<0.05, and MVD and CVF (r=-0.798, P<0.05. It was indicated that high-dose tongxinluo effectively improved cardiac function in rat model of DCM.

Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats.

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Mao, Chenggang; Hou, Xu; Wang, Benzhen; Chi, Jingwei; Jiang, Yanjie; Zhang, Caining; Li, Zipu

2017-01-28

Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model. A DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy. Injection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity. Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium.

Effects of local cardiac denervation on cardiac innervation and ventricular arrhythmia after chronic myocardial infarction.

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Xudong Liu

Full Text Available Modulation of the autonomic nervous system (ANS has already been demonstrated to display antiarrhythmic effects in patients and animals with MI. In this study, we investigated whether local cardiac denervation has any beneficial effects on ventricular electrical stability and cardiac function in the chronic phase of MI.Twenty-one anesthetized dogs were randomly assigned into the sham-operated, MI and MI-ablation groups, respectively. Four weeks after local cardiac denervation, LSG stimulation was used to induce VPCs and VAs. The ventricular fibrillation threshold (VFT and the incidence of inducible VPCs were measured with electrophysiological protocol. Cardiac innervation was determined with immunohistochemical staining of growth associated protein-43 (GAP43 and tyrosine hydroxylase (TH. The global cardiac and regional ventricular function was evaluated with doppler echocardiography in this study.Four weeks after operation, the incidence of inducible VPC and VF in MI-ablation group were significantly reduced compared to the MI dogs (p<0.05. Moreover, local cardiac denervation significantly improved VFT in the infarcted border zone (p<0.05. The densities of GAP43 and TH-positive nerve fibers in the infarcted border zone in the MI-ablation group were lower than those in the MI group (p<0.05. However, the local cardiac denervation did not significantly improve cardiac function in the chronic phase of MI, determined by the left ventricle diameter (LV, left atrial diameter (LA, ejection fraction (EF.Summarily, in the chronic phase of MI, local cardiac denervation reduces the ventricular electrical instability, and attenuates spatial heterogeneity of sympathetic nerve reconstruction. Our study suggests that this methodology might decrease malignant ventricular arrhythmia in chronic MI, and has a great potential for clinical application.

Acute effects of firefighting on cardiac performance.

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Fernhall, Bo; Fahs, Christopher A; Horn, Gavin; Rowland, Thomas; Smith, Denise

2012-02-01

This study examined standard echocardiographic measures of cardiac size and performance in response to a 3-h firefighting training exercise. Forty experienced male personnel completed a standardized 3 h live firefighting exercise. Before and after the firefighting activities, participants were weighed, height, heart rate, blood pressure and blood samples were obtained, and echocardiographic measurements were made. Firefighting produced significant decreases in left ventricular diastolic dimension, stroke volume, fractional shortening, and mitral E velocity, tachycardia, a rise in core temperature, and a reduction in calculated plasma volume. On tissue Doppler imaging, there were no changes in systolic contractile function, but a decreased lateral wall diastolic velocity was observed. These findings show that 3 h of live firefighting produced cardiac changes consistent with cardiac fatigue, coupled with a decrease in systemic arterial compliance. These data show that live firefighting produces significant cardiovascular changes and future work is needed to evaluate if these changes are related to the increase in cardiovascular risk during live firefighting.

Simple regional strain pattern analysis to predict response to cardiac resynchronization therapy

DEFF Research Database (Denmark)

Risum, Niels; Jons, Christian; Olsen, Niels T

2012-01-01

A classical strain pattern of early contraction in one wall and prestretching of the opposing wall followed by late contraction has previously been associated with left bundle branch block (LBBB) activation and short-term response to cardiac resynchronization therapy (CRT). Aims of this study were...... to establish the long-term predictive value of an LBBB-related strain pattern and to identify changes in contraction patterns during short-term and long-term CRT....

Vascular calcification and cardiac function according to residual renal function in patients on hemodialysis with urination.

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Dong Ho Shin

Full Text Available Vascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD. However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis.This study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU to measure residual renal function. First, abdominal aortic calcification score (AACS and brachial-ankle pulse wave velocity (baPWV were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment.The median KRU was 0.9 (0.3-2.5 mL/min/1.73m2. AACS (4.0 [1.0-10.0] vs. 3.0 [0.0-8.0], p = 0.05 and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01 were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002 and baPWV (ß = -0.19, P = 0.05 after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05. Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08.Residual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

Effect of Cardiac Rehabilitation on Heart Rate and Functional Capacity in Patients After Myocardial Infarction

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Mandana Parvand

2016-09-01

Discussion: Cardiac rehabilitation can increase the performance of blood circulation and uptake of oxygen in body. Due to these changes, there was a significant increase in the functional capacity and an insignificant reduction in the heart rate.

Comparing the effects of a cardiac rehabilitation program on functional capacity of obese and non-obese women with coronary artery disease

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Masoumeh Sadeghi

2012-06-01

Full Text Available    BACKGROUND: Obesity and sedentary lifestyle are known as important risk factors of coronary artery disease. The prevalence of obesity has increased among both men and women in the world. Therefore, the present study tried to evaluate the effectiveness of a cardiac rehabilitation program on functional capacity and body mass index (BMI in obese and non-obese women with coronary artery disease.    METHODS: In an observational study during 2000-11, we evaluated a total of 205 women with coronary artery disease who referred to the cardiac rehabilitation unit of Isfahan Cardiovascular Research Institute, Isfahan, Iran. BMI and functional capacity of each patient were assessed before and after the program. The patients were categorized as obese or non-obese based on their BMI. All participants completed the full course of the program. Data was analyzed by independent t-test and paired t-test in SPSS15.    RESULTS: Our finding showed that an 8-week cardiac rehabilitation program had significant effects on functional capacity in obese and non-obese female patients (P < 0.01 for both. The program also resulted in BMI improvements in both groups (P < 0.01 for both. Comparing the changes in the two groups did not reveal any significant differences in functional capacity. However, the two groups were significantly different in terms of BMI changes.    CONCLUSION: Cardiac rehabilitation programs are a major step in restoration of functional capacity and improvement of BMI in obese and non-obese women with coronary artery disease.         Keywords: Cardiac Rehabilitation Program, Coronary Artery Disease, Obesity, Functional Capacity, Body Mass Index.

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

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

2015-11-15

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. Copyright © 2015 the American Physiological Society.

Protective effects of acute exercise prior to doxorubicin on cardiac function of breast cancer patients: A proof-of-concept RCT.

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Kirkham, A A; Shave, R E; Bland, K A; Bovard, J M; Eves, N D; Gelmon, K A; McKenzie, D C; Virani, S A; Stöhr, E J; Warburton, D E R; Campbell, K L

2017-10-15

Preclinical studies have reported that a single treadmill session performed 24h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24h prior to treatment changes this response. Breast cancer patients were randomized to either 30min of vigorous-intensity exercise 24h prior to the first doxorubicin treatment (n=13), or no vigorous exercise for 72h prior to treatment (control, n=11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24-48h after the treatment. Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p≤0.01). Whereas systemic vascular resistance (pvolume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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

2013-01-01

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

Fermitins, the orthologs of mammalian Kindlins, regulate the development of a functional cardiac syncytium in Drosophila melanogaster.

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James H Catterson

Full Text Available The vertebrate Kindlins are an evolutionarily conserved family of proteins critical for integrin signalling and cell adhesion. Kindlin-2 (KIND2 is associated with intercalated discs in mice, suggesting a role in cardiac syncytium development; however, deficiency of Kind2 leads to embryonic lethality. Morpholino knock-down of Kind2 in zebrafish has a pleiotropic effect on development that includes the heart. It therefore remains unclear whether cardiomyocyte Kind2 expression is required for cardiomyocyte junction formation and the development of normal cardiac function. To address this question, the expression of Fermitin 1 and Fermitin 2 (Fit1, Fit2, the two Drosophila orthologs of Kind2, was silenced in Drosophila cardiomyocytes. Heart development was assessed in adult flies by immunological methods and videomicroscopy. Silencing both Fit1 and Fit2 led to a severe cardiomyopathy characterised by the failure of cardiomyocytes to develop as a functional syncytium and loss of synchrony between cardiomyocytes. A null allele of Fit1 was generated but this had no impact on the heart. Similarly, the silencing of Fit2 failed to affect heart function. In contrast, the silencing of Fit2 in the cardiomyocytes of Fit1 null flies disrupted syncytium development, leading to severe cardiomyopathy. The data definitively demonstrate a role for Fermitins in the development of a functional cardiac syncytium in Drosophila. The findings also show that the Fermitins can functionally compensate for each other in order to control syncytium development. These findings support the concept that abnormalities in cardiomyocyte KIND2 expression or function may contribute to cardiomyopathies in humans.

Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy.

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Galán, María; Varona, Saray; Guadall, Anna; Orriols, Mar; Navas, Miquel; Aguiló, Silvia; de Diego, Alicia; Navarro, María A; García-Dorado, David; Rodríguez-Sinovas, Antonio; Martínez-González, José; Rodriguez, Cristina

2017-09-01

Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic LOX (TgLOX) mouse model with a strong cardiac expression of human LOX. TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H 2 O 2 production and with cardiofibroblast reprogramming. LOX overexpression promoted an age-associated concentric remodeling of the left ventricle and impaired diastolic function. Furthermore, LOX transgenesis aggravated angiotensin II (Ang II)-induced cardiac hypertrophy and dysfunction, which triggered a greater fibrotic response that was characterized by stronger collagen deposition and cross-linking and high expression of fibrotic markers. In addition, LOX transgenesis increased the Ang II-induced myocardial inflammatory infiltrate, exacerbated expression of proinflammatory markers, and decreased that of cardioprotective factors. Mechanistically, LOX overexpression enhanced oxidative stress and potentiated the Ang II-mediated cardiac activation of p38 MAPK while reducing AMPK activation. Our findings suggest that LOX induces an age-dependent disturbance of diastolic function and aggravates Ang II-induced hypertrophy, which provides novel insights into the role of LOX in cardiac performance.-Galán, M., Varona, S., Guadall, A., Orriols, M., Navas, M., Aguiló, S., de Diego, A., Navarro, M. A., García-Dorado, D., Rodríguez-Sinovas, A., Martínez-González, J., Rodriguez, C. Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy. © FASEB.

Traction force microscopy of engineered cardiac tissues.

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Pasqualini, Francesco Silvio; Agarwal, Ashutosh; O'Connor, Blakely Bussie; Liu, Qihan; Sheehy, Sean P; Parker, Kevin Kit

2018-01-01

Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.

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

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Stefano Toldo

2016-06-01

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

UCP3 Ablation Exacerbates High-Salt Induced Cardiac Hypertrophy and Cardiac Dysfunction

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Hongmei Lang

2018-04-01

Full Text Available Background/Aims: Excessive salt intake and left ventricular hypertrophy (LVH are both critical for the development of hypertension and heart failure. The uncoupling protein 3 (UCP3 plays a cardio-protective role in early heart failure development. However, the potential role for UCP3 in salt intake and LVH is unclear. Methods: UCP3-/- and C57BL/6 mice were placed on either a normal-salt (NS, 0.5% or a high-salt (HS, 8% diet for 24 weeks. The cardiac function, endurance capacity, energy expenditure, and mitochondrial functional capacity were measured in each group. Results: Elevated blood pressure was only observed in HS-fed UCP3-/- mice. High salt induced cardiac hypertrophy and dysfunction were observed in both C57BL/6 and UCP3-/- mice. However, the cardiac lesions were more profound in HS-fed UCP3-/- mice. Furthermore, HS-fed UCP3-/-mice experienced more severe mitochondrial respiratory dysfunction compared with HS-fed C57BL/6 mice, represented by the decreased volume of oxygen consumption and heat production at the whole-body level. Conclusion: UCP3 protein was involved in the incidence of high-salt induced hypertension and the progression of cardiac dysfunction in the early stages of heart failure. UCP3 ablation exacerbated high-salt-induced cardiac hypertrophy and cardiac dysfunction.

Evaluation of cardiac function using multi-shot echo planar imaging

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Nakanishi, Tadashi; Tanitame, Nobuko; Hata, Ryoichiro; Hirai, Nobuhiko; Ikeda, Midori; Ono, Chiaki; Fukuoka, Haruhito; Ito, Katsuhide [Hiroshima Univ. (Japan). School of Medicine

1998-01-01

In this study, we performed multi-shot echo planar imaging (8 shot, TR/TE/FL=55 ms/18 ms/60 degrees) and k-space segmented fast gradient echo sequence (8 views per segment, TR/TE/FL=9.9 ms/1.8 ms/30 degrees) to assess cardiac function in healthy volunteers. Transaxial sections of the entire heart were obtained with both sequences in ECG triggered, breath hold, and with a 256 x 128 matrix. Resulting temporal resolution was 55 ms for echo planar imaging, and 71 ms for k-space segmented fast gradient echo sequence, respectively. Ventricular volume and ejection fraction of both ventricles and left ventricular mass obtained with multi-shot echo planar imaging were assessed in comparison with k-space segmented fast gradient echo sequence. Measurements of left ventricular volume, ejection fraction and mass obtained with multi-shot echo planar imaging demonstrated close correlation with those obtained with k-space segmented fast gradient echo sequence. Right ventricular volumes obtained with echo planar imaging were significantly higher than those obtained with k-space segmented fast gradient echo sequence. This tendency is considered to be due to differing contrast between right ventricular myocardium and fat tissue observed with echo planar imaging relative to that observed with fast gradient echo sequence, because fat suppression is always performed in echo planar images. Multi-shot echo planar imaging can be a reliable tool for measurement of cardiac functional parameters, although wall motion analysis of the left ventricle requires higher temporal resolution and a short axial section. (K.H.)

Cardiac hypertrophy and IGF-1 response to testosterone propionate treatment in trained male rats

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Żebrowska Aleksandra

2017-04-01

Full Text Available Several studies have suggested that testosterone exerts a growth-promoting effect in the heart. Limited data are available regarding interactions between possible endocrine/paracrine effects in response to exercise training. Therefore, we examined supraphysiological testosterone-induced heart hypertrophy and cardiac insulin-like growth factor (IGF-1 content in sedentary and exercise-trained rats.

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

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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

CARDIAC AND BEHAVIORAL-RESPONSES OF LONG-TERM OBESE AND LEAN ZUCKER RATS TO EMOTIONAL-STRESS

NARCIS (Netherlands)

NYAKAS, C; BALKAN, B; STEFFENS, AB; BOHUS, B

1995-01-01

Obesity is known as a risk factor in stress-related cardiovascular pathology in man. The length of obesity can be an important interacting variable. Therefore, cardiac and behavioral responses to emotional stress were studied in 1-year-old, genetically obese (fa/fa) and lean (Fa/-) male Zucker rats,

Age- and gender-specific differences in left and right ventricular cardiac function and mass determined by cine magnetic resonance imaging

International Nuclear Information System (INIS)

Sandstede, J.; Lipke, C.; Beer, M.; Hofmann, S.; Pabst, T.; Kenn, W.; Hahn, D.; Neubauer, S.

2000-01-01

We examined possible age- and gender-specific differences in the function and mass of left (LV) and right (RV) ventricles in 36 healthy volunteers using cine gradient-recalled echo magnetic resonance imaging. Subjects were divided into four groups (nine men and nine women in each): men aged under 45 years (32 ± 7), women aged under 45 (27 ± 6), men aged over 45 (59 ± 8), and women aged over 45 (57 ± 9). Functional analysis of cardiac volume and mass and of LV wall motion was performed by manual segmentation of the endocardial and epicardial borders of the end-diastolic and end-systolic frame; both absolute and normalized (per square meter body surface area) values were evaluated. With age there was a significant decrease in both absolute and normalized LV and RV chamber volumes (EDV, ESV), while LV and RV masses remained unchanged. Gender-specific differences were found in cardiac mass and volume (for men and women, respectively: LV mass, 155 ± 18 and 110 ± 16 g; LV EDV, 118 ± 27 and 96 ± 21 ml; LV ESV, 40 ± 13 and 29 ± 9 ml; RV mass, 52 ± 10 and 39 ± 5 g; RV EDV, 131 ± 28 and 100 ± 23 ml; RV ESV, 53 ± 17 and 33 ± 15 ml). Normalization to body surface area eliminated differences in LV volumes but not those in LV mass, RV mass, or RV function. Functional parameters such as cardiac output and LV ejection fraction showed nonsignificant or only slight differences and were thus largely independent of age and gender. Intra- and interobserver variability ranged between 1.4 % and 5.9 % for all parameters. Cine magnetic resonance imaging thus shows age- and gender-specific differences in cardiac function, and therefore the evaluation of cardiac function in patients should consider age- and gender-matched normative values. (orig.)

Nppa and Nppb act redundantly during zebrafish cardiac development to confine AVC marker expression and reduce cardiac jelly volume.

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Grassini, Daniela R; Lagendijk, Anne K; De Angelis, Jessica E; Da Silva, Jason; Jeanes, Angela; Zettler, Nicole; Bower, Neil I; Hogan, Benjamin M; Smith, Kelly A

2018-05-11

Atrial natriuretic peptide ( nppa/anf ) and brain natriuretic peptide ( nppb/bnp ) form a gene cluster with expression in the chambers of the developing heart. Despite restricted expression, a function in cardiac development has not been demonstrated by mutant analysis. This is attributed to functional redundancy however their genomic location in cis has impeded formal analysis. Using genome-editing, we generated mutants for nppa and nppb and found single mutants indistinguishable from wildtype whereas nppa / nppb double mutants display heart morphogenesis defects and pericardial oedema. Analysis of atrioventricular canal (AVC) markers show expansion of bmp4 , tbx2b, has2 and versican expression into the atrium of double mutants. This expanded expression correlates with increased extracellular matrix in the atrium. Using a biosensor for Hyaluronic acid to measure the cardiac jelly (cardiac extracellular matrix), we confirm cardiac jelly expansion in nppa / nppb double mutants. Finally, bmp4 knockdown rescues the expansion of has2 expression and cardiac jelly in double mutants. This definitively shows that nppa and nppb function redundantly during cardiac development to restrict gene expression to the AVC, preventing excessive cardiac jelly synthesis in the atrial chamber. © 2018. Published by The Company of Biologists Ltd.

Cardiac effects of electrically induced intrathoracic autonomic reflexes.

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Armour, J A

1988-06-01

Electrical stimulation of the afferent components in one cardiopulmonary nerve (the left vagosympathetic complex at a level immediately caudal to the origin of the left recurrent laryngeal nerve) in acutely decentralized thoracic autonomic ganglionic preparations altered cardiac chronotropism and inotropism in 17 of 44 dogs. Since these neural preparations were acutely decentralized, the effects were mediated presumably via intrathoracic autonomic reflexes. The lack of consistency of these reflexly generated cardiac responses presumably were due in part to anatomical variation of afferent axons in the afferent nerve stimulated. As stimulation of the afferent components in the same neural structure caudal to the heart (where cardiopulmonary afferent axons are not present) failed to elicit cardiac responses in any dog, it is presumed that when cardiac responses were elicited by the more cranially located stimulations, these were due to activation of afferent axons arising from the heart and (or) lungs. When cardiac responses were elicited, intramyocardial pressures in the right ventricular conus as well as the ventral and lateral walls of the left ventricle were augmented. Either bradycardia or tachycardia was elicited. Following hexamethonium administration no responses were produced, demonstrating that nicotonic cholinergic synaptic mechanisms were involved in these intrathoracic cardiopulmonary-cardiac reflexes. In six of the animals, when atropine was administered before hexamethonium, reflexly generated responses were attenuated. The same thing occurred when morphine was administered in four animals. In contrast, in four animals following administration of phentolamine, the reflexly generated changes were enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of Bystander Cardiopulmonary Resuscitation and Survival According to Ambulance Response Times After Out-of-Hospital Cardiac Arrest.

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Rajan, Shahzleen; Wissenberg, Mads; Folke, Fredrik; Hansen, Steen Møller; Gerds, Thomas A; Kragholm, Kristian; Hansen, Carolina Malta; Karlsson, Lena; Lippert, Freddy K; Køber, Lars; Gislason, Gunnar H; Torp-Pedersen, Christian

2016-12-20

Bystander-initiated cardiopulmonary resuscitation (CPR) increases patient survival after out-of-hospital cardiac arrest, but it is unknown to what degree bystander CPR remains positively associated with survival with increasing time to potential defibrillation. The main objective was to examine the association of bystander CPR with survival as time to advanced treatment increases. We studied 7623 out-of-hospital cardiac arrest patients between 2005 and 2011, identified through the nationwide Danish Cardiac Arrest Registry. Multiple logistic regression analysis was used to examine the association between time from 911 call to emergency medical service arrival (response time) and survival according to whether bystander CPR was provided (yes or no). Reported are 30-day survival chances with 95% bootstrap confidence intervals. With increasing response times, adjusted 30-day survival chances decreased for both patients with bystander CPR and those without. However, the contrast between the survival chances of patients with versus without bystander CPR increased over time: within 5 minutes, 30-day survival was 14.5% (95% confidence interval [CI]: 12.8-16.4) versus 6.3% (95% CI: 5.1-7.6), corresponding to 2.3 times higher chances of survival associated with bystander CPR; within 10 minutes, 30-day survival chances were 6.7% (95% CI: 5.4-8.1) versus 2.2% (95% CI: 1.5-3.1), corresponding to 3.0 times higher chances of 30-day survival associated with bystander CPR. The contrast in 30-day survival became statistically insignificant when response time was >13 minutes (bystander CPR vs no bystander CPR: 3.7% [95% CI: 2.2-5.4] vs 1.5% [95% CI: 0.6-2.7]), but 30-day survival was still 2.5 times higher associated with bystander CPR. Based on the model and Danish out-of-hospital cardiac arrest statistics, an additional 233 patients could potentially be saved annually if response time was reduced from 10 to 5 minutes and 119 patients if response time was reduced from 7 (the median

Functional Near-Infrared Fluorescence Imaging for Cardiac Surgery and Targeted Gene Therapy

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Akira Nakayama

2002-10-01

Full Text Available Cardiac revascularization is presently performed without realtime visual assessment of myocardial blood flow or perfusion. Moreover, gene therapy of the heart cannot, at present, be directed to specific territories at risk for myocardial infarction. We have developed a surgical imaging system that exploits the low autofluorescence, deep tissue penetration, low tissue scatter, and invisibility of near-infrared (NIR fluorescent light. By completely isolating visible and NIR light paths, one is able to visualize, simultaneously, the anatomy and/or function of the heart, or any desired tissue. In rat model systems, we demonstrate that the heptamethine indocyanine-type NIR fluorophores IR-786 and the carboxylic acid form of IRDye78 can be injected intravenously in the living animal to provide real-time visual assessment of myocardial blood flow or perfusion intraoperatively. This imaging system may prove useful for the refinement of revascularization techniques, and for the administration of cardiac gene therapy.

Cardiac retransplantation is an efficacious therapy for primary cardiac allograft failure

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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.

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

NARCIS (Netherlands)

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

2013-01-01

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

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

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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.

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

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Laila Elsherif

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

Regular physical exercise improves cardiac autonomic and muscle vasodilatory responses to isometric exercise in healthy elderly

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Sarmento AO

2017-06-01

Full Text Available Adriana de Oliveira Sarmento,1–3 Amilton da Cruz Santos,1,4 Ivani Credidio Trombetta,2,5 Marciano Moacir Dantas,1 Ana Cristina Oliveira Marques,1,4 Leone Severino do Nascimento,1,4 Bruno Teixeira Barbosa,1,2 Marcelo Rodrigues Dos Santos,2 Maria do Amparo Andrade,3 Anna Myrna Jaguaribe-Lima,3,6 Maria do Socorro Brasileiro-Santos1,3,4 1Laboratory of Physical Training Studies Applied to Health, Department of Physical Education, Federal University of Paraiba, João Pessoa, Brazil; 2Unit of Cardiovascular Rehabilitation and Exercise Physiology – Heart Institute (InCor/HC-FMUSP, University of São Paulo, São Paulo, Brazil; 3Graduate Program in Physiotherapy, Federal University of Pernambuco, Recife, Brazil; 4Associate Graduate Program in Physical Education UPE/UFPB, João Pessoa, Brazil; 5Graduate Program in Medicine, Universidade Nove de Julho (UNINOVE, São Paulo, Brazil; 6Department of Morphology and Animal Physiology, Federal Rural University of Pernambuco, Recife, Brazil Abstract: The objective of this study was to evaluate cardiac autonomic control and muscle vasodilation response during isometric exercise in sedentary and physically active older adults. Twenty healthy participants, 10 sedentary and 10 physically active older adults, were evaluated and paired by gender, age, and body mass index. Sympathetic and parasympathetic cardiac activity (spectral and symbolic heart rate analysis and muscle blood flow (venous occlusion plethysmography were measured for 10 minutes at rest (baseline and during 3 minutes of isometric handgrip exercise at 30% of the maximum voluntary contraction (sympathetic excitatory maneuver. Variables were analyzed at baseline and during 3 minutes of isometric exercise. Cardiac autonomic parameters were analyzed by Wilcoxon and Mann–Whitney tests. Muscle vasodilatory response was analyzed by repeated-measures analysis of variance followed by Tukey’s post hoc test. Sedentary older adults had higher cardiac

Sympathetic- and parasympathetic-linked cardiac function and prediction of externalizing behavior, emotion regulation, and prosocial behavior among preschoolers treated for ADHD.

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

2013-06-01

To evaluate measures of cardiac activity and reactivity as prospective biomarkers of treatment response to an empirically supported behavioral intervention for attention-deficit/hyperactivity disorder (ADHD). Cardiac preejection period (PEP), an index of sympathetic-linked cardiac activity, and respiratory sinus arrhythmia (RSA), an index of parasympathetic-linked cardiac activity, were assessed among 99 preschool children (ages 4-6 years) with ADHD both at rest and in response to behavioral challenge, before participants and their parents completed 1 of 2 versions of the Incredible Years parent and child interventions. Main effects of PEP activity and reactivity and of RSA activity and reactivity were found. Although samplewide improvements in behavior were observed at posttreatment, those who exhibited lengthened cardiac PEP at rest and reduced PEP reactivity to incentives scored higher on measures of conduct problems and aggression both before and after treatment. In contrast, children who exhibited lower baseline RSA and greater RSA withdrawal scored lower on prosocial behavior before and after treatment. Finally, children who exhibited greater RSA withdrawal scored lower on emotion regulation before and after treatment. We discuss these findings in terms of (a) individual differences in underlying neurobiological systems subserving appetitive (i.e., approach) motivation, emotion regulation, and social affiliation and (b) the need to develop more intensive interventions targeting neurobiologically vulnerable children.

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

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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.

Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.

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Yao Song

Full Text Available AIMS: It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo. METHODS AND RESULTS: We generated a cardiac-specific CARP-overexpressing transgenic mouse. Although such animals did not display any overt physiological abnormality, they developed less cardiac hypertrophy in response to pressure overload than did wildtype mice, as indicated by heart weight/body weight ratios, echocardiographic and histological analyses, and expression of hypertrophic markers. These mice also exhibited less cardiac hypertrophy after infusion of isoproterenol. To gain a molecular insight into how CARP attenuated heart hypertrophy, we examined expression of the mitogen-activated protein kinase cascade and found that the concentrations of phosphorylated ERK1/2 and MEK were markedly reduced in the hearts of transgenic mice subjected to pressure overload. In addition, the expressions of TGF-β and phosphorylated Smad3 were significantly downregulated in the hearts of CARP Tg mice in response to pressure overload. Furthermore, addition of human TGF-β1 could reverse the inhibitory effect of CARP on the hypertrophic response induced by phenylephrine in cardiomyocytes. It was also evidenced that the inhibitory effect of CARP on cardiac hypertrophy was not attributed to apoptosis. CONCLUSION: CARP attenuates cardiac hypertrophy, in which the ERK and TGF-β pathways may be involved. Our findings highlight the significance of CARP as an anti-hypertrophic factor in therapy of cardiac hypertrophy.

Biomaterials for cardiac regeneration

CERN Document Server

Ruel, Marc

2015-01-01

This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation.

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Esra Cagavi

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

Echocardiography and cardiac resynchronisation therapy, friends or foes?

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van Everdingen, W M; Schipper, J C; van 't Sant, J; Ramdat Misier, K; Meine, M; Cramer, M J

2016-01-01

Echocardiography is used in cardiac resynchronisation therapy (CRT) to assess cardiac function, and in particular left ventricular (LV) volumetric status, and prediction of response. Despite its widespread applicability, LV volumes determined by echocardiography have inherent measurement errors, interobserver and intraobserver variability, and discrepancies with the gold standard magnetic resonance imaging. Echocardiographic predictors of CRT response are based on mechanical dyssynchrony. However, parameters are mainly tested in single-centre studies or lack feasibility. Speckle tracking echocardiography can guide LV lead placement, improving volumetric response and clinical outcome by guiding lead positioning towards the latest contracting segment. Results on optimisation of CRT device settings using echocardiographic indices have so far been rather disappointing, as results suffer from noise. Defining response by echocardiography seems valid, although re-assessment after 6 months is advisable, as patients can show both continuous improvement as well as deterioration after the initial response. Three-dimensional echocardiography is interesting for future implications, as it can determine volume, dyssynchrony and viability in a single recording, although image quality needs to be adequate. Deformation patterns from the septum and the derived parameters are promising, although validation in a multicentre trial is required. We conclude that echocardiography has a pivotal role in CRT, although clinicians should know its shortcomings.

Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

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Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

2006-10-03

We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

Action Potential Shortening and Impairment of Cardiac Function by Ablation of Slc26a6.

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Sirish, Padmini; Ledford, Hannah A; Timofeyev, Valeriy; Thai, Phung N; Ren, Lu; Kim, Hyo Jeong; Park, Seojin; Lee, Jeong Han; Dai, Gu; Moshref, Maryam; Sihn, Choong-Ryoul; Chen, Wei Chun; Timofeyeva, Maria Valeryevna; Jian, Zhong; Shimkunas, Rafael; Izu, Leighton T; Chiamvimonvat, Nipavan; Chen-Izu, Ye; Yamoah, Ebenezer N; Zhang, Xiao-Dong

2017-10-01

Intracellular pH (pH i ) is critical to cardiac excitation and contraction; uncompensated changes in pH i impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH i regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl - /HCO 3 - exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pH i , but also cardiac excitability. To test the mechanistic role of Slc26a6 in the heart, we took advantage of Slc26a6 knockout ( Slc26a6 -/ - ) mice using both in vivo and in vitro analyses. Consistent with our prediction of its electrogenic activities, ablation of Slc26a6 results in action potential shortening. There are reduced Ca 2+ transient and sarcoplasmic reticulum Ca 2+ load, together with decreased sarcomere shortening in Slc26a6 -/ - cardiomyocytes. These abnormalities translate into reduced fractional shortening and cardiac contractility at the in vivo level. Additionally, pH i is elevated in Slc26a6 -/ - cardiomyocytes with slower recovery kinetics from intracellular alkalization, consistent with the Cl - /HCO 3 - exchange activities of Slc26a6. Moreover, Slc26a6 -/ - mice show evidence of sinus bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6 in cardiac conduction system. Our study provides mechanistic insights into Slc26a6, a unique cardiac electrogenic Cl - /HCO 3 - transporter in ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pH i , excitability, and contractility. pH i is a critical regulator of other membrane and contractile proteins. Future studies are needed to investigate possible changes in these proteins in Slc26a6 -/ - mice. © 2017 American Heart Association, Inc.

Natriuretic peptides in developing medaka embryos: implications in cardiac development by loss-of-function studies.

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Miyanishi, Hiroshi; Okubo, Kataaki; Nobata, Shigenori; Takei, Yoshio

2013-01-01

Cardiac natriuretic peptides (NPs), atrial NP (ANP) and B-type NP (BNP), and their receptor, guanylyl cyclase (GC)-A have attracted attention of many basic and clinical researchers because of their potent renal and cardiovascular actions. In this study, we used medaka, Oryzias latipes, as a model species to pursue the physiological functions of NPs because it is a suitable model for developmental analyses. Medaka has two ligands, BNP and C-type NP3 (CNP3) (but not ANP), that have greater affinity for the two O. latipes GC-A receptors (OLGC), OLGC7 and OLGC2, respectively. CNP3 is the ancestral molecule of cardiac NPs. Initially, we examined developmental expression of cardiac NP/receptor combinations, BNP/OLGC7 and CNP3/OLGC2, using quantitative real-time PCR and in situ hybridization. BNP and CNP3 mRNA increased at stages 25 (onset of ventricular formation) and 22 (appearance of heart anlage), respectively, whereas both receptor mRNAs increased at as early as stage 12. BNP/OLGC7 transcripts were found in arterial/ventricular tissues and CNP3/OLGC2 transcripts in venous/atrial tissues by in situ hybridization. Thus, BNP and CNP3 can act locally on cardiac myocytes in a paracrine/autocrine fashion. Double knockdown of BNP/OLGC7 genes impaired ventricular development by causing hypoplasia of ventricular myocytes as evidenced by reduced bromodeoxyuridine incorporation. CNP3 knockdown induced hypertrophy of atria and activated the renin-angiotensin system. Collectively, it appears that BNP is important for normal ventricular, whereas CNP3 is important for normal atrial development and performance, a role usually taken by ANP in other vertebrates. The current study provides new insights into the role of cardiac NPs in cardiac development in vertebrates.

Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction.

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Wang, Wei; Zhang, Fuyang; Xia, Yunlong; Zhao, Shihao; Yan, Wenjun; Wang, Helin; Lee, Yan; Li, Congye; Zhang, Ling; Lian, Kun; Gao, Erhe; Cheng, Hexiang; Tao, Ling

2016-11-01

Cardiac metabolic remodeling is a central event during heart failure (HF) development following myocardial infarction (MI). It is well known that myocardial glucose and fatty acid dysmetabolism contribute to post-MI cardiac dysfunction and remodeling. However, the role of amino acid metabolism in post-MI HF remains elusive. Branched chain amino acids (BCAAs) are an important group of essential amino acids and function as crucial nutrient signaling in mammalian animals. The present study aimed to determine the role of cardiac BCAA metabolism in post-MI HF progression. Utilizing coronary artery ligation-induced murine MI models, we found that myocardial BCAA catabolism was significantly impaired in response to permanent MI, therefore leading to an obvious elevation of myocardial BCAA abundance. In MI-operated mice, oral BCAA administration further increased cardiac BCAA levels, activated the mammalian target of rapamycin (mTOR) signaling, and exacerbated cardiac dysfunction and remodeling. These data demonstrate that BCAAs act as a direct contributor to post-MI cardiac pathologies. Furthermore, these BCAA-mediated deleterious effects were improved by rapamycin cotreatment, revealing an indispensable role of mTOR in BCAA-mediated adverse effects on cardiac function/structure post-MI. Of note, pharmacological inhibition of branched chain ketoacid dehydrogenase kinase (BDK), a negative regulator of myocardial BCAA catabolism, significantly improved cardiac BCAA catabolic disorders, reduced myocardial BCAA levels, and ameliorated post-MI cardiac dysfunction and remodeling. In conclusion, our data provide the evidence that impaired cardiac BCAA catabolism directly contributes to post-MI cardiac dysfunction and remodeling. Moreover, improving cardiac BCAA catabolic defects may be a promising therapeutic strategy against post-MI HF. Copyright © 2016 the American Physiological Society.

Medico-legal perspectives on sudden cardiac death in young athletes.

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Oliva, Antonio; Grassi, Vincenzo M; Campuzano, Oscar; Brion, Maria; Arena, Vincenzo; Partemi, Sara; Coll, Monica; Pascali, Vincenzo L; Brugada, Josep; Carracedo, Angel; Brugada, Ramon

2017-03-01

Sudden cardiac death (SCD) in a young athlete represents a dramatic event, and an increasing number of medico-legal cases have addressed this topic. In addition to representing an ethical and medico-legal responsibility, prevention of SCD is directly correlated with accurate eligibility/disqualification decisions, with an inappropriate pronouncement in either direction potentially leading to legal controversy. This review summarizes the common causes of SCD in young athletes, divided into structural (hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, congenital coronary artery anomalies, etc.), electrical (Brugada, congenital LQT, Wolf-Parkinson-White syndrome, etc.), and acquired cardiac abnormalities (myocarditis, etc.). In addition, the roles of hereditary cardiac anomalies in SCD in athletes and the effects of a positive result on them and their families are discussed. The medico-legal relevance of pre-participation screening is analyzed, and recommendations from the American Heart Association and European Society of Cardiology are compared. Finally, the main issues concerning the differentiation between physiologic cardiac adaptation in athletes and pathologic findings and, thereby, definition of the so-called gray zone, which is based on exact knowledge of the mechanism of cardiac remodeling including structural or functional adaptions, will be addressed.

Echocardiographic Evaluation of Pulmonary Pressures and Right Ventricular Function after Pediatric Cardiac Surgery: A Simple Approach for the Intensivist

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Maurice Beghetti

2017-08-01

Full Text Available Pulmonary hypertension (PH is diagnosed using cardiac catheterization and is defined as an elevation of mean pulmonary artery pressure (PAP greater than 25 mmHg. Although invasive hemodynamics remains the gold standard and is mandatory for disease confirmation, transthoracic echocardiography (TTE is an extremely useful non-invasive and widely available tool that allows for screening and follow-up, in particular, in the acute setting. TTE may be a valuable alternative, allowing for direct measurement and/or indirect assessment of PAP. Because of the complex geometric shape and pattern of contraction of the right ventricle (RV, as well as the inherent complexity of cardiac repair, no single view or measurement can provide definite information on RV function and PAP and/or pulmonary vascular resistance. In addition, specific training and expertise may be necessary to obtain the views and measurements required. Some simple measurements may be of help when rapid evaluation is mandatory and potentially life saving: the assessment of tricuspid and/or pulmonary valve regurgitant jet and the use of the Bernoulli equation allow for measurement of PAP. Measurements such as the analysis of the pulmonary Doppler wave flow, the septal curvature, or the eccentricity index, assessing ventricular interdependence, are useful for indirect assessment. A four-chamber view of the RV gives information on its size, hypertrophy, function (fractional area change, and tricuspid annular plane systolic excursion as an evaluation of the longitudinal function. Based on these simple measurements, TTE can provide detection of PH, measurement or estimation of PAP, and assessment of cardiac function. TTE is also of importance in follow up of PH as well as providing an assessment of therapeutic strategies in the postoperative setting of cardiac surgery. However, PAP may be misleading as it is dependent on cardiac output and requires accurate measurements. In the presence of

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

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Tian, Fangyun; Liu, Tiecheng; Xu, Gang; Li, Duan; Ghazi, Talha; Shick, Trevor; Sajjad, Azeem; Wang, Michael M.; Farrehi, Peter; Borjigin, Jimo

2018-01-01

Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients. PMID:29487541

Adrenergic Blockade Bi-directionally and Asymmetrically Alters Functional Brain-Heart Communication and Prolongs Electrical Activities of the Brain and Heart during Asphyxic Cardiac Arrest

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Fangyun Tian

2018-02-01

Full Text Available Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG and electroencephalogram (EEG signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.

Impact of Bystander Automated External Defibrillator Use on Survival and Functional Outcomes in Shockable Observed Public Cardiac Arrests.

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Pollack, Ross A; Brown, Siobhan P; Rea, Thomas; Aufderheide, Tom; Barbic, David; Buick, Jason E; Christenson, James; Idris, Ahamed H; Jasti, Jamie; Kampp, Michael; Kudenchuk, Peter; May, Susanne; Muhr, Marc; Nichol, Graham; Ornato, Joseph P; Sopko, George; Vaillancourt, Christian; Morrison, Laurie; Weisfeldt, Myron

2018-02-26

Background - Survival following out-of-hospital cardiac arrest (OHCA) with shockable rhythms can be improved with early defibrillation. Although shockable OHCA accounts for only ≈25% of overall arrests, ≈60% of public OHCAs are shockable, offering the possibility of restoring thousands of individuals to full recovery with early defibrillation by bystanders. We sought to determine the association of bystander automated external defibrillator use with survival and functional outcomes in shockable observed public OHCA. Methods - From 2011 to 2015, the Resuscitation Outcomes Consortium prospectively collected detailed information on all cardiac arrests at 9 regional centers. The exposures were shock administration by a bystander-applied automated external defibrillator in comparison with initial defibrillation by emergency medical services. The primary outcome measure was discharge with normal or near-normal (favorable) functional status defined as a modified Rankin Score ≤2. Survival to hospital discharge was the secondary outcome measure. Results -Among 49 555 OHCAs, 4115 (8.3%) observed public OHCAs were analyzed, of which 2500 (60.8%) were shockable. A bystander shock was applied in 18.8% of the shockable arrests. Patients shocked by a bystander were significantly more likely to survive to discharge (66.5% versus 43.0%) and be discharged with favorable functional outcome (57.1% versus 32.7%) than patients initially shocked by emergency medical services. After adjusting for known predictors of outcome, the odds ratio associated with a bystander shock was 2.62 (95% confidence interval, 2.07-3.31) for survival to hospital discharge and 2.73 (95% confidence interval, 2.17-3.44) for discharge with favorable functional outcome. The benefit of bystander shock increased progressively as emergency medical services response time became longer. Conclusions - Bystander automated external defibrillator use before emergency medical services arrival in shockable observed

[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

Cardiac CT

International Nuclear Information System (INIS)

Dewey, Marc

2011-01-01

Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)