WorldWideScience

Sample records for cardiac electrical remodeling

  1. Cardiac electrical remodeling in health and disease

    OpenAIRE

    Cutler, Michael J.; Jeyaraj, Darwin; Rosenbaum, David S.

    2011-01-01

    Electrical remodeling of the heart occurs in response to both functional (i.e. altered electrical activation) and structural (i.e. heart failure, myocardial infarction, etc.) stressors. These electrophysiological changes produce a substrate that is vulnerable to malignant ventricular arrhythmias. Understanding the cellular and molecular mechanisms of electrical remodeling is important in elucidating potential therapeutic targets designed to alter maladaptive electrical remodeling. For example...

  2. Cardiac remodelling and RAS inhibition.

    Science.gov (United States)

    Ferrario, Carlos M

    2016-06-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  3. Cardiac Remodeling After Atrial Fibrillation Ablation

    Directory of Open Access Journals (Sweden)

    Li-Wei Lo, MD; Shih-Ann Chen, MD

    2013-06-01

    Full Text Available Radiofrequency catheter ablation procedures are considered a reasonable option for patients with symptomatic, drug refractory atrial fibrillation (AF. Ablation procedures have been reported to effectively restore sinus rhythm and provide long-term relief of symptoms. Both electrical and structural remodeling occurs with AF. A reversal of the electrical remodeling develops within 1 week after restoration to sinus rhythm following the catheter ablation. The recovery rate is faster in the right atrium than the left atrium. Reverse structural remodeling takes longer and is still present 2 to 4 months after restoration of sinus rhythm. The left atrial transport function also improves after successful catheter ablation of AF. Left atrial strain surveys from echocardiography are able to identify patients who respond to catheter ablation with significant reverse remodeling after ablation. Pre-procedural delayed enhancement magnetic resonance imaging is also able to determine the degree of atrial fibrosis and is another tool to predict the reverse remodeling after ablation. The remodeling process is complex if recurrence develops after ablation. Recent evidence shows that a combined reverse electrical and structural remodeling occurs after ablation of chronic AF when recurrence is paroxysmal AF. Progressive electrical remodeling without any structural remodeling develops in those with recurrence involving chronic AF. Whether progressive atrial remodeling is the cause or consequence during the recurrence of AF remains obscure and requires further study.

  4. Cardiac electrical stunning is a common feature of cardiac arrhythmias.

    Science.gov (United States)

    Li, Guangping; Liu, Tong; Liu, Enzhao

    2006-01-01

    There are many published papers focused on the topic of atrial electrical remodeling, which defined as the shortening and dispersion of effective refractory period (ERP) in patients with paroxysmal or persistent tachyarrhythmias or in animals with long-term rapid atrial pacing. Heart failure could produce the electrical remodeling of sinus node, manifesting the prolongation of corrected sinus node recovery time and sinus cycle length. It might be attributed to decreased hyperpolarization-activated cyclic nucleotide expression of sinus node. Rapid atrial pacing for only 10-15 min, simulating transient atrial tachyarrhythmias, alters sinus node function in human. Termination of atrial flutter by ablation induces reversible changes in sinus node function. After atrial fibrillation (AF) ablation, there was a significant improvement of sinus node function, with an increase in the mean heart rate, maximal heart rate and heart rate range significantly. Reverse electrical remodeling of the ERP occurs at different rates in different regions of the atrium. Previous experiments showed that electrical remodeling of atrial myocardium could be induced by autonomic nervous transmitters and suggested that autonomic nerve activity was an important factor to promote AF episodes. We postulated that electrical remodeling and reverse electrical remodeling are common features of the heart, including atrium, ventricle, sinus node, and conductive system. Inappropriate very rapid or slow electrical depolarization may cause electrical remodeling of the heart, but appropriate rates of electrical depolarization and cessation of rapid stimulation may contribute to the reverse electrical remodeling. So, we forward that a concept defined as cardiac electrical stunning, including electrical remodeling and reverse electrical remodeling, should be a common characteristic and mechanism of cardiac arrhythmias. PMID:16759818

  5. Atrial Electrical Remodeling and Sleep Disordered Breathing

    Directory of Open Access Journals (Sweden)

    Adrian Baranchuk; Diego Conde

    2013-08-01

    . The results of this study have shown that patients with severe SDB have a longer SAPW duration than controls (131.9 ± 10.4 vs 122.8 ± 10.5 ms; p = 0.04 and that a significant reduction of the SAPW duration occurs after treatment with C-PAP (131.9 ± 10.4 to 126.2 ± 8.8 ms; p < 0.001 (Figure 1 (4. The shortening of SAPW duration and surface P-wave duration represents more rapid inter-atrial conduction and provides evidence for reverse atrial electrical remodeling. This may indicate an additional benefit of treating patients with C-PAP, as this evidence suggests that C-PAP may improve the anatomical and electrical substrate for AFib. Reverse atrial electrical remodeling is a concept in evolution, and several cardiovascular treatments may improve atrial dynamics (5. It is of utmost importance, in the times of considering AFib ablation as first line therapy for recurrent AFib; to be familiarized with the impact of non-recognized/non-treated SDBs over the cardiac electrical system. Conventional treatment for SDB as C-PAP may also represent a benefit in terms of facilitating normal atrial conduction and reducing the risks associated with AFib.

  6. Potassium Channel Interacting Protein 2 (KChIP2) is not a transcriptional regulator of cardiac electrical remodeling.

    Science.gov (United States)

    Winther, Sine V; Tuomainen, Tomi; Borup, Rehannah; Tavi, Pasi; Antoons, Gudrun; Thomsen, Morten B

    2016-01-01

    The heart-failure relevant Potassium Channel Interacting Protein 2 (KChIP2) augments CaV1.2 and KV4.3. KChIP3 represses CaV1.2 transcription in cardiomyocytes via interaction with regulatory DNA elements. Hence, we tested nuclear presence of KChIP2 and if KChIP2 translocates into the nucleus in a Ca(2+) dependent manner. Cardiac biopsies from human heart-failure patients and healthy donor controls showed that nuclear KChIP2 abundance was significantly increased in heart failure; however, this was secondary to a large variation of total KChIP2 content. Administration of ouabain did not increase KChIP2 content in nuclear protein fractions in anesthetized mice. KChIP2 was expressed in cell lines, and Ca(2+) ionophores were applied in a concentration- and time-dependent manner. The cell lines had KChIP2-immunoreactive protein in the nucleus in the absence of treatments to modulate intracellular Ca(2+) concentration. Neither increasing nor decreasing intracellular Ca(2+) concentrations caused translocation of KChIP2. Microarray analysis did not identify relief of transcriptional repression in murine KChIP2(-/-) heart samples. We conclude that although there is a baseline presence of KChIP2 in the nucleus both in vivo and in vitro, KChIP2 does not directly regulate transcriptional activity. Moreover, the nuclear transport of KChIP2 is not dependent on Ca(2+). Thus, KChIP2 does not function as a conventional transcription factor in the heart. PMID:27349185

  7. Ouabain induces cardiac remodeling in rats independent of blood pressure

    Institute of Scientific and Technical Information of China (English)

    Xing JIANG; Yan-ping REN; Zhuo-ren L(U)

    2007-01-01

    Aim: To investigate the ouabain's effects on cardiac remodeling in rats. Methods:Male Sprague-Dawley rats were treated with ouabain. Systolic blood pressure(SBP) was recorded weekly. After 4 and 6 weeks, echocardiography were performed,hemodynamic parameters were measured by invasive cardiac catheterization,changes in cardiac ultrastructure were analyzed using transmission electron microscopy, the collagen fraction of the left ventricle was assessed with Picrosirius red stain, and RT-PCR was applied to evaluate the mRNA level of myosin heavy chain-α and-β in the left ventricle. Results: Having been treated with ouabain for 4 weeks, there was no significant difference in the mean SBP of the two groups.However, left ventricular hypertrophy, myocardial ultrastructure deterioration,and extracellular matrix remodeling were induced by ouabain treatment; meanwhile,cardiac systolic and diastolic performance were both worsened. Moreover, the cardiac MHC-β mRNA was upregulated by ouabain treatment, whereas MHC-αmRNA was downregulated. After 4 weeks, the mean SBP in the ouabain group began to increase and was significantly higher than that in control group after 6 weeks (P<0.01); the rats' cardiac structure and function were worsened.Conclusion: These results suggested that ouabain induces alterations in cardiac structure and function, and the effects happened before the increase of blood pressure. The results indicated that ouabain induced cardiac remodeling in rats independent of blood pressure.

  8. Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

    Directory of Open Access Journals (Sweden)

    Marcos Minicucci

    2016-01-01

    Full Text Available Abstract Background: Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. Objective: The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Methods: Wistar rats were distributed in four groups: Control (C, Pentoxifylline (PX, Tobacco Smoke (TS, and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. Results: TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt, and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA and citrate synthase (CS. PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. Conclusion: TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

  9. Hypothyroidism and its rapid correction alter cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    Georges Hajje

    Full Text Available The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10 group and a group treated with 6-propyl-2-thiouracil (PTU (n = 20 to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP, tumor necrosis factor alpha (TNF-α, interleukin 6 (IL6 and pro-fibrotic transforming growth factor beta 1 (TGF-β1, were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP and cardiac troponin T (cTnT were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

  10. Mitochondrial Protein Dynamics in Cardiac Remodeling

    OpenAIRE

    Lau, Edward

    2014-01-01

    The cardiac mitochondrial proteome contains ~1,500 distinct proteins that carry out necessary metabolic and energetic processes in the heart. To sustain cardiac function, the mitochondrial proteome must be maintained in constant renewal, or turnover, especially under stress conditions. Disruptions of protein turnover can lead to protein damage and proteotoxicity, a hallmark of many heart disease etiologies. Current quantitative proteomics experiments largely focus on the measurement of the st...

  11. Intradialytic Hypotension and Cardiac Remodeling: A Vicious Cycle

    Directory of Open Access Journals (Sweden)

    Chia-Ter Chao

    2015-01-01

    Full Text Available Hemodynamic instability during hemodialysis is a common but often underestimated issue in the nephrologist practice. Intradialytic hypotension, namely, a decrease of systolic or mean blood pressure to a certain level, prohibits the safe and smooth achievement of ultrafiltration and solute removal goal in chronic dialysis patients. Studies have elucidated the potential mechanisms involved in the development of Intradialytic hypotension, including excessive ultrafiltration and loss of compensatory mechanisms for blood pressure maintenance. Cardiac remodeling could also be one important piece of the puzzle. In this review, we intend to discuss the role of cardiac remodeling, including left ventricular hypertrophy, in the development of Intradialytic hypotension. In addition, we will also provide evidence that a bidirectional relationship might exist between Intradialytic hypotension and left ventricular hypertrophy in chronic dialysis patients. A more complete understanding of the complex interactions in between could assist the readers in formulating potential solutions for the reduction of both phenomena.

  12. Pay attention to cardiac remodeling in cancer cachexia.

    Science.gov (United States)

    Zheng, Yawen; Chen, Han; Li, Xiaoqing; Sun, Yuping

    2016-07-01

    Cancer cachexia is a complex and multifaceted disease state characterized by fatigue, weakness, and loss of skeletal muscle and adipose tissue. Recently, the profound negative effects of cancer cachexia on cardiac tissue draw much attention, which is likely to contribute to mortality in tumor-bearing animals. The mechanism of cardiac remodeling is not so clear and involved with a series of molecular alterations. In cancer cachexia model, progressive loss of left ventricular mass and decrease in myocardial function is observed and cardiac autonomic functions are altered. Levels of several emerging cardiovascular neurohormones are found elevating in patients with cancer, but it is still controversial whether the changes could reflect the heart injury accurately. The remedy for cardiac remodeling has been explored. It is showed that exercise can modulate signaling pathways activated by wasting cytokines and impact on the resulting outcomes on heart adaptation. Some drugs, such as bisoprolol, spironolactone, perindopril, tandospirone, and simvastatin, can mitigate adverse effects of the tumor on the heart and prolong survival. PMID:27108265

  13. Cardiac remodeling and physical training post myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Michael; A; Garza; Emily; A; Wason; John; Q; Zhang

    2015-01-01

    After myocardial infarction(MI), the heart undergoes extensive myocardial remodeling through the accumulation of fibrous tissue in both the infarcted and noninfarcted myocardium, which distorts tissue structure, increases tissue stiffness, and accounts for ventricular dysfunction. There is growing clinical consensus that exercise training may beneficially alter the course of post-MI myocardial remodeling and improve cardiac function. This review summarizes the present state of knowledge regarding the effect of post-MI exercise training on infarcted hearts. Due to the degree of difficulty to study a viable human heart at both protein and molecular levels, most of the detailed studies have been performed by using animal models. Although there are some negative reports indicating that post-MI exercise may further cause deterioration of the wounded hearts, a growing body of research from both human and animal experiments demonstrates that post-MI exercise may beneficially alter the course of wound healing and improve cardiac function. Furthermore, the improved function is likely due to exercise training-induced mitigation of reninangiotensin-aldosterone system, improved balance between matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, favorable myosin heavy chain isoform switch, diminished oxidative stress, enhanced antioxidant capacity, improved mitochondrial calcium handling, and boosted myocardial angiogenesis. Additionally, meta-analyses revealed that exercise-based cardiac rehabilitation has proven to be effective, and remains one of the least expensive therapies for both the prevention and treatment of cardiovascular disease, and prevents re-infarction.

  14. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

    Directory of Open Access Journals (Sweden)

    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  15. miR-222 is Necessary for Exercise-induced Cardiac Growth and Protects Against Pathological Cardiac Remodeling

    OpenAIRE

    Liu, Xiaojun; Xiao, Junjie; Zhu, Han; Wei, Xin; Platt, Colin; Damilano, Federico; Xiao, Chunyang; Bezzerides, Vassilios; Boström, Pontus; Che, Lin; Zhang, Chunxiang; Spiegelman, Bruce M.; Rosenzweig, Anthony

    2015-01-01

    Exercise induces physiological cardiac growth and protects the heart against pathological remodeling. Recent work suggests exercise also enhances the heart’s capacity for repair, which could be important for regenerative therapies. While microRNAs are important in certain cardiac pathologies, less is known about their functional roles in exercise-induced cardiac phenotypes. We profiled cardiac microRNA expression in two distinct models of exercise and found microRNA-222 (miR-222) was upregula...

  16. Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression

    Institute of Scientific and Technical Information of China (English)

    Bing-yan GUO; Yong-jun LI; Rui HAN; Shao-1ing YANG; Ying-hui SHI; De-rong HAN; Hong ZHOU; Mei WANG

    2011-01-01

    Aim:To investigate whether telmisartan(Telm)pretreatment attenuates isoproterenol(Iso)-induced postinfarction remodeling(PIR)in rats, and whether the effect of Telm is associated with cardiac expression of adiponectin.Methods:PIR was induced in male Wistar rats with two consecutive injections of Iso(80 mg/kg,sc)at an interval of 24 h.Primary Culture of ventricular myocytes from neonatal rats was prepared.Iso-induced cardiomyocyte injury was assessed based on cell growth and lactate dehydrogenase(LDH)activity.Cardiac adiponectin expression was measured using qRT-PCR and immunoblot analysis.Results:In the rats with PIR.Telm(10 mg·kg-1·d-1,po for 65 d)suppressed lso-induced increases in gravimetric parameters.cardiomyocyte diameter and collagen volume fraction,but had no effect on Iso-induced myocardial hypertrophy and interstitial fibrosis.The protective effect of Telm was associated with enhanced protein expression of cardiac adiponectin.In cultured cardiomyocytes,Telm (5-20 μmol/L)inhibited the celI death and LDH release induced by lSO(10 μmol/L).and reversed Iso-induced reduction in adiponectinprotein expression.In cardiomyocytes exposed to Iso(20 μmol/L).GW9662(30 μmol/L),a selective antagonist of PPAR-v,blocked the effects of Telm Dretreatment on adiponectin protein expression,as well as the protective effects of Telm on Iso-induced celI injUry.Conclusion:Telm attenuates Iso-induced cardiac remodeling and cell injury,which is associated with induction of cardiac adiponectin expression.

  17. Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice.

    Directory of Open Access Journals (Sweden)

    Luca Carnevali

    Full Text Available In humans, variants of the fat mass and obesity associated (FTO gene have recently been associated with obesity. However, the physiological function of FTO is not well defined. Previous investigations in mice have linked FTO deficiency to growth retardation, loss of white adipose tissue, increased energy metabolism and enhanced systemic sympathetic activation. In this study we investigated for the first time the effects of global knockout of the mouse FTO gene on cardiac function and its autonomic neural regulation. ECG recordings were acquired via radiotelemetry in homozygous knockout (n = 12 and wild-type (n = 8 mice during resting and stress conditions, and analyzed by means of time- and frequency-domain indexes of heart rate variability. In the same animals, cardiac electrophysiological properties (assessed by epicardial mapping and structural characteristics were investigated. Our data indicate that FTO knockout mice were characterized by (i higher heart rate values during resting and stress conditions, (ii heart rate variability changes (increased LF to HF ratio, (iii larger vulnerability to stress-induced tachyarrhythmias, (iv altered ventricular repolarization, and (v cardiac hypertrophy compared to wild-type counterparts. We conclude that FTO deficiency in mice leads to an imbalance of the autonomic neural modulation of cardiac function in the sympathetic direction and to a potentially proarrhythmic remodeling of electrical and structural properties of the heart.

  18. Fibroblast growth factor-2 regulates human cardiac myofibroblast-mediated extracellular matrix remodeling

    OpenAIRE

    Svystonyuk, Daniyil A; Ngu, Janet MC; Mewhort, Holly EM; Lipon, Brodie D; Teng, Guoqi; Guzzardi, David G; Malik, Getanshu; Belke, Darrell D.; Fedak, Paul WM

    2015-01-01

    Background Tissue fibrosis and chamber remodeling is a hallmark of the failing heart and the final common pathway for heart failure of diverse etiologies. Sustained elevation of pro-fibrotic cytokine transforming growth factor-beta1 (TGFβ1) induces cardiac myofibroblast-mediated fibrosis and progressive structural tissue remodeling. Objectives We examined the effects of low molecular weight fibroblast growth factor (LMW-FGF-2) on human cardiac myofibroblast-mediated extracellular matrix (ECM)...

  19. Cardiac remodeling and myocardial dysfunction in obese spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Linz Dominik

    2012-09-01

    Full Text Available Abstract Background The additive effects of obesity and metabolic syndrome on left ventricular (LV maladaptive remodeling and function in hypertension are not characterized. Methods We compared an obese spontaneously hypertensive rat model (SHR-ob with lean spontaneously hypertensive rats (SHR-lean and normotensive controls (Ctr. LV-function was investigated by cardiac magnetic resonance imaging and invasive LV-pressure measurements. LV-interstitial fibrosis was quantified and protein levels of phospholamban (PLB, Serca2a and glucose transporters (GLUT1 and GLUT4 were determined by immunohistochemistry. Results Systolic blood pressure was similar in SHR-lean and SHR-ob (252 ± 7 vs. 242 ± 7 mmHg, p = 0.398 but was higher when compared to Ctr (155 ± 2 mmHg, p  Conclusion In addition to hypertension alone, metabolic syndrome and obesity adds to the myocardial phenotype by aggravating diastolic dysfunction and a progression towards systolic dysfunction. SHR-ob may be a useful model to develop new interventional and pharmacological treatment strategies for hypertensive heart disease and metabolic disorders.

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

    Science.gov (United States)

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

    2013-02-15

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

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

    OpenAIRE

    Jessica Jen-Chu Wang; Christoph Rau; Rozeta Avetisyan; Shuxun Ren; Romay, Milagros C.; Gabriel Stolin; Ke Wei Gong; Yibin Wang; Lusis, Aldons J.

    2016-01-01

    We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with ...

  2. Connexin43 Cardiac Gap Junction Remodeling: Lessons from Genetically Engineered Murine Models

    OpenAIRE

    Remo, Benjamin F.; Giovannone, Steven; Fishman, Glenn I.

    2012-01-01

    Sudden cardiac death is responsible for several hundred thousand deaths each year in the United States. Multiple lines of evidence suggest that perturbation of gap junction expression and function in the heart, or what has come to be known as cardiac gap junction remodeling, plays a key mechanistic role in the pathophysiology of clinically significant cardiac arrhythmias. Here we review recent studies from our laboratory using genetically engineered murine models to explore mechanisms implica...

  3. Role of matricellular proteins in cardiac tissue remodeling after myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Yutaka; Matsui; Junko; Morimoto; Toshimitsu; Uede

    2010-01-01

    After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes in LV shape,size,and function are termed cardiac remodeling.If the cardiac healing after MI does not proceed properly,it could lead to cardiac rupture or maladaptive cardiac remodeling,such as further LV dilatation and dysfunction,and ultimately death.Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated,this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix(ECM) proteins.The components of ECM include basic structural proteins such as collagen,elastin and specialized proteins such as fibronectin,proteoglycans and matricellular proteins.Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors,other matrix proteins,and soluble extracellular factors such as growth factors and cytokines.This small group of proteins,which includesosteopontin,thrombospondin-1/2,tenascin,periostin,and secreted protein,acidic and rich in cysteine,shows a low level of expression in normal adult tissue,but is markedly upregulated during wound healing and tissue remodeling,including MI.In this review,we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI.

  4. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice

    DEFF Research Database (Denmark)

    Patrick, David M; Montgomery, Rusty L; Qi, Xiaoxia;

    2010-01-01

    cardiac hypertrophy and fibrosis in rodents in response to pressure overload. In contrast, we have shown here that miR-21-null mice are normal and, in response to a variety of cardiac stresses, display cardiac hypertrophy, fibrosis, upregulation of stress-responsive cardiac genes, and loss of cardiac......MicroRNAs inhibit mRNA translation or promote mRNA degradation by binding complementary sequences in 3' untranslated regions of target mRNAs. MicroRNA-21 (miR-21) is upregulated in response to cardiac stress, and its inhibition by a cholesterol-modified antagomir has been reported to prevent...... contractility comparable to wild. type littermates. Similarly, inhibition of miR-21 through intravenous delivery of a locked nucleic acid-modified (LNA-modified) antimiR oligonucleotide also failed to block the remodeling response of the heart to stress. We therefore conclude that miR-21 is not essential for...

  5. Effects of candesartan on electrical remodeling in the hearts of inherited dilated cardiomyopathy model mice.

    Directory of Open Access Journals (Sweden)

    Fuminori Odagiri

    Full Text Available Inherited dilated cardiomyopathy (DCM is characterized by dilatation and dysfunction of the ventricles, and often results in sudden death or heart failure (HF. Although angiotensin receptor blockers (ARBs have been used for the treatment of HF, little is known about the effects on postulated electrical remodeling that occurs in inherited DCM. The aim of this study was to examine the effects of candesartan, one of the ARBs, on cardiac function and electrical remodeling in the hearts of inherited DCM model mice (TNNT2 ΔK210. DCM mice were treated with candesartan in drinking water for 2 months from 1 month of age. Control, non-treated DCM mice showed an enlargement of the heart with prolongation of QRS and QT intervals, and died at t1/2 of 70 days. Candesartan dramatically extended the lifespan of DCM mice, suppressed cardiac dilatation, and improved the functional parameters of the myocardium. It also greatly suppressed prolongation of QRS and QT intervals and action potential duration (APD in the left ventricular myocardium and occurrence of ventricular arrhythmia. Expression analysis revealed that down-regulation of Kv4.2 (Ito channel protein, KChIP2 (auxiliary subunit of Kv4.2, and Kv1.5 (IKur channel protein in DCM was partially reversed by candesartan administration. Interestingly, non-treated DCM heart had both normal-sized myocytes with moderately decreased Ito and IKur and enlarged cells with greatly reduced K+ currents (Ito, IKur IK1 and Iss. Treatment with candesartan completely abrogated the emergence of the enlarged cells but did not reverse the Ito, and IKur in normal-sized cells in DCM hearts. Our results indicate that candesartan treatment suppresses structural remodeling to prevent severe electrical remodeling in inherited DCM.

  6. Cardiac remodelling and function with primary mitral valve insufficiency studied by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Aplin, Mark; Kyhl, Kasper; Bjerre, Jenny;

    2016-01-01

    AIMS: Evaluation of patients with primary mitral valve insufficiency (MI) is best supported by quantitative measures. Cardiovascular magnetic resonance imaging (CMR) offers flow and cardiac chamber volume quantification. We studied cardiac remodelling with CMR to determine MI regurgitation volumes...... (P < 0.05). In surgical patients, the MIVol correlated to the decrease in LV dimension after valve surgery (P < 0.02). CONCLUSION: CMR provides a reproducible quantitative technique for evaluation of MI, as MIVol and cardiac chamber volumes can be held against diagnostic cut-off values. The Aoflow...

  7. Effects of Hypertension and Exercise on Cardiac Proteome Remodelling

    Directory of Open Access Journals (Sweden)

    Bernardo A. Petriz

    2014-01-01

    Full Text Available Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular signalling, gene expression, and proteome alteration. Proteomic research has revealed that several molecular targets are associated with pathologic cardiac hypertrophy, including angiotensin II, endothelin-1 and isoproterenol. Several metabolic, contractile, and stress-related proteins are shown to be altered in cardiac hypertrophy derived by hypertension. On the other hand, exercise is a nonpharmacologic agent used for hypertension treatment, where cardiac hypertrophy induced by exercise training is characterized by improvement in cardiac function and resistance against ischemic insult. Despite the scarcity of proteomic research performed with exercise, healthy and pathologic heart proteomes are shown to be modulated in a completely different way. Hence, the altered proteome induced by exercise is mostly associated with cardioprotective aspects such as contractile and metabolic improvement and physiologic cardiac hypertrophy. The present review, therefore, describes relevant studies involving the molecular characteristics and alterations from hypertensive-induced and exercise-induced hypertrophy, as well as the main proteomic research performed in this field. Furthermore, proteomic research into the effect of hypertension on other target-demerged organs is examined.

  8. Adenoviral short hairpin RNA targeting phosphodiesterase 5 attenuates cardiac remodeling and cardiac dysfunction following myocardial infarction in mice

    Institute of Scientific and Technical Information of China (English)

    张健

    2014-01-01

    Objective To observe the impact of PDE5shRNA on cardiac remodeling and heart function following myocardial infarction in mice.Methods Myocardial infarction(MI)was induced in mice by left coronary artery ligation.Mice were randomly assigned to sham operation group(n=6),PDE5shRNA group(n=12),common adenovirus group(n=15)and DMEM group(n=8).Four weeks post-MI,the survival rate was evaluated.

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

    Directory of Open Access Journals (Sweden)

    Shanshan Zhou

    2014-01-01

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

  10. Sex-specific cardiac cardiolipin remodelling after doxorubicin treatment

    OpenAIRE

    Moulin, Maryline; Solgadi, Audrey; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée; Chaminade, Pierre

    2015-01-01

    Background Imbalance in lipid metabolism and membrane lipid homeostasis has been observed in numerous diseases including heart failure and cardiotoxicity. Growing evidence links phospholipid alterations especially cardiolipins (CLs) to defects in mitochondrial function and energy metabolism in heart failure. We have shown recently that doxorubicin cardiotoxicity is more severe in male than female Wistar rats. We aimed to study whether this sex specificity is linked to differences in cardiac p...

  11. Early remodeling of rat cardiac muscle induced by swimming training

    Directory of Open Access Journals (Sweden)

    Verzola R.M.M.

    2006-01-01

    Full Text Available The aim of the present investigation was to study the effect of acute swimming training with an anaerobic component on matrix metallopeptidase (MMP activity and myosin heavy chain gene expression in the rat myocardium. Animals (male Wistar rats, weighing approximately 180 g were trained for 6 h/day in 3 sessions of 2 h each for 1 to 5 consecutive days (N = 5 rats per group. Rats swam in basins 47 cm in diameter and 60 cm deep filled with water at 33 to 35ºC. After the training period a significant increase (P < 0.05 was observed in the heart weight normalized to body weight by about 22 and 35% in the groups that trained for 96 and 120 h, respectively. Blood lactate levels were significantly increased (P < 0.05 in all groups after all training sessions, confirming an anaerobic component. However, lactate levels decreased (P < 0.05 with days of training, suggesting that the animals became adapted to this protocol. Myosin heavy chain-ß gene expression, analyzed by real time PCR and normalized with GAPDH gene expression, showed a significant two-fold increase (P < 0.01 after 5 days of training. Zymography analysis of myocardium extracts indicated a single ~60-kDa activity band that was significantly increased (P < 0.05 after 72, 96, and 120 h, indicating an increased expression of MMP-2 and suggesting precocious remodeling. Furthermore, the presence of MMP-2 was confirmed by Western blot analysis, but not the presence of MMP-1 and MMP-3. Taken together, our results indicate that in these training conditions, the rat heart undergoes early biochemical and functional changes required for the adaptation to the new physiological condition by tissue remodeling.

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

    Directory of Open Access Journals (Sweden)

    Jessica Jen-Chu Wang

    2016-07-01

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

  13. TRPV1 gene deletion exacerbates inflammation and atypical cardiac remodeling after myocardial infarction

    OpenAIRE

    Huang, Wei; Rubinstein, Jack; Prieto, Alejandro R.; Thang, Loc Vinh; Wang, Donna H.

    2008-01-01

    The transient receptor potential vanilloid (TRPV1) channels expressed in sensory afferent fibers innervating the heart may be activated by proton or endovanilloids released during myocardial ischemia (MI), leading to angina. Although our previous in vitro data indicate that TRPV1 activation may preserve cardiac function after ischemia-reperfusion (I/R) injury, the underlying mechanisms are largely unknown. To test the hypothesis that TRPV1 modulates inflammatory and early remodeling processes...

  14. Endocrine Alterations Are the Main Determinants of Cardiac Remodelling in Restrictive Anorexia Nervosa

    OpenAIRE

    Guido Carlomagno; Valentina Mercurio; Antonio Ruvolo; Ignazio Senatore; Irina Halinskaya; Valeria Fazio; Flora Affuso; Serafino Fazio

    2011-01-01

    Objective. Anorexia nervosa is a condition of reduced hemodynamic load, characterized by varying degrees of cardiac remodelling, only in part related to reduced body mass; the mechanism for such variability, as well as its clinical significance, remains unknown. Aim of the study was to assess the possible influence of a great number of clinical, biochemical, and endocrine factors on cardiovascular parameters in restrictive anorexia nervosa. Method. Twenty-five female patients hospitalized for...

  15. Gender Differences in Adiponectin Modulation of Cardiac Remodeling in Mice Deficient in Endothelial Nitric Oxide Synthase

    OpenAIRE

    Durand, Jorge L.; Nawrocki, Andrea R.; Scherer, Philipp E.; Jelicks, Linda A.

    2012-01-01

    Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels...

  16. Aging and the cardiac collagen matrix: Novel mediators of fibrotic remodelling.

    Science.gov (United States)

    Horn, Margaux A; Trafford, Andrew W

    2016-04-01

    Cardiovascular disease is a leading cause of death worldwide and there is a pressing need for new therapeutic strategies to treat such conditions. The risk of developing cardiovascular disease increases dramatically with age, yet the majority of experimental research is executed using young animals. The cardiac extracellular matrix (ECM), consisting predominantly of fibrillar collagen, preserves myocardial integrity, provides a means of force transmission and supports myocyte geometry. Disruptions to the finely balanced control of collagen synthesis, post-synthetic deposition, post-translational modification and degradation may have detrimental effects on myocardial functionality. It is now well established that the aged heart is characterized by fibrotic remodelling, but the mechanisms responsible for this are incompletely understood. Furthermore, studies using aged animal models suggest that interstitial remodelling with disease may be age-dependent. Thus with the identification of new therapeutic strategies targeting fibrotic remodelling, it may be necessary to consider age-dependent mechanisms. In this review, we discuss remodelling of the cardiac collagen matrix as a function of age, whilst highlighting potential novel mediators of age-dependent fibrotic pathways. PMID:26578393

  17. Monocytes increase human cardiac myofibroblast-mediated extracellular matrix remodeling through TGF-β1.

    Science.gov (United States)

    Mewhort, Holly E M; Lipon, Brodie D; Svystonyuk, Daniyil A; Teng, Guoqi; Guzzardi, David G; Silva, Claudia; Yong, V Wee; Fedak, Paul W M

    2016-03-15

    Following myocardial infarction (MI), cardiac myofibroblasts remodel the extracellular matrix (ECM), preventing mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis, and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity; however, the mechanisms are unclear. We assessed the influence of peripheral blood monocytes on human cardiac myofibroblast activity in a three-dimensional (3D) ECM microenvironment. Human cardiac myofibroblasts isolated from surgical biopsies of the right atrium and left ventricle were seeded into 3D collagen matrices. Peripheral blood monocytes were isolated from healthy human donors and cocultured with myofibroblasts. Monocytes increased myofibroblast activity measured by collagen gel contraction (baseline: 57.6 ± 5.9% vs. coculture: 65.2 ± 7.1% contraction; P < 0.01) and increased local ECM remodeling quantified by confocal microscopy. Under coculture conditions that allow indirect cellular interaction via paracrine factors but prevent direct cell-cell contact, monocytes had minimal effects on myofibroblast activity (17.9 ± 11.1% vs. 6.4 ± 7.0% increase, respectively; P < 0.01). When cells were cultured under direct contact conditions, multiplex analysis of the coculture media revealed an increase in the paracrine factors TGF-β1 and matrix metalloproteinase 9 compared with baseline (122.9 ± 10.1 pg/ml and 3,496.0 ± 190.4 pg/ml, respectively, vs. 21.5 ± 16.3 pg/ml and 183.3 ± 43.9 pg/ml; P < 0.001). TGF-β blockade abolished the monocyte-induced increase in cardiac myofibroblast activity. These data suggest that direct cell-cell interaction between monocytes and cardiac myofibroblasts stimulates TGF-β-mediated myofibroblast activity and increases remodeling of local matrix. Peripheral blood monocyte interaction with human cardiac myofibroblasts stimulates myofibroblast activity through release of TGF-β1

  18. Electrical stunning and hibernation: suggestion of new terms for short- and long-term cardiac memory.

    Science.gov (United States)

    Zoghi, Mehdi; Nalbantgil, Sanem

    2004-09-01

    Persistent T wave changes following resumption of sinus rhythm induced by pacing or arrhythmias that cause altering of ventricular activation sequence are named "cardiac memory". After this initial definition there has been a discussion whether such T wave changes are primary, secondary or pseudoprimary. In addition according to the results of pathophysiological studies investigating the mechanism and nature of this repolarization abnormality some authors have preferred to use the term "electrical remodelling" instead of cardiac memory. But these two terms are still not well defined. In this article, the previous terms are discussed and a new term instead of cardiac memory is introduced. PMID:15294266

  19. Temporal patterns of electrical remodeling in canine ventricular hypertrophy: Focus on I-Ks downregulation and blunted beta-adrenergic activation

    NARCIS (Netherlands)

    M. Stengl; C. Ramakers; D.W. Donker; A. Nabar; A.V. Rybin; R.L.H.M.G. Spatjens; T. van der Nagel; W.K.W.H. Wodzig; K.R. Sipido; G. Antoons; A.F.M. Moorman; M.A. Vos; P.G.A. Volders

    2006-01-01

    Objectives: Electrical remodeling in cardiac hypertrophy often involves the downregulation of K+ currents, including beta-adrenergic (beta-A)-sensitive I-Ks. Temporal patterns of ion-channel downregulation are poorly resolved. In dogs with complete atrioventricular block (AVB), we examined (1) the t

  20. Temporal and Molecular Analyses of Cardiac Extracellular Matrix Remodeling following Pressure Overload in Adiponectin Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Keith Dadson

    Full Text Available Adiponectin, circulating levels of which are reduced in obesity and diabetes, mediates cardiac extracellular matrix (ECM remodeling in response to pressure overload (PO. Here, we performed a detailed temporal analysis of progressive cardiac ECM remodelling in adiponectin knockout (AdKO and wild-type (WT mice at 3 days and 1, 2, 3 and 4 weeks following the induction of mild PO via minimally invasive transverse aortic banding. We first observed that myocardial adiponectin gene expression was reduced after 4 weeks of PO, whereas increased adiponectin levels were detected in cardiac homogenates at this time despite decreased circulating levels of adiponectin. Scanning electron microscopy and Masson's trichrome staining showed collagen accumulation increased in response to 2 and 4 weeks of PO in WT mice, while fibrosis in AdKO mice was notably absent after 2 weeks but highly apparent after 4 weeks of PO. Time and intensity of fibroblast appearance after PO was not significantly different between AdKO and WT animals. Gene array analysis indicated that MMP2, TIMP2, collagen 1α1 and collagen 1α3 were induced after 2 weeks of PO in WT but not AdKO mice. After 4 weeks MMP8 was induced in both genotypes, MMP9 only in WT mice and MMP1α only in AdKO mice. Direct stimulation of primary cardiac fibroblasts with adiponectin induced a transient increase in total collagen detected by picrosirius red staining and collagen III levels synthesis, as well as enhanced MMP2 activity detected via gelatin zymography. Adiponectin also enhanced fibroblast migration and attenuated angiotensin-II induced differentiation to a myofibroblast phenotype. In conclusion, these data indicate that increased myocardial bioavailability of adiponectin mediates ECM remodeling following PO and that adiponectin deficiency delays these effects.

  1. Post-mortem cardiac diffusion tensor imaging: detection of myocardial infarction and remodeling of myofiber architecture

    Energy Technology Data Exchange (ETDEWEB)

    Winklhofer, Sebastian; Berger, Nicole; Stolzmann, Paul [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); Stoeck, Christian T.; Kozerke, Sebastian [Institute for Biomedical Engineering University and ETH Zurich, Zurich (Switzerland); Thali, Michael [University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); Manka, Robert [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Institute for Biomedical Engineering University and ETH Zurich, Zurich (Switzerland); University Hospital Zurich, Clinic for Cardiology, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2014-11-15

    To investigate the accuracy of post-mortem diffusion tensor imaging (DTI) for the detection of myocardial infarction (MI) and to demonstrate the feasibility of helix angle (HA) calculation to study remodelling of myofibre architecture. Cardiac DTI was performed in 26 deceased subjects prior to autopsy for medicolegal reasons. Fractional anisotropy (FA) and mean diffusivity (MD) were determined. Accuracy was calculated on per-segment (AHA classification), per-territory, and per-patient basis, with pathology as reference standard. HAs were calculated and compared between healthy segments and those with MI. Autopsy demonstrated MI in 61/440 segments (13.9 %) in 12/26 deceased subjects. Healthy myocardial segments had significantly higher FA (p < 0.01) and lower MD (p < 0.001) compared to segments with MI. Multivariate logistic regression demonstrated that FA (p < 0.10) and MD (p = 0.01) with the covariate post-mortem time (p < 0.01) predicted MI with an accuracy of 0.73. Analysis of HA distribution demonstrated remodelling of myofibre architecture, with significant differences between healthy segments and segments with chronic (p < 0.001) but not with acute MI (p > 0.05). Post-mortem cardiac DTI enablesdifferentiation between healthy and infarcted myocardial segments by means of FA and MD. HA assessment allows for the demonstration of remodelling of myofibre architecture following chronic MI. (orig.)

  2. Amlodipine and Atorvastatin Improved Hypertensive Cardiac Remodeling through Regulation of MMPs/TIMPs in SHR Rats

    Directory of Open Access Journals (Sweden)

    Jingchao Lu

    2016-06-01

    Full Text Available Background: MMPs/TIMPs system is well known to play important roles in pressure overload-induced cardiac remodeling, and Amlodipine and Atorvastatin have been showed to exert favourable protective effects on cardiovascular disease, however, it is not clear whether Amlodipine and Atorvastatin can improve hypertensive cardiac remodeling and whether the MMPs/TIMPs system is involved. The present study aims to answer these questions. Methods: 36 weeks old male spontaneous hypertension (SHR rats were randomly divided into four groups: 1. SHR control group, 2. Amlodipine alone (10 mg/kg/d group, 3. Atorvastatin alone (10 mg/kg/d group, 4.Combination of Amlodipine and Atorvastatin (10 mg/kg/d for each group. Same gender, weight and age of Wistar-Kyoto (WKY rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The blood pressure and left ventricle mass index were measured. Enzyme activity of MMP-2 and MMP-9 was assessed with Gelatin zymography. MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA and protein expression was studied by RT-PCR and Western blot. Single factor ANOVA and LSD-t test were used in statistical analysis. Results: Treatment with Amlodipine alone or combination with atorvastatin significantly decreased blood pressure, left ventricle mass index in SHR rats (P Conclusion: Amlodipine and Atorvastatin could improve ventricular remodeling in SHR rats through intervention with the imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 system.

  3. MicroRNA Expression Signature Is Altered in the Cardiac Remodeling Induced by High Fat Diets.

    Science.gov (United States)

    Guedes, Elaine Castilho; França, Gustavo Starvaggi; Lino, Caroline Antunes; Koyama, Fernanda Christtanini; Moreira, Luana do Nascimento; Alexandre, Juliana Gomes; Barreto-Chaves, Maria Luiza M; Galante, Pedro Alexandre Favoretto; Diniz, Gabriela Placoná

    2016-08-01

    Recent studies have revealed the involvement of microRNAs (miRNAs) in the control of cardiac hypertrophy and myocardial function. In addition, several reports have demonstrated that high fat (HF) diet induces cardiac hypertrophy and remodeling. In the current study, we investigated the effect of diets containing different percentages of fat on the cardiac miRNA expression signature. To address this question, male C57Bl/6 mice were fed with a low fat (LF) diet or two HF diets, containing 45 kcal% fat (HF45%) and 60 kcal% fat (HF60%) for 10 and 20 weeks. HF60% diet promoted an increase on body weight, fasting glycemia, insulin, leptin, total cholesterol, triglycerides, and induced glucose intolerance. HF feeding promoted cardiac remodeling, as evidenced by increased cardiomyocyte transverse diameter and interstitial fibrosis. RNA sequencing analysis demonstrated that HF feeding induced distinct miRNA expression patterns in the heart. HF45% diet for 10 and 20 weeks changed the abundance of 64 and 26 miRNAs in the heart, respectively. On the other hand, HF60% diet for 10 and 20 weeks altered the abundance of 27 and 88 miRNAs in the heart, respectively. Bioinformatics analysis indicated that insulin signaling pathway was overrepresented in response to HF diet. An inverse correlation was observed between cardiac levels of GLUT4 and miRNA-29c. Similarly, we found an inverse correlation between expression of GSK3β and the expression of miRNA-21a-3p, miRNA-29c-3p, miRNA-144-3p, and miRNA-195a-3p. In addition, miRNA-1 overexpression prevented cardiomyocyte hypertrophy. Taken together, our results revealed differentially expressed miRNA signatures in the heart in response to different HF diets. J. Cell. Physiol. 231: 1771-1783, 2016. © 2015 Wiley Periodicals, Inc. PMID:26638879

  4. Relationship Between Reverse Remodeling and Cardiopulmonary Exercise Capacity in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H; Sant, Jetske Van't; Versteeg, Henneke;

    2016-01-01

    BACKGROUND: Studies on the relationship between left ventricular reverse remodeling and cardiopulmonary exercise capacity in heart failure patients undergoing cardiac resynchronization therapy (CRT) are scarce and inconclusive. METHODS AND RESULTS: Eighty-four patients with a 1st-time CRT......-defibrillator (mean age 65 ± 11; 73% male) underwent echocardiography and cardiopulmonary exercise testing (CPX) before implantation (baseline) and 6 months after implantation. At baseline, patients also completed a set of questionnaires measuring mental and physical health. The association between echocardiographic...... echocardiographic responders showed improvements in ventilatory efficiency during follow-up. Multivariable repeated measures analyses revealed that, besides reverse remodeling, New York Heart Association functional class II and good patient-reported health status before implantation were the most important...

  5. Aerobic Training after Myocardial Infarction: Remodeling Evaluated by Cardiac Magnetic Resonance

    Directory of Open Access Journals (Sweden)

    Nataly Lino Izeli

    2016-04-01

    Full Text Available Abstract Background: Numerous studies show the benefits of exercise training after myocardial infarction (MI. Nevertheless, the effects on function and remodeling are still controversial. Objectives: To evaluate, in patients after (MI, the effects of aerobic exercise of moderate intensity on ventricular remodeling by cardiac magnetic resonance imaging (CMR. Methods: 26 male patients, 52.9 ± 7.9 years, after a first MI, were assigned to groups: trained group (TG, 18; and control group (CG, 8. The TG performed supervised aerobic exercise on treadmill twice a week, and unsupervised sessions on 2 additional days per week, for at least 3 months. Laboratory tests, anthropometric measurements, resting heart rate (HR, exercise test, and CMR were conducted at baseline and follow-up. Results: The TG showed a 10.8% reduction in fasting blood glucose (p = 0.01, and a 7.3-bpm reduction in resting HR in both sitting and supine positions (p < 0.0001. There was an increase in oxygen uptake only in the TG (35.4 ± 8.1 to 49.1 ± 9.6 mL/kg/min, p < 0.0001. There was a statistically significant decrease in the TG left ventricular mass (LVmass (128.7 ± 38.9 to 117.2 ± 27.2 g, p = 0.0032. There were no statistically significant changes in the values of left ventricular end-diastolic volume (LVEDV and ejection fraction in the groups. The LVmass/EDV ratio demonstrated a statistically significant positive remodeling in the TG (p = 0.015. Conclusions: Aerobic exercise of moderate intensity improved physical capacity and other cardiovascular variables. A positive remodeling was identified in the TG, where a left ventricular diastolic dimension increase was associated with LVmass reduction.

  6. Cardiac remodeling following percutaneous mitral valve repair. Initial results assessed by cardiovascular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Radunski, U.K [University Heart Center, Hamburg (Germany). Cardiology; Franzen, O. [Rigshospitalet, Copenhagen (Denmark). Cardiology; Barmeyer, A. [Klinikum Dortmund (Germany). Kardiologie; and others

    2014-10-15

    Percutaneous mitral valve repair with the MitraClip device (Abbott Vascular, Redwood City, California, USA) is a novel therapeutic option in patients with mitral regurgitation. This study evaluated the feasibility of cardiac volume measurements by cardiovascular magnetic resonance imaging (CMR) to assess reverse myocardial remodeling in patients after MitraClip implantation. 12 patients underwent CMR at baseline (BL) before and at 6 months follow-up (FU) after MitraClip implantation. Cine-CMR was performed in short- and long-axes for the assessment of left ventricular (LV), right ventricular (RV) and left atrial (LA) volumes. Assessment of endocardial contours was not compromised by the device-related artifact. No significant differences in observer variances were observed for LV, RV and LA volume measurements between BL and FU. LV end-diastolic (median 127 [IQR 96-150] vs. 112 [86-150] ml/m{sup 2}; p=0.03) and LV end-systolic (82 [54-91] vs. 69 [48-99] ml/m{sup 2}; p=0.03) volume indices decreased significantly from BL to FU. No significant differences were found for RV end-diastolic (94 [75-103] vs. 99 [77-123] ml/m{sup 2}; p=0.91), RV end-systolic (48 [42-80] vs. 51 [40-81] ml/m{sup 2}; p=0.48), and LA (87 [55-124] vs. 92 [48-137]R ml/m{sup 2}; p=0.20) volume indices between BL and FU. CMR enables the assessment of cardiac volumes in patients after MitraClip implantation. Our CMR findings indicate that percutaneous mitral valve repair results in reverse LV but not in RV or LA remodeling.

  7. ATP-sensitive K+ channel knockout induces cardiac proteome remodeling predictive of heart disease susceptibility.

    Science.gov (United States)

    Arrell, D Kent; Zlatkovic, Jelena; Kane, Garvan C; Yamada, Satsuki; Terzic, Andre

    2009-10-01

    Forecasting disease susceptibility requires detection of maladaptive signatures prior to onset of overt symptoms. A case-in-point are cardiac ATP-sensitive K+ (K(ATP)) channelopathies, for which the substrate underlying disease vulnerability remains to be identified. Resolving molecular pathobiology, even for single genetic defects, mandates a systems platform to reliably diagnose disease predisposition. High-throughput proteomic analysis was here integrated with network biology to decode consequences of Kir6.2 K(ATP) channel pore deletion. Differential two-dimensional gel electrophoresis reproducibly resolved >800 protein species from hearts of asymptomatic wild-type and Kir6.2-knockout counterparts. K(ATP) channel ablation remodeled the cardiac proteome, significantly altering 71 protein spots, from which 102 unique identities were assigned following hybrid linear ion trap quadrupole-Orbitrap tandem mass spectrometry. Ontological annotation stratified the K(ATP) channel-dependent protein cohort into a predominant bioenergetic module (63 resolved identities), with additional focused sets representing signaling molecules (6), oxidoreductases (8), chaperones (6), and proteins involved in catabolism (6), cytostructure (8), and transcription and translation (5). Protein interaction mapping, in conjunction with expression level changes, localized a K(ATP) channel-associated subproteome within a nonstochastic scale-free network. Global assessment of the K(ATP) channel deficient environment verified the primary impact on metabolic pathways and revealed overrepresentation of markers associated with cardiovascular disease. Experimental imposition of graded stress precipitated exaggerated structural and functional myocardial defects in the Kir6.2-knockout, decreasing survivorship and validating the forecast of disease susceptibility. Proteomic cartography thus provides an integral view of molecular remodeling in the heart induced by K(ATP) channel deletion, establishing a

  8. Gender-Based Differences in Cardiac Remodeling and ILK Expression after Myocardial Infarction

    Energy Technology Data Exchange (ETDEWEB)

    Sofia, Renato Rodrigues [Programa de Pós-graduação em Ciências da Reabilitação - Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Departamento de Cardiologia - Universidade Federal de São Paulo, São Paulo, SP (Brazil); Serra, Andrey Jorge, E-mail: andreyserra@gmail.com; Silva, Jose Antonio Jr [Programa de Pós-graduação em Ciências da Reabilitação - Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Antonio, Ednei Luiz [Departamento de Cardiologia - Universidade Federal de São Paulo, São Paulo, SP (Brazil); Manchini, Martha Trindade [Programa de Pós-graduação em Ciências da Reabilitação - Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Oliveira, Fernanda Aparecida Alves de [Departamento de Cardiologia - Universidade Federal de São Paulo, São Paulo, SP (Brazil); Teixeira, Vicente Paulo Castro [Departamento de Patologia - Universidade Federal de São Paulo, São Paulo, SP (Brazil); Tucci, Paulo José Ferreira [Departamento de Cardiologia - Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-08-15

    Gender can influence post-infarction cardiac remodeling. To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function.

  9. Gender-Based Differences in Cardiac Remodeling and ILK Expression after Myocardial Infarction

    International Nuclear Information System (INIS)

    Gender can influence post-infarction cardiac remodeling. To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function

  10. Effect of carvedilol on cardiac function and left ventricular remodeling in rats after acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    张军; 贾国良; 王海昌

    2003-01-01

    Objective: To observe the effect of carvedilol injection on left ventricular function and collagen remodeling in rat with myocardial infarction. Methods: Sixty rats with a model of myocardial infarction were randomly divided into nine groups. The rats of therapeutical group were treated with carvedilol injection (2 mg/d intraperitoneal injection) and/or captopil (2 g/L drinking water). Acute myocardial infarction (AMI) group did not receive drug treatment. The animals were sacrificed at 4 weeks and 8 weeks after coronary artery ligation. The levels of plasma angiotensin Ⅱ and plasma aldosterone and left ventricle function were determined at different time. The collagen content and the ratio of type I and Ⅲ collagen of noninfarcted area were also assessed. Results: Compared with AMI group, the levels of plasma and myocardium angiotensin Ⅱ and plasma aldosterone in both carvedilol and captopil group decreased at the eighth week (P<0.05). In addition, carvedilol improved systolic and diastolic function (P<0.05). Compared with sham group, both collagen content and the ratio of type Ⅰ/Ⅲ collagen of noninfarcted area increased in AMI4 and AMI8 group (P<0.05). The hydroxyproline levels and the ratio of type Ⅰ/Ⅲ collagen significantly decreased after carvedilol and/or captopil treatment , compared with AMI group at 4 or 8 week (P<0.05). Conclusion: Carvedilol can improve cardiac function after myocardial infarction and has beneficial effect on left ventricular remodeling.

  11. Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats.

    Science.gov (United States)

    Lee, Young Sook; Choi, Joung-Woo; Oh, Jung-Eun; Yun, Chae-Ok; Kim, Sung Wan

    2016-08-01

    In consensus, myocardial infarction (MI) is defined as irreversible cell death secondary to prolonged ischemia in heart. The aim of our study was to evaluate the therapeutic potential of anti-fibrotic human Relaxin-expressing plasmid DNA with hypoxia response element (HRE) 12 copies (HR1) delivered by a dendrimer type PAM-ABP polymer G0 (HR1/G0) after MI on functional, hemodynamic, geometric, and cardiac extracellular matrix (ECM) remodeling in rats. HR1/G0 demonstrated significantly improved LV systolic function, hemodynamic parameters, and geometry on 1 wk and 4 wks after MI in rats, compared with I/R group. The resolution of regional wall motional abnormalities and the increased blood flow of infarct-related coronary artery supported functional improvements of HR1/G0. Furthermore, HR1/G0 polyplex showed favorable post-infarct cardiac ECM remodeling reflected on the favorable cardiac ECM compositions. Overall, this is the first study, which presented an advanced platform for the gene therapy that reverses adverse cardiac remodeling after MI with a HR1 gene delivered by a bioreducible dendrimer polymer in the cardiac ECM. PMID:27174688

  12. Cardiac remodeling following percutaneous mitral valve repair - initial results assessed by cardiovascular magnetic resonance imaging

    DEFF Research Database (Denmark)

    Radunski, U K; Franzen, O; Barmeyer, A;

    2014-01-01

    PURPOSE: Percutaneous mitral valve repair with the MitraClip device (Abbott Vascular, Redwood City, California, USA) is a novel therapeutic option in patients with mitral regurgitation. This study evaluated the feasibility of cardiac volume measurements by cardiovascular magnetic resonance imaging...... mitral valve repair results in reverse LV but not in RV or LA remodeling. KEY POINTS: • Volume measurements by cardiovascular magnetic resonance imaging are feasible following percutaneous mitral valve repair despite device-related artifacts.• A significant reduction of left ventricular volume was found...... end-systolic (48 [42 - 80] vs. 51 [40 - 81] ml/m(2); p = 0.48), and LA (87 [55 - 124] vs. 92 [48 - 137] ml/m(2); p = 0.20) volume indices between BL and FU. CONCLUSION: CMR enables the assessment of cardiac volumes in patients after MitraClip implantation. Our CMR findings indicate that percutaneous...

  13. Deficiency of Smad7 enhances cardiac remodeling induced by angiotensin II infusion in a mouse model of hypertension.

    Directory of Open Access Journals (Sweden)

    Li Hua Wei

    Full Text Available Smad7 has been shown to negatively regulate fibrosis and inflammation, but its role in angiotensin II (Ang II-induced hypertensive cardiac remodeling remains unknown. Therefore, the present study investigated the role of Smad7 in hypertensive cardiopathy induced by angiotensin II infusion. Hypertensive cardiac disease was induced in Smad7 gene knockout (KO and wild-type (WT mice by subcutaneous infusion of Ang II (1.46 mg/kg/day for 28 days. Although equal levels of high blood pressure were developed in both Smad7 KO and WT mice, Smad7 KO mice developed more severe cardiac injury as demonstrated by impairing cardiac function including a significant increase in left ventricular (LV mass (P<0.01,reduction of LV ejection fraction(P<0.001 and fractional shortening(P<0.001. Real-time PCR, Western blot and immunohistochemistry detected that deletion of Smad7 significantly enhanced Ang II-induced cardiac fibrosis and inflammation, including upregulation of collagen I, α-SMA, interleukin-1β, TNF-α, and infiltration of CD3(+ T cells and F4/80(+ macrophages. Further studies revealed that enhanced activation of the Sp1-TGFβ/Smad3-NF-κB pathways and downregulation of miR-29 were mechanisms though which deletion of Smad7 promoted Ang II-mediated cardiac remodeling. In conclusions, Smad7 plays a protective role in AngII-mediated cardiac remodeling via mechanisms involving the Sp1-TGF-β/Smad3-NF.κB-miR-29 regulatory network.

  14. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    OpenAIRE

    Zhipeng Zeng; Kunwu Yu; Long Chen; Weihua Li; Hong Xiao; Zhengrong Huang

    2016-01-01

    CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significant...

  15. Haptoglobin genotype is a determinant of survival and cardiac remodeling after myocardial infarction in diabetic mice

    Directory of Open Access Journals (Sweden)

    Frisch Avi

    2009-06-01

    Full Text Available Abstract Background We have recently demonstrated in man that a functional allelic polymorphism in the Haptoglobin (Hp gene plays a major role in determining survival and congestive heart failure after myocardial infarction (MI. We sought to recapitulate the effect of Hp type on outcomes and cardiac remodeling after MI in transgenic mice. Methods The Hp 2 allele exists only in man. Wild type C57Bl/6 mice carry the Hp 1 allele with high homology to the human Hp 1 allele. We genetically engineered a murine Hp 2 allele and targeted its insertion by homologous recombination to the murine Hp locus to create Hp 2 mice. Diabetes Mellitus (DM was induced with streptozotocin. MI was produced by occlusion of the left anterior descending artery in DM C57Bl/6 mice carrying the Hp 1 or Hp 2 allele. MI size was determined with TTC staining. Left ventricular (LV function and dimensions were assessed by 2-dimensional echocardiography. Results In the absence of DM, Hp 1-1 and Hp 2-2 mice had similar LV dimensions and LV function. MI size was similar in DM Hp 1-1 and 2-2 mice 24 hours after MI (50.2 ± 2.1%and 46.9 ± 5.5%, respectively, p = 0.6. However, DM Hp 1-1 mice had a significantly lower mortality rate than DM Hp 2-2 mice 30 days after MI (HR 0.41, 95% CI (0.19–0.95, p = 0.037 by log rank. LV chamber dimensions were significantly increased in DM Hp 2-2 mice compared to DM Hp 1-1 mice 30 days after MI (0.196 ± 0.01 cm2 vs. 0.163 ± 0.01 cm2, respectively; p = 0.029. Conclusion In DM mice the Hp 2-2 genotype is associated with increased mortality and more severe cardiac remodeling 30 days after MI.

  16. Effects of Losartan on acute atrial electrical remodeling

    Institute of Scientific and Technical Information of China (English)

    李悦; 李为民; 薛竟宜; 韩薇; 杨树森; 谷宏越

    2004-01-01

    Background Atrial electrical remodeling (AER) contributes to the maintainance of atrial fibrillation (AF). This study was to compare the effects of Losartan with those of Diltiazem on tachycardia-induced acute AER in rabbits.Methods Twenty-one rabbits paced with maximal atrial capture rate for 3 hours in the right atrium (RA) were randomly divided into saline group, Diltiazem group and Losartan group. After autonomic blockage, we measured atrial effective refractory period (AERP), AERP rate adapting feature, AERP dispersion and RA conduction time at basic cycle lengths (BCLs) of 200 ms and 150 ms at baseline, 0.5 hour, 1 hour, 2 and 3 hours after rapid atrial pacing. Results In the saline group, there was a prompt decrease in AERP as a result of rapid atrial pacing, and AERP200 and AERP150 were shortened sharply within 0.5 hour of pacing (30.2±10.5 ms and 24.1±9.1 ms, respectively). The AERP did not change dramatically in the Diltiazem and Losartan groups. In the saline group, the value of (AERP200-AERP150)/50 ms in high RA was 0.17±0.08 at baseline and became significantly smaller at 0.5 hour (0.08±0.06), 1 hour (0.09±0.06), 2 hours (0.08±0.04) and 3 hours (0.09±0.05) (all P<0.05), suggesting a reduction of rate adaptation of AERP. The value of (AERP200-AERP150)/50 ms in high RA did not change during the 3 hours of pacing in both Diltiazem and Losartan groups. In the saline group, AERP dispersion increased significantly at 2 and 3 hours (P<0.05). However, Diltiazem could not prevent the increase of AERP dispersion at 3 hours (P<0.05). During Losartan infusion, the AERP dispersion was no longer increased after rapid atrial pacing. There was no significant difference in RA conduction time among the three groups.Conclusion Like calcium antagonist Diltiazem, Losartan could prevent AERP shortening and preserve rate adaptation of AERP after rapid atrial pacing. Losartan is more effective than Diltiazem in inhibiting the increase of AERP dispersion.

  17. Cell death and serum markers of collagen metabolism during cardiac remodeling in Cavia porcellus experimentally infected with Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Yagahira E Castro-Sesquen

    Full Text Available We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP and procollagen type III amino-terminal propeptide (PIIINP. Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response predominated throughout the course of infection; IgG1 (Th2 response was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively. These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection.

  18. Cell death and serum markers of collagen metabolism during cardiac remodeling in Cavia porcellus experimentally infected with Trypanosoma cruzi.

    Science.gov (United States)

    Castro-Sesquen, Yagahira E; Gilman, Robert H; Paico, Henry; Yauri, Verónica; Angulo, Noelia; Ccopa, Fredy; Bern, Caryn

    2013-01-01

    We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV) deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP). Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response) predominated throughout the course of infection; IgG1 (Th2 response) was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively). These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection. PMID:23409197

  19. Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

    DEFF Research Database (Denmark)

    Heijnen, Bart Fj; Pelkmans, Leonie Pj; Danser, Ah Jan;

    2013-01-01

    administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically and...... the hearts were excised for molecular and immunohistochemical analyses. Echocardiographic studies revealed that four weeks of RAS-stimulation incited a cardiac remodeling process characterized by increased left ventricular (LV) wall thickness, decreased LV volumes, and shortening of the left ventricle...

  20. Increased cardiac myocyte PDE5 levels in human and murine pressure overload hypertrophy cntribute to adverse LV remodeling

    OpenAIRE

    Vandenwijngaert, Sara; Pokreisz, Peter; Hermans, Hadewich; Gillijns, Hilde; Pellens, Marijke; Bax, Noortje A M; Coppiello, Giulia; Oosterlinck, Wouter; Balogh, Agnes; Papp, Zoltan; Bouten, Carlijn V. C.; Bartunek, Jozef; D'Hooge, Jan; Luttun, Aernout; Verbeken, Erik

    2013-01-01

    Background: The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC). Methodology/Principal Findings: In patients with severe aortic stenosi...

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  3. Aerobic exercise improves the inflammatory profile correlated with cardiac remodeling and function in chronic heart failure rats

    Directory of Open Access Journals (Sweden)

    Ramiro B. Nunes

    2013-06-01

    Full Text Available OBJECTIVE: The aim of the present study was to evaluate the effect of 8 weeks of aerobic exercise training on cardiac functioning and remodeling and on the plasma levels of inflammatory cytokines in chronic heart failure rats. METHODS: Wistar rats were subjected to myocardial infarction or sham surgery and assigned to 4 groups: chronic heart failure trained (n = 7, chronic heart failure sedentary (n = 6, sham trained (n = 8 and sham sedentary (n = 8. Four weeks after the surgical procedures, the rats were subjected to aerobic training in the form of treadmill running (50 min/day, 5 times per week, 16 m/min. At the end of 8 weeks, the rats were placed under anesthesia, the hemodynamic variables were recorded and blood samples were collected. Cardiac hypertrophy was evaluated using the left ventricular weight/body weight ratio, and the collagen volume fraction was assessed using histology. RESULTS: The chronic heart failure trained group showed a reduction in left ventricular end-diastolic pressure, a lower left ventricular weight/body weight ratio and a lower collagen volume fraction compared with the chronic heart failure sedentary group. In addition, exercise training reduced the plasma levels of TNF-α and IL-6 and increased the plasma level of IL-10. CONCLUSION: An 8-week aerobic exercise training program improved the inflammatory profile and cardiac function and attenuated cardiac remodeling in chronic heart failure rats.

  4. Postnatal ablation of Foxm1 from cardiomyocytes causes late onset cardiac hypertrophy and fibrosis without exacerbating pressure overload-induced cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    Craig Bolte

    Full Text Available Heart disease remains a leading cause of morbidity and mortality in the industrialized world. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1 transcription factor (also known as HFH-11B, Trident, Win or MPP2 plays an important role in the pathogenesis of various cancers and is a critical mediator of post-injury repair in multiple organs. Foxm1 has been previously shown to be essential for heart development and proliferation of embryonic cardiomyocytes. However, the role of Foxm1 in postnatal heart development and in cardiac injury has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, αMHC-Cre/Foxm1(fl/fl mice were generated. Surprisingly, αMHC-Cre/Foxm1(fl/fl mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had no defects in cardiac structure or function but developed cardiac hypertrophy and fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac fibrosis in aged Foxm1-deficient mice was associated with reduced expression of Hey2, an important regulator of cardiac homeostasis, and increased expression of genes critical for cardiac remodeling, including MMP9, αSMA, fibronectin and vimentin. We also found that following aortic constriction Foxm1 mRNA and protein were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate cardiac hypertrophy or fibrosis following chronic pressure overload. Our results demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte hypertrophy and cardiac fibrosis.

  5. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Zhipeng Zeng

    2016-01-01

    Full Text Available CD4+CD25+Foxp3+ regulatory T cells (Treg cells have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI. We hypothesize that the interleukin- (IL- 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1 attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th cells among the CD4+Foxp3− T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically.

  6. Intramyocardial delivery of mesenchymal stem cell-seeded hydrogel preserves cardiac function and attenuates ventricular remodeling after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Eva Mathieu

    Full Text Available BACKGROUND: To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC hydrogel seeded with MSC (MSC+hydrogel could preserve cardiac function and attenuate left ventricular (LV remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDING: Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. CONCLUSION/SIGNIFICANCE: These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium.

  7. Effects of Amiodarone plus Losartan on Electrical Remodeling in Rapid Atrial Pacing in Rabbits

    Institute of Scientific and Technical Information of China (English)

    Liye Wei; Yue Xia; Guoqing Qi; Qingwen Zhang

    2008-01-01

    Objectives To investigate the electrical remodeling and the effects of amiodarone and losartan on electrical remode-ling in rapid atrial pacing on rabbit model. Methods 40 normal rabbits were randomly divided into 4 groups: the sa-line group (control group), amiodarone group, losartan group, ami + los group. All rabbits were raised drugs in a week. The atrial effective refractory period (AERP) was measured. Then, take a rapid atrial pacing (600 bpm) and the AERP was measured after 0. 5, 1, 2, 4, 6 and 8 hours pacing and 30 minutes after the termination of rapid pacing. Results ① In control group, after 8 hours rapid pacing, AERP 200 and AERP 150 were significantly shortened 16. 11%± 3. 1% (P <0. 01) and 9. 99%±4. 2% (P <0. 01). And the degree of AERP shortening induced by rapid pacing was greater at basic cycle lengths of 200 ms (BCL200) than that at BCL150. The AERP of amiodarone, losartan group and anti + los group were not shortened during rapid pacing.② In the control group, after the termination of rapid pacing, the AERP gradually increased. The AERP at all of the BCLS examined recovered to almost the 95.78% and 96. 76% of baseline values within the first 10 minutes and recovered to almost the 99. 07% and 99. 39% of baseline values within the first 30 minutes. Condusions Short-term atrial rapid pacing can induce the atrial electrical remodeling. Amiodarone and losartan can prevent the electrical remodeling.

  8. Effects of spironolactone on electrical and structural remodeling of atrium in congestive heart failure dogs

    Institute of Scientific and Technical Information of China (English)

    YANG Shu-sen; XIU Chun-hong; LI Wei-min; HAN Wei; ZHOU Hong-yan; DONG Guo; WANG Bai-chun; HUO Hong; WEI Na; CAO Yong; ZHOU Guo

    2008-01-01

    Background Renin-angiotensin-aldosterone System has been demonstrated to be associated with both congestive heart failure (CHF) and atrial fibrillation (AF). This study investigated the effects of spironolactone, a kind of aldosterone antagonist, on atrial electrical remodeling and fibrosis in CHF dogs induced by chronic rapid ventricular pacing. Methods Twenty one dogs were randomly divided into sham-operated group, control group, and spironolactone group. In control group and spironolactone group, dogs were ventricular paced at 220 beats per minute for 6 weeks. Additionally, spironolactone at 15 mg·kg-1·d-1 was given to dogs 1 week before rapid ventricular pacing until pacing stopped. Transthoracic and transoesophageal echocardiographic examinations were performed to detect structural and functional changes of the atrium. Swan2 Ganz floating catheters were used to measure hemadynamics variances. Atrial effective refractory period (AERP), AERP dispersion (AERPd), intra- and inter-atrium conduction time (CT) and intra-atrium conduction velocity (CV) were determined. The inducibility and duration of AF were also measured in all groups. Finally, atrial fibrosis was quantified with Massen staining.Results AERP did not change significantly after dogs were ventricular paced for 6 weeks. However, AERPd, intra- and inter-atrium CT increased significantly, and CV decreased apparently, which was negatively correlated to the atrial fibrosis (r=-0.74, P<0.05). Simultaneously, left atriums were enlarged and cardiac hemadynamics worsened in pacing dogs. Although spironolactone could not affect cardiac hemadynamics effectively, it can obviously improve left atrial ejection fraction (P<0.05). Spironolactone treatment did not alter AERP duration, but this medicine dramatically decreased AERPd (P<0.05), shortened intra- and inter-atrium conduction time (P<0.05), and increased atrium CV. Moreover, spironolactone decreased the inducibility and duration of AF (P<0.05),as

  9. Cardiac fibrillation risks with TASER conducted electrical weapons.

    Science.gov (United States)

    Panescu, Dorin; Kroll, Mark; Brave, Michael

    2015-01-01

    The TASER(®) conducted electrical weapon (CEW) delivers electrical pulses that can temporarily incapacitate subjects. We analyzed the cardiac fibrillation risk with TASER CEWs. Our risk model accounted for realistic body mass index distributions, used a new model of effects of partial or oblique dart penetration and used recent epidemiological CEW statics. PMID:26736265

  10. SERCA2a superinhibition by human phospholamban triggers electrical and structural remodeling in mouse hearts

    OpenAIRE

    Arvanitis, D. A.; Dong, M; E.G. Kranias; Lam, C. K.; Niklewski, P. J.; Sanoudou, D; Wang, H. -S.; Zhao, W

    2011-01-01

    Phospholamban (PLN), the reversible inhibitor of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), is a key regulator of myocyte Ca2+ cycling with a significant role in heart failure. We previously showed that the single amino acid difference between human and mouse PLN results in increased inhibition of Ca2+ cycling and cardiac remodeling and attenuated stress responses in transgenic mice expressing the human PLN (hPLN) in the null background. Here we dissect the molecular and electrop...

  11. A transgenic platform for testing drugs intended for reversal of cardiac remodeling identifies a novel 11βHSD1 inhibitor rescuing hypertrophy independently of re-vascularization.

    Directory of Open Access Journals (Sweden)

    Oren Gordon

    Full Text Available RATIONALE: Rescuing adverse myocardial remodeling is an unmet clinical goal and, correspondingly, pharmacological means for its intended reversal are urgently needed. OBJECTIVES: To harness a newly-developed experimental model recapitulating progressive heart failure development for the discovery of new drugs capable of reversing adverse remodeling. METHODS AND RESULTS: A VEGF-based conditional transgenic system was employed in which an induced perfusion deficit and a resultant compromised cardiac function lead to progressive remodeling and eventually heart failure. Ability of candidate drugs administered at sequential remodeling stages to reverse hypertrophy, enlarged LV size and improve cardiac function was monitored. Arguing for clinical relevance of the experimental system, clinically-used drugs operating on the Renin-Angiotensin-Aldosterone-System (RAAS, namely, the ACE inhibitor Enalapril and the direct renin inhibitor Aliskerin fully reversed remodeling. Remodeling reversal by these drugs was not accompanied by neovascularization and reached a point-of-no-return. Similarly, the PPARγ agonist Pioglitazone was proven capable of reversing all aspects of cardiac remodeling without affecting the vasculature. Extending the arsenal of remodeling-reversing drugs to pathways other than RAAS, a specific inhibitor of 11β-hydroxy-steroid dehydrogenase type 1 (11β HSD1, a key enzyme required for generating active glucocorticoids, fully rescued myocardial hypertrophy. This was associated with mitigating the hypertrophy-associated gene signature, including reversing the myosin heavy chain isoform switch but in a pattern distinguishable from that associated with neovascularization-induced reversal. CONCLUSIONS: A system was developed suitable for identifying novel remodeling-reversing drugs operating in different pathways and for gaining insights into their mechanisms of action, exemplified here by uncoupling their vascular affects.

  12. Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy

    Directory of Open Access Journals (Sweden)

    Tamara P. Martin

    2014-01-01

    Full Text Available Phosphorylated heat shock protein 20 (HSP20 is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20–phosphodiesterase 4D (PDE4D complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20–PDE4D interaction leads to attenuation of pathological cardiac remodelling.

  13. iPSC-derived human cardiac progenitor cells improve ventricular remodelling via angiogenesis and interstitial networking of infarcted myocardium.

    Science.gov (United States)

    Ja, Kp Myu Mia; Miao, Qingfeng; Zhen Tee, Nicole Gui; Lim, Sze Yun; Nandihalli, Manasi; J A Ramachandra, Chrishan; Mehta, Ashish; Shim, Winston

    2016-02-01

    We investigate the effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived progenitors and cardiomyocytes into acutely infarcted myocardium in severe combined immune deficiency mice. A total of 2 × 10(5) progenitors, cardiomyocytes or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Myocardial function was assessed at 2-week and 4-week post-infarction by using echocardiography and pressure-volume catheterization. Early myocardial remodelling was observed at 2-week with echocardiography derived stroke volume (SV) in saline (20.45 ± 7.36 μl, P EDV: 23.24 ± 5.01 μl, P EDV: 26.45 ± 5.69 μl, P EDV: 15.26 ± 2.96 μl; ESV: 8.41 ± 2.94 μl). In contrast, cardiac progenitors (EDV: 20.09 ± 7.76 μl; ESV: 13.98 ± 6.74 μl) persistently protected chamber geometry against negative cardiac remodelling. Similarly, as compared to sham control (54.64 ± 11.37%), LV ejection fraction was preserved in progenitor group from 2-(38.68 ± 7.34%) to 4-week (39.56 ± 13.26%) while cardiomyocyte (36.52 ± 11.39%, P < 0.05) and saline (35.34 ± 11.86%, P < 0.05) groups deteriorated early at 2-week. Improvements of myocardial function in the progenitor group corresponded to increased vascularization (16.12 ± 1.49/mm(2) to 25.48 ± 2.08/mm(2) myocardial tissue, P < 0.05) and coincided with augmented networking of cardiac telocytes in the interstitial space of infarcted zone. PMID:26612359

  14. External cardiac compression may be harmful in some scenarios of pulseless electrical activity.

    LENUS (Irish Health Repository)

    Hogan, T S

    2012-10-01

    Pulseless electrical activity occurs when organised or semi-organised electrical activity of the heart persists but the product of systemic vascular resistance and the increase in systemic arterial flow generated by the ejection of the left venticular stroke volume is not sufficient to produce a clinically detectable pulse. Pulseless electrical activity encompasses a very heterogeneous variety of severe circulatory shock states ranging in severity from pseudo-cardiac arrest to effective cardiac arrest. Outcomes of cardiopulmonary resuscitation for pulseless electrical activity are generally poor. Impairment of cardiac filling is the limiting factor to cardiac output in many scenarios of pulseless electrical activity, including extreme vasodilatory shock states. There is no evidence that external cardiac compression can increase cardiac output when impaired cardiac filling is the limiting factor to cardiac output. If impaired cardiac filling is the limiting factor to cardiac output and the heart is effectively ejecting all the blood returning to it, then external cardiac compression can only increase cardiac output if it increases venous return and cardiac filling. Repeated cardiac compression asynchronous with the patient\\'s cardiac cycle and raised mean intrathoracic pressure due to chest compression can be expected to reduce rather than to increase cardiac filling and therefore to reduce rather than to increase cardiac output in such circumstances. The hypothesis is proposed that the performance of external cardiac compression will have zero or negative effect on cardiac output in pulseless electrical activity when impaired cardiac filling is the limiting factor to cardiac output. External cardiac compression may be both directly and indirectly harmful to significant sub-groups of patients with pulseless electrical activity. We have neither evidence nor theory to provide comfort that external cardiac compression is not harmful in many scenarios of pulseless

  15. [Electromagnetic interference of electrical dental equipment with cardiac pacemakers].

    Science.gov (United States)

    Brand, H S; van der Hoeff, E V; Schrama, T A M; Entjes, M L; van Nieuw, Amerongen A

    2007-09-01

    Eight different electrical dental appliances were tested at different intervals for their ability to interfere with the function of a contemporary cardiac pacemaker. The normal atrial and ventricular pacing was inhibited by an ultrasonic bath cleaner at a distance of less than 15 cm. In contrast, a dental chair, an electrosurgical unit, an ultrasonic tooth scaler, 2 handpieces, and 2 amalgamators failed to produce electromagnetic interference at the minimum distance of 2.5 cm. In conclusion, the results suggest that normal clinical use of dental electrical equipment does not have any significant effect on the cardiac pacemaker tested. PMID:17937372

  16. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    Science.gov (United States)

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  17. Triterpenoid dihydro-CDDO-trifluoroethyl amide protects against maladaptive cardiac remodeling and dysfunction in mice: a critical role of Nrf2.

    Directory of Open Access Journals (Sweden)

    Yifan Xing

    Full Text Available BACKGROUND AND AIMS: Nuclear factor E2-related factor 2 (Nrf2 appears to be an attractive therapeutic target for the treatment of cardiac disease. We investigated whether a synthetic triterpenoid derivative of dihydro-CDDO-trifluoroethylamide (dh404, a novel Nrf2 activator, protects against pathological cardiac responses to hemodynamic stress in mice. METHODS: Cardiac maladaptive remodeling and dysfunction were established by transverse aortic constriction (TAC in mice. Hypertrophic growth of rat neonatal cardiomyocytes was induced by angiotensin II (Ang II. Cell death of rat neonatal cardiomyocytes was induced with hydrogen peroxide (H₂O₂. Cellular proliferation of rat neonatal cardiac fibroblasts was induced by Ang II, norepinephrine (NE and phenylephrine (PE. Protein expression was assessed by immunochemical staining and Western blots. Gene expression was determined by real time reverse transcription-polymerase chain reaction (Q-PCR. RESULTS: TAC suppressed myocardial Nrf2 expression, increased myocardial 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine levels, and induced cardiac hypertrophy, fibrosis and apoptosis, and overt heart failure and death in mice. Administration of dh404 inhibited the pathological cardiac remodeling and dysfunction, and reduced the mortality. Moreover, dhd404 elevated myocardial levels of Nrf2 and Nrf2 nuclear translocation with a dramatic suppression of the oxidative stress in the heart. Dh404 inhibited hypertrophic growth and death in primary culture of rat neonatal cardiomyocytes and suppressed proliferation in primary culture of rat neonatal cardiac fibroblasts. However, these effects of dh404 were blunted by knocking down of Nrf2. CONCLUSION: These findings demonstrate that dh404 prevents pathological cardiac remodeling and dysfunction by activating Nrf2, indicating a therapeutic potential of dh404 for cardiac disease.

  18. Carbon monoxide pollution promotes cardiac remodeling and ventricular arrhythmia in healthy rats.

    OpenAIRE

    Andre, Lucas; Boissière, Julien; Reboul, Cyril; Perrier, Romain; Zalvidea, Santiago; Meyer, Gregory; Thireau, Jérôme; Tanguy, Stéphane; Bideaux, Patrice; Hayot, Maurice; Boucher, François; Obert, Philippe; Cazorla, Olivier; Richard, Sylvain

    2010-01-01

    RATIONALE: Epidemiologic studies associate atmospheric carbon monoxide (CO) pollution with adverse cardiovascular outcomes and increased cardiac mortality risk. However, there is a lack of data regarding cellular mechanisms in healthy individuals. OBJECTIVES: To investigate the chronic effects of environmentally relevant CO levels on cardiac function in a well-standardized healthy animal model. METHODS: Wistar rats were exposed for 4 weeks to filtered air (CO < 1 ppm) or air enriched with CO ...

  19. Electrical stimulation to optimize cardioprotective exosomes from cardiac stem cells.

    Science.gov (United States)

    Campbell, C R; Berman, A E; Weintraub, N L; Tang, Y L

    2016-03-01

    Injured or ischemic cardiac tissue has limited intrinsic capacity for regeneration. While stem cell transplantation is a promising approach to stimulating cardiac repair, its success in humans has thus far been limited. Harnessing the therapeutic benefits of stem cells requires a better understanding of their mechanisms of action and methods to optimize their function. Cardiac stem cells (CSC) represent a particularly effective cellular source for cardiac repair, and pre-conditioning CSC with electrical stimulation (EleS) was demonstrated to further enhance their function, although the mechanisms are unknown. Recent studies suggest that transplanted stem cells primarily exert their effects through communicating with endogenous tissues via the release of exosomes containing cardioprotective molecules such as miRNAs, which upon uptake by recipient cells may stimulate survival, proliferation, and angiogenesis. Exosomes are also effective therapeutic agents in isolation and may provide a feasible alternative to stem cell transplantation. We hypothesize that EleS enhances CSC-mediated cardiac repair through its beneficial effects on production of cardioprotective exosomes. Moreover, we hypothesize that the beneficial effects of biventricular pacing in patients with heart failure may in part result from EleS-induced preconditioning of endogenous CSC to promote cardiac repair. With future research, our hypothesis may provide applications to optimize stem cell therapy and augment current pacing protocols, which may significantly advance the treatment of patients with heart disease. PMID:26880625

  20. TWEAK-Fn14 cytokine-receptor axis: a new player of myocardial remodeling and cardiac failure

    Directory of Open Access Journals (Sweden)

    Tatyana eNovoyatleva

    2014-02-01

    Full Text Available Tumor necrosis factor (TNF has been firmly established as a pathogenic factor in heart failure, a significant socio-economic burden. In this review we will explore the role of other members of the TNF/TNF receptor superfamily (TNFSF/TNFRSF in cardiovascular diseases (CVDs focusing on TWEAK and its receptor Fn14, new players in myocardial remodeling and heart failure. The TWEAK/Fn14 pathway controls a variety of cellular activities such as proliferation, differentiation and apoptosis and has diverse biological functions in pathological mechanisms like inflammation and fibrosis that are associated with CVDs. Furthermore, it has recently been shown that the TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy and that deletion of Fn14 receptor protects from right heart fibrosis and dysfunction. We discuss the potential use of the TWEAK/Fn14 axis as biomarker for CVDs as well as therapeutic target for future treatment of human heart failure based on supporting data from animal models and in vitro studies. Collectively, existing data strongly suggest the TWEAK/Fn14 axis as a potential new therapeutic target for achieving cardiac protection in patients with CVDs.

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

    Directory of Open Access Journals (Sweden)

    Tanya M Holloway

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

  2. Multiscale characterization of cardiac remodeling induced by intrauterine growth restriction, at organ, cellular and subcellular level

    OpenAIRE

    González Tendero, Anna

    2014-01-01

    Tesi realitzada a l'Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) INTRODUCTION: Intrauterine growth restriction (IUGR) due to placental insufficiency affects up to 7-10% of pregnancies and is a major cause of perinatal mortality and long term morbidity. IUGR results in low birth weight, which is associated with increased risk of cardiovascular mortality in adulthood, and is thought to be mediated by fetal cardiovascular programming. IUGR fetuses show signs of cardiac s...

  3. ATP-Sensitive K+ Channel Knockout Induces Cardiac Proteome Remodeling Predictive of Heart Disease Susceptibility

    OpenAIRE

    Arrell, D. Kent; Zlatkovic, Jelena; Kane, Garvan C; Yamada, Satsuki; Terzic, Andre

    2009-01-01

    Forecasting disease susceptibility requires detection of maladaptive signatures prior to onset of overt symptoms. A case-in-point are cardiac ATP-sensitive K+ (KATP) channelopathies, for which the substrate underlying disease vulnerability remains to be identified. Resolving molecular pathobiology, even for single genetic defects, mandates a systems platform to reliably diagnose disease predisposition. High-throughput proteomic analysis was here integrated with network biology to decode conse...

  4. Myocardial stress and hypertrophy: a complex interface between biophysics and cardiac remodeling

    OpenAIRE

    Grossman, William; Paulus, Walter J.

    2013-01-01

    Pressure and volume overload results in concentric and eccentric hypertrophy of cardiac ventricular chambers with, respectively, parallel and series replication of sarcomeres. These divergent patterns of hypertrophy were related 40 years ago to disparate wall stresses in both conditions, with systolic wall stress eliciting parallel replication of sarcomeres and diastolic wall stress, series replication. These observations are relevant to clinical practice, as they relate to the excessive hype...

  5. Design of Electrical Stimulation Bioreactors for Cardiac Tissue Engineering

    OpenAIRE

    Tandon, N.; Marsano, A.; Cannizzaro, C; Voldman, J.; Vunjak-Novakovic, G.

    2008-01-01

    Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance s...

  6. High Molecular Weight Fibroblast Growth Factor-2 in the Human Heart Is a Potential Target for Prevention of Cardiac Remodeling

    Science.gov (United States)

    Santiago, Jon-Jon; McNaughton, Leslie J.; Koleini, Navid; Ma, Xin; Bestvater, Brian; Nickel, Barbara E.; Fandrich, Robert R.; Wigle, Jeffrey T.; Freed, Darren H.; Arora, Rakesh C.; Kardami, Elissavet

    2014-01-01

    Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD) and 68% (±25 SD) of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs) expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II) up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2) reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial) tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes deleterious

  7. Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes.

    LENUS (Irish Health Repository)

    Phelan, Dermot

    2012-11-01

    In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g\\/m(2), p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

  8. High molecular weight fibroblast growth factor-2 in the human heart is a potential target for prevention of cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    Jon-Jon Santiago

    Full Text Available Fibroblast growth factor 2 (FGF-2 is a multifunctional protein synthesized as high (Hi- and low (Lo- molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD and 68% (±25 SD of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2 reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes

  9. Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes.

    Directory of Open Access Journals (Sweden)

    Dermot Phelan

    Full Text Available In asymptomatic subjects B-type natriuretic peptide (BNP is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS and peripheral serum from patients with low (n = 14 and high BNP (n = 27. Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001. CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008, CITP (r = 0.35, p = 0.03 and PIIINP (r = 0.35, p = 0.001, and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002, IL-6 (r = 0.35, p = 0.04, and IL-8 (r = 0.54, p<0.001. The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007, TNF-α (3.2±0.5 versus 3.7±1.1, p = 003, IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02 and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04, and greater left ventricular mass index (97±20 versus 118±26 g/m(2, p = 0.03 and left atrial volume index (18±2 versus 21±4, p = 0.008. Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

  10. Sirtuin1-p53, forkhead box O3a, p38 and post-infarct cardiac remodeling in the spontaneously diabetic Goto-Kakizaki rat

    Directory of Open Access Journals (Sweden)

    Kytö Ville

    2010-01-01

    Full Text Available Abstract Background Diabetes is associated with changes in myocardial stress-response pathways and is recognized as an independent risk factor for cardiac remodeling. Using spontaneously diabetic Goto Kakizaki rats as a model of type 2 DM we investigated whether post-translational modifications in the Akt - FOXO3a pathway, Sirt1 - p53 pathway and the mitogen activated protein kinase p38 regulator are involved in post-infarct cardiac remodeling Methods Experimental myocardial infarction (MI was induced by left anterior descending coronary artery ligation in spontaneously diabetic Goto-Kakizaki rats and non-diabetic Wistar controls. Cardiac function was studied by echocardiography. Myocardial hypertrophy, cardiomyocyte apoptosis and cardiac fibrosis were determined histologically 12 weeks post MI or Sham operation. Western blotting was used to study Caspase-3, Bax, Sirt1, acetylation of p53 and phosphorylation of p38, Akt and FOXO3a. Electrophoretic mobility shift assay was used to assess FOXO3a activity and its nuclear localization. Results Post-infarct heart failure in diabetic GK rats was associated with pronounced cardiomyocyte hypertrophy, increased interstitial fibrosis and sustained cardiomyocyte apoptosis as compared with their non-diabetic Wistar controls. In the GK rat myocardium, Akt- and FOXO3a-phosphorylation was decreased and nuclear localization of FOXO3a was increased concomitantly with increased PTEN protein expression. Furthermore, increased Sirt1 protein expression was associated with decreased p53 acetylation, and phosphorylation of p38 was increased in diabetic rats with MI. Conclusions Post-infarct heart failure in diabetic GK rats was associated with more pronounced cardiac hypertrophy, interstitial fibrosis and sustained cardiomyocyte apoptosis as compared to their non-diabetic controls. The present study suggests important roles for Akt-FOXO3a, Sirt1 - p53 and p38 MAPK in the regulation of post-infarct cardiac remodeling

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

    Directory of Open Access Journals (Sweden)

    Anne-Mari Moilanen

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

  12. Functional suppression of Kcnq1 leads to early sodium channel remodelling and cardiac conduction system dysmorphogenesis

    Czech Academy of Sciences Publication Activity Database

    De la Rosa, A. J.; Domínguez, J. N.; Sedmera, D.; Šaňková, Barbora; Hove-Madsen, L.; Franco, D.; Aránega, A. E.

    2013-01-01

    Roč. 98, č. 3 (2013), s. 504-514. ISSN 0008-6363 R&D Projects: GA ČR(CZ) GA304/08/0615; GA ČR(CZ) GAP302/11/1308; GA ČR(CZ) GD204/09/H084; GA ČR(CZ) GA13-12412S Institutional research plan: CEZ:AV0Z50110509 Institutional support : RVO:67985823 Keywords : ion channels * Long-QT syndrome * sudden death * cardiac hypertrophy Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 5.808, year: 2013

  13. Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis.

    Science.gov (United States)

    Frunza, Olga; Russo, Ilaria; Saxena, Amit; Shinde, Arti V; Humeres, Claudio; Hanif, Waqas; Rai, Vikrant; Su, Ya; Frangogiannis, Nikolaos G

    2016-05-01

    The β-galactoside-binding animal lectin galectin-3 is predominantly expressed by activated macrophages and is a promising biomarker for patients with heart failure. Galectin-3 regulates inflammatory and fibrotic responses; however, its role in cardiac remodeling remains unclear. We hypothesized that galectin-3 may be up-regulated in the pressure-overloaded myocardium and regulate hypertrophy and fibrosis. In normal mouse myocardium, galectin-3 was constitutively expressed in macrophages and was localized in atrial but not ventricular cardiomyocytes. In a mouse model of transverse aortic constriction, galectin-3 expression was markedly up-regulated in the pressure-overloaded myocardium. Early up-regulation of galectin-3 was localized in subpopulations of macrophages and myofibroblasts; however, after 7 to 28 days of transverse aortic constriction, a subset of cardiomyocytes in fibrotic areas contained large amounts of galectin-3. In vitro, cytokine stimulation suppressed galectin-3 synthesis by macrophages and cardiac fibroblasts. Correlation studies revealed that cardiomyocyte- but not macrophage-specific galectin-3 localization was associated with adverse remodeling and dysfunction. Galectin-3 knockout mice exhibited accelerated cardiac hypertrophy after 7 days of pressure overload, whereas female galectin-3 knockouts had delayed dilation after 28 days of transverse aortic constriction. However, galectin-3 loss did not affect survival, systolic and diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy in the pressure-overloaded heart. Despite its potential role as a prognostic biomarker, galectin-3 is not a critical modulator of cardiac fibrosis but may delay the hypertrophic response. PMID:26948424

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

    Directory of Open Access Journals (Sweden)

    Tim Peters

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

  15. High-fat Diet Promotes Cardiac Remodeling in an Experimental Model of Obesity

    Directory of Open Access Journals (Sweden)

    Fernando Martins

    2015-01-01

    Full Text Available AbstractBackground:Although nutritional, metabolic and cardiovascular abnormalities are commonly seen in experimental studies of obesity, it is uncertain whether these effects result from the treatment or from body adiposity.Objective:To evaluate the influence of treatment and body composition on metabolic and cardiovascular aspects in rats receiving high saturated fat diet.Methods:Sixteen Wistar rats were used, distributed into two groups, the control (C group, treated with isocaloric diet (2.93 kcal/g and an obese (OB group, treated with high-fat diet (3.64 kcal/g. The study period was 20 weeks. Analyses of nutritional behavior, body composition, glycemia, cholesterolemia, lipemia, systolic arterial pressure, echocardiography, and cardiac histology were performed.Results:High-fat diet associates with manifestations of obesity, accompanied by changes in glycemia, cardiomyocyte hypertrophy, and myocardial interstitial fibrosis. After adjusting for adiposity, the metabolic effects were normalized, whereas differences in morphometric changes between groups were maintained.Conclusion:It was concluded that adiposity body composition has a stronger association with metabolic disturbances in obese rodents, whereas the high-fat dietary intervention is found to be more related to cardiac morphological changes in experimental models of diet-induced obesity.

  16. Hypoxic remodelling of Ca{sup 2+} stores does not alter human cardiac myofibroblast invasion

    Energy Technology Data Exchange (ETDEWEB)

    Riches, K.; Hettiarachchi, N.T.; Porter, K.E. [Leeds Institute for Genetics, Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT (United Kingdom); Peers, C., E-mail: c.s.peers@leeds.ac.uk [Leeds Institute for Genetics, Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT (United Kingdom)

    2010-12-17

    Research highlights: {yields} Bradykinin promotes migration and proliferation of myofibroblasts. {yields} Such activity is Ca{sup 2+}-dependent and occurs under hypoxic conditions. {yields} Hypoxia increased myofibroblast Ca{sup 2+} stores but not influx evoked by bradykinin. {yields} Myofibroblast migration and proliferation was unaffected by hypoxia. -- Abstract: Cardiac fibroblasts are the most abundant cell type in the heart, and play a key role in the maintenance and repair of the myocardium following damage such as myocardial infarction by transforming into a cardiac myofibroblast (CMF) phenotype. Repair occurs through controlled proliferation and migration, which are Ca{sup 2+} dependent processes, and often requires the cells to operate within a hypoxic environment. Angiotensin converting enzyme (ACE) inhibitors reduce infarct size through the promotion of bradykinin (BK) stability. Although CMF express BK receptors, their activity under the reduced O{sub 2} conditions that occur following infarct are entirely unexplored. Using Fura-2 microfluorimetry on primary human CMF, we found that hypoxia significantly increased the mobilisation of Ca{sup 2+} from intracellular stores in response to BK whilst capacitative Ca{sup 2+} entry (CCE) remained unchanged. The enhanced store mobilisation was due to a striking increase in CMF intracellular Ca{sup 2+}-store content under hypoxic conditions. However, BK-induced CMF migration or proliferation was not affected following hypoxic exposure, suggesting that Ca{sup 2+} influx rather than mobilisation is of primary importance in CMF migration and proliferation.

  17. Relationship of cardiac arrhythmias to myocar- dial remodeling and expression of adhesion molecules in patients with mitral valve prolapse

    Directory of Open Access Journals (Sweden)

    A.V. Yagoda

    Conclusion. Myocardial remodeling and dysregulation of cell adhesion proteins are recorded in young patients with MVP and arrhythmias. Relaionship of severity of arrhythmic syndrome to myocardial remodeling and VCAM-1 level was revealed.

  18. Whole-thorax irradiation induces hypoxic respiratory failure, pleural effusions and cardiac remodeling

    International Nuclear Information System (INIS)

    To study the mechanisms of death following a single lethal dose of thoracic radiation, WAG/RijCmcr (Wistar) rats were treated with 15 Gy to the whole thorax and followed until they were morbid or sacrificed for invasive assays at 6 weeks. Lung function was assessed by breathing rate and arterial oxygen saturation. Lung structure was evaluated histologically. Cardiac structure and function were examined by echocardiography. The frequency and characteristics of pleural effusions were determined. Morbidity from 15 Gy radiation occurred in all rats 5 to 8 weeks after exposure, coincident with histological pneumonitis. Increases in breathing frequencies peaked at 6 weeks, when profound arterial hypoxia was also recorded. Echocardiography analysis at 6 weeks showed pulmonary hypertension and severe right ventricular enlargement with impaired left ventricular function and cardiac output. Histologic sections of the heart revealed only rare foci of lymphocytic infiltration. Total lung weight more than doubled. Pleural effusions were present in the majority of the irradiated rats and contained elevated protein, but low lactate dehydrogenase, when compared with serum from the same animal. Pleural effusions had a higher percentage of macrophages and large monocytes than neutrophils and contained mast cells that are rarely present in other pathological states. Lethal irradiation to rat lungs leads to hypoxia with infiltration of immune cells, edema and pleural effusion. These changes may contribute to pulmonary vascular and parenchymal injury that result in secondary changes in heart structure and function. We report that conditions resembling congestive heart failure contribute to death during radiation pneumonitis, which indicates new targets for therapy. (author)

  19. Cardiac-Restricted IGF-1Ea Overexpression Reduces the Early Accumulation of Inflammatory Myeloid Cells and Mediates Expression of Extracellular Matrix Remodelling Genes after Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Enrique Gallego-Colon

    2015-01-01

    Full Text Available Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin-like growth factor-1 Ea (IGF-1Ea propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac-specific IGF-1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF-1Ea regulated expression of key metalloproteinases (MMP-2 and MMP-9, their inhibitors (TIMP-1 and TIMP-2, and collagen types (Col 1α1 and Col 1α3 in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti-inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF-1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function.

  20. Role of Bradykinin on Left Ventricular Remodeling and Cardiac Function after Myocardial Infarction in Rats

    Institute of Scientific and Technical Information of China (English)

    Hai-zhu ZHANG; Li-quan LEI; Chang-cong CUI; Jian LIU

    2009-01-01

    Objectives To investigate the influences of bradykinin (BK) on hemodynamics, left ventricular hypertrophy and interstitial collagen metabolism after myocardial infarction (MI) in rats and the contribution of BK in angiotensin-con-verting enzyme (ACE) inhibition therapy. Methods By means of hemodynamic measurements, morphometric study of myocyte hypertrophy and SDS-PAGE technique ,the effects of enalapril pressure (500μg·kg-1·day-1) ,enalapril(500μg·kg-1·day-1) with BK B2 receptor antagonist Hoe-140 (500μg·kg-1·day-1),angiotensin Ⅱ (AgII) type 1 (AT1) receptor antagonist losartan(3mg·kg-1·day-1)on mean arterial pressure (MAP) ,left ventricular end-dias-tolic pressure (LVEDP), as well as maximum positive left ventricular pressure change (+ dp/dtmax), Ⅴ(m) n, col-lagen content and the ratio of type Ⅰ to type Ⅲ collagen (Ⅰ / Ⅲ) of noninfarcted area were observed in rats after MI. Treatments were started on the 3rd day after MI and continued for another 28 days. Results Enalapril reduced LV-EDP, Ⅴ(m) n and collagen content as well as collagen Ⅰ/Ⅲ compared with the untreated MI group (P < 0. 05), and all of these effects of enalapril were partly blunted by concomitant treatment with hoe-140 (P < 0. 05). Losartan was less effective than enalapril (P < 0. 05). However, three treatment groups had no significant differences in + dp/dtmax and had similar reductions in MAP compared with untreated MI group. Conclusions BK can improve cardiac function and prevent left ventricular hypertrophy with myocardial fibrosis independent of blood pressure. The mechanisms of ACEI are both blockade of Ang Ⅱ formation and inhibition of BK degradation.

  1. Hydrogen Sulfide Mitigates Cardiac Remodeling During Myocardial Infarction via Improvement of Angiogenesis

    Directory of Open Access Journals (Sweden)

    Natia Qipshidze, Naira Metreveli, Paras K. Mishra, David Lominadze, Suresh C. Tyagi

    2012-01-01

    Full Text Available Exogenous hydrogen sulfide (H2S leads to down-regulation of inflammatory responses and provides myocardial protection during acute ischemia/reperfusion injury; however its role during chronic heart failure (CHF due to myocardial infarction (MI is yet to be unveiled. We previously reported that H2S inhibits antiangiogenic factors such, as endostatin and angiostatin, but a little is known about its effect on parstatin (a fragment of proteinase-activated receptor-1, PAR-1. We hypothesize that H2S inhibits parstatin formation and promotes VEGF activation, thus promoting angiogenesis and significantly limiting the extent of MI injury. To verify this hypothesis MI was created in 12 week-old male mice by ligation of left anterior descending artery (LAD. Sham surgery was performed except LAD ligation. After the surgery mice were treated with sodium hydrogen sulfide (30 μmol/l NaHS, a donor for H2S, in drinking water for 4 weeks. The LV tissue was analyzed for VEGF, flk-1 and flt-1, endostatin, angiostatin and parstatin. The expression of VEGF, flk-1 and flt-1 were significantly increased in treated mice while the level of endostatin, angiostatin and parstatin were decreased compared to in untreated mice. The echocardiography in mice treated with H2S showed the improvement of heart function compared to in untreated mice. The X-ray and Doppler blood flow measurements showed enhancement of cardiac-angiogenesis in mice treated with H2S. This observed cytoprotection was associated with an inhibition of anti-angiogenic proteins and stimulation of angiogenic factors. We established that administration of H2S at the time of MI ameliorated infarct size and preserved LV function during development of MI in mice. These results suggest that H2S is cytoprotective and angioprotective during evolution of MI.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Renal denervation mitigates cardiac remodeling and renal damage in Dahl rats: a comparison with β-receptor blockade.

    Science.gov (United States)

    Watanabe, Heitaro; Iwanaga, Yoshitaka; Miyaji, Yuki; Yamamoto, Hiromi; Miyazaki, Shunichi

    2016-04-01

    Chronic activation of the sympathetic nervous system (SNS) contributes to cardiac remodeling and the transition to heart failure (HF). Renal sympathetic denervation (RDN) may ameliorate this damage by improving renal function and sympathetic cardioregulation in hypertensive HF patients with renal injury. The efficacy may be comparable to that of chronic β-blocker treatment. Dahl salt-sensitive hypertensive rats were subjected to RDN in the hypertrophic stage. Another group of Dahl rats were subjected to sham operations and treated chronically with vehicle (CONT) or β-blocker bisoprolol (BISO). Neither RDN nor BISO altered the blood pressure; however, BISO significantly reduced the heart rate (HR). Both RDN and BISO significantly prolonged survival (22.2 and 22.4 weeks, respectively) compared with CONT (18.3 weeks). Echocardiography revealed reduced left ventricular (LV) hypertrophy and improved LV function, and histological analysis demonstrated the amelioration of LV myocyte hypertrophy and fibrosis in the RDN and BISO rats at the HF stage. Tyrosine hydroxylase and β1-adrenergic receptor (ADR) expression levels in the LV myocardium significantly increased only in the RDN rats, whereas the α1b-, α1d- and α2c-ADR expression levels increased only in the BISO rats. In both groups, renal damage and dysfunction were also reduced, and this reduction was accompanied by the suppression of endothelin-1, renin and angiotensin-converting enzyme mRNAs. RDN ameliorated the progression of both myocardial and renal damage in the hypertensive rats independent of blood pressure changes. The overall effects were similar to those of β-receptor blockade with favorable effects on HR and α-ADR expression. These findings may be associated with the restoration of the myocardial SNS and renal protection. PMID:26631854

  4. The Combined Effect of Endurance Training and Various Doses of Atorvastatin on Cardiac Remodeling after Myocardial Infarction in Male Rats

    Directory of Open Access Journals (Sweden)

    Hadi Abdi

    2015-12-01

    Full Text Available Introduction: Statins and exercise have beneficial effects in preventing cardiovascular diseases. However, prolonged use of statins particularly at high doses has unpleasant side effects. This study aimed to investigate the combined effect of endurance training and three doses of Atorvastatin on cardiac remodeling after myocardial infarction in male rats.Methods: 75 male wistar rats (weighing 210-250g were randomly divided to 9 groups. Sham, control, endurance training, Atorvastatin (5, 10 and 15 mg/kg, and exercise plus Atorvastatin (5, 10 and 15 mg/kg: Myocardial infarction was induced by subcutaneous injection of isoprenaline (150 mg/kg in two consecutive days. Drug and training intervention was initiated 2 days after infarction and continued for 4 weeks. In order to assess the necrosis lesion and fibrosis tissue, hematoxylin & eosin and masson trichrome staining were used respectively.Results: The combination of endurance training and various doses of Atorvastatin significantly reduced the amount of necrosis and fibrosis tissue compared with the control group (P<0.01. Endurance exercise training alone did not cause significant changes in the extent of necrosis damage, but significantly increased fibrosis tissue compared with the control group (P<0.001. Various doses of Atorvastatin alone significantly reduced necrosis damage (P<0.001, but the difference between these groups and the control group in terms of fibrous tissue was statistically significant only at dose of 15 mg/kg (P<0.001.Conclusion: The results of this study showed that the combination of training and various doses of Atorvastatin are more effective in improving of tissue damage caused by myocardial infarction than exercise and Atorvastatin alone. However, the use of endurance training with medical therapy can not reduce the dose of Atorvastatin.

  5. Serum MMP-8: A Novel Indicator of Left Ventricular Remodeling and Cardiac Outcome in Patients after Acute Myocardial Infarction

    OpenAIRE

    Marie Fertin; Gilles Lemesle; Annie Turkieh; Olivia Beseme; Maggy Chwastyniak; Philippe Amouyel; Christophe Bauters; Florence Pinet

    2013-01-01

    OBJECTIVE: Left ventricular (LV) remodeling following myocardial infarction (MI) is characterized by progressive alterations of structure and function, named LV remodeling. Although several risk factors such as infarct size have been identified, LV remodeling remains difficult to predict in clinical practice. Changes within the extracellular matrix, involving matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), are an integral part of left ventricular (LV) rem...

  6. Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc

    OpenAIRE

    Heineke, Joerg; Ruetten, Hartmut; Willenbockel, Christian; Gross, Sandra C.; Naguib, Marian; Schaefer, Arnd; Kempf, Tibor; Hilfiker-Kleiner, Denise; Caroni, Pico; Kraft, Theresia; Kaiser, Robert A.; Molkentin, Jeffery D; Drexler, Helmut; Wollert, Kai C.

    2005-01-01

    Adverse left ventricular (LV) remodeling after myocardial infarction (MI) is a major cause for heart failure. Molecular modifiers of the remodeling process remain poorly defined. Patients with heart failure after MI have reduced LV expression levels of muscle LIM protein (MLP), a component of the sarcomeric Z-disk that is involved in the integration of stress signals in cardiomyocytes. By using heterozygous MLP mutant (MLP+/—) mice, we explored the role of MLP in post-MI remodeling. LV dimens...

  7. Structural and Electrical Myocardial Remodeling in a Rodent Model of Depression

    NARCIS (Netherlands)

    Carnevali, Luca; Trombini, Mimosa; Rossi, Stefano; Graiani, Gallia; Manghi, Massimo; Koolhaas, Jaap M.; Quaini, Federico; Macchi, Emilio; Nalivaiko, Eugene; Sgoifo, Andrea; Boer, S.F. de; Gugten, J. van der; Slangen, J.L.

    2013-01-01

    Objective: Despite a well-documented association between stress and depression with cardiac morbidity and mortality, there is no satisfactory explanation for the mechanisms linking affective and cardiac disorders. This study investigated cardiac electrophysiological properties in an animal model of

  8. Effects of Long-term Ramipril on Ventricular Remodeling, Cardiac Function and Survival in Rat Congestive Heart Failure after Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    陶则伟; 黄元伟

    2004-01-01

    Objectives The purpose of this study was to investigate the effects of long-term ramipril on ventricular remodeling, cardiac function and survival in rat congestive heart failure after myocardial infarction. Methods Myocardial infarction (MI) was caused by ligation of the left anterior descending coronary artery in rats. 7 days after the surgery, the surviving rats were randomly assigned to the following treatment protocols: 1) MI rats with no therapy, 2) MI rats treated with ramipril 3 mg/kg per day, 3) Sham-operated control rats, and 4) Sham-operated rats treated with ramipril 3 mg/kg per day. At 22 weeks, cardiac hemodynamic parameters such as MAP, LVSP, ±dP/dtmax and LVEDP were measured,and cardiac morphometric parameters such as HW,LVW and LVCA were measured, mRNA of cardiacmolecule genes, such as βMHC, BNP, collagen Ⅰ and Ⅲ, and TGF-β1, were quantified, and survival rates were calculated. Results Compared with sham-operated rats, MI rats without therapy showed significant increases in cardiac morphological parameters as well as in mRAN expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly impaired (P<0.01), and survival rate shortened (P<0.05). Compared with MI rats with no therapy, MI rats treated with ramipril showed significant attenuation of mRAN expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly impaired (P<0.01), and survival rate shortened (P<0.05). Compared with MI rats with no therapy, MI rats treated with ramipril showed significant attenuation of mRAN expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly improved (P<0.05 or P<0.01), and survival rates prolonged (P<0.05). Conclusions Treatment with long-term ramipril may improve LV remodeling, cardiac function and survival in rat congestive heart failure after MI.

  9. Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction

    OpenAIRE

    Li, Longhu; Haider, Husnain Kh; WANG, Linlin; Lu, Gang; Ashraf, Muhammad

    2012-01-01

    We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary...

  10. Effect of nifekalant on acute electrical remodelling in rapid atrial pacing canine model

    Institute of Scientific and Technical Information of China (English)

    TANG Min; ZHANG Shu; SUN Qi; HUA Wei; HUANG Cong-xin

    2006-01-01

    inhibited ERP shortening and ERP heterogeneity increasing,decreased AF induction. Nifekalant can reverse acute electrical remodeling effect in this model.

  11. Effect of transcutaneous electric stimulation on the cardiac electrical activity in New Zealand white rabbits

    Directory of Open Access Journals (Sweden)

    Wang ZHANG

    2015-10-01

    Full Text Available Objective To study the effect of transcutaneous electric stimulation on the cardiac electrical activity in New Zealand white rabbits, in order to search a safety threshold for clinical electrical stimulation therapy, as to provide the theoretical basis for the design of in vitro pacemaker. Methods New Zealand white rabbits were randomly assigned into 17 groups (6 each. Rabbits in 16 experimental groups were given 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75 and 80V electrical stimulation, respectively, with the stimulating site designated at epigastric region. BL -420F biological function experimental system was employed to supply the power and acquire the ECG, with the output pulse electrical stimulation frequency set at 270 times/minute, and the stimulating wave as square wave. A control group was set, in which the stimulating voltage was set to 35V, the stimulant anode was located in the anterior chest area, and the cathode was on the skin surface of back corresponding to the site of the heart, and the rest was the same as in experimental groups. Results No stimulation rhythm was observed in rabbits of those experimental groups with voltage ≤35V, but all stimulation rhythm was observed in rabbits of control group. No arrhythmia occurred in rabbits of those experimental groups with voltage ≤30V, while the heart rate was slowed down after stimulation in rabbits of the experimental groups with voltage ≥45V stimulation. In rabbits receiving stimulation with voltage ≤35V there was no dystropy or light dystropy, but with no visible injury to the local tissues. No visible injury was observed in the rabbits undergoing stimulation with voltage ≤40V. Conclusion Pulse electric stimulation with voltage ≤35V in the epigastric region would not affect the cardiac electrical activity in rabbits, while stimulation with 35V will lead to all pacing rhythm of the heart without affecting the cardiac electrical activity in rabbits

  12. Impact of pulmonary vein isolation on atrial vagal activity and atrial electrical remodeling

    Institute of Scientific and Technical Information of China (English)

    Yingxue Dong; Shulong Zhang; Lianjun Gao; Hongwei Zhao; Donghui Yang; Yunlong Xia; Yanzong Yang

    2008-01-01

    Objective Mechanisms of pulmonary vein isolation (PVI) for atrial fibrillation remain controversy.This study aimed to investigate the impact of PVI on vagal modulation to atria.Methods Eighteen adult mongrel dogs under general anesthesia were randomly divided into two groups.Bilateral cervical sympathovagal trunks were decentralized and sympathetic effects was blocked by metoprolol administration.Atrial electrical remodeling (AER) was established by rapid right atrial pacing at the rate of 600 bpm for 30 minutes.PVI was performed in group A.Atrial effective refractory period (ERP),vulnerability window (VW) of atrial fibrillation,and sinus rhythm cycle length (SCL) were measured at baseline and during vagal stimulation before and after atrial rapid pacing with and without PVI at fight atrial appendage (RAA),left atrial appendage (LAA),distal coronary sinus (CSd) and proximal coronary sinus (CSp).Results (1) Effects of PVI on vagal modulation:Shortening of SCL during vagal stimulation decreased significantly after PVI compared with that before PVI in group A (P<0.001).Shortening of ERP during vagal stimulation decreaseed significantly after PVI compared with that before PVI (P<0.05).VW of atrial fibrillation during vagal stimulation decreased significantly after PVI compared with that before PVI (P<0.05).(2) Effects of PVI on AER:shortening of ERP before and after atrial rapid pacing increased significantly at baseline and vagal stimulation in group B compared with that in group A (P<0.05).VW during vagal stimulation increased significantly after atrial rapid pacing in group B (P<0.05).Conclusion PVI attenuates the vagal modulation to the atria,thereby decreases the susceptibility to atrial fibrillation mediated by vagal activity.PVI releases AER,which maybe contributes to the vagal denervation.Our study indicates that PVI not only can eradicate triggered foci but also modify substrates for AF.(J Geriatr Cardiol 2008;5:28-32)

  13. Serum MMP-8: a novel indicator of left ventricular remodeling and cardiac outcome in patients after acute myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Marie Fertin

    Full Text Available OBJECTIVE: Left ventricular (LV remodeling following myocardial infarction (MI is characterized by progressive alterations of structure and function, named LV remodeling. Although several risk factors such as infarct size have been identified, LV remodeling remains difficult to predict in clinical practice. Changes within the extracellular matrix, involving matrix metalloproteinases (MMPs and tissue inhibitors of metalloproteinases (TIMPs, are an integral part of left ventricular (LV remodeling after myocardial infarction (MI. We investigated the temporal profile of circulating MMPs and TIMPs and their relations with LV remodeling at 1 year and clinical outcome at 3 years in post-MI patients. METHODS: This prospective multicentre study included 246 patients with a first anterior MI. Serial echocardiographic studies were performed at hospital discharge, 3 months, and 1 year after MI, and analysed at a core laboratory. LV remodeling was defined as the percent change in LV end-diastolic volume (EDV from baseline to 1 year. Serum samples were obtained at hospital discharge, 1, 3, and 12 months. Multiplex technology was used for analysis of MMP-1, -2, -3, -8, -9, -13, and TIMP-1, -2, -3, -4 serum levels. RESULTS: Baseline levels of MMP-8 and MMP-9 were positively associated with changes in LVEDV (P = 0.01 and 0.02, respectively. When adjusted for major baseline characteristics, MMP-8 levels remained an independent predictor LV remodeling (P = 0.025. By univariate analysis, there were positive relations between cardiovascular death or hospitalization for heart failure during the 3-year follow-up and the baseline levels of MMP-2 (P = 0.03, MMP-8 (P = 0.002, and MMP-9 (P = 0.03. By multivariate analysis, MMP-8 was the only MMP remaining significantly associated with clinical outcome (P = 0.02. CONCLUSION: Baseline serum MMP-8 is a significant predictor of LV remodeling and cardiovascular outcome after MI and may help to improve

  14. Understanding cardiac electrical phenotypes in the genomic era

    OpenAIRE

    Milano, A

    2015-01-01

    Sudden cardiac death (SCD) is defined as unexpected death due to a cardiac cause. It most often results from life-threatening ventricular fibrillation (VF) and ranks among the most common causes of death worldwide, with an incidence in the community varying between 0.6 and >1.4 per 1,000 individuals. Because SCD mostly occurs in individuals without previously known cardiac disease, the identification of patients at risk for SCD and implementation of preventive measures could save many lives. ...

  15. Structural and Electrical Myocardial Remodeling in a Rodent Model of Depression

    OpenAIRE

    Carnevali, Luca; Trombini, Mimosa; Rossi, Stefano; Graiani, Gallia; Manghi, Massimo; Koolhaas, Jaap M.; Quaini, Federico; Macchi, Emilio; Nalivaiko, Eugene; Sgoifo, Andrea; Boer, S.F. de; Gugten, J. van der; Slangen, J.L.

    2013-01-01

    Objective: Despite a well-documented association between stress and depression with cardiac morbidity and mortality, there is no satisfactory explanation for the mechanisms linking affective and cardiac disorders. This study investigated cardiac electrophysiological properties in an animal model of depression. Methods: Depression-relevant physiological and behavioral parameters were measured in adult male wild-type rats during and after a period of intermittent social defeat stress (n = 12) o...

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

    OpenAIRE

    Damián Hernández; Rodney Millard; Priyadharshini Sivakumaran; Wong, Raymond C. B.; Crombie, Duncan E.; Hewitt, Alex W.; Helena Liang; Hung, Sandy S. C.; Alice Pébay; Shepherd, Robert K.; Gregory J Dusting; Lim, Shiang Y

    2016-01-01

    Background. Human induced pluripotent stem cells (iPSCs) are an attractive source of cardiomyocytes for cardiac repair and regeneration. In this study, we aim to determine whether acute electrical stimulation of human iPSCs can promote their differentiation to cardiomyocytes. Methods. Human iPSCs were differentiated to cardiac cells by forming embryoid bodies (EBs) for 5 days. EBs were then subjected to brief electrical stimulation and plated down for 14 days. Results. In iPS(Foreskin)-2 cell...

  17. Understanding cardiac electrical phenotypes in the genomic era

    NARCIS (Netherlands)

    A. Milano

    2015-01-01

    Sudden cardiac death (SCD) is defined as unexpected death due to a cardiac cause. It most often results from life-threatening ventricular fibrillation (VF) and ranks among the most common causes of death worldwide, with an incidence in the community varying between 0.6 and >1.4 per 1,000 individuals

  18. Blunt cardiac rupture with prehospital pulseless electrical activity: a rare successful experience.

    Science.gov (United States)

    Lu, Li-Hua; Choi, Wai-Mau; Wu, Hsueh-Ru; Liu, Hung-Chang; Chiu, Wen-Ta; Tsai, Shin-Han

    2005-12-01

    Blunt cardiac rupture is highly associated with mortality. In the recent literature, the reported mortality rates of cardiac rupture ranged from 59.7% to 100%. The probability of survival for those with prehospital pulseless electrical activity was extremely low. This case report describes a rare example of survival of a female patient with life-threatening cardiac rupture and cardiac tamponade after a major car accident. The victim developed pulseless electrical activity at admission. She recovered from the accident, however, without developing any signs of neurologic deficits. This case study emphasizes the value of the primary survey of patients and prompt and accurate interventions, including focused abdominal sonography for trauma, pericardiocentesis, and an urgent thoracotomy in the operating room for primary repair of cardiac rupture without applying a cardiopulmonary bypass system. The study showed that early diagnosis and aggressive interventions are crucial factors to the successful outcome of patient's survival. PMID:16394928

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

    OpenAIRE

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

    2015-01-01

    There has been re-emerging interest and significant work dedicated to investigating the metabolic effects of high intensity interval training (HIIT) in recent years. HIIT is considered to be a time efficient alternative to classic endurance training (ET) that elicits similar metabolic responses in skeletal muscle. However, there is a lack of information on the impact of HIIT on cardiac muscle in disease. Therefore, we determined the efficacy of ET and HIIT to alter cardiac muscle characterist...

  20. Non-invasive determination of cardiac output by Doppler echocardiography and electrical bioimpedance

    OpenAIRE

    Silke, Bernard

    1990-01-01

    Cardiac output measured by thermodilution in 25 patients within 24 hours of acute myocardial infarction was compared with cardiac output measured by Doppler echocardiography (24 patients) and electrical bioimpedance (25 patients). The mean (range) cardiac outputs measured by Doppler (4.03 (2.2-6.0) 1/min) and electrical bioimpedance (3.79 (1.1-6.2) 1/min) were similar to the mean thermodilution value (3.95 (2.1-6.2) 1/min). Both non-invasive techniques agreed closely with thermodilution in mo...

  1. Combined score using clinical, electrocardiographic, and echocardiographic parameters to predict left ventricular remodeling in patients having had cardiac resynchronization therapy six months earlier.

    Science.gov (United States)

    Brunet-Bernard, Anne; Maréchaux, Sylvestre; Fauchier, Laurent; Guiot, Aurélie; Fournet, Maxime; Reynaud, Amélie; Schnell, Frédéric; Leclercq, Christophe; Mabo, Philippe; Donal, Erwan

    2014-06-15

    The aim of this study was to evaluate whether a scoring system integrating clinical, electrocardiographic, and echocardiographic measurements can predict left ventricular reverse remodeling after cardiac resynchronization therapy (CRT). The derivation cohort consisted of 162 patients with heart failure implanted with a CRT device. Baseline clinical, electrocardiographic, and echocardiographic characteristics were entered into univariate and multivariate models to predict reverse remodeling as defined by a ≥15% reduction in left ventricular end-systolic volume at 6 months (60%). Combinations of predictors were then tested under different scoring systems. A new 7-point CRT response score termed L2ANDS2: Left bundle branch block (2 points), Age >70 years, Nonischemic origin, left ventricular end-diastolic Diameter 5 had a high positive likelihood ratio (+LR = 5.64), whereas a score <2 had a high negative likelihood ratio (-LR = 0.19). In conclusion, this L2ANDS2 score provides an easy-to-use tool for the clinician to assess the pretest probability of a patient being a CRT responder. PMID:24793667

  2. Proarrhythmic electrical remodelling is associated with increased beat-to-beat variability of repolarisation

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard; Oros, Avram; Schoenmakers, Marieke; van Opstal, Jurren M; Maas, Joep N; Beekman, Jet D M; Vos, Marc A

    2007-01-01

    Acquired long-QT syndrome in combination with increased beat-to-beat variability of repolarisation duration (BVR) is associated with lethal torsades de pointes arrhythmias (TdP) in dogs with remodelled heart after atrioventricular block (AVB). We evaluated the relative contributions of bradycardi...

  3. Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling

    Science.gov (United States)

    Dietrich, Johannes W.; Müller, Patrick; Schiedat, Fabian; Schlömicher, Markus; Strauch, Justus; Chatzitomaris, Apostolos; Klein, Harald H.; Mügge, Andreas; Köhrle, Josef; Rijntjes, Eddy; Lehmphul, Ina

    2015-01-01

    Background Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. Methods Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T4) and T3, reverse (r)T3, 3-iodothyronamine (3-T1AM) and 3,5-diiodothyronine (3,5-T2) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. Results Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T3 and/or low T4 syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT3 concentrations were significantly decreased, but still within their reference ranges. 3,5-T2 concentrations directly correlated with rT3 concentrations and inversely correlated with FT3 concentrations. Furthermore, 3,5-T2 concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT3, 3,5-T2, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. Conclusion This study confirms reduced FT3 concentrations in patients with POAF and is the first to report on elevated 3,5-T2 concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms. PMID:26279999

  4. Effects of Potassium Currents upon Action Potential of Cardiac Cells Exposed to External Electric fields

    Institute of Scientific and Technical Information of China (English)

    An-Ying Zhang; Xiao-Feng Pang

    2008-01-01

    Previous studies show that exposure to high-voltage electric fields would influence the electro cardiogram both in experimental animate and human beings. The effects of the external electric fields upon action potential of cardiac cells are studied in this paper based on the dynamical model, LR91. Fourth order Runger-Kuta is used to analyze the change of potassium ion channels exposed to external electric fields in detail. Results indicate that external electric fields could influence the current of potassium ion by adding an induced component voltage on membrane. This phenomenon might be one of the reasons of heart rate anomaly under the high-voltage electric fields.

  5. Sudden cardiac death in dogs with remodeled hearts is associated with larger beat-to-beat variability of repolarization

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard; Truin, Michiel; van Opstal, Jurren M;

    2005-01-01

    diminished reserve and larger propensity for repolarization-dependent ventricular arrhythmia. A subset of chronic AVB dogs (10%) suffers sudden cardiac death (SCD). With the assumption that repolarization defects constitute a potentially lethal proarrhythmic substrate, we hypothesized that BVR in SCD dogs...... group. All other electrophysiological parameters (RR, QT and MAP durations) were comparable for the two groups. Extending the number of animals and groups confirmed a larger BVR in the SCD group (SCD: 5.1 +/- 2.7; n = 11 versus control: 2.5 +/- 0.4 ms; n = 61; P <0.05) and showed reverse-use dependence...

  6. The muscle-enriched gene SYNPO2L is associated with cardiac remodeling%新基因SYNPO2L参与心肌重构

    Institute of Scientific and Technical Information of China (English)

    王晓建; 甄一松; 王继征; 苏明; 祝领; 王长鑫; 俞莉萍; 刘继斌; 惠汝太

    2012-01-01

    目的 肌肉富集表达基因在心肌重构的发生发展中发挥重要的作用.为了深入理解心肌重构的分子机制、为临床提供治疗和干预的靶点,我们需要寻找参与心肌重构的新基因.方法和结果 我们使用自主研发的CardiacScan对多个人源组织表达谱数据库进行扫描,发现了一个新的肌肉富集表达基因——SYNPO2L.RT-PCR显示,SYNPO2L在小鼠的心脏和骨骼肌高表达.实时荧光定量PCR显示,在跑步训练诱导的小鼠生理性心肌重构模型中,SYNPO2L的表达下降为对照组的0.6倍(P<0.05).在主动脉缩窄手术诱导的病理性心肌重构中,SYNPO2L的表达逐渐升高,并在术后9周(心功能失代偿阶段)升高为对照组的2.4倍(P<0.0001).结论 SYNPO2L是一个新的在肌肉富集表达的基因,参与了多种不同形式的心肌重构过程,可能在心肌重构中发挥重要的作用.%Purpose Muscle-enriched gene play an improtant role in the development of cardiac remodeling and heart failure. Up to date, however, the number of muscle-enriched gene is limited. Therefore, we need to clone more muscle-enriched genes. Methods and Results To explore novel muscle-enriched genes, we scaned three human multiple-tissue transcriptional databases using self-developed program Card iacScan. SYNPO2L was identified as novlc muslce-enriched gene. Real-time PCR analysis demonstrated that expression of SYNPO2L was down-regulated by 0.6 fold (P<0.0S) in physiological cardiac hypertrophy induced by treadmill training, but up-regulated by 2.4 fold(P<0.0001) in heart failure induced by transverse aortic constriction surgery. Conclusion SYNPO2L is a novle muscle-enriched gene which is involved in cardiac remodeling.

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

    Science.gov (United States)

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

    2015-01-01

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

  8. An evaluation of two conducted electrical weapons using a swine comparative cardiac safety model.

    Science.gov (United States)

    Dawes, Donald M; Ho, Jeffrey D; Moore, Johanna C; Laudenbach, Andrew P; Reardon, Robert F; Miner, James R

    2014-09-01

    Arrest-related deaths proximate to the use of a conducted electrical weapon (CEW) continue to generate controversy despite a better understanding of the multi-factorial nature of many of these deaths. With the rapid adoption of this technology by law enforcement, and the proliferation of companies entering the marketplace, it is important to have a method to assess the relative safety of these weapons. We had previously developed a model to assess the relative cardiac safety of CEWs. In this study, we use this model to compare the TASER X2 and the Karbon Arms MPID. Our results suggest that the TASER X2 may have an improved cardiac safety margin over the Karbon Arms MPID as determined by a smaller area of cardiac pacing on the anterior chest in our model. This model seems to offer a reproducible means of comparing the cardiac effects of CEWs. PMID:24895072

  9. Improvement of cardiac function and reversal of gap junction remodeling by Neuregulin-1β in volume-overloaded rats with heart failure

    Institute of Scientific and Technical Information of China (English)

    Xue-Hui Wang; Xiao-Zhen Zhuo; Ya-Juan Ni; Min Gong; Ting-Zhong Wang; Qun Lu; Ai-Qun Ma

    2012-01-01

    Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 μg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.

  10. Changes in the cardiac muscle electric activity as a result of Coronary Artery Bypass Graft operation

    Science.gov (United States)

    Grajek, Magdalena; Krzyminiewski, Ryszard; Kalawski, Ryszard; Kulczak, Mariusz

    2008-01-01

    Many bioelectric signals have a complex internal structure that can be a rich source of information on the tissue or cell processes. The structure of such signals can be analysed in detail by applying digital methods of signal processing. Therefore, of substantial use in diagnosis of the coronary arterial disease is the method of digital enhancement of increasing signal resolution ECG (NURSE-ECG), permitting detection of temporary changes in the electric potentials in the cardiac muscle in the process of depolarisation. Thanks to the application of NURSE-ECG it has become possible to detect relatively small changes in the electric activity of particular fragments of the cardiac muscle undetectable by the standard ECG method, caused by ischemia, the effect of a drug or infarct. The aim of this study was to identify and analyse changes in the electric activity of the cardiac muscle as a result of the Coronary Artery Bypass Graft (CABG) operation. In this study the method of NURSE-ECG has been applied in order to identify and analyse changes in the electric activity of the cardiac muscle as a result of the CABG operation. In the study performed in cooperation of the Institute of Physics Adam Mickiewicz University and the Strus Hospital, Cardiac Surgery Ward, 37 patients with advanced coronary arterial disease were asked to participate. The patients were examined prior to the operation, on the day after the operation and two months after the operation and a year after the operation. The ECG recordings were subjected to a numerical procedure of resolution enhancement by a NURSE-ECG program to reveal the tentative changes in the electric potential of the cardiac muscle on its depolarisation. Results of the study have shown that the NURSE ECG method can be applied to monitor changes in the electric activity of the cardiac muscle occurring as a result of CABG operation. One the second day after the operation in the majority of patients (70%) a rapid decrease of the total

  11. Assessment of cardiac remodeling in asymptomatic mitral regurgitation for surgery timing: a comparative study of echocardiography and magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Ozdogan Oner

    2010-08-01

    Full Text Available Abstract Background Early surgery is recommended for asymptomatic severe mitral regurgitation (MR, because of increased postoperative left ventricular (LV dysfunction in patients with late surgery. On the other hand, recent reports emphasized a "watchful waiting" process for the determination of the proper time of mitral valve surgery. In our study, we compared magnetic resonance imaging (MRI and transthoracic echocardiography to evaluate the LV and left atrial (LA remodeling; for better definitions of patients that may benefit from early valve surgery. Methods Twenty-one patients with moderate to severe asymptomatic MR were evaluated by echocardiography and MRI. LA and LV ejection fractions (EFs were calculated by echocardiography and MRI. Pulmonary veins (PVs were measured from vein orifices in diastole and systole from the tangential of an imaginary circle that completed LA wall. Right upper PV indices were calculated with the formula; (Right upper PV diastolic diameter- Right upper PV systolic diameter/Right upper PV diastolic diameter. Results In 9 patients there were mismatches between echocardiography and MRI measurements of LV EF. LV EFs were calculated ≥60% by echocardiography, meanwhile 0.05. However, both right upper PV indices (0.16 ± 0.06 vs. 0.24 ± 0.08, p: 0.024 and LA EFs (0.19 ± 0.09 vs. 0.33 ± 0.14, p: 0.025 were significantly decreased in patients with depressed EFs when compared to patients with normal EFs. Conclusions MRI might be preferred when small changes in functional parameters like LV EF, LA EF, and PV index are of clinical importance to disease management like asymptomatic MR patients that we follow up for appropriate surgery timing.

  12. Successful treatment of cardiac electrical storm in dilated cardiomyopathy using esmolol: A case report

    OpenAIRE

    Li, Li; Zhou, Yuan-Li; Zhang, Xue-Jing; Wang, Hua-ting

    2016-01-01

    The present study reports a case of electrical storm occurring in a 43-year-old woman with dilated cardiomyopathy. The patient suffered from a cardiac electrical storm, with 98 episodes of ventricular tachycardia rapidly degenerating to ventricular fibrillation in hospital. The patient was converted with a total of 120 defibrillations. Recurrent ventricular tachycardia/fibrillation was initiated by premature ventricular beats. The patient did not respond to the use of amiodaronum. However, th...

  13. Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration

    Directory of Open Access Journals (Sweden)

    Kenneth R. Boheler

    2011-01-01

    Full Text Available Pluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardiac-restricted ncx1 promoter-driven puromycin resistance cassette together with a mass culture system to isolate ESC-CMs that display traits characteristic of very immature CMs. The cells display properties of proliferation, CM-restricted markers, reduced mitochondrial mass, and hypoxia-resistance. Following transplantation into rodent hearts, bioluminescence imaging revealed that immature cells, but not more mature CMs, survived for at least one month following injection. These data and comparisons with more mature cells lead us to conclude that immature hypoxia resistant ESC-CMs can be isolated in mass in vitro and, following injection into heart, form grafts that may mediate long-term recovery of global and regional myocardial contractile function following infarction.

  14. Dynamic separation of pulmonary and cardiac changes in electrical impedance tomography

    International Nuclear Information System (INIS)

    In spontaneously breathing or ventilated subjects, it is difficult to image cardiac-related conductivity changes using electrical impedance tomography (EIT) due to the high amplitude of the ventilation component. Previous attempts to separate these components included either electrocardiogram-gated averaging, frequency domain filtering or holding the breath while performing the measurements. However, such methods are either not able to produce continuous real-time images or to fully separate cardiac and pulmonary changes. The aim of this work was to develop a new dynamic filtering method for the online separation of pulmonary and cardiac changes avoiding the drawbacks of the previous attempts. The approach is based on estimating template functions for the pulmonary and cardiac components by means of principal component analysis and frequency domain filtering. Then, these templates are fitted into the input signals. The new method enables an observer to examine the variation of the cardiac signal beat-by-beat after a one-time setup period of 20 s. Preliminary in vivo results of two healthy subjects are presented. The results are superior to frequency domain filtering and in good agreement with signals averaged over several cardiac cycles. The method does not depend on ECG or other a priori knowledge. The apparent validity of the method's ability to separate cardiac and pulmonary changes in EIT images was shown and has to be confirmed in future studies. The algorithm opens up new possibilities for future clinical trials on continuous monitoring by means of EIT and for the examination of the relation between the cardiac component and lung perfusion

  15. Bio mathematical aspects of chronic cardiac electric stimulation

    International Nuclear Information System (INIS)

    In the framework a mathematical model of the electrode-tissue system new several concepts are introduced(global versus local threshold variables,critical region for electric stimulation,mechanical hysteresis amongst others) several well known facts are explained,and some guidelines for electrode design are derived

  16. Intrinsic Cardiac Autonomic Ganglionated Plexi within Epicardial Fats Modulate the Atrial Substrate Remodeling: Experiences with Atrial Fibrillation Patients Receiving Catheter Ablation

    Science.gov (United States)

    Singhal, Rahul; Lo, Li-Wei; Lin, Yenn-Jiang Lin; Chang, Shih-Lin; Hu, Yu-Feng; Chao, Tze-Fan; Chung, Fa-Po; Chiou, Cheun-Wang; Tsao, Hsuan-Ming; Chen, Shih-Ann

    2016-01-01

    Background A recent study reported the close relationship between high dominant frequent (DF) sites [atrial fibrillation (AF) nest] and the intrinsic cardiac autonomic nervous system. The aim of this study was to investigate the correlation between the regional distribution of epicardial fat and the properties of the biatrial substrates in AF patients. Methods We studied 32 patients with paroxysmal (n = 23) and persistent (n = 9) AF. The epicardial fat volume around the left atrium (LA) was evaluated using 64-slice multidetector computed tomography and the topographic distribution of the fat volume was assessed. The biatrial DFs, voltages, and total activation times (TATs) were obtained during sinus rhythm. Results Out of the 8 divided LA regions, a significant linear correlation existed between the LA fat and mean DF values in the right upper anterior LA, left upper anterior LA, right lower anterior LA, right upper posterior LA, left upper posterior LA, and left lower posterior LA. There was no significant correlation between the regional LA fat distribution and regional LA peak-to-peak bipolar voltage and TAT. During a mean follow-up of 17 ± 8 months, 22 of the 32 (69%) patients were free of AF. In the multivariate analysis, only the mean LA DF was found to be a significant predictor of recurrence. Conclusions There was a close association between the regional distribution of the LA epicardial fat and the atrial substrate manifesting high frequency during sinus rhythm (AF nest). Those nests were related to ablation outcome. Hence, epicardial fat may play a significant role in atrial substrate remodeling and thereby in the pathogenesis and maintenance of AF. PMID:27122948

  17. In-Hospital Cardiac Arrest: An Update on Pulseless Electrical Activity and Asystole.

    Science.gov (United States)

    Attin, Mina; Tucker, Rebecca G; Carey, Mary G

    2016-09-01

    Nonshockable rhythms, including pulseless electrical activity (PEA) and asystole, precede more than 70% of in-hospital cardiac arrests (I-HCA). Compared with shockable rhythms (ventricular fibrillation and ventricular tachycardia), nonshockable rhythms have higher mortality and morbidity. Therefore, investigating the underlying mechanisms of these arrhythmias to improve the quality of care and outcome for patients who suffer cardiac arrest is a priority. As the first responders to I-HCA, nurses must have the proper knowledge and training to provide timely and efficient cardiopulmonary resuscitation therapy. This article provides an overview of nonshockable cardiac arrhythmias preceding I-HCA as a means of addressing the gap between science and clinical practice. PMID:27484665

  18. Quantification of cardiac autonomic nervous activities in ambulatory dogs by eliminating cardiac electric activities using cubic smoothing spline

    International Nuclear Information System (INIS)

    With the development of an implantable radio transmitter system, direct measurement of cardiac autonomic nervous activities (CANAs) became possible for ambulatory animals for a couple of months. However, measured CANAs include not only CANA but also cardiac electric activity (CEA) that can affect the quantification of CANAs. In this study, we propose a novel CEA removal method using moving standard deviation and cubic smoothing spline. This method consisted of two steps of detecting CEA segments and eliminating CEAs in detected segments. Using implanted devices, we recorded stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA) and superior left ganglionated plexi nerve activity (SLGPNA) directly from four ambulatory dogs. The CEA-removal performance of the proposed method was evaluated and compared with commonly used high-pass filtration (HPF) for various heart rates and CANA amplitudes. Results tested with simulated CEA and simulated true CANA revealed stable and excellent performance of the suggested method compared to the HPF method. The averaged relative error percentages of the proposed method were less than 0.67%, 0.65% and 1.76% for SGNA, VNA and SLGPNA, respectively. (paper)

  19. Automated non-invasive measurement of cardiac output: comparison of electrical bioimpedance and carbon dioxide rebreathing techniques.

    OpenAIRE

    Smith, S A; Russell, A.E.; West, M. J.; Chalmers, J

    1988-01-01

    Two commercial automated, non-invasive systems for estimation of cardiac output were evaluated. Values of cardiac output obtained by electrical bioimpedance cardiography (BoMed NCCOM3 machine) were compared with values derived from an indirect Fick technique that uses carbon dioxide rebreathing (Gould 9000 IV system) during 103 simultaneous measurements made at rest in 19 randomly selected subjects and on exercise in 11 subjects. Cardiac output values obtained with impedance cardiography were...

  20. Remodelling of the contractile apparatus of striated muscle stimulated electrically in a shortened position.

    OpenAIRE

    Jakubiec-Puka, A; Carraro, U

    1991-01-01

    The aim of this study was to examine reorganisation of the contractile apparatus during adaptation to function when the length of a muscle is decreased. The rat soleus muscle was maintained in a shortened position and simultaneously stimulated electrically at a low frequency for 1-45 h. This experimental model decreased the length of the muscle and made the contractile apparatus irregular. The length of the sarcomeres decreased and became variable. The Z-line appeared wavy or fragmented. Foci...

  1. Numerically simulated cardiac exposure to electric current densities induced by TASER X-26 pulses in adult men

    Science.gov (United States)

    Leitgeb, N.; Niedermayr, F.; Neubauer, R.; Loos, G.

    2010-10-01

    There is still an ongoing debate whether or not electronic stun devices (ESDs) induce cardiac fibrillation. To assess the ventricular fibrillation risk of law enforcing electronic control devices, quantitative estimates of cardiac electric current densities induced by delivered electric pulses are essential. Numerical simulations were performed with the finite integration technique and the anatomical model of a standardized European man (NORMAN) segmented into 2 mm voxels and 35 different tissues. The load-dependent delivery of TASER X-26 pulses has been taken into account. Cardiac exposure to electric current densities of vertically and horizontally aligned dart electrodes was quantified and different hit scenarios compared. Since fibrillation thresholds critically depend on exposed volume, the provided quantitative data are essential for risk assessment. The maximum cardiac rms current densities amounted to 7730 A m-2. Such high current densities and exposed cardiac volumes do not exclude ventricular fibrillation.

  2. Numerically simulated cardiac exposure to electric current densities induced by TASER X-26 pulses in adult men

    International Nuclear Information System (INIS)

    There is still an ongoing debate whether or not electronic stun devices (ESDs) induce cardiac fibrillation. To assess the ventricular fibrillation risk of law enforcing electronic control devices, quantitative estimates of cardiac electric current densities induced by delivered electric pulses are essential. Numerical simulations were performed with the finite integration technique and the anatomical model of a standardized European man (NORMAN) segmented into 2 mm voxels and 35 different tissues. The load-dependent delivery of TASER X-26 pulses has been taken into account. Cardiac exposure to electric current densities of vertically and horizontally aligned dart electrodes was quantified and different hit scenarios compared. Since fibrillation thresholds critically depend on exposed volume, the provided quantitative data are essential for risk assessment. The maximum cardiac rms current densities amounted to 7730 A m-2. Such high current densities and exposed cardiac volumes do not exclude ventricular fibrillation.

  3. Numerically simulated cardiac exposure to electric current densities induced by TASER X-26 pulses in adult men

    Energy Technology Data Exchange (ETDEWEB)

    Leitgeb, N; Niedermayr, F; Neubauer, R; Loos, G, E-mail: norbert.leitgeb@tugraz.a [Institute of Clinical Engineering with European Notified Body of Medical Devices, Graz University of Technology, Inffeldgasse 18, A-8010 Graz (Austria)

    2010-10-21

    There is still an ongoing debate whether or not electronic stun devices (ESDs) induce cardiac fibrillation. To assess the ventricular fibrillation risk of law enforcing electronic control devices, quantitative estimates of cardiac electric current densities induced by delivered electric pulses are essential. Numerical simulations were performed with the finite integration technique and the anatomical model of a standardized European man (NORMAN) segmented into 2 mm voxels and 35 different tissues. The load-dependent delivery of TASER X-26 pulses has been taken into account. Cardiac exposure to electric current densities of vertically and horizontally aligned dart electrodes was quantified and different hit scenarios compared. Since fibrillation thresholds critically depend on exposed volume, the provided quantitative data are essential for risk assessment. The maximum cardiac rms current densities amounted to 7730 A m{sup -2}. Such high current densities and exposed cardiac volumes do not exclude ventricular fibrillation.

  4. Decomposition method of an electrical bio-impedance signal into cardiac and respiratory components

    International Nuclear Information System (INIS)

    The paper presents a method for adaptive decomposition of an electrical bio-impedance (BI) signal into two components: cardiac and respiratory. The decomposition of a BI signal is not a trivial process because of the non-stationarity of the signal components and overlapping of their harmonic spectra. An application specific orthonormal basis (ASOB) was designed to solve the decomposition task using the Jacobi weighting function in the standard Gram–Schmidt process. The key element of the bio-impedance signal decomposer (BISD) is a model of the cardiac BI signal, which is constructed from the components of the ASOB and is intended for use in the BISD for on-line tracking of the cardiac BI signal. It makes it possible to separate the cardiac and respiratory components of the total BI signal in non-stationary conditions. In combination with the signal-shape locked loop (SSLL), the BISD allows us to decompose the BI signals with partially overlapping spectra. The proposed BISD based method is accomplished as a PC software digital system, but it is oriented towards applications in portable and stationary cardiac devices and in clinical settings

  5. Decomposition method of an electrical bio-impedance signal into cardiac and respiratory components.

    Science.gov (United States)

    Krivoshei, A; Kukk, V; Min, M

    2008-06-01

    The paper presents a method for adaptive decomposition of an electrical bio-impedance (BI) signal into two components: cardiac and respiratory. The decomposition of a BI signal is not a trivial process because of the non-stationarity of the signal components and overlapping of their harmonic spectra. An application specific orthonormal basis (ASOB) was designed to solve the decomposition task using the Jacobi weighting function in the standard Gram-Schmidt process. The key element of the bio-impedance signal decomposer (BISD) is a model of the cardiac BI signal, which is constructed from the components of the ASOB and is intended for use in the BISD for on-line tracking of the cardiac BI signal. It makes it possible to separate the cardiac and respiratory components of the total BI signal in non-stationary conditions. In combination with the signal-shape locked loop (SSLL), the BISD allows us to decompose the BI signals with partially overlapping spectra. The proposed BISD based method is accomplished as a PC software digital system, but it is oriented towards applications in portable and stationary cardiac devices and in clinical settings. PMID:18544800

  6. A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

    Science.gov (United States)

    Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

    2016-03-01

    Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle. PMID:27087101

  7. Identification of hub genes of cardiac remodeling by weighted gene co-expression network analysis%用权重基因共表达网络分析识别心脏重构关键节点基因

    Institute of Scientific and Technical Information of China (English)

    钟诗龙; 余细勇; 伍虹; 杨敏; 刘晓颖; 郑志伟; 林秋雄; 符永恒; 麦丽萍; 周志凌

    2011-01-01

    Cardiac remodeling after acute myocardial infarction is the main pathologic change of chronic heart failure. The balance of ACEI and ACE2 plays an important role in pathogenesis and treatment of chronic heart failure. However its upstream regulation mechanism is unclear. This study aimed to identify the hub genes of cardiac remodeling by mining publically available data sets using weighted gene co-expression network analysis ( WGCNA ) and to study their relationship with ACEI and ACE2 gene. Methods Two genome-wide expression data sets, GSE7487 and GSE738 . of cardiac remodeling after myocardial infarction were downloaded from NCBI GEO database.WGCNA was used to construct gene coexpression network. identify the modules and hub genes associated with cardiac remodeling. The correlation of expression of hub genes with ACEI and ACE2 was calculated and verified in an animal model of cardiac remodeling after myocardial infarction. Result Seventeen modules were found in GSE7487 and among which, 6 were significantlv correlated with cardiac remodeling and enriched in 16 KEGG pathways. Sixteen modules were found in GSE738 and among which, 5 were significantly correlated with cardiac remodeling and enriched in 15 KEGG pathways, 10 of which were the same as in the first dataset. Many signaling pathways involved pathological cardiac hypertrophy , oxidative phosphorylation ,and metabolism. A number of key regulatory genes of cardiac remodeling were further identified through module connectivity and gene significance. One of the key regulatory genes, calcium-dependent phosphatase regulon ( RCANI ). was found to be highly correlated with ACEI, but not ACE2. Their relationships were confirmed in an animal model. Conclusions Weighted gene co-expression network analysis is a robust systematic biological tool and can be used to identify the key regulatory genes of cardiac remodeling efficiently.RCANI may play an important role in regulating the balance of ACE1-ACE2 in renin

  8. Effects of Persistent Atrial Fibrillation-Induced Electrical Remodeling on Atrial Electro-Mechanics – Insights from a 3D Model of the Human Atria

    OpenAIRE

    Adeniran, Ismail; Maclver, David H.; Garratt, Clifford J.; Ye, Jianqiao; Hancox, Jules C.; Zhang, Henggui

    2015-01-01

    Aims Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics. Methods and Results A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on...

  9. Data-driven estimation of cardiac electrical diffusivity from 12-lead ECG signals.

    Science.gov (United States)

    Zettinig, Oliver; Mansi, Tommaso; Neumann, Dominik; Georgescu, Bogdan; Rapaka, Saikiran; Seegerer, Philipp; Kayvanpour, Elham; Sedaghat-Hamedani, Farbod; Amr, Ali; Haas, Jan; Steen, Henning; Katus, Hugo; Meder, Benjamin; Navab, Nassir; Kamen, Ali; Comaniciu, Dorin

    2014-12-01

    Diagnosis and treatment of dilated cardiomyopathy (DCM) is challenging due to a large variety of causes and disease stages. Computational models of cardiac electrophysiology (EP) can be used to improve the assessment and prognosis of DCM, plan therapies and predict their outcome, but require personalization. In this work, we present a data-driven approach to estimate the electrical diffusivity parameter of an EP model from standard 12-lead electrocardiograms (ECG). An efficient forward model based on a mono-domain, phenomenological Lattice-Boltzmann model of cardiac EP, and a boundary element-based mapping of potentials to the body surface is employed. The electrical diffusivity of myocardium, left ventricle and right ventricle endocardium is then estimated using polynomial regression which takes as input the QRS duration and electrical axis. After validating the forward model, we computed 9500 EP simulations on 19 different DCM patients in just under three seconds each to learn the regression model. Using this database, we quantify the intrinsic uncertainty of electrical diffusion for given ECG features and show in a leave-one-patient-out cross-validation that the regression method is able to predict myocardium diffusion within the uncertainty range. Finally, our approach is tested on the 19 cases using their clinical ECG. 84% of them could be personalized using our method, yielding mean prediction errors of 18.7ms for the QRS duration and 6.5° for the electrical axis, both values being within clinical acceptability. By providing an estimate of diffusion parameters from readily available clinical data, our data-driven approach could therefore constitute a first calibration step toward a more complete personalization of cardiac EP. PMID:24857832

  10. Comparison of Transcutaneous Electrical Nerve Stimulation and Parasternal Block for Postoperative Pain Management after Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Nilgun Kavrut Ozturk

    2016-01-01

    Full Text Available Background. Parasternal block and transcutaneous electrical nerve stimulation (TENS have been demonstrated to produce effective analgesia and reduce postoperative opioid requirements in patients undergoing cardiac surgery. Objectives. To compare the effectiveness of TENS and parasternal block on early postoperative pain after cardiac surgery. Methods. One hundred twenty patients undergoing cardiac surgery were enrolled in the present randomized, controlled prospective study. Patients were assigned to three treatment groups: parasternal block, intermittent TENS application, or a control group. Results. Pain scores recorded 4 h, 5 h, 6 h, 7 h, and 8 h postoperatively were lower in the parasternal block group than in the TENS and control groups. Total morphine consumption was also lower in the parasternal block group than in the TENS and control groups. It was also significantly lower in the TENS group than in the control group. There were no statistical differences among the groups regarding the extubation time, rescue analgesic medication, length of intensive care unit stay, or length of hospital stay. Conclusions. Parasternal block was more effective than TENS in the management of early postoperative pain and the reduction of opioid requirements in patients who underwent cardiac surgery through median sternotomy. This trial is registered with Clinicaltrials.gov number NCT02725229.

  11. Renal sympathetic denervation provides ventricular rate control but does not prevent atrial electrical remodeling during atrial fibrillation.

    Science.gov (United States)

    Linz, Dominik; Mahfoud, Felix; Schotten, Ulrich; Ukena, Christian; Hohl, Mathias; Neuberger, Hans-Ruprecht; Wirth, Klaus; Böhm, Michael

    2013-01-01

    Renal denervation (RDN) reduces renal efferent and afferent sympathetic activity thereby lowering blood pressure in resistant hypertension. The effect of modulation of the autonomic nervous system by RDN on atrial electrophysiology and ventricular rate control during atrial fibrillation (AF) is unknown. Here we report a reduction of ventricular heart rate in a patient with permanent AF undergoing RDN. Subsequently, we investigated the effect of RDN on AF-induced shortening of atrial effective refractory period, AF inducibility, and ventricular rate control during AF maintained by rapid atrial pacing in 12 pigs undergoing RDN (n=7) or sham procedure (n=5). During sinus rhythm, RDN reduced heart rate (RR-interval, 708±12 versus 577±19 ms; P=0.0021) and increased atrioventricular node conduction time (PQ-interval, 112±12 versus 88±9 ms; P=0.0001). Atrial tachypacing for 30 minutes increased AF inducibility and decreased AF cycle length. This was not influenced by RDN. RDN reduced ventricular rate during AF episodes by ≈24% (119±9 versus 158±19 bpm; P=0.0001). AF episodes were shorter after RDN compared with sham (12±3 versus 34±4 s; P=0.0091), but atrial effective refractory period was not modified by RDN. RDN reduced heart rate and reduced atrioventricular node conduction time during sinus rhythm and provided rate control during AF. AF-induced atrial electrical remodeling, AF inducibility, and AF cycle length were not modified, but duration of AF episodes was shorter after RDN. Modulation of the autonomic nervous system by RDN might provide rate control and reduce susceptibility to AF. Whether RDN may provide rate control in a larger number of patients with AF deserves further clinical studies. PMID:23150501

  12. Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation.

    Science.gov (United States)

    Xu, Guo-Jun; Gan, Tian-Yi; Tang, Bao-Peng; Chen, Zu-Heng; Mahemuti, Ailiman; Jiang, Tao; Song, Jian-Guo; Guo, Xia; Li, Yao-Dong; Zhou, Xian-Hui; Zhang, Yu; Li, Jin-Xin

    2013-11-01

    The aim of this study was to investigate the correlation between the change in the expression of atrial calpains and electrical, molecular and structural remodeling during aging and atrial fibrillation (AF). Adult and aged canines in sinus rhythm (SR) and with persistent AF (induced by rapid atrial pacing) were investigated. A whole-cell patch clamp was used to measure the L-type Ca2+ current (ICa-L) in cells in the left atrium. The mRNA and protein expression of the L-type calcium channel alc subunit (LVDCCa1c) and calpains were measured by quantitative (q)PCR and western blot analysis. Histopathological and ultrastructural changes were analyzed via light and electron microscopy. The quantity of apoptotic myocytes was determined by a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) assay. In SR groups, atrial cells of the aged canines exhibited a longer action potential (AP) duration to 90% repolarization (APD90), lower AP plateau potential and peak ICa-L current densities (Pcontrol group, the mRNA and protein expression levels of LVDCCa1c were decreased in the aged groups; however, the mRNA and protein expression of calpain 1 was increased in the adult and the aged groups with AF (Patrial tissue exhibited abnormal histopathological and ultrastructural changes, such as accelerated fibrosis and apoptosis with aging and in AF. Age-related alterations in atrial tissues were attributed to the increased expression of calpain 1. The general pathophysiological alterations in normal aged atria may therefore produce a substrate that is conducive to AF. PMID:24043247

  13. Successful treatment of cardiac electrical storm in dilated cardiomyopathy using esmolol: A case report

    Science.gov (United States)

    LI, LI; ZHOU, YUAN-LI; ZHANG, XUE-JING; WANG, HUA-TING

    2016-01-01

    The present study reports a case of electrical storm occurring in a 43-year-old woman with dilated cardiomyopathy. The patient suffered from a cardiac electrical storm, with 98 episodes of ventricular tachycardia rapidly degenerating to ventricular fibrillation in hospital. The patient was converted with a total of 120 defibrillations. Recurrent ventricular tachycardia/fibrillation was initiated by premature ventricular beats. The patient did not respond to the use of amiodaronum. However, the administration of esmolol stabilized the patient's heart rhythm. A moderate dose of the β-blocker esmolol, administered as an 0.5-mg intravenous bolus injection followed by an infusion at a rate of 0.15 mg/kg/min, inhibited the recurrence of ventricular fibrillation and normalized the electrocardiographic pattern. The results suggest that esmolol may be able to improve the survival rate of patients with electrical storm in dilated cardiomyopathy and should be considered as a primary therapy in the management of cardiac electrical storms. PMID:27347024

  14. A Transgenic Platform for Testing Drugs Intended for Reversal of Cardiac Remodeling Identifies a Novel 11βHSD1 Inhibitor Rescuing Hypertrophy Independently of Re-Vascularization

    OpenAIRE

    Oren Gordon; Zhiheng He; Dan Gilon; Sabine Gruener; Sherrie Pietranico-Cole; Amit Oppenheim; Eli Keshet

    2014-01-01

    RATIONALE: Rescuing adverse myocardial remodeling is an unmet clinical goal and, correspondingly, pharmacological means for its intended reversal are urgently needed. OBJECTIVES: To harness a newly-developed experimental model recapitulating progressive heart failure development for the discovery of new drugs capable of reversing adverse remodeling. METHODS AND RESULTS: A VEGF-based conditional transgenic system was employed in which an induced perfusion deficit and a resultant compromised ca...

  15. A guide to modelling cardiac electrical activity in anatomically detailed ventricles.

    Science.gov (United States)

    Clayton, R H; Panfilov, A V

    2008-01-01

    One of the most recent trends in cardiac electrophysiology is the development of integrative anatomically accurate models of the heart, which include description of cardiac activity from sub-cellular and cellular level to the level of the whole organ. In order to construct this type of model, a researcher needs to collect a wide range of information from books and journal articles on various aspects of biology, physiology, electrophysiology, numerical mathematics and computer programming. The aim of this methodological article is to survey recent developments in integrative modelling of electrical activity in the ventricles of the heart, and to provide a practical guide to the resources and tools that are available for work in this exciting and challenging area. PMID:17825362

  16. Echocardiography integrated ACLS protocol versus conventional cardiopulmonary resuscitation in patients with pulseless electrical activity cardiac arrest

    Institute of Scientific and Technical Information of China (English)

    Mojtaba Chardoli; Farhad Heidari; Helaleh Rabiee; Mahdi Sharif-Alhoseini; Hamid Shokoohi; Vafa Rahimi-Movaghar

    2012-01-01

    Objective: To examine the utility of bedside echocardiography in detecting the reversible causes of pulseless electrical activity (PEA) cardiac arrest and predicting the resuscitation outcomes.Methods: In this prospective interventional study,patients presenting with PEA cardiac arrest were randomized into two groups.In Group A,ultrasound trained emergency physicians performed echocardiography evaluating cardiac activity,right ventricle dilation,left ventricle function,pericardial effusion/tamponade and ⅣC size along with the advanced cardiac life support (ACLS) protocol.Patients in Group B solely underwent ACLS protocol without applying echocardiography.The presence or absence of mechanical ventricular activity (MVA) and evidences of PEA reversible causes were recorded.The return of spontaneous circulation (ROSC) and death were evaluated in both groups.Results: One hundred patients with the mean age of (58±6.1) years were enrolled in this study.Fifty patients (Group A) had echocardiography detected in parallel with cardiopulmonary resuscitation (CPR).Among them,7 patients (14%) had pericardial effusion,11 (22%) had hypovolemia,and 39 (78%) were revealed the presence of MVA.In the pseudo PEA subgroup (presence of MVA),43% had ROSC (positive predictive value) and in the true PEA subgroup with cardiac standstill (absence of MVA),there was no recorded ROSC (negative predictive value).Among patients in Group B,no reversible etiology was detected.There was no significant difference in resuscitation results between Groups A and B observed (P=0.52).Conclusion: Bedside echocardiography can identify some reversible causes of PEA.However,there are no significant changes in survival outcome between the echo group and those with traditional CPR.

  17. Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering.

    Science.gov (United States)

    Baei, Payam; Jalili-Firoozinezhad, Sasan; Rajabi-Zeleti, Sareh; Tafazzoli-Shadpour, Mohammad; Baharvand, Hossein; Aghdami, Nasser

    2016-06-01

    Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues. PMID:27040204

  18. Reconstructing three-dimensional reentrant cardiac electrical wave dynamics using data assimilation

    Science.gov (United States)

    Hoffman, M. J.; LaVigne, N. S.; Scorse, S. T.; Fenton, F. H.; Cherry, E. M.

    2016-01-01

    For many years, reentrant scroll waves have been predicted and studied as an underlying mechanism for cardiac arrhythmias using numerical techniques, and high-resolution mapping studies using fluorescence recordings from the surfaces of cardiac tissue preparations have confirmed the presence of visible spiral waves. However, assessing the three-dimensional dynamics of these reentrant waves using experimental techniques has been limited to verifying stable scroll-wave dynamics in relatively thin preparations. We propose a different approach to recovering the three-dimensional dynamics of reentrant waves in the heart. By applying techniques commonly used in weather forecasting, we combine dual-surface observations from a particular experiment with predictions from a numerical model to reconstruct the full three-dimensional time series of the experiment. Here, we use model-generated surrogate observations from a numerical experiment to evaluate the performance of the ensemble Kalman filter in reconstructing such time series for a discordant alternans state in one spatial dimension and for scroll waves in three dimensions. We show that our approach is able to recover time series of both observed and unobserved variables matching the truth. Where nearby observations are available, the error is reduced below the synthetic observation error, with a smaller reduction with increased distance from observations. Our findings demonstrate that state reconstruction for spatiotemporally complex cardiac electrical dynamics is possible and will lead naturally to applications using real experimental data.

  19. Separation of cardiac and respiratory components from the electrical bio-impedance signal using PCA and fast ICA

    OpenAIRE

    Mughal, Yar M.; Krivoshei, A.; Annus, P.

    2013-01-01

    This paper is an attempt to separate cardiac and respiratory signals from an electrical bio-impedance (EBI) dataset. For this two well-known algorithms, namely Principal Component Analysis (PCA) and Independent Component Analysis (ICA), were used to accomplish the task. The ability of the PCA and the ICA methods first reduces the dimension and attempt to separate the useful components of the EBI, the cardiac and respiratory ones accordingly. It was investigated with an assumption, that no mot...

  20. Myocardial area at risk after ST-elevation myocardial infarction measured with the late gadolinium enhancement after scar remodeling and T2-weighted cardiac magnetic resonance imaging

    DEFF Research Database (Denmark)

    Lønborg, Jacob; Engstrøm, Thomas; Mathiasen, Anders B;

    2012-01-01

    To evaluate the myocardial area at risk (AAR) measured by the endocardial surface area (ESA) method on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) when applied after scar remodeling (3 months after index infarction) compared to T2-weighted CMR imaging. One hundred and...

  1. Myocardial area at risk after ST-elevation myocardial infarction measured with the late gadolinium enhancement after scar remodeling and T2-weighted cardiac magnetic resonance imaging

    DEFF Research Database (Denmark)

    Lønborg, Jacob; Engstrøm, Thomas; Mathiasen, Anders B;

    2011-01-01

    To evaluate the myocardial area at risk (AAR) measured by the endocardial surface area (ESA) method on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) when applied after scar remodeling (3 months after index infarction) compared to T2-weighted CMR imaging. One hundred and...

  2. Assessment of nonpenetrating captive bolt stunning followed by electrical induction of cardiac arrest in veal calves.

    Science.gov (United States)

    Bartz, B; Collins, M; Stoddard, G; Appleton, A; Livingood, R; Sobcynski, H; Vogel, K D

    2015-09-01

    The purpose of this study was to evaluate the impact of nonpenetrating captive bolt stunning followed by electrical induction of cardiac arrest on veal calf welfare, veal quality, and blood yield. Ninety calves from the same farm were randomly assigned to 1 of 2 treatment groups in a balanced unpaired comparison design. The first treatment group (the "head-only" method-application of the pneumatic nonpenetrating stun to the frontal plate of the skull at the intersection of 2 imaginary lines extending from the lateral canthus to the opposite poll [CONTROL]) was stunned with a nonpenetrating captive bolt gun ( = 45). The second group ( = 45) was stunned with a nonpenetrating captive bolt gun followed by secondary electrical induction of cardiac arrest (the "head/heart" method-initial application of the pneumatic nonpenetrating captive bolt stun followed by 1 s application of an electrical stun to the ventral region of the ribcage directly caudal to the junction of the humerus and scapula while the stunned calf was in lateral recumbence [HEAD/HEART]). Stunning efficacy was the indicator of animal welfare used in this study. All calves were instantly rendered insensible by the initial stun and did not display common indicators of return to consciousness. For meat quality evaluation, all samples were collected from the 12th rib region of the longissimus thoracis. Meat samples were evaluated for color, drip loss, ultimate pH, cook loss, and Warner-Bratzler shear force. The L* values (measure of meat color lightness) were darker ( 0.05) observed in a* (redness) and b* (yellowness) values between treatments. No differences ( > 0.05) were observed in drip loss, ultimate pH, cook loss, and Warner-Bratzler shear force. The blood yield from the CONTROL group (7,217.9 ± 143.5 g) was greater ( veal calves. PMID:26440354

  3. Rapid electrical immunoassay of the cardiac biomarker troponin I through dielectrophoretic concentration using imbedded electrodes.

    Science.gov (United States)

    Sharma, Abhinav; Han, Chang-Ho; Jang, Jaesung

    2016-08-15

    Rapidity and high sensitivity are critical factors for the diagnoses of heart attacks, and cardiac troponin I (cTnI) is at present a clinical standard for its diagnosis. Here we report a rapid, label-free, and highly sensitive single-walled carbon nanotube (SWCNT) electrical immunosensor, featuring two pairs of electrodes. Two concentration electrodes (gaps: 25 and 80µm) and two detection electrodes (source and drain; gap: 20µm; width: 50µm) were used for dielectrophoretic concentration of cTnI on the SWCNT channels and resistance measurements of the dielectrophoresis (DEP)-concentrated cTnI, respectively. The two concentration electrodes were imbedded between upper and lower dielectric layers, facing each other, underneath the -COOH-functionalized SWCNT channels deposited between the detection electrodes. Therefore, the gap between these imbedded concentration electrodes can be reduced to maximize the electric field intensity for DEP-mediated concentration of cTnI, thereby greatly reducing the detection time (1min) and enhancing the limit of detection (0.7-0.8pgmL(-)(1)). Relative resistance changes of the SWCNTs were measured as cTnI concentration in Tris-Borate-EDTA (TBE; 0.0025×) and human serum diluted 500-fold with 0.0025× TBE decreased from 100ngmL(-)(1) to 1pgmL(-1), and they were shown to be linear with the logarithm of cTnI concentration (R(2)=0.99 and 0.97, respectively). These immunosensors also showed high specificity over another cardiac biomarker, myoglobin, TBE medium (0.0025×), and 500-fold diluted human serum. The DEP-capture of cTnI depended on the frequency of the applied electric field, demonstrating the qualitative nature of the real part of the Clausius-Mossotti factor for cTnI. PMID:27043478

  4. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

    DEFF Research Database (Denmark)

    Grubb, Søren Jahn; Aistrup, Gary L; Koivumäki, Jussi T;

    2015-01-01

    Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with...

  5. 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.

  6. Bioreactor for modulation of cardiac microtissue phenotype by combined static stretch and electrical stimulation

    International Nuclear Information System (INIS)

    We describe here a bioreactor capable of applying electrical field stimulation in conjunction with static strain and on-line force of contraction measurements. It consisted of a polydimethylsiloxane (PDMS) tissue chamber and a pneumatically driven stretch platform. The chamber contained eight tissue microwells (8.05 mm in length and 2.5 mm in width) with a pair of posts (2.78 mm in height and 0.8 mm in diameter) in each well to serve as fixation points and for measurements of contraction force. Carbon rods, stimulating electrodes, were placed into the PDMS chamber such that one pair stimulated four microwells. For feasibility studies, neonatal rat cardiomyocytes were seeded in collagen gels into the microwells. Following 3 days of gel compaction, electrical field stimulation at 3–4 V cm−1 and 1 Hz, mechanical stimulation of 5% static strain or electromechanical stimulation (field stimulation at 3–4 V cm−1, 1 Hz and 5% static strain) were applied for 3 days. Cardiac microtissues subjected to electromechanical stimulation exhibited elevated amplitude of contraction and improved sarcomere structure as evidenced by sarcomeric α-actinin, actin and troponin T staining compared to microtissues subjected to electrical or mechanical stimulation alone or non-stimulated controls. The expression of atrial natriuretic factor and brain natriuretic peptide was also elevated in the electromechanically stimulated group. (papers)

  7. THE EFFICACY OF MELDONIUM IN REDUCTION OF CARDIAC ELECTRICAL INSTABILITY IN PATIENTS WITH ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    A. A. Abdullaev

    2015-09-01

    Full Text Available Aim. To study meldonium effect in the combination therapy for ventricular repolarization disorders and cardiac electrical instability in patients with ischemic stroke.Material and methods. Patients (n=46 with acute phase of ischemic stroke were included in a randomized, open-label, uncontrolled study. Patients were randomized into two groups. Group 1 patients (n=25 had been receiving meldonium (Mildronate;Grindex,Latvia;Pharmstandard,Russia, 1.0 g/day intravenously once daily, as a part of standard therapy for 10 days since admission to the hospital. Group 2 patients (n=21 had standard therapy alone. A standart 12-lead ECG, ventricular late potentials (VLP, 24-hour Holter monitoring, troponin test were performed at the baseline and after 10 days.Results. Patients of the group 1 as compared to the group 2 demonstrated more significant positive effect on the clinical condition of patients with ischemic stroke, ventricular repolarization, reduction of frequency (from 3.7±0.5 to 2.1±0.4; p<0.05 and duration (from 6.6±1, 3 to 4.0±1.1 min; p<0.05 of painless myocardial ischemia episodes and VLP (from 48 to 32%.Conclusion. Adding meldonium to standard therapy in patients with acute phase of ischemic stroke can have a positive effect on the clinical condition, repolarization disorders on ECG, frequency of VLP and episodes of painless myocardial ischemia detection. This may have a positive effect on the electrical stability and prevention of cardiac arrhythmias. 

  8. Electrical stimulation directs engineered cardiac tissue to an age-matched native phenotype

    Directory of Open Access Journals (Sweden)

    Richard A Lasher

    2012-07-01

    Full Text Available Quantifying structural features of native myocardium in engineered tissue is essential for creating functional tissue that can serve as a surrogate for in vitro testing or the eventual replacement of diseased or injured myocardium. We applied three-dimensional confocal imaging and image analysis to quantitatively describe the features of native and engineered cardiac tissue. Quantitative analysis methods were developed and applied to test the hypothesis that environmental cues direct engineered tissue toward a phenotype resembling that of age-matched native myocardium. The analytical approach was applied to engineered cardiac tissue with and without the application of electrical stimulation as well as to age-matched and adult native tissue. Individual myocytes were segmented from confocal image stacks and assigned a coordinate system from which measures of cell geometry and connexin-43 spatial distribution were calculated. The data were collected from 9 nonstimulated and 12 electrically stimulated engineered tissue constructs and 5 postnatal day 12 and 7 adult hearts. The myocyte volume fraction was nearly double in stimulated engineered tissue compared to nonstimulated engineered tissue (0.34 ± 0.14 vs 0.18 ± 0.06 but less than half of the native postnatal day 12 (0.90 ± 0.06 and adult (0.91 ± 0.04 myocardium. The myocytes under electrical stimulation were more elongated compared to nonstimulated myocytes and exhibited similar lengths, widths, and heights as in age-matched myocardium. Furthermore, the percentage of connexin-43-positive membrane staining was similar in the electrically stimulated, postnatal day 12, and adult myocytes, whereas it was significantly lower in the nonstimulated myocytes. Connexin-43 was found to be primarily located at cell ends for adult myocytes and irregularly but densely clustered over the membranes of nonstimulated, stimulated, and postnatal day 12 myocytes. These findings support our hypothesis and reveal

  9. The association between biventricular pacing and cardiac resynchronization therapy-defibrillator efficacy when compared with implantable cardioverter defibrillator on outcomes and reverse remodelling

    DEFF Research Database (Denmark)

    Ruwald, Anne-Christine; Kutyifa, Valentina; Ruwald, Martin H;

    2015-01-01

    AIMS: Previous studies on biventricular (BIV) pacing and cardiac resynchronization therapy-defibrillator (CRT-D) efficacy have used arbitrarily chosen BIV pacing percentages, and no study has employed implantable cardioverter defibrillator (ICD) patients as a control group. METHODS AND RESULTS...

  10. Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101 - Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI

    International Nuclear Information System (INIS)

    MANTICORE 101 - Breast (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research) is a randomized trial to determine if conventional heart failure pharmacotherapy (angiotensin converting enzyme inhibitor or beta-blocker) can prevent trastuzumab-mediated left ventricular remodeling, measured with cardiac MRI, among patients with HER2+ early breast cancer. One hundred and fifty-nine patients with histologically confirmed HER2+ breast cancer will be enrolled in a parallel 3-arm, randomized, placebo controlled, double-blind design. After baseline assessments, participants will be randomized in a 1:1:1 ratio to an angiotensin-converting enzyme inhibitor (perindopril), beta-blocker (bisoprolol), or placebo. Participants will receive drug or placebo for 1 year beginning 7 days before trastuzumab therapy. Dosages for all groups will be systematically up-titrated, as tolerated, at 1 week intervals for a total of 3 weeks. The primary objective of this randomized clinical trial is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer, as measured by 12 month change in left ventricular end-diastolic volume using cardiac MRI. Secondary objectives include 1) determine the evolution of left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer, 2) understand the mechanism of trastuzumab mediated cardiac toxicity by assessing for the presence of myocardial injury and apoptosis on serum biomarkers and cardiac MRI, and 3) correlate cardiac biomarkers of myocyte injury and extra-cellular matrix remodeling with left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer. Cardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, MANTICORE will be the first randomized trial testing proven heart failure pharmacotherapy in

  11. Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101 - Breast: a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI

    Directory of Open Access Journals (Sweden)

    Ezekowitz Justin

    2011-07-01

    Full Text Available Abstract Background MANTICORE 101 - Breast (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research is a randomized trial to determine if conventional heart failure pharmacotherapy (angiotensin converting enzyme inhibitor or beta-blocker can prevent trastuzumab-mediated left ventricular remodeling, measured with cardiac MRI, among patients with HER2+ early breast cancer. Methods/Design One hundred and fifty-nine patients with histologically confirmed HER2+ breast cancer will be enrolled in a parallel 3-arm, randomized, placebo controlled, double-blind design. After baseline assessments, participants will be randomized in a 1:1:1 ratio to an angiotensin-converting enzyme inhibitor (perindopril, beta-blocker (bisoprolol, or placebo. Participants will receive drug or placebo for 1 year beginning 7 days before trastuzumab therapy. Dosages for all groups will be systematically up-titrated, as tolerated, at 1 week intervals for a total of 3 weeks. The primary objective of this randomized clinical trial is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer, as measured by 12 month change in left ventricular end-diastolic volume using cardiac MRI. Secondary objectives include 1 determine the evolution of left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer, 2 understand the mechanism of trastuzumab mediated cardiac toxicity by assessing for the presence of myocardial injury and apoptosis on serum biomarkers and cardiac MRI, and 3 correlate cardiac biomarkers of myocyte injury and extra-cellular matrix remodeling with left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer. Discussion Cardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, MANTICORE will be the first

  12. Remodeling in the ischemic heart: the stepwise progression for heart

    Directory of Open Access Journals (Sweden)

    J.G. Mill

    2011-09-01

    Full Text Available Abstract Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI has decreased in the last decades. However, the incidence of heart failure (HF in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

  13. 先心病心脏重构患者血清血管紧张素转化酶2水平研究%The Serum Levels of Angiotensin-converting Enzyme2 in Patients of Congenital Heart Disease with Cardiac Remodeling

    Institute of Scientific and Technical Information of China (English)

    郭玥; 吕宁; 尹小龙

    2013-01-01

    目的 观察先心病(congenital heart disease,CHD)伴心脏重构(Cardiac remodeling)患者血管紧张素转化酶2 (angiotensin-convertirg enzyrre 2,ACE2)含量和活性的变化,探讨它们与心脏重构的关系.方法 收集被确诊为先心病的患者104例, (其中无心脏重构组80例,合并心脏重构组24例),正常对照组33例.抽取受试者静脉血,应用酶联免疫吸附法(ELISA)检测血清ACE2酶含量,用比色法检测ACE2酶活性的水平,所得实验数据使用SPSS统计软件进行分析.结果 (1)正常对照组、先心病无心脏重构组、先心病心脏重构组ACE2酶含量测定值分别为(15.79± 5.03) U/L、(18.85±6.46) U/L、(14.80±4.58) U/L.正常对照组与先心病无心脏重构组比较,ACE2含量差异有统计学意义(P<0.05);正常对照组与先心病心脏重构组比较,ACE2含量无差异(P>0.05);先心病无心脏重构组与心脏重构组比较,ACE2含量差异有统计学意义(P<0.01); (2)正常对照组、先心病无心脏重构组、先心病心脏重构组ACE2酶活性测定值分别为(1.75±0.82) U/L、(1.85±0.62) U/L、(158±0.52) U/L,3组间比较差异无统计学意义(P>0.05).结论 (1)先心病无心脏重构患者血清中的ACE2酶含量显著升高; (2)先心病无心脏重构患者与心脏重构患者血清中ACE2酶活性无变化.%Objective To observe the Angiotensin-converting enzyme2 (ACE2) protein contents and activity in the serum of patients with Congenital Heart Disease (CHD) combined with cardiac remodeling (CR) , and investigate the correlation of those with cardiac remodeling. Methods 104 patients with Congenital Heart Disease and 33 normal control patients were collected. The patients with congenital heart disease were divided into 80 cases of non-cardiac remodeling group, and 24 cases of cardiac remodeling group. The serum levels of ACE2 protein were detected by enzyme-linked immunosorbent assay ( ELISA) , ACE2 activity was detected by colorimetric

  14. Accelerated cardiac remodeling in desmoplakin transgenic mice in response to endurance exercise is associated with perturbed Wnt/β-catenin signaling.

    Science.gov (United States)

    Martherus, Ruben; Jain, Rahul; Takagi, Ken; Mendsaikhan, Uzmee; Turdi, Subat; Osinska, Hanna; James, Jeanne F; Kramer, Kristen; Purevjav, Enkhsaikhan; Towbin, Jeffrey A

    2016-01-15

    Arrhythmogenic ventricular cardiomyopathy (AVC) is a frequent underlying cause for arrhythmias and sudden cardiac death especially during intense exercise. The mechanisms involved remain largely unknown. The purpose of this study was to investigate how chronic endurance exercise contributes to desmoplakin (DSP) mutation-induced AVC pathogenesis. Transgenic mice with overexpression of desmoplakin, wild-type (Tg-DSP(WT)), or the R2834H mutant (Tg-DSP(R2834H)) along with control nontransgenic (NTg) littermates were kept sedentary or exposed to a daily running regimen for 12 wk. Cardiac function and morphology were analyzed using echocardiography, electrocardiography, histology, immunohistochemistry, RNA, and protein analysis. At baseline, 4-wk-old mice from all groups displayed normal cardiac function. When subjected to exercise, all mice retained normal cardiac function and left ventricular morphology; however, Tg-DSP(R2834H) mutants displayed right ventricular (RV) dilation and wall thinning, unlike NTg and Tg-DSP(WT). The Tg-DSP(R2834H) hearts demonstrated focal fat infiltrations in RV and cytoplasmic aggregations consisting of desmoplakin, plakoglobin, and connexin 43. These aggregates coincided with disruption of the intercalated disks, intermediate filaments, and microtubules. Although Tg-DSP(R2834H) mice already displayed high levels of p-GSK3-β(Ser9) and p-AKT1(Ser473) under sedentary conditions, decrease of nuclear GSK3-β and AKT1 levels with reduced p-GSK3-β(Ser9), p-AKT1(Ser473), and p-AKT1(Ser308) and loss of nuclear junctional plakoglobin was apparent after exercise. In contrast, Tg-DSP(WT) showed upregulation of p-AKT1(Ser473), p-AKT1(Ser308), and p-GSK3-β(Ser9) in response to exercise. Our data suggest that endurance exercise accelerates AVC pathogenesis in Tg-DSP(R2834H) mice and this event is associated with perturbed AKT1 and GSK3-β signaling. Our study suggests a potential mechanism-based approach to exercise management in patients with AVC

  15. Aetiologies of pulseless electrical activity in out-of-hospital cardiac arrests:A retrospective study and analysis of specific causes

    OpenAIRE

    Beun, L

    2014-01-01

    Background: Pulseless electrical activity (PEA) cardiac arrest is defined as a cardiac arrest (CA) presenting with a residual organized electrical activity on the electrocardiogram. In the last decades, the incidence of PEA has regularly increased, compared to other types of CA like ventricular fibrillation or pulseless ventricular tachycardia. PEA is frequently induced by reversible conditions. The "4 (or 5) H" & "4 (or 5) T" are proposed as a mnemonic to asses for Hypoxia, Hypovolemia, ...

  16. The relationship between gap junctional remodeling and human atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    李大强; 冯义柏; 张会琴

    2004-01-01

    @@ Atrial fibrillation (AF) is currently the most common cardiac tachyarrhythmia in clinical practice. AF has a tendency to become more persistent over time. Progression of an underlying disease is one explanation. Another possible explanation is electrical, structural, and gap junctional remodeling of the atrium by repetitive induction of AF.1 The expression level and distribution of it have close relation with the conduction velocity of electrical activation in the atrium. The aim of the present study was to investigate the alternations of the expression and distribution of (connexin 40, Cx 40) and (connexin 43, Cx 43) in the right atrial appendages of the patients with AF by laser confocal scanning microscopy and Western blot technique.

  17. Removal of pinned scroll waves in cardiac tissues by electric fields in a generic model of three-dimensional excitable media.

    Science.gov (United States)

    Pan, De-Bei; Gao, Xiang; Feng, Xia; Pan, Jun-Ting; Zhang, Hong

    2016-01-01

    Spirals or scroll waves pinned to heterogeneities in cardiac tissues may cause lethal arrhythmias. To unpin these life-threatening spiral waves, methods of wave emission from heterogeneities (WEH) induced by low-voltage pulsed DC electric fields (PDCEFs) and circularly polarized electric fields (CPEFs) have been used in two-dimensional (2D) cardiac tissues. Nevertheless, the unpinning of scroll waves in three-dimensional (3D) cardiac systems is much more difficult than that of spiral waves in 2D cardiac systems, and there are few reports on the removal of pinned scroll waves in 3D cardiac tissues by electric fields. In this article, we investigate in detail the removal of pinned scroll waves in a generic model of 3D excitable media using PDCEF, AC electric field (ACEF) and CPEF, respectively. We find that spherical waves can be induced from the heterogeneities by these electric fields in initially quiescent excitable media. However, only CPEF can induce spherical waves with frequencies higher than that of the pinned scroll wave. Such higher-frequency spherical waves induced by CPEF can be used to drive the pinned scroll wave out of the cardiac systems. We hope this remarkable ability of CPEF can provide a better alternative to terminate arrhythmias caused by pinned scroll waves. PMID:26905367

  18. Separation of cardiac and respiratory components from the electrical bio-impedance signal using PCA and fast ICA

    CERN Document Server

    Mughal, Yar M; Annus, P

    2013-01-01

    This paper is an attempt to separate cardiac and respiratory signals from an electrical bio-impedance (EBI) dataset. For this two well-known algorithms, namely Principal Component Analysis (PCA) and Independent Component Analysis (ICA), were used to accomplish the task. The ability of the PCA and the ICA methods first reduces the dimension and attempt to separate the useful components of the EBI, the cardiac and respiratory ones accordingly. It was investigated with an assumption, that no motion artefacts are present. To carry out this procedure the two channel complex EBI measurements were provided using classical Kelvin type four electrode configurations for the each complex channel. Thus four real signals were used as inputs for the PCA and fast ICA. The results showed, that neither PCA nor ICA nor combination of them can not accurately separate the components at least are used only two complex (four real valued) input components.

  19. Prototype Development of an Electrical Impedance Based Simultaneous Respiratory and Cardiac Monitoring System for Gated Radiotherapy

    OpenAIRE

    Kohli, Kirpal; Liu, Jeff; Schellenberg, Devin; Karvat, Anand; Parameswaran, Ash; Grewal, Parvind; Thomas, Steven

    2014-01-01

    Background In radiotherapy, temporary translocations of the internal organs and tumor induced by respiratory and cardiac activities can undesirably lead to significantly lower radiation dose on the targeted tumor but more harmful radiation on surrounding healthy tissues. Respiratory and cardiac gated radiotherapy offers a potential solution for the treatment of tumors located in the upper thorax. The present study focuses on the design and development of simultaneous acquisition of respira...

  20. Mechanical cardiac remodeling and new-onset atrial fibrillation in long-term follow-up of subjects with chronic Chagas' disease

    Directory of Open Access Journals (Sweden)

    P.R. Benchimol-Barbosa

    2009-03-01

    Full Text Available Atrial fibrillation (AF affects subjects with Chagas' disease and is an indicator of poor prognosis. We investigated clinical, echocardiographic and electrocardiographic variables of Chagas' disease in a long-term longitudinal study as predictors of a new-onset AF episode lasting >24 h, nonfatal embolic stroke and cardiac death. Fifty adult outpatients (34 to 74 years old, 62% females staged according to the Los Andes classification were enrolled. During a follow-up of (mean ± SD 84.2 ± 39.0 months, 9 subjects developed AF (incidence: 3.3 ± 1.0%/year, 5 had nonfatal stroke (incidence: 1.3 ± 1.0%/year, and nine died (mortality rate: 2.3 ± 0.8%/year. The progression rate of left ventricular mass and left ventricular ejection fraction was significantly greater in subjects who experienced AF (16.4 ± 20.0 g/year and -8.6 ± 7.6%/year, respectively than in those who did not (8.2 ± 8.4 g/year; P = 0.03, and -3.0 ± 2.5%/year; P = 0.04, respectively. In univariate analysis, left atrial diameter ≥3.2 cm (P = 0.002, pulmonary arterial hypertension (P = 0.035, frequent premature supraventricular and ventricular contraction counts/24 h (P = 0.005 and P = 0.007, respectively, ventricular couplets/24 h (P = 0.002, and ventricular tachycardia (P = 0.004 were long-term predictors of AF. P-wave signal-averaged ECG revealed a limited long-term predictive value for AF. In chronic Chagas' disease, large left atrial diameter, pulmonary arterial hypertension, frequent supraventricular and ventricular premature beats, and ventricular tachycardia are long-term predictors of AF. The rate of left ventricular mass enlargement and systolic function deterioration impact AF incidence in this population.

  1. Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial Parasympathetic Remodeling through MAPKs/Neurturin Pathway

    Directory of Open Access Journals (Sweden)

    Lei Liu

    2015-07-01

    Full Text Available Background/Aims: Angiotensin II receptor blockers (ARBs have been proved to be effective in preventing atrial structural and electrical remodelinq in atrial fibrillation (AF. Previous studies have shown that parasympathetic remodeling plays an important role in AF. However, the effects of ARBs on atrial parasympathetic remodeling in AF and the underlying mechanisms are still unknown. Methods: Canines were divided into sham-operated, pacing and valsartan + pacing groups. Rats and HL-1 cardiomyocytes were divided into control, angiotensin II (Ang II and Ang II + valsartan groups, respectively. Atrial parasympathetic remodeling was quantified by immunocytochemical staining with anti-choline acetyltransferase (ChAT antibody. Western blot was used to analysis the protein expression of neurturin. Results: Both inducibility and duration were increased in chronic atrial rapid-pacing canine model, which was significantly inhibited by the treatment with valsartan. The density of ChAT-positive nerves and the protein level of neurturin in the atria of pacing canines were both increased than those in sham-operated canines. Ang II treatment not only induced atrial parasympathetic remodeling in rats, but also up-regulated the protein expression of neurturin. Valsartan significantly prevented atrial parasympathetic remodeling, and suppressed the protein expression of neurturin. Meanwhile, valsartan inhibited Ang II -induced up-regulation of neurturin and MAPKs in cultured cardiac myocytes. Inhibition of MAPKs dramatically attenuated neurturin up-regulation induced by Ang II. Conclusion: Parasympathetic remodeling was present in animals subjected to rapid pacing or Ang II infusion, which was mediated by MAPKs/neurturin pathway. Valsartan is able to prevent atrial parasympathetic remodeling and the occurrence of AF via inhibiting MAPKs/neurturin pathway.

  2. An evaluation of two conducted electrical weapons and two probe designs using a swine comparative cardiac safety model.

    Science.gov (United States)

    Dawes, Donald Murray; Ho, Jeffrey D; Moore, Johanna C; Miner, James R

    2013-09-01

    Despite human laboratory and field studies that have demonstrated a reasonable safety profile for TASER brand conducted electrical weapons (CEW), the results of some swine studies and arrest related deaths temporal to the use of the CEWs continue to raise questions regarding cardiac safety. TASER International, Inc., has released a new CEW, the TASER X2, touted to have a better safety profile than its long-standing predecessor, the TASER X26. We have developed a model to assess the relative cardiac safety of CEWs and used it to compare the TASER X2 and the TASER X26. This safety model was also used to assess the relative safety of an experimental probe design as compared to the standard steel probe. Our results suggest that the TASER X2 has an improved safety margin over the TASER X26. The new probe design also has promise for enhanced cardiac safety, although may have some disadvantages when compared to the existing design which would make field use impractical. PMID:23543462

  3. Electrical wave propagation in an anisotropic model of the left ventricle based on analytical description of cardiac architecture.

    Directory of Open Access Journals (Sweden)

    Sergey F Pravdin

    Full Text Available We develop a numerical approach based on our recent analytical model of fiber structure in the left ventricle of the human heart. A special curvilinear coordinate system is proposed to analytically include realistic ventricular shape and myofiber directions. With this anatomical model, electrophysiological simulations can be performed on a rectangular coordinate grid. We apply our method to study the effect of fiber rotation and electrical anisotropy of cardiac tissue (i.e., the ratio of the conductivity coefficients along and across the myocardial fibers on wave propagation using the ten Tusscher-Panfilov (2006 ionic model for human ventricular cells. We show that fiber rotation increases the speed of cardiac activation and attenuates the effects of anisotropy. Our results show that the fiber rotation in the heart is an important factor underlying cardiac excitation. We also study scroll wave dynamics in our model and show the drift of a scroll wave filament whose velocity depends non-monotonically on the fiber rotation angle; the period of scroll wave rotation decreases with an increase of the fiber rotation angle; an increase in anisotropy may cause the breakup of a scroll wave, similar to the mother rotor mechanism of ventricular fibrillation.

  4. Efficient simulation of cardiac electrical propagation using high order finite elements

    Science.gov (United States)

    Arthurs, Christopher J.; Bishop, Martin J.; Kay, David

    2012-05-01

    We present an application of high order hierarchical finite elements for the efficient approximation of solutions to the cardiac monodomain problem. We detail the hurdles which must be overcome in order to achieve theoretically-optimal errors in the approximations generated, including the choice of method for approximating the solution to the cardiac cell model component. We place our work on a solid theoretical foundation and show that it can greatly improve the accuracy in the approximation which can be achieved in a given amount of processor time. Our results demonstrate superior accuracy over linear finite elements at a cheaper computational cost and thus indicate the potential indispensability of our approach for large-scale cardiac simulation.

  5. Biomimetic material strategies for cardiac tissue engineering

    International Nuclear Information System (INIS)

    Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.

  6. Influence on left cardiac remodeling and left ventricular function in coronary heart disease by performing percutaneous transluminal coronary angioplasty and stent implantation and drug re-intervention therapy%冠心病PTCA+支架术及药物再干预对左心重构和左室功能的影响

    Institute of Scientific and Technical Information of China (English)

    赵文强; 王俊; 谢红珍; 吴艳君; 潘啸东

    2008-01-01

    Objective To study influence of percutaneous transluminal coronary angioplasty (PTCA) and stent implantation on left cardiac remodeling and left ventricular function and clinical effect of drug re-inter- vention in coronary heart disease. Methods 98 patients with coronary heart disease were divided into 4 groups one year after performing percutaneous coronary intervention (PCI), clinical and echocardiographic indexes of left cardiac remodeling and left ventricular function were examined by comparison of 4 groups of post-PCI versus pre-PCI, influences of different PCI strategy and different drug re-interventions on left cardiac remodeling and left cardiac function were analysed. Results NYHA cardiac function grade,6 minute's walk test,left atrial volume index( LAVI), left ventricular diastolic-end volume index (LVDEVI), eject fraction (EF), ventricular Wall movement loss fraction(WMLF) in 4 groups of post-PCI were better than those in pre-PCI(all P < 0.001). Those in 6 months group and 12 months group of post-PCI were also better than those in 1 week group of post-PCI(all P<0.01). LAVI, LVEDVI, EF and WMLF were significantly different among different groups of PCI strategy, and better by comparison of Group simvastatin and Group irbesartan versus group of routine drug, but little different by Group tirofiban versus group of routine drug in patients undergoing drug re-intervention of post-PCL Concluslan Left cardiac remodeling and left ventricular function in coronary heart disease have a significant improvement in post-PCIone year, suitable PCI strategy and drug re-intervention have further influence on bettering left cardiac remodeling and left ventricular function.%目的 研究PTCA+支架术对左心重构和左室功能的影响及药物再干预的效果.方法 对98例冠心病患者经皮冠状动脉介入治疗(PCI)术后1年内4组与术前左心重构、左室功能的临床与超声指标对比研究,对不同PCI策略和不同药物干预效应与

  7. Dynamic boundary estimation of human heart within a complete cardiac cycle using electrical impedance tomography

    Science.gov (United States)

    Rashid, A.; Kim, B. S.; Khambampati, A. K.; Liu, Dong; Kim, S.; Kim, K. Y.

    2010-04-01

    This paper presents an EKF based boundary estimation algorithm to estimate the shape and size of human heart ventricle during a complete cardiac cycle. First-order kinematic model is used as a state evolution model. The boundary of the heart is expressed as coefficients of truncated Fourier series and the conductivity distribution inside the thorax region is assumed to be known a priori. The proposed method is tested with the use of a realistic chest shape FEM mesh.

  8. Correlations between the Signal Complexity of Cerebral and Cardiac Electrical Activity: A Multiscale Entropy Analysis

    OpenAIRE

    Pei-Feng Lin; Men-Tzung Lo; Jenho Tsao; Yi-Chung Chang; Chen Lin; Yi-Lwun Ho

    2014-01-01

    The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG) and a 19-channel eye-closed routine electroencepha...

  9. Pulse Wave Velocity and Cardiac Output vs. Heart Rate in Patients with an Implanted Pacemaker Based on Electric Impedance Method Measurement

    International Nuclear Information System (INIS)

    The methods and device for estimation of cardiac output and measurement of pulse wave velocity simultaneously is presented here. The beat-to-beat cardiac output as well as pulse wave velocity measurement is based on application of electrical impedance method on the thorax and calf. The results are demonstrated in a study of 24 subjects. The dependence of pulse wave velocity and cardiac output on heart rate during rest in patients with an implanted pacemaker was evaluated. The heart rate was changed by pacemaker programming while neither exercise nor drugs were applied. The most important result is that the pulse wave velocity, cardiac output and blood pressure do not depend significantly on heart rate, while the stroke volume is reciprocal proportionally to the heart rate.

  10. Cardiac Remodelling in Thermally Acclimated Fish

    OpenAIRE

    Fenna, Andrew

    2013-01-01

    Fish are subject to a variety of long and short term environmental and physical insults during their life; however they manage to adapt, ensuring physiological processes remain effective, enabling the animal to thrive in a wide range of conditions. One major environmental fluctuation that can occur rapidly or over a long period of time is temperature. Teleost fish, such as the rainbow trout (Oncorhynchus mykiss) are ectothermic, meaning their body temperature is regulated by environmental tem...

  11. Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.

    Directory of Open Access Journals (Sweden)

    Juan F Gomez

    Full Text Available Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure.In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations.The electrical activity of human transmural ventricular tissue (5 cm × 5 cm was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW for reentry was evaluated following cross-field stimulation.No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components.Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity.

  12. Evaluation of cerebral electrical activity and cardiac output after patent ductus arteriosus ligation in preterm infants.

    LENUS (Irish Health Repository)

    Leslie, A T F S

    2013-11-01

    To characterize and investigate the relationship between systemic blood flow and pre- and postoperative cerebral electrical activity in preterm neonates undergoing patent ductus arteriosus (PDA) ligation.

  13. Effect of simvastatin on cardiac function and left ventricular remodeling in patients with heart failure%辛伐他汀对心力衰竭患者心脏功能及左心室重构的影响

    Institute of Scientific and Technical Information of China (English)

    李国锋; 孙立伟; 黎笑冰

    2011-01-01

    Objectives To observing the effect of simvastatin on cardiac function and left ventricular remodeling in patients with heart failure. Methods Sixty one cases with non-ischemic heart failure were randomly divided into observation group (n=30) and control group (n=31 ) in The People's Hospital of Dongguan from Jan 2008 to Jul 2009. The two groups were given conventional therapy. Observation group was given simvastatin 20 mg/d in a course of 6 months. Heart function and biochemical changes of the two groups were observed and compared. Results After 6 months of treatment, the New York Heart Association (NYHA) classification [(2.0±0.4) grade vs. (2.5±0.4) grade, P<0.01 ]and left ventricular ejection fraction (LVEF)[58.7% ± 5.2% vs. 43.0% ± 5.7%, P<0.01 ]of observation group were improved significantly (P<0.01). NYHA classification of control group was improved [(2.1 ±0.4) grade vs. (2.4±0.4) grade, P<0.05]. LVEF of control group showed improved tendence, but had no significance (47.6% ± 5.3% vs. 40.9% ± 6.3%, P=0.052). Conclusions Patients with non-ischemic heart failure treated with simvastatin on the base of conventional treatment can significantly improve cardiac function and left ventricular remodeling, and it is safe and effective.%目的 观察小剂量辛伐他汀对心力衰竭患者心脏功能及左心室重构的影响.方法 选取2008年1月至2009年7月东莞市人民医院确诊为非缺血性心力衰竭的患者61例为研究对象.按电脑随机数字表法将入选对象分为观察组(n=30)与对照组(n=31),观察组在标准心力衰竭治疗基础上加服辛伐他汀(20 mg/d,治疗期6个月).比较两组治疗前后患者心脏功能、生化指标的变化.结果 经过6个月的治疗,观察组纽约心脏协会心功能分级[(2.0±0.4)级vs.(2.5±0.4)级,P<0.01]和左心室射血分数(58.7%±5.2% vs.43.0%±5.7%,P<0.01)显著改善,差异有统计学意义;对照组纽约心脏协会心功能

  14. Cardiac Pacemakers

    International Nuclear Information System (INIS)

    A complete survey of physiological biophysical,clinical and engineering aspects of cardiac facing,including the history and an assessment of possible future developments.Among the topics studied are: pacemakers, energy search, heart stimulating with pacemakers ,mathematical aspects of the electric cardio stimulation chronic, pacemaker implants,proceeding,treatment and control

  15. A modified algorithm of the combined ensemble empirical mode decomposition and independent component analysis for the removal of cardiac artifacts from neuromuscular electrical signals

    International Nuclear Information System (INIS)

    Neuronal and muscular electrical signals contain useful information about the neuromuscular system, with which researchers have been investigating the relationship of various neurological disorders and the neuromuscular system. However, neuromuscular signals can be critically contaminated by cardiac electrical activity (CEA) such as the electrocardiogram (ECG) which confounds data analysis. The purpose of our study is to provide a method for removing cardiac electrical artifacts from the neuromuscular signals recorded. We propose a new method for cardiac artifact removal which modifies the algorithm combining ensemble empirical mode decomposition (EEMD) and independent component analysis (ICA). We compare our approach with a cubic smoothing spline method and the previous combined EEMD and ICA for various signal-to-noise ratio measures in simulated noisy physiological signals using a surface electromyogram (sEMG). Finally, we apply the proposed method to two real-life sets of data such as sEMG with ECG artifacts and ambulatory dog cardiac autonomic nervous signals measured from the ganglia near the heart, which are also contaminated with CEA. Our method can not only extract and remove artifacts, but can also preserve the spectral content of the neuromuscular signals. (paper)

  16. Correlations between the signal complexity of cerebral and cardiac electrical activity: a multiscale entropy analysis.

    Directory of Open Access Journals (Sweden)

    Pei-Feng Lin

    Full Text Available The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG and a 19-channel eye-closed routine electroencephalography (EEG. Multiscale entropy (MSE analysis was applied to three epochs (resting-awake state, photic stimulation of fast frequencies (fast-PS, and photic stimulation of slow frequencies (slow-PS of EEG in the 1-58 Hz frequency range, and three RR interval (RRI time series (awake-state, sleep and that concomitant with the EEG for each subject. The low-to-high frequency power (LF/HF ratio of RRI was calculated to represent sympatho-vagal balance. With statistics after Bonferroni corrections, we found that: (a the summed MSE value on coarse scales of the awake RRI (scales 11-20, RRI-MSE-coarse were inversely correlated with the summed MSE value on coarse scales of the resting-awake EEG (scales 6-20, EEG-MSE-coarse at Fp2, C4, T6 and T4; (b the awake RRI-MSE-coarse was inversely correlated with the fast-PS EEG-MSE-coarse at O1, O2 and C4; (c the sleep RRI-MSE-coarse was inversely correlated with the slow-PS EEG-MSE-coarse at Fp2; (d the RRI-MSE-coarse and LF/HF ratio of the awake RRI were correlated positively to each other; (e the EEG-MSE-coarse at F8 was proportional to the cognitive test score; (f the results conform to the cholinergic hypothesis which states that cognitive impairment causes reduction in vagal cardiac modulation; (g fast-PS significantly lowered the EEG-MSE-coarse globally. Whether these heart-brain correlations could be fully explained by the central autonomic network is unknown and needs further exploration.

  17. Correlations between the signal complexity of cerebral and cardiac electrical activity: a multiscale entropy analysis.

    Science.gov (United States)

    Lin, Pei-Feng; Lo, Men-Tzung; Tsao, Jenho; Chang, Yi-Chung; Lin, Chen; Ho, Yi-Lwun

    2014-01-01

    The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG) and a 19-channel eye-closed routine electroencephalography (EEG). Multiscale entropy (MSE) analysis was applied to three epochs (resting-awake state, photic stimulation of fast frequencies (fast-PS), and photic stimulation of slow frequencies (slow-PS)) of EEG in the 1-58 Hz frequency range, and three RR interval (RRI) time series (awake-state, sleep and that concomitant with the EEG) for each subject. The low-to-high frequency power (LF/HF) ratio of RRI was calculated to represent sympatho-vagal balance. With statistics after Bonferroni corrections, we found that: (a) the summed MSE value on coarse scales of the awake RRI (scales 11-20, RRI-MSE-coarse) were inversely correlated with the summed MSE value on coarse scales of the resting-awake EEG (scales 6-20, EEG-MSE-coarse) at Fp2, C4, T6 and T4; (b) the awake RRI-MSE-coarse was inversely correlated with the fast-PS EEG-MSE-coarse at O1, O2 and C4; (c) the sleep RRI-MSE-coarse was inversely correlated with the slow-PS EEG-MSE-coarse at Fp2; (d) the RRI-MSE-coarse and LF/HF ratio of the awake RRI were correlated positively to each other; (e) the EEG-MSE-coarse at F8 was proportional to the cognitive test score; (f) the results conform to the cholinergic hypothesis which states that cognitive impairment causes reduction in vagal cardiac modulation; (g) fast-PS significantly lowered the EEG-MSE-coarse globally. Whether these heart-brain correlations could be fully explained by the central autonomic network is unknown and needs further exploration. PMID:24498375

  18. Effects of acupuncture at the acupoints of 12 meridians on gastrointestinal and cardiac electricity in healthy adults.

    Science.gov (United States)

    Chang, Xiao-Rong; Yan, Jie; Shen, Jing; Liu, Mi; Wang, Xiao-Juan

    2010-09-01

    The effect of acupuncture at the acupoints of 12 meridians on gastrointestinal and cardiac electricity in healthy adults was studied. Specific regulation between meridian points and viscera was also investigated. An electrogastrogram (EGG), electrointestinogram (EIG), carotid pulse graph, phonocardiogram and electrocardiogram were obtained in 30 healthy adults before and after acupuncture at various acupoints of 12 meridians. The effects of acupuncture on the amplitude and frequency of the EGG, EIG, pre-ejection period and the left ventricular ejection time were then analyzed. Acupuncture revealed that LR3 decreased the amplitude of the EGG while LI11 (Quchi), SJ5 (Waiguan), ST36 (Zusanli), SP9 (Yinlingquan) and SI6 (Yanglao) increased the amplitude. Multiple comparisons among the latter five acupoints indicated that there were significant differences between SP9, LI11, SJ5 and ST36 (p < 0.01, p < 0.01, p < 0.05) and SI6, LI11 and SJ5 (p < 0.01, p < 0.05). SP9 effected EGG amplitude the most, followed by SI6, ST36, SJ5 and LI11. Four acupoints increased the amplitude of the EIG (p < 0.05), including HT5 (Tongli), GB34 (Yanglingquan), SP9 and SI6. No significant differences were observed between these acupoints, but SI6 showed the most obvious effect on EIG amplitude, followed by GB34, SP9 and HT5. No significant effects on the frequency of the gastrointestinal slow wave or on cardiac function indexes were observed. Effects were observed, however, on pre-ejection period and left ventricular ejection time. Routine acupuncture had no detrimental effects on the stomach, intestine and heart in healthy adults, but instead regulated physiological function within a normal range. These findings demonstrate the existence of specific connections between the meridian points and the viscera. The results suggest that multiple meridians control the same viscus, and the same meridian can regulate the functions of multiple viscera. PMID:20869017

  19. Ranolazine reduces remodeling of the right ventricle and provoked arrhythmias in rats with pulmonary hypertension.

    Science.gov (United States)

    Liles, John T; Hoyer, Kirsten; Oliver, Jason; Chi, Liguo; Dhalla, Arvinder K; Belardinelli, Luiz

    2015-06-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that often results in right ventricular (RV) failure and death. During disease progression, structural and electrical remodeling of the right ventricle impairs pump function, creates proarrhythmic substrates, and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in patients with PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an antianginal, anti-ischemic drug that has cardioprotective effects in experimental and clinical settings of left-sided heart dysfunction. RAN also has antiarrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. We therefore hypothesized that RAN could reduce the maladaptive structural and electrical remodeling of the right ventricle and could prevent triggered ventricular arrhythmias in the monocrotaline rat model of PAH. Indeed, in both in vivo and ex vivo experimental settings, chronic RAN treatment reduced electrical heterogeneity (right ventricular-left ventricular action potential duration dispersion), shortened heart-rate corrected QT intervals in the right ventricle, and normalized RV dysfunction. Chronic RAN treatment also dose-dependently reduced ventricular hypertrophy, reduced circulating levels of B-type natriuretic peptide, and decreased the expression of fibrotic markers. In addition, the acute administration of RAN prevented isoproterenol-induced ventricular tachycardia/ventricular fibrillation and subsequent cardiovascular death in rats with established PAH. These results support the notion that RAN can improve the electrical and functional properties of the right ventricle, highlighting its potential benefits in the setting of RV impairment. PMID:25770134

  20. Noninvasive reconstruction of cardiac electrical activity: update on current methods, applications and challenges

    OpenAIRE

    Cluitmans, M.J.M.; Peeters, R.L.M.; Westra, R.L.; Volders, P. G. A.

    2015-01-01

    Electrical activity at the level of the heart muscle can be noninvasively reconstructed from body-surface electrocardiograms (ECGs) and patient-specific torso-heart geometry. This modality, coined electrocardiographic imaging, could fill the gap between the noninvasive (low-resolution) 12-lead ECG and invasive (high-resolution) electrophysiology studies. Much progress has been made to establish electrocardiographic imaging, and clinical studies appear with increasing frequency. However, many ...

  1. Measurement of ventilation and cardiac related impedance changes with electrical impedance tomography

    OpenAIRE

    Grant, Caroline A; Pham, Trang; Hough, Judith; Riedel, Thomas; Stocker, Christian; Schibler, Andreas

    2011-01-01

    Introduction Electrical impedance tomography (EIT) has been shown to be able to distinguish both ventilation and perfusion. With adequate filtering the regional distributions of both ventilation and perfusion and their relationships could be analysed. Several methods of separation have been suggested previously, including breath holding, electrocardiograph (ECG) gating and frequency filtering. Many of these methods require interventions inappropriate in a clinical setting. This study ther...

  2. Electrical and Hemodynamic Evaluation of Ventricular and Supraventricular Tachycardias with an Implantable Cardiac Stimulator

    OpenAIRE

    Claudio Pandozi MD; Franco Di Gregorio BiolScD; Carlo Lavalle MD; Renato Pietro Ricci MD; Sabina Ficili MD; Marco Galeazzi MD; Maurizio Russo MD; Angela Pandozi MD; Furio Colivicchi MD; Massimo Santini MD

    2014-01-01

    The discrimination between ventricular and supraventricular tachycardia and the evaluation of their hemodynamic impact are essential issues in the arrhythmia management. A new pacing device features a tachycardia diagnostic system relying on simultaneous recording of the transvalvular impedance (TVI) and the iECG, which is an integrated electric signal derived by the whole set of endocardial electrodes. The iECG waveform is sensitive to the pattern of ventricular activation, similarly to the ...

  3. Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial

    DEFF Research Database (Denmark)

    Daubert, Claude; Gold, Michael R; Abraham, William T;

    2009-01-01

    dimensions were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left v...

  4. Postmyocardial Infarct Remodeling and Heart Failure: Potential Contributions from Pro- and Antiaging Factors

    OpenAIRE

    Idikio, Halliday A.

    2011-01-01

    Myocardial infarction and adverse postinfarct remodeling in older persons lead to poor outcome and need greater understanding of the contributions of age-related factors on abnormal cardiac function and management. In this perspective, how normal aging processes could contribute to the events of post-myocardial infarction and remodeling is reviewed. Post-myocardial infarction and remodeling involve cardiomechanical factors and neurohormonal response. Many factors prevent or accelerate aging...

  5. Head-only followed by cardiac arrest electrical stunning is an effective alternative to head-only electrical stunning in pigs.

    Science.gov (United States)

    Vogel, K D; Badtram, G; Claus, J R; Grandin, T; Turpin, S; Weyker, R E; Voogd, E

    2011-05-01

    Many small slaughter facilities use head-only electrical stunning to render swine unconscious and insensible to pain before slaughter. Head-only electrical stunning is a reversible procedure that is optimally effective for approximately 15 s after stun completion. In many small North American slaughter plants, the authors have observed hoist speeds that are too slow to achieve a short enough stun-to-bleed interval to maintain insensibility through exsanguination. Unlike many European plants, there is no separate high-speed hoist for pigs and exsanguination on the floor is not condoned. As a result, a 2-stage stunning method was proposed where head-only stunning for 3 s was immediately followed by application of the same stunning wand to the cardiac region of the animal for 3 s while lying in lateral recumbancy. A paired-comparison study was conducted on 89 pigs in a small slaughter facility to compare the head-only method applied for 6 s with the head/heart method. The objective was to evaluate signs of return to sensibility, stun-to-bleed time, blood lactate concentration, muscle pH, drip loss, and fresh meat color to validate the head/heart electrical stunning method for small slaughter plants. Incidence of corneal reflex was not different (P > 0.05) between head/heart (93.8%) and head only (85%) stunning. Nose twitching was more common (P 0.05) between stunning methods (head only: 8.8 ± 0.7 mmol/L, head/heart: 7.8 ± 0.7 mmol/L). Stun-to-bleed time did not differ (P > 0.05; head only: 32 ± 1 s, head/heart: 33 ± 1 s). Mean time to loss of heartbeat with the head-only method was 121 ± 5 s. No heartbeat was observed with the head/heart method. Longissimus thoracis pH, color, and drip loss were not different (P > 0.05) between stunning methods. This study determined that the head/heart electrical stunning method reduces the incidence of signs of return to sensibility without significant effects on meat quality, plant operation speed, or blood lactate

  6. The influence of anatomical and physiological parameters on the interference voltage at the input of unipolar cardiac pacemakers in low frequency electric fields

    Science.gov (United States)

    Joosten, S.; Pammler, K.; Silny, J.

    2009-02-01

    The problem of electromagnetic interference of electronic implants such as cardiac pacemakers has been well known for many years. An increasing number of field sources in everyday life and occupational environment leads unavoidably to an increased risk for patients with electronic implants. However, no obligatory national or international safety regulations exist for the protection of this patient group. The aim of this study is to find out the anatomical and physiological worst-case conditions for patients with an implanted pacemaker adjusted to unipolar sensing in external time-varying electric fields. The results of this study with 15 volunteers show that, in electric fields, variation of the interference voltage at the input of a cardiac pacemaker adds up to 200% only because of individual factors. These factors should be considered in human studies and in the setting of safety regulations.

  7. A coupled 3D-1D numerical monodomain solver for cardiac electrical activation in the myocardium with detailed Purkinje network

    Science.gov (United States)

    Vergara, Christian; Lange, Matthias; Palamara, Simone; Lassila, Toni; Frangi, Alejandro F.; Quarteroni, Alfio

    2016-03-01

    We present a model for the electrophysiology in the heart to handle the electrical propagation through the Purkinje system and in the myocardium, with two-way coupling at the Purkinje-muscle junctions. In both the subproblems the monodomain model is considered, whereas at the junctions a resistor element is included that induces an orthodromic propagation delay from the Purkinje network towards the heart muscle. We prove a sufficient condition for convergence of a fixed-point iterative algorithm to the numerical solution of the coupled problem. Numerical comparison of activation patterns is made with two different combinations of models for the coupled Purkinje network/myocardium system, the eikonal/eikonal and the monodomain/monodomain models. Test cases are investigated for both physiological and pathological activation of a model left ventricle. Finally, we prove the reliability of the monodomain/monodomain coupling on a realistic scenario. Our results underlie the importance of using physiologically realistic Purkinje-trees with propagation solved using the monodomain model for simulating cardiac activation.

  8. Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat/cholesterol diet

    OpenAIRE

    Yongming, Pan; Zhaowei, Cai; Yichao, Ma; Keyan, Zhu; Liang, Chen; Fangming, Chen; Xiaoping, Xu; Quanxin, Ma; Minli, Chen

    2015-01-01

    Background A long-term high-fat/cholesterol (HFC) diet leads to insulin resistance (IR), which is associated with inflammation, atherosclerosis (AS), cardiac sympathovagal imbalance, and cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) and nuclear factor ĸB (NF-κB) are involved in the development of IR-AS. Thus, we elucidated the pathological molecular mechanism of IR-AS by feeding an HFC diet to Tibetan minipigs to induce IR and AS. Methods Male Tibetan minipigs were ...

  9. Detection of optimal PEEP for equal distribution of tidal volume by volumetric capnography and electrical impedance tomography during decreasing levels of PEEP in post cardiac-surgery patients

    OpenAIRE

    Blankman, P; Shono, A.; Hermans, B. J. M.; Wesselius, T.; Hasan, D; Gommers, D

    2016-01-01

    Background Homogeneous ventilation is important for prevention of ventilator-induced lung injury. Electrical impedance tomography (EIT) has been used to identify optimal PEEP by detection of homogenous ventilation in non-dependent and dependent lung regions. We aimed to compare the ability of volumetric capnography and EIT in detecting homogenous ventilation between these lung regions. Methods Fifteen mechanically-ventilated patients after cardiac surgery were studied. Ventilator settings wer...

  10. Impact of Additional Transthoracic Electrical Cardioversion on Cardiac Function and Atrial Fibrillation Recurrence in Patients with Persistent Atrial Fibrillation Who Underwent Radiofrequency Catheter Ablation

    Science.gov (United States)

    Wang, Deguo; Zhang, Fengxiang; Wang, Ancai

    2016-01-01

    Backgrounds and Objective. During the procession of radiofrequency catheter ablation (RFCA) in persistent atrial fibrillation (AF), transthoracic electrical cardioversion (ECV) is required to terminate AF. The purpose of this study was to determine the impact of additional ECV on cardiac function and recurrence of AF. Methods and Results. Persistent AF patients received extensive encircling pulmonary vein isolation (PVI) and additional line ablation. Patients were divided into two groups based on whether they need transthoracic electrical cardioversion to terminate AF: electrical cardioversion (ECV group) and nonelectrical cardioversion (NECV group). Among 111 subjects, 35 patients were returned to sinus rhythm after ablation by ECV (ECV group) and 76 patients had AF termination after the ablation processions (NECV group). During the 12-month follow-ups, the recurrence ratio of patients was comparable in ECV group (15/35) and NECV group (34/76) (44.14% versus 44.74%, P = 0.853). Although left atrial diameters (LAD) decreased significantly in both groups, there were no significant differences in LAD and left ventricular cardiac function between ECV group and NECV group. Conclusions. This study revealed that ECV has no significant impact on the maintenance of SR and the recovery of cardiac function. Therefore, ECV could be applied safely to recover SR during the procedure of catheter ablation of persistent atrial fibrillation. PMID:27022500

  11. Electroactive polyurethane/siloxane derived from castor oil as a versatile cardiac patch, part II: HL-1 cytocompatibility and electrical characterizations.

    Science.gov (United States)

    Baheiraei, Nafiseh; Gharibi, Reza; Yeganeh, Hamid; Miragoli, Michele; Salvarani, Nicolò; Di Pasquale, Elisa; Condorelli, Gianluigi

    2016-06-01

    In first part of this experiment, biocompatibility of the newly developed electroactive polyurethane/siloxane films containing aniline tetramer moieties was demonstrated with proliferation and differentiation of C2C12 myoblasts. Here we further assessed the cytocompatibility of the prepared samples with HL1-cell line, the electrophysiological properties and the patch clamp recording of the seeded cells over the selected electroactive sample. Presence of electroactive aniline tetramer in the structure of polyurethane/siloxane led to the increased expression of cardiac-specific genes of HL-1 cells involved in muscle contraction and electrical coupling. Our results showed that expression of Cx43, TrpT-2, and SERCA genes was significantly increased in conductive sample compared to tissue culture plate and the corresponding non-conductive analogous. The prepared materials were not only biocompatible in terms of cellular toxicity, but did not alter the intrinsic electrical characteristics of HL-1 cells. Embedding the electroactive moiety into the prepared films improved the properties of these polymeric cardiac construct through the enhanced transmission of electrical signals between the cells. Based on morphological observation, calcium imaging and electrophysiological recordings, we demonstrated the potential applicability of these materials for cardiac tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1398-1407, 2016. PMID:26822463

  12. Iron deposition following chronic myocardial infarction as a substrate for cardiac electrical anomalies: initial findings in a canine model.

    Directory of Open Access Journals (Sweden)

    Ivan Cokic

    Full Text Available PURPOSE: Iron deposition has been shown to occur following myocardial infarction (MI. We investigated whether such focal iron deposition within chronic MI lead to electrical anomalies. METHODS: Two groups of dogs (ex-vivo (n = 12 and in-vivo (n = 10 were studied at 16 weeks post MI. Hearts of animals from ex-vivo group were explanted and sectioned into infarcted and non-infarcted segments. Impedance spectroscopy was used to derive electrical permittivity ([Formula: see text] and conductivity ([Formula: see text]. Mass spectrometry was used to classify and characterize tissue sections with (IRON+ and without (IRON- iron. Animals from in-vivo group underwent cardiac magnetic resonance imaging (CMR for estimation of scar volume (late-gadolinium enhancement, LGE and iron deposition (T2* relative to left-ventricular volume. 24-hour electrocardiogram recordings were obtained and used to examine Heart Rate (HR, QT interval (QT, QT corrected for HR (QTc and QTc dispersion (QTcd. In a fraction of these animals (n = 5, ultra-high resolution electroanatomical mapping (EAM was performed, co-registered with LGE and T2* CMR and were used to characterize the spatial locations of isolated late potentials (ILPs. RESULTS: Compared to IRON- sections, IRON+ sections had higher[Formula: see text], but no difference in[Formula: see text]. A linear relationship was found between iron content and [Formula: see text] (p1.5% with similar scar volumes (7.28% ± 1.02% (Iron (1.5%, p = 0.51 but markedly different iron volumes (1.12% ± 0.64% (Iron (1.5%, p = 0.02, QT and QTc were elevated and QTcd was decreased in the group with the higher iron volume during the day, night and 24-hour period (p<0.05. EAMs co-registered with CMR images showed a greater tendency for ILPs to emerge from scar regions with iron versus without iron. CONCLUSION: The electrical behavior of infarcted hearts with iron appears to be different from those without iron. Iron within infarcted zones may

  13. Noninvasive reconstruction of cardiac electrical activity: update on current methods, applications and challenges.

    Science.gov (United States)

    Cluitmans, M J M; Peeters, R L M; Westra, R L; Volders, P G A

    2015-06-01

    Electrical activity at the level of the heart muscle can be noninvasively reconstructed from body-surface electrocardiograms (ECGs) and patient-specific torso-heart geometry. This modality, coined electrocardiographic imaging, could fill the gap between the noninvasive (low-resolution) 12-lead ECG and invasive (high-resolution) electrophysiology studies. Much progress has been made to establish electrocardiographic imaging, and clinical studies appear with increasing frequency. However, many assumptions and model choices are involved in its execution, and only limited validation has been performed. In this article, we will discuss the technical details, clinical applications and current limitations of commonly used methods in electrocardiographic imaging. It is important for clinicians to realise the influence of certain assumptions and model choices for correct and careful interpretation of the results. This, in combination with more extensive validation, will allow for exploitation of the full potential of noninvasive electrocardiographic imaging as a powerful clinical tool to expedite diagnosis, guide therapy and improve risk stratification. PMID:25896779

  14. Cardiomyopathy induced by artificial cardiac pacing: myth or reality sustained by evidence?

    Directory of Open Access Journals (Sweden)

    Andrés Di Leoni Ferrari

    2014-09-01

    Full Text Available Implantable cardiac pacing systems are a safe and effective treatment for symptomatic irreversible bradycardia. Under the proper indications, cardiac pacing might bring significant clinical benefit. Evidences from literature state that the action of the artificial pacing system, mainly when the ventricular lead is located at the apex of the right ventricle, produces negative effects to cardiac structure (remodeling, dilatation and function (dissinchrony. Patients with previously compromised left ventricular function would benefit the least with conventional right ventricle apical pacing, and are exposed to the risk of developing higher incidence of morbidity and mortality for heart failure. However, after almost 6 decades of cardiac pacing, just a reduced portion of patients in general would develop these alterations. In this context, there are not completely clear some issues related to cardiac pacing and the development of this cardiomyopathy. Causality relationships among QRS widening with a left bundle branch block morphology, contractility alterations within the left ventricle, and certain substrates or clinical (previous systolic dysfunction, structural heart disease, time from implant or electrical conditions (QRS duration, percentage of ventricular stimulation are still subjecte of debate. This review analyses contemporary data regarding this new entity, and discusses alternatives of how to use cardiac pacing in this context, emphasizing cardiac resynchronization therapy.

  15. Electrical and Hemodynamic Evaluation of Ventricular and Supraventricular Tachycardias with an Implantable Cardiac Stimulator

    Directory of Open Access Journals (Sweden)

    Claudio Pandozi MD; Franco Di Gregorio BiolScD; Carlo Lavalle MD; Renato Pietro Ricci MD; Sabina Ficili MD; Marco Galeazzi MD; Maurizio Russo MD; Angela Pandozi MD; Furio Colivicchi MD; Massimo Santini MD

    2014-06-01

    Full Text Available The discrimination between ventricular and supraventricular tachycardia and the evaluation of their hemodynamic impact are essential issues in the arrhythmia management. A new pacing device features a tachycardia diagnostic system relying on simultaneous recording of the transvalvular impedance (TVI and the iECG, which is an integrated electric signal derived by the whole set of endocardial electrodes. The iECG waveform is sensitive to the pattern of ventricular activation, similarly to the surface ECG. The TVI increases in systole and decreases in diastole, and the amplitude of its cyclic fluctuation is an expression of the effectiveness of the pump function. In order to test the value of these signals in the analysis of a tachycardia, we have assessed the iECG and TVI modifications induced by different SVTs and tolerated and non-tolerated VTs, during electrophysiological studies. In case of SVT, the ventricular component of the iECG maintained the same morphology as in sinus rhythm. The peak-peak amplitude of the TVI fluctuation was reduced to 66 ± 11 % of the individual sinus rhythm reference, but the signal was present at every beat and showed a remarkable stability (variation coefficient 0.19 ± 0.01. In case of a VT, the ventricular component of the iECG was strikingly different than in sinus rhythm. Regular TVI fluctuation was observed with tolerated VTs (peak-peak amplitude 74 ± 6 %; variation coefficient 0.21 ± 0.04. In contrast, with non-tolerated VTs the TVI amplitude was depressed below 40%, and the signal was virtually absent in the event of very fast VT or VF. Our results confirm that the iECG is a reliable tool to quickly discriminate VTs from SVTs and that TVI can provide information on the severity of the hemodynamic impairment produced by a tachycardia, with potential clinical benefit in the follow-up of pacemaker patients. Furthermore, the application of these signals in automatic algorithms of arrhythmia recognition might

  16. Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 1D Simulation Study

    OpenAIRE

    Gómez García, Juan Francisco; Romero Pérez, Lucia; Ferrero De Loma-Osorio, José María; Trenor Gomis, Beatriz Ana

    2014-01-01

    Background: Heart failure is a final common pathway or descriptor for various cardiac pathologies. It is associated with sudden cardiac death, which is frequently caused by ventricular arrhythmias. Electrophysiological remodeling, intercellular uncoupling, fibrosis and autonomic imbalance have been identified as major arrhythmogenic factors in heart failure etiology and progression. Objective: In this study we investigate in silico the role of electrophysiological and structur...

  17. Myocardial remodeling and bioelectric changes in tachycardia-induced heart failure in dogs

    International Nuclear Information System (INIS)

    In this study, electrical and structural remodeling of ventricles was examined in tachycardia-induced heart failure (HF). We studied two groups of weight-matched adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms of congestive HF were observed in both groups. Their hemodynamic parameters were determined and the severity of the HF was evaluated by M-mode echocardiography. Changes in heart morphology were observed by scanning electron and light microscopy. Ventricular action potential duration (APD), as well as the 50 and 90% APD were measured in both groups. All dogs exhibited clinical symptoms of congestive HF after rapid right ventricular pacing for 3 weeks. These data indicate that rapid, right ventricular pacing produces a useful experimental model of low-output HF in dogs, characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility. Electrical and structural myocardial remodeling play an essential role in congestive HF progression, and should thus be prevented

  18. Myocardial remodeling and bioelectric changes in tachycardia-induced heart failure in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Song, B.; Wang, B.N.; Chen, D.N.; Luo, Z.G. [Department of Cardiovascular Medicine, The First Affiliated Hospital, Anhui Medical University, HeFei, Anhui Province (China)

    2013-09-06

    In this study, electrical and structural remodeling of ventricles was examined in tachycardia-induced heart failure (HF). We studied two groups of weight-matched adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms of congestive HF were observed in both groups. Their hemodynamic parameters were determined and the severity of the HF was evaluated by M-mode echocardiography. Changes in heart morphology were observed by scanning electron and light microscopy. Ventricular action potential duration (APD), as well as the 50 and 90% APD were measured in both groups. All dogs exhibited clinical symptoms of congestive HF after rapid right ventricular pacing for 3 weeks. These data indicate that rapid, right ventricular pacing produces a useful experimental model of low-output HF in dogs, characterized by biventricular pump dysfunction, biventricular cardiac dilation, and non-ischemic impairment of left ventricular contractility. Electrical and structural myocardial remodeling play an essential role in congestive HF progression, and should thus be prevented.

  19. Berberine treatment prevents cardiac dysfunction and remodeling through activation of 5'-adenosine monophosphate-activated protein kinase in type 2 diabetic rats and in palmitate-induced hypertrophic H9c2 cells.

    Science.gov (United States)

    Chang, Wenguang; Zhang, Ming; Meng, Zhaojie; Yu, Yang; Yao, Fan; Hatch, Grant M; Chen, Li

    2015-12-15

    Diabetic cardiomyopathy is the major cause of death in type 2 diabetic patients. Berberine is an isoquinoline alkaloid extract from traditional chinese herbs and its hypoglycemic and hypolipidemic effects make it a promising drug for treatment of type 2 diabetes. We examined if berberine improved cardiac function and attenuated cardiac hypertrophy and fibrosis in high fat diet and streptozotocin induced-type 2 diabetic rats in vivo and reduced expression of hypertrophy markers in palmitate-induced hypertrophic H9c2 cells in vitro. Treatment of diabetic animals with berberine partially improved cardiac function and restored fasting blood insulin, fasting blood glucose, total cholesterol, and triglyceride levels to that of control. In addition, berberine treatment of diabetic animals increased cardiac 5'-adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (AKT) activation and reduced glycogen synthase kinase 3 beta (GSK3β) activation compared to control. Palmitate incubation of H9c2 cells resulted in cellular hypertrophy and decreased expression of alpha-myosin heavy chain (α-MHC) and increased expression of beta-myosin heavy chain (β-MHC) compared to controls. Berberine treatment of palmitate-incubated H9c2 cells reduced hypertrophy, increased α-MHC expression and decreased β-MHC expression. In addition, berberine treatment of palmitate-incubated H9c2 cells increased AMPK and AKT activation and reduced GSK3β activation. The presence of the AMPK inhibitor Compound C attenuated the effects of berberine. The results strongly indicate that berberine treatment may be protective against the development of diabetic cardiomyopathy. PMID:26522928

  20. Comparison of transthoracic electrical bioimpedance cardiac output measurement with thermodilution method in post coronary artery bypass graft patients

    Directory of Open Access Journals (Sweden)

    Sharma Vikas

    2011-01-01

    Full Text Available Transthoracic electrical bioimpedance (TEB has been proposed as a non-invasive, continuous, and cost-effective method of cardiac output (CO measurement. In this prospective, non-randomized, clinical study, we measured CO with NICOMON (Larsen and Toubro Ltd., Mysore, India and compared it with thermodilution (TD method in patients after off-pump coronary artery bypass (OPCAB graft surgery. We also evaluated the effect of ventilation (mechanical and spontaneous on the measurement of CO by the two methods. Forty-six post-OPCAB patients were studied at five predefined time points during controlled ventilation and at five time points when breathing spontaneously. A total of 230 data pairs of CO were obtained. During controlled ventilation, TD CO values ranged from 2.29 to 6.74 L/min (mean 4.45 ± 0.85 L/min, while TEB CO values ranged from 1.70 to 6.90 L/min (mean 4.43 ± 0.94 L/min. The average correlation (r was 0.548 (P = 0.0002, accompanied by a bias of 0.015 L/min and precision of 0.859 L/min. In spontaneously breathing patients, TD CO values ranged from 2.66 to 6.92 L/min (mean 4.66 ± 0.76 L/min, while TEB CO values ranged from 3.08 to 6.90 L/min (mean 4.72 ± 0.82 L/min. Their average correlation was relatively poor (r = 0.469, P= 0.002, accompanied by a bias of −0.059 L/min and precision of 0.818 L/min. The overall percent errors between TD CO and TEB CO were 19.3% (during controlled ventilation and 17.4% (during spontaneous breathing, respectively. To conclude, a fair correlation was found between TD CO and TEB CO measurements among post-OPCAB patients during controlled ventilation. However, the correlation was weak in spontaneously breathing patients.

  1. Mouse models of SCN5A-related cardiac arrhythmias

    Directory of Open Access Journals (Sweden)

    Flavien eCharpentier

    2012-06-01

    Full Text Available Mutations of SCN5A gene, which encodes the α-subunit of the voltage-gated Na+ channel NaV1.5, underlie hereditary cardiac arrhythmic syndromes such as the type 3 long QT syndrome, cardiac conduction diseases, the Brugada syndrome, the sick sinus syndrome, atrial standstill and numerous overlap syndromes. Patch-clamp studies in heterologous expression systems have provided important information to understand the genotype-phenotype relationships of these diseases. However, they could not clarify how SCN5A mutations can be responsible for such a large spectrum of diseases, for the late age of onset or the progressiveness of some of these diseases and for the overlapping syndromes. Genetically modified mice rapidly appeared as promising tools for understanding the pathophysiological mechanisms of cardiac SCN5A-related arrhythmic syndromes and several mouse models have been established. This paper reviews some of the results obtained on these models that, for most of them, recapitulate the clinical phenotypes of the patients. It also points out that these models also have their own limitations. Overall, mouse models appear as powerful tools to elucidate the pathophysiological mechanisms of SCN5A-related diseases and offer the opportunity to investigate the secondary cellular consequences of SCN5A mutations such as the expression remodelling of other genes that might participate to the overall phenotype. Finally, they constitute useful tools for addressing the role of genetic and environmental modifiers on cardiac electrical activity.

  2. Adverse Remodeling of the Electrophysiological Response to Ischemia-Reperfusion in Human Heart Failure Is Associated with Remodeling of Metabolic Gene Expression

    Science.gov (United States)

    Ng, Fu Siong; Holzem, Katherine M.; Koppel, Aaron C.; Janks, Deborah; Gordon, Fabiana; Wit, Andrew L.; Peters, Nicholas S.; Efimov, Igor R.

    2014-01-01

    Background Ventricular arrhythmias occur more frequently in heart failure during episodes of ischemia-reperfusion (I-R), although the mechanisms underlying this in humans are unclear. We assessed, in explanted human hearts, the remodeled electrophysiological response to acute I-R in heart failure, and its potential causes, including the remodeling of metabolic gene expression. Methods and Results We optically mapped coronary-perfused left ventricular wedge preparations from 6 human end-stage failing hearts (F) and 6 donor hearts rejected for transplantation (D). Preparations were subjected to 30 minutes of global ischemia, followed by 30 minutes of reperfusion. Failing hearts had exaggerated electrophysiological responses to I-R, with greater action potential duration (APD) shortening (p<0.001 at 8 minutes ischemia; p=0.001 at 12 minutes ischemia) and greater conduction slowing during ischemia, delayed recovery of electrical excitability following reperfusion (F 4.8±1.8 vs. D 1.0±0 mins, p<0.05), and incomplete restoration of APD and conduction velocity early after reperfusion. Expression of 46 metabolic genes were probed using custom-designed TaqMan arrays, using extracted RNA from 15 failing and 9 donor hearts. Ten genes important in cardiac metabolism were downregulated in heart failure, with SLC27A4 and KCNJ11 significantly downregulated at a false discovery rate of 0%. Conclusions We demonstrate, for the first time in human hearts, that the electrophysiological response to I-R in heart failure is accelerated during ischemia with slower recovery following reperfusion. This can enhance spatial conduction and repolarization gradients across the ischemic border and increase arrhythmia susceptibility. This adverse response was associated with downregulation of expression of cardiac metabolic genes. PMID:25114062

  3. Effect of spironolactone on atrial structural remodeling and electrical remodeling in the canine atrial fibrillation model%螺内酯在犬心房颤动模型中对心房结构重构及电重构的影响

    Institute of Scientific and Technical Information of China (English)

    吕云波; 曾秋棠; 钟金鹏

    2013-01-01

    Obiective:To observe the effect of spironolactone on atrial structure remodeling and electrical remodeling in the canine atrial fibrillation model.Method:Twenty-four healthy adult dogs were selected and randomly divided into control group (n=8,normal feeding),atrial fibrillation group (n=8,pacemaker implantation and normal feeding) and spironolactone group (n=8,pacemaker implantation and spironolactone intervention).Pacemaker implantation and rapid atrial pacing were adopted to establish the canine atrial fibrillation model.After a week the model was successfully established and left atrial tissue was taken to determination the level of matrix metalloproteinase (MMP)-9,tissue inhibitor-1 of MMP (TIMP-1) and miRNA-101.Then we compared the above indexes between different groups.Result:Compared to control group,the level of MMP-9,MMP-9/TIMP-1 ratio were significantly higher in atrial fibrillation group and spironolactone group (both P<0.01),the level of TIMP1 was significantly lower in atrial fibrillation group (P<0.01) and was significantly higher in spironolactone group (P<0.01); Compared to atrial fibrillation group,the level of MMP-9 in spironolactone group was lower (P<0.05),the expression of TIMP-1 was higher (P < 0.05),the ratio of MMP-9/TIMP-1 declined (P< 0.05).Quantitative analysis showed that the miRNA-101 in atrial fibrillation group obviously down-regulated compared with in control group and spironolactone group (both P<0.05),and it didn't show statistically significant difference between spironolactone group and control group.Conclusion:Atrial fibrillation caused by rapid atrial pacing could lead atrial structural remodeling and electrical remodeling.Spironolactone intervention could up-regulate miRNA-101,decrease MMP-9 levels and elevate TIMP-1 levels,which play a role of prevention and treatment for atrial fibrillation.%目的:观察螺内酯在犬心房颤动(房颤)模型中对心房结构重构和电重构的影响.方法:24只健康

  4. Immunoregulation of bone remodelling

    Science.gov (United States)

    Singh, Ajai; Mehdi, Abbass A; Srivastava, Rajeshwer N; Verma, Nar Singh

    2012-01-01

    Remodeling, a continuous physiological process maintains the strength of the bones, which maintains a delicate balance between bone formation and resorption process. This review gives an insight to the complex interaction and correlation between the bone remodeling and the corresponding changes in host immunological environment and also summarises the most recent developments occuring in the understanding of this complex field. T cells, both directly and indirectly increase the expression of receptor activator of nuclear factor kB ligand (RANKL); a vital step in the activation of osteoclasts, thus positively regulates the osteoclastogenesis. Though various cytokines, chemikines, transcription factors and co-stimulatory molecules are shared by both skeletal and immune systems, but researches are being conducted to establish and analyse their role and / or control on this complex but vital process. The understanding of this part of research may open new horizons in the management of inflammatory and autoimmune diseases, resulting into bone loss and that of osteoporosis also. PMID:22837895

  5. 二尖瓣环位移对肥厚性重构患者左室收缩功能的评估作用%Evaluation of left ventricular systolic dysfunction by mitral annular displacement in patients with cardiac hypertrophy and remodeling

    Institute of Scientific and Technical Information of China (English)

    吴卫华; 黄艳; 陆静; 马兰; 魏松霞; 谢晓奕; 刘奇志; 王雷; 杨玲

    2011-01-01

    目的 应用超声二维斑点追踪显像技术测定二尖瓣环位移(MAD),探讨其在评估肥厚性重构所致的早期左室收缩功能减退方面的临床应用价值.方法 选择86例左室射血分数(LVEF)正常(>50%)的各类心肌肥厚(左室壁厚度≥12 mm)患者作为研究对象.采用Philips Sonos iE33超声仪进行检查,先通过M型超声计算出相对室壁厚度(RWT),然后取心尖四腔观分别采集二维和实时三维全容积(RT3D)图像.应用QLAB 6.2在机量化分析软件分别获取MAD相关参数(包括二尖瓣环中点位移和左室长轴缩短率)和经RT3D图像测得左室射血分数(RT3D-LVEF);计算三维心肌重构指标,包括左室舒末容积指数(LVEDVI)和左室质量指数(LVMI).将心肌肥厚患者中RWT<0.45且LVMI在正常范围内的患者归入肥厚正常几何构型组(HNG组),其余归入肥厚重构组(HR组);以46名年龄相匹配的健康志愿者作为正常对照组.结果 HNG组、HR组和正常对照组的RT3D-LVEF均在正常范围内,两两比较差异均无统计学意义(P>0.05).HR组的MAD各值和LVEDVI均显著低于HNG组和正常对照组,差异均有统计学意义(P<0.01或P<0.05);HNG组与正常对照组MAD相关参数值和LVEDVI比较差异均无统计学意义(P>0.05).Bland-Altman分析显示MAD各值的可重复性较高.结论 在心肌肥厚性重构患者中,与LVEF比较,MAD能更早地反映患者的左室收缩功能减退情况.%Objective To investigate the value of mitral annular displacement (MAD) by two-dimensional speckle tracking in evaluating left ventricular systolic dysfunction in patients with cardiac hypertrophy and remodeling.Methods Eightysix patients with cardiac hypertrophy ( left ventricular wall thickness ≥ 12 mm) and normal left ventricular ejection fraction (LVEF) ( > 50% ) were selected.Philips Sonos iE33 ultrasound device was used for examinations.Relative wall thickness (IRWT) was calculated by M mode ultrasound, and two

  6. Restenosis and remodeling

    International Nuclear Information System (INIS)

    Percutaneous Transluminal Coronary Angioplasty (PTCA) remains limited by restenosis that occurs in 30 to 50% of patients with coronary artery disease. During the last decade, numerous agents have been used to prevent restenosis. Despite positive results in animal models, no pharmacological therapy has been found to significantly decrease the risk of restenosis in humans. These discrepancies between animal models and clinical situation were probably related to an incomplete understanding of the mechanism of restenosis. Neointimal thickening occurs in response to experimental arterial injury with a balloon catheter. Neointimal formation involves different steps: smooth muscle cell activation, proliferation and migration, and the production of extracellular matrix. The factors that control neointimal hyperplasia include growth factors humoral factors and mechanical factors. Arterial remodeling also plays a major role in the restenosis process. Studies performed in animal and human subjects have established the potentials for 'constrictive remodeling' to reduce the post-angioplasty vessel area, thereby indirectly narrowing the vessel lumen and thus contributing to restenosis. The reduction of restenosis rate in patients with intracoronary stent implantation has been attributed to the preventive effect of stent itself for this negative remodeling. In addition to these mechanism for restenosis, intraluminal or intra-plaque thrombus formation, reendothelialization and apoptosis theories have been introduced and confirmed at least in part

  7. Diagnostic Accuracy of a New Cardiac Electrical Biomarker for Detection of Electrocardiogram Changes Suggestive of Acute Myocardial Ischemic Injury

    OpenAIRE

    Schreck, David M; Fishberg, Robert D

    2013-01-01

    Objective A new cardiac “electrical” biomarker (CEB) for detection of 12-lead electrocardiogram (ECG) changes indicative of acute myocardial ischemic injury has been identified. Objective was to test CEB diagnostic accuracy. Methods This is a blinded, observational retrospective case-control, noninferiority study. A total of 508 ECGs obtained from archived digital databases were interpreted by cardiologist and emergency physician (EP) blinded reference standards for presence of acute myocardi...

  8. Cardiac sympathetic denervation in patients with refractory ventricular arrhythmias or electrical storm: Intermediate and long-term follow-up

    OpenAIRE

    Vaseghi, M; Gima, J; Kanaan, C; Ajijola, OA; Marmureanu, A; Mahajan, A.; Shivkumar, K

    2014-01-01

    Background Left and bilateral cardiac sympathetic denervation (CSD) have been shown to reduce burden of ventricular arrhythmias acutely in a small number of patients with ventricular tachyarrhythmia (VT) storm. The effects of this procedure beyond the acute setting are unknown. Objective The purpose of this study was to evaluate the intermediate and long-term effects of left and bilateral CSD in patients with cardiomyopathy and refractory VT or VT storm. Methods Retrospective analysis of medi...

  9. Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-β1 expression and fibrosis in minipigs with ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    LU Lin; SHEN Wei-feng; ZHANG Qi; XU Yan; ZHU Zheng-bin; GENG Liang; WANG Ling-jie; JIN Cao; CHEN Qiu-jing; Ann Marie Schmidt

    2010-01-01

    Background The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n=5) or saline (control group, n=5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-β1was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 5.1) to (32.3 5.6) ml, P <0.05) and end-systolic volume (from (8.3 3.2) to (15.2 4.1) ml, P <0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 13.3)% to (50.2 11.9)%, P<0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P<0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P<0.05). Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

  10. Myocardial reverse remodeling: how far can we rewind?

    Science.gov (United States)

    Rodrigues, Patrícia G; Leite-Moreira, Adelino F; Falcão-Pires, Inês

    2016-06-01

    Heart failure (HF) is a systemic disease that can be divided into HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). HFpEF accounts for over 50% of all HF patients and is typically associated with high prevalence of several comorbidities, including hypertension, diabetes mellitus, pulmonary hypertension, obesity, and atrial fibrillation. Myocardial remodeling occurs both in HFrEF and HFpEF and it involves changes in cardiac structure, myocardial composition, and myocyte deformation and multiple biochemical and molecular alterations that impact heart function and its reserve capacity. Understanding the features of myocardial remodeling has become a major objective for limiting or reversing its progression, the latter known as reverse remodeling (RR). Research on HFrEF RR process is broader and has delivered effective therapeutic strategies, which have been employed for some decades. However, the RR process in HFpEF is less clear partly due to the lack of information on HFpEF pathophysiology and to the long list of failed standard HF therapeutics strategies in these patient's outcomes. Nevertheless, new proteins, protein-protein interactions, and signaling pathways are being explored as potential new targets for HFpEF remodeling and RR. Here, we review recent translational and clinical research in HFpEF myocardial remodeling to provide an overview on the most important features of RR, comparing HFpEF with HFrEF conditions. PMID:26993225

  11. 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.

  12. A exposição crônica à fumaça do cigarro resulta em remodelação cardíaca e prejuízo da função ventricular em ratos Chronic cigarette smoke exposure results in cardiac remodeling and impaired ventricular function in rats

    Directory of Open Access Journals (Sweden)

    Édson Castardeli

    2005-04-01

    Full Text Available OBJETIVO: Determinar as alterações cardíacas estruturais e funcionais causadas pela exposição à fumaça do cigarro em ratos. MÉTODOS: Os animais foram aleatoriamente distribuídos em dois grupos: fumante (F, composto por 10 animais, expostos à fumaça do cigarro, na taxa de 40 cigarros/dia e controle (C, constituído por 10 animais não submetidos à exposição. Após 4 meses, os animais foram submetidos a estudo morfológico e funcional por meio do ecocardiograma. As variáveis estudadas foram analisadas pelo teste t ou pelo teste de Mann-Whitney. RESULTADOS: Os ratos fumantes apresentaram maior átrio esquerdo (F=4,2± 0,7mm; C=3,5±0,6mm; pOBJECTIVE: To determine the cardiac structural and functional alterations caused by cigarette smoke exposure in rats. METHODS: The animals were randomly distributed into the following 2 groups: 1 smokers (S, comprising 10 animals exposed to cigarette smoke at a rate of 40 cigarettes/day; and 2 control (C, comprising 10 animals not exposed to cigarette smoke. After 4 months, the animals underwent morphological and functional study with echocardiography. The variables studied were analyzed by use of the t test or the Mann-Whitney test. RESULTS: The smoking rats had a greater left atrium (S=4.2±0.7mm; C=3.5±0.6mm; P<0.05, and greater left ventricular diastolic (S=7.9±0.7mm; C=7.2±0.5mm; P<0.05 and systolic (S=4.1±0.5; C=3.4±0.5; P<0.05 diameters. The left ventricular mass index was greater in the smoking animals (S=1.5mg/kg±0.2; C=1.3mg/kg±0.2; P<0.05, and the ejection fraction (S=0.85±0.03; C=0.89±0.03; P<0.05 and the shortening fraction (S=47.8%±3.7; C=52.7%±4.6; P<0.05 were greater in the control group. No differences were observed in the diastolic transmitral flow variables (E wave, A wave, and E/A ratio. CONCLUSION: Chronic cigarette smoke exposure results in cardiac remodeling with a decrease in ventricular functional capacity.

  13. No-Regrets Remodeling, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  14. Physiological and pathological cardiac hypertrophy.

    Science.gov (United States)

    Shimizu, Ippei; Minamino, Tohru

    2016-08-01

    The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy. PMID:27262674

  15. An open source HPC-enabled model of cardiac defibrillation of the human heart

    OpenAIRE

    Bernabeu Llinares, Miguel Oscar; Pitt-Francis, Joe; Rodriguez, Blanca; Kay, David

    2011-01-01

    Sudden cardiac death following cardiac arrest is a major killer in the industrialised world. The leading cause of sudden cardiac death are disturbances in the normal electrical activation of cardiac tissue, known as cardiac arrhythmia, which severely compromise the ability of the heart to fulfill the body's demand of oxygen. Ventricular fibrillation (VF) is the most deadly form of cardiac arrhythmia. Furthermore, electrical defibrillation through the application of strong electric shocks to t...

  16. Implantable Defibrillators Improve Survival in Patients With Mildly Symptomatic Heart Failure Receiving Cardiac Resynchronization Therapy

    DEFF Research Database (Denmark)

    Gold, Michael R; Daubert, Jean-Claude; Abraham, William T;

    2013-01-01

    Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. These benefits have been noted with both CRT-pacemakers as well as those devices with defibrillator backup (CRT...

  17. 上腔静脉内低强度迷走神经刺激调控心房急性电重构%The neural regulation of atria acute electrical remodeling by nerve stimulation

    Institute of Scientific and Technical Information of China (English)

    江洪; 赵劲波; 李元红; 余锂镭; 鲁志兵; 黄兵; 何文博

    2013-01-01

    Objective To investigate the effects of superior vena cava low level vagal nerve stimulation on left atrial acute electrical remodeling.Methods 12 adult dogs were underwent left and right fourth intercostal thoracotomy after anesthesia,and then were randomly divided into two groups.The control group (n =6) was only received 6 h-LARP(left atrial rapid pacing) ; The SVC-LLS (superior vena cava low level vagal nerve stimulation)) group (n =6) with 6 h-LARP was 50% threshold SVC-LLS during later 3 h.The threshold was defined as the lowest voltage that slowed down sinus rhythm or atrioventricular conduction via SVC-LLS.Atrial and pulmonary vein effective refractory period (ERP) and atrial fibrillation window of vulnerability (AFWOV) were measured after each hour pacing.Results ①In the control group,LARP significantly shortened ERP in the first 3 hours (P<0.01) but not in the later 3 hours.In SVC-LLS group,ERP was gradually shortened in the first 3 hours with significant shorten at 3 hours(P<0.05),while in the later 3 hours,ERP was gradually prolonged and ERP at 6 hours was significantly prolonged while compared to 3 hours.②In the control group,∑ AFWOV ascended gradually with significance both at 3 hours(P<0.01) and 6 hours (P<0.01),ERP dispersion was significantly rised at 3 hours(P<0.01)but not 6 hours.In SVC-LLS group,both ∑AFWOV and ERP dispersion ascended gradually in the first 3 hours but declined in the later 3 hours with a significance differences between 6 hours and 3 hours.Conclusions The acute electrical remodeling from LARP can be reversed by SVC-LLS.%目的 探讨上腔静脉内低强度迷走神经刺激(SVC-LLS)对左房急性电重构的影响.方法 12只成年犬,麻醉后经左、右第4肋间开胸,通过6h左房快速起搏(LARP)诱导心房急性电重构.犬随机分为2组:对照组6只,为6h的LARP;SVC-LLS组6只,在6 hLARP中的后3h内同时给予50%阈电压的SVC-LLS.上腔静脉内刺激迷走神经引起窦性心率

  18. The effects of cytoskeletal disruption and mechanical load on cardiac conduction

    OpenAIRE

    Wright, Adam Thomas

    2010-01-01

    Myocardial disease is often associated with altered cardiac conduction and increased incidence of arrhythmia. Underlying mechanisms responsible for changes in conduction include altered calcium handling, myocardial remodeling, and mechanically induced changes in electrophysiology. The goal of this work was to utilize optical mapping experimental techniques and genetically modified mouse models to investigate two of these mechanisms: myocardial remodeling associated with disruption of the cyto...

  19. Vitamin D and Cardiac Differentiation.

    Science.gov (United States)

    Kim, Irene M; Norris, Keith C; Artaza, Jorge N

    2016-01-01

    Calcitriol (1,25-dihydroxycholecalciferol or 1,25-D3) is the hormonally active metabolite of vitamin D. Experimental studies of vitamin D receptors and 1,25-D3 establish calcitriol to be a critical regulator of the structure and function of the heart. Clinical studies link vitamin D deficiency with cardiovascular disease (CVD). Emerging evidence demonstrates that calcitriol is highly involved in CVD-related signaling pathways, particularly the Wnt signaling pathway. Addition of 1,25-D3 to cardiomyocyte cells and examination of its effects on cardiomyocytes and mainly Wnt11 signaling allowed the specific characterization of the role of calcitriol in cardiac differentiation. 1,25-D3 is demonstrated to: (i) inhibit cell proliferation without promoting apoptosis; (ii) decrease expression of genes related to the regulation of the cell cycle; (iii) promote formation of cardiomyotubes; (iv) induce expression of casein kinase-1-α1, a negative regulator of the canonical Wnt signaling pathway; and (v) increase expression of noncanonical Wnt11, which has been recognized to induce cardiac differentiation during embryonic development and in adult cells. Thus, it appears that vitamin D promotes cardiac differentiation through negative modulation of the canonical Wnt signaling pathway and upregulation of noncanonical Wnt11 expression. Future work to elucidate the role(s) of vitamin D in cardiovascular disorders will hopefully lead to improvement and potentially prevention of CVD, including abnormal cardiac differentiation in settings such as postinfarction cardiac remodeling. PMID:26827957

  20. High Methionine Diet Poses Cardiac Threat: A Molecular Insight.

    Science.gov (United States)

    Chaturvedi, Pankaj; Kamat, Pradip K; Kalani, Anuradha; Familtseva, Anastasia; Tyagi, Suresh C

    2016-07-01

    High methionine diet (HMD) for example red meat which includes lamb, beef, pork can pose cardiac threat and vascular dysfunction but the mechanisms are unclear. We hypothesize that a diet rich in methionine can malfunction the cardiovascular system in three ways: (1) by augmenting oxidative stress; (2) by inflammatory manifestations; and (3) by matrix/vascular remodeling. To test this hypothesis we used four groups of mice: (1) WT; (2) WT + methionine; (3) CBS(+/-) ; (4) CBS(+/-) +methionine. We observed high oxidative stress in mice fed with methionine which was even higher in CBS(+/-) and CBS(+/-) +methionine. Higher oxidative stress was indicated by high levels of SOD-1 in methionine fed mouse hearts whereas IL-1β, IL-6, TNFα, and TLR4 showed high inflammatory manifestations. The upregulated levels of eNOS/iNOS and upregulated levels of MMP2/MMP9 along with high collagen deposition indicated vascular and matrix remodeling in methionine fed mouse. We evaluated the cardiac function which was dysregulated in the mice fed with HMD. These mice had decreased ejection fraction and left ventricular dysfunction which subsequently leads to adverse cardiac remodeling. In conclusion, our study clearly shows that HMD poses a cardiac threat by increasing oxidative stress, inflammatory manifestations, matrix/vascular remodeling, and decreased cardiac function. J. Cell. Physiol. 231: 1554-1561, 2016. © 2015 Wiley Periodicals, Inc. PMID:26565991

  1. Cardiac tissue engineering

    Directory of Open Access Journals (Sweden)

    MILICA RADISIC

    2005-03-01

    Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

  2. Electrical admittance for filling of the heart during lower body negative pressure in humans

    DEFF Research Database (Denmark)

    Cai, Yan; Holm, Søren; Jenstrup, Morten; Strømstad, Morten; Eigtved, Annika; Warberg, Jørgen; Højgaard, Liselotte; Friberg, Lars; Secher H., Niels

    cardiac output, electrical impedance, heart rate, positron emission tomography, technetium-labeled erythrocytes......cardiac output, electrical impedance, heart rate, positron emission tomography, technetium-labeled erythrocytes...

  3. Protective role of heme oxygenase-1 in atrial remodeling.

    Science.gov (United States)

    Yeh, Yung-Hsin; Hsu, Lung-An; Chen, Ying-Hwa; Kuo, Chi-Tai; Chang, Gwo-Jyh; Chen, Wei-Jan

    2016-09-01

    Structural and electrical remodeling in the atrium constitutes the main feature of atrial fibrillation (AF), which is characterized by increased oxidative stress. Heme oxygenase-1 (HO-1) is a potent anti-oxidant system that may provide protection against various oxidative stress-related diseases. The aim of this study is to investigate whether HO-1 has a protective effect on AF-related remodeling. Cultured atrium-derived myocytes (HL-1 cell line) were used to evaluate tachypacing-induced oxidative stress, structural, and electrical remodeling. Transforming growth factor-β (TGF-β) was utilized to assess collagen (a main fibrosis-related protein) expression in atrial fibroblasts. Tachypacing in HL-1 myocytes and treatment of atrial fibroblasts with TGF-β enhanced the expression of HO-1, both of which were mediated by the activation of nuclear factor erythroid-2-related factor 2. Over-expression of HO-1 in HL-1 cells attenuated tachypacing-induced oxidative stress, myofibril degradation, down-regulation of L-type calcium channel, and shortening of action potential duration. Furthermore, HO-1 over-expression in atrial fibroblasts blocked the up-regulation of collagen by TGF-β, implicating a protective role of HO-1 in structural and electrical remodeling in the atrium. In vivo, HO-1(-/-) mice exhibited a higher degree of oxidative stress, myofibril degradation, and collagen deposit in their atria than wild-type mice. Moreover, burst atrial pacing induced a greater susceptibility to AF in HO-1(-/-) mice than in wild-type mice. In conclusion, a negative-feedback regulation of HO-1 in activated atrial myocytes and fibroblasts may provide protection against AF-related remodeling and AF development. PMID:27562817

  4. Cardiac Tissue Engineering

    OpenAIRE

    MILICA RADISIC; GORDANA VUNJAK-NOVAKOVIC

    2009-01-01

    We hypothesized that clinically sized (1-5 mm thick),compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3) can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of p...

  5. Simulated Microgravity and Recovery-Induced Remodeling of the Left and Right Ventricle

    Science.gov (United States)

    Zhong, Guohui; Li, Yuheng; Li, Hongxing; Sun, Weijia; Cao, Dengchao; Li, Jianwei; Zhao, Dingsheng; Song, Jinping; Jin, Xiaoyan; Song, Hailin; Yuan, Xinxin; Wu, Xiaorui; Li, Qi; Xu, Qing; Kan, Guanghan; Cao, Hongqing; Ling, Shukuan; Li, Yingxian

    2016-01-01

    Physiological adaptations to microgravity involve alterations in cardiovascular systems. These adaptations result in cardiac remodeling and orthostatic hypotension. However, the response of the left ventricle (LV) and right ventricle (RV) following hindlimb unloading (HU) and hindlimb reloading (HR) is not clear and the underlying mechanism remains to be understood. In this study, three groups of mice were subjected to HU by tail suspension for 28 days. Following this, two groups were allowed to recover for 7 or 14 days. The control group was treated equally, with the exception of tail suspension. Echocardiography was performed to detect the structure and function changes of heart. Compared with the control, the HU group of mice showed reduced LV-EF (ejection fraction), and LV-FS (fractional shortening). However, mice that were allowed to recover for 7 days after HU (HR-7d) showed increased LVIDs (systolic LV internal diameter) and LV Vols (systolic LV volume). Mice that recovered for 14 days (HR-14d) returned to the normal state. In comparison, RV-EF and RV-FS didn't recover to the normal conditions till being reloaded for 14 days. Compared with the control, RVIDd (diastolic RV internal diameter), and RV Vold (diastolic RV volume) were reduced in HU group and recovered to the normal conditions in HR-7d and HR-14d groups, in which groups RVIDs (systolic RV internal diameter) and RV Vols (systolic RV volume) were increased. Histological analysis and cardiac remodeling gene expression results indicated that HU induces left and right ventricular remodeling. Western blot demonstrated that the phosphorylation of HDAC4 and ERK1/2 and the ratio of LC3-II / LC3-I, were increased following HU and recovered following HR in both LV and RV, and the phosphorylation of AMPK was inhibited in both LV and RV following HU, but only restored in LV following HR for 14 days. These results indicate that simulated microgravity leads to cardiac remodeling, and the remodeling changes can

  6. Remodeling of alveolar septa after murine pneumonectomy.

    Science.gov (United States)

    Ysasi, Alexandra B; Wagner, Willi L; Bennett, Robert D; Ackermann, Maximilian; Valenzuela, Cristian D; Belle, Janeil; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-06-15

    In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P > 0.05), but a significant decrease in the length of a subset of septal ends ("E"). Septal retraction, observed in 20-30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung (P surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling. PMID:26078396

  7. Calpain inhibition prevents pacing-induced cellular remodeling in a HL-1 myocyte model for atrial fibrillation

    NARCIS (Netherlands)

    Brundel, BJJM; Kampinga, HH; Henning, RH

    2004-01-01

    Objective: Atrial fibrillation (AF) is a progressive disease. Previously, clinical and animal experimental studies in AF revealed a variety of myocyte remodeling processes including L-type Ca(2+) channel reduction and structural changes, which finally result in electrical remodeling and contractile

  8. Cardiac rehabilitation

    Science.gov (United States)

    ... attack or other heart problem. You might consider cardiac rehab if you have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery Heart transplant Procedures such as angioplasty and stenting In some ...

  9. Cardiac Rehabilitation

    Science.gov (United States)

    Cardiac rehabilitation (rehab) is a medically supervised program to help people who have A heart attack Angioplasty or coronary artery bypass grafting for coronary heart disease A heart valve repair or replacement A ...

  10. Cardiac sarcoidosis

    OpenAIRE

    Costello BT; Nadel J.; Taylor AJ

    2016-01-01

    Benedict T Costello,1,2 James Nadel,3 Andrew J Taylor,1,21Department of Cardiovascular Medicine, The Alfred Hospital, 2Baker IDI Heart and Diabetes Research Institute, Melbourne, VIC, 3School of Medicine, University of Notre Dame, Sydney, NSW, Australia Abstract: Cardiac sarcoidosis is a rare but life-threatening condition, requiring a high degree of clinical suspicion and low threshold for investigation to make the diagnosis. The cardiac manifestations include heart failure, conducting syst...

  11. Postmyocardial Infarct Remodeling and Heart Failure: Potential Contributions from Pro- and Antiaging Factors

    Directory of Open Access Journals (Sweden)

    Halliday A. Idikio

    2011-01-01

    Full Text Available Myocardial infarction and adverse postinfarct remodeling in older persons lead to poor outcome and need greater understanding of the contributions of age-related factors on abnormal cardiac function and management. In this perspective, how normal aging processes could contribute to the events of post-myocardial infarction and remodeling is reviewed. Post-myocardial infarction and remodeling involve cardiomechanical factors and neurohormonal response. Many factors prevent or accelerate aging including immunosenescence, recruitment and regeneration of stem cells, telomere shortening, oxidative damage, antiaging hormones klotho and melatonin, nutrition, and Sirtiun protein family, and these factors could affect post-MI remodeling and heart failure. Interest in stem cell repair of myocardial infarcts to mitigate post-MI remodeling needs more information on aging of stem cells, and potential effects on stem cell use in infarct repair. Integrating genomics and proteomics methods may help find clinically novel therapy in the management of post-MI remodeling and heart failure in aged individuals.

  12. The effect of endotoxin on the controllability of cardiac rhythm in rats

    International Nuclear Information System (INIS)

    Decreased heart rate variability (HRV) has both diagnostic and prognostic value in patients with sepsis. However, it is not known whether reduced HRV in sepsis reflects an altered input from the autonomic nervous system or a remodeling of the cardiac pacemaker cells by inflammatory mediators. The present study aimed to investigate the effect of endotoxin on the heart rate dynamics of a denervated isolated heart in rats. Saline or endotoxin was injected into rats and their hearts were isolated and perfused. Atrial electrical activity was recorded and memory length in the time-series was assessed using inverse statistical analysis. Memory was defined as a statistical feature that lasts for a period of time and distinguishes the time-series from a random process. Endotoxaemic hearts exhibited a prolonged memory compared to the controls with respect to observing rare events. This indicates that a sudden decelerating event could potentially affect the cardiac rhythm of an endotoxaemic heart for a longer time than the controls. The prolongation of memory is indirectly linked to a reduced controllability in a complex system; therefore our data may provide evidence for a reduced controllability in cardiac rhythm following endotoxaemia. (paper)

  13. Chronic hypoxia inhibits MMP-2 activation and cellular invasion in human cardiac myofibroblasts

    OpenAIRE

    Riches, Kirsten; Morley, Michael E.; Turner, Neil A; O'Regan, David J; Ball, Stephen G; Peers, Chris; Porter, Karen E

    2009-01-01

    Cardiac myofibroblasts are pivotal to adaptive remodelling after myocardial infarction (MI). These normally quiescent cells invade and proliferate as a wound healing response, facilitated by activation of matrix metalloproteinases, particularly MMP-2. Following MI these reparative events occur under chronically hypoxic conditions yet the mechanisms by which hypoxia might modulate MMP-2 activation and cardiac myofibroblast invasion have not been investigated. Human cardiac myofibroblasts cultu...

  14. Maternal cardiac adaptations to a physical exercise program during pregnancy

    OpenAIRE

    Perales, María; Santos-Lozano, Alejandro; Sanchís-Gomar, Fabián; Luaces, María; Pareja Galeano, Helios; Garatachea, Nuria; Barakat, Rubén; Lucía Mulas, Alejandro

    2016-01-01

    INTRODUCTION: Scarce evidence exists regarding the effects of regular pregnancy exercise on maternal cardiovascular health. We aimed to study, using a randomized controlled trial design, the effects of pregnancy exercise on: echocardiographic indicators of hemodynamics, cardiac remodeling and left ventricular function, and cardiovascular disease (CVD) risk factors. METHODS: 241 healthy pregnant women were assigned to a control (standard care) or intervention (exercise) group (initi...

  15. Reversal of pulmonary vein remodeling after catheter ablation of atrial fibrillation

    OpenAIRE

    Wu, Jia-hui; Li, Hung-Kei; Couri, Daniel M; Araoz, Philip A; Lee, Ying-Hsiang; Ma, Chang-Sheng; Packer, Douglas L.; Cha, Yong-Mei

    2016-01-01

    Background Pulmonary veins (PV) and the atria undergo electrical and structural remodeling in atrial fibrillation (AF). This study aimed to determine PV and left atrial (LA) reverse remodeling after catheter ablation for AF assessed by chest computed tomography (CT). Methods PV electrophysiologic studies and catheter ablation were performed in 63 patients (68% male; mean ± SD age: 56 ± 10 years) with symptomatic AF (49% paroxysmal, 51% persistent). Chest CT was performed before and 3 months a...

  16. 胰岛素对大鼠心肌梗死后心室重构和心脏功能的影响及其机制%Effects of insulin on ventricular remodeling and cardiac functions after myocardial infarction and its underlying mechanism

    Institute of Scientific and Technical Information of China (English)

    韦广洪; 付锋; 马斌; 薛洋; 李嘉; 张利华

    2013-01-01

    目的:探讨胰岛素对大鼠心肌梗死(MI)后心室重构和心脏功能的影响及其机制.方法:80只成年雄性Sprague-Dawley大鼠行冠状动脉左前降支(LAD)结扎制备MI模型,随机分为5组:即假手术(Sham)组(n=20)、生理盐水对照(MI+ NS)组(n=20)、胰岛素治疗(MI+ Ins)组(n=20)、肿瘤坏死因子α(TNF-α)拮抗剂益赛普治疗(MI+ En)组(n=10)及Ins+ En治疗(MI+ Ins+ En)组(n=10).用ELISA法检测各组大鼠在MI后1周和4周时,心肌及血清TNF-α的水平.超声心动图测定各组大鼠左室射血分数(EF)、缩短分数(FS)和左心室舒张末内径(LVEDD)、左心室收缩末内径(LVESD)、经右颈总动脉插管测定血压(BP)、左室舒张压(LVDP)和最大左室舒张压/收缩压变化速率(±LVdp/dtmax).结果:大鼠MI后心肌中TNF-α增加,Ins治疗可明显降低大鼠心肌中TNF-α的含量(P<0.05,n=6).Ins治疗组大鼠EF、FS、LVDP和±LVdp/dtmax均明显高于对照组(P <0.05,n=10),LVESD明显低于对照组(P<0.05,n=10).与单独En治疗组相比,Ins+ En治疗组大鼠EF、FS、LVDP和±LVdp/dtmax明显升高、LVESD明显降低(P <0.05,n=10).结论:Ins可抑制MI后心室的扩张,改善心脏功能,但其机制不依赖于抑制心肌TNF-α的产生.%AIM: To investigate the effect of insulin treatment on ventricular remodeling and cardiac functions after myocardial infarction (MI) and the underlying mechanism. METHODS: MI models were established by ligation of the left anterior descending coronary artery (LAD). Eighty male adult Sprague Dawley rats were randomly divided into five groups: sham (n = 20) , MI + saline ( n = 20) , MI + insulin (n = 20) , MI + etanercept ( n = 10) , and MI + etanercept + insulin ( n = 10 ) . Serum and myocardial tumor necrosis factor-α (TNF-α) were measured at 1 week and 4 weeks after MI. Left ventricular (LV) fractional shortening ( FS) , ejection fraction ( EF) , LV end-diastolic diameter ( LVEDD) and end-systolic diameter (LVESD) were measured

  17. Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Šimko, F.; Pecháňová, Olga; Pelouch, Václav; Krajčírovičová, K.; Müllerová, M.; Bednárová, K.; Adamcová, M.; Paulis, L.

    2009-01-01

    Roč. 27, Suppl.6 (2009), S5-S10. ISSN 0263-6352 R&D Projects: GA ČR GA305/09/0336 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiac hypertrophy * fibrosis * ventricular remodeling Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.988, year: 2009

  18. Left ventricular structure and remodeling in patients with COPD

    Science.gov (United States)

    Pelà, Giovanna; Li Calzi, Mauro; Pinelli, Silvana; Andreoli, Roberta; Sverzellati, Nicola; Bertorelli, Giuseppina; Goldoni, Matteo; Chetta, Alfredo

    2016-01-01

    Background Data on cardiac alterations such as left ventricular (LV) hypertrophy, diastolic dysfunction, and lower stroke volume in patients with COPD are discordant. In this study, we investigated whether early structural and functional cardiac changes occur in patients with COPD devoid of manifest cardiovascular disease, and we assessed their associations with clinical and functional features. Methods Forty-nine patients with COPD belonging to all Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes were enrolled and compared with 36 controls. All subjects underwent clinical history assessment, lung function testing, blood pressure measurement, electrocardiography, and conventional and Doppler tissue echocardiography. Patients were also subjected to computed tomography to quantify emphysema score. Results Patients with COPD had lower LV cavity associated with a marked increase in relative wall thickness (RWT), suggesting concentric remodeling without significant changes in LV mass. RWT was significantly associated with ratio of the forced expiratory volume in 1 second to the forced vital capacity and emphysema score and was the only cardiac parameter that – after multivariate analysis – significantly correlated with COPD conditions in all individuals. Receiver operating characteristic curve analysis showed that RWT (with a cutoff point of 0.42) predicted the severity of COPD with 83% specificity and 56% sensitivity (area under the curve =0.69, 95% confidence interval =0.59–0.81). Patients with COPD showed right ventricular to be functional but no structural changes. Conclusion Patients with COPD without evident cardiovascular disease exhibit significant changes in LV geometry, resulting in concentric remodeling. In all individuals, RWT was significantly and independently related to COPD. However, its prognostic role should be determined in future studies. PMID:27257378

  19. Focused Cardiac Ultrasound Diagnosis of Cor Triatriatum Sinistrum in Pediatric Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Thompson Kehrl,

    2015-10-01

    Full Text Available Cardiac arrest in the adolescent population secondary to congenital heart disease (CHD is rare. Focused cardiac ultrasound (FoCUS in the emergency department (ED can yield important clinical information, aid in resuscitative efforts during cardiac arrest and is commonly integrated into the evaluation of patients with pulseless electrical activity (PEA. We report a case of pediatric cardiac arrest in which FoCUS was used to diagnose a critical CHD known as cor triatriatum sinistrum as the likely cause for PEA cardiac arrest and help direct ED resuscitation.

  20. Neural remodeling in retinal degeneration.

    Science.gov (United States)

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  1. Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2011-07-01

    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.)

  2. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  3. Chromatin remodeling, development and disease

    International Nuclear Information System (INIS)

    Development is a stepwise process in which multi-potent progenitor cells undergo lineage commitment, differentiation, proliferation and maturation to produce mature cells with restricted developmental potentials. This process is directed by spatiotemporally distinct gene expression programs that allow cells to stringently orchestrate intricate transcriptional activation or silencing events. In eukaryotes, chromatin structure contributes to developmental progression as a blueprint for coordinated gene expression by actively participating in the regulation of gene expression. Changes in higher order chromatin structure or covalent modification of its components are considered to be critical events in dictating lineage-specific gene expression during development. Mammalian cells utilize multi-subunit nuclear complexes to alter chromatin structure. Histone-modifying complex catalyzes covalent modifications of histone tails including acetylation, methylation, phosphorylation and ubiquitination. ATP-dependent chromatin remodeling complex, which disrupts histone-DNA contacts and induces nucleosome mobilization, requires energy from ATP hydrolysis for its catalytic activity. Here, we discuss the diverse functions of ATP-dependent chromatin remodeling complexes during mammalian development. In particular, the roles of these complexes during embryonic and hematopoietic development are reviewed in depth. In addition, pathological conditions such as tumor development that are induced by mutation of several key subunits of the chromatin remodeling complex are discussed, together with possible mechanisms that underlie tumor suppression by the complex

  4. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  5. Cardiac sarcoidosis

    Science.gov (United States)

    Smedema, J.P.; Zondervan, P.E.; van Hagen, P.; ten Cate, F.J.; Bresser, P.; Doubell, A.F.; Pattynama, P.; Hoogsteden, H.C.; Balk, A.H.M.M.

    2002-01-01

    Sarcoidosis is a multi-system granulomatous disorder of unknown aetiology. Symptomatic cardiac involvement occurs in approximately 5% of patients. The prevalence of sarcoidosis in the Netherlands is unknown, but estimated to be approximately 20 per 100,000 population (3200 patients). We report on five patients who presented with different manifestations of cardiac sarcoidosis, and give a brief review on the current management of this condition. Magnetic Resonance Imaging (MRI) can be of great help in diagnosing this condition as well as in the follow-up of the response to therapy. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:25696121

  6. Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

    OpenAIRE

    Gomez, Juan F.; Cardona, Karen; Martinez, Laura; Saiz, Javier; Trenor, Beatriz

    2014-01-01

    Background Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure. Objective In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiolog...

  7. Arrhythmogenic remodelling of activation and repolarization in the failing human heart

    OpenAIRE

    Holzem, Katherine M.; Efimov, Igor R.

    2012-01-01

    Heart failure is a major cause of disability and death worldwide, and approximately half of heart failure-related deaths are sudden and presumably due to ventricular arrhythmias. Patients with heart failure have been shown to be at 6- to 9-fold increased risk of sudden cardiac death compared to the general population. (AHA. Heart Disease and Stroke Statistics—2003 Update. Heart and Stroke Facts. Dallas, TX: American Heart Association; 2002) Thus, electrophysiological remodelling associated wi...

  8. Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

    OpenAIRE

    Gómez García, Juan Francisco; Saiz Rodríguez, Francisco Javier; Trenor Gomis, Beatriz Ana

    2014-01-01

    Background: Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure. Objective: In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established ...

  9. Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure

    OpenAIRE

    Distefano Giuseppe; Sciacca Pietro

    2012-01-01

    Abstract It is well known that the natural history of chronic heart failure (CHF),regardless of age and aetiology,is characterized by progressive cardiac dysfunction refractory to conventional cardiokinetic, diuretic and peripheral vasodilator therapy. Several previous studies, both in animals and humans, showed that the key pathogenetic element of CHF negative clinical evolution is constituted by myocardial remodeling. This is a complex pathologic process of ultrastructural rearrangement of ...

  10. Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure

    Directory of Open Access Journals (Sweden)

    Distefano Giuseppe

    2012-09-01

    Full Text Available Abstract It is well known that the natural history of chronic heart failure (CHF,regardless of age and aetiology,is characterized by progressive cardiac dysfunction refractory to conventional cardiokinetic, diuretic and peripheral vasodilator therapy. Several previous studies, both in animals and humans, showed that the key pathogenetic element of CHF negative clinical evolution is constituted by myocardial remodeling. This is a complex pathologic process of ultrastructural rearrangement of the heart induced by various neuro-humoral factors released by cardiac fibrocells in response to biomechanical stress connected to chronic haemodynamic overload. Typical features of myocardial remodeling are represented by cardiomyocytes hypertrophy and apoptosis, extracellular matrix alterations, mesenchymal fibrotic and phlogistic processes and by cardiac gene expression modifications with fetal genetic program reactivation. In the last years, increasing knowledge of subtle molecular and cellular mechanisms involved in myocardial remodeling has led to the discovery of some new potential therapeutic targets capable of inducing its regression. In this paper our attention is focused on the possible use of antiapoptotic and antifibrotic agents, and on the fascinating perspectives offered by the development of myocardial gene therapy and, in particular, by myocardial regenerative therapy.

  11. Left ventricular structure and remodeling in patients with COPD

    Directory of Open Access Journals (Sweden)

    Pelà G

    2016-05-01

    Full Text Available Giovanna Pelà,1 Mauro Li Calzi,1 Silvana Pinelli,1 Roberta Andreoli,1 Nicola Sverzellati,2 Giuseppina Bertorelli,1 Matteo Goldoni,1 Alfredo Chetta11Department of Clinical and Experimental Medicine, 2Department of Surgery, University Medical School, University Hospital Parma, Parma, ItalyBackground: Data on cardiac alterations such as left ventricular (LV hypertrophy, diastolic dysfunction, and lower stroke volume in patients with COPD are discordant. In this study, we investigated whether early structural and functional cardiac changes occur in patients with COPD devoid of manifest cardiovascular disease, and we assessed their associations with clinical and functional features.Methods: Forty-nine patients with COPD belonging to all Global Initiative for Chronic Obstructive Lung Disease (GOLD classes were enrolled and compared with 36 controls. All subjects underwent clinical history assessment, lung function testing, blood pressure measurement, electrocardiography, and conventional and Doppler tissue echocardiography. Patients were also subjected to computed tomography to quantify emphysema score.Results: Patients with COPD had lower LV cavity associated with a marked increase in relative wall thickness (RWT, suggesting concentric remodeling without significant changes in LV mass. RWT was significantly associated with ratio of the forced expiratory volume in 1 second to the forced vital capacity and emphysema score and was the only cardiac parameter that – after multivariate analysis – significantly correlated with COPD conditions in all individuals. Receiver operating characteristic curve analysis showed that RWT (with a cutoff point of 0.42 predicted the severity of COPD with 83% specificity and 56% sensitivity (area under the curve =0.69, 95% confidence interval =0.59–0.81. Patients with COPD showed right ventricular to be functional but no structural changes.Conclusion: Patients with COPD without evident cardiovascular disease

  12. Cardiac extracellular matrix proteomics: Challenges, techniques, and clinical implications.

    Science.gov (United States)

    Chang, Chia Wei; Dalgliesh, Ailsa J; López, Javier E; Griffiths, Leigh G

    2016-01-01

    Extracellular matrix (ECM) has emerged as a dynamic tissue component, providing not only structural support, but also functionally participating in a wide range of signaling events during development, injury, and disease remodeling. Investigation of dynamic changes in cardiac ECM proteome is challenging due to the relative insolubility of ECM proteins, which results from their macromolecular nature, extensive post-translational modification (PTM), and tendency to form protein complexes. Finally, the relative abundance of cellular and mitochondrial proteins in cardiac tissue further complicates cardiac ECM proteomic approaches. Recent developments of various techniques to enrich and analyze ECM proteins are playing a major role in overcoming these challenges. Application of cardiac ECM proteomics in disease tissues can further provide spatial and temporal information relevant to disease diagnosis, prognosis, treatment, and engineering of therapeutic candidates for cardiac repair and regeneration. PMID:26200932

  13. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J; Partridge, Nicola C

    2010-01-01

    Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to the traditional bone cells (osteoclasts, osteoblasts, and osteocytes) that are necessary for bone remodeling, several immune cells have also been implicated in bone disease. This minireview discusses physiological bone remodeling, outlining the traditional bone biology dogma in light of emerging ...

  14. Inhibition of miR-15 Protects Against Cardiac Ischemic Injury

    Science.gov (United States)

    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

  15. Calmodulin 2 Mutation N98S Is Associated with Unexplained Cardiac Arrest in Infants Due to Low Clinical Penetrance Electrical Disorders

    Science.gov (United States)

    Jiménez-Jáimez, Juan; Palomino Doza, Julián; Ortega, Ángeles; Macías-Ruiz, Rosa; Perin, Francesca; Rodríguez-Vázquez del Rey, M. Mar; Ortiz-Genga, Martín; Monserrat, Lorenzo; Barriales-Villa, Roberto; Blanca, Enrique; Álvarez, Miguel; Tercedor, Luis

    2016-01-01

    Background Calmodulin 1, 2 and 3 (CALM) mutations have been found to cause cardiac arrest in children at a very early age. The underlying aetiology described is long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT) and idiopathic ventricular fibrillation (IVF). Little phenotypical data about CALM2 mutations is available. Objectives The aim of this paper is to describe the clinical manifestations of the Asn98Ser mutation in CALM2 in two unrelated children in southern Spain with apparently unexplained cardiac arrest/death. Methods Two unrelated children aged 4 and 7, who were born to healthy parents, were studied. Both presented with sudden cardiac arrest. The first was resuscitated after a VF episode, and the second died suddenly. In both cases the baseline QTc interval was within normal limits. Peripheral blood DNA was available to perform targeted gene sequencing. Results The surviving 4-year-old girl had a positive epinephrine test for LQTS, and polymorphic ventricular ectopic beats were seen on a previous 24-hour Holter recording from the deceased 7-year-old boy, suggestive of a possible underlying CPVT phenotype. A p.Asn98Ser mutation in CALM2 was detected in both cases. This affected a highly conserved across species residue, and the location in the protein was adjacent to critical calcium binding loops in the calmodulin carboxyl-terminal domain, predicting a high pathogenic effect. Conclusions Human calmodulin 2 mutation p.Asn98Ser is associated with sudden cardiac death in childhood with a variable clinical penetrance. Our results provide new phenotypical information about clinical behaviour of this mutation. PMID:27100291

  16. Cardiac rhabdomyosarcoma

    OpenAIRE

    Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

    2001-01-01

    Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical stain...

  17. Cardiac Calcification

    Directory of Open Access Journals (Sweden)

    Morteza Joorabian

    2011-05-01

    Full Text Available There is a spectrum of different types of cardiac"ncalcifications with the importance and significance"nof each type of cardiac calcification, especially"ncoronary artery calcification. Radiologic detection of"ncalcifications within the heart is quite common. The"namount of coronary artery calcification correlates"nwith the severity of coronary artery disease (CAD."nCalcification of the aortic or mitral valve may indicate"nhemodynamically significant valvular stenosis."nMyocardial calcification is a sign of prior infarction,"nwhile pericardial calcification is strongly associated"nwith constrictive pericarditis. A spectrum of different"ntypes of cardiac calcifications (linear, annular,"ncurvilinear,... could be seen in chest radiography and"nother imaging modalities. So a carful inspection for"ndetection and reorganization of these calcifications"nshould be necessary. Numerous modalities exist for"nidentifying coronary calcification, including plain"nradiography, fluoroscopy, intravascular ultrasound,"nMRI, echocardiography, and conventional, helical and"nelectron-beam CT (EBCT. Coronary calcifications"ndetected on EBCT or helical CT can be quantifie,"nand a total calcification score (Cardiac Calcification"nScoring may be calculated. In an asymptomatic"npopulation and/or patients with concomitant risk"nfactors like diabetes mellitus, determination of the"npresence of coronary calcifications identifies the"npatients at risk for future myocardial infarction and"ncoronary artery disease. In patients without coronary"ncalcifications, future cardiovascular events could"nbe excluded. Therefore, detecting and recognizing"ncalcification related to the heart on chest radiography"nand other imaging modalities such as fluoroscopy, CT"nand echocardiography may have important clinical"nimplications.

  18. Chronic vagal stimulation for the treatment of low ejection fraction heart failure : results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

    NARCIS (Netherlands)

    Zannad, Faiez; De Ferrari, Gaetano M; Tuinenburg, Anton E; Wright, David; Brugada, Josep; Butter, Christian; Klein, Helmut; Stolen, Craig; Meyer, Scott; Stein, Kenneth M; Ramuzat, Agnes; Schubert, Bernd; Daum, Doug; Neuzil, Petr; Botman, Cornelis; Castel, Maria Angeles; D'Onofrio, Antonio; Solomon, Scott D; Wold, Nicholas; Ruble, Stephen B

    2015-01-01

    AIM: The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure p

  19. Tricuspid annular plane systolic excursion and response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; Ghio, Stefano; St John Sutton, Martin;

    2011-01-01

    The aims of this study were to evaluate tricuspid annular plane systolic excursion (TAPSE) as a predictor of left ventricular (LV) reverse remodeling and clinical benefit of cardiac synchronization therapy (CRT) and to evaluate the effect of CRT on TAPSE in patients with mildly symptomatic systolic...... heart failure as a substudy of the REsyncronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) trial....

  20. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Pier Andrea Nicolosi

    2016-01-01

    Full Text Available Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc. The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment.

  1. Remodeling dan Repairing Vaskular pada Nefropati Hipertensif

    OpenAIRE

    Rasyid, Haerani; Wijaya, Johnson; Bakri, Syakib

    2011-01-01

    Latar Belakang: Ketidakseimbangan proses remodeling dan repairing vaskular diduga berperan penting pada kekakuan dan ketebalan vaskular yang akhirnya menyebabkan komplikasi hipertensi. Petanda dini komplikasi hipertensi pada ginjal adalah adanya mikroalbuminuria (MA). Tujuan Penelitian: Untuk mengetahui perbedaan konsentrasi TGF-??1 (sebagai petanda remodeling) dan VEGFR-2 (sebagai petanda repairing) pada subyek normotensi, hipertensi normoalbuminuria (NA) dan hipertensi MA. Metode: P...

  2. Multiscale Simulation of Protein Mediated Membrane Remodeling

    OpenAIRE

    Ayton, Gary S.; Voth, Gregory A.

    2009-01-01

    Proteins interacting with membranes can result in substantial membrane deformations and curvatures. This effect is known in its broadest terms as membrane remodeling. This review article will survey current multiscale simulation methodologies that have been employed to examine protein-mediated membrane remodeling.

  3. Dietary ω-3 Fatty Acids Alter Cardiac Mitochondrial Phospholipid Composition and Delay Ca2+-Induced Permeability Transition

    OpenAIRE

    O’Shea, Karen M.; Khairallah, Ramzi J.; Sparagna, Genevieve C.; Xu, Wenhong; Hecker, Peter A; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Kristian, Tibor; Robert C. Murphy; Fiskum, Gary; Stanley, William C.

    2009-01-01

    Consumption of ω-3 fatty acids from fish oil, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), decreases risk for heart failure and attenuates pathologic cardiac remodeling in response to pressure overload. Dietary supplementation with EPA+DHA may also impact cardiac mitochondrial function and energetics through alteration of membrane phospholipids. We assessed the role of EPA+DHA supplementation on left ventricular (LV) function, cardiac mitochondrial membrane phospho...

  4. C-Reactive Protein Inhibits Survivin Expression via Akt/mTOR Pathway Downregulation by PTEN Expression in Cardiac Myocytes

    OpenAIRE

    Beom Seob Lee; Soo Hyuk Kim; Jaewon Oh; Taewon Jin; Eun Young Choi; Sungha Park; Sang-Hak Lee; Ji Hyung Chung; Seok-Min Kang

    2014-01-01

    C-reactive protein (CRP) is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We ...

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

    Science.gov (United States)

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

    2016-05-01

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

  6. Nucleosome dynamics during chromatin remodeling in vivo.

    Science.gov (United States)

    Ramachandran, Srinivas; Henikoff, Steven

    2016-01-01

    Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation. PMID:26933790

  7. Evaluation of left ventricular remodelling in patients with chronic ischemic heart disease using multislice computer tomography and magnetic resonance tomography

    International Nuclear Information System (INIS)

    The article presents the results of MSCT and MRI of the heart in 57 patients with chronic coronary heart disease. It determined the relationship between structural and functional changes in the left ventricle and the degree of left coronary artery stenosis. Also determined were the link between the ischemic left ventricular remodeling and depth of myocardial damage in patients with coronary heart disease and postinfarction cardiosclerosis. MSCT and MRI are highly reliable imaging technique used to evaluate the infarcted and viable myocardium and post infarct cardiac remodeling process

  8. Cardiac conduction system

    Science.gov (United States)

    The cardiac conduction system is a group of specialized cardiac muscle cells in the walls of the heart that send signals ... to contract. The main components of the cardiac conduction system are the SA node, AV node, bundle ...

  9. Thyroid Hormone and Vascular Remodeling.

    Science.gov (United States)

    Ichiki, Toshihiro

    2016-03-01

    Both hyperthyroidism and hypothyroidism affect the cardiovascular system. Hypothyroidism is known to be associated with enhanced atherosclerosis and ischemic heart diseases. The accelerated atherosclerosis in the hypothyroid state has been traditionally ascribed to atherogenic lipid profile, diastolic hypertension, and impaired endothelial function. However, recent studies indicate that thyroid hormone has direct anti-atherosclerotic effects, such as production of nitric oxide and suppression of smooth muscle cell proliferation. These data suggest that thyroid hormone inhibits atherogenesis through direct effects on the vasculature as well as modification of risk factors for atherosclerosis. This review summarizes the basic and clinical studies on the role of thyroid hormone in vascular remodeling. The possible application of thyroid hormone mimetics to the therapy of hypercholesterolemia and atherosclerosis is also discussed. PMID:26558400

  10. Obesity and carotid artery remodeling

    DEFF Research Database (Denmark)

    Kozakova, M; Palombo, C; Morizzo, C;

    2015-01-01

    BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions...... and CCA LD (266 healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese...... subjects without CV complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was...

  11. 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

  12. Cardiovascular function, compliance, and connective tissue remodeling in the turtle, Trachemys scripta, following thermal acclimation.

    Science.gov (United States)

    Keen, Adam N; Shiels, Holly A; Crossley, Dane A

    2016-07-01

    Low temperature directly alters cardiovascular physiology in freshwater turtles, causing bradycardia, arterial hypotension, and a reduction in systemic blood pressure. At the same time, blood viscosity and systemic resistance increase, as does sensitivity to cardiac preload (e.g., via the Frank-Starling response). However, the long-term effects of these seasonal responses on the cardiovascular system are unclear. We acclimated red-eared slider turtles to a control temperature (25°C) or to chronic cold (5°C). To differentiate the direct effects of temperature from a cold-induced remodeling response, all measurements were conducted at the control temperature (25°C). In anesthetized turtles, cold acclimation reduced systemic resistance by 1.8-fold and increased systemic blood flow by 1.4-fold, resulting in a 2.3-fold higher right to left (R-L; net systemic) cardiac shunt flow and a 1.8-fold greater shunt fraction. Following a volume load by bolus injection of saline (calculated to increase stroke volume by 5-fold, ∼2.2% of total blood volume), systemic resistance was reduced while pulmonary blood flow and systemic pressure increased. An increased systemic blood flow meant the R-L cardiac shunt was further pronounced. In the isolated ventricle, passive stiffness was increased following cold acclimation with 4.2-fold greater collagen deposition in the myocardium. Histological sections of the major outflow arteries revealed a 1.4-fold higher elastin content in cold-acclimated animals. These results suggest that cold acclimation alters cardiac shunting patterns with an increased R-L shunt flow, achieved through reducing systemic resistance and increasing systemic blood flow. Furthermore, our data suggests that cold-induced cardiac remodeling may reduce the stress of high cardiac preload by increasing compliance of the vasculature and decreasing compliance of the ventricle. Together, these responses could compensate for reduced systolic function at low temperatures in

  13. Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Quan He

    2014-01-01

    Full Text Available Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.

  14. Mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes.

    Science.gov (United States)

    He, Quan; Harris, Nicole; Ren, Jun; Han, Xianlin

    2014-01-01

    Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress. PMID:25247053

  15. Local heterogeneities in cardiac systems suppress turbulence by generating multi-armed rotors

    Science.gov (United States)

    Zhang, Zhihui; Steinbock, Oliver

    2016-05-01

    Ventricular fibrillation is an extremely dangerous cardiac arrhythmia that is linked to rotating waves of electric activity and chaotically moving vortex lines. These filaments can pin to insulating, cylindrical heterogeneities which swiftly become the new rotation backbone of the local wave field. For thin cylinders, the stabilized rotation is sufficiently fast to repel the free segments of the turbulent filament tangle and annihilate them at the system boundaries. The resulting global wave pattern is periodic and highly ordered. Our cardiac simulations show that also thicker cylinders can establish analogous forms of tachycardia. This process occurs through the spontaneous formation of pinned multi-armed vortices. The observed number of wave arms N depends on the cylinder radius and is associated to stability windows that for N = 2, 3 partially overlap. For N = 1, 2, we find a small gap in which the turbulence is removed but the pinned rotor shows complex temporal dynamics. The relevance of our findings to human cardiology are discussed in the context of vortex pinning to more complex-shaped anatomical features and remodeled myocardium.

  16. Role of atrial tissue remodeling on rotor dynamics: an in vitro study.

    Science.gov (United States)

    Climent, Andreu M; Guillem, María S; Fuentes, Lucia; Lee, Peter; Bollensdorff, Christian; Fernández-Santos, María Eugenia; Suárez-Sancho, Susana; Sanz-Ruiz, Ricardo; Sánchez, Pedro Luis; Atienza, Felipe; Fernández-Avilés, Francisco

    2015-12-01

    The objective of this article is to present an in vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1 ± 1.3 and 9.7 ± 0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e., relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in nonfibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in vitro fibrillation [e.g., density of phase singularities (PS/cm(2)), dominant frequency, and rotor meandering] analyzed by means of optical mapping were compared with the degree of electrophysiological remodeling. Fibrillating cell cultures showed a differential ion channel gene expression associated with atrial tissue remodeling (i.e., decreased SCN5A, CACN1C, KCND3, and GJA1 and increased KCNJ2) not present in nonfibrillating cell cultures. Also, fibrillatory complexity was increased in late- vs. early stage cultures (1.12 ± 0.14 vs. 0.43 ± 0.19 PS/cm(2), P rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF. PMID:26408535

  17. Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis

    Science.gov (United States)

    Jung, Joanna; Dyck, Jason R. B.; Lopaschuk, Gary D.; Agellon, Luis B.; Michalak, Marek

    2016-01-01

    Background Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR) pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function. Methodology/Principal Findings We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER) homeostasis, transient activation of the unfolded protein response (UPR) pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA) is sufficient to prevent cardiac fibrosis, and improved exercise tolerance. Conclusions We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function. PMID:27441395

  18. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  19. Cellular signaling underlying atrial tachycardia remodeling of L-type calcium current

    NARCIS (Netherlands)

    Qi, Xiao Yan; Yeh, Yung-Hsin; Xiao, Ling; Burstein, Brett; Maguy, Ange; Chartier, Denis; Villeneuve, Louis R.; Brundel, Bianca J. J. M.; Dobrev, Dobromir; Nattel, Stanley

    2008-01-01

    Atrial tachycardia (AT) downregulates L-type Ca2+ current (I-CaL) and causes atrial fibrillation -promoting electric remodeling. This study assessed potential underlying signal transduction. Cultured adult canine atrial cardiomyocytes were paced at 0, 1, or 3 Hz (P0, P1, P3) for up to 24 hours. Cell

  20. [Cardiac potassium channels: molecular structure, physiology, pathophysiology and therapeutic implications].

    Science.gov (United States)

    Mironov, N Iu; Golitsyn, S P

    2013-01-01

    Potassium channels and currents play essential roles in cardiac repolarization. Potassium channel blockade by class III antiarrhythmic drugs prolongs cardiac repolarization and results in termination and prevention of cardiac arrhythmias. Excessive inhomogeneous repolarization prolongation may lead to electrical instability and proarrhythmia (Torsade de Pointes tachycardia). This review focuses on molecular structure, physiology, pathophysiology and therapeutic potential of potassium channels of cardiac conduction system and myocardium providing information on recent findings in pathogenesis of cardiac arrhythmias, including inherited genetic abnormalities, and future perspectives. PMID:24654438

  1. Assessment of Left Ventricular Structural Remodelling in Patients with Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance

    Science.gov (United States)

    Zhang, Xiaochun; Leng, Weiling

    2016-01-01

    Background. Diabetic cardiomyopathy (DCM) is always accompanied with alteration of left ventricular structure and function. The aims of this study were to assess the structural remodelling in patients with DCM by cardiovascular magnetic resonance (CMR) and correlation of structural remodelling with severity of DCM. Methods. Twenty-five patients (53.8 ± 8.8 years, 52.0% males) with DCM and thirty-one normal healthy controls (51.9 ± 13.6 years, 45.2% males) were scanned by CMR cine to assess function and structure of left ventricular. Length of diabetic history and results of cardiac echocardiography (E′, A′, and E′/A′) were also measured. Results. Compared with normal controls group, DCM group was associated with significantly increased ratio of left ventricular mass at end diastole to end-diastolic volume (MVR) (P 0.05). The ratio correlated with both length of diabetic history and echocardiographic Doppler tissue imaging E′ (all P < 0.05). Conclusions. CMR can be a powerful technique to assess LV remodelling, and MVR may be considered as an imaging marker to evaluate the severity of LV remodelling in patients with DCM.

  2. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  3. Maxillary Mucocele with Orbital Floor Remodelling

    OpenAIRE

    Tahrina Salam; Maryam Zamani; Jane Olver

    2012-01-01

    A 79-year-old man presents with signs of an orbital mass. A CT scan revealed a large maxillary mucocele eroding through the orbital floor. Surgical drainage of the mucocele and conservative postoperative care, returned all ophthalmic signs to normal and bony remodelling of the orbital floor was demonstrated. Maxillary mucoceles should be assessed by both ENT and Ophthalmic surgeons. Postoperative remodelling of the orbital floor can be illustrated with serial CT Scans.

  4. Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation

    OpenAIRE

    Stembridge, Mike; Ainslie, Philip N; Hughes, Michael G.; Stöhr, Eric J.; Cotter, James D.; Nio, Amanda Q. X.; Shave, Rob

    2014-01-01

    Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at s...

  5. Dynamics of the ethanolamine glycerophospholipid remodeling network.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    Full Text Available Acyl chain remodeling in lipids is a critical biochemical process that plays a central role in disease. However, remodeling remains poorly understood, despite massive increases in lipidomic data. In this work, we determine the dynamic network of ethanolamine glycerophospholipid (PE remodeling, using data from pulse-chase experiments and a novel bioinformatic network inference approach. The model uses a set of ordinary differential equations based on the assumptions that (1 sn1 and sn2 acyl positions are independently remodeled; (2 remodeling reaction rates are constant over time; and (3 acyl donor concentrations are constant. We use a novel fast and accurate two-step algorithm to automatically infer model parameters and their values. This is the first such method applicable to dynamic phospholipid lipidomic data. Our inference procedure closely fits experimental measurements and shows strong cross-validation across six independent experiments with distinct deuterium-labeled PE precursors, demonstrating the validity of our assumptions. In contrast, fits of randomized data or fits using random model parameters are worse. A key outcome is that we are able to robustly distinguish deacylation and reacylation kinetics of individual acyl chain types at the sn1 and sn2 positions, explaining the established prevalence of saturated and unsaturated chains in the respective positions. The present study thus demonstrates that dynamic acyl chain remodeling processes can be reliably determined from dynamic lipidomic data.

  6. Diagnostic tools assessing airway remodelling in asthma.

    Science.gov (United States)

    Manso, L; Reche, M; Padial, M A; Valbuena, T; Pascual, C

    2012-01-01

    Asthma is an inflammatory disease of the lower airways characterised by the presence of airway inflammation, reversible airflow obstruction and airway hyperresponsiveness and alterations on the normal structure of the airways, known as remodelling. Remodelling is characterised by the presence of metaplasia of mucous glands, thickening of the lamina reticularis, increased angiogenesis, subepithelial fibrosis and smooth muscle hypertrophy/hyperplasia. Several techniques are being optimised at present to achieve a suitable diagnosis for remodelling. Diagnostic tools could be divided into two groups, namely invasive and non-invasive methods. Invasive techniques bring us information about bronchial structural alterations, obtaining this information directly from pathological tissue, and permit measure histological modification placed in bronchi layers as well as inflammatory and fibrotic cell infiltration. Non-invasive techniques were developed to reduce invasive methods disadvantages and measure airway remodelling-related markers such as cytokines, inflammatory mediators and others. An exhaustive review of diagnostic tools used to analyse airway remodelling in asthma, including the most useful and usually employed methods, as well as the principal advantages and disadvantages of each of them, bring us concrete and summarised information about all techniques used to evaluate alterations on the structure of the airways. A deep knowledge of these diagnostic tools will make an early diagnosis of airway remodelling possible and, probably, early diagnosis will play an important role in the near future of asthma. PMID:22236733

  7. Echocardiographic abnormalities in the assessment of cardiac organ damage in never-treated hypertensive patients.

    Science.gov (United States)

    Milan, Alberto; Avenatti, Eleonora; Puglisi, Elisabetta; Abram, Sara; Magnino, Corrado; Naso, Diego; Tosello, Francesco; Fabbri, Ambra; Vairo, Alessandro; Mulatero, Paolo; Rabbia, Franco; Veglio, Franco

    2012-01-01

    Hypertension-related cardiac organ damage, other than left ventricular (LV) hypertrophy (LVH), has been described: in particular, concentric remodeling, LV diastolic dysfunction (DD), and left atrial (LA) enlargement are significantly associated with cardiovascular morbility and mortality in different populations. This study evaluated the prevalence of these latter morphofunctional abnormalities, in never-treated essential hypertensive patients and the role of such a serial assessment of hypertensive cardiac damage in improving cardiovascular risk stratification in these patients. A total of 100 never-treated essential hypertensive subjects underwent a complete clinical and echocardiographic evaluation. Left ventricular morphology, systolic and diastolic function, and LA dimension (linear and volume) were evaluated by echocardiography. Left ventricular hypertrophy was present in 14% of the patients, whereas concentric remodeling was present in 25% of the subjects. Among patients free from LV morphology abnormalities, the most frequent abnormality was LA enlargement (global prevalence 57%); the percentage of patients with at least one parameter consistent with DD was 22% in the entire population, but DD was present as the only cardiac abnormality in 1% of our patient. Left atrial volume indexed for body surface area was the most sensitive parameter in identifying hypertension-related cardiac modification. The global prevalence of cardiac alteration reached 73% in never-treated hypertensive patients. Left ventricular remodeling and LA enlargement evaluation may grant a better assessment of cardiac organ damage and cardiovascular risk stratification of hypertensive patients without evidence of LVH after routine examination. PMID:22738434

  8. Immunologic and inflammatory mechanisms that drive asthma progression to remodeling

    OpenAIRE

    Broide, David H.

    2008-01-01

    Although histologic features of airway remodeling have been well characterized in asthma, the immunologic and inflammatory mechanisms that drive progression of asthma to remodeling are still incompletely understood. Conceptually, airway remodeling may be due to persistent inflammation and/or aberrant tissue repair mechanisms. It is likely that several immune and inflammatory cell types and mediators are involved in mediating airway remodeling. In addition, different features of airway remodel...

  9. Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency

    Directory of Open Access Journals (Sweden)

    Xuejun Yang

    2014-01-01

    Full Text Available Objective: To observe the efficacy of Shenxinning Decoction (SXND in ventricular remodeling in AT1 receptor-knockout (AT1-KO mice with chronic renal insufficiency (CRI. Materials and Methods: AT1-KO mice modeled with subtotal (5/6 nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN, serum creatinine (SCr, brain natriuretic peptide (BNP, echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF, collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1 of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. Results: AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice′s BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. Conclusion: SXND may antagonize the renin-angiotensin system (RAS and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1.

  10. Leptin as a mediator between obesity and cardiac dysfunction

    Directory of Open Access Journals (Sweden)

    Joanna Karbowska

    2012-05-01

    Full Text Available  Obesity is now recognised as one of the most important risk factors for heart disease. Obese individuals have high circulating levels of leptin, a hormone secreted by adipose tissue and in­volved in energy homeostasis. Growing evidence suggests that leptin may contribute to the development of cardiac dysfunction. In a large prospective study leptin has been shown to be an independent risk factor for coronary heart disease. An independent positive association has also been found between plasma leptin levels and heart rate in hypertensive patients and heart transplant recipients. In animal studies chronic leptin infusion increased heart rate and blood pressure. It has also been demonstrated that circulating leptin levels are elevated in patients with heart failure. The level of plasma leptin was associated with increased myocardial wall thickness and correlated with left ventricular mass, suggesting a role for this hormone in mediating left ventricular hypertrophy in humans. Moreover, leptin directly induced hypertrophy and hyperplasia in human and rodent cardiomyocytes, accompanied by cardiac extracellular matrix remodelling. Leptin may also influence energy substrate utilisation in cardiac tissue.These findings suggest that leptin acting directly or through the sympathetic nervous system may have adverse effects on cardiac structure and function, and that chronic hyperleptinaemia may greatly increase the risk of cardiac disorders. Additional studies are needed to define the role of leptin in cardiac physiology and pathophysiology, nevertheless the reduction in plasma leptin levels with caloric restriction and weight loss may prevent cardiac dysfunction in obese patients.

  11. Cardiac perception and cardiac control. A review.

    Science.gov (United States)

    Carroll, D

    1977-12-01

    The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks. PMID:348240

  12. Toward microendoscopy-inspired cardiac optogenetics in vivo: technical overview and perspective

    Science.gov (United States)

    Klimas, Aleksandra; Entcheva, Emilia

    2014-08-01

    The ability to perform precise, spatially localized actuation and measurements of electrical activity in the heart is crucial in understanding cardiac electrophysiology and devising new therapeutic solutions for control of cardiac arrhythmias. Current cardiac imaging techniques (i.e. optical mapping) employ voltage- or calcium-sensitive fluorescent dyes to visualize the electrical signal propagation through cardiac syncytium in vitro or in situ with very high-spatiotemporal resolution. The extension of optogenetics into the cardiac field, where cardiac tissue is genetically altered to express light-sensitive ion channels allowing electrical activity to be elicited or suppressed in a precise cell-specific way, has opened the possibility for all-optical interrogation of cardiac electrophysiology. In vivo application of cardiac optogenetics faces multiple challenges and necessitates suitable optical systems employing fiber optics to actuate and sense electrical signals. In this technical perspective, we present a compendium of clinically relevant access routes to different parts of the cardiac electrical conduction system based on currently employed catheter imaging systems and determine the quantitative size constraints for endoscopic cardiac optogenetics. We discuss the relevant technical advancements in microendoscopy, cardiac imaging, and optogenetics and outline the strategies for combining them to create a portable, miniaturized fiber-based system for all-optical interrogation of cardiac electrophysiology in vivo.

  13. A fly's view of neuronal remodeling.

    Science.gov (United States)

    Yaniv, Shiri P; Schuldiner, Oren

    2016-09-01

    Developmental neuronal remodeling is a crucial step in sculpting the final and mature brain connectivity in both vertebrates and invertebrates. Remodeling includes degenerative events, such as neurite pruning, that may be followed by regeneration to form novel connections during normal development. Drosophila provides an excellent model to study both steps of remodeling since its nervous system undergoes massive and stereotypic remodeling during metamorphosis. Although pruning has been widely studied, our knowledge of the molecular and cellular mechanisms is far from complete. Our understanding of the processes underlying regrowth is even more fragmentary. In this review, we discuss recent progress by focusing on three groups of neurons that undergo stereotypic pruning and regrowth during metamorphosis, the mushroom body γ neurons, the dendritic arborization neurons and the crustacean cardioactive peptide peptidergic neurons. By comparing and contrasting the mechanisms involved in remodeling of these three neuronal types, we highlight the common themes and differences as well as raise key questions for future investigation in the field. WIREs Dev Biol 2016, 5:618-635. doi: 10.1002/wdev.241 For further resources related to this article, please visit the WIREs website. PMID:27351747

  14. Electrophysiological Remodeling in Heart Failure

    OpenAIRE

    Wang, Yanggan; Hill, Joseph A.

    2010-01-01

    Heart failure affects nearly 6 million Americans, with a half-million new cases emerging each year. Whereas up to 50% of heart failure patients die of arrhythmia, the diverse mechanisms underlying heart failure-associated arrhythmia are poorly understood. As a consequence, effectiveness of antiarrhythmic pharmacotherapy remains elusive. Here, we review recent advances in our understanding of heart failure-associated molecular events impacting the electrical function of the myocardium. We appr...

  15. Encapsulation of cardiomyocytes in a fibrin hydrogel for cardiac tissue engineering.

    Science.gov (United States)

    Yuan Ye, Kathy; Sullivan, Kelly Elizabeth; Black, Lauren Deems

    2011-01-01

    Culturing cells in a three dimensional hydrogel environment is an important technique for developing constructs for tissue engineering as well as studying cellular responses under various culture conditions in vitro. The three dimensional environment more closely mimics what the cells observe in vivo due to the application of mechanical and chemical stimuli in all dimensions (1). Three-dimensional hydrogels can either be made from synthetic polymers such as PEG-DA (2) and PLGA (3) or a number of naturally occurring proteins such as collagen (4), hyaluronic acid (5) or fibrin (6,7). Hydrogels created from fibrin, a naturally occurring blood clotting protein, can polymerize to form a mesh that is part of the body's natural wound healing processes (8). Fibrin is cell-degradable and potentially autologous (9), making it an ideal temporary scaffold for tissue engineering. Here we describe in detail the isolation of neonatal cardiomyocytes from three day old rat pups and the preparation of the cells for encapsulation in fibrin hydrogel constructs for tissue engineering. Neonatal myocytes are a common cell source used for in vitro studies in cardiac tissue formation and engineering (4). Fibrin gel is created by mixing fibrinogen with the enzyme thrombin. Thrombin cleaves fibrinopeptides FpA and FpB from fibrinogen, revealing binding sites that interact with other monomers (10). These interactions cause the monomers to self-assemble into fibers that form the hydrogel mesh. Because the timing of this enzymatic reaction can be adjusted by altering the ratio of thrombin to fibrinogen, or the ratio of calcium to thrombin, one can injection mold constructs with a number of different geometries (11,12). Further we can generate alignment of the resulting tissue by how we constrain the gel during culture (13). After culturing the engineered cardiac tissue constructs for two weeks under static conditions, the cardiac cells have begun to remodel the construct and can generate a

  16. What Is Cardiac Rehabilitation?

    Science.gov (United States)

    ANSWERS by heart Treatments + Tests What Is Cardiac Rehabilitation? A cardiac rehabilitation (rehab) program takes place in a hospital or ... special help in making lifestyle changes. During your rehabilitation program you’ll… • Have a medical evaluation to ...

  17. Unveiling nonischemic cardiomyopathies with cardiac magnetic resonance.

    Science.gov (United States)

    Aggarwal, Niti R; Peterson, Tyler J; Young, Phillip M; Araoz, Philip A; Glockner, James; Mankad, Sunil V; Williamson, Eric E

    2014-02-01

    Cardiomyopathy is defined as a heterogeneous group of myocardial disorders with mechanical or electrical dysfunction. Identification of the etiology is important for accurate diagnosis, treatment and prognosis, but continues to be challenging. The ability of cardiac MRI to non-invasively obtain 3D-images of unparalleled resolution without radiation exposure and to provide tissue characterization gives it a distinct advantage over any other diagnostic tool used for evaluation of cardiomyopathies. Cardiac MRI can accurately visualize cardiac morphology and function and also help identify myocardial edema, infiltration and fibrosis. It has emerged as an important diagnostic and prognostic tool in tertiary care centers for work up of patients with non-ischemic cardiomyopathies. This review covers the role of cardiac MRI in evaluation of nonischemic cardiomyopathies, particularly in the context of other diagnostic and prognostic imaging modalities. PMID:24417294

  18. Ataxia telangiectasia-mutated kinase deficiency exacerbates left ventricular dysfunction and remodeling late after myocardial infarction.

    Science.gov (United States)

    Daniel, Laura L; Scofield, Stephanie L C; Thrasher, Patsy; Dalal, Suman; Daniels, Christopher R; Foster, Cerrone R; Singh, Mahipal; Singh, Krishna

    2016-08-01

    Ataxia telangiectasia-mutated kinase (ATM), a cell cycle checkpoint protein, is activated in response to DNA damage and oxidative stress. We have previously shown that ATM deficiency is associated with increased apoptosis and fibrosis and attenuation of cardiac dysfunction early (1-7 days) following myocardial infarction (MI). Here, we tested the hypothesis that enhanced fibrosis and apoptosis, as observed early post-MI during ATM deficiency, exacerbate cardiac dysfunction and remodeling in ATM-deficient mice late post-MI. MIs were induced in wild-type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery. Left ventricular (LV) structural and functional parameters were assessed by echocardiography 14 and 28 days post-MI, whereas biochemical parameters were measured 28 days post-MI. hKO-MI mice exhibited exacerbated LV dysfunction as observed by increased LV end-systolic volume and decreased percent fractional shortening and ejection fraction. Infarct size and thickness were not different between the two genotypes. Myocyte cross-sectional area was greater in hKO-MI group. The hKO-MI group exhibited increased fibrosis in the noninfarct and higher expression of α-smooth muscle actin (myofibroblast marker) in the infarct region. Apoptosis and activation of GSK-3β (proapoptotic kinase) were significantly lower in the infarct region of hKO-MI group. Matrix metalloproteinase 2 (MMP-2) expression was not different between the two genotypes. However, MMP-9 expression was significantly lower in the noninfarct region of hKO-MI group. Thus ATM deficiency exacerbates cardiac remodeling late post-MI with effects on cardiac function, fibrosis, apoptosis, and myocyte hypertrophy. PMID:27288435

  19. Retinal Remodeling: Concerns, Emerging Remedies, and Future Prospects

    Directory of Open Access Journals (Sweden)

    Vidhyasankar eKrishnamoorthy

    2016-02-01

    Full Text Available Deafferentation results not only in sensory loss, but also in a variety of alterations in the postsynaptic circuitry. These alterations may have detrimental impact on potential treatment strategies. Progressive loss of photoreceptors in retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration, leads to several changes in the remnant retinal circuitry. Müller glial cells undergo hypertrophy and form a glial seal. The second- and third-order retinal neurons undergo morphological, biochemical and physiological alterations. A result of these alterations is that retinal ganglion cells (RGCs, the output neurons of the retina, become hyperactive and exhibit spontaneous, oscillatory bursts of spikes. This aberrant electrical activity degrades the signal-to-noise ratio in RGC responses, and thus the quality of information they transmit to the brain. These changes in the remnant retina, collectively termed retinal remodeling, pose challenges for genetic, cellular and bionic approaches to restore vision. It is therefore crucial to understand the nature of retinal remodeling, how it affects the ability of remnant retina to respond to novel therapeutic strategies, and how to ameliorate its effects. In this article, we discuss these topics, and suggest that the pathological state of the retinal output following photoreceptor loss is reversible, and therefore, amenable to restorative strategies.

  20. Biomechanical Remodeling of the Diabetic Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Liao, Donghua; Yang, Jian;

    2010-01-01

    several years, several studies demonstrated that experimental diabetes induces GI morphological and biomechanical remodeling. Following the development of diabetes, the GI wall becomes thicker and the stiffness of the GI wall increases in a time-dependent manner. It is well known that mechanosensitive...... the biomechanical environment of the mechanosensitive nerve endings, therefore, the structure as well as the tension, stress and strain distribution in the GI wall is important for the sensory and motor function. Biomechanical remodeling of diabetic GI tract including alterations of residual strain and increase...

  1. Diffuse infiltrative cardiac tuberculosis

    International Nuclear Information System (INIS)

    We present the cardiac magnetic resonance images of an unusual form of cardiac tuberculosis. Nodular masses in a sheet-like distribution were seen to infiltrate the outer myocardium and pericardium along most of the cardiac chambers. The lesions showed significant resolution on antitubercular therapy

  2. Cardiac Abnormalities in Youth with Obesity and Type 2 Diabetes.

    Science.gov (United States)

    Bacha, Fida; Gidding, Samuel S

    2016-07-01

    Childhood obesity has been linked to cardiovascular disease (CVD) risk in adulthood. Of great concern is the expected increase in the population's CVD burden in relation to childhood obesity. This is compounded by the risk related to chronic hyperglycemia exposure in youth with type 2 diabetes. We herein provide an overview of the spectrum of early cardiovascular disease manifestation in youth with obesity and type 2 diabetes, in particular abnormalities in cardiac structure and function. Cardiac remodeling and adverse target organ damage is already evident in the pediatric age group in children with obesity and type 2 diabetes. This supports the importance of intensifying obesity prevention efforts and early intervention to treat comorbidities of obesity in the pediatric age group to prevent cardiac events in early adulthood. PMID:27168062

  3. Observations of super early left ventricular remodeling experimental myocardial infarction

    International Nuclear Information System (INIS)

    Purpose: Ventricular remodeling is defined as the changes in the shape and size of the entire left ventricle after acute myocardial infarction (AMI). Many investigators have shown that left ventricular remodeling is related to clinical outcomes, including mortality, that represent the natural history, of the heart failure syndrome. The aim of this study was to demonstrate that it is possible to observe super early left ventricular remodeling by 99mTc-MIBI myocardial imaging in the dog model of acute experimental myocardial infarction. Methods: Experimental subjects: Twenty-three healthy mongrel dogs (14-25 kg) of either sex were studied under general anesthesia (sodium pentobarbital, 30 mg/kg). The left anterior descending (LAD) coronary artery was dissected and ligated between the first and second diagonal branches. Seven dogs died of ventricular fibrillation after the LAD coronary artery ligation. The 16 remaining dogs were divided into two groups: Group A (GA) received 99mTc-MIBI myocardial imaging (n=8): Group B (GB) received 99mTc-MIBI myocardial imaging combined with echocardiography (n=8). 99mTc-MIBI myocardial perfusion imaging :Static 99mTc-MIBI myocardial imaging was taken with ADAC Vertex Dual-head SPECT. 99mTc-MIBI kit was manufactured in Syncor, China. Each dog served as its own control, and was scanned by 99mTc-MIBI myocardial imaging and chocardiography at 48-72 hours before ligation. The mean time of the first acquisition was 21.87 ± 11.03 (14-48) minutes post-operatively in GA, 57.63±22.83 (30-99) minutes for 99mTc-MIBI imaging in GB, 26.00±15.07 (12-50) minutes for echocardiography in GB. Acquisition techniques for Gated SPECT: ECG synchronized data collection: R wave trigger, 8 Frames/Cardiac cycle. Images were gathered by rotating the detectors 180 degrees at 6 degrees per frame. Each frame took 40 seconds. The dog position was supine. The images were acquired and recorded for 6 hours following the LAD coronary artery ligation. After 6 hours

  4. Cardiac arrest: resuscitation and reperfusion.

    Science.gov (United States)

    Patil, Kaustubha D; Halperin, Henry R; Becker, Lance B

    2015-06-01

    The modern treatment of cardiac arrest is an increasingly complex medical procedure with a rapidly changing array of therapeutic approaches designed to restore life to victims of sudden death. The 2 primary goals of providing artificial circulation and defibrillation to halt ventricular fibrillation remain of paramount importance for saving lives. They have undergone significant improvements in technology and dissemination into the community subsequent to their establishment 60 years ago. The evolution of artificial circulation includes efforts to optimize manual cardiopulmonary resuscitation, external mechanical cardiopulmonary resuscitation devices designed to augment circulation, and may soon advance further into the rapid deployment of specially designed internal emergency cardiopulmonary bypass devices. The development of defibrillation technologies has progressed from bulky internal defibrillators paddles applied directly to the heart, to manually controlled external defibrillators, to automatic external defibrillators that can now be obtained over-the-counter for widespread use in the community or home. But the modern treatment of cardiac arrest now involves more than merely providing circulation and defibrillation. As suggested by a 3-phase model of treatment, newer approaches targeting patients who have had a more prolonged cardiac arrest include treatment of the metabolic phase of cardiac arrest with therapeutic hypothermia, agents to treat or prevent reperfusion injury, new strategies specifically focused on pulseless electric activity, which is the presenting rhythm in at least one third of cardiac arrests, and aggressive post resuscitation care. There are discoveries at the cellular and molecular level about ischemia and reperfusion pathobiology that may be translated into future new therapies. On the near horizon is the combination of advanced cardiopulmonary bypass plus a cocktail of multiple agents targeted at restoration of normal metabolism and

  5. Cardiac biomarkers in children with congenital heart disease

    Institute of Scientific and Technical Information of China (English)

    Masaya Sugimoto; Seiko Kuwata; Clara Kurishima; Jeong Hye Kim; Yoich Iwamoto; Hideaki Senzaki

    2015-01-01

    Background: Most congenital heart diseases (CHDs) have specific hemodynamics, including volume and pressure overload, as well as cyanosis and pulmonary hypertension, associated with anatomical abnormalities. Such hemodynamic abnormalities can cause activation of neurohormones, inflammatory cytokines, fibroblasts, and vascular endothelial cells, which in turn contribute to the development of pathologic conditions such as cardiac hypertrophy,fi brosis, and cardiac cell damages and death. Measuring biomarker levels facilitates the prediction of these pathological changes, and provides information about the stress placed on the myocardial cells, the severity of the damage, the responses of neurohumoral factors, and the remodeling of the ventricle. Compared to the ample information on cardiac biomarkers in adult heart diseases, data from children with CHD are still limited. Data sources: We reviewed cardiac biomarkers-specifi cally focusing on troponin as a biomarker of myocardial damage, amino-terminal procollagen type III peptide (PIIIP) as a biomarker of myocardialfi brosis and stromal remodeling, and B-type natriuretic peptide (BNP)/N-terminal proBNP as biomarkers of cardiac load and heart failure, by introducing relevant publications, including our own, on pediatric CHD patients as well as adults. Results: Levels of highly sensitive troponin I are elevated in patients with atrial septal defects (ASDs) and ventricular septal defects (VSDs). PIIIP levels are also elevated in patients with ASD, VSD, pulmonary stenosis, and Tetralogy of Fallot. Measurement of BNP and N-terminal proBNP levels shows good correlation with heart failure score in children. Conclusions: In the treatment of children with CHD requiring delicate care, it is vital to know the specifi c degree of myocardial damage and severity of heart failure. Cardiac biomarkers are useful tools for ascertaining the condition of CHDs with ease and are likely to be useful in determining the appropriate care of

  6. Recipient-derived EDA fibronectin promotes cardiac allograft fibrosis.

    Science.gov (United States)

    Booth, Adam J; Wood, Sherri C; Cornett, Ashley M; Dreffs, Alyssa A; Lu, Guanyi; Muro, Andrés F; White, Eric S; Bishop, D Keith

    2012-03-01

    Advances in donor matching and immunosuppressive therapies have decreased the prevalence of acute rejection of cardiac grafts; however, chronic rejection remains a significant obstacle for long-term allograft survival. While initiating elements of anti-allograft immune responses have been identified, the linkage between these factors and the ultimate development of cardiac fibrosis is not well understood. Tissue fibrosis resembles an exaggerated wound healing response, in which extracellular matrix (ECM) molecules are central. One such ECM molecule is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin (FN), termed extra domain A-containing cellular fibronectin (EDA cFN). EDA cFN is instrumental in fibrogenesis; thus, we hypothesized that it might also regulate fibrotic remodelling associated with chronic rejection. We compared the development of acute and chronic cardiac allograft rejection in EDA cFN-deficient (EDA(-/-)) and wild-type (WT) mice. While EDA(-/-) mice developed acute cardiac rejection in a manner indistinguishable from WT controls, cardiac allografts in EDA(-/-) mice were protected from fibrosis associated with chronic rejection. Decreased fibrosis was not associated with differences in cardiomyocyte hypertrophy or intra-graft expression of pro-fibrotic mediators. Further, we examined expression of EDA cFN and total FN by whole splenocytes under conditions promoting various T-helper lineages. Conditions supporting regulatory T-cell (Treg) development were characterized by greatest production of total FN and EDA cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These findings indicate that recipient-derived EDA cFN is dispensable for acute allograft rejection responses but that it promotes the development of fibrosis associated with chronic rejection. Further, conditions favouring the development of regulatory T cells, widely considered graft-protective, may drive production of ECM molecules which enhance

  7. The pathogenesis and treatment of cardiac atrophy in cancer cachexia.

    Science.gov (United States)

    Murphy, Kate T

    2016-02-15

    Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia is described as cardiac cachexia. The cardiac alterations may be due to underlying heart disease, the cancer itself, or problems initiated by the cancer treatment and, unfortunately, remains largely underappreciated by clinicians and basic scientists. Despite recent major advances in the treatment of cancer, little progress has been made in the treatment of cardiac cachexia in cancer, and much of this is due to lack of information regarding the mechanisms. This review focuses on the cardiac atrophy associated with cancer cachexia, describing some of the known mechanisms and discussing the current and future therapeutic strategies to treat this condition. Above all else, improved awareness of the condition and an increased focus on identification of mechanisms and therapeutic targets will facilitate the eventual development of an effective treatment for cardiac atrophy in cancer cachexia. PMID:26718971

  8. Exercise, Nrf2 and Antioxidant Signaling in Cardiac Aging.

    Science.gov (United States)

    Narasimhan, Madhusudhanan; Rajasekaran, Namakkal S

    2016-01-01

    Aging is represented by a progressive decline in cellular functions. The age-related deformities in cardiac behaviors are the loss of cardiac myocytes through apoptosis or programmed cell death. Oxidative stress (OS) and its deleterious consequence contribute to age-related mechanical remodeling, reduced regenerative capacity, and apoptosis in cardiac tissue. The pathogenesis of OS in the elderly can predispose the heart to other cardiac complications such as atherosclerosis, hypertension, ischemic heart disease, cardiac myopathy, and so on. At the molecular level, oxidant-induced activation of Nrf2 (Nuclear erythroid-2-p45-related factor-2), a transcription factor, regulates several genes containing AREs (Antioxidant Response Element) and bring the respective translates to counteract the reactive radicals and establish homeostasis. Myriad of Nrf2 gene knockout studies in various organs such as lung, liver, kidney, brain, etc. have shown that dysregulation of Nrf2 severely affects the oxidant/ROS sensitivity and predispose the system to several pathological changes with aberrant cellular lesions. On the other hand, its gain of function chemical interventions exhibited oxidant stress resistance and cytoprotection. However, thus far, only a few investigations have shown the potential role of Nrf2 and its non-pharmacological induction in cardiac aging. Therefore, here we review the involvement of Nrf2 signaling along with its responses and ramifications on the cascade of OS under acute exercise stress (AES), moderate exercise training (MET), and endurance exercise stress (EES) conditions in the aging heart. PMID:27378947

  9. Performance Requirements on Remodeling Apartment Housing and TOPSIS Evaluation

    OpenAIRE

    Jaeho Cho; Jaeyoul Chun

    2015-01-01

    Functional improvement needed in remodeling projects is determined by users in a complex manner since remodeling projects require performance improvement against deterioration. This study defines fundamental Remodeling Performance Criteria (RPC) for apartment housing by referring to performance criteria of both domestic and international performance-related systems. In this case study, performance evaluation of Construction Element Method (CEM) for remodeling projects was conducted based on R...

  10. 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

    2016-06-01

    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.

  11. New predictive model for monitoring bone remodeling

    Czech Academy of Sciences Publication Activity Database

    Bougherara, H.; Klika, Václav; Maršík, František; Mařík, I.; Yahia, L.H.

    95A, č. 1 (2010), s. 9-24. ISSN 1549-3296 R&D Projects: GA ČR GA106/03/1073; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z20760514 Keywords : bone remodeling * open system thermodynamics * bone biochemistry Subject RIV: BJ - Thermodynamics Impact factor: 3.044, year: 2010

  12. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A

    2014-04-01

    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

  13. Interleukin-20 promotes airway remodeling in asthma.

    Science.gov (United States)

    Gong, Wenbin; Wang, Xin; Zhang, Yuguo; Hao, Junqing; Xing, Chunyan; Chu, Qi; Wang, Guicheng; Zhao, Jiping; Wang, Junfei; Dong, Qian; Liu, Tian; Zhang, Yuanyuan; Dong, Liang

    2014-12-01

    Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma. PMID:25028099

  14. Connexin Remodeling Contributes to Atrial Fibrillation

    OpenAIRE

    Michelle M Jennings; J Kevin Donahue

    2013-01-01

    Atrial fibrillation significantly contributes to mortality and morbidity through increased risk of stroke, heart failure and myocardial infarcts. Investigations of mechanisms responsible for the development and maintenance of atrial fibrillation have highlighted the importance of gap junctional remodeling. Connexins 40 and 43, the major atrial gap junctional proteins, undergo considerable alterations in expression and localization in atrial fibrillation, creating an environment conducive to s...

  15. Remodelling of flash furnace for coal firing

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Z.

    1982-05-01

    The Chichiku Cement Co. has succeeded in re-converting all its cement plants from oil to coal firing system with no impairment at all to production rate or to unit energy consumption. The reconversion wea achieved by remodelling four of its five principal kilns from a system of suspension preheater with calciner to the C-SF kiln system.

  16. MYOCARDIAL REMODELING IN ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    A. N. Zakirova

    2016-01-01

    Full Text Available Aim. To study the myocardial remodeling features in patients with stable angina depending on disease severity and experienced myocardial infarction (MI.Material and methods. 148 male patients with stable angina were examined and randomized into 3 groups (G1-G3. 52 patients of G1 had angina of I-II functional class (FC. 49 patients of G2 had angina of III FC, and 47 patients of G3 had angina of IV FC. History of MI had 79,5, 87.2 and 92.6% of patients in G1, G2 and G3 respectively. 35 healthy men were included into control group. Coronarography, bicycle ergometry and 24-hour ECG monitoring was performed. Left ventricular (LV function and remodeling was assessed with echocardiography.Results. G3 patients had LV eccentric hypertrophy as a result of postinfarction cardiosclerosis which accompanied with LV systolic dysfunction, a myocardial stress increasing and LV spherification. G1 patients had no any significant disorders of LV systolic function.Conclusion. Severe ischemic heart disease is associated with a dysadaptive remodeling unlike mild ischemic heart disease, which is associated with an adaptive myocardial remodeling.

  17. Re-Modelling as De-Professionalisation

    Science.gov (United States)

    Thompson, Meryl

    2006-01-01

    The article sets out the consequences of the British Government's remodelling agenda and its emphasis on less demarcation, for the professional status of teachers in England. It describes how the National Agreement on Raising Standards and Tackling Workload, reached between five of the six trade unions for teachers and headteachers paves the way…

  18. Stem cell factor receptor induces progenitor and natural killer cell-mediated cardiac survival and repair after myocardial infarction

    OpenAIRE

    Ayach, Bilal B.; Yoshimitsu, Makoto; Dawood, Fayez; Sun, Mei; Arab, Sara; Chen, Manyin; HIGUCHI, KOJI; Siatskas, Christopher; Lee, Paul; Lim, Hilda; Zhang, Jane; Cukerman, Eva; Stanford, William L.; Medin, Jeffrey A; Liu, Peter P.

    2006-01-01

    Inappropriate cardiac remodeling and repair after myocardial infarction (MI) predisposes to heart failure. Studies have reported on the potential for lineage negative, steel factor positive (c-kit+) bone marrow-derived hematopoetic stem∕progenitor cells (HSPCs) to repair damaged myocardium through neovascularization and myogenesis. However, the precise contribution of the c-kit signaling pathway to the cardiac repair process has yet to be determined. In this study, we sought to directly eluci...

  19. Plasma tissue inhibitor of matrix metalloproteinase-1 (TIMP-1): an independent predictor of poor response to cardiac resynchronization therapy

    OpenAIRE

    Tolosana, Jose María; Mont, Lluís; Sitges, Marta; Berruezo, Antonio; Delgado, Victoria; Vidal, Bàrbara; Tamborero, David; Morales, Manel; Batlle, Montserrat; Roig, Eulalia; Castel, M. Angeles; Pérez-Villa, Félix; Godoy, Miguel; Brugada, Josep

    2010-01-01

    Aims Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular structural remodelling. The aim of our study was to analyse MMP-2 and TIMP-1 levels as predictors of poor response to cardiac resynchronization therapy (CRT). Methods and results A cohort of 42 CRT patients from our centre was prospectively evaluated at baseline and after 12-month follow-up. MMP-2 and TIMP-1 assays were performed prior to CRT implant. Cardiac resynchronization therapy res...

  20. Cardiac tumours in children

    Directory of Open Access Journals (Sweden)

    Parsons Jonathan M

    2007-03-01

    Full Text Available Abstract Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT and Magnetic Resonance Imaging (MRI of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

  1. Time course of infarct healing and left ventricular remodelling in patients with reperfused ST segment elevation myocardial infarction using comprehensive magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ganame, Javier [University Hospitals Leuven, Cardiology Department, Leuven (Belgium); University Hospitals Leuven, Radiology Department, Leuven (Belgium); Messalli, Giancarlo; Dymarkowski, Steven; Abbasi, Kayvan; Bogaert, Jan [University Hospitals Leuven, Radiology Department, Leuven (Belgium); Masci, Pier Giorgio [University Hospitals Leuven, Radiology Department, Leuven (Belgium); MRI Unit, Monasterio Foundation, CNR, Pisa (Italy); Werf, Frans van de; Janssens, Stefan [University Hospitals Leuven, Cardiology Department, Leuven (Belgium)

    2011-04-15

    To describe the time course of myocardial infarct (MI) healing and left ventricular (LV) remodelling and to assess factors predicting LV remodelling using cardiac MRI. In 58 successfully reperfused MI patients, MRI was performed at baseline, 4 months (4M), and 1 year (1Y) post MI Infarct size decreased between baseline and 4M (p < 0.001), but not at 1Y; i.e. 18 {+-} 11%, 12 {+-} 8%, 11 {+-} 6% of LV mass respectively; this was associated with LV mass reduction. Infarct and adjacent wall thinning was found at 4M, whereas significant remote wall thinning was measured at 1Y. LV end-diastolic and end-systolic volumes significantly increased at 1Y, p < 0.05 at 1Y vs. baseline and vs. 4M; this was associated with increased LV sphericity index. No regional or global LV functional improvement was found at follow-up. Baseline infarct size was the strongest predictor of adverse LV remodelling. Infarct healing, with shrinkage of infarcted myocardium and wall thinning, occurs early post-MI as reflected by loss in LV mass and adjacent myocardial remodelling. Longer follow-up demonstrates ongoing remote myocardial and ventricular remodelling. Infarct size at baseline predicts long-term LV remodelling and represents an important parameter for tailoring future post-MI pharmacological therapies designed to prevent heart failure. (orig.)

  2. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

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

  3. Endogenous resident c-Kit cardiac stem cells increase in mice with an exercise-induced, physiologically hypertrophied heart

    Directory of Open Access Journals (Sweden)

    Camila Ferreira Leite

    2015-07-01

    Full Text Available Physical activity evokes well-known adaptations in the cardiovascular system. Although exercise training induces cardiac remodeling, whether multipotent stem cells play a functional role in the hypertrophic process remains unknown. To evaluate this possibility, C57BL/6 mice were subjected to swimming training aimed at achieving cardiac hypertrophy, which was morphologically and electrocardiographically characterized. Subsequently, c-Kit+Lin− and Sca-1+Lin− cardiac stem cells (CSCs were quantified using flow cytometry while cardiac muscle-derived stromal cells (CMSCs, also known as cardiac-derived mesenchymal stem cells were assessed using in vitro colony-forming unit fibroblast assay (CFU-F. Only the number of c-Kit+Lin− cells increased in the hypertrophied heart. To investigate a possible extracardiac origin of these cells, a parabiotic eGFP transgenic/wild-type mouse model was used. The parabiotic pairs were subjected to swimming, and the wild-type heart in particular was tested for eGFP+ stem cells. The results revealed a negligible number of extracardiac stem cells in the heart, allowing us to infer a cardiac origin for the increased amount of detected c-Kit+ cells. In conclusion, the number of resident Sca-1+Lin− cells and CMSCs was not changed, whereas the number of c-Kit+Lin− cells was increased during physiological cardiac hypertrophy. These c-Kit+Lin− CSCs may contribute to the physiological cardiac remodeling that result from exercise training.

  4. 辛伐他汀对大鼠心肌梗死后心室电重构及室颤阈值的影响%Effects of simvastatin on ventricular electrical remodeling and ventricular fibrillation threshold in rats with myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    李帅; 李京波; 朱伟; 余涛; 顾北音; 魏盟

    2011-01-01

    Objective To investigate the effects of simvastatin on ventricular electrical remodeling and ventricular fibrillation threshold after myocardial infarction (MI). Methods MI was induced by ligation of the anterior descending coronary arteries in rats, and the rats survived were randomized to MI group ( n = 8), medium dose simvastatin group ( M-SIM group, n = 8) and high dose simvastatin group ( H-SIM group, n = 8). Another eight rats were served as sham operation controls( sham group). Twenty-four hours after MI, 1 mg· kg - 1· d -1 and 10 mg· kg- 1 · d - 1 simvastatin was dissolved in distilled water and given by gavage to M-SIM group and H-SIM group for 4 weeks, respectively. Isovolume distilled water was given by garage to MI group and Sham group, respectively. Four weeks after MI, echocardiography was conducted, and in vivo electrophysiological examinations were performed. Results There was no significant difference in QTc intervals in each group before MI (P > 0.05). Four weeks after operation, compared with Sham group, QTc intervals was significantly prolonged in MI group ( P < O. 05), effective refractory period (ERP) was shortened in MI group, resulting in downward shifting of ERP-frequency curves (P < 0.05). The incidence of inducible ventricular tachyarrhythmias (IVT) was higher in MI group (P < O. 05), with lower threshold of ventricular fibrillation ( P < 0.05). In M1 group, ERP was significantly prolonged at S1 S1 intervals of 90 ms and 80 ms compared with that at S1 S1 interval of 120 ms ( P < O. 05). QTc intervals in M-SIM group and H-SIM group were significantly shorter than those in MI group (P < 0.05), resulting in upward shifting of ERP-frequency curves, with no significant difference in ERP between S1S1 intervals (P > 0.05). The incidences of IVT in M-SIM group and H-SIM group were also significantly decreased, with significantly higher thresholds of ventricular fibrillation ( P < O. 05). There was no significant difference

  5. Living cardiac tissue slices: an organotypic pseudo two-dimensional model for cardiac biophysics research.

    Science.gov (United States)

    Wang, Ken; Terrar, Derek; Gavaghan, David J; Mu-U-Min, Razik; Kohl, Peter; Bollensdorff, Christian

    2014-08-01

    Living cardiac tissue slices, a pseudo two-dimensional (2D) preparation, have received less attention than isolated single cells, cell cultures, or Langendorff-perfused hearts in cardiac biophysics research. This is, in part, due to difficulties associated with sectioning cardiac tissue to obtain live slices. With moderate complexity, native cell-types, and well-preserved cell-cell electrical and mechanical interconnections, cardiac tissue slices have several advantages for studying cardiac electrophysiology. The trans-membrane potential (Vm) has, thus far, mainly been explored using multi-electrode arrays. Here, we combine tissue slices with optical mapping to monitor Vm and intracellular Ca(2+) concentration ([Ca(2+)]i). This combination opens up the possibility of studying the effects of experimental interventions upon action potential (AP) and calcium transient (CaT) dynamics in 2D, and with relatively high spatio-temporal resolution. As an intervention, we conducted proof-of-principle application of stretch. Mechanical stimulation of cardiac preparations is well-established for membrane patches, single cells and whole heart preparations. For cardiac tissue slices, it is possible to apply stretch perpendicular or parallel to the dominant orientation of cells, while keeping the preparation in a constant focal plane for fluorescent imaging of in-slice functional dynamics. Slice-to-slice comparison furthermore allows one to assess transmural differences in ventricular tissue responses to mechanical challenges. We developed and tested application of axial stretch to cardiac tissue slices, using a manually-controlled stretching device, and recorded Vm and [Ca(2+)]i by optical mapping before, during, and after application of stretch. Living cardiac tissue slices, exposed to axial stretch, show an initial shortening in both AP and CaT duration upon stretch application, followed in most cases by a gradual prolongation of AP and CaT duration during stretch maintained

  6. Synaptic Remodeling Generates Synchronous Oscillations in the Degenerated Outer Mouse Retina

    Directory of Open Access Journals (Sweden)

    Wadood eHaq

    2014-09-01

    Full Text Available During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs establish contacts with remnant cone photoreceptors (cones as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca2+ imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs, we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from HCs. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells.

  7. Suppressor of IKKɛ is an essential negative regulator of pathological cardiac hypertrophy

    Science.gov (United States)

    Deng, Ke-Qiong; Wang, Aibing; Ji, Yan-Xiao; Zhang, Xiao-Jing; Fang, Jing; Zhang, Yan; Zhang, Peng; Jiang, Xi; Gao, Lu; Zhu, Xue-Yong; Zhao, Yichao; Gao, Lingchen; Yang, Qinglin; Zhu, Xue-Hai; Wei, Xiang; Pu, Jun; Li, Hongliang

    2016-01-01

    Although pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide, our understanding of the molecular mechanisms underlying this disease is still poor. Here, we demonstrate that suppressor of IKKɛ (SIKE), a negative regulator of the interferon pathway, attenuates pathological cardiac hypertrophy in rodents and non-human primates in a TANK-binding kinase 1 (TBK1)/AKT-dependent manner. Sike-deficient mice develop cardiac hypertrophy and heart failure, whereas Sike-overexpressing transgenic (Sike-TG) mice are protected from hypertrophic stimuli. Mechanistically, SIKE directly interacts with TBK1 to inhibit the TBK1-AKT signalling pathway, thereby achieving its anti-hypertrophic action. The suppression of cardiac remodelling by SIKE is further validated in rats and monkeys. Collectively, these findings identify SIKE as a negative regulator of cardiac remodelling in multiple animal species due to its inhibitory regulation of the TBK1/AKT axis, suggesting that SIKE may represent a therapeutic target for the treatment of cardiac hypertrophy and heart failure. PMID:27249321

  8. Hypoxia preconditioned mesenchymal stem cells prevent cardiac fibroblast activation and collagen production via leptin.

    Directory of Open Access Journals (Sweden)

    Panpan Chen

    Full Text Available Activation of cardiac fibroblasts into myofibroblasts constitutes a key step in cardiac remodeling after myocardial infarction (MI, due to interstitial fibrosis. Mesenchymal stem cells (MSCs have been shown to improve post-MI remodeling an effect that is enhanced by hypoxia preconditioning (HPC. Leptin has been shown to promote cardiac fibrosis. The expression of leptin is significantly increased in MSCs after HPC but it is unknown whether leptin contributes to MSC therapy or the fibrosis process. The objective of this study was to determine whether leptin secreted from MSCs modulates cardiac fibrosis.Cardiac fibroblast (CF activation was induced by hypoxia (0.5% O2. The effects of MSCs on fibroblast activation were analyzed by co-culturing MSCs with CFs, and detecting the expression of α-SMA, SM22α, and collagen IαI in CFs by western blot, immunofluorescence and Sirius red staining. In vivo MSCs antifibrotic effects on left ventricular remodeling were investigated using an acute MI model involving permanent ligation of the left anterior descending coronary artery.Co-cultured MSCs decreased fibroblast activation and HPC enhanced the effects. Leptin deficit MSCs from Ob/Ob mice did not decrease fibroblast activation. Consistent with this, H-MSCs significantly inhibited cardiac fibrosis after MI and mediated decreased expression of TGF-β/Smad2 and MRTF-A in CFs. These effects were again absent in leptin-deficient MSCs.Our data demonstrate that activation of cardiac fibroblast was inhibited by MSCs in a manner that was leptin-dependent. The mechanism may involve blocking TGF-β/Smad2 and MRTF-A signal pathways.

  9. Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways

    Directory of Open Access Journals (Sweden)

    Dan Bao

    2015-08-01

    Full Text Available Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnTR92Q transgenic mice and thoracic aorta constriction (TAC-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy.

  10. Preoperative cardiac risk management

    OpenAIRE

    Vidaković Radosav; Poldermans Don; Nešković Aleksandar N.

    2011-01-01

    Approximately 100 million people undergo noncardiac surgery annually worldwide. It is estimated that around 3% of patients undergoing noncardiac surgery experience a major adverse cardiac event. Although cardiac events, like myocardial infarction, are major cause of perioperative morbidity or mortality, its true incidence is difficult to assess. The risk of perioperative cardiac complications depends mainly on two conditions: 1) identified risk factors, and 2) the type of the surgical p...

  11. Historical perspectives of cardiac electrophysiology.

    Science.gov (United States)

    Lüderitz, Berndt

    2009-01-01

    The diagnosis and treatment of clinical electrophysiology has a long and fascinating history. From earliest times, no clinical symptom impressed the patient (and the physician) more than an irregular heart beat. Although ancient Chinese pulse theory laid the foundation for the study of arrhythmias and clinical electrophysiology in the 5th century BC, the most significant breakthrough in the identification and treatment of cardiac arrhythmias first occurred in this century. In the last decades, our knowledge of electrophysiology and pharmacology has increased exponentially. The enormous clinical significance of cardiac rhythm disturbances has favored these advances. On the one hand, patients live longer and thus are more likely to experience arrhythmias. On the other hand, circulatory problems of the cardiac vessels have increased enormously, and this has been identified as the primary cause of cardiac rhythm disorders. Coronary heart disease has become not just the most significant disease of all, based on the statistics for cause of death. Arrhythmias are the main complication of ischemic heart disease, and they have been directly linked to the frequently arrhythmogenic sudden death syndrome, which is now presumed to be an avoidable "electrical accident" of the heart. A retrospective look--often charming in its own right--may not only make it easier to sort through the copious details of this field and so become oriented in this universe of important and less important facts: it may also provide the observer with a chronological vantage point from which to view the subject. The study of clinical electrophysiology is no dry compendium of facts and figures, but rather a dynamic field of study evolving out of the competition between various ideas, intentions and theories. PMID:19196616

  12. Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

    OpenAIRE

    Zannad, Faiez; De Ferrari, Gaetano M.; Tuinenburg, Anton E.; Wright, David; Brugada, Josep; Butter, Christian; Klein, Helmut; Stolen, Craig; Meyer, Scott; Stein, Kenneth M.; Ramuzat, Agnes; Schubert, Bernd; Daum, Doug; Neuzil, Petr; Botman, Cornelis

    2014-01-01

    Aim The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy. Methods: Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or contro...

  13. Adult cardiac fibroblast proliferation is modulated by calcium/calmodulin-dependent protein kinase II in normal and hypertrophied hearts.

    Science.gov (United States)

    Martin, Tamara P; Lawan, Ahmed; Robinson, Emma; Grieve, David J; Plevin, Robin; Paul, Andrew; Currie, Susan

    2014-02-01

    Increased adult cardiac fibroblast proliferation results in an increased collagen deposition responsible for the fibrosis accompanying pathological remodelling of the heart. The mechanisms regulating cardiac fibroblast proliferation remain poorly understood. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy, we have assessed fibrosis and cardiac fibroblast proliferation. We have investigated whether calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) regulates proliferation in fibroblasts isolated from normal and hypertrophied hearts. It is known that CaMKIIδ plays a central role in cardiac myocyte contractility, but nothing is known of its role in adult cardiac fibroblast function. The MTAB model used here produces extensive hypertrophy and fibrosis. CaMKIIδ protein expression and activity is upregulated in MTAB hearts and, specifically, in cardiac fibroblasts isolated from hypertrophied hearts. In response to angiotensin II, cardiac fibroblasts isolated from MTAB hearts show increased proliferation rates. Inhibition of CaMKII with autocamtide inhibitory peptide inhibits proliferation in cells isolated from both sham and MTAB hearts, with a significantly greater effect evident in MTAB cells. These results are the first to show selective upregulation of CaMKIIδ in adult cardiac fibroblasts following cardiac hypertrophy and to assign a previously unrecognised role to CaMKII in regulating adult cardiac fibroblast function in normal and diseased hearts. PMID:23881186

  14. Metabolic remodeling associated with subchronic doxorubicin cardiomyopathy

    International Nuclear Information System (INIS)

    Doxorubicin (Adriamycin®) is a potent and broad-spectrum antineoplastic agent, the clinical utility of which is restricted by a cumulative and progressive cardiomyopathy that develops with repeated dosing. Fundamental to the cardiac failure is an interference with mitochondrial respiration and inhibition of oxidative phosphorylation. Global gene expression arrays in cardiac tissue indicate that inhibition of mitochondrial oxidative phosphorylation by doxorubicin (DOX) is accompanied by a decreased expression of genes related to aerobic fatty acid oxidation and a corresponding increase in expression of genes involved in anaerobic glycolysis, possibly as an alternate source for ATP production. The aim of this investigation was to determine whether this is also manifest at the metabonomic level as a switch in metabolic flux in cardiac tissue, and whether this can be averted by co-administering the cardioprotective drug, dexrazoxane (DZR). 13C-isotopomer analysis of isolated perfused hearts from male Sprague-Dawley rats receiving 6 weekly s.c. injections of 2 mg/kg DOX demonstrated a shift from the preferential oxidation of fatty acids to enhanced oxidation of glucose and lactate plus pyruvate, indicative of a compensatory shift towards increased pyruvate dehydrogenase activity. Substrate-selective isotopomer analysis combined with western blots indicate an inhibition of long-chain fatty acid oxidation and not MCAD activity or fatty acyl-carnitine transport. Co-administering DZR averted many treatment-related changes in cardiac substrate metabolism, consistent with DZR being an effective cardioprotective agent against DOX-induced cardiomyopathy. This switch in substrate metabolism resembles that described for other models of cardiac failure; accordingly, this change in metabolic flux may represent a general compensatory response of cardiac tissue to imbalances in bioenergetic demand and supply, and not a characteristic unique to DOX-induced cardiac failure itself.

  15. Eosinophil-Mediated Cholinergic Nerve Remodeling

    OpenAIRE

    Durcan, Niamh; Costello, Richard W; McLean, W. Graham; Blusztajn, Jan; Madziar, Beata; Fenech, Anthony G; Hall, Ian P; Gleich, Gerard J.; McGarvey, Lorcan; Walsh, Marie-Therese

    2006-01-01

    Eosinophils are observed to localize to cholinergic nerves in a variety of inflammatory conditions such as asthma, rhinitis, eosinophilic gastroenteritis, and inflammatory bowel disease, where they are also responsible for the induction of cell signaling.Wehypothesized that a consequence of eosinophil localization to cholinergic nerves would involve a neural remodeling process. Eosinophil co-culture with cholinergic IMR32 cells led to increased expression of the M2 muscar...

  16. PHAGOCYTOSIS AND REMODELING OF COLLAGEN MATRICES

    OpenAIRE

    Abraham, Leah C.; Dice, J. Fred; Lee, Kyongbum; Kaplan, David L.

    2007-01-01

    The biodegradation of collagen and the deposition of new collagen-based extracellular matrices are of central importance in tissue remodeling and function. Similarly, for collagen-based biomaterials used in tissue engineering, the degradation of collagen scaffolds with accompanying cellular infiltration and generation of new extracellular matrix is critical for integration of in vitro grown tissues in vivo. In earlier studies we observed significant impact of collagen structure on primary lun...

  17. Cell wall remodeling under abiotic stress

    OpenAIRE

    Tenhaken, Raimund

    2015-01-01

    Plants exposed to abiotic stress respond to unfavorable conditions on multiple levels. One challenge under drought stress is to reduce shoot growth while maintaining root growth, a process requiring differential cell wall synthesis and remodeling. Key players in this process are the formation of reactive oxygen species (ROS) and peroxidases, which initially cross-link phenolic compounds and glycoproteins of the cell walls causing stiffening. The function of ROS shifts after having converted a...

  18. Application of Petri Nets in Bone Remodeling

    Directory of Open Access Journals (Sweden)

    Lingxi Li

    2009-07-01

    Full Text Available Understanding a mechanism of bone remodeling is a challenging task for both life scientists and model builders, since this highly interactive and nonlinear process can seldom be grasped by simple intuition. A set of ordinary differential equations (ODEs have been built for simulating bone formation as well as bone resorption. Although solving ODEs numerically can provide useful predictions for dynamical behaviors in a continuous time frame, an actual bone remodeling process in living tissues is driven by discrete events of molecular and cellular interactions. Thus, an event-driven tool such as Petri nets (PNs, which may dynamically and graphically mimic individual molecular collisions or cellular interactions, seems to augment the existing ODE-based systems analysis. Here, we applied PNs to expand the ODE-based approach and examined discrete, dynamical behaviors of key regulatory molecules and bone cells. PNs have been used in many engineering areas, but their application to biological systems needs to be explored. Our PN model was based on 8 ODEs that described an osteoprotegerin linked molecular pathway consisting of 4 types of bone cells. The models allowed us to conduct both qualitative and quantitative evaluations and evaluate homeostatic equilibrium states. The results support that application of PN models assists understanding of an event-driven bone remodeling mechanism using PN-specific procedures such as places, transitions, and firings.

  19. Azelnidipine protects myocardium in hyperglycemia-induced cardiac damage

    Directory of Open Access Journals (Sweden)

    Puranik Amrutesh S

    2010-12-01

    Full Text Available Abstract Background Azelnidipine (AZL, a long-acting dihydropyridine-based calcium antagonist, has been recently approved and used for treating ischemic heart disease and cardiac remodeling after myocardial infarction, however, its effect on hyperglycemia-induced cardiac damage has not been studied. Methods This study examined the effect of AZL on circulating markers of cardiac damage, altered lipid and cytokines profile and markers of oxidative stress including homocysteine in diabetic rats. Results STZ induced diabetes caused a significant increase in blood glucose levels. It also resulted in an increase in the levels of homocysteine and cardiac damage markers, like Troponin-1, CK-MB, CK-NAC, uric acid, LDH and alkaline phosphatase. Moreover, there was an increase in the levels of proinflammatory cytokines like TNF-α, IFN-γ, and TGF-β and decrease in the levels of IL-4 and IL-10. Additionally, there was increase in the levels of cholesterol, triglycerides, LDL, VLDL and a decrease in HDL in these animals. There was an altered antioxidant enzyme profile which resulted in a notable increase in the levels of oxidative stress markers like lipid peroxides, nitric oxide and carbonylated proteins. Compared with the untreated diabetic rats, AZL treatment significantly reduced the levels of troponin-1 (P Conclusion Our results indicate that AZL treatment can reduce the risk of hyperglycemia induced metabolic disorders and its role can be further extended to explore its therapeutic potential in diabetic patients with cardiac complications.

  20. [THE RELATIONSHIP BETWEEN DISORDERS-OF EXTERNAL RESPIRATION AND RIGHT HEART REMODELING IN PATIENTS WITH ATOPIC BRONCHIAL ASTHMA].

    Science.gov (United States)

    Solov'eva, I A; Sobko, E A; Ryazanova, N G; Krapohsina, A Yu; Gorgeeva, N V; Demko, I V

    2015-01-01

    This study aimed at the evaluation of the state of the respiratory system and its possible influence on the structural and functional characteristics of the right heart in patients with atopic bronchial asthma (BA) with a view to optimizing diagnostics and prevention of cardiovascular complications. The study included 189 subjects of whom 148 with BA were divided into 3 groups depending on the severity of the disease. Forty practically healthy volunteers comprised the control group. The external respiration function and right ventricle functional parameters were the main variables measured in all the participants of the study. It was shown that disorders of external respiration and pulmonary hyperinflation progressed with severity of BA and thereby promoted right ventricular myocardium remodeling and dysfunction that in turn led to chronic cardiac insufficiency. It is concluded that functional changes in the right heart in of patients with BA of different severity are associated with remodeling of the respiratory tract. PMID:26964462

  1. Central airways remodeling in COPD patients

    Directory of Open Access Journals (Sweden)

    Pini L

    2014-09-01

    Full Text Available Laura Pini,1 Valentina Pinelli,2 Denise Modina,1 Michela Bezzi,3 Laura Tiberio,4 Claudio Tantucci1 1Unit of Respiratory Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 2Department of Respiratory Medicine, Spedali Civili di Brescia, 3Department Bronchoscopy, Spedali Civili di Brescia, 4Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Background: The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. Objectives: The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM area and the extracellular matrix (ECM protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Methods: Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. Results: The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. Conclusion: These findings indicate that airway remodeling also affects

  2. Increased infarct wall thickness by a bio-inert material is insufficient to prevent negative left ventricular remodeling after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Aboli A Rane

    Full Text Available BACKGROUND: Several injectable materials have been shown to preserve or improve cardiac function as well as prevent or slow left ventricular (LV remodeling post-myocardial infarction (MI. However, it is unclear as to whether it is the structural support or the bioactivity of these polymers that lead to beneficial effects. Herein, we examine how passive structural enhancement of the LV wall by an increase in wall thickness affects cardiac function post-MI using a bio-inert, non-degradable synthetic polymer in an effort to better understand the mechanisms by which injectable materials affect LV remodeling. METHODS AND RESULTS: Poly(ethylene glycol (PEG gels of storage modulus G' = 0.5±0.1 kPa were injected and polymerized in situ one week after total occlusion of the left coronary artery in female Sprague Dawley rats. The animals were imaged using magnetic resonance imaging (MRI at 7±1 day(s post-MI as a baseline and again post-injection 49±4 days after MI. Infarct wall thickness was statistically increased in PEG gel injected vs. control animals (p<0.01. However, animals in the polymer and control groups showed decreases in cardiac function in terms of end diastolic volume, end systolic volume and ejection fraction compared to baseline (p<0.01. The cellular response to injection was also similar in both groups. CONCLUSION: The results of this study demonstrate that passive structural reinforcement alone was insufficient to prevent post-MI remodeling, suggesting that bioactivity and/or cell infiltration due to degradation of injectable materials are likely playing a key role in the preservation of cardiac function, thus providing a deeper understanding of the influencing properties of biomaterials necessary to prevent post-MI negative remodeling.

  3. Blunt cardiac rupture.

    Science.gov (United States)

    Martin, T D; Flynn, T C; Rowlands, B J; Ward, R E; Fischer, R P

    1984-04-01

    Blunt injury to the heart ranges from contusion to disruption. This report comprises 14 patients seen during a 6-year period with cardiac rupture secondary to blunt trauma. Eight patients were injured in automobile accidents, two patients were injured in auto-pedestrian accidents, two were kicked in the chest by ungulates, and two sustained falls. Cardiac tamponade was suspected in ten patients. Five patients presented with prehospital cardiac arrest or arrested shortly after arrival. All underwent emergency department thoracotomy without survival. Two patients expired in the operating room during attempted cardiac repair; both had significant extracardiac injury. Seven patients survived, three had right atrial injuries, three had right ventricular injuries, and one had a left atrial injury. Cardiopulmonary bypass was not required for repair of the surviving patients. There were no significant complications from the cardiac repair. The history of significant force dispersed over a relatively small area of the precordium as in a kicking injury from an animal or steering wheel impact should alert the physician to possible cardiac rupture. Cardiac rupture should be considered in patients who present with signs of cardiac tamponade or persistent thoracic bleeding after blunt trauma. PMID:6708151

  4. 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 ...

  5. Mathematical cardiac electrophysiology

    CERN Document Server

    Colli Franzone, Piero; Scacchi, Simone

    2014-01-01

    This book covers the main mathematical and numerical models in computational electrocardiology, ranging from microscopic membrane models of cardiac ionic channels to macroscopic bidomain, monodomain, eikonal models and cardiac source representations. These advanced multiscale and nonlinear models describe the cardiac bioelectrical activity from the cell level to the body surface and are employed in both the direct and inverse problems of electrocardiology. The book also covers advanced numerical techniques needed to efficiently carry out large-scale cardiac simulations, including time and space discretizations, decoupling and operator splitting techniques, parallel finite element solvers. These techniques are employed in 3D cardiac simulations illustrating the excitation mechanisms, the anisotropic effects on excitation and repolarization wavefronts, the morphology of electrograms in normal and pathological tissue and some reentry phenomena. The overall aim of the book is to present rigorously the mathematica...

  6. A case of thyroid storm with cardiac arrest

    Directory of Open Access Journals (Sweden)

    Nakashima Y

    2014-05-01

    Full Text Available Yutaka Nakashima,1 Tsuneaki Kenzaka,2 Masanobu Okayama,3 Eiji Kajii31Department for Support of Rural Medicine, Yamaguchi Grand Medical Center, 2Division of General Medicine, Center for Community Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan; 3Division of Community and Family Medicine, Center for Community Medicine, Jichi Medical University School of Medicine, Shimotsuke, JapanAbstract: A 23-year-old man became unconscious while jogging. He immediately received basic life support from a bystander and was transported to our hospital. On arrival, his spontaneous circulation had returned from a state of ventricular fibrillation and pulseless electrical activity. Following admission, hyperthyroidism led to a suspicion of thyroid storm, which was then diagnosed as a possible cause of the cardiac arrest. Although hyperthyroidism-induced cardiac arrest including ventricular fibrillation is rare, it should be considered when diagnosing the cause of treatable cardiac arrest.Keywords: hyperthyroidism, ventricular fibrillation, treatable cardiac arrest, cardiac arrest, cardiopulmonary arrest

  7. Map-based model of the cardiac action potential

    International Nuclear Information System (INIS)

    A simple computationally efficient model which is capable of replicating the basic features of cardiac cell action potential is proposed. The model is a four-dimensional map and demonstrates good correspondence with real cardiac cells. Various regimes of cardiac activity, which can be reproduced by the proposed model, are shown. Bifurcation mechanisms of these regimes transitions are explained using phase space analysis. The dynamics of 1D and 2D lattices of coupled maps which model the behavior of electrically connected cells is discussed in the context of synchronization theory. -- Highlights: → Recent experimental-data based models are complicated for analysis and simulation. → The simplified map-based model of the cardiac cell is constructed. → The model is capable for replication of different types of cardiac activity. → The spatio-temporal dynamics of ensembles of coupled maps are investigated. → Received data are analyzed in context of biophysical processes in the myocardium.

  8. [Cardiac evaluation before non-cardiac surgery].

    Science.gov (United States)

    Menzenbach, Jan; Boehm, Olaf

    2016-07-01

    Before non-cardiac surgery, evaluation of cardiac function is no frequent part of surgical treatment. European societies of anesthesiology and cardiology published consensus-guidelines in 2014 to present a reasonable approach for preoperative evaluation. This paper intends to differentiate the composite of perioperative risk and to display the guidelines methodical approach to handle it. Features to identify patients at risk from an ageing population with comorbidities, are the classification of surgical risk, functional capacity and risk indices. Application of diagnostic means, should be used adjusted to this risk estimation. Cardiac biomarkers are useful to discover risk of complications or mortality, that cannot be assessed by clinical signs. After preoperative optimization and perioperative cardiac protection, the observation of the postoperative period remains, to prohibit complications or even death. In consideration of limited resources of intensive care department, postoperative ward rounds beyond intensive care units are considered to be an appropriate instrument to avoid or recognize complications early to reduce postoperative mortality. PMID:27479258

  9. Role of arginase in vessel wall remodeling

    Directory of Open Access Journals (Sweden)

    William eDurante

    2013-05-01

    Full Text Available Arginase metabolizes the semi-essential amino acid L-arginine to L-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and L-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages towards an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide synthesis by competing with nitric oxide synthase for substrate, L-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease.

  10. Anti‐Remodeling and Anti‐Fibrotic Effects of the Neuregulin‐1β Glial Growth Factor 2 in a Large Animal Model of Heart Failure

    Science.gov (United States)

    Galindo, Cristi L.; Kasasbeh, Ehab; Murphy, Abigail; Ryzhov, Sergey; Lenihan, Sean; Ahmad, Farhaan A.; Williams, Philip; Nunnally, Amy; Adcock, Jamie; Song, Yanna; Harrell, Frank E.; Tran, Truc‐Linh; Parry, Tom J.; Iaci, Jen; Ganguly, Anindita; Feoktistov, Igor; Stephenson, Matthew K.; Caggiano, Anthony O.; Sawyer, Douglas B.; Cleator, John H.

    2014-01-01

    Background Neuregulin‐1β (NRG‐1β) is a growth factor critical for cardiac development and repair with therapeutic potential for heart failure. We previously showed that the glial growth factor 2 (GGF2) isoform of NRG‐1β improves cardiac function in rodents after myocardial infarction (MI), but its efficacy in a large animal model of cardiac injury has not been examined. We therefore sought to examine the effects of GGF2 on ventricular remodeling, cardiac function, and global transcription in post‐MI swine, as well as potential mechanisms for anti‐remodeling effects. Methods and Results MI was induced in anesthetized swine (n=23) by intracoronary balloon occlusion. At 1 week post‐MI, survivors (n=13) received GGF2 treatment (intravenous, biweekly for 4 weeks; n=8) or were untreated (n=5). At 5 weeks post‐MI, fractional shortening was higher (32.8% versus 25.3%, P=0.019), and left ventricular (LV) end‐diastolic dimension lower (4.5 versus 5.3 cm, P=0.003) in GGF2‐treated animals. Treatment altered expression of 528 genes, as measured by microarrays, including collagens, basal lamina components, and matricellular proteins. GGF2‐treated pigs exhibited improvements in LV cardiomyocyte mitochondria and intercalated disk structures and showed less fibrosis, altered matrix structure, and fewer myofibroblasts (myoFbs), based on trichrome staining, electron microscopy, and immunostaining. In vitro experiments with isolated murine and rat cardiac fibroblasts demonstrate that NRG‐1β reduces myoFbs, and suppresses TGFβ‐induced phospho‐SMAD3 as well as αSMA expression. Conclusions These results suggest that GGF2/NRG‐1β prevents adverse remodeling after injury in part via anti‐fibrotic effects in the heart. PMID:25341890

  11. MYOCARDIAL REMODELING IN ISCHEMIC HEART DISEASE

    OpenAIRE

    A.N. Zakirova; R.G. Oganov; N.E. Zakirova; G. R. Klochkova; F.S. Musina

    2016-01-01

    Aim. To study the myocardial remodeling features in patients with stable angina depending on disease severity and experienced myocardial infarction (MI).Material and methods. 148 male patients with stable angina were examined and randomized into 3 groups (G1-G3). 52 patients of G1 had angina of I-II functional class (FC). 49 patients of G2 had angina of III FC, and 47 patients of G3 had angina of IV FC. History of MI had 79,5, 87.2 and 92.6% of patients in G1, G2 and G3 respectively. 35 healt...

  12. AT2 Receptors Targeting Cardiac Protection Post-Myocardial Infarction

    DEFF Research Database (Denmark)

    Kaschina, Elena; Lauer, Dilyara; Schmerler, Patrick; Unger, Thomas; Steckelings, Ulrike Muscha

    2014-01-01

    The angiotensin AT2-receptor mediates tissue protective actions. Its regenerative potential has been tested in multiple disease models including models of myocardial infarction. These studies used different experimental approaches in order to detect AT2-receptor-related effects such as AT2-receptor...... deficiency or overexpression, treatment with an AT1-receptor blocker leading to indirect stimulation of the unopposed AT2-receptor, or studies using AT2-receptor agonists. It is a common finding in these studies that the AT2-receptor improves cardiac function in the early phase post-MI, and that this effect...... is preserved over periods of up to four months. Depending on the experimental protocol, the AT2R also attenuates post-MI left ventricular remodeling or protects the heart from early left ventricular thinning and rupture. In combination with AT1-receptor blockade or deficiency, post-MI cardiac...

  13. Cardiac metabolism and arrhythmias

    OpenAIRE

    Barth, Andreas S.; Tomaselli, Gordon F.

    2009-01-01

    Sudden cardiac death remains a leading cause of mortality in the Western world, accounting for up to 20% of all deaths in the U.S.1, 2 The major causes of sudden cardiac death in adults age 35 and older are coronary artery disease (70–80%) and dilated cardiomyopathy (10–15%).3 At the molecular level, a wide variety of mechanisms contribute to arrhythmias that cause sudden cardiac death, ranging from genetic predisposition (rare mutations and common polymorphisms in ion channels and structural...

  14. [Cardiac Rehabilitation 2015].

    Science.gov (United States)

    Hoffmann, Andreas

    2015-11-25

    The goals of cardiac rehabilitation are (re-)conditioning and secondary prevention in patients with heart disease or an elevated cardiovascular risk profile. Rehabilitation is based on motivation through education, on adapted physical activity, instruction of relaxation techniques, psychological support and optimized medication. It is performed preferably in groups either in outpatient or inpatient settings. The Swiss working group on cardiac rehabilitation provides a network of institutions with regular quality auditing. Positive effects of rehabilitation programs on mortality and morbidity have been established by numerous studies. Although a majority of patients after cardiac surgery are being referred to rehabilitation, these services are notoriously underused after catheter procedures. PMID:26602848

  15. Comprehensive cardiac rehabilitation

    DEFF Research Database (Denmark)

    Kruse, Marie; Hochstrasser, Stefan; Zwisler, Ann-Dorthe O;

    2006-01-01

    OBJECTIVES: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed. METHODS: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed for...... uncertain and may be as high as euro 1.877. CONCLUSIONS: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective....

  16. Molecular Basis of Cardiac Myxomas

    Directory of Open Access Journals (Sweden)

    Pooja Singhal

    2014-01-01

    Full Text Available Cardiac tumors are rare, and of these, primary cardiac tumors are even rarer. Metastatic cardiac tumors are about 100 times more common than the primary tumors. About 90% of primary cardiac tumors are benign, and of these the most common are cardiac myxomas. Approximately 12% of primary cardiac tumors are completely asymptomatic while others present with one or more signs and symptoms of the classical triad of hemodynamic changes due to intracardiac obstruction, embolism and nonspecific constitutional symptoms. Echocardiography is highly sensitive and specific in detecting cardiac tumors. Other helpful investigations are chest X-rays, magnetic resonance imaging and computerized tomography scan. Surgical excision is the treatment of choice for primary cardiac tumors and is usually associated with a good prognosis. This review article will focus on the general features of benign cardiac tumors with an emphasis on cardiac myxomas and their molecular basis.

  17. PARP inhibition and postinfarction myocardial remodeling.

    Science.gov (United States)

    Halmosi, Robert; Deres, Laszlo; Gal, Roland; Eros, Krisztian; Sumegi, Balazs; Toth, Kalman

    2016-08-01

    Coronary artery disease accounts for the greatest proportion of cardiovascular diseases therefore it is the major cause of death worldwide. Its therapeutic importance is indicated by still high mortality of myocardial infarction, which is one of the most severe forms of CVDs. Moreover, the risk of developing heart failure is very high among survivors. Heart failure is accompanied by high morbidity and mortality rate, therefore this topic is in the focus of researchers' interest. After a myocardial infarct, at first ventricular hypertrophy develops as a compensatory mechanism to decrease wall stress but finally leads to left ventricular dilation. This phenomenon is termed as myocardial remodeling. The main characteristics of underlying mechanisms involve cardiomyocyte growth, vessel changes and increased collagen production, in all of which several mechanical stress induced neurohumoral agents, oxidative stress and signal transduction pathways are involved. The long term activation of these processes ultimately leads to left ventricular dilation and heart failure with decreased systolic function. Oxidative stress causes DNA breaks producing the activation of nuclear poly(ADP-ribose) polymerase-1 (PARP-1) enzyme that leads to energy depletion and unfavorable modulation of different kinase cascades (Akt-1/GSK-3β, MAPKs, various PKC isoforms) and thus it promotes the development of heart failure. Therefore inhibition of PARP enzyme could offer a promising new therapeutical approach to prevent the onset of heart failure among postinfarction patients. The purpose of this review is to give a comprehensive summary about the most significant experimental results and mechanisms in postinfarction remodeling. PMID:27392900

  18. Abnormal bone remodelling in inflammatory arthritis

    Science.gov (United States)

    Bogoch, Earl R.; Moran, Erica

    1998-01-01

    Osteopenia is responsible for substantial comorbidity in patients suffering from rheumatoid arthritis and is an important factor in the surgical management of joint disease. In animal models of bone loss stimulated by inflammatory arthritis, increased bone remodelling and altered microstructure of bone have been documented. The subchondral bone plate near the joint surface is narrow and perforated by vascular inflammatory invasion, and in the shaft the thin cortices are weakened by giant resorption defects. Biomechanical tests and a mathematical model of bone strength suggest that cortical defects, much larger than those found in normal osteonal remodelling, are principally responsible for the experimentally observed loss of strength. Similarly, these defects may explain the increased femoral fracture risk in rheumatoid arthritis. The osteoclast, the cell resorbing bone, is demonstrated in increased number and activity in rheumatoid arthritis and in animal models. Bisphosphonates, drugs that inhibit osteoclast function, have been shown experimentally to reduce both focal and generalized osteopenia and to prevent loss of bone strength. Bisphosphonates also protect articular cartilage from damage characteristic of inflammatory arthritis. The mechanism of chondroprotection may be prevention of subchondral bone resorption by the osteoclast and also an altered distribution of bone marrow cells. Thus, bisphosphonates, currently in clinical use for other bone metabolic diseases, appear to have potential as prophylaxis and treatment for osteopenia and joint damage in inflammatory arthritis. PMID:9711159

  19. Histamine in regulation of bone remodeling processes

    Directory of Open Access Journals (Sweden)

    Marek Wiercigroch

    2013-08-01

    Full Text Available Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H1 receptor antagonists are widely used in the treatment of allergic conditions, H2 receptor antagonists in peptic ulcer disease, and betahistine (an H3 receptor antagonist and H1 receptor agonist is used in the treatment of Ménière’s disease.Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results.Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts. Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H1 and H2 receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed.

  20. [Histamine in regulation of bone remodeling processes].

    Science.gov (United States)

    Wiercigroch, Marek; Folwarczna, Joanna

    2013-01-01

    Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H₁ receptor antagonists are widely used in the treatment of allergic conditions, H₂ receptor antagonists in peptic ulcer disease, and betahistine (an H₃ receptor antagonist and H₁ receptor agonist) is used in the treatment of Ménière's disease. Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results. Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts). Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H₁ and H₂ receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed. PMID:24018454

  1. Epithelial Cell Apoptosis and Lung Remodeling

    Institute of Scientific and Technical Information of China (English)

    Kazuyoshi Kuwano

    2007-01-01

    Lung epithelium is the primary site of lung damage in various lung diseases. Epithelial cell apoptosis has been considered to be initial event in various lung diseases. Apoptosis signaling is classically composed of two principle pathways. One is a direct pathway from death receptor ligation to caspase cascade activation and cell death. The other pathway triggered by stresses such as drugs, radiation, infectious agents and reactive oxygen species is mediated by mitochondria. Endoplasmic reticulum has also been shown to be the organelle to mediate apoptosis.Epithelial cell death is followed by remodeling processes, which consist of epithelial and fibroblast activation,cytokine production, activation of coagulation pathway, neoangiogenesis, re-epithelialization and fibrosis.Epithelial and mesenchymal interaction plays important roles in these processes. Further understanding of apoptosis signaling and its regulation by novel strategies may lead to effective treatments against various lung diseases. We review the recent advances in the understanding of apoptosis signaling and discuss the involvement of apoptosis in lung remodeling.

  2. Atrial remodeling, fibrosis, and atrial fibrillation.

    Science.gov (United States)

    Jalife, José; Kaur, Kuljeet

    2015-08-01

    The fundamental mechanisms governing the perpetuation of atrial fibrillation (AF), the most common arrhythmia seen in clinical practice, are poorly understood, which explains in part why AF prevention and treatment remain suboptimal. Although some clinical parameters have been identified as predicting a transition from paroxysmal to persistent AF in some patients, the molecular, electrophysiological, and inflammation changes leading to such a progression have not been described in detail. Oxidative stress, atrial dilatation, calcium overload, inflammation, microRNAs, and myofibroblast activation are all thought to be involved in AF-induced atrial remodeling. However, it is unknown to what extent and at which time points such alterations influence the remodeling process that perpetuates AF. Here we postulate a working model that might open new pathways for future investigation into mechanisms of AF perpetuation. We start from the premise that the progression to AF perpetuation is the result of interplay among manifold signaling pathways with differing kinetics. Some such pathways have relatively fast kinetics (e.g., oxidative stress-mediated shortening of refractory period); others likely depend on molecular processes with slower kinetics (e.g., transcriptional changes in myocyte ion channel protein expression mediated through inflammation and fibroblast activation). We stress the need to fully understand the relationships among such pathways should one hope to identify novel, truly effective targets for AF therapy and prevention. PMID:25661032

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Current guidelines recommend cardiac resynchronization therapy (CRT) in mild heart failure (HF) patients with QRS prolongation and ejection fraction (EF) ≤30%. To assess the effect of CRT in less severe systolic dysfunction, outcomes in the REsynchronization reVErses Remodeling in Systolic left v......Entricular dysfunction (REVERSE) study were evaluated in which patients with left ventricular (LV) ejection fraction (LVEF) >30% were included....

  4. Dilation and Hypertrophy: A Cell-Based Continuum Mechanics Approach Towards Ventricular Growth and Remodeling

    Science.gov (United States)

    Ulerich, J.; Göktepe, S.; Kuhl, E.

    This manuscript presents a continuum approach towards cardiac growth and remodeling that is capable to predict chronic maladaptation of the heart in response to changes in mechanical loading. It is based on the multiplicative decomposition of the deformation gradient into and elastic and a growth part. Motivated by morphological changes in cardiomyocyte geometry, we introduce an anisotropic growth tensor that can capture both hypertrophic wall thickening and ventricular dilation within one generic concept. In agreement with clinical observations, we propose wall thickening to be a stress-driven phenomenon whereas dilation is introduced as a strain-driven process. The features of the proposed approach are illustrated in terms of the adaptation of thin heart slices and in terms overload-induced dilation in a generic bi-ventricular heart model.

  5. Automatic Implantable Cardiac Defibrillator

    Medline Plus

    Full Text Available Automatic Implantable Cardiac Defibrillator February 19, 2009 Halifax Health Medical Center, Daytona Beach, FL Welcome to Halifax Health Daytona Beach, Florida. Over the next hour you' ...

  6. Sudden Cardiac Arrest

    Science.gov (United States)

    ... scan, or MUGA, which shows how well your heart is pumping blood. Magnetic resonance imaging (MRI) which gives doctors detailed pictures of your heart. How is SCA treated? Sudden cardiac arrest should ...

  7. Sudden Cardiac Arrest

    Science.gov (United States)

    ... Heart Risk Factors & Prevention Heart Diseases & Disorders Atrial Fibrillation (AFib) Sudden Cardiac Arrest (SCA) SCA: Who's At Risk? Prevention of SCA What Causes SCA? SCA Awareness Atrial Flutter Heart Block Heart Failure Sick Sinus Syndrome Substances & Heart Rhythm Disorders Symptoms & ...

  8. Sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Aranđelović Aleksandra Č.

    2004-01-01

    Full Text Available Sudden cardiac death in an athlete is rare and tragic event. An athlete's death draws high public attention given that athletes are considered the healthiest category of society. The vast majority of sudden cardiac death in young athletes is due to congenital cardiac malformations such as hypertrophie cardiomyopathy and various coronary artery anomalies. In athletes over age 35, the usual cause of sudden cardiac death is coronary artery disease. With each tragic death of a young athlete, there is a question why this tragedy has not been prevented. The American College of Sports Medicine and the American Heart Association recommend that a pre-participation exam should include a complete cardiovascular history and physical examination.

  9. Cardiac Risk Assessment

    Science.gov (United States)

    ... to assess cardiac risk include: High-sensitivity C-reactive protein (hs-CRP) : Studies have shown that measuring ... LDL-C but does not respond to typical strategies to lower LDL-C such as diet, exercise, ...

  10. Cardiac arrest - cardiopulmonary resuscitation

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Besnik Elshani; Nehat Baftiu; Kelmend Pallaska; Kadir Hyseni; Njazi Gashi; Nexhbedin Karemani; Ilaz Bunjaku; Taxhidin Zaimi; Arianit Jakupi

    2014-01-01

    Objective:To investigate application of cardiopulmonary resuscitation(CPR) measures within the golden minutes inEurope.Methods:The material was taken from theUniversityClinical Center ofKosovo -EmergencyCentre inPristina, during the two(2) year period(2010-2011).The collected date belong to the patients with cardiac arrest have been recorded in the patients' log book protocol at the emergency clinic.Results:During the2010 to2011 in the emergency center of theCUCK inPristina have been treated a total of269 patients with cardiac arrest, of whom159 or59.1% have been treated in2010, and110 patients or40.9% in2011.Of the269 patients treated in the emergency centre,93 or34.6% have exited lethally in the emergency centre, and176 or 65.4% have been transferred to other clinics.In the total number of patients with cardiac arrest, males have dominated with186 cases, or69.1%.The average age of patients included in the survey was56.7 year oldSD±16.0 years.Of the269 patients with cardiac arrest, defibrillation has been applied for93 or34.6% of patients.In the outpatient settings defibrillation has been applied for3 or3.2% of patients.Patients were defibrillated with application of one to four shocks. Of27 cases with who have survived cardiac arrest, none of them have suffered cardiac arrest at home,3 or11.1% of them have suffered cardiac arrest on the street, and24 or88.9% of them have suffered cardiac arrest in the hospital.5 out of27 patients survived have ended with neurological impairment.Cardiac arrest cases were present during all days of the week, but frequently most reported cases have been onMonday with32.0% of cases, and onFriday with24.5% of cases. Conclusions:All survivors from cardiac arrest have received appropriate medical assistance within10 min from attack, which implies that if cardiac arrest occurs near an institution health care(with an opportunity to provide the emergent health care) the rate of survival is higher.

  11. Effects of Perindopril on Left Ventricular Remodeling and Osteopontin Expression in Rats With Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To observe the effects of perindopril on left ventricular remodeling and myocardial osteopontin expression in rats with myocardial infarction. Methods In this study male adult SD rats were randomly divided into 3groups: sham-operation group, MI-saline group and MI-perindopril group. Left anterior descending artery was ligated to generate myocardial infarction. Perindopril (2 mg/kg body weight/day) was administered from the next day of MI.Four weeks later, left ventricular diameter (LVEDD and LVESD) and left ventricular ejection fraction was estimated with echocardiography, LVSP, LVEDP and ± dp/dtmax was detected with hemodynamic measurement, cardiomyocyte diameter and interstitial fibrosis infiltration were evaluated with histological methods, and myocardium osteopontin protein expression level was detected with western blot. Results ①Compared with the sham-operation group, all rats with MI developed significant systolic and diastolic dysfunction, as was indicated by decreased LVEF, LVSP and ± dp/dtmax, as well as increased LVEDP. ②Rats with MI showed significantly dilated left ventricles and higher ventricular weight / body weight ratio, significantly increased cardiomyocyte diameter and marked interstitial fibrosis in the non-infarction area. ③Perindopril treatment partly prevented cardiac dysfunction and left ventricular remodeling as indicated by the parameters mentioned above. ④No osteopontin protein was detected in myocardium of sham-operation rats. In rats with MI, high level osteopontin protein expression was significantly inhibited by perindopril treatment. Conclusions In rats with MI, perindopril treatment significantly prevented left ventricular remodeling and myocardium osteopontin protein expression.

  12. Awareness in cardiac anesthesia.

    LENUS (Irish Health Repository)

    Serfontein, Leon

    2010-02-01

    Cardiac surgery represents a sub-group of patients at significantly increased risk of intraoperative awareness. Relatively few recent publications have targeted the topic of awareness in this group. The aim of this review is to identify areas of awareness research that may equally be extrapolated to cardiac anesthesia in the attempt to increase understanding of the nature and significance of this scenario and how to reduce it.

  13. Safety in cardiac surgery

    OpenAIRE

    Siregar, S.

    2013-01-01

    The monitoring of safety in cardiac surgery is a complex process, which involves many clinical, practical, methodological and statistical issues. The objective of this thesis was to measure and to compare safety in cardiac surgery in The Netherlands using the Netherlands Association for Cardio-Thoracic Surgery (NVT) database. The safety of care is usually measured using patient outcomes. If outcomes are not available, the process and structure of care may be used. Outcomes should be adjusted ...

  14. Cardiac rehabilitation in Germany.

    Science.gov (United States)

    Karoff, Marthin; Held, Klaus; Bjarnason-Wehrens, Birna

    2007-02-01

    The purpose of this review is to give an overview of the rehabilitation measures provided for cardiac patients in Germany and to outline its legal basis and outcomes. In Germany the cardiac rehabilitation system is different from rehabilitation measures in other European countries. Cardiac rehabilitation in Germany since 1885 is based on specific laws and the regulations of insurance providers. Cardiac rehabilitation has predominantly been offered as an inpatient service, but has recently been complemented by outpatient services. A general agreement on the different indications for offering these two services has yet to be reached. Cardiac rehabilitation is mainly offered after an acute cardiac event and bypass surgery. It is also indicated in severe heart failure and special cases of percutaneous coronary intervention. Most patients are men (>65%) and the age at which events occur is increasing. The benefits obtained during the 3-4 weeks after an acute event, and confirmed in numerous studies, are often later lost under 'usual care' conditions. Many attempts have been made by rehabilitation institutions to improve this deficit by providing intensive aftercare. One instrument set up to achieve this is the nationwide institution currently comprising more than 6000 heart groups with approximately 120000 outpatients. After coronary artery bypass grafting or acute coronary syndrome cardiac rehabilitation can usually be started within 10 days. The multidisciplinary rehabilitation team consists of cardiologists, psychologists, exercise therapists, social workers, nutritionists and nurses. The positive effects of cardiac rehabilitation are also important economically, for example, for the improvement of secondary prevention and vocational integration. PMID:17301623

  15. Ranolazine in Cardiac Arrhythmia.

    Science.gov (United States)

    Saad, Marwan; Mahmoud, Ahmed; Elgendy, Islam Y; Richard Conti, C

    2016-03-01

    Ranolazine utilization in the management of refractory angina has been established by multiple randomized clinical studies. However, there is growing evidence showing an evolving role in the field of cardiac arrhythmias. Multiple experimental and clinical studies have evaluated the role of ranolazine in prevention and management of atrial fibrillation, with ongoing studies on its role in ventricular arrhythmias. In this review, we will discuss the pharmacological, experimental, and clinical evidence behind ranolazine use in the management of various cardiac arrhythmias. PMID:26459200

  16. Cardiac tumours in infancy

    OpenAIRE

    Yadava, O.P.

    2012-01-01

    Cardiac tumours in infancy are rare and are mostly benign with rhabdomyomas, fibromas and teratomas accounting for the majority. The presentation depends on size and location of the mass as they tend to cause cavity obstruction or arrhythmias. Most rhabdomyomas tend to regress spontaneously but fibromas and teratomas generally require surgical intervention for severe haemodynamic or arrhythmic complications. Other relatively rare cardiac tumours too are discussed along with an Indian perspect...

  17. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenchao; Wang, Hui; Zhang, Wei [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Lv, Ruijuan [Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wang, Zhihao [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Geriatrics, Qilu Hospital of Shandong University, Jinan (China); Shang, Yuanyuan; Zhang, Yun; Zhong, Ming [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo; Tang, Mengxiong, E-mail: tangmengxiongsdu8@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)

    2013-08-15

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.

  18. EFFECTIVE INVERSION OF LEFT HEART REMODELING BY PHENYLALANINE IN ESSENTIAL HYPERTENSION

    Institute of Scientific and Technical Information of China (English)

    赵光胜; 邱慧丽; 范明昌; 张伟忠

    2000-01-01

    Objective The aim is to ascertain whether phenylalanine (Phe) can inverse the left heart "remodeling" in patients with essential hypertension. Methods The changes of echocardiographic variables were compared after 3,6 and 9 months of observation between the Phe intervention group (Phe lg/d + amiloride complex 1 tablet/d, 20 cases) and control group (placebo lg/d+amiloride complex 1 tablet/d, 20 cases) with either interventricular septum and (or) post-wall thickness≥12mm, and were carried on further to compare in cross-over trial. Results (1) Phe improved effectively the left heart and systolic dysfunction; while the improvement, also shown in control group due to the concurrent use of diuretic antihypertensive drug-amiloride complex, was much less evident than that in Phe group. (2) The disturbed left heart structure and systolic function were improved prominently while placebo was crossed over to Phe, and the improvement decreased after Phe was crrossed over to placebo. (3) The changes almost attained to its peak level after 6 months and not improved further at 9 months. (4) The differences seen between above 2 groups could not be explained by their diverse drops of blood pressure. Conclusion Phe does exert an independent inverse effect on cardiac "remodeling", which might implicate an important clinical application upon the prevention and control of essential hypertension and its complications.

  19. Effect of Wenxin Granule on Ventricular Remodeling and Myocardial Apoptosis in Rats with Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Aiming Wu

    2013-01-01

    Full Text Available Aim. To determine the effect of a Chinese herbal compound named Wenxin Granule on ventricular remodeling and myocardial apoptosis in rats with myocardial infarction (MI. Methods. Male Sprague-Dawley (SD rats were randomly divided into four groups: the control group, the model group, the metoprolol group, and the Wenxin Granule group (WXKL group with sample size (n of 7 rats in each group. An MI model was established in all rats by occlusion of the left anterior descending coronary artery (the control group was without occlusion. Wenxin Granule (1.35 g/kg/day, metoprolol (12 mg/kg/day, and distilled water (5 mL/kg/day for the control and model groups were administered orally for 4 weeks. Ultrasonic echocardiography was used to examine cardiac structural and functional parameters. Myocardial histopathological changes were observed using haematoxylin and eosin (H&E dyeing. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL staining. Serum angiotensin II (Ang II concentration was measured using the enzyme-linked immunosorbent assay (ELISA. Results. It was found that Wenxin Granule could partially reverse ventricular remodeling, improve heart function, alleviate the histopathological damage, inhibit myocardial apoptosis, and reduce Ang II concentration in rats with MI. Conclusions. The results of the current study suggest that Wenxin Granule may be a potential alternative and complementary medicine for the treatment of MI.

  20. MicroRNA与心血管重构%MicroRNA and cardiovascular remodeling

    Institute of Scientific and Technical Information of China (English)

    邓璧

    2013-01-01

    MicroRNA is a short (18-25 nuucleotides) and single-stranded non-coding RNA which is involved in almost all pathological and physiological process of diseases.Cardiovascular remodeling is the pathological basis of development of multiple cardiovascular diseases,in which microRNA plays an important role.In cardiac diseases,microRNAs affect myocardial cell hypertrophy,apoptosis,and interstitial fibrosis through a variety of mechanisms.In vascular remodeling diseases,microRNAs regulate proliferation and secretion of vascular smooth muscle cells through multiple signaling pathways.%MicroRNA为短小(18~25个核苷酸组成)单链非编码RNAs,几乎参与所有疾病的病理生理过程.心血管重构是多种心血管疾病发生与发展的病理基础,而microRNA在心血管重构中起重要调控作用.在心肌性疾病中,microRNA通过多种机制影响心肌细胞肥大、凋亡和间质纤维化;在血管重构性疾病中,不同microRNA通过多条信号通路调节血管平滑肌细胞增殖和分泌.

  1. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

    International Nuclear Information System (INIS)

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients

  2. A novel approach for assessing cardiac fibrosis using label-free second harmonic generation.

    Science.gov (United States)

    Martin, Tamara P; Norris, Greg; McConnell, Gail; Currie, Susan

    2013-12-01

    To determine whether second harmonic generation (SHG) can be used as a novel and improved label-free technique for detection of collagen deposition in the heart. To verify whether SHG will allow accurate quantification of altered collagen deposition in diseased hearts following hypertrophic remodelling. Minimally invasive transverse aortic banding (MTAB) of mouse hearts was used to generate a reproducible model of cardiac hypertrophy. Physiological and functional assessment of hypertrophic development was performed using echocardiography and post-mortem analysis of remodelled hearts. Cardiac fibroblasts were isolated from sham-operated and hypertrophied hearts and proliferation rates compared. Multi-photon laser scanning microscopy was used to capture both two-photon excited autofluorescence (TPEF) and SHG images simultaneously in two channels. TPEF images were subtracted from SHG images and the resulting signal intensities from ventricular tissue sections were calculated. Traditional picrosirius red staining was used to verify the suitability of the SHG application. MTAB surgery induced significant hypertrophic remodelling and increased cardiac fibroblast proliferation. A significant increase in the density of collagen fibres between hypertrophic and control tissues (p < 0.05) was evident using SHG. Similar increases and patterns of staining were observed using parallel traditional picrosirius red staining of collagen. Label-free SHG microscopy provides a new alternative method for quantifying collagen deposition in fibrotic hearts. PMID:23921804

  3. Epigenetic and lncRNA regulation of cardiac pathophysiology.

    Science.gov (United States)

    Chang, Ching-Pin; Han, Pei

    2016-07-01

    Our developmental studies provide an insight into the pathogenesis of heart failure in adults. These studies reveal a mechanistic link between fetal cardiomyocytes and pathologically stressed adult cardiomyocytes at the level of chromatin regulation. In embryos, chromatin-regulating factors within the cardiomyocytes respond to developmental signals to program cardiac gene expression to promote cell proliferation and inhibit premature cell differentiation. In the neonatal period, the activity of these developmental chromatin regulators is quickly turned off in cardiomyocytes, coinciding with the cessation of cell proliferation and advance in cell differentiation toward adult maturity. When the mature hearts are pathologically stressed, those chromatin regulators essential for cardiomyocyte development in embryos are reactivated, triggering gene reprogramming to a fetal-like state and pathological cardiac hypertrophy. Furthermore, in the study of chromatin regulation and cardiac gene expression, we identified a long noncoding RNA that interacts with chromatin remodeling factor to regulate the cardiac response to environmental changes. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26969820

  4. Prenatal programming: adverse cardiac programming by gestational testosterone excess.

    Science.gov (United States)

    Vyas, Arpita K; Hoang, Vanessa; Padmanabhan, Vasantha; Gilbreath, Ebony; Mietelka, Kristy A

    2016-01-01

    Adverse events during the prenatal and early postnatal period of life are associated with development of cardiovascular disease in adulthood. Prenatal exposure to excess testosterone (T) in sheep induces adverse reproductive and metabolic programming leading to polycystic ovarian syndrome, insulin resistance and hypertension in the female offspring. We hypothesized that prenatal T excess disrupts insulin signaling in the cardiac left ventricle leading to adverse cardiac programming. Left ventricular tissues were obtained from 2-year-old female sheep treated prenatally with T or oil (control) from days 30-90 of gestation. Molecular markers of insulin signaling and cardiac hypertrophy were analyzed. Prenatal T excess increased the gene expression of molecular markers involved in insulin signaling and those associated with cardiac hypertrophy and stress including insulin receptor substrate-1 (IRS-1), phosphatidyl inositol-3 kinase (PI3K), Mammalian target of rapamycin complex 1 (mTORC1), nuclear factor of activated T cells -c3 (NFATc3), and brain natriuretic peptide (BNP) compared to controls. Furthermore, prenatal T excess increased the phosphorylation of PI3K, AKT and mTOR. Myocardial disarray (multifocal) and increase in cardiomyocyte diameter was evident on histological investigation in T-treated females. These findings support adverse left ventricular remodeling by prenatal T excess. PMID:27328820

  5. Cardiac Image Registration

    Directory of Open Access Journals (Sweden)

    2008-09-01

    Full Text Available Long procedure time and somewhat suboptimal results hinder the widespread use of catheter ablation of complex arrhythmias such as atrial fibrillation (AF. Due to lack of contrast differentiation between the area of interest and surrounding structures in a moving organ like heart, there is a lack of proper intraprocedural guidance using current imaging techniques for ablation. Cardiac image registration is currently under investigation and is in clinical use for AF ablation. Cardiac image registration, which involves integration of two images in the context of left atrium (LA, is intermodal, with the acquired image and the real-time reference image residing in different image spaces, and involves optimization, where one image space is transformed into the other. Unlike rigid body registration, cardiac image registration is unique and challenging due to cardiac motion during the cardiac cycle and due to respiration. This review addresses the basic principles of the emerging technique of registration and the inherent limitations as they relate to cardiac imaging and registration.

  6. Cardiac Image Registration

    Directory of Open Access Journals (Sweden)

    Jasbir Sra

    2008-09-01

    Full Text Available Long procedure time and somewhat suboptimal results hinder the widespread use of catheter ablation of complex arrhythmias such as atrial fibrillation (AF. Due to lack of contrast differentiation between the area of interest and surrounding structures in a moving organ like heart, there is a lack of proper intraprocedural guidance using current imaging techniques for ablation. Cardiac image registration is currently under investigation and is in clinical use for AF ablation. Cardiac image registration, which involves integration of two images in the context of the left atrium (LA, is intermodal, with the acquired image and the real-time reference image residing in different image spaces, and involves optimization, where one image space is transformed into the other. Unlike rigid body registration, cardiac image registration is unique and challenging due to cardiac motion during the cardiac cycle and due to respiration. This review addresses the basic principles of the emerging technique of registration and the inherent limitations as they relate to cardiac imaging and registration.

  7. Straining mode-dependent collagen remodeling in engineered cardiovascular tissue

    NARCIS (Netherlands)

    Rubbens, M.P.; Mol, A.; Marion, M.H. van; Hanemaaijer, R.; Bank, R.A.; Baaijens, F.P.T.; Bouten, C.V.C.

    2009-01-01

    Similar to native cardiovascular tissues, the mechanical properties of engineered cardiovascular constructs depend on the composition and quality of the extracellular matrix, which is a net result of matrix remodeling processes within the tissue. To improve tissue remodeling, and hence tissue mechan

  8. Impact of QRS duration on the relationship between left ventricle lead electrical delay and clinical response after cardiac resynchronization therapy%QRS时限对左心室导线电延迟与心脏再同步治疗长期疗效相关性的影响

    Institute of Scientific and Technical Information of China (English)

    樊晓寒; 华伟; 陈柯萍; 孙欣; 杨新伟; 刘志敏; 郑黎辉; 张澍

    2014-01-01

    目的 探讨QRS时限是否影响左心室导线电延迟(LVLED)与心脏再同步治疗(CRT)长期疗效的相关性.方法 前瞻性入选2011年10月至2013年3月在阜外心血管病医院成功植入CRT患者,在围术期测量Q波起始到左心室导线感知波最高峰的时间间距(QLV)反映LVLED.根据患者基线QRS时限分为宽QRS组(≥150 ms)和窄QRS组(<150 ms),基线及术后定期检查超声心动图及随访情况.CRT有反应定义为术后最后1次随访时左心室射血分数提高≥0.05.结果 共入选93例患者,81例患者完成(15±3)个月的随访.平均年龄(60.1±10.4)岁,72%为左束支阻滞,80%为非缺血性心肌病,37.0%为女性.宽QRS组61例,窄QRS组20例.宽QRS组的QLV显著长于窄QRS组[(109.9±38.1) ms对(77.5±37.6) ms,P<0.05].整体CRT有反应率为66.7%.宽QRS组CRT有反应率显著高于窄QRS组(72.1%对50%,P<0.05).在宽QRS组,CRT有反应率随QLV四分位分组显著增加(57.0%,73.3%,80.0%,87.5%,P=0.017).但窄QRS组QLV四分位组间CRT有反应率差异无统计学意义(P>0.05).多因素回归分析校正年龄、性别、束支阻滞和缺血性心肌病后,宽QRS组长QLV与CRT有反应显著相关(OR4.12,95% CI 2.17~8.68,P=0.012).但窄QRS组QLV与CRT反应无相关性(P>0.05).结论 只有当基线QRS时限≥150 ms时,应用LVLED指导左心室导线位置有助于提高CRT的长期疗效.%Objective The left ventricle lead electrical delay (LVLED)has been associated with reverse remodeling after cardiac resynchronization therapy(CRT).The impact of QRS duration on the relationship between LVLED and CRT clinical response remains unclear.Methods We prospectively enrolled a series of consecutive patients undergoing CRT implantation according to standard clinical indications.The LVLED was measured from the onset of the surface electrco cardiogram QRS complex to the first large peak of the unipolar LV tip to can intracardiac electrogram during spontaneous

  9. Postoperative cardiac arrest due to cardiac surgery complications

    International Nuclear Information System (INIS)

    To examine the role of anesthetists in the management of cardiac arrest occurring in association with cardiac anesthesia. In this retrospective study we studied the potential performances for each of the relevant incidents among 712 patients undergoing cardiac operations at Golestan and Naft Hospitals Ahwaz between November 2006 and July 2008. Out of total 712 patients undergoing cardiac surgery, cardiac arrest occurred in 28 cases (3.9%) due to different postoperative complications. This included massive bleeding (50% of cardiac arrest cases, 1.9% of patients); pulseless supra ventricular tachycardia (28.5% of cardiac arrest cases, 1.1% of patients); Heart Failure (7% of cardiac arrest cases, 0.2% of patients); Aorta Arc Rapture (3.5% of cardiac arrest cases, 0.1% of patients); Tamponade due to pericardial effusion (3.5% of cardiac arrest cases, 0.1% of total patients); Right Atrium Rupture (3.5% of cardiac arrest cases, 0.1% of patients) were detected after cardiac surgery. Out of 28 cases 7 deaths occurred (25% of cardiac arrest cases, 0.1% of patients). The most prevalent reason for cardiac arrest during post operative phase was massive bleeding (50%) followed by pulseless supra ventricular tachycardia (28.5%). Six patients had some morbidity and the remaining 15 patients recovered. There are often multiple contributing factors to a cardiac arrest under cardiac anesthesia, as much a complete systematic assessment of the patient, equipment, and drugs should be completed. We also found that the diagnosis and management of cardiac arrest in association with cardiac anesthesia differs considerably from that encountered elsewhere. (author)

  10. Cardiac size of high-volume resistance trained female athletes: shaping the body but not the heart.

    Science.gov (United States)

    Venckunas, T; Simonavicius, J; Marcinkeviciene, J E

    2016-03-01

    Introduction Exercise training, besides many health benefits, may result in cardiac remodelling which is dependent on the type and amount of exercise performed. It is not clear, however, whether significant adaptation in cardiac structure is possible in females undergoing resistance type of exercise training. Rigorous high volume training of most muscle groups emphasising resistance exercises are being undertaken by athletes of some aesthetic sports such as female fitness (light bodybuilding). The impact of this type of training on cardiac adaptation has not been investigated until now. The aim of the current study was to disclose the effect of high volume resistance training on cardiac structure and function. Methods 11 top-level female fitness athletes and 20 sedentary age-matched controls were recruited to undergo two-dimensional echocardiography. Results Cardiac structure did not differ between elite female fitness athletes and controls (p > 0.05), and fitness athletes had a tendency for a smaller (p = 0.07) left ventricular (LV) mass indexed to lean body mass. Doppler diastolic function index (E/A ratio) and LV ejection fraction were similar between the groups (p > 0.05). Conclusions Elite female fitness athletes have normal cardiac size and function that do not differ from matched sedentary controls. Consequently, as high volume resistance training has no easily observable effect on adaptation of cardiac structure, when cardiac hypertrophy is present in young resistance-trained lean female, other reasons such as inherited cardiac disease are to be considered carefully. PMID:27030632

  11. Multiscale Bone Remodelling with Spatial P Systems

    CERN Document Server

    Cacciagrano, Diletta; Merelli, Emanuela; Tesei, Luca; 10.4204/EPTCS.40.6

    2010-01-01

    Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as ...

  12. Matrix Remodeling in Pulmonary Fibrosis and Emphysema.

    Science.gov (United States)

    Kulkarni, Tejaswini; O'Reilly, Philip; Antony, Veena B; Gaggar, Amit; Thannickal, Victor J

    2016-06-01

    Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. PMID:26741177

  13. Renovascular hypertension causes cerebral vascular remodeling

    Institute of Scientific and Technical Information of China (English)

    Yamei Tang; Xiangpen Li; Yi Li; Qingyu Shen; Xiaoming Rong; Ruxun Huang; Ying Peng

    2011-01-01

    Renovascular hypertensive rats (RHRs) were developed using the 2-kidney, 2-clip method. All RHRs at 10 weeks displayed high permeability of the cerebral surface blood vessels. Vascular casts of the RHRs showed that the vascular network was sparse. The arterioles of the RHRs at 10 weeks had smaller lumen diameters, but thicker vessel walls with hyalinosis formation compared with control animals. The endothelial cell membrane appeared damaged, and microthrombus formed. After ischemia, the infarction size was larger in RHRs than in control animals. These results suggest that cerebral arterioles in RHRs underwent structural remodeling. High blood pressure may aggravate the severity of brain injury in cerebral ischemia and affect the recovery of ischemia.

  14. Paroxetine-mediated GRK2 inhibition reverses cardiac dysfunction and remodeling after myocardial infarction

    OpenAIRE

    Schumacher, Sarah M.; Gao, Erhe; Zhu, Weizhong; Chen, Xiongwen; Chuprun, J. Kurt; Feldman, Arthur M.; Tesmer, John J.G.; Koch, Walter J.

    2015-01-01

    Heart failure (HF) is a disease of epidemic proportion and is associated with exceedingly high health care costs. G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptor (GPCR) kinase 2 (GRK2), which is up-regulated in the failing human heart, appears to play a critical role in HF progression in part because enhanced GRK2 activity promotes dysfunctional adrenergic signaling and myocyte death. Recently, we found that the selective serotonin reuptake inhibitor (SSRI) paro...

  15. PNPLA3 mediates hepatocyte triacylglycerol remodeling.

    Science.gov (United States)

    Ruhanen, Hanna; Perttilä, Julia; Hölttä-Vuori, Maarit; Zhou, You; Yki-Järvinen, Hannele; Ikonen, Elina; Käkelä, Reijo; Olkkonen, Vesa M

    2014-04-01

    The I148M substitution in patatin-like phospholipase domain containing 3 (PNPLA3(I148M)) determines a genetic form of nonalcoholic fatty liver disease. To elucidate the mode of PNPLA3 action in human hepatocytes, we studied effects of WT PNPLA3 (PNPLA3(WT)) and PNPLA3(I148M) on HuH7 cell lipidome after [(13)C]glycerol labeling, cellular turnover of oleic acid labeled with 17 deuterium atoms ([D17]oleic acid) in triacylglycerols (TAGs), and subcellular distribution of the protein variants. PNPLA3(I148M) induced a net accumulation of unlabeled TAGs, but not newly synthesized total [(13)C]TAGs. Principal component analysis (PCA) revealed that both PNPLA3(WT) and PNPLA3(I148M) induced a relative enrichment of TAGs with saturated FAs or MUFAs, with concurrent enrichment of polyunsaturated phosphatidylcholines. PNPLA3(WT) associated in PCA with newly synthesized [(13)C]TAGs, particularly 52:1 and 50:1, while PNPLA3(I148M) associated with similar preexisting TAGs. PNPLA3(WT) overexpression resulted in increased [D17]oleic acid labeling of TAGs during 24 h, and after longer incubations their turnover was accelerated, effects not detected with PNPLA3(I148M). PNPLA3(I148M) localized more extensively to lipid droplets (LDs) than PNPLA3(WT), suggesting that the substitution alters distribution of PNPLA3 between LDs and endoplasmic reticulum/cytosol. This study reveals a function of PNPLA3 in FA-selective TAG remodeling, resulting in increased TAG saturation. A defect in TAG remodeling activity likely contributes to the TAG accumulation observed in cells expressing PNPLA3(I148M). PMID:24511104

  16. Effect of Astragalus Injection on Left Ventricular Remodeling in Aged Patients with Acute Early-stage Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jin-guo (张金国); LIU Ya-jie(刘雅洁); GAO Dong-sheng (高东升); YANG Na (杨娜); LIU Li-xin (刘立新); HE Hua (何华); DONG Hai-xin (董海新); LIU Xue-ling (刘雪玲); CHEN Ting (陈廷); WANG Xue-zhong (王学忠)

    2003-01-01

    Objective: To observe the effect of Astragalus Injection (AI) on left ventricular remodeling in aged patients with acute myocardial infarction (AMI).Methods: Patients with AMI were randomly divided into the AI group (46 cases) treated with AI and the control group (46 cases) treated conventionally. Left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), anterior endocardial segmental length (ASL) and posterior endocardial segmental length (PSL) were all assessed by echocardiogram after 1 week and 4 weeks treatment. The cardiac systolic and diastolic functions were detected by nuclide gating cardiac blood pool imaging at the 4th week. Results: After four weeks' treatment, no obvious change of LVEDVI, LVESVI and ASL in the AI group was found, but these indexes increased significantly in the control group, with significant difference shown between the two groups (P<0.05). As compared with the control group, the left ventricular ejection fraction (LVEF), left ventricular peak ejecting rate (LVPER) and left ventricular peak filling rate (LVPFR) were heightened, the time for peak filling rate (LVTPFR) in the left ventricle was shortened in the AI group.Conclusion: AI is one of the effective drugs in reversing left ventricular remodeling in aged patients with AMI.

  17. Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study*

    OpenAIRE

    Zhan, He-qing; Xia, Ling; Shou, Guo-fa; Zang, Yun-liang; Liu, Feng; Crozier, Stuart

    2014-01-01

    In this study, the effects of cardiac fibroblast proliferation on cardiac electric excitation conduction and mechanical contraction were investigated using a proposed integrated myocardial-fibroblastic electromechanical model. At the cellular level, models of the human ventricular myocyte and fibroblast were modified to incorporate a model of cardiac mechanical contraction and cooperativity mechanisms. Cellular electromechanical coupling was realized with a calcium buffer. At the tissue level...

  18. EPAC expression and function in cardiac fibroblasts and myofibroblasts

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-15

    In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF were treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in cardiac

  19. EPAC expression and function in cardiac fibroblasts and myofibroblasts

    International Nuclear Information System (INIS)

    In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF were treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in cardiac

  20. Recipient–derived EDA fibronectin promotes cardiac allograft fibrosis

    Science.gov (United States)

    Booth, Adam J; Wood, Sherri C; Cornett, Ashley M; Dreffs, Alyssa A; Lu, Guanyi; Muro, Andrés F; White, Eric S; Bishop, D Keith

    2014-01-01

    Advances in donor matching and immunosuppressive therapies have decreased the prevalence of acute rejection of cardiac grafts; however, chronic rejection remains a significant obstacle for long-term allograft survival. While initiating elements of anti-allograft immune responses have been identified, the linkage between these factors and the ultimate development of cardiac fibrosis is not well understood. Tissue fibrosis resembles an exaggerated wound healing response, in which extracellular matrix (ECM) molecules are central. One such ECM molecule is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin (FN), termed extra domain A-containing cellular fibronectin (EDA cFN). EDA cFN is instrumental in fibrogenesis; thus, we hypothesized that it might also regulate fibrotic remodelling associated with chronic rejection. We compared the development of acute and chronic cardiac allograft rejection in EDA cFN-deficient (EDA−/−) and wild-type (WT) mice. While EDA−/− mice developed acute cardiac rejection in a manner indistinguishable from WT controls, cardiac allografts in EDA−/− mice were protected from fibrosis associated with chronic rejection. Decreased fibrosis was not associated with differences in cardiomyocyte hypertrophy or intra-graft expression of pro-fibrotic mediators. Further, we examined expression of EDA cFN and total FN by whole splenocytes under conditions promoting various T-helper lineages. Conditions supporting regulatory T-cell (Treg) development were characterized by greatest production of total FN and EDA cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These findings indicate that recipient-derived EDA cFN is dispensable for acute allograft rejection responses but that it promotes the development of fibrosis associated with chronic rejection. Further, conditions favouring the development of regulatory T cells, widely considered graft-protective, may drive production of ECM molecules which

  1. [Effect of dosed diet restriction on physiological remodeling and bioelectric properties of bone].

    Science.gov (United States)

    Levashov, M I; Ianko, R V; Chaka, E G; Safonov, S L

    2014-07-01

    The effect of dosed diet restriction on the physiological remodeling and bioelectric properties of bone tissue was studied in 48 male Wistar rats 3- and 18-months of age. The rate of bone tissue apposition was studied by the dynamic histomorphometry method (intravital tetracycline labeling). Electric potentials on the periosteal surface of the freshly isolated femurs were recorded. The magnitude of dielectric loss factor was determined to assess the quality of bone tissue. The control rats received a standard diet. The experimental rats received a limited diet (60 % of the standard mass) for 28 days. The magnitude and rate of the bone tissue apposition on the endosteal and periosteal surface of the tibia were less by 38.4% and 122.7% respectively in experimental rats after dosed diet restriction. Electric potential in the metaphyseal-epiphyseal growth zones of the femur was 29.7% lower, and the dielectric loss factor increased by 15.8%. The bone tissue apposition rate and the electric potential magnitude were increased 10 days after completion of the dosed diet restriction. The magnitude of the dielectric loss factor decreased after returning to the standard diet. Key words: dosed diet restriction, bone, remodelling, bioelectric properties. PMID:25669112

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

    Science.gov (United States)

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

    2016-01-01

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

  3. Generation of cardiac pacemaker cells by programming and differentiation.

    Science.gov (United States)

    Husse, Britta; Franz, Wolfgang-Michael

    2016-07-01

    A number of diseases are caused by faulty function of the cardiac pacemaker and described as "sick sinus syndrome". The medical treatment of sick sinus syndrome with electrical pacemaker implants in the diseased heart includes risks. These problems may be overcome via "biological pacemaker" derived from different adult cardiac cells or pluripotent stem cells. The generation of cardiac pacemaker cells requires the understanding of the pacing automaticity. Two characteristic phenomena the "membrane-clock" and the "Ca(2+)-clock" are responsible for the modulation of the pacemaker activity. Processes in the "membrane-clock" generating the spontaneous pacemaker firing are based on the voltage-sensitive membrane ion channel activity starting with slow diastolic depolarization and discharging in the action potential. The influence of the intracellular Ca(2+) modulating the pacemaker activity is characterized by the "Ca(2+)-clock". The generation of pacemaker cells started with the reprogramming of adult cardiac cells by targeted induction of one pacemaker function like HCN1-4 overexpression and enclosed in an activation of single pacemaker specific transcription factors. Reprogramming of adult cardiac cells with the transcription factor Tbx18 created cardiac cells with characteristic features of cardiac pacemaker cells. Another key transcription factor is Tbx3 specifically expressed in the cardiac conduction system including the sinoatrial node and sufficient for the induction of the cardiac pacemaker gene program. For a successful cell therapeutic practice, the generated cells should have all regulating mechanisms of cardiac pacemaker cells. Otherwise, the generated pacemaker cells serve only as investigating model for the fundamental research or as drug testing model for new antiarrhythmics. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel

  4. Changes in microRNAs expression are involved in age-related atrial structural remodeling and atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    XU Guo-jun; GAN Tian-yi; TANG Bao-peng; CHEN Zu-heng; Mahemuti Ailiman; ZHOU Xian-hui; JIANG Tao

    2013-01-01

    Background Small noncoding microRNAs regulate gene expression in cardiac development and disease and have been implicated in the aging process and in the regulation of extracellular matrix proteins.However,their role in age-related cardiac remodeling and atrial fibrillation (AF) was not well understood.The present study was designed to decipher molecular mechanisms underlying age-related atrial structural remodeling and AF.Methods Three groups of dogs were studied:adult and aged dogs in sinus rhythm and with persistent AF induced by rapid atrial pacing.The expressions of microRNAs were measured by quantitative real-time polymerase chain reaction.Pathohistological and ultrastructural changes were tested by light and electron microscopy.Apoptosis index of myocytes was detected by TUNEL.Results Samples of atrial tissue showed the abnormal pathohistological and ultrastructural changes,the accelerated fibrosis,and apoptosis with aging and/or in AF dogs.Compared to the adult group,the expressions of microRNAs-21 and -29 were significantly increased,whereas the expressions of microRNAs-1 and-133 showed obvious downregulation tendency in the aged group.Compared to the aged group,the expressions of microRNAs-1,-21,and-29 was significantly increased in the old group in AF; contrastingly,the expressions of microRNA-133 showed obvious downregulation tendency.Conclusion These multiple aberrantly expressed microRNAs may be responsible for modulating the transition from adaptation to pathological atrial remodeling with aging and/or in AF.

  5. Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation.

    Science.gov (United States)

    Stembridge, Mike; Ainslie, Philip N; Hughes, Michael G; Stöhr, Eric J; Cotter, James D; Nio, Amanda Q X; Shave, Rob

    2014-08-01

    Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at sea level (SL) and following 10 ± 3 days at 5,050 m (n = 9; 34 ± 7 yr; mass 82 ± 10 kg; height 177 ± 6 cm) using conventional and speckle-tracking echocardiography. At HA, PASP was higher in Sherpa and lowlanders compared with lowlanders at SL (both P stroke volumes than lowlanders at SL with lower RV systolic strain (P < 0.05) but similar LV systolic mechanics. In contrast to LV systolic mechanics, LV diastolic, untwisting velocity was significantly lower in Sherpa compared with lowlanders at both SL and HA. After partial acclimatization, lowlanders demonstrated no change in the RV end-diastolic area; however, both RV strain and LV end-diastolic volume were reduced. In conclusion, short-term hypoxia induced a reduction in RV systolic function that was also evident in Sherpa following chronic exposure. We propose that this was consequent to a persistently higher PASP. In contrast to the RV, remodeling of LV volumes and normalization of systolic mechanics indicate structural and functional adaptation to HA. However, altered LV diastolic relaxation after chronic hypoxic exposure may reflect differential remodeling of systolic and diastolic LV function. PMID:24876358

  6. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2008-12-01

    Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

  7. Impaired glutathione redox system paradoxically suppresses angiotensin II-induced vascular remodeling.

    Directory of Open Access Journals (Sweden)

    Kazuma Izawa

    Full Text Available BACKGROUND: Angiotensin II (AII plays a central role in vascular remodeling via oxidative stress. However, the interaction between AII and reduced glutathione (GSH redox status in cardiovascular remodeling remains unknown. METHODS: In vivo: The cuff-induced vascular injury model was applied to Sprague Dawley rats. Then we administered saline or a GSH inhibitor, buthionine sulfoximine (BSO, 30 mmol/L in drinking water for a week, subsequently administered 4 more weeks by osmotic pump with saline or AII (200 ng/kg/minute to the rats. In vitro: Incorporation of bromodeoxyuridine (BrdU was measured to determine DNA synthesis in cultured rat vascular smooth muscle cells (VSMCs. RESULTS: BSO reduced whole blood GSH levels. Systolic blood pressure was increased up to 215 ± 4 mmHg by AII at 4 weeks (p<0.01, which was not affected by BSO. Superoxide production in vascular wall was increased by AII and BSO alone, and was markedly enhanced by AII+BSO. The left ventricular weight to body weight ratio was significantly increased in AII and AII+BSO as compared to controls (2.52 ± 0.08, 2.50 ± 0.09 and 2.10 ± 0.07 mg/g respectively, p<0.05. Surprisingly, the co-treatment of BSO totally abolished these morphological changes. Although the vascular circumferential wall stress was well compensated in AII, significantly increased in AII+BSO. The anti-single-stranded DNA staining revealed increasing apoptotic cells in the neointima of injured arteries in BSO groups. BrdU incorporation in cultured VSMCs with AII was increased dose-dependently. Furthermore it was totally abolished by BSO and was reversed by GSH monoethyl ester. CONCLUSIONS: We demonstrated that a vast oxidative stress in impaired GSH redox system totally abolished AII-induced vascular, not cardiac remodeling via enhancement of apoptosis in the neointima and suppression of cell growth in the media. The drastic suppression of remodeling may result in fragile vasculature intolerable to mechanical

  8. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    Science.gov (United States)

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  9. Pediatric cardiac postoperative care

    Directory of Open Access Journals (Sweden)

    Auler Jr. José Otávio Costa

    2002-01-01

    Full Text Available The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

  10. Update on the Pathogenic Implications and Clinical Potential of microRNAs in Cardiac Disease

    Directory of Open Access Journals (Sweden)

    Mario Notari

    2015-01-01

    Full Text Available miRNAs, a unique class of endogenous noncoding RNAs, are highly conserved across species, repress gene translation upon binding to mRNA, and thereby influence many biological processes. As such, they have been recently recognized as regulators of virtually all aspects of cardiac biology, from the development and cell lineage specification of different cell populations within the heart to the survival of cardiomyocytes under stress conditions. Various miRNAs have been recently established as powerful mediators of distinctive aspects in many cardiac disorders. For instance, acute myocardial infarction induces cardiac tissue necrosis and apoptosis but also initiates a pathological remodelling response of the left ventricle that includes hypertrophic growth of cardiomyocytes and fibrotic deposition of extracellular matrix components. In this regard, recent findings place various miRNAs as unquestionable contributing factors in the pathogenesis of cardiac disorders, thus begging the question of whether miRNA modulation could become a novel strategy for clinical intervention. In the present review, we aim to expose the latest mechanistic concepts regarding miRNA function within the context of CVD and analyse the reported roles of specific miRNAs in the different stages of left ventricular remodelling as well as their potential use as a new class of disease-modifying clinical options.

  11. Update on the Pathogenic Implications and Clinical Potential of microRNAs in Cardiac Disease.

    Science.gov (United States)

    Notari, Mario; Pulecio, Julián; Raya, Ángel

    2015-01-01

    miRNAs, a unique class of endogenous noncoding RNAs, are highly conserved across species, repress gene translation upon binding to mRNA, and thereby influence many biological processes. As such, they have been recently recognized as regulators of virtually all aspects of cardiac biology, from the development and cell lineage specification of different cell populations within the heart to the survival of cardiomyocytes under stress conditions. Various miRNAs have been recently established as powerful mediators of distinctive aspects in many cardiac disorders. For instance, acute myocardial infarction induces cardiac tissue necrosis and apoptosis but also initiates a pathological remodelling response of the left ventricle that includes hypertrophic growth of cardiomyocytes and fibrotic deposition of extracellular matrix components. In this regard, recent findings place various miRNAs as unquestionable contributing factors in the pathogenesis of cardiac disorders, thus begging the question of whether miRNA modulation could become a novel strategy for clinical intervention. In the present review, we aim to expose the latest mechanistic concepts regarding miRNA function within the context of CVD and analyse the reported roles of specific miRNAs in the different stages of left ventricular remodelling as well as their potential use as a new class of disease-modifying clinical options. PMID:26221581

  12. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene B; Levin Andersen, Thomas; Marcussen, Niels;

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling is...... lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels on...

  13. Estrogen modulates the influence of cardiac inflammatory cells on function of cardiac fibroblasts

    Directory of Open Access Journals (Sweden)

    McLarty JL

    2013-08-01

    untreated group resulted in: 1 an increased fibroblast proliferation, collagen production and matrix metalloproteinase activity; and 2 a loss of ß1 integrin protein and a reduced ability to contract collagen gels. In contrast, inflammatory cells from the treated group resulted in: 1 an attenuated fibroblast proliferation; 2 a nonsignificant reduction in collagen production; 3 the prevention of matrix metalloproteinase activation and the loss of β1 integrin by fibroblasts and 4 a preservation of the fibroblasts’ ability to contract collagen gels. The TNF-α neutralizing antibody attenuated or prevented the untreated inflammatory cell-induced fibroblast proliferation, collagen production, matrix metalloproteinase activation and loss of β1 integrin protein as well as preserved fibroblast contractile ability. Incubation with TNF-α yielded changes in the cardiac fibroblast parameters that were directionally similar to the results obtained with untreated inflammatory cells. Conclusion: These results and those of our previous in vivo studies suggest that a major mechanism by which estrogen provides cardioprotection is its ability to modulate synthesis of TNF-α by inflammatory cells, thereby preventing inflammatory cell induction of cardiac fibroblast events that contribute to adverse extracellular matrix remodeling. Keywords: tumor necrosis factor-alpha, neutralizing antibody, fibroblast proliferation, matrix metalloproteinase activity, β1 integrin, collagen gel contraction

  14. Retinoic acid signalling is activated in the postischemic heart and may influence remodelling.

    Directory of Open Access Journals (Sweden)

    Dusan Bilbija

    Full Text Available BACKGROUND: All-trans retinoic acid (atRA, an active derivative of vitamin A, regulates cell differentiation, proliferation and cardiac morphogenesis via transcriptional activation of retinoic acid receptors (RARs acting on retinoic acid response elements (RARE. We hypothesized that the retinoic acid (RA signalling pathway is activated in myocardial ischemia and postischemic remodelling. METHODS AND FINDINGS: Myocardial infarction was induced through ligating the left coronary artery in mice. In vivo cardiac activation of the RARs was measured by imaging RARE-luciferase reporter mice, and analysing expression of RAR target genes and proteins by real time RT-PCR and western blot. Endogenous retinoids in postinfarcted hearts were analysed by triple-stage liquid chromatography/tandem mass spectrometry. Cardiomyocytes (CM and cardiofibroblasts (CF were isolated from infarcted and sham operated RARE luciferase reporter hearts and monitored for RAR activity and expression of target genes. The effect of atRA on CF proliferation was evaluated by EdU incorporation. Myocardial infarction increased thoracic RAR activity in vivo (p<0.001, which was ascribed to the heart through ex vivo imaging (p = 0.002 with the largest signal 1 week postinfarct. This was accompanied by increased cardiac gene and protein expression of the RAR target genes retinol binding protein 1 (p = 0.01 for RNA, p = 0,006 for protein and aldehyde dehydrogenase 1A2 (p = 0.04 for RNA, p = 0,014 for protein, while gene expression of cytochrome P450 26B1 was downregulated (p = 0.007. Concomitantly, retinol accumulated in the infarcted zone (p = 0.02. CM and CF isolated from infarcted hearts had higher luminescence than those from sham operated hearts (p = 0.02 and p = 0.008. AtRA inhibited CF proliferation in vitro (p = 0.02. CONCLUSION: The RA signalling pathway is activated in postischemic hearts and may play a role in regulation of damage and

  15. Giant Cardiac Cavernous Hemangioma.

    Science.gov (United States)

    Unger, Eric; Costic, Joseph; Laub, Glenn

    2015-07-01

    We report the case of an asymptomatic giant cardiac cavernous hemangioma in a 71-year-old man. The intracardiac mass was discovered incidentally during surveillance for his prostate cancer; however, the patient initially declined intervention. On presentation to our institution 7 years later, the lesion had enlarged significantly, and the patient consented to excision. At surgery, an 8 × 6.5 × 4.8 cm intracardiac mass located on the inferior heart border was excised with an intact capsule through a median sternotomy approach. The patient had an uneventful postoperative course. We discuss the diagnostic workup, treatment, and characteristics of this rare cardiac tumor. PMID:26140782

  16. Radiography in cardiology [cardiac disorders, cardiac insufficiency

    International Nuclear Information System (INIS)

    The diagnostic procedure in cardiology nearly always requires an X-ray examination of the thorax. This examination is very informative when it is correctly performed and interpreted. The radiographs need to be read precisely and comprehensively: this includes the evaluation of the silhouette of the heart (size, form and position) as well as the examination of extra-cardiac thoracic structures allowing among other things to search for signs of cardiac insufficiency. The conclusion of the X-ray examination can be drawn after having brought together information concerning the case history, the clinical examination and the study of the radiographs. The radiologist finds himself in one of three situations: (1) the information provided by the X-ray pictures is characteristic of a disease and permits a diagnosis, (2) the X-ray pictures indicate a group of hypotheses; further complementary tests could be useful and (3) the X-ray pictures provide ambiguous even contradictory information; it is necessary to complete the radiological examination by other techniques such as an ultrasonographic study of the heart

  17. Mapping cardiac fiber orientations from high-resolution DTI to high-frequency 3D ultrasound

    Science.gov (United States)

    Qin, Xulei; Wang, Silun; Shen, Ming; Zhang, Xiaodong; Wagner, Mary B.; Fei, Baowei

    2014-03-01

    The orientation of cardiac fibers affects the anatomical, mechanical, and electrophysiological properties of the heart. Although echocardiography is the most common imaging modality in clinical cardiac examination, it can only provide the cardiac geometry or motion information without cardiac fiber orientations. If the patient's cardiac fiber orientations can be mapped to his/her echocardiography images in clinical examinations, it may provide quantitative measures for diagnosis, personalized modeling, and image-guided cardiac therapies. Therefore, this project addresses the feasibility of mapping personalized cardiac fiber orientations to three-dimensional (3D) ultrasound image volumes. First, the geometry of the heart extracted from the MRI is translated to 3D ultrasound by rigid and deformable registration. Deformation fields between both geometries from MRI and ultrasound are obtained after registration. Three different deformable registration methods were utilized for the MRI-ultrasound registration. Finally, the cardiac fiber orientations imaged by DTI are mapped to ultrasound volumes based on the extracted deformation fields. Moreover, this study also demonstrated the ability to simulate electricity activations during the cardiac resynchronization therapy (CRT) process. The proposed method has been validated in two rat hearts and three canine hearts. After MRI/ultrasound image registration, the Dice similarity scores were more than 90% and the corresponding target errors were less than 0.25 mm. This proposed approach can provide cardiac fiber orientations to ultrasound images and can have a variety of potential applications in cardiac imaging.

  18. 血管活性肠肽拮抗剂[D-p-Cl-Phe6,Leu17]-VIP对快速心房肌电重构的影响%Effects of [D-p-Cl-Phe6, Leu17]-VIP, a vasoactive intestinal peptide antagonist, on rapid atrial electrical remodeling

    Institute of Scientific and Technical Information of China (English)

    肖宪杰; 杨东辉; 高连君; 尹晓盟; 常栋; 杨延宗

    2013-01-01

    目的 探讨血管活性肠肽拮抗剂[D-p-Cl-Phe6,Leu17]-VIP对快速心房肌电重构的影响.方法 成年杂种犬(12只)分别经右股静脉和颈内静脉穿刺放置导管于右心耳(RAA)和冠状静脉窦导管于冠状静脉窦(CS),经右股动脉放置6F猪尾导管于主动脉根部,全麻机械通气(使血氧饱和度保持在95%以上),下行双侧颈交感-迷走神经干分离.右心耳400次/min高频刺激5h,同时给予双侧颈交感-迷走神经刺激(20 Hz),导致二度房室阻滞以上或窦性心率下降大于30次/min.静脉应用美托洛尔(首次静脉推注1 mg/kg,随之给予0.5 mg·kg-1 ·h-1静脉泵维持)阻断交感神经活性.完全随机分2组:对照组(n=6),经主动脉根部注射生理盐水;实验组(n=6),经主动脉根部首次推注VIP拮抗剂[D-p-Cl-Phe6,Leu17]-VIP 0.5 μg/kg,随后持续注射0.25μg· kg-1 ·h-1;分别在基础状态和心房高频刺激后每小时测量CS及RAA的有效不应期(ERP)、窦性心率及迷走神经刺激时心率.结果 对照组中,基础状态与5h快速心房起搏后窦性心率及交感-迷走神经干刺激时心率差异无统计学意义(P>0.05);经过5h的高频心房起搏和迷走-交感神经干刺激后心房ERP明显缩短[ERP缩短值分别为1 h(-14.5±10.0)ms,2h(-18.4±9.0)ms,3 h(-21.9±11.2)ms,4 h(-25.4±10.3)ms,5 h(-25.9±13.1)ms,P<0.05].实验组中,基础状态与高频心房起搏和交感-迷走神经干刺激后1~5h,窦性心率差异无统计学意义(P>0.05);基础状态下、给予VIP拮抗剂负荷量后、高频心房起搏和迷走-交感神经干刺激后1~5h,ERP没有明显变化(P>0.05).结论 VIP拮抗剂[D-p-Cl-Phe6,Leu17]-VIP能抑制高频心房起搏和迷走-交感神经干刺激所致的快速心房电重构.%Objective To determine the effect of [D-p-Cl-Phe6,Leu17]-VIP,a vasoactive intestinal peptide antagonist,on rapid atrial electrical remodeling (AER).Methods Twelve adult mongrel dogs were subject to catheterization in

  19. Serum myoglobin after cardiac catheterisation.

    OpenAIRE

    McComb, J. M.; McMaster, E A

    1982-01-01

    Study of 80 consecutive patients undergoing elective diagnostic cardiac catheterisation showed that after the procedure 25 (31%) developed myoglobinaemia. This was attributed to complications of the catheterisation in two. The remaining 23 had received premedication by intramuscular injection. In patients without intramuscular injections myoglobinaemia did not occur after uncomplicated cardiac catheterisation. The study did not support the proposition that cardiac catheterisation results in m...

  20. The role of cardiac magnetic resonance imaging following acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Dennis T.L.; Richardson, James D.; Puri, Rishi; Nelson, Adam J.; Teo, Karen S.L.; Worthley, Matthew I. [Royal Adelaide Hospital, Cardiovascular Research Centre, Adelaide (Australia); University of Adelaide, Department of Medicine, Adelaide (Australia); Bertaso, Angela G. [Royal Adelaide Hospital, Cardiovascular Research Centre, Adelaide (Australia); Worthley, Stephen G. [Royal Adelaide Hospital, Cardiovascular Research Centre, Adelaide (Australia); University of Adelaide, Department of Medicine, Adelaide (Australia); Cardiovascular Investigational Unit, Adelaide, SA (Australia)

    2012-08-15

    Advances in the management of myocardial infarction have resulted in substantial reductions in morbidity and mortality. However, after acute treatment a number of diagnostic and prognostic questions often remain to be answered, whereby cardiac imaging plays an essential role. For example, some patients will sustain early mechanical complications after infarction, while others may develop significant ventricular dysfunction. Furthermore, many individuals harbour a significant burden of residual coronary disease for which clarification of functional ischaemic status and/or viability of the suspected myocardial territory is required. Cardiac magnetic resonance (CMR) imaging is well positioned to fulfil these requirements given its unparalleled capability in evaluating cardiac function, stress ischaemia testing and myocardial tissue characterisation. This review will focus on the utility of CMR in resolving diagnostic uncertainty, evaluating early complications following myocardial infarction, assessing inducible ischaemia, myocardial viability, ventricular remodelling and the emerging role of CMR-derived measures as endpoints in clinical trials. (orig.)

  1. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Directory of Open Access Journals (Sweden)

    Dong-Hai Liu

    Full Text Available Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  2. Mammary remodelling and metabolic activity in dairy goats

    DEFF Research Database (Denmark)

    Safayi, Sina

    ) differences between PP and MP animals with respect to milk production and lactation persistency may be related to differences in mammary growth and remodelling also during lactation, 2) the factors responsible for interfering with mammary remodelling in continuous lactation throughout the dry period into the...... present thesis aimed to address the hypotheses that 1) differences between PP and MP animals with respect to milk production and lactation persistency may be related to differences in mammary growth and remodelling also during lactation, 2) the factors responsible for interfering with mammary remodelling...... be effectively renewed as one lactation comes to an end and prior to onset of the next lactation. Generally, the level of milk production and the changes in milk yield over the course of lactation depend on three main factors: 1) the number of MEC, which in turn is affected by the balance between the...

  3. A gene-centric study of common carotid artery remodelling

    NARCIS (Netherlands)

    Harrison, Seamus C.; Zabaneh, Delilah; Asselbergs, Folkert W.; Drenos, Fotios; Jones, Gregory T.; Shah, Sonia; Gertow, Karl; Sennblad, Bengt; Strawbridge, Rona J.; Gigante, Bruna; Holewijn, Suzanne; De Graaf, Jacqueline; Vermeulen, Sita; Folkersen, Lasse; van Rij, Andre M.; Baldassarre, Damiano; Veglia, Fabrizio; Talmud, Philippa J.; Deanfield, John E.; Agu, Obi; Kivimaki, Mika; Kumari, Meena; Bown, Matthew J.; Nyyssonen, Kristiina; Rauramaa, Rainer; Smit, Andries J.; Franco-Cereceda, Anders; Giral, Philippe; Mannarino, Elmo; Silveira, Angela; Syvanen, Ann-Christine; de Borst, Gert J.; van der Graaf, Yolanda; de Faire, Ulf; Baas, Annette F.; Blankensteijn, Jan D.; Wareham, Nicholas J.; Fowkes, Gerry; Tzoulaki, Ionna; Price, Jacqueline F.; Tremoli, Elena; Hingorani, Aroon D.; Eriksson, Per; Hamsten, Anders; Humphries, Steve E.

    2013-01-01

    Background: Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized. Methods: Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IM

  4. Nitric Oxide and Hydrogen Sulfide Regulation of Ischemic Vascular Remodeling.

    Science.gov (United States)

    Yuan, Shuai; Kevil, Christopher G

    2016-02-01

    Blockage or restriction of blood flow through conduit arteries results in tissue ischemia downstream of the disturbed area. Local tissues can adapt to this challenge by stimulating vascular remodeling through angiogenesis and arteriogenesis thereby restoring blood perfusion and removal of wastes. Multiple molecular mechanisms of vascular remodeling during ischemia have been identified and extensively studied. However, therapeutic benefits from these findings and insights are limited due to the complexity of various signaling networks and a lack of understanding central metabolic regulators governing these responses. The gasotransmitters NO and H2 S have emerged as master regulators that influence multiple molecular targets necessary for ischemic vascular remodeling. In this review, we discuss how NO and H2 S are individually regulated under ischemia, what their roles are in angiogenesis and arteriogenesis, and how their interaction controls ischemic vascular remodeling. PMID:26381654

  5. Hepato-cardiac disorders

    Institute of Scientific and Technical Information of China (English)

    Yasser; Mahrous; Fouad; Reem; Yehia

    2014-01-01

    Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases

  6. Primary cardiac tumors

    International Nuclear Information System (INIS)

    Cardiac tumors happen to be among the less known pathologies without clear treatment standards. Even one decade ago most of the cardiac tumor diagnosis were made post mortem, and only reports of isolated cases could be found in the literature, showing the lack of interest in the investigation of these pathologies by cardiology and cardiovascular surgery specialists. With the development of echocardiography and of cardiovascular surgery, more cases of primary and metastatic cardiac tumors have been diagnosed. Many cases have been treated by palliative or curative surgical interventions, thus increasing the reports in the world literature and the experience in this field, and pointing out the real incidence of these pathologies, not being as bizarre as it had been considered. a revision of the literature will be made, in which the frequency and the suggested interventions will be reported, as well as the cases of cardiac pathology in two cardiovascular centers of the country known by the author. The echocardiographic, pathologic and histological characteristics of the representative cases will be presented, without a greater evidence level, due to the problem's incidence and the few cases reported by these centers

  7. Cardiac MRI tagging

    International Nuclear Information System (INIS)

    Cardiac MRI tagging is an original technique based upon the perturbation of the magnetization of determined regions of the myocardium (tags). The motion of the tags accurately reflects the deformation of the underlying tissue. Data analysis requires special techniques to reconstruct the 3D motion of the heart, and to evaluate the myocardial strain, locally and throughout the whole heart. (authors)

  8. Automatic Implantable Cardiac Defibrillator

    Medline Plus

    Full Text Available ... Over the next hour you'll see the implantation of an automated implantable cardiac defibrillator. The surgery ... evening we're going to be discussing the implantation of a defibrillator. It’s a battery-powered implantable ...

  9. Cardiac effects of vasopressin.

    Science.gov (United States)

    Pelletier, Jean-Sébastien; Dicken, Bryan; Bigam, David; Cheung, Po-Yin

    2014-07-01

    Vasopressin is an essential hormone involved in the maintenance of cardiovascular homeostasis. It has been in use therapeutically for many decades, with an emphasis on its vasoconstrictive and antidiuretic properties. However, this hormone has a ubiquitous influence and has specific effects on the heart. Although difficult to separate from its powerful vascular effects in the clinical setting, a better understanding of vasopressin's direct cardiac effects could lead to its more effective clinical use for a variety of shock states by maximizing its therapeutic benefit. The cardiac-specific effects of vasopressin are complex and require further elucidation. Complicating our understanding include the various receptors and secondary messengers involved in vasopressin's effects, which may lead to various results based on differing doses and varying environmental conditions. Thus, there have been contradictory reports on vasopressin's action on the coronary vasculature and on its effect on inotropy. However, beneficial results have been found and warrant further study to expand the potential therapeutic role of vasopressin. This review outlines the effect of vasopressin on the coronary vasculature, cardiac contractility, and on hypertrophy and cardioprotection. These cardiac-specific effects of vasopressin represent an interesting area for further study for potentially important therapeutic benefits. PMID:24621650

  10. Cardiac pacemaker power sources

    International Nuclear Information System (INIS)

    A review of chemical and radioisotope batteries used in cardiac pacemakers is presented. The battery systems are examined in terms of longevity, reliability, cost, size and shape, energy density, weight, internal resistance versus time, end-of-life voltage, chemical compatibility, and potential failure mechanisms

  11. Cutaneous remodeling and photorejuvenation using radiofrequency devices

    Directory of Open Access Journals (Sweden)

    Elsaie Mohamed

    2009-01-01

    Full Text Available Radio frequency (RF is electromagnetic radiation in the frequency range of 3-300GHz. The primary effects of RF energy on living tissue are considered to be thermal. The goal of the new devices based on these frequency ranges is to heat specific layers of the skin. The directed use of RF can induce dermal heating and cause collagen degeneration. Wound healing mechanisms promote the remodeling of collagen and wound contraction, which ultimately clinically enhances the appearance of mild to moderate skin laxity. Preliminary studies have reported efficacy in the treatment of laxity that involves the periorbital area and jowls. Because RF energy is not dependent on specific chromophore interaction, epidermal melanin is not at risk of destruction and treatment of all skin types is possible. As such, radiofrequency-based systems have been used successfully for nonablative skin rejuvenation, atrophic scar revision and treatment of unwanted hair, vascular lesions and inflammatory acne. The use of RF is becoming more popular, although a misunderstanding exists regarding the mechanisms and limitations of its actions. This concise review serves as an introduction and guide to many aspects of RF in the non ablative rejuvenation of skin.

  12. Dynamics of wave fronts and filaments in anisotropic cardiac tissue

    CERN Document Server

    Dierckx, Hans J F M

    2015-01-01

    The heartbeat is mediated between cardiac cells by waves of electrical depolarisation. During cardiac arrhythmias, electrical activity was found to be organised in scroll waves which rotate around a dynamical filament curve. In this thesis, a curved-space approach is used to mathematically capture anisotropy of wave propagation. We derive for the first time the covariant laws of motion for traveling wave fronts and scroll wave filaments in anisotropic excitable media such as cardiac tissue. We show that locally varying anisotropy yields non-zero Riemann tensor components, which may alter the stability of scroll wave filaments. The instability of scroll wave filaments has been linked to transition from ventricular tachycardia to fibrillation.

  13. Simvastatin induces apoptosis by a Rho-dependent mechanism in cultured cardiac fibroblasts and myofibroblasts

    International Nuclear Information System (INIS)

    Several clinical trials have shown the beneficial effects of statins in the prevention of coronary heart disease. Additionally, statins promote apoptosis in vascular smooth muscle cells, in renal tubular epithelial cells and also in a variety of cell lines; yet, the effects of statins on cardiac fibroblast and myofibroblast, primarily responsible for cardiac tissue healing are almost unknown. Here, we investigated the effects of simvastatin on cardiac fibroblast and myofibroblast viability and studied the molecular cell death mechanism triggered by simvastatin in both cell types. Methods: Rat neonatal cardiac fibroblasts and myofibroblasts were treated with simvastatin (0.1-10 μM) up to 72 h. Cell viability and apoptosis were evaluated by trypan blue exclusion method and by flow cytometry, respectively. Caspase-3 activation and Rho protein levels and activity were also determined by Western blot and pull-down assay, respectively. Results: Simvastatin induces caspase-dependent apoptosis of cardiac fibroblasts and myofibroblasts in a concentration- and time-dependent manner, with greater effects on fibroblasts than myofibroblasts. These effects were prevented by mevalonate, farnesylpyrophosphate and geranylgeranylpyrophosphate, but not squalene. These last results suggest that apoptosis was dependent on small GTPases of the Rho family rather than Ras. Conclusion: Simvastatin triggered apoptosis of cardiac fibroblasts and myofibroblasts by a mechanism independent of cholesterol synthesis, but dependent of isoprenilation of Rho protein. Additionally, cardiac fibroblasts were more susceptible to simvastatin-induced apoptosis than cardiac myofibroblasts. Thus simvastatin could avoid adverse cardiac remodeling leading to a less fibrotic repair of the damaged tissues. - Research Highlights: → Simvastatin decreases CF and CMF viability independent of cholesterol synthesis. → Simvastatin induces CF and CMF apoptosis in a caspase-dependent manner being CMF more resistant

  14. Remodeling of the bone material containing microcracks: A theoretical analysis

    Science.gov (United States)

    Ramtani, S.; Zidi, M.

    1999-12-01

    The question is, what happens when the bone loses its ability for load-driven adaptation, when damage is no longer repaired as it seems to be the case for bone loss associated with age, medication or disease? In this study, we tempt to show how damage can influence the remodeling process. A thermodynamic theoretical framework is therefore provided as a basis for a consistent formulation of bone remodeling involving a chemical reaction and mass transfer between two constituents in presence of microcracks.

  15. Collagen scaffold remodeling by human mesenchymal stem cells

    OpenAIRE

    Han, SJ; Chan, BP

    2011-01-01

    Type I collagen has been widely used as scaffold for tissue engineering because of its excellent biocompatibility and negligible immunogenicity. We previously have developed a collagen microencapsulation technology entrapping many cells including human mesenchymal stem cells (hMSCs) in microspheres made of nanofibrous collagen meshwork. Nevertheless, little is understood about how stem cells interact with and remodel the collagen meshwork. This study aims to investigate collagen remodeling by...

  16. The relationship between eosinophilia and airway remodelling in mild asthma

    OpenAIRE

    Wilson, S J; Rigden, H.M.; Ward, J. A.; Laviolette, M.; Jarjour, N N; Djukanović, R.

    2013-01-01

    Background Eosinophilia is a marker of corticosteroid responsiveness and risk of exacerbation in asthma; although it has been linked to submucosal matrix deposition, its relationship with other features of airway remodelling is less clear. Objective The aim of this study was to investigate the relationship between airway eosinophilia and airway remodelling. Methods Bronchial biopsies from subjects (n = 20 in each group) with mild steroid-naïve asthma, with either low (0–0....

  17. Apocynin attenuates oxidative stress and cardiac fibrosis in angiotensin Ⅱ-induced cardiac diastolic dysfunction in mice

    Institute of Scientific and Technical Information of China (English)

    Yu-qiong LI; Xiao-bo LI; Shu-jie GUO; Shao-li CHU; Ping-jin GAO; Ding-liang ZHU; Wen-quan NIU

    2013-01-01

    Aim:To investigate whether apocynin,a NADPH oxidase inhibitor,produced cardioproteictive effects in Ang Ⅱ-induced hypertensive mice,and to elucidate the underlying mechanisms.Methods:C57BL/6 mice were subcutaneously infused Ang Ⅱ for 4 weeks to mimic cardiac remodeling and fibrosis.Concomitantly the mice were administered apocynin (100 mg· kg-1·d-1) or/and the aldosterone receptor blocker eplerenone (200 mg·kg-1d-1) via gavage for 4 weeks.Systolic blood pressure (SBP) and heart rate were measured,and transthoracic echocardiography was performed.For in vitro study,cardiac fibroblasts were treated with Ang Ⅱ (10 7 mol/L) in the presence of apocynin (105 mol/L) or/and eplerenone (105 mol/L).Immunohistochemistry and Western blotting were used to quantify the expression levels of NADPH oxidase and osteopontin (OPN) proteins in the cells.Results:Both apocynin and eplerenone significantly decreased SBP,and markedly improved diastolic dysfunction in Ang Ⅱ-induced hypertensive mice,accompanied with ameliorated oxidative stress and cardiac fibrosis.In the Ang Ⅱ-treated cardiac fibroblasts,the expression levels of NOX4 and OPN proteins were markedly upregulated.Both Apocynin and eplerenone significantly suppressed the increased expression levels of NOX4 and OPN proteins in the Ang Ⅱ-treated cells.In all the experiments,apocynin and eplerenone produced comparable effects.Co-administration of the two agents did not produce synergic effects.Conclusion:Apocynin produces cardioproteictive effects comparable to those of eplerenone.The beneficial effects of apocynin on myocardial oxidative stress and cardiac fibrosis might be mediated partly through a pathway involving NADPH oxidase and OPN.

  18. [Cardiac amyloidosis. General review].

    Science.gov (United States)

    Laraki, R

    1994-04-01

    Cardiac amyloidosis, most often of AL type, is a non-exceptional disease as it represents 5 to 10% of non-ischemic cardiomyopathies. It realizes typically a restrictive cardiomyopathy. Nevertheless the wide diversity of possible presentation makes it a "big shammer" which must be evoked in front of every unexplained cardiopathy after the age of forty. If some associated manifestations can rapidly suggest the diagnosis, as a peripheric neuropathy especially a carpal tunnel syndrome or palpebral ecchymosis, cardiac involvement can also evolve in an apparently isolated way. The most suggestive paraclinic elements for the diagnosis are, in one hand, the increased myocardial echogenicity with a "granular sparkling" appearance seen throughout all walls of the left ventricle and, in the other hand, the association of a thickened left ventricle and a low voltage (electrocardiogram could also show pseudo-infarct Q waves). In front of such aspects, the proof of amyloidosis is brought by an extra-cardiac biopsy or by scintigraphy with labelled serum amyloid P component, so that the indications of endomyocardial biopsy are very limited today. The identification of the amyloid nature of a cardiopathy has an direct therapeutic implication: it contra-indicates the use of digitalis, calcium channel blockers and beta-blockers. The treatment of AL amyloidosis (chemotherapy with alkylant agents) remains very unsatisfactory especially in the cardiac involvement which is the most frequent cause of death (in AL amyloidosis). Last, cardiac amyloidosis is a bad indication for transplantation which results are burden by rapid progression of deposits especially in the gastro-intestinal tract and the nervous system. PMID:8059146

  19. Cardiac surgery outcomes.

    Science.gov (United States)

    Halpin, Linda S; Barnett, Scott D; Beachy, Jim

    2003-01-01

    Accrediting organizations and payers are demanding valid and reliable data that demonstrate the value of services. Federal agencies, healthcare industry groups, and healthcare watchdog groups are increasing the demand for public access to outcomes data. A new and growing outcomes dynamic is the information requested by prospective patients in an increasingly consumer-oriented business. Patients demand outcomes, and resources are developing to meet these demands. Physicians are increasingly confronted with requests for information about their mortality and morbidity rates, malpractice suits, and disciplinary actions received. For example, in Virginia, prospective patients have access to data provided by the nonprofit group Virginia Health Information. After numerous resolutions by the Virginia Senate since 1999, the prospective Virginia medical consumer now has access to several annual publications: Virginia Hospitals: A Consumer's Guide, 1999 Annual Report and Strategic Plan Update, and the 1999 Industry Report: Virginia Hospitals and Nursing Facilities. Consumers have access to cardiac outcomes data stratified by hospital, gender, and cardiac service line (cardiac surgery, noninvasive cardiology, and invasive cardiology). This is particularly relevant to IHI because Virginia Health Information specifically targets cardiac care. IHI has a sizable investment in cardiovascular outcomes and has found outcomes measurement and research are key to providing quality care. IHI's goal is to move from an outcomes management model to a disease management model. The hope is to incorporate all aspects of the patient's continuum of care, from preoperative and diagnostic services through cardiac interventions to postoperative rehabilitation. Furthermore, every step along the way will be supported with functional status and quality of life assessments. Although these goals are ambitious and expensive, the return on investment is high. PMID:14618772

  20. Epac contributes to cardiac hypertrophy and amyloidosis induced by radiotherapy but not fibrosis

    International Nuclear Information System (INIS)

    Background: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and this translational study was initiated to characterize radiation-induced cardiac side effects in a population of breast cancer patients and in experimental models in order to identify novel therapeutic target. Methods: The size of the heart was evaluated in CO-HO-RT patients by measuring the Cardiac-Contact-Distance before and after radiotherapy (48 months of follow-up). In parallel, fibrogenic signals were studied in a severe case of human radiation-induced pericarditis. Lastly, radiation-induced cardiac damage was studied in mice and in rat neonatal cardiac cardiomyocytes. Results: In patients, time dependent enhancement of the CCD was measured suggesting occurrence of cardiac hypertrophy. In the case of human radiation-induced pericarditis, we measured the activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals. In irradiated mice, we documented decreased contractile function, enlargement of the ventricular cavity and long-term modification of the time constant of decay of Ca2+ transients. Both hypertrophy and amyloid deposition were correlated with the induction of Epac-1; whereas radiation-induced fibrosis correlated with Rho/CTGF activation. Transactivation studies support Epac contribution in hypertrophy stimulation and showed that radiotherapy and Epac displayed specific and synergistic signals. Conclusion: Epac-1 has been identified as a novel regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in the heart

  1. Reactive Oxygen Species, Endoplasmic Reticulum Stress and Mitochondrial Dysfunction: The Link with Cardiac Arrhythmogenesis

    Science.gov (United States)

    Tse, Gary; Yan, Bryan P.; Chan, Yin W. F.; Tian, Xiao Yu; Huang, Yu

    2016-01-01

    Background: Cardiac arrhythmias represent a significant problem globally, leading to cerebrovascular accidents, myocardial infarction, and sudden cardiac death. There is increasing evidence to suggest that increased oxidative stress from reactive oxygen species (ROS), which is elevated in conditions such as diabetes and hypertension, can lead to arrhythmogenesis. Method: A literature review was undertaken to screen for articles that investigated the effects of ROS on cardiac ion channel function, remodeling and arrhythmogenesis. Results: Prolonged endoplasmic reticulum stress is observed in heart failure, leading to increased production of ROS. Mitochondrial ROS, which is elevated in diabetes and hypertension, can stimulate its own production in a positive feedback loop, termed ROS-induced ROS release. Together with activation of mitochondrial inner membrane anion channels, it leads to mitochondrial depolarization. Abnormal function of these organelles can then activate downstream signaling pathways, ultimately culminating in altered function or expression of cardiac ion channels responsible for generating the cardiac action potential (AP). Vascular and cardiac endothelial cells become dysfunctional, leading to altered paracrine signaling to influence the electrophysiology of adjacent cardiomyocytes. All of these changes can in turn produce abnormalities in AP repolarization or conduction, thereby increasing likelihood of triggered activity and reentry. Conclusion: ROS plays a significant role in producing arrhythmic substrate. Therapeutic strategies targeting upstream events include production of a strong reducing environment or the use of pharmacological agents that target organelle-specific proteins and ion channels. These may relieve oxidative stress and in turn prevent arrhythmic complications in patients with diabetes, hypertension, and heart failure. PMID:27536244

  2. Inherited Cardiac Diseases Caused by Mutations in the Nav1.5 Sodium Channel

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Jacob; Winkel, Bo Gregers; Grunnet, Morten;

    2009-01-01

    Cardiac Diseases Caused by SCN5A Mutations. A prerequisite for a normal cardiac function is a proper generation and propagation of electrical impulses. Contraction of the heart is obtained through a delicate matched transmission of the electrical impulses. A pivotal element of the impulse propaga......-QT syndrome, Brugada syndrome, and AF, reported to be associated with mutations in SCN5A, are thoroughly described. (J Cardiovasc Electrophysiol, Vol. pp. 1-9)....

  3. Cell Matrix Remodeling Ability Shown by Image Spatial Correlation

    Directory of Open Access Journals (Sweden)

    Chi-Li Chiu

    2013-01-01

    Full Text Available Extracellular matrix (ECM remodeling is a critical step of many biological and pathological processes. However, most of the studies to date lack a quantitative method to measure ECM remodeling at a scale comparable to cell size. Here, we applied image spatial correlation to collagen second harmonic generation (SHG images to quantitatively evaluate the degree of collagen remodeling by cells. We propose a simple statistical method based on spatial correlation functions to determine the size of high collagen density area around cells. We applied our method to measure collagen remodeling by two breast cancer cell lines (MDA-MB-231 and MCF-7, which display different degrees of invasiveness, and a fibroblast cell line (NIH/3T3. We found distinct collagen compaction levels of these three cell lines by applying the spatial correlation method, indicating different collagen remodeling ability. Furthermore, we quantitatively measured the effect of Latrunculin B and Marimastat on MDA-MB-231 cell line collagen remodeling ability and showed that significant collagen compaction level decreases with these treatments.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    causes, 108 (63.9%) deemed cardiac, and 61 (36.1%) non-cardiac. In multivariate analysis, increased baseline creatinine was significantly associated with both cardiac and non-cardiac deaths [hazard ratio (HR) 2.97, P ...AIMS: To understand modes of death and factors associated with the risk for cardiac and non-cardiac deaths in patients with cardiac resynchronization therapy with implantable cardioverter-defibrillator (CRT-D) vs. implantable cardioverter-defibrillator (ICD) therapy, which may help clarify...

  5. Proinflammatory Protein CARD9 Is Essential for Infiltration of Monocytic Fibroblast Precursors and Cardiac Fibrosis Caused by Angiotensin II Infusion

    OpenAIRE

    Ren, Jingyuan; YANG, MIN; Qi, Guanming; Zheng, Jiao; Jia, LiXin; Cheng, Jizhong; Tian, Cui; Li, Huihua; Lin, Xin; Du, Jie

    2011-01-01

    Background Angiotensin II (Ang II)–induced cardiac remodeling with the underlying mechanisms involving inflammation and fibrosis has been well documented. Cytosolic adaptor caspase recruitment domain 9 (CARD9) has been implicated in the innate immune response. We aimed to examine the role of CARD9 in inflammation and cardiac fibrosis induced by Ang II. Methods Two-month-old CARD9-deficient (CARD9−/−) and wild-type (WT) male mice were infused with Ang II (1,500 ng/kg/min) or saline for 7 days....

  6. Functional role of anion channels in cardiac diseases

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  7. Cardiac stimulation with high voltage discharge from stun guns

    OpenAIRE

    Nanthakumar, Kumaraswamy; Massé, Stephane; Umapathy, Karthikeyan; Dorian, Paul; Sevaptsidis, Elias; Waxman, Menashe

    2008-01-01

    The ability of an electrical discharge to stimulate the heart depends on the duration of the pulse, the voltage and the current density that reaches the heart. Stun guns deliver very short electrical pulses with minimal amount of current at high voltages. We discuss external stimulation of the heart by high voltage discharges and review studies that have evaluated the potential of stun guns to stimulate cardiac muscle. Despite theoretical analyses and animal studies which suggest that stun gu...

  8. Complexity of cardiac signals for predicting changes in alpha-waves after stress in patients undergoing cardiac catheterization

    Science.gov (United States)

    Chiu, Hung-Chih; Lin, Yen-Hung; Lo, Men-Tzung; Tang, Sung-Chun; Wang, Tzung-Dau; Lu, Hung-Chun; Ho, Yi-Lwun; Ma, Hsi-Pin; Peng, Chung-Kang

    2015-08-01

    The hierarchical interaction between electrical signals of the brain and heart is not fully understood. We hypothesized that the complexity of cardiac electrical activity can be used to predict changes in encephalic electricity after stress. Most methods for analyzing the interaction between the heart rate variability (HRV) and electroencephalography (EEG) require a computation-intensive mathematical model. To overcome these limitations and increase the predictive accuracy of human relaxing states, we developed a method to test our hypothesis. In addition to routine linear analysis, multiscale entropy and detrended fluctuation analysis of the HRV were used to quantify nonstationary and nonlinear dynamic changes in the heart rate time series. Short-time Fourier transform was applied to quantify the power of EEG. The clinical, HRV, and EEG parameters of postcatheterization EEG alpha waves were analyzed using change-score analysis and generalized additive models. In conclusion, the complexity of cardiac electrical signals can be used to predict EEG changes after stress.

  9. Cardiac fusion and complex congenital cardiac defects in thoracopagus twins: diagnostic value of cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Goo, Hyun Woo [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Park, Jeong-Jun [University of Ulsan College of Medicine, Asan Medical Center, Department of Pediatric Cardiac Surgery, Seoul (Korea, Republic of); Kim, Ellen Ai-Rhan [University of Ulsan College of Medicine, Asan Medical Center, Division of Neonatology, Department of Pediatrics, Seoul (Korea, Republic of); Won, Hye-Sung [University of Ulsan College of Medicine, Asan Medical Center, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of)

    2014-09-15

    Most thoracopagus twins present with cardiac fusion and associated congenital cardiac defects, and assessment of this anatomy is of critical importance in determining patient care and outcome. Cardiac CT with electrocardiographic triggering provides an accurate and quick morphological assessment of both intracardiac and extracardiac structures in newborns, making it the best imaging modality to assess thoracopagus twins during the neonatal period. In this case report, we highlight the diagnostic value of cardiac CT in thoracopagus twins with an interatrial channel and complex congenital cardiac defects. (orig.)

  10. A system for seismocardiography-based identification of quiescent heart phases: implications for cardiac imaging.

    Science.gov (United States)

    Wick, Carson A; Su, Jin-Jyh; McClellan, James H; Brand, Oliver; Bhatti, Pamela T; Buice, Ashley L; Stillman, Arthur E; Tang, Xiangyang; Tridandapani, Srini

    2012-09-01

    Seismocardiography (SCG), a representation of mechanical heart motion, may more accurately determine periods of cardiac quiescence within a cardiac cycle than the electrically derived electrocardiogram (EKG) and, thus, may have implications for gating in cardiac computed tomography. We designed and implemented a system to synchronously acquire echocardiography, EKG, and SCG data. The device was used to study the variability between EKG and SCG and characterize the relationship between the mechanical and electrical activity of the heart. For each cardiac cycle, the feature of the SCG indicating Aortic Valve Closure was identified and its time position with respect to the EKG was observed. This position was found to vary for different heart rates and between two human subjects. A color map showing the magnitude of the SCG acceleration and computed velocity was derived, allowing for direct visualization of quiescent phases of the cardiac cycle with respect to heart rate. PMID:22581141

  11. General guidelines for athletes screening, clearing for and disqualification from sports with regard to sudden cardiac death risk

    OpenAIRE

    Anna Malwina Kamelska

    2012-01-01

    The following review presents cardiological recommendations for clearing for or disqualifying from participation in sports as means of preventing sudden cardiac deaths on the sports field. The discussion involves pre-participation screening. The state of screening programs implemented in Europe, USA and Poland, targeting mainly changes in cardiovascular system, is presented here too; so is physiological and pathological heart remodeling resulting from physical exercise stimulation. The limits...

  12. Biventricular Finite Element Modeling of the Acorn CorCap Cardiac Support Device on a Failing Heart

    OpenAIRE

    Wenk, JF; L. Ge; Zhang, Z; Mojsejenko, D; Potter, DD; Tseng, EE; Guccione, JM; Ratcliffe, MB

    2013-01-01

    Background: The Acorn CorCap Cardiac Support Device (CSD; Acorn Cardiovascular Inc, St. Paul, MN) is a woven polyester jacket that is placed around the heart and designed to reverse the progressive remodeling associated with dilated cardiomyopathy. However, the effects of the Acorn CSD on myofiber stress and ventricular function remain unknown. We tested the hypothesis that the Acorn CSD reduces end-diastolic (ED) myofiber stress. Methods: A previously described weakly coupled biventricular f...

  13. Mesenchymal stem cell transplantation for the infarcted heart: a role in minimizing abnormalities in cardiac-specific energy metabolism

    OpenAIRE

    Hughey, Curtis C.; Johnsen, Virginia L.; Ma, Lianli; James, Freyja D.; Young, Pampee P.; Wasserman, David H.; Rottman, Jeffrey N.; Hittel, Dustin S.; Shearer, Jane

    2011-01-01

    Intense interest has been focused on cell-based therapy for the infarcted heart given that stem cells have exhibited the ability to reduce infarct size and mitigate cardiac dysfunction. Despite this, it is unknown whether mesenchymal stem cell (MSC) therapy can prevent metabolic remodeling following a myocardial infarction (MI). This study examines the ability of MSCs to rescue the infarcted heart from perturbed substrate uptake in vivo. C57BL/6 mice underwent chronic ligation of the left ant...

  14. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    International Nuclear Information System (INIS)

    Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula’s material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element’s remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than

  15. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Gulshan B., E-mail: gbsharma@ucalgary.ca [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States); University of Calgary, Schulich School of Engineering, Department of Mechanical and Manufacturing Engineering, Calgary, Alberta T2N 1N4 (Canada); Robertson, Douglas D., E-mail: douglas.d.robertson@emory.edu [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States)

    2013-07-01

    Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula’s material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element’s remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than

  16. Ankyrin-G participates in INa remodeling in myocytes from the border zones of infarcted canine heart.

    Directory of Open Access Journals (Sweden)

    Wen Dun

    Full Text Available Cardiac Na channel remodeling provides a critical substrate for generation of reentrant arrhythmias in border zones of the infarcted canine heart. Recent studies show that Nav1.5 assembly and function are linked to ankyrin-G, gap, and mechanical junction proteins. In this study our objective is to expound the status of the cardiac Na channel, its interacting protein ankyrinG and the mechanical and gap junction proteins at two different times post infarction when arrhythmias are known to occur; that is, 48 hr and 5 day post coronary occlusion. Previous studies have shown the origins of arrhythmic events come from the subendocardial Purkinje and epicardial border zone. Our Purkinje cell (Pcell voltage clamp study shows that INa and its kinetic parameters do not differ between Pcells from the subendocardium of the 48hr infarcted heart (IZPCs and control non-infarcted Pcells (NZPCs. Immunostaining studies revealed that disturbances of Nav1.5 protein location with ankyrin-G are modest in 48 hr IZPCs. Therefore, Na current remodeling does not contribute to the abnormal conduction in the subendocardial border zone 48 hr post myocardial infarction as previously defined. In addition, immunohistochemical data show that Cx40/Cx43 co-localize at the intercalated disc (IDs of control NZPCs but separate in IZPCs. At the same time, Purkinje cell desmoplakin and desmoglein2 immunostaining become diffuse while plakophilin2 and plakoglobin increase in abundance at IDs. In the epicardial border zone 5 days post myocardial infarction, immunoblot and immunocytochemical analyses showed that ankyrin-G protein expression is increased and re-localized to submembrane cell regions at a time when Nav1.5 function is decreased. Thus, Nav1.5 and ankyrin-G remodeling occur later after myocardial infarction compared to that of gap and mechanical junctional proteins. Gap and mechanical junctional proteins remodel in IZPCs early, perhaps to help maintain Nav1.5 subcellular

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

    Directory of Open Access Journals (Sweden)

    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.

  18. An integrated electromechanical-growth heart model for simulating cardiac therapies.

    Science.gov (United States)

    Lee, Lik Chuan; Sundnes, Joakim; Genet, Martin; Wenk, Jonathan F; Wall, Samuel T

    2016-08-01

    An emerging class of models has been developed in recent years to predict cardiac growth and remodeling (G&R). We recently developed a cardiac G&R constitutive model that predicts remodeling in response to elevated hemodynamics loading, and a subsequent reversal of the remodeling process when the loading is reduced. Here, we describe the integration of this G&R model to an existing strongly coupled electromechanical model of the heart. A separation of timescale between growth deformation and elastic deformation was invoked in this integrated electromechanical-growth heart model. To test our model, we applied the G&R scheme to simulate the effects of myocardial infarction in a realistic left ventricular (LV) geometry using the finite element method. We also simulate the effects of a novel therapy that is based on alteration of the infarct mechanical properties. We show that our proposed model is able to predict key features that are consistent with experiments. Specifically, we show that the presence of a non-contractile infarct leads to a dilation of the left ventricle that results in a rightward shift of the pressure volume loop. Our model also predicts that G&R is attenuated by a reduction in LV dilation when the infarct stiffness is increased. PMID:26376641

  19. Cardiac fibrillation risk of Taser weapons.

    Science.gov (United States)

    Leitgeb, Norbert

    2014-06-01

    The debate on potential health hazards associated with delivering electric discharges to incapacitated subjects, in particular on whether electric discharge weapons are lethal, less lethal or non-lethal, is still controversial. The cardiac fibrillation risks of Taser weapons X26 and X3 have been investigated by measuring the delivered high-tension pulses in dependence on load impedance. Excitation thresholds and sinus-to-Taser conversion factors have been determined by numerical modeling of endocardial, myocardial, and epicardial cells. Detailed quantitative assessment of cardiac electric exposure has been performed by numerical simulation at the normal-weighted anatomical model NORMAN. The impact of anatomical variation has been quantified at an overweight model (Visible Man), both with a spatial resolution of 2 × 2 × 2 mm voxels. Spacing and location of dart electrodes were systematically varied and the worst-case position determined. Based on volume-weighted cardiac exposure assessment, the fibrillation probability of the worst-case hit was determined to 30% (Taser X26) and 9% (Taser X3). The overall risk assessment of Taser application accounting for realistic spatial hit distributions was derived from training sessions of police officers under realistic scenarios and by accounting for the influence of body (over-)weight as well as gender. The analysis of the results showed that the overall fibrillation risk of Taser use is not negligible. It is higher at Taser X26 than at Taser X3 and amounts to about 1% for Europeans with an about 20% higher risk for Asians. Results demonstrate that enhancement as well as further reduction of fibrillation risk depends on responsible use or abuse of Taser weapons. PMID:24776896

  20. Gated cardiac blood pool studies in arrhythmias

    International Nuclear Information System (INIS)

    Biventricular phase analysis a gated blood pool studies may help to solve two fundamental questions raised by patients suffering from arrhythmias: localization of an electrical cardiac activation abnormality by means of contraction mapping and assesment of an underlying organic disease using the phase histograms and their standard deviations. Three groups of patients have been evaluated to demonstrate the usefulness of radioisotopic techniques in arrhythmias: 36 patients with a Wolff-Parkinson-White syndrom, 27 patients studied during a ventricular tachycardia attack and 32 patients suspected of arrhythmogenic ventricular dysplasia. Correlations with invasive electrophysiologic studies are presented and the diagnostic and therapeutic implications of these results are discussed

  1. Gated cardiac blood pool studies in arrhythmias

    Energy Technology Data Exchange (ETDEWEB)

    Itti, R.; Casset, D.; Philippe, L.; Cosnay, P.; Fauchier, J.P.

    1988-01-01

    Biventricular phase analysis a gated blood pool studies may help to solve two fundamental questions raised by patients suffering from arrhythmias: localization of an electrical cardiac activation abnormality by means of contraction mapping and assesment of an underlying organic disease using the phase histograms and their standard deviations. Three groups of patients have been evaluated to demonstrate the usefulness of radioisotopic techniques in arrhythmias: 36 patients with a Wolff-Parkinson-White syndrom, 27 patients studied during a ventricular tachycardia attack and 32 patients suspected of arrhythmogenic ventricular dysplasia. Correlations with invasive electrophysiologic studies are presented and the diagnostic and therapeutic implications of these results are discussed.

  2. Cardiac arrest in children

    Directory of Open Access Journals (Sweden)

    Tress Erika

    2010-01-01

    Full Text Available Major advances in the field of pediatric cardiac arrest (CA were made during the last decade, starting with the publication of pediatric Utstein guidelines, the 2005 recommendations by the International Liaison Committee on Resuscitation, and culminating in multicenter collaborations. The epidemiology and pathophysiology of in-hospital and out-of-hospital CA are now well described. Four phases of CA are described and the term "post-cardiac arrest syndrome" has been proposed, along with treatment goals for each of its four phases: immediate post-arrest, early post-arrest, intermediate and recovery phase. Hypothermia is recommended to be considered as a therapy for post-CA syndrome in comatose patients after CA, and large multicenter prospective studies are underway. We reviewed landmark articles related to pediatric CA published during the last decade. We present the current knowledge of epidemiology, pathophysiology and treatment of CA relevant to pre-hospital and acute care health practitioners.

  3. Cardiac arrest in children.

    Science.gov (United States)

    Tress, Erika E; Kochanek, Patrick M; Saladino, Richard A; Manole, Mioara D

    2010-07-01

    Major advances in the field of pediatric cardiac arrest (CA) were made during the last decade, starting with the publication of pediatric Utstein guidelines, the 2005 recommendations by the International Liaison Committee on Resuscitation, and culminating in multicenter collaborations. The epidemiology and pathophysiology of in-hospital and out-of-hospital CA are now well described. Four phases of CA are described and the term "post-cardiac arrest syndrome" has been proposed, along with treatment goals for each of its four phases: immediate post-arrest, early post-arrest, intermediate and recovery phase. Hypothermia is recommended to be considered as a therapy for post-CA syndrome in comatose patients after CA, and large multicenter prospective studies are underway. We reviewed landmark articles related to pediatric CA published during the last decade. We present the current knowledge of epidemiology, pathophysiology and treatment of CA relevant to pre-hospital and acute care health practitioners. PMID:20930971

  4. Socially differentiated cardiac rehabilitation

    DEFF Research Database (Denmark)

    Meillier, Lucette Kirsten; Nielsen, Kirsten Melgaard; Larsen, Finn Breinholt;

    2012-01-01

    recruitment and participation among low educated and socially vulnerable patients must be addressed to lower inequality in post-MI health. Our aim was to improve referral, attendance, and adherence rates among socially vulnerable patients by systematic screening and by offering a socially differentiated...... standard rehabilitation programme (SRP). If patients were identified as socially vulnerable, they were offered an extended version of the rehabilitation programme (ERP). Excluded patients were offered home visits by a cardiac nurse. Concordance principles were used in the individualised programme elements......%. Patients were equally distributed to the SRP and the ERP. No inequality was found in attendance and adherence among referred patients. Conclusions: It seems possible to overcome unequal referral, attendance, and adherence in cardiac rehabilitation by organisation of systematic screening and social...

  5. Cardiac metastases of osteosarcoma

    International Nuclear Information System (INIS)

    Osteosarcoma is a malignancy whose various sites of metastasis greatly modify its ultimate prognosis. We report a case of simultaneous pulmonary and cardiac metastases in a 41-year-old male patient with osteosarcoma of the tibia, presenting after more then one year of completion of adjuvant therapy with progressive dyspnea and cyanosis. Diagnosis was made on computerized tomogram and echocardiogram. The metastatic mass entirely occupying the right ventricle and the pulmonary artery proved fatal. (author)

  6. Cardiac developmental toxicity

    OpenAIRE

    Mahler, Gretchen J.; Jonathan T Butcher

    2011-01-01

    Congenital heart disease is a highly prevalent problem with mostly unknown origins. Many cases of CHD likely involve an environmental exposure coupled with genetic susceptibility, but practical and ethical considerations make nongenetic causes of CHD difficult to assess in humans. The development of the heart is highly conserved across all vertebrate species, making animal models an excellent option for screening potential cardiac teratogens. This review will discuss exposures known to cause ...

  7. Penetrating Cardiac Injuries

    OpenAIRE

    ÖZYAZICIOĞLU, Ahmet

    2002-01-01

    Objectives: To present our experience of penetrating cardiac injuries treated at Atatürk University hospital; in 17 years 38 patients were analyzed. Methods: Patients were classified into three groups: group A (stable), 12; group B (shock), 21; and group C (agonal), five. Five patients were treated by pericardial window and three by pericardiocentesis. Two patients in group C, 19 patients in group B and five patients in group A underwent median sternotomy or thoracotomy in the operating room...

  8. Genetic and physiologic dissection of the vertebrate cardiac conduction system.

    Directory of Open Access Journals (Sweden)

    Neil C Chi

    2008-05-01

    Full Text Available Vertebrate hearts depend on highly specialized cardiomyocytes that form the cardiac conduction system (CCS to coordinate chamber contraction and drive blood efficiently and unidirectionally throughout the organism. Defects in this specialized wiring system can lead to syncope and sudden cardiac death. Thus, a greater understanding of cardiac conduction development may help to prevent these devastating clinical outcomes. Utilizing a cardiac-specific fluorescent calcium indicator zebrafish transgenic line, Tg(cmlc2:gCaMP(s878, that allows for in vivo optical mapping analysis in intact animals, we identified and analyzed four distinct stages of cardiac conduction development that correspond to cellular and anatomical changes of the developing heart. Additionally, we observed that epigenetic factors, such as hemodynamic flow and contraction, regulate the fast conduction network of this specialized electrical system. To identify novel regulators of the CCS, we designed and performed a new, physiology-based, forward genetic screen and identified for the first time, to our knowledge, 17 conduction-specific mutations. Positional cloning of hobgoblin(s634 revealed that tcf2, a homeobox transcription factor gene involved in mature onset diabetes of the young and familial glomerulocystic kidney disease, also regulates conduction between the atrium and the ventricle. The combination of the Tg(cmlc2:gCaMP(s878 line/in vivo optical mapping technique and characterization of cardiac conduction mutants provides a novel multidisciplinary approach to further understand the molecular determinants of the vertebrate CCS.

  9. Excessive interatrial adiposity is associated with left atrial remodeling, augmented contractile performance in asymptomatic population

    Directory of Open Access Journals (Sweden)

    Yau-Huei Lai

    2016-05-01

    Full Text Available Purpose: Pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. Data regarding the mechanistic link between such measures and left atrial (LA structural/functional remodeling, a clinical hallmark of early stage heart failure (HF and atrial fibrillation (AF incidence, in asymptomatic population remain largely unexplored. Methods: This retrospective analysis includes 356 subjects free from significant valvular disorders, atrial fibrillation, or clinical HF. Regional adipose tissue including pericardial and periaortic fat volumes, interatrial septal (IAS, and left atrioventricular groove (AVG fat thickness were all measured by multidetector computed tomography (MDCT (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA. We measured LA volumes, booster performance, reservoir capacity as well as conduit function, and analyzed their association with adiposity measures. Results: All four adiposity measures were positively associated with greater LA volumes (all P < 0.05, while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P < 0.01. In multivariate models, IAS fat thickness remained independently associated with larger LA volumes, increased LA kinetic energy and ejection force (β-coef: 0.17 & 0.15, both P < 0.05, and impaired LA reservoir and conduit function (β-coef: −0.20 & −0.12, both P < 0.05 after adjusting for clinical variables. Conclusion: Accumulated visceral adiposity, especially interatrial fat depots, was associated with certain LA structural/functional remodeling characterized by impaired LA reservoir and conduit function though augmented kinetic energy and ejection performance. Our data suggested that interatrial fat burden may be associated with certain detrimental LA functions with compensatory LA adaptation in an asymptomatic population.

  10. Benign cardiac tumours: cardiac CT and MRI imaging appearances

    International Nuclear Information System (INIS)

    Full text: Primary benign cardiac tumours are rarely found in clinical practice and are generally evaluated with echocardiography. However, with the increasing usage of helical multislice CT, the initial detection and evaluation of these masses may be made by the radiologist during routine daily practice for other indications. The echocardiographic, CT and cardiac MRI appearances of various benign cardiac tumours and masses are described and illustrated in this review

  11. Age, Gender and Load-Related Influences on Left Ventricular Geometric Remodeling, Systolic Mid-Wall Function, and NT-ProBNP in Asymptomatic Asian Population

    Science.gov (United States)

    Chen, Chi; Sung, Kuo-Tzu; Shih, Shou-Chuan; Liu, Chuan-Chuan; Kuo, Jen-Yuan; Hou, Charles Jia-Yin; Hung, Chung-Lieh; Yeh, Hung-I

    2016-01-01

    Background Advanced age is associated with left ventricle (LV) remodeling and impaired cardiac function that may increase the risk of heart failure. Even so, studies regarding age-related cardiac remodeling in a large, asymptomatic Asian population remain limited. Materials and Methods We studied 8,410 asymptomatic participants (49.7 ±11.7 y, 38.9% women) in a health evaluation cohort (2004–2012) at a tertiary center in Northern Taiwan. We analyzed age-related alterations for all echocardiography-derived cardiac structures/functions and the associations with circulating N-terminal prohormone of brain natriuretic peptide (NT-proBNP). We also explored sex-related differences in these measures. Results In our cohort of 8,410 participants, advanced age was associated with greater LV wall thickness, larger LV total mass (+5.08 g/decade), and greater LV mass index (4.41 g/m2/decade), as well as increased serum NT-proBNP level (+18.89 pg/mL/decade). An accompanying reduction of stress-corrected midwall fractional shortening (–0.1%/decade) with aging was apparent in women after multi-variate adjustment (–0.09%/decade, p = 0.001). Furthermore, women demonstrated greater overall increase in LV wall thickness, LV mass index, and NT-proBNP compared to men (p for interaction: <0.001). All blood pressure components, including systolic, diastolic, and pulse pressures were independently associated with greater wall thickness and LV mass index after adjustment for confounders (all p <0.001). The associations between age and cardiac remodeling or mid-wall functions were further confirmed in a subset of study subjects with repeated follow up by GEE model. Conclusions Significant associations of unfavorable LV remodeling and advanced age in our asymptomatic Asian population were observed, along with sex differences. These data may help explain the incidence of some diverse gender-related cardiovascular diseases, especially heart failure. PMID:27280886

  12. The temperature dependence of electrical excitability in fish hearts.

    Science.gov (United States)

    Vornanen, Matti

    2016-07-01

    Environmental temperature has pervasive effects on the rate of life processes in ectothermic animals. Animal performance is affected by temperature, but there are finite thermal limits for vital body functions, including contraction of the heart. This Review discusses the electrical excitation that initiates and controls the rate and rhythm of fish cardiac contraction and is therefore a central factor in the temperature-dependent modulation of fish cardiac function. The control of cardiac electrical excitability should be sensitive enough to respond to temperature changes but simultaneously robust enough to protect against cardiac arrhythmia; therefore, the thermal resilience and plasticity of electrical excitation are physiological qualities that may affect the ability of fishes to adjust to climate change. Acute changes in temperature alter the frequency of the heartbeat and the duration of atrial and ventricular action potentials (APs). Prolonged exposure to new thermal conditions induces compensatory changes in ion channel expression and function, which usually partially alleviate the direct effects of temperature on cardiac APs and heart rate. The most heat-sensitive molecular components contributing to the electrical excitation of the fish heart seem to be Na(+) channels, which may set the upper thermal limit for the cardiac excitability by compromising the initiation of the cardiac AP at high temperatures. In cardiac and other excitable cells, the different temperature dependencies of the outward K(+) current and inward Na(+) current may compromise electrical excitability at temperature extremes, a hypothesis termed the temperature-dependent depression of electrical excitation. PMID:27385752

  13. Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

    Science.gov (United States)

    Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

    2015-04-01

    Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats. PMID:24905340

  14. Indeterminacy of Spatiotemporal Cardiac Alternans

    CERN Document Server

    Zhao, Xiaopeng

    2007-01-01

    Cardiac alternans, a beat-to-beat alternation in action potential duration (at the cellular level) or in ECG morphology (at the whole heart level), is a marker of ventricular fibrillation, a fatal heart rhythm that kills hundreds of thousands of people in the US each year. Investigating cardiac alternans may lead to a better understanding of the mechanisms of cardiac arrhythmias and eventually better algorithms for the prediction and prevention of such dreadful diseases. In paced cardiac tissue, alternans develops under increasingly shorter pacing period. Existing experimental and theoretical studies adopt the assumption that alternans in homogeneous cardiac tissue is exclusively determined by the pacing period. In contrast, we find that, when calcium-driven alternans develops in cardiac fibers, it may take different spatiotemporal patterns depending on the pacing history. Because there coexist multiple alternans solutions for a given pacing period, the alternans pattern on a fiber becomes unpredictable. Usin...

  15. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac p...... competent endocrine cells. The structurally related atrial natriuretic peptide will be mentioned where appropriate, whereas C-type natriuretic peptide will not be considered as a cardiac peptide of relevance in mammalian physiology....... characterized. An ongoing characterization of the molecular heterogeneity will help appreciate the biosynthetic capacity of the endocrine heart and could introduce new diagnostic possibilities. Notably, different biosynthetic products may not be equal markers of the same pathophysiological processes. An...... inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...

  16. Biosynthesis of cardiac natriuretic peptides

    DEFF Research Database (Denmark)

    Goetze, Jens Peter

    2010-01-01

    Cardiac-derived peptide hormones were identified more than 25 years ago. An astonishing amount of clinical studies have established cardiac natriuretic peptides and their molecular precursors as useful markers of heart disease. In contrast to the clinical applications, the biogenesis of cardiac...... inefficient post-translational prohormone maturation will also affect the biology of the cardiac natriuretic peptide system. This review aims at summarizing the myocardial synthesis of natriuretic peptides focusing on B-type natriuretic peptide, where new data has disclosed cardiac myocytes as highly...... competent endocrine cells. The structurally related atrial natriuretic peptide will be mentioned where appropriate, whereas C-type natriuretic peptide will not be considered as a cardiac peptide of relevance in mammalian physiology....

  17. An overview of cardiac morphogenesis.

    Science.gov (United States)

    Schleich, Jean-Marc; Abdulla, Tariq; Summers, Ron; Houyel, Lucile

    2013-11-01

    Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In this article we review the different steps of heart development, focusing on the processes of alignment and septation. We also show, as often as possible, the links between abnormalities of cardiac development and the main congenital heart defects. The development of animal models has permitted the unraveling of many mechanisms that potentially lead to cardiac malformations. A next step towards a better knowledge of cardiac development could be multiscale cardiac modelling. PMID:24138816

  18. Effect of renal sympathetic denervation on atrial substrate remodeling in ambulatory canines with prolonged atrial pacing.

    Directory of Open Access Journals (Sweden)

    Xule Wang

    Full Text Available We have previously demonstrated that catheter-based renal sympathetic denervation (RSD could suppress atrial fibrillation (AF in canines with short-time rapid right atrial pacing (RAP. However, the role of renal denervation on atrial remodeling is unclear. The aim of the present study was to explore the long-term effect of RSD on the atrial remodeling during prolonged RAP. Twenty mongrel dogs were implanted with a high-frequency cardiac pacemaker with a transvenous lead inserted into the right atrial appendage. The dogs were divided into three groups: a sham-operated group (n = 6, the chronic RAP (CRAP group (n = 7, and the CRAP+RSD group (n = 7. In the CRAP+RSD group, a pacemaker was implanted 6 weeks after RSD was performed bilaterally for recovery. RAP was maintained for 5 weeks in CRAP group and CRAP+RSD group. The plasma levels of Angiotensin II and aldosterone were significantly increased in CRAP group compared with sham-operated group, but the increasing trend was inhibited in CRAP+RSD group compared with CRAP group (P<0.05. Similarly, RSD suppressed the increasing trend that prolonged RAP produced in the left atrial levels of ANP, TNF-α and IL-6. Compared with the sham-operated group, the CRAP group had significantly increased levels of caspase-3, bax and Cx40 whereas the level of Bcl-2 decreased (P<0.05. RSD markedly reduced the upregulation of caspase-3, bax and Cx40 and the downregulation of Bcl-2 expression compared with the CRAP group (P<0.05. Picric acid-sirius red staining study suggested that RSD could markedly alleviate the lesion degree of cardic fibrosis induced by CRAP (P<0.05. Immunohistochemistry results showed that the densities of TH- and GAP43- positive nerves were significantly elevated in the CRAP group compared with the sham-operated group, while RSD operation signicantly inhibited the these changes produced by CRAP. These findings suggest that renal denervation could suppress the atrial remodeling after

  19. Minor groove binder distamycin remodels chromatin but inhibits transcription.

    Directory of Open Access Journals (Sweden)

    Parijat Majumder

    Full Text Available The condensed structure of chromatin limits access of cellular machinery towards template DNA. This in turn represses essential processes like transcription, replication, repair and recombination. The repression is alleviated by a variety of energy dependent processes, collectively known as "chromatin remodeling". In a eukaryotic cell, a fine balance between condensed and de-condensed states of chromatin helps to maintain an optimum level of gene expression. DNA binding small molecules have the potential to perturb such equilibrium. We present herein the study of an oligopeptide antibiotic distamycin, which binds to the minor groove of B-DNA. Chromatin mobility assays and circular dichroism spectroscopy have been employed to study the effect of distamycin on chromatosomes, isolated from the liver of Sprague-Dawley rats. Our results show that distamycin is capable of remodeling both chromatosomes and reconstituted nucleosomes, and the remodeling takes place in an ATP-independent manner. Binding of distamycin to the linker and nucleosomal DNA culminates in eviction of the linker histone and the formation of a population of off-centered nucleosomes. This hints at a possible corkscrew type motion of the DNA with respect to the histone octamer. Our results indicate that distamycin in spite of remodeling chromatin, inhibits transcription from both DNA and chromatin templates. Therefore, the DNA that is made accessible due to remodeling is either structurally incompetent for transcription, or bound distamycin poses a roadblock for the transcription machinery to advance.

  20. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

    Directory of Open Access Journals (Sweden)

    Alberto J Lopez

    2015-04-01

    Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.