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Sample records for attenuates cardiac dysfunction

  1. Transdermal Nicotine Application Attenuates Cardiac Dysfunction after Severe Thermal Injury

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    Leif Claassen

    2015-01-01

    Full Text Available Background. Severe burn trauma leads to an immediate and strong inflammatory response inciting cardiac dysfunction that is associated with high morbidity and mortality. The aim of this study was to determine whether transdermal application of nicotine could influence the burn-induced cardiac dysfunction via its known immunomodulatory effects. Material and Methods. A standardized rat burn model was used in 35 male Sprague Dawley rats. The experimental animals were divided into a control group, a burn trauma group, a burn trauma group with additional nicotine treatment, and a sham group with five experimental animals per group. The latter two groups received nicotine administration. Using microtip catheterization, functional parameters of the heart were assessed 12 or 24 hours after infliction of burn trauma. Results. Burn trauma led to significantly decreased blood pressure (BP values whereas nicotine administration normalized BP. As expected, burn trauma also induced a significant deterioration of myocardial contractility and relaxation parameters. After application of nicotine these adverse effects were attenuated. Conclusion. The present study showed that transdermal nicotine administration has normalizing effects on burn-induced myocardial dysfunction parameters. Further research is warranted to gain insight in molecular mechanisms and pathways and to evaluate potential treatment options in humans.

  2. Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome.

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    Gao, Ling; Cao, Jia-Tian; Liang, Yan; Zhao, Yi-Chao; Lin, Xian-Hua; Li, Xiao-Cui; Tan, Ya-Jing; Li, Jing-Yi; Zhou, Cheng-Liang; Xu, Hai-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-05-01

    Polycystic ovary syndrome (PCOS) is a complex reproductive and metabolic disorder affecting 10 % of reproductive-aged women, and is well associated with an increased prevalence of cardiovascular risk factors. However, there are few data concerning the direct association of PCOS with cardiac pathologies. The present study aims to investigate the changes in cardiac structure, function, and cardiomyocyte survival in a PCOS model, and explore the possible effect of calcitriol administration on these changes. PCOS was induced in C57BL/6J female mice by chronic dihydrotestosterone administration, as evidenced by irregular estrous cycles, obesity and dyslipidemia. PCOS mice progressively developed cardiac abnormalities including cardiac hypertrophy, interstitial fibrosis, myocardial apoptosis, and cardiac dysfunction. Conversely, concomitant administration of calcitriol significantly attenuated cardiac remodeling and cardiomyocyte apoptosis, and improved cardiac function. Molecular analysis revealed that the beneficial effect of calcitriol was associated with normalized autophagy function by increasing phosphorylation levels of AMP-activated protein kinase and inhibiting phosphorylation levels of mammalian target of rapamycin complex. Our findings provide the first evidence for the presence of cardiac remodeling in a PCOS model, and vitamin D supplementation may be a potential therapeutic strategy for the prevention and treatment of PCOS-related cardiac remodeling.

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

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

    2014-12-01

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

  4. Combination of Epinephrine with Esmolol Attenuates Post-Resuscitation Myocardial Dysfunction in a Porcine Model of Cardiac Arrest

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    Qian Zhang; Chunsheng Li

    2013-01-01

    BACKGROUND: Recent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of post resuscitation myocardial dysfunction. The aim of the study was to investigate whether the short-acting β₁-selective adrenergic blocking agent, esmolol, would attenuate post resuscitation myocardial dysfunction in a porcine model of cardiac arrest. METHODS AND RESULTS: After 8 min of untreated ventricular fibrillation and 2 min of basic li...

  5. Celastrol-Induced Suppression of the MiR-21/ERK Signalling Pathway Attenuates Cardiac Fibrosis and Dysfunction

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    Mian Cheng

    2016-05-01

    Full Text Available Backgroud: Myocardial fibrosis results in myocardial remodelling and dysfunction. Celastrol, a traditional oriental medicine, has been suggested to have cardioprotective effects. However, its underlying mechanism is unknown. This study investigated the ability of celastrol to prevent cardiac fibrosis and dysfunction and explored the underlying mechanisms. Methods: Animal and cell models of cardiac fibrosis were used in this study. Myocardial fibrosis was induced by transverse aortic constriction (TAC in mice. Cardiac hypertrophy and fibrosis were evaluated based on histological and biochemical measurements. Cardiac function was evaluated by echocardiography. The levels of transforming growth factor beta 1 (TGF-β1, extracellular signal regulated kinases 1/2 (ERK1/2 signalling were measured using Western blotting, while the expression of miR-21was analyzed by real-time qRT-PCR in vitro and in vivo. In vitro studies, cultured cardiac fibroblasts (CFs were treated with TGF-β1 and transfected with microRNA-21(miR21. Results: Celastrol treatment reduced the increased collagen deposition and down-regulated α-smooth muscle actin (α-SMA, atrial natriuretic peptide (ANP, brain natriuretic peptides (BNP, beta-myosin heavy chain (β-MHC, miR-21 and p-ERK/ERK. Cardiac dysfunction was significantly attenuated by celastrol treatment in the TAC mice model. Celastrol treatment reduced myocardial fibroblast viability and collagen content and down-regulated α-SMA in cultured CFs in vitro. Celastrol also inhibited the miR-21/ERK signalling pathway. Celastrol attenuated miR-21 up-regulation by TGF-β1 and decreased elevated p-ERK/ERK levels in CFs transfected with miR-21. Conclusion: MiR-21/ERK signalling could be a potential therapeutic pathway for the prevention of myocardial fibrosis. Celastrol ameliorates myocardial fibrosis and cardiac dysfunction, these probably related to miR-21/ERK signaling pathways in vitro and in vivo.

  6. Combination of epinephrine with esmolol attenuates post-resuscitation myocardial dysfunction in a porcine model of cardiac arrest.

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    Qian Zhang

    Full Text Available BACKGROUND: Recent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of post resuscitation myocardial dysfunction. The aim of the study was to investigate whether the short-acting β₁-selective adrenergic blocking agent, esmolol, would attenuate post resuscitation myocardial dysfunction in a porcine model of cardiac arrest. METHODS AND RESULTS: After 8 min of untreated ventricular fibrillation and 2 min of basic life support, 24 pigs were randomized to three groups (n = 8 per group, which received central venous injection of either epinephrine combined with esmolol (EE group, epinephrine (EP group, or saline (SA group. Hemodynamic status and blood samples were obtained at 0, 30, 60, 120, 240 and 360 min after return of spontaneous circulation (ROSC. Surviving pigs were euthanatized at 24 h after ROSC, and the hearts were removed for analysis by electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay. Compared with the EP and SA groups, EE group had a better outcome in hemodynamic function, (improved dp/dt maxima and minima and cardiac output (P<0.05, and improved oxygen metabolism (oxygen delivery and oxygen consumption (P<0.05, which suggesting that EE can protect myocardial tissue from injury and improve post-resuscitation myocardial dysfunction. The protective effect of EE also correlated with reducing cardiomyocyte apoptosis, evidenced by reducing TUNEL-positive cells, increasing anti-apoptotic Bcl-2/Bax ratio and suppression of caspase-3 activity in myocardium. CONCLUSIONS: Esmolol, a short-acting β₁-selective adrenergic blocking agent, given during CPR has significant effects on attenuating post resuscitation myocardial dysfunction. The current study provides a potential pharmacologic target for post resuscitation myocardial dysfunction.

  7. Silencing of miR-34a attenuates cardiac dysfunction in a setting of moderate, but not severe, hypertrophic cardiomyopathy.

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    Bianca C Bernardo

    Full Text Available Therapeutic inhibition of the miR-34 family (miR-34a,-b,-c, or miR-34a alone, have emerged as promising strategies for the treatment of cardiac pathology. However, before advancing these approaches further for potential entry into the clinic, a more comprehensive assessment of the therapeutic potential of inhibiting miR-34a is required for two key reasons. First, miR-34a has ∼40% fewer predicted targets than the miR-34 family. Hence, in cardiac stress settings in which inhibition of miR-34a provides adequate protection, this approach is likely to result in less potential off-target effects. Secondly, silencing of miR-34a alone may be insufficient in settings of established cardiac pathology. We recently demonstrated that inhibition of the miR-34 family, but not miR-34a alone, provided benefit in a chronic model of myocardial infarction. Inhibition of miR-34 also attenuated cardiac remodeling and improved heart function following pressure overload, however, silencing of miR-34a alone was not examined. The aim of this study was to assess whether inhibition of miR-34a could attenuate cardiac remodeling in a mouse model with pre-existing pathological hypertrophy. Mice were subjected to pressure overload via constriction of the transverse aorta for four weeks and echocardiography was performed to confirm left ventricular hypertrophy and systolic dysfunction. After four weeks of pressure overload (before treatment, two distinct groups of animals became apparent: (1 mice with moderate pathology (fractional shortening decreased ∼20% and (2 mice with severe pathology (fractional shortening decreased ∼37%. Mice were administered locked nucleic acid (LNA-antimiR-34a or LNA-control with an eight week follow-up. Inhibition of miR-34a in mice with moderate cardiac pathology attenuated atrial enlargement and maintained cardiac function, but had no significant effect on fetal gene expression or cardiac fibrosis. Inhibition of miR-34a in mice with severe

  8. 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.

  9. Prostaglandins attenuate cardiac contractile dysfunction produced by free radical generation but not by hydrogen peroxide.

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    Zimmer, K M; Karmazyn, M

    1997-11-01

    The aim of this study was to examine and compare the potential influence of cyclooxygenase or lipoxygenase derived metabolites of arachidonic acid on myocardial injury produced either by a free radical generating system consisting of purine plus xanthine oxidase or that produced by hydrogen peroxide. A free radical generating system consisting of purine (2.3 mM) and xanthine oxidase (10 U/L) as well as hydrogen peroxide (75 microM) produced significant functional changes in the absence of either significant deficits in high energy phosphates or ultrastructural damage. Prostaglandin F2 alpha (30 nM) significantly attenuated both the negative inotropic effect of purine plus xanthine oxidase as well as the ability of the free radical generator to elevate diastolic pressure. An identical concentration of prostaglandin 12 (prostacyclin) significantly reduced diastolic pressure elevation only and had no effect on contractile depression. The salutary effects of the two PGs occurred in the absence of any inhibitory influence on superoxide anion generation produced by the purine and xanthine oxidase reaction. None of prostaglandins modulated the response to hydrogen peroxide. In addition, neither prostaglandin E2 nor leukotrienes exerted any effect on changes produced by either type of oxidative stress. A 5 fold elevation in the concentrations of free radical generators or hydrogen peroxide produced extensive injury as characterized by a virtual total loss in contractility, 400% elevation in diastolic pressure, ultrastructural damage and significant depletions in high energy phosphate content. None of these effects were modulated by eicosanoid treatment. Our results therefore demonstrate a selective ability of both prostaglandin F2 alpha and to a lesser extent prostacyclin, to attenuate dysfunction produced by purine plus xanthine oxidase but not hydrogen peroxide. It is possible that these eicosanoids may represent endogenous protective factors under conditions of enhanced

  10. Inhibition of CaMKII does not attenuate cardiac hypertrophy in mice with dysfunctional ryanodine receptor.

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    Asima Chakraborty

    Full Text Available In cardiac muscle, the release of calcium ions from the sarcoplasmic reticulum through ryanodine receptor ion channels (RyR2s leads to muscle contraction. RyR2 is negatively regulated by calmodulin (CaM and by phosphorylation of Ca2+/CaM-dependent protein kinase II (CaMKII. Substitution of three amino acid residues in the CaM binding domain of RyR2 (RyR2-W3587A/L3591D/F3603A, RyR2ADA impairs inhibition of RyR2 by CaM and results in cardiac hypertrophy and early death of mice carrying the RyR2ADA mutation. To test the cellular function of CaMKII in cardiac hypertrophy, mutant mice were crossed with mice expressing the CaMKII inhibitory AC3-I peptide or the control AC3-C peptide in the myocardium. Inhibition of CaMKII by AC3-I modestly reduced CaMKII-dependent phosphorylation of RyR2 at Ser-2815 and markedly reduced CaMKII-dependent phosphorylation of SERCA2a regulatory subunit phospholamban at Thr-17. However the average life span and heart-to-body weight ratio of Ryr2ADA/ADA mice expressing the inhibitory peptide were not altered compared to control mice. In Ryr2ADA/ADA homozygous mice, AC3-I did not alter cardiac morphology, enhance cardiac function, improve sarcoplasmic reticulum Ca2+ handling, or suppress the expression of genes implicated in cardiac remodeling. The results suggest that CaMKII was not required for the rapid development of cardiac hypertrophy in Ryr2ADA/ADA mice.

  11. 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.

  12. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

    Science.gov (United States)

    Benter, Ibrahim F.; Babiker, Fawzi; Al-Rashdan, Ibrahim; Yousif, Mariam; Akhtar, Saghir

    2013-01-01

    Aims. We evaluated the effects of RU28318 (RU), a selective mineralocorticoid receptor (MR) antagonist, Captopril (Capt), an angiotensin converting enzyme inhibitor, and Losartan (Los), an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R-) induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I) followed by a period of 30 min of reperfusion (R). Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple). Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving −dP/dt (a measure of diastolic function) when administered to diabetic hearts after ischemia. PMID:24066305

  13. RU28318, an Aldosterone Antagonist, in Combination with an ACE Inhibitor and Angiotensin Receptor Blocker Attenuates Cardiac Dysfunction in Diabetes

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    Ibrahim F. Benter

    2013-01-01

    Full Text Available Aims. We evaluated the effects of RU28318 (RU, a selective mineralocorticoid receptor (MR antagonist, Captopril (Capt, an angiotensin converting enzyme inhibitor, and Losartan (Los, an angiotensin receptor blocker, alone or in combination with ischemia/reperfusion- (I/R- induced cardiac dysfunction in hearts obtained from normal and diabetic rats. Methods. Isolated hearts were perfused for 30 min and then subjected to 30 min of global ischemia (I followed by a period of 30 min of reperfusion (R. Drugs were administered for 30 min either before or after ischemia. Drug regimens tested were RU, Capt, Los, RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple. Recovery of cardiac hemodynamics was evaluated. Results. Recovery of cardiac function was up to 5-fold worse in hearts obtained from diabetic animals compared to controls. Treatment with RU was generally better in preventing or reversing ischemia-induced cardiac dysfunction in normal hearts compared to treatment with Capt or Los alone. In diabetic hearts, RU was generally similarly effective as Capt or Los treatment. Conclusions. RU treatment locally might be considered as an effective therapy or preventative measure in cardiac I/R injury. Importantly, RU was the most effective at improving -dP/dt (a measure of diastolic function when administered to diabetic hearts after ischemia.

  14. Mechanical ventilation with high tidal volumes attenuates myocardial dysfunction by decreasing cardiac edema in a rat model of LPS-induced peritonitis

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    Smeding Lonneke

    2012-03-01

    Full Text Available Abstract Background Injurious mechanical ventilation (MV may augment organ injury remote from the lungs. During sepsis, myocardial dysfunction is common and increased endothelial activation and permeability can cause myocardial edema, which may, among other factors, hamper myocardial function. We investigated the effects of MV with injuriously high tidal volumes on the myocardium in an animal model of sepsis. Methods Normal rats and intraperitoneal (i.p. lipopolysaccharide (LPS-treated rats were ventilated with low (6 ml/kg and high (19 ml/kg tidal volumes (Vt under general anesthesia. Non-ventilated animals served as controls. Mean arterial pressure (MAP, central venous pressure (CVP, cardiac output (CO and pulmonary plateau pressure (Pplat were measured. Ex vivo myocardial function was measured in isolated Langendorff-perfused hearts. Cardiac expression of endothelial vascular cell adhesion molecule (VCAM-1 and edema were measured to evaluate endothelial inflammation and leakage. Results MAP decreased after LPS-treatment and Vt-dependently, both independent of each other and with interaction. MV Vt-dependently increased CVP and Pplat and decreased CO. LPS-induced peritonitis decreased myocardial function ex vivo but MV attenuated systolic dysfunction Vt-dependently. Cardiac endothelial VCAM-1 expression was increased by LPS treatment independent of MV. Cardiac edema was lowered Vt-dependently by MV, particularly after LPS, and correlated inversely with systolic myocardial function parameters ex vivo. Conclusion MV attenuated LPS-induced systolic myocardial dysfunction in a Vt-dependent manner. This was associated with a reduction in cardiac edema following a lower transmural coronary venous outflow pressure during LPS-induced coronary inflammation.

  15. Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

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    Maria E Danoviz

    Full Text Available BACKGROUND: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDINGS: 99mTc-labeled ASCs (1x10(6 cells isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C, or culture medium (ASC/M as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively. Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT and control groups (culture medium, fibrin, or collagen alone. Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW, a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. CONCLUSIONS: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.

  16. Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

    Science.gov (United States)

    Danoviz, Maria E.; Nakamuta, Juliana S.; Marques, Fabio L. N.; dos Santos, Leonardo; Alvarenga, Erica C.; dos Santos, Alexandra A.; Antonio, Ednei L.; Schettert, Isolmar T.; Tucci, Paulo J.; Krieger, Jose E.

    2010-01-01

    Background Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). Methodology/Principal Findings 99mTc-labeled ASCs (1×106 cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by γ-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8±2.0 and 26.8±2.4% vs. 4.8±0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. Conclusions We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers. PMID:20711471

  17. Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by the GPER agonist G-1 in female mRen2.Lewis rats.

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    Jewell A Jessup

    Full Text Available INTRODUCTION: The G protein-coupled estrogen receptor (GPER is expressed in various tissues including the heart. Since the mRen2.Lewis strain exhibits salt-dependent hypertension and early diastolic dysfunction, we assessed the effects of the GPER agonist (G-1, 40 nmol/kg/hr for 14 days or vehicle (VEH, DMSO/EtOH on cardiac function and structure. METHODS: Intact female mRen2.Lewis rats were fed a normal salt (0.5% sodium; NS diet or a high salt (4% sodium; HS diet for 10 weeks beginning at 5 weeks of age. RESULTS: Prolonged intake of HS in mRen2.Lewis females resulted in significantly increased blood pressure, mildly reduced systolic function, and left ventricular (LV diastolic compliance (as signified by a reduced E deceleration time and E deceleration slope, increased relative wall thickness, myocyte size, and mid-myocardial interstitial and perivascular fibrosis. G-1 administration attenuated wall thickness and myocyte hypertrophy, with nominal effects on blood pressure, LV systolic function, LV compliance and cardiac fibrosis in the HS group. G-1 treatment significantly increased LV lusitropy [early mitral annular descent (e'] independent of prevailing salt, and improved the e'/a' ratio in HS versus NS rats (P<0.05 as determined by tissue Doppler. CONCLUSION: Activation of GPER improved myocardial relaxation in the hypertensive female mRen2.Lewis rat and reduced cardiac myocyte hypertrophy and wall thickness in those rats fed a high salt diet. Moreover, these advantageous effects of the GPER agonist on ventricular lusitropy and remodeling do not appear to be associated with overt changes in blood pressure.

  18. Silencing MicroRNA-155 Attenuates Cardiac Injury and Dysfunction in Viral Myocarditis via Promotion of M2 Phenotype Polarization of Macrophages.

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    Zhang, Yingying; Zhang, Mengying; Li, Xueqin; Tang, Zongsheng; Wang, Xiangmin; Zhong, Min; Suo, Qifeng; Zhang, Yao; Lv, Kun

    2016-01-01

    Macrophage infiltration is a hallmark feature of viral myocarditis. As studies have shown that microRNA-155 regulates the differentiation of macrophages, we aimed to investigate the role of microRNA-155 in VM. We report that silencing microRNA-155 protects mice from coxsackievirus B3 induced myocarditis. We found that microRNA-155 expression was upregulated and localized primarily in heart-infiltrating macrophages and CD4(+) T lymphocytes during acute myocarditis. In contrast with wildtype (WT) mice, microRNA-155(-/-) mice developed attenuated viral myocarditis, which was characterized by decreased cardiac inflammation and decreased intracardiac CD45(+) leukocytes. Hearts of microRNA-155(-/-) mice expressed decreased levels of the IFN-γ and increased levels of the cytokines IL-4 and IL-13. Although total CD4(+) and regulatory T cells were unchanged in miR-155(-/-) spleen proportionally, the activation of T cells and CD4(+) T cell proliferation in miR-155(-/-) mice were significantly decreased. Beyond the acute phase, microRNA-15(5-/-) mice had reduced mortality and improved cardiac function during 5 weeks of follow-up. Moreover, silencing microRNA-155 led to increased levels of alternatively-activated macrophages (M2) and decreased levels of classically-activated macrophages (M1) in the heart. Combined, our studies suggest that microRNA-155 confers susceptibility to viral myocarditis by affecting macrophage polarization, and thus may be a potential therapeutic target for viral myocarditis. PMID:26931072

  19. Endothelial dysfunction after non-cardiac surgery

    DEFF Research Database (Denmark)

    Søndergaard, E S; Fonnes, S; Gögenur, I

    2015-01-01

    transplantation and vascular surgery respectively) had an improvement in endothelial dysfunction 1 month after surgery. CONCLUSION: Endothelial function changes in relation to surgery. Assessment of endothelial function by non-invasive measures has the potential to guide clinicians in the prevention or treatment......BACKGROUND: More than 50% of patients with increased troponin levels after non-cardiac surgery have an impaired endothelial function pre-operatively. Non-invasive markers of endothelial function have been developed for the assessment of endothelial dysfunction. The aim of this paper...... was to systematically review the literature to evaluate the association between non-cardiac surgery and non-invasive markers of endothelial function. METHODS: A systematic search was conducted in MEDLINE, EMBASE and Cochrane Library Database according to the PRISMA guidelines. Endothelial dysfunction was described only...

  20. Sexual Dysfunction before and after Cardiac Rehabilitation

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    Jörg Schumann

    2010-01-01

    variables. Methods. Analysis of patients participating in a 12-week exercise-based outpatient cardiac rehabilitation program (OCR between April 1999 and December 2007. Exercise capacity (ExC and quality of life including sexual function were assessed before and after OCR. Results. Complete data were available in 896 male patients. No sexual activity at all was indicated by 23.1% at baseline and 21.8% after OCR, no problems with sexual activity by 40.8% at baseline and 38.6% after OCR. Patients showed an increase in specific problems (erectile dysfunction and lack of orgasm from 18% to 23% (<.0001 during OCR. We found the following independent positive and negative predictors of sexual problems after OCR: hyperlipidemia, age, CABG, baseline ExC and improvement of ExC, subjective physical and mental capacity, and sense of affiliation. Conclusions. Sexual dysfunction is present in over half of the patients undergoing OCR with no overall improvement during OCR. Age, CABG, low exercise capacity are independent predictors of sexual dysfunction after OCR.

  1. Troponin Ⅰ,cardiac diastolic dysfunction and restrictive cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    Xu-pei HUANG; Jian-feng DU

    2004-01-01

    Cardiomyopathies are diseases of heart muscle that are associated with cardiac dysfunction. Molecular genetic studies performed to date have demonstrated that the damage or mutations in several sarcomeric contractile protein genes are associated with the development of the diseases. In this review, cardiac troponin Ⅰ, one of the sarcomeric thin filament protein, will be discussed regarding its role in cardiac function, its deficiency-related diastolic dysfunction, and the mutation of this protein-mediated restrictive cardiomyopathy.

  2. Transgenic Knockdown of Cardiac Sodium/Glucose Cotransporter 1 (SGLT1) Attenuates PRKAG2 Cardiomyopathy, Whereas Transgenic Overexpression of Cardiac SGLT1 Causes Pathologic Hypertrophy and Dysfunction in Mice

    OpenAIRE

    Ramratnam, Mohun; Sharma, Ravi K.; D'Auria, Stephen; Lee, So Jung; Wang, David; Huang, Xue Yin N.; Ahmad, Ferhaan

    2014-01-01

    Background The expression of a novel cardiac glucose transporter, SGLT1, is increased in glycogen storage cardiomyopathy secondary to mutations in PRKAG2. We sought to determine the role of SGLT1 in the pathogenesis of PRKAG2 cardiomyopathy and its role in cardiac structure and function. Methods and Results Transgenic mice with cardiomyocyte‐specific overexpression of human T400N mutant PRKAG2 cDNA (TGT400N) and transgenic mice with cardiomyocyte‐specific RNA interference knockdown of SGLT1 (...

  3. Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice

    DEFF Research Database (Denmark)

    Soltysinska, Ewa; Speerschneider, Tobias; Winther, Sine V;

    2014-01-01

    recovery time was prolonged in diabetic mice. Adrenoreceptor stimulation increased heart rate in all mice and elicited cardiac arrhythmias in db/db mice only. The arrhythmias emanated from the SAN and were characterized by large RR fluctuations. Moreover, nerve density was reduced in the SAN region.......ConclusionsEnhanced systolic function and reduced diastolic function indicates early ventricular remodeling in obese and diabetic mice. They have SAN dysfunction, and adrenoreceptor stimulation triggers cardiac arrhythmia originating in the SAN. Thus, dysfunction of the intrinsic cardiac pacemaker and remodeling...

  4. Breath-hold CT attenuation correction for quantitative cardiac SPECT

    OpenAIRE

    Koshino, Kazuhiro; Fukushima, Kazuhito; Fukumoto, Masaji; Sasaki, Kazunari; Moriguchi, Tetsuaki; Hori, Yuki; Zeniya, Tsutomu; Nishimura, Yoshihiro; Kiso, Keisuke; Iida, Hidehiro

    2012-01-01

    Background Attenuation correction of a single photon emission computed tomography (SPECT) image is possible using computed tomography (CT)-based attenuation maps with hybrid SPECT/CT. CT attenuation maps acquired during breath holding can be misaligned with SPECT, generating artifacts in the reconstructed images. The purpose of this study was to investigate the effects of respiratory phase during breath-hold CT acquisition on attenuation correction of cardiac SPECT imaging. Methods A series o...

  5. Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction by Increasing Interleukin 10

    Directory of Open Access Journals (Sweden)

    Varun eKesherwani

    2015-04-01

    Full Text Available Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α and attenuation of anti-inflammatory cytokine such as interleukin10 (IL-10 contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, eight week old, female C57BL/6J mice were fed with HFD and exercised (swimming 1hr/day for 5 days/week for eight weeks. The four treatment groups: normal diet (ND, HFD, HFD + exercise (HFD + Ex and ND + Ex were analyzed for mean body weight, blood glucose level, TNF-α, IL-10, cardiac fibrosis by Masson Trichrome, and cardiac dysfunction by echocardiography. Mean body weights were increased in HFD but comparatively less in HFD + Ex. The level of TNF-α was elevated and IL-10 was downregulated in HFD but ameliorated in HFD + Ex. Cardiac fibrosis increased in HFD and was attenuated by exercise in the HFD + Ex group. The percentage ejection fraction and fractional shortening were decreased in HFD but comparatively increased in HFD + Ex. There was no difference between ND and ND + Ex for the above parameters except an increase in IL-10 level following exercise. Based on these results, we conclude that exercise mitigates HFD- induced cardiomyopathy by decreasing obesity, inducing IL-10, and reducing TNF-α in mice.

  6. Cardiac-specific knockout of ETA receptor mitigates low ambient temperature-induced cardiac hypertrophy and contractile dysfunction

    Institute of Scientific and Technical Information of China (English)

    Yingmei Zhang; Linlin Li; Yinan Hua; Jennifer M. Nunn; Feng Dong; Masashi Yanagisawa; Jun Ren

    2012-01-01

    Cold exposure is associated with oxidative stress and cardiac dysfunction.The endothelin (ET) system,which plays a key role in myocardial homeostasis,may participate in cold exposure-induced cardiovascular dysfunction.This study was designed to examine the role of ET-1 in cold stress-induced cardiac geometric and contractile responses.Wild-type (WT) and ETA receptor knockout (ETAKO) mice were assigned to normal or cold exposure (4℃) environment for 2 and 5 weeks prior to evaluation of cardiac geometry,contractile,and intracellular Ca2+ properties.Levels of the temperature sensor transient receptor potential vanlllold (TRPV1),mitochondrlal proteins for biogenesis and oxidative phosphorylatlon,Including UCP2,HSP90,and PGC1α were evaluated.Cold stress triggered cardiac hypertrophy,depressed myocardial contractile capacity,including fractional shortening,peak shortening,and maximal velocity of shortening/relengthening,reduced intracellular Ca2+ release,prolonged intracellular Ca2+ decay and relengthening duration,generation of ROS and superoxide,as well as apoptosls,the effects of which were blunted by ETAKO.Western blotting revealed downregulated TRPV1 and PGC1α as well as upregulated UCP2 and activation of GSK3β,GATA4,and CREB in cold-stressed WT mouse hearts,which were obliterated by ETAKO.Levels of HSP90,an essential regulator for thermotolerance,were unchanged.The TRPV1 agonist SA13353 attenuated whereas TRPV1 antagonist capsazepino mimicked cold stress- or ET-1-induced cardiac anomalies.The GSK3β Inhibitor SB216763 ablated cold stress-induced cardiac contractile (but not remodeling) changes and ET-1-induced TRPV1 downregulation.These data suggest that ETAKO protects against cold exposure-induced cardiac remodeling and dysfunction mediated through TRPV1 and mitochondrlal function.

  7. Disruption of Epac1 protects the heart from adenylyl cyclase type 5-mediated cardiac dysfunction.

    Science.gov (United States)

    Cai, Wenqian; Fujita, Takayuki; Hidaka, Yuko; Jin, Huiling; Suita, Kenji; Prajapati, Rajesh; Liang, Chen; Umemura, Masanari; Yokoyama, Utako; Sato, Motohiko; Okumura, Satoshi; Ishikawa, Yoshihiro

    2016-06-17

    Type 5 adenylyl cyclase (AC5) plays an important role in the development of chronic catecholamine stress-induced heart failure and arrhythmia in mice. Epac (exchange protein activated by cAMP), which is directly activated by cAMP independent of protein kinase A, has been recently identified as a novel mediator of cAMP signaling in the heart. However, the role of Epac in AC5-mediated cardiac dysfunction and arrhythmias remains poorly understood. We therefore generated AC5 transgenic mice (AC5TG) with selective disruption of the Epac1 gene (AC5TG-Epac1KO), and compared their phenotypes with those of AC5TG after chronic isoproterenol (ISO) infusion. Decreased cardiac function as well as increased susceptibility to pacing-induced atrial fibrillation (AF) in response to ISO were significantly attenuated in AC5TG-Epac1KO mice, compared to AC5TG mice. Increased cardiac apoptosis and cardiac fibrosis were also concomitantly attenuated in AC5TG-Epac1KO mice compared to AC5TG mice. These findings indicate that Epac1 plays an important role in AC5-mediated cardiac dysfunction and AF susceptibility. PMID:27117748

  8. Sexual Dysfunction before and after Cardiac Rehabilitation

    OpenAIRE

    Jörg Schumann; Zellweger, Michael J.; Marcello Di Valentino; Simone Piazzalonga; Andreas Hoffmann

    2010-01-01

    Background. The aim of this study was to assess sexual function before and after cardiac rehabilitation in relation to medical variables. Methods. Analysis of patients participating in a 12-week exercise-based outpatient cardiac rehabilitation program (OCR) between April 1999 and December 2007. Exercise capacity (ExC) and quality of life including sexual function were assessed before and after OCR. Results. Complete data were available in 896 male patients. No sexual activity at all was indic...

  9. Milrinone for cardiac dysfunction in critically ill adult patients

    DEFF Research Database (Denmark)

    Koster, Geert; Bekema, Hanneke J; Wetterslev, Jørn;

    2016-01-01

    review was performed according to The Cochrane Handbook for Systematic Reviews of Interventions. Searches were conducted until November 2015. Patients with cardiac dysfunction were included. The primary outcome was serious adverse events (SAE) including mortality at maximum follow-up. The risk of bias...... analyses displayed statistical and/or clinical heterogeneity of patients, interventions, comparators, outcomes, and/or settings and all featured missing data. DISCUSSION: The current evidence on the use of milrinone in critically ill adult patients with cardiac dysfunction suffers from considerable risks...

  10. 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.

  11. Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice

    Institute of Scientific and Technical Information of China (English)

    Jian Wang; Dawei Zhan; Lagabaiyila Zha; Yang Cao; Zhenhua Li; Xuan Cheng; Youyi Zhang; XiaoYang; Yao Song; Yan Zhang; Han Xiao; Qiang Sun; Ning Hou; Shuilong Guo; Youliang Wang; Kaiji Fan

    2012-01-01

    Recent studies have begun to reveal critical roles of microRNAs(miRNAs)in the pathogenesis of cardiac hypertrophy and dysfunction.In this study,we tested whether a transforming growth factor-β(TGF-β)-regulated miRNA played a pivotal role in the development of cardiac hypertrophy and heart failure(HF).We observed that miR-27b was upregulated in hearts of cardiomyocyte-specific Smad4 knockout mice,which developed cardiac hypertrophy.In vitro experiments showed that the miR-27b expression could be inhibited by TGF-β1 and that its overexpression promoted hypertrophic cell growth,while the miR-27b suppression led to inhibition of the hypertrophic cell growth caused by phenylephrine(PE)treatment.Furthermore,the analysis of transgenic mice with cardiomyocyte-specific overexpression of miR-27b revealed that miR-27b overexpression was sufficient to induce cardiac hypertrophy and dysfunction.We validated the peroxisome proliferator-activated receptor-γ(PPAR-γ)as a direct target of miR-27b in cardiomyocyte.Consistently,the miR-27b transgenic mice displayed significantly lower levels of PPAR-γ than the control mice.Furthermore,in vivo silencing of miR-27b using a specific antagomir in a pressure-overload-induced mouse model of HF increased cardiac PPAR-γ expression,attenuated cardiac hypertrophy and dysfunction.The results of our study demonstrate that TGF-β1-regulated miR-27b is involved in the regulation of cardiac hypertrophy,and validate miR-27b as an efficient therapeutic target for cardiac diseases.

  12. 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.

  13. Neuregulin-1 attenuates mitochondrial dysfunction in a rat model of heart failure

    Institute of Scientific and Technical Information of China (English)

    GUO Yong-fang; ZHANG Xiao-xia; LIU Yong; DUAN Hong-yan; JIE Bing-zhang; WU Xue-si

    2012-01-01

    Background Mitochondrial dysfunction plays a pivotal role in the progression of left ventricular (LV) remodeling and heart failure (HF).Recombinant human neuregulin-1 (rhNRG-1)improves cardiac function in models of experimental HF and in clinical trials; however,its impact on mitochondrial function during chronic HF remains largely unknown.The purpose of this study was to investigate whether rhNRG-1 could attenuate the functional and structural changes that occur in cardiac mitochondria in a rat model of HF induced by myocardial infarction.Methods Sixty adult rats underwent sham or coronary ligation to induce HF.Four weeks after ligation,29 animals with LV ejective fraction <50% were randomized to receive either vehicle or rhNRG-1 (10 μg·kg-1·d-1,I.V.) for 10 days,another 12 sham-operated animals were given no treatment.Echocardiography was used to determine physiological changes.Mitochondrial membrane potential (MMP),respiratory function and tissue adenosine triphosphate (ATP) production were analyzed.Cytochrome c expression and cardiomyocyte apoptosis were determined.Oxidative stress was evaluated by reactive oxygen species production using fluorescence assays and gene expression of glutathione peroxidase measured by real-time quantitative PCR.Results Compared with sham-operated animals,vehicle treated HF rats exhibited severe LV remodeling and dysfunction,significant mitochondrial dysfunction,increased mitochondrial cytochrome c release,increased myocyte apoptosis and enhanced oxidative stress.Short-term treatment with rhNRG-1 significantly attenuated LV remodeling and cardiac function.Concomitant with this change,mitochondrial dysfunction was significantly attenuated; with ATP production,MMP and respiratory function restored,cytochrome c release and apoptosis inhibited,and oxidative stress reduced.Conclusion The present study demonstrated that rhNRG-1 can significantly improve LV remodeling and cardiac function in the failing heart,this beneficial effect

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

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    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.

  15. Cardiac dysfunction in a porcine model of pediatric malnutrition

    DEFF Research Database (Denmark)

    Fabiansen, Christian; Lykke, Mikkel; Nielsen, Anne-Louise Hother;

    2015-01-01

    and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model. METHODS AND RESULTS: Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire) were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12) or a reference diet......BACKGROUND: Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition. OBJECTIVE: To determine malnutrition-induced echocardiographic disturbances...... (AGE-REF, n = 12) for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8). Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased...

  16. Proteasome inhibitors attenuated cholesterol-induced cardiac hypertrophy in H9c2 cells

    Science.gov (United States)

    Lee, Hyunjung; Park, Jinyoung; Kim, Eunice EunKyeong; Yoo, Young Sook; Song, Eun Joo

    2016-01-01

    The Ubiquitin proteasome system (UPS) plays roles in protein degradation, cell cycle control, and growth and inflammatory cell signaling. Dysfunction of UPS in cardiac diseases has been seen in many studies. Cholesterol acts as an inducer of cardiac hypertrophy. In this study, the effect of proteasome inhibitors on the cholesterol-induced hypertrophic growth in H9c2 cells is examined in order to observe whether UPS is involved in cardiac hypertrophy. The treatment of proteasome inhibitors MG132 and Bortezomib markedly reduced cellular surface area and mRNA expression of β-MHC in cholesterol-induced cardiac hypertrophy. In addition, activated AKT and ERK were significantly attenuated by MG132 and Bortezomib in cholesterol-induced cardiac hypertrophy. We demonstrated that cholesterol-induced cardiac hypertrophy was suppressed by proteasome inhibitors. Thus, regulatory mechanism of cholesterol-induced cardiac hypertrophy by proteasome inhibitors may provide a new therapeutic strategy to prevent the progression of heart failure. [BMB Reports 2016; 49(5): 270-275] PMID:26592933

  17. Testosterone deprivation accelerates cardiac dysfunction in obese male rats.

    Science.gov (United States)

    Pongkan, Wanpitak; Pintana, Hiranya; Sivasinprasasn, Sivaporn; Jaiwongkam, Thidarat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2016-06-01

    Low testosterone level is associated with increased risks of cardiovascular diseases. As obese-insulin-resistant condition could impair cardiac function and that the incidence of obesity is increased in aging men, a condition of testosterone deprivation could aggravate the cardiac dysfunction in obese-insulin-resistant subjects. However, the mechanism underlying this adverse effect is unclear. This study investigated the effects of obesity on metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function in testosterone-deprived rats. Orchiectomized or sham-operated male Wistar rats (n=36per group) were randomly divided into groups and were given either a normal diet (ND, 19.77% of energy fat) or a high-fat diet (HFD, 57.60% of energy fat) for 12weeks. Metabolic parameters, HRV, LV function, and cardiac mitochondrial function were determined at 4, 8, and 12weeks after starting each feeding program. We found that insulin resistance was observed after 8weeks of the consumption of a HFD in both sham (HFS) and orchiectomized (HFO) rats. Neither the ND sham (NDS) group nor ND orchiectomized (NDO) rats developed insulin resistance. The development of depressed HRV, LV contractile dysfunction, and increased cardiac mitochondrial reactive oxygen species production was observed earlier in orchiectomized (NDO and HFO) rats at week 4, whereas HFS rats exhibited these impairments later at week 8. These findings suggest that testosterone deprivation accelerates the impairment of cardiac autonomic regulation and LV function via increased oxidative stress and impaired cardiac mitochondrial function in obese-orchiectomized male rats. PMID:27000685

  18. Leptin as a mediator between obesity and cardiac dysfunction

    OpenAIRE

    Joanna Karbowska; Zdzisław Kochan

    2012-01-01

     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 plasm...

  19. Postoperative Pulmonary Dysfunction and Mechanical Ventilation in Cardiac Surgery

    OpenAIRE

    Rafael Badenes; Angels Lozano; F. Javier Belda

    2015-01-01

    Postoperative pulmonary dysfunction (PPD) is a frequent and significant complication after cardiac surgery. It contributes to morbidity and mortality and increases hospitalization stay and its associated costs. Its pathogenesis is not clear but it seems to be related to the development of a systemic inflammatory response with a subsequent pulmonary inflammation. Many factors have been described to contribute to this inflammatory response, including surgical procedure with sternotomy incision,...

  20. Cardiac Dysfunction in a Porcine Model of Pediatric Malnutrition.

    Directory of Open Access Journals (Sweden)

    Christian Fabiansen

    Full Text Available Half a million children die annually of severe acute malnutrition and cardiac dysfunction may contribute to the mortality. However, cardiac function remains poorly examined in cases of severe acute malnutrition.To determine malnutrition-induced echocardiographic disturbances and longitudinal changes in plasma pro-atrial natriuretic peptide and cardiac troponin-T in a pediatric porcine model.Five-week old piglets (Duroc-x-Danish Landrace-x-Yorkshire were fed a nutritionally inadequate maize-flour diet to induce malnutrition (MAIZE, n = 12 or a reference diet (AGE-REF, n = 12 for 7 weeks. Outcomes were compared to a weight-matched reference group (WEIGHT-REF, n = 8. Pro-atrial natriuretic peptide and cardiac troponin-T were measured weekly. Plasma pro-atrial natriuretic peptide decreased in both MAIZE and AGE-REF during the first 3 weeks but increased markedly in MAIZE relative to AGE-REF during week 5-7 (p ≤ 0.001. There was overall no difference in plasma cardiac troponin-T between groups. However, further analysis revealed that release of cardiac troponin-T in plasma was more frequent in AGE-REF compared with MAIZE (OR: 4.8; 95%CI: 1.2-19.7; p = 0.03. However, when release occurred, cardiac troponin-T concentration was 6.9-fold higher (95%CI: 3.0-15.9; p < 0.001 in MAIZE compared to AGE-REF. At week 7, the mean body weight in MAIZE was lower than AGE-REF (8.3 vs 32.4 kg, p < 0.001, whereas heart-weight relative to body-weight was similar across the three groups. The myocardial performance index was 86% higher in MAIZE vs AGE-REF (p < 0.001 and 27% higher in MAIZE vs WEIGHT-REF (p = 0.025.Malnutrition associates with cardiac dysfunction in a pediatric porcine model by increased myocardial performance index and pro-atrial natriuretic peptide and it associates with cardiac injury by elevated cardiac troponin-T. Clinical studies are needed to see if the same applies for children suffering from malnutrition.

  1. Endothelial ROS and Impaired Myocardial Oxygen Consumption in Sepsis-induced Cardiac Dysfunction

    OpenAIRE

    Potz, Brittany A; Sellke, Frank W.; Abid, M. Ruhul

    2016-01-01

    Sepsis is known as the presence of a Systemic Inflammatory Response Syndrome (SIRS) in response to an infection. In the USA alone, 750,000 cases of severe sepsis are diagnosed annually. More than 70% of sepsis-related deaths occur due to organ failure and more than 50% of septic patients demonstrate cardiac dysfunction. Patients with sepsis who develop cardiac dysfunction have significantly higher mortality, and thus cardiac dysfunction serves as a predictor of survival in sepsis.

  2. Lipotoxicity in obesity and diabetes-related cardiac dysfunction.

    Science.gov (United States)

    Zlobine, Igor; Gopal, Keshav; Ussher, John R

    2016-10-01

    Patients with type 2 diabetes (T2D) are at increased risk for cardiovascular diseases including diabetic cardiomyopathy, which is ventricular dysfunction independent of underlying coronary artery disease and/or hypertension. With numerous advancements in our ability to detect ventricular dysfunction, as well as the molecular mechanisms contributing to ventricular dysfunction in diabetic patients, it is now appreciated that diabetic cardiomyopathy is becoming more prevalent in our population. In spite of these advancements, we do not have any specific therapies currently approved for treating this condition. As obesity increases the risk for both T2D and cardiovascular disease, it has been postulated that obesity-mediated alterations in myocardial lipid metabolism are critical to the pathophysiology of diabetic cardiomyopathy. Indeed, animal studies have provided strong evidence that alterations in either myocardial fatty acid uptake or fatty acid β-oxidation lead to the accumulation of various lipid intermediates including triacylglycerol, diacylglycerol, ceramide, long-chain acyl CoA, acylcarnitine, and many others that are tightly linked to the progression of ventricular dysfunction. We review herein why lipid intermediates accumulate in the heart during obesity and/or T2D, with a focus on which of these various lipid intermediates may be responsible for cardiac lipotoxicity, and whether findings in animal models are relevant to humans. An improved understanding of how these lipid intermediates accumulate in the heart and how they produce cardiac toxicity may lead to the discovery of novel targets to pursue for the treatment of human diabetic cardiomyopathy. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26899197

  3. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    Directory of Open Access Journals (Sweden)

    Kandadi Machender R

    2012-11-01

    Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

  4. Angiotensin II Induced Cardiac Dysfunction on a Chip.

    Science.gov (United States)

    Horton, Renita E; Yadid, Moran; McCain, Megan L; Sheehy, Sean P; Pasqualini, Francesco S; Park, Sung-Jin; Cho, Alexander; Campbell, Patrick; Parker, Kevin Kit

    2016-01-01

    In vitro disease models offer the ability to study specific systemic features in isolation to better understand underlying mechanisms that lead to dysfunction. Here, we present a cardiac dysfunction model using angiotensin II (ANG II) to elicit pathological responses in a heart-on-a-chip platform that recapitulates native laminar cardiac tissue structure. Our platform, composed of arrays of muscular thin films (MTF), allows for functional comparisons of healthy and diseased tissues by tracking film deflections resulting from contracting tissues. To test our model, we measured gene expression profiles, morphological remodeling, calcium transients, and contractile stress generation in response to ANG II exposure and compared against previous experimental and clinical results. We found that ANG II induced pathological gene expression profiles including over-expression of natriuretic peptide B, Rho GTPase 1, and T-type calcium channels. ANG II exposure also increased proarrhythmic early after depolarization events and significantly reduced peak systolic stresses. Although ANG II has been shown to induce structural remodeling, we control tissue architecture via microcontact printing, and show pathological genetic profiles and functional impairment precede significant morphological changes. We assert that our in vitro model is a useful tool for evaluating tissue health and can serve as a platform for studying disease mechanisms and identifying novel therapeutics.

  5. Angiotensin II Induced Cardiac Dysfunction on a Chip.

    Directory of Open Access Journals (Sweden)

    Renita E Horton

    Full Text Available In vitro disease models offer the ability to study specific systemic features in isolation to better understand underlying mechanisms that lead to dysfunction. Here, we present a cardiac dysfunction model using angiotensin II (ANG II to elicit pathological responses in a heart-on-a-chip platform that recapitulates native laminar cardiac tissue structure. Our platform, composed of arrays of muscular thin films (MTF, allows for functional comparisons of healthy and diseased tissues by tracking film deflections resulting from contracting tissues. To test our model, we measured gene expression profiles, morphological remodeling, calcium transients, and contractile stress generation in response to ANG II exposure and compared against previous experimental and clinical results. We found that ANG II induced pathological gene expression profiles including over-expression of natriuretic peptide B, Rho GTPase 1, and T-type calcium channels. ANG II exposure also increased proarrhythmic early after depolarization events and significantly reduced peak systolic stresses. Although ANG II has been shown to induce structural remodeling, we control tissue architecture via microcontact printing, and show pathological genetic profiles and functional impairment precede significant morphological changes. We assert that our in vitro model is a useful tool for evaluating tissue health and can serve as a platform for studying disease mechanisms and identifying novel therapeutics.

  6. CXCR4 Antagonism Attenuates the Development of Diabetic Cardiac Fibrosis.

    Directory of Open Access Journals (Sweden)

    Po-Yin Chu

    Full Text Available Heart failure (HF is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice or type II diabetes (Israeli Sand-rats and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach.

  7. Patient position alters attenuation effects in multipinhole cardiac SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Timmins, Rachel; Ruddy, Terrence D.; Wells, R. Glenn, E-mail: gwells@ottawaheart.ca [Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7 (Canada)

    2015-03-15

    Purpose: Dedicated cardiac cameras offer improved sensitivity over conventional SPECT cameras. Sensitivity gains are obtained by large numbers of detectors and novel collimator arrangements such as an array of multiple pinholes that focus on the heart. Pinholes lead to variable amounts of attenuation as a source is moved within the camera field of view. This study evaluated the effects of this variable attenuation on myocardial SPECT images. Methods: Computer simulations were performed for a set of nine point sources distributed in the left ventricular wall (LV). Sources were placed at the location of the heart in both an anthropomorphic and a water-cylinder computer phantom. Sources were translated in x, y, and z by up to 5 cm from the center. Projections were simulated with and without attenuation and the changes in attenuation were compared. A LV with an inferior wall defect was also simulated in both phantoms over the same range of positions. Real camera data were acquired on a Discovery NM530c camera (GE Healthcare, Haifa, Israel) for five min in list-mode using an anthropomorphic phantom (DataSpectrum, Durham, NC) with 100 MBq of Tc-99m in the LV. Images were taken over the same range of positions as the simulations and were compared based on the summed perfusion score (SPS), defect width, and apparent defect uptake for each position. Results: Point sources in the water phantom showed absolute changes in attenuation of ≤8% over the range of positions and relative changes of ≤5% compared to the apex. In the anthropomorphic computer simulations, absolute change increased to 20%. The changes in relative attenuation caused a change in SPS of <1.5 for the water phantom but up to 4.2 in the anthropomorphic phantom. Changes were larger for axial than for transverse translations. These results were supported by SPS changes of up to six seen in the physical anthropomorphic phantom for axial translations. Defect width was also seen to significantly increase. The

  8. 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.

  9. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid

    Directory of Open Access Journals (Sweden)

    Li Chun-jun

    2012-06-01

    Full Text Available Abstract Background Alpha-lipoic acid (ALA, a naturally occurring compound, exerts powerful protective effects in various cardiovascular disease models. However, its role in protecting against diabetic cardiomyopathy (DCM has not been elucidated. In this study, we have investigated the effects of ALA on cardiac dysfunction, mitochondrial oxidative stress (MOS, extracellular matrix (ECM remodeling and interrelated signaling pathways in a diabetic rat model. Methods Diabetes was induced in rats by I.V. injection of streptozotocin (STZ at 45 mg/kg. The animals were randomly divided into 4 groups: normal groups with or without ALA treatment, and diabetes groups with or without ALA treatment. All studies were carried out 11 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate cardiac function. Mitochondrial oxidative biochemical parameters were measured by spectophotometeric assays. Extracellular matrix content (total collagen, type I and III collagen was assessed by staining with Sirius Red. Gelatinolytic activity of Pro- and active matrix metalloproteinase-2 (MMP-2 levels were analyzed by a zymogram. Cardiac fibroblasts differentiation to myofibroblasts was evaluated by Western blot measuring smooth muscle actin (α-SMA and transforming growth factor–β (TGF-β. Key components of underlying signaling pathways including the phosphorylation of c-Jun N-terminal kinase (JNK, p38 MAPK and ERK were also assayed by Western blot. Results DCM was successfully induced by the injection of STZ as evidenced by abnormal heart mass and cardiac function, as well as the imbalance of ECM homeostasis. After administration of ALA, left ventricular dysfunction greatly improved; interstitial fibrosis also notably ameliorated indicated by decreased collagen deposition, ECM synthesis as well as enhanced ECM degradation. To further assess the underlying mechanism of improved DCM by ALA, redox status and cardiac remodeling associated

  10. Cardiac sarcoplasmic reticulum calcium leak: basis and roles in cardiac dysfunction.

    Science.gov (United States)

    Bers, Donald M

    2014-01-01

    Synchronized SR calcium (Ca) release is critical to normal cardiac myocyte excitation-contraction coupling, and ideally this release shuts off completely between heartbeats. However, other SR Ca release events are referred to collectively as SR Ca leak (which includes Ca sparks and waves as well as smaller events not detectable as Ca sparks). Much, but not all, of the SR Ca leak occurs via ryanodine receptors and can be exacerbated in pathological states such as heart failure. The extent of SR Ca leak is important because it can (a) reduce SR Ca available for release, causing systolic dysfunction; (b) elevate diastolic [Ca]i, contributing to diastolic dysfunction; (c) cause triggered arrhythmias; and (d) be energetically costly because of extra ATP used to repump Ca. This review addresses quantitative aspects and manifestations of SR Ca leak and its measurement, and how leak is modulated by Ca, associated proteins, and posttranslational modifications in health and disease. PMID:24245942

  11. Activation of retinoid receptor-mediated signaling ameliorates diabetes-induced cardiac dysfunction in Zucker diabetic rats.

    Science.gov (United States)

    Guleria, Rakeshwar S; Singh, Amar B; Nizamutdinova, Irina T; Souslova, Tatiana; Mohammad, Amin A; Kendall, Jonathan A; Baker, Kenneth M; Pan, Jing

    2013-04-01

    Diabetic cardiomyopathy (DCM) is a significant contributor to the morbidity and mortality associated with diabetes and metabolic syndrome. Retinoids, through activation of retinoic acid receptor (RAR) and retinoid x receptor (RXR), have been linked to control glucose and lipid homeostasis, with effects on obesity and diabetes. However, the functional role of RAR and RXR in the development of DCM remains unclear. Zucker diabetic fatty (ZDF) and lean rats were treated with Am580 (RARα agonist) or LGD1069 (RXR agonist) for 16 weeks, and cardiac function and metabolic alterations were determined. Hyperglycemia, hyperlipidemia and insulin resistance were observed in ZDF rats. Diabetic cardiomyopathy was characterized in ZDF rats by increased oxidative stress, apoptosis, fibrosis, inflammation, activation of MAP kinases and NF-κB signaling and diminished Akt phosphorylation, along with decreased glucose transport and increased cardiac lipid accumulation, and ultimately diastolic dysfunction. Am580 and LGD1069 attenuated diabetes-induced cardiac dysfunction and the pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signaling pathways. Am580 inhibited body weight gain, attenuated the increased cardiac fatty acid uptake, β-oxidation and lipid accumulation in the hearts of ZDF rats. However, LGD1069 promoted body weight gain, hyperlipidemia and cardiac lipid accumulation. In conclusion, our data suggest that activation of RAR and RXR may have therapeutic potential in the treatment of diabetic cardiomyopathy. However, further studies are necessary to clarify the role of RAR and RXR in the regulation of lipid metabolism and homeostasis.

  12. Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

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    Mohammad T. Elnakish

    2015-01-01

    Full Text Available Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Cristiane Delgado Alves Rodrigues

    2015-02-01

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

  15. Centella asiatica Attenuates D-Galactose-Induced Cognitive Impairment, Oxidative and Mitochondrial Dysfunction in Mice

    Directory of Open Access Journals (Sweden)

    Anil Kumar

    2011-01-01

    l (D-galactose. Centella asiatica also attenuated enhanced acetylcholine esterase enzyme level in D-galactose senescence mice. Present study highlights the protective effect of Centella asiatica against D-galactose induced behavioral, biochemical and mitochondrial dysfunction in mice.

  16. Late gadolinium enhancement and subclinical cardiac dysfunction on cardiac MRI in asymptomatic HIV-positive men

    Directory of Open Access Journals (Sweden)

    A Loy

    2012-11-01

    Full Text Available Background: HIV is associated with an increased risk of cardiovascular disease (CVD and related clinical events. While traditional risk factors play an important role in the pathology of cardiovascular disease, HIV infection and its sequelae of immune activation and inflammation may have significant effects on the myocardium before becoming clinically evident. Cardiac MRI (CMR can be used to detect the pattern of these subclinical changes. This will lead to a better understanding of risk factors contributing to cardiovascular disease prior to it becoming clinically significant in HIV-positive patients. Methods: Prospective cohort study of 127 asymptomatic HIV-positive men on ART compared to 35 matched controls. Baseline demographics, HIV parameters, 12-lead ECG, routine biochemistry, and traditional cardiovascular risk factors were recorded. Images were acquired on a 3T Achieva Philips MRI scanner with 5 channel phase array cardiac coil and weight-based IV gadolinium was given at 0.15 mmol/kg dose with post-contrast inversion recovery imaging after 10 minutes. Results: 6/127 (4.7% of asymptomatic HIV-positive men had late gadolinium enhancement (LGE on MRI verses 1/35 (2.9% in the control group. In 3/6 (50% of cases this was in a classical infarction pattern with subendocardial involvement. 3/6 (50% were consistent with prior myocarditis. There was no significant difference in mean LVEF (66.93% vs 65.18%, LVMI (60.05g/m2 vs 55.94g/m2 or posterolateral wall thickness (8.28 mm and 8.16 mm between cases and controls respectively. There was significantly more diastolic dysfunction, E:A ratio < 1, found in the HIV-positive group, 18% vs 7% of controls (p = 0.037. Framingham risk did not predict either of these outcomes. Conclusions: There is an increased incidence of LGE detected on CMR in this asymptomatic HIV-positive cohort. Two distinct pathological processes were identifed as causing these changes, myocardial infarction and myocarditis

  17. Sodium hydrosulfide attenuates hyperhomocysteinemia rat myocardial injury through cardiac mitochondrial protection.

    Science.gov (United States)

    Wang, Yuwen; Shi, Sa; Dong, Shiyun; Wu, Jichao; Song, Mowei; Zhong, Xin; Liu, Yanhong

    2015-01-01

    Hydrogen sulfide (H2S) plays an important role during rat myocardial injury. However, little is known about the role of H2S in hyperhomocysteinemia (HHcy)-induced cardiac dysfunction as well as the underlying mechanisms. In this study, we investigated whether sodium hydrosulfide (NaHS, a H2S donor) influences methionine-induced HHcy rat myocardial injury in intact rat hearts and primary neonatal rat cardiomyocytes. HHcy rats were induced by methionine (2.0 g/kg) and the daily administration of 80 μmol/L NaHS in the HHcy + NaHS treatment group. At the end of 4, 8, and 12 weeks, the ultrastructural alterations and functions of the hearts were observed using transmission electron microscopy and echocardiography system. The percentage of apoptotic cardiomyocytes, the mitochondrial membrane potential, and the production of reactive oxygen species (ROS) were measured. The expressions of cystathionine-γ-lyase (CSE), Bax and Bcl-2, caspase-3, phospho-endothelial nitric oxide synthase and the mitochondrial NOX4 and cytochrome c were analyzed by Western blotting. The results showed the cardiac dysfunction, the ultrastructural changes, and the apoptotic rate increase in the HHcy rat hearts. In the primary neonatal rat cardiomyocytes of HHcy group, ROS production was increased markedly, whereas the expression of CSE was decreased. However, treatment with NaHS significantly improved the HHcy rat hearts function, the ultrastructural changes, and decreased the levels of ROS in the primary neonatal rat cardiomyocytes administrated with HHcy group. Furthermore, NaHS down-regulated the expression of mitochondrial NOX4 and caspase-3 and Bax and inhibited the release of cytochrome c from mitochondria. In conclusion, H2S is involved in the attenuation of HHcy myocardial injury through the protection of cardiac mitochondria.

  18. A review of postoperative cognitive dysfunction and neuroinflammation associated with cardiac surgery and anaesthesia

    NARCIS (Netherlands)

    van Harten, A. E.; Scheeren, T. W. L.; Absalom, A. R.

    2012-01-01

    Postoperative cognitive dysfunction is receiving increasing attention, particularly as it mainly affects the (growing) elderly population. Until recently, cognitive deficits after cardiac surgery were thought to be caused by physiological disturbances associated with the cardiopulmonary bypass techn

  19. The heart as an extravascular target of endothelin-1 in particulate matter-induced cardiac dysfunction

    Science.gov (United States)

    Exposure to particulate matter air pollution has been causally linked to cardiovascular disease in humans. Several broad and overlapping hypotheses describing the biological mechanisms by which particulate matter exposure leads to cardiovascular disease and cardiac dysfunction ha...

  20. Cardiac-Specific Knockout of ETA Receptor Mitigates Paraquat-Induced Cardiac Contractile Dysfunction.

    Science.gov (United States)

    Wang, Jiaxing; Lu, Songhe; Zheng, Qijun; Hu, Nan; Yu, Wenjun; Li, Na; Liu, Min; Gao, Beilei; Zhang, Guoyong; Zhang, Yingmei; Wang, Haichang

    2016-07-01

    Paraquat (1,1'-dim ethyl-4-4'-bipyridinium dichloride), a highly toxic quaternary ammonium herbicide widely used in agriculture, exerts potent toxic prooxidant effects resulting in multi-organ failure including the lung and heart although the underlying mechanism remains elusive. Recent evidence suggests possible involvement of endothelin system in paraquat-induced acute lung injury. This study was designed to examine the role of endothelin receptor A (ETA) in paraquat-induced cardiac contractile and mitochondrial injury. Wild-type (WT) and cardiac-specific ETA receptor knockout mice were challenged to paraquat (45 mg/kg, i.p.) for 48 h prior to the assessment of echocardiographic, cardiomyocyte contractile and intracellular Ca(2+) properties, as well as apoptosis and mitochondrial damage. Levels of the mitochondrial proteins for biogenesis and oxidative phosphorylation including UCP2, HSP90 and PGC1α were evaluated. Our results revealed that paraquat elicited cardiac enlargement, mechanical anomalies including compromised echocardiographic parameters (elevated left ventricular end-systolic and end-diastolic diameters as well as reduced factional shortening), suppressed cardiomyocyte contractile function, intracellular Ca(2+) handling, overt apoptosis and mitochondrial damage. ETA receptor knockout itself failed to affect myocardial function, apoptosis, mitochondrial integrity and mitochondrial protein expression. However, ETA receptor knockout ablated or significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) defect, apoptosis and mitochondrial damage. Taken together, these findings revealed that endothelin system in particular the ETA receptor may be involved in paraquat-induced toxic myocardial contractile anomalies possibly related to apoptosis and mitochondrial damage. PMID:26089164

  1. Cardiac fibroblasts contribute to myocardial dysfunction in mice with sepsis: the role of NLRP3 inflammasome activation.

    Directory of Open Access Journals (Sweden)

    Wenbo Zhang

    Full Text Available Myocardial contractile dysfunction in sepsis is associated with the increased morbidity and mortality. Although the underlying mechanisms of the cardiac depression have not been fully elucidated, an exaggerated inflammatory response is believed to be responsible. Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3 inflammasome is an intracellular platform that is involved in the maturation and release of interleukin (IL-1β. The aim of the present study is to evaluate whether sepsis activates NLRP3 inflammasome/caspase-1/IL-1β pathway in cardiac fibroblasts (CFs and whether this cytokine can subsequently impact the function of cardiomyocytes (cardiac fibroblast-myocyte cross-talk. We show that treatment of CFs with lipopolysaccharide (LPS induces upregulation of NLRP3, activation of caspase-1, as well as the maturation (activation and release of IL-1β. In addition, the genetic (small interfering ribonucleic acid [siRNA] and pharmacological (glyburide inhibition of the NLRP3 inflammasome in CFs can block this signaling pathway. Furthermore, the inhibition of the NLRP3 inflammasome in cardiac fibroblasts ameliorated the ability of LPS-challenged CFs to impact cardiomyocyte function as assessed by intracellular cyclic adenosine monophosphate (cAMP responses in cardiomyocytes. Salient features of this the NLP3 inflammasome/ caspase-1 pathway were confirmed in in vivo models of endotoxemia/sepsis. We found that inhibition of the NLRP3 inflammasome attenuated myocardial dysfunction in mice with LPS and increased the survival rate in mice with feces-induced peritonitis. Our results indicate that the activation of the NLRP3 inflammasome in cardiac fibroblasts is pivotal in the induction of myocardial dysfunction in sepsis.

  2. Cardiac dysfunction in cirrhosis - does adrenal function play a role? A hypothesis

    DEFF Research Database (Denmark)

    Theocharidou, Eleni; Krag, Aleksander; Bendtsen, Flemming;

    2012-01-01

    conditions, such as sepsis, bleeding and surgery. CCM reverses after liver transplantation and potentially has a role in the pathogenesis of hepatorenal syndrome. In adrenal insufficiency (AI), cardiac dysfunction is a feature with low ejection fraction, decreased left ventricular chamber size and...... to both cardiac conditions. Thus, AI may play a role in CCM. Steroid replacement therapy reverses cardiac changes in AI, and may do so for CCM, with important therapeutic implications; this needs formal evaluation....

  3. Induction of Myocardial PDCD4 in Coronary Microembolization-Related Cardiac Dysfunction: Evidence from a Large-Animal Study

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    Qiang Su

    2014-08-01

    Full Text Available Background/Aims: Coronary microembolization (CME has been linked to myocardial inflammation and apoptosis. This study aims to investigate the role of the apoptotic protein PDCD4 in the myocardium after CME in minipigs. Methods: Seventy Bama minipigs were randomized into four groups: control, CME, CME plus PDCD4-siRNA and CME plus control siRNA. CME was induced by injecting polyethylene microspheres into the left anterior descending artery. Cardiac function was evaluated. HE and HBFP staining were used to observe the degree of infarction. Western blotting and qPCR were used to evaluate the expression of PDCD4, TNF-α and caspase-3. The measurements were performed at 0, 3, 6, 9, 12 and 24 h after CME modeling in the CME and control groups. Results: Cardiac function in the CME group was significantly decreased compared with the control group (P0.05. Furthermore, PDCD4-siRNA improved cardiac function and reduced PDCD4 and TNF-α expression compared with the CME plus control siRNA group at 9 h after modeling (P Conclusion: PDCD4 induction may be involved in CME-related cardiac dysfunction, and PDCD4 inhibition via siRNA may attenuate the cardiac impairment and be used as a treatment strategy for CME.

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

    Directory of Open Access Journals (Sweden)

    Emil D Bartels

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

  5. Variable linesource response in attenuation corrected cardiac SPECT

    International Nuclear Information System (INIS)

    Full text: Varying line source response can result in errors due to the reference scan being inappropriate. The incidence of this problem and its effect on cardiac perfusion SPECT was investigated. Acquisitions of transmission data without the bed or a patient were used to determine the variation in global sensitivity and uniformity of the transmission with respect to camera position over a period of 4 months. The average variations for various parameters were: Influence of variations in regional sensitivity on the reconstructed attenuation map and ultimately the patient study was investigated. Counts in selected sections of patient transmission images were reduced by 5 to 30 percent and then reconstructed in the patient study with iterative reconstruction for 30 iterations (Butterworth 0.66 nyquist frequency order 10). The reconstructed scans were compared to the original study which had minimal linesource misalignment and the percentage differences were calculated to determine the effect of regional sensitivity differences with angle. At the level of variation of regional sensitivity (5-10%) it was found data varied by up to 20% in portions of the patient myocardium compared to the original data. Additional line source quality control is essential and variation in transmission counts with rotation minimised. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  6. Cine CT for Attenuation Correction in Cardiac PET/CT

    OpenAIRE

    Alessio, Adam M.; Kohlmyer, Steve; Branch, Kelley; Chen, Grace; Caldwell, James; Kinahan, Paul

    2007-01-01

    In dual-modality PET/CT systems, the CT scan provides the attenuation map for PET attenuation correction. The current clinical practice of obtaining a single helical CT scan provides only a snapshot of the respiratory cycle, whereas PET occurs over multiple respiratory cycles. Misalignment of the attenuation map and emission image because of respiratory motion causes errors in the attenuation correction factors and artifacts in the attenuation-corrected PET image. To rectify this problem, we ...

  7. Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Junqueira Junior

    2012-04-01

    Full Text Available INTRODUCTION: Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. METHODS: Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. RESULTS: We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. CONCLUSIONS: Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

  8. Sodium Channel (Dys)Function and Cardiac Arrhythmias

    NARCIS (Netherlands)

    C.A. Remme; C.R. Bezzina

    2010-01-01

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

  9. Cardiac dysfunction is reversed upon successful treatment of Cushing's syndrome

    NARCIS (Netherlands)

    A.M. Pereira (Alberto); V. Delgado (Victoria); J.A. Romijn (Johannes); J.W.A. Smit (Jan); J.J. Bax (Jeroen); R.A. Feelders (Richard)

    2010-01-01

    textabstractObjective: In patients with active Cushing's syndrome (CS), cardiac structural and functional changes have been described in a limited number of patients. It is unknown whether these changes reverse after successful treatment. We therefore evaluated the changes in cardiac structure and d

  10. Phosphodiesterase-3 inhibitor (cilostazol) attenuates oxidative stress-induced mitochondrial dysfunction in the heart

    Institute of Scientific and Technical Information of China (English)

    Siriporn C.Chattipakorn; Savitree Thummasorn; Jantira Sanit; Nipon Chattipakorn

    2014-01-01

    Background Cilostazol is a type 3 phosphodiesterase inhibitor which has been previously demonstrated to prevent the occurrence of tachyarrhythmia and improve defibrillation efficacy. However, the mechanism for this beneficial effect is still unclear. Since cardiac mito-chondria have been shown to play a crucial role in fatal cardiac arrhythmias and that oxidative stress is one of the main contributors to arr-hythmia generation, we tested the effects of cilostazol on cardiac mitochondria under severe oxidative stress. Methods Mitochondria were isolated from rat hearts and treated with H2O2 to induce oxidative stress. Cilostazol, at various concentrations, was used to study its protective effects. Pharmacological interventions, including a mitochondrial permeability transition pore (mPTP) blocker, cyclosporine A (CsA), and an inner membrane anion channel (IMAC) blocker, 4’-chlorodiazepam (CDP), were used to investigate the mechanistic role of cilostazol on cardiac mitochondria. Cardiac mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential change and mi-tochondrial swelling were determined as indicators of cardiac mitochondrial function. Results Cilostazol preserved cardiac mitochondrial function when exposed to oxidative stress by preventing mitochondrial depolarization, mitochondrial swelling, and decreasing ROS produc-tion. Conclusions Our findings suggest that cardioprotective effects of cilostazol reported previously could be due to its prevention of car-diac mitochondrial dysfunction caused by severe oxidative stress.

  11. Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation

    Institute of Scientific and Technical Information of China (English)

    Yong-nan FU; Han XIAO; Xiao-wei MA; Sheng-yang JIANG; Ming XU; You-yi ZHANG

    2011-01-01

    Aim: To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect.Methods: Wild type and AMPKα2 knockout (AMPKα2-/-) littermates were subjected to left ventricular pressure overload caused by evaluated using echocardiography and anatomic and histological methods. The antihypertrophic mechanism of metformin was analyzed using Western blotting.Results: Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKx2-/- mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKα2-/-mice.Conclusion: Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.

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

    Science.gov (United States)

    Levine, Benjamin D.; Bungo, Michael W.; Platts, Steven H.; Hamilton, Douglas R.; Johnston, Smith L.

    2009-01-01

    Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.

  13. Incidence of sexual dysfunction in men after cardiac surgery in Afshar hospital, Yazd

    OpenAIRE

    Seyed Khalil Foruzan-Nia; Mohammad Hassan Abdollahi; Seyed Hossein Hekmatimoghaddam; Seyedeh Mahdiyeh Namayandeh; Mohammad Hadi Mortazavi

    2011-01-01

    Background: Successful rehabilitation of cardiac surgery patients should include consideration of their sexual activity, but there is paucity of data regarding this matter. Objective: This study determined the incidence and type of sexual dysfunction in our patients. Materials and Methods: Two hundred-seventy nine men with age under 70 years old who had coronary artery bypass graft (CABG), valvular, or other types of cardiac surgery from Dec. 2006 until Dec. 2007 were enrolled in this descrip...

  14. Therapeutic attenuation of mitochondrial dysfunction and oxidative stress in neurotoxin models of Parkinson's disease

    OpenAIRE

    Stack, Edward C.; Ferro, Joellyn L.; Kim, Jinho; Del Signore, Steven J.; Goodrich, Sarah; Matson, Samantha; Hunt, Bonnie B.; Cormier, Kerry; Smith, Karen; Matson, Wayne R.; Ryu, Hoon; Ferrante, Robert J.

    2008-01-01

    Therapeutic attenuation of mitochondrial dysfunction and oxidative stress in neurotoxin models of Parkinson?s disease correspondence: Corresponding author. GRECC Unit 182B, Bedford VA Medical Center, 200 Springs Road, Bedford, MA 01730, USA. Tel.: +1 781 687 2908; fax: +1 781 687 3515. (Ferrante, Robert J.) (Ferrante, Robert J.) Department of Neurology, Boston University School of Medicine - Boston--> , MA 02118--> ...

  15. ACE2/Ang 1-7 axis: A critical regulator of epicardial adipose tissue inflammation and cardiac dysfunction in obesity.

    Science.gov (United States)

    Patel, Vaibhav B; Basu, Ratnadeep; Oudit, Gavin Y

    2016-01-01

    Obesity is characterized by an excessive fat accumulation in adipose tissues leading to weight gain and is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; activated RAS and angiotensin (Ang) II production results in worsening of cardiovascular diseases and angiotensin converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. ACE2 is expressed in the adipocytes and its expression is upregulated in response to high fat diet induced obesity in mice. Loss of ACE2 results in heart failure with preserved ejection fraction which is mediated in part by epicardial adipose tissue inflammation. Angiotensin 1-7 reduces the obesity associated cardiac dysfunction predominantly via its role in adiponectin expression and attenuation of epicardial adipose tissue inflammation. Human heart disease is also linked with inflammed epicardial adipose tissue. Here, we discuss the important interpretation of the novel of ACE2/Ang 1-7 pathway in obesity associated cardiac dysfunction. PMID:27617176

  16. High Glucose Causes Human Cardiac Progenitor Cell Dysfunction by Promoting Mitochondrial Fission: Role of a GLUT1 Blocker

    Science.gov (United States)

    Choi, He Yun; Park, Ji Hye; Jang, Woong Bi; Ji, Seung Taek; Jung, Seok Yun; Kim, Da Yeon; Kang, Songhwa; Kim, Yeon Ju; Yun, Jisoo; Kim, Jae Ho; Baek, Sang Hong; Kwon, Sang-Mo

    2016-01-01

    Cardiovascular disease is the most common cause of death in diabetic patients. Hyperglycemia is the primary characteristic of diabetes and is associated with many complications. The role of hyperglycemia in the dysfunction of human cardiac progenitor cells that can regenerate damaged cardiac tissue has been investigated, but the exact mechanism underlying this association is not clear. Thus, we examined whether hyperglycemia could regulate mitochondrial dynamics and lead to cardiac progenitor cell dysfunction, and whether blocking glucose uptake could rescue this dysfunction. High glucose in cardiac progenitor cells results in reduced cell viability and decreased expression of cell cycle-related molecules, including CDK2 and cyclin E. A tube formation assay revealed that hyperglycemia led to a significant decrease in the tube-forming ability of cardiac progenitor cells. Fluorescent labeling of cardiac progenitor cell mitochondria revealed that hyperglycemia alters mitochondrial dynamics and increases expression of fission-related proteins, including Fis1 and Drp1. Moreover, we showed that specific blockage of GLUT1 improved cell viability, tube formation, and regulation of mitochondrial dynamics in cardiac progenitor cells. To our knowledge, this study is the first to demonstrate that high glucose leads to cardiac progenitor cell dysfunction through an increase in mitochondrial fission, and that a GLUT1 blocker can rescue cardiac progenitor cell dysfunction and downregulation of mitochondrial fission. Combined therapy with cardiac progenitor cells and a GLUT1 blocker may provide a novel strategy for cardiac progenitor cell therapy in cardiovascular disease patients with diabetes. PMID:27350339

  17. Incretin attenuates diabetes-induced damage in rat cardiac tissue.

    Science.gov (United States)

    AbdElmonem Elbassuoni, Eman

    2014-09-01

    Glucagon-like peptide-1 (GLP-1), as a member of the incretin family, has a role in glucose homeostasis, its receptors distributed throughout the body, including the heart. The aim was to investigate cardiac lesions following diabetes induction, and the potential effect of GLP-1 on this type of lesions and the molecular mechanism driving this activity. Adult male rats were classified into: normal, diabetic, 4-week high-dose exenatide-treated diabetic rats, 4-week low-dose exenatide-treated diabetic rats, and 1-week exenatide-treated diabetic rats. The following parameters were measured: in blood: glucose, insulin, lactate dehydrogenase (LDH), total creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), and CK-MB relative index; in cardiac tissue: lipid peroxide (LPO) and some antioxidant enzymes. The untreated diabetic group displayed significant increases in blood level of glucose, LDH, and CK-MB, and cardiac tissue LPO, and a significant decrease in cardiac tissue antioxidant enzymes. GLP-1 supplementation in diabetic rats definitely decreased the hyperglycemia and abolished the detrimental effects of diabetes on the cardiac tissue. The effect of GLP-1 on blood glucose and on the heart also appeared after a short supplementation period (1 week). It can be concluded that GLP-1 has beneficial effects on diabetes-induced oxidative cardiac tissue damage, most probably via its antioxidant effect directly acting on cardiac tissue and independent of its hypoglycemic effect. PMID:25011640

  18. Cardiac dysfunction after aneurysmal subarachnoid hemorrhage : Relationship with outcome

    NARCIS (Netherlands)

    van der Bilt, Ivo; Hasan, Djo; van den Brink, Renee; Cramer, Maarten-Jan; van der Jagt, Mathieu; van Kooten, Fop; Meertens, John; van den Berg, Maarten; Groen, Rob; ten Cate, Folkert; Kamp, Otto; Goette, Marco; Horn, Janneke; Groeneveld, Johan; Vandertop, Peter; Algra, Ale; Visser, Frans; Wilde, Arthur; Rinkel, Gabriel

    2014-01-01

    OBJECTIVE: To assess whether cardiac abnormalities after aneurysmal subarachnoid hemorrhage (aSAH) are associated with delayed cerebral ischemia (DCI) and clinical outcome, independent from known clinical risk factors for these outcomes. METHODS: In a prospective, multicenter cohort study, we perfor

  19. Ginsenoside Rg1 Attenuates Isoflurane-induced Caspase-3 Activation via Inhibiting Mitochondrial Dysfunction

    Institute of Scientific and Technical Information of China (English)

    MIAO Hui Hui; ZHEN Yu; DING Guan Nan; HONG Fang Xiao; XIE Zhong Cong; TIAN Ming

    2015-01-01

    Objective The inhalation anesthetic isoflurane has been shown to induce mitochondrial dysfunction and caspase activation, which may lead to learning and memory impairment. Ginsenoside Rg1 is reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rg1 can attenuate isoflurane-induced caspase activation via inhibiting mitochondrial dysfunction. Methods We investigated the effects of ginsenoside Rg1 at concentrations of 12.5, 25, and 50 µmol/L and pretreatment times of 12 h and 24 h on isoflurane-induced caspase-3 activation in H4 naïve and stably transfected H4 human neuroglioma cells that express full-length human amyloid precursor protein (APP) (H4-APP cells). For mitochondrial dysfunction, we assessed mitochondrial permeability transition pore (mPTP) and adenosine-5’-triphosphate (ATP) levels. We employed Western blot analysis, chemiluminescence, and flowcytometry. Results Here we show that pretreatment with 50 µmol/L ginsenoside Rg1 for 12 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in H4-APP cells, while pretreatment with 25 and 50 µmol/L ginsenoside Rg1 for 24 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in both H4 naïve and H4-APP cells. Conclusion These data suggest that ginsenoside Rg1 may ameliorate isoflurane-induced caspase-3 activation by inhibiting mitochondrial dysfunction. Pending further studies, these findings might recommend the use of ginsenoside Rg1 in preventing and treating isoflurane-induced neurotoxicity.

  20. [Detection and therapy of respiratory dysfunction by implantable (cardiac) devices].

    Science.gov (United States)

    Fox, H; Oldenburg, O; Nölker, G; Horstkotte, D; Gutleben, K-J

    2014-02-01

    Sleep-disordered breathing (SDB) represents a common comorbidity in cardiac patients. The prevalence of obstructive sleep apnea (OSA) and central sleep apnea (CSA) is very high, particularly in patients with heart rhythm disorders and heart failure (HF). Patients with pacemakers (PM) and implantable defibrillators (ICD) including cardiac resynchronization therapy (CRT) show SDB prevalences up to 75%. However, some modern PM, ICD and CRT devices allow the detection of SDB via transthoracic impedance analysis with high sensitivity compared to polysomnographic (PSG) controls. Thus, this method could be of relevance in screening and monitoring SDB in patients with implantable cardiac devices. Preliminary studies demonstrated the possibility to treat OSA in selected patients by stimulation of the cranial nerves, especially the hypoglossal nerve. However, this requires extensive diagnostics and advanced surgical approaches including many medical disciplines and is not part of this review article. However, unilateral and transvenous stimulation of the phrenic nerve to treat central sleep apnea and Cheyne-Stokes respiration in HF patients in particular can be performed by cardiologists. This article summarizes preliminary data on the results of this promising therapy. PMID:24638158

  1. Nrf2-Mediated Cardiac Maladaptive Remodeling and Dysfunction in a Setting of Autophagy Insufficiency.

    Science.gov (United States)

    Qin, Qingyun; Qu, Chen; Niu, Ting; Zang, Huimei; Qi, Lei; Lyu, Linmao; Wang, Xuejun; Nagarkatti, Mitzi; Nagarkatti, Prakash; Janicki, Joseph S; Wang, Xing Li; Cui, Taixing

    2016-01-01

    Nuclear factor erythroid-2-related factor 2 (Nrf2) appears to exert either a protective or detrimental effect on the heart; however, the underlying mechanism remains poorly understood. Herein, we uncovered a novel mechanism for turning off the Nrf2-mediated cardioprotection and switching on Nrf2-mediated cardiac dysfunction. In a murine model of pressure overload-induced cardiac remodeling and dysfunction via transverse aortic arch constriction, knockout of Nrf2 enhanced myocardial necrosis and death rate during an initial stage of cardiac adaptation when myocardial autophagy function is intact. However, knockout of Nrf2 turned out to be cardioprotective throughout the later stage of cardiac maladaptive remodeling when myocardial autophagy function became insufficient. Transverse aortic arch constriction -induced activation of Nrf2 was dramatically enhanced in the heart with impaired autophagy, which is induced by cardiomyocyte-specific knockout of autophagy-related gene (Atg)5. Notably, Nrf2 activation coincided with the upregulation of angiotensinogen (Agt) only in the autophagy-impaired heart after transverse aortic arch constriction. Agt5 and Nrf2 gene loss-of-function approaches in combination with Jak2 and Fyn kinase inhibitors revealed that suppression of autophagy inactivated Jak2 and Fyn and nuclear translocation of Fyn, while enhancing nuclear translocation of Nrf2 and Nrf2-driven Agt expression in cardiomyocytes. Taken together, these results indicate that the pathophysiological consequences of Nrf2 activation are closely linked with the functional integrity of myocardial autophagy during cardiac remodeling. When autophagy is intact, Nrf2 is required for cardiac adaptive responses; however, autophagy impairment most likely turns off Fyn-operated Nrf2 nuclear export thus activating Nrf2-driven Agt transcription, which exacerbates cardiac maladaptation leading to dysfunction. PMID:26573705

  2. Evaluation of early cardiac dysfunction in patients with systemic lupus erythematosus with or without anticardiolipin antibodies.

    Science.gov (United States)

    Barutcu, A; Aksu, F; Ozcelik, F; Barutcu, C A E; Umit, G E; Pamuk, O N; Altun, A

    2015-09-01

    The aim of this study was to use transthoracic Doppler echocardiographic (TTE) imaging methods to identify cardiac dysfunction, an indicator of subclinical atherosclerosis in asymptomatic systemic lupus erythematosus (SLE) patients in terms of cardiac effects. This study involved 80 patients: a study group (n = 50) and control group (n = 30). They were categorized into four subgroups: anticardiolipin antibodies (aCL) (+) (n = 14) and aCL (-) (n = 36); systemic lupus erythematosus disease activity index (SLEDAI) ≥ 6 (n = 15) and SLEDAI 5 years group compared with the disease period <5 years group (p < 0.01, p < 0.05, respectively). Carrying out regular scans with TTE image of SLE patients is important in order to identify early cardiac involvement during monitoring and treatment. Identifying early cardiac involvement in SLE may lead to a reduction in mortality and morbidity rates.

  3. Hydrogen-Rich Saline Attenuates Lipopolysaccharide-Induced Heart Dysfunction by Restoring Fatty Acid Oxidation in Rats by Mitigating C-Jun N-Terminal Kinase Activation.

    Science.gov (United States)

    Tao, Bingdong; Liu, Lidan; Wang, Ni; Tong, Dongyi; Wang, Wei; Zhang, Jin

    2015-12-01

    Sepsis is common in intensive care units (ICU) and is associated with high mortality. Cardiac dysfunction complicating sepsis is one of the most important causes of this mortality. This dysfunction is due to myocardial inflammation and reduced production of energy by the heart. A number of studies have shown that hydrogen-rich saline (HRS) has a beneficial effect on sepsis. Therefore, we tested whether HRS prevents cardiac dysfunction by increasing cardiac energy. Four groups of rats received intraperitoneal injections of one of the following solutions: normal saline (NS), HRS, lipopolysaccharide (LPS), and LPS plus HRS. Cardiac function was measured by echocardiography 8 h after the injections. Gene and protein expression related to fatty acid oxidation (FAO) were measured by quantitative polymerase chain reaction (PCR) and Western blot analysis. The injection of LPS compromised heart function through decreased fractional shortening (FS) and increased left ventricular diameter (LVD). The addition of HRS increased FS, palmitate triphosphate, and the ratio of phosphocreatinine (PCr) to adenosine triphosphate (ATP) as well as decreasing LVD. The LPS challenge reduced the expression of genes related to FAO, including perioxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), perioxisome proliferator-activated receptor alpha (PPARα), Estrogen-related receptor alpha (ERRα), and their downstream targets, in mRNA and protein level, which were attenuated by HRS. However, HRS had little effect on glucose metabolism. Furthermore, HRS inhibited c-Jun N-terminal kinase (JNK) activation in the rat heart. Inhibition of JNK by HRS showed beneficial effects on LPS-challenged rats, at least in part, by restoring cardiac FAO.

  4. Cardiogenic shock and coronary endothelial dysfunction predict cardiac allograft vasculopathy after heart transplantation.

    Science.gov (United States)

    Lopez-Fernandez, Silvia; Manito-Lorite, Nicolas; Gómez-Hospital, Joan Antoni; Roca, Josep; Fontanillas, Carles; Melgares-Moreno, Rafael; Azpitarte-Almagro, José; Cequier-Fillat, Angel

    2014-12-01

    Cardiac allograft vasculopathy remains one of the major causes of death post-heart transplantation. Its etiology is multifactorial and prevention is challenging. The aim of this study was to prospectively determine factors related to cardiac allograft vasculopathy after heart transplantation. This research was planned on 179 patients submitted to heart transplant. Performance of an early coronary angiography with endothelial function evaluation was scheduled at three-month post-transplant. Patients underwent a second coronary angiography after five-yr follow-up. At the 5- ± 2-yr follow-up, 43% of the patients had developed cardiac allograft vasculopathy (severe in 26% of them). Three independent predictors of cardiac allograft vasculopathy were identified: cardiogenic shock at the time of the transplant operation (OR: 6.49; 95% CI: 1.86-22.7, p = 0.003); early coronary endothelial dysfunction (OR: 3.9; 95% CI: 1.49-10.2, p = 0.006), and older donor age (OR: 1.05; 95% CI: 1.00-1.10, p = 0.044). Besides early endothelial coronary dysfunction and older donor age, a new predictor for development of cardiac allograft vasculopathy was identified: cardiogenic shock at the time of transplantation. In these high-risk patient subgroups, preventive measures (treatment of cardiovascular risk factors, use of novel immunosuppressive agents such as mTOR inhibitors) should be earlier and much more aggressive.

  5. Cardiac Dysfunction in the BACHD Mouse Model of Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Analyne M Schroeder

    Full Text Available While Huntington's disease (HD is classified as a neurological disorder, HD patients exhibit a high incidence of cardiovascular events leading to heart failure and death. In this study, we sought to better understand the cardiovascular phenotype of HD using the BACHD mouse model. The age-related decline in cardiovascular function was assessed by echocardiograms, electrocardiograms, histological and microarray analysis. We found that structural and functional differences between WT and BACHD hearts start at 3 months of age and continue throughout life. The aged BACHD mice develop cardiac fibrosis and ultimately apoptosis. The BACHD mice exhibited adaptive physiological changes to chronic isoproterenol treatment; however, the medication exacerbated fibrotic lesions in the heart. Gene expression analysis indicated a strong tilt toward apoptosis in the young mutant heart as well as changes in genes involved in cellular metabolism and proliferation. With age, the number of genes with altered expression increased with the large changes occurring in the cardiovascular disease, cellular metabolism, and cellular transport clusters. The BACHD model of HD exhibits a number of changes in cardiovascular function that start early in the disease progress and may provide an explanation for the higher cardiovascular risk in HD.

  6. Measures of endothelial dysfunction predict response to cardiac resynchronisation therapy

    Science.gov (United States)

    Warriner, David R; Lawford, Patricia; Sheridan, Paul J

    2016-01-01

    Objectives Cardiac resynchronisation therapy (CRT) improves morbidity and mortality in heart failure (HF). Impaired endothelial function, as measured by flow-mediated dilation (FMD) is associated with increased morbidity and mortality in HF and may help to differentiate responders from non-responders. Methods 19 patients were recruited, comprising 94% men, mean age 69±8 years, New York Heart Association functional classes II–IV, QRSd 161±21 ms and mean left ventricular ejection fraction 26±8%. Markers of response and FMD were measured at baseline, 6 and 12 months following CRT. Results 14 patients were responders to CRT. Responders had significant improvements in VO2 (12.6±1.7 to 14.7±1.5 mL/kg/min, pFMD in responders was 2.9±1.9% and 7.4±3.73% in non-responders (pFMD. This study confirms that FMD identifies responders to CRT, due to endothelium-dependent mechanisms alone. PMID:27335654

  7. Cardiac dysfunction and hypothalamic activation during a social crowding stressor in prairie voles

    OpenAIRE

    Grippo, Angela J.; Sgoifo, Andrea; Mastorci, Francesca; McNeal, Neal; Trahanas, Diane M.

    2010-01-01

    Cardiac dysfunction and hypothalamic activation during a social crowding stressor in prairie voles. – Negative social interactions produce several detrimental consequences in humans and non-human animals; and conversely, positive social interactions may have stress-buffering effects on both behavior and physiology. However, the mechanisms underlying specific stressor-responsiveness in the context of the social environment are not well understood. The present study investigated the integration...

  8. 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

  9. Modulation of Cardiac Autonomic Dysfunction in Ischemic Stroke following Ayurveda (Indian System of Medicine Treatment

    Directory of Open Access Journals (Sweden)

    Sriranjini Sitaram Jaideep

    2014-01-01

    Full Text Available Objectives. Cardiac autonomic dysfunction in stroke has implications on morbidity and mortality. Ayurveda (Indian system of medicine describes stroke as pakshaghata. We intended to study the effect of Ayurveda therapies on the cardiac autonomic dysfunction. Methods. Fifty patients of ischemic stroke (middle cerebral artery territory (mean age 39.26 ± 9.88 years; male 43, female 7 were recruited within one month of ictus. All patients received standard allopathic medications as advised by neurologist. In addition, patients were randomized to receive physiotherapy (Group I or Ayurveda treatment (Group II for 14 days. Continuous electrocardiogram and finger arterial pressure were recorded for 15 min before and after treatments and analyzed offline to obtain heart rate and blood pressure variability and baroreflex sensitivity (BRS. Results were analysed by RMANOVA. Results. Patients in Group II showed statistically significant improvement in cardiac autonomic parameters. The standard deviation of normal to normal intervals,and total and low frequency powers were significantly enhanced (F=8.16, P=0.007, F=9.73, P=0.004, F=13.51, and P=0.001, resp.. The BRS too increased following the treatment period (F=10.129, P=0.004. Conclusions. The current study is the first to report a positive modulation of cardiac autonomic activity after adjuvant Ayurveda treatment in ischemic stroke. Further long term studies are warranted.

  10. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs

    Directory of Open Access Journals (Sweden)

    Marilisa Molinaro

    2015-01-01

    Full Text Available Along with the improvement of survival after cancer, cardiotoxicity due to antineoplastic treatments has emerged as a clinically relevant problem. Potential cardiovascular toxicities due to anticancer agents include QT prolongation and arrhythmias, myocardial ischemia and infarction, hypertension and/or thromboembolism, left ventricular (LV dysfunction, and heart failure (HF. The latter is variable in severity, may be reversible or irreversible, and can occur soon after or as a delayed consequence of anticancer treatments. In the last decade recent advances have emerged in clinical and pathophysiological aspects of LV dysfunction induced by the most widely used anticancer drugs. In particular, early, sensitive markers of cardiac dysfunction that can predict this form of cardiomyopathy before ejection fraction (EF is reduced are becoming increasingly important, along with novel therapeutic and cardioprotective strategies, in the attempt of protecting cardiooncologic patients from the development of congestive heart failure.

  11. Cardiac Effects of Attenuating Gsα - Dependent Signaling.

    Directory of Open Access Journals (Sweden)

    Marcus R Streit

    Full Text Available Inhibition of β-adrenergic signalling plays a key role in treatment of heart failure. Gsα is essential for β-adrenergic signal transduction. In order to reduce side-effects of beta-adrenergic inhibition diminishing β-adrenergic signalling in the heart at the level of Gsα is a promising option.We analyzed the influence of Gsα on regulation of myocardial function and development of cardiac hypertrophy, using a transgenic mouse model (C57BL6/J mice overexpressing a dominant negative Gsα-mutant under control of the α-MHC-promotor. Cardiac phenotype was characterized in vivo and in vitro and under acute and chronic β-adrenergic stimulation. At rest, Gsα-DN-mice showed bradycardia (602 ± 13 vs. 660 ± 17 bpm, p<0.05 and decreased dp/dtmax (5037 ± 546- vs. 6835 ± 505 mmHg/s, p = 0.02. No significant differences were found regarding ejection fraction, heart weight and cardiomyocyte size. β-blockade by propranolol revealed no baseline differences of hemodynamic parameters between wildtype and Gsα-DN-mice. Acute adrenergic stimulation resulted in decreased β-adrenergic responsiveness in Gsα-DN-mice. Under chronic adrenergic stimulation, wildtype mice developed myocardial hypertrophy associated with increase of LV/BW-ratio by 23% (4.4 ± 0.2 vs. 3.5 ± 0.1 mg/g, p<0.01 and cardiac myocyte size by 24% (14927 ± 442 px vs. 12013 ± 583 px, p<0.001. In contrast, both parameters were unchanged in Gsα-DN-mice after chronic isoproterenol stimulation.Overexpression of a dominant negative mutant of Gsα leads to decreased β-adrenergic responsiveness and is protective against isoproterenol-induced hypertrophy. Thus, Gsα-DN-mice provide novel insights into β-adrenergic signal transduction and its modulation in myocardial overload and failure.

  12. Burn-Induced Organ Dysfunction: Vagus Nerve Stimulation Improves Cardiac Function

    OpenAIRE

    Niederbichler, Andreas D; Papst, Stephan; Claassen, Leif; Jokuszies, Andreas; Ipaktchi, Kyros; Reimers, Kerstin; Hirsch, Tobias; Steinstraesser, Lars; Kraft, Theresia; Vogt, Peter M.

    2010-01-01

    Introduction: Many studies have demonstrated the existence of an anti-inflammatory, parasympathetic pathway, termed as the inflammatory reflex. Burn-induced heart failure has been investigated in many previous studies. Proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6, have been shown to play a key pathogenetic role and vagus nerve stimulation attenuates proinflammatory cytokine production. This study was designed to evaluate postburn alterations of cardiac functional parameters after...

  13. Montelukast attenuates lipopolysaccharide-induced cardiac injury in rats.

    Science.gov (United States)

    Khodir, A E; Ghoneim, H A; Rahim, M A; Suddek, G M

    2016-04-01

    This study investigates the possible protective effects of montelukast (MNT) against lipopolysaccharide (LPS)-induced cardiac injury, in comparison to dexamethasone (DEX), a standard anti-inflammatory. Male Sprague Dawley rats (160-180 g) were assigned to five groups (n = 8/group): (1) control; (2) LPS (10 mg/kg, intraperitoneal (i.p.)); (3) LPS + MNT (10 mg/kg, per os (p.o.)); (4) LPS + MNT (20 mg/kg, p.o.); and (5) LPS + DEX (1 mg/kg, i.p.). Twenty-four hours after LPS injection, heart/body weight (BW) ratio and percent survival of rats were determined. Serum total protein, creatine kinase muscle/brain (CK-MB), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities were measured. Heart samples were taken for histological assessment and for determination of malondialdehyde (MDA) and glutathione (GSH) contents. Cardiac tumor necrosis factor α (TNF-α) expression was evaluated immunohistochemically. LPS significantly increased heart/BW ratio, serum CK-MB, ALP, and LDH activities and decreased percent survival and serum total protein levels. MDA content increased in heart tissues with a concomitant reduction in GSH content. Immunohistochemical staining of heart specimens from LPS-treated rats revealed high expression of TNF-α. MNT significantly reduced percent mortality and suppressed the release of inflammatory and oxidative stress markers when compared with LPS group. Additionally, MNT effectively preserved tissue morphology as evidenced by histological evaluation. MNT (20 mg/kg) was more effective in alleviating LPS-induced heart injury when compared with both MNT (10 mg/kg) and DEX (1 mg/kg), as evidenced by decrease in positive staining by TNF-α immunohistochemically, decrease MDA, and increase GSH content in heart tissue. This study demonstrates that MNT might have cardioprotective effects against the inflammatory process during endotoxemia. This effect can be attributed to its antioxidant and/or anti-inflammatory properties. PMID:26089034

  14. The effect of preoperative renal dysfunction with or without dialysis on early postoperative outcome following cardiac surgery.

    LENUS (Irish Health Repository)

    Al-Sarraf, Nael

    2011-01-01

    Although previous studies have shown increased mortality in renal dysfunction patients undergoing cardiac surgery, there is lack of data on the pattern of postoperative complications that occur in such patients and their distribution among dialysis and non-dialysis dependent renal dysfunction.

  15. Influence of metabolic dysfunction on cardiac mechanics in decompensated hypertrophy and heart failure.

    Science.gov (United States)

    Tewari, Shivendra G; Bugenhagen, Scott M; Vinnakota, Kalyan C; Rice, J Jeremy; Janssen, Paul M L; Beard, Daniel A

    2016-05-01

    Alterations in energetic state of the myocardium are associated with decompensated heart failure in humans and in animal models. However, the functional consequences of the observed changes in energetic state on mechanical function are not known. The primary aim of the study was to quantify mechanical/energetic coupling in the heart and to determine if energetic dysfunction can contribute to mechanical failure. A secondary aim was to apply a quantitative systems pharmacology analysis to investigate the effects of drugs that target cross-bridge cycling kinetics in heart failure-associated energetic dysfunction. Herein, a model of metabolite- and calcium-dependent myocardial mechanics was developed from calcium concentration and tension time courses in rat cardiac muscle obtained at different lengths and stimulation frequencies. The muscle dynamics model accounting for the effect of metabolites was integrated into a model of the cardiac ventricles to simulate pressure-volume dynamics in the heart. This cardiac model was integrated into a simple model of the circulation to investigate the effects of metabolic state on whole-body function. Simulations predict that reductions in metabolite pools observed in canine models of heart failure can cause systolic dysfunction, blood volume expansion, venous congestion, and ventricular dilation. Simulations also predict that myosin-activating drugs may partially counteract the effects of energetic state on cross-bridge mechanics in heart failure while increasing myocardial oxygen consumption. Our model analysis demonstrates how metabolic changes observed in heart failure are alone sufficient to cause systolic dysfunction and whole-body heart failure symptoms. PMID:27085901

  16. Ablation of C/EBP homologous protein increases the acute phase mortality and doesn't attenuate cardiac remodeling in mice with myocardial infarction.

    Science.gov (United States)

    Luo, Guangjin; Li, Qingman; Zhang, Xiajun; Shen, Liang; Xie, Jiahe; Zhang, Jingwen; Kitakaze, Masafumi; Huang, Xiaobo; Liao, Yulin

    2015-08-14

    Endoplasmic reticulum stress is a proapoptotic and profibrotic stimulus. Ablation of C/EBP homologous protein (CHOP) is reported to reverse cardiac dysfunction by attenuating cardiac endoplasmic reticulum stress in mice with pressure overload or ischemia/reperfusion, but it is unclear whether loss of CHOP also inhibits cardiac remodeling induced by permanent-infarction. In mice with permanent ligation of left coronary artery, we found that ablation of CHOP increased the acute phase mortality. For the mice survived to 4 weeks, left ventricular anterior (LV) wall thickness was larger in CHOP knockout mice than in the wildtype littermates, while no difference was noted on posterior wall thickness, LV dimensions, LV fractional shortening and ejection fraction. Similarly, invasive assessment of LV hemodynamics, morphological analysis of heart and lung weight indexes, myocardial fibrosis and TUNEL-assessed apoptosis showed no significant differences between CHOP knockout mice and their wildtype ones, while in mice with ischemia for 45 min and reperfusion for 1 week, myocardial fibrosis and apoptosis in the infarct area were significantly attenuated in CHOP knockout mice. These findings indicate that ablation of CHOP doesn't ameliorate cardiac remodeling induced by permanent-myocardial infarction, which implicates that early reperfusion is a prerequisite for ischemic myocardium to benefit from CHOP inhibition.

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

    Directory of Open Access Journals (Sweden)

    Ivana Y Kuo

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

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

    Science.gov (United States)

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

    2016-01-01

    Mutations in the gene for polycystin 2 (Pkd2) lead to polycystic kidney disease, however the main cause of mortality in humans is cardiac related. We previously showed that 5 month old Pkd2+/- mice have altered calcium-contractile activity in cardiomyocytes, but have preserved cardiac function. Here, we examined 1 and 9 month old Pkd2+/- mice to determine if decreased amounts of functional polycystin 2 leads to impaired cardiac function with aging. We observed changes in calcium handling proteins in 1 month old Pkd2+/- mice, and these changes were exacerbated in 9 month old Pkd2+/- mice. Anatomically, the 9 month old Pkd2+/- mice had thinner left ventricular walls, consistent with dilated cardiomyopathy, and the left ventricular ejection fraction was decreased. Intriguingly, in response to acute isoproterenol stimulation to examine β-adrenergic responses, the 9 month old Pkd2+/- mice exhibited a stronger contractile response, which also coincided with preserved localization of the β2 adrenergic receptor. Importantly, the Pkd2+/- mice did not have any renal impairment. We conclude that the cardiac-related impact of decreased polycystin 2 progresses over time towards cardiac dysfunction and altered adrenergic signaling. These results provide further evidence that polycystin 2 provides a critical function in the heart, independent of renal involvement. PMID:27081851

  19. The exenatide analogue AC3174 attenuates hypertension, insulin resistance, and renal dysfunction in Dahl salt-sensitive rats

    Directory of Open Access Journals (Sweden)

    Fernandez Rayne

    2010-08-01

    Full Text Available Abstract Background Activation of glucagon-like peptide-1 (GLP-1 receptors improves insulin sensitivity and induces vasodilatation and diuresis. AC3174 is a peptide analogue with pharmacologic properties similar to the GLP-1 receptor agonist, exenatide. Hypothetically, chronic AC3174 treatment could attenuate salt-induced hypertension, cardiac morbidity, insulin resistance, and renal dysfunction in Dahl salt-sensitive (DSS rats. Methods DSS rats were fed low salt (LS, 0.3% NaCl or high salt (HS, 8% NaCl diets. HS rats were treated with vehicle, AC3174 (1.7 pmol/kg/min, or GLP-1 (25 pmol/kg/min for 4 weeks via subcutaneous infusion. Other HS rats received captopril (150 mg/kg/day or AC3174 plus captopril. Results HS rat survival was improved by all treatments except GLP-1. Systolic blood pressure (SBP was lower in LS rats and in GLP-1, AC3174, captopril, or AC3174 plus captopril HS rats than in vehicle HS rats (p Conclusions Thus, AC3174 had antihypertensive, cardioprotective, insulin-sensitizing, and renoprotective effects in the DSS hypertensive rat model. Furthermore, AC3174 improved animal survival, an effect not observed with GLP-1.

  20. RELATION OF PERIOPERATIVE SERUM THYROID HORMONE CHANGES TO HEART DYSFUNCTION IN PATIENTS UNDERGONE CARDIAC VALVE REPLACEMENT

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To explore the relationship between perioperative serum thyroid hormone changes and heart dysfunction in patients undergone cardiac valve replacement. Methods The serum concentrations of free tri- iodothyronine (),free thyroxine (),total total reverse and thyroid-stimulating hor- mone (TSH) in 20 patients undergone routine rheumatic mitral valve replacement were determined by radioim- munoassay at preoperation, the end of myocardial ischemia, and 2,6,12,24 and 48h postoperation, respectively. The alteration hormones above mentioned were comparatively analysed of the normal heart function group (group I,n = 14) and heart dysfunction group (group I ,n=6) after surgery. Results In comparing group I with group I , the more severe the chronic congestive heart failure, the lower the thyroid hormone level before operation;and subse- quently both progressively lowered T3 level and acute heart dysfunction emerged after operation. The decreased extent of serum thyroid hormone was closely parallel to the severity of heart dysfunction. Gonclusion Perioperatively, de- creased serum FT3 and TT3 concentrations are at least an important humoral factor aggravating heart dysfunction, and the patients with preoperative low T3 should be considered as high-risk valvular surgical cases.

  1. [Autonomic dysfunction syndrome and diabetic cardiac autonomic neuropathy in children with diabetes mellitus type I. The correction method].

    Science.gov (United States)

    Manukian, V Iu; Bolotova, N V; Aver'ianov, A P; Filina, N Iu; Raĭgorodskiĭ, Iu M

    2011-01-01

    We assessed the state of the autonomic nervous system in 90 children with diabetes mellitus type I. The autonomic dysfunction syndrome was found in 58,9% and diabetic cardiac autonomic neuropathy in 28,9% of patients. We revealed the high risk of the development of diabetic cardiac autonomic neuropathy in children with diabetes mellitus type I in the presence of the autonomic dysfunction syndrome. It has been shown that the early treatment of functional disturbances of the autonomic nervous system using transcranial magnetic stimulation is necessary to prevent the manifestation of diabetic cardiac autonomic neuropathy.

  2. Matrix metalloproteinase inhibition attenuates right ventricular dysfunction and improves responses to dobutamine during acute pulmonary thromboembolism

    Science.gov (United States)

    Neto-Neves, Evandro M; Sousa-Santos, Ozelia; Ferraz, Karina C; Rizzi, Elen; Ceron, Carla S; Romano, Minna M D; Gali, Luis G; Maciel, Benedito C; Schulz, Richard; Gerlach, Raquel F; Tanus-Santos, Jose E

    2013-01-01

    Activated matrix metalloproteinases (MMPs) cause cardiomyocyte injury during acute pulmonary thromboembolism (APT). However, the functional consequences of this alteration are not known. We examined whether doxycycline (a MMP inhibitor) improves right ventricle function and the cardiac responses to dobutamine during APT. APT was induced with autologous blood clots (350 mg/kg) in anaesthetized male lambs pre-treated with doxycycline (Doxy, 10 mg/kg/day, intravenously) or saline. Non-embolized control lambs received doxycycline pre-treatment or saline. The responses to intravenous dobutamine (Dob, 1, 5, 10 μg/kg/min.) or saline infusions at 30 and 120 min. after APT induction were evaluated by echocardiography. APT increased mean pulmonary artery pressure and pulmonary vascular resistance index by ∼185%. Doxycycline partially prevented APT-induced pulmonary hypertension (P  0.05). RV dysfunction on stress echocardiography was observed in embolized lambs (APT+Dob group) but not in embolized animals pre-treated with doxycycline (Doxy+APT+Dob). APT increased MMP-9 activity, oxidative stress and gelatinolytic activity in the RV. Although doxycycline had no effects on RV MMP-9 activity, it prevented the increases in RV oxidative stress and gelatinolytic activity (P < 0.05). APT increased serum cardiac troponin I concentrations (P < 0.05), doxycycline partially prevented this alteration (P < 0.05). We found evidence to support that doxycycline prevents RV dysfunction and improves the cardiac responses to dobutamine during APT. PMID:24199964

  3. Left atrial dysfunction in type 2 diabetes mellitus: insights from cardiac MRI

    Energy Technology Data Exchange (ETDEWEB)

    Graca, Bruno; Donato, Paulo; Caseiro-Alves, Filipe [University of Coimbra, Faculty of Medicine, Coimbra (Portugal); Coimbra' s Hospital Centre and University, Medical Imaging Department, Coimbra (Portugal); Joao Ferreira, Maria [University of Coimbra, Faculty of Medicine, Coimbra (Portugal); Coimbra' s Hospital Centre and University, Cardiology Department, Coimbra (Portugal); Gomes, Leonor [University of Coimbra, Faculty of Medicine, Coimbra (Portugal); Coimbra' s Hospital Centre and University, Endocrinology Department, Coimbra (Portugal); Castelo-Branco, Miguel [University of Coimbra, Faculty of Medicine, Coimbra (Portugal)

    2014-11-15

    The left atrium (LA) modulates left ventricular filling through reservoir, conduit and booster pump functions. Only limited data exist on LA involvement in type 2 diabetes mellitus (DM2). This study sought to assess LA function in asymptomatic DM2 with cardiac MRI. We hypothesized that cardiac MRI can detect LA dysfunction in asymptomatic DM2. Forty-five patients with asymptomatic DM2 and 24 normoglycaemic controls were studied. MRI cine imaging was performed to measure LA maximal and minimal volumes. A flow-sensitive phase-contrast gradient-echo sequence was used for flow measurements perpendicular to the orifice of the mitral valve, to quantify active LA stroke volume. LA total, passive and active emptying volumes and fractions were calculated. LA reservoir function, namely LA total ejection fraction, was significantly greater in controls compared to patients with DM2 (62.2 ± 5.2 vs 57.0 ± 7.6 %, P = 0.004). LA passive ejection fraction was also greater in the controls (26.2 ± 9.5 vs 16.1 ± 11.0 %, P < 0.001). Regarding parameters of LA booster pump function, LA active ejection fraction was not significantly different between groups. DM2 was demonstrated to be an independent determinant of LA function. Cardiac MRI enables the detection of LA dysfunction in asymptomatic DM2, characterized by a reduction in LA reservoir and conduit functions. (orig.)

  4. Possible Protective Role of Carnosine against gamma-Radiation-Induced Cardiac Dysfunction in Mice

    International Nuclear Information System (INIS)

    Oxidative Stress with subsequent production of reactive oxygen species (ROS) has been postulated as one of the mechanisms of cardiac toxicity. Carnosine (β-alanyl-L-histidine) a biological antioxidant, is a relatively non-toxic dipeptide which possesses many functions (antiglycator, scavenger of ions of zinc and copper, toxic aldehydes and protein carbonyls) that are likely to suppress oxidative stress. The aim of the present work is to investigate the possible protective effects of carnosine on gamma-radiation-induced cardiac damage in mice. Carnosine was supplemented daily to mice (50 mg/ Kg body wt), by gavage, 10 days before whole body gamma-irradiation at a dose of 5 Gy (applied as a shot dose). The results obtained showed that whole body gamma-irradiation of mice produced biochemical alteration in levels of serum glucose and lipid profile fractions. Furthermore, some markers of cardiac injury enzymes as serum lactate dehydrogenase (LDH), creatin phosphokinase (CPK) and aspartate transaminase (AST) activities showed significant increases associated with alteration in the antioxidant status of cardiac tissues. Significant increases of lipid peroxidation end product malonaldehyde (MDA) and protein carbonyl levels, xanthine oxidase (XO) activity along with reduction in the activity of cardiac antioxidant enzymes; glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were observed. Carnosine-treatment prior irradiation has attenuated the cardiotoxic effects of radiation obvious by reduction in the levels of MDA and protein carbonyl and XO activity, rescued the depletion of endogenous antioxidant enzymes and diminished the increases of cardiac injury markers. It could be postulated that carnosine as a multi-functional dietary supplement could exert a modulator role in the radiation-induced cardiac damage and serum biochemical changes through its antioxidant properties

  5. Oroxylin A, but Not Vasopressin, Ameliorates Cardiac Dysfunction of Endotoxemic Rats

    Directory of Open Access Journals (Sweden)

    Chin-Hung Liu

    2012-01-01

    Full Text Available The mortality in septic patients with myocardial dysfunction is higher than those without it. Beneficial effects of flavonoid oroxylin A (Oro-A on endotoxemic hearts were evaluated and compared with that of arginine vasopressin (AVP which is used to reverse hypotension in septic patients. Endotoxemia in rats was induced by one-injection of lipopolysaccharides (LPS, 10 mg/kg, i.p., and hearts were isolated 5-hrs or 16-hrs later. Isolated hearts with constant-pressure or constant-flow mode were examined by Langendorff technique. Rate and force of contractions of isolated atrial and ventricular strips were examined by tissue myography. Isolated endotoxemic hearts were characterized by decreased or increased coronary flow (CF in LPS-treated-for-5hr and LPS-treated-for-16-hr groups, respectively, with decreased inotropy in both groups. Oro-A-perfusion ameliorated while AVP-perfusion worsened the decreased CF and inotropy in both preparations. Oro-A and AVP, however, did not affect diminished force or rate of contraction of atrial and ventricular strips of endotoxemic hearts. Oro-A-induced CF increase was not affected following coronary endothelium-denudation with saponin. These results suggest that Oro-A ameliorates LPS-depressed cardiac functions by increasing CF, leading to positive inotropy. In contrast, AVP aggravates cardiac dysfunction by decreasing CF. Oro-A is a potentially useful candidate for treating endotoxemia complicated with myocardial dysfunction.

  6. PTRF/Cavin-1 Deficiency Causes Cardiac Dysfunction Accompanied by Cardiomyocyte Hypertrophy and Cardiac Fibrosis

    Science.gov (United States)

    Ogata, Takehiro; Kasahara, Takeru; Nakanishi, Naohiko; Miyagawa, Kotaro; Naito, Daisuke; Hamaoka, Tetsuro; Nishi, Masahiro; Matoba, Satoaki; Ueyama, Tomomi

    2016-01-01

    Mutations in the PTRF/Cavin-1 gene cause congenital generalized lipodystrophy type 4 (CGL4) associated with myopathy. Additionally, long-QT syndrome and fatal cardiac arrhythmia are observed in patients with CGL4 who have homozygous PTRF/Cavin-1 mutations. PTRF/Cavin-1 deficiency shows reductions of caveolae and caveolin-3 (Cav3) protein expression in skeletal muscle, and Cav3 deficiency in the heart causes cardiac hypertrophy with loss of caveolae. However, it remains unknown how loss of PTRF/Cavin-1 affects cardiac morphology and function. Here, we present a characterization of the hearts of PTRF/Cavin-1-null (PTRF−/−) mice. Electron microscopy revealed the reduction of caveolae in cardiomyocytes of PTRF−/− mice. PTRF−/− mice at 16 weeks of age developed a progressive cardiomyopathic phenotype with wall thickening of left ventricles and reduced fractional shortening evaluated by echocardiography. Electrocardiography revealed that PTRF−/− mice at 24 weeks of age had low voltages and wide QRS complexes in limb leads. Histological analysis showed cardiomyocyte hypertrophy accompanied by progressive interstitial/perivascular fibrosis. Hypertrophy-related fetal gene expression was also induced in PTRF−/− hearts. Western blotting analysis and quantitative RT-PCR revealed that Cav3 expression was suppressed in PTRF−/− hearts compared with that in wild-type (WT) ones. ERK1/2 was activated in PTRF−/− hearts compared with that in WT ones. These results suggest that loss of PTRF/Cavin-1 protein expression is sufficient to induce a molecular program leading to cardiomyocyte hypertrophy and cardiomyopathy, which is partly attributable to Cav3 reduction in the heart. PMID:27612189

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

    Science.gov (United States)

    Escobales, Nelson; Nuñez, Rebeca E; Jang, Sehwan; Parodi-Rullan, Rebecca; Ayala-Peña, Sylvette; Sacher, Joshua R; Skoda, Erin M; Wipf, Peter; Frontera, Walter; Javadov, Sabzali

    2014-12-01

    Mitochondria-generated reactive oxygen species (ROS) play a crucial role in the pathogenesis of aging and age-associated diseases. In this study, we evaluated the effects of XJB-5-131 (XJB), a mitochondria-targeted ROS and electron scavenger, on cardiac resistance to ischemia-reperfusion (IR)-induced oxidative stress in aged rats. Male adult (5-month old, n=17) and aged (29-month old, n=19) Fischer Brown Norway (F344/BN) rats were randomly assigned to the following groups: adult (A), adult+XJB (AX), aged (O), and aged+XJB (OX). XJB was administered 3 times per week (3mg/kg body weight, IP) for four weeks. At the end of the treatment period, cardiac function was continuously monitored in excised hearts using the Langendorff technique for 30 min, followed by 20 min of global ischemia, and 60-min reperfusion. XJB improved post-ischemic recovery of aged hearts, as evidenced by greater left ventricular developed-pressures and rate-pressure products than the untreated, aged-matched group. The state 3 respiration rates at complexes I, II and IV of mitochondria isolated from XJB-treated aged hearts were 57% (P<0.05), 25% (P<0.05) and 28% (P<0.05), respectively, higher than controls. Ca(2+)-induced swelling, an indicator of permeability transition pore opening, was reduced in the mitochondria of XJB-treated aged rats. In addition, XJB significantly attenuated the H2O2-induced depolarization of the mitochondrial inner membrane as well as the total and mitochondrial ROS levels in cultured cardiomyocytes. This study underlines the importance of mitochondrial ROS in aging-induced cardiac dysfunction and suggests that targeting mitochondrial ROS may be an effective therapeutic approach to protect the aged heart against IR injury. PMID:25451170

  8. Saturated hydrogen saline attenuates endotoxin-induced acute liver dysfunction in rats.

    Science.gov (United States)

    Xu, X-F; Zhang, J

    2013-01-01

    To determine the effect of saturated hydrogen saline on lipopolysaccharide (LPS)-induced acute liver dysfunction, rats were divided into control, LPS, and LPS plus saturated hydrogen saline (LPS+H(2)) groups. Treatment with saturated hydrogen saline prolonged the median survival time and reduced liver dysfunction. Moreover, saturated hydrogen saline significantly reduced pathological alterations in liver tissues, the number of ballooned hepatocytes, serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels, and myeloperoxidase (MPO) and malondialdehyde (MDA) levels in liver tissues (Phydrogen saline treatment. Saturated hydrogen saline also decreased phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated Jun kinase (p-JNK), nuclear factor-kappa B (NF-kappaB), and second mitochondria-derived activator of caspase (Smac) levels, and increased p38 activation (Phydrogen saline may attenuate LPS-induced acute liver dysfunction in rats, possibly by reducing inflammation and cell apoptosis. Mitogen-activated protein kinase (MAPK), NF-kappaB, and Smac may contribute to saturated hydrogen saline-mediated liver protection.

  9. Renal sympathetic denervation prevents the development of pulmonary arterial hypertension and cardiac dysfunction in dogs.

    Science.gov (United States)

    Hu, Wei; Yu, Sheng-Bo; Chen, Liao; Guo, Rui-Qiang; Zhao, Qing-Yan

    2015-08-01

    The renin-angiotensin-aldosterone system is activated in pulmonary arterial hypertension (PAH) patients, and this activation may have long-term negative effects on the progression of PAH. The purpose of this study was to evaluate the effects of transcatheter renal sympathetic denervation (RSD) on the development of pulmonary arterial hypertension and cardiac dysfunction in dogs using two-dimensional speckle tracking imaging. Twenty-two dogs were randomly divided into three groups: control group (n = 7), PAH group (n = 8), and PAH + RSD group (n = 7). All dogs were assessed using two-dimensional speckle tracking imaging. The ventricular strain, ventricular synchrony, left ventricular (LV) twist, and torsion rate were analyzed to evaluate cardiac function. After 8 weeks, the right ventricular lateral longitudinal strain and the septum longitudinal strain were reduced in the PAH group compared with the control group (p dogs.

  10. Cardiac dysfunction and hypothalamic activation during a social crowding stressor in prairie voles.

    Science.gov (United States)

    Grippo, Angela J; Sgoifo, Andrea; Mastorci, Francesca; McNeal, Neal; Trahanas, Diane M

    2010-08-25

    Negative social interactions produce several detrimental consequences in humans and non-human animals; and conversely, positive social interactions may have stress-buffering effects on both behavior and physiology. However, the mechanisms underlying specific stressor-responsiveness in the context of the social environment are not well understood. The present study investigated the integration of behavior, cardiac function, and Fos-immunoreactivity in the hypothalamic paraventricular nucleus during an acute social stressor in female, socially monogamous prairie voles exposed to previous long-term pairing (control conditions) or isolation. Animals previously exposed to social isolation displayed increased heart rate, attenuated heart rate variability, and increased incidence of cardiac arrhythmias during an acute crowding stressor versus animals previously exposed to social pairing; these cardiac alterations were not secondary to behavioral changes during the crowding stressor. Furthermore, social isolation was associated with increased c-Fos-immunoreactivity in the hypothalamic paraventricular nucleus following the crowding stressor, versus social pairing. The prairie vole provides a useful model for understanding how the social environment contributes to changes in behavior, cardiac function, and central stress-regulatory processes in humans. PMID:20347401

  11. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin induced cardiac injury in mice

    Directory of Open Access Journals (Sweden)

    Yousif Nasser

    2011-10-01

    Full Text Available Abstract Background Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin induced cardiac toxicity. Toll-like receptors (TLRs are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity. Methods Seven days after a single injection of herceptin (2 mg/kg; i.p., left ventricular pressure volume loops were measured in HeN compotent (TLR4+/+ and HeJ mutant (TLR4-/- treated with trastuzumab and control mice. Immunofluorescent staining for monocyte infiltration and analyses of plasma by (ELISAs for different chemokines including: MCP-1and tumor necrosis factor-α (TNF-α, Western immunoblotting assay for ICAM-1, and used troponin I for cardiac injury marker. Results Trastuzumab injection resulted in an impairment of left ventricular function in TLR-4 competent (HeN, in contrast TLR4-/- trastuzumab mice showed improved left ventricular function EF%, CO; p -/-; p -/-, marked reduction of myocardial troponin-I levels in TLR4-deficient mice. Data are presented as means ± SE; n = 8 in each group p Conclusions Treatment with trastuzumab induces an inflammatory response that contributes to myocardial tissue TLR4 mediates chemokine expression (TNF-α, MCP-1and ICAM-1, so in experimental animals TLR4 deficiency improves left ventricular function and attenuates pathophysiological key mechanisms in trastuzumab induced cardiomyopathy.

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

    Science.gov (United States)

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

    2013-11-15

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

  13. Activation of the Cardiac Renin-Angiotensin System in High Oxygen-Exposed Newborn Rats: Angiotensin Receptor Blockade Prevents the Developmental Programming of Cardiac Dysfunction.

    Science.gov (United States)

    Bertagnolli, Mariane; Dios, Anne; Béland-Bonenfant, Sarah; Gascon, Gabrielle; Sutherland, Megan; Lukaszewski, Marie-Amélie; Cloutier, Anik; Paradis, Pierre; Schiffrin, Ernesto L; Nuyt, Anne Monique

    2016-04-01

    Newborn rats exposed to high oxygen (O2), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin-angiotensin system activation in O2-exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O2 exposure), P5, P10 (end of O2), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O2-exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-β/SMAD3 pathway, and upregulation of cardiac angiotensin-converting enzyme 2. In conclusion, short-term Ang II blockade during neonatal high O2 prevents the development of cardiac alterations later in life in rats. These findings highlight the key role of neonatal renin-angiotensin system activation in the developmental programming of cardiac dysfunction induced by deleterious neonatal conditions. PMID:26857347

  14. Activation of the Cardiac Renin-Angiotensin System in High Oxygen-Exposed Newborn Rats: Angiotensin Receptor Blockade Prevents the Developmental Programming of Cardiac Dysfunction.

    Science.gov (United States)

    Bertagnolli, Mariane; Dios, Anne; Béland-Bonenfant, Sarah; Gascon, Gabrielle; Sutherland, Megan; Lukaszewski, Marie-Amélie; Cloutier, Anik; Paradis, Pierre; Schiffrin, Ernesto L; Nuyt, Anne Monique

    2016-04-01

    Newborn rats exposed to high oxygen (O2), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin-angiotensin system activation in O2-exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O2 exposure), P5, P10 (end of O2), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O2-exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-β/SMAD3 pathway, and upregulation of cardiac angiotensin-converting enzyme 2. In conclusion, short-term Ang II blockade during neonatal high O2 prevents the development of cardiac alterations later in life in rats. These findings highlight the key role of neonatal renin-angiotensin system activation in the developmental programming of cardiac dysfunction induced by deleterious neonatal conditions.

  15. Carbamazepine alone and in combination with doxycycline attenuates isoproterenol-induced cardiac hypertrophy

    Directory of Open Access Journals (Sweden)

    Harold Ray Garner

    2010-02-01

    Full Text Available β-adrenergic signaling is involved in the development of cardiac hypertrophy (CH, justifying the use of β-blockers as a therapy to minimize and postpone the consequences of this disease. Evidence suggests that adenylate cyclase, a downstream effector of the β-adrenergic pathway, might be a therapeutic target. We examined the effects of the anti-epileptic drug carbamazepine (CBZ, an inhibitor of adenylate cyclase. In a murine cardiac hypertrophy model, carbamazepine significantly attenuates isoproteronol (ISO-induced cardiac hypertrophy. Carbamazepine also has an effect in transverse aortic banding induced cardiac hypertrophy (TAB (P=0.07. When carbamazepine was given in combination with the antibiotic doxycycline (DOX, which inhibits matrix metalloproteinases (MMPs, therapeutic outcome measured by heart weight-to-body weight and heart weight-to-tibia length ratios was improved compared to either drug alone. Additionally, the combination therapy resulted in an increase in the survival rate over a 56-day period compared to that of untreated mice with cardiac hypertrophy or either drug used alone. Moreover, in support of a role for carbamaze­pine as a β-adrenergic antagonist via cAMP inhibition, a lower heart rate and a lower level of the activated phosphorylated form of the cAMP Response Element-Binding (CREB were observed in heart extracts from mice treated with carbamazepine. Gene expression analysis identified 19 genes whose expression is significantly altered in treated animals and might be responsible for the added benefit provided by the combination therapy. These results suggest that carbamazepine acts as a β-adrenergic antagonist. Carbamazepine and doxycycline are approved by the US Food and Drug Administration (FDA as drugs that might complement medications for cardiac hypertrophy or serve as an alternative therapy to traditional β-blockers. Furthermore, these agents reproducibly impact the expression of genes that may serve as

  16. Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes

    DEFF Research Database (Denmark)

    Brouwers, Olaf; Niessen, Petra M G; Miyata, Toshio;

    2014-01-01

    of streptozotocin. Mesenteric arteries were isolated to study ex vivo vascular reactivity with a wire myograph and kidneys were processed for histological examination. Glycation was determined by mass spectrometry and immunohistochemistry. Markers for inflammation, endothelium dysfunction and renal dysfunction were...... podocyte number and diabetes-induced elevation of urinary markers albumin, osteopontin, kidney-inflammation-molecule-1 and nephrin) were attenuated by Glo1 overexpression. In line with this, downregulation of Glo1 in cultured endothelial cells resulted in increased expression of inflammation...

  17. Matrix Metalloproteinase-9 Production following Cardiopulmonary Bypass Was Not Associated with Pulmonary Dysfunction after Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Tso-Chou Lin

    2015-01-01

    Full Text Available Background. Cardiopulmonary bypass (CPB causes release of matrix metalloproteinase- (MMP- 9, contributing to pulmonary infiltration and dysfunction. The aims were to investigate MMP-9 production and associated perioperative variables and oxygenation following CPB. Methods. Thirty patients undergoing elective cardiac surgery were included. Arterial blood was sampled at 6 sequential points (before anesthesia induction, before CPB and at 2, 4, 6, and 24 h after beginning CPB for plasma MMP-9 concentrations by ELISA. The perioperative laboratory data and variables, including bypass time, PaO2/FiO2, and extubation time, were also recorded. Results. The plasma MMP-9 concentrations significantly elevated at 2–6 h after beginning CPB (P<0.001 and returned to the preanesthesia level at 24 h (P=0.23, with predominant neutrophil counts after surgery (P<0.001. The plasma MMP-9 levels at 4 and 6 h were not correlated with prolonged CPB time and displayed no association with postoperative PaO2/FiO2, regardless of reduced ratio from preoperative 342.9±81.2 to postoperative 207.3±121.3 mmHg (P<0.001. Conclusion. Elective cardiac surgery with CPB induced short-term elevation of plasma MMP-9 concentrations within 24 hours, however, without significant correlation with CPB time and postoperative pulmonary dysfunction, despite predominantly increased neutrophils and reduced oxygenation.

  18. Pulmonary arterial hypertension secondary to chronic left-sided cardiac dysfunction in dogs.

    Science.gov (United States)

    Stepien, Rebecca L

    2009-09-01

    Pulmonary arterial hypertension is a description of a physiological finding rather than a diagnosis. Pulmonary arterial pressure is the result of interactions among pulmonary blood flow (right ventricular cardiac output), pulmonary vascular impedance and post-capillary pressure (typically reflecting left atrial pressure). When elevations in pulmonary arterial pressure (systolic/diastolic pulmonary arterial pressure > approximately 30/19 mmHg at rest) are accompanied by increased left atrial pressure, pulmonary arterial hypertension may be considered secondary to left-heart failure. Introduction of Doppler methods to diagnose pulmonary arterial hypertension has increased the awareness of the prevalence and importance of pulmonary arterial hypertension dogs with left-heart failure. Increasing understanding of the mechanism of development of pulmonary venous hypertension and reactive pulmonary arterial hypertension in dogs with left-heart disease has led to the development of successful additive therapies for progressive clinical signs in the setting of chronic therapy for congestive heart failure due to left-sided valvular and myocardial dysfunction. Because effective therapies for pulmonary arterial hypertension secondary to chronic left-sided cardiac dysfunction are now available, screening for pulmonary arterial hypertension should be a regular part of the Doppler echocardiographic examination in a clinical setting of chronic therapy for left-sided congestive heart failure due to valvular or myocardial disease.

  19. Conjugated linoleic acid and nitrite attenuate mitochondrial dysfunction during myocardial ischemia.

    Science.gov (United States)

    Van Hoose, Patrick M; Kelm, Natia Qipshidze; Piell, Kellianne M; Cole, Marsha P

    2016-08-01

    Cardiovascular health is influenced by dietary composition and the western diet is composed of varying types/amounts of fat. Conjugated linoleic acid (cLA) is an abundant dietary unsaturated fatty acid associated with health benefits but its biological signaling is not well understood. Nitrite is enriched in vegetables within the diet and can impact signaling of unsaturated fatty acids; however, its role on cLA signaling is not well understood. Elucidating how nitrite may impact the biological signaling of cLA is important due to the dietary consumption of both cLA and nitrite in the western diet. Since co-administration of cLA and nitrite results in cardioprotection during myocardial infarction (MI), it was hypothesized that cLA and nitrite may affect cardiac mitochondrial respiratory function and complex activity in MI. C57BL/6J mice were treated with cLA and nitrite for either 10 or 13days, where MI was induced on day 3. Following treatment, respiration and complex activity were measured. Among the major findings of this study, cLA treatment (10days) decreases state 3 respiration in vivo. Following MI, nitrite alone and in combination with cLA attenuates increased state 3 respiration and decreases hydrogen peroxide levels. Further, nitrite and cLA co-treatment attenuates increased complex III activity after MI. These results suggest that cLA, nitrite and the combination significantly alter cardiac mitochondrial respiratory and electron transport chain activity in vivo and following MI. Overall, the daily consumption of cLA and nitrite in the diet can have diverse cardiovascular implications, some of which occur at the mitochondrial level. PMID:27156147

  20. Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Bing Ji

    2015-07-01

    Full Text Available Background: Uncoupling protein 2 (UCP2 is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC, and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls. ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

  1. Resveratrol attenuates methylglyoxal-induced mitochondrial dysfunction and apoptosis by Sestrin2 induction

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Kyuhwa; Seo, Suho; Han, Jae Yun; Ki, Sung Hwan; Shin, Sang Mi, E-mail: smshin@chosun.ac.kr

    2014-10-15

    Methylglyoxal is found in high levels in the blood and other tissues of diabetic patients and exerts deleterious effects on cells and tissues. Previously, we reported that resveratrol, a polyphenol in grapes, induced the expression of Sestrin2 (SESN2), a novel antioxidant protein, and inhibited hepatic lipogenesis. This study investigated whether resveratrol protects cells from the methylglyoxal-induced toxicity via SESN2 induction. Methylglyoxal significantly induced cell death in HepG2 cells. However, cells pretreated with resveratrol were rescued from methylglyoxal-induced apoptosis. Resveratrol attenuated glutathione (GSH) depletion and ROS production promoted by methylglyoxal. Moreover, mitochondrial damage was observed by methylglyoxal treatment, but resveratrol restored mitochondrial function, as evidenced by the observed lack of mitochondrial permeability transition and increased ADP/ATP ratio. Resveratrol treatment inhibited SESN2 depletion elicited by methylglyoxal. SESN2 overexpression repressed methylglyoxal-induced mitochondrial dysfunction and apoptosis. Likewise, rotenone-induced cytotoxicity was not observed in SESN2 overexpressed cells. Furthermore, siRNA knockdown of SESN2 reduced the ability of resveratrol to prevent methylglyoxal-induced mitochondrial permeability transition. In addition, when mice were exposed to methylglyoxal after infection of Ad-SESN2, the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and GSH depletion by methylglyoxal in liver was reduced in Ad-SESN2 infected mice. Our results demonstrated that resveratrol is capable of protecting cells from methylglyoxal-induced mitochondrial dysfunction and oxidative stress via SESN2 induction. - Highlights: • Resveratrol decreased methylglyoxal-induced apoptosis. • Resveratrol attenuated GSH depletion and ROS production promoted by methylglyoxal. • Resveratrol restored the mitochondrial function by Sestrin2 induction. • Induction of Sestrin2

  2. Rapamycin attenuates mitochondrial dysfunction via activation of mitophagy in experimental ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qiang [Department of Neurology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China); Department of Neurology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Zhang, Ting [Department of Neurology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China); Wang, Jixian [Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030 (China); Zhang, Zhijun [Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030 (China); Zhai, Yu [Department of Neurology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China); Yang, Guo-Yuan, E-mail: gyyang0626@gmail.com [Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030 (China); Sun, Xiaojiang, E-mail: sunxj19@gmail.com [Department of Neurology, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233 (China)

    2014-02-07

    Highlights: • Rapamycin enhances mitophagy via increasing p62 translocation to the mitochondria. • Rapamycin attenuates brain ischemic damage and improves mitochondrial function. • The protection of rapamycin to mitochondrial is linked to enhanced mitophagy. - Abstract: Rapamycin has been demonstrated to exhibit neuroprotective functions via the activation of autophagy in a cerebral ischemia model. However, the involvement of mitophagy in this process and its contribution to the protection of mitochondrial function remains unknown. The present study explored the characteristics of mitophagy after cerebral ischemia and the effect of rapamycin on mitochondrial function. Male Sprague–Dawley rats underwent transient middle cerebral artery occlusion (tMCAO). Neurological deficits scores; infarct volumes; mitophagy morphology; and the levels of malondialdehyde (MDA), adenosine triphosphate (ATP) and mitochondrial membrane potentials (Δψm) were examined. The expression of LC3, Beclin-1 and p62 in the mitochondrial fraction combined with transmission electronic microscopy were used to explore mitophagic activity after ischemia. We also blocked autophagosome formation using 3-methyladenine (3-MA) to check the linkage between the mitochondrial protective effect of rapamycin and enhanced mitophagy. We observed that rapamycin significantly enhanced mitophagy, as evidenced by the increase in LC3-II and Beclin-1 expression in the mitochondria and p62 translocation to the mitochondria. Rapamycin reduced infarct volume, improved neurological outcomes and inhibited mitochondrial dysfunction compared with the control animals (p < 0.05). However, these protective effects were reversed by 3-methyladenine treatment after rapamycin. The present study indicates that rapamycin treatment attenuates mitochondrial dysfunction following cerebral ischemia, which is linked to enhanced mitophagy.

  3. Rapamycin attenuates mitochondrial dysfunction via activation of mitophagy in experimental ischemic stroke

    International Nuclear Information System (INIS)

    Highlights: • Rapamycin enhances mitophagy via increasing p62 translocation to the mitochondria. • Rapamycin attenuates brain ischemic damage and improves mitochondrial function. • The protection of rapamycin to mitochondrial is linked to enhanced mitophagy. - Abstract: Rapamycin has been demonstrated to exhibit neuroprotective functions via the activation of autophagy in a cerebral ischemia model. However, the involvement of mitophagy in this process and its contribution to the protection of mitochondrial function remains unknown. The present study explored the characteristics of mitophagy after cerebral ischemia and the effect of rapamycin on mitochondrial function. Male Sprague–Dawley rats underwent transient middle cerebral artery occlusion (tMCAO). Neurological deficits scores; infarct volumes; mitophagy morphology; and the levels of malondialdehyde (MDA), adenosine triphosphate (ATP) and mitochondrial membrane potentials (Δψm) were examined. The expression of LC3, Beclin-1 and p62 in the mitochondrial fraction combined with transmission electronic microscopy were used to explore mitophagic activity after ischemia. We also blocked autophagosome formation using 3-methyladenine (3-MA) to check the linkage between the mitochondrial protective effect of rapamycin and enhanced mitophagy. We observed that rapamycin significantly enhanced mitophagy, as evidenced by the increase in LC3-II and Beclin-1 expression in the mitochondria and p62 translocation to the mitochondria. Rapamycin reduced infarct volume, improved neurological outcomes and inhibited mitochondrial dysfunction compared with the control animals (p < 0.05). However, these protective effects were reversed by 3-methyladenine treatment after rapamycin. The present study indicates that rapamycin treatment attenuates mitochondrial dysfunction following cerebral ischemia, which is linked to enhanced mitophagy

  4. "Western" diet, but not high fat diet, causes maladaptation of cardiac fatty acid metabolism and cardiac dysfunction in the Wistar rat

    Science.gov (United States)

    Obesity and diabetes are associated with increased fatty acid availability in excess of fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction. We tested the hypothesis that a "western" or a high fat diet will lead to maladaptation of cardia...

  5. Western diet, but not high fat diet, causes maladaptation of cardiac fatty acid metabolism and cardiac dysfunction in the Wistar rat

    Science.gov (United States)

    Obesity and diabetes are associated with increased fatty acid availability in excess of fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction. We tested the hypothesis that a "western" or a high fat diet will lead to maladaptation of cardia...

  6. Neonatal cardiac dysfunction and transcriptome changes caused by the absence of Celf1

    Science.gov (United States)

    Giudice, Jimena; Xia, Zheng; Li, Wei; Cooper, Thomas A.

    2016-01-01

    The RNA binding protein Celf1 regulates alternative splicing in the nucleus and mRNA stability and translation in the cytoplasm. Celf1 is strongly down-regulated during mouse postnatal heart development. Its re-induction in adults induced severe heart failure and reversion to fetal splicing and gene expression patterns. However, the impact of Celf1 depletion on cardiac transcriptional and posttranscriptional dynamics in neonates has not been addressed. We found that homozygous Celf1 knock-out neonates exhibited cardiac dysfunction not observed in older homozygous animals, although homozygous mice are smaller than wild type littermates throughout development. RNA-sequencing of mRNA from homozygous neonatal hearts identified a network of cell cycle genes significantly up-regulated and down-regulation of ion transport and circadian genes. Cell cycle genes are enriched for Celf1 binding sites supporting a regulatory role in mRNA stability of these transcripts. We also identified a cardiac splicing network coordinated by Celf1 depletion. Target events contain multiple Celf1 binding sites and enrichment in GU-rich motifs. Identification of direct Celf1 targets will advance our knowledge in the mechanisms behind developmental networks regulated by Celf1 and diseases where Celf1 is mis-regulated. PMID:27759042

  7. Mechanisms of pulmonary dysfunction after on-pump and off-pump cardiac surgery: a prospective cohort study

    OpenAIRE

    Jansen Evert K; Groeneveld AB Johan; Verheij Joanne

    2007-01-01

    Abstract Background Pulmonary dysfunction following cardiac surgery is believed to be caused, at least in part, by a lung vascular injury and/or atelectasis following cardiopulmonary bypass (CPB) perfusion and collapse of non-ventilated lungs. Methods To test this hypothesis, we studied the postoperative pulmonary leak index (PLI) for 67Ga-transferrin and (transpulmonary) extravascular lung water (EVLW) in consecutive patients undergoing on-pump (n = 31) and off-pump (n = 8) cardiac surgery. ...

  8. Changes in cardiac heparan sulfate proteoglycan expression and streptozotocin-induced diastolic dysfunction in rats

    Directory of Open Access Journals (Sweden)

    Cestari Ismar N

    2011-04-01

    Full Text Available Abstract Background Changes in the proteoglycans glypican and syndecan-4 have been reported in several pathological conditions, but little is known about their expression in the heart during diabetes. The aim of this study was to investigate in vivo heart function changes and alterations in mRNA expression and protein levels of glypican-1 and syndecan-4 in cardiac and skeletal muscles during streptozotocin (STZ-induced diabetes. Methods Diabetes was induced in male Wistar rats by STZ administration. The rats were assigned to one of the following groups: control (sham injection, after 24 hours, 10 days, or 30 days of STZ administration. Echocardiography was performed in the control and STZ 10-day groups. Western and Northern blots were used to quantify protein and mRNA levels in all groups. Immunohistochemistry was performed in the control and 30-day groups to correlate the observed mRNA changes to the protein expression. Results In vivo cardiac functional analysis performed using echocardiography in the 10-day group showed diastolic dysfunction with alterations in the peak velocity of early (E diastolic filling and isovolumic relaxation time (IVRT indices. These functional alterations observed in the STZ 10-day group correlated with the concomitant increase in syndecan-4 and glypican-1 protein expression. Cardiac glypican-1 mRNA and skeletal syndecan-4 mRNA and protein levels increased in the STZ 30-day group. On the other hand, the amount of glypican in skeletal muscle was lower than that in the control group. The same results were obtained from immunohistochemistry analysis. Conclusion Our data suggest that membrane proteoglycans participate in the sequence of events triggered by diabetes and inflicted on cardiac and skeletal muscles.

  9. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

    International Nuclear Information System (INIS)

    We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

  10. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Xiao-Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Jia, Lin-Lin; Qi, Jie; Song, Xin-Ai; Tan, Hong [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University School of Basic Medical Sciences, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University Health Science Center, Xi' an 710061 (China)

    2015-05-01

    We hypothesized that chronic inhibition of NF-κB activity in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

  11. Low-dose exposure of silica nanoparticles induces cardiac dysfunction via neutrophil-mediated inflammation and cardiac contraction in zebrafish embryos.

    Science.gov (United States)

    Duan, Junchao; Yu, Yang; Li, Yang; Li, Yanbo; Liu, Hongcui; Jing, Li; Yang, Man; Wang, Ji; Li, Chunqi; Sun, Zhiwei

    2016-06-01

    The toxicity mechanism of nanoparticles on vertebrate cardiovascular system is still unclear, especially on the low-level exposure. This study was to explore the toxic effect and mechanisms of low-dose exposure of silica nanoparticles (SiNPs) on cardiac function in zebrafish embryos via the intravenous microinjection. The dosage of SiNPs was based on the no observed adverse effect level (NOAEL) of malformation assessment in zebrafish embryos. The mainly cardiac toxicity phenotypes induced by SiNPs were pericardial edema and bradycardia but had no effect on atrioventricular block. Using o-Dianisidine for erythrocyte staining, the cardiac output of zebrafish embryos was decreased in a dose-dependent manner. Microarray analysis and bioinformatics analysis were performed to screen the differential expression genes and possible pathway involved in cardiac function. SiNPs induced whole-embryo oxidative stress and neutrophil-mediated cardiac inflammation in Tg(mpo:GFP) zebrafish. Inflammatory cells were observed in atrium of SiNPs-treated zebrafish heart by histopathological examination. In addition, the expression of TNNT2 protein, a cardiac contraction marker in heart tissue had been down-regulated compared to control group using immunohistochemistry. Confirmed by qRT-PCR and western blot assays, results showed that SiNPs inhibited the calcium signaling pathway and cardiac muscle contraction via the down-regulated of related genes, such as ATPase-related genes (atp2a1l, atp1b2b, atp1a3b), calcium channel-related genes (cacna1ab, cacna1da) and the regulatory gene tnnc1a for cardiac troponin C. Moreover, the protein level of TNNT2 was decreased in a dose-dependent manner. For the first time, our results demonstrated that SiNPs induced cardiac dysfunction via the neutrophil-mediated cardiac inflammation and cardiac contraction in zebrafish embryos. PMID:26551753

  12. Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure.

    Science.gov (United States)

    Sinha-Hikim, Indrani; Shen, Ruoqing; Nzenwa, Ify; Gelfand, Robert; Mahata, Sushil K; Sinha-Hikim, Amiya P

    2011-06-01

    This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15-21 (E15-E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocycline. Pups were killed on postnatal day 15 (P15). Additional pregnant dams received twice daily IP injections of cocaine (from E15-E21) + oral administration of a relatively higher (37.5 mg/kg BW) dose of minocycline. Minocycline treatment continued from E15 until the pups were sacrificed on P15. In utero cocaine exposure resulted in an increase in oxidative stress and fetal cardiac myocyte apoptosis through activation of c-Jun-NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK)-mediated mitochondria-dependent apoptotic pathway. Continued minocycline treatment from E15 through P15 significantly prevented oxidative stress, kinase activation, perturbation of BAX/BCL-2 ratio, cytochrome c release, caspase activation, and attenuated fetal cardiac myocyte apoptosis after prenatal cocaine exposure. These results demonstrate in vivo cardioprotective effects of minocycline in preventing fetal cardiac myocyte death after prenatal cocaine exposure. Given its proven clinical safety and ability to cross the placental barrier and enter into the fetal circulation, minocycline may be an effective therapy for preventing cardiac consequences of in utero cocaine exposure. PMID:21424555

  13. Correlation between changes in diastolic dysfunction and health-related quality of life after cardiac rehabilitation program in dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Sherin H.M. Mehani

    2013-03-01

    Full Text Available Chronic heart failure (CHF is a complex syndrome characterized by progressive decline in left ventricular function, low exercise tolerance and raised mortality and morbidity. Left ventricular diastolic dysfunction plays a major role in CHF and progression of most cardiac diseases. The current recommended goals can theoretically be accomplished via exercise and pharmacological therapy so the aim of the present study was to evaluate the impact of cardiac rehabilitation program on diastolic dysfunction and health related quality of life and to determine the correlation between changes in left ventricular diastolic dysfunction and domains of health-related quality of life (HRQoL. Forty patients with chronic heart failure were diagnosed as having dilated cardiomyopathy (DCM with systolic and diastolic dysfunction. The patients were equally and randomly divided into training and control groups. Only 30 of them completed the study duration. The training group participated in rehabilitation program in the form of circuit-interval aerobic training adjusted according to 55–80% of heart rate reserve for a period of 7 months. Circuit training improved both diastolic and systolic dysfunction in the training group. On the other hand, only a significant correlation was found between improvement in diastolic dysfunction and health related quality of life measured by Kansas City Cardiomyopathy Questionnaire. It was concluded that improvement in diastolic dysfunction as a result of rehabilitation program is one of the important underlying mechanisms responsible for improvement in health-related quality of life in DCM patients.

  14. Fractal Dimension in Quantifying Experimental-Pulmonary-Hypertension-Induced Cardiac Dysfunction in Rats

    Science.gov (United States)

    Pacagnelli, Francis Lopes; Sabela, Ana Karênina Dias de Almeida; Mariano, Thaoan Bruno; Ozaki, Guilherme Akio Tamura; Castoldi, Robson Chacon; do Carmo, Edna Maria; Carvalho, Robson Francisco; Tomasi, Loreta Casquel; Okoshi, Katashi; Vanderlei, Luiz Carlos Marques

    2016-01-01

    Background Right-sided heart failure has high morbidity and mortality, and may be caused by pulmonary arterial hypertension. Fractal dimension is a differentiated and innovative method used in histological evaluations that allows the characterization of irregular and complex structures and the quantification of structural tissue changes. Objective To assess the use of fractal dimension in cardiomyocytes of rats with monocrotaline-induced pulmonary arterial hypertension, in addition to providing histological and functional analysis. Methods Male Wistar rats were divided into 2 groups: control (C; n = 8) and monocrotaline-induced pulmonary arterial hypertension (M; n = 8). Five weeks after pulmonary arterial hypertension induction with monocrotaline, echocardiography was performed and the animals were euthanized. The heart was dissected, the ventricles weighed to assess anatomical parameters, and histological slides were prepared and stained with hematoxylin/eosin for fractal dimension analysis, performed using box-counting method. Data normality was tested (Shapiro-Wilk test), and the groups were compared with non-paired Student t test or Mann Whitney test (p < 0.05). Results Higher fractal dimension values were observed in group M as compared to group C (1.39 ± 0.05 vs. 1.37 ± 0.04; p < 0.05). Echocardiography showed lower pulmonary artery flow velocity, pulmonary acceleration time and ejection time values in group M, suggesting function worsening in those animals. Conclusion The changes observed confirm pulmonary-arterial-hypertension-induced cardiac dysfunction, and point to fractal dimension as an effective method to evaluate cardiac morphological changes induced by ventricular dysfunction. PMID:27223643

  15. Feasibility of using respiration-averaged MR images for attenuation correction of cardiac PET/MR imaging.

    Science.gov (United States)

    Ai, Hua; Pan, Tinsu

    2015-01-01

    Cardiac imaging is a promising application for combined PET/MR imaging. However, current MR imaging protocols for whole-body attenuation correction can produce spatial mismatch between PET and MR-derived attenuation data owing to a disparity between the two modalities' imaging speeds. We assessed the feasibility of using a respiration-averaged MR (AMR) method for attenuation correction of cardiac PET data in PET/MR images. First, to demonstrate the feasibility of motion imaging with MR, we used a 3T MR system and a two-dimensional fast spoiled gradient-recalled echo (SPGR) sequence to obtain AMR images ofa moving phantom. Then, we used the same sequence to obtain AMR images of a patient's thorax under free-breathing conditions. MR images were converted into PET attenuation maps using a three-class tissue segmentation method with two sets of predetermined CT numbers, one calculated from the patient-specific (PS) CT images and the other from a reference group (RG) containing 54 patient CT datasets. The MR-derived attenuation images were then used for attenuation correction of the cardiac PET data, which were compared to the PET data corrected with average CT (ACT) images. In the myocardium, the voxel-by-voxel differences and the differences in mean slice activity between the AMR-corrected PET data and the ACT-corrected PET data were found to be small (less than 7%). The use of AMR-derived attenuation images in place of ACT images for attenuation correction did not affect the summed stress score. These results demonstrate the feasibility of using the proposed SPGR-based MR imaging protocol to obtain patient AMR images and using those images for cardiac PET attenuation correction. Additional studies with more clinical data are warranted to further evaluate the method. PMID:26218995

  16. Astragalus Polysaccharide Attenuated Iron Overload-Induced Dysfunction of Mesenchymal Stem Cells via Suppressing Mitochondrial ROS

    Directory of Open Access Journals (Sweden)

    Fan Yang

    2016-09-01

    Full Text Available Background/Aims: Bone marrow-derived mesenchymal stem cells (BMSCs have the ability to differentiate into multilineage cells such as osteoblasts, chondrocytes, and cardiomyocytes. Dysfunction of BMSCs in response to pathological stimuli participates in the development of diseases such as osteoporosis. Astragalus polysaccharide (APS is a major active ingredient of Astragalus membranaceus, a commonly used anti-aging herb in traditional Chinese medicine. The aim of this study was to investigate whether APS protects against iron overload-induced dysfunction of BMSCs and its underlying mechanisms. Methods: BMSCs were exposed to ferric ammonium citrate (FAC with or without different concentrations of APS. The viability and proliferation of BMSCs were assessed by CCK-8 assay and EdU staining. Cell apoptosis, senescence and pluripotency were examined utilizing TUNEL staining, β-galactosidase staining and qRT-PCR respectively. The reactive oxygen species (ROS level was assessed in BMSCs with a DCFH-DA probe and MitoSOX Red staining. Results: Firstly, we found that iron overload induced by FAC markedly reduced the viability and proliferation of BMSCs, but treatment with APS at 10, 30 and 100 μg/mL was able to counter the reduction of cell proliferation. Furthermore, exposure to FAC led to apoptosis and senescence in BMSCs, which were partially attenuated by APS. The pluripotent genes Nanog, Sox2 and Oct4 were shown to be downregulated in BMSCs after FAC treatment, however APS inhibited the reduction of Nanog, Sox2 and Oct4 expression. Further study uncovered that APS treatment abrogated the increase of intracellular and mitochondrial ROS level in FAC-treated BMSCs. Conclusion: Treatment of BMSCs with APS to impede mitochondrial ROS accumulation can remarkably inhibit apoptosis, senescence, and the reduction of proliferation and pluripotency of BMSCs caused by FAC-induced iron overload.

  17. Cardiac magnetic resonance determinants of functional mitral regurgitation in ischemic and non ischemic left ventricular dysfunction.

    Science.gov (United States)

    Fernández-Golfín, Covadonga; De Agustin, Alberto; Manzano, M Carmen; Bustos, Ana; Sánchez, Tibisay; Pérez de Isla, Leopoldo; Fuentes, Manuel; Macaya, Carlos; Zamorano, José

    2011-04-01

    Functional mitral regurgitation (FMR) is frequent in left ventricular (LV) dilatation/dysfunction. Echocardiographic predictors of FMR are known. However, cardiac magnetic resonance (CMR) predictors of FMR have not been fully addressed. The aim of the study was to evaluate CMR mitral valve (MV) parameters associated with FMR in ischemic and non ischemic LV dysfunction. 80 patients with LV ejection fraction below 45% and/or left ventricular dilatation of ischemic and non ischemic etiology were included. Cine-MR images (steady state free-precession) were acquired in a short-axis and 4 chambers views where MV evaluation was performed. Delayed enhancement was performed as well. Significant FMR was established as more than mild MR according to the echocardiographic report. Mean age was 59 years, males 79%. FMR was detected in 20 patients (25%) Significant differences were noted in LV functional parameters and in most MV parameters according to the presence of significant FMR. However, differences were noted between ischemic and non ischemic groups. In the first, differences in most MV parameters remained significant while in the non ischemic, only systolic and diastolic interpapillary muscle distance (1.60 vs. 2.19 cm, P = 0.001; 2. 51 vs. 3.04, P = 0.008) were predictors of FMR. FMR is associated with a more severe LV dilatation/dysfunction in the overall population. CMR MV parameters are associated with the presence of significant FMR and are different between ischemic and non ischemic patients. CMR evaluation of these patients may help in risk stratification as well as in surgical candidate selection.

  18. CHBPR N-Acetyl-Seryl-Aspartyl-Lysyl-Proline Attenuates Renal Injury and Dysfunction in Hypertensive Rats with Reduced Renal Mass

    OpenAIRE

    LIAO, Tang-dong; Yang, Xiao-Ping; D’Ambrosio, Martin; Zhang, Yanlu; Rhaleb, Nour-Eddine; Carretero, Oscar A.

    2009-01-01

    N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring peptide whose plasma concentration is increased 4- to 5-fold by angiotensin-converting enzyme inhibitors. We previously reported that in models of both hypertension and postmyocardial infarction, Ac-SDKP reduces cardiac inflammation and fibrosis. However, it is unknown whether Ac-SDKP can prevent or reverse renal injury and dysfunction in hypertension. In the present study, we tested the hypothesis that in rats with 5/6 ...

  19. Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System.

    Science.gov (United States)

    Xu, Qing-Qing; Xu, Yi-Jun; Yang, Cong; Tang, Ying; Li, Lin; Cai, Hao-Bin; Hou, Bo-Nan; Chen, Hui-Fang; Wang, Qi; Shi, Xu-Guang; Zhang, Shi-Jie

    2016-01-01

    Sodium Tanshinone IIA sulfonate (STS) is a derivative of Tanshinone IIA (Tan IIA). Tan IIA has been reported to possess neuroprotective effects against Alzheimer's disease (AD). However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP-) induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg) and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE) and increased the activity of choline acetyltransferase (ChAT) in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3). STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction. PMID:27556046

  20. Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System

    Directory of Open Access Journals (Sweden)

    Qing-Qing Xu

    2016-01-01

    Full Text Available Sodium Tanshinone IIA sulfonate (STS is a derivative of Tanshinone IIA (Tan IIA. Tan IIA has been reported to possess neuroprotective effects against Alzheimer’s disease (AD. However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP- induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE and increased the activity of choline acetyltransferase (ChAT in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD and decreased the levels of malondialdehyde (MDA and reactive oxygen species (ROS in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3. STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction.

  1. Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction.

    Science.gov (United States)

    Das, Anindita; Durrant, David; Mitchell, Clint; Mayton, Eric; Hoke, Nicholas N; Salloum, Fadi N; Park, Margaret A; Qureshi, Ian; Lee, Ray; Dent, Paul; Kukreja, Rakesh C

    2010-10-19

    We have shown that the potent phosphodiesterase-5 (PDE-5) inhibitor sildenafil (Viagra) induces a powerful effect on reduction of infarct size following ischemia/reperfusion injury and improvement of left ventricular dysfunction in the failing heart after myocardial infarction or doxorubicin (DOX) treatment. In the present study, we further investigated the potential effects of sildenafil on improving antitumor efficacy of DOX in prostate cancer. Cotreatment with sildenafil enhanced DOX-induced apoptosis in PC-3 and DU145 prostate cancer cells, which was mediated by enhanced generation of reactive oxygen species, up-regulation of caspase-3 and caspase-9 activities, reduced expression of Bcl-xL, and phosphorylation of Bad. Overexpression of Bcl-xL or dominant negative caspase 9 attenuated the synergistic effect of sildenafil and DOX on prostate cancer cell killing. Furthermore, treatment with sildenafil and DOX in mice bearing prostate tumor xenografts resulted in significant inhibition of tumor growth. The reduced tumor size was associated with amplified apoptotic cell death and increased expression of activated caspase 3. Doppler echocardiography showed that sildenafil treatment ameliorated DOX-induced left ventricular dysfunction. In conclusion, these results provide provocative evidence that sildenafil is both a powerful sensitizer of DOX-induced killing of prostate cancer while providing concurrent cardioprotective benefit. PMID:20884855

  2. Cardiac dysfunction assessed by echocardiographic tissue Doppler imaging is an independent predictor of mortality in the general population

    DEFF Research Database (Denmark)

    Mogelvang, Rasmus; Sogaard, Peter; Pedersen, Sune A;

    2009-01-01

    parameters, left ventricular dysfunction by TDI is a powerful and independent predictor of death, especially when systolic performance and diastolic performance are considered together, recognizing their interdependency and their complex relation to deteriorating cardiac function.......BACKGROUND: Tissue Doppler imaging (TDI) detects left ventricular dysfunction in patients with heart failure and normal ejection fraction, but the prognostic significance of left ventricular dysfunction by TDI in the general population is unknown. METHODS AND RESULTS: Within the Copenhagen City...... quantified by a combined index (eas index) of diastolic and systolic performance: e'/(a' x s'). During follow-up (median, 5.3 years), 90 participants died. Left ventricular dysfunction by TDI, in terms of low s' (hazard ratio, 1.23 per 1-cm/s decrease; P

  3. Molecular mechanism of carvedilol in attenuating the reversion to fetal energy metabolism during cardiac hypertrophy development

    Institute of Scientific and Technical Information of China (English)

    胡琴; 李隆贵

    2003-01-01

    Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdominal aorta (CAA) in male Wistar rats. Methods: Hemodynamic and ventricular remodeling parameters, free fatty acid content in the serum were measured in the experimental animals at 16 weeks after the surgical CAA, the rats receiving carvedilol intervention (CAR) after CAA, and those with sham operation (SH). The expressions of muscle carnitine palmitoyltransferaseⅠ (M-CPTⅠ) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the cardiac myocytes from every group were studied with RT-PCR. Results: Significant left ventricular hypertrophy were observed in the rats 16 weeks after coarctation operation (P<0.05), together with significant free fatty acids accumulation and downregulation of M-CPTⅠ and MCAD mRNA (P<0.05) in CAA group. Carvedilol at a dose of 30 mg/kg/d for 12 weeks inhibited the left ventricular hypertrophy induced by pressure overload and enhanced the gene expressions of rate-limiting enzyme (M-CPTⅠ) and key enzyme of fatty acid (MCAD) in the CAR group compared with CAA group (P<0.05). Conclusion: Pressure overload-induced hypertrophy in CAA rats causes the reversion back towards fetal enery metabolism, that is, downregulates the expressions of rate-limiting enzyme and key enzyme of fatty acid oxidation. The intervention therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates the reversion of the metabolic gene expression to fetal type through upregulating M-CPTⅠ and MCAD mRNA expressions. Thus, carvedilol may exert cardioprotective effects on heart failure by the mechanism of preserving the adult metabolic gene regulation.

  4. Discriminating between cardiac and pulmonary dysfunction in the general population with dyspnea by plasma pro-B-type natriuretic peptide

    DEFF Research Database (Denmark)

    Mogelvang, R; Goetze, JP; Schnohr, P;

    2007-01-01

    OBJECTIVES: This study was designed to determine whether measurement of plasma pro-B-type natriuretic peptide (proBNP) could be used in discriminating between cardiac and pulmonary dyspnea in the general population. BACKGROUND: Natriuretic peptides are useful markers in ruling out acute cardiac...... estimate the expected concentration of plasma proBNP based on age and gender was established for dyspneic subjects: an actual plasma proBNP concentration below half of the expected value ruled out left ventricular systolic and diastolic dysfunction (sensitivity 100%, 95% CI 100% to 100%; specificity 15...

  5. Senescence marker protein 30 has a cardio-protective role in doxorubicin-induced cardiac dysfunction.

    Directory of Open Access Journals (Sweden)

    Makiko Miyata

    Full Text Available BACKGROUND: Senescence marker protein 30 (SMP30, which was originally identified as an aging marker protein, is assumed to act as a novel anti-aging factor in the liver, lungs and brain. We hypothesized that SMP30 has cardio-protective function due to its anti-aging and anti-oxidant effects on doxorubicin (DOX-induced cardiac dysfunction. METHODS AND RESULTS: SMP30 knockout (SMP30 KO mice, SMP30 transgenic (SMP30 TG mice with cardiac-specific overexpression of SMP30 gene and wild-type (WT littermate mice at 12-14 weeks of age were given intra-peritoneal injection of DOX (20 mg/kg or saline. Five days after DOX injection, echocardiography revealed that left ventricular ejection fraction was more severely reduced in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but was preserved in the DOX-treated SMP30 TG mice. Generation of reactive oxygen species and oxidative DNA damage in the myocardium were greater in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but much less in the SMP30 TG mice. The numbers of deoxynucleotidyltransferase-mediated dUTP nick end-labeling positive nuclei in the myocardium, apoptotic signaling pathways such as caspase-3 activity, Bax/Bcl-2 ratio and phosphorylation activity of c-Jun N-terminal kinase were increased in SMP30 KO mice and decreased in SMP30 TG mice compared with WT mice after DOX injection. CONCLUSIONS: SMP30 has a cardio-protective role by anti-oxidative and anti-apoptotic effects in DOX-induced cardiotoxicity, and can be a new therapeutic target to prevent DOX-induced heart failure.

  6. Endothelial cells overexpressing IL-8 receptor reduce cardiac remodeling and dysfunction following myocardial infarction.

    Science.gov (United States)

    Zhao, Xiangmin; Zhang, Wei; Xing, Dongqi; Li, Peng; Fu, Jinyan; Gong, Kaizheng; Hage, Fadi G; Oparil, Suzanne; Chen, Yiu-Fai

    2013-08-15

    The endothelium is a dynamic component of the cardiovascular system that plays an important role in health and disease. This study tested the hypothesis that targeted delivery of endothelial cells (ECs) overexpressing neutrophil membrane IL-8 receptors IL8RA and IL8RB reduces acute myocardial infarction (MI)-induced left ventricular (LV) remodeling and dysfunction and increases neovascularization in the area at risk surrounding the infarcted tissue. MI was created by ligating the left anterior descending coronary artery in 12-wk-old male Sprague-Dawley rats. Four groups of rats were studied: group 1: sham-operated rats without MI or EC transfusion; group 2: MI rats with intravenous vehicle; group 3: MI rats with transfused ECs transduced with empty adenoviral vector (Null-EC); and group 4: MI rats with transfused ECs overexpressing IL8RA/RB (1.5 × 10⁶ cells post-MI). Two weeks after MI, LV function was assessed by echocardiography; infarct size was assessed by triphenyltetrazolium chloride (live tissue) and picrosirus red (collagen) staining, and capillary density and neutrophil infiltration in the area at risk were measured by CD31 and MPO immunohistochemical staining, respectively. When compared with the MI + vehicle and MI-Null-EC groups, transfusion of IL8RA/RB-ECs decreased neutrophil infiltration and pro-inflammatory cytokine expression and increased capillary density in the area at risk, decreased infarct size, and reduced MI-induced LV dysfunction. These findings provide proof of principle that targeted delivery of ECs is effective in repairing injured cardiac tissue. Targeted delivery of ECs to infarcted hearts provides a potential novel strategy for the treatment of acute MI in humans.

  7. Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

    2008-01-01

    The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

  8. Fenofibrate attenuates nicotine-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Chakkarwar, Vishal Arvind

    2011-01-01

    The study has been designed to investigate the effect of fenofibrate on nicotine-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) was administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy of thoracic aorta. The expression of mRNA for p22phox and eNOS was assessed by using reverse transcriptase-polymerase chain reaction. Serum thiobarbituric acid reactive substances concentration (TBARS) and aortic superoxide anion concentration were estimated to assess oxidative stress. Moreover, the serum lipid profile was assessed by estimating serum cholesterol, triglycerides and high density lipoprotein. The administration of nicotine induces VED by increased oxidative stress, altered lipid profile and impaired the integrity of vascular endothelium as assessed in terms of decrease in expression of mRNA for endothelial nitric oxide synthase (eNOS), impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine produced oxidative stress, assessed in terms of increase in serum TBARS and aortic superoxide anion generation and increase in expression of mRNA for p22phox. Nicotine altered the lipid profile by increasing the serum cholesterol, triglycerides and decreasing the high density lipoprotein. However, treatment with fenofibrate (32 mg/kg, p.o.) markedly prevented nicotine-induced VED by decreasing oxidative stress and improving integrity of vascular endothelium, normalising the altered lipid profile, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic

  9. Comparison of ordered subsets expectation maximization and Chang's attenuation correction method in quantitative cardiac SPET: a phantom study.

    Science.gov (United States)

    Dey, D; Slomka, P J; Hahn, L J; Kloiber, R

    1998-12-01

    Photon attenuation is one of the primary causes of artifacts in cardiac single photon emission tomography (SPET). Several attenuation correction algorithms have been proposed. The aim of this study was to compare the effect of using the ordered subsets expectation maximization (OSEM) reconstruction algorithm and Chang's non-uniform attenuation correction method on quantitative cardiac SPET. We performed SPET scans of an anthropomorphic phantom simulating normal and abnormal myocardial studies. Attenuation maps of the phantom were obtained from computed tomographic images. The SPET projection data were corrected for attenuation using OSEM reconstruction, as well as Chang's method. For each defect scan and attenuation correction method, we calculated three quantitative parameters: average radial maximum (ARM) ratio of the defect-to-normal area, maximum defect contrast (MDC) and defect volume, using automated three-dimensional quantitation. The differences between the two methods were less than 4% for defect-to-normal ARM ratio, 19% for MDC and 13% for defect volume. These differences are within the range of estimated statistical variation of SPET. The calculation times of the two methods were comparable. For all SPET studies, OSEM attenuation correction gave a more correct activity distribution, with respect to both the homogeneity of the radiotracer and the shape of the cardiac insert. The difference in uniformity between OSEM and Chang's method was quantified by segmental analysis and found to be less than 8% for the normal study. In conclusion, OSEM and Chang's attenuation correction are quantitatively equivalent, with comparable calculation times. OSEM reconstruction gives a more correct activity distribution and is therefore preferred.

  10. Effect of Left Ventricular Dysfunction and Viral Load on Risk of Sudden Cardiac Death In Patients with Human Immunodeficiency Virus

    OpenAIRE

    Moyers, Brian S.; Secemsky, Eric A.; Vittinghoff, Eric; Wong, Joseph K.; Diane V Havlir; Priscilla Y Hsue; Tseng, Zian H

    2014-01-01

    Human Immunodeficiency Virus-infected patients are disproportionately affected by cardiovascular disease and sudden cardiac death (SCD). Whether left ventricular (LV) dysfunction predicts SCD in those with human immunodeficiency virus (HIV) is unknown. We sought to determine the impact of LV on SCD in patients with HIV. We previously characterized all SCDs and AIDS deaths in 2860 consecutive patients in a public HIV clinic between 2000 and 2009. Transthoracic echocardiograms (TTEs) performed ...

  11. Level of complement activity predicts cardiac dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    2009-01-01

    BACKGROUND: The positive effect of reperfusion after ST-elevation myocardial infarction (STEMI) can be reduced by ischemic/reperfusion (I/R) injury.Mannose-binding-lectin (MBL) and soluble C5b-9 (membrane-attack-complex) are involved in complement-driven cell lysis and may play a role in human...... descending coronary artery who were successfully treated with pPCI. Cardiac dysfunction was defined as left ventricular ejection fraction LVEF or = 35%. After adjustment...

  12. Serum from Diesel Exhaust-Exposed Rats with Cardiac Dysfunction Alters Aortic Endothelial Cell Function In Vitro: Circulating Mediators as Causative Factors?

    Science.gov (United States)

    Although circulating inflammatory mediators are strongly associated with adverse cardiovascular outcomes triggered by inhaled air pollution, direct cause-effect linkage has not been established. Given that endothelial toxicity often precedes and precipitates cardiac dysfunction, ...

  13. Detection of Left Ventricular Regional Dysfunction and Myocardial Abnormalities Using Complementary Cardiac Magnetic Resonance Imaging in Patients with Systemic Sclerosis without Cardiac Symptoms: A Pilot Study.

    Science.gov (United States)

    Kobayashi, Yasuyuki; Kobayashi, Hitomi; T Giles, Jon; Yokoe, Isamu; Hirano, Masaharu; Nakajima, Yasuo; Takei, Masami

    2016-01-01

    Objective We sought to detect the presence of left ventricular regional dysfunction and myocardial abnormalities in systemic sclerosis (SSc) patients without cardiac symptoms using a complementary cardiac magnetic resonance (CMR) imaging approach. Methods Consecutive patients with SSc without cardiac symptoms and healthy controls underwent CMR on a 1.5 T scanner. The peak systolic regional function in the circumferential and radial strain (Ecc, % and Err, %) were calculated using a feature tracking analysis on the mid-left ventricular slices obtained with cine MRI. In addition, we investigated the myocardial characteristics by contrast MRI. Pharmacological stress and rest perfusion scans were performed to assess perfusion defect (PD) due to micro- or macrovascular impairment, and late gadolinium enhancement (LGE) images were obtained for the assessment of myocarditis and/or fibrosis. Results We compared 15 SSc patients with 10 healthy controls. No statistically significant differences were observed in the baseline characteristics between the patients and healthy controls. The mean peak Err and Ecc of all segments was significantly lower in the patients than the controls (p=0.011 and p=0.003, respectively). Four patients with LGE (28.6%) and seven patients with PD (50.0%) were observed. PD was significantly associated with digital ulcers (p=0.005). Utilizing a linear regression model, the presence of myocardial LGE was significantly associated with the peak Ecc (p=0.024). After adjusting for age, the association between myocardial LGE and the peak Ecc was strengthened. Conclusion A subclinical myocardial involvement, as detected by CMR, was prevalent in the SSc patients without cardiac symptoms. Regional dysfunction might predict the myocardial abnormalities observed in SSc patients without cardiac symptoms.

  14. Low Molecular Weight Fucoidan Alleviates Cardiac Dysfunction in Diabetic Goto-Kakizaki Rats by Reducing Oxidative Stress and Cardiomyocyte Apoptosis

    Directory of Open Access Journals (Sweden)

    Xinfeng Yu

    2014-01-01

    Full Text Available Diabetic cardiomyopathy (DCM is characterized by cardiac dysfunction and cardiomyocyte apoptosis. Oxidative stress is suggested to be the major contributor to the development of DCM. This study was intended to evaluate the protective effect of low molecular weight fucoidan (LMWF against cardiac dysfunction in diabetic rats. Type 2 diabetic goto-kakizaki rats were untreated or treated with LMWF (50 and 100 mg/kg/day for three months. The establishment of DCM model and the effects of LMWF on cardiac function were evaluated by echocardiography and isolated heart perfusion. Ventricle staining with H-E or Sirius Red was performed to investigate the structural changes in myocardium. Functional evaluation demonstrated that LMWF has a beneficial effect on DCM by enhancing myocardial contractility and mitigating cardiac fibrosis. Additionally, LMWF exerted significant inhibitory effects on the reactive oxygen species production and myocyte apoptosis in diabetic hearts. The depressed activity of superoxide dismutase in diabetic heart was also improved by intervention with LMWF. Moreover, LMWF robustly inhibited the enhanced expression of protein kinase C β, an important contributor to oxidative stress, in diabetic heart and high glucose-treated cardiomyocytes. In conclusion, LMWF possesses a protective effect against DCM through ameliorations of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis in diabetes.

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

    DEFF Research Database (Denmark)

    Bartels, Emil D; Nielsen, Jan M; Hellgren, Lars I;

    2009-01-01

    Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and beta-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via...... secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism...... remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression...

  16. The Impacts of Cardiac Rehabilitation Program on Echocardiographic Parameters in Coronary Artery Disease Patients with Left Ventricular Dysfunction

    Directory of Open Access Journals (Sweden)

    Masoumeh Sadeghi

    2013-01-01

    Full Text Available Introduction. The accurate impact of exercise on coronary artery disease (CAD patients with left ventricular dysfunction is still debatable. We studied the effects of cardiac rehabilitation (CR on echocardiography parameters in CAD patients with ventricular dysfunction. Methods. Patients with CAD who had ventricular dysfunction were included into an exercise-based rehabilitation program and received rehabilitation for eight weeks. All subjects underwent echocardiography before and at the end of the rehabilitation program. The echocardiography parameters, including left ventricular ejection fraction (LVEF, LV end-diastolic (LVEDD and end-systolic diameters (LVESD, and peak exercise capacity measured in metabolic equivalents (METs, were assessed. Results. Seventy patients (mean age = 57.5 ± 10.2 years, 77.1% males were included into the study. At the end of rehabilitation period, the LVEF increased from 45.14 ± 5.77% to 50.44 ± 8.70% (P<0.001, and the peak exercise capacity increased from 8.00 ± 2.56 to 10.08 ± 3.00 METs (P<0.001. There was no significant change in LVEDD (54.63 ± 12.96 to 53.86 ± 8.95 mm, P=0.529 or in LVESD (38.91 ± 10.83 to 38.09 ± 9.04 mm, P=0.378 after rehabilitation. Conclusion. Exercise training in postmyocardial infarction patients with ventricular dysfunction could have beneficial effects on cardiac function without adversely affecting LV remodeling or causing serious cardiac complications.

  17. The DNA methylation inhibitor induces telomere dysfunction and apoptosis of leukemia cells that is attenuated by telomerase over-expression.

    Science.gov (United States)

    Zhang, Xiaolu; Li, Bingnan; de Jonge, Nick; Björkholm, Magnus; Xu, Dawei

    2015-03-10

    DNA methyltransferase inhibitors (DNMTIs) such as 5-azacytidine (5-AZA) have been used for treatment of acute myeloid leukemia (AML) and other malignancies. Although inhibiting global/gene-specific DNA methylation is widely accepted as a key mechanism behind DNMTI anti-tumor activity, other mechanisms are likely involved in DNMTI's action. Because telomerase reverse transcriptase (TERT) plays key roles in cancer through telomere elongation and telomere lengthening-independent activities, and TERT has been shown to confer chemo- or radio-resistance to cancer cells, we determine whether DNMTIs affect telomere function and whether TERT/telomerase interferes with their anti-cancer efficacy. We showed that 5-AZA induced DNA damage and telomere dysfunction in AML cell lines by demonstrating the presence of 53-BP1 foci and the co-localization of 53-BP1 foci with telomere signals, respectively. Telomere dysfunction was coupled with diminished TERT expression, shorter telomere and apoptosis in 5-AZA-treated cells. However, 5-AZA treatment did not lead to changes in the methylation status of subtelomere regions. Down-regulation of TERT expression similarly occurred in primary leukemic cells derived from AML patients exposed to 5-AZA. TERT over-expression significantly attenuated 5-AZA-mediated DNA damage, telomere dysfunction and apoptosis of AML cells. Collectively, 5-AZA mediates the down-regulation of TERT expression, and induces telomere dysfunction, which consequently exerts an anti-tumor activity. PMID:25682873

  18. Fresh frozen plasma resuscitation attenuates platelet dysfunction compared with normal saline in a large animal model of multisystem trauma

    DEFF Research Database (Denmark)

    Sillesen, Martin; Johansson, Pär I; Rasmussen, Lars S;

    2014-01-01

    BACKGROUND: Platelet dysfunction following trauma has been identified as an independent predictor of mortality. We hypothesized that fresh frozen plasma (FFP) resuscitation would attenuate platelet dysfunction compared with 0.9% normal saline (NS). METHODS: Twelve swine were subjected...... volume FFP (n = 6) and monitored for 6 hours. Platelet function was assessed by adenosine diphosphate (ADP)-induced platelet aggregation at baseline, after 2 hours of shock following resuscitation, and 6 hours after resuscitation. Fibrinogen levels and markers of platelet activation (transforming growth...... factor β [TGF-β], sP-Selectin, and CD40L) as well as endothelial injury (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]) were also assayed. Thromboelastography was used to measure clotting activity. RESULTS: ADP-induced platelet aggregation was significantly higher...

  19. Dysfunction of pre- and post-operative cardiac autonomic nervous system in elderly patients with diabetes mellitus.

    Science.gov (United States)

    Zhang, Junlong; Tu, Weifeng; Dai, Jianqiang; Lv, Qing; Yang, Xiaoqi

    2011-01-01

    The pre- and post-operative cardiac autonomic nervous functions were compared in elderly, non-cardiac surgery patients with diabetes mellitus (DM) and without diabetes mellitus (NDM). A group of 30 unpremedicated elderly patients scheduled to undergo elective non-cardiac surgery were studied, including 15 DM patients and 15 NDM patients. Each component of heart rate variability (HRV) analysis in the frequency domain was monitored with Holter during the nights of the day before and on 1st and 2nd day after operation. After surgery, total power (TP), high frequency (HF), low frequency (LF) and very low frequency (VLF) significantly decreased as compared to the baseline values before operation in both groups (p<0.05). The LF/HF ratio was significantly changed in DM group but did not change in NDM group. On the 2nd postoperative day, TP, HF, LF and VLF in DM group were further decreased as compared to those on the 1st postoperative day and were significantly lower than those in NDM group (p<0.01 or 0.05), but these indices in NDM group did not show significant decreases. Surgery induced the cardiac autonomic nervous dysfunction in elderly patients not only with DM but also without diabetes. On the 2nd postoperative day, the disturbances of cardiac autonomic nervous activity were more sever in DM patients, compared to the 1st postoperative day, but was not significantly more sever than in the NDM patients.

  20. Heme Oxygenase Gene Targeting to Adipocyte Attenuates Adiposity and Vascular Dysfunction in Mice Fed a High Fat Diet

    OpenAIRE

    Cao, Jian; Peterson, Stephen J; Sodhi, Komal; Vanella, Luca; Barbagallo, Ignazio; Rodella, Luigi F.; Schwartzman, Michal L.; Abraham, Nader G.; Kappas, Attallah

    2012-01-01

    We examined the hypothesis that adipocyte dysfunction in mice fed a high fat (HF) diet can be prevented by lentiviral-mediated and adipocyte specific-targeting delivery of the human heme oxygenase-1 (aP2-HO-1). A bolus intracardial injection of aP2-HO-1 resulted in expression of human HO-1 for up to 9.5 months. Transduction of aP2-HO-1 increased human HO-1 expression in fat tissues without affecting murine HO-1. In mice fed a HF diet, aP2-HO-1 transduction attenuated the increases in body wei...

  1. 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

  2. Cinnamon polyphenols attenuate cell swelling and mitochondrial dysfunction following oxygen-glucose deprivation in glial cells

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    Astrocyte swelling is an integral component of cytotoxic brain edema in ischemic injury. While mechanisms underlying astrocyte swelling are likely multifactorial, oxidative stress and mitochondrial dysfunction are hypothesized to contribute to such swelling. We investigated the protective effects of...

  3. Mechanisms of pulmonary dysfunction after on-pump and off-pump cardiac surgery: a prospective cohort study

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    Jansen Evert K

    2007-02-01

    Full Text Available Abstract Background Pulmonary dysfunction following cardiac surgery is believed to be caused, at least in part, by a lung vascular injury and/or atelectasis following cardiopulmonary bypass (CPB perfusion and collapse of non-ventilated lungs. Methods To test this hypothesis, we studied the postoperative pulmonary leak index (PLI for 67Ga-transferrin and (transpulmonary extravascular lung water (EVLW in consecutive patients undergoing on-pump (n = 31 and off-pump (n = 8 cardiac surgery. We also studied transfusion history, radiographs, ventilatory and gas exchange variables. Results The postoperative PLI and EVLW were elevated above normal in 42 and 29% after on-pump surgery and 63 and 37% after off-pump surgery, respectively (ns. Transfusion of red blood cell (RBC concentrates, PLI, EVLW, occurrence of atelectasis, ventilatory variables and duration of mechanical ventilation did not differ between groups, whereas patients with atelectasis had higher venous admixture and airway pressures than patients without atelectasis (P = 0.037 and 0.049. The PLI related to number of RBC concentrates infused (P = 0.025. Conclusion The lung vascular injury in about half of patients after cardiac surgery is not caused by CPB perfusion but by trauma necessitating RBC transfusion, so that off-pump surgery may not afford a benefit in this respect. However, atelectasis rather than lung vascular injury is a major determinant of postoperative pulmonary dysfunction, irrespective of CPB perfusion.

  4. Nitric Oxide Bioavailability and Adiponectin Production in Chronic Systolic Heart Failure: Relation to Severity of Cardiac Dysfunction

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    Tang, W.H. Wilson; Shrestha, Kevin; Tong, Wilson; Wang, Zeneng; Troughton, Richard W.; Borowski, Allen G.; Klein, Allan L.; Hazen, Stanley L.

    2013-01-01

    Adiponectin is an anti-inflammatory, anti-atherogenic adipokine elevated in heart failure (HF) that may protect against endothelial dysfunction by influencing underlying nitric oxide bioavailablity. In this study, we examine the relationship between plasma adiponectin levels and measures of nitric oxide bioavailability and myocardial performance in patients with chronic systolic HF. In 139 ambulatory patients with stable, chronic systolic HF (left ventricular [LV] ejection fraction ≤40%, New York Heart Association [NYHA] class I to IV), we measured plasma levels of adiponectin, asymmetric dimethylarginine (ADMA) and global arginine bioavailability (GABR), and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse events (all-cause mortality or cardiac transplantation) were prospectively tracked for a median of 39 months. Plasma adiponectin levels directly correlated with plasma ADMA levels (Spearman’s r=0.41, p<0.001) and NT-proBNP levels (r=0.55, p<0.001), inversely correlated with GABR (r= −0.39, p<0.001), and were not associated with hsCRP (p=0.81) or MPO (p=0.07). Interestingly, increased plasma adiponectin levels remained positively correlated with plasma ADMA levels only in patients with elevated NT-proBNP levels (r= 0.33, p=0.009). Higher plasma adiponectin levels were associated with worse LV diastolic dysfunction (rank sums p=0.002), RV systolic dysfunction (rank sums p=0.002), and RV diastolic dysfunction (rank sums p=0.011), but not after adjustment for plasma ADMA and NT-proBNP levels. Plasma adiponectin levels predicted increased risk of adverse clinical events (HR [95% CI]: 1.45 [1.02–2.07], p=0.038) but not after adjustment for plasma ADMA and NT-proBNP levels, or echocardiographic indices of diastolic or RV systolic dysfunction. In patients with chronic systolic HF, adiponectin production is more closely linked with nitric oxide bioavailability than inflammation, and appears to be more robust

  5. Chronic treatment with metformin suppresses toll-like receptor 4 signaling and attenuates left ventricular dysfunction following myocardial infarction.

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    Soraya, Hamid; Clanachan, Alexander S; Rameshrad, Maryam; Maleki-Dizaji, Nasrin; Ghazi-Khansari, Mahmoud; Garjani, Alireza

    2014-08-15

    Acute treatment with metformin has a protective effect in myocardial infarction by suppression of inflammatory responses due to activation of AMP-activated protein kinase (AMPK). In the present study, the effect of chronic pre-treatment with metformin on cardiac dysfunction and toll-like receptor 4 (TLR4) activities following myocardial infarction and their relation with AMPK were assessed. Male Wistar rats were randomly assigned to one of 5 groups (n=6): normal control and groups were injected isoproterenol after chronic pre-treatment with 0, 25, 50, or 100mg/kg of metformin twice daily for 14 days. Isoproterenol (100mg/kg) was injected subcutaneously on the 13th and 14th days to induce acute myocardial infarction. Isoproterenol alone decreased left ventricular systolic pressure and myocardial contractility indexed as LVdp/dtmax and LVdp/dtmin. The left ventricular dysfunction was significantly lower in the groups treated with 25 and 50mg/kg of metformin. Metfromin markedly lowered isoproterenol-induced elevation in the levels of TLR4 mRNA, myeloid differentiation protein 88 (MyD88), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) in the heart tissues. Similar changes were also seen in the serum levels of TNF-α and IL-6. However, the lower doses of 25 and 50mg/kg were more effective than 100mg/kg. Phosphorylated AMPKα (p-AMPK) in the myocardium was significantly elevated by 25mg/kg of metformin, slightly by 50mg/kg, but not by 100mg/kg. Chronic pre-treatment with metformin reduces post-myocardial infarction cardiac dysfunction and suppresses inflammatory responses, possibly through inhibition of TLR4 activities. This mechanism can be considered as a target to protect infarcted myocardium.

  6. MR-based attenuation correction for cardiac FDG PET on a hybrid PET/MRI scanner: comparison with standard CT attenuation correction

    Energy Technology Data Exchange (ETDEWEB)

    Vontobel, Jan; Liga, Riccardo; Possner, Mathias; Clerc, Olivier F.; Mikulicic, Fran; Veit-Haibach, Patrick; Voert, Edwin E.G.W. ter; Fuchs, Tobias A.; Stehli, Julia; Pazhenkottil, Aju P.; Benz, Dominik C.; Graeni, Christoph; Gaemperli, Oliver; Herzog, Bernhard; Buechel, Ronny R.; Kaufmann, Philipp A. [University Hospital Zurich, Department of Nuclear Medicine, Zurich (Switzerland)

    2015-09-15

    The aim of this study was to evaluate the feasibility of attenuation correction (AC) for cardiac {sup 18}F-labelled fluorodeoxyglucose (FDG) positron emission tomography (PET) using MR-based attenuation maps. We included 23 patients with no known cardiac history undergoing whole-body FDG PET/CT imaging for oncological indications on a PET/CT scanner using time-of-flight (TOF) and subsequent whole-body PET/MR imaging on an investigational hybrid PET/MRI scanner. Data sets from PET/MRI (with and without TOF) were reconstructed using MR AC and semi-quantitative segmental (20-segment model) myocardial tracer uptake (per cent of maximum) and compared to PET/CT which was reconstructed using CT AC and served as standard of reference. Excellent correlations were found for regional uptake values between PET/CT and PET/MRI with TOF (n = 460 segments in 23 patients; r = 0.913; p < 0.0001) with narrow Bland-Altman limits of agreement (-8.5 to +12.6 %). Correlation coefficients were slightly lower between PET/CT and PET/MRI without TOF (n = 460 segments in 23 patients; r = 0.851; p < 0.0001) with broader Bland-Altman limits of agreement (-12.5 to +15.0 %). PET/MRI with and without TOF showed minimal underestimation of tracer uptake (-2.08 and -1.29 %, respectively), compared to PET/CT. Relative myocardial FDG uptake obtained from MR-based attenuation corrected FDG PET is highly comparable to standard CT-based attenuation corrected FDG PET, suggesting interchangeability of both AC techniques. (orig.)

  7. Autonomic Dysfunction Predicts Early Cardiac Affection in Patients with Systemic Sclerosis

    OpenAIRE

    Othman, Khaled M.; Naglaa Youssef Assaf; Hanan Mohamed Farouk; Iman M. Aly Hassan

    2010-01-01

    Objective: To detect the early preclinical alterations in cardiac autonomic control as well as altered cardiac function in systemic sclerosis (SSc) patients and their relevance to the clinical features of the disease using noninvasive methods. Methods: 30 SSc patients and 15 healthy controls matched for age and sex underwent clinical examination, serological analysis, and echocardiographic assessment including Doppler flow imaging to evaluate cardiac function, and 24-hour Holter monitoring an...

  8. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice

    OpenAIRE

    Yousif Nasser; Al-amran Fadhil G

    2011-01-01

    Abstract Background Cardiac inflammation and generation of oxidative stress are known to contribute to trastuzumab (herceptin) induced cardiac toxicity. Toll-like receptors (TLRs) are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signaling, we investigated whether or not TLR4 is involved in trastuzumab induced cardiotoxicity. Methods Seven days after a single injection of herceptin (2 mg/kg; i.p.)...

  9. Sepsis-induced cardiac mitochondrial dysfunction involves altered mitochondrial-localization of tyrosine kinase Src and tyrosine phosphatase SHP2.

    Directory of Open Access Journals (Sweden)

    Qun S Zang

    Full Text Available Our previous research demonstrated that sepsis produces mitochondrial dysfunction with increased mitochondrial oxidative stress in the heart. The present study investigated the role of mitochondria-localized signaling molecules, tyrosine kinase Src and tyrosine phosphatase SHP2, in sepsis-induced cardiac mitochondrial dysfunction using a rat pneumonia-related sepsis model. SD rats were given an intratracheal injection of Streptococcus pneumoniae, 4×10(6 CFU per rat, (or vehicle for shams; heart tissues were then harvested and subcellular fractions were prepared. By Western blot, we detected a gradual and significant decrease in Src and an increase in SHP2 in cardiac mitochondria within 24 hours post-inoculation. Furthermore, at 24 hours post-inoculation, sepsis caused a near 70% reduction in tyrosine phosphorylation of all cardiac mitochondrial proteins. Decreased tyrosine phosphorylation of certain mitochondrial structural proteins (porin, cyclophilin D and cytochrome C and functional proteins (complex II subunit 30kD and complex I subunit NDUFB8 were evident in the hearts of septic rats. In vitro, pre-treatment of mitochondrial fractions with recombinant active Src kinase elevated OXPHOS complex I and II-III activity, whereas the effect of SHP2 phosphatase was opposite. Neither Src nor SHP2 affected complex IV and V activity under the same conditions. By immunoprecipitation, we showed that Src and SHP2 consistently interacted with complex I and III in the heart, suggesting that complex I and III contain putative substrates of Src and SHP2. In addition, in vitro treatment of mitochondrial fractions with active Src suppressed sepsis-associated mtROS production and protected aconitase activity, an indirect marker of mitochondrial oxidative stress. On the contrary, active SHP2 phosphatase overproduced mtROS and deactivated aconitase under the same in vitro conditions. In conclusion, our data suggest that changes in mitochondria

  10. ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity.

    Science.gov (United States)

    Patel, Vaibhav B; Mori, Jun; McLean, Brent A; Basu, Ratnadeep; Das, Subhash K; Ramprasath, Tharmarajan; Parajuli, Nirmal; Penninger, Josef M; Grant, Maria B; Lopaschuk, Gary D; Oudit, Gavin Y

    2016-01-01

    Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance.

  11. The serum nT-proBnP in Patients with Cirrhosis:Relationship to Cardiac dysfunction and liver Function

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Objective To detect the values of NT-proBNP and evaluate its relationship with liver function, cardiac structure, and cardiac function which was evaluated by echocardiography in patients with liver cirrhosis. Methods A total of 50 liver cirrhotic patients and 11 healthy controls were studied by two dimensional Doppler echocardiography. Liver cirrhotic patients were divided into group A, B and C according to the Child-Pugh score. Cardiac dimensions and left and right ventricular functions were also evaluated. At the same time, the serum NT-proBNP of liver cirrhotic patients and healthy controls were detected, respectively. Results By Comparison between two groups, we found that the values of LVd, LAs, LVPW, AAO, A Wave, RVOTs, PV and NT-proBNP in liver cirrhosis group were higher than those in control group, whereas the value of E/A decreased. As for the value of LAs and serum NT-proBNP, A and B group were all lower than C group. With LAs>35 mm, the number of cases in liver cirrhosis group was higher than that in control group. So did that With E/A Conclusions The cardiac dysfunction confirmed the existence of cirrhotic cardiomyopathy. More clinical implications were found in liver cirrhotic patients with increased values of serum NT-proBNP.

  12. Early detection of cardiac dysfunction in the type 1 diabetic heart using speckle-tracking based strain imaging.

    Science.gov (United States)

    Shepherd, Danielle L; Nichols, Cody E; Croston, Tara L; McLaughlin, Sarah L; Petrone, Ashley B; Lewis, Sara E; Thapa, Dharendra; Long, Dustin M; Dick, Gregory M; Hollander, John M

    2016-01-01

    Enhanced sensitivity in echocardiographic analyses may allow for early detection of changes in cardiac function beyond the detection limits of conventional echocardiographic analyses, particularly in a small animal model. The goal of this study was to compare conventional echocardiographic measurements and speckle-tracking based strain imaging analyses in a small animal model of type 1 diabetes mellitus. Conventional analyses revealed differences in ejection fraction, fractional shortening, cardiac output, and stroke volume in diabetic animals relative to controls at 6-weeks post-diabetic onset. In contrast, when assessing short- and long-axis speckle-tracking based strain analyses, diabetic mice showed changes in average systolic radial strain, radial strain rate, radial displacement, and radial velocity, as well as decreased circumferential and longitudinal strain rate, as early as 1-week post-diabetic onset and persisting throughout the diabetic study. Further, we performed regional analyses for the LV and found that the free wall region was affected in both the short- and long-axis when assessing radial dimension parameters. These changes began 1-week post-diabetic onset and remained throughout the progression of the disease. These findings demonstrate the use of speckle-tracking based strain as an approach to elucidate cardiac dysfunction from a global perspective, identifying left ventricular cardiac regions affected during the progression of type 1 diabetes mellitus earlier than contractile changes detected by conventional echocardiographic measurements.

  13. Erythrocyte transketolase activity, markers of cardiac dysfunction and the diagnosis of infantile beriberi.

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    Douangdao Soukaloun

    Full Text Available BACKGROUND: Infantile beriberi is a potentially lethal manifestation of thiamin deficiency, associated with traditional post-partum maternal food avoidance, which persists in the Lao PDR (Laos. There are few data on biochemical markers of infantile thiamin deficiency or indices of cardiac dysfunction as potential surrogate markers. METHODOLOGY/PRINCIPAL FINDINGS: A case control study of 47 infants with beriberi and age-matched afebrile and febrile controls was conducted in Vientiane, Laos. Basal and activated erythrocyte transketolase activities (ETK and activation (α coefficients were assayed along with plasma brain natriuretic peptide, N-terminal pro-brain natriuretic peptide and troponin T. Basal ETK (and to a lesser extent activated ETK and plasma troponin T were the only infant biochemical markers that predicted infantile beriberi. A basal ETK ≤ 0.59 micromoles/min/gHb gave a sensitivity (95%CI of 75.0 (47.6 to 92.7% and specificity (95%CI of 85.2 (66.3 to 95.8% for predicting infantile beriberi (OR (95%CI 15.9 (2.03-124.2; p = 0.008 (area under ROC curve = 0.80. In contrast, the α coefficient did not discriminate between cases and controls. Maternal basal ETK was linearly correlated with infant basal ETK (Pearson's r = 0.66, p < 0.001. The odds of beriberi in infants with detectable plasma troponin T was 3.4 times higher in comparison to infants without detectable troponin T (OR 3.4, 95%CI 1.22-9.73, p = 0.019. Detectable troponin T had a sensitivity (95%CI of 78.6 (59.0 to 91.7 % and specificity (95%CI of 56.1 (39.7 to 71.5 % for predicting infantile beriberi. CONCLUSIONS/SIGNIFICANCE: Basal ETK is a more accurate biochemical marker of infantile beriberi than the activation coefficient. Raised plasma troponin T may be a useful indicator of infantile beriberi in infants at risk and in the absence of other evident causes.

  14. Effect of left ventricular dysfunction and viral load on risk of sudden cardiac death in patients with human immunodeficiency virus.

    Science.gov (United States)

    Moyers, Brian S; Secemsky, Eric A; Vittinghoff, Eric; Wong, Joseph K; Havlir, Diane V; Hsue, Priscilla Y; Tseng, Zian H

    2014-04-01

    Human immunodeficiency virus (HIV)-infected patients are disproportionately affected by cardiovascular disease and sudden cardiac death (SCD). Whether left ventricular (LV) dysfunction predicts SCD in those with HIV is unknown. We sought to determine the impact of LV dysfunction on SCD in patients with HIV. We previously characterized all SCDs and acquired immunodeficiency syndrome (AIDS) deaths in 2,860 consecutive patients in a public HIV clinic from 2000 to 2009. Transthoracic echocardiograms (TTEs) performed during the study period were identified. The effect of ejection fraction (EF), diastolic dysfunction, pulmonary artery pressure, and LV mass on SCD and AIDS death were evaluated: 423 patients had at least 1 TTE; 13 SCDs and 55 AIDS deaths had at least 1 TTE. In the propensity-adjusted analysis, EF 30% to 39% and EF<30% predicted SCD (hazard ratio [HR] 9.5, 95% confidence interval [CI] 1.7 to 53.3, p=0.01 and HR 38.5, 95% CI 7.6 to 195.0, p<0.001, respectively) but not AIDS death. Diastolic dysfunction also predicted SCD (HR 14.8, 95% CI 4.0 to 55.4, p<0.001) but not AIDS death, even after adjusting for EF. The association between EF<40% and SCD was greater in subjects with detectable versus undetectable HIV RNA (adjusted HR 11.7, 95% CI 2.9 to 47.2, p=0.001 vs HR 2.7, 95% CI 0.3 to 27.6, p=0.41; p=0.07 for interaction). In conclusion, LV systolic dysfunction and diastolic dysfunction predict SCD but not AIDS death in a large HIV cohort, with greater effect in those with detectable HIV RNA. Further investigation is needed to thoroughly evaluate the effect of low EF and HIV factors on SCD incidence and the potential benefit of implantable cardioverter-defibrillator therapy in this high-risk population. PMID:24521717

  15. Clinical study on the adriamycin induced cardiomyopathy using the cardiac magnetic resonance imaging. Total dose and cardiac dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, Kyoko; Teraoka, Kunihiko; Hirano, Masaharu [Tokyo Medical Coll. (Japan)

    2001-05-01

    We studied cardiac functional disorders caused by Adoriamycin using gadolinium (Gd) contrast cine MRI. Forty-eight patients were given ACT (31 men and 17 women; mean age, 52{+-}15 years). First, the relationship between dose and the left ventricular volume, cardiac function, left ventricular cardiac mass and localized wall motion were examined in all patients. Patients given a total dose of 300 mg/m{sup 2} or higher were assigned to the high dose group and those given doses under 300 mg/m{sup 2} to the low dose group. The same parameters were studied in both groups and compared. A 1.5-Tesla superconductive MRI was used for all studies. Cine images of the long and short axes at the papillary muscle level were obtained by ECG R-wave synchronized Gd contrast cine MRI. Left ventricular volume and cardiac function were analyzed using the long-axis cine images and the wall thickness in diastole and systole was measured at each site using the short-axis cine images. The percentage of wall thickness was calculated at each site. The mean ACT dose was 273.3{+-}218.2 mg/m{sup 2}. In all patients the total dose directly correlated with ESVI and inversely correlated with the ejection fraction (EF). In the high dose group, the total dose and EF were inversely correlated, but no significant differences were observed in the low dose group. In the high dose group, the ESVI was significantly greater and the SVI and EF were more significantly reduced than in the low dose group. In the high dose group, the thickness of the anterior, lateral and posterior walls, excluding the septum, was significantly lower than in the low dose group. However, changes in wall thickness were not significantly different between the groups. Gd contrast cine MRI was useful in examining cardiac functional disorders caused by anthracyclines. The total dose of anthracycline correlated directly with the ESVI, and inversely with the EF. A total dose of 300 mg/m{sup 2} appeared to be the borderline dose beyond

  16. Pharmacological preconditioning with erythropoietin attenuates the organ injury and dysfunction induced in a rat model of hemorrhagic shock

    Directory of Open Access Journals (Sweden)

    Kiran K. Nandra

    2013-05-01

    Pre-treatment with erythropoietin (EPO has been demonstrated to exert tissue-protective effects against ‘ischemia-reperfusion’-type injuries. This protection might be mediated by mobilization of bone marrow endothelial progenitor cells (EPCs, which are thought to secrete paracrine factors. These effects could be exploited to protect against tissue injury induced in cases where hemorrhage is foreseeable, for example, prior to major surgery. Here, we investigate the effects of EPO pre-treatment on the organ injury and dysfunction induced by hemorrhagic shock (HS. Recombinant human EPO (1000 IU/kg/day i.p. was administered to rats for 3 days. Rats were subjected to HS on day 4 (pre-treatment protocol. Mean arterial pressure was reduced to 35±5 mmHg for 90 minutes, followed by resuscitation with 20 ml/kg Ringer’s lactate for 10 minutes and 50% of the shed blood for 50 minutes. Rats were sacrificed 4 hours after the onset of resuscitation. EPC (CD34+/flk-1+ cell mobilization was measured following the 3-day pre-treatment with EPO and was significantly increased compared with rats pre-treated with phosphate-buffered saline. EPO pre-treatment significantly attenuated organ injury and dysfunction (renal, hepatic and neuromuscular caused by HS. In livers from rats subjected to HS, EPO enhanced the phosphorylation of Akt (activation, glycogen synthase kinase-3β (GSK-3β; inhibition and endothelial nitric oxide synthase (eNOS; activation. In the liver, HS also caused an increase in nuclear translocation of p65 (activation of NF-κB, which was attenuated by EPO. This data suggests that repetitive dosing with EPO prior to injury might protect against the organ injury and dysfunction induced by HS, by a mechanism that might involve mobilization of CD34+/flk-1+ cells, resulting in the activation of the Akt-eNOS survival pathway and inhibition of activation of GSK-3β and NF-κB.

  17. Cardiac diastolic dysfunction is associated with cerebral white matter lesions in elderly patients with risk factors for atherosclerosis

    International Nuclear Information System (INIS)

    Cerebral white matter lesions on magnetic resonance imaging (MRI) are considered to be the result of brain ischemic injury and a risk factor for clinical stroke. The purpose of this study was to elucidate the relationship between the cardiac diastolic function and cerebral white matter lesions in elderly patients with risk factors for atherosclerosis. The study subjects were 55 patients (75±7 years) with risk factors for atherosclerosis including hypertension, diabetes mellitus, and dyslipidemia. Patients with symptomatic cerebrovascular events were excluded from the study. Cerebral white matter lesions, which were defined as exhibiting high intensity regions on brain MRI, were evaluated with the degrees of periventricular hyperintensity (PVH) according to the Japanese Brain Dock Guidelines of 2003. Peak early diastolic mitral annular velocity (E' velocity) was measured by tissue Doppler echocardiography, and was used as a parameter of cardiac diastolic function. The mean value of E' velocity was decreased due to the cardiac diastolic dysfunction (5.2±1.4 cm/s). In addition, the E' velocity was inversely correlated with the degree of PVH (ρ=-0.701, p<0.001). Stepwise regression analysis showed that the decrease in the E' velocity (β coefficient=-0.42, p<0.001) and the presence of hypertension (β coefficient=0.31, p=0.001) were independent determinants of the degree of PVH. Thus, cardiac diastolic dysfunction is correlated to the severity of cerebral white matter lesions, suggesting the cardio-cerebral connection in elderly patients with risk factors for atherosclerosis. (author)

  18. Miso (Japanese soybean paste) soup attenuates salt-induced sympathoexcitation and left ventricular dysfunction in mice with chronic pressure overload.

    Science.gov (United States)

    Ito, Koji; Hirooka, Yoshitaka; Sunagawa, Kenji

    2014-02-01

    The hypothalamic mineralocorticoid receptor (MR)-angiotensin II type 1 receptor (AT1R) pathway is activated in mice with chronic pressure overload (CPO). When this activation is combined with high salt intake, it leads to sympathoexcitation, hypertension, and left ventricular (LV) dysfunction. Salt intake is thus an important factor that contributes to heart failure. Miso, a traditional Japanese food made from fermented soybeans, rice, wheat, or oats, can attenuate salt-induced hypertension in rats. However, its effects on CPO mice with salt-induced sympathoexcitation and LV dysfunction are unclear. Here, we investigated whether miso has protective effects in these mice. We also evaluated mechanisms associated with the hypothalamic MR-AT1R pathway. Aortic banding was used to produce CPO, and a sham operation was performed for controls. At 2 weeks after surgery, the mice were given water containing high NaCl levels (0.5%, 1.0%, and 1.5%) for 4 weeks. The high salt loading in CPO mice increased excretion of urinary norepinephrine (uNE), a marker of sympathetic activity, in an NaCl concentration-dependent manner; however, this was not observed in Sham mice. Subsequently, CPO mice were administered 1.0% NaCl water (CPO-H) or miso soup (1.0% NaCl equivalent, CPO-miso). The expression of hypothalamic MR, serum glucocorticoid-induced kinase-1 (SGK-1), and AT1R was higher in the CPO-H mice than in the Sham mice; however, the expression of these proteins was attenuated in the CPO-miso group. Although the CPO-miso mice had higher sodium intake, salt-induced sympathoexcitation was lower in these mice than in the CPO-H group. Our findings indicate that regular intake of miso soup attenuates salt-induced sympathoexcitation in CPO mice via inhibition of the hypothalamic MR-AT1R pathway. PMID:24908908

  19. In Vivo TLR9 Inhibition Attenuates CpG-Induced Myocardial Dysfunction

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    O. Boehm

    2013-01-01

    Full Text Available The involvement of toll-like receptor 9 (TLR9, a receptor for bacterial DNA, in septic cardiac depression has not been clarified in vivo. Thus, the aim of the study was to test possible TLR9 inhibitors (H154-thioate, IRS954-thioate, and chloroquine for their ability to protect the cardiovascular system in a murine model of CpG oligodeoxynucleotide- (ODN- dependent systemic inflammation. Sepsis was induced by i.p. application of the TLR9 agonist 1668-thioate in C57BL/6 wild type (WT and TLR9-deficient (TLR9-D mice. Thirty minutes after stimulation TLR9 antagonists were applied i.v. Survival was monitored up to 18 h after stimulation. Cardiac mRNA expression of inflammatory mediators was analyzed 2 h and 6 h after stimulation with 1668-thioate and hemodynamic parameters were monitored at the later time point. Stimulation with 1668-thioate induced a severe sepsis-like state with significant drop of body temperature and significantly increased mortality in WT animals. Additionally, there was a time-dependent increase of inflammatory mediators in the heart accompanied by development of septic heart failure. These effects were not observed in TLR9-D mice. Inhibition of TLR9 by the suppressive ODN H154-thioate significantly ameliorated cardiac inflammation, preserved cardiac function, and improved survival. This suppressive ODN was the most efficient inhibitor of the tested substances.

  20. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway.

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    Chen Li

    Full Text Available Although extracellular-regulated kinases (ERK are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy.In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed.Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

  1. Selumetinib, an Oral Anti-Neoplastic Drug, May Attenuate Cardiac Hypertrophy via Targeting the ERK Pathway

    Science.gov (United States)

    Yang, Hao; Luo, Fangbo; Chen, Lihong; Cai, Huawei; Li, Yajiao; You, Guiying; Long, Dan; Li, Shengfu; Zhang, Qiuping; Rao, Li

    2016-01-01

    Aims Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. Methods and Results In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. Conclusions Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials. PMID:27438013

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

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    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.

  3. Assessment of cardiac troponin I in patients with pulmonary emboli and its relationship with right ventricular dysfunction

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    Sasan Tavana

    2009-01-01

    Full Text Available (Received 16 December, 2008; Accepted 27 May, 2009AbstractBackground and purpose: Right ventricular dysfunction is common in major pulmonary embolisms. The purpose of this study was to evaluate the prevalence and diagnostic utility of cardiac troponin I and also to identify patients with RV dysfunction in pulmonary embolism.Materials and methods: This study was conducted on 42 patients with pulmonary embolism in Ekbatan Hospital, in Hamedan city. Data from history, echocardiogram, and lung perfusion scan was obtained from medical records. Blood samples were obtained immediately after pulmonary embolism was diagnosed. Cardiac troponin was measured using chromatographic assay.Results: Two patients (4.8% had positive troponin I (≥0.5µg/l, and 40 patients (95.2% had negative troponin I (0.05. Conclusion: Our data demonstrates that troponin I measurement is not able to distinguish specifically between coronary and non- coronary causes of chest pain.J Mazand Univ Med Sci 2009; 19(70: 72-75 (Persian

  4. Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

    OpenAIRE

    Lee Jung Eun; Yi Chin-ok; Jeon Byeong Tak; Shin Hyun Joo; Kim Soo Kyoung; Jung Tae Sik; Choi Jun Young; Roh Gu Seob

    2012-01-01

    Abstract Background Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA) on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF) rats. Methods Animals were se...

  5. HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets

    OpenAIRE

    Zeid Khitan; Mohit Harsh; Komal Sodhi; Shapiro, Joseph I; Nader G. Abraham

    2014-01-01

    Background. Fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ROS. HO-1 is a potent antioxidant gene that plays a key role in decreasing ROS and isoprostanes. We examined whether the fructose-mediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction of HO-1 would decrease both isoprostane levels and adipogenesis. Methods and Results. We examined the effect of fructose, on adi...

  6. Advanced cardiac imaging in heart failure : from subclinical myocardial dysfunction to therapy optimization

    NARCIS (Netherlands)

    Auger, Dominique

    2014-01-01

    Advanced echocardiographic techniques permit assessment of left ventricular dyssynchrony in overt heart failure patients and provide important prognostic data. These techniques may guide patients’ selection for cardiac resynchronization therapy and device optimization. Global left ventricular longit

  7. An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction

    OpenAIRE

    Niederbichler, Andreas D; Hoesel, Laszlo M.; Westfall, Margaret V.; Gao, Hongwei; Ipaktchi, Kyros R; Sun, Lei; Zetoune, Firas S.; Su, Grace L; Arbabi, Saman; Sarma, J. Vidya; Wang, Stewart C.; Hemmila, Mark R.; Ward, Peter A.

    2006-01-01

    Defective cardiac function during sepsis has been referred to as “cardiomyopathy of sepsis.” It is known that sepsis leads to intensive activation of the complement system. In the current study, cardiac function and cardiomyocyte contractility have been evaluated in rats after cecal ligation and puncture (CLP). Significant reductions in left ventricular pressures occurred in vivo and in cardiomyocyte contractility in vitro. These defects were prevented in CLP rats given blocking antibody to C...

  8. Chagas cardiomyopathy: the potential of diastolic dysfunction and brain natriuretic peptide in the early identification of cardiac damage.

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    Ana Garcia-Alvarez

    Full Text Available INTRODUCTION: Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the role of diastolic dysfunction, abnormal myocardial strain and elevated brain natriuretic peptide (BNP in the early identification of cardiac involvement in Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-four patients divided into 3 groups--group 1 (undetermined form: positive serology without ECG or 2D-echocardiographic abnormalities; N = 32, group 2 (typical ECG abnormalities of Chagas disease but normal 2D-echocardiography; N = 14, and group 3 (regional wall motion abnormalities, left ventricular [LV] end-diastolic diameter >55 mm or LV ejection fraction 37 pg/ml were noted in 0%, 13%, 29% and 63% in controls and groups 1 to 3, respectively. Half of patients in the undetermined form had impaired relaxation patterns, whereas half of patients with ECG abnormalities suggestive of Chagas cardiomyopathy had normal diastolic function. In group 1, BNP levels were statistically higher in patients with diastolic dysfunction as compared to those with normal diastolic function (27 ± 26 vs. 11 ± 8 pg/ml, p = 0.03. CONCLUSION/SIGNIFICANCE: In conclusion, the combination of diastolic function and BNP measurement adds important information that could help to better stratify patients with Chagas disease.

  9. Resveratrol treatment reduces cardiac progenitor cell dysfunction and prevents morpho-functional ventricular remodeling in type-1 diabetic rats.

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    Francesca Delucchi

    Full Text Available Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM. We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i the progenitor cell pool, and (ii the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n = 128 with streptozotocin-induced type-1 diabetes were either untreated (D group; n = 54 or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n = 64. Twenty-five rats constituted the control group (C. After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic "milieu" on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1 a significant reduction in ±dP/dt in comparison with C group, 2 a prolongation of isovolumic contraction/relaxation times, 3 an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing

  10. Patients without myocardial accumulation of {sup 123}I-metaiodobenzylguanidine. Does it always reflect cardiac adrenergic dysfunction?

    Energy Technology Data Exchange (ETDEWEB)

    Narita, Michihiro; Kurihara, Tadashi; Honda, Minoru; Hohjoh, Osamu [Sumitomo Hospital, Osaka (Japan)

    1994-12-01

    Since December 1992 to March 1994, we have performed myocardial imaging with {sup 123}I-metaiodobenzylguanidine ({sup 123}I-MIBG) in 110 patients to examine myocardial sympathetic integrity. Among them 11 patients (10%) showed no accumulation of {sup 123}I-MIBG in the heart. So we have examined the mechanisms of no myocardial {sup 123}I-MIBG accumulation. {sup 123}I-MIBG imaging was obtained at 20 min and 3 h after intravenous injection of {sup 123}I-MIBG (148 MBq) at rest. In addition to routine tomography, anterior planar imaging of the heart and the whole body imaging were performed. Eleven patients without myocardial {sup 123}I-MIBG accumulation consisted of 5 patients with orthostatic hypotension (including 3 patients with diabetic neuropathy). four patients with hypertrophic cardiomyopathy (HCM), one patient with hypertension and one normal subject. In patients with orthostatic hypotension, standing test showed cardiac sympathetic dysfunction. In addition to no myocardial {sup 123}I-MIBG accumulation, accumulation of {sup 123}I-MIBG in the salivary glands was not found in all them. These indicated that in patients with orthostatic hypotension, generalized sympathetic dysfunction caused no myocardial {sup 123}I-MIBG accumulation. But in other 6 patients there was no evidence which suggested the cardiac sympathetic nerve dysfunction. Age, sex, serum norepinephrine level, myocardial perfusion and the medication were not different between the patients with and without myocardial {sup 123}I-MIBG accumulation. So the mechanism of no myocardial {sup 123}I-MIBG accumulation was not clear in these patients. But it was noteworthy that in patients with HCM, no myocardial {sup 123}I-MIBG accumulation appeared in 17% (4/24), and the frequency of no myocardial {sup 123}I-MIBG accumulation in HCM was significantly (p<0.05) higher than in other disease entities when patients with orthostatic hypotension were excluded. (author).

  11. Cardiac dysfunction in cirrhosis - does adrenal function play a role? A hypothesis

    DEFF Research Database (Denmark)

    Theocharidou, Eleni; Krag, Aleksander; Bendtsen, Flemming;

    2013-01-01

    Cirrhotic cardiomyopathy (CCM), a condition of unknown pathogenesis, is characterized by suboptimal ventricular contractile response to stress, diastolic dysfunction and QT interval prolongation. It is most often found in patients with advanced cirrhosis. It is clinically relevant during stressfu...

  12. Exercise-induced ventricular arrhythmias and vagal dysfunction in Chagas disease patients with no apparent cardiac involvement

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    Henrique Silveira Costa

    2015-04-01

    Full Text Available INTRODUCTION : Exercise-induced ventricular arrhythmia (EIVA and autonomic imbalance are considered as early markers of heart disease in Chagas disease (ChD patients. The objective of the present study was to verify the differences in the occurrence of EIVA and autonomic maneuver indexes between healthy individuals and ChD patients with no apparent cardiac involvement. METHODS : A total of 75 ChD patients with no apparent cardiac involvement, aged 44.7 (8.5 years, and 38 healthy individuals, aged 44.0 (9.2 years, were evaluated using echocardiography, symptom-limited treadmill exercise testing and autonomic function tests. RESULTS : The occurrence of EIVA was higher in the chagasic group (48% than in the control group (23.7% during both the effort and the recovery phases. Frequent ventricular contractions occurred only in the patient group. Additionally, the respiratory sinus arrhythmia index was significantly lower in the chagasic individuals compared with the control group. CONCLUSIONS : ChD patients with no apparent cardiac involvement had a higher frequency of EIVA as well as more vagal dysfunction by respiratory sinus arrhythmia. These results suggest that even when asymptomatic, ChD patients possess important arrhythmogenic substrates and subclinical disease.

  13. Overexpression of junctophilin-2 does not enhance baseline function but attenuates heart failure development after cardiac stress.

    Science.gov (United States)

    Guo, Ang; Zhang, Xiaoying; Iyer, Venkat Ramesh; Chen, Biyi; Zhang, Caimei; Kutschke, William J; Weiss, Robert M; Franzini-Armstrong, Clara; Song, Long-Sheng

    2014-08-19

    Heart failure is accompanied by a loss of the orderly disposition of transverse (T)-tubules and a decrease of their associations with the junctional sarcoplasmic reticulum (jSR). Junctophilin-2 (JP2) is a structural protein responsible for jSR/T-tubule docking. Animal models of cardiac stresses demonstrate that down-regulation of JP2 contributes to T-tubule disorganization, loss of excitation-contraction coupling, and heart failure development. Our objective was to determine whether JP2 overexpression attenuates stress-induced T-tubule disorganization and protects against heart failure progression. We therefore generated transgenic mice with cardiac-specific JP2 overexpression (JP2-OE). Baseline cardiac function and Ca(2+) handling properties were similar between JP2-OE and control mice. However, JP2-OE mice displayed a significant increase in the junctional coupling area between T-tubules and the SR and an elevated expression of the Na(+)/Ca(2+) exchanger, although other excitation-contraction coupling protein levels were not significantly changed. Despite similar cardiac function at baseline, overexpression of JP2 provided significantly protective benefits after pressure overload. This was accompanied by a decreased percentage of surviving mice that developed heart failure, as well as preservation of T-tubule network integrity in both the left and right ventricles. Taken together, these data suggest that strategies to maintain JP2 levels can prevent the progression from hypertrophy to heart failure. PMID:25092313

  14. Silybum marianum oil attenuates oxidative stress and ameliorates mitochondrial dysfunction in mice treated with D-galactose

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    Shu Yun Zhu

    2014-01-01

    Full Text Available Background: Silybum marianum has been used as herbal medicine for the treatment of liver disease, liver cirrhosis, and to prevent liver cancer in Europe and Asia since ancient times. Silybum marianum oil (SMO, a by-product of silymarin production, is rich in essential fatty acids, phospholipids, sterols, and vitamin E. However, it has not been very good development and use. Objective: In the present study, we used olive oil as a control to investigate the antioxidant and anti-aging effect of SMO in D-galactose (D-gal-induced aging mice. Materials and Methods: D-gal was injected intraperitoneally (500 mg/kg body weight daily for 7 weeks while SMO was simultaneously administered orally. The triglycerides (TRIG and cholesterol (CHOL levels were estimated in the serum. Superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, total antioxidant capacity (T-AOC, monoamine oxidase (MAO, malondialdehyde (MDA, caspase-3, and Bcl-2 were determined in the liver and brain. The activities of Na + -K + -adenosine triphosphatase (ATPase, Ca 2+ -Mg 2+ -ATPase, membrane potential (ΔΨm, and membrane fluidity of the liver mitochondrial were estimated. Results: SMO decreased levels of TRIG and CHOL in aging mice. SMO administration elevated the activities of SOD, GSH-Px, and T-AOC, which are suppressed by aging. The levels of MAO and MDA in the liver and brain were reduced by SMO administration in aging mice. Enzyme linked immunosorbent assay showed that SMO significantly decreased the concentration of caspase-3 and improved the activity of Bcl-2 in the liver and brain of aging mice. Furthermore, SMO significantly attenuated the D-gal induced liver mitochondrial dysfunction by improving the activities of Na + -K + -ATPase, Ca 2+ -Mg 2+ -ATPase, membrane potential (ΔΨm, and membrane fluidity. Conclusion: These results indicate that SMO effectively attenuated oxidative damage and improved apoptosis related factors as well as liver mitochondrial dysfunction in

  15. Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion.Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins,Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion,enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group.Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion,expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl

  16. Escin, a novel triterpene, mitigates chronic MPTP/p-induced dopaminergic toxicity by attenuating mitochondrial dysfunction, oxidative stress, and apoptosis.

    Science.gov (United States)

    Selvakumar, Govindasamy Pushpavathi; Manivasagam, Thamilarasan; Rekha, Karamkolly R; Jayaraj, Richard L; Elangovan, Namasivayam

    2015-01-01

    Parkinson's disease (PD) is a common, chronic, and debilitating neurodegenerative disorder characterized by progressive loss of nigrostriatal dopaminergic neurons due to unknown factors. In the present study, we have evaluated if escin, a triterpene saponin from seeds of horse chestnut tree (Aesculus hippocastanum), offers neuroprotection against chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced toxicity using a mouse model. Chronic administration of MPTP/p deteriorated the loss of TH immunoreactivity in striatum. Subsequently, MPTP/p also enhanced oxidative stress by mitochondrial complex I inhibition, thereby ensuing dopaminergic denervation via modulation of Bcl-2, Bax, Cyto-C, and cleaved caspases expressions. However, we observed that pretreatment with escin (4 mg/kg) significantly attenuated MPTP/p-induced mitochondrial dysfunction, oxidative stress, and apoptosis. Furthermore, behavioral studies and ultrastructural analysis of mitochondria and intracellular components were in support of these findings. Therefore, we speculate that escin might be a promising candidate for the prevention of mitochondrial dysfunction-induced apoptosis in neurodegenerative disorders such as PD. PMID:24788336

  17. Activation of sonic hedgehog signaling attenuates oxidized low-density lipoprotein-stimulated brain microvascular endothelial cells dysfunction in vitro.

    Science.gov (United States)

    Jiang, Xiu-Long; Chen, Ting; Zhang, Xu

    2015-01-01

    The study was performed to investigate the role of sonic hedgehog (SHH) in the oxidized low-density lipoprotein (oxLDL)-induced blood-brain barrier (BBB) disruption. The primary mouse brain microvascular endothelial cells (MBMECs) were exposed to oxLDL. The results indicated that treatment of MBMECs with oxLDL decreased the cell viability, and oxidative stress was involved in oxLDL-induce MBMECs dysfunction with increasing intracellular ROS and MDA formation as well as decreasing NO release and eNOS mRNA expression. In addition, SHH signaling components, such as SHH, Smo and Gli1, mRNA and protein levels were significantly decreased after incubation with increasing concentrations of oxLDL. Treatment with oxLDL alone or SHH loss-of-function significantly increased the permeability of MBMECs, and overexpression of SHH attenuated oxLDL-induced elevation of permeability in MBMECs. Furthermore, SHH gain-of-function could reverse oxLDL-induced apoptosis through inhibition caspase3 and caspase8 levels in MBMECs. Taken together, these results demonstrated that the suppression of SHH in MBMECs might contribute to the oxLDL-induced disruption of endothelial barrier. However, the overexpression of SHH could reverse oxLDL-induced endothelial cells dysfunction in vitro. PMID:26722472

  18. 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...

  19. Acute nicotine treatment attenuates lipopolysaccharide-induced cognitive dysfunction by increasing BDNF expression and inhibiting neuroinflammation in the rat hippocampus.

    Science.gov (United States)

    Wei, Penghui; Liu, Qingshen; Li, Dong; Zheng, Qiang; Zhou, Jinfeng; Li, Jianjun

    2015-09-14

    Although nicotine has been shown to improve cognitive function in various studies, the mechanisms underlying acute nicotine treatment-induced neuroprotection remain incompletely understood. In this study, we evaluated the effect of acute nicotine treatment on the cognitive impairment induced by lipopolysaccharide (LPS) and explored the underlying mechanism. We found that acute nicotine injection markedly attenuated LPS-elicited cognitive deficits and suppressed the strong LPS-induced release of IL-1β, IL-6, and TNF-α into serum and the dorsal hippocampus at 4 and 24h after LPS injection. Western blot analysis indicated a clear increase in the levels of cleaved caspase-3 in LPS-treated animals but not in nicotine- or saline-treated animals. Furthermore, nicotine administration led to a significant increase in BDNF mRNA expression at 4 and 24h and in BDNF protein expression at 24h after LPS injection in the dorsal hippocampus. Taken together, acute nicotine administration attenuated LPS-induced cognitive dysfunction, and this neuroprotective effect may be related to the up-regulation of BDNF and the inhibition of neuroinflammation and apoptosis-related proteins in the dorsal hippocampus. PMID:26259694

  20. Knockdown of IRF6 Attenuates Hydrogen Dioxide-Induced Oxidative Stress via Inhibiting Mitochondrial Dysfunction in HT22 Cells.

    Science.gov (United States)

    Guo, Xiao-Min; Chen, Bo; Lv, Jian-Meng; Lei, Qi; Pan, Ya-Juan; Yang, Qian

    2016-10-01

    Oxidative stress-induced cell damage is involved in many neurological diseases. Interferon regulatory factor 6 (IRF6), a member of the IRF family of transcription factors, is required for the differentiation of skin, breast epithelium, and oral epithelium. However, the regulation and function of IRF6 in central nervous system remain unknown. This study aimed to investigate the role of IRF6 in hydrogen peroxide (H2O2)-induced oxidative neuronal injury in HT22 mouse hippocampal cells. Treatment with H2O2 significantly increased the expression of IRF6 at both mRNA and protein levels, and knockdown of IRF6 using specific small interfering RNA reduced H2O2-induced cytotoxicity, as evidenced by increased cell viability and decreased apoptosis. Knockdown of IRF6 attenuated intracellular reactive oxygen species (ROS) generation and lipid peroxidation, and also preserved endogenous antioxidant enzyme activities. The inhibitory effect of IRF6 knockdown on mitochondrial dysfunction was demonstrated by reduced mitochondrial oxidative level, preserved mitochondrial membrane potential (MMP) and ATP generation, as well as attenuated mitochondrial swelling. In addition, down-regulation of IRF6 inhibited the activation of mitochondrial apoptotic factors, whereas IRF6 knockdown together with caspase inhibitors had no extra effect on cell viability and LDH release. These results suggest that knockdown of IRF6 has protective effects against H2O2-induced oxidative stress by reducing ROS accumulation and apoptosis, and these protective effects are dependent on preservation of mitochondrial function. PMID:26620051

  1. 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.

  2. 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.

  3. Attenuation of phosphamidon-induced oxidative stress and immune dysfunction in rats treated with N-acetylcysteine

    Directory of Open Access Journals (Sweden)

    S.G. Suke

    2008-09-01

    Full Text Available The effect of N-acetylcysteine, a thiolic antioxidant, on attenuation of phosphamidon-induced oxidative stress and immune dysfunction was evaluated in adult male Wistar rats weighing 200-250 g. Rats were divided into four groups, 8 animals/group, and treated with phosphamidon, N-acetylcysteine or the combination of both for 28 days. Oral administration of phosphamidon (1.74 mg/kg, an organophosphate insecticide, increased serum malondialdehyde (3.83 ± 0.18 vs 2.91 ± 0.24 nmol/mL; P < 0.05 and decreased erythrocyte superoxide dismutase (567.8 ± 24.36 vs 749.16 ± 102.61 U/gHb; P < 0.05, catalase activity (1.86 ± 0.18 vs 2.43 ± 0.08 U/gHb; P < 0.05 and whole blood glutathione levels (1.25 ± 0.21 vs 2.28 ± 0.08 mg/gHb; P < 0.05 showing phosphamidon-induced oxidative stress. Phosphamidon exposure markedly suppressed humoral immune response as assessed by antibody titer to ovalbumin (4.71 ± 0.51 vs 8.00 ± 0.12 -log2; P < 0.05, and cell-mediated immune response as assessed by leukocyte migration inhibition (25.24 ± 1.04 vs 70.8 ± 1.09%; P < 0.05 and macrophage migration inhibition (20.38 ± 0.99 vs 67.16 ± 5.30%; P < 0.05 response. Phosphamidon exposure decreased IFN-у levels (40.7 ± 3.21 vs 55.84 ± 3.02 pg/mL; P < 0.05 suggesting a profound effect of phosphamidon on cell-mediated immune response. A phosphamidon-induced increase in TNF-α level (64.19 ± 6.0 vs 23.16 ± 4.0 pg/mL; P < 0.05 suggests a contributory role of immunocytes in oxidative stress. Co-administration of N-acetylcysteine (3.5 mmol/kg, orally with phosphamidon attenuated the adverse effects of phosphamidon. These findings suggest that oral N-acetylcysteine treatment exerts protective effect and attenuates free radical injury and immune dysfunction caused by subchronic phosphamidon exposure.

  4. Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines.

    Science.gov (United States)

    Lauriol, Jessica; Cabrera, Janel R; Roy, Ashbeel; Keith, Kimberly; Hough, Sara M; Damilano, Federico; Wang, Bonnie; Segarra, Gabriel C; Flessa, Meaghan E; Miller, Lauren E; Das, Saumya; Bronson, Roderick; Lee, Kyu-Ho; Kontaridis, Maria I

    2016-08-01

    Hypertrophic cardiomyopathy is a common cause of mortality in congenital heart disease (CHD). Many gene abnormalities are associated with cardiac hypertrophy, but their function in cardiac development is not well understood. Loss-of-function mutations in PTPN11, which encodes the protein tyrosine phosphatase (PTP) SHP2, are implicated in CHD and cause Noonan syndrome with multiple lentigines (NSML), a condition that often presents with cardiac hypertrophic defects. Here, we found that NSML-associated hypertrophy stems from aberrant signaling mechanisms originating in developing endocardium. Trabeculation and valvular hyperplasia were diminished in hearts of embryonic mice expressing a human NSML-associated variant of SHP2, and these defects were recapitulated in mice expressing NSML-associated SHP2 specifically in endothelial, but not myocardial or neural crest, cells. In contrast, mice with myocardial- but not endothelial-specific NSML SHP2 expression developed ventricular septal defects, suggesting that NSML-associated mutations have both cell-autonomous and nonautonomous functions in cardiac development. However, only endothelial-specific expression of NSML-associated SHP2 induced adult-onset cardiac hypertrophy. Further, embryos expressing the NSML-associated SHP2 mutation exhibited aberrant AKT activity and decreased downstream forkhead box P1 (FOXP1)/FGF and NOTCH1/EPHB2 signaling, indicating that SHP2 is required for regulating reciprocal crosstalk between developing endocardium and myocardium. Together, our data provide functional and disease-based evidence that aberrant SHP2 signaling during cardiac development leads to CHD and adult-onset heart hypertrophy. PMID:27348588

  5. Autonomic Dysfunction Predicts Early Cardiac Affection in Patients with Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Khaled M. Othman

    2010-05-01

    Full Text Available Objective: To detect the early preclinical alterations in cardiac autonomic control as well as altered cardiac function in systemic sclerosis (SSc patients and their relevance to the clinical features of the disease using noninvasive methods. Methods: 30 SSc patients and 15 healthy controls matched for age and sex underwent clinical examination, serological analysis, and echocardiographic assessment including Doppler flow imaging to evaluate cardiac function, and 24-hour Holter monitoring analyzed for arrhythmia and heart rate variability (HRV in the time and frequency domains. Results: The trans-mitral Doppler of early to atrial wave (E/A ratio was reversed in five patients (16.6% and the tricuspid E/A ratio was reversed in 10 patients (33.3%. Holter analysis for SSc patients revealed an increased prevalence of premature ventricular contractions (PVC $ 10/h (P = 0.02, supra-ventricular tachycardias (SVTs (P = 0.2, and total PVC count (P = 0.0000. Highly significant (P = 0.000 impairment in all HRV parameters was demonstrated in the SSc patients. Total skin thickness score (TSS, Raynaud’s phenomenon and anti-scleroderma 70 (anti-SCL70 showed significant positive correlations with all arrhythmia parameters, while showing a significant negative correlation with the impaired ventricular diastolic function and various HRV parameters. No correlation was found between arrhythmia and HRV parameters and disease duration, disease type, or presence of anti-centromere antibodies. Conclusion: Low heart rate variability, increased TSS and the presence of anti-SCL70 are correlated with preclinical cardiac involvement in SSc patients and may predict the likelihood of malignant arrhythmia and sudden cardiac death. Therefore, noninvasive HRV evaluation before clinical cardiac involvement in these patients might be beneficial when added to the clinical and laboratory assessments in detecting high-risk patients, and may allow for implementation of preventive

  6. Sick sinus syndrome in a patient with extensive cardiac lipomatosis (sinus node dysfunction in lipomatosis).

    Science.gov (United States)

    Kadmon, Ehud; Paz, Rami; Kusniec, Jairo; Strasberg, Boris

    2010-04-01

    We present a case of a 45-year-old man with an incidental and longstanding diagnosis of extensive mediastinal and cardiac lipomatosis. Along the years, he had experienced various arrhythmias, mainly bradyarrhythmias, mostly asymptomatic. Recently after documenting a sinus pause of 6 seconds and runs of nonsustained ventricular tachycardias, he underwent an implantation of a cardioverter-defibrillator. There are many reports of cardiac lipomatosis in the literature, including reports of related ventricular arrhythmias, some of which are fatal. (PACE 2010; 513-515).

  7. Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy.

    Science.gov (United States)

    Liang, Lei; Shou, Xi-Ling; Zhao, Hai-Kang; Ren, Gu-Qun; Wang, Jian-Bang; Wang, Xi-Hui; Ai, Wen-Ting; Maris, Jackie R; Hueckstaedt, Lindsay K; Ma, Ai-Qun; Zhang, Yingmei

    2015-02-01

    Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a variety of biological processes including obesity. However, the precise mechanism of action behind obesity-induced changes in autophagy still remains elusive. This study was designed to examine the role of the antioxidant catalase in high fat diet-induced changes in cardiac geometry and function as well as the underlying mechanism of action involved with a focus on autophagy. Wild-type (WT) and transgenic mice with cardiac overexpression of catalase were fed low or high fat diet for 20 weeks prior to assessment of myocardial geometry and function. High fat diet intake triggered obesity, hyperinsulinemia, and hypertriglyceridemia, the effects of which were unaffected by catalase transgene. Myocardial geometry and function were compromised with fat diet intake as manifested by cardiac hypertrophy, enlarged left ventricular end systolic and diastolic diameters, fractional shortening, cardiomyocyte contractile capacity and intracellular Ca²⁺ mishandling, the effects of which were ameliorated by catalase. High fat diet intake promoted reactive oxygen species production and suppressed autophagy in the heart, the effects of which were attenuated by catalase. High fat diet intake dampened phosphorylation of inhibitor kappa B kinase β(IKKβ), AMP-activated protein kinase (AMPK) and tuberous sclerosis 2 (TSC2) while promoting phosphorylation of mTOR, the effects of which were ablated by catalase. In vitro study revealed that palmitic acid compromised cardiomyocyte autophagy and contractile function in a manner reminiscent of fat diet intake, the effect of which was significantly alleviated by inhibition of IKKβ, activation of AMPK and induction of autophagy. Taken together, our data revealed that the antioxidant catalase counteracts against high fat diet-induced cardiac geometric and functional anomalies possibly via an IKKβ-AMPK-dependent restoration of myocardial

  8. 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.

  9. Valproic acid attenuates the multiple-organ dysfunction in a rat model of septic shock

    Institute of Scientific and Technical Information of China (English)

    SHANG You; JIANG Yuan-xu; Ding Ze-jun; Shen Ai-ling; XU San-peng; YUAN Shi-ying; YAO Shang-long

    2010-01-01

    Background Valproic acid (VPA) improves early survival and organ function in a highly lethal poly-trauma and hemorrhagic shock model or other severe insults. We assessed whether VPA could improve organ function in a rat model of septic shock and illustrated the possible mechanisms.Methods Forty Sprague-Dawley rats were randomly assigned to four groups (n=10): control group, VPA group, LPS group, and LPS+VPA group. Lipopolysaccharide (LPS) (10 mg/kg) was injected intravenously to replicate the experimental model of septic shock. Rats were treated with VPA (300 mg/kg, i.v.) or saline. Six hours after LPS injection,blood was sampled for gas analysis, measurement of serum alanine aminotransferase, aspartate aminotransferase,urine nitrogen, creatinine and tumor necrosis factor-alpha. Lung, liver and kidney were collected for histopathological assessment. In addition, myeloperoxidase activity and tumor necrosis factor-α in pulmonary tissue were measured.Acetylation of histone H3 in lung was also evaluated by Western blotting.Results LPS resulted in a significant decrease in PaO2, which was increased by VPA administration followed LPS injection. In addition, LPS also induced an increase in the serum levels of alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine, and tumor necrosis factor-alpha. However, these increases were attenuated in the LPS+VPA group. The lungs, liver and kidneys from the LPS group were significantly damaged compared with the control group. However, the damage was attenuated in the LPS+VPA group. Myeloperoxidase activity and tumor necrosis factor-alpha levels in pulmonary tissue increased significantly in the LPS group compared with the control group. These increases were significantly inhibited in the LPS+VPA group. Acetylation of histone H3 in lung tissue in the LPS group was inhibited compared with the control. However, the level of acetylation of histone H3 in the LPS+VPA group was markedly elevated in contrast to the

  10. ICD function and dysfunction in patients with arrhythmogenic cardiac diseases: the role of home monitoring

    NARCIS (Netherlands)

    Asmundis, C. de; Ricciardi, D.; Namdar, M.; Pappaert, G.; Rodriguez-Manero, M.; Wauters, K.; Casado-Arroyo, R.; Rao, J.J.; Bayrak, F.; Chierchia, G.B.; Sarkozy, A.; Brugada, P.

    2013-01-01

    BACKGROUND: Since their implementation in clinical practice, remote home monitoring systems (HM) have undoubtedly become an added value in patients with implantable devices for cardiac rhythm management. The aim of this study was to investigate the impact of HM on clinical management and outcome in

  11. Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis

    Directory of Open Access Journals (Sweden)

    Kain Vasundhara

    2011-11-01

    Full Text Available Abstract Background Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic condition. Methods This study was designed to examine the effect of long-acting calcium channel blocker (CCB, Azelnidipine (AZL on contractile dysfunction, intracellular calcium (Ca2+ cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP injection of streptozotocin (STZ. Contractile functions were traced from live diabetic rats to isolated individual cardiomyocytes including peak shortening (PS, time-to-PS (TPS, time-to-relengthening (TR90, maximal velocity of shortening/relengthening (± dL/dt and intracellular Ca2+ fluorescence. Results Diabetic heart showed significantly depressed PS, ± dL/dt, prolonged TPS, TR90 and intracellular Ca2+ clearing and showed an elevated resting intracellular Ca2+. AZL itself exhibited little effect on myocyte mechanics but it significantly alleviated STZ-induced myocyte contractile dysfunction. Diabetes increased the levels of superoxide, enhanced expression of the cardiac damage markers like troponin I, p67phox NADPH oxidase subunit, restored the levels of the mitochondrial superoxide dismutase (Mn-SOD, calcium regulatory proteins RyR2 and SERCA2a, and suppressed the levels of the anti-apoptotic Bcl-2 protein. All of these STZ-induced alterations were reconciled by AZL treatment. Conclusion Collectively, the data suggest beneficial effect of AZL in diabetic cardiomyopathy via altering intracellular Ca2+ handling proteins and preventing apoptosis by its antioxidant property.

  12. Cardiac Function and Diastolic Dysfunction in Behcet’s Disease: A Systematic Review and Meta-Analysis

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    Fawad Aslam

    2016-01-01

    Full Text Available Background. Cardiovascular involvement in Behcet’s disease (BD is reported and has variable manifestations. It is not clear if diastolic dysfunction (DD is increased in BD. Our objective was to evaluate the existing literature to determine if cardiac dysfunction, particularly DD, was more prevalent in these patients. Methods. A systematic review and meta-analysis of the available studies analyzing the echocardiographic findings in BD was conducted using a random-effects model. Mean differences were used to calculate the effect sizes of the echocardiographic parameters of interest. Results. A total of 22 studies with 1624 subjects were included in the analysis. Patients with BD had statistically significantly larger mean left atrial dimension (0.08, p=0.0008, greater aortic diameter (0.16, p=0.02, significantly reduced ejection fraction (−1.08, p<0.0001, significantly prolonged mitral deceleration time (14.20, p<0.0001, lower E/A ratio (−0.24, p=0.05, and increased isovolumetric relaxation time (7.29, p<0.00001. Conclusion. DD is increased in patients with BD by the presence of several echocardiographic parameters favoring DD as compared to controls. The meta-analysis also identified that LA dimension is increased in BD patients. EF has also been found to be lower in BD patients. Aortic diameter was also increased in BD patients as compared to controls.

  13. Ecstasy (MDMA) Alters Cardiac Gene Expression and DNA Methylation: Implications for Circadian Rhythm Dysfunction in the Heart.

    Science.gov (United States)

    Koczor, Christopher A; Ludlow, Ivan; Hight, Robert S; Jiao, Zhe; Fields, Earl; Ludaway, Tomika; Russ, Rodney; Torres, Rebecca A; Lewis, William

    2015-11-01

    MDMA (ecstasy) is an illicit drug that stimulates monoamine neurotransmitter release and inhibits reuptake. MDMA's acute cardiotoxicity includes tachycardia and arrhythmia which are associated with cardiomyopathy. MDMA acute cardiotoxicity has been explored, but neither long-term MDMA cardiac pathological changes nor epigenetic changes have been evaluated. Microarray analyses were employed to identify cardiac gene expression changes and epigenetic DNA methylation changes. To identify permanent MDMA-induced pathogenetic changes, mice received daily 10- or 35-day MDMA, or daily 10-day MDMA followed by 25-day saline washout (10 + 25 days). MDMA treatment caused differential gene expression (p 1.5) in 752 genes following 10 days, 558 genes following 35 days, and 113 genes following 10-day MDMA + 25-day saline washout. Changes in MAPK and circadian rhythm gene expression were identified as early as 10 days. After 35 days, circadian rhythm genes (Per3, CLOCK, ARNTL, and NPAS2) persisted to be differentially expressed. MDMA caused DNA hypermethylation and hypomethylation that was independent of gene expression; hypermethylation of genes was found to be 71% at 10 days, 68% at 35 days, and 91% at 10 + 25 days washout. Differential gene expression paralleled DNA methylation in 22% of genes at 10-day treatment, 17% at 35 days, and 48% at 10 + 25 days washout. We show here that MDMA induced cardiac epigenetic changes in DNA methylation where hypermethylation predominated. Moreover, MDMA induced gene expression of key elements of circadian rhythm regulatory genes. This suggests a fundamental organism-level event to explain some of the etiologies of MDMA dysfunction in the heart.

  14. Cardiac autonomic dysfunction in patients with schizophrenia and their healthy relatives – a small review

    Directory of Open Access Journals (Sweden)

    Karl Juergen Bär

    2015-06-01

    Full Text Available The majority of excess mortality among people with schizophrenia seems to be caused by cardiovascular complications, and in particular, coronary heart disease. In addition, the prevalence of heart failure and arrhythmias is increased in this population. Reduced efferent vagal activity, which has been consistently described in these patients and their healthy first-degree relatives, might be one important mechanism contributing to their increased cardiac mortality. A decrease in heart rate variability (HRV and complexity was often shown in unmedicated patients when compared to healthy controls. In addition, faster breathing rates, accompanied by shallow breathing, seem to influence autonomic cardiac functioning in acute unmedicated patients substantially. Moreover, low physical fitness is a further and independent cardiac risk factor present in this patient population. Interestingly, new studies describe chronotropic incompetence during physical exercise as an important additional risk factor in patients with schizophrenia. Some studies report a correlation of the autonomic imbalance with the degree of positive symptoms (i.e. delusions and some with the duration of disease. The main body of psychiatric research is focused on mental aspects of the disease, thereby neglecting obvious physical health needs of these patients. Here, a joint effort is needed to design interventional strategies in everyday clinical settings to improve physical health and quality of life.

  15. A novel method for incorporating respiratory-matched attenuation correction in the motion correction of cardiac PET-CT studies

    Science.gov (United States)

    McQuaid, Sarah J.; Lambrou, Tryphon; Hutton, Brian F.

    2011-05-01

    Mismatches between PET and CT datasets due to respiratory effects can lead to artefactual perfusion defects. To overcome this, we have proposed a method of aligning a single CT with each frame of a gated PET study in a semi-automatic manner, incorporating a statistical shape model of the diaphragm and a rigid registration of the heart. This ensures that the structures that could influence the appearance of the reconstructed cardiac activity are correctly matched between emission and transmission datasets. When tested on two patient studies, it was found in both cases that attenuation correction using the proposed technique resulted in PET images that were closer to the gold standard of attenuation correction with a gated CT, compared with scenarios where only heart matching was considered (and not the diaphragm) or where no transformation was performed (i.e. where a single CT frame was used to attenuation-correct all PET frames). These preliminary results suggest that diaphragm matching between PET and CT improves the quantitative accuracy of reconstructed PET images and that the proposed method of using a statistical shape model to describe the diaphragm shape and motion, in combination with a rigid registration to determine respiratory-induced heart motion, is a feasible method of achieving this.

  16. Recent Advances on Pathophysiology, Diagnostic and Therapeutic Insights in Cardiac Dysfunction Induced by Antineoplastic Drugs

    OpenAIRE

    Marilisa Molinaro; Pietro Ameri; Giancarlo Marone; Mario Petretta; Pasquale Abete; Fabio Di Lisa; Sabino De Placido; Domenico Bonaduce; Tocchetti, Carlo G

    2015-01-01

    Along with the improvement of survival after cancer, cardiotoxicity due to antineoplastic treatments has emerged as a clinically relevant problem. Potential cardiovascular toxicities due to anticancer agents include QT prolongation and arrhythmias, myocardial ischemia and infarction, hypertension and/or thromboembolism, left ventricular (LV) dysfunction, and heart failure (HF). The latter is variable in severity, may be reversible or irreversible, and can occur soon after or as a delayed cons...

  17. Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction

    OpenAIRE

    Das, Anindita; Durrant, David; Mitchell, Clint; Mayton, Eric; Hoke, Nicholas N.; Fadi N Salloum; Park, Margaret A.; Qureshi, Ian; Lee, Ray; Dent, Paul; Kukreja, Rakesh C.

    2010-01-01

    We have shown that the potent phosphodiesterase-5 (PDE-5) inhibitor sildenafil (Viagra) induces a powerful effect on reduction of infarct size following ischemia/reperfusion injury and improvement of left ventricular dysfunction in the failing heart after myocardial infarction or doxorubicin (DOX) treatment. In the present study, we further investigated the potential effects of sildenafil on improving antitumor efficacy of DOX in prostate cancer. Cotreatment with sildenafil enhanced DOX-induc...

  18. 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...

  19. Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

    Science.gov (United States)

    Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido-Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramírez-Fernández, Alicia; Alcaide Torres, Juan; Fernandez, Concepción Santiago; Navarro Arce, Isabel; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, José

    2016-01-01

    Purpose To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. Methods This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. Results After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. Conclusion Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery. PMID:27143905

  20. Standardized Extract of Bacopa monniera Attenuates Okadaic Acid Induced Memory Dysfunction in Rats: Effect on Nrf2 Pathway

    Directory of Open Access Journals (Sweden)

    Subhash Dwivedi

    2013-01-01

    Full Text Available The aim of the present study is to investigate the effect of standardized extract of Bacopa monnieri (memory enhancer and Melatonin (an antioxidant on nuclear factor erythroid 2 related factor 2 (Nrf2 pathway in Okadaic acid induced memory impaired rats. OKA (200 ng was administered intracerebroventricularly (ICV to induce memory impairment in rats. Bacopa monnieri (BM-40 and 80 mg/kg and Melatonin (20 mg/kg were administered 1 hr before OKA injection and continued daily up to day 13. Memory functions were assessed by Morris water maze test on days 13–15. Rats were sacrificed for biochemical estimations of oxidative stress, neuroinflammation, apoptosis, and molecular studies of Nrf2, HO1, and GCLC expressions in cerebral cortex and hippocampus brain regions. OKA caused a significant memory deficit with oxidative stress, neuroinflammation, and neuronal loss which was concomitant with attenuated expression of Nrf2, HO1, and GCLC. Treatment with BM and Melatonin significantly improved memory dysfunction in OKA rats as shown by decreased latency time and path length. The treatments also restored Nrf2, HO1, and GCLC expressions and decreased oxidative stress, neuroinflammation, and neuronal loss. Thus strengthening the endogenous defense through Nrf2 modulation plays a key role in the protective effect of BM and Melatonin in OKA induced memory impairment in rats.

  1. Preoperative Cardiac Variables of Diastolic Dysfunction and Clinical Outcomes in Lung Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Ajay Yadlapati

    2013-01-01

    Full Text Available Background. Orthotopic lung transplantation is now widely performed in patients with advanced lung disease. Patients with moderate or severe ventricular systolic dysfunction are typically excluded from lung transplantation; however, there is a paucity of data regarding the prognostic significance of abnormal left ventricular diastolic function and elevated pretransplant pulmonary pressures. Methods. We reviewed the characteristics of 111 patients who underwent bilateral and unilateral lung transplants from 200 to 2009 in order to evaluate the prognostic significance of preoperative markers of diastolic function, including invasively measured pulmonary capillary wedge pressure (PCWP and echocardiographic variables of diastolic dysfunction including mitral A>E and A′>E′. Results. Out of 111 patients, 62 were male (56% and average age was 54.0 ± 10.5 years. Traditional echocardiographic Doppler variables of abnormal diastolic function, including A′>E′ and A>E, did not predict adverse events (P=0.49. Mildly elevated pretransplant PCWP (16–20 mmHg and moderately/severely elevated PCWP (>20 mmHg were not associated with adverse clinical events after transplant (P=0.30. Additionally, all clinical endpoints did not show any statistical significance between the two groups. Conclusions. Pre-lung transplant invasive and echocardiographic findings of elevated pulmonary pressures and abnormal left ventricular diastolic function are not predictive of adverse posttransplant clinical events.

  2. Desmodium gangeticum root extract attenuates isoproterenol-induced cardiac hypertrophic growth in rats.

    OpenAIRE

    Divya Hitler; Parthasarathy Arumugam; Mathivanan Narayanasamy; Elangovan Vellaichamy

    2014-01-01

    Context: Desmodium gangeticum (L) DC (Fabaceae; DG), a medicinal plant that grows in tropical habitats, is widely used to treat various ailments including digestive and inflammatory disorders. Aims: To investigate the possible cardioprotective activity of a DG root extract against isoproterenol (ISO)-induced left ventricular cardiac hypertrophy (LVH) in adult Wistar rats. Methods: Daily intraperitoneal administration of ISO (10 mg/kg body weight, single injection) for 7 days induced LVH...

  3. Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

    Directory of Open Access Journals (Sweden)

    Lee Jung Eun

    2012-09-01

    Full Text Available Abstract Background Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF rats. Methods Animals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry. Results Western blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1 and connective tissue growth factor (CTGF were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA. Conclusions ALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.

  4. 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

  5. Low-dose interpolated average CT for attenuation correction in cardiac PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tung-Hsin [Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taiwan (China); Zhang, Geoffrey [Department of Radiation Oncology, Moffitt Cancer Center, Florida (United States); Wang, Shyh-Jen [Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taiwan (China); Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Chen, Chih-Hao [Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Yang, Bang-Hung [Department of Biomedical Imaging and Radiological Sciences, National Yang Ming University, Taiwan (China); Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Wu, Nien-Yun [Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Huang, Tzung-Chi, E-mail: tzungchi.huang@mail.cmu.edu.t [Department of Biomedical Imaging and Radiological Science, China Medical University, Taiwan (China)

    2010-07-21

    Because of the advantages in the use of high photon flux and thus the short scan times of CT imaging, the traditional {sup 68}Ge scans for positron emission tomography (PET) image attenuation correction have been replaced by CT scans in the modern PET/CT technology. The combination of fast CT scan and slow PET scan often causes image misalignment between the PET and CT images due to respiration motion. Use of the average CT derived from cine CT images is reported to reduce such misalignment. However, the radiation dose to patients is higher with cine CT scans. This study introduces a method that uses breath-hold CT images and their interpolations to generate the average CT for PET image attenuation correction. Breath-hold CT sets are taken at end-inspiration and end-expiration. Deformable image registration is applied to generate a voxel-to-voxel motion matrix between the two CT sets. The motion is equally divided into 5 steps from inspiration to expiration and 5 steps from expiration to inspiration, generating a total of 8 phases of interpolated CT sets. An average CT image is generated from all the 10 phase CT images, including original inhale/exhale CT and 8 interpolated CT sets. Quantitative comparison shows that the reduction of image misalignment artifacts using the average CT from the interpolation technique for PET attenuation correction is at a similar level as that using cine average CT, while the dose to the patient from the CT scans is reduced significantly. The interpolated average CT method hence provides a low dose alternative to cine CT scans for PET attenuation correction.

  6. Low-dose interpolated average CT for attenuation correction in cardiac PET/CT

    International Nuclear Information System (INIS)

    Because of the advantages in the use of high photon flux and thus the short scan times of CT imaging, the traditional 68Ge scans for positron emission tomography (PET) image attenuation correction have been replaced by CT scans in the modern PET/CT technology. The combination of fast CT scan and slow PET scan often causes image misalignment between the PET and CT images due to respiration motion. Use of the average CT derived from cine CT images is reported to reduce such misalignment. However, the radiation dose to patients is higher with cine CT scans. This study introduces a method that uses breath-hold CT images and their interpolations to generate the average CT for PET image attenuation correction. Breath-hold CT sets are taken at end-inspiration and end-expiration. Deformable image registration is applied to generate a voxel-to-voxel motion matrix between the two CT sets. The motion is equally divided into 5 steps from inspiration to expiration and 5 steps from expiration to inspiration, generating a total of 8 phases of interpolated CT sets. An average CT image is generated from all the 10 phase CT images, including original inhale/exhale CT and 8 interpolated CT sets. Quantitative comparison shows that the reduction of image misalignment artifacts using the average CT from the interpolation technique for PET attenuation correction is at a similar level as that using cine average CT, while the dose to the patient from the CT scans is reduced significantly. The interpolated average CT method hence provides a low dose alternative to cine CT scans for PET attenuation correction.

  7. Low-dose interpolated average CT for attenuation correction in cardiac PET/CT

    Science.gov (United States)

    Wu, Tung-Hsin; Zhang, Geoffrey; Wang, Shyh-Jen; Chen, Chih-Hao; Yang, Bang-Hung; Wu, Nien-Yun; Huang, Tzung-Chi

    2010-07-01

    Because of the advantages in the use of high photon flux and thus the short scan times of CT imaging, the traditional 68Ge scans for positron emission tomography (PET) image attenuation correction have been replaced by CT scans in the modern PET/CT technology. The combination of fast CT scan and slow PET scan often causes image misalignment between the PET and CT images due to respiration motion. Use of the average CT derived from cine CT images is reported to reduce such misalignment. However, the radiation dose to patients is higher with cine CT scans. This study introduces a method that uses breath-hold CT images and their interpolations to generate the average CT for PET image attenuation correction. Breath-hold CT sets are taken at end-inspiration and end-expiration. Deformable image registration is applied to generate a voxel-to-voxel motion matrix between the two CT sets. The motion is equally divided into 5 steps from inspiration to expiration and 5 steps from expiration to inspiration, generating a total of 8 phases of interpolated CT sets. An average CT image is generated from all the 10 phase CT images, including original inhale/exhale CT and 8 interpolated CT sets. Quantitative comparison shows that the reduction of image misalignment artifacts using the average CT from the interpolation technique for PET attenuation correction is at a similar level as that using cine average CT, while the dose to the patient from the CT scans is reduced significantly. The interpolated average CT method hence provides a low dose alternative to cine CT scans for PET attenuation correction.

  8. A knowledge-based method for reducing attenuation artefacts caused by cardiac appliances in myocardial PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Hamill, James J [Siemens Medical Solutions, Molecular Imaging, 810 Innovation Dr., Knoxville, TN (United States); Brunken, Richard C [Department of Molecular and Functional Imaging, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH (United States); Bybel, Bohdan [Department of Molecular and Functional Imaging, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH (United States); DiFilippo, Frank P [Department of Molecular and Functional Imaging, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH (United States); Faul, David D [Siemens Medical Solutions, Molecular Imaging, 810 Innovation Dr., Knoxville, TN (United States)

    2006-06-07

    Attenuation artefacts due to implanted cardiac defibrillator leads have previously been shown to adversely impact cardiac PET/CT imaging. In this study, the severity of the problem is characterized, and an image-based method is described which reduces the resulting artefact in PET. Automatic implantable cardioverter defibrillator (AICD) leads cause a moving-metal artefact in the CT sections from which the PET attenuation correction factors (ACFs) are derived. Fluoroscopic cine images were measured to demonstrate that the defibrillator's highly attenuating distal shocking coil moves rhythmically across distances on the order of 1 cm. Rhythmic motion of this magnitude was created in a phantom with a moving defibrillator lead. A CT study of the phantom showed that the artefact contained regions of incorrect, very high CT values and adjacent regions of incorrect, very low CT values. The study also showed that motion made the artefact more severe. A knowledge-based metal artefact reduction method (MAR) is described that reduces the magnitude of the error in the CT images, without use of the corrupted sinograms. The method modifies the corrupted image through a sequence of artefact detection procedures, morphological operations, adjustments of CT values and three-dimensional filtering. The method treats bone the same as metal. The artefact reduction method is shown to run in a few seconds, and is validated by applying it to a series of phantom studies in which reconstructed PET tracer distribution values are wrong by as much as 60% in regions near the CT artefact when MAR is not applied, but the errors are reduced to about 10% of expected values when MAR is applied. MAR changes PET image values by a few per cent in regions not close to the artefact. The changes can be larger in the vicinity of bone. In patient studies, the PET reconstruction without MAR sometimes results in anomalously high values in the infero-septal wall. Clinical performance of MAR is assessed by

  9. Dasatinib Attenuates Pressure Overload Induced Cardiac Fibrosis in a Murine Transverse Aortic Constriction Model.

    Directory of Open Access Journals (Sweden)

    Sundaravadivel Balasubramanian

    Full Text Available Reactive cardiac fibrosis resulting from chronic pressure overload (PO compromises ventricular function and contributes to congestive heart failure. We explored whether nonreceptor tyrosine kinases (NTKs play a key role in fibrosis by activating cardiac fibroblasts (CFb, and could potentially serve as a target to reduce PO-induced cardiac fibrosis. Our studies were carried out in PO mouse myocardium induced by transverse aortic constriction (TAC. Administration of a tyrosine kinase inhibitor, dasatinib, via an intraperitoneally implanted mini-osmotic pump at 0.44 mg/kg/day reduced PO-induced accumulation of extracellular matrix (ECM proteins and improved left ventricular geometry and function. Furthermore, dasatinib treatment inhibited NTK activation (primarily Pyk2 and Fak and reduced the level of FSP1 positive cells in the PO myocardium. In vitro studies using cultured mouse CFb showed that dasatinib treatment at 50 nM reduced: (i extracellular accumulation of both collagen and fibronectin, (ii both basal and PDGF-stimulated activation of Pyk2, (iii nuclear accumulation of Ki67, SKP2 and histone-H2B and (iv PDGF-stimulated CFb proliferation and migration. However, dasatinib did not affect cardiomyocyte morphologies in either the ventricular tissue after in vivo administration or in isolated cells after in vitro treatment. Mass spectrometric quantification of dasatinib in cultured cells indicated that the uptake of dasatinib by CFb was greater that that taken up by cardiomyocytes. Dasatinib treatment primarily suppressed PDGF but not insulin-stimulated signaling (Erk versus Akt activation in both CFb and cardiomyocytes. These data indicate that dasatinib treatment at lower doses than that used in chemotherapy has the capacity to reduce hypertrophy-associated fibrosis and improve ventricular function.

  10. Minocycline suppresses oxidative stress and attenuates fetal cardiac myocyte apoptosis triggered by in utero cocaine exposure

    OpenAIRE

    Sinha-Hikim, Indrani; Shen, Ruoqing; Nzenwa, Ify; GELFAND, ROBERT; Mahata, Sushil K.; Sinha-Hikim, Amiya P.

    2011-01-01

    This study investigates the molecular mechanisms by which minocycline, a second generation tetracycline, prevents cardiac myocyte death induced by in utero cocaine exposure. Timed mated pregnant Sprague-Dawley (SD) rats received one of the following treatments twice daily from embryonic (E) day 15–21 (E15–E21): (i) intraperitoneal (IP) injections of saline (control); (ii) IP injections of cocaine (15 mg/kg BW); and (iii) IP injections of cocaine + oral administration of 25 mg/kg BW of minocyc...

  11. Cardiac diastolic dysfunction in high-fat diet fed mice is associated with lipotoxicity without impairment of cardiac energetics in vivo

    NARCIS (Netherlands)

    Abdurrachim, Desiree; Ciapaite, Jolita; Wessels, Bart; Nabben, Miranda; Luiken, Joost J. F. P.; Nicolay, Klaas; Prompers, Jeanine J.

    2014-01-01

    Obesity is often associated with abnormalities in cardiac morphology and function. This study tested the hypothesis that obesity-related cardiomyopathy is caused by impaired cardiac energetics. In a mouse model of high-fat diet (HFD)-induced obesity, we applied in vivo cardiac P-31 magnetic resonanc

  12. Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia

    Science.gov (United States)

    Schäfer, Michaela; Oeing, Christian U.; Rohm, Maria; Baysal-Temel, Ezgi; Lehmann, Lorenz H.; Bauer, Ralf; Volz, H. Christian; Boutros, Michael; Sohn, Daniela; Sticht, Carsten; Gretz, Norbert; Eichelbaum, Katrin; Werner, Tessa; Hirt, Marc N.; Eschenhagen, Thomas; Müller-Decker, Karin; Strobel, Oliver; Hackert, Thilo; Krijgsveld, Jeroen; Katus, Hugo A.; Berriel Diaz, Mauricio; Backs, Johannes; Herzig, Stephan

    2015-01-01

    Objectives Cancer cachexia affects the majority of tumor patients and significantly contributes to high mortality rates in these subjects. Despite its clinical importance, the identity of tumor-borne signals and their impact on specific peripheral organ systems, particularly the heart, remain mostly unknown. Methods and results By combining differential colon cancer cell secretome profiling with large-scale cardiomyocyte phenotyping, we identified a signature panel of seven “cachexokines”, including Bridging integrator 1, Syntaxin 7, Multiple inositol-polyphosphate phosphatase 1, Glucosidase alpha acid, Chemokine ligand 2, Adamts like 4, and Ataxin-10, which were both sufficient and necessary to trigger cardiac atrophy and aberrant fatty acid metabolism in cardiomyocytes. As a prototypical example, engineered secretion of Ataxin-10 from non-cachexia-inducing cells was sufficient to induce cachexia phenotypes in cardiomyocytes, correlating with elevated Ataxin-10 serum levels in murine and human cancer cachexia models. Conclusions As Ataxin-10 serum levels were also found to be elevated in human cachectic cancer patients, the identification of Ataxin-10 as part of a cachexokine cocktail now provides a rational approach towards personalized predictive, diagnostic and therapeutic measures in cancer cachexia. PMID:26909315

  13. Persistent Maternal Cardiac Dysfunction After Preeclampsia Identifies Patients at Risk for Recurrent Preeclampsia.

    Science.gov (United States)

    Valensise, Herbert; Lo Presti, Damiano; Gagliardi, Giulia; Tiralongo, Grazia Maria; Pisani, Ilaria; Novelli, Gian Paolo; Vasapollo, Barbara

    2016-04-01

    The purpose of our study was to assess cardiac function in nonpregnant women with previous early preeclampsia before a second pregnancy to highlight the cardiovascular pattern, which may take a risk for recurrent preeclampsia. Seventy-five normotensive patients with previous preeclampsia and 147 controls with a previous uneventful pregnancy were enrolled in a case-control study and submitted to echocardiographic examination in the nonpregnant state 12 to 18 months after the first delivery. All patients included in the study had pregnancy within 24 months from the echocardiographic examination and were followed until term. Twenty-two (29%) of the 75 patients developed recurrent preeclampsia. In the nonpregnant state, patients with recurrent preeclampsia compared with controls and nonrecurrent preeclampsia had lower stroke volume (63 ± 14 mL versus 73 ± 12 mL and 70 ± 11 mL, Ppreeclampsia compared with controls (30.0 ± 6.3 g/m(2.7) and 30.4 ± 6.8 g/m(2.7) versus 24.8 ± 5.0 g/m(2.7), Ppreeclampsia. Previous preeclamptic patients with nonrecurrent preeclampsia show left ventricular structural and functional features intermediate with respect to controls and recurrent preeclampsia.

  14. Myocardial overexpression of Mecr, a gene of mitochondrial FAS II leads to cardiac dysfunction in mouse.

    Directory of Open Access Journals (Sweden)

    Zhijun Chen

    Full Text Available It has been recently recognized that mammalian mitochondria contain most, if not all, of the components of fatty acid synthesis type II (FAS II. Among the components identified is 2-enoyl thioester reductase/mitochondrial enoyl-CoA reductase (Etr1/Mecr, which catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters, generating saturated acyl-groups. Although the FAS type II pathway is highly conserved, its physiological role in fatty acid synthesis, which apparently occurs simultaneously with breakdown of fatty acids in the same subcellular compartment in mammals, has remained an enigma. To study the in vivo function of the mitochondrial FAS in mammals, with special reference to Mecr, we generated mice overexpressing Mecr under control of the mouse metallothionein-1 promoter. These Mecr transgenic mice developed cardiac abnormalities as demonstrated by echocardiography in vivo, heart perfusion ex vivo, and electron microscopy in situ. Moreover, the Mecr transgenic mice showed decreased performance in endurance exercise testing. Our results showed a ventricular dilatation behind impaired heart function upon Mecr overexpression, concurrent with appearance of dysmorphic mitochondria. Furthermore, the data suggested that inappropriate expression of genes of FAS II can result in the development of hereditary cardiomyopathy.

  15. Translocation and cleavage of myocardial dystrophin as a common pathway to advanced heart failure: A scheme for the progression of cardiac dysfunction

    OpenAIRE

    Toyo-Oka, Teruhiko; Kawada, Tomie; Nakata, Jumi; Xie, Han; Urabe, Masashi; Masui, Fujiko; Ebisawa, Takashi; Tezuka, Asaki; Iwasawa, Kuniaki; Nakajima, Toshiaki; Uehara, Yoshio; Kumagai, Hiroyuki; Kostin, Sawa; Schaper, Jutta; Nakazawa, Mikio

    2004-01-01

    Advanced heart failure (HF) is the leading cause of death in developed countries. The mechanism underlying the progression of cardiac dysfunction needs to be clarified to establish approaches to prevention or treatment. Here, using TO-2 hamsters with hereditary dilated cardiomyopathy, we show age-dependent cleavage and translocation of myocardial dystrophin (Dys) from the sarcolemma (SL) to the myoplasm, increased SL permeability in situ, and a close relationship between the loss of Dys and h...

  16. Neuroendocrine and cardiac metabolic dysfunction and NLRP3 inflammasome activation in adipose tissue and pancreas following chronic spinal cord injury in the mouse

    Directory of Open Access Journals (Sweden)

    Mark S. Nash

    2013-09-01

    Full Text Available CVD (cardiovascular disease represents a leading cause of mortality in chronic SCI (spinal cord injury. Several component risk factors are observed in SCI; however, the underlying mechanisms that contribute to these risks have not been defined. Central and peripheral chronic inflammation is associated with metabolic dysfunction and CVD, including adipokine regulation of neuroendocrine and cardiac function and inflammatory processes initiated by the innate immune response. We use female C57 Bl/6 mice to examine neuroendocrine, cardiac, adipose and pancreatic signaling related to inflammation and metabolic dysfunction in response to experimentally induced chronic SCI. Using immuno-histochemical, -precipitation, and -blotting analysis, we show decreased POMC (proopiomelanocortin and increased NPY (neuropeptide-Y expression in the hypothalamic ARC (arcuate nucleus and PVN (paraventricular nucleus, 1-month post-SCI. Long-form leptin receptor (Ob-Rb, JAK2 (Janus kinase/STAT3 (signal transducer and activator of transcription 3/p38 and RhoA/ROCK (Rho-associated kinase signaling is significantly increased in the heart tissue post-SCI, and we observe the formation and activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3 inflammasome in VAT (visceral adipose tissue and pancreas post-SCI. These data demonstrate neuroendocrine signaling peptide alterations, associated with central inflammation and metabolic dysfunction post-SCI, and provide evidence for the peripheral activation of signaling mechanisms involved in cardiac, VAT and pancreatic inflammation and metabolic dysfunction post-SCI. Further understanding of biological mechanisms contributing to SCI-related inflammatory processes and metabolic dysfunction associated with CVD pathology may help to direct therapeutic and rehabilitation countermeasures.

  17. EXERCISE STRESS ECHOCARDIOGRAPHY WITH TISSUE DOPPLER IMAGING (TDI DETECTS EARLY SYSTOLIC DYSFUNCTION IN BETA-THALASSEMIA MAJOR PATIENTS WITHOUT CARDIAC IRON OVERLOAD

    Directory of Open Access Journals (Sweden)

    Umberto Barbero

    2012-06-01

    Full Text Available Iron Overload Cardiomyopathy (IOC is still the main cause of death in thalassemia major (TM patients. Unfortunately, Conventional Echocardiography fails to predict early cardiac dysfunction. As Tissue Doppler Imaging (TDI may demonstrate regional myocardial dysfunction, we wondered if exercise may reveal abnormalities at TDI which are not evident at rest. To try to evaluate left and right myocardial performances at rest and after maximal exercise by both conventional and TDI parameters, 46 beta-TM adult patients and 39 control subjects were enrolled. All patients had a liver iron quantification by Superconducting Quantum Interference Device (SQUID and also a cardiac iron assessment by MRI (T2*: 38 TM patients had no evidence of cardiac iron overload. Whereas TM patients did not shown diastolic dysfunction and all of them presented a good global response to exercise, TDI detected a reduced increase of the S’ waves of left ventricle basal segment during exercise. This finding seems to have some weak but interesting relations with iron overload markers. In conclusion, in our study, exercise stress TDI-echocardiography was able to demonstrate subtle systolic abnormalities that were missed by Conventional Echocardiography. Further studies are required to determine the meaning and the clinical impact of these results.

  18. Distinctive cardiac autonomic dysfunction following stress exposure in both sexes in an animal model of PTSD.

    Science.gov (United States)

    Koresh, Ori; Kaplan, Zeev; Zohar, Joseph; Matar, Michael A; Geva, Amir B; Cohen, Hagit

    2016-07-15

    It is unclear whether the poor autonomic flexibility or dysregulation observed in patients with posttraumatic stress disorder (PTSD) represents a pre-trauma vulnerability factor or results from exposure to trauma. We used an animal model of PTSD to assess the association between the behavioral response to predator scent stress (PSS) and the cardiac autonomic modulation in male and female rats. The rats were surgically implanted with radiotelemetry devices to measure their electrocardiograms and locomotor activity (LMA). Following baseline telemetric monitoring, the animals were exposed to PSS or sham-PSS. Continuous telemetric monitoring (24h/day sampling) was performed over the course of 7days. The electrocardiographic recordings were analyzed using the time- and frequency-domain indexes of heart rate variability (HRV). The behavioral response patterns were assessed using the elevated plus maze and acoustic startle response paradigms for the retrospective classification of individuals according to the PTSD-related cut-off behavioral criteria. During resting conditions, the male rats had significantly higher heart rates (HR) and lower HRV parameters than the female rats during both the active and inactive phases of the daily cycle. Immediately after PSS exposure, both the female and male rats demonstrated a robust increase in HR and a marked drop in HRV parameters, with a shift of sympathovagal balance towards sympathetic predominance. In both sexes, autonomic system habituation and recovery were selectively inhibited in the rats whose behavior was extremely disrupted after exposure to PSS. However, in the female rats, exposure to the PSS produced fewer EBR rats, with a more rapid recovery curve than that of the male rats. PSS did not induce changes to the circadian rhythm of the LMA. According to our results, PTSD can be conceptualized as a disorder that is related to failure-of-recovery mechanisms that impede the restitution of physiological homeostasis. PMID

  19. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Suo, Yu-Ping [Department of Obstetrics and Gynecology, Shanxi Provincial People' s Hospital, Taiyuan 030012 (China); Yue, Li-Ying [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China)

    2014-02-01

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

  20. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

  1. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xin-Ai; Jia, Lin-Lin [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Cui, Wei [Department of Endocrinology and Metabolism, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Zhang, Meng [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Chen, Wensheng [Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Yuan, Zu-Yi [Department of Cardiovascular Medicine, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Guo, Jing [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Li, Hui-Hua [Key Laboratory of Remodeling-related Cardiovascular Diseases, Department of Pathology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Liu, Hao, E-mail: haoliu75@163.com [Department of Neurosurgery, First Affiliated Hospital of Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China); Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi' an Jiaotong University Cardiovascular Research Center, Xi' an Jiaotong University School of Medicine, Xi' an 710061 (China)

    2014-11-15

    We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

  2. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    International Nuclear Information System (INIS)

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

  3. Respective roles of scatter, attenuation, depth-dependent collimator response and finite spatial resolution in cardiac single-photon emission tomography quantitation: a Monte Carlo study

    Energy Technology Data Exchange (ETDEWEB)

    El Fakhri, G.N.; Buvat, I.; Pelegrini, M.; Benali, H.; Todd-Pokropek, A.; Paola, R. di [Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Necker, 75 - Paris (France); Almeida, P.; Bendriem, B. [SHFJ, Groupe Instrumentation PET/SPET, Orsay (France)

    1999-05-01

    The purpose of this study was to investigate the relative influence of scatter, attenuation, depth-dependent collimator response and finite spatial resolution upon the image characteristics in cardiac single-photon emission tomography (SPET). An acquisition of an anthropomorphic cardiac phantom was performed together with corresponding SPET Monte Carlo simulations. The cardiac phantom and the Monte Carlo simulations were designed so that the effect of scatter, attenuation, depth-dependent collimator response and finite spatial resolution could be studied individually and in combination. The impact of each physical effect and of combinations of effects was studied in terms of absolute and relative quantitative accuracy, spatial resolution and signal-to-noise ratio (SNR) in the resulting images. No corrections for these effects were assessed. Results obtained from Monte Carlo simulations and real acquisitions were in excellent agreement. Attenuation introduced about 90% activity underestimation in a 10-mm-thick left ventricle wall while finite spatial resolution alone introduced about 30% activity underestimation. Scatter had a negligible impact on quantitative accuracy in the recontructed slices when attenuation was present. Neither bull`s eye map homogeneity nor contrast between a hot and a cold region were affected by depth-dependent collimator response or finite spatial resolution. Bull`s eye map homogeneity was severely affected by attenuation but not by scatter. Attenuation and scatter reduced contrast by about 20% each. Both attenuation and scatter increased the full-width at half-maximum (FWHM) characterizing the spatial resolution of the imaging system by {approx}1 mm each but the main effect responsible for the observed 11-mm FWHM spatial resolution was the depth-dependent collimator response. SNR was reduced by a factor of {approx}2.5 because of attenuation, while scattered counts increased SNR by {approx}10%. In conclusion, the quantification of the

  4. Long-Lived αMUPA Mice Show Attenuation of Cardiac Aging and Leptin-Dependent Cardioprotection.

    Directory of Open Access Journals (Sweden)

    Esther Levy

    Full Text Available αMUPA transgenic mice spontaneously consume less food compared with their wild type (WT ancestors due to endogenously increased levels of the satiety hormone leptin. αMUPA mice share many benefits with mice under caloric restriction (CR including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of αMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, αMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while αMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in αMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in αMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin abrogated the αMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the αMUPA myocardium. αMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of αMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in αMUPA mice, indicating the attenuation of cardiac aging. αMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR.

  5. Acute lung injury induces cardiovascular dysfunction

    DEFF Research Database (Denmark)

    Suda, Koichi; Tsuruta, Masashi; Eom, Jihyoun;

    2011-01-01

    Acute lung injury (ALI) is associated with systemic inflammation and cardiovascular dysfunction. IL-6 is a biomarker of this systemic response and a predictor of cardiovascular events, but its possible causal role is uncertain. Inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) down......-regulate the systemic expression of IL-6, but whether they can ameliorate the cardiovascular dysfunction related to ALI is uncertain. We sought to determine whether IL-6 contributes to the cardiovascular dysfunction related to ALI, and whether budesonide/formoterol ameliorates this process. Wild-type mice were...... these impairments (vasodilatory responses to acetylcholine, P = 0.005; cardiac output, P = 0.025). Pretreatment with the combination of budesonide and formoterol, but not either alone, ameliorated the vasodilatory responses to acetylcholine (P = 0.018) and cardiac output (P drugs also attenuated...

  6. Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM{sub 10})

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Ryohei; Hiraiwa, Kunihiko; Cheng, Jui Chih [UBC James Hogg Research Centre, St. Paul' s Hospital, University of British Columbia, Vancouver (Canada); Bai, Ni [UBC James Hogg Research Centre, St. Paul' s Hospital, University of British Columbia, Vancouver (Canada); Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver (Canada); Vincent, Renaud [Environmental Health Sciences and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa (Canada); Francis, Gordon A.; Sin, Don D. [UBC James Hogg Research Centre, St. Paul' s Hospital, University of British Columbia, Vancouver (Canada); Van Eeden, Stephan F., E-mail: Stephan.vanEeden@hli.ubc.ca [UBC James Hogg Research Centre, St. Paul' s Hospital, University of British Columbia, Vancouver (Canada)

    2013-10-01

    Exposure to ambient air particulate matter (particles less than 10 μm or PM{sub 10}) has been shown to be an independent risk factor for the development and progression of atherosclerosis. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have well-established anti-inflammatory properties. The aim of this study was to determine the impact of statins on the adverse functional and morphological changes in blood vessels induced by PM{sub 10}. New Zealand White rabbits fed with a high fat diet were subjected to balloon injury to their abdominal aorta followed by PM{sub 10}/saline exposure for 4 weeks ± lovastatin (5 mg/kg/day) treatment. PM{sub 10} exposure accelerated balloon catheter induced plaque formation and increased intimal macrophages and lipid accumulation while lovastatin attenuated these changes and promoted smooth muscle cell recruitment into plaques. PM{sub 10} impaired vascular acetylcholine (Ach) responses and increased vasoconstriction induced by phenylephrine as assessed by wire myograph. Supplementation of nitric oxide improved the impaired Ach responses. PM{sub 10} increased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in blood vessels and increased the plasma levels of endothelin-1 (ET-1). Incubation with specific inhibitors for iNOS, COX-2 or ET-1 in the myograph chambers significantly improved the impaired vascular function. Lovastatin decreased the expression of these mediators in atherosclerotic lesions and improved endothelial dysfunction. However, lovastatin was unable to reduce blood lipid levels to the baseline level in rabbits exposed to PM{sub 10}. Taken together, statins protect against PM{sub 10}-induced cardiovascular disease by reducing atherosclerosis and improving endothelial function via their anti-inflammatory properties. - Highlights: • Coarse particulate matter (PM{sub 10}) accelerated balloon injury-induced plaque formation. • Lovastatin decreased intimal

  7. The Protective Effect of Fasudil on the Structure and Function of Cardiac Mitochondria from Rats with Type 2 Diabetes Induced by Streptozotocin with a High-Fat Diet Is Mediated by the Attenuation of Oxidative Stress

    OpenAIRE

    Guo, Rong; Liu, Baoxin; Zhou, Shunping; ZHANG, BUCHUN; XU, YAWEI

    2013-01-01

    Dysfunction of cardiac mitochondria appears to play a substantial role in cardiomyopathy or myocardial dysfunction and is a promising therapeutic target for many cardiovascular diseases. We investigated the effect of the Rho/Rho-associated protein kinase (ROCK) inhibitor fasudil on cardiac mitochondria from rats in which diabetes was induced by a combination of streptozotocin (STZ) and a sustained high-fat diet. Eight weeks after diabetes was induced by a single intraperitoneal injection of 5...

  8. Minocycline attenuates brain tissue levels of TNF-α produced by neurons after prolonged hypothermic cardiac arrest in rats

    Science.gov (United States)

    Drabek, Tomas; Janata, Andreas; Wilson, Caleb D.; Stezoski, Jason; Janesko-Feldman, Keri; Tisherman, Samuel A.; Foley, Lesley M.; Verrier, Jonathan; Kochanek, Patrick M.

    2014-01-01

    Neuro-cognitive disabilities are a well-recognized complication of hypothermic circulatory arrest. We and others have reported that prolonged cardiac arrest (CA) produces neuronal death and microglial proliferation and activation that are only partially mitigated by hypothermia. Microglia, and possibly other cells, are suggested to elaborate tumor necrosis factor alpha (TNF-α) which can trigger neuronal death cascades and exacerbate edema after CNS insults. Minocycline is neuroprotective in some brain ischemia models in part by blunting the microglial response. We tested the hypothesis that minocycline would attenuate neuroinflammation as reflected by brain tissue levels of TNF-α after hypothermic CA in rats. Rats were subjected to rapid exsanguination, followed by a 6 min normothermic CA. Hypothermia (30 °C) was then induced by an aortic saline flush. After a total of 20 min CA, resuscitation was achieved via cardiopulmonary bypass (CPB). After 5 min reperfusion, minocycline (90 mg/kg; n=6) or vehicle (PBS; n=6) were given. Hypothermia (34 °C) was maintained for 6 h. Rats were sacrificed at 6 or 24 h. TNF-α was quantified (ELISA) in four brain regions (cerebellum, CEREB; cortex, CTX; hippocampus, HIP; striatum, STRI). Naïve rats (n=6) and rats subjected to the same anesthesia and CPB but no CA served as controls (n=6). Immunocytochemistry was used to localize TNF-α. Naïve rats and CPB controls had no detectable TNF-α in any brain region. CA markedly increased brain TNF-α. Regional differences were seen, with the highest TNF-α levels in striatum in CA groups (10-fold higher, P<0.05 vs. all other brain regions). TNF-α was undetectable at 24 h. Minocycline attenuated TNF-α levels in CTX, HIP and STRI (P<0.05). TNF-α showed unique co-localization with neurons. In conclusion, we report region-dependent early increases in brain TNF-α levels after prolonged hypothermic CA, with maximal increases in striatum. Surprisingly, TNF-α co-localized in neurons and

  9. Alcohol Dehydrogenase Protects against Endoplasmic Reticulum Stress-Induced Myocardial Contractile Dysfunction via Attenuation of Oxidative Stress and Autophagy: Role of PTEN-Akt-mTOR Signaling.

    Directory of Open Access Journals (Sweden)

    Jiaojiao Pang

    Full Text Available The endoplasmic reticulum (ER plays an essential role in ensuring proper folding of the newly synthesized proteins. Aberrant ER homeostasis triggers ER stress and development of cardiovascular diseases. ADH is involved in catalyzing ethanol to acetaldehyde although its role in cardiovascular diseases other than ethanol metabolism still remains elusive. This study was designed to examine the impact of ADH on ER stress-induced cardiac anomalies and underlying mechanisms involved using cardiac-specific overexpression of alcohol dehydrogenase (ADH.ADH and wild-type FVB mice were subjected to the ER stress inducer tunicamycin (1 mg/kg, i.p., for 48 hrs. Myocardial mechanical and intracellular Ca(2+ properties, ER stress, autophagy and associated cell signaling molecules were evaluated.ER stress compromised cardiac contractile function (evidenced as reduced fractional shortening, peak shortening, maximal velocity of shortening/relengthening, prolonged relengthening duration and impaired intracellular Ca(2+ homeostasis, oxidative stress and upregulated autophagy (increased LC3B, Atg5, Atg7 and p62, along with dephosphorylation of PTEN, Akt and mTOR, all of which were attenuated by ADH. In vitro study revealed that ER stress-induced cardiomyocyte anomaly was abrogated by ADH overexpression or autophagy inhibition using 3-MA. Interestingly, the beneficial effect of ADH was obliterated by autophagy induction, inhibition of Akt and mTOR. ER stress also promoted phosphorylation of the stress signaling ERK and JNK, the effect of which was unaffected by ADH transgene.Taken together, these findings suggested that ADH protects against ER stress-induced cardiac anomalies possibly via attenuation of oxidative stress and PTEN/Akt/mTOR pathway-regulated autophagy.

  10. Arsenic trioxide attenuated the rejection of major histocompatibility complex fully-mismatched cardiac allografts in mice.

    Science.gov (United States)

    Yan, S; Zhang, Q Y; Zhou, B; Xue, L; Chen, H; Wang, Y; Zheng, S S

    2009-06-01

    We investigated the effects of arsenic trioxide (As(2)O(3)) on allogeneic immune response using a mouse heart transplantation model. Mice were randomly divided into 4 groups of 6 animals each. The control group received phosphate-buffered saline (PBS); the As(2)O(3)-treated group, intraperitoneal (IP) injection of As(2)O(3) (1 mg/kg) from days -3 to 10 after heart transplantation. The cyclosporine (CsA)-treated group was given a subtherapeutic dose of CsA (10 mg/kg) IP, and the As(2)O(3) plus CsA-treated group, a combined protocol of As(2)O(3) and CsA. Six days after transplantation, cardiac allografts were harvested for immunohistology and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The survival of the allografts was significantly improved among the As(2)O(3)-treated group compared with the control group (17.2 +/- 1.9 vs 8.0 +/- 0.9 days; P < .05). A marked prolongation (28.6 +/- 6.0 days) of graft survival was achieved by the combined protocol compared with the CsA-treated group (9.6 +/- 3.0 days; P < .05) or the As(2)O(3)-treated group. Allografts of As(2)O(3)-treated and As(2)O(3) plus CsA-treated mice showed a changing pattern of Th1/Th2 cytokine mRNA expression. Allograft rejection was apparently alleviated by low-dose As(2)O(3), and particularly when combined with a subtherapeutic CsA dose. PMID:19545743

  11. Desmodium gangeticum root extract attenuates isoproterenol-induced cardiac hypertrophic growth in rats.

    Directory of Open Access Journals (Sweden)

    Divya Hitler

    2014-10-01

    Full Text Available Context: Desmodium gangeticum (L DC (Fabaceae; DG, a medicinal plant that grows in tropical habitats, is widely used to treat various ailments including digestive and inflammatory disorders. Aims: To investigate the possible cardioprotective activity of a DG root extract against isoproterenol (ISO-induced left ventricular cardiac hypertrophy (LVH in adult Wistar rats. Methods: Daily intraperitoneal administration of ISO (10 mg/kg body weight, single injection for 7 days induced LVH in rats. The LVH rats were post-treated orally with DG (100 mg/kg body weight for a period of 30 days. Thereafter, changes in heart weight (HW and body weight (BW, HW/BW ratio, percent of hypertrophy, collagen accumulation, activities of matrix metalloproteinase (MMP -2 and -9, superoxide dismutase (SOD and catalase (CAT enzymes, and the level of an oxidative stress marker, lipid peroxide (LPO, were determined. Results: HW/BW ratio, an indicator of hypertrophic growth, was significantly reduced in DG root post-treated LVH rats as compared with that for the non-treated LVH rats. The altered levels of ventricular LPO, collagen, MMPs-2 and -9, and antioxidant enzymes in the ISO-treated animals reverted back to near normal upon DG treatment. Further, the anti-hypertrophic activity of DG was comparable to that of the standard drug losartan (10 mg/kg. Conclusions: The results of the present study suggest that the aqueous root extract of DG exhibited anti-hypertrophic activity in-vivo by inhibiting ISO-induced ROS generation and MMP activities.

  12. Predictive Value of Beat-to-Beat QT Variability Index across the Continuum of Left Ventricular Dysfunction: Competing Risks of Non-cardiac or Cardiovascular Death, and Sudden or Non-Sudden Cardiac Death

    Science.gov (United States)

    Tereshchenko, Larisa G.; Cygankiewicz, Iwona; McNitt, Scott; Vazquez, Rafael; Bayes-Genis, Antoni; Han, Lichy; Sur, Sanjoli; Couderc, Jean-Philippe; Berger, Ronald D.; de Luna, Antoni Bayes; Zareba, Wojciech

    2012-01-01

    Background The goal of this study was to determine the predictive value of beat-to-beat QT variability in heart failure (HF) patients across the continuum of left ventricular dysfunction. Methods and Results Beat-to-beat QT variability index (QTVI), heart rate variance (LogHRV), normalized QT variance (QTVN), and coherence between heart rate variability and QT variability have been measured at rest during sinus rhythm in 533 participants of the Muerte Subita en Insuficiencia Cardiaca (MUSIC) HF study (mean age 63.1±11.7; males 70.6%; LVEF >35% in 254 [48%]) and in 181 healthy participants from the Intercity Digital Electrocardiogram Alliance (IDEAL) database. During a median of 3.7 years of follow-up, 116 patients died, 52 from sudden cardiac death (SCD). In multivariate competing risk analyses, the highest QTVI quartile was associated with cardiovascular death [hazard ratio (HR) 1.67(95%CI 1.14-2.47), P=0.009] and in particular with non-sudden cardiac death [HR 2.91(1.69-5.01), P<0.001]. Elevated QTVI separated 97.5% of healthy individuals from subjects at risk for cardiovascular [HR 1.57(1.04-2.35), P=0.031], and non-sudden cardiac death in multivariate competing risk model [HR 2.58(1.13-3.78), P=0.001]. No interaction between QTVI and LVEF was found. QTVI predicted neither non-cardiac death (P=0.546) nor SCD (P=0.945). Decreased heart rate variability (HRV) rather than increased QT variability was the reason for increased QTVI in this study. Conclusions Increased QTVI due to depressed HRV predicts cardiovascular mortality and non-sudden cardiac death, but neither SCD nor excracardiac mortality in HF across the continuum of left ventricular dysfunction. Abnormally augmented QTVI separates 97.5% of healthy individuals from HF patients at risk. PMID:22730411

  13. 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

    that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex. METHODS: We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS > or =120 ms and LV ejection fraction......OBJECTIVES: The aim of this study was to determine the long-term effects of cardiac resynchronization therapy (CRT) in the European cohort of patients enrolled in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. BACKGROUND: Previous data suggest...... composite response. The main secondary study end point was left ventricular end-systolic volume index (LVESVi). RESULTS: In the CRT ON group, 19% of patients were worsened versus 34% in the CRT OFF group (p = 0.01). The LVESVi decreased by a mean of 27.5 +/- 31.8 ml/m(2) in the CRT ON group versus 2...

  14. Activation of mitochondrial STAT-3 and reduced mitochondria damage during hypothermia treatment for post-cardiac arrest myocardial dysfunction.

    Science.gov (United States)

    Huang, Chien-Hua; Tsai, Min-Shan; Chiang, Chih-Yen; Su, Yu-Jen; Wang, Tzung-Dau; Chang, Wei-Tien; Chen, Huei-Wen; Chen, Wen-Jone

    2015-11-01

    While therapeutic hypothermia improves the outcomes of individuals in cardiac arrest, the hemodynamic responses and mechanisms which underlie hypothermia-induced cardioprotection are not fully understood. Therefore, we investigated the mechanism by which induced hypothermia preserves cardiac function and protects against mitochondrial damage following cardiac arrest. Cardiac arrest was induced in adult male Wistar rats by asphyxiation for 8.5 min. Following resuscitation, the animals were randomly assigned to a hypothermia (32 °C) or normothermia (37 °C) group. Monitoring results showed that cardiac output at the fourth hour after resuscitation was significantly better in rats treated with hypothermia when compared to rats treated with normothermia (P mitochondrial permeability transition pores occurred less frequently in the hypothermic group. While complex I/III activity in the electron transport reaction was damaged after cardiac arrest and resuscitation, the degree of injury was ameliorated by hypothermia treatment (P mitochondrial integrity and electron transport activity.

  15. Cardiac Shock Wave Therapy Attenuates H9c2 Myoblast Apoptosis by Activating the AKT Signal Pathway

    Directory of Open Access Journals (Sweden)

    Weiwei Yu

    2014-04-01

    Full Text Available Background: Previous studies have demonstrated that Cardiac Shock Wave Therapy (CSWT improves myocardial perfusion and cardiac function in a porcine model of chronic myocardial ischemia and also ameliorates myocardial ischemia in patients with severe coronary artery disease (CAD. Apoptosis plays a key role in ischemic myocardial pathogenesis. However, it remains unclear whether CSWT is beneficial for ischemia/hypoxia (I/H-induced myocardial cell apoptosis and by which mechanism CSWT could improve heart function. We put forward the hypothesis that CSWT might protect heart function during ischemia/hypoxia by decreasing apoptosis. Methods: We generated ischemia/hypoxia (I/H-induced apoptosis in the H9c2 myoblast cell line to examine the CSWT function and possible mechanisms. H9c2 cells were treated under hypoxic serum-starved conditions for 24 h and then treated with or without CSWT (500 shots, 0.06, 0.09, 0.12mJ/mm2. The apoptotic cell rate was determined by flow cytometry assay, cell viability was examined by the MTT assay, nuclear fragmentation was detected by Hoechst 33342 staining, and the mitochondrial-mediated intrinsic pathway of apoptosis was assessed by the expression of Bax and Bcl-2 protein and Caspase3 activation. Results: First, apoptosis could be induced by ischemia/hypoxia in H9c2 cells. Second, CSWT attenuates the cell death and decreases the H9c2 cell apoptosis rate induced by ischemia and hypoxia. Third, CSWT suppresses the expression of apoptosis molecules that regulate the intrinsic pathway of apoptosis in H9c2 cells. Fourth, CSWT increases the phosphorylation of AKT, which indicates the activation of the PI3K-AKT pathway. Conclusions: These results indicate that CSWT exerts a protective effect against I/H-induced cell death, potentially by preventing the activation of components of the mitochondrial-dependent intrinsic apoptotic pathway. We also demonstrate that the PI3K-Akt pathway may be involved in the CSWT effects on

  16. Left ventricular dysfunction with reduced functional cardiac reserve in diabetic and non-diabetic LDL-receptor deficient apolipoprotein B100-only mice

    Directory of Open Access Journals (Sweden)

    Bosch Fatima

    2011-06-01

    Full Text Available Abstract Background Lack of suitable mouse models has hindered the studying of diabetic macrovascular complications. We examined the effects of type 2 diabetes on coronary artery disease and cardiac function in hypercholesterolemic low-density lipoprotein receptor-deficient apolipoprotein B100-only mice (LDLR-/-ApoB100/100. Methods and results 18-month-old LDLR-/-ApoB100/100 (n = 12, diabetic LDLR-/-ApoB100/100 mice overexpressing insulin-like growth factor-II (IGF-II in pancreatic beta cells (IGF-II/LDLR-/-ApoB100/100, n = 14 and age-matched C57Bl/6 mice (n = 15 were studied after three months of high-fat Western diet. Compared to LDLR-/-ApoB100/100 mice, diabetic IGF-II/LDLR-/-ApoB100/100 mice demonstrated more calcified atherosclerotic lesions in aorta. However, compensatory vascular enlargement was similar in both diabetic and non-diabetic mice with equal atherosclerosis (cross-sectional lesion area ~60% and consequently the lumen area was preserved. In coronary arteries, both hypercholesterolemic models showed significant stenosis (~80% despite positive remodeling. Echocardiography revealed severe left ventricular systolic dysfunction and anteroapical akinesia in both LDLR-/-ApoB100/100 and IGF-II/LDLR-/-ApoB100/100 mice. Myocardial scarring was not detected, cardiac reserve after dobutamine challenge was preserved and ultrasructural changes revealed ischemic yet viable myocardium, which together with coronary artery stenosis and slightly impaired myocardial perfusion suggest myocardial hibernation resulting from chronic hypoperfusion. Conclusions LDLR-/-ApoB100/100 mice develop significant coronary atherosclerosis, severe left ventricular dysfunction with preserved but diminished cardiac reserve and signs of chronic myocardial hibernation. However, the cardiac outcome is not worsened by type 2 diabetes, despite more advanced aortic atherosclerosis in diabetic animals.

  17. Deficiency of cardiac Acyl-CoA synthetase-1 induces diastolic dysfunction, but pathologic hypertrophy is reversed by rapamycin

    DEFF Research Database (Denmark)

    Paul, David S; Grevengoed, Trisha J; Pascual, Florencia;

    2014-01-01

    In mice with temporally-induced cardiac-specific deficiency of acyl-CoA synthetase-1 (Acsl1(H-/-)), the heart is unable to oxidize long-chain fatty acids and relies primarily on glucose for energy. These metabolic changes result in the development of both a spontaneous cardiac hypertrophy and inc...

  18. Early exercise training normalizes myofilament function and attenuates left ventricular pump dysfunction in mice with a large myocardial infarction

    NARCIS (Netherlands)

    M.C. de Waard (Monique); J. van der Velden (Jolanda); V. Bito (Virginie); S. Ozdemir (Semir); L. Biesmans (Liesbeth); N.M. Boontje (Nicky); D.H. Dekkers (Dick); K. Schoonderwoerd (Kees); J.C.H. Schuurbiers (Johan); R. de Crom (Rini); G.J.M. Stienen (Ger); K.R. Sipido (Karin); J.M.J. Lamers (Jos); D.J.G.M. Duncker (Dirk)

    2007-01-01

    textabstractThe extent and mechanism of the cardiac benefit of early exercise training following myocardial infarction (MI) is incompletely understood, but may involve blunting of abnormalities in Ca-handling and myofilament function. Consequently, we investigated the effects of 8-weeks of voluntary

  19. Elafin, a serine elastase inhibitor, attenuates post-cardiac transplant coronary arteriopathy and reduces myocardial necrosis in rabbits afer heterotopic cardiac transplantation.

    OpenAIRE

    Cowan, B.; Baron, O; Crack, J; Coulber, C; Wilson, G.J.; Rabinovitch, M

    1996-01-01

    We have related experimentally induced post-cardiac transplant coronary arteriopathy to increased elastolytic activity, IL-1beta, fibronectin-mediated inflammatory and smooth muscle cell (SMC) migration, and SMC proliferation. Since our in vitro studies show that a serine elastase releases SMC mitogens and facilitates IL-lbeta induction of fibronectin, we hypothesized that administration in vivo of the specific serine elastase inhibitor, elafin, would decrease the post-cardiac transplant coro...

  20. Scintigraphic differentiation between two forms of primary dysautonomia early after onset of autonomic dysfunction: value of cardiac and pulmonary iodine-123 MIBG uptake

    International Nuclear Information System (INIS)

    Primary dysfunction of the autonomic nervous system can be observed in patients with Parkinson's disease and those with multiple system atrophy. However, the fate of the two diseases differs considerably and leads to different strategies for patient management. Differentiation of the two diseases currently requires a combination of several clinical and electrophysiological tests. First studies of myocardial innervation using iodine-123 metaiodobenzylguanidine (MIBG) indicated a possible role of scintigraphy for this purpose. An increase in the pulmonary uptake of 123I-MIBG has been reported in secondary dysautonomias. Whether sympathetic innervation of the lung is affected in primary dysautonomias is currently unknown. Therefore, cardiac and pulmonary uptake of 123I-MIBG was studied in 21 patients with Parkinson's disease, 7 patients with multiple system atrophy and 13 age- and sex-matched controls. Thoracic images were obtained in the anterior view 4 h after intravenous injection of 185 MBq 123I-MIBG, at which time the maximum neuronal uptake is reached. All patients with Parkinson's disease had significantly lower cardiac uptake of 123I-MIBG than patients with multiple system atrophy and controls. Sympathetic innervation of the lung was not affected in either disease. It is concluded that scintigraphy with 123I-MIBG appears to be a useful tool for differentiation between Parkinson's disease and multiple system atrophy early after onset of autonomic dysfunction. (orig.)

  1. Scintigraphic differentiation between two forms of primary dysautonomia early after onset of autonomic dysfunction: value of cardiac and pulmonary iodine-123 MIBG uptake

    Energy Technology Data Exchange (ETDEWEB)

    Reinhardt, M.J.; Juengling, F.D.; Krause, T.M. [Dept. of Nuclear Medicine, Freiburg University Hospital (Germany); Braune, S. [Dept. of Neurology, Freiburg University Hospital (Germany)

    2000-05-01

    Primary dysfunction of the autonomic nervous system can be observed in patients with Parkinson's disease and those with multiple system atrophy. However, the fate of the two diseases differs considerably and leads to different strategies for patient management. Differentiation of the two diseases currently requires a combination of several clinical and electrophysiological tests. First studies of myocardial innervation using iodine-123 metaiodobenzylguanidine (MIBG) indicated a possible role of scintigraphy for this purpose. An increase in the pulmonary uptake of {sup 123}I-MIBG has been reported in secondary dysautonomias. Whether sympathetic innervation of the lung is affected in primary dysautonomias is currently unknown. Therefore, cardiac and pulmonary uptake of {sup 123}I-MIBG was studied in 21 patients with Parkinson's disease, 7 patients with multiple system atrophy and 13 age- and sex-matched controls. Thoracic images were obtained in the anterior view 4 h after intravenous injection of 185 MBq {sup 123}I-MIBG, at which time the maximum neuronal uptake is reached. All patients with Parkinson's disease had significantly lower cardiac uptake of {sup 123}I-MIBG than patients with multiple system atrophy and controls. Sympathetic innervation of the lung was not affected in either disease. It is concluded that scintigraphy with {sup 123}I-MIBG appears to be a useful tool for differentiation between Parkinson's disease and multiple system atrophy early after onset of autonomic dysfunction. (orig.)

  2. Coronary artery calcification is associated with atherogenic lipid changes, cardiac dysfunction and morphologic abnormalities in HIV-1 infected black adults

    Institute of Scientific and Technical Information of China (English)

    MENG Qing-yi; DU Jie-fu; LAI Hong; LAI Sheng-han

    2005-01-01

    @@ The heart is an organ frequently affected in the acquired immunodeficiency syndrome.1 But there is little information as to whether the coronary artery calcification can identify asymptomatic individuals at high risk for having cardiac morphological and functional abnormalities and cardiac risk factors in human immunodeficiency virus (HIV)-infected persons. Accordingly, the purpose of this study was to determine whether coronary artery calcification was associated with cardiac morphological and functional abnormalities, atherogenic lipid and C-reactive protein (CRP) changes in a black adult population with HIV-1 infection.

  3. Zinc deficiency exacerbates while zinc supplement attenuates cardiac hypertrophy in high-fat diet-induced obese mice through modulating p38 MAPK-dependent signaling.

    Science.gov (United States)

    Wang, Shudong; Luo, Manyu; Zhang, Zhiguo; Gu, Junlian; Chen, Jing; Payne, Kristen McClung; Tan, Yi; Wang, Yuehui; Yin, Xia; Zhang, Xiang; Liu, Gilbert C; Wintergerst, Kupper; Liu, Quan; Zheng, Yang; Cai, Lu

    2016-09-01

    Childhood obesity often leads to cardiovascular diseases, such as obesity-related cardiac hypertrophy (ORCH), in adulthood, due to chronic cardiac inflammation. Zinc is structurally and functionally essential for many transcription factors; however, its role in ORCH and underlying mechanism(s) remain unclear and were explored here in mice with obesity induced with high-fat diet (HFD). Four week old mice were fed on either HFD (60%kcal fat) or normal diet (ND, 10% kcal fat) for 3 or 6 months, respectively. Either diet contained one of three different zinc quantities: deficiency (ZD, 10mg zinc per 4057kcal), normal (ZN, 30mg zinc per 4057kcal) or supplement (ZS, 90mg zinc per 4057kcal). HFD induced a time-dependent obesity and ORCH, which was accompanied by increased cardiac inflammation and p38 MAPK activation. These effects were worsened by ZD in HFD/ZD mice and attenuated by ZS in HFD/ZS group, respectively. Also, administration of a p38 MAPK specific inhibitor in HFD mice for 3 months did not affect HFD-induced obesity, but completely abolished HFD-induced, and zinc deficiency-worsened, ORCH and cardiac inflammation. In vitro exposure of adult cardiomyocytes to palmitate induced cell hypertrophy accompanied by increased p38 MAPK activation, which was heightened by zinc depletion with its chelator TPEN. Inhibition of p38 MAPK with its specific siRNA also prevented the effects of palmitate on cardiomyocytes. These findings demonstrate that ZS alleviates but ZD heightens cardiac hypertrophy in HFD-induced obese mice through suppressing p38 MAPK-dependent cardiac inflammatory and hypertrophic pathways. PMID:27346292

  4. Chagas Cardiomiopathy: The Potential of Diastolic Dysfunction and Brain Natriuretic Peptide in the Early Identification of Cardiac Damage

    OpenAIRE

    Ana Garcia-Alvarez; Marta Sitges; María-Jesús Pinazo; Ander Regueiro-Cueva; Elizabeth Posada; Silvia Poyatos; José Tomás Ortiz-Pérez; Magda Heras; Manel Azqueta; Joaquim Gascon; Ginés Sanz

    2010-01-01

    INTRODUCTION: Chagas disease remains a major cause of mortality in several countries of Latin America and has become a potential public health problem in non-endemic countries as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac involvement is desirable, since early treatment may improve prognosis. This study aimed to assess the r...

  5. Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling

    OpenAIRE

    Silva, Marcondes A. B.; Bruder-Nascimento, Thiago; Cau, Stefany B. A.; Lopes, Rheure A. M.; Mestriner, Fabiola L. A. C.; Fais, Rafael S.; Touyz, Rhian M.; Tostes, Rita C.

    2015-01-01

    Type 2 diabetes (DM2) increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR) with spironolactone decreases reactive oxygen species (ROS)-associated vascular dysfunction and improves vascular nitric oxide (NO) signaling in diabetes. Leptin receptor knockout [LepRdb/LepRdb (db/db)] mice, a model of DM2, and their ...

  6. Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling

    OpenAIRE

    Marcondes Alves Barbosa Da Silva; Thiago eBruder-Nascimento; Stêfany Bruno Assis Cau; Rheure AM Lopes; Fabiola LAC Mestriner; Fais, Rafael S.; Touyz, Rhian M.; Tostes, Rita C.

    2015-01-01

    Type 2 diabetes (DM2) increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR) with spironolactone decreases ROS-associated vascular dysfunction and improves vascular NO signaling in diabetes. Leptin receptor knockout [LepRdb/LepRdb (db/db)] mice, a model of DM2, and their counterpart controls [LepRdb/LepR+, (db/+...

  7. Allogeneic cardiospheres delivered via percutaneous transendocardial injection increase viable myocardium, decrease scar size, and attenuate cardiac dilatation in porcine ischemic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Kristine Yee

    Full Text Available Epicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI, but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy.We studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22 post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled ("dose optimization" study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16. Finally, the superior product and dose (150 million cardiospheres were tested in a blinded, randomized, placebo-controlled ("pivotal" study (n = 22. Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo.Dose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration.

  8. Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling.

    Science.gov (United States)

    Silva, Marcondes A B; Bruder-Nascimento, Thiago; Cau, Stefany B A; Lopes, Rheure A M; Mestriner, Fabiola L A C; Fais, Rafael S; Touyz, Rhian M; Tostes, Rita C

    2015-01-01

    Type 2 diabetes (DM2) increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR) with spironolactone decreases reactive oxygen species (ROS)-associated vascular dysfunction and improves vascular nitric oxide (NO) signaling in diabetes. Leptin receptor knockout [LepR(db)/LepR(db) (db/db)] mice, a model of DM2, and their counterpart controls [LepR(db)/LepR(+), (db/+) mice] received spironolactone (50 mg/kg body weight/day) or vehicle (ethanol 1%) via oral per gavage for 6 weeks. Spironolactone treatment abolished endothelial dysfunction and increased endothelial nitric oxide synthase (eNOS) phosphorylation (Ser(1177)) in arteries from db/db mice, determined by acetylcholine-induced relaxation and Western Blot analysis, respectively. MR antagonist therapy also abrogated augmented ROS-generation in aorta from diabetic mice, determined by lucigenin luminescence assay. Spironolactone treatment increased superoxide dismutase-1 and catalase expression, improved sodium nitroprusside and BAY 41-2272-induced relaxation, and increased soluble guanylyl cyclase (sGC) β subunit expression in arteries from db/db mice. Our results demonstrate that spironolactone decreases diabetes-associated vascular oxidative stress and prevents vascular dysfunction through processes involving increased expression of antioxidant enzymes and sGC. These findings further elucidate redox-sensitive mechanisms whereby spironolactone protects against vascular injury in diabetes. PMID:26500555

  9. Spironolactone treatment attenuates vascular dysfunction in type 2 diabetic mice by decreasing oxidative stress and restoring NO/GC signaling

    Directory of Open Access Journals (Sweden)

    Marcondes Alves Barbosa Da Silva

    2015-10-01

    Full Text Available Type 2 diabetes (DM2 increases the risk of cardiovascular disease. Aldosterone, which has pro-oxidative and pro-inflammatory effects in the cardiovascular system, is positively regulated in DM2. We assessed whether blockade of mineralocorticoid receptors (MR with spironolactone decreases ROS-associated vascular dysfunction and improves vascular NO signaling in diabetes. Leptin receptor knockout [LepRdb/LepRdb (db/db] mice, a model of DM2, and their counterpart controls [LepRdb/LepR+, (db/+ mice] received spironolactone (50 mg/kg body weight/day or vehicle (ethanol 1% via oral per gavage for 6 weeks. Spironolactone treatment abolished the endothelial dysfunction and increased endothelial nitric oxide synthase (eNOS phosphorylation (Ser1177, determined by acetylcholine-induced relaxation and Western Blot analysis, respectively. MR antagonist therapy also abrogated augmented ROS-generation in aorta from diabetic mice, determined by lucigenin luminescence assay. Spironolactone treatment increased superoxide dismutase-1 (SOD1 and catalase expression, improved sodium nitroprusside (SNP and BAY 41-2272-induced relaxation, as well as increased soluble guanylyl cyclase (sGC subunit β protein expression in arteries from db/db mice. Our results demonstrate that spironolactone decreases diabetes-associated vascular oxidative stress and prevents vascular dysfunction through processes involving increased expression of antioxidant enzymes and sGC. These findings further elucidate redox-sensitive mechanisms whereby spironolactone protects against vascular injury in diabetes.

  10. Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice.

    Science.gov (United States)

    Chaudhry, Kamaljit K; Shukla, Pradeep K; Mir, Hina; Manda, Bhargavi; Gangwar, Ruchika; Yadav, Nikki; McMullen, Megan; Nagy, Laura E; Rao, RadhaKrishna

    2016-01-01

    Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of Gln in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed with Gln-free diet and absent in mice fed with Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury. PMID:26365579

  11. Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice.

    Science.gov (United States)

    Chaudhry, Kamaljit K; Shukla, Pradeep K; Mir, Hina; Manda, Bhargavi; Gangwar, Ruchika; Yadav, Nikki; McMullen, Megan; Nagy, Laura E; Rao, RadhaKrishna

    2016-01-01

    Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of Gln in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed with Gln-free diet and absent in mice fed with Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury.

  12. Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise.

    Science.gov (United States)

    Willis, Monte S; Min, Jin-Na; Wang, Shaobin; McDonough, Holly; Lockyer, Pamela; Wadosky, Kristine M; Patterson, Cam

    2013-12-01

    The carboxyl terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase/cochaperone critical for the maintenance of cardiac function. Mice lacking CHIP (CHIP-/-) suffer decreased survival, enhanced myocardial injury and increased arrhythmias compared with wild-type controls following challenge with cardiac ischaemia reperfusion injury. Recent evidence implicates a role for CHIP in chaperone-assisted selective autophagy, a process that is associated with exercise-induced cardioprotection. To determine whether CHIP is involved in cardiac autophagy, we challenged CHIP-/- mice with voluntary exercise. CHIP-/- mice respond to exercise with an enhanced autophagic response that is associated with an exaggerated cardiac hypertrophy phenotype. No impairment of function was identified in the CHIP-/- mice by serial echocardiography over the 5 weeks of running, indicating that the cardiac hypertrophy was physiologic not pathologic in nature. It was further determined that CHIP plays a role in inhibiting Akt signalling and autophagy determined by autophagic flux in cardiomyocytes and in the intact heart. Taken together, cardiac CHIP appears to play a role in regulating autophagy during the development of cardiac hypertrophy, possibly by its role in supporting Akt signalling, induced by voluntary running in vivo.

  13. Chagas cardiomyopathy: The potential effect of benznidazole treatment on diastolic dysfunction and cardiac damage in dogs chronically infected with Trypanosoma cruzi.

    Science.gov (United States)

    Santos, Fabiane M; Mazzeti, Ana L; Caldas, Sérgio; Gonçalves, Karolina R; Lima, Wanderson G; Torres, Rosália M; Bahia, Maria Terezinha

    2016-09-01

    Cardiac involvement represents the main cause of mortality among patients with Chagas disease, and the relevance of trypanocidal treatment to improving diastolic dysfunction is still doubtful. In the present study, we used a canine model infected with the benznidazole-sensitive Berenice-78 Trypanosoma cruzi strain to verify the efficacy of an etiologic treatment in reducing the parasite load and ameliorating cardiac muscle tissue damage and left ventricular diastolic dysfunction in the chronic phase of the infection. The effect of the treatment on reducing the parasite load was monitored by blood PCR and blood culture assays, and the effect of the treatment on the outcome of heart tissue damage and on diastolic function was evaluated by histopathology and echo Doppler cardiogram. The benefit of the benznidazole-treatment in reducing the parasite burden was demonstrated by a marked decrease in positive blood culture and PCR assay results until 30days post-treatment. At this time, the PCR and blood culture assays yielded negative results for 82% of the treated animals, compared with only 36% of the untreated dogs. However, a progressive increase in the parasite load could be detected in the peripheral blood for one year post-treatment, as evidenced by a progressive increase in positive results for both the PCR and the blood culture assays at follow-up. The parasite load reduction induced by treatment was compatible with the lower degree of tissue damage among animals euthanized in the first month after treatment and with the increased cardiac damage after this period, reaching levels similar to those in untreated animals at the one-year follow-up. The two infected groups also presented similar, significantly smaller values for early tissue septal velocity (E' SIV) than the non-infected dogs did at this later time. Moreover, in the treated animals, an increase in the E/E' septal tissue filling pressure ratio was observed when compared with basal values as well as with

  14. Protective Effect of Quercetin on Posttraumatic Cardiac Injury.

    Science.gov (United States)

    Jing, Zehao; Wang, Zhuorun; Li, Xiujie; Li, Xintao; Cao, Tingting; Bi, Yue; Zhou, Jicheng; Chen, Xu; Yu, Deqin; Zhu, Liang; Li, Shuzhuang

    2016-01-01

    Quercetin is an important dietary flavonoid present in fruits and vegetables and has attracted attention because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play important roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This study investigates the protective effect of quercetin on trauma-induced secondary cardiac injury and the mechanisms involved. Widely accepted nonlethal mechanical trauma models were established. In vivo, cardiomyocyte apoptosis and cardiac dysfunction in rats were assessed using TUNEL staining and a biological mechanic experiment system. In vitro, cell viability, tumour necrosis factor-α (TNF-α), reactive oxygen species (ROS) and [Ca(2+)]i of H9c2 cells were detected using an MTT assay, ELISA, and 2',7'-dichlorofluorescin diacetate and fluo-4 acetoxymethyl ester assays respectively. Quercetin pretreatment (20 mg/kg i.p.; 0.5 h before trauma) significantly improved posttraumatic cardiomyocyte apoptosis and cardiac dysfunction. Pretreatment with quercetin (20 μM; 24 h before trauma plasma addition) significantly attenuated trauma-induced viability decreases, TNF-α increases, ROS overproduction and [Ca(2+)]i overload in H9c2 cells. In conclusion, quercetin may reverse posttraumatic cardiac dysfunction by reducing cardiomyocyte apoptosis through the suppression of TNF-α increases, ROS overproduction and Ca(2+) overload in cardiomyocytes, representing a potential preventive approach for the treatment of secondary cardiac injury after mechanical trauma. PMID:27470932

  15. Serum High-Sensitivity Cardiac Troponin T Is a Significant Biomarker of Left-Ventricular Diastolic Dysfunction in Subjects with Non-Diabetic Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Masashi Kitagawa

    2011-10-01

    Full Text Available Background: Chronic kidney disease (CKD is associated with left-ventricular (LV diastolic dysfunction (LVDD which progresses to diastolic heart failure. However, biomarkers predicting LVDD in patients with CKD are largely unknown. Methods: In 93 patients with non-diabetic CKD, the relationships among echocardiography, high-sensitivity cardiac troponin T (hs-cTnT, B-type natriuretic peptide (BNP, and renal function were evaluated. LV mass index, peak early diastolic mitral filling velocity (E, peak early diastolic mitral annular velocity (E′, and E/E′ were recorded. Results: The E′ values were significantly decreased and E/E′, BNP, and hs-cTnT increased with increasing CKD stage. The CKD patients with LVDD with E′ Conclusions: These data suggest that hs-cTnT may be a useful biomarker of LVDD in non- diabetic CKD patients.

  16. CYP2J2 and its metabolites (EETs) attenuate cardiac hypertrophy by activating AMPKα2 and enhancing nuclear translocation of Akt1

    Institute of Scientific and Technical Information of China (English)

    WANG Bei; ZENG He-song; WEN Zheng; CHEN Chen; WANG Dao-wen

    2016-01-01

    AIM:Cytochrome P450 epoxygenase 2J2 and epoxyeicosatrienoic acids ( EETs) are known to protect against cardiac hypertrophy and heart failure, which involve activation of 5′-AMP-activated protein kinase ( AMPK) and Akt.Although the functional roles of AMPK and Akt are well established , the significance of crosstalk between them in the development of cardiac hypertrophy and anti -hy-pertrophy of CYP2J2 and EETs remains unclear .Here, we investigated whether CYP 2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1.Moreover, we tested whether EETs enhanced crosstalk between AMPKα2 and phosphorylated Akt1 ( p-Akt1), and stimulated the nuclear translocation of p-Akt1, to exert their anti-hypertrophic effects. METHODS:The recombinant rAAV9 vector was coupled to CYP2J2 and the rAAV9-CYP2J2 construct was injected into the caudal vein of AMPKα2-/-and littermate control mice .AMPKα2 -/-and littermate control mice that overexpressed CYP 2J2 in heart were treated with angiotensin II (Ang II) for 2 weeks.Hemodynamic and cardiac functions were also evaluated after 14 days of infusion with Ang II or saline.RESULTS:Interestingly, the overexpression of CYP2J2 suppressed cardiac hypertrophy , including decreased heart size, cross sectional area of cardiomyocytes , markers of cardiac hypertrophy [ brain natriuretic peptide ( BNP) ,β-myosin heavy chain (β-MHC) and skeletal muscle α-actin (ACTA1)] and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild-type mice but not AMPKα2 -/-mice.Measurement of left ventricular ejection fraction and fractional shortening showed that CYP2J2 overexpression prevented Ang II-induced ventricular systolic dysfunction in mice .Moreover, an Ang II-induced reduction in cardiac function, demonstrated by decreased dp/dtmax and dp/dtmin, was prevented by overexpression of CYP2J2.Mechanistically, the CYP2J2 metabolites 11,12-EET activated AMPKα2 to induce the nuclear

  17. An Altered Pattern of Myocardial Histopathological and Molecular Changes Underlies the Different Characteristics of Type-1 and Type-2 Diabetic Cardiac Dysfunction

    Directory of Open Access Journals (Sweden)

    Tamás Radovits

    2015-01-01

    Full Text Available Increasing evidence suggests that both types of diabetes mellitus (DM lead to cardiac structural and functional changes. In this study we investigated and compared functional characteristics and underlying subcellular pathological features in rat models of type-1 and type-2 diabetic cardiomyopathy. Type-1 DM was induced by streptozotocin. For type-2 DM, Zucker Diabetic Fatty (ZDF rats were used. Left ventricular pressure-volume analysis was performed to assess cardiac function. Myocardial nitrotyrosine immunohistochemistry, TUNEL assay, hematoxylin-eosin, and Masson’s trichrome staining were performed. mRNA and protein expression were quantified by qRT-PCR and Western blot. Marked systolic dysfunction in type-1 DM was associated with severe nitrooxidative stress, apoptosis, and fibrosis. These pathological features were less pronounced or absent, while cardiomyocyte hypertrophy was comparable in type-2 DM, which was associated with unaltered systolic function and increased diastolic stiffness. mRNA-expression of hypertrophy markers c-fos, c-jun, and β-MHC, as well as pro-apoptotic caspase-12, was elevated in type-1, while it remained unaltered or only slightly increased in type-2 DM. Expression of the profibrotic TGF-β1 was upregulated in type-1 and showed a decrease in type-2 DM. We compared type-1 and type-2 diabetic cardiomyopathy in standard rat models and described an altered pattern of key pathophysiological features in the diabetic heart and corresponding functional consequences.

  18. HSF1 and NF-κB p65 participate in the process of exercise preconditioning attenuating pressure overload-induced pathological cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Tongyi [Department of Cardiothoracic Surgery, No. 401 Hospital of PLA, Qingdao (China); Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Zhang, Ben [Centre of Cardiovascular Surgery, Guangzhou General Hospital of Guangzhou Military Region, Guangzhou (China); Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Yang, Fan; Cai, Chengliang; Wang, Guokun [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Han, Qingqi, E-mail: handoctor@gmail.com [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Zou, Liangjian, E-mail: zouliangjiansh@gmail.com [Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2015-05-08

    Pathological cardiac hypertrophy, often accompanied by hypertension, aortic stenosis and valvular defects, is typically associated with myocyte remodeling and cardiac dysfunction. Exercise preconditioning (EP) has been proven to enhance the tolerance of the myocardium to cardiac ischemia-reperfusion injury. However, the effects of EP in pathological cardiac hypertrophy are rarely reported. 10-wk-old male Sprague–Dawley rats (n = 80) were randomly divided into four groups: sham, TAC, EP + sham and EP + TAC. Two EP groups were subjected to 4 weeks of treadmill training, and the EP + TAC and TAC groups were followed by TAC operations. The sham and EP + sham groups underwent the same operation without aortic constriction. Eight weeks after the surgery, we evaluated the effects of EP by echocardiography, morphology, and histology and observed the expressions of the associated proteins. Compared with the respective control groups, hypertrophy-related indicators were significantly increased in the TAC and EP + TAC groups (p < 0.05). However, between the TAC and EP + TAC groups, all of these changes were effectively inhibited by EP treatment (p < 0.05). Furthermore, EP treatment upregulated the expression of HSF1 and HSP70, increased the HSF1 levels in the nuclear fraction, inhibited the expression of the NF-κB p65 subunit, decreased the NF-κB p65 subunit levels in the nuclear fraction, and reduced the IL2 levels in the myocardia of rats. EP could effectively reduce the cardiac hypertrophic responses induced by TAC and may play a protective role by upregulating the expressions of HSF1 and HSP70, activating HSF1 and then inhibiting the expression of NF-κB p65 and nuclear translocation. - Highlights: • EP could effectively reduce the cardiac hypertrophic responses induced by TAC. • EP may play a protective role by upregulating the expressions of HSF1 and HSP70 and then activating HSF1. • EP may play a protective role by inhibiting the expression

  19. Benefit of combining quantitative cardiac CT parameters with troponin I for predicting right ventricular dysfunction and adverse clinical events in patients with acute pulmonary embolism

    International Nuclear Information System (INIS)

    Objective: To prospectively evaluate the diagnostic accuracy of quantitative cardiac CT parameters alone and in combination with troponin I for the assessment of right ventricular dysfunction (RVD) and adverse clinical events in patients with acute pulmonary embolism (PE). Materials and results: This prospective study had institutional review board approval and was HIPAA compliant. In total 83 patients with confirmed PE underwent echocardiography and troponin I serum level measurements within 24 h. Three established cardiac CT measurements for the assessment of RVD were obtained (RV/LVaxial, RV/LV4-CH, and RV/LVvolume). CT measurements and troponin I serum levels were correlated with RVD found on echocardiography and adverse clinical events according to Management Strategies and Prognosis in Pulmonary Embolism Trial-3 (MAPPET-3 criteria. 31 of 83 patients with PE had RVD on echocardiography and 39 of 83 patients had adverse clinical events. A RV/LVvolume ratio > 1.43 showed the highest area under the curve (AUC) (0.65) for the prediction of adverse clinical events when compared to RV/LVaxial, RV/LV4Ch and troponin I. The AUC for the detection of RVD of RV/LVaxial, RV/LV4Ch, RV/LVvolume, and troponin I were 0.86, 0.86, 0.92, and 0.69, respectively. Combination of RV/LVaxial, RV/LV4Ch, RV/LVvolume with troponin I increased the AUC to 0.87, 0.87 and 0.93, respectively. Conclusion: A combination of cardiac CT parameters and troponin I measurements improves the diagnostic accuracy for detecting RVD and predicting adverse clinical events if compared to either test alone.

  20. Cardiac Magnetic Resonance Imaging Findings in a Patient with Ebstein’s Anomaly and Left Ventricular Dysfunction

    OpenAIRE

    Nasim Naderi; Ahmad Amin; Hamidreza Pouraliakbar

    2013-01-01

    Ebstein anomaly is characterized by apical displacement of the septal and posterior tricuspid valve leaflets, leading to atrialization of the right ventricle and could be diagnosed in a routine transthoracic echocardiography exam. We reported a young man with right sided heart failure symptoms who was found to have biventricular failure with suspected apical displacement of septal leaflet of tricuspid valve. For better evaluation, cardiac magnetic resonance imaging (CMR) was performed and nic...

  1. Low-dose vasopressin infusion results in increased mortality and cardiac dysfunction following ischemia-reperfusion injury in mice

    OpenAIRE

    Indrambarya, Toonchai; Boyd, John H; Wang, Yingjin; McConechy, Melissa; Keith R Walley

    2009-01-01

    Introduction Arginine vasopressin is a vasoactive drug commonly used in distributive shock states including mixed shock with a cardiac component. However, the direct effect of arginine vasopressin on the function of the ischemia/reperfusion injured heart has not been clearly elucidated. Methods We measured left ventricular ejection fraction using trans-thoracic echocardiography in C57B6 mice, both in normal controls and following ischemia/reperfusion injury induced by a one hour ligation of t...

  2. Atorvastatin therapy during the peri-infarct period attenuates left ventricular dysfunction and remodeling after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Xian-Liang Tang

    Full Text Available Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI. Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14 received oral atorvastatin (10 mg/kg/d daily for 3 wk before and 4 wk after MI, while group I (n = 12 received equivalent doses of vehicle. Infarct size (Masson's trichrome-stained sections was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF and fractional area change (FAC were higher while LV end-diastolic volume (LVEDV and LV end-systolic and end-diastolic diameters (LVESD and LVEDD were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dt(max, end-systolic elastance (Ees, and preload recruitable stroke work (PRSW and lower LV end-diastolic pressure (LVEDP. Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis.

  3. Hydrogen sulfide attenuated tumor necrosis factor-α-induced inflammatory signaling and dysfunction in vascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Li-Long Pan

    Full Text Available BACKGROUND: Hydrogen sulfide (H(2S, the third physiologically relevant gaseous molecule, is recognized increasingly as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the effects and mechanisms of sodium hydrosulfide (NaHS, a H(2S donor on tumor necrosis factor (TNF-α-induced human umbilical vein endothelial cells (HUVEC dysfunction. METHODOLOGY AND PRINCIPAL FINDINGS: Application of NaHS concentration-dependently suppressed TNF-α-induced mRNA and proteins expressions of intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1, mRNA expression of P-selectin and E-selectin as well as U937 monocytes adhesion to HUVEC. Western blot analysis revealed that the expression of the cytoprotective enzyme, heme oxygenase-1 (HO-1, was induced and coincident with the anti-inflammatory action of NaHS. Furthermore, TNF-α-induced NF-κB activation assessed by IκBα degradation and p65 phosphorylation and nuclear translocation and ROS production were diminished in cells subjected to treatment with NaHS. SIGNIFICANCE: H(2S can exert an anti-inflammatory effect in endothelial cells through a mechanism that involves the up-regulation of HO-1.

  4. Uric Acid-Induced Adipocyte Dysfunction Is Attenuated by HO-1 Upregulation: Potential Role of Antioxidant Therapy to Target Obesity

    Directory of Open Access Journals (Sweden)

    Komal Sodhi

    2016-01-01

    Full Text Available Increased uric acid levels have been implicated in the pathogenesis of metabolic syndrome. To examine the mechanisms by which this occurs, we hypothesized that an increase in heme oxygenase 1, a potent antioxidant gene, will decrease uric acid levels and adipocyte dysfunction via suppression of ROS and xanthine oxidase (XO levels. We examined the effect of uric acid on adipogenesis in human mesenchymal stem cells (MSCs in the presence and absence of cobalt protoporphyrin (CoPP, an HO-1 inducer, and tin mesoporphyrin (SnMP, an HO activity inhibitor. Uric acid increased adipogenesis by increasing NADPH oxidase expression and elevation in the adipogenesis markers C/EBPα, PPARγ, and Mest, while decreasing small lipid droplets and Wnt10b levels. We treated MSCs with fructose, a fuel source that increases uric acid levels. Our results showed that fructose increased XO expression as compared to the control and concomitant treatment with CoPP significantly decreased XO expression and uric acid levels. These beneficial effects of CoPP were reversed by SnMP, supporting a role for HO activity in mediating these effects. These findings demonstrate that increased levels of HO-1 appear crucial in modulating the phenotype of adipocytes exposed to uric acid and in downregulating XO and NADPH oxidase levels.

  5. Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice.

    Science.gov (United States)

    Ramanathan, Muthiah; Abdul, Khadar K; Justin, Antony

    2016-10-01

    Glutamate, an excitatory neurotransmitter in the brain, produces excitotoxicity through its agonistic action on postsynaptic N-methyl-D-aspartate receptor, resulting in neurodegeneration. We hypothesized that the administration of low doses of glutamate in cerebral ischemia could attenuate the excitotoxicity in neurons through its autoreceptor regulatory mechanism, and thereby control neurodegeneration. To test the hypothesis, the effect of L-glutamic acid (L-GA) 400 μmol/l/kg was evaluated in a bilateral common carotid artery occlusion-induced global ischemic mouse model. Memantine was used as a positive control. Global ischemia in mice was induced by occlusion of both the common carotid artery (bilateral common carotid artery occlusion) for 20 min, followed by reperfusion injury. L-GA was infused slowly through the tail vein 30 min before the surgery and every 24 h thereafter until the end of the experiment. The time-dependent change in cerebral blood flow was monitored using a laser Doppler image analyzer. The neurotransmitters glutamate and γ-aminobutyric acid (GABA) and the neurobiochemicals ATP, glutathione, and nitric oxide were measured in the different regions of brain at 0, 24, 48, and 72 h after reperfusion injury. L-GA increased locomotor activity, muscle coordination, and cerebral blood flow in ischemic mice at 72 h after ischemic insult. L-GA reduced glutamate levels in the cortex, striatum, and hippocampus at 72 h, whereas GABA levels were elevated in all three brain regions studied. Further, L-GA elevated glutathione levels and attenuated nitric oxide levels, but failed to restore ATP levels 72 h after ischemia-reperfusion. We conclude that the gradual reduction of glutamate along with elevation of GABA in different brain regions could have contributed toward the neuroprotective effect of L-GA. Hence, a slow infusion of a low dose of L-GA could be beneficial in controlling excitotoxicity-induced neurodegeneration following ischemia

  6. Silencing of PKC-α, TRPC1 or NF-κB expression attenuates cisplatin-induced ICAM-1 expression and endothelial dysfunction.

    Science.gov (United States)

    Bodiga, Vijaya Lakshmi; Kudle, Madhukar Rao; Bodiga, Sreedhar

    2015-11-01

    Platinum-based chemotherapy has been associated with increased long-term cardiovascular events. Also noteworthy is the accumulating awareness of early vascular toxicity occurring at the time of chemotherapy or immediately thereafter. The objective of the study was to delineate the molecular mechanisms associated with the early vascular toxicity and test the molecular silencing approach towards attenuating the endothelial dysfunction during platinum-based chemotherapy. Human umbilical vein endothelial cells (HUVECs) were treated with varying concentrations of cisplatin (1.0-10.0μg/ml) or vehicle control (0.1% dimethyl sulfoxide) for monitoring the changes in Intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression viz. a viz. altered activation of protein kinase C (PKC) isoforms, transient receptor potential channel (TRPC) 1 expression, Nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB), Store Operated Ca(2+) Entry (SOCE) in cisplatin-induced endothelial permeability and adherence of the activated endothelial cells to human monocyte-like U937 cells. Silencing of either PKC-α, TRPC1 or p65 subunit of NF-κB, all resulted in significant alleviation of cisplatin-induced endothelial dysfunction. At concentrations ≥8μg/ml, cisplatin induced a significant increase in the expression of ICAM-1 mRNA as well as protein. This was mediated by changes in PKC-α membrane translocation, NF-κB activation, increased expression as well as phosphorylation of TRPC1 and enhanced SOCE, leading to hyperpermeability and leakage of albumin. Increased adherence of U937 monocytes to cisplatin-activated endothelial cells was evident. Cisplatin challenge activates PKC-α, which in turn phosphorylated TRPC1 resulting in enhanced Ca(2+) entry. Increased Ca(2+) flux is required for activation of NF-κB and ICAM-1 expression. Enhanced ICAM-1 expression promotes monocyte binding to endothelial cells and increased endothelial hyperpermeability. PMID:26300057

  7. A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model

    Directory of Open Access Journals (Sweden)

    McNamara Laurie K

    2007-09-01

    Full Text Available Abstract Background An accumulating body of evidence is consistent with the hypothesis that excessive or prolonged increases in proinflammatory cytokine production by activated glia is a contributor to the progression of pathophysiology that is causally linked to synaptic dysfunction and hippocampal behavior deficits in neurodegenerative diseases such as Alzheimer's disease (AD. This raises the opportunity for the development of new classes of potentially disease-modifying therapeutics. A logical candidate CNS target is p38α MAPK, a well-established drug discovery molecular target for altering proinflammatory cytokine cascades in peripheral tissue disorders. Activated p38 MAPK is seen in human AD brain tissue and in AD-relevant animal models, and cell culture studies strongly implicate p38 MAPK in the increased production of proinflammatory cytokines by glia activated with human amyloid-beta (Aβ and other disease-relevant stressors. However, the vast majority of small molecule drugs do not have sufficient penetrance of the blood-brain barrier to allow their use as in vivo research tools or as therapeutics for neurodegenerative disorders. The goal of this study was to test the hypothesis that brain p38α MAPK is a potential in vivo target for orally bioavailable, small molecules capable of suppressing excessive cytokine production by activated glia back towards homeostasis, allowing an improvement in neurologic outcomes. Methods A novel synthetic small molecule based on a molecular scaffold used previously was designed, synthesized, and subjected to analyses to demonstrate its potential in vivo bioavailability, metabolic stability, safety and brain uptake. Testing for in vivo efficacy used an AD-relevant mouse model. Results A novel, CNS-penetrant, non-toxic, orally bioavailable, small molecule inhibitor of p38α MAPK (MW01-2-069A-SRM was developed. Oral administration of the compound at a low dose (2.5 mg/kg resulted in attenuation of

  8. Limiting collagen turnover via collagenase-resistance attenuates right ventricular dysfunction and fibrosis in pulmonary arterial hypertension.

    Science.gov (United States)

    Golob, Mark J; Wang, Zhijie; Prostrollo, Anthony J; Hacker, Timothy A; Chesler, Naomi C

    2016-06-01

    Pulmonary arterial hypertension (PAH) is a severe form of pulmonary hypertension in which right ventricular (RV) afterload is increased and death typically occurs due to decompensated RV hypertrophy and failure. Collagen accumulation has been implicated in pulmonary artery remodeling, but how it affects RV performance remains unclear. Here, we sought to identify the role of collagen turnover, defined as the balance between collagen synthesis and degradation, in RV structure and function in PAH To do so, we exposed mutant (Col1a1(R/R)) mice, in which collagen type I degradation is impaired such that collagen turnover is reduced, and wild-type (Col1a1(+/+)) littermates to 14 days of chronic hypoxia combined with SUGEN treatment (HySu) to recapitulate characteristics of clinical PAH RV structure and function were measured by echocardiography, RV catheterization, and histology. Despite comparable increases in RV systolic pressure (Col1a1(+/+): 46 ± 2 mmHg; Col1a1(R/R): 47 ± 3 mmHg), the impaired collagen degradation in Col1a1(R/R) mice resulted in no RV collagen accumulation, limited RV hypertrophy, and maintained right ventricular-pulmonary vascular coupling with HySu exposure. The preservation of cardiac function in the mutant mice indicates a beneficial role of limited collagen turnover via impaired degradation in RV remodeling in response to chronic pressure overload. Our results suggest novel treatments that reduce collagen turnover may offer a new therapeutic strategy for PAH patients. PMID:27252252

  9. 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...

  10. NAC attenuates LPS-induced toxicity in aspirin-sensitized mouse macrophages via suppression of oxidative stress and mitochondrial dysfunction.

    Directory of Open Access Journals (Sweden)

    Haider Raza

    Full Text Available Bacterial endotoxin lipopolysaccharide (LPS induces the production of inflammatory cytokines and reactive oxygen species (ROS under in vivo and in vitro conditions. Acetylsalicylic acid (ASA, aspirin is a commonly used anti-inflammatory drug. Our aim was to study the effects of N-acetyl cysteine (NAC, an antioxidant precursor of GSH synthesis, on aspirin-sensitized macrophages treated with LPS. We investigated the effects of LPS alone and in conjunction with a sub-toxic concentration of ASA, on metabolic and oxidative stress, apoptosis, and mitochondrial function using J774.2 mouse macrophage cell line. Protection from LPS-induced toxicity by NAC was also studied. LPS alone markedly induced ROS production and oxidative stress in macrophage cells. When ASA was added to LPS-treated macrophages, the increase in oxidative stress was significantly higher than that with LPS alone. Similarly, alteration in glutathione-dependent redox metabolism was also observed in macrophages after treatment with LPS and ASA. The combination of LPS and ASA selectively altered the CYP 3A4, CYP 2E1 and CYP 1A1 catalytic activities. Mitochondrial respiratory complexes and ATP production were also inhibited by LPS-ASA treatment. Furthermore a higher apoptotic cell death was also observed in LPS-ASA treated macrophages. NAC pre-treatment showed protection against oxidative stress induced apoptosis and mitochondrial dysfunction. These effects are presumed, at least in part, to be associated with alterations in NF-κB/Nrf-2 mediated cell signaling. These results suggest that macrophages are more sensitive to LPS when challenged with ASA and that NAC pre-treatment protects the macrophages from these deleterious effects.

  11. Berberine in combination with yohimbine attenuates sepsis-induced neutrophil tissue infiltration and multiorgan dysfunction partly via IL-10-mediated inhibition of CCR2 expression in neutrophils.

    Science.gov (United States)

    Wang, Yuan; Wang, Faqiang; Yang, Duomeng; Tang, Xiangxu; Li, Hongmei; Lv, Xiuxiu; Lu, Daxiang; Wang, Huadong

    2016-06-01

    Infiltration of activated neutrophils into the vital organs contributes to the multiple organ dysfunctions in sepsis. In the present study, we investigated the effects of berberine in combination with yohimbine (BY) on neutrophil tissue infiltration and multiple organ damage during sepsis, and further elucidated the involved mechanisms. Sepsis was induced in mice by cecal ligation and puncture (CLP). BY or CCR2 antagonist was administered 2h after CLP, and anti-IL-10 antibody (IL-10 Ab) or control IgG was injected intraperitoneally just before BY treatment. We found that IL-10 production was enhanced by BY therapy in septic mice. BY significantly attenuated neutrophil tissue infiltration and multiple organ injury in CLP-challenged mice, all of which were completely reversed by IL-10 Ab pretreatment. The levels of KC, MCP-1, MIP-1α and MIP-2 in the lung, liver and kidney were markedly increased 6h after CLP. BY reduced the tissue concentrations of these chemokines in septic mice, but IL-10 Ab pretreatment did not completely eliminate these inhibitory effects of BY. Particularly, dramatically increased CCR2 expression in circulating neutrophils of septic mice was reduced by BY and this effect was completely abolished by IL-10 Ab pretreatment. Furthermore, CCR2 antagonist also inhibited lung and renal injury and neutrophil infiltration in septic mice. Taken together, our data strongly suggest that BY therapy attenuates neutrophil tissue infiltration and multiple organ injury in septic mice, at least in part, via IL-10-mediated inhibition of CCR2 expression in circulating neutrophils. PMID:27082997

  12. Attenuated Cardiac Mitochondrial-Dependent Apoptotic Effects by Li-Fu Formula in Hamsters Fed with a Hypercholesterol Diet

    Directory of Open Access Journals (Sweden)

    Wei-Wen Kuo

    2011-01-01

    Full Text Available Apoptosis involves in the pathogenesis of various cardiac abnormalities. This study intends to evaluate the effects of Li-Fu formula on cardiac apoptosis induced by hyper-cholesterol diet. Twenty-four male Golden Syrian hamsters were randomly divided into Control, Cholesterol and Li-Fu formula groups. Histopathological analysis, western blotting and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assays were performed to measure the effects of Li-Fu formula on left ventricle. Significantly reduced TUNEL-positive cells and mitochondria- dependent apoptosis were observed in the left ventricle of hamsters from Li-Fu formula group compared to the Cholesterol group. Additionally, induced cardiac insulin like growth factor I receptor (IGFIR-dependent survival pathway was detected in the Li-Fu formula group compared to the Cholesterol group. Besides, minor fibrosis, increased collagen deposition, and myofibril disarray was detected in the Cholesterol group, whereas the reductions of collagen deposition and myofibril disarray were observed in the Li-Fu formula group. This study demonstrated that Li-Fu formula not only reduced the mitochondria-dependent apoptosis and fibrosis, but also enhanced the IGF-I survival pathway in the left ventricle from high cholesterol-fed hamsters. We suggest the protective effects of Li-Fu formula on cardiac apoptosis and therapeutic potentials against cardiovascular disease.

  13. The association between renal impairment and cardiac structure and function in patients with acute myocardial infarction

    DEFF Research Database (Denmark)

    Ersbøll, Mads; Valeur, Nana; Hassager, Christian;

    2014-01-01

    BACKGROUND: Renal dysfunction in patients with acute myocardial infarction (MI) is an important predictor of short- and long-term outcome. Cardiac abnormalities dominated by left ventricular (LV) hypertrophy are common in patients with chronic renal dysfunction. However, limited data exists...... on the association between LV systolic- and diastolic function assessed by comprehensive echocardiography and renal dysfunction in contemporary unselected patients with acute MI. METHODS: We prospectively included 1054 patients with acute MI (mean age 63 years, 73% male) and performed echocardiographic assessment...... fraction or GLS attenuated its importance considerably. CONCLUSION: Renal dysfunction in patients with acute MI is independently associated with echocardiographic evidence of increased LV filling pressure. However, the prognostic importance of renal dysfunction is attenuated to a greater degree by LV...

  14. Effects of adding intravenous nicorandil to standard therapy on cardiac sympathetic nerve activity and myocyte dysfunction in patients with acute decompensated heart failure

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Funada, Ryuichi; Takama, Noriaki; Koitabashi, Norimichi; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Suzuki, Yasuyuki; Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Sato, Yuichi [Health Park Clinic, Department of Imaging, Takasaki, Gunma (Japan)

    2015-04-01

    Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in ischemic heart disease or chronic heart failure. However, its effects on CSNA and myocyte dysfunction in acute heart failure (AHF) remain unclear. We investigated the effects of adding intravenous nicorandil to standard therapy on CSNA and myocyte dysfunction in AHF. We selected 70 patients with mild to moderate nonischemic AHF who were treated with standard conventional therapy soon after admission. Thirty-five patients were assigned to additionally receive intravenous nicorandil (4-12 mg/h; group A), whereas the remaining patients continued their current drug regimen (group B). Delayed total defect score (TDS), delayed heart to mediastinum count (H/M) ratio, and washout rate (WR) were determined by {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy within 3 days of admission and 4 weeks later. High sensitivity troponin T (hs-TnT) level was also measured at the same time points. After treatment, MIBG scintigraphic parameters significantly improved in both groups. However, the extent of the changes in these parameters in group A significantly exceeded the extent of the changes in group B [TDS -11.3 ± 4.3 in group A vs -4.0 ± 6.0 in group B (p < 0.01); H/M ratio 0.31 ± 0.16 vs 0.14 ± 0.16 (p < 0.01); WR -13.8 ± 7.8 % vs -6.1 ± 8.9 % (p < 0.01)]. The hs-TnT level decreased significantly from 0.052 ± 0.043 to 0.041 ± 0.033 ng/ml (p < 0.05) in group A, but showed no significant change in group B. Moreover, in both groups, no relationships between the extent of changes in MIBG parameters and hs-TnT level were observed. Adding intravenous nicorandil to standard therapy provides additional benefits for CSNA and myocyte dysfunction over conventional therapy alone in AHF patients. Furthermore, the mechanisms of improvement in CSNA and myocyte dysfunction after nicorandil treatment in AHF patients were distinct. (orig.)

  15. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects.

    Directory of Open Access Journals (Sweden)

    Viswanathan Rajagopalan

    Full Text Available A large body of evidence suggests that thyroid hormones (THs are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3 treatment in myocardial infarction (MI rats increased left ventricular (LV contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI.Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day was available in drinking water ad libitum immediately following MI and continuing for 2 month(s (mo. Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy.Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.

  16. Clinical usefulness of {sup 123}I-metaiodobenzylguanidine myocardial scintigraphy in diabetic patients with cardiac sympathetic nerve dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Miyanaga, Hajime; Yoneyama, Satoshi; Kamitani, Tadaaki; Kawasaki, Shingo; Takahashi, Toru; Kunishige, Hiroshi [Matsushita Memorial Hospital, Osaka (Japan)

    1995-09-01

    To assess the clinical utility of {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy in evaluating cardiac sympathetic nerve disturbance in diabetic patients, we performed MIBG scintigraphy in 18 diabetic patients and 11 normal controls. Diabetic patients with symptomatic neuropathy (DM2) had a significantly lower heart to mediastinum uptake ratio than did those without neuropathy or normal controls in initial and delayed images (initial image, 1.90{+-}0.27 vs 2.32{+-}0.38, 2.41{+-}0.40, p<0.01; delayed image, 1.80{+-}0.31 vs 2.48{+-}0.35, 2.56{+-}0.28, p<001, respectively). Defect score, assessed visually, were higher in DM2 patients than in patients in the other two groups (initial image, 7{+-}2.6 vs 1.5{+-}1.9, 0.7{+-}0.9; delayed image 10.6{+-}3.3 vs 4.0{+-}2.5, 1.7{+-}1.6 p<0.01, respectively). The maximum washout rate in DM2 patients was also higher than those in patients in the other two groups. The findings of these indices obtained from MIBG scintigraphy coincided with the % low-frequency power extracted from heart rate fluctuations using a power spectral analysis and the results of the Schellong test, which were used to evaluate sympathetic function. These results suggest that MIBG scintigraphy may be useful for evaluating cardiac sympathetic nerve disturbance in patients with diabetes. (author).

  17. Cardiac dysfunction in critical ill patients:pathophysiology and treatment%重症患者的心功能障碍:病理生理与治疗

    Institute of Scientific and Technical Information of China (English)

    严静; 汪月奔

    2015-01-01

    重症患者常常发生心功能障碍,其病理生理的改变涉及多种机制,包括血流动力学的变化,神经、内分泌因素的作用,炎症反应,心肌损伤和重构。除了心脏本身病变引起心功能异常外,心外器官如肺、肾、脑、胃肠道等发生功能障碍时亦可引起心功能障碍。对于心功能障碍的重症患者,在改善心功能的同时,需维持血流动力学稳定、加强心外器官的功能支持。%Cardiac dysfunction often happens in critical ill patients with multiple pathophysiological mechanisms, including hemodynamic changes, nerve and endocrine factors, inflammatory reaction, myocardial injury and remodeling. Not only heart disease but also dysfunction of extracardiac organs such as lung, kidney, brain, gastrointestinal can lead to cardiac dysfunction. It is essential to enhance the heart function, maintain the hemodynamic stability and strengthen extracardiac organs function support is also important for critical ill patients with cardiac dysfunction at the same time.

  18. Pre-Conditioning with CDP-Choline Attenuates Oxidative Stress-Induced Cardiac Myocyte Death in a Hypoxia/Reperfusion Model

    Directory of Open Access Journals (Sweden)

    Héctor González-Pacheco

    2014-01-01

    Full Text Available Background. CDP-choline is a key intermediate in the biosynthesis of phosphatidylcholine, which is an essential component of cellular membranes, and a cell signalling mediator. CDP-choline has been used for the treatment of cerebral ischaemia, showing beneficial effects. However, its potential benefit for the treatment of myocardial ischaemia has not been explored yet. Aim. In the present work, we aimed to evaluate the potential use of CDP-choline as a cardioprotector in an in vitro model of ischaemia/reperfusion injury. Methods. Neonatal rat cardiac myocytes were isolated and subjected to hypoxia/reperfusion using the coverslip hypoxia model. To evaluate the effect of CDP-choline on oxidative stress-induced reperfusion injury, the cells were incubated with H2O2 during reperfusion. The effect of CDP-choline pre- and postconditioning was evaluated using the cell viability MTT assay, and the proportion of apoptotic and necrotic cells was analyzed using the Annexin V determination by flow cytometry. Results. Pre- and postconditioning with 50 mg/mL of CDP-choline induced a significant reduction of cells undergoing apoptosis after hypoxia/reperfusion. Preconditioning with CDP-choline attenuated postreperfusion cell death induced by oxidative stress. Conclusion. CDP-choline administration reduces cell apoptosis induced by oxidative stress after hypoxia/reperfusion of cardiac myocytes. Thus, it has a potential as cardioprotector in ischaemia/reperfusion-injured cardiomyocytes.

  19. The implication of tissue Doppler echocardiography and cardiopulmonary exercise in early detection of cardiac dysfunction in systemic lupus erythematosus patients

    Science.gov (United States)

    Elnady, Basant M.; Abdelghafar, Ayman Saeed Mohamed; Khalik, El Shazly Abdul; Algethami, Mohammed Mesfer; Basiony, A.S.; Al-otaibi, Mona Dhaif Allah; Al-otaibi, Maram Eidhah

    2016-01-01

    Objective Systemic lupus erythematosus (SLE) can present limitations to exercise capacity and quality of life (QoL) because of various clinical conditions, such as pulmonary disease or heart disease. Tissue Doppler echocardiography (TDE) offers the promise of an objective measurement to quantify regional and global ventricular function through the assessment of myocardial velocity data. This study aimed to assess the intensity of left ventricular (LV) and right ventricular (RV) systolic and diastolic dysfunction in SLE patients by means of TDE and cardiopulmonary exercise (CPX) testing to determine their impact on QoL. Material and Methods Overall, 56 SLE patients within two tertiary healthcare centers as well as 50 healthy controls were examined with TDE after the exclusion of cardiovascular risk factors. TDE was performed for maximal systolic (S), early diastolic (E′), and late diastolic (A′) velocities of the mitral and tricuspid annulus. Pulsed wave (PW) Doppler of mitral and tricuspid valve inflow was performed in addition to the estimation of the left ventricle ejection fraction and assessment of right ventricle systolic function by tricuspid annular plane systolic excursion (TAPSE). Disease activity was assessed by the Systemic Lupus Activity Measure (SLAM), and the damage index was assessed by the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). CPX tests according to the modified Bruce protocol were performed. Results SLE patients in both subgroups had more or less similar laboratory data and statistically higher values of ESR, CRP, and anticardiolipin (aCL) antibodies compared to the control group. LV function showed statistically insignificant EF compared to the control group, being lower in the patient group. Tissue Doppler image revealed that E′ and A′ of the mitral annulus were lower in the patient group than in the control group. Concerning RV, TAPSE in the patient group was

  20. Diazoxide Attenuates Postresuscitation Brain Injury in a Rat Model of Asphyxial Cardiac Arrest by Opening Mitochondrial ATP-Sensitive Potassium Channels.

    Science.gov (United States)

    Wu, Haidong; Wang, Peng; Li, Yi; Wu, Manhui; Lin, Jiali; Huang, Zitong

    2016-01-01

    Objective. We investigated whether and how diazoxide can attenuate brain injury after cardiopulmonary resuscitation (CPR) by selective opening of mitochondrial ATP-sensitive potassium (mitoKATP) channels. Methods. Adult male Sprague-Dawley rats with induced cerebral ischemia (n = 10 per group) received an intraperitoneal injection of 0.1% dimethyl sulfoxide (1 mL; vehicle group), diazoxide (10 mg/kg; DZ group), or diazoxide (10 mg/kg) plus 5-hydroxydecanoate (5 mg/kg; DZ + 5-HD group) 30 min after CPR. The control group (sham group, n = 5) underwent sham operation, without cardiac arrest. Mitochondrial respiratory control rate (RCR) was determined. Brain cell apoptosis was assessed using TUNEL staining. Expression of Bcl-2, Bax, and protein kinase C epsilon (PKCε) in the cerebral cortex was determined by Western blotting and immunohistochemistry. Results. The neurological deficit scores (NDS) in the vehicle group decreased significantly at 24 h and 48 h after CPR. Diazoxide significantly improved NDS and mitochondrial RCR after CPR at both time points; 5-HD cotreatment abolished these effects. Diazoxide decreased TUNEL-positive cells following CPR, upregulated Bcl-2 and PKCε, downregulated Bax, and increased the Bcl-2/Bax ratio; 5-HD cotreatment reversed these effects. Conclusions. Diazoxide attenuates postresuscitation brain injury, protects mitochondrial function, inhibits brain cell apoptosis, and activates the PKC pathway by opening mitoKATP channels. PMID:27648441

  1. Cardiac Ischemia and Ischemia/Reperfusion Cause Wide Proteolysis of the Coronary Endothelial Luminal Membrane: Possible Dysfunctions

    Science.gov (United States)

    Arroyo-Flores, Blanca; Chi-Ahumada, Erika; Briones-Cerecero, Erika; Barajas-Espinosa, Alma; Perez-Aguilar, Sandra; de la Rosa, Ana Barba; Knabb, Maureen; Rubio, Rafael

    2011-01-01

    Background: Ischemia and ischemia-reperfusion (I/R) are common clinical insults that disrupt the molecular structure of coronary vascular endothelial luminal membrane (VELM) that result in diverse microvasculature dysfunctions. However, the knowledge of the associated biochemical changes is meager. We hypothesized that ischemia and I/R-induced structural and functional VELM alterations result from biochemical changes. First, these changes need to be described and later the mechanisms behind be identified. Methods: During control conditions, in isolated perfused rat hearts VELM proteins were labeled with biotin. The groups of hearts were: control (C), no flow ischemia (I; 25 min), and I/R (I; 25 min, reperfusion 30 min). The biotinylated luminal endothelial membrane proteins in these three different groups were examined by 2-D electrophoresis and identified. But, it must be kept in mind the proteins were biotin-labeled during control. Results: A comparative analysis of the protein profiles under the 3 conditions following 2D gel electrophoresis showed differences in the molecular weight distribution such that MWC > MWI > MWI/R. Similar analysis for isoelectric points (pHi) showed a shift toward more acidic pHi under ischemic conditions. Of 100 % proteins identified during control 66% and 88% changed their MW-pHi during ischemia and I/R respectively. Among these lost proteins there were 9 proteins identified as adhesins and G-protein coupled receptors. General significance: I and I/R insults alter MW-pHi of most luminal glycocalyx proteins due to the activation of nonspecific hydrolizing mechanisms; suspect metalloproteases and glycanases. This makes necessary the identification of hydrolyzing enzymes reponsible of multiple microvascular dysfunctions in order to maintain the integrity of vascular endothelial membrane. VELM must become a target of future therapeutics. PMID:22262983

  2. Effects of neutral sulfate berberine on LPS-induced cardiomyocyte TNF-αsecretion, abnormal calcium cycling, and cardiac dysfunction in rats

    Institute of Scientific and Technical Information of China (English)

    Jing YANG; Hua-dong WANG; Da-xiang LU; Yan-ping WANG; Ren-bin QI; Jing LI; Fei LI; Chu-jie LI

    2006-01-01

    Aim: To evaluate the effect of neutral sulfate berberine on cardiac function, tumornecrosis factor α (TNF-α) release, and intracellular calcium concentration ([Ca2+]i)in cardiomyocytes exposed to lipopolysaccharide (LPS). Methods: Primary cultured rat cardiomyocytes were prepared from ventricles of 3-4-day old SpragueDawley rats. TNF-α concentrations in cell-conditioned media were measured by using a Quantikine enzyme-linked immunosorbent assay kit, and cardiomyocyte [Ca2+]i was measured by using Fura-2/AM. The isolated rat hearts were perfused in the Langendorff mode. Results: LPS at doses of 1, 5, 10, and 20 μg/mL markedly stimulated TNF-α secretion from cardiomyocytes, and neutral sulfate berberine inhibited LPS-induced TNF-α production. Intracellular calcium concentration was significantly decreased after LPS stimulation for 1 h, and increased 2 h after LPS treatment. Pretreatment with neutral sulfate berberine reversed the LPS-induced [Ca2+]i alterations, although neutral sulfate berberine did not inhibit a rapid increase in cardiomyocyte [Ca2+]i induced by LPS. Perfusion of isolated hearts with LPS (100 μg/mL) for 20 min resulted in significantly impaired cardiac performance at 120 min after LPS challenge: the maximal rate of left ventricular pressure rise and fall (±dp/dtmax) decreased compared with the control. In contrast, ±dp/dtmax at 120min in hearts perfused with neutral sulfate berberine (1 μmol/L) for 10 min followed by 20 min LPS (100 μg/mL) was greater than the corresponding value in the LPS group. Conclusion: Neutral sulfate berberine inhibits LPS-stimulated myocardial TNF-α production, impairs calcium cycling, and improves LPS-induced contractile dysfunction in intact heart.

  3. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

    Science.gov (United States)

    Gulati, Geeta; Heck, Siri Lagethon; Ree, Anne Hansen; Hoffmann, Pavel; Schulz-Menger, Jeanette; Fagerland, Morten W.; Gravdehaug, Berit; von Knobelsdorff-Brenkenhoff, Florian; Bratland, Åse; Storås, Tryggve H.; Hagve, Tor-Arne; Røsjø, Helge; Steine, Kjetil; Geisler, Jürgen; Omland, Torbjørn

    2016-01-01

    Aims Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. Conclusion In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function. PMID:26903532

  4. FAK-related nonkinase attenuates hypertrophy induced by angiotensin-Ⅱ in cultured neonatal rat cardiac myocytes

    Institute of Scientific and Technical Information of China (English)

    Jin QIN; Zheng-xiang LIU

    2006-01-01

    Aim: To examine the inhibitory effect of FAK-related nonkinase (FRNK) in cardiac hypertrophy in vitro and investigate the possible mechanisms. Methods: A functional fragment of FRNK cDNA was amplified by reverse transcription-polymerase chain reaction and cloned into the vector pcDNA3.1. Hypertrophy in neonatal rat cardiac myocytes was established with angiotensin-Ⅱ stimulation. The pcDNA3.1-FRNK or pcDNA3.1 was respectively transfected into cardiomyocytes by Lipofectamine 2000. The surface area and mRNA expression of atrial natriuretic peptide (ANP) of myocytes were employed to detect cardiac hypertrophy. NF-κB p65 protein in nuclear extracts, phosphorylation levels of ERK1/2 (p-ERK1/2) and AKT (p-AKT), as well as total ERK1/2, and AKT in variant treated cardiomyocytes were determined by Western blot. Results: Under the stimulation of angiotensin Ⅱ, the surface area of myocytes and levels of ANP mRNA were significantly increased. But transient transfection with pcDNA3.1-FRNK in advance may reduce the surface area and expression of ANP mRNA of hypertrophic myocytes. The protein levels of NF-κB p65 in nuclear extracts and p-ERK1/2, p-AKT in FRNK treated cardiomyocytes were significantly decreased compared with that in angiotensin-Ⅱ induced cardiomyocytes, while different treatments had little effect on total ERK1/2 and AKT. Conclusion: FRNK may inhibit angiotensin-Ⅱ-induced cardiomyocyte hypertrophy via decreasing phosphorylation levels at ERK1/2 and AKT, consequently downregulating nuclear translocation of NF-κB p65.

  5. Butanolic fraction of Moringa oleifera Lam. (Moringaceae) attenuates isoprotrenol induced cardiac necrosis and oxidative stress in rats: an EPR study

    OpenAIRE

    Panda, Sunanda

    2015-01-01

    The preventive effect of Moringa oleifera polyphenolic fraction (MOPF) on cardiac damage was evaluated in isoproterenol (ISO) induced cardiotoxicity model of Wistar rats. Male rats in different groups were treated with MOPF orally at the dose of 50, 100 and 150 mg/kg/day for 28 days and were subsequently administered (s.c.) with ISO (85 mg/kg body weight) for the last two days. At the end of the experiment levels of serum troponin-T, creatine kinase-MB, lactate dehydrogenase, content of malon...

  6. Subclinical Cardiac Dysfunction Detected by Strain Imaging During Breast Irradiation With Persistent Changes 6 Weeks After Treatment

    International Nuclear Information System (INIS)

    Purpose: To evaluate 2-dimensional strain imaging (SI) for the detection of subclinical myocardial dysfunction during and after radiation therapy (RT). Methods and Materials: Forty women with left-sided breast cancer, undergoing only adjuvant RT to the left chest, were prospectively recruited. Standard echocardiography and SI were performed at baseline, during RT, and 6 weeks after RT. Strain (S) and strain rate (Sr) parameters were measured in the longitudinal, circumferential, and radial planes. Correlation of change in global longitudinal strain (GLS % and Δ change) and the volume of heart receiving 30 Gy (V30) and mean heart dose (MHD) were examined. Results: Left ventricular ejection fraction was unchanged; however, longitudinal systolic S and Sr and radial S were significantly reduced during RT and remained reduced at 6 weeks after treatment [longitudinal S (%) −20.44 ± 2.66 baseline vs −18.60 ± 2.70* during RT vs −18.34 ± 2.86* at 6 weeks after RT; longitudinal Sr (s−1) −1.19 ± 0.21 vs −1.06 ± 0.18* vs −1.06 ± 0.16*; radial S (%) 56.66 ± 18.57 vs 46.93 ± 14.56* vs 49.22 ± 15.81*; *P<.05 vs baseline]. Diastolic Sr were only reduced 6 weeks after RT [longitudinal E Sr (s−1) 1.47 ± 0.32 vs 1.29 ± 0.27*; longitudinal A Sr (s−1) 1.19 ± 0.31 vs 1.03 ± 0.24*; *P<.05 vs baseline], whereas circumferential strain was preserved throughout. A modest correlation between S and Sr and V30 and MHD was observed (GLS Δ change and V30 ρ = 0.314, P=.05; GLS % change and V30 ρ = 0.288, P=.076; GLS Δ change and MHD ρ = 0.348, P=.03; GLS % change and MHD ρ = 0.346, P=.031). Conclusions: Subclinical myocardial dysfunction was detected by 2-dimensional SI during RT, with changes persisting 6 weeks after treatment, though long-term effects remain unknown. Additionally, a modest correlation between strain reduction and radiation dose was observed

  7. Subclinical Cardiac Dysfunction Detected by Strain Imaging During Breast Irradiation With Persistent Changes 6 Weeks After Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Queenie [University of New South Wales, Sydney, NSW (Australia); Liverpool Hospital, Sydney, NSW (Australia); Hee, Leia; Batumalai, Vikneswary [University of New South Wales, Sydney, NSW (Australia); Liverpool Hospital, Sydney, NSW (Australia); Ingham Institute of Applied Medical Research, Liverpool, NSW (Australia); Allman, Christine [Liverpool Hospital, Sydney, NSW (Australia); MacDonald, Peter [University of New South Wales, Sydney, NSW (Australia); St. Vincent' s Hospital, Sydney, NSW (Australia); Delaney, Geoff P. [University of New South Wales, Sydney, NSW (Australia); Liverpool Hospital, Sydney, NSW (Australia); Ingham Institute of Applied Medical Research, Liverpool, NSW (Australia); Lonergan, Denise [Liverpool Hospital, Sydney, NSW (Australia); Ingham Institute of Applied Medical Research, Liverpool, NSW (Australia); Thomas, Liza, E-mail: l.thomas@unsw.edu.au [University of New South Wales, Sydney, NSW (Australia); Liverpool Hospital, Sydney, NSW (Australia)

    2015-06-01

    Purpose: To evaluate 2-dimensional strain imaging (SI) for the detection of subclinical myocardial dysfunction during and after radiation therapy (RT). Methods and Materials: Forty women with left-sided breast cancer, undergoing only adjuvant RT to the left chest, were prospectively recruited. Standard echocardiography and SI were performed at baseline, during RT, and 6 weeks after RT. Strain (S) and strain rate (Sr) parameters were measured in the longitudinal, circumferential, and radial planes. Correlation of change in global longitudinal strain (GLS % and Δ change) and the volume of heart receiving 30 Gy (V30) and mean heart dose (MHD) were examined. Results: Left ventricular ejection fraction was unchanged; however, longitudinal systolic S and Sr and radial S were significantly reduced during RT and remained reduced at 6 weeks after treatment [longitudinal S (%) −20.44 ± 2.66 baseline vs −18.60 ± 2.70* during RT vs −18.34 ± 2.86* at 6 weeks after RT; longitudinal Sr (s{sup −1}) −1.19 ± 0.21 vs −1.06 ± 0.18* vs −1.06 ± 0.16*; radial S (%) 56.66 ± 18.57 vs 46.93 ± 14.56* vs 49.22 ± 15.81*; *P<.05 vs baseline]. Diastolic Sr were only reduced 6 weeks after RT [longitudinal E Sr (s{sup −1}) 1.47 ± 0.32 vs 1.29 ± 0.27*; longitudinal A Sr (s{sup −1}) 1.19 ± 0.31 vs 1.03 ± 0.24*; *P<.05 vs baseline], whereas circumferential strain was preserved throughout. A modest correlation between S and Sr and V30 and MHD was observed (GLS Δ change and V30 ρ = 0.314, P=.05; GLS % change and V30 ρ = 0.288, P=.076; GLS Δ change and MHD ρ = 0.348, P=.03; GLS % change and MHD ρ = 0.346, P=.031). Conclusions: Subclinical myocardial dysfunction was detected by 2-dimensional SI during RT, with changes persisting 6 weeks after treatment, though long-term effects remain unknown. Additionally, a modest correlation between strain reduction and radiation dose was observed.

  8. Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion.

    Science.gov (United States)

    Yang, Mingzhu; Orgah, John; Zhu, Jie; Fan, Guanwei; Han, Jihong; Wang, Xiaoying; Zhang, Boli; Zhu, Yan

    2016-07-01

    Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects. PMID:27107944

  9. Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion.

    Science.gov (United States)

    Yang, Mingzhu; Orgah, John; Zhu, Jie; Fan, Guanwei; Han, Jihong; Wang, Xiaoying; Zhang, Boli; Zhu, Yan

    2016-07-01

    Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V1A and V2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects.

  10. Effect on short- and long-term major adverse cardiac events of statin treatment in patients with acute myocardial infarction and renal dysfunction.

    Science.gov (United States)

    Lim, Sang Yup; Bae, Eun Hui; Choi, Joon Seok; Kim, Chang Seong; Park, Jeong Woo; Ma, Seong Kwon; Jeong, Myung Ho; Kim, Soo Wan

    2012-05-15

    The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduce major adverse cardiac events (MACE) and mortality in patients with acute coronary syndrome. We investigated the effectiveness of statin therapy in reducing MACE in patients with acute myocardial infarction (AMI) and renal dysfunction (RD). In the present retrospective study of 12,853 patients with AMI, the patients were categorized into 4 groups: group I, statin therapy and no RD (estimated glomerular filtration rate ≥60 ml/min/1.73 m(2)); group II, neither statin therapy nor RD; group III, statin therapy and RD; group IV, no statin therapy but RD. The primary end points were death and complications during the hospital course. The secondary end points were MACE during 1 year of follow-up after AMI. Significant differences in the composite MACE during 12 months of follow-up were observed among the 4 groups (group I, 11.7%; group II, 19.0%; group III, 26.7%; and group IV, 45.5%; p <0.001). In a Cox proportional hazards model, mortality at 12 months increased stepwise from group II to IV compared to group I. Moreover, MACE-free survival in the severe RD group (estimated glomerular filtration rate <30 mL/min/1.73 m(2)) was also greater in the statin-treated group. In conclusion, statin therapy reduced MACE at 1 year of follow-up in patients with AMI regardless of RD.

  11. Ac-cel, a novel antioxidant, protects against hydrogen peroxide-induced injury in PC12 cells via attenuation of mitochondrial dysfunction.

    Science.gov (United States)

    Guo, Xianjun; Chen, Yuting; Liu, Qunfang; Wu, Jian; Wang, Luoyi; Tang, Xican; Zhao, Weimin; Zhang, Haiyan

    2013-07-01

    Oxidative stress has been implicated in pathophysiology of many neurodegenerative diseases (ND) and increased oxidative stress is closely associated with mitochondrial dysfunction. As a result, looking for potent antioxidants, especially those targeting mitochondria, has become an attractive strategy in ND therapy. In this study, we explored protective effects and potential mechanism of Ac-cel, a novel compound, against hydrogen peroxide (H(2)O(2))-induced injury in PC12 cells. Pretreatment of PC12 cells with Ac-cel prior to 24 h of H(2)O(2) exposure markedly attenuated cytotoxicity induced by H(2)O(2) as evidenced by morphological changes and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Ac-cel also exhibited potent antiapoptotic effect demonstrated by results of annexin V and PI staining. The above beneficial effects of Ac-cel were accompanied by improved mitochondrial function, reduced caspase-3 cleavage as well as upregulated ratio of Bcl-2/Bax protein expression. Moreover, Ac-cel pretreatment markedly reversed intracellular reactive oxygen species (ROS) accumulation following 30 min of H(2)O(2) exposure in PC12 cells. Further, subcellular investigation indicated that Ac-cel significantly reduced production of mitochondrial ROS in isolated rat cortical mitochondria. Taken together, the present study, for the first time, reports that Ac-cel pretreatment inhibits H(2)O(2)-stimulated early accumulation of intracellular ROS possibly via reducing mitochondrial ROS production directly and leads to subsequent preservation of mitochondrial function. These results indicate that Ac-cel is a potential drug candidate for treatment of oxidative stress-associated ND.

  12. 睡眠呼吸暂停与心功能不全%Sleep apnea and cardiac dysfunction

    Institute of Scientific and Technical Information of China (English)

    姚菲菲; 张希龙

    2011-01-01

    呼吸系统和循环系统必须协同作用在细胞及其外循环间运送氧和二氧化碳.循环在呼吸时的变化和持续变化的肺泡通气在心血管系统中均发挥重要作用.这些作用在阻塞性睡眠呼吸暂停患者中表现的尤为明显.近期更多证据表明阻塞性睡眠呼吸暂停会引起和加速左心室肥大和左心功能不全.陈-施呼吸是中枢性睡眠呼吸暂停的一种形式,多见于充血性心力衰竭患者,大量研究表明充血性心力衰竭合并陈-施呼吸会形成恶性循环,通过进一步加重心脏负担而增加患者病死率.%The respiratory and cardiovascular systems must act in concert to transfer oxygen (O2)and carbon dioxide (CO2) between the atmosphere and the cells. Both cyclic changes in breathing and sustained changes in alveolar ventilation exert important effects on the cardiovascular system. These effects are particularly prominent in patients with obstructive sleep apnea (OSA). More recently, there is a growing body of evidence implicating OSA in the development or progression of left ventricular hypertrophy and dysfunction. Cheyne-Stokes respiration (CSR) is a form of central sleep apnea (CSA), it is common in patients with congestive heart failure (CHF), and there is increasing evidence to suggest that CSR-CSA in patients with CHF participates in a vicious cycle that further stresses the failing heart and, in doing so, increases the risk of mortality.

  13. Olmesartan, an AT1 Antagonist, Attenuates Oxidative Stress, Endoplasmic Reticulum Stress and Cardiac Inflammatory Mediators in Rats with Heart Failure Induced by Experimental Autoimmune Myocarditis

    Directory of Open Access Journals (Sweden)

    Vijayakumar Sukumaran, Kenichi Watanabe, Punniyakoti T. Veeraveedu, Narasimman Gurusamy, Meilei Ma, Rajarajan A. Thandavarayan, Arun Prasath Lakshmanan, Ken'ichi Yamaguchi, Kenji Suzuki, Makoto Kodama

    2011-01-01

    Full Text Available Studies have demonstrated that angiotensin II has been involved in immune and inflammatory responses which might contribute to the pathogenesis of immune-mediated diseases. Recent evidence suggests that oxidative stress may play a role in myocarditis. Here, we investigated whether olmesartan, an AT1R antagonist protects against experimental autoimmune myocarditis (EAM by suppression of oxidative stress, endoplasmic reticulum (ER stress and inflammatory cytokines. EAM was induced in Lewis rats by immunization with porcine cardiac myosin, were divided into two groups and treated with either olmesartan (10 mg/kg/day or vehicle for a period of 21 days. Myocardial functional parameters measured by hemodynamic and echocardiographic analyses were significantly improved by the treatment with olmesartan compared with those of vehicle-treated rats. Treatment with olmesartan attenuated the myocardial mRNA expressions of proinflammatory cytokines, [Interleukin (IL-1β, monocyte chemoattractant protein-1, tumor necrosis factor-α and interferon-γ] and the protein expression of tumor necrosis factor-α compared with that of vehicle-treated rats. Myocardial protein expressions of AT1R, NADPH oxidase subunits (p47phox, p67phox, gp91phox and the expression of markers of oxidative stress (3-nitrotyrosine and 4-hydroxy-2-nonenal, and the cardiac apoptosis were also significantly decreased by the treatment with olmesartan compared with those of vehicle-treated rats. Furthermore, olmesartan treatment down-regulated the myocardial expressions of glucose regulated protein-78, growth arrest and DNA damage-inducible gene, caspase-12, phospho-p38 mitogen-activated protein kinase (MAPK and phospho-JNK. These findings suggest that olmesartan protects against EAM in rats, at least in part via suppression of oxidative stress, ER stress and inflammatory cytokines.

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

    Science.gov (United States)

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

    2007-03-01

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

  15. Apigenin Attenuates β-Receptor-Stimulated Myocardial Injury Via Safeguarding Cardiac Functions and Escalation of Antioxidant Defence System.

    Science.gov (United States)

    Buwa, Chhabildas C; Mahajan, Umesh B; Patil, Chandragouda R; Goyal, Sameer N

    2016-07-01

    Apigenin (AP) is a flavone in dietary flavonoids reported as strong antioxidant and elite modulator of PPARγ. The current study evaluated the consequence of AP in isoproterenol (ISO)-induced oxidative stress and myocardial infarction during β-adrenergic receptor stimulus in rats by persistent hemodynamic, biochemical and histopathological changes. Rats received AP (25, 50 and 75 mg/kg/day) or vehicle i.p. for 14 days and ISO (100 mg/kg, s.c.) on 13th and 14th days for initiation of cardiotoxicity. ISO-treated rats showed evidence of significant dwindle in systolic and diastolic arterial pressures, maximal positive rate of developed left ventricular pressure. In totting up, a noteworthy diminution in activities of creatine kinase-MB isoenzyme, reduced glutathione, superoxide dismutase, catalase and level along with rise in malondialdehyde content were observed. The shielding function of AP on isoproterenol-induced myocardial damage was observed by attenuating all the endogenous parameters and the membrane-bound enzymes. It was confirmed by histopathological examinations. The effect of AP at the doses of 50 and 75 mg/kg showed added apparent than at the dose of 25 mg/kg. Current study thus provides confirmation for protective effects of AP on myocardium in experimentally induced myocardial infarction. PMID:26186996

  16. Work flow with manual re-registration of cardiac 18F-FDG PET and attenuation correction CT to compensate for respiratory motion: Effects and inter-operator variability

    DEFF Research Database (Denmark)

    Juhl, Christian; Christensen, Nana Louise; Møller, Lone W.;

    , attenuation artefacts are often observed on the lateral wall of the left ventricle. Many strategies has been proposed to reduce these artefacts, including averaging multiple CTs, respiratory gating and manual re-registration1-3. However, for scanner platform-independent implementation, manual re......Aim: Cardiac PET exams with CT for attenuation correction are increasing in number. However, due to different natures of the PET (average over many respiratory cycles) and the CT exam (snap-shot during one respiratory cycle) and the large difference in density of the cardiac and lung tissue......-registration is currently the most feasible. In this study, we examine both the effect on misalignment artefacts and the inter-operator variability of manual re-registration performed by the technologist in a step before the final image reconstruction and verified by a second technologist before image analysis. Method: 40...

  17. Pre-treatment with bone marrow-derived mesenchymal stem cells inhibits systemic intravascular coagulation and attenuates organ dysfunction in lipopolysaccharide-induced disseminated intravascular coagulation rat model

    Institute of Scientific and Technical Information of China (English)

    WANG Biao; WU Shu-ming; WANG Tao; LIU Kai; ZHANG Gong; ZHANG Xi-quan; YU Jian-hua; LIU Chuan-zhen; FANG Chang-cun

    2012-01-01

    attenuate organ dysfunction and inhibit systemic intravascular coagulation effectively via the regulatory effect on immune ceils and proinflammatory cytokines in LPS-induced DIG rat model.

  18. Cardiac sympathetic dysfunction in Parkinson's disease. Relationship between results of 123I-MIBG scintigraphy and autonomic nervous function evaluated by the Valsalva maneuver

    International Nuclear Information System (INIS)

    correlated with early and delayed H/M ratios. No other significant correlations were detected. The early H/M ratio in the patients with PD who had IVp within the normal range was lower than the early H/M ratio in control subjects. Our results show that early and delayed H/M ratio correlates with cardiac autonomic function, evaluated on the basis of QTc interval and the Valsalva maneuver, but not with BRS or vasomotor autonomic function. Our findings suggest that silent cardiac autonomic dysfunction may be evaluated by 123I-MIBG scintigraphy, because early and delayed H/M ratios were lower in the patients with PD who had normal IVp than in the control subjects. (author)

  19. Hydrogen sulfide ameliorates cardiovascular dysfunction induced by cecal ligation and puncture in rats.

    Science.gov (United States)

    Abdelrahman, R S; El-Awady, M S; Nader, M A; Ammar, E M

    2015-10-01

    Hydrogen sulfide (H2S) is an endogenously produced gaseous messenger that participates in regulation of cardiovascular functions. This study evaluates the possible protective effect of H2S in cardiovascular dysfunction induced by cecal ligation and puncture (CLP) in rats. After 24 h of induction of CLP, heart rate (HR), mortality, cardiac and inflammation biomarkers (creatine kinase-MB (CK-MB) isozyme, cardiac troponin I (cTnI), C-reactive protein (CRP), and lactate dehydrogenase (LDH)), in vitro vascular reactivity, histopathological examination, and oxidative biomarkers (malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD)) were determined. CLP induced elevations in HR, mortality, serum CK-MB, cTnI, CRP, and LDH, in addition to impaired aortic contraction to potassium chloride and phenylephrine and relaxation to acetylcholine without affecting sodium nitroprusside responses. Moreover, CLP increased cardiac and aortic MDA and decreased SOD, without affecting GSH and caused a marked subserosal and interstitial inflammation in endocardium. Sodium hydrosulfide, but not the irreversible inhibitor of H2S synthesis dl-propargyl glycine, protected against CLP-induced changes in HR, mortality, cardiac and inflammatory biomarkers, oxidative stress, and myocardium histopathological changes without affecting vascular dysfunction. Our results confirm that H2S can attenuate CLP-induced cardiac, but not vascular, dysfunction possibly through its anti-inflammatory and antioxidant effects.

  20. Protein kinase C betaII peptide inhibitor exerts cardioprotective effects in rat cardiac ischemia/reperfusion injury.

    Science.gov (United States)

    Omiyi, Didi; Brue, Richard J; Taormina, Philip; Harvey, Margaret; Atkinson, Norrell; Young, Lindon H

    2005-08-01

    Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. A cell-permeable protein kinase C (PKC) betaII peptide inhibitor was used to test the hypothesis that PKC betaII inhibition could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs and increase NO release from vascular endothelium. The effects of the PKC betaII peptide inhibitor were examined in isolated ischemic (20 min) and reperfused (45 min) rat hearts with PMNs. The PKC betaII inhibitor (10 microM; n = 7) significantly attenuated PMN-induced cardiac dysfunction compared with I/R hearts (n = 9) receiving PMNs alone in left ventricular developed pressure (LVDP) and the maximal rate of LVDP (+dP/dt(max)) cardiac function indices (p < 0.01). The PKC betaII inhibitor at 10 microM significantly increased endothelial NO release from a basal value of 1.85 +/- 0.18 pmol NO/mg tissue to 3.49 +/- 0.62 pmol NO/mg tissue from rat aorta. It also significantly inhibited superoxide release (i.e., absorbance) from N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated rat PMNs from 0.13 +/- 0.01 to 0.02 +/- 0.004 (p < 0.01) at 10 microM. Histological analysis of the left ventricle of representative rat hearts from each group showed that the PKC betaII peptide inhibitor-treated hearts experienced a marked reduction in PMN vascular adherence and infiltration into the postreperfused cardiac tissue compared with I/R + PMN hearts (p < 0.01). These results suggest that the PKC betaII peptide inhibitor attenuates PMN-induced post-I/R cardiac contractile dysfunction by increasing endothelial NO release and by inhibiting superoxide release from PMNs. PMID:15878997

  1. Silencing MicroRNA-155 Attenuates Cardiac Injury and Dysfunction in Viral Myocarditis via Promotion of M2 Phenotype Polarization of Macrophages

    OpenAIRE

    Yingying Zhang; Mengying Zhang; Xueqin Li; Zongsheng Tang; Xiangmin Wang; Min Zhong; Qifeng Suo; Yao Zhang; Kun Lv

    2016-01-01

    Macrophage infiltration is a hallmark feature of viral myocarditis. As studies have shown that microRNA-155 regulates the differentiation of macrophages, we aimed to investigate the role of microRNA-155 in VM. We report that silencing microRNA-155 protects mice from coxsackievirus B3 induced myocarditis. We found that microRNA-155 expression was upregulated and localized primarily in heart-infiltrating macrophages and CD4+ T lymphocytes during acute myocarditis. In contrast with wildtype (WT)...

  2. Pycnogenol attenuates the symptoms of immune dysfunction through restoring a cellular antioxidant status in low micronutrient-induced immune deficient mice

    OpenAIRE

    Lee, Jeongmin; Nam, Da-Eun; Kim, Ok-Kyung; Lee, Myung-Yul

    2014-01-01

    BACKGROUND/OBJECTIVES We investigated the effect of Pycnogenol (Pyc) on survival and immune dysfunction of C57BL/6 mice induced by low micronutrient supplementation. MATERIALS/METHODS Female C57/BL/6 mice were fed a diet containing 7.5% of the recommended amount of micronutrients for a period of 12 wks (immunological assay) and 18 wks (survival test). For immunological assay, lymphocyte proliferation, cytokine regulation, and hepatic oxidative status were determined. RESLUTS Pyc supplementati...

  3. O polimorfismo AGT*M235T na disfunção cardíaca de etiologia isquêmica aguda: projeto gisca AGT*M235T polymorphism in acute ischemic cardiac dysfunction: the gisca project

    Directory of Open Access Journals (Sweden)

    Claudia Guerra Murad Saud

    2010-08-01

    Full Text Available FUNDAMENTO: O polimorfismo AGT*M235T tem sido associado a elevados níveis séricos de angiotensinogênio (AGT, hipertensão arterial sistêmica e disfunção cardíaca (DC. OBJETIVO: Testar a hipótese de haver associação entre polimorfismo AGT*M235T e o risco de desenvolver disfunção cardíaca (insuficiência cardíaca ou disfunção sistólica ventricular esquerda assintomática pós-síndrome coronariana aguda (SCA, durante o período de internação hospitalar. MÉTODOS: Foram estudados 363 pacientes (idade média 62 ± 12 anos, sendo 233 (64% homens e 130 (36% mulheres, todos da mesma coorte, internados por SCA. Compararam-se dados clínicos e genéticos dos 117 (32,2% que evoluíram com disfunção cardíaca (grupo caso com os dos 246 (67,8%, que não desenvolveram tal condição (grupo controle. O polimorfismo AGT*M235T foi determinado por análise de sequenciamento e estava em equilíbrio de Hardy-Weinberg. RESULTADOS: Houve diferença significativa na distribuição dos genótipos nas mulheres, com predomínio do genótipo *235MM no grupo controle (p = 0,001 e do alelo *235T no grupo caso. Em ambos os sexos, nos modelos de regressão logística, o diagnóstico de infarto de parede anterior na admissão foi fator de incremento no risco de DC, enquanto angina instável na admissão, ausência do alelo *235T, glicemia 60 e BACKGROUND: AGT*M235T polymorphism has been associated with high serum angiotensinogen (AGT levels, systemic hypertension and cardiac dysfunction (CD. OBJECTIVE: To test the hypothesis of AGT*M235T polymorphism being associated with the risk of developing cardiac dysfunction (heart failure or asymptomatic left ventricular systolic dysfunction after acute coronary syndrome (ACS during hospitalization. METHODS: A total of 363 patients (mean age of 62 ± 12 years, of whom 233 (64% were men and 130 (36% were women, all from the same cohort and hospitalized for ACS, were studied. Clinical and genetic data from the 117

  4. Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction.

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    Full Text Available BACKGROUND: Left ventricular hypertrophy is enhanced by an inflammatory state and stimulation of various cytokines. Pentraxin 3 (PTX3 is rapidly produced in response to inflammatory signals, and high plasma PTX3 levels are seen in patients with heart failure. This study aimed to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction with respect to pressure overload. METHODS AND RESULTS: PTX3 systemic knockout (PTX3-KO mice, transgenic mice with cardiac-specific overexpression of PTX3 (PTX3-TG, and the respective wild-type (WT littermate mice were subjected to transverse aortic constriction (TAC or a sham operation. Cardiac PTX3 expression increased after TAC in WT mice. In vitro, hydrogen peroxide induced the expression of PTX3 in both cardiac myocytes and cardiac fibroblasts. Recombinant PTX3 phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2 in cardiac fibroblasts. Phosphorylation of cardiac ERK1/2 and nuclear factor kappa-B after TAC was attenuated in the PTX3-KO mice but was enhanced in the PTX3-TG mice compared with WT mice. Interleukin-6 and connective tissue growth factor production was lower in the PTX3-KO mice than in the WT mice, but this was augmented in the PTX3-TG mice than in the WT mice. Echocardiography revealed that adverse remodeling with left ventricular dysfunction, as well as with increased interstitial fibrosis, was enhanced in PTX3-TG mice, while these responses were suppressed in PTX3-KO mice. CONCLUSION: The local inflammatory mediator PTX3 directly modulates the hypertrophic response and ventricular dysfunction following an increased afterload.

  5. [Cardiac amyloidosis].

    Science.gov (United States)

    Hoyer, Caroline; Angermann, Christiane E; Knop, Stefan; Ertl, Georg; Störk, Stefan

    2008-03-15

    Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment. PMID:18344065

  6. Omega-3 Fatty Acid Supplementation Appears to Attenuate Particulate Air Pollution-induced Cardiac Effects and Lipid Changes in Healthy Middle-aged Adults.

    Science.gov (United States)

    Context: Air pollution exposure has been associated with adverse cardiovascular effects. A recent epidemiologic study reported that omega-3 fatty acid (fish oil) supplementation blunted the cardiac responses to air pollution exposure. Objective: To evaluate in a randomized contro...

  7. Ubiquitin-Specific Protease 4 Is an Endogenous Negative Regulator of Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    He, Ben; Zhao, Yi-Chao; Gao, Ling-Chen; Ying, Xiao-Ying; Xu, Long-Wei; Su, Yuan-Yuan; Ji, Qing-Qi; Lin, Nan; Pu, Jun

    2016-06-01

    Dysregulation of the ubiquitin proteasome system components ubiquitin ligases and proteasome plays an important role in the pathogenesis of cardiac hypertrophy. However, little is known about the role of another ubiquitin proteasome system component, the deubiquitinating enzymes, in cardiac hypertrophy. Here, we revealed a crucial role of ubiquitin specific protease 4 (USP4), a deubiquitinating enzyme prominently expressed in the heart, in attenuating pathological cardiac hypertrophy and dysfunction. USP4 levels were consistently decreased in human failing hearts and in murine hypertrophied hearts. Adenovirus-mediated gain- and loss-of-function approaches indicated that deficiency of endogenous USP4 promoted myocyte hypertrophy induced by angiotensin II in vitro, whereas restoration of USP4 significantly attenuated the prohypertrophic effect of angiotensin II. To corroborate the role of USP4 in vivo, we generated USP4 global knockout mice and mice with cardiac-specific overexpression of USP4. Consistent with the in vitro study, USP4 depletion exacerbated the hypertrophic phenotype and cardiac dysfunction in mice subjected to pressure overload, whereas USP4 transgenic mice presented ameliorated pathological cardiac hypertrophy compared with their control littermates. Molecular analysis revealed that USP4 deficiency augmented the activation of the transforming growth factor β-activated kinase 1 (TAK1)-(JNK1/2)/P38 signaling in response to hypertrophic stress, and blockage of TAK1 activation abolished the pathological effects of USP4 deficiency in vivo. These findings provide the first evidence for the involvement of USP4 in cardiac hypertrophy, and shed light on the therapeutic potential of targeting USP4 in the treatment of cardiac hypertrophy.

  8. Diuretics Prevent Thiazolidinedione-Induced Cardiac Hypertrophy without Compromising Insulin-Sensitizing Effects in Mice

    Science.gov (United States)

    Chang, Cherng-Shyang; Tsai, Pei-Jane; Sung, Junne-Ming; Chen, Ju-Yi; Ho, Li-Chun; Pandya, Kumar; Maeda, Nobuyo; Tsai, Yau-Sheng

    2015-01-01

    Much concern has arisen regarding critical adverse effects of thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, on cardiac tissue. Although TZD-induced cardiac hypertrophy (CH) has been attributed to an increase in plasma volume or a change in cardiac nutrient preference, causative roles have not been established. To test the hypothesis that volume expansion directly mediates rosiglitazone-induced CH, mice were fed a high-fat diet with rosiglitazone, and cardiac and metabolic consequences were examined. Rosiglitazone treatment induced volume expansion and CH in wild-type and PPARγ heterozygous knockout (Pparg+/−) mice, but not in mice defective for ligand binding (PpargP465L/+). Cotreatment with the diuretic furosemide in wild-type mice attenuated rosiglitazone-induced CH, hypertrophic gene reprogramming, cardiomyocyte apoptosis, hypertrophy-related signal activation, and left ventricular dysfunction. Similar changes were observed in mice treated with pioglitazone. The diuretics spironolactone and trichlormethiazide, but not amiloride, attenuated rosiglitazone effects on volume expansion and CH. Interestingly, expression of glucose and lipid metabolism genes in the heart was altered by rosiglitazone, but these changes were not attenuated by furosemide cotreatment. Importantly, rosiglitazone-mediated whole-body metabolic improvements were not affected by furosemide cotreatment. We conclude that releasing plasma volume reduces adverse effects of TZD-induced volume expansion and cardiac events without compromising TZD actions in metabolic switch in the heart and whole-body insulin sensitivity. PMID:24287404

  9. CD44-deficiency attenuates the immunologic responses to LPS and delays the onset of endotoxic shock-induced renal inflammation and dysfunction.

    Directory of Open Access Journals (Sweden)

    Elena Rampanelli

    Full Text Available Acute kidney injury (AKI is a common complication during systemic inflammatory response syndrome (SIRS, a potentially deadly clinical condition characterized by whole-body inflammatory state and organ dysfunction. CD44 is a ubiquitously expressed cell-surface transmembrane receptor with multiple functions in inflammatory processes, including sterile renal inflammation. The present study aimed to assess the role of CD44 in endotoxic shock-induced kidney inflammation and dysfunction by using CD44 KO and WT mice exposed intraperitoneally to LPS for 2, 4, and 24 hours . Upon LPS administration, CD44 expression in WT kidneys was augmented at all time-points. At 2 and 4 hours, CD44 KO animals showed a preserved renal function in comparison to WT mice. In absence of CD44, the pro-inflammatory cytokine levels in plasma and kidneys were lower, while renal expression of the anti-inflammatory cytokine IL-10 was higher. The cytokine levels were associated with decreased leukocyte influx and endothelial activation in CD44 KO kidneys. Furthermore, in vitro assays demonstrated a role of CD44 in enhancing macrophage cytokine responses to LPS and leukocyte migration. In conclusion, our study demonstrates that lack of CD44 impairs the early pro-inflammatory cytokine response to LPS, diminishes leukocyte migration/chemotaxis and endothelial activation, hence, delays endotoxic shock-induced AKI.

  10. Elevated sensitivity to cardiac ischemia in proteinuric rats is independent of adverse cardiac remodeling

    NARCIS (Netherlands)

    Szymanski, Mariusz K.; Hillege, Hans L.; Danser, A. H. Jan; Garrelds, Ingrid M.; Schoemaker, Regien G.

    2013-01-01

    Objectives: Chronic renal dysfunction severely increases cardiovascular risk. Adverse cardiac remodeling is suggested to play a major role as predisposition for increased cardiac ischemic vulnerability. The aim of the present study was to examine the role of adverse cardiac remodeling in cardiac sen

  11. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group

    DEFF Research Database (Denmark)

    Køber, L; Torp-Pedersen, C; Carlsen, J E;

    1995-01-01

    BACKGROUND. Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces mortality among survivors of acute myocardial infarction, but whether to use ACE inhibitors in all patients or only in selected patients is uncertain. METHODS. We screened 6676 consecutive patients with 7001...... myocardial infarctions confirmed by enzyme studies. A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction (ejection fraction,

  12. Nebivolol Ameliorates Cardiac NLRP3 Inflammasome Activation in a Juvenile-Adolescent Animal Model of Diet-Induced Obesity

    Science.gov (United States)

    Xie, Qihai; Wei, Tong; Huang, Chenglin; Liu, Penghao; Sun, Mengwei; Shen, Weili; Gao, Pingjin

    2016-01-01

    NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d). Treatment with nebivolol prevented HFD-induced obesity associated excess cardiac lipid accumulation as well as myocardial mitochondrial dysfunction. Nebivolol attenuated pro-inflammatory cytokines secretion and NLRP3 inflammasome activation in myocardium of obese rats. In parallel, nebivolol treatment of obese animals increased cardiac β3-AR expression, reversing the reduction of endothelial nitric oxide synthase (eNOS). In vitro, nebivolol treatment of palmitate-incubated H9C2 cells suppressed autophagy, restored mitochondrial biogenesis, leading to decreased mitochondrial reactive oxygen species (mtROS) generation, and suppressed NLRP3 inflammasome activation. Meanwhile the presence of shRNA against β3-AR or against eNOS deteriorated the protective effects of nebivolol. These data suggest the beneficial effect of nebivolol on myocardial lipotoxicity contributing to inhibiting NLRP3 inflammasome activation possibly via improved mitochondrial dysfunction. PMID:27686325

  13. Orchidectomy attenuates high-salt diet-induced increases in blood pressure, renovascular resistance, and hind limb vascular dysfunction: role of testosterone.

    Science.gov (United States)

    Oloyo, Ahmed K; Sofola, Olusoga A; Yakubu, Momoh A

    2016-09-01

    Sex hormone-dependent vascular reactivity is an underlying factor contributing to sex differences in salt-dependent hypertension. This study evaluated the role of androgens (testosterone) in high salt-induced increase in blood pressure (BP) and altered vascular reactivity in renal blood flow and perfused hind limb preparation. Weanling male rats (8 weeks old, 180-200 g) were bilaterally orchidectomised or sham operated with or without testosterone replacement (Sustanon 250, 10 mg/kg intramuscularly once in 3 weeks) and placed on a normal (0.3%) or high (4.0%) NaCl diet for 6 weeks. The high-salt diet (HSD) increased arterial BP, renal vascular resistance (RVR) and positive fluid balance (FB). These changes were accompanied by decreased plasma nitric oxide levels. The increased BP, RVR and FB observed in the rats fed a HSD were reversed by orchidectomy while testosterone replacement prevented the reversal. Phenylephrine (PE)-induced increased vascular resistance in the perfused hind limb vascular bed was enhanced by HSD, the enhanced vascular resistance was prevented by orchidectomy and testosterone replacement reversed orchidectomy effect. Vasorelaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were impaired in HSD groups, orchidectomy attenuated the impairment, while testosterone replacement prevented the orchidectomy attenuation. These data suggested that eNOS-dependent and independently-mediated pathways were equally affected by HSD in vascular function impairment and this effect is testosterone-dependent in male Sprague-Dawley rats. PMID:27197589

  14. Garlic attenuates cardiac oxidative stress via activation of PI3K/AKT/Nrf2-Keap1 pathway in fructose-fed diabetic rat.

    Directory of Open Access Journals (Sweden)

    Raju Padiya

    Full Text Available BACKGROUND: Cardiovascular complication due to diabetes has remained a major cause of death. There is an urgent need to intervene the cardiac complications in diabetes by nutritional or pharmacological agents. Thus the present study was designed to find out the effectiveness of garlic on cardiac complications in insulin-resistant diabetic rats. METHODS AND RESULTS: SD rats were fed high fructose (65% diet alone or along with raw garlic homogenate (250 mg/kg/day or nutrient-matched (65% corn starch control diet for 8 weeks. Fructose-fed diabetic rats showed cardiac hypertrophy, increased NFkB activity and increased oxidative stress. Administration of garlic significantly decreased (p<0.05 cardiac hypertrophy, NFkB activity and oxidative stress. Although we did not observe any changes in myocardial catalase, GSH and GPx in diabetic heart, garlic administration showed significant (p<0.05 increase in all three antioxidant/enzymes levels. Increased endogenous antioxidant enzymes and gene expression in garlic treated diabetic heart are associated with higher protein expression of Nrf2. Increased myocardial H2S levels, activation of PI3K/Akt pathway and decreased Keap levels in fructose-fed heart after garlic administration might be responsible for higher Nrf2 levels. CONCLUSION: Our study demonstrates that raw garlic homogenate is effective in reducing cardiac hypertrophy and fructose-induced myocardial oxidative stress through PI3K/AKT/Nrf2-Keap1 dependent pathway.

  15. Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction.

    Science.gov (United States)

    Okamoto, Y; Chaves, A; Chen, J; Kelley, R; Jones, K; Weed, H G; Gardner, K L; Gangi, L; Yamaguchi, M; Klomkleaw, W; Nakayama, T; Hamlin, R L; Carnes, C; Altschuld, R; Bauer, J; Hai, T

    2001-08-01

    Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the alpha-myosin heavy chain promoter have atrial enlargement, and atrial and ventricular hypertrophy. Microscopic examination showed myocyte degeneration and fibrosis. Functionally, the transgenic heart has reduced contractility and aberrant conduction. Interestingly, expression of sorcin, a gene whose product inhibits the release of calcium from sarcoplasmic reticulum, is increased in these transgenic hearts. Taken together, our results indicate that expression of ATF3, a stress-inducible gene, in the heart leads to altered gene expression and impaired cardiac function. PMID:11485922

  16. Detection of viable myocardium by FDG coincidence SPECT predicts major adverse cardiac events in patients with coronary artery disease and LV dysfunction

    International Nuclear Information System (INIS)

    Introduction and Methods: PET imaging with 18F-fluorodeoxyglucose (FDG) is the gold standard for detection of myocardial viability. However, the use of PET is limited and, coincidence SPECT imaging with FDG has been proposed as a viable alternative. SPECT imaging using Thallium, on the other hand, though more widely available, has lower specificity compared to PET imaging. We compared coincidence SPECT imaging using FDG and Thallium (T1-201Chloride) to coronary angiograms in 51 patients (age 60±SD 14 years; 41 male, 10 females) with known CAD (32 pts with >3 vessel, 19 patients with 5% of total myocardium) on the FDG SPECT images. Four patients had cardiac death, all showing multiple coronary territory nonviable tissue on both FDG and Thallium imaging and all had LVEF 5% of total myocardium) on the FDG coincidence SPECT predicts major adverse cardiac events better compared to conventional imaging with Thallium. (authors)

  17. Cardiac Function in Patients with Early Cirrhosis during Maximal Beta-Adrenergic Drive

    DEFF Research Database (Denmark)

    Krag, Aleksander; Bendtsen, Flemming; Dahl, Emilie Kristine;

    2014-01-01

    BACKGROUND AND AIM: Cardiac dysfunction in patients with early cirrhosis is debated. We investigated potential cardiac dysfunction by assessing left ventricular systolic performance during a dobutamine stress test in patients with early cirrhosis. PATIENTS AND METHODS: Nineteen patients with Chil...

  18. Cardiovascular dysfunction in infants with neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Armstrong, Katey

    2012-04-01

    Severe perinatal asphyxia with hypoxic ischaemic encephalopathy occurs in approximately 1-2\\/1000 live births and is an important cause of cerebral palsy and associated neurological disabilities in children. Multiorgan dysfunction commonly occurs as part of the asphyxial episode, with cardiovascular dysfunction occurring in up to a third of infants. This narrative paper attempts to review the literature on the importance of early recognition of cardiac dysfunction using echocardiography and biomarkers such as troponin and brain type natriuretic peptide. These tools may allow accurate assessment of cardiac dysfunction and guide therapy to improve outcome.

  19. Transgenic Mice with Cardiac-Specific Expression of Activating Transcription Factor 3, a Stress-Inducible Gene, Have Conduction Abnormalities and Contractile Dysfunction

    OpenAIRE

    Okamoto, Yoshichika; Chaves, Alysia; Chen, Jingchun; Kelley, Robert; Jones, Keith; Weed, Harrison G.; Gardner, Kevin L.; Gangi, Lisa; Yamaguchi, Mamoru; Klomkleaw, Wuthichai; Nakayama, Tomohiro; HAMLIN, Robert L.; Carnes, Cynthia; Altschuld, Ruth; Bauer, John

    2001-01-01

    Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the α-myosin heavy chain promoter have atrial enlargement, and a...

  20. Administration of NaHS attenuates footshock-induced pathologies and emotional and cognitive dysfunction in triple transgenic Alzheimer’s mice

    Directory of Open Access Journals (Sweden)

    Hei-Jen eHuang

    2015-11-01

    Full Text Available Alzheimer's disease (AD is characterized by progressive cognitive decline and neuropsychiatric symptoms. Increasing evidence indicates that environmental risk factors in young adults may accelerate cognitive loss in AD and that hydrogen sulfide (H2S may represent an innovative treatment to slow the progression of AD. Therefore, the aim of this study was to evaluate the effects of NaHS, an H2S donor, in a triple transgenic AD mouse model (3×Tg-AD under footshock with situational reminders (SRs. Inescapable footshock with SRs induced anxiety and cognitive dysfunction as well as a decrease in the levels of plasma H2S and GSH and an increase in IL-6 levels in 3×Tg-AD mice. Under footshock with SR stimulus, amyloid deposition, tau protein hyperphosphorylation, and microgliosis were highly increased in the stress-responsive brain structures, including the hippocampus and amygdala, of the AD mice. Oxidative stress, inflammatory response, and β-site APP cleaving enzyme 1 (BACE1 levels were also increased, and the level of inactivated glycogen synthase kinase-3β (GSK3β (pSer9 was decreased in the hippocampi of AD mice subjected to footshock with SRs. Furthermore, the numbers of cholinergic neurons in the medial septum/diagonal band of Broca (MS/DB and noradrenergic neurons in the locus coeruleus (LC were also decreased in the 3×Tg-AD mice under footshock with SRs. These biochemical hallmarks and pathological presentations were all alleviated by the semi-acute administration of NaHS in the AD mice. Together, these findings suggest that footshock with SRs induces the impairment of spatial cognition and emotion, which involve pathological changes in the peripheral and central systems, including the hippocampus, MS/DB, LC, and BLA, and that the administration of NaHS may be a candidate strategy to ameliorate the progression of neurodegeneration.

  1. Computed tomography calcium score scan for attenuation correction of N-13 ammonia cardiac positron emission tomography : effect of respiratory phase and registration method

    NARCIS (Netherlands)

    Zaidi, Habib; Nkoulou, Rene; Bond, Sarah; Baskin, Aylin; Schindler, Thomas; Ratib, Osman; Declerck, Jerome

    2013-01-01

    The use of coronary calcium scoring (CaScCT) for attenuation correction (AC) of N-13-ammonia PET/CT studies (NH3) is still being debated. We compare standard ACCT to CaScCT using various respiratory phases and co-registration methods for AC. Forty-one patients underwent a stress/rest NH3. Standard A

  2. Termination of dobutamine infusion causes transient rebound left heart diastolic dysfunction in healthy elderly women but not in men: a cardiac magnetic resonance study.

    Science.gov (United States)

    Ahtarovski, Kiril A; Iversen, Kasper K; Lønborg, Jacob T; Madsen, Per L; Engstrøm, Thomas; Vejlstrup, Niels G

    2013-10-01

    Men and women are known to react differently to stress. Thus, stress cardiomyopathy almost solely strikes women. Stress cardiomyopathy is suggested to relate to sex differences in catecholamine reaction. Left heart function during dobutamine stress is well described, but sex-specific inotropic and lusitropic response to abrupt termination of dobutamine stress is not. We aimed to investigate sex differences in left ventricular (LV) and atrial (LA) function during and after dobutamine stress. We enrolled 20 healthy elderly subjects (60-70 yr, 10 females) and measured their LV and LA volumes throughout the cardiac cycle by cardiac magnetic resonance imaging at rest, during dobutamine stress (15 μg·kg(-1)·min(-1)), 15 min after termination (T15), and 30 min after termination (T30) of dobutamine stress. We calculated LV ejection fractions, LV stroke volumes, LV peak filling rates, and LA passive, active, and conduit volumes. Sex differences were not observed at rest or during dobutamine stress. Compared with prestress values, at T15 a rebound decrease in LV peak filling rate was observed in women (-22 ± 3%, P causes greater stress to the female heart. This is revealed after termination of dobutamine stress where the left heart recovers in men, whereas women experience rebound LV stiffening with reduced diastolic relaxation. This is the first report of a sex-specific transient rebound phenomenon in cardiovascular response to catecholamines.

  3. Reduction of sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure progression and improves cardiac function after myocardial infarction.

    Science.gov (United States)

    Lymperopoulos, Anastasios; Rengo, Giuseppe; Gao, Erhe; Ebert, Steven N; Dorn, Gerald W; Koch, Walter J

    2010-05-21

    Chronic heart failure (HF) is characterized by sympathetic overactivity and enhanced circulating catecholamines (CAs), which significantly increase HF morbidity and mortality. We recently reported that adrenal G protein-coupled receptor kinase 2 (GRK2) is up-regulated in chronic HF, leading to enhanced CA release via desensitization/down-regulation of the chromaffin cell alpha(2)-adrenergic receptors that normally inhibit CA secretion. We also showed that adrenal GRK2 inhibition decreases circulating CAs and improves cardiac inotropic reserve and function. Herein, we hypothesized that adrenal-targeted GRK2 gene deletion before the onset of HF might be beneficial by reducing sympathetic activation. To specifically delete GRK2 in the chromaffin cells of the adrenal gland, we crossed PNMTCre mice, expressing Cre recombinase under the chromaffin cell-specific phenylethanolamine N-methyltransferase (PNMT) gene promoter, with floxedGRK2 mice. After confirming a significant ( approximately 50%) reduction of adrenal GRK2 mRNA and protein levels, the PNMT-driven GRK2 knock-out (KO) offspring underwent myocardial infarction (MI) to induce HF. At 4 weeks post-MI, plasma levels of both norepinephrine and epinephrine were reduced in PNMT-driven GRK2 KO, compared with control mice, suggesting markedly reduced post-MI sympathetic activation. This translated in PNMT-driven GRK2 KO mice into improved cardiac function and dimensions as well as amelioration of abnormal cardiac beta-adrenergic receptor signaling at 4 weeks post-MI. Thus, adrenal-targeted GRK2 gene KO decreases circulating CAs, leading to improved cardiac function and beta-adrenergic reserve in post-MI HF. GRK2 inhibition in the adrenal gland might represent a novel sympatholytic strategy that can aid in blocking HF progression.

  4. Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/p53 signaling.

    Directory of Open Access Journals (Sweden)

    Rajarajan A Thandavarayan

    Full Text Available Doxorubicin (Dox is a highly effective antineoplastic drug. However, Dox-induced apoptosis in cardiomyocytes leads to irreversible degenerative cardiomyopathy, which limits Dox clinical application. Schisandrin B (Sch B, a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to protect against oxidative damage in liver, heart and brain tissues in rodents. In current study, we investigated possible protective effects of Sch B against Dox-induced cardiomyopathy in mice. Mice received a single injection of Dox (20 mg/kg IP. Five days after Dox administration, left ventricular (LV performance was significantly depressed and was improved by Sch B treatment. Sch B prevented the Dox-induced increase in lipid peroxidation, nitrotyrosine formation, and metalloproteinase activation in the heart. In addition, the increased expression of phospho-p38 MAPK and phospho-MAPK activated mitogen kinase 2 levels by Dox were significantly suppressed by Sch B treatment. Sch B also attenuated Dox-induced higher expression of LV proinflammatory cytokines, cardiomyocyte DNA damage, myocardial apoptosis, caspase-3 positive cells and phopho-p53 levels in mice. Moreover, LV expression of NADPH oxidase subunits and reactive oxygen species were significantly less in Sch B treatment mice after Dox injection. These findings suggest that Sch B attenuates Dox-induced cardiotoxicity via antioxidative and anti-inflammatory effects.

  5. 3-Hydroxy-3-methylglutaric and 3-methylglutaric acids impair redox status and energy production and transfer in rat heart: relevance for the pathophysiology of cardiac dysfunction in 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency.

    Science.gov (United States)

    da Rosa, Mateus Struecker; Seminotti, Bianca; Ribeiro, César Augusto João; Parmeggiani, Belisa; Grings, Mateus; Wajner, Moacir; Leipnitz, Guilhian

    2016-09-01

    3-Hydroxy-3-methylglutaryl-coenzyme A lyase (HL) deficiency is characterized by tissue accumulation of 3-hydroxy-3-methylglutaric (HMG), and 3-methylglutaric (MGA) acids. Affected patients present cardiomyopathy, whose pathomechanisms are not yet established. We investigated the effects of HMG and MGA on energy and redox homeostasis in rat heart using in vivo and in vitro models. In vivo experiments showed that intraperitoneal administration of HMG and MGA decreased the activities of the respiratory chain complex II and creatine kinase (CK), whereas HMG also decreased the activity of complex II-III. Furthermore, HMG and MGA injection increased reactive species production and carbonyl formation, and decreased glutathione concentrations. Regarding the enzymatic antioxidant defenses, HMG and MGA increased glutathione peroxidase (GPx) and glutathione reductase (GR) activities, while only MGA diminished the activities of superoxide dismutase (SOD) and catalase, as well as the protein content of SOD1. Pre-treatment with melatonin (MEL) prevented MGA-induced decrease of CK activity and SOD1 levels. In vitro results demonstrated that HMG and MGA increased reactive species formation, induced lipid peroxidation and decreased glutathione. We also verified that reactive species overproduction and glutathione decrease provoked by HMG and MGA were abrogated by MEL and lipoic acid (LA), while only MEL prevented HMG- and MGA-induced lipoperoxidation. Allopurinol (ALP) also prevented reactive species overproduction caused by both metabolites. Our data provide solid evidence that bioenergetics dysfunction and oxidative stress are induced by HMG and MGA in heart, which may explain the cardiac dysfunction observed in HL deficiency, and also suggest that antioxidant supplementation could be considered as adjuvant therapy for affected patients.

  6. Partial deletion of eNOS gene causes hyperinsulinemic state, unbalance of cardiac insulin signaling pathways and coronary dysfunction independently of high fat diet.

    Directory of Open Access Journals (Sweden)

    Cecilia Vecoli

    Full Text Available Abnormalities in eNOS gene, possibly interacting with high fat diet (HFD, affect peripheral vascular function and glucose metabolism. The relative role of eNOS gene, HFD and metabolic derangement on coronary function has not been fully elucidated. We test whether eNOS gene deficiency per se or in association with HFD modulates coronary function through mechanisms involving molecular pathways related to insulin signaling. Wild type (WT, eNOS-/- and eNOS+/- mice were studied. WT and eNOS+/- mice were fed with either standard or HF diet for 16 weeks and compared with standard diet fed eNOS-/-. Glucose and insulin tolerance tests were performed during the last week of diet. Coronary resistance (CR was measured at baseline and during infusions of acetylcholine (Ach or sodium-nitroprusside (SNP to evaluate endothelium-dependent or independent vasodilation, in the Langendorff isolated hearts. Cardiac expression of Akt and ERK genes as evaluation of two major insulin-regulated signaling pathways involved in the control of vascular tone were assessed by western blot. HFD-fed mice developed an overt diabetic state. Conversely, chow-fed genetically modified mice (in particular eNOS-/- showed a metabolic pattern characterized by normoglycemia and hyperinsulinemia with a limited degree of insulin resistance. CR was significantly higher in animals with eNOS gene deletions than in WT, independently of diet. Percent decrease in CR, during Ach infusion, was significantly lower in both eNOS-/- and eNOS+/- mice than in WT, independently of diet. SNP reduced CR in all groups except eNOS-/-. The cardiac ERK1-2/Akt ratio, increased in animals with eNOS gene deletions compared with WT, independently of diet. These results suggest that the eNOS genetic deficiency, associated or not with HFD, has a relevant effect on coronary vascular function, possibly mediated by increase in blood insulin levels and unbalance in insulin-dependent signaling in coronary vessels

  7. 心脏康复锻炼对伴有左室功能不全冠心病患者的影响%The impacts of cardiac rehabilitation program on coronary artery disease patients with left ventricular dysfunction

    Institute of Scientific and Technical Information of China (English)

    张文芳

    2015-01-01

    目的:探讨心脏康复锻炼对冠心病患者运动能力、生活质量及功能状态的影响。方法对70例伴有轻度至中度左心功能不全的冠心病患者进行连续8周以运动为主的康复锻炼。对所有患者康复锻炼前及康复锻炼后8周进行评价。采用SF-36问卷调查评估患者生活质量。功能状态评估项目包括:睡眠时间、步行、骑自行车、运动及工作时间。结果康复锻炼后,患者最大运动负荷量代谢当量单位由康复前(7.00±2.36)增至康复后(9.08±2.95)(P﹤0.001),运动持续时间从康复前(13.17±5.25)分钟增加到康复后(18.11±4.85)分钟(P﹤0.001)。SF-36评估患者生活质量,患者在身体和心理方面康复前后有显著差异( P﹤0.05)。患者骑自行车、步行及运动时间康复前后有显著差异( P﹤0.05)。结论心脏康复锻炼能够改善轻至中度左心功能不全的冠心病患者的运动能力、生活质量及功能状态。医护人员应鼓励患者参加并遵循标准的康复锻炼计划。%Objective:To determine the impacts of cardiac rehabilitation on exercise capacity,quality of life( QOL), and functional status in patients with coronary artery disease( CAD). Methods:Seventy CAD patients with mild to moder-ate left ventricular dysfunction participated in an exercise-based rehabilitation program for eight consecutive weeks. Subjects underwent an exercise test before and 8 weeks after rehabilitation. QOL was assessed with the SF-36 questionnaire. Func-tional status was assessed in terms of sleep time,walking,cycling,exercise,and working duration. Results:After rehabil-itation,peak exercise capacity increased from(7. 00 ± 2. 36)to(9. 08 ± 2. 95)METs(P﹤0. 001)and exercise duration in-creased from(13. 17 ± 5. 25min)to(18. 11 ± 4. 85min)(P﹤0. 001). Patients′QOL improved in physical and psychologi-cal dimensions(P﹤0. 05). Cycling,walking,and exercising status

  8. Prevalencia de disfunción cardiaca contráctil y tiroidea en pacientes con taquicardia sinusual inapropiada Cardiac Contractile and Thyroid Dysfunction in Patients with Inappropriate Sinus Tachycardia

    Directory of Open Access Journals (Sweden)

    Oswaldo Gutiérrez-Sotelo

    2010-03-01

    the prevalence of cardiac contractile and thyroid dysfunction Materials and methods: We selected from all 24 hour Holter studies performed during 2006 at the Cardiology Service of the México Hospital (Costa Rica those of patients with inappropriate sinus tachycardia, defined as mean heart rate equal o greater than 80 beats per minute (bpm or multiple episodes of sinus tachycardia without physiologic explanation. We analyzed demographic data, echocardiographic presence or absence of systolic cardiac dysfunction and thyroid function by means of TSH and total T3-4. We excluded from the analysis those patients with known cardiac disease. Results: We selected 105 Holter registries from 380 studies, 27,6% or 81 were women, and 24 men. Mean age was 38,97 years old (range 9-81. The mean heart rate was 86,23 bpm (108-71, mean maximal heart rate 143,19 (189-111 and mean minimal heart rate 55,7 (89-22 bpm. In 49 patients an ejection fraction was available; a normal mean value of 0,6 (0,7-0,45 was reported. In 29 patients thyroid function tests were obtained and the mean value of free-T4 y TSH were between normal limits (1,48 ng/dL and 1,7 mUI/L respectively. Conclusion: The majority of patients consulting for palpitations and in whom a Holter analysis results in inappropriate sinus tachycardia, have no cardiac contractility nor thyroid dysfunction. Therefore, in this group of patients it is not justified to evaluate these parameters routinely.

  9. [Erectile and Ejaculatory Dysfunction].

    Science.gov (United States)

    Gross, Oliver; Sulser, Tullio; Eberli, Daniel

    2015-11-25

    The inability to achieve an erection of the penis sufficient for sexual activity is called erectile dysfunction (ED). In most cases, the diagnosis can be made by medical history. The prevalence of ED in men at the age of 65 has been reported to be up to 50%. Premature ejaculation has a prevalence, up to 20% and is the most frequent ejaculatory dysfunction. The etiology of ED can involve psychological, vascular, neurogenic, hormonal or urogenital pathologies. The main pathophysiological mechanisms of ED are vascular disorders such as diabetes mellitus and atherosclerosis. Because of the common pathophysiology, patients diagnosed with ED should have a diagnostic work-up for systemic vascular pathologies to prevent concomitant cardiac events. Treatment options include invasive and non-invasive procedures. PMID:26602851

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  11. The regional myocardial microvascular dysfunction differences in hypertrophic cardiomyopathy patients with or without left ventricular outflow tract obstruction: Assessment with first-pass perfusion imaging using 3.0-T cardiac magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Hua-yan [Department of Radiology, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Yang, Zhi-gang, E-mail: yangzg666@163.com [Department of Radiology, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Sun, Jia-yu; Wen, Ling-yi; Zhang, Ge; Zhang, Shuai [Department of Radiology, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Guo, Ying-kun [Department of Radiology, West China Second University Hospital, Sichuan University (China)

    2014-04-15

    Purpose: To assess regional myocardial microvascular dysfunction differences in hypertrophic cardiomyopathy (HCM) patients with or without left ventricular outflow tract obstruction using 3.0-T cardiac magnetic resonance (CMR) first-pass perfusion imaging. Materials and methods: Forty-two HCM patients, including 25 HCM patients with left ventricular outflow tract obstruction (HOCM), 17 HCM patients without left ventricular outflow tract obstruction (NOHCM), and 14 healthy subjects underwent CMR. The left ventricular (LV) function, left ventricular end-diastolic wall thickness (EDTH), and diameter of left ventricular outflow tract (LVOT) were measured and calculated. Based on the signal–time curve of the first-pass myocardium perfusion imaging, perfusion parameters including upslope, time to peak, and peak intensity, were assessed and compared by using one-way analysis of variance and independent t tests. Results: On the first-pass perfusion imaging, lower upslope and peak intensity and longer time to peak were found in HCM patients compared with normal subjects (all p < 0.05). In contrast to the NOHCM group, the average time to peak of the HOCM group was increased (13.30 ± 4.82 s vs 16.28 ± 4.90 s, p < 0.05), but first-pass perfusion upslope was reduced (4.96 ± 2.55 vs 2.58 ± 0.77, p < 0.05). According to the bull's-eye model, the HOCM group's average thickness of basal segments was thicker than the NOHCM group, especially the anteroseptal, inferolateral, and anterior wall values, with a corresponding lower first-pass perfusion upslope than the NOHCM group (all p < 0.05). A significant correlation was observed between first-pass perfusion upslope and LV EDTH (r = −0.551, p < 0.001) and LVOT diameter (r = 0.472, p < 0.001). Conclusions: The regional myocardial microvascular dysfunction differences in hypertrophic cardiomyopathy (HCM) patients with or without left ventricular outflow tract obstruction can be detected with first-pass perfusion CMR

  12. Mild hypothermia attenuates post-resuscitation brain injury through a V-ATPase mechanism in a rat model of cardiac arrest.

    Science.gov (United States)

    Zhang, J C; Lu, W; Xie, X M; Pan, H; Wu, Z Q; Yang, G T

    2016-01-01

    Although therapeutic hypothermia is an effective treatment for post-resuscitation brain injury after cardiac arrest (CA), the underlying mechanism remains unclear. Vacuolar H(+)-ATPase (V-ATPase) plays a key role in cellular adaption to a hypoxic environment. This study sought to evaluate the effect of mild hypothermia on V-ATPase and its involvement in neuroprotection after CA. Male Sprague-Dawley rats were subjected to a 6-min CA, resuscitated successfully, and then assigned to either the normothermia (NT) group or the hypothermia (HT) group. Rats were further divided into 2 subgroups based on the time of euthanasia, either 3 or 24 h after CA (NT-3 h, HT-3 h; NT-24 h, HT-24 h). Mild hypothermia was induced following CA and maintained at 33°C for 2 h. Neurologic deficit scores were used to determine the status of neurological function. Brain specimens were analyzed by TUNEL assay, western blotting, and immunohistochemistry. V-ATPase activity was estimated by subtracting total ATP hydrolysis from the bafilomycin-sensitive activity. Mild hypothermia improved the neurological outcome (HT-24 h: 34.3 ± 16.4 vs NT-24 h: 50.3 ± 17.4) and significantly decreased neurocyte apoptosis 24 h after resuscitation. Mild hypothermia significantly increased V0a1 compared to NT-3 h; V0a1 expression was associated with a decrease in the cleaved caspase 3 expression. These findings suggested that mild hypothermia inhibits CA-induced apoptosis in the hippocampus, which may be associated with reduced V-ATPase impairment. These data provide new insights into the protective effects of hypothermia in vivo. PMID:27323115

  13. Impaired coronary metabolic dilation in the metabolic syndrome is linked to mitochondrial dysfunction and mitochondrial DNA damage.

    Science.gov (United States)

    Guarini, Giacinta; Kiyooka, Takahiko; Ohanyan, Vahagn; Pung, Yuh Fen; Marzilli, Mario; Chen, Yeong Renn; Chen, Chwen Lih; Kang, Patrick T; Hardwick, James P; Kolz, Christopher L; Yin, Liya; Wilson, Glenn L; Shokolenko, Inna; Dobson, James G; Fenton, Richard; Chilian, William M

    2016-05-01

    Mitochondrial dysfunction in obesity and diabetes can be caused by excessive production of free radicals, which can damage mitochondrial DNA. Because mitochondrial DNA plays a key role in the production of ATP necessary for cardiac work, we hypothesized that mitochondrial dysfunction, induced by mitochondrial DNA damage, uncouples coronary blood flow from cardiac work. Myocardial blood flow (contrast echocardiography) was measured in Zucker lean (ZLN) and obese fatty (ZOF) rats during increased cardiac metabolism (product of heart rate and arterial pressure, i.v. norepinephrine). In ZLN increased metabolism augmented coronary blood flow, but in ZOF metabolic hyperemia was attenuated. Mitochondrial respiration was impaired and ROS production was greater in ZOF than ZLN. These were associated with mitochondrial DNA (mtDNA) damage in ZOF. To determine if coronary metabolic dilation, the hyperemic response induced by heightened cardiac metabolism, is linked to mitochondrial function we introduced recombinant proteins (intravenously or intraperitoneally) in ZLN and ZOF to fragment or repair mtDNA, respectively. Repair of mtDNA damage restored mitochondrial function and metabolic dilation, and reduced ROS production in ZOF; whereas induction of mtDNA damage in ZLN reduced mitochondrial function, increased ROS production, and attenuated metabolic dilation. Adequate metabolic dilation was also associated with the extracellular release of ADP, ATP, and H2O2 by cardiac myocytes; whereas myocytes from rats with impaired dilation released only H2O2. In conclusion, our results suggest that mitochondrial function plays a seminal role in connecting myocardial blood flow to metabolism, and integrity of mtDNA is central to this process. PMID:27040114

  14. 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

  15. 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.

  16. Importance of Attenuating Quadriceps Activation Deficits after Total Knee Arthroplasty

    OpenAIRE

    Thomas, Abbey C.; Jennifer E Stevens-Lapsley

    2012-01-01

    Total knee arthroplasty (TKA) is associated with persistent quadriceps dysfunction. Since quadriceps dysfunction impairs functional performance, minimizing quadriceps dysfunction by attenuating central activation deficits early after surgery may improve function later in life. Rehabilitation strategies incorporating neuromuscular electrical stimulation and early, aggressive quadriceps strengthening may prove beneficial. Further, surgical approaches such as minimally invasive TKA may minimize ...

  17. Cardiac imaging in patients with chronic liver disease

    DEFF Research Database (Denmark)

    Wiese, Signe; Hove, Jens D; Møller, Søren

    2016-01-01

    dysfunction at rest by application of new myocardial strain techniques. Experience with other modalities such as cardiac magnetic resonance imaging and cardiac computed tomography is limited. Future studies exploring these imaging modalities are necessary to characterize and monitor the cardiac changes...

  18. AC序贯紫杉醇联合曲妥珠单抗对乳腺癌患者心功能影响的随机对照研究%Assessment of Cardiac Dysfunction in a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel,with or without Trastuzumab in Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    徐兵河; 林雪挺

    2006-01-01

    @@ 1文献类型 治疗. 2证据水平 1b. 3文献来源 Tan-Chiu E, Yothers G, Romond E, et al.Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by Paclitaxel,with or without Trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer:NSABP B-31 [J]. J Clin Onco,2005,23(31) :7811-7819.

  19. Mitochondrial dysfunction in heart failure.

    Science.gov (United States)

    Rosca, Mariana G; Hoppel, Charles L

    2013-09-01

    Heart failure (HF) is a complex chronic clinical syndrome. Energy deficit is considered to be a key contributor to the development of both cardiac and skeletal myopathy. In HF, several components of cardiac and skeletal muscle bioenergetics are altered, such as oxygen availability, substrate oxidation, mitochondrial ATP production, and ATP transfer to the contractile apparatus via the creatine kinase shuttle. This review focuses on alterations in mitochondrial biogenesis and respirasome organization, substrate oxidation coupled with ATP synthesis in the context of their contribution to the chronic energy deficit, and mechanical dysfunction of the cardiac and skeletal muscle in HF. We conclude that HF is associated with decreased mitochondrial biogenesis and function in both heart and skeletal muscle, supporting the concept of a systemic mitochondrial cytopathy. The sites of mitochondrial defects are located within the electron transport and phosphorylation apparatus and differ with the etiology and progression of HF in the two mitochondrial populations (subsarcolemmal and interfibrillar) of cardiac and skeletal muscle. The roles of adrenergic stimulation, the renin-angiotensin system, and cytokines are evaluated as factors responsible for the systemic energy deficit. We propose a cyclic AMP-mediated mechanism by which increased adrenergic stimulation contributes to the mitochondrial dysfunction.

  20. Extracerebral Organ Dysfunction and Sleep Disorders in Subarachnoid Hemorrhage

    NARCIS (Netherlands)

    Schuiling, Wouter Jan

    2006-01-01

    Cardiac and pulmonary complications are common in subarachnoid hemorrhage (SAH), but also other extracerebral complications are frequently observed. This thesis focuses on the occurrence of extracerebral organ dysfunction and the additional value of markers of these medical complications in prognost

  1. 葡萄糖干预对电磁辐射所致大鼠学习记忆功能障碍的影响%Glucose intervention attenuates learning and memory dysfunction induced by electromagnetic radiation in rats

    Institute of Scientific and Technical Information of China (English)

    卢永辉; 何旻蒂; 张彦文; 周舟; 张广斌; 余争平; 钟敏

    2011-01-01

    of MW and MW + GLU group received 30 mW/cm2 microwave exposure 20 min per day for 28 d, and then their learning and memory were detected by Morris water maze. In 30 min before training, the MW + GLU group were administered intraperitoneally 500 mg/kg of glucose every day from the start of training. Another 30 rats received 30 mW/cm2 microwave exposure 20 rain once a day were sacrificed in 0, 7, 14, 21, and 28 d respectively, 6 for each time point, and then glucose uptake in the hippocampus was determined by liquid scintillation counter. Results After exposure to 30 mW/cm2 microwave for 28 d, the escape latency of MW group was increased in 4, 5, 6 and 7 d after training when compared to the control ( P < 0.05 ), but there was no significant difference in MW + GLU group and control (P > 0. 05 ). The time in target quadrant and the number of times through virtual platform were also decreased in MW group than in control ( 18.66 ±2.77 vs 30.75 ± 8.02 s, and 1.60 ±0.54 vs 2.80 ±0.83, respectively, P < 0. 05 ), but there was no significant difference in MW + GLU group and control (26.84 ± 4.75 s and 3.20 ± 1.03 respectively, P > 0. 05 ). The glucose uptake in the hippocampus was significantly decreased in 21 and 28 d after exposure compared to control (3 959 ± 390 and 3 764 ± 192 vs 5 284 ± 711, P < 0.05 ). Conclusion Glucose treatment attenuates the impairment of learning and memory induced by EMR, and the reduction of hippocampal glucose uptake may be a reason of learning and memory dysfunction induced by EMR.

  2. Fisioterapia respiratória na disfunção pulmonar pós-cirurgia cardíaca Respiratory physiotherapy in the pulmonary dysfunction after cardiac surgery

    Directory of Open Access Journals (Sweden)

    Julia Alencar Renault

    2008-12-01

    respiratory physiotherapy used following cardiac surgery and this effectiveness in reverting pulmonary dysfunction. It has been used as reference publications in English and Portuguese using as key words thoracic surgery, respiratory exercises, physical therapy modalities, postoperative complications and myocardial revascularization, contained in the following databases BIREME, SciELO Brazil, LILACS, PUBMED, from 1997 to 2007. A secondary search of the reference list of identified articles also was made. It has been selected eleven randomized trials (997 patients. For the articles included incentive spirometry was used in three; deep breathing exercises in six; deep breathing exercises added to positive expiratory pressure in four and positive airway pressure added to inspiratory resistance in two. Three trials used intermittent positive pressure breathing. Continuous positive airway pressure and bi-level positive airway pressure has been used in three and two trials. The protocols used in the studies were varied and the co interventions were present in a big part of these. The different analyzed varieties and the time of postoperatory follow up make a comparative analysis difficult. Pulmonary dysfunction is evident in the postoperatory period of cardiac surgery. The use of noninvasive ventilation has been associated with good results in the first postoperatory days. Despite the known importance of postoperatory respiratory physiotherapy, until now, there is no literary consensus about the superiority of one technique over the others.

  3. Cardiac arrest

    Science.gov (United States)

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  4. All-trans retinoic acid attenuates cardiac allograft vasculopathy and myocardial fibrosis%全反式维甲酸减轻大鼠移植心脏血管病变及纤维化

    Institute of Scientific and Technical Information of China (English)

    张明奎; 吴清玉; 胡建国

    2009-01-01

    目的 探讨全反式维甲酸(atRA)对大鼠移植心脏血管病变(CAV)及心肌纤维化的影响及可能机制.方法 以近交系Wistar大鼠为供者,SD大鼠为受者,进行异位心脏移植,一组受者术后接受环孢素A(CsA,10 nag·kg-1·d-1)皮下注射,同时以atRA(10 mg·kg-1·d-1)灌胃(atRA治疗组),另一组受者术后接受CsA皮下注射(慢性排斥组).术后60 d,取移植心脏,行Masson染色观察心肌组织纤维化程度,Van Gieson染色分析血管狭窄程度,免疫组织化学染色(sP法)观察心肌组织中CD68+细胞浸润情况,逆转录聚合酶链反应分析心肌组织中血小板生长因子(PDGF)A mRNA的相对含量.结果 慢性排斥组和atRA治疗组心肌纤维化指数分别为64.0±11.9和34.7±6.3,慢性排斥组纤维化指数明显高于atRA治疗组(P<0.01).慢性排斥组的血管狭窄指数为62.9±17.2,atRA治疗组为40.1±8.2,二者比较,差异有统计学意义(P<0.01).慢性排斥组CD68+细胞数为(32.1±9.3)个,atRA治疗组CD68+细胞数为(17.6±4.2)个,慢性排斥组明显高于atRA治疗组(P<0.01).慢性排斥组PDGF-AmRNA的相对含量为0.94±0.11,atRA治疗组为0.46±0.08,慢性排斥组明显高于atRA治疗组(P<0.01).结论 atRA能减轻大鼠心脏移植后的CAV及心肌纤维化,机制可能与其抑制CD68+细胞浸润及PDGF A mRNA表达有关.%Objective To investigate the mechanism of albtrans retinoic acid (atRA)attenuating cardiac allograft vasculopathy and myocardial fibrosis. Methods With inbred Wistar rats as donors and Sprague Dawley (SD) rats as recipients, heterotopic heart transplantation model was rejection group received same doses of cyclosporine A for 60 days. Grafts were removed on the day 60 post-transplant. Paraffin-embedded sections of cardiac allograft were stained with Masson's trichrome and Van Gieson for examination of myocardial fibrosis and vascular stenosis. Immunohistochemistry was performed to observe CD68 positive cell infiltration. Platelet

  5. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Tomoyuki [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Saotome, Masao, E-mail: msaotome@hama-med.ac.jp [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Funaki, Makoto [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan); Hayashi, Hideharu [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan)

    2014-05-01

    Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin

  6. 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

  7. High-density lipoprotein, mitochondrial dysfunction and cell survival mechanisms.

    Science.gov (United States)

    White, C Roger; Giordano, Samantha; Anantharamaiah, G M

    2016-09-01

    Ischemic injury is associated with acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting and open heart surgery. The timely re-establishment of blood flow is critical in order to minimize cardiac complications. Reperfusion after a prolonged ischemic period, however, can induce severe cardiomyocyte dysfunction with mitochondria serving as a major target of ischemia/reperfusion (I/R) injury. An increase in the formation of reactive oxygen species (ROS) induces damage to mitochondrial respiratory complexes leading to uncoupling of oxidative phosphorylation. Mitochondrial membrane perturbations also contribute to calcium overload, opening of the mitochondrial permeability transition pore (mPTP) and the release of apoptotic mediators into the cytoplasm. Clinical and experimental studies show that ischemic preconditioning (ICPRE) and postconditioning (ICPOST) attenuate mitochondrial injury and improve cardiac function in the context of I/R injury. This is achieved by the activation of two principal cell survival cascades: 1) the Reperfusion Injury Salvage Kinase (RISK) pathway; and 2) the Survivor Activating Factor Enhancement (SAFE) pathway. Recent data suggest that high density lipoprotein (HDL) mimics the effects of conditioning protocols and attenuates myocardial I/R injury via activation of the RISK and SAFE signaling cascades. In this review, we discuss the roles of apolipoproteinA-I (apoA-I), the major protein constituent of HDL, and sphingosine 1-phosphate (S1P), a lysosphingolipid associated with small, dense HDL particles as mediators of cardiomyocyte survival. Both apoA-I and S1P exert an infarct-sparing effect by preventing ROS-dependent injury and inhibiting the opening of the mPTP. PMID:27150975

  8. Diastolic dysfunction in cirrhosis.

    Science.gov (United States)

    Møller, Søren; Wiese, Signe; Halgreen, Hanne; Hove, Jens D

    2016-09-01

    Development of esophageal varices, ascites, and hepatic nephropathy is among the major complications of cirrhosis. The presence of cirrhotic cardiomyopathy, which includes a left ventricular diastolic dysfunction (DD), seems to deteriorate the course of the disease and the prognosis. Increased stiffness of the cirrhotic heart may decrease the compliance and result in DD. The prevalence of DD in cirrhotic patients averages about 50 %. It can be evaluated by transmitral Doppler echocardiography, tissue Doppler echocardiography, and cardiac magnetic resonance imaging. There seems to be a relation between DD and the severity of liver dysfunction and the presence of ascites. After liver transplantation, DD worsens the prognosis and increases the risk of graft rejection, but DD improves after few months. Insertion of a transjugular intrahepatic portosystemic shunt increases left ventricular diastolic volumes, and DD is a predictor of poorer survival in these patients. Future studies should aim at disclosing pathophysiological mechanisms behind the developing of DD in cirrhosis in relation to patient characteristics, development of complications, treatment, and risk associated with interventional procedures. PMID:27075496

  9. Diastolic and autonomic dysfunction in early cirrhosis

    DEFF Research Database (Denmark)

    Dahl, Emilie Kristine; Møller, Søren; Kjær, Andreas;

    2014-01-01

    OBJECTIVE. Presence of cardiac dysfunction in patients with advanced cirrhosis is widely accepted, but data in early stages of cirrhosis are limited. Systolic and diastolic functions, dynamics of QT-interval, and pro-atrial natriuretic peptide (pro-ANP) are investigated in patients with early stage...

  10. Ischemic Hepatitis as the Presenting Manifestation of Cardiac Amyloidosis

    Directory of Open Access Journals (Sweden)

    Chelsey A. Petz MD

    2014-11-01

    Full Text Available An abrupt elevation in aminotransferases without clear etiology may be attributed to hypoxic hepatitis. Underlying cardiac dysfunction, an important clinical clue, is often overlooked as a cause of hypoxic hepatitis, and understanding the interdependence of the heart and liver is crucial in making this diagnosis. Causes of cardiac dysfunction may include any of many different diagnoses; infiltrative heart disease is a rare cause of cardiac dysfunction, with amyloidosis being the most common among this category of pathologies. More advanced imaging techniques have improved the ability to diagnose infiltrative heart disease, thus allowing quicker diagnosis of conditions such as amyloidosis.

  11. 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

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

    Directory of Open Access Journals (Sweden)

    Watson Chris J

    2012-07-01

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

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

    LENUS (Irish Health Repository)

    Watson, Chris J

    2012-07-07

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

  14. Dysfunctional voiding.

    Science.gov (United States)

    Chiozza, M L

    2002-01-01

    Wetting may be considered the Cinderella of paediatric medicine. Before discussing dysfunctional voiding, the milestones of the normal development of continence in the child and the definitions used to describe this topic are presented. Bladder storage requires (1): accommodation of increasing volumes of urine at low intravesical pressure and with appropriate sensation; (2): a bladder outlet that is closed and not modified during increase in intra-abdominal pressure; (3): absence of involuntary bladder contractions. Development of continence in the child involves three independent factors maturing concomitantly: (1) development of normal bladder capacity; (2) maturation of urethral sphincter function; (3) development of neural control over bladder-sphincter function. All these processes are discussed. Abnormalities of any of these maturational sequences, which run parallel and overlapping, may result in clinically evident abnormalities of bladder sphincter control. Although dysfunctional voiding (DV) in children is very common its prevalence has not been well studied and, to date, and its origin is not well known. In a correct evaluation of functional voiding we must take into account different elements: the bladder capacity (that increases during the first 8 years of life roughly 30 ml per year), the micturition frequency, post-void residual volumes, bladder dynamics, urinary flow rates. Thus the correct assessment of children with lower urinary tract dysfunction should include a detailed history. Signs of DV range from urge syndrome to complex incontinence patterns during the day and the night. In addition to incontinence problems, children may have frequency, urgency, straining to void, weak or interrupted urinary stream, urinary tract infections (UTIs) and chronic constipation with or without encopresis. DV are also referred in enuretic children who wet the bed more than one time per night and have a functional bladder capacity lower than attended for age

  15. Toll-like receptor 4 knockout alleviates paraquat-induced cardiomyocyte contractile dysfunction through an autophagy-dependent mechanism.

    Science.gov (United States)

    Wang, Shuyi; Zhu, Xiaoling; Xiong, Lize; Zhang, Yingmei; Ren, Jun

    2016-08-22

    Paraquat, a quarternary nitrogen herbicide, is a toxic prooxidant leading to multi-organ failure including the heart although the underlying mechanism remains poorly understood. This study was designed to examine the role of the innate proinflammatory mediator toll-like receptor 4 (TLR4) in paraquat-induced cardiac contractile anomalies and the underlying mechanisms involved with a focus on autophagy, a conservative machinery governing protein and organelle degradation and recycling for cardiac homeostasis. Wild-type (WT) and TLR4 knockout (TLR4(-/-)) mice were challenged with paraquat (45mg/kg, i.p.) for 48h. Paraquat challenge did not affect mRNA levels of TLR2, TLR4 and TLR9 in WT mice nor did paraquat treatment alter TREM-1 levels. Paraquat challenge elicited cardiac mechanical defects including compromised cardiomyocyte contractile function, intracellular Ca(2+) handling, and overt autophagy as manifested by increased LC3BII-to-LC3BI ratio, Atg5, Atg7 and p62 levels. Interestingly, TLR4 knockout significantly attenuated paraquat-induced cardiac contractile and intracellular Ca(2+) derangement as well as alterations of autophagy markers. Paraquat-elicited changes in cardiac autophagy markers (LC3BII, LC3BII-to-LC3BI ratio and p62) were augmented by lysosomal inhibition using bafilomycin A1 in WT mice. TLR4 knockout significantly attenuated or negated paraquat-elicited increase in LC3BII, LC3BII-to-LC3BI ratio and p62 levels in the presence of lysosomal inhibition. In addition, paraquat challenge promoted phosphorylation of AMPK while suppressing the phosphorylation of mTOR and ULK1 (the autophagy inhibitory Ser(757)), the effects of which were significantly attenuated by TLR4 ablation. In vitro study revealed that AMPK activation using AICAR or mTOR inhibition using rapamycin effectively negated the beneficial cardiomyocyte mechanical effects of TLR4 inhibition (CLI-095) against paraquat toxicity, supporting a permissive role for AMPK-mTOR in TLR4 inhibition

  16. Renal dysfunction, restrictive left ventricular filling pattern and mortality risk in patients admitted with heart failure

    DEFF Research Database (Denmark)

    Schou, Morten; Kjaergaard, Jesper; Torp-Pedersen, Christian;

    2013-01-01

    Renal dysfunction is associated with a variety of cardiac alterations including left ventricular (LV) hypertrophy, LV dilation, and reduction in systolic and diastolic function. It is common and associated with an increased mortality risk in heart failure (HF) patients. This study was designed...... to evaluate whether severe diastolic dysfunction contribute to the increased mortality risk observed in HF patients with renal dysfunction....

  17. Evaluation of Known or Suspected Cardiac Sarcoidosis.

    Science.gov (United States)

    Blankstein, Ron; Waller, Alfonso H

    2016-03-01

    Sarcoidosis is a multisystem disorder of unknown cause, and cardiac sarcoidosis affects at least 25% of patients and accounts for substantial mortality and morbidity from this disease. Cardiac sarcoidosis may present with heart failure, left ventricular systolic dysfunction, AV block, atrial or ventricular arrhythmias, and sudden cardiac death. Cardiac involvement can be challenging to detect and diagnose because of the focal nature of the disease, as well as the fact that clinical criteria have limited diagnostic accuracy. Nevertheless, the diagnosis of cardiac sarcoidosis can be enhanced by integrating both clinical and imaging findings. This article reviews the various roles that different imaging modalities provide in the evaluation and management of patients with known or suspected cardiac sarcoidosis. PMID:26926267

  18. Cardiac Malpositions

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Shi Joon; Im, Chung Gie; Yeon, Kyung Mo; Hasn, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    Cardiac Malposition refers to any position of the heart other than a left-sided heart in a situs solitus individual. Associated cardiac malformations are so complex that even angiocardiographic and autopsy studies may not afford an accurate information. Although the terms and classifications used to describe the internal cardiac anatomy and their arterial connections in cardiac malpositions differ and tend to be confusing, common agreement exists on the need for a segmental approach to diagnosis. Authors present 18 cases of cardiac malpositions in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between 1971 and 1979. Authors analyzed the clinical, radiographic, operative and autopsy findings with the emphasis on the angiocardiographic findings. The results are as follows: 1. Among 18 cases with cardiac malpositions, 6 cases had dextrocardia with situs inversus, 9 cases had dextrocardia with situs solitus and 3 cases had levocardia with situs inversus. 2. There was no genuine exception to visceroatrial concordance rule. 3. Associated cardiac malpositions were variable and complex with a tendency of high association of transposition and double outlet varieties with dextrocardia in situs solitus and levocardia in situs inversus. Only one in 6 cases of dextrocardia with situs inversus had pure transposition. 4. In two cases associated pulmonary atresia was found at surgery which was not predicted by angiocardiography. 5. Because many of the associated complex lesions can be corrected surgically provided the diagnosis is accurate, the selective biplane angiocardiography with or without cineradiography is essential.

  19. Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment

    Directory of Open Access Journals (Sweden)

    Qian Guo

    2015-01-01

    Full Text Available The clinical application of doxorubicin (DOX is compromised by its cardiac toxic effect. Cyclovirobuxine D (CVB-D is a steroid alkaloid extracted from a traditional Chinese medicine, Buxus microphylla. Our results showed that CVB-D pretreatment markedly attenuated DOX-induced cardiac contractile dysfunction and histological alterations. By using TUNEL assay and western blot analysis, we found that CVB-D pretreatment reduced DOX-induced apoptosis of myocardial cells and mitochondrial cytochrome c release to cytosol. CVB-D pretreatment ameliorated DOX-induced cardiac oxidative damage including lipid peroxidation and protein carbonylation and a decrease in the ratio of reduced glutathione (GSH to oxidized glutathione (GSSG. Moreover, CVB-D was found to prevent DOX-induced mitochondrial biogenesis impairment as evidenced by preservation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α and nuclear respiratory factor 1 (NRF1, as well as mitochondrial DNA copy number. These findings demonstrate that CVB-D protects against DOX-induced cardiomyopathy, at least in part, by suppression of oxidative damage and mitochondrial biogenesis impairment.

  20. Interaction of TNF with angiotensin II contributes to mitochondrial oxidative stress and cardiac damage in rats.

    Directory of Open Access Journals (Sweden)

    Nithya Mariappan

    Full Text Available Recent evidence suggests that tumor necrosis factor alpha (TNF and angiotensin II (ANGII induce oxidative stress contribute to cardiovascular disease progression. Here, we examined whether an interaction between TNF and ANGII contributes to altered cardiac mitochondrial biogenesis and ATP production to cause cardiac damage in rats. Rats received intraperitoneal injections of TNF (30 µg/kg, TNF + losartan (LOS, 1 mg/kg, or vehicle for 5 days. Left ventricular (LV function was measured using echocardiography. Rats were sacrificed and LV tissues removed for gene expression, electron paramagnetic resonance and mitochondrial assays. TNF administration significantly increased expression of the NADPH oxidase subunit, gp91phox, and the angiotensin type 1 receptor (AT-1R and decreased eNOS in the LV of rats. Rats that received TNF only had increased production rates of superoxide, peroxynitrite and total reactive oxygen species (ROS in the cytosol and increased production rates of superoxide and hydrogen peroxide in mitochondria. Decreased activities of mitochondrial complexes I, II, and III and mitochondrial genes were observed in rats given TNF. In addition, TNF administration also resulted in a decrease in fractional shortening and an increase in Tei index, suggesting diastolic dysfunction. TNF administration with concomitant LOS treatment attenuated mitochondrial damage, restored cardiac function, and decreased expression of AT1-R and NADPH oxidase subunits. Mitochondrial biogenesis and function is severely impaired by TNF as evidenced by downregulation of mitochondrial genes and increased free radical production, and may contribute to cardiac damage. These defects are independent of the downregulation of mitochondrial gene expression, suggesting novel mechanisms for mitochondrial dysfunction in rats given TNF.

  1. Angiotensin type 2 receptor stimulation ameliorates left ventricular fibrosis and dysfunction via regulation of tissue inhibitor of matrix metalloproteinase 1/matrix metalloproteinase 9 axis and transforming growth factor β1 in the rat heart.

    Science.gov (United States)

    Lauer, Dilyara; Slavic, Svetlana; Sommerfeld, Manuela; Thöne-Reineke, Christa; Sharkovska, Yuliya; Hallberg, Anders; Dahlöf, Bjorn; Kintscher, Ulrich; Unger, Thomas; Steckelings, Ulrike Muscha; Kaschina, Elena

    2014-03-01

    Left ventricular (LV) remodeling is the main reason for the development of progressive cardiac dysfunction after myocardial infarction (MI). This study investigated whether stimulation of the angiotensin type 2 receptor is able to ameliorate post-MI cardiac remodeling and what the underlying mechanisms may be. MI was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with the angiotensin type 2 receptor agonist compound 21 (0.03 mg/kg) was started 6 hours post-MI and continued for 6 weeks. Hemodynamic parameters were measured by echocardiography and intracardiac catheter. Effects on proteolysis were studied in heart tissue and primary cardiac fibroblasts. Compound 21 significantly improved systolic and diastolic functions, resulting in improved ejection fraction (71.2±4.7% versus 53.4±7.0%; Pventricular filling velocities, and maximum and minimum rate of LV pressure rise (P<0.05). Compound 21 improved arterial stiffness parameters and reduced collagen content in peri-infarct myocardium. Tissue inhibitor of matrix metalloproteinase 1 was strongly upregulated, whereas matrix metalloproteinases 2 and 9 and transforming growth factor β1 were diminished in LV of treated animals. In cardiac fibroblasts, compound 21 initially induced tissue inhibitor of matrix metalloproteinase 1 expression followed by attenuated matrix metalloproteinase 9 and transforming growth factor β1 secretion. In conclusion, angiotensin type 2 receptor stimulation improves cardiac function and prevents cardiac remodeling in the late stage after MI, suggesting that angiotensin type 2 receptor agonists may be considered a future pharmacological approach for the improvement of post-MI cardiac dysfunction.

  2. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D

    2012-04-01

    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  3. Mst1 inhibits CMECs autophagy and participates in the development of diabetic coronary microvascular dysfunction

    Science.gov (United States)

    Lin, Jie; Zhang, Lei; Zhang, Mingming; Hu, Jianqiang; Wang, Tingting; Duan, Yu; Man, Wanrong; Wu, Bin; Feng, Jiaxu; Sun, Lei; Li, Congye; Zhang, Rongqing; Wang, Haichang; Sun, Dongdong

    2016-01-01

    Cardiovascular complications account for a substantial proportion of morbidity and mortality in diabetic patients. Abnormalities of cardiac microvascular endothelial cells (CMECs) lead to impaired cardiac microvascular vessel integrity and subsequent cardiac dysfunction, underlining the importance of coronary microvascular dysfunction. In this study, experimental diabetes models were constructed using Mst1 transgenic, Mst1 knockout and sirt1 knockout mice. Diabetic Mst1 transgenic mice exhibited impaired cardiac microvessel integrity and decreased cardiac function. Mst1 overexpression deceased CMECs autophagy as evidenced by decreased LC3 expression and enhanced protein aggregation when subjected to high glucose culture. Mst1 knockout improved cardiac microvessel integrity and enhanced cardiac functions in diabetic mice. Mst1 knockdown up-regulated autophagy as indicated by more typical autophagosomes and increased LC3 expression in CMECs subjected to high glucose cultures. Mst1 knockdown also promoted autophagic flux in the presence of bafilomycin A1. Mst1 overexpression increased CMECs apoptosis, whereas Mst1 knockout decreased CMECs apoptosis. Sirt1 knockout abolished the effects of Mst1 overexpression in cardiac microvascular injury and cardiac dysfunction. In conclusion, Mst1 knockout preserved cardiac microvessel integrity and improved cardiac functions in diabetic mice. Mst1 decreased sirt1 activity, inhibited autophagy and enhanced apoptosis in CMECs, thus participating in the pathogenesis of diabetic coronary microvascular dysfunction. PMID:27680548

  4. Depression and Cardiac Disease: Epidemiology, Mechanisms, and Diagnosis

    OpenAIRE

    Huffman, Jeff C.; Christopher M Celano; Beach, Scott R.; Shweta R. Motiwala; Januzzi, James L.

    2013-01-01

    In patients with cardiovascular disease (CVD), depression is common, persistent, and associated with worse health-related quality of life, recurrent cardiac events, and mortality. Both physiological and behavioral factors—including endothelial dysfunction, platelet abnormalities, inflammation, autonomic nervous system dysfunction, and reduced engagement in health-promoting activities—may link depression with adverse cardiac outcomes. Because of the potential impact of depression on quality of...

  5. Haemochromatosis presenting as congestive cardiac failure.

    OpenAIRE

    Porter, J; Cary, N; Schofield, P

    1995-01-01

    A 24 year old man with congestive cardiac failure was found to have grossly increased transferrin saturations, raised serum ferritin, and an iron-laden myocardium on biopsy. Initial treatment with the iron chelator desferrioxamine was replaced by weekly venesection. He was placed on the cardiac transplant list because of severe left ventricular dysfunction but was later removed because his symptoms and function improved. He remains well with few symptoms and is maintained on regular venesecti...

  6. Preoperative respiratory physical therapy in cardiac surgery

    OpenAIRE

    Hulzebos, H.J.

    2006-01-01

    Cardiac surgery is one of the most common surgical procedures and accounts for more resources expended in cardiovascular medicine than any other single procedure. Because cardiac surgery involves sternal incision and cardiopulmonary bypass, patients usually have a restricted respiratory function in the postoperative period. Moreover, anesthesia and analgesia affect respiratory function during and after the surgical intervention, causing changes in lung volume, diaphragmatic dysfunction, respi...

  7. Acute leukaemoid reaction following cardiac surgery

    Directory of Open Access Journals (Sweden)

    Webb Stephen T

    2007-01-01

    Full Text Available Abstract Chronic myelomonocytic leukaemia is an atypical myeloproliferative disorder with a natural history of progression to acute myeloid leukaemia, a complex and poorly understood response by the bone marrow to stress. Cardiac surgery activates many inflammatory cascades and may precipitate a systemic inflammatory response syndrome. We present a case of undiagnosed chronic myelomonocytic leukaemia who developed rapidly fatal multi-organ dysfunction following cardiac surgery due to an acute leukaemoid reaction.

  8. Mitochondria in cardiac hypertrophy and heart failure

    OpenAIRE

    Rosca, Mariana G.; Tandler, Bernard; Hoppel, Charles L.

    2012-01-01

    Heart failure (HF) frequently is the unfavorable outcome of pathological heart hypertrophy. In contrast to physiological cardiac hypertrophy, which occurs in response to exercise and leads to full adaptation of contractility to the increased wall stress, pathological hypertrophy occurs in response to volume or pressure overload, ultimately leading to contractile dysfunction and HF. Because cardiac hypertrophy impairs the relationship between ATP demand and production, mitochondrial bioenerget...

  9. Inhibition of IκB kinase reduces the multiple organ dysfunction caused by sepsis in the mouse

    Directory of Open Access Journals (Sweden)

    Sina M. Coldewey

    2013-07-01

    Nuclear factor κB (NF-κB plays a pivotal role in sepsis. Activation of NF-κB is initiated by the signal-induced ubiquitylation and subsequent degradation of inhibitors of kappa B (IκBs primarily via activation of the IκB kinase (IKK. This study was designed to investigate the effects of IKK inhibition on sepsis-associated multiple organ dysfunction and/or injury (MOD and to elucidate underlying signaling mechanisms in two different in vivo models: male C57BL/6 mice were subjected to either bacterial cell wall components [lipopolysaccharide and peptidoglycan (LPS/PepG] or underwent cecal ligation and puncture (CLP to induce sepsis-associated MOD. At 1 hour after LPS/PepG or CLP, mice were treated with the IKK inhibitor IKK 16 (1 mg/kg body weight. At 24 hours, parameters of organ dysfunction and/or injury were assessed in both models. Mice developed a significant impairment in systolic contractility (echocardiography, and significant increases in serum creatinine, serum alanine aminotransferase and lung myeloperoxidase activity, thus indicating cardiac dysfunction, renal dysfunction, hepatocellular injury and lung inflammation, respectively. Treatment with IKK 16 attenuated the impairment in systolic contractility, renal dysfunction, hepatocellular injury and lung inflammation in LPS/PepG-induced MOD and in polymicrobial sepsis. Compared with mice that were injected with LPS/PepG or underwent CLP, immunoblot analyses of heart and liver tissues from mice that were injected with LPS/PepG or underwent CLP and were also treated with IKK 16 revealed: (1 significant attenuation of the increased phosphorylation of IκBα; (2 significant attenuation of the increased nuclear translocation of the NF-κB subunit p65; (3 significant attenuation of the increase in inducible nitric oxide synthase (iNOS expression; and (4 a significant increase in the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS. Here, we report for the first time that delayed IKK

  10. Dietary supplementation with long-chain monounsaturated fatty acids attenuates obesity-related metabolic dysfunction and increases expression of PPAR gamma in adipose tissue in type 2 diabetic KK-Ay mice

    Directory of Open Access Journals (Sweden)

    Yang Zhi-Hong

    2013-01-01

    Full Text Available Abstract The objective of present study was to examine the effect of long-chain monounsaturated fatty acids (LC-MUFAs with chain lengths longer than 18 (i.e., C20:1 and C22:1 isomers combined on obesity-related metabolic dysfunction and its molecular mechanisms. Type-2 diabetic KK-Ay mice (n = 20 were randomly assigned to the 7% soybean oil-diet group (control group and 4% LC-MUFA concentrate-supplemented-diet group (LC-MUFA group. At 8 weeks on the diet, the results showed that plasma, liver and adipose tissue levels of C20:1 and C22:1 isomers increased significantly with LC-MUFA treatment. Supplementation with LC-MUFAs markedly reduced white fat pad weight as well as adipocyte size in the mice. The levels of plasma free fatty acids, insulin, and leptin concentration in the obese diabetic mice of the LC-MUFA group were also decreased as compared with the mice in the soybean oil-diet control group. Dietary LC-MUFAs significantly increased the mRNA expression of peroxisome proliferator-activated receptor gamma (Pparg, lipoprotein lipase (Lpl, fatty acid transport protein (Fatp, fatty acid translocase/CD36 (Cd36, as well as mRNA expression of genes involved in lipid oxidation such as carnitine palmitoyltransferase-1A (Cpt1a and citrate synthase (Cs, and decreased the mRNA expression of inflammatory marker serum amyloid A 3 (Saa3 in the adipose tissues of diabetic mice. The results suggest that LC-MUFAs may ameliorate obesity-related metabolic dysfunction partly through increased expression of Pparg as well as its target genes, and decreased inflammatory marker expression in white adipose tissue.

  11. Circulating Fibroblast Growth Factor 21 is Associated with Diastolic Dysfunction in Heart Failure Patients with Preserved Ejection Fraction.

    Science.gov (United States)

    Chou, Ruey-Hsing; Huang, Po-Hsun; Hsu, Chien-Yi; Chang, Chun-Chin; Leu, Hsin-Bang; Huang, Chin-Chou; Chen, Jaw-Wen; Lin, Shing-Jong

    2016-01-01

    Fibroblast growth factor 21 (FGF21), a polypeptide ligand promoted glucose homeostasis and lipids metabolism, was recently reported to attenuate cardiac hypertrophy. The aim of this study was to investigate the impact of FGF21 in diastolic heart failure. Subjects admitted for coronary angiogram were screened for heart failure, and those with left ventricular (LV) ejection fraction functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Plasma levels of FGF21 and N-terminal Pro-Brain Natriuretic Peptide (NT-pro-BNP) were determined. All patients were followed up for 1 year, or till the occurrence of heart failure readmission or death. Totally 95 patients with diastolic dysfunction and 143 controls were enrolled. Circulating FGF21 level was correlated with echocardiographic parameters of diastolic function and LV end-diastolic pressure (LVEDP). In multivariate logistic analysis, FGF21 was significantly associated with diastolic dysfunction, either identified by echocardiographic criteria (odds ratio: 2.97, p = 0.012) or confirmed with LVEDP level (odds ratio: 3.73, p = 0.030). Both plasma FGF21 (log rank p < 0.0001) and NT-pro-BNP levels (log rank p = 0.0057) showed good predictive power to the 1-year adverse cardiac events. This finding suggested FGF21 could be involved in the pathophysiology of diastolic heart failure. PMID:27650781

  12. 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 ...

  13. Cardiac and Respiratory Disease in Aged Horses.

    Science.gov (United States)

    Marr, Celia M

    2016-08-01

    Respiratory and cardiac diseases are common in older horses. Advancing age is a specific risk factor for cardiac murmurs and these are more likely in males and small horses. Airway inflammation is the most common respiratory diagnosis. Recurrent airway obstruction can lead to irreversible structural change and bronchiectasis; with chronic hypoxia, right heart dysfunction and failure can develop. Valvular heart disease most often affects the aortic and/or the mitral valve. Management of comorbidity is an essential element of the therapeutic approach to cardiac and respiratory disease in older equids.

  14. Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation.

    Science.gov (United States)

    Kang, Lin-Lin; Zhang, Dong-Mei; Ma, Chun-Hua; Zhang, Jian-Hua; Jia, Ke-Ke; Liu, Jia-Hui; Wang, Rong; Kong, Ling-Dong

    2016-01-01

    Fructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti-inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury, and cardioprotective effects of cinnamaldehyde and allopurinol are not completely understood. In this study, fructose-fed rats displayed metabolic syndrome with elevated serum ox-LDL, cardiac oxidative stress, inflammation and fibrosis. Scavenger receptor CD36, Toll-like receptor 4 (TLR4), TLR6, IL-1R-associated kinase 4/1 (IRAK4/1), nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin-1β, transforming growth factor-β (TGF-β), drosophila mothers against DPP homolog (Smad) 2/3 phosphorylation and Smad4 were increased in animal and H9c2 cell models. These pathological processes were further evaluated in ox-LDL or fructose-exposed H9c2 cells pretreated with ROS scavenger and CD36 specific inhibitor, or IRAK1/4 inhibitor, and transfected with CD36, NLRP3, or IRAK4/1 siRNA, demonstrating that NLPR3 inflammasome activation through CD36-mediated TLR4/6-IRAK4/1 signaling may promote cardiac inflammation and fibrosis. Cinnamaldehyde and allopurinol reduced cardiac oxidative stress to suppress NLPR3 inflammasome activation and TGF-β/Smads signaling by inhibiting CD36-mediated TLR4/6-IRAK4/1 signaling under fructose induction. These results suggest that the blockage of CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation by cinnamaldehyde and allopurinol may protect against fructose-induced cardiac inflammation and fibrosis. PMID:27270216

  15. Involvement of the H1 histamine receptor, p38 MAP kinase, MLCK, and Rho/ROCK in histamine-induced endothelial barrier dysfunction

    Science.gov (United States)

    Adderley, Shaquria P.; Zhang, Xun E.; Breslin, Jerome W.

    2015-01-01

    Objective The mechanisms by which histamine increases microvascular permeability remain poorly understood. We tested the hypothesis that H1 receptor activation disrupts the endothelial barrier and investigated potential downstream signals. Methods We used confluent endothelial cell (EC) monolayers, assessing transendothelial electrical resistance (TER) as an index of barrier function. Human umbilical vein EC (HUVEC), cardiac microvascular EC (HCMEC), and dermal microvascular EC (HDMEC) were compared. Receptor expression was investigated using Western blotting, immunofluorescence (IF) confocal microscopy and RT-PCR. Receptor function and downstream signaling pathways were tested using pharmacologic antagonists and inhibitors, respectively. Results We identified H1-H4 receptors on all three EC types. H1 antagonists did not affect basal TER but prevented the histamine-induced decrease in TER. Blockade of H2 or H3 attenuated the histamine response only in HDMEC, while inhibition of H4 attenuated the response only in HUVEC. Combined inhibition of both PKC and PI3K caused exaggerated histamine-induced barrier dysfunction in HDMEC, whereas inhibition of p38 MAP kinase attenuated the histamine response in all three EC types. Inhibition of RhoA, ROCK, or MLCK also prevented the histamine-induced decrease in TER in HDMEC. Conclusion The data suggest that multiple signaling pathways contribute to histamine-induced endothelial barrier dysfunction via the H1 receptor. PMID:25582918

  16. Diastolic Dysfunction Induced by a High-Fat Diet Is Associated with Mitochondrial Abnormality and Adenosine Triphosphate Levels in Rats

    OpenAIRE

    Kang, Ki-Woon; Kim, Ok-Soon; Chin, Jung Yeon; Kim, Won Ho; Park, Sang Hyun; Choi, Yu Jeong; Shin, Jong Ho; Jung, Kyung Tae; Lim, Do-Seon; Lee, Seong-Kyu

    2015-01-01

    Background Obesity is well-known as a risk factor for heart failure, including diastolic dysfunction. However, this mechanism in high-fat diet (HFD)-induced obese rats remain controversial. The purpose of this study was to investigate whether cardiac dysfunction develops when rats are fed with a HFD for 10 weeks; additionally, we sought to investigate the association between mitochondrial abnormalities, adenosine triphosphate (ATP) levels and cardiac dysfunction. Methods We examined myocardia...

  17. Right Ventricular Dysfunction in Chronic Lung Disease

    OpenAIRE

    Kolb, Todd M.; Hassoun, Paul M.

    2012-01-01

    Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, ex...

  18. Cardiac function in trisomy 21 fetuses

    NARCIS (Netherlands)

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

    2011-01-01

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

  19. Gender differences in cardiac hypertrophic remodeling.

    Science.gov (United States)

    Patrizio, Mario; Marano, Giuseppe

    2016-01-01

    Cardiac remodeling is a complex process that occurs in response to different types of cardiac injury such as ischemia and hypertension, and that involves cardiomyocytes, fibroblasts, vascular smooth muscle cells, vascular endothelial cells, and inflammatory cells. The end result is cardiomyocyte hypertrophy, fibrosis, inflammation, vascular, and electrophysiological remodeling. This paper reviews a large number of studies on the influence of gender on pathological cardiac remodeling and shows how sex differences result in different clinical outcomes and therapeutic responses, with males which generally develop greater cardiac remodeling responses than females. Although estrogens appear to have an important role in attenuating adverse cardiac remodeling, the mechanisms through which gender modulates myocardial remodeling remain to be identified. PMID:27364397

  20. Attenuation of hyperlipidemia- and diabetes-induced early-stage apoptosis and late-stage renal dysfunction via administration of fibroblast growth factor-21 is associated with suppression of renal inflammation.

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    Full Text Available BACKGROUND: Lipotoxicity is a key feature of the pathogenesis of diabetic kidney disease, and is attributed to excessive lipid accumulation (hyperlipidemia. Increasing evidence suggests that fibroblast growth factor (FGF21 has a crucial role in lipid metabolism under diabetic conditions. OBJECTIVE: The present study investigated whether FGF21 can prevent hyperlipidemia- or diabetes-induced renal damage, and if so, the possible mechanism. METHODS: Mice were injected with free fatty acids (FFAs, 10 mg/10 g body weight or streptozotocin (150 mg/kg to establish a lipotoxic model or type 1 diabetic model, respectively. Simultaneously the mice were treated with FGF21 (100 µg/kg for 10 or 80 days. The kidney weight-to-tibia length ratio and renal function were assessed. Systematic and renal lipid levels were detected by ELISA and Oil Red O staining. Renal apoptosis was examined by TUNEL assay. Inflammation, oxidative stress, and fibrosis were assessed by Western blot. RESULTS: Acute FFA administration and chronic diabetes were associated with lower kidney-to-tibia length ratio, higher lipid levels, severe renal apoptosis and renal dysfunction. Obvious inflammation, oxidative stress and fibrosis also observed in the kidney of both mice models. Deletion of the fgf21 gene further enhanced the above pathological changes, which were significantly prevented by administration of exogenous FGF21. CONCLUSION: These results suggest that FFA administration and diabetes induced renal damage, which was further enhanced in FGF21 knock-out mice. Administration of FGF21 significantly prevented both FFA- and diabetes-induced renal damage partially by decreasing renal lipid accumulation and suppressing inflammation, oxidative stress, and fibrosis.

  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. Association between the polymorphism of A9570G in angiotensin I converting enzyme 2 gene and cardiac dysfunction and ventricular remodeling after myocardial infarction%ACE2基因多态性与心肌梗死后心功能不全及心室重构的相关性研究

    Institute of Scientific and Technical Information of China (English)

    陈文忠; 周永健; 周劲东; 李志樑; 徐春生

    2010-01-01

    Objective To determine the effects of polymorphism of A9570G in angiotensin I converting enzyme 2 gene ( ACE2) gene on cardiac dysfunction and ventricular remodeling after myocardial infarction. Methods 252 patients with old myccardial infarction were included in this study. They were classified according to their polymorphisms of ACE 2 gene analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Echocardiograms were used to determine left ventricular end diastolic diameters (LVEDd) , Left ventricular mass index (LVMI) , mitral flow pattern early diastolic and late diastolic peak flow ratio (E/A) and left ventricular ejection fraction ( LVEF). Results In male, LVEDd, LVMI, and LVEF had significant difference among ACE2 genotypes ( t = 2. 609,3.527and 2.063, P =0.010,0.001 and 0.041), and no significant differences in E/A( t =0.689,P =0.492). In female,LVEDd, LVMI, E/A and LVEF had no significant difference among ACE2 genotypes( F =0. 848, 0.077,0. 985 and 1.611, P = 0. 432,0. 926,0. 377 and 0. 205 ). Conclusion The polymorphism of A9570G in ACE2 gene may be associated with cardiac dysfunction and ventricular remodeling after myocardial infarction in male. ACE 2 gene polymorphism may be a genetic factor on cardiac dysfunction and ventricular remodeling after myocardial infarction.%目的 研究血管紧张素转换酶2基因A9570G多态性与心肌梗死后心功能不全及心室重构的关系.方法 收集252例陈旧性心肌梗死患者,采取外周血2ml提取DNA,多聚酶链扩增反应及限制性内切酶法检测ACE2基因A9570G基因型,按基因型进行分组,采用超声心动图比较不同基因型间患者LVEF,E/A,LVEDd及LVMI的差异.结果 在男性,G基因型组LVEF、LVEDd、LVMI与A基因型组比较,差异有统计学意义(t=2.609、3.527、2.063,P0.05);在女性,3种基因型间患者LVEF、E/A、LVEDd及LVMI差异均无统计学意义(P>0.05).结论 ACE2基因A9570G多态性与男性心肌梗死后

  4. 血清中AngⅡ水平升高与机械创伤后迟发性心功能障碍的相关性实验研究%Relation between Levels of Angiotensin Ⅱ and Delayed Cardiac Dysfunction Induced by Mechanical Trauma

    Institute of Scientific and Technical Information of China (English)

    曹成章; 郭丽; 燕子; 温永金; 王洁; 郭勇; 梁峰

    2013-01-01

    Objective To investigate the stress response and inflammation activity after mechanical trauma. Methods Traumatic rat models were established by Noble - Collip drum. Cardiac function in vitro was assessed by the maximal positive and negative values of the first derivative of left ventricular pressure (+ dp/dtmax and -dp/dtmax) through langendorff heart perfusion apparatus. The contents of serum epinephrine, high sensitivity C - reactive protein (hs - CRP), and angiotensin Ⅱ (Ang Ⅱ) were detected by enzyme linked immunosorbent assay(ELISA) at 0 h, 6 h, 12 h, and 24 h after trauma. Results Compared with the sham group, the cardiac functions of rats at 24h after trauma were significantly decreased. Epinephrine, hs - CRP and Ang Ⅱ in serum at 6 h, 12 h, 24 h after trauma were gradually increased in trauma groups and the contents of Ang Ⅱ in serum were negatively correlated with +dp/dtmax (r= -0. 574, P0. 05). Conclusion The excessive activation of Ang Ⅱ in circulatory system might be correlation with delayed cardiac dysfunction induced by mechanical trauma and the concentration of serum Ang Ⅱ might be treated as a screening indicator for delayed cardiac dysfunction induced by mechanical trauma.%目的 观察创伤后应激反应情况、炎症活动性等指标,筛选出一种可能的指标,帮助降低创伤后发生迟发性心脏功能减退患者的临床漏诊率.方法 利用Noble-Collip机械创伤仪制备机械创伤模型,通过离体心脏灌流技术检测大鼠离体心脏功能,ELISA方法检测机械创伤后0 h、6 h、12 h、24 h血清肾上腺素(NE)、超敏C反应蛋白(hs-CRP)和血管紧张素Ⅱ(AngⅡ)浓度的动态变化.结果与伪创伤组相比,机械创伤后24 h大鼠离体心功能降低;创伤组创伤后24 h内各时间点血清NE、hs-CRP和Ang Ⅱ浓度均逐步增高;机械创伤后24 h大鼠血清中AngⅡ浓度与+dp/dtmax呈负相关(r=-0.574,P0.05).结论 循环AngⅡ的过度激活与机械性创伤导致心肌

  5. Shengmai San Ameliorates Myocardial Dysfunction and Fibrosis in Diabetic db/db Mice.

    Science.gov (United States)

    Zhao, Juan; Cao, Tong-Tong; Tian, Jing; Chen, Hui-Hua; Zhang, Chen; Wei, Hong-Chang; Guo, Wei; Lu, Rong

    2016-01-01

    In this study, we mainly investigated the effects of Shengmai San (SMS) on diabetic cardiomyopathy (DCM) in db/db mice. The db/db mice were randomly divided into model group and SMS group, while C57BLKS/J inbred mice were used as controls. After 24-week treatment, blood glucose, body weight, and heart weight were determined. Hemodynamic changes in the left ventricle were measured using catheterization. The myocardial structure and subcellular structural changes were observed by HE staining and electron microscopy; the myocardium collagen content was quantified by Masson staining. To further explore the protective mechanism of SMS, we analyzed the expression profiles of fibrotic related proteins. Compared to nondiabetic mice, db/db mice exhibited enhanced diastolic myocardial dysfunction and adverse structural remodeling. Higher expression of profibrotic proteins and lower levels of extracellular matrix degradation were also observed. After SMS oral administration for 24 weeks, cardiac dysfunction, hypertrophy, and fibrosis in diabetic mice were greatly improved. Moreover, increased profibrotic protein expression was strongly reversed by SMS treatment in db/db mice. The results demonstrate that SMS exerts a cardioprotective effect against DCM by attenuating myocardial hypertrophy and fibrosis via a TGF-β dependent pathway. PMID:27200101

  6. Shengmai San Ameliorates Myocardial Dysfunction and Fibrosis in Diabetic db/db Mice

    Directory of Open Access Journals (Sweden)

    Juan Zhao

    2016-01-01

    Full Text Available In this study, we mainly investigated the effects of Shengmai San (SMS on diabetic cardiomyopathy (DCM in db/db mice. The db/db mice were randomly divided into model group and SMS group, while C57BLKS/J inbred mice were used as controls. After 24-week treatment, blood glucose, body weight, and heart weight were determined. Hemodynamic changes in the left ventricle were measured using catheterization. The myocardial structure and subcellular structural changes were observed by HE staining and electron microscopy; the myocardium collagen content was quantified by Masson staining. To further explore the protective mechanism of SMS, we analyzed the expression profiles of fibrotic related proteins. Compared to nondiabetic mice, db/db mice exhibited enhanced diastolic myocardial dysfunction and adverse structural remodeling. Higher expression of profibrotic proteins and lower levels of extracellular matrix degradation were also observed. After SMS oral administration for 24 weeks, cardiac dysfunction, hypertrophy, and fibrosis in diabetic mice were greatly improved. Moreover, increased profibrotic protein expression was strongly reversed by SMS treatment in db/db mice. The results demonstrate that SMS exerts a cardioprotective effect against DCM by attenuating myocardial hypertrophy and fibrosis via a TGF-β dependent pathway.

  7. Sublingual Microcirculation is Impaired in Post-cardiac Arrest Patients

    DEFF Research Database (Denmark)

    G. Omar, Yasser; Massey, Michael; Wiuff Andersen, Lars;

    2013-01-01

    AIM: We hypothesized that microcirculatory dysfunction, similar to that seen in sepsis, occurs in post-cardiac arrest patients and that better microcirculatory flow will be associated with improved outcome. We also assessed the association between microcirculatory dysfunction and inflammatory...... markers in the post-cardiac arrest state. METHODS: We prospectively evaluated the sublingual microcirculation in post-cardiac arrest patients, severe sepsis/septic shock patients, and healthy control patients using Sidestream Darkfield microscopy. Microcirculatory flow was assessed using...... the microcirculation flow index (MFI) at 6 and 24h in the cardiac arrest patients, and within 6h of emergency department admission in the sepsis and control patients. RESULTS: We evaluated 30 post-cardiac arrest patients, 16 severe sepsis/septic shock patients, and 9 healthy control patients. Sublingual...

  8. Fetal cardiac interventions: clinical and experimental research.

    Science.gov (United States)

    Yuan, Shi-Min; Humuruola, Gulimila

    2016-01-01

    Fetal cardiac interventions for congenital heart diseases may alleviate heart dysfunction, prevent them evolving into hypoplastic left heart syndrome, achieve biventricular outcome and improve fetal survival. Candidates for clinical fetal cardiac interventions are now restricted to cases of critical aortic valve stenosis with evolving hypoplastic left heart syndrome, pulmonary atresia with an intact ventricular septum and evolving hypoplastic right heart syndrome, and hypoplastic left heart syndrome with an intact or highly restrictive atrial septum as well as fetal heart block. The therapeutic options are advocated as prenatal aortic valvuloplasty, pulmonary valvuloplasty, creation of interatrial communication and fetal cardiac pacing. Experimental research on fetal cardiac intervention involves technical modifications of catheter-based cardiac clinical interventions and open fetal cardiac bypass that cannot be applied in human fetuses for the time being. Clinical fetal cardiac interventions are plausible for midgestation fetuses with the above-mentioned congenital heart defects. The technical success, biventricular outcome and fetal survival are continuously being improved in the conditions of the sophisticated multidisciplinary team, equipment, techniques and postnatal care. Experimental research is laying the foundations and may open new fields for catheter-based clinical techniques. In the present article, the clinical therapeutic options and experimental fetal cardiac interventions are described. PMID:27279868

  9. Secoisolariciresinol Diglucoside Abrogates Oxidative Stress-Induced Damage in Cardiac Iron Overload Condition

    OpenAIRE

    Stephanie Puukila; Sean Bryan; Anna Laakso; Jessica Abdel-Malak; Carli Gurney; Adrian Agostino; Adriane Belló-Klein; Kailash Prasad; Neelam Khaper

    2015-01-01

    Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and ...

  10. Sexual Dysfunction and Infertility

    Science.gov (United States)

    ... Sexual dysfunction is a problem in a person’s sexual desire, arousal, or orgasm. Sexual dysfunction is common. It ... find they have times when they have less sexual desire and satisfaction because of emotional distress or the ...

  11. Erectile Dysfunction (ED)

    Science.gov (United States)

    ... age. Is erectile dysfunction just a part of old age? Erectile dysfunction doesn't have to be a ... episode of impotence Feeling stressed, including stress from work or family situations Being troubled by problems in ...

  12. Speckle Tracking Based Strain Analysis Is Sensitive for Early Detection of Pathological Cardiac Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Xiangbo An

    Full Text Available Cardiac hypertrophy is a key pathological process of many cardiac diseases. However, early detection of cardiac hypertrophy is difficult by the currently used non-invasive method and new approaches are in urgent need for efficient diagnosis of cardiac malfunction. Here we report that speckle tracking-based strain analysis is more sensitive than conventional echocardiography for early detection of pathological cardiac hypertrophy in the isoproterenol (ISO mouse model. Pathological hypertrophy was induced by a single subcutaneous injection of ISO. Physiological cardiac hypertrophy was established by daily treadmill exercise for six weeks. Strain analysis, including radial strain (RS, radial strain rate (RSR and longitudinal strain (LS, showed marked decrease as early as 3 days after ISO injection. Moreover, unlike the regional changes in cardiac infarction, strain analysis revealed global cardiac dysfunction that affects the entire heart in ISO-induced hypertrophy. In contrast, conventional echocardiography, only detected altered E/E', an index reflecting cardiac diastolic function, at 7 days after ISO injection. No change was detected on fractional shortening (FS, E/A and E'/A' at 3 days or 7 days after ISO injection. Interestingly, strain analysis revealed cardiac dysfunction only in ISO-induced pathological hypertrophy but not the physiological hypertrophy induced by exercise. Taken together, our study indicates that strain analysis offers a more sensitive approach for early detection of cardiac dysfunction than conventional echocardiography. Moreover, multiple strain readouts distinguish pathological cardiac hypertrophy from physiological hypertrophy.

  13. Speckle Tracking Based Strain Analysis Is Sensitive for Early Detection of Pathological Cardiac Hypertrophy.

    Science.gov (United States)

    An, Xiangbo; Wang, Jingjing; Li, Hao; Lu, Zhizhen; Bai, Yan; Xiao, Han; Zhang, Youyi; Song, Yao

    2016-01-01

    Cardiac hypertrophy is a key pathological process of many cardiac diseases. However, early detection of cardiac hypertrophy is difficult by the currently used non-invasive method and new approaches are in urgent need for efficient diagnosis of cardiac malfunction. Here we report that speckle tracking-based strain analysis is more sensitive than conventional echocardiography for early detection of pathological cardiac hypertrophy in the isoproterenol (ISO) mouse model. Pathological hypertrophy was induced by a single subcutaneous injection of ISO. Physiological cardiac hypertrophy was established by daily treadmill exercise for six weeks. Strain analysis, including radial strain (RS), radial strain rate (RSR) and longitudinal strain (LS), showed marked decrease as early as 3 days after ISO injection. Moreover, unlike the regional changes in cardiac infarction, strain analysis revealed global cardiac dysfunction that affects the entire heart in ISO-induced hypertrophy. In contrast, conventional echocardiography, only detected altered E/E', an index reflecting cardiac diastolic function, at 7 days after ISO injection. No change was detected on fractional shortening (FS), E/A and E'/A' at 3 days or 7 days after ISO injection. Interestingly, strain analysis revealed cardiac dysfunction only in ISO-induced pathological hypertrophy but not the physiological hypertrophy induced by exercise. Taken together, our study indicates that strain analysis offers a more sensitive approach for early detection of cardiac dysfunction than conventional echocardiography. Moreover, multiple strain readouts distinguish pathological cardiac hypertrophy from physiological hypertrophy.

  14. 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

  15. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik Sahl

    2002-01-01

    The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed "cirrhotic cardiomyopathy", which is an...... stress the heart such as shunt implantation and liver transplantation....

  16. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2002-01-01

    The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed "cirrhotic cardiomyopathy", which is an...

  17. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2002-01-01

    The systemic circulation in patients with cirrhosis is hyperdynamic with an increased cardiac output and heart rate and a reduced systemic vascular resistance as the most pronounced alterations. The concomitant cardiac dysfunction has recently been termed "cirrhotic cardiomyopathy", which is an e...... stress the heart such as shunt implantation and liver transplantation....

  18. 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...

  19. Nutritional Status and Cardiac Autophagy

    Directory of Open Access Journals (Sweden)

    Jihyun Ahn

    2013-02-01

    Full Text Available Autophagy is necessary for the degradation of long-lasting proteins and nonfunctional organelles, and is activated to promote cellular survival. However, overactivation of autophagy may deplete essential molecules and organelles responsible for cellular survival. Lifelong calorie restriction by 40% has been shown to increase the cardiac expression of autophagic markers, which suggests that it may have a cardioprotective effect by decreasing oxidative damage brought on by aging and cardiovascular diseases. Although cardiac autophagy is critical to regulating protein quality and maintaining cellular function and survival, increased or excessive autophagy may have deleterious effects on the heart under some circumstances, including pressure overload-induced heart failure. The importance of autophagy has been shown in nutrient supply and preservation of energy in times of limitation, such as ischemia. Some studies have suggested that a transition from obesity to metabolic syndrome may involve progressive changes in myocardial inflammation, mitochondrial dysfunction, fibrosis, apoptosis, and myocardial autophagy.

  20. The Link Between Stress Disorders and Autonomic Dysfunction in Muscular Dystrophy

    OpenAIRE

    Rasna eSabharwal

    2014-01-01

    Muscular dystrophy is a progressive disease of muscle weakness, muscle atrophy and cardiac dysfunction. Patients afflicted with muscular dystrophy exhibit autonomic dysfunction along with cognitive impairment, severe depression, sadness, and anxiety. Although the psychological aspects of cardiovascular disorders and stress disorders are well known, the physiological mechanism underlying this relationship is not well understood, particularly in muscular dystrophy. Therefore, the goal of this p...

  1. Genetics and Sinus Node Dysfunction

    Directory of Open Access Journals (Sweden)

    Eyal Nof MD

    2009-04-01

    Full Text Available Sinus node dysfunction (SND is commonly encountered in the clinic. The clinical phenotype ranges from asymptomatic sinus bradycardia to complete atrial standstill. In some cases, sinus bradycardia is associated with other myocardial conditions such as congenital abnormalities, myocarditis, dystrophies, cardiomyopathies as well as fibrosis or other structural remodeling of the SA node.1-8 Although there are many etiologies for symptomatic slow heart rates, the only effective treatment available today is the implantation of a pacemaker. The predominant ion channel currents contributing to the pacemaker activity in the sinoatrial node (SAN include currents flowing through hyperpolarization-activated, cyclic nucleotide-gated (HCN channels,9 L- type Ca, T- type Ca,10 delayed rectifier K,1112 and acetylcholine (ACh-activated13,14 channels. However, their relative contribution remains a matter of debate and the cellular mechanisms contributing to abnormal sinus node function leading to bradycardia are not fully elucidated. Sodium channel current (INa, encoded by SCN5A, is responsible for the cardiac action potential (AP upstroke and therefore has an important role in initiation and propagation of the cardiac action potential. Although it is largely absent in the sinus node, it plays an important role at the periphery of the sinus node in transmitting electrical activity from the sinus node to the rest of the atria.

  2. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction

    OpenAIRE

    Moustafa Elsheshtawy; Priatharsini Sriganesh; Vasudev Virparia; Falgun Patel; Ashok Khanna

    2016-01-01

    Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

  3. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice.

    Science.gov (United States)

    De Angelis, Katia; Senador, Danielle D; Mostarda, Cristiano; Irigoyen, Maria C; Morris, Mariana

    2012-04-15

    Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.

  4. Novel Roles of Epoxyeicosanoids in Regulating Cardiac Mitochondria

    Science.gov (United States)

    El-Sikhry, Haitham E.; Alsaleh, Nasser; Dakarapu, Rambabu; Falck, John R.; Seubert, John M.

    2016-01-01

    Maintenance of a healthy pool of mitochondria is important for the function and survival of terminally differentiated cells such as cardiomyocytes. Epoxyeicosatrienoic acids (EETs) are epoxy lipids derived from metabolism of arachidonic acid by cytochrome P450 epoxygenases. We have previously shown that EETs trigger a protective response limiting mitochondrial dysfunction and reducing cellular death. The aim of this study was to investigate whether EET-mediated effects influence mitochondrial quality in HL-1 cardiac cells during starvation. HL-1 cells were subjected to serum- and amino acid free conditions for 24h. We employed a dual-acting synthetic analog UA-8 (13-(3-propylureido)tridec-8-enoic acid), possessing both EET-mimetic and soluble epoxide hydrolase (sEH) inhibitory properties, or 14,15-EET as model EET molecules. We demonstrated that EET-mediated events significantly improved mitochondrial function as assessed by preservation of the ADP/ATP ratio and oxidative respiratory capacity. Starvation induced mitochondrial hyperfusion observed in control cells was attenuated by UA-8. However, EET-mediated events did not affect the expression of mitochondrial dynamic proteins Fis1, DRP-1 or Mfn2. Rather we observed increased levels of OPA-1 oligomers and increased mitochondrial cristae density, which correlated with the preserved mitochondrial function. Increased DNA binding activity of pCREB and Nrf1/2 and increased SIRT1 activity together with elevated mitochondrial proteins suggest EET-mediated events led to preserved mitobiogenesis. Thus, we provide new evidence for EET-mediated events that preserve a healthier pool of mitochondria in cardiac cells following starvation-induced stress. PMID:27494529

  5. Cardiac left ventricular function before and during early thyroxine treatment in severe hypothyroidism.

    Science.gov (United States)

    Bernstein, R; Müller, C; Midtbø, K; Haug, E; Nakken, K F; Hertzenberg, L; Kjørstad, K E

    1991-12-01

    In some patients with severe hypothyroidism, thyroxine replacement therapy precipitates or aggravates angina pectoris, whereas in other patients angina pectoris is ameliorated or even cured. Cardiac function in eight severely hypothyroid patients was studied by means of radionuclide ventriculography (RNV) at rest and during supine bicycle exercise before thyroxine treatment, and repeated during treatment before and after administration of 160 mg of oral verapamil. There was an exercise-induced fall in left ventricular ejection fraction (LVEF) in two patients before therapy, and in two additional subjects after 17 d on suboptimal doses of thyroxine. Verapamil attenuated the fall and induced a significant increase in LVEF during exercise (P less than 0.014). No abnormal regional cardiac wall movement (RWM) was observed. After 2 months of thyroxine treatment, LVEF increased significantly during exercise both before and after verapamil (P less than 0.012 and P less than 0.005). These findings are indicative of reversible coronary artery dysfunction. We recommend that, if feasible, thyroxine should be supplemented with verapamil during the early phase of treatment. PMID:1748858

  6. Hypercapnia attenuates ventilator-induced diaphragm atrophy and modulates dysfunction

    NARCIS (Netherlands)

    Schellekens, W.J.M.; Hees, H.W.H. van; Kox, M.; Linkels, M.; Acuna, G.L.; Dekhuijzen, P.N.R.; Scheffer, G.J.; Hoeven, J.G. van der; Heunks, L.M.A.

    2014-01-01

    INTRODUCTION: Diaphragm weakness induced by prolonged mechanical ventilation may contribute to difficult weaning from the ventilator. Hypercapnia is an accepted side effect of low tidal volume mechanical ventilation, but the effects of hypercapnia on respiratory muscle function are largely unknown.

  7. Role of Sodium-Hydrogen Exchanger-1 (NHE-1) in the Effect of Exercise on Intermittent Hypoxia-Induced Left Ventricular Dysfunction.

    Science.gov (United States)

    Chen M, Yu-Chih; Yang, Kun-Ta; Shen, Yan-Jhih; Cheng, Ching-Feng; Tu, Wei-Chia; Chen, Tsung-I

    2015-08-31

    Intermittent hypoxia (IH) occurs frequently in patients with obstructive sleep apnoea and can cause ventricular dysfunction. However, whether myocardial inflammation and sodium-hydrogen exchanger-1 (NHE-1) expression play an important role in IH-induced ventricular dysfunction remains unclear. This study aimed to investigate whether short-term exercise provides a protective effect on IH-induced left ventricular (LV) function impairment. Male Sprague-Dawley rats were randomly assigned to 4 groups: control (CON), IH, exercise (EXE) or IH interspersed with EXE (IHEXE). IH rats were exposed to repetitive hypoxia/reoxygenation cycles (2%-6% O₂ for 2-5 s per 75 s, followed by 21% O₂ for 6 h/day) during the light phase for 12 consecutive days. EXE rats were habituated to treadmill running for 5 days, permitted 2 days of rest, and followed by 5 exercise bouts (30 m/min for 60 min on a 2% grade) on consecutive days during the dark phase. IHEXE rats were exposed to IH during the light phase interspersed with exercise programs during the dark phase on the same day. Cardiac function was quantified by echocardiographic evaluation. Myocardial levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and NHE-1 were determined. IH rats showed LV dysfunction characterized by lower LV fractional shortening (LVFS%) and LV ejection fraction (LVEF%). LV dysfunction was associated with higher myocardial levels of TNF-α, IL-6 and NHE-1 mRNA and protein. These changes were not observed in IHEXE rats (P > 0.05 for all). EXE rats showed lower levels of NHE-1 protein than CON rats (P 0.05 for all). These data indicated that exercise may provide a protective effect on IH-induced LV dysfunction by attenuating IH-induced myocardial NHE-1 hyperactivity. PMID:26211649

  8. Protective effects of tetrahydroxystilbeneglucoside on cardiac dysfunction in experimental diabetic cardiomyopathy%二苯乙烯苷对糖尿病大鼠心肌损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    李彩蓉; 甘受益; 黄红霞; 蔡飞

    2016-01-01

    Aim To study the protective effect of tetra-hydroxystilbeneglucoside ( TSG ) on cardiac injury and the mechanism involved in silent mating type informa-tion regulation 2 homolog 1 ( SIRT1 ) and adenosine monophosphate-activated protein kinase( AMPK) in the diabetic rats. Methods Type 2 diabetic rats were sac-rificed after administration with TSG for 8 weeks. Blood glucose, blood lipids, liverfunction,creatine ki-nase ( CK ) , lactate dehydrogenase ( LDH ) as well as myocardial nonesterified fatty acids( NEFA) were deter-mined by using biochemical test. The concentration of myocardial fatty acid transport proteins ( FATPs ) and-fatty acid β-oxidase ( FA-β-oxidase ) , and the levels of tumor necrosis factor alpha ( TNF-α) , interleukin -6 ( IL-6 ) , interleukin-1β( IL-1β) in serum were also measured by ELISA method and radio immunoassay re-spectively. The protein expressions of TNF-α, IL-6, IL-1β, SIRT1 and AMPK were detected by Western blot. Results Treatment of TSG reduced the contentof blood lipids, NEFA and collagen without affecting the content of blood glucose and insulin. The levels of TNF-α, IL-6 and IL-1βin serum as well as the protein expressions of TNF-α, IL-6 and IL-1β of cardia were also inhibited by administration with TSG. Treatment of TSG caused a significantly increased concentration of myocaidial FATPs and FA-β-oxidase, and dramatically restored the decreased protein expressions of SIRT1 and pAMPK in diabetic rats. Conclusion The protec-tive mechanisms of TSG against diabetic rats are in-volved in the alleviation of inflammatory mediator injury and improving energy metabolism.%目的:探讨二苯乙烯苷( TSG)对糖尿病大鼠心肌损伤的作用及对沉默信息调节因子2的哺乳动物同源体1(SIRT1)和磷酸腺苷活化的蛋白激酶(AMPK)蛋白影响。方法建立2型糖尿病大鼠模型,分组给药,16周时处死大鼠,生化法测定血糖、血脂、肝功能及肌酸激酶( CK)、乳酸脱氢酶( LDH)

  9. Cardiac involvement in Duchenne and Becker muscular dystrophy

    OpenAIRE

    Mavrogeni, Sophie; Markousis-Mavrogenis, George; Papavasiliou, Antigoni; Kolovou, Genovefa

    2015-01-01

    Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked muscular diseases responsible for over 80% of all muscular dystrophies. Cardiac disease is a common manifestation, not necessarily related to the degree of skeletal myopathy; it may be the predominant manifestation with or without any other evidence of muscular disease. Death is usually due to ventricular dysfunction, heart block or malignant arrhythmias. Not only DMD/BMD patients, but also female carriers may present cardiac invol...

  10. 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.

  11. Early detection of myocardial dysfunction in children with mitochondrial disease: An ultrasound and two-dimensional strain echocardiography study

    NARCIS (Netherlands)

    Marcus, K.A.; Barends, M.; Morava, E.; Feuth, T.; Korte, C.L. de; Kapusta, L.

    2011-01-01

    BACKGROUND: Myocardial dysfunction in children diagnosed with mitochondrial disease is an ominous sign and has been associated with substantial increased mortality rates. Early detection of cardiac involvement would therefore be desirable. Two dimensional strain echocardiography (2DSTE) has proven t

  12. GPR30 decreases cardiac chymase/angiotensin II by inhibiting local mast cell number

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Zhuo [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Department of Cardiology, Jinan Central Hospital, Affiliated with Shandong University, 105 Jiefang Road, Jinan, 250013 (China); Wang, Hao; Lin, Marina [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Groban, Leanne, E-mail: lgroban@wakehealth.edu [Department of Anesthesiology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27159-1009 (United States); Hypertension and Vascular Disease Center, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States); Office of Women in Medicine and Science, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States)

    2015-03-27

    Chronic activation of the novel estrogen receptor GPR30 by its agonist G1 mitigates the adverse effects of estrogen (E2) loss on cardiac structure and function. Using the ovariectomized (OVX) mRen2.Lewis rat, an E2-sensitive model of diastolic dysfunction, we found that E2 status is inversely correlated with local cardiac angiotensin II (Ang II) levels, likely via Ang I/chymase-mediated production. Since chymase is released from cardiac mast cells during stress (e.g., volume/pressure overload, inflammation), we hypothesized that GPR30-related cardioprotection after E2 loss might occur through its opposing actions on cardiac mast cell proliferation and chymase production. Using real-time quantitative PCR, immunohistochemistry, and immunoblot analysis, we found mast cell number, chymase expression, and cardiac Ang II levels were significantly increased in the hearts of OVX-compared to ovary-intact mRen2.Lewis rats and the GPR30 agonist G1 (50 mg/kg/day, s.c.) administered for 2 weeks limited the adverse effects of estrogen loss. In vitro studies revealed that GPR30 receptors are expressed in the RBL-2H3 mast cell line and G1 inhibits serum-induced cell proliferation in a dose-dependent manner, as determined by cell counting, BrdU incorporation assay, and Ki-67 staining. Using specific antagonists to estrogen receptors, blockage of GPR30, but not ERα or ERβ, attenuated the inhibitory effects of estrogen on BrdU incorporation in RBL-2H3 cells. Further study of the mechanism underlying the effect on cell proliferation showed that G1 inhibits cyclin-dependent kinase 1 (CDK1) mRNA and protein expression in RBL-2H3 cells in a dose-dependent manner. - Highlights: • GPR30 activation limits mast cell number in hearts from OVX mRen2.Lewis rats. • GPR30 activation decreases cardiac chymase/angiotensin II after estrogen loss. • GPR30 activation inhibits RBL-2H3 mast cell proliferation and CDK1 expression.

  13. A COMPARATIVE STUDY OF PEDIATRIC CARDIAC CATHETERIZATION PROCEDURE UNDER GENERAL ANESTHESIA WITH OR WITHOUT FEMORAL NERVE BLOCK

    OpenAIRE

    Jigisha; Bhavesh; Parineeta; Tarun

    2016-01-01

    OBJECTIVE Anesthetic management for interventional cardiac procedures/cardiac catheterization in pediatric patients is challenging. Cardiac anomalies vary from simple to complex congenital cardiac anomalies, shunts may be present at multiple levels and patients may be profoundly cyanotic, may be with ventricular dysfunction. They usually require sedation and analgesia to maintain steady stable state. In adults, such type of procedures can be well managed with local anesthesia....

  14. Cardiovascular autonomic dysfunction in Parkinson's disease.

    Science.gov (United States)

    Ziemssen, Tjalf; Reichmann, Heinz

    2010-02-15

    Symptoms of cardiovascular dysautonomia are a common occurrence in Parkinson's disease (PD). In addition to this dysautonomia as part of PD itself, dysfunction of the autonomic nervous system (ANS) can be triggered as a side-effect of drug treatment interacting with the ANS or - if prominent and early - an indication of a different disease such as multiple system atrophy (MSA). Various diagnostic tests are available to demonstrate autonomic failure. While autonomic function tests can differentiate parasympathetic from sympathetic dysfunction, cardiac imaging can define the pathophysiologically involved site of a lesion. Standard tests such as 24-h ambulatory blood pressure measurements can identify significant autonomic failure which needs treatment. The most frequent and disturbing symptom of cardiovascular autonomic dysfunction is orthostatic hypotension. Symptoms include generalized weakness, light-headiness, mental "clouding" up to syncope. Factors like heat, food, alcohol, exercise, activities which increase intrathoraric pressure (e.g. defecation, coughing) and certain drugs (e.g. vasodilators) can worsen a probably asymptomatic orthostatic hypotension. Non-medical and medical therapies can help the patient to cope with a disabling symptomatic orthostatic hypotension. Supine hypertension is often associated with orthostatic hypotension. The prognostic role of cardiovagal and baroreflex dysfunction is still not yet known.

  15. 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

  16. Sudden cardiac death risk stratification.

    Science.gov (United States)

    Deyell, Marc W; Krahn, Andrew D; Goldberger, Jeffrey J

    2015-06-01

    Arrhythmic sudden cardiac death (SCD) may be caused by ventricular tachycardia/fibrillation or pulseless electric activity/asystole. Effective risk stratification to identify patients at risk of arrhythmic SCD is essential for targeting our healthcare and research resources to tackle this important public health issue. Although our understanding of SCD because of pulseless electric activity/asystole is growing, the overwhelming majority of research in risk stratification has focused on SCD-ventricular tachycardia/ventricular fibrillation. This review focuses on existing and novel risk stratification tools for SCD-ventricular tachycardia/ventricular fibrillation. For patients with left ventricular dysfunction or myocardial infarction, advances in imaging, measures of cardiac autonomic function, and measures of repolarization have shown considerable promise in refining risk. Yet the majority of SCD-ventricular tachycardia/ventricular fibrillation occurs in patients without known cardiac disease. Biomarkers and novel imaging techniques may provide further risk stratification in the general population beyond traditional risk stratification for coronary artery disease alone. Despite these advances, significant challenges in risk stratification remain that must be overcome before a meaningful impact on SCD can be realized.

  17. Cardiac MRI in restrictive cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-02-15

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

  18. 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

  19. Delirium is associated with early postoperative cognitive dysfunction

    DEFF Research Database (Denmark)

    Rudolph, J.L.; Marcantonio, E.R.; Culley, D.J.;

    2008-01-01

    The purpose of this analysis was to determine if postoperative delirium was associated with early postoperative cognitive dysfunction (at 7 days) and long-term postoperative cognitive dysfunction (at 3 months). The International Study of Postoperative Cognitive Dysfunction recruited 1218 subjects...... >or= 60 years old undergoing elective, non-cardiac surgery. Postoperatively, subjects were evaluated for delirium using the criteria of the Diagnostic and Statistical Manual. Subjects underwent neuropsychological testing pre-operatively and postoperatively at 7 days (n = 1018) and 3 months (n = 946......). Postoperative cognitive dysfunction was defined as a composite Z-score > 2 across tests or at least two individual test Z-scores > 2. Subjects with delirium were significantly less likely to participate in postoperative testing. Delirium was associated with an increased incidence of early postoperative...

  20. Photonic Crystal Fiber Attenuator

    Institute of Scientific and Technical Information of China (English)

    Joo Beom Eom; Hokyung Kim; Jinchae Kim; Un-Chul Paek; Byeong Ha Lee

    2003-01-01

    We propose a novel fiber attenuator based on photonic crystal fibers. The difference in the modal field diameters of a conventional single mode fiber and a photonic crystal fiber was used. A variable optical attenuator was also achieved by applying macro-bending on the PCF part of the proposed attenuator

  1. Renal-sparing strategies in cardiac transplantation

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Ross, Heather J

    2009-01-01

    PURPOSE OF REVIEW: Renal dysfunction due to calcineurin inhibitor (CNI) toxicity is a major clinical problem in cardiac transplantation. The aim of the article is to review the efficacy and safety of various renal sparing strategies in cardiac transplantation. RECENT FINDINGS: Small studies have...... documented that late initiation of CNI is safe in patients treated with induction therapy at the time of transplantation. Use of mycophenolate is superior when compared with azathioprine to allow for CNI reduction. More substantial reduction in CNI levels is safe and effective with the introduction...... of sirolimus or everolimus. However, studies that use very early CNI discontinuation have found an increased risk of allograft rejection, and this strategy requires further study before it can be routinely recommended. CNI discontinuation late after cardiac transplantation seems more effective than CNI...

  2. Sildenafil and FDP-Sr attenuate diabetic cardiomyopathy by suppressing abnormal expression of myocardial CASQ2,FKBPl2.6,and SERCA2a in rats

    Institute of Scientific and Technical Information of China (English)

    Yu-si CHENG; De-zai DAI; Hui JI; Qi ZHANG; Yin DAI

    2011-01-01

    Alm:To study whether calcium-modulating proteins CASQ2,FKBPl2.6 and SERCA2a participate in diabetic cardiomyopathy,and whether the beneficial actions of testosterone,sildenafil or fructose diphosphate Sr(FDP-Sr)in the treatment of diabetic cardiomyopathy result from suppressing these molecules.Methods:Fifry male Sprague-Dawley(SD)rats were divided into five groups.Except for the normal gmup(non-diabetic), the other four groups were injected with streptozotocin(STZ,60 mg/kg,ip)to induce diabetes.Four weeks after STZ injection,the four groups received sildenafil(12 mg·kg-1·d-1,ig,for 4 week).FDP-Sr(200 mg/kg,ig for 4 week),testosterone propionate(4 mg·kg-1·d-1,sc,for 4 week),or no treatment,respectively.Results:In the diabetic rats.blood glucose.free fatty acids.triglycerides.total cholesterol.and low-density lipoprotein cholesterol (LDL-C)were significantly increased.while high-density lipoprotein cholesterol(HDL-C)was significantly reduced.as compared to the non-dlabetic rats.Cardiac dysfunction and myocardial hypertrophy of the diabetic rats were associated with increased mRNA and protein expression of iNOS,OBRb,and PKCε.while expression of CASQ2,SERCA2a.and FKBPl2.6 was significantly down-regulated.Sildenafil and FDp-St,but not testosterone.significantly attenuated the biomarker abnormalities, without changing the metabolic abnormalities.Conclusion:CASQ2.FKBPl2.6 and SERCA2a were down.regulated in diabetic cardiomyopathy.Sildenafil and FDP-Sr, but not testosterone, attenuated the cardiac dysfunction in diabetic cardiomyopathy,without changing the metabolic abnormalities,which may results from inhibiting oxidative and inflammatory cytokines and improving calcium homeostasis.

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Resorcylidene Aminoguanidine (RAG) Improves Cardiac Mitochondrial Bioenergetics Impaired by Hyperglycaemia in a Model of Experimental Diabetes

    OpenAIRE

    Zofia Jozwiak; Karolina Siewiera; Magdalena Labieniec-Watala

    2011-01-01

    Diabetes is associated with a mitochondrial dysfunction. Hyperglycaemia is also clearly recognized as the primary culprit in the pathogenesis of cardiac complications. In response to glycation and oxidative stress, cardiac mitochondria undergo cumulative alterations, often leading to heart deterioration. There is a continuous search for innovative treatment strategies for protecting the heart mitochondria from the destructive impact of diabetes. Aminoguanidine derivatives have been successful...

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

    OpenAIRE

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

    2005-01-01

    Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro.Long-term oral administration of PGF extract (500 mg kg−1) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholestero...

  6. Quadricuspid aortic valve by cardiac magnetic resonance imaging: a case report and review of the literature.

    Science.gov (United States)

    Khan, Shamruz Khan Akerem; Tamin, Syahidah Syed; Araoz, Philip A

    2011-01-01

    Quadricuspid aortic valve (QAV) is a rare congenital cardiac entity. The recognition of QAV has clinical significance as it causes aortic valve dysfunction, commonly aortic regurgitation, and is often associated with other congenital cardiac abnormalities. We showed the important role played by cardiac magnetic resonance imaging in detecting QAV and review the available literature to explain its incidence, diagnosis, classifications, embryology, correlation between morphology of the QAV and its function, associated conditions, and management. PMID:21926862

  7. Sexual Dysfunction in Women

    Science.gov (United States)

    ... also cause sexual dysfunction. You may have less sexual desire during pregnancy, right after childbirth or when you are breastfeeding. After menopause many women feel less sexual desire, have vaginal dryness or have pain during sex ...

  8. Spinal Cord Dysfunction (SCD)

    Data.gov (United States)

    Department of Veterans Affairs — The Spinal Cord Dysfunction (SCD) module supports the maintenance of local and national registries for the tracking of patients with spinal cord injury and disease...

  9. Diastolic dysfunction in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Wiese, Signe; Halgreen, Hanne;

    2016-01-01

    Development of esophageal varices, ascites, and hepatic nephropathy is among the major complications of cirrhosis. The presence of cirrhotic cardiomyopathy, which includes a left ventricular diastolic dysfunction (DD), seems to deteriorate the course of the disease and the prognosis. Increased...

  10. Immune dysfunction in cirrhosis

    OpenAIRE

    Sipeki Nóra; Antal-Szalmás Péter (1968-) (laboratóriumi szakorvos, laboratóriumi hematológus és immunológus, klinikai farmakológus szakorvos); Lakatos Péter László; Papp Mária (1975-) (belgyógyász, gasztroenterológus)

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific comp...

  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. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

    Science.gov (United States)

    Drosatos, Konstantinos

    2016-01-01

    Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor-α, β-adrenergic receptor desensitization, and mitochondrial dysfunction as underlying mechanisms for the lipid-driven age-related cardiomyopathy are presented with the aim to indicate potential therapeutic targets for cardiac aging. PMID:27558317

  13. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Konstantinos Drosatos

    2016-08-01

    Full Text Available Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor-α, β-adrenergic receptor desensitization, and mitochondrial dysfunction as underlying mechanisms for the lipid-driven age-related cardiomyopathy are presented with the aim to indicate potential therapeutic targets for cardiac aging.

  14. Treating cardiac arrhythmias detected with an implantable cardiac monitor in patients after an acute myocardial infarction

    DEFF Research Database (Denmark)

    Jøns, Christian; Thomsen, Poul Erik Bloch

    2012-01-01

    OPINION STATEMENT: Using an implantable cardiac monitor (ICM) in patients with acute myocardial infarction (MI) allows continuous electrocardiogram monitoring and provides a much more detailed picture of the incidence of brady- and tachyarrhythmias than conventional follow-up. The CARISMA study...... was the first to use the ICM in post-MI patients with moderate to severe left ventricular systolic dysfunction. Atrial fibrillation (AF) events lasting longer than 30 s were associated with an almost threefold increase in the risk of major cardiac events. This confirms the current definition of clinically...... causes of AF such as progressive left ventricular dysfunction or myocardial ischemia. Asymptomatic, especially nightly, bradycardia episodes including high-degree 2°-3° atrioventricular (AV) block, sinus bradycardia, and sinus arrest were frequently documented by ICM in the CARISMA study. Ten percent...

  15. Short-Chain Fatty Acid Propionate Alleviates Akt2 Knockout-Induced Myocardial Contractile Dysfunction

    Directory of Open Access Journals (Sweden)

    Linlin Li

    2012-01-01

    Full Text Available Background and Aims. Dysregulation of Akt has been implicated in diseases such as cancer and diabetes, although little is known about the role of Akt deficiency on cardiomyocyte contractile function. This study was designed to examine the effect of Akt2 knockout-induced cardiomyocyte contractile response and the effect of dietary supplementation of short-chain fatty acid propionate on Akt2 knockout-induced cardiac dysfunction, if any. Methods and Results. Adult male wild-type (WT and Akt2 knockout mice were treated with propionate (0.3 g/kg, p.o. or vehicle for 7 days. Oral glucose tolerance test (OGTT was performed. Cardiomyocyte contractile function and mitochondrial membrane potential were assessed. Expression of insulin-signaling molecules Akt, PTEN, GSK3β, and eNOS receptors for short-chain fatty acids GPR41, and GPR43 as well as protein phosphatase PP2AA, PP2AB, PP2C were evaluated using Western blot analysis. Our results revealed that Akt2 knockout led to overt glucose intolerance, compromised cardiomyocyte contractile function (reduced peak shortening and maximal velocity of shortening/relengthening as well as prolonged relengthening, loss of mitochondrial membrane potential, decreased GPR41 and elevated GPR43 expression, all of which, with the exception of glucose intolerance and elevated GPR43 level, were significantly attenuated by propionate. Neither Akt2 knockout nor propionate affected the expression of protein phosphatases, eNOS, pan, and phosphorylated PTEN and GSK3β. Conclusions. Taken together, these data depicted that Akt2 knockout may elicit cardiomyocyte contractile and mitochondrial defects and a beneficial role of propionate or short-chain fatty acids against Akt2 deficiency-induced cardiac anomalies.

  16. Protective effects of Nigella sativa against hypertension-induced oxidative stress and cardiovascular dysfunction in rats

    Directory of Open Access Journals (Sweden)

    Nur Taşar

    2012-05-01

    Full Text Available We investigated the protective effect of Nigella sativa against oxidative injury in the heart and kidney tissues of rats with renovascular hypertension (RVH. RVH model was induced by placing a renal artery clip (2-kidney-1-clip, 2K1C in Wistar albino rats (n= 8, while sham rats (n= 8 had no clip placement. Starting on the 3rd week after the operation, rats received Nigella sativa (0.2 ml/kg/day, intraperitoneally or vehicle for the following 6 weeks. Blood pressures (BP were recorded at the beginning of the study and at the end of the 3rd and 9th weeks. Cardiac functions were assessed using transthoracic echocardiography before the rats were decapitated. Plasma samples were obtained to assay asymmetric dimethylarginine (ADMA, nitric oxide (NO, creatine kinase (CK and lactate dehydrogenase (LDH levels. Production of reactive oxidants was monitored by chemiluminescence (CL assay in the cardiac and renal tissues. Moreover oxidative injury was examined through malondialdehyde (MDA and glutathione (GSH levels and Na+,K+-ATPase activity in these tissues. 2K1C caused increased BP and left ventricular (LV dysfunction, while plasma ADMA, CK, and LDH levels were increased (p<0.05-0.001. Moreover, hypertension caused significant decreases in plasma NO levels, as well as in tissue Na+,K+-ATPase activities and GSH contents, while MDA levels in both tissues were increased (p<0.05-0.001. On the other hand, Nigella sativa treatment significantly reduced BP, attenuated oxidative injury and improved LV function. Nigella sativa protected against hypertension-induced tissue damage and improved cardiovascular function via its antioxidant and antihypertensive actions, suggesting a therapeutic potential of Nigella sativa in renovascular hypertension.

  17. Cardiac Dysfunction in the BACHD Mouse Model of Huntington's Disease

    OpenAIRE

    Schroeder, Analyne M.; Huei Bin Wang; Saemi Park; Jordan, Maria C.; Fuying Gao; Giovanni Coppola; Fishbein, Michael C; Kenneth P Roos; Ghiani, Cristina A.; Colwell, Christopher S.

    2016-01-01

    While Huntington’s disease (HD) is classified as a neurological disorder, HD patients exhibit a high incidence of cardiovascular events leading to heart failure and death. In this study, we sought to better understand the cardiovascular phenotype of HD using the BACHD mouse model. The age-related decline in cardiovascular function was assessed by echocardiograms, electrocardiograms, histological and microarray analysis. We found that structural and functional differences between WT and BACHD ...

  18. Mitochondrial injury and dysfunction in hypertension-induced cardiac damage

    OpenAIRE

    Eirin, Alfonso; Lerman, Amir; Lerman, Lilach O.

    2014-01-01

    Hypertension remains an important modifiable risk factor for cardiovascular disease, associated with increased morbidity and mortality. Deciphering the mechanisms involved in the pathogenesis of hypertension is critical, as its prevalence continues increasing worldwide. Mitochondria, the primary cellular energy producers, are numerous in parenchymal cells of the heart, kidney, and brain, major target organs in hypertension. These membrane-bound organelles not only maintain cellular respiratio...

  19. The FoxO Family in Cardiac Function and Dysfunction

    Science.gov (United States)

    Ronnebaum, Sarah M.; Patterson, Cam

    2010-01-01

    The Forkhead family of transcription factors mediates many aspects of physiology, including stress response, metabolism, commitment to apoptosis, and development. The Forkhead box subfamily O (FoxO) proteins have garnered particular interest due to their involvement in the modulation of cardiovascular biology. In this review, we discuss the mechanisms of FoxO regulation and outcomes of FoxO signaling under normal and pathological cardiovascular contexts. PMID:20148668

  20. Cardiac metastasis from colorectal cancer: A case report

    Institute of Scientific and Technical Information of China (English)

    Pyong Wha Choi; Chul Nam Kim; Sun Hee Chang; Woo Ik Chang; Chang Young Kim; Hyun Min Choi

    2009-01-01

    The heart is an unusual site of metastasis from any malignancy. We report a case of cardiac metastasis from colorectal cancer. A 70-year-old woman was referred with a presumptive diagnosis of sigmoid colon cancer with cardiac myxoma. Two-dimensional echocardiography showed a 4 cm × 4.5 cm mobile mass on the lateral right atrial wall, and computed tomography revealed a low attenuated lobulating mass in the right atrium. The patient underwent anterior resection for sigmoid colon cancer (T4N2). Thereafter, she experienced progressive shortness of breath. Therefore, a cardiac operation was performed 2 wk after the colorectal operation.Histological examination revealed adenocarcinoma,which was identical to the primary lesion. Although twodimensional echocardiography has become the diagnostic test of choice for detecting cardiac tumors, in patients with colorectal cancer showing a cardiac mass, further diagnostic evaluation such as a magnetic resonance imaging might be necessary.

  1. Cardiac fluid dynamics anticipates heart adaptation.

    Science.gov (United States)

    Pedrizzetti, Gianni; Martiniello, Alfonso R; Bianchi, Valter; D'Onofrio, Antonio; Caso, Pio; Tonti, Giovanni

    2015-01-21

    Hemodynamic forces represent an epigenetic factor during heart development and are supposed to influence the pathology of the grown heart. Cardiac blood motion is characterized by a vortical dynamics, and it is common belief that the cardiac vortex has a role in disease progressions or regression. Here we provide a preliminary demonstration about the relevance of maladaptive intra-cardiac vortex dynamics in the geometrical adaptation of the dysfunctional heart. We employed an in vivo model of patients who present a stable normal heart function in virtue of the cardiac resynchronization therapy (CRT, bi-ventricular pace-maker) and who are expected to develop left ventricle remodeling if pace-maker was switched off. Intra-ventricular fluid dynamics is analyzed by echocardiography (Echo-PIV). Under normal conditions, the flow presents a longitudinal alignment of the intraventricular hemodynamic forces. When pacing is temporarily switched off, flow forces develop a misalignment hammering onto lateral walls, despite no other electro-mechanical change is noticed. Hemodynamic forces result to be the first event that evokes a physiological activity anticipating cardiac changes and could help in the prediction of longer term heart adaptations.

  2. Variable laser attenuator

    Science.gov (United States)

    Foltyn, Stephen R.

    1988-01-01

    The disclosure relates to low loss, high power variable attenuators comprng one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength.

  3. [Cardiac reserve in Parkinson's disease and exercise therapy].

    Science.gov (United States)

    Hirayama, Masaaki; Nakamura, Tomohiko; Sobue, Gen

    2013-01-01

    The clinical feature of Parkinson's disease (PD) is not based on the identification of the extrapyramidal symptom such as bradykinesia, restinbg tremor, rigidity, but also other non-motor symptom (REM sleep disorder, autonomic dysfunction, hyposmia etc). According to the cardio-sympathetic dysfunction, it is well known abnormal MIBG and orthostatic hypotension finding was seen in early disease stage. Furthermore denervation supersensitivity using β1 stimulant correlates the severity of MIBG image, so that this abnormal cardiac function induces inadequate cardiac capacity for exercise. Inadequate cardiac capacity makes easy fatigability, which correlates the abnormal MIBG image and cardio-sympathetic damage. So it is difficult to prescribe a specific exercise program to meet individual PD patients needs. Music therapy and trunk exercise (for example Tai-Chi exercise) are better suited for PD patients. PMID:24291996

  4. Action of SNAIL1 in Cardiac Myofibroblasts Is Important for Cardiac Fibrosis following Hypoxic Injury

    Science.gov (United States)

    Biswas, Hirak; Longmore, Gregory D.

    2016-01-01

    Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor implicated in fibrosis following organ injury and cancer. To determine if the action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 expression is upregulated in the infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I increase SNAIL1 protein level. SNAIL1 is required in cardiac fibroblasts for the adoption of myofibroblast fate, collagen I expression and expression of fibrosis-related genes. Taken together this data suggests that SNAIL1 expression is induced in the cardiac fibroblasts after hypoxic injury and contributes to myofibroblast phenotype and a fibrotic scar formation. Resultant collagen deposition in the scar can maintain elevated SNAIL1 expression in the myofibroblasts and help propagate fibrosis. PMID:27706205

  5. Aconitine Challenge Test Reveals a Single Exposure to Air Pollution Causes Increased Cardiac Arrhythmia Risk in Hypertensive Rats - Abstract

    Science.gov (United States)

    Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...

  6. 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.

  7. Biomimetic material strategies for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakaran, Molamma P., E-mail: nnimpp@nus.edu.sg [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Venugopal, J. [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Kai, Dan [NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore (Singapore); Ramakrishna, Seeram [Health Care and Energy Materials Laboratory, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore)

    2011-04-08

    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.

  8. Adiponectin is required for cardiac MEF2 activation during pressure overload induced hypertrophy.

    Science.gov (United States)

    Dadson, Keith; Turdi, Subat; Hashemi, Sarah; Zhao, Jianzhong; Polidovitch, Nazar; Beca, Sanja; Backx, Peter H; McDermott, John C; Sweeney, Gary

    2015-09-01

    Cardiomyocyte (CM) hypertrophy and increased heart mass in response to pressure overload are associated with hyper-activation of the myocyte enhancer factor-2 (MEF2) family of transcriptional regulators, and concomitant initiation of the fetal gene program. Adiponectin, an adipokine that is reduced in individuals with obesity and diabetes, has been characterized both as a negative regulator or permissive factor in cardiac hypertrophy. We therefore sought to analyze temporal regulation of MEF2 activity in response to pressure overload (PO) and changes in adiponectin status. To address this we crossed a well characterized transgenic MEF2 "sensor" mouse (MEF2-lacZ) with adiponectin null mice (Ad-KO) to create compound MEF2 lacZ/Ad-KO mice. Initially, we established that transverse aortic banding induced PO in wild-type (WT) mice increased heart mass and CM hypertrophy from 1 to 4weeks following surgery, indicated by increased CM diameter and heart weight/tibia length ratio. This was associated with cardiac dysfunction determined by echocardiography. Hypertrophic changes and dysfunction were observed in Ad-KO mice 4weeks following surgery. MEF2 lacZ activity and endogenous ANF mRNA levels, used as indicators of hypertrophic gene activation, were both robustly increased in WT mice after MTAB but attenuated in the Ad-KO background. Furthermore, activation of the pro-hypertrophic molecule p38 was increased following MTAB surgery in WT mice, but not in Ad-KO animals, and treatment of primary isolated CM with recombinant adiponectin induced p38 phosphorylation in a time dependent manner. Adiponectin also increased MEF2 activation in primary cardiomyocytes, an effect attenuated by p38 MAPK inhibition. In conclusion, our data indicate that robust hypertrophic MEF2 activation in the heart in vivo requires a background of adiponectin signaling and that adiponectin signaling in primary isolated CM directly enhances MEF2 activity through activation of p38 MAPK. We conclude that

  9. Tamoxifen Injection induce transient myocardiac dysfunction in mice

    Institute of Scientific and Technical Information of China (English)

    Yan; Yan; Wang; Sheng; Liu; Bin; Yu

    2014-01-01

    Tamoxifen inducible cre-loxp system has been employed as a very powerful tool for cardiology research in mice. It enables researchers to control their interested gene expression in tight control in terms of tissue specification and time specification. Here, we reported that in the absence of loxp transgenes,tamoxifen injection can lead to myocardiac dysfunction 3 days after drug administration but cardiac function start recover from 2 days later.

  10. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction

    Directory of Open Access Journals (Sweden)

    Moustafa Elsheshtawy

    2016-01-01

    Full Text Available Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools.

  11. Synthetic Marijuana Induced Acute Nonischemic Left Ventricular Dysfunction.

    Science.gov (United States)

    Elsheshtawy, Moustafa; Sriganesh, Priatharsini; Virparia, Vasudev; Patel, Falgun; Khanna, Ashok

    2016-01-01

    Synthetic marijuana is an uptrending designer drug currently widely spread in the US. We report a case of acute deterioration of nonischemic left ventricular dysfunction after exposure to synthetic marijuana. This case illustrates the importance of history taking in cardiac patients and identifies a negative cardiovascular effect of synthetic marijuana known as K2, not yet well detected by urine toxicology screening tools. PMID:27119030

  12. Voiding dysfunction - A review

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2005-01-01

    Full Text Available In a child who is toilet trained the sudden onset of daytime wetting with frequency or urgency is alarming to the parents. Initially this subject was subdivided into a number of descriptive clinical conditions which led to a lot of confusion in recognition and management. Subsequently, the term elimination dysfunction was coined by Stephen Koff to emphasise the association between recurrent urinary infection, wetting, constipation and bladder overactivity. From a urodynamic point of view, in voiding dysfunction, there is either detrusor overactivity during bladder filling or dyssynergic action between the detrusor and the external sphincter during voiding. Identifying a given condition as a ′filling phase dysfunction′ or ′voiding phase dysfunction′ helps to provide appropriate therapy. Objective clinical criteria should be used to define voiding dysfunction. These include bladder wall thickening, large capacity bladder and infrequent voiding, bladder trabeculation and spinning top deformity of the urethra and a clinically demonstrated Vincent′s curtsy. The recognition and treatment of constipation is central to the adequate treatment of voiding dysfunction. Transcutaneous electric nerve stimuation for the treatment of detrusor overactivity, biofeedback with uroflow EMG to correct dyssynergic voiding, and behavioral therapy all serve to correct voiding dysfunction in its early stages. In established neurogenic bladder disease the use of Botulinum Toxin A injections into the detrusor or the external sphincter may help in restoring continence especially in those refractory to drug therapy. However in those children in whom the upper tracts are threatened, augmentation of the bladder may still be needed.