Identification, purification, and localization of tissue kallikrein in rat heart.

OpenAIRE

Xiong, W; Chen, L M; Woodley-Miller, C; Simson, J A; Chao, J

1990-01-01

A tissue kallikrein has been isolated from rat heart extracts by DEAE-Sepharose and aprotinin-affinity column chromatography. The purified cardiac enzyme has both N-tosyl-L-arginine methyl ester esterolytic and kinin-releasing activities, and displays parallelism with standard curves in a kallikrein radioimmunoassay, indicating it to have immunological identity with tissue kallikrein. The enzyme is inhibited by aprotinin, antipain, leupeptin and by high concentrations of soybean trypsin inhib...

Metabolic and cardiac changes in high cholesterol-fructose-fed rats

DEFF Research Database (Denmark)

Axelsen, Lene N; Pedersen, Henrik D; Petersen, Jørgen S

2010-01-01

Introduction: High cholesterol-fructose (HCF) fed rats have previously been described as an animal model of impaired cardiac insulin signaling and decreased contractile performance. In this study, we evaluated the metabolic and cardiac effects of a HCF diet in rats. Methods: Male Sprague-Dawley r......Introduction: High cholesterol-fructose (HCF) fed rats have previously been described as an animal model of impaired cardiac insulin signaling and decreased contractile performance. In this study, we evaluated the metabolic and cardiac effects of a HCF diet in rats. Methods: Male Sprague...

Differential cardiac effects in rats exposed to atmospheric ...

Science.gov (United States)

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

Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.

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Daniel Biermann

Full Text Available The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12. Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3 revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.

Effect of silymarin on sodium fluoride-induced toxicity and oxidative stress in rat cardiac tissues

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Seyed M. Nabavi

2012-12-01

Full Text Available This study aim to evaluate the protective effect of silymarin on sodium fluoride-induced oxidative stress in rat cardiac tissues. Animals were pretreated with silymarin at 20 and 10 mg/kg prior to sodium fluoride consumption (600 ppm through drinking water. Vitamin C at 10 mg/kg was used as standard antioxidant. There was a significant increase in thiobarbituric acid reactive substances level (59.36 ± 2.19 nmol MDA eq/g tissue along with a decrease in antioxidant enzymes activity (64.27 ± 1.98 U/g tissue for superoxide dismutase activity and 29.17 ± 1.01 µmol/min/mg protein for catalase activity and reduced glutathione level (3.8 ± 0.15 µg/mg protein in the tissues homogenates of the sodium fluoride-intoxicated rats. Silymarin administration to animals before sodium fluoride consumption modified the levels of biochemical parameters.Este estudo objetiva avaliar o efeito protetor da silimarina em fluoreto de sódio induzida por estresse oxidativo em tecido cardíaco de ratos. Os animais foram pré-tratados com silimarina a 20 e 10 mg/kg antes do consumo de fluoreto de sódio (600 ppm através da água de beber. A vitamina C a 10 mg/kg foi utilizada como antioxidante padrão. Houve um aumento significativo no nível de substâncias tiobarbitúrico reativo de ácido (59,36 ± 2.19 nmol MDA eq/g tecido, juntamente com uma diminuição da atividade de enzimas antioxidantes (64,27 ± 1,98 U/g tecido para a atividade de superóxido dismutase e 29,7 ± 1,01 mmol/min/mg de proteína para a atividade da catalase e nível de glutationa reduzida (3,8 ± 0,15 mg/mg de proteína nos homogeneizados de tecidos dos fluoreto de sódio-intoxicados ratos. Administração de silimarina a animais, antes do consumo de fluoreto de sódio modifou os níveis de parâmetros bioquímicos.

Cardiac oxidative stress following maternal separation stress was mitigated following adolescent voluntary exercise in adult male rat.

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Sahafi, Ehtramolsadat; Peeri, Maghsoud; Hosseini, Mir-Jamal; Azarbyjani, Mohammad Ali

2018-01-01

Early life stress (ELS) is known as a risk factor for the development of depression and its associated comorbidities, such as cardiomyopathy in depressed patients. Mitochondrial dysfunction plays a critical role in the pathophysiology of depression and cardiovascular diseases. Evidence indicates that regular physical activity has therapeutic effects on both mood and cardiovascular disorders. Therefore, the voluntary running wheel exercise (RW) during adolescence may be able to attenuate the negative impact of maternal separation stress (MS) as a valid animal model of depression on the behavior and cardiac mitochondrial function of adult rats. To do this, we applied MS to rat pups by separating them from their mothers for 180min during the postnatal day (PND) 2 to PND 14. Next, the animals were randomly divided into different treatment groups (fluoxetine [FLX] and RW) and received the treatments during adolescence, between PND 28 to PND 60. Then, we evaluated the effects of MS on the rat behaviors test, and finally, we assessed reactive oxygen species, mitochondrial glutathione, ATP and cytochrome c release in the cardiac tissue of animals. Our results showed that depressive-like behaviors following MS in adult male rats were associated with oxidative stress in cardiac tissue. Further, we found that treating animals with chronic FLX or RW during adolescence improved animal's behavior as well as cardiac mitochondrial function. The results of this study highlight the importance of adolescence as a period during which treating animals with non-pharmacological agents has significant protective effects against the negative influence of ELS on mood and cardiac energy hemostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Biomimetic material strategies for cardiac tissue engineering

International Nuclear Information System (INIS)

Prabhakaran, Molamma P.; Venugopal, J.; Kai, Dan; Ramakrishna, Seeram

2011-01-01

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.

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.

Abatement by Naringenin of Doxorubicin-Induced Cardiac Toxicity in Rats

International Nuclear Information System (INIS)

Arafa, H.M.; Abd-Ellah, M.F.; Hafez, H.F.

2005-01-01

Doxorubicin is one of the most active cytotoxic agents in current use. It has proven efficacy in various malignancies either alone or combined with other cytocidal agents. The clinical usefulness of the anthracycline drug has been precluded by cardiac toxicity. Many therapeutic interventions have been attempted to improve the therapeutic benefits of the drug. Few, however, have been efficacious in this setting. Purpose: We have addressed in the current study the possible protective effects of naringenin, a flavonoid known to have anti-oxidant properties, on doxorubicin induced cardiac toxicity in male Swiss albino rats. Methods: Forty male Swiss albino rats were used in this study. Naringenin (25 mg/kg body weight) was administered daily by gavage for 7 consecutive days before a cumulative single dose of doxorubicin (15 mg/kg body weight, ip). Doxorubicin induced marked biochemical alterations characteristic of cardiac toxicity including, elevated activities of serum total lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), enhanced lipid peroxidation measured as malonaldehyde (MDA). The anthracycline drug has also reduced the cardiac enzymatic activities of superoxide dismutase (SOD), glutathione-Stransferase (GST) and catalase (CAT). Besides, it reduced significantly the reduced glutathione (GSH) level, but it increased the total NO content in heart tissue. Prior administration of naringenin ahead of doxorubicin challenge ameliorated all these biochemical markers. Taken together, one could conclude that naringenin has a protective role in the abatement of doxorubicin-induced cardiac toxicity that resides, at least in part, on its anti-radical effects and regulatory role on NO production

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

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Liu, Zhong-wei; Wang, Jun-kui; Qiu, Chuan; Guan, Gong-chang; Liu, Xin-hong; Li, Shang-jian; Deng, Zheng-rong

2015-03-01

Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

Ginsenoside Rh2 Improves Cardiac Fibrosis via PPARδ–STAT3 Signaling in Type 1-Like Diabetic Rats

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Shih-Hsiang Lo

2017-06-01

Full Text Available Ginsenoside Rh2 (Rh2 is an active principal ingredient contained in ginseng (Panax ginseng Meyer, a medicinal herb used to enhance health worldwide. The present study is designed to investigate the effect of Rh2 on myocardial fibrosis in diabetic rats. In a streptozotocin-induced model of type-1 diabetic rats (STZ-diabetic rats, the increased fasting blood glucose levels and heart weight/body weight (HW/BW ratio were substantially alleviated by Rh2. Moreover, Rh2 improved cardiac performance in STZ-diabetic rats. Histological results from Masson staining showed that Rh2 attenuated cardiac fibrosis in STZ-diabetic rats. The effects of Rh2 were reversed by GSK0660 at a dose sufficient to inhibit peroxisome proliferator-activated receptor δ (PPARδ in STZ-diabetic rats. The role of PPARδ was subsequently investigated in vitro. Rh2 restored the decreased PPARδ expression level in high glucose-cultured cardiomyocytes. Moreover, increased protein levels of fibrotic signals, including signal transducer and activator of transcription 3 (STAT3, connective tissue growth factor (CCN2 and fibronectin, were reduced by Rh2 in high glucose-cultured cardiomyocytes. These effects of Rh2 were reversed by GSK0660 or siRNA specific for PPARδ Taken together, PPARδ activation may inhibit STAT3 activation to reduce CCN2 and fibronectin expression in diabetic rats with cardiac fibrosis. Moreover, Rh2 improves cardiac function and fibrosis by increasing PPARδ signaling. Therefore, Rh2 is suitable to develop as an alternative remedy for cardiac fibrosis.

Pre-transplantation specification of stem cells to cardiac lineage for regeneration of cardiac tissue.

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Mayorga, Maritza; Finan, Amanda; Penn, Marc

2009-03-01

Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.

Pioglitazone reverses down-regulation of cardiac PPARγ expression in Zucker diabetic fatty rats

International Nuclear Information System (INIS)

Pelzer, Theo; Jazbutyte, Virginija; Arias-Loza, Paula Anahi; Segerer, Stephan; Lichtenwald, Margit; Law, Marilyn P.; Schaefers, Michael; Ertl, Georg; Neyses, Ludwig

2005-01-01

Peroxisome proliferator-activated receptor-γ (PPARγ) plays a critical role in peripheral glucose homeostasis and energy metabolism, and inhibits cardiac hypertrophy in non-diabetic animal models. The functional role of PPARγ in the diabetic heart, however, is not fully understood. Therefore, we analyzed cardiac gene expression, metabolic control, and cardiac glucose uptake in male Zucker diabetic fatty rats (ZDF fa/fa) and lean ZDF rats (+/+) treated with the high affinity PPARγ agonist pioglitazone or placebo from 12 to 24 weeks of age. Hyperglycemia, hyperinsulinemia, and hypertriglyceridemia as well as lower cardiac PPARγ, glucose transporter-4 and α-myosin heavy chain expression levels were detected in diabetic ZDF rats compared to lean animals. Pioglitazone increased body weight and improved metabolic control, cardiac PPARγ, glut-4, and α-MHC expression levels in diabetic ZDF rats. Cardiac [ 18 F]fluorodeoxyglucose uptake was not detectable by micro-PET studies in untreated and pioglitazone treated ZDF fa/fa rats but was observed after administration of insulin to pioglitazone treated ZDF fa/fa rats. PPARγ agonists favorably affect cardiac gene expression in type-2 diabetic rats via activation and up-regulation of cardiac PPARγ expression whereas improvement of impaired cardiac glucose uptake in advanced type-2 diabetes requires co-administration of insulin

Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats.

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Moreno, Juan Manuel; Rodríguez Gómez, Isabel; Wangensteen, Rosemary; Osuna, Antonio; Bueno, Pablo; Vargas, Félix

2005-11-01

This study evaluated the activity of cardiac and renal antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR)] and whether chronic treatment with tempol, a cell membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism. Two experiments were performed. In experiment I, the following four groups of male Wistar rats were used: control group and three groups that received thyroxine (T4) at 10, 50, or 75 microg x rat(-1) x day(-1). In experiment II, tempol was orally administered (18 mg x kg(-1) x day(-1)) to control and T4-treated (75 microg x rat(-1) x day(-1)) rats. All treatments were maintained for 6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were measured one time a week, and direct BP and morphological, metabolic, plasma, and renal variables were measured at the end of the experiment. Enzymatic activities were measured in renal cortex and medulla and right and left ventricles. In renal cortex, SOD activity was decreased in the T4-75 group, and there was a dose-related increase in CAT activity and decrease in GPX and GR activities in T4-treated groups. Activity of all antioxidant enzymes was reduced in left ventricle in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol reduced BP, plasma malondialdehyde, and total urinary excretion of F2 isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did not improve cardiac hypertrophy, proteinuria, or creatinine clearance in hyperthyroid rats. In conclusion, the results obtained indicate that the activity of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism and that antioxidant treatment with tempol ameliorates T4-induced hypertension.

Estrogen deprivation aggravates cardiac hypertrophy in nonobese Type 2 diabetic Goto-Kakizaki (GK) rats.

Science.gov (United States)

Apaijai, Nattayaporn; Charoenphandhu, Narattaphol; Ittichaichareon, Jitjiroj; Suntornsaratoon, Panan; Krishnamra, Nateetip; Aeimlapa, Ratchaneevan; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2017-10-31

Both Type 2 diabetes mellitus (T2DM) and estrogen deprivation have been shown to be associated with the development of cardiovascular disease and adverse cardiac remodeling. However, the role of estrogen deprivation on adverse cardiac remodeling in nonobese T2DM rats has not been clearly elucidated. We hypothesized that estrogen-deprivation aggravates adverse cardiac remodeling in Goto-Kakizaki (GK) rats. Wild-type (WT) and GK rats at the age of 9 months old were divided into two subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) ( n = 6/subgroup). Four months after the operation, the rats were killed, and the heart was excised rapidly. Metabolic parameters, cardiomyocytes hypertrophy, cardiac fibrosis, and biochemical parameters were determined. GK rats had hyperglycemia with hypoinsulinemia, and estrogen deprivation did not increase the severity of T2DM. Cardiac hypertrophy, cardiac oxidative stress, and phosphor-antinuclear factor κB were higher in WTO and GKS rats than WTS rats, and they markedly increased in GKO rats compared with GKS rats. Furthermore, cardiac fibrosis, transforming growth factor-β, Bax, phosphor-p38, and peroxisome proliferator- activated receptor γ coactivator-1α expression were increased in GKS and GKO rats compared with the lean rats. However, mitochondrial dynamics proteins including dynamin-related protein 1 and mitofusin-2 were not altered by T2DM and estrogen deprivation. Although estrogen deprivation did not aggravate T2DM in GK rats, it increased the severity of cardiac hypertrophy by provoking cardiac inflammation and oxidative stress in nonobese GK rats. © 2017 The Author(s).

Cardiac effects of MDMA on the metabolic profile determined with 1H-magnetic resonance spectroscopy in the rat.

Science.gov (United States)

Perrine, Shane A; Michaels, Mark S; Ghoddoussi, Farhad; Hyde, Elisabeth M; Tancer, Manuel E; Galloway, Matthew P

2009-05-01

Despite the potential for deleterious (even fatal) effects on cardiac physiology, 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) abuse abounds driven mainly by its euphoric effects. Acute exposure to MDMA has profound cardiovascular effects on blood pressure and heart rate in humans and animals. To determine the effects of MDMA on cardiac metabolites in rats, MDMA (0, 5, or 10 mg/kg) was injected every 2 h for a total of four injections; animals were sacrificed 2 h after the last injection (8 h drug exposure), and their hearts removed and tissue samples from left ventricular wall dissected. High resolution magic angle spinning proton magnetic resonance spectroscopy ((1)H-MRS) at 11.7 T, a specialized version of MRS aptly suited for analysis of semi-solid materials such as intact tissue samples, was used to measure the cardiac metabolomic profile, including alanine, lactate, succinate, creatine, and carnitine, in heart tissue from rats treated with MDMA. MDMA effects on MR-visible choline, glutamate, glutamine, and taurine were also determined. Body temperature was measured following each MDMA administration and serotonin and norepinephrine (NE) levels were measured by high pressure liquid chromatography (HPLC) in heart tissue from treated animals. MDMA significantly and dose-dependently increased body temperature, a hallmark of amphetamines. Serotonin, but not NE, levels were significantly and dose-dependently decreased by MDMA in the heart wall. MDMA significantly altered the MR-visible profile with an increase in carnitine and no change in other key compounds involved in cardiomyocyte energy metabolomics. Finally, choline levels were significantly decreased by MDMA in heart. The results are consistent with the notion that MDMA has significant effects on cardiovascular serotonergic tone and disrupts the metabolic homeostasis of energy regulation in cardiac tissue, potentially increasing utilization of fatty acid metabolism. The contributions of serotonergic

Hypoxic-induced stress protein expression in rat cardiac myocytes

International Nuclear Information System (INIS)

Howard, G.; Geoghegan, T.E.

1986-01-01

Mammalian stress proteins can be induced in cells and tissues exposed to a variety of conditions including hyperthermia and diminished O 2 supply. The authors have previously shown that the expression of three stress proteins (71, 85, and 95 kDa) was induced in cardiac tissue from mice exposed to hypoxic conditions. The expression of mRNAs coding for the 85 and 95 kDa proteins increase with time of exposure to hypoxia, while the mRNA coding for the 71 kDa protein is transiently induced. The authors extended these studies to investigate the expression of stress proteins in isolated rat cardiac myocytes. Freshly prepared myocytes were exposed to control, hypoxic, anoxic, or heat-shock environments for up to 16 h. The proteins were then labeled for 6 hours with [ 35 S]methionine. Analysis of the solubilized proteins by SDS-PAGE and autoradiography showed that there was a 6-fold increase in synthesis of the 85 kDa protein upon exposure to hypoxia but not heat-shock conditions. The 71 kDa protein was present at high levels in both control and treated myocyte protein preparations, and presumably had been induced during the isolation procedure. Total RNA isolated from intact rat heart and isolated myocytes was compared by cell-free translation analysis and showed induction of RNAs coding for several stress proteins in the myocyte preparation. The induced proteins at 85 and 95 kDa have molecular weights similar to reported cell stress and/or glucose-regulated proteins

Adult Bone Marrow Mesenchymal Stem Cells Primed for fhe Repair of Damaged Cardiac Tissue After Myocardial Infarction

Science.gov (United States)

Marks, Edward D.

The burden of cardiovascular disease around the world is growing, despite improvements in hospital care and time to treatment. As more people survive an initial myocardial infarction (MI), the decompensated heart tissue is strained, leading to heart failure (HF) and an increased risk for a second MI. While extensive progress has been made in treating the symptoms after MI, including HF and angina, little success has come from repairing the damaged heart tissue to alleviate the progression to these end- stage symptoms. One promising area of regenerative research has been the use of adult stem cells, particularly from the bone marrow (BMSCs). These cells can differentiate towards the cardiac cell lineage in vitro while producing trophic factors that can repair damaged tissue. When placed in the heart after MI though, BMSCs have mixed results, producing profound changes in some patients but zero or even negative effects in others. In this report, we used BMSCs as a stem cell base for a regenerative medicine system for the repair of damaged cardiac tissue. These cells are seeded on a polycaprolactone nanoscaffolding support system, which provides a growth substrate for in vitro work, as well as a housing system for protected in vivo delivery. When the nanoscaffold is pre-coated with a novel combination of a cardiac protein, thymosin beta4 (Tbeta4), and a small molecule effector of the WNT protein pathway, IWP-2, BMSCs differentiated towards the cardiac lineage in as little as 24hours. When injected into rat hearts that have been given an ischemic MI, the nanoscaffolding system slowly dissolves, leaving the cells in place of the damaged cardiac tissue. After two weeks of monitoring, BMSCs are present within the damaged hearts, as evidenced by immunofluorescence and nanoparticle tracking. Injections of the nanoscaffolding/cell system led to robust healing of the rat hearts that had been given small- and medium- damage heart attacks, outperforming PBS sham and cell

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

Science.gov (United States)

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

2011-11-22

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

Eicosapentenoic Acid Attenuates Allograft Rejection in an HLA-B27/EGFP Transgenic Rat Cardiac Transplantation Model.

Science.gov (United States)

Liu, Zhong; Hatayama, Naoyuki; Xie, Lin; Kato, Ken; Zhu, Ping; Ochiya, Takahiro; Nagahara, Yukitoshi; Hu, Xiang; Li, Xiao-Kang

2012-01-01

The development of an animal model bearing definite antigens is important to facilitate the evaluation and modulation of specific allo-antigen responses after transplantation. In the present study, heterotopic cardiac transplantation was performed from F344/EGFPTg and F344/HLA-B27Tg rats to F344 rats. The F344 recipients accepted the F344/EGFPTg transplants, whereas they rejected the cardiac tissue from the F344/HLA-B27Tg rats by 39.4 ± 6.5 days, due to high production of anti-HLA-B27 IgM- and IgG-specific antibodies. In addition, immunization of F344 rats with skin grafts from F344/HLA-B27Tg rats resulted in robust production of anti- HLA-B27 IgM and IgG antibodies and accelerated the rejection of a secondary cardiac allograft (7.4 ± 1.9 days). Of interest, the F344 recipients rejected cardiac grafts from double transgenic F344/HLA-B27&EGFPTg rats within 9.0 ± 3.2 days, and this was associated with a significant increase in the infiltration of lymphocytes by day 7, suggesting a role for cellular immune rejection. Eicosapentenoic acid (EPA), one of the ω-3 polyunsaturated fatty acids in fish oil, could attenuate the production of anti-HLA IgG antibodies and B-cell proliferation, significantly prolonging double transgenic F344HLA-B27&EGFPTg to F344 rat cardiac allograft survival (36.1 ± 13.6 days). Moreover, the mRNA expression in the grafts was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), revealing an increase in the expression of the HO-1, IL-10, TGF-β, IDO, and Foxp3 genes in the EPA-treated group. Hence, our data indicate that HLA-B27 and/or GFP transgenic proteins are useful for establishing a unique animal transplantation model to clarify the mechanism underlying the allogeneic cellular and humoral immune response, in which the transplant antigens are specifically presented. Furthermore, we also demonstrated that EPA was effective in the treatment of rat cardiac allograft rejection and may allow the development of

Engineering Cardiac Muscle Tissue: A Maturating Field of Research.

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Weinberger, Florian; Mannhardt, Ingra; Eschenhagen, Thomas

2017-04-28

Twenty years after the initial description of a tissue engineered construct, 3-dimensional human cardiac tissues of different kinds are now generated routinely in many laboratories. Advances in stem cell biology and engineering allow for the generation of constructs that come close to recapitulating the complex structure of heart muscle and might, therefore, be amenable to industrial (eg, drug screening) and clinical (eg, cardiac repair) applications. Whether the more physiological structure of 3-dimensional constructs provides a relevant advantage over standard 2-dimensional cell culture has yet to be shown in head-to-head-comparisons. The present article gives an overview on current strategies of cardiac tissue engineering with a focus on different hydrogel methods and discusses perspectives and challenges for necessary steps toward the real-life application of cardiac tissue engineering for disease modeling, drug development, and cardiac repair. © 2017 American Heart Association, Inc.

Vildagliptin reduces cardiac ischemic-reperfusion injury in obese orchiectomized rats.

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

2016-10-01

Obesity and testosterone deprivation are associated with coronary artery disease. Testosterone and vildagliptin (dipeptidyl peptidase-4 inhibitors) exert cardioprotection during ischemic-reperfusion (I/R) injury. However, the effect of these drugs on I/R heart in a testosterone-deprived, obese, insulin-resistant model is unclear. This study investigated the effects of testosterone and vildagliptin on cardiac function, arrhythmias and the infarct size in I/R heart of testosterone-deprived rats with obese insulin resistance. Orchiectomized (O) or sham operated (S) male Wistar rats were divided into 2 groups to receive normal diet (ND) or high-fat diet (HFD) for 12 weeks. Orchiectomized rats in each diet were divided to receive testosterone (2 mg/kg), vildagliptin (3 mg/kg) or the vehicle daily for 4 weeks. Then, I/R was performed by a 30-min left anterior descending coronary artery ligation, followed by a 120-min reperfusion. LV function, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. HFD groups developed insulin resistance at week 12. At week 16, cardiac function was impaired in NDO, HFO and HFS rats, but was restored in all testosterone- and vildagliptin-treated rats. During I/R injury, arrhythmia scores, infarct size and cardiac mitochondrial dysfunction were prominently increased in NDO, HFO and HFS rats, compared with those in NDS rats. Treatment with either testosterone or vildagliptin similarly attenuated these impairments during I/R injury. These finding suggest that both testosterone replacement and vildagliptin share similar efficacy for cardioprotection during I/R injury by decreasing the infarct size and attenuating cardiac mitochondrial dysfunction caused by I/R injury in testosterone-deprived rats with obese insulin resistance. © 2016 Society for Endocrinology.

Sphingosine-1-Phosphate (S1P) Lyase Inhibition Causes Increased Cardiac S1P Levels and Bradycardia in Rats.

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Harris, Christopher M; Mittelstadt, Scott; Banfor, Patricia; Bousquet, Peter; Duignan, David B; Gintant, Gary; Hart, Michelle; Kim, Youngjae; Segreti, Jason

2016-10-01

Inhibition of the sphingosine-1-phosphate (S1P)-catabolizing enzyme S1P lyase (S1PL) elevates the native ligand of S1P receptors and provides an alternative mechanism for immune suppression to synthetic S1P receptor agonists. S1PL inhibition is reported to preferentially elevate S1P in lymphoid organs. Tissue selectivity could potentially differentiate S1PL inhibitors from S1P receptor agonists, the use of which also results in bradycardia, atrioventricular block, and hypertension. But it is unknown if S1PL inhibition would also modulate cardiac S1P levels or cardiovascular function. The S1PL inhibitor 6-[(2R)-4-(4-benzyl-7-chlorophthalazin-1-yl)-2-methylpiperazin-1-yl]pyridine-3-carbonitrile was used to determine the relationship in rats between drug concentration, S1P levels in select tissues, and circulating lymphocytes. Repeated oral doses of the S1PL inhibitor fully depleted circulating lymphocytes after 3 to 4 days of treatment in rats. Full lymphopenia corresponded to increased levels of S1P of 100- to 1000-fold in lymph nodes, 3-fold in blood (but with no change in plasma), and 9-fold in cardiac tissue. Repeated oral dosing of the S1PL inhibitor in telemeterized, conscious rats resulted in significant bradycardia within 48 hours of drug treatment, comparable in magnitude to the bradycardia induced by 3 mg/kg fingolimod. These results suggest that S1PL inhibition modulates cardiac function and does not provide immune suppression with an improved cardiovascular safety profile over fingolimod in rats. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4-Induced Liver Cirrhosis

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Ping-Chun Li

2012-01-01

Full Text Available We used the carbon tetrachloride (CCl4 induced liver cirrhosis model to test the molecular mechanism of action involved in cirrhosis-associated cardiac hypertrophy and the effectiveness of Ocimum gratissimum extract (OGE and silymarin against cardiac hypertrophy. We treated male wistar rats with CCl4 and either OGE (0.02 g/kg B.W. or 0.04 g/kg B.W. or silymarin (0.2 g/kg B.W.. Cardiac eccentric hypertrophy was induced by CCl4 along with cirrhosis and increased expression of cardiac hypertrophy related genes NFAT, TAGA4, and NBP, and the interleukin-6 (IL-6 signaling pathway related genes MEK5, ERK5, JAK, and STAT3. OGE or silymarin co-treatment attenuated CCl4-induced cardiac abnormalities, and lowered expression of genes which were elevated by this hepatotoxin. Our results suggest that the IL-6 signaling pathway may be related to CCl4-induced cardiac hypertrophy. OGE and silymarin were able to lower liver fibrosis, which reduces the chance of cardiac hypertrophy perhaps by lowering the expressions of IL-6 signaling pathway related genes. We conclude that treatment of cirrhosis using herbal supplements is a viable option for protecting cardiac tissues against cirrhosis-related cardiac hypertrophy.

Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker

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2013-01-01

Background Diabetic cardiomyopathy (DCM) is defined as structural and functional changes in the myocardium due to metabolic and cellular abnormalities induced by diabetes mellitus (DM). The impact of prediabetic conditions on the cardiac tissue remains to be elucidated. The goal of this study was to elucidate whether cardiac dysfunction is already present in a state of prediabetes, in the presence of insulin resistance, and to unravel the underlying mechanisms, in a rat model without obesity and hypertension as confounding factors. Methods Two groups of 16-week-old Wistar rats were tested during a 9 week protocol: high sucrose (HSu) diet group (n = 7) – rats receiving 35% of sucrose in drinking water vs the vehicle control group (n = 7). The animal model was characterized in terms of body weight (BW) and the glycemic, insulinemic and lipidic profiles. The following parameters were assessed to evaluate possible early cardiac alterations and underlying mechanisms: blood pressure, heart rate, heart and left ventricle (LV) trophism indexes, as well as the serum and tissue protein and/or the mRNA expression of markers for fibrosis, hypertrophy, proliferation, apoptosis, angiogenesis, endothelial function, inflammation and oxidative stress. Results The HSu-treated rats presented normal fasting plasma glucose (FPG) but impaired glucose tolerance (IGT), accompanied by hyperinsulinemia and insulin resistance (P prediabetic. Furthermore, although hypertriglyceridemia (P prediabetes/insulin resistance could be an important tool to evaluate the early cardiac impact of dysmetabolism (hyperinsulinemia and impaired glucose tolerance with fasting normoglycemia), without confounding factors such as obesity and hypertension. Left ventricle hypertrophy is already present and brain natriuretic peptide seems to be the best early marker for this condition. PMID:23497124

Chronically elevated bilirubin protects from cardiac reperfusion injury in the male Gunn rat.

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Bakrania, B; Du Toit, E F; Ashton, K J; Wagner, K-H; Headrick, J P; Bulmer, A C

2017-08-01

Bilirubin is associated with reduced risk of cardiovascular disease, as evidenced in conditions of mild hyperbilirubinaemia (Gilbert's Syndrome). Little is known regarding myocardial stress resistance in hyperbilirubinaemic conditions or whether life-long exposure modifies cardiac function, which might contribute to protection from cardiovascular disease. Hyperbilirubinaemic rats and littermate controls underwent echocardiography at 3, 6 and 12 months of age, with hearts subsequently assessed for resistance to 30 min of ischaemia. Heart tissue was then collected for assessment of bilirubin content. No difference in baseline cardiac function was evident until 6 months onwards, where Gunn rats demonstrated aortic dilatation and reduced peak ejection velocities. Additionally, duration of ventricular ejection increased progressively, indicating a negative inotropic effect of bilirubin in vivo. Ex vivo analysis of baseline function revealed reduced left ventricular pressure development (LVDP) and contractility in hyperbilirubinaemic rats. Furthermore, stress resistance was improved in Gunn hearts: post-ischaemic recoveries of LVDP (76 ± 22% vs. 29 ± 17% Control, P bilirubin exerts sex-independent effects on vascular structure, myocardial function and ischaemic tolerance, the latter likely mediated via bilirubin's antioxidant properties. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Cardiac Hypertrophy and Brain Natriuretic Peptide Levels in an Ovariectomized Rat Model Fed a High-Fat Diet

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Goncalves, Gleisy Kelly; de Oliveira, Thiago Henrique Caldeira; de Oliveira Belo, Najara

2017-01-01

Background Heart failure in women increases around the time of menopause when high-fat diets may result in obesity. The heart produces brain natriuretic peptide (BNP), also known as B-type natriuretic peptide. This aims of this study were to assess cardiac hypertrophy and BNP levels in ovariectomized rats fed a high-fat diet. Material/Methods Forty-eight female Wistar rats were divided into four groups: sham-operated rats fed a control diet (SC) (n=12); ovariectomized rats fed a control diet (OC) (n=12); sham-operated rats fed a high-fat diet (SF) (n=12); and ovariectomized rats fed a high-fat diet (OF) (n=12). Body weight and blood pressure were measured weekly for 24 weeks. Rats were then euthanized, and plasma samples and heart tissue were studied for gene expression, hydroxyproline levels, and histological examination. Results A high-fat diet and ovariectomy (group OF) increased the weight body and the systolic blood pressure after three months and five months, respectively. Cardiomyocyte hypertrophy was associated with increased expression of ventricular BNP, decreased natriuretic peptide receptor (NPR)-A and increased levels of hydroxyproline and transforming growth factor (TGF)-β. The plasma levels of BNP and estradiol were inversely correlated; expression of estrogen receptor (ER)β and ERα were reduced. Conclusions The findings of this study showed that, in the ovariectomized rats fed a high-fat diet, the BNP-NPR-A receptor complex was involved in cardiac remodeling. BNP may be a marker of cardiac hypertrophy in this animal model. PMID:29249795

Loss of vagal tone aggravates systemic inflammation and cardiac impairment in endotoxemic rats.

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Schulte, Astrid; Lichtenstern, Christoph; Henrich, Michael; Weigand, Markus A; Uhle, Florian

2014-05-15

During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus, has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N. vagus, there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function. We performed stimulation of the right cervical branch of the N. vagus in vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats. Hemodynamic parameters were assessed over time using a left ventricular pressure-volume catheter. After the experiments, hearts and blood plasma were collected, and the expression of proinflammatory cytokines was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. After vagotomy, the inflammatory response was aggravated, measurable by elevated cytokine levels in plasma and ventricular tissue. In concordance, cardiac impairment during septic shock was pronounced in these animals. To reverse both hemodynamic and immunologic effects of diminished vagal tone, even a brief stimulation of the N. vagus was enough during initial LPS infusion. Overall, the N. vagus might play a major role in maintaining hemodynamic stability and cardiac immune homeostasis during septic shock. Copyright © 2014 Elsevier Inc. All rights reserved.

Mechanostimulation Protocols for Cardiac Tissue Engineering

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Marco Govoni

2013-01-01

Full Text Available Owing to the inability of self-replacement by a damaged myocardium, alternative strategies to heart transplantation have been explored within the last decades and cardiac tissue engineering/regenerative medicine is among the present challenges in biomedical research. Hopefully, several studies witness the constant extension of the toolbox available to engineer a fully functional, contractile, and robust cardiac tissue using different combinations of cells, template bioscaffolds, and biophysical stimuli obtained by the use of specific bioreactors. Mechanical forces influence the growth and shape of every tissue in our body generating changes in intracellular biochemistry and gene expression. That is why bioreactors play a central role in the task of regenerating a complex tissue such as the myocardium. In the last fifteen years a large number of dynamic culture devices have been developed and many results have been collected. The aim of this brief review is to resume in a single streamlined paper the state of the art in this field.

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

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

2013-01-01

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

Characterization of Glutamatergic Neurons in the Rat Atrial Intrinsic Cardiac Ganglia that Project to the Cardiac Ventricular Wall

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Wang, Ting; Miller, Kenneth E.

2016-01-01

The intrinsic cardiac nervous system modulates cardiac function by acting as an integration site for regulating autonomic efferent cardiac output. This intrinsic system is proposed to be composed of a short cardio-cardiac feedback control loop within the cardiac innervation hierarchy. For example, electrophysiological studies have postulated the presence of sensory neurons in intrinsic cardiac ganglia for regional cardiac control. There is still a knowledge gap, however, about the anatomical location and neurochemical phenotype of sensory neurons inside intrinsic cardiac ganglia. In the present study, rat intrinsic cardiac ganglia neurons were characterized neurochemically with immunohistochemistry using glutamatergic markers: vesicular glutamate transporters 1 and 2 (VGLUT1; VGLUT2), and glutaminase (GLS), the enzyme essential for glutamate production. Glutamatergic neurons (VGLUT1/VGLUT2/GLS) in the ICG that have axons to the ventricles were identified by retrograde tracing of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in the ventricular wall. Co-labeling of VGLUT1, VGLUT2, and GLS with the vesicular acetylcholine transporter (VAChT) was used to evaluate the relationship between post-ganglionic autonomic neurons and glutamatergic neurons. Sequential labeling of VGLUT1 and VGLUT2 in adjacent tissue sections was used to evaluate the co-localization of VGLUT1 and VGLUT2 in ICG neurons. Our studies yielded the following results: (1) intrinsic cardiac ganglia contain glutamatergic neurons with GLS for glutamate production and VGLUT1 and 2 for transport of glutamate into synaptic vesicles; (2) atrial intrinsic cardiac ganglia contain neurons that project to ventricle walls and these neurons are glutamatergic; (3) many glutamatergic ICG neurons also were cholinergic, expressing VAChT. (4) VGLUT1 and VGLUT2 co-localization occurred in ICG neurons with variation of their protein expression level. Investigation of both glutamatergic and cholinergic ICG

Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

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Jie Wu

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

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

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Lee, Eunjo; Song, Min-Ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

2016-09-01

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

Diagnosis of cardiac allograft rejection with indium-111 labeled platelets in cyclosporin treated rats

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Fawwaz, R.A.; Iga, C.; Hardy, M.A.; Alderson, P.O.

1984-01-01

Rejection of heart transplants remains difficult to diagnose. Indium-111 (In-111) labeled lymphocytes accumulate in rat cardiac allografts when recipients are treated with Cyclosporin (Cy), even in the absence of clinical rejection. This presumably occurs because of the non-specific 'interstitial infiltration' caused by Cy. This study examines the usefulness of In-111 labeled platelets in differentiating experimental cardiac allograft rejection from Cy-induced tissue changes. The authors initially examined the migration patterns of syngeneic In-111 labeled platelets in groups of Lewis recipients of ACI cardiac allografts treated with IM Cy (10mg/kg) for 6-14 days. In addition, 10 control animals were not immunosuppressed, and 10 were treated with Cy but received Lewis cardiac isografts. Syngeneic In-111 platelets were injected IV into each animal 24 hours prior to sacrifice. Three to five rats from each group were killed at 3 ,7, 14, 21 and 28 days after transplantation and the % ID/gm in the transplanted hearts and native hearts were determined and correlated with histopathology. Untreated Lewis recipients rejected ACI hearts in 6.5 +- 0.4 days while Cy prolonged allograft survival in a variable fashion. In-111 platelet accumulation correlated well with the degree of rejection determined independently by histopathology. No significant In-111 platelet accumulation was detected in non-rejecting cardiac transplants or in native hearts in Cy treated or control animals. The results suggest that In-111 labeled platelets will be an effective agent for diagnosis of cardiac rejection, even in the presence of Cy treatment

The articulo-cardiac sympathetic reflex in spinalized, anesthetized rats.

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Nakayama, Tomohiro; Suzuki, Atsuko; Ito, Ryuzo

2006-04-01

Somatic afferent regulation of heart rate by noxious knee joint stimulation has been proven in anesthetized cats to be a reflex response whose reflex center is in the brain and whose efferent arc is a cardiac sympathetic nerve. In the present study we examined whether articular stimulation could influence heart rate by this efferent sympathetic pathway in spinalized rats. In central nervous system (CNS)-intact rats, noxious articular movement of either the knee or elbow joint resulted in an increase in cardiac sympathetic nerve activity and heart rate. However, although in acutely spinalized rats a noxious movement of the elbow joint resulted in a significant increase in cardiac sympathetic nerve activity and heart rate, a noxious movement of the knee joint had no such effect and resulted in only a marginal increase in heart rate. Because this marginal increase was abolished by adrenalectomy suggests that it was due to the release of adrenal catecholamines. In conclusion, the spinal cord appears to be capable of mediating, by way of cardiac sympathetic nerves, the propriospinally induced reflex increase in heart rate that follows noxious stimulation of the elbow joint, but not the knee joint.

The dynamics of spiral tip adjacent to inhomogeneity in cardiac tissue

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Zhang, Juan; Tang, Jun; Ma, Jun; Luo, Jin Ming; Yang, Xian Qing

2018-02-01

Rotating spiral waves in cardiac tissue are implicated in life threatening cardiac arrhythmias. Experimental and theoretical evidences suggest the inhomogeneities in cardiac tissue play a significant role in the dynamics of spiral waves. Based on a modified 2D cardiac tissue model, the interaction of inhomogeneity on the nearby rigidly rotating spiral wave is numerically studied. The adjacent area of the inhomogeneity is divided to two areas, when the initial rotating center of the spiral tip is located in the two areas, the spiral tip will be attracted and anchor on the inhomogeneity finally, or be repulsed away. The width of the area is significantly dependent on the intensity and size of the inhomogeneity. Our numerical study sheds some light on the mechanism of the interaction of inhomogeneity on the spiral wave in cardiac tissue.

Engineered Biomaterials to Enhance Stem Cell-Based Cardiac Tissue Engineering and Therapy.

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Hasan, Anwarul; Waters, Renae; Roula, Boustany; Dana, Rahbani; Yara, Seif; Alexandre, Toubia; Paul, Arghya

2016-07-01

Cardiovascular disease is a leading cause of death worldwide. Since adult cardiac cells are limited in their proliferation, cardiac tissue with dead or damaged cardiac cells downstream of the occluded vessel does not regenerate after myocardial infarction. The cardiac tissue is then replaced with nonfunctional fibrotic scar tissue rather than new cardiac cells, which leaves the heart weak. The limited proliferation ability of host cardiac cells has motivated investigators to research the potential cardiac regenerative ability of stem cells. Considerable progress has been made in this endeavor. However, the optimum type of stem cells along with the most suitable matrix-material and cellular microenvironmental cues are yet to be identified or agreed upon. This review presents an overview of various types of biofunctional materials and biomaterial matrices, which in combination with stem cells, have shown promises for cardiac tissue replacement and reinforcement. Engineered biomaterials also have applications in cardiac tissue engineering, in which tissue constructs are developed in vitro by combining stem cells and biomaterial scaffolds for drug screening or eventual implantation. This review highlights the benefits of using biomaterials in conjunction with stem cells to repair damaged myocardium and give a brief description of the properties of these biomaterials that make them such valuable tools to the field. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Surface-modified polymers for cardiac tissue engineering.

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Moorthi, Ambigapathi; Tyan, Yu-Chang; Chung, Tze-Wen

2017-09-26

Cardiovascular disease (CVD), leading to myocardial infarction and heart failure, is one of the major causes of death worldwide. The physiological system cannot significantly regenerate the capabilities of a damaged heart. The current treatment involves pharmacological and surgical interventions; however, less invasive and more cost-effective approaches are sought. Such new approaches are developed to induce tissue regeneration following injury. Hence, regenerative medicine plays a key role in treating CVD. Recently, the extrinsic stimulation of cardiac regeneration has involved the use of potential polymers to stimulate stem cells toward the differentiation of cardiomyocytes as a new therapeutic intervention in cardiac tissue engineering (CTE). The therapeutic potentiality of natural or synthetic polymers and cell surface interactive factors/polymer surface modifications for cardiac repair has been demonstrated in vitro and in vivo. This review will discuss the recent advances in CTE using polymers and cell surface interactive factors that interact strongly with stem cells to trigger the molecular aspects of the differentiation or formulation of cardiomyocytes for the functional repair of heart injuries or cardiac defects.

Protective effects of isorhynchophylline on cardiac arrhythmias in rats and guinea pigs.

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Gan, Runtao; Dong, Guo; Yu, Jiangbo; Wang, Xu; Fu, Songbin; Yang, Shusen

2011-09-01

As one important constituent extracted from a traditional Chinese medicine, Uncaria Rhynchophylla Miq Jacks, isorhynchophylline has been used to treat hypertension, epilepsy, headache, and other illnesses. Whether isorhynchophylline protects hearts against cardiac arrhythmias is still incompletely investigated. This study was therefore aimed to examine the preventive effects of isorhynchophylline on heart arrhythmias in guinea pigs and rats and then explore their electrophysiological mechanisms. In vivo, ouabain and calcium chloride were used to establish experimental arrhythmic models in guinea pigs and rats. In vitro, the whole-cell patch-lamp technique was used to study the effect of isorhynchophylline on action potential duration and calcium channels in acutely isolated guinea pig and rat cardiomyocytes. The dose of ouabain required to induce cardiac arrhythmias was much larger in guinea pigs administered with isorhynchophylline. Additionally, the onset time of cardiac arrhythmias induced by calcium chloride was prolonged, and the duration was shortened in rats pretreated with isorhynchophylline. The further study showed that isorhynchophylline could significantly decrease action potential duration and inhibit calcium currents in isolated guinea pig and rat cardiomyocytes in a dose-dependent manner. In summary, isorhynchophylline played a remarkably preventive role in cardiac arrhythmias through the inhibition of calcium currents in rats and guinea pigs. © Georg Thieme Verlag KG Stuttgart · New York.

The impact of obesity in the cardiac lipidome and its consequences in the cardiac damage observed in obese rats.

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Marín-Royo, Gema; Martínez-Martínez, Ernesto; Gutiérrez, Beatriz; Jurado-López, Raquel; Gallardo, Isabel; Montero, Olimpio; Bartolomé, Mª Visitación; Román, José Alberto San; Salaices, Mercedes; Nieto, María Luisa; Cachofeiro, Victoria

To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O 2 ), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals. Cardiac lipid profile analysis showed a significant increase in triglycerides, especially those enriched with palmitic, stearic, and arachidonic acid. An increase in levels of diacylglycerol (DAG) was also observed. No changes in cardiac levels of diacyl phosphatidylcholine, or even a reduction in total levels of diacyl phosphatidylethanolamine, diacyl phosphatidylinositol, and sphingomyelins (SM) was observed in HFD, as compared with control animals. After adjustment for other variables (oxidative stress, HOMA, cardiac hypertrophy), total levels of DAG were independent predictors of cardiac fibrosis while the levels of total SM were independent predictors of the cardiac levels of GLUT 4. These data suggest that obesity has a significant impact on cardiac lipid composition, although it does not modulate the different species in a similar manner. Nonetheless, these changes are likely to participate in the cardiac damage in the context of obesity, since total DAG levels can facilitate the development of cardiac fibrosis, and SM levels predict GLUT4 levels. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

[Expression of connective tissue growth factor in cardiomyocyte of young rats with heart failure and benazepril intervention].

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Zhang, Qin; Yi, Qi-jian; Qian, Yong-ru; Li, Rong; Deng, Bing; Wang, Qiao

2006-10-01

Ventricular remodeling is an important pathologic progress in almost all end stage heart failure (HF), and it is characterized by ventricular thickening and cardiac fibrosis with poor prognosis. The connective tissue growth factor (CTGF), a new growth factor with multi-function, has an important role in fibrosis of tissue and organs. It has been demonstrated that angiotensin-converting enzyme inhibitor (ACEI) can prevent the development of cardiomyocyte from remodeling and improve cardiac function. Researchers try to test the hypothesis that cardiac function improvement attributable to ACEI is associated with inhibiting expression of CTGF in patients with HF. The aim of this study was to observe changes in CTGF expression in cardiomyocyte of young rats with HF and effect of benazepril on CTGF. The animal model of HF was established by constriction of abdominal aorta. Five weeks old rats were randomly divided into 3 groups after 6 weeks of operation: (1) HF group without treatment (n = 15); (2) HF group where rats were treated with benazepril (n = 15); (3) sham-operated group (n = 15) where rats were administered benazepril through direct gastric gavage. After 4 weeks of treatment, the high frequency ultrasound was performed. The expression of CTGF was detected by immunohistochemistry and semi-quantative reverse transcription-polymerase chain reaction. Compared with the sham-operated group, left ventricular diastolic dimension (LVEDD), left ventricular systolic dimension (LVESD), interventricular septal thickness at end-diastole (IVSTd), interventricular septal thickness at end-systole (IVSTs), left ventricular posterior wall thickness at end-diastole (LVPWTd), left ventricular posterior wall thickness at end-systole (LVPWTs), left ventricular relative weight (LVRW), and right ventricular relative weight (RVRW) were all increased (P benazepril when compared with HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were higher (P benazepril

Potential of Bioactive Glasses for Cardiac and Pulmonary Tissue Engineering

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Saeid Kargozar

2017-12-01

Full Text Available Repair and regeneration of disorders affecting cardiac and pulmonary tissues through tissue-engineering-based approaches is currently of particular interest. On this matter, different families of bioactive glasses (BGs have recently been given much consideration with respect to treating refractory diseases of these tissues, such as myocardial infarction. The inherent properties of BGs, including their ability to bond to hard and soft tissues, to stimulate angiogenesis, and to elicit antimicrobial effects, along with their excellent biocompatibility, support these newly proposed strategies. Moreover, BGs can also act as a bioactive reinforcing phase to finely tune the mechanical properties of polymer-based constructs used to repair the damaged cardiac and pulmonary tissues. In the present study, we evaluated the potential of different forms of BGs, alone or in combination with other materials (e.g., polymers, in regards to repair and regenerate injured tissues of cardiac and pulmonary systems.

Exercise training prior to myocardial infarction attenuates cardiac deterioration and cardiomyocyte dysfunction in rats

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Luiz Henrique Marchesi Bozi

2013-04-01

Full Text Available OBJECTIVES: The present study was performed to investigate 1 whether aerobic exercise training prior to myocardial infarction would prevent cardiac dysfunction and structural deterioration and 2 whether the potential cardiac benefits of aerobic exercise training would be associated with preserved morphological and contractile properties of cardiomyocytes in post-infarct remodeled myocardium. METHODS: Male Wistar rats underwent an aerobic exercise training protocol for eight weeks. The rats were then assigned to sham surgery (SHAM, sedentary lifestyle and myocardial infarction or exercise training and myocardial infarction groups and were evaluated 15 days after the surgery. Left ventricular tissue was analyzed histologically, and the contractile function of isolated myocytes was measured. Student's t-test was used to analyze infarct size and ventricular wall thickness, and the other parameters were analyzed by the Kruskal-Wallis test followed by Dunn's test or a one-way analysis of variance followed by Tukey's test (p<0.05. RESULTS: Myocardial infarctions in exercise-trained animals resulted in a smaller myocardial infarction extension, a thicker infarcted wall and less collagen accumulation as compared to myocardial infarctions in sedentary animals. Myocardial infarction-induced left ventricular dilation and cardiac dysfunction, as evaluated by +dP/dt and -dP/dt, were both prevented by previous aerobic exercise training. Moreover, aerobic exercise training preserved cardiac myocyte shortening, improved the maximum shortening and relengthening velocities in infarcted hearts and enhanced responsiveness to calcium. CONCLUSION: Previous aerobic exercise training attenuated the cardiac dysfunction and structural deterioration promoted by myocardial infarction, and such benefits were associated with preserved cardiomyocyte morphological and contractile properties.

Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: Modulation of cardiac PPAR-α-mediated transcription of fatty acid metabolic genes

International Nuclear Information System (INIS)

Huang, Tom H.-W.; Yang Qinglin; Harada, Masaki; Uberai, Jasna; Radford, Jane; Li, George Q.; Yamahara, Johji; Roufogalis, Basil D.; Li Yuhao

2006-01-01

Excess cardiac triglyceride accumulation in diabetes and obesity induces lipotoxicity, which predisposes the myocytes to death. On the other hand, increased cardiac fatty acid (FA) oxidation plays a role in the development of myocardial dysfunction in diabetes. PPAR-α plays an important role in maintaining homeostasis of lipid metabolism. We have previously demonstrated that the extract from Salacia oblonga root (SOE), an Ayurvedic anti-diabetic and anti-obesity medicine, improves hyperlipidemia in Zucker diabetic fatty (ZDF) rats (a genetic model of type 2 diabetes and obesity) and possesses PPAR-α activating properties. Here we demonstrate that chronic oral administration of SOE reduces cardiac triglyceride and FA contents and decreases the Oil red O-stained area in the myocardium of ZDF rats, which parallels the effects on plasma triglyceride and FA levels. Furthermore, the treatment suppressed cardiac overexpression of both FA transporter protein-1 mRNA and protein in ZDF rats, suggesting inhibition of increased cardiac FA uptake as the basis for decreased cardiac FA levels. Additionally, the treatment also inhibited overexpression in ZDF rat heart of PPAR-α mRNA and protein and carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase mRNAs and restored the downregulated acetyl-CoA carboxylase mRNA. These results suggest that SOE inhibits cardiac FA oxidation in ZDF rats. Thus, our findings suggest that improvement by SOE of excess cardiac lipid accumulation and increased cardiac FA oxidation in diabetes and obesity occurs by reduction of cardiac FA uptake, thereby modulating cardiac PPAR-α-mediated FA metabolic gene transcription

The muscle contraction mode determines lymphangiogenesis differentially in rat skeletal and cardiac muscles by modifying local lymphatic extracellular matrix microenvironments.

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Greiwe, L; Vinck, M; Suhr, F

2016-05-01

Lymphatic vessels are of special importance for tissue homeostasis, and increases of their density may foster tissue regeneration. Exercise could be a relevant tool to increase lymphatic vessel density (LVD); however, a significant lack of knowledge remains to understand lymphangiogenesis in skeletal muscles upon training. Interestingly, training-induced lymphangiogenesis has never been studied in the heart. We studied lymphangiogenesis and LVD upon chronic concentric and chronic eccentric muscle contractions in both rat skeletal (Mm. Edl and Sol) and cardiac muscles. We found that LVD decreased in both skeletal muscles specifically upon eccentric training, while this contraction increased LVD in cardiac tissue. These observations were supported by opposing local remodelling of lymphatic vessel-specific extracellular matrix components in skeletal and cardiac muscles and protein levels of lymphatic markers (Lyve-1, Pdpn, Vegf-C/D). Confocal microscopy further revealed transformations of lymphatic vessels into vessels expressing both blood (Cav-1) and lymphatic (Vegfr-3) markers upon eccentric training specifically in skeletal muscles. In addition and phenotype supportive, we found increased inflammation (NF-κB/p65, Il-1β, Ifn-γ, Tnf-α and MPO(+) cells) in eccentrically stressed skeletal, but decreased levels in cardiac muscles. Our data provide novel mechanistic insights into lymphangiogenic processes in skeletal and cardiac muscles upon chronic muscle contraction modes and demonstrate that both tissues adapt in opposing manners specifically to eccentric training. These data are highly relevant for clinical applications, because eccentric training serves as a sufficient strategy to increase LVD and to decrease inflammation in cardiac tissue, for example in order to reduce tissue abortion in transplantation settings. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Proangiogenic scaffolds as functional templates for cardiac tissue engineering.

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

2010-08-24

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.

Morphometric and biochemical characteristics of short-term effects of ethanol on rat cardiac muscle.

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Mihailović, D; Nikolić, J; Bjelaković, B B; Stanković, B N; Bjelaković, G

1999-11-01

Alcoholism is a very important cause of congestive cardiomyopathy in man. The aim of this study was to examine a short-term effect of ethanol in rat cardiac muscle, using histologic, morphometric and biochemical methods. Experiments were carried out in Wistar male albino rats, divided into two groups: the control group consisting of eight animals receiving tap water, and the experimental group comprising eight animals received ethyl alcohol for ten days, in a single daily dose of 3 g ethanol/kg body weight, per os, using esophageal intubation. The mean volume weighted nuclear volume of cardiac myocytes was estimated by point sampled intercept method, by objective x 100. The mean cubed nuclear intercept length was multiplied by pi and divided by 3. For biochemical analysis, a 10% water tissue homogenate from the left ventricle was made. In the experimental group, the mean volume-weighted nuclear volume (15.08 +/- 5.20 microm3) was significantly lower than in the control group (51.32 +/- 7.83 microm3) (p energy production.

Cardiac tissue engineering using perfusion bioreactor systems

Science.gov (United States)

Radisic, Milica; Marsano, Anna; Maidhof, Robert; Wang, Yadong; Vunjak-Novakovic, Gordana

2009-01-01

This protocol describes tissue engineering of synchronously contractile cardiac constructs by culturing cardiac cell populations on porous scaffolds (in some cases with an array of channels) and bioreactors with perfusion of culture medium (in some cases supplemented with an oxygen carrier). The overall approach is ‘biomimetic’ in nature as it tends to provide in vivo-like oxygen supply to cultured cells and thereby overcome inherent limitations of diffusional transport in conventional culture systems. In order to mimic the capillary network, cells are cultured on channeled elastomer scaffolds that are perfused with culture medium that can contain oxygen carriers. The overall protocol takes 2–4 weeks, including assembly of the perfusion systems, preparation of scaffolds, cell seeding and cultivation, and on-line and end-point assessment methods. This model is well suited for a wide range of cardiac tissue engineering applications, including the use of human stem cells, and high-fidelity models for biological research. PMID:18388955

Role of Exercise-Induced Cardiac Remodeling in Ovariectomized Female Rats

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Renáta Szabó

2018-01-01

Full Text Available Myocardial extracellular matrix (ECM is essential for proper cardiac function and structural integrity; thus, the disruption of ECM homeostasis is associated with several pathological processes. Female Wistar rats underwent surgical ovariectomy (OVX or sham operation (SO and were then divided into eight subgroups based on the type of diet (standard chow or high-triglyceride diet/HT and exercise (with or without running. After 12 weeks, cardiac MMP-2 activity, tissue inhibitor of metalloproteinase-2, content of collagen type I, the level of nitrotyrosine (3-NT and glutathione (GSH, and the ratio of infarct size were determined. Our results show that OVX and HT diet caused an excessive accumulation of collagen; however, this increase was not observed in the trained animals. Twelve weeks of exercise promoted elevation in the levels of 3-NT and GSH and similarly an increase in MMP-2 activity of both SO and OVX animals. The high infarct-size ratio caused by OVX and HT diet was mitigated by physical exercise. Our findings demonstrate that ovarian estrogen loss and HT diet caused collagen accumulation and increased ratio of the infarct size. However, exercise-induced cardiac remodeling serves as a compensatory mechanism by enhancing MMP-2 activity and reducing fibrosis, thus minimizing the ischemia/reperfusion injury.

Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

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Das, Joydeep; Vasan, Vandana; Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in

2012-01-15

Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ► Taurine controls blood glucose via protection of pancreatic β cells in diabetic rat. ► Taurine controls blood glucose via increasing the insulin level in diabetic rat. ► Taurine improves cardiac AKT/GLUT4 signaling

Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

International Nuclear Information System (INIS)

Das, Joydeep; Vasan, Vandana; Sil, Parames C.

2012-01-01

Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ► Taurine controls blood glucose via protection of pancreatic β cells in diabetic rat. ► Taurine controls blood glucose via increasing the insulin level in diabetic rat. ► Taurine improves cardiac AKT/GLUT4 signaling

Inverse relationship between tumour proliferation markers and connexin expression in a malignant cardiac tumour originating from mesenchymal stem cell engineered tissue in a rat in-vivo model.

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Cathleen eSpath

2013-04-01

Full Text Available Background: Recently, we demonstrated the beneficial effects of engineered heart tissues for the treatment of dilated cardiomyopathy in rats. For further development of this technique we started to produce engineered tissue (ET from mesenchymal stem cells. Interestingly, we observed a malignant tumour invading the heart with an inverse relationship between proliferation markers and connexin-expression.Methods: Commercial CD54+/CD90+/CD34-/CD45- bone marrow derived mesenchymal rat stem cells (cBM-MSC, characterized were used for production of mesenchymal stem-cell-ET (MSC-ET by suspending them in a collagen-I, matrigel-mixture and cultivating for 14 days with electrical stimulation. 3 MSC-ET were implanted around the beating heart of adult rats for days. Another 3 MSC-ET were produced from freshly isolated rat bone marrow derived stem cells (sBM-MSC.Results: 3 weeks after implantation of the MSC-ETs the hearts were surgically excised. While in 5/6 cases the ET was clearly distinguishable and was found as a ring containing mostly connective tissue around the heart, in 1/6 the heart was completely surrounded by a huge, undifferentiated, pleomorphic tumour originating from the cMSC-ET (cBM-MSC, classified as a high grade malignant sarcoma. Quantitatively we found a clear inverse relationship between cardiac connexin-expression (Cx43, Cx40 or Cx45 and increased Ki-67 expression (Cx43: p<0.0001, Cx45: p<0.03, Cx40: p<0.014. At the tumour-heart border there were significantly more Ki-67 positive cells (p=0.001, and only 2% Cx45 and Ki-67-expressing cells, while the other connexins were nearly completely absent (p<0.0001.Conclusions and hypothesis: These observations strongly suggest the hypothesis, that invasive tumour growth is accompanied by reduction in connexins. This implicates that gap junction communication between tumour and normal tissue is reduced or absent, which could mean that growth and differentiation signals can not be exchanged.

Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering

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Rogozhnikov, Dmitry; O'Brien, Paul J.; Elahipanah, Sina; Yousaf, Muhammad N.

2016-12-01

There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.

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

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

2015-01-01

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

Elimination of spiral waves in cardiac tissue by multiple electrical shocks

NARCIS (Netherlands)

Panfilov, A.V.; Müller, Stefan C.; Zykov, Vladimir S.; Keener, James P.

1999-01-01

We study numerically the elimination of a spiral wave in cardiac tissue by application of multiple shocks of external current. To account for the effect of shocks we apply a recently developed theory for the interaction of the external current with cardiac tissue. We compare two possible feedback

Rutin ameliorates glycemic index, lipid profile and enzymatic activities in serum, heart and liver tissues of rats fed with a combination of hypercaloric diet and chronic ethanol consumption.

Science.gov (United States)

Chuffa, Luiz Gustavo A; Fioruci-Fontanelli, Beatriz A; Bordon, Juliana G; Pires, Rafaelle B; Braga, Camila P; Seiva, Fábio R F; Fernandes, Ana Angélica H

2014-06-01

Alcoholism and obesity are strongly associated with several disorders including heart and liver diseases. This study evaluated the effects of rutin treatment in serum, heart and liver tissues of rats subjected to a combination of hypercaloric diet (HD) and chronic ethanol consumption. Rats were divided into three groups: Control: rats fed a standard diet and drinking water ad libitum; G1: rats fed the HD and receiving a solution of 10% (v/v) ethanol; and G2: rats fed the HD and ethanol solution, followed by injections of 50 mg/kg(-1) rutin as treatment. After 53 days of HD and ethanol exposure, the rutin was administered every three days for nine days. At the end of the experimental period (95 days), biochemical analyses were carried out on sera, cardiac and hepatic tissues. Body weight gain and food consumption were reduced in both the G1 and G2 groups compared to control animals. Rutin effectively reduced the total lipids (TL), triglycerides (TG), total cholesterol (TC), VLDL, LDL-cholesterol and glucose levels, while it increased the HDL-cholesterol in the serum of G2 rats, compared to G1. Although rutin had no effect on total protein, albumin, uric acid and cretinine levels, it was able to restore serum activities of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) in animals fed HD and receiving ethanol. Glycogen stores were replenished in both hepatic and cardiac tissues after rutin treatment. Moreover, rutin consistently reduced hepatic levels of TG and TC and cardiac AST, ALT and CK activities. Thus, rutin treatment was effective in reducing the risk factors for cardiac and hepatic disease caused by both HD and chronic ethanol consumption.

Cardiac rhythm disturbance in athletes with cardiac connective tissue dysplasia syndrome

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Shahrjerdi Sh

2007-06-01

Full Text Available Background: Cardiac connective tissue dysplasia syndrome consists of mitral valve prolapse (MVP, anomalously located chordae tendinae of the left ventricle, or a combination of the two. MVP is marked by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. The nonclassic form of MVP carries a low risk of complications. Patients with severe classic MVP can suffer from mitral regurgitation (MR, infective endocarditis, and, infrequently, sudden death from cardiac arrest. Anomalously located left ventricular chordae tendinae are fibrous or fibromuscular bands that stretch across the left ventricle from the septum to the free wall. They have been associated with murmurs and arrhythmias. The purpose of this study is to assess the performance, as measured by the physical working capacity (PWC170 and maximal oxygen consumption (VO2 max, in athletes with cardiac connective tissue dysplasia syndrome. Methods: Of the 183 male athletes studied, 158 had cardiac connective tissue dysplasia syndrome and 25 were normal, healthy controls. Their mean age was 16.23 (± 5.48 years and mean training time was 5.2 (±- 4.6 years. Athletes with cardiac connective tissue dysplasia syndrome were divided to four groups. Group 1 consisted of those with MVP; Group 2 had patients with an additional cord in left ventricle; Group 3 was made up of athletes with a combination of MVP and additional cord; Group 4 contained athletes with a combination of MVP and MR. All sportsmen were studied by echocardiograph, veloergometer, and those with arrhythmias were studied and recorded using a Holter monitor. Results: The most common form of this syndrome in our study groups was MVP. The PWC170and VO2 max among the athletes with the combination of MVP+MR (Group 4 was lower than that of athletes in other groups (P<0.05. The most common arrhythmia among the athletes with anomalously located left ventricular chordae, Group 2, was Wolf

Fabrication and characterization of bio-engineered cardiac pseudo tissues

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Xu Tao; Boland, Thomas [Department of Bioengineering, 420 Rhodes Hall, Clemson University, Clemson, SC 29634 (United States); Baicu, Catalin; Aho, Michael; Zile, Michael, E-mail: tboland@clemson.ed [Department of Medicine, Medical University of South Carolina, Charleston, SC 29425 (United States)

2009-09-15

We report on fabricating functional three-dimensional (3D) tissue constructs using an inkjet based bio-prototyping method. With the use of modified inkjet printers, contractile cardiac hybrids that exhibit the forms of the 3D rectangular sheet and even the 'half heart' (with two connected ventricles) have been fabricated by arranging alternate layers of biocompatible alginate hydrogels and mammalian cardiac cells according to pre-designed 3D patterns. In this study, primary feline adult and H1 cardiomyocytes were used as model cardiac cells. Alginate hydrogels with controlled micro-shell structures were built by spraying cross-linkers in micro-drops onto un-gelled alginic acid. The cells remained viable in constructs as thick as 1 cm due to the programmed porosity. Microscopic and macroscopic contractile functions of these cardiomyocyte constructs were observed in vitro. These results suggest that the inkjet bio-prototyping method could be used for hierarchical design of functional cardiac pseudo tissues, balanced with porosity for mass transport and structural support.

Fabrication and characterization of bio-engineered cardiac pseudo tissues

International Nuclear Information System (INIS)

Xu Tao; Boland, Thomas; Baicu, Catalin; Aho, Michael; Zile, Michael

2009-01-01

We report on fabricating functional three-dimensional (3D) tissue constructs using an inkjet based bio-prototyping method. With the use of modified inkjet printers, contractile cardiac hybrids that exhibit the forms of the 3D rectangular sheet and even the 'half heart' (with two connected ventricles) have been fabricated by arranging alternate layers of biocompatible alginate hydrogels and mammalian cardiac cells according to pre-designed 3D patterns. In this study, primary feline adult and H1 cardiomyocytes were used as model cardiac cells. Alginate hydrogels with controlled micro-shell structures were built by spraying cross-linkers in micro-drops onto un-gelled alginic acid. The cells remained viable in constructs as thick as 1 cm due to the programmed porosity. Microscopic and macroscopic contractile functions of these cardiomyocyte constructs were observed in vitro. These results suggest that the inkjet bio-prototyping method could be used for hierarchical design of functional cardiac pseudo tissues, balanced with porosity for mass transport and structural support.

Preventive effects of garlic (Allium sativum) on oxidative stress and histopathology of cardiac tissue in streptozotocin-induced diabetic rats.

Science.gov (United States)

Naderi, R; Mohaddes, G; Mohammadi, M; Alihemmati, A; Badalzadeh, R; Ghaznavi, R; Ghyasi, R; Mohammadi, Sh

2015-12-01

Since some complications of diabetes mellitus may be caused or exacerbated by an oxidative stress, the protective effects of garlic (Allium sativum) were investigated in the blood and heart of streptozotocin-induced diabetic rats. Twenty-eight male Wistar rats were randomly divided into four groups: control, garlic, diabetic, and diabetic+garlic. Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (50 mg/kg) in male rats. Rats were fed with raw fresh garlic homogenate (250 mg/kg) six days a week by gavage for a period of 6 weeks. At the end of the 6th week blood samples and heart tissues were collected and used for determination of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and histological evaluation. Induction of diabetes increased MDA levels in blood and homogenates of heart. In diabetic rats treated with garlic, MDA levels decreased in blood and heart homogenates. Treatment of diabetic rats with garlic increased SOD, GPX and CAT in blood and heart homogenates. Histopathological finding of the myocardial tissue confirmed a protective role for garlic in diabetic rats. Thus, the present study reveals that garlic may effectively modulate antioxidants status in the blood and heart of streptozotocin induced-diabetic rats.

Age-related changes of neurochemically different subpopulations of cardiac spinal afferent neurons in rats.

Science.gov (United States)

Guić, Maja Marinović; Runtić, Branka; Košta, Vana; Aljinović, Jure; Grković, Ivica

2013-08-01

This study investigated the effect of aging on cardiac spinal afferent neurons in the rat. A patch loaded with retrograde tracer Fast Blue (FB) was applied to all chambers of the rat heart. Morphological and neurochemical characteristics of labeled cardiac spinal afferent neurons were assessed in young (2 months) and old (2 years) rats using markers for likely unmyelinated (isolectin B4; IB4) and myelinated (neurofilament 200; N52) neurons. The number of cardiac spinal afferent neurons decreased in senescence to 15% of that found in young rats (1604 vs. 248). The size of neuronal soma as well as proportion of IB4+ neurons increased significantly, whereas the proportion of N52+ neurons decreased significantly in senescence. Unlike somatic spinal afferents, neurochemically different populations of cardiac spinal afferent neurons experience morphological and neurochemical changes related to aging. A major decrease in total number of cardiac spinal afferent neurons occurs in senescence. The proportion of N52+ neurons decreased in senescence, but it seems that nociceptive innervation is preserved due to increased proportion and size of IB4+ unmyelinated neurons. Copyright © 2013 Elsevier Inc. All rights reserved.

Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

International Nuclear Information System (INIS)

Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

2014-01-01

Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

Thallium kinetics in rat cardiac transplant rejection

International Nuclear Information System (INIS)

Barak, J.H.; LaRaia, P.J.; Boucher, C.A.; Fallon, J.T.; Buckley, M.J.

1988-01-01

Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection

Caffeic acid phenethyl ester prevents cadmium-induced cardiac impairment in rat

International Nuclear Information System (INIS)

Mollaoglu, Hakan; Gokcimen, Alpaslan; Ozguner, Fehmi; Oktem, Faruk; Koyu, Ahmet; Kocak, Ahmet; Demirin, Hilmi; Gokalp, Osman; Cicek, Ekrem

2006-01-01

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine the effect of CAPE on cadmium (Cd)-induced hypertension and cardiomyopathy in rats. In particular, nitric oxide (NO) may contribute to the pathophysiology of Cd induced cardiac impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels and nitric oxide (NO, a vasodilator) levels were used as markers Cd-induced cardiac impairment and the success of CAPE treatment. Also, the findings have been supported by the histopathologic evidences. The rats were randomly divided into three experimental groups each (12), as follows: the control group, Cd-treated group (Cd) and Cd plus CAPE-treated group (Cd + CAPE). CdCl 2 in 0.9% NaCl was administrated intraperitoneally (i.p.) with a dose of 1 mg/kg/day. CAPE was co-administered i.p. a dose of 10 μM/kg for 15 days. Hypertension was found to be induced by intraperitoneal administration of Cd in a dose of 1 mg/kg/day on the measurements taken 15 days later. MDA levels were increased (p < 0.001) in cardiac tissue and NO levels were decreased (p < 0.05) in serum in the Cd group than those of the control group had. On the other hand, there was a slight difference (increase) in MDA levels in the Cd + CAPE group than the ones in the control group (p < 0.003). In addition, MDA levels were decreased and NO levels were increased in the Cd + CAPE group compared with the Cd group (p < 0.001, p < 0.0001, respectively). As a result, treatment with CAPE significantly reversed the increased lipid peroxidation (LPO) product, MDA, and decreased NO levels in Cd treated animals. In the histopathologic examination, a significant hypertrophy in atrial and ventricular myofibrils was observed in only Cd administered group, in comparison with the control group. There was no statistically significant difference

Effects of aerobic exercise training on cardiac renin-angiotensin system in an obese Zucker rat strain.

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Diego Lopes Mendes Barretti

Full Text Available OBJECTIVE: Obesity and renin angiotensin system (RAS hyperactivity are profoundly involved in cardiovascular diseases, however aerobic exercise training (EXT can prevent obesity and cardiac RAS activation. The study hypothesis was to investigate whether obesity and its association with EXT alter the systemic and cardiac RAS components in an obese Zucker rat strain. METHODS: THE RATS WERE DIVIDED INTO THE FOLLOWING GROUPS: Lean Zucker rats (LZR; lean Zucker rats plus EXT (LZR+EXT; obese Zucker rats (OZR and obese Zucker rats plus EXT (OZR+EXT. EXT consisted of 10 weeks of 60-min swimming sessions, 5 days/week. At the end of the training protocol heart rate (HR, systolic blood pressure (SBP, cardiac hypertrophy (CH and function, local and systemic components of RAS were evaluated. Also, systemic glucose, triglycerides, total cholesterol and its LDL and HDL fractions were measured. RESULTS: The resting HR decreased (∼12% for both LZR+EXT and OZR+EXT. However, only the LZR+EXT reached significance (p<0.05, while a tendency was found for OZR versus OZR+EXT (p = 0.07. In addition, exercise reduced (57% triglycerides and (61% LDL in the OZR+EXT. The systemic angiotensin I-converting enzyme (ACE activity did not differ regardless of obesity and EXT, however, the OZR and OZR+EXT showed (66% and (42%, respectively, less angiotensin II (Ang II plasma concentration when compared with LZR. Furthermore, the results showed that EXT in the OZR prevented increase in CH, cardiac ACE activity, Ang II and AT2 receptor caused by obesity. In addition, exercise augmented cardiac ACE2 in both training groups. CONCLUSION: Despite the unchanged ACE and lower systemic Ang II levels in obesity, the cardiac RAS was increased in OZR and EXT in obese Zucker rats reduced some of the cardiac RAS components and prevented obesity-related CH. These results show that EXT prevented the heart RAS hyperactivity and cardiac maladaptive morphological alterations in obese Zucker rats.

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration.

Science.gov (United States)

Formiga, Fabio R; Pelacho, Beatriz; Garbayo, Elisa; Imbuluzqueta, Izaskun; Díaz-Herráez, Paula; Abizanda, Gloria; Gavira, Juan J; Simón-Yarza, Teresa; Albiasu, Edurne; Tamayo, Esther; Prósper, Felipe; Blanco-Prieto, Maria J

2014-01-10

Acidic fibroblast growth factor (FGF1) and neuregulin-1 (NRG1) are growth factors involved in cardiac development and regeneration. Microparticles (MPs) mediate cytokine sustained release, and can be utilized to overcome issues related to the limited therapeutic protein stability during systemic administration. We sought to examine whether the administration of microparticles (MPs) containing FGF1 and NRG1 could promote cardiac regeneration in a myocardial infarction (MI) rat model. We investigated the possible underlying mechanisms contributing to the beneficial effects of this therapy, especially those linked to endogenous regeneration. FGF1- and NRG1-loaded MPs were prepared using a multiple emulsion solvent evaporation technique. Seventy-three female Sprague-Dawley rats underwent permanent left anterior descending coronary artery occlusion, and MPs were intramyocardially injected in the peri-infarcted zone four days later. Cardiac function, heart tissue remodeling, revascularization, apoptosis, cardiomyocyte proliferation, and stem cell homing were evaluated one week and three months after treatment. MPs were shown to efficiently encapsulate FGF1 and NRG1, releasing the bioactive proteins in a sustained manner. Three months after treatment, a statistically significant improvement in cardiac function was detected in rats treated with growth factor-loaded MPs (FGF1, NRG1, or FGF1/NRG1). The therapy led to inhibition of cardiac remodeling with smaller infarct size, a lower fibrosis degree and induction of tissue revascularization. Cardiomyocyte proliferation and progenitor cell recruitment were detected. Our data support the therapeutic benefit of NRG1 and FGF1 when combined with protein delivery systems for cardiac regeneration. This approach could be scaled up for use in pre-clinical and clinical studies. © 2013.

Hyperbaric environment up-regulates CD15s expression on leukocytes, down-regulates CD77 expression on renal cells and up-regulates CD34 expression on pulmonary and cardiac cells in rat

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Danka Đevenica

2016-08-01

Full Text Available Objective(s: The aim of this study was to estimate effects of hyperbaric (HB treatment by determination of CD15s and CD11b leukocyte proinflammatory markers expression.  In addition, this study describes changes in CD77 and CD34 expression on rat endothelial cells in renal, pulmonary and cardiac tissue following exposure to hyperbaric pressure. Materials and Methods:Expression of CD11b and CD15s on leukocytes, as well as CD77 and CD34 expression on endothelial cells in cell suspensions of renal, pulmonary and cardiac tissue in rats after hyperbaric treatment and in control rats were determined by flow cytometry. Results: Hyperbaric treatment significantly increased percentage of leukocytes expressing CD15s+CD11b- (from 1.71±1.11 to 23.42±2.85, P

Gold nanorod-incorporated gelatin-based conductive hydrogels for engineering cardiac tissue constructs.

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Navaei, Ali; Saini, Harpinder; Christenson, Wayne; Sullivan, Ryan Tanner; Ros, Robert; Nikkhah, Mehdi

2016-09-01

The development of advanced biomaterials is a crucial step to enhance the efficacy of tissue engineering strategies for treatment of myocardial infarction. Specific characteristics of biomaterials including electrical conductivity, mechanical robustness and structural integrity need to be further enhanced to promote the functionalities of cardiac cells. In this work, we fabricated UV-crosslinkable gold nanorod (GNR)-incorporated gelatin methacrylate (GelMA) hybrid hydrogels with enhanced material and biological properties for cardiac tissue engineering. Embedded GNRs promoted electrical conductivity and mechanical stiffness of the hydrogel matrix. Cardiomyocytes seeded on GelMA-GNR hybrid hydrogels exhibited excellent cell retention, viability, and metabolic activity. The increased cell adhesion resulted in abundance of locally organized F-actin fibers, leading to the formation of an integrated tissue layer on the GNR-embedded hydrogels. Immunostained images of integrin β-1 confirmed improved cell-matrix interaction on the hybrid hydrogels. Notably, homogeneous distribution of cardiac specific markers (sarcomeric α-actinin and connexin 43), were observed on GelMA-GNR hydrogels as a function of GNRs concentration. Furthermore, the GelMA-GNR hybrids supported synchronous tissue-level beating of cardiomyocytes. Similar observations were also noted by, calcium transient assay that demonstrated the rhythmic contraction of the cardiomyocytes on GelMA-GNR hydrogels as compared to pure GelMA. Thus, the findings of this study clearly demonstrated that functional cardiac patches with superior electrical and mechanical properties can be developed using nanoengineered GelMA-GNR hybrid hydrogels. In this work, we developed gold nanorod (GNR) incorporated gelatin-based hydrogels with suitable electrical conductivity and mechanical stiffness for engineering functional cardiac tissue constructs (e.g. cardiac patches). The synthesized conductive hybrid hydrogels properly

Calorie restriction attenuates cardiac remodeling and diastolic dysfunction in a rat model of metabolic syndrome.

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Takatsu, Miwa; Nakashima, Chieko; Takahashi, Keiji; Murase, Tamayo; Hattori, Takuya; Ito, Hiromi; Murohara, Toyoaki; Nagata, Kohzo

2013-11-01

Calorie restriction (CR) can modulate the features of obesity-related metabolic and cardiovascular diseases. We have recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. DS/obese rats develop hypertension and manifest left ventricular remodeling and diastolic dysfunction, as well as increased cardiac oxidative stress and inflammation. We have now investigated the effects of CR on cardiac pathophysiology in DS/obese rats. DS/obese rats were fed either normal laboratory chow ad libitum or a calorie-restricted diet (65% of the average food intake for ad libitum) from 9 to 13 weeks. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean) littermates served as controls. CR reduced body weight in both DS/obese and DS/lean rats, as well as attenuated the development of hypertension in DS/obese rats without affecting blood pressure in DS/lean rats. CR also reduced body fat content, ameliorated left ventricular hypertrophy, fibrosis, and diastolic dysfunction, and attenuated cardiac oxidative stress and inflammation in DS/obese rats. In addition, it increased serum adiponectin concentration, as well as downregulated the expression of angiotensin-converting enzyme and angiotensin II type 1A receptor genes in the heart of DS/obese rats. Our results thus show that CR attenuated obesity and hypertension, as well as left ventricular remodeling and diastolic dysfunction in DS/obese rats, with these latter effects being associated with reduced cardiac oxidative stress and inflammation.

Relationship between CGRP level and acute reject reaction in cardiac allograft recipient in rats

International Nuclear Information System (INIS)

Li Lusheng; Zhao Xin; Song Guangmin; Yang Xixiu; Song Huimin

2001-01-01

Objective: To investigate the relationship between the calcitonin gene related peptide (CGRP) and acute reject reaction in the cardiac allograft in rat. Methods: There were 28 wistar rats with inbreeding line as donors and SD rats as recipients. Cervical heart allograft model was used. Blood was sampled from the third day after grafting to terminal reject reaction when the acceptors were killed. 32 rats without allograft were regarded as the normal controls. Results: The mean survival time of the experimental group was 7.21±2.36 days. Volume of the allografts was greatly increased with hyperemia and edema. CGRP level in the plasma of experimental rats was 180.18±69.77 ng/L, while the level of control rats was 277.41 ± 79.02 ng/L. The deference was statistically significant (P<0.05). Conclusion: In the acute reject reaction, CGRP level is greatly decreased in the plasma of cardiac allograft recipients. Further studies are therefore needed to investigate the application of CGRP measurement in the prevention and treatment of rejection reaction of cardiac allograft

Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

OpenAIRE

Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

1999-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, ...

Exercise attenuates intermittent hypoxia-induced cardiac fibrosis associated with sodium-hydrogen exchanger-1 in rats

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Tsung-I Chen

2016-10-01

Full Text Available Purpose: To investigate the role of sodium–hydrogen exchanger-1 (NHE-1 and exercise training on intermittent hypoxia-induced cardiac fibrosis in obstructive sleep apnea (OSA, using an animal model mimicking the intermittent hypoxia of OSA. Methods: Eight-week-old male Sprague–Dawley rats were randomly assigned to control (CON, intermittent hypoxia (IH, exercise (EXE or IH combined with exercise (IHEXE groups. These groups were randomly assigned to subgroups receiving either a vehicle or the NHE-1 inhibitor cariporide. The EXE and IHEXE rats underwent exercise training on an animal treadmill for 10 weeks (5 days/week, 60 minutes/day, 24–30 m/minute, 2–10% grade. The IH and IHEXE rats were exposed to 14 days of IH (30 seconds of hypoxia - nadir of 2-6% O2 - followed by 45 seconds of normoxia for 8 hours/day. At the end of 10 weeks, rats were sacrificed and then hearts were removed to determine the myocardial levels of fibrosis index, oxidative stress, antioxidant capacity and NHE-1 activation. Results: Compared to the CON rats, IH induced higher cardiac fibrosis, lower myocardial catalase and superoxidative dismutase activities, higher myocardial lipid and protein peroxidation and higher NHE-1 activation (p < 0.05 for each, which were all abolished by cariporide. Compared to the IH rats, lower cardiac fibrosis, higher myocardial antioxidant capacity, lower myocardial lipid and protein peroxidation and lower NHE-1 activation were found in the IHEXE rats (p < 0.05 for each. Conclusion: IH-induced cardiac fibrosis was associated with NHE-1 hyperactivity. However, exercise training and cariporide exerted an inhibitory effect to prevent myocardial NHE-1 hyperactivity, which contributed to reduced IH-induced cardiac fibrosis. Therefore, NHE-1 plays a critical role in the effect of exercise on IH-induced increased cardiac fibrosis.

A hybrid stimulation strategy for suppression of spiral waves in cardiac tissue

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Xu Binbin, E-mail: xubinbin@hotmail.fr [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France); Jacquir, Sabir, E-mail: sjacquir@u-bourgogne.fr [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France); Laurent, Gabriel; Bilbault, Jean-Marie [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France); Binczak, Stephane, E-mail: stbinc@u-bourgogne.fr [LE2I, CNRS UMR 5158, Universite de Bourgogne, Dijon (France)

2011-08-15

Highlights: > Simulation of a cardiac tissue by a modified 2D FitzHugh-Nagumo model. > Stimulation of monophasic impulsions from a grid of electrodes to the cardiac tissue. > Propose a method by modifying the tissue's sodium channels and electrical stimulation. > The method leading to suppress spiral waves without generating new ones. > Optimal parameters of a successful suppression of spiral waves are investigated. - Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia whose mechanisms are thought to be mainly due to the self perpetuation of spiral waves (SW). To date, available treatment strategies (antiarrhythmic drugs, radiofrequency ablation of the substrate, electrical cardioversion) to restore and to maintain a normal sinus rhythm have limitations and are associated with AF recurrences. The aim of this study was to assess a way of suppressing SW by applying multifocal electrical stimulations in a simulated cardiac tissue using a 2D FitzHugh-Nagumo model specially convenient for AF investigations. We identified stimulation parameters for successful termination of SW. However, SW reinduction, following the electrical stimuli, leads us to develop a hybrid strategy based on sodium channel modification for the simulated tissue.

Proangiogenic scaffolds as functional templates for cardiac tissue engineering

OpenAIRE

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

2010-01-01

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

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

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Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

2013-02-01

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

International Nuclear Information System (INIS)

Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

2013-01-01

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [ 3 H]glucose and 2-deoxy[ 14 C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats

The effect of N-acetylcysteine on cardiac contractility to dobutamine in rats with streptozotocin-induced diabetes.

Science.gov (United States)

Cheng, Xing; Xia, Zhengyuan; Leo, Joyce M; Pang, Catherine C Y

2005-09-05

We examined if myocardial depression at the acute phase of diabetes (3 weeks after injection of streptozotocin, 60 mg/kg i.v.) is due to activation of inducible nitric oxide synthase and production of peroxynitrite, and if treatment with N-acetylcysteine (1.2 g/day/kg for 3 weeks, antioxidant) improves cardiac function. Four groups of rats were used: control, N-acetylcysteine-treated control, diabetic and N-acetylcysteine-treated diabetic. Pentobarbital-anaesthetized diabetic rats, relative to the controls, had reduced left ventricular contractility to dobutamine (1-57 microg/min/kg). The diabetic rats also had increased myocardial levels of thiobarbituric acid reactive substances, immunostaining of inducible nitric oxide synthase and nitrotyrosine, and similar baseline 15-F2t-isoprostane. N-acetylcysteine did not affect responses in the control rats; but increased cardiac contractility to dobutamine, reduced myocardial immunostaining of inducible nitric oxide synthase and nitrotyrosine and level of 15-F2t-isoprostane, and increased cardiac contractility to dobutamine in the diabetic rats. Antioxidant supplementation in diabetes reduces oxidative stress and improves cardiac function.

Effect of exogenous apelin-13 on cardiac stem cell mobilization in rats with myocardial infarction

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Nan ZHENG

2013-11-01

Full Text Available Objective　To explore the protective effect of exogenous apelin-13 on heart after acute myocardial infarction (AMI in rats and its mechanism. Methods　SD rats were randomly divided into 3 groups: sham-operated group (n=6, control group (AMI + saline solution, n=12, experimental group (AMI + apelin-13, n=12. Four rats died in the control group, and five in the experimental group. The rest rats of both control and experimental groups underwent intramyocardial injection with saline solution 20μl and apelin-13 0.2μg/20μl within 5min after coronary artery ligation, respectively. The rats of sham-operated group underwent thoracic surgery without both coronary artery ligation and drug injection. Echocardiography was performed and myocardial infarct size was measured to evaluate the changes of cardiac function. Immunohistochemical staining method was used to detect the positive expression of C-kit, Flk1 and Sca1 in myocardial tissue. Western blotting and RT-PCR were used to quantitatively examine the expression levels of C-kit, Flk1 and Sca1 protein and mRNA in myocardial tissue. Results　The results of echocardiography and myocardial infarct size measurement showed that cardiac function of rats was improved more significantly in experimental group than in control group (EF: 68.43%±2.06% in experimental group and 46.40%±15.18% in control group; FS: 33.70%±1.55% in experimental group and 20.73%±8.14% in control group; infarction myocardial area percentage: 16.10%±3.08% in experimental group and 33.83%±5.64% in control group; P<0.05. Immunohistochemical staining of C-kit, Flk1 and Sca1 was negative in sham-operated group and positive or strong positive both in experimental group and control group. Western blotting and RT-PCR showed that the protein and mRNA expression of C-kit, Flk1 and Sca1 were significantly higher in experimental group than in control group (protein level: C-kit 0.48±0.17 vs 1.05±0.08, Flk1 0.40±0.26 vs 0.88±0.10, Sca1

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

Science.gov (United States)

Hasan, Wohaib; Smith, Peter G

2014-04-01

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

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

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

2016-11-01

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

Cardiac tissue engineering and regeneration using cell-based therapy

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Alrefai MT

2015-05-01

Full Text Available Mohammad T Alrefai,1–3 Divya Murali,4 Arghya Paul,4 Khalid M Ridwan,1,2 John M Connell,1,2 Dominique Shum-Tim1,2 1Division of Cardiac Surgery, 2Division of Surgical Research, McGill University Health Center, Montreal, QC, Canada; 3King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia; 4Department of Chemical and Petroleum Engineering, School of Engineering, University of Kansas, Lawrence, KS, USA Abstract: Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. Keywords: stem cells, cardiomyocytes, cardiac surgery, heart failure, myocardial ischemia, heart, scaffolds, organoids, cell sheet and tissue engineering

Two-photon induced collagen cross-linking in bioartificial cardiac tissue

Science.gov (United States)

Kuetemeyer, Kai; Kensah, George; Heidrich, Marko; Meyer, Heiko; Martin, Ulrich; Gruh, Ina; Heisterkamp, Alexander

2011-08-01

Cardiac tissue engineering is a promising strategy for regenerative therapies to overcome the shortage of donor organs for transplantation. Besides contractile function, the stiffness of tissue engineered constructs is crucial to generate transplantable tissue surrogates with sufficient mechanical stability to withstand the high pressure present in the heart. Although several collagen cross-linking techniques have proven to be efficient in stabilizing biomaterials, they cannot be applied to cardiac tissue engineering, as cell death occurs in the treated area. Here, we present a novel method using femtosecond (fs) laser pulses to increase the stiffness of collagen-based tissue constructs without impairing cell viability. Raster scanning of the fs laser beam over riboflavin-treated tissue induced collagen cross-linking by two-photon photosensitized singlet oxygen production. One day post-irradiation, stress-strain measurements revealed increased tissue stiffness by around 40% being dependent on the fibroblast content in the tissue. At the same time, cells remained viable and fully functional as demonstrated by fluorescence imaging of cardiomyocyte mitochondrial activity and preservation of active contraction force. Our results indicate that two-photon induced collagen cross-linking has great potential for studying and improving artificially engineered tissue for regenerative therapies.

EFFICACY OF TOMATO AND / OR GARLIC IN AMELIORATING CARDIAC DISORDERS INDUCED BY FEEDING RATS FRYING OIL

International Nuclear Information System (INIS)

OSMAN, N.N.

2007-01-01

Tomato (Lycopersicon esculentum) and garlic (Allium cepa) are important constituents of the human diet. Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidaemia, thrombosis, hypertension and diabetes. Tomato has anti-mutagenic activities and contains lycopene (a powerful antioxidant) that appears to prevent oxidation of low density lipoprotein cholesterol (LDL-c) and reduces the risk of developing atherosclerosis and coronary heart disease. The present study was carried out to investigate the potential protective effects of tomato or garlic alone or their combination against cardiac disorders in rats fed commercial diet fortified with frying oil (15% w/w) for 30 days. Thirty male Wistar albino rats were used and were divided into five groups; group 1, control (rats fed diet containing 15% w/w fresh oil); group 2, animals fed diets fortified with frying oil; groups 3-5, rats fed as in group 2 and received tomato (500 mg/kg body weight), garlic (125 mg/kg body weight) and a combination of tomato and garlic by gavage, respectively.Total cholesterol (TC), triacylglycerols (TAG), phospholipids (PL), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c),and very low density lipoprotein cholesterol (VLDL-c) were estimated in the serum of different animal groups. Lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate aminotransferase (AST) alanine aminotransferase (ALT), triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) were determined in the serum as well as lipid peroxidation level (TBARS) and reduced glutathione (GSH) content were assessed in cardiac tissues.The results obtained revealed that, feeding rats on frying oil induced a notable increase in lipid profile, LDL-c, VLDL-c and TBARS associated with a marked depletion in GSH. Elevation in specific heart enzymes, LDL, CPK, ALT

Cardiac tissue slices: preparation, handling, and successful optical mapping.

Science.gov (United States)

Wang, Ken; Lee, Peter; Mirams, Gary R; Sarathchandra, Padmini; Borg, Thomas K; Gavaghan, David J; Kohl, Peter; Bollensdorff, Christian

2015-05-01

Cardiac tissue slices are becoming increasingly popular as a model system for cardiac electrophysiology and pharmacology research and development. Here, we describe in detail the preparation, handling, and optical mapping of transmembrane potential and intracellular free calcium concentration transients (CaT) in ventricular tissue slices from guinea pigs and rabbits. Slices cut in the epicardium-tangential plane contained well-aligned in-slice myocardial cell strands ("fibers") in subepicardial and midmyocardial sections. Cut with a high-precision slow-advancing microtome at a thickness of 350 to 400 μm, tissue slices preserved essential action potential (AP) properties of the precutting Langendorff-perfused heart. We identified the need for a postcutting recovery period of 36 min (guinea pig) and 63 min (rabbit) to reach 97.5% of final steady-state values for AP duration (APD) (identified by exponential fitting). There was no significant difference between the postcutting recovery dynamics in slices obtained using 2,3-butanedione 2-monoxime or blebistatin as electromechanical uncouplers during the cutting process. A rapid increase in APD, seen after cutting, was caused by exposure to ice-cold solution during the slicing procedure, not by tissue injury, differences in uncouplers, or pH-buffers (bicarbonate; HEPES). To characterize intrinsic patterns of CaT, AP, and conduction, a combination of multipoint and field stimulation should be used to avoid misinterpretation based on source-sink effects. In summary, we describe in detail the preparation, mapping, and data analysis approaches for reproducible cardiac tissue slice-based investigations into AP and CaT dynamics. Copyright © 2015 the American Physiological Society.

Vitamin D treatment attenuates cardiac FGF23/FGFR4 signaling and hypertrophy in uremic rats.

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Leifheit-Nestler, Maren; Grabner, Alexander; Hermann, Laura; Richter, Beatrice; Schmitz, Karin; Fischer, Dagmar-Christiane; Yanucil, Christopher; Faul, Christian; Haffner, Dieter

2017-09-01

Vitamin D deficiency and excess of circulating fibroblast growth factor 23 (FGF23) contribute to cardiovascular mortality in patients with chronic kidney disease (CKD). FGF23 activates FGF receptor 4 and (FGFR4) calcineurin/nuclear factor of activated T cells (NFAT) signaling in cardiac myocytes, thereby causing left ventricular hypertrophy (LVH). Here, we determined if 1,25-dihydroxyvitamin D (calcitriol) inhibits FGF23-induced cardiac signaling and LVH. 5/6 nephrectomized (5/6 Nx) rats were treated with different doses of calcitriol for 4 or 10 weeks and cardiac expression of FGF23/FGFR4 and activation of calcineurin/NFAT as well as LVH were analyzed. FGFR4 activation and hypertrophic cell growth were studied in cultured cardiac myocytes that were co-treated with FGF23 and calcitriol. In 5/6Nx rats with LVH, we detected elevated FGF23 expression in bone and myocardium, increased cardiac expression of FGFR4 and elevated cardiac activation of calcineurin/NFAT signaling. Cardiac expression levels of FGF23 and FGFR4 significantly correlated with the presence of LVH in uremic rats. Treatment with calcitriol reduced LVH as well as cardiac FGFR4 expression and calcineurin/NFAT activation. Bone and cardiac FGF23 expression were further stimulated by calcitriol in a dose-dependent manner, but levels of intact cardiac FGF23 protein were suppressed by high-dose calcitriol. In cultured cardiac myocytes, co-treatment with calcitriol blocked FGF23-induced activation of FGFR4 and hypertrophic cell growth. Our data suggest that in CKD, cardioprotective effects of calcitriol stem from its inhibitory actions on the cardiac FGF23/FGFR4 system, and based on their counterbalancing effects on cardiac myocytes, high FGF23 and low calcitriol synergistically contribute to cardiac hypertrophy. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Study on the effect of hypoxia on apoptosis of cultured newly born rat cardiac myocytes

International Nuclear Information System (INIS)

Su Weidong; Li Huiqiang; Yao Zhi

2005-01-01

Objective: To investigate the possible hypoxia-mediated cellular apoptosis after ischemic cardiac injury via a model of cultured newly born rat cardiac myocytes. Methods: Cardiac myocytes cultures from newly born rats (1-3d) were examined for apoptosis with HE stain and flow cytometry after cultured 96h and again examined after exposure to hypoxic environment for 16h. Results: Apoptotic changes were evident in the hypoxic culture cells. The HE stain revealed cellular shrinkage, nuclear chromosomal condensation with cytoplasmic eosinophilia. Also, distinct apoptosis peak was observed in the flow cytometry. Conclusion: This experiment proved that hypoxic model of cardiac myocyte culture showed definite apoptosis of the cells. (authors)

Cardiac fatty acid uptake and metabolism in the rat model of polycystic ovary syndrome.

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Tepavčević, Snežana; Milutinović, Danijela Vojnović; Macut, Djuro; Stojiljković, Mojca; Nikolić, Marina; Božić-Antić, Ivana; Ćulafić, Tijana; Bjekić-Macut, Jelica; Matić, Gordana; Korićanac, Goran

2015-09-01

Polycystic ovary syndrome (PCOS) is associated with an altered plasma lipid profile and increased risk for cardiovascular diseases. We hypothesized that molecular mechanisms underlying cardiac pathology in PCOS involve changes in expression and subcellular localization of several key proteins involved in cardiac lipid transport and metabolism, such as fatty acid transporter CD36, lipin 1, peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ coactivator-1 (PGC1), and carnitine palmitoyltransferase 1 (CPT1). We used the animal model of PCOS obtained by treating female rats with dihydrotestosterone (DHT). Protein levels of CD36, lipin 1, PPARα, PGC1, and antioxidative enzymes were assessed by Western blot in different cardiac cell compartments. Cardiac triglycerides (TG) and lipid peroxidation were also measured. The content of CD36 was decreased in both the cardiac plasma membranes and intracellular pool. On the other hand, total content of cardiac lipin 1 in DHT-treated rats was elevated, in contrast to decreased microsomal lipin 1 content. An increase in nuclear content of lipin 1 was observed together with elevation of nuclear PPARα and PGC1, and an increase in CPT1 expression. However, lipid peroxidation was reduced in the heart, without alterations in antioxidative enzymes expression and cardiac TG content. The results indicate that treatment of female rats with DHT is accompanied by a decrease of fatty acid uptake and a reduction of lipid peroxidation in the heart. The observed elevation of lipin 1, PPARα, PGC1, and CPT1 expression suggests that cardiac fatty acid metabolism is shifted toward mitochondrial beta oxidation.

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

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Chiaki Nagai-Okatani

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

Electrospun biocomposite nanofibrous patch for cardiac tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Prabhakaran, Molamma P; 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); Kai, Dan [NUS Graduate School of Integrative Sciences and Engineering, National University of Singapore (Singapore); Ghasemi-Mobarakeh, Laleh, E-mail: nnimpp@nus.edu.s [Islamic Azad University, Najafabad Branch, Isfahan (Iran, Islamic Republic of)

2011-10-15

A bioengineered construct that matches the chemical, mechanical, biological properties and extracellular matrix morphology of native tissue could be suitable as a cardiac patch for supporting the heart after myocardial infarction. The potential of utilizing a composite nanofibrous scaffold of poly(dl-lactide-co-glycolide)/gelatin (PLGA/Gel) as a biomimetic cardiac patch is studied by culturing a population of cardiomyocyte containing cells on the electrospun scaffolds. The chemical characterization and mechanical properties of the electrospun PLGA and PLGA/Gel nanofibers were studied by Fourier transform infrared spectroscopy, scanning electron microscopy and tensile measurements. The biocompatibility of the scaffolds was also studied and the cardiomyocytes seeded on PLGA/Gel nanofibers were found to express the typical functional cardiac proteins such as alpha-actinin and troponin I, showing the easy integration of cardiomyocytes on PLGA/Gel scaffolds. Our studies strengthen the application of electrospun PLGA/Gel nanofibers as a bio-mechanical support for injured myocardium and as a potential substrate for induction of endogenous cardiomyocyte proliferation, ultimately reducing the cardiac dysfunction and improving cardiac remodeling.

Lactate up-regulates the expression of lactate oxidation complex-related genes in left ventricular cardiac tissue of rats.

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Daniele Gabriel-Costa

Full Text Available Besides its role as a fuel source in intermediary metabolism, lactate has been considered a signaling molecule modulating lactate-sensitive genes involved in the regulation of skeletal muscle metabolism. Even though the flux of lactate is significantly high in the heart, its role on regulation of cardiac genes regulating lactate oxidation has not been clarified yet. We tested the hypothesis that lactate would increase cardiac levels of reactive oxygen species and up-regulate the expression of genes related to lactate oxidation complex.Isolated hearts from male adult Wistar rats were perfused with control, lactate or acetate (20mM added Krebs-Henseleit solution during 120 min in modified Langendorff apparatus. Reactive oxygen species (O2●-/H2O2 levels, and NADH and NADPH oxidase activities (in enriched microsomal or plasmatic membranes, respectively were evaluated by fluorimetry while SOD and catalase activities were evaluated by spectrophotometry. mRNA levels of lactate oxidation complex and energetic enzymes MCT1, MCT4, HK, LDH, PDH, CS, PGC1α and COXIV were quantified by real time RT-PCR. Mitochondrial DNA levels were also evaluated. Hemodynamic parameters were acquired during the experiment. The key findings of this work were that lactate elevated cardiac NADH oxidase activity but not NADPH activity. This response was associated with increased cardiac O2●-/H2O2 levels and up-regulation of MCT1, MCT4, LDH and PGC1α with no changes in HK, PDH, CS, COXIV mRNA levels and mitochondrial DNA levels. Lactate increased NRF-2 nuclear expression and SOD activity probably as counter-regulatory responses to increased O2●-/H2O2.Our results provide evidence for lactate-induced up-regulation of lactate oxidation complex associated with increased NADH oxidase activity and cardiac O2●-/H2O2 driving to an anti-oxidant response. These results unveil lactate as an important signaling molecule regulating components of the lactate oxidation complex in

Effects of chronic delta-9-THC treatment on cardiac beta-adrenoceptors in rats

Energy Technology Data Exchange (ETDEWEB)

Evans, E.B.; Seifen, E.; Kennedy, R.H.; Kafiluddi, R.; Paule, M.G.; Scallet, A.C.; Ali, S.F.; Slikker, W. Jr.

1987-10-01

This study was designed to determine if chronic treatment with delta-9-tetrahydrocannabinol (THC) alters cardiac beta-adrenoceptors in the rat. Following daily oral administration of 10 or 20 mg/kg THC or an equivalent volume of control solvent for 90 days, rats were sacrificed, and sarcolemmal membranes were prepared from ventricular myocardium. Beta-adrenoceptor density and binding affinity estimated with (-)(/sup 3/H)dihydroalprenolol; a beta-adrenergic antagonist, were not significantly affected by treatment with THC when compared to vehicle controls. These results suggest that the tolerance to cardiovascular effects of THC which develops during chronic exposure in the rat is not associated with alterations in cardiac beta-adrenoceptors as monitored by radiolabeled antagonist binding.

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

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (United States)

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

2015-11-21

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

Macrophage populations and cardiac sympathetic denervation during L-NAME-induced hypertension in rats

DEFF Research Database (Denmark)

Neves, S R S; Machado, C R S; Pinto, A M T

2006-01-01

The rat model of hypertension induced by prolonged treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) has been extensively used. However, the effects on cardiac autonomic innervation are unknown. Here, the cardiac sympathetic innervation is analyzed in parallel with myocardial lesions a...

Low intensity exercise prevents disturbances in rat cardiac insulin signaling and endothelial nitric oxide synthase induced by high fructose diet.

Science.gov (United States)

Stanišić, Jelena; Korićanac, Goran; Ćulafić, Tijana; Romić, Snježana; Stojiljković, Mojca; Kostić, Milan; Pantelić, Marija; Tepavčević, Snežana

2016-01-15

Increase in fructose consumption together with decrease in physical activity contributes to the development of metabolic syndrome and consequently cardiovascular diseases. The current study examined the preventive role of exercise on defects in cardiac insulin signaling and function of endothelial nitric oxide synthase (eNOS) in fructose fed rats. Male Wistar rats were divided into control, sedentary fructose (received 10% fructose for 9 weeks) and exercise fructose (additionally exposed to low intensity exercise) groups. Concentration of triglycerides, glucose, insulin and visceral adipose tissue weight were determined to estimate metabolic syndrome development. Expression and/or phosphorylation of cardiac insulin receptor (IR), insulin receptor substrate 1 (IRS1), tyrosine-specific protein phosphatase 1B (PTP1B), Akt, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and eNOS were evaluated. Fructose overload increased visceral adipose tissue, insulin concentration and homeostasis model assessment index. Exercise managed to decrease visceral adiposity and insulin level and to increase insulin sensitivity. Fructose diet increased level of cardiac PTP1B and pIRS1 (Ser307), while levels of IR and ERK1/2, as well as pIRS1 (Tyr 632), pAkt (Ser473, Thr308) and pERK1/2 were decreased. These disturbances were accompanied by reduced phosphorylation of eNOS at Ser1177. Exercise managed to prevent most of the disturbances in insulin signaling caused by fructose diet (except phosphorylation of IRS1 at Tyr 632 and phosphorylation and protein expression of ERK1/2) and consequently restored function of eNOS. Low intensity exercise could be considered as efficient treatment of cardiac insulin resistance induced by fructose diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

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Camilla Figueiredo Grans

2014-07-01

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-07-15

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

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

Science.gov (United States)

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

2014-01-01

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

Adverse cardiac effects of exogenous angiotensin 1-7 in rats with subtotal nephrectomy are prevented by ACE inhibition.

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Louise M Burrell

Full Text Available We previously reported that exogenous angiotensin (Ang 1-7 has adverse cardiac effects in experimental kidney failure due to its action to increase cardiac angiotensin converting enzyme (ACE activity. This study investigated if the addition of an ACE inhibitor (ACEi to Ang 1-7 infusion would unmask any beneficial effects of Ang 1-7 on the heart in experimental kidney failure. Male Sprague-Dawley rats underwent subtotal nephrectomy (STNx and were treated with vehicle, the ACEi ramipril (oral 1mg/kg/day, Ang 1-7 (subcutaneous 24 μg/kg/h or dual therapy (all groups, n = 12. A control group (n = 10 of sham-operated rats were also studied. STNx led to hypertension, renal impairment, cardiac hypertrophy and fibrosis, and increased both left ventricular ACE2 activity and ACE binding. STNx was not associated with changes in plasma levels of ACE, ACE2 or angiotensin peptides. Ramipril reduced blood pressure, improved cardiac hypertrophy and fibrosis and inhibited cardiac ACE. Ang 1-7 infusion increased blood pressure, cardiac interstitial fibrosis and cardiac ACE binding compared to untreated STNx rats. Although in STNx rats, the addition of ACEi to Ang 1-7 prevented any deleterious cardiac effects of Ang 1-7, a limitation of the study is that the large increase in plasma Ang 1-7 with ramipril may have masked any effect of infused Ang 1-7.

Biologically improved nanofibrous scaffolds for cardiac tissue engineering

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Bhaarathy, V. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Department of Nanoscience and Technology, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Lee Kong Chian School of Medicine, Nanyang Technological University, 138673 (Singapore); Venugopal, J., E-mail: nnijrv@nus.edu.sg [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Gandhimathi, C. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Ponpandian, N.; Mangalaraj, D. [Department of Nanoscience and Technology, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Ramakrishna, S. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore)

2014-11-01

Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(L-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering. - Highlights: • Fabricated nanofibrous scaffolds are porous, beadless and uniform structures. • PLACL/SF/AV nanofibers improve the

Biologically improved nanofibrous scaffolds for cardiac tissue engineering

International Nuclear Information System (INIS)

Bhaarathy, V.; Venugopal, J.; Gandhimathi, C.; Ponpandian, N.; Mangalaraj, D.; Ramakrishna, S.

2014-01-01

Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(L-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering. - Highlights: • Fabricated nanofibrous scaffolds are porous, beadless and uniform structures. • PLACL/SF/AV nanofibers improve the

Effects of Kefir on the Cardiac Autonomic Tones and Baroreflex Sensitivity in Spontaneously Hypertensive Rats.

Science.gov (United States)

Klippel, Brunella F; Duemke, Licia B; Leal, Marcos A; Friques, Andreia G F; Dantas, Eduardo M; Dalvi, Rodolfo F; Gava, Agata L; Pereira, Thiago M C; Andrade, Tadeu U; Meyrelles, Silvana S; Campagnaro, Bianca P; Vasquez, Elisardo C

2016-01-01

It has been previously shown that the probiotic kefir (a symbiotic matrix containing acid bacteria and yeasts) attenuated the hypertension and the endothelial dysfunction in spontaneously hypertensive rats (SHR). In the present study, the effect of chronic administration of kefir on the cardiac autonomic control of heart rate (HR) and baroreflex sensitivity (BRS) in SHR was evaluated. SHR were treated with kefir (0.3 mL/100 g body weight) for 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Cardiac autonomic vagal (VT) and sympathetic (ST) tones were estimated through the blockade of the cardiac muscarinic receptors (methylatropine) and the blockade of β1-adrenoceptor (atenolol). The BRS was evaluated by the tachycardia and bradycardia responses to vasoactive drug-induced decreases and increases in arterial blood pressure (BP), respectively. Additionally, spontaneous BRS was estimated by autoregressive spectral analysis. Kefir-treated SHR exhibited significant attenuation of basal BP, HR, and cardiac hypertrophy compared to non-treated SHR (12, 13, and 21%, respectively). Cardiac VT and ST were significantly altered in the SHR (~40 and ~90 bpm) compared with Wistar rats (~120 and ~30 bpm) and were partially recovered in SHR-kefir (~90 and ~25 bpm). SHR exhibited an impaired bradycardic BRS (~50%) compared with Wistar rats, which was reduced to ~40% in the kefir-treated SHR and abolished by methylatropine in all groups. SHR also exhibited a significant impairment of the tachycardic BRS (~23%) compared with Wistar rats and this difference was reduced to 8% in the SHR-kefir. Under the action of atenolol the residual reflex tachycardia was smaller in SHR than in Wistar rats and kefir attenuated this abnormality. Spectral analysis revealed increased low frequency components of BP (~3.5-fold) and pulse interval (~2-fold) compared with Wistar rats and these differences were reduced by kefir-treatment to ~1.6- and ~1.5-fold, respectively

Effects of Kefir on the Cardiac Autonomic Tones and Baroreflex Sensitivity in Spontaneously Hypertensive Rats

Science.gov (United States)

Klippel, Brunella F.; Duemke, Licia B.; Leal, Marcos A.; Friques, Andreia G. F.; Dantas, Eduardo M.; Dalvi, Rodolfo F.; Gava, Agata L.; Pereira, Thiago M. C.; Andrade, Tadeu U.; Meyrelles, Silvana S.; Campagnaro, Bianca P.; Vasquez, Elisardo C.

2016-01-01

Aims: It has been previously shown that the probiotic kefir (a symbiotic matrix containing acid bacteria and yeasts) attenuated the hypertension and the endothelial dysfunction in spontaneously hypertensive rats (SHR). In the present study, the effect of chronic administration of kefir on the cardiac autonomic control of heart rate (HR) and baroreflex sensitivity (BRS) in SHR was evaluated. Methods: SHR were treated with kefir (0.3 mL/100 g body weight) for 60 days and compared with non-treated SHR and with normotensive Wistar-Kyoto rats. Cardiac autonomic vagal (VT) and sympathetic (ST) tones were estimated through the blockade of the cardiac muscarinic receptors (methylatropine) and the blockade of β1−adrenoceptor (atenolol). The BRS was evaluated by the tachycardia and bradycardia responses to vasoactive drug-induced decreases and increases in arterial blood pressure (BP), respectively. Additionally, spontaneous BRS was estimated by autoregressive spectral analysis. Results: Kefir-treated SHR exhibited significant attenuation of basal BP, HR, and cardiac hypertrophy compared to non-treated SHR (12, 13, and 21%, respectively). Cardiac VT and ST were significantly altered in the SHR (~40 and ~90 bpm) compared with Wistar rats (~120 and ~30 bpm) and were partially recovered in SHR-kefir (~90 and ~25 bpm). SHR exhibited an impaired bradycardic BRS (~50%) compared with Wistar rats, which was reduced to ~40% in the kefir-treated SHR and abolished by methylatropine in all groups. SHR also exhibited a significant impairment of the tachycardic BRS (~23%) compared with Wistar rats and this difference was reduced to 8% in the SHR-kefir. Under the action of atenolol the residual reflex tachycardia was smaller in SHR than in Wistar rats and kefir attenuated this abnormality. Spectral analysis revealed increased low frequency components of BP (~3.5-fold) and pulse interval (~2-fold) compared with Wistar rats and these differences were reduced by kefir-treatment to ~1

A comparison of the effects of Portulaca oleracea seeds hydro-alcoholic extract and Vitamin C on biochemical, hemodynamic and functional parameters in cardiac tissue of rats with subclinical hyperthyroidism

Science.gov (United States)

Khodadadi, Hadi; Pakdel, Roghayeh; Khazaei, Majid; Niazmand, Said; Bavarsad, Kowsar; Hadjzadeh, Mousa AL-Reza

2018-01-01

Objective: The present study was performed to evaluate the effects of hydro-alcoholic extract of Portulaca oleracea (P. oleracea) seeds and Vitamin C on biochemical and hemodynamic parameters in cardiac tissue of rats with subclinical hyperthyroidism. Materials and Methods: Forty eight male rats were divided into six groups of 8 and treated for 4 weeks. T4 group received daily injection of levothyroxine sodium (20 μg/kg) and control group was given daily injection of saline. T4-Po groups were given T4 plus 100, 200, and 400 mg/kg of P. oleracea seeds extract in drinking water daily. T4-Vit C group received T4 plus daily injection of Vitamin C (100 mg/kg). At the end of the experiment, body weight, serum free T4 level, left ventricular developed pressure (LVDP), malondialdehyde (MDA) and total thiol levels were measured. Results: Free T4 levels were increased in all groups that were treated with T4. Weight gain was decreased in T4 and T4-Po100 groups compared to control group (p<0.001 and p<0.05). However, body weight was increased in T4-Po (200 and 400) and T4-Vit C groups compared to T4 group. LVDP was increased in T4 group compared to control group but, LVDP was decreased in T4-Po and T4-Vit C groups. Malondialdehyde was decreased in T4-Po groups and T4-Vit C group compared to T4 group. Total thiol groups were increased in T4-Po (200 and 400) and T4-Vit C groups compared to T4 group. Conclusion: The results showed that P. oleracea extract has a protective effect on cardiac dysfunction due to subclinical hyperthyroidism induced by levothyroxine sodium in rats. PMID:29632847

Phosphorus nuclear magnetic resonance studies on normoxic and ischemic cardiac tissue.

Science.gov (United States)

Gadian, D G; Hoult, D I; Radda, G K; Seeley, P J; Chance, B; Barlow, C

1976-12-01

The intact heart of a young rat was excised rapidly and cooled to 0 degree C; its energy-rich compounds were examined by 31P Fourier Transform nuclear magnetic resonance. The heart showed the characteristic spectrum of sugar phosphates, inorganic phosphate, phosphocreatine, and magniesium phates, inorganic phosphate, phosphocreatine, and magnesium ATP, characteristics of the energizing state of the nonbeating tissue. Warming to 30 degrees C imposes an energy load upon the heart consistent with short-term resumption of beating, concomitant intracellular acidosis, and decomposition of all detectable energy-rich compounds. The intracellular acidity causes a shift from pH 7.0 to 6.0. The effects of possible interferences with this pH measurement are considered. The method appears to have wide usefulness in cardiac infarct models for detecting the fraction of the total volume occupied by the infarct and for studying the effect of various proposed therapies upon this infarcted volume.

Myocardial uptake of thallium-201 in rat with cardiac hypertrophy

International Nuclear Information System (INIS)

Torii, Yukio; Adachi, Haruhiko; Kizu, Akira; Nakagawa, Masao; Ijichi, Hamao

1985-01-01

The thallium-201 (TL) has been used in order to diagnose myocardial infarction and ischemia. Although it is well known that TL distributes in the myocardium in proportion to the distribution of coronary blood flow, the biological property of TL in the loaded myocardium remains unclear. We studied the myocardial uptake of TL in rat with cardiac hypertrophy. Experiments were performed in 30 anesthetized rats devided into 3 groups; control group (C,N=14), hypertrophy group (H,N=6) and diltiazem group (D, 0.3 mg/kg/min. IV. N=10). Cardiac hypertrophy was produced with the banding of the ascending aorta. Myocardial blood flow (MBF) was measured by microspheres labeled with Strontium-85. Cardiac weight was increased in H, and both MBF and TL uptake were proportionally increased. MBF was negatively correlated with the extraction fraction in C (r=-0.71), in H (r=-0.66) and in D (r=-0.85), and this relationship in H was significantly different from it in C (p<0.05), but not in D. From these results, we concluded that TL uptake in H is not always dependant on MBF and affected by the altered metabolism of hypertrophied myocardium. (author)

Melt Electrospinning Writing of Poly-Hydroxymethylglycolide-co-ε-Caprolactone-Based Scaffolds for Cardiac Tissue Engineering

NARCIS (Netherlands)

Castilho, Miguel; Feyen, Dries; Flandes-Iparraguirre, María; Hochleitner, Gernot; Groll, Jürgen; Doevendans, Pieter A.F.; Vermonden, Tina; Ito, Keita; Sluijter, Joost P G; Malda, Jos

2017-01-01

Current limitations in cardiac tissue engineering revolve around the inability to fully recapitulate the structural organization and mechanical environment of native cardiac tissue. This study aims at developing organized ultrafine fiber scaffolds with improved biocompatibility and architecture in

Melt Electrospinning Writing of Poly-Hydroxymethylglycolide-co-ε-Caprolactone-Based Scaffolds for Cardiac Tissue Engineering

NARCIS (Netherlands)

Castilho, Miguel; Feyen, Dries; Flandes-Iparraguirre, María; Hochleitner, Gernot; Groll, Jürgen; Doevendans, Pieter A.F.; Vermonden, Tina; Ito, Keita; Sluijter, Joost P.G.; Malda, Jos

Current limitations in cardiac tissue engineering revolve around the inability to fully recapitulate the structural organization and mechanical environment of native cardiac tissue. This study aims at developing organized ultrafine fiber scaffolds with improved biocompatibility and architecture in

Melt electrospinning writing of poly-Hydroxymethylglycolide-co-ε-Caprolactone-based scaffolds for cardiac tissue engineering

NARCIS (Netherlands)

Castilho, M.; Feyen, D.; Flandes-Iparraguirre, M.; Hochleitner, G.; Groll, J.; Doevendans, P.A.F.; Vermonden, T.; Ito, K.; Sluijter, J.P.G.; Malda, J.

2017-01-01

Current limitations in cardiac tissue engineering revolve around the inability to fully recapitulate the structural organization and mechanical environment of native cardiac tissue. This study aims at developing organized ultrafine fiber scaffolds with improved biocompatibility and architecture in

Differential cardiac effects in rats exposed to atmospheric smog generated from isoprene versus toluene

Science.gov (United States)

The results of this study demonstrate that atmospheric smog generated from both isoprene and toluene cause cardiac effects in rats. In addition, it appears that smog from toluene is more toxic in terms of cardiac arrhythmogenicity. Smog, which is a comple...

Cardiac protein expression patterns are associated with distinct inborn exercise capacity in non-selectively bred rats

Directory of Open Access Journals (Sweden)

L.P. Ribeiro

2018-01-01

Full Text Available In the present study, we successfully demonstrated for the first time the existence of cardiac proteomic differences between non-selectively bred rats with distinct intrinsic exercise capacities. A proteomic approach based on two-dimensional gel electrophoresis coupled to mass spectrometry was used to study the left ventricle (LV tissue proteome of rats with distinct intrinsic exercise capacity. Low running performance (LRP and high running performance (HRP rats were categorized by a treadmill exercise test, according to distance run to exhaustion. The running capacity of HRPs was 3.5-fold greater than LRPs. Protein profiling revealed 29 differences between HRP and LRP rats (15 proteins were identified. We detected alterations in components involved in metabolism, antioxidant and stress response, microfibrillar and cytoskeletal proteins. Contractile proteins were upregulated in the LVs of HRP rats (α-myosin heavy chain-6, myosin light chain-1 and creatine kinase, whereas the LVs of LRP rats exhibited upregulation in proteins associated with stress response (aldehyde dehydrogenase 2, α-crystallin B chain and HSPβ-2. In addition, the cytoskeletal proteins desmin and α-actin were upregulated in LRPs. Taken together, our results suggest that the increased contractile protein levels in HRP rats partly accounted for their improved exercise capacity, and that proteins considered risk factors to the development of cardiovascular disease were expressed in higher amounts in LRP animals.

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

Science.gov (United States)

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

2016-01-01

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

Impact of obesity on hypertension-induced cardiac remodeling: role of oxidative stress and its modulation by gemfibrozil treatment in rats.

Science.gov (United States)

Singh, Randhir; Singh, Amrit Pal; Singh, Manjeet; Krishan, Pawan

2011-01-15

This study investigated the possible synergistic role of obesity in hypertension-induced cardiac remodeling and its modulation by gemfibrozil treatment in rats. Male Wistar rats were fed a high-fat diet (HFD) for 90 days. Normal rats were subjected to hypertension by partial abdominal aortic constriction (PAAC) for 28 days. In the HFD+PAAC control group, rats on HFD were subjected to PAAC on the 62nd day and were sacrificed on the 90th day. HFD and PAAC individually resulted in significant cardiac hypertrophy and fibrosis along with increased oxidative stress and mean arterial blood pressure (MABP) in rats as evidenced by various morphological, biochemical, and histological parameters. Moreover, the HFD + PAAC control group showed marked cardiac remodeling compared to rats subjected to HFD or PAAC alone. The HFD+gemfibrozil and HFD+PAAC+gemfibrozil groups showed significant reduction in cardiac remodeling along with reduction in oxidative stress and MABP. Hence, it may be concluded that oxidative stress plays a key role in obesity-mediated synergistic effects on induction and progression of PAAC-induced cardiac remodeling, and its deleterious effects could be reversed by gemfibrozil treatment in rats through its antioxidant activity. Copyright © 2010 Elsevier Inc. All rights reserved.

L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats.

Science.gov (United States)

Rodríguez-Gómez, Isabel; Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

2016-03-01

This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. © 2015 by the Society for Experimental Biology and Medicine.

Induced pluripotent stem cell-derived cardiac progenitors differentiate to cardiomyocytes and form biosynthetic tissues.

Directory of Open Access Journals (Sweden)

Nicolas Christoforou

Full Text Available The mammalian heart has little capacity to regenerate, and following injury the myocardium is replaced by non-contractile scar tissue. Consequently, increased wall stress and workload on the remaining myocardium leads to chamber dilation, dysfunction, and heart failure. Cell-based therapy with an autologous, epigenetically reprogrammed, and cardiac-committed progenitor cell source could potentially reverse this process by replacing the damaged myocardium with functional tissue. However, it is unclear whether cardiac progenitor cell-derived cardiomyocytes are capable of attaining levels of structural and functional maturity comparable to that of terminally-fated cardiomyocytes. Here, we first describe the derivation of mouse induced pluripotent stem (iPS cells, which once differentiated allow for the enrichment of Nkx2-5(+ cardiac progenitors, and the cardiomyocyte-specific expression of the red fluorescent protein. We show that the cardiac progenitors are multipotent and capable of differentiating into endothelial cells, smooth muscle cells and cardiomyocytes. Moreover, cardiac progenitor selection corresponds to cKit(+ cell enrichment, while cardiomyocyte cell-lineage commitment is concomitant with dual expression of either cKit/Flk1 or cKit/Sca-1. We proceed to show that the cardiac progenitor-derived cardiomyocytes are capable of forming electrically and mechanically coupled large-scale 2D cell cultures with mature electrophysiological properties. Finally, we examine the cell progenitors' ability to form electromechanically coherent macroscopic tissues, using a physiologically relevant 3D culture model and demonstrate that following long-term culture the cardiomyocytes align, and form robust electromechanical connections throughout the volume of the biosynthetic tissue construct. We conclude that the iPS cell-derived cardiac progenitors are a robust cell source for tissue engineering applications and a 3D culture platform for pharmacological

Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats.

Science.gov (United States)

Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S

2013-06-01

The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress

Science.gov (United States)

Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

2016-01-01

Objective The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Methods Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Results Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=−0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=−0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=−0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction

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

Science.gov (United States)

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

2016-06-01

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

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

Science.gov (United States)

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

2016-01-01

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

Cardiac magnetic resonance radiofrequency tissue tagging for diagnosis of constrictive pericarditis: A proof of concept study.

Science.gov (United States)

Power, John A; Thompson, Diane V; Rayarao, Geetha; Doyle, Mark; Biederman, Robert W W

2016-05-01

Invasive cardiac catheterization is the venerable "gold standard" for diagnosing constrictive pericarditis. However, its sensitivity and specificity vary dramatically from center to center. Given the ability to unequivocally define segments of the pericardium with the heart via radiofrequency tissue tagging, we hypothesize that cardiac magnetic resonance has the capability to be the new gold standard. All patients who were referred for cardiac magnetic resonance evaluation of constrictive pericarditis underwent cardiac magnetic resonance radiofrequency tissue tagging to define visceral-parietal pericardial adherence to determine constriction. This was then compared with intraoperative surgical findings. Likewise, all preoperative cardiac catheterization testing was reviewed in a blinded manner. A total of 120 patients were referred for clinical suspicion of constrictive pericarditis. Thirty-nine patients were defined as constrictive pericarditis positive solely via radiofrequency tissue-tagging cardiac magnetic resonance, of whom 21 were positive, 4 were negative, and 1 was equivocal for constrictive pericarditis, as defined by cardiac catheterization. Of these patients, 16 underwent pericardiectomy and were surgically confirmed. There was 100% agreement between cardiac magnetic resonance-defined constrictive pericarditis positivity and postsurgical findings. No patients were misclassified by cardiac magnetic resonance. In regard to the remaining constrictive pericarditis-positive patients defined by cardiac magnetic resonance, 10 were treated medically, declined, were ineligible for surgery, or were lost to follow-up. Long-term follow-up of those who were constrictive pericarditis negative by cardiac magnetic resonance showed no early or late crossover to the surgery arm. Cardiac magnetic resonance via radiofrequency tissue tagging offers a unique, efficient, and effective manner of defining clinically and surgically relevant constrictive pericarditis

Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

Science.gov (United States)

Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

The in vivo pharmacokinetics, tissue distribution and excretion investigation of mesaconine in rats and its in vitro intestinal absorption study using UPLC-MS/MS.

Science.gov (United States)

Liu, Xiuxiu; Tang, Minghai; Liu, Taohong; Wang, Chunyan; Tang, Qiaoxin; Xiao, Yaxin; Yang, Ruixin; Chao, Ruobing

2017-12-27

1. Mesaconine, an ingredient from Aconitum carmichaelii Debx., has been proven to have cardiac effect. For further development and better pharmacological elucidation, the in vivo process and intestinal absorptive behavior of mesaconine should be investigated comprehensively. 2. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitation of mesaconine in rat plasma, tissue homogenates, urine and feces to investigate the in vivo pharmacokinetic profiles, tissue distribution and excretion. The intestinal absorptive behavior of mesaconine was investigated using in vitro everted rat gut sac model. 3. Mesaconine was well distributed in tissues and a mass of unchanged form was detected in feces. It was difficultly absorbed into blood circulatory system after oral administration. The insufficient oral bioavailability of mesaconine may be mainly attributed to its low intestinal permeability due to a lack of lipophilicity. The absorption of mesaconine in rat's intestine is a first-order process with the passive diffusion mechanism.

Effect of valsartan on cardiac senescence and apoptosis in a rat model of cardiotoxicity.

Science.gov (United States)

Sakr, Hussein F; Abbas, Amr M; Elsamanoudy, Ayman Z

2016-06-01

The clinical application of doxorubicin is limited by its cardiotoxicity. The present study investigated the effect of valsartan on doxorubicin-induced cardiotoxicity in rats. Rats were divided into 6 groups: control, control + valsartan (10 mg/kg, for 14 days, orally), doxorubicin-treated (2.5 mg/kg, 3 times/week for 2 weeks, intraperitoneally), valsartan then doxorubicin, valsartan + doxorubicin, and doxorubicin then valsartan. ECG, isolated heart, lipid peroxidation (thiobaribituric acid reactive substances (TBARS)), total antioxidant capacity (TAC), and Bax, Bcl-2, and senescence marker protein 30 (SMP30) gene expression were measured in cardiac tissue. Blood samples were collected to measure lactate dehydrogenase (LDH) and creatine kinase MB (CK-MB). Doxorubicin significantly increased LDH, CK-MB, TBARS, heart rate (HR), Bax gene expression, and -dP/dtmax and decreased TAC, Bcl-2 and SMP30 gene expression, left ventricular developed pressure (LVDP), and +dP/dtmax. Also, doxorubicin lengthened ST, QT, and QTc intervals. Concurrent or post- but not pre-treatment of doxorubicin-treated rats with valsartan reduced LDH, CK-MB, TBARS, HR, Bax gene expression, -dP/dtmax, and ST, QT, and QTc intervals and increased TAC, Bcl-2 and SMP30 gene expression, LVDP, and +dP/dtmax. Therefore, we conclude that concurrent or post- but not pre-treatment of doxorubicin-induced rats with valsartan attenuated doxorubicin-induced cardiotoxicity through inhibiting oxidative stress, apoptosis, and senescence.

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

NARCIS (Netherlands)

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

1992-01-01

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

Chronic type 1 diabetes in spontaneously hypertensive rats leads to exacerbated cardiac fibrosis.

Science.gov (United States)

Black, Mary Jane; D'Amore, Angelo; Auden, Alana; Stamp, Laura; Osicka, Tanya; Panagiotopoulos, Sianna; Jerums, George

2010-01-01

Diabetes in human subjects is often associated with hypertension. The aim of this study was to examine the development of cardiac fibrosis following induction of type 1 diabetes in genetically hypertensive rats. Diabetes was induced by streptozotocin (STZ) injection in 8-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) for a duration of 16 or 24 weeks. Aged-matched, nondiabetic WKY and SHRs were used as controls. At termination of treatment, the rats were anaesthetized, hearts arrested in diastole and perfusion fixed. A comprehensive examination of cardiac fibrosis throughout the right and left ventricles was undertaken in picrosirius red-stained sections, using image analysis and by undertaking collagen type I and type III immunohistochemistry. Induction of diabetes in the SHRs led to a marked increase in the levels of interstitial fibrosis in the left ventricle plus septum (LV+S) at both 16 and 24 weeks duration (59% and 43% increase, respectively) and also in the right ventricle after 24 weeks duration of diabetes (35% increase compared to the nondiabetic SHR). Exacerbated perivascular fibrosis was also observed in the LV+S in the diabetic-hypertensive rats at the later time point. These effects of induction of diabetes were not observed in the normotensive strain. Our findings clearly demonstrate elevations in cardiac fibrosis when type 1 diabetes is combined with hypertension. Our findings thus stress the importance of closely monitoring both blood pressure and glucose levels in type 1 diabetic patients in order to prevent myocardial collagen deposition. Copyright © 2010 Elsevier Inc. All rights reserved.

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

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

2017-12-01

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

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

Science.gov (United States)

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

2007-05-01

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

Cardiac impairment evaluated by transesophageal echocardiography and invasive measurements in rats undergoing sinoaortic denervation.

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Raquel A Sirvente

Full Text Available BACKGROUND: Sympathetic hyperactivity may be related to left ventricular (LV dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE using intracardiac echocardiographic catheter. METHODS AND RESULTS: We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD. The rats (n = 32 were divided into 4 groups: 16 Wistar (W with (n = 8 or without SAD (n = 8 and 16 spontaneously hypertensive rats (SHR with (n = 8 or without SAD (SHRSAD (n = 8. Blood pressure (BP and heart rate (HR did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. CONCLUSIONS: Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease.

Desipramine increases cardiac parasympathetic activity via α2-adrenergic mechanism in rats.

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Kawada, Toru; Akiyama, Tsuyoshi; Shimizu, Shuji; Fukumitsu, Masafumi; Kamiya, Atsunori; Sugimachi, Masaru

2017-07-01

Desipramine (DMI) is a blocker of neuronal norepinephrine (NE) uptake transporter. Although intravenous DMI has been shown to cause centrally-mediated sympathoinhibition and peripheral NE accumulation, its parasympathetic effect remains to be elucidated. We hypothesized that intravenous DMI activates the cardiac vagal nerve via an α 2 -adrenergic mechanism. Using a cardiac microdialysis technique, changes in myocardial interstitial acetylcholine (ACh) levels in the left ventricular free wall in response to intravenous DMI (1mg·kg -1 ) were examined in anesthetized rats. In rats with intact vagi (n=7), intravenous DMI increased ACh from 1.67±0.43 to 2.48±0.66nM (Padrenergic stimulation in experimental settings in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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 malondialdehyde (MDA), activities/levels of different cellular antioxidants were estimated in control and experimental groups. Additionally, scavenging potential to the hydroxyl radical of the fraction was measured by electron paramagnetic resonance (EPR). ISO administered rats showed significant increase in the levels of serum troponin-I, creatine kinase, lactate dehydrogenase, and heart tissue MDA content. Furthermore, marked reduction in the activities of antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione levels were observed. EPR study showed an increase in signal intensity in ISO-induced rats. Triphenyl tetrazolium chloride (TTC) staining of heart section revealed a marked increase in infarcted area in ISO-induced rats. Histological features of the heart also indicated a disruption in the structure of cardiac myofibrils in these animals. MOPF (100 mg/kg body weight) pretreatment prevented all these adverse effects of ISO. Present results show that the rich polyphenolic content of Moringa oleifera significantly reduced the myocardial damage and decreased the oxidative stress, possibly through hydroxyl radical scavenging activity as evidenced from the EPR spectra. PMID:26417351

Electrospun conductive nanofibrous scaffolds for engineering cardiac tissue and 3D bioactuators.

Science.gov (United States)

Wang, Ling; Wu, Yaobin; Hu, Tianli; Guo, Baolin; Ma, Peter X

2017-09-01

Mimicking the nanofibrous structure similar to extracellular matrix and conductivity for electrical propagation of native myocardium would be highly beneficial for cardiac tissue engineering and cardiomyocytes-based bioactuators. Herein, we developed conductive nanofibrous sheets with electrical conductivity and nanofibrous structure composed of poly(l-lactic acid) (PLA) blending with polyaniline (PANI) for cardiac tissue engineering and cardiomyocytes-based 3D bioactuators. Incorporating of varying contents of PANI from 0wt% to 3wt% into the PLA polymer, the electrospun nanofibrous sheets showed enhanced conductivity while maintaining the same fiber diameter. These PLA/PANI conductive nanofibrous sheets exhibited good cell viability and promoting effect on differentiation of H9c2 cardiomyoblasts in terms of maturation index and fusion index. Moreover, PLA/PANI nanofibrous sheets enhanced the cell-cell interaction, maturation and spontaneous beating of primary cardiomyocytes. Furthermore, the cardiomyocytes-laden PLA/PANI conductive nanofibrous sheets can form 3D bioactuators with tubular and folding shapes, and spontaneously beat with much higher frequency and displacement than that on cardiomyocytes-laden PLA nanofibrous sheets. Therefore, these PLA/PANI conductive nanofibrous sheets with conductivity and extracellular matrix like nanostructure demonstrated promising potential in cardiac tissue engineering and cardiomyocytes-based 3D bioactuators. Cardiomyocytes-based bioactuators have been paid more attention due to their spontaneous motion by integrating cardiomyocytes into polymer structures, but developing suitable scaffolds for bioactuators remains challenging. Electrospun nanofibrous scaffolds have been widely used in cardiac tissue engineering because they can mimic the extracellular matrix of myocardium. Developing conductive nanofibrous scaffolds by electrospinning would be beneficial for cardiomyocytes-based bioactuators, but such scaffolds have been

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

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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.

Detection of Angiostrongylus cantonensis in the Blood and Peripheral Tissues of Wild Hawaiian Rats (Rattus rattus by a Quantitative PCR (qPCR Assay.

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Susan I Jarvi

Full Text Available The nematode Angiostrongylus cantonensis is a rat lungworm, a zoonotic pathogen that causes human eosinophilic meningitis and ocular angiostrongyliasis characteristic of rat lungworm (RLW disease. Definitive diagnosis is made by finding and identifying A. cantonensis larvae in the cerebral spinal fluid or by using a custom immunological or molecular test. This study was conducted to determine if genomic DNA from A. cantonensis is detectable by qPCR in the blood or tissues of experimentally infected rats. F1 offspring from wild rats were subjected to experimental infection with RLW larvae isolated from slugs, then blood or tissue samples were collected over multiple time points. Blood samples were collected from 21 rats throughout the course of two trials (15 rats in Trial I, and 6 rats in Trial II. In addition to a control group, each trial had two treatment groups: the rats in the low dose (LD group were infected by approximately 10 larvae and the rats in the high dose (HD group were infected with approximately 50 larvae. In Trial I, parasite DNA was detected in cardiac bleed samples from five of five LD rats and five of five HD rats at six weeks post-infection (PI, and three of five LD rats and five of five HD rats from tail tissue. In Trial II, parasite DNA was detected in peripheral blood samples from one of two HD rats at 53 minutes PI, one of two LD rats at 1.5 hours PI, one of two HD rats at 18 hours PI, one of two LD rats at five weeks PI and two of two at six weeks PI, and two of two HD rats at weeks five and six PI. These data demonstrate that parasite DNA can be detected in peripheral blood at various time points throughout RLW infection in rats.

Detection of Angiostrongylus cantonensis in the Blood and Peripheral Tissues of Wild Hawaiian Rats (Rattus rattus) by a Quantitative PCR (qPCR) Assay.

Science.gov (United States)

Jarvi, Susan I; Pitt, William C; Farias, Margaret E; Shiels, Laura; Severino, Michael G; Howe, Kathleen M; Jacquier, Steven H; Shiels, Aaron B; Amano, Karis K; Luiz, Blaine C; Maher, Daisy E; Allison, Maureen L; Holtquist, Zachariah C; Scheibelhut, Neil T

2015-01-01

The nematode Angiostrongylus cantonensis is a rat lungworm, a zoonotic pathogen that causes human eosinophilic meningitis and ocular angiostrongyliasis characteristic of rat lungworm (RLW) disease. Definitive diagnosis is made by finding and identifying A. cantonensis larvae in the cerebral spinal fluid or by using a custom immunological or molecular test. This study was conducted to determine if genomic DNA from A. cantonensis is detectable by qPCR in the blood or tissues of experimentally infected rats. F1 offspring from wild rats were subjected to experimental infection with RLW larvae isolated from slugs, then blood or tissue samples were collected over multiple time points. Blood samples were collected from 21 rats throughout the course of two trials (15 rats in Trial I, and 6 rats in Trial II). In addition to a control group, each trial had two treatment groups: the rats in the low dose (LD) group were infected by approximately 10 larvae and the rats in the high dose (HD) group were infected with approximately 50 larvae. In Trial I, parasite DNA was detected in cardiac bleed samples from five of five LD rats and five of five HD rats at six weeks post-infection (PI), and three of five LD rats and five of five HD rats from tail tissue. In Trial II, parasite DNA was detected in peripheral blood samples from one of two HD rats at 53 minutes PI, one of two LD rats at 1.5 hours PI, one of two HD rats at 18 hours PI, one of two LD rats at five weeks PI and two of two at six weeks PI, and two of two HD rats at weeks five and six PI. These data demonstrate that parasite DNA can be detected in peripheral blood at various time points throughout RLW infection in rats.

DOPA, norepinephrine, and dopamine in rat tissues

DEFF Research Database (Denmark)

Eldrup, E; Richter, Erik; Christensen, N J

1989-01-01

We studied the effect of unilateral sympathectomy on rat quadriceps and gastrocnemius muscle concentrations of endogenous dihydroxyphenylalanine (DOPA), dopamine (DA), and norepinephrine (NE) and assessed the relationships between these catecholamines in several rat tissues. Catecholamines were...

C-Psilocin tissue distribution in pregnant rats after intravenous administration

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Francis C.P. Law

2014-06-01

Full Text Available Background: Many species of hallucinogenic mushrooms have been found in the genus Psilocybe. The main psychoactive chemicals of Psilocybe mushrooms are psilocin and its phosphoryloxy derivative, psilocybin. In addition to its psychedelic effects, psilocybin is an effective agent to lift the mood of depressed patients with terminal cancers. Objective: To study the dispositional kinetics of 14C-psilocin in pregnant rats after intravenous injection, to calculate tissue dose surrogates i.e., tissue 14C concentration and area under the concentration-time curve using the experimental data, to quantify trans-placental passage of psilocin and/or its metabolites, and to identify new psilocin metabolite(s in rat urine. Methods: A group of 15 pregnant Wistar rats weighing between 0.30-0.36 kg was used in the study. Each rat was given a single dose of 7.5 mg/kg 14C-psilocin i.v. Three rats were randomly selected and sacrificed at 0.5, 1.0, 2.0, 4.0, and 8.0 hr post-dosing. The maternal and fetal tissues were quickly removed and the radioactivity in these tissues determined by liquid scintillation counting. In a separate study, urine samples were collected from 6 male Wistar rats after administering 15 mg/kg of unlabeled psilocin i.p. The urine samples were collected and extracted by chloroform-methanol (9:1 v/v and analyzed using a gas chromatograph/mass spectrometer. Results: 14C-Psilocin crossed the placental barrier of pregnant rats readily after i.v. administration; maternal tissue 14C concentrations were found to be much higher than those in fetal tissues. The areas under the curve for maternal tissues also were much higher than the fetal tissues. In general, maternal tissues could be divided into the fast eliminating organ group, which included the brain (elimination half-life 13 hr. A new psilocin metabolite tentatively identified as dihydroxyindoleacetic acid was found in the urine. Conclusion: Our study showed that psilocin readily crossed the

Textile-templated electrospun anisotropic scaffolds for regenerative cardiac tissue engineering.

Science.gov (United States)

Şenel Ayaz, H Gözde; Perets, Anat; Ayaz, Hasan; Gilroy, Kyle D; Govindaraj, Muthu; Brookstein, David; Lelkes, Peter I

2014-10-01

For patients with end-stage heart disease, the access to heart transplantation is limited due to the shortage of donor organs and to the potential for rejection of the donated organ. Therefore, current studies focus on bioengineering approaches for creating biomimetic cardiac patches that will assist in restoring cardiac function, by repairing and/or regenerating the intrinsically anisotropic myocardium. In this paper we present a simplified, straightforward approach for creating bioactive anisotropic cardiac patches, based on a combination of bioengineering and textile-manufacturing techniques in concert with nano-biotechnology based tissue-engineering stratagems. Using knitted conventional textiles, made of cotton or polyester yarns as template targets, we successfully electrospun anisotropic three-dimensional scaffolds from poly(lactic-co-glycolic) acid (PLGA), and thermoplastic polycarbonate-urethane (PCU, Bionate(®)). The surface topography and mechanical properties of textile-templated anisotropic scaffolds significantly differed from those of scaffolds electrospun from the same materials onto conventional 2-D flat-target electrospun scaffolds. Anisotropic textile-templated scaffolds electrospun from both PLGA and PCU, supported the adhesion and proliferation of H9C2 cardiac myoblasts cell line, and guided the cardiac tissue-like anisotropic organization of these cells in vitro. All cell-seeded PCU scaffolds exhibited mechanical properties comparable to those of a human heart, but only the cells on the polyester-templated scaffolds exhibited prolonged spontaneous synchronous contractility on the entire engineered construct for 10 days in vitro at a near physiologic frequency of ∼120 bpm. Taken together, the methods described here take advantage of straightforward established textile manufacturing strategies as an efficient and cost-effective approach to engineering 3D anisotropic, elastomeric PCU scaffolds that can serve as a cardiac patch. Copyright �

Effect of triorganotin compounds on calcium transport mechanisms in rat cardiac sarcoplasmic reticulum

International Nuclear Information System (INIS)

Cameron, J.A.; Kodavanti, P.R.S.; Yallapragada, P.R.; Desaiah, D.

1990-01-01

Although organotin compounds, in general, are neurotoxicants, recent studies indicate that these tin compounds affect heme metabolism as well as cardiovascular system. Sarcoplasmic reticulum (SR) calcium pump together with phosphorylation of phospholamban has an important role in myocardial contraction and relaxation. Since organotin compounds interfere with cardiovascular system, we have studied the in vitro as well as in vivo effects of tributyltin bromide (TBT), triethyltin bromide (TET) and trimethyltin chloride (TMT) on cardiac SR Ca 2+ -pump activity, in order to know the relative potency of these tin compounds. SR was isolated from heart ventricles of male Sprague-Dawley rats and used for in vitro studies. For in vivo studies, rats were treated orally in corn oil for 6 days with different doses of TET (0.5, 1.0 and 1.5 mg/kg/d), TMT (0.75, 1.5 and 2.5 mg/kg/d) and TBT (0.75, 1.5 and 2.5 mg/kg/d). Rats were sacrificed 24 hr after the last dosage and cardiac SR was prepared. Cardiac SR Ca 2+ -ATPase and 45 Ca-uptake were measured. All the three tin compounds inhibited Ca 2+ -ATPase and 45 Ca-uptake in vitro in a concentration dependent manner. The order of potency for Ca 2+ -ATPase as determined IC 50 , is TBT (2 uM) > TET (63 uM) > TMT (280 uM). For 45 Ca-uptake, if followed the same order i.e., TBT (0.35 uM) > TET (10 uM) > TMT (440 uM). In agreement with in vitro results, both SR Ca 2+ -ATPase and 45 Ca-uptake were significantly inhibited in rats treated with these tin compounds. These studies indicate that triorganotin compounds affect Ca 2+ -pumping mechanisms and thereby alter cardiac contraction-relaxation process

Simultaneous characterization of metabolic, cardiac, vascular and renal phenotypes of lean and obese SHHF rats.

Science.gov (United States)

Youcef, Gina; Olivier, Arnaud; L'Huillier, Clément P J; Labat, Carlos; Fay, Renaud; Tabcheh, Lina; Toupance, Simon; Rodriguez-Guéant, Rosa-Maria; Bergerot, Damien; Jaisser, Frédéric; Lacolley, Patrick; Zannad, Faiez; Laurent Vallar; Pizard, Anne

2014-01-01

Individuals with metabolic syndrome (MetS) are prone to develop heart failure (HF). However, the deleterious effects of MetS on the continuum of events leading to cardiac remodeling and subsequently to HF are not fully understood. This study characterized simultaneously MetS and cardiac, vascular and renal phenotypes in aging Spontaneously Hypertensive Heart Failure lean (SHHF(+/?) regrouping (+/+) and (+/cp) rats) and obese (SHHF(cp/cp), "cp" defective mutant allele of the leptin receptor gene) rats. We aimed to refine the milestones and their onset during the progression from MetS to HF in this experimental model. We found that SHHF(cp/cp )but not SHHF(+/?) rats developed dyslipidemia, as early as 1.5 months of age. This early alteration in the lipidic profile was detectable concomitantly to impaired renal function (polyuria, proteinuria but no glycosuria) and reduced carotid distensibility as compared to SHHF(+/?) rats. By 3 months of age SHHFcp/cp animals developed severe obesity associated with dislipidemia and hypertension defining the onset of MetS. From 6 months of age, SHHF(+/?) rats developed concentric left ventricular hypertrophy (LVH) while SHHF(cp/cp) rats developed eccentric LVH apparent from progressive dilation of the LV dimensions. By 14 months of age only SHHF(cp/cp) rats showed significantly higher central systolic blood pressure and a reduced ejection fraction resulting in systolic dysfunction as compared to SHHF(+/?). In summary, the metabolic and hemodynamic mechanisms participating in the faster decline of cardiac functions in SHHF(cp/cp) rats are established long before their physiological consequences are detectable. Our results suggest that the molecular mechanisms triggered within the first three months after birth of SHHF(cp/cp) rats should be targeted preferentially by therapeutic interventions in order to mitigate the later HF development.

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

Science.gov (United States)

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

2016-06-01

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

Gene expression in cardiac tissues from infants with idiopathic conotruncal defects

Directory of Open Access Journals (Sweden)

Lofland Gary K

2011-01-01

Full Text Available Abstract Background Tetralogy of Fallot (TOF is the most commonly observed conotruncal congenital heart defect. Treatment of these patients has evolved dramatically in the last few decades, yet a genetic explanation is lacking for the failure of cardiac development for the majority of children with TOF. Our goal was to perform genome wide analyses and characterize expression patterns in cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot. Methods We employed genome wide gene expression microarrays to characterize cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery obtained at the time of reconstructive surgery from 19 children with TOF (16 idiopathic and three with 22q11.2 deletions and compared gene expression patterns to normally developing subjects. Results We detected a signal from approximately 26,000 probes reflecting expression from about half of all genes, ranging from 35% to 49% of array probes in the three tissues. More than 1,000 genes had a 2-fold change in expression in the right ventricle (RV of children with TOF as compared to the RV from matched control infants. Most of these genes were involved in compensatory functions (e.g., hypertrophy, cardiac fibrosis and cardiac dilation. However, two canonical pathways involved in spatial and temporal cell differentiation (WNT, p = 0.017 and Notch, p = 0.003 appeared to be generally suppressed. Conclusions The suppression of developmental networks may represent a remnant of a broad malfunction of regulatory pathways leading to inaccurate boundary formation and improper structural development in the embryonic heart. We suggest that small tissue specific genomic and/or epigenetic fluctuations could be cumulative, leading to regulatory network disruption and failure of proper cardiac development.

Cardiac Time Intervals by Tissue Doppler Imaging M-Mode

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Biering-Sørensen, Tor; Mogelvang, Rasmus; de Knegt, Martina Chantal

2016-01-01

PURPOSE: To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-mode through the mitral valve (MV). Furthermore, to evaluate the association of the myocardial performance index (MPI) obtained by TDI M-mode (MPITDI) and the conventional method of obtaining...

Dihydrotestosterone deteriorates cardiac insulin signaling and glucose transport in the rat model of polycystic ovary syndrome.

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Tepavčević, Snežana; Vojnović Milutinović, Danijela; Macut, Djuro; Žakula, Zorica; Nikolić, Marina; Božić-Antić, Ivana; Romić, Snježana; Bjekić-Macut, Jelica; Matić, Gordana; Korićanac, Goran

2014-05-01

It is supposed that women with polycystic ovary syndrome (PCOS) are prone to develop cardiovascular disease as a consequence of multiple risk factors that are mostly related to the state of insulin resistance and consequent hyperinsulinemia. In the present study, we evaluated insulin signaling and glucose transporters (GLUT) in cardiac cells of dihydrotestosterone (DHT) treated female rats as an animal model of PCOS. Expression of proteins involved in cardiac insulin signaling pathways and glucose transporters, as well as their phosphorylation or intracellular localization were studied by Western blot analysis in DHT-treated and control rats. Treatment with DHT resulted in increased body mass, absolute mass of the heart, elevated plasma insulin concentration, dyslipidemia and insulin resistance. At the molecular level, DHT treatment did not change protein expression of cardiac insulin receptor and insulin receptor substrate 1, while phosphorylation of the substrate at serine 307 was increased. Unexpectedly, although expression of downstream Akt kinase and its phosphorylation at threonine 308 were not altered, phosphorylation of Akt at serine 473 was increased in the heart of DHT-treated rats. In contrast, expression and phosphorylation of extracellular signal regulated kinases 1/2 were decreased. Plasma membrane contents of GLUT1 and GLUT4 were decreased, as well as the expression of GLUT4 in cardiac cells at the end of androgen treatment. The obtained results provide evidence for alterations in expression and especially in functional characteristics of insulin signaling molecules and glucose transporters in the heart of DHT-treated rats with PCOS, indicating impaired cardiac insulin action. Copyright © 2014 Elsevier Ltd. All rights reserved.

Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression.

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Knowlton, K U; Baracchini, E; Ross, R S; Harris, A N; Henderson, S A; Evans, S M; Glembotski, C C; Chien, K R

1991-04-25

To study the mechanisms which mediate the transcriptional activation of cardiac genes during alpha adrenergic stimulation, the present study examined the regulated expression of three cardiac genes, a ventricular embryonic gene (atrial natriuretic factor, ANF), a constitutively expressed contractile protein gene (cardiac MLC-2), and a cardiac sodium channel gene. alpha 1-Adrenergic stimulation activates the expression and release of ANF from neonatal ventricular cells. As assessed by RNase protection analyses, treatment with alpha-adrenergic agonists increases the steady-state levels of ANF mRNA by greater than 15-fold. However, a rat cardiac sodium channel gene mRNA is not induced, indicating that alpha-adrenergic stimulation does not lead to an increase in the expression of all cardiac genes. Studies employing a series of rat ANF luciferase and rat MLC-2 luciferase fusion genes identify 315- and 92-base pair cis regulatory sequences within an embryonic gene (ANF) and a constitutively expressed contractile protein gene (MLC-2), respectively, which mediate alpha-adrenergic-inducible gene expression. Transfection of various ANF luciferase reporters into neonatal rat ventricular cells demonstrated that upstream sequences which mediate tissue-specific expression (-3003 to -638) can be segregated from those responsible for inducibility. The lack of inducibility of a cardiac Na+ channel gene, and the segregation of ANF gene sequences which mediate cardiac specific from those which mediate inducible expression, provides further insight into the relationship between muscle-specific and inducible expression during cardiac myocyte hypertrophy. Based on these results, a testable model is proposed for the induction of embryonic cardiac genes and constitutively expressed contractile protein genes and the noninducibility of a subset of cardiac genes during alpha-adrenergic stimulation of neonatal rat ventricular cells.

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

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Fang-Fang Shen

2014-01-01

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

Cardiac, Metabolic and Molecular Profiles of Sedentary Rats in the Initial Moment of Obesity

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Bruno Barcellos Jacobsen

2017-10-01

Full Text Available Abstract Background: Different types of high-fat and/or high-energy diets have been used to induce obesity in rodents. However, few studies have reported on the effects observed at the initial stage of obesity induced by high-fat feeding on cardiac functional and structural remodelling. Objective: To characterize the initial moment of obesity and investigate both metabolic and cardiac parameters. In addition, the role of Ca2+ handling in short-term exposure to obesity was verified. Methods: Thirty-day-old male Wistar rats were randomized into two groups (n = 19 each: control (C; standard diet and high-fat diet (HF, unsaturated high-fat diet. The initial moment of obesity was defined by weekly measurement of body weight (BW complemented by adiposity index (AI. Cardiac remodelling was assessed by morphological, histological, echocardiographic and papillary muscle analysis. Ca2+ handling proteins were determined by Western Blot. Results: The initial moment of obesity occurred at the 3rd week. Compared with C rats, the HF rats had higher final BW (4%, body fat (20%, AI (14.5%, insulin levels (39.7%, leptin (62.4% and low-density lipoprotein cholesterol (15.5% but did not exhibit alterations in systolic blood pressure. Echocardiographic evaluation did not show alterations in cardiac parameters. In the HF group, muscles were observed to increase their +dT/dt (C: 52.6 ± 9.0 g/mm2/s and HF: 68.0 ± 17.0 g/mm2/s; p < 0.05. In addition, there was no changes in the cardiac expression of Ca2+ handling proteins. Conclusion: The initial moment of obesity promotes alterations to hormonal and lipid profiles without cardiac damage or changes in Ca2+ handling.

Effect of irradiation on glycosaminoglycans connect in rat tissue

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Drozdz, M; Kucharz, E; Glowacki, A; Zylka, J

1981-01-01

Glycosaminoglycan (GAGs) fractions were determined in tissues (skin, liver, lungs, aortic wall) and blood serum of rats irradiated with a single dose of 500 R. An increase of total GAGs as well as changes in the fractions were found in the tissues and urine of exposed rats.

Brain stem death as the vital determinant for resumption of spontaneous circulation after cardiac arrest in rats.

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Alice Y W Chang

Full Text Available BACKGROUND: Spontaneous circulation returns to less than half of adult cardiac arrest victims who received in-hospital resuscitation. One clue for this disheartening outcome arises from the prognosis that asystole invariably takes place, after a time lag, on diagnosis of brain stem death. The designation of brain stem death as the point of no return further suggests that permanent impairment of the brain stem cardiovascular regulatory machinery precedes death. It follows that a crucial determinant for successful revival of an arrested heart is that spontaneous circulation must resume before brain stem death commences. Here, we evaluated the hypothesis that maintained functional integrity of the rostral ventrolateral medulla (RVLM, a neural substrate that is intimately related to brain stem death and central circulatory regulation, holds the key to the vital time-window between cardiac arrest and resumption of spontaneous circulation. METHODOLOGY/PRINCIPAL FINDINGS: An animal model of brain stem death employing the pesticide mevinphos as the experimental insult in Sprague-Dawley rats was used. Intravenous administration of lethal doses of mevinphos elicited an abrupt cardiac arrest, accompanied by elevated systemic arterial pressure and anoxia, augmented neuronal excitability and enhanced microvascular perfusion in RVLM. This period represents the vital time-window between cardiac arrest and resumption of spontaneous circulation in our experimental model. Animals with restored spontaneous circulation exhibited maintained neuronal functionality in RVLM beyond this critical time-window, alongside resumption of baseline tissue oxygen and enhancement of local blood flow. Intriguingly, animals that subsequently died manifested sustained anoxia, diminished local blood flow, depressed mitochondrial electron transport activities and reduced ATP production, leading to necrotic cell death in RVLM. That amelioration of mitochondrial dysfunction and

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

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Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

2017-01-01

Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

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

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

2010-02-01

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

Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

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Götz Pilarczyk

2016-01-01

Full Text Available The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds.

5α-reductase activity in rat adipose tissue

International Nuclear Information System (INIS)

Zyirek, M.; Flood, C.; Longcope, C.

1987-01-01

We measured the 5 α-reductase activity in isolated cell preparations of rat adipose tissue using the formation of [ 3 H] dihydrotestosterone from [ 3 H] testosterone as an endpoint. Stromal cells were prepared from the epididymal fat pad, perinephric fat, and subcutaneous fat of male rats and from perinephric fat of female rats. Adipocytes were prepared from the epididymal fat pad and perinephric fat of male rats. Stromal cells from the epididymal fat pad and perinephric fat contained greater 5α-reductase activity than did the adipocytes from these depots. Stromal cells from the epididymal fat pad contained greater activity than those from perinephric and subcutaneous depots. Perinephric stromal cells from female rats were slightly more active than those from male rats. Estradiol (10 -8 M), when added to the medium, caused a 90% decrease in 5α-reductase activity. Aromatase activity was minimal, several orders of magnitude less than 5α-reductase activity in each tissue studied

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

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

2016-04-01

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

Serotonin-promoted elevation of ROS levels may lead to cardiac pathologies in diabetic rat

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Ali Tahir

2015-01-01

Full Text Available Patients with diabetes mellitus (DM develop tendencies toward heart disease. Hyperglycemia induces the release of serotonin from enterochromaffin cells (EC. Serotonin was observed to elevate reactive oxygen species (ROS and downregulate antioxidant enzymes. As a result, elevated levels of serotonin could contribute to diabetic complications, including cardiac hypertrophy. In the present study, diabetes mellitus was induced in rats by alloxan administration; this was followed by the administration of serotonin to experimental animals. ROS, catalase (CAT, superoxide dismutase (SOD, B-type natriuretic peptide (BNP expression, and histopathological assessments were performed. Elevated ROS concentrations and decreased antioxidant enzyme activities were detected. Further, we observed an increase in cell surface area and elevated BNP expression which suggests that events associated with cardiac hypertrophy were increased in serotonin-administered diabetic rats. We conclude that serotonin secretion in diabetes could contribute to diabetic complications, including cardiac hypertrophy, through enhanced ROS production.

Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model.

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Wei, Qin; Bian, Yeping; Yu, Fuchao; Zhang, Qiang; Zhang, Guanghao; Li, Yang; Song, Songsong; Ren, Xiaomei; Tong, Jiayi

2016-11-01

Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneous intermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5 weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis, and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), end-systolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fraction and fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normal arrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia induced factor (HIF)-1α, NF-kB, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of rats exposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronic intermittent hypoxia, which is associated with increased expression of HIF-1α and NF-kB signaling molecules and development of cardiac inflammation, apoptosis and fibrosis. © 2016 by the Journal of Biomedical Research. All rights reserved.

Characterization of upper thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in diabetic rats

DEFF Research Database (Denmark)

Ghorbani, Marie Louise M; Qin, Chao; Wu, Mingyuan

2011-01-01

The aim of the present study was to examine spinal processing of cardiac and somatic nociceptive input in rats with STZ-induced diabetes. Type 1 diabetes was induced with streptozotocin (50mg/kg) in 14 male Sprague-Dawley rats and citrate buffer was injected in 14 control rats. After 4-11weeks...

Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress

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Machi JF

2016-03-01

Full Text Available Jacqueline Freire Machi,1,2 Danielle da Silva Dias,3 Sarah Cristina Freitas,3 Oscar Albuquerque de Moraes,1 Maikon Barbosa da Silva,1 Paula Lázara Cruz,1 Cristiano Mostarda,4 Vera M C Salemi,1 Mariana Morris,2 Kátia De Angelis,3 Maria-Cláudia Irigoyen1 1Hypertension Unit, Heart Institute (InCor, School of Medicine, University of Sao Paulo, São Paulo, Brazil; 2Institute of Neuro-Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA; 3Laboratory of Translational Physiology, Universidade Nove de Julho (UNINOVE, São Paulo, 4Health Adult and Child, Federal University of Maranhao (UFMA, São Luiz, Maranhão, Brazil Objective: The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX. Methods: Female Wistar rats (3 or 22 months old were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal. After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Results: Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG was reduced in young ovariectomized, old controls, and old ovariectomized

Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats.

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Hu, Zhaoyang; Chen, Mou; Zhang, Ping; Liu, Jin; Abbott, Geoffrey W

2017-04-26

Sudden cardiac death (SCD), a leading cause of global mortality, most commonly arises from a substrate of cardiac ischemia, but requires an additional trigger. Diabetes mellitus (DM) predisposes to SCD even after adjusting for other DM-linked cardiovascular pathology such as coronary artery disease. We previously showed that remote liver ischemia preconditioning (RLIPC) is highly protective against cardiac ischemia reperfusion injury (IRI) linked ventricular arrhythmias and myocardial infarction, via induction of the cardioprotective RISK pathway, and specifically, inhibitory phosphorylation of GSK-3β (Ser 9). We evaluated the impact of acute streptozotocin-induced DM on coronary artery ligation IRI-linked ventricular arrhythmogenesis and RLIPC therapy in rats. Post-IRI arrhythmia induction was similar in nondiabetic and DM rats, but, unexpectedly, DM rats exhibited lower incidence of SCD during reperfusion (41 vs. 100%), suggesting uncontrolled hyperglycemia does not acutely predispose to SCD. RLIPC was highly effective in both nondiabetic and DM rats at reducing incidence and duration of, and increasing latency to, all classes of ventricular tachyarrhythmias. In contrast, atrioventricular block (AVB) was highly responsive to RLIPC in nondiabetic rats (incidence reduced from 72 to 18%) but unresponsive in DM rats. RISK pathway induction was similar in nondiabetic and DM rats, thus not explaining the DM-specific resistance of AVB to therapy. Our findings uncover important acute DM-specific differences in responsiveness to remote preconditioning for ventricular tachyarrhythmias versus AVB, which may have clinical significance given that AVB is a malignant arrhythmia twofold more common in human diabetics than nondiabetics, and correlated to plasma glucose levels >10 mmol/L.

Creation of Cardiac Tissue Exhibiting Mechanical Integration of Spheroids Using 3D Bioprinting.

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Ong, Chin Siang; Fukunishi, Takuma; Nashed, Andrew; Blazeski, Adriana; Zhang, Huaitao; Hardy, Samantha; DiSilvestre, Deborah; Vricella, Luca; Conte, John; Tung, Leslie; Tomaselli, Gordon; Hibino, Narutoshi

2017-07-02

This protocol describes 3D bioprinting of cardiac tissue without the use of biomaterials, using only cells. Cardiomyocytes, endothelial cells and fibroblasts are first isolated, counted and mixed at desired cell ratios. They are co-cultured in individual wells in ultra-low attachment 96-well plates. Within 3 days, beating spheroids form. These spheroids are then picked up by a nozzle using vacuum suction and assembled on a needle array using a 3D bioprinter. The spheroids are then allowed to fuse on the needle array. Three days after 3D bioprinting, the spheroids are removed as an intact patch, which is already spontaneously beating. 3D bioprinted cardiac patches exhibit mechanical integration of component spheroids and are highly promising in cardiac tissue regeneration and as 3D models of heart disease.

Traditional Chinese Medicine ShenZhuGuanXin Granules Mitigate Cardiac Dysfunction and Promote Myocardium Angiogenesis in Myocardial Infarction Rats by Upregulating PECAM-1/CD31 and VEGF Expression

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Dan-Ping Xu

2017-01-01

Full Text Available Background. Myocardial infarction (MI is the main cause of global mortality and morbidity despite the development of therapeutic approaches. ShenZhuGuanXin granules (SG have been shown to possess cardioprotective effects against coronary heart disease (CHD. However, little is known about its specific mechanism. The present study aimed to investigate the therapeutic effect of SG in cardiac dysfunction and to demonstrate whether SG can promote myocardium angiogenesis by establishing a rat model of myocardial infarction with left anterior descending ligating. Methods and Results. Three days after MI, rats were randomly divided into six groups: sham group (sham, MI group (MI, MI + low dose SG (SG-L group, MI + middle dose SG (SG-M group, MI + high dose SG (SG-H group, and MI + compound Danshen dropping pills (CDDP group as a positive control. Four weeks after administration, rats underwent hemodynamics and echocardiography study. Ventricle tissues were processed for histology and immunohistochemistry studies. Compared with MI group, SG treatment dose-dependently improved cardiac hemodynamic function, attenuated infarct size, increased microvessel density, and increased the expression of PECAM-1/CD31 and VEGF. Conclusions. SG dose-dependently improved cardiac hemodynamic function and attenuated infarct size by promoting angiogenesis through upregulating PECAM-1/CD31 and VEGF expression.

Extract of Lycopus europaeus L. reduces cardiac signs of hyperthyroidism in rats.

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Vonhoff, Christian; Baumgartner, Andreas; Hegger, Mirjam; Korte, Brigitte; Biller, Andreas; Winterhoff, Hilke

2006-02-02

Extracts from the plant Lycopus europaeus L. are traditionally used in mild forms of hyperthyroidism. High doses caused a reduction of TSH or thyroid hormone levels in animal experiments, whereas in hyperthyroid patients treated with low doses of Lycopus an improvement of cardiac symptoms was reported without major changes in TSH or thyroid hormone concentrations. Lycopus extract was tested in thyroxine treated hyperthyroid rats (0.7 mg/kg BW i.p.). Co-treatment with an hydroethanolic extract from L. europaeus L. started one week later than T4-application and lasted 5.5 weeks. As reference substance atenolol was used. The raised body temperature was reduced very effectively even by the low dose of the plant extract, whereas the reduced gain of body weight and the increased food intake remained unaffected by any treatment. No significant changes of thyroid hormone concentrations or TSH levels were observed. Lycopus extract and atenolol reduced the increased heart rate and blood pressure. The cardiac hypertrophy was alleviated significantly by both treatment regimes. beta-Adrenoceptor density in heart tissue was significantly reduced by the Lycopus extract or the beta-blocking agent showing an almost equal efficacy. Although the mode of action remains unclear, these organo-specific anti-T4-effects seem to be of practical interest, for example in patients with latent hyperthyroidism.

In vitro assessment of cardiac performance after irradiation using an isolated working rat heart preparation

International Nuclear Information System (INIS)

Wondergem, J.; Laarse, A. van der; Ravels, F.J.M. van; Wermeskerken, A.-M. van; Verhoeve, H.R.; Graaf, B.W. de; Leer, J.W.H.

1991-01-01

The effect of irradiation on cardiac function was assessed using an isolated working rat heart preparation. The animals were given single doses of X-rays in the range 15-30 Gy to their hearts. Cardiac output (CO = aortic flow + coronary flow), heart weight and body weight were followed for a period of 10 months after treatment. Irradiation led to a decrease in cardiac function. This reduction was dose-dependent and progressive with time after treatment. The shape of the Frank-Starling curves constructed for irradiated hearts suggests a loss of contractile function of the myocardium. Coronary flow rates measured in 'working' hearts and in 'Langendorff' hearts were not significantly changed by the irradiation treatment. The isolated working rat heart preparation proved to be a simple and suitable animal model for the investigation of irradiation-induced cardiotoxicity. (author)

Identification and target prediction of miRNAs specifically expressed in rat neural tissue

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Tu Kang

2009-05-01

Full Text Available Abstract Background MicroRNAs (miRNAs are a large group of RNAs that play important roles in regulating gene expression and protein translation. Several studies have indicated that some miRNAs are specifically expressed in human, mouse and zebrafish tissues. For example, miR-1 and miR-133 are specifically expressed in muscles. Tissue-specific miRNAs may have particular functions. Although previous studies have reported the presence of human, mouse and zebrafish tissue-specific miRNAs, there have been no detailed reports of rat tissue-specific miRNAs. In this study, Home-made rat miRNA microarrays which established in our previous study were used to investigate rat neural tissue-specific miRNAs, and mapped their target genes in rat tissues. This study will provide information for the functional analysis of these miRNAs. Results In order to obtain as complete a picture of specific miRNA expression in rat neural tissues as possible, customized miRNA microarrays with 152 selected miRNAs from miRBase were used to detect miRNA expression in 14 rat tissues. After a general clustering analysis, 14 rat tissues could be clearly classified into neural and non-neural tissues based on the obtained expression profiles with p values Conclusion Our work provides a global view of rat neural tissue-specific miRNA profiles and a target map of miRNAs, which is expected to contribute to future investigations of miRNA regulatory mechanisms in neural systems.

Ciprofloxacin, an antibiotic with cardiac actions on isolated rat hearts

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Loipa Galán-Martínez

2018-04-01

Full Text Available Context: Ciprofloxacin is the most commonly used fluoroquinolone and is prescribed as the antibiotic of choice in the treatment of several microbial infections. Some clinical reports have suggested that ciprofloxacin may induce QT-interval prolongation and Torsades de Pointes arrhythmias. This drug is a weak inhibitor of a rapid component of the cardiac delayed rectifier potassium current IKr, but there are few electrophysiological data available to assess whether ciprofloxacin has the potency to provoke QT prolongation and subsequent Torsades de Pointes arrhythmias. Aims: To evaluate the effect of ciprofloxacin on the contractile and electrical activity of isolated rat hearts. Methods: The Langendorff technique was performed in rat hearts, and the effects of ciprofloxacin (0.001 – 100 μM were measured on the cardiac force of contraction and on the RR, QRS and QTc intervals. The arrhythmogenic potential and the ventricular fibrillation threshold were evaluated with ciprofloxacin. Results: Ciprofloxacin decreased the force of contraction of all hearts studied, in a concentration-dependent manner. The estimated IC50 for the inotropic negative effect was 0.15 ± 0.04 μM. Ciprofloxacin significantly prolonged the QRS complex, QTc and RR interval. Significant arrhythmic effects with ciprofloxacin were shown and the ventricular fibrillation threshold was decreased. Conclusions: These results suggest that ciprofloxacin exerted effects on cardiac Na+, K+ and Ca2+ channels. The actions of ciprofloxacin require further studies at the cellular level. These conclusions may account for clinical data that have been reported previously.

Three-Dimensional Human Cardiac Tissue Engineered by Centrifugation of Stacked Cell Sheets and Cross-Sectional Observation of Its Synchronous Beatings by Optical Coherence Tomography.

Science.gov (United States)

Haraguchi, Yuji; Hasegawa, Akiyuki; Matsuura, Katsuhisa; Kobayashi, Mari; Iwana, Shin-Ichi; Kabetani, Yasuhiro; Shimizu, Tatsuya

2017-01-01

Three-dimensional (3D) tissues are engineered by stacking cell sheets, and these tissues have been applied in clinical regenerative therapies. The optimal fabrication technique of 3D human tissues and the real-time observation system for these tissues are important in tissue engineering, regenerative medicine, cardiac physiology, and the safety testing of candidate chemicals. In this study, for aiming the clinical application, 3D human cardiac tissues were rapidly fabricated by human induced pluripotent stem (iPS) cell-derived cardiac cell sheets with centrifugation, and the structures and beatings in the cardiac tissues were observed cross-sectionally and noninvasively by two optical coherence tomography (OCT) systems. The fabrication time was reduced to approximately one-quarter by centrifugation. The cross-sectional observation showed that multilayered cardiac cell sheets adhered tightly just after centrifugation. Additionally, the cross-sectional transmissions of beatings within multilayered human cardiac tissues were clearly detected by OCT. The observation showed the synchronous beatings of the thicker 3D human cardiac tissues, which were fabricated rapidly by cell sheet technology and centrifugation. The rapid tissue-fabrication technique and OCT technology will show a powerful potential in cardiac tissue engineering, regenerative medicine, and drug discovery research.

Evolution from increased cardiac mechanical function towards cardiomyopathy in the obese rat due to unbalanced high fat and abundant equilibrated diets

Directory of Open Access Journals (Sweden)

Mourmoura Evangelia

2015-07-01

Full Text Available The aim of our study was to know whether high dietary energy intake (HDEI with equilibrated and unbalanced diets in term of lipid composition modify the fatty acid profile of cardiac phospholipids and function of various cardiac cells and to know if the changes in membrane lipid composition can explain the modifications of cellular activity. Wistar rats were fed either a control or high-fat (HF diet for 12 weeks and Zucker diabetic fatty (ZDF rats as well as their lean littermate (ZL a control diet between week 7 to 11 of their life. Energy intake and abdominal obesity was increased in HF-fed and ZDF rats. Circulating lipids were also augmented in both strains although hyperglycemia was noticed only in ZDF rats. HDEI induced a decrease in linoleate and increase in arachidonate in membrane phospholipids which was more pronounced in the ZDF rats compared to the HF-fed rats. In vivo cardiac function (CF was improved in HF-fed rats whereas ex vivo cardiac function was unchanged, suggesting that environmental factors such as catecholamines stimulated the in vivo CF. The unchanged ex vivo CF was associated with an increased cardiac mass which indicated development of fibrosis and/or hypertrophy. The increased in vivo CF was sustained by an augmented coronary reserve which was related to the cyclooxygenase pathway and accumulation of arachidonate in membrane phospholipids. In conclusion, before triggering a diabetic cardiomyopathy, HDEI stimulated the CF. The development of cardiomyopathy seems to result from fibrosis and/or hypertrophy which augments myocardial stiffness and decreases contractility.

Acid-base balance and cardiac index in SO2-bronchitic, papaine-emphysematous and paraquat-fibrotic rats after isoproterenol treatment.

Science.gov (United States)

Vértes, K; Debreczeni, L A

1990-01-01

SO2-bronchitis, papaine-emphysema and paraquat fibrosis were induced in Wistar rats. Blood pressure, cardiac index, total peripheral resistance, arterial blood gas values, parameters of acid-base balance were determined. Effects of 0.1 and 0.3 microgram.-1.min-1 isoproterenol iv. infusion were examined. Morphologic alterations of the lungs were verified by histopathological examinations. All the parameters investigated were found to be normal in the control rats. The treated groups differed from the normal ones: an increased blood pressure was observed in emphysema and fibrosis. A decreased cardiac index was characteristic of chronic bronchitis, high cardiac index of emphysema, high TPR of bronchitis and arterial hypoxaemy of fibrosis. The groups reacted differently to beta adrenergic stimulation: in bronchitic and fibrotic rats the cardiac index was augmented, whereas in emphysematous ones the increase proved to be smaller. The effects of isoproterenol infusion can be related to the altered beta-receptor function in the various experimental pulmonary diseases.

Taurine content of tissues of irradiated rats

International Nuclear Information System (INIS)

Akhalaya, M.Ya.; Bogatyrev, G.P.; Kudryashov, Yu.B.; Yartsev, E.I.

1976-01-01

The taurine content of tissues (liver, stomach, small intestine and spleen) of rats irradiated with doses of 700 and 450 rads has been studied. Phase changes have been found in the taurine content of radiosensitive tissues in the course of radiation injury development

Simulation of electrochemical processes in cardiac tissue based on cellular automaton

International Nuclear Information System (INIS)

Avdeev, S A; Bogatov, N M

2014-01-01

A new class of cellular automata using special accumulative function for nonuniformity distribution is presented. Usage of this automata type for simulation of excitable media applied to electrochemical processes in human cardiac tissue is shown

Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism.

Science.gov (United States)

Hassan, Wafaa A; Rahman, Taghride Abdel; Aly, Mona S; Shahat, Asmaa S

2013-08-01

The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Cardiac retention of PET neuronal imaging agent LMI1195 in different species: Impact of norepinephrine uptake-1 and -2 transporters

International Nuclear Information System (INIS)

Yu, Ming; Bozek, Jody; Kagan, Mikhail; Guaraldi, Mary; Silva, Paula; Azure, Michael; Onthank, David; Robinson, Simon P.

2013-01-01

Introduction: Released sympathetic neurotransmitter norepinephrine (NE) in the heart is cleared by neuronal uptake-1 and extraneuronal uptake-2 transporters. Cardiac uptake-1 and -2 expression varies among species, but the uptake-1 is the primary transporter in humans. LMI1195 is an NE analog labeled with 18 F for PET evaluation of cardiac neuronal function. This study investigated the impact of cardiac neuronal uptake-1 associated with different species on LMI1195 heart uptake. Methods: Cardiac uptake-1 was blocked by desipramine, a selective uptake-1 inhibitor, and sympathetic neuronal denervation was induced by 6-hydroxydopamine, a neurotoxin, in rats, rabbits and nonhuman primates (NHP). Tissue biodistribution and cardiac imaging of LMI1195 and 123 I-metaiodobenzylguanidine (MIBG) were performed. Results: In rats, uptake-1 blockade did not alter LMI1195 heart uptake compared to the control at 60-min post injection [1.41 ± 0.07 vs. 1.47 ± 0.23 % injected dose per gram tissue (%ID/g)]. In contrast, LMI1195 heart uptake was reduced by 80% in uptake-1 blocked rabbits. In sympathetically denervated rats, LMI1195 heart uptake was similar to the control (2.18 ± 0.40 vs. 2.58 ± 0.76 %ID/g). However, the uptake decreased by 79% in denervated rabbits. Similar results were found in MIBG heart uptake in rats and rabbits with uptake-1 blockade. Consistently, LMI1195 cardiac imaging showed comparable myocardial activity in uptake-1 blocked or sympathetically denervated rats to the control, but marked activity reduction in uptake-1 blocked or denervated rabbits and NHPs. Conclusions: LMI1195 is retained in the heart of rabbits and NHPs primarily via the neuronal uptake-1 with high selectivity and can be used for evaluation of cardiac sympathetic denervation. Similar to the human, the neuronal uptake-1 is the dominant transporter for cardiac retention of NE analogs in rabbits and NHPs, but not in rats

Cardiac time intervals by tissue Doppler imaging M-mode echocardiography

DEFF Research Database (Denmark)

Biering-Sørensen, Tor

2016-01-01

for myocardial myocytes to achieve an LV pressure equal to that of aorta increases, resulting in a prolongation of the isovolumic contraction time (IVCT). Furthermore, the ability of myocardial myocytes to maintain the LV pressure decreases, resulting in reduction in the ejection time (ET). As LV diastolic...... of whether the LV is suffering from impaired systolic or diastolic function. A novel method of evaluating the cardiac time intervals has recently evolved. Using tissue Doppler imaging (TDI) M-mode through the mitral valve (MV) to estimate the cardiac time intervals may be an improved method reflecting global...

Cardiac function of the naked mole-rat: ecophysiological responses to working underground.

Science.gov (United States)

Grimes, Kelly M; Voorhees, Andrew; Chiao, Ying Ann; Han, Hai-Chao; Lindsey, Merry L; Buffenstein, Rochelle

2014-03-01

The naked mole-rat (NMR) is a strictly subterranean rodent with a low resting metabolic rate. Nevertheless, it can greatly increase its metabolic activity to meet the high energetic demands associated with digging through compacted soils in its xeric natural habitat where food is patchily distributed. We hypothesized that the NMR heart would naturally have low basal function and exhibit a large cardiac reserve, thereby mirroring the species' low basal metabolism and large metabolic scope. Echocardiography showed that young (2-4 yr old) healthy NMRs have low fractional shortening (28 ± 2%), ejection fraction (43 ± 2%), and cardiac output (6.5 ± 0.4 ml/min), indicating low basal cardiac function. Histology revealed large NMR cardiomyocyte cross-sectional area (216 ± 10 μm(2)) and cardiac collagen deposition of 2.2 ± 0.4%. Neither of these histomorphometric traits was considered pathological, since biaxial tensile testing showed no increase in passive ventricular stiffness. NMR cardiomyocyte fibers showed a low degree of rotation, contributing to the observed low NMR cardiac contractility. Interestingly, when the exercise mimetic dobutamine (3 μg/g ip) was administered, NMRs showed pronounced increases in fractional shortening, ejection fraction, cardiac output, and stroke volume, indicating an increased cardiac reserve. The relatively low basal cardiac function and enhanced cardiac reserve of NMRs are likely to be ecophysiological adaptations to life in an energetically taxing environment.

The Effects of Mangiferin (Mangifera indica L) in Doxorubicin-induced Cardiotoxicity in Rats.

Science.gov (United States)

Arozal, W; Suyatna, F D; Juniantito, V; Rosdiana, D S; Amurugam, S; Aulia, R; Monayo, E R; Siswandi, R

2015-11-01

The cardiotoxicity effect of doxorubicin (DOX), a widely used antitumor agent has restricted its clinical application. The aim of the current study was to explore the potential protective effect of mangiferin, a naturally occurring glucosylxanthone, that have antioxidant activity by its iron-complexing ability in mitochondria, against DOX-induced cardiac toxicity in rats in comparison with other antioxidants namely Sylimarin (SYL) and Vitamin E (VitE). Mangiferin was given orally to rats at a dose of 50, and 100 mg/kg for 5 weeks, and DOX was injected at a total dose of 15 mg/kg. Cardiac toxicity was evaluated by lactate dehydrogenase and creatine kinase in the serum, malondialdehyde (MDA) level in plasma and cardiac tissue, and antioxidant enzyme superoxide dismutase (SOD) in cardiac tissue. Mangiferin protected against DOX-induced increased mortality and electrocardiogram abnormality and decreased biochemical markers of cardiac toxicity i. e., lactate dehydrogenase and creatine phosphokinase isoenzyme. In addition, elevation of plasma and cardiac tissue levels of MDA in response to DOX treatment were significantly attenuated. The reduction of cardiac activity of SOD was significantly reduced in contrast with the other antioxidant SYL and Vit E. Histopathologically, mangiferin treatment showed significant reduction in inflammatory cell number, fibrotic area, and necrotic foci as compared with DOX only-treated rats. These results suggested that mangiferin had better protective effect against DOX-induced cardiac toxicity in comparison with SYL and VitE, thus besides the antioxidant activity, different mechanism may be involved in the action of mangiferin and need to be clarified in the future studies. © Georg Thieme Verlag KG Stuttgart · New York.

Dyrk1A-ASF-CaMKIIδ Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats.

Science.gov (United States)

Yao, Jian; Qin, Xiaotong; Zhu, Jianhua; Sheng, Hongzhuan

2016-01-01

It is known that the expression, activity and alternative splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) are dysregulated in the cardiac remodeling process. Recently, we found a further signaling pathway, by which dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) regulates the alternative splicing of CaMKIIδ via the alternative splicing factor (ASF), i.e., Dyrk1A-ASF-CaMKIIδ. In this study, we aimed to investigate whether Dyrk1A-ASF-CaMKIIδ signaling was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats. Rats were subjected to two kidney-one clip (2K1C) surgery and then treated with valsartan (30 mg/kg/day) for 8 weeks. Hypertrophic parameter analysis was then performed. Western blot analysis was used to determine the protein expression of Dyrk1A and ASF and RT-PCR was used to analyze the alternative splicing of CaMKIIδ in the left ventricular (LV) sample. Valsartan attenuated cardiac hypertrophy in 2K1C rats but without impairment of cardiac systolic function. Increased protein expression of Dyrk1A and decreased protein expression of ASF were observed in the LV sample of 2K1C rats. Treatment of 2K1C rats with valsartan reversed the changes in Dyrk1A and ASF expression in the LV sample. Valsartan adjusted the 2K1C-induced imbalance in alternative splicing of CaMKIIδ by upregulating the mRNA expression of CaMKIIδC and downregulating the mRNA expression of CaMKIIδA and CaMKIIδB. Valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats was mediated, at least partly, by Dyrk1A-ASF-CaMKIIδ signaling. © 2015 S. Karger AG, Basel.

Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylp ropylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats

International Nuclear Information System (INIS)

Samnick, Samuel; Scheuer, Claudia; Muenks, Sven; El-Gibaly, Amr M.; Menger, Michael D.; Kirsch, Carl-Martin

2004-01-01

In developing technetium-99m-based radioligands for in vivo studies of cardiac adrenergic neurons, we compared the uptake characteristics of the 99m Tc-labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylpropylamino)-piperidine ( 99m Tc-FBPBAT) with those of the clinically established meta-[ 123 I]iodobenzylguanidine ( 123 I-MIBG) in rat vascular smooth muscle cells and neonatal cardiac myocytes. Furthermore, the cardiac and extracardiac uptake of both radiopharmaceuticals was assessed in intact rats and in rats pretreated with various α- and β-adrenoceptor drugs, and adrenergic reuptake blocking agents. The uptake of 99m Tc-FBPBAT and 123 I-MIBG into vascular smooth muscle cells and neonatal cardiac myocytes was rapid; more than 85% of the radioactivity accumulation into the cells occurring within the first 3 minutes. Radioactivity uptake after a 60-minute incubation at 37 degree sign C (pH 7.4) varied from 15% to 65% of the total loaded activity per million cells. In all cases, 99m Tc-FBPBAT showed the higher uptake, relative to 123 I-MIBG, at any given cell concentration. The cellular uptake of 99m Tc-FBPBAT was lower at 4 degree sign C and 20 degree sign C than at 37 degree sign C. In contrast, the 123 I-MIBG uptake was only slightly temperature dependent. Inhibition experiments confirmed that the cellular uptake of 123 I-MIBG is mediated by the uptake-I carrier, whereas α 1 - and β 1 -adrenoceptors were predominantly involved in the uptake of 99m Tc-FBPBAT into the cardiovascular tissues. Biodistribution studies in rats showed that 99m Tc-FBPBAT accumulated in myocardium after intravenous injection. Radioactivity in rat heart amounted to 2.32% and 1.91% of the injected dose per gram at 15 and 60 minutes postinjection, compared with 3.10% and 2.21% injected dose per gram of tissue (%ID/g) in the experiment with 123 I-MIBG, respectively. Prazosin, urapidil, and metoprolol were as effective as treatment with other adrenergic

Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylp ropylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats

Energy Technology Data Exchange (ETDEWEB)

Samnick, Samuel E-mail: rassam@uniklinik-saarland.de; Scheuer, Claudia; Muenks, Sven; El-Gibaly, Amr M.; Menger, Michael D.; Kirsch, Carl-Martin

2004-05-01

In developing technetium-99m-based radioligands for in vivo studies of cardiac adrenergic neurons, we compared the uptake characteristics of the {sup 99m}Tc-labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylpropylamino)-piperidine ({sup 99m}Tc-FBPBAT) with those of the clinically established meta-[{sup 123}I]iodobenzylguanidine ({sup 123}I-MIBG) in rat vascular smooth muscle cells and neonatal cardiac myocytes. Furthermore, the cardiac and extracardiac uptake of both radiopharmaceuticals was assessed in intact rats and in rats pretreated with various {alpha}- and {beta}-adrenoceptor drugs, and adrenergic reuptake blocking agents. The uptake of {sup 99m}Tc-FBPBAT and {sup 123}I-MIBG into vascular smooth muscle cells and neonatal cardiac myocytes was rapid; more than 85% of the radioactivity accumulation into the cells occurring within the first 3 minutes. Radioactivity uptake after a 60-minute incubation at 37 degree sign C (pH 7.4) varied from 15% to 65% of the total loaded activity per million cells. In all cases, {sup 99m}Tc-FBPBAT showed the higher uptake, relative to {sup 123}I-MIBG, at any given cell concentration. The cellular uptake of {sup 99m}Tc-FBPBAT was lower at 4 degree sign C and 20 degree sign C than at 37 degree sign C. In contrast, the {sup 123}I-MIBG uptake was only slightly temperature dependent. Inhibition experiments confirmed that the cellular uptake of {sup 123}I-MIBG is mediated by the uptake-I carrier, whereas {alpha}{sub 1}- and {beta}{sub 1}-adrenoceptors were predominantly involved in the uptake of {sup 99m}Tc-FBPBAT into the cardiovascular tissues. Biodistribution studies in rats showed that {sup 99m}Tc-FBPBAT accumulated in myocardium after intravenous injection. Radioactivity in rat heart amounted to 2.32% and 1.91% of the injected dose per gram at 15 and 60 minutes postinjection, compared with 3.10% and 2.21% injected dose per gram of tissue (%ID/g) in the experiment with {sup 123}I

Implementation of near-infrared spectroscopy in a rat model of cardiac arrest and resuscitation

Science.gov (United States)

Rodriguez, Juan G.; Xiao, Feng; Ferrara, Davon; Ewing, Jennifer; Zhang, Shu; Alexander, Steven; Battarbee, Harold

2002-07-01

Transient global cerebral ischemia accompanying cardiac arrest (CA) often leads to permanent brain damage with poor neurological outcome. The precise chain of events underlying the cerebral damage after CA is still not fully understood. Progress in this area may profit from the development of new non-invasive tools that provide real-time information on the vascular and cellular processes preceding the damage. One way to assess these processes is through near-IR spectroscopy, which has demonstrated the ability to quantify changes in blood volume, hemoglobin oxygenation, cytochrome oxidase redox state, and tissue water content. Here we report on the successful implementation of this form of spectroscopy in a rat model of asphyxial CA and resuscitation, under hypothermic and normothermic conditions. Preliminary results are shown that provide a new temporal insight into the cerebral circulation during CA and post-resuscitation.

Development and Implementation of Discrete Polymeric Microstructural Cues for Applications in Cardiac Tissue Engineering

Science.gov (United States)

Pinney, James Richardson

Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. Despite care in the acute setting of MI, subsequent development of scar tissue and a lack of treatments for this maladaptive response lead to a poor prognosis. This has increased burdens on the cost of healthcare due to chronic disability. Here a novel therapeutic strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructural cues to attenuate the fibrotic response and improve functional outcomes is presented. Additionally, applications of integrated chemical functionalizations into discrete, micro-scale polymer structures are discussed in the realm of tissue engineering in order to impart enhancements in in vivo localization, three-dimensional manipulation and drug delivery. Polymeric microstructures, termed "microrods" and "microcubes", were fabricated using photolithographic techniques and studied in three-dimensional culture models of the fibrotic environment and by direct injection into the infarct zone of adult Sprague-Dawley rats. In vitro gene expression and functional and histological results were analyzed, showing a dose-dependent down-regulation fibrotic indicators and improvement in cardiac function. Furthermore, iron oxide nanoparticles and functionalized fluorocarbons were incorporated into the polymeric microdevices to promote in situ visualization by magnetic resonance imaging as well as to facilitate the manipulation and alignment of microstructural cues in a tissue-realistic environment. Lastly, successful encapsulation of native MGF peptide within microrods is demonstrated with release over two weeks as a proof of concept in the ability to locally deliver myogenic or supportive pharmacotherapeutics to the injured myocardium. This work demonstrates the efficacy and versatility of discrete microtopographical cues to attenuate the fibrotic response after MI and suggests a novel

Real time assessment of RF cardiac tissue ablation with optical spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Demos, S G; Sharareh, S

2008-03-20

An optical spectroscopy approach is demonstrated allowing for critical parameters during RF ablation of cardiac tissue to be evaluated in real time. The method is based on incorporating in a typical ablation catheter transmitting and receiving fibers that terminate at the tip of the catheter. By analyzing the spectral characteristics of the NIR diffusely reflected light, information is obtained on such parameters as, catheter-tissue proximity, lesion formation, depth of penetration of the lesion, formation of char during the ablation, formation of coagulum around the ablation site, differentiation of ablated from healthy tissue, and recognition of micro-bubble formation in the tissue.

Time-dependent responses of rat troponin I and cardiac injury following isoproterenol administration

Directory of Open Access Journals (Sweden)

Sabaheta Hasić

2011-02-01

Full Text Available Aim To develop a rat model of myocardial infarction induced by isoproterenol (ISO. We investigated a type of histological myocardial changes and cardiac troponin I (TnI kinetic. Methods The study has used adult, male, Wistar strain rats. Rats were distributed in ISO and control groups. Rats treated with ISO were divided into groups according to the time of cTnI and myocardial lesion analyses: ISO I (30’, ISO II (60’, ISO III (120’ and ISO IV (240’. We determined cTnI (Life Diagnostics Inc. West Chester PA, USA in the serum by ELISA method. We performed histological analysis on the specimens of left ventricular wall stained by hematoxillin-eosin (HE method. Results The irst statistically signiicant rise of cTnI was noted 30 minutes after the ISO administration. There was no statistically signiicant difference between cTnI mean values among the ISO groups. Observed myocardial histological changes were time dependent. Conclusions This model can be suitable for cardioprotective and cardiotoxicity supstance investigations followed by cTnI measurement in blood. The similarity between induced myocardial lesion on animal model in our study and human myocardial lesion in ischemia give us suficient impulse for further preclinical researches of new cardiac markers.

Tritium metabolism in rat tissues

International Nuclear Information System (INIS)

Takeda, H.

1982-01-01

As part of a series of studies designed to evaluate the relative radiotoxicity of various tritiated compounds, metabolism of tritium in rat tissues was studied after administration of tritiated water, leucine, thymidine, and glucose. The distribution and retention of tritium varied widely, depending on the chemical compound administered. Tritium introduced as tritiated water behaved essentially as body water and became uniformly distributed among the tissues. However, tritium administered as organic compounds resulted in relatively high incorporation into tissue constituents other than water, and its distribution differed among the various tissues. Moreover, the excretion rate of tritium from tissues was slower for tritiated organic compounds than for tritiated water. Administrationof tritiated organic compounds results in higher radiation doses to the tissues than does administration of tritiated water. Among the tritiated compounds examined, for equal radioactivity administered, leucine gave the highest radiation dose, followed in turn by thymidine, glucose, and water. (author)

Endogenous synthesis of taurine and GABA in rat ocular tissues

Energy Technology Data Exchange (ETDEWEB)

Heinaemaeki, A.A.

1988-01-01

The endogenous production of taurine and ..gamma..-aminobutyric acid (GABA) in rat ocular tissues was investigated. The activities of taurine-producing enzyme, cysteine sulfinic acid decarboxylase (CSAD), and GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), were observed in the retina, lens, iris-ciliary body and cornea. The highest specific activity of CSAD was in the cornea and that of GAD in the retina. The discrepancy between CSAD activity and taurine content within the ocular tissues indicates that intra- or extraocular transport processes may regulate the concentration of taurine on the rat eye. The GAD activity and the content of GABA were distributed in parallel within the rat ocular tissues. The quantitative results suggest that the GAD/GABA system has functional significance only in the retina of the rat eye.

Endogenous synthesis of taurine and GABA in rat ocular tissues

International Nuclear Information System (INIS)

Heinaemaeki, A.A.

1988-01-01

The endogenous production of taurine and γ-aminobutyric acid (GABA) in rat ocular tissues was investigated. The activities of taurine-producing enzyme, cysteine sulfinic acid decarboxylase (CSAD), and GABA-synthesizing enzyme, glutamic acid decarboxylase (GAD), were observed in the retina, lens, iris-ciliary body and cornea. The highest specific activity of CSAD was in the cornea and that of GAD in the retina. The discrepancy between CSAD activity and taurine content within the ocular tissues indicates that intra- or extraocular transport processes may regulate the concentration of taurine on the rat eye. The GAD activity and the content of GABA were distributed in parallel within the rat ocular tissues. The quantitative results suggest that the GAD/GABA system has functional significance only in the retina of the rat eye. (author)

Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators

Science.gov (United States)

Shin, Su Ryon; Jung, Sung Mi; Zalabany, Momen; Kim, Keekyoung; Zorlutuna, Pinar; Kim, Sang bok; Nikkhah, Mehdi; Khabiry, Masoud; Azize, Mohamed; Kong, Jing; Wan, Kai-tak; Palacios, Tomas; Dokmeci, Mehmet R.; Bae, Hojae; Tang, Xiaowu (Shirley); Khademhosseini, Ali

2013-01-01

We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT) incorporated photocrosslinkable gelatin methacrylate (GelMA) hydrogel. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework is the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell-cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity. PMID:23363247

Flexible shape-memory scaffold for minimally invasive delivery of functional tissues

Science.gov (United States)

Montgomery, Miles; Ahadian, Samad; Davenport Huyer, Locke; Lo Rito, Mauro; Civitarese, Robert A.; Vanderlaan, Rachel D.; Wu, Jun; Reis, Lewis A.; Momen, Abdul; Akbari, Saeed; Pahnke, Aric; Li, Ren-Ke; Caldarone, Christopher A.; Radisic, Milica

2017-10-01

Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold’s shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved.

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

Science.gov (United States)

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

2017-01-28

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

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

OpenAIRE

Lee, Eunjo; Song, Min-ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

2016-01-01

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats...

Influence of the polyol pathway on norepinephrine transporter reduction in diabetic cardiac sympathetic nerves: implications for heterogeneous accumulation of MIBG

International Nuclear Information System (INIS)

Kiyono, Yasushi; Kajiyama, Satomi; Fujiwara, Hiromi; Kanegawa, Naoki; Saji, Hideo

2005-01-01

Cardiac scintigraphic studies using 123 I-labeled metaiodobenzylguanidine ([ 123 I]MIBG) have demonstrated heterogeneous myocardial accumulation of MIBG in diabetes. The accumulation has been found to correlate with a heterogeneous decrease in the expression of norepinephrine transporter (NET). In diabetic peripheral nerve tissue, polyol pathways are activated and cause nerve dysfunction and degeneration. However, there has been little research on the polyol pathway and cardiac sympathetic nerves. Therefore, to assess the influence of the polyol pathway on cardiac sympathetic nervous function, we investigated the regional accumulation of MIBG and NET protein expression in diabetic model rats treated with aldose reductase inhibitor (ARI) for the blockade of polyol pathways. Rats were given a single intravenous injection of streptozotocin (n=76, STZ-D rats). Starting the day after STZ injection, ARI was administered daily to 42 of the rats for 4 weeks (ARI-D rats). To assess the cardiac sympathetic nervous function, [ 125 I]MIBG autoradiographic experiments were carried out. Finally, NET protein expression was assessed with a saturation binding assay. The myocardial sorbitol concentration was significantly higher in STZ-D rats than in ARI-D rats. There was no heterogeneous accumulation of MIBG in ARI-D rats. There was a heterogeneous decrease of NET expression in STZ-D rats, but not in ARI-D or control rats. The gathered data indicate that the enhanced polyol pathway correlates with the decrease in regional cardiac sympathetic nervous function, and this impairment may lead to the reduction of NET protein in cardiac sympathetic nerves of the diabetic inferior wall. (orig.)

Toxicity of aerosol propellants in the respiratory and circulatory systems. VI. Influence of cardiac and pulmonary vascular lesions in the rat.

Science.gov (United States)

Doherty, R E; Aviado, D M

1975-01-01

Three propellants were selected for investigation in rats because of their non-uniform effect in mice and monkeys. Trichlorofluoromethane (FC 11) provoked arrhythmia in all three animal species, dichlorodifluoromethane (FC 12) in monkeys and rats but not in mice, and difluoroethane (FC 152a) only in rats. In rats the alterations in heart rate and electrocardiographic pattern during inhalation of these propellants are largely brought about by release of catecholamines from the adrenal gland, because adrenalectomy or prior injection of beta-adrenergic blocking drugs decreased the incidence of cardiac effects. Rats that have pulmonary vascular thrombosis or cardiac necrosis become more sensitive to proarrhythmic activity of these propellants.

Lak of influence of glucagon on glucose homeostasis after prolonged exercise in rats

DEFF Research Database (Denmark)

Galbo, H; Richter, Erik; Holst, J J

1977-01-01

The significance of glucagon for post-exercise glucose homeostasis has been studied in rats fasted overnight. Immediately after exhaustive swimming either rabbit-antiglucagon serum or normal rabbit serum was injected by cardiac puncture. Cardiac blood and samples of liver and muscle tissue were...

Low body weight and cardiac tolerance to ischemia in neonatal rats

Czech Academy of Sciences Publication Activity Database

Chvojková, Zuzana; Ošťádalová, Ivana; Ošťádal, Bohuslav

2005-01-01

Roč. 54, č. 4 (2005), s. 357-362 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA305/00/1659; GA MŠk(CZ) LN00A069 Institutional research plan: CEZ:AV0Z5011922 Keywords : low body weight * cardiac tolerance to ischemia * neonatal rats Subject RIV: ED - Physiology Impact factor: 1.806, year: 2005

Towards modeling of cardiac micro-structure with catheter-based confocal microscopy: a novel approach for dye delivery and tissue characterization.

Science.gov (United States)

Lasher, Richard A; Hitchcock, Robert W; Sachse, Frank B

2009-08-01

This work presents a methodology for modeling of cardiac tissue micro-structure. The approach is based on catheter-based confocal imaging systems, which are emerging as tools for diagnosis in various clinical disciplines. A limitation of these systems is that a fluorescent marker must be available in sufficient concentration in the imaged region. We introduce a novel method for the local delivery of fluorescent markers to cardiac tissue based on a hydro-gel carrier brought into contact with the tissue surface. The method was tested with living rabbit cardiac tissue and applied to acquire three-dimensional image stacks with a standard inverted confocal microscope and two-dimensional images with a catheter-based confocal microscope. We processed these image stacks to obtain spatial models and quantitative data on tissue microstructure. Volumes of atrial and ventricular myocytes were 4901 +/- 1713 and 10 299 +/-3598 mum (3) (mean+/-sd), respectively. Atrial and ventricular myocyte volume fractions were 72.4 +/-4.7% and 79.7 +/- 2.9% (mean +/-sd), respectively. Atrial and ventricular myocyte density was 165 571 +/- 55 836 and 86 957 +/- 32 280 cells/mm (3) (mean+/-sd), respectively. These statistical data and spatial descriptions of tissue microstructure provide important input for modeling studies of cardiac tissue function. We propose that the described methodology can also be used to characterize diseased tissue and allows for personalized modeling of cardiac tissue.

Thicker three-dimensional tissue from a "symbiotic recycling system" combining mammalian cells and algae.

Science.gov (United States)

Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

2017-01-31

In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro "symbiotic recycling system" composed of mammalian cells and algae.

Assessment of biodistribution of 131-IPPA in cardiac and non-cardiac tissues in laboratory animals by imaging

International Nuclear Information System (INIS)

Moradkani, S.; Sadadi, F.; Matloubi, M.; Jalilian, A. R.; Shafaie, K.; Karimian, A. R.; Daneshvari, S.

2007-01-01

The main substrate of myocardial metabolism is fatty acids which constitutes the principal agent for myocardial consumption and provides almost 60-80% of the energy utilized by the heart in the resting state. Evaluation of cardiac metabolism is important for the assessment of some of cardiac disorders such as Ischemic Heart disease (IHD), cardiomyopathy (functional disorders) and Hypertensive cardiac disorders. Today, almost in all of the developed countries, PET is the first step for diagnosis and assessment of cardiac metabolic disorders. It is, however, too expensive to be used in all centers and are not available in all countries. In this regards, 123-IPPA was introduced as a substitute of PET system for evaluation of cardiac function (metabolism) and it is a complementary method for other Para-clinical methods. We decided to have a preliminary study on IPPA and due to the lack of 123-I, we had to use 131-I. The labeling of IPPA by 131-I, purification and sterilization of 131-1PPA done by the Chemistry Group of Cyclotron Ward and the bio-kinetic and imaging of rat, mice (Laboratory Animals) were performed in the Nuclear Medicine Group. After injection of a proper dose of this radiotracer, the imaging was performed in an appropriate time. In our first images, there were intensive accumulation of tracer in animals' thyroid glands, though after the intake of Lugol solution, the thyroid did not appear and we had a number of excellent images of animal heart that was the target organ

Decrease in rat cardiac beta1- and beta2- adrenoceptors by training and endurance exercise

International Nuclear Information System (INIS)

Werle, E.O.; Strobel, G.; Weicker, H.

1990-01-01

The cardiac β-adrenoceptor adaptation to physical activity was investigated in rats which were subjected to a six-week endurance swimming training (ET; n=7) and a training of high intensity (MT; n=7). In addition, the effect of a single bout of endurance exercise without preceding training (EE; n=7) was evaluated. These groups were compared with a sedentary control group (C; n=9). Beta-adrenergic receptors in rat myocardial membranes were labelled using the high affinity antagonist radioligand (-) 125 iodocyanopindolol (ICYP). Computer modelling techniques provided estimates of the maximal binding capacity (B max ) and the dissociation constants (K D ). Tissue was constantly kept at temperatures of ≤4 degrees C and incubated at 4 degrees C for 18 h in buffer containing 100 μM GTP so as to prevent masking of β-adrenoceptors by endogenous norepinephrine. In comparison with the C group computerized coanalyses of saturation binding data of ET, MT, and EE revealed a 13.0%, 25.5%, and 16.6% decrease in B max , respectively, without significantly differing K D values. We provide the first evidence that acute exercise lowers the sarcolemmal β-adrenoceptor number in the rat heart. In the competition radioligand binding, CGP20712A and ICI118.551 were employed as subtype-selective antagonists of β 1 - and β 2 -adrenoceptors, respectively, to determine the relative proportions of the receptor subtypes

Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats

Energy Technology Data Exchange (ETDEWEB)

Junqueira, Adriana, E-mail: francispacagnelli@unoeste.br [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Cicogna, Antônio Carlos [Universidade Estadual Paulista (UNESP), Campus Botucatu, SP (Brazil); Engel, Letícia Estevam; Aldá, Maiara Almeida [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Tomasi, Loreta Casquel de [Universidade Estadual Paulista (UNESP), Campus Botucatu, SP (Brazil); Giuffrida, Rogério; Giometti, Inês Cristina [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Freire, Ana Paula Coelho Figueira [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Universidade Estadual Paulista (UNESP), Campus Presidente Prudente, SP (Brazil); Aguiar, Andreo Fernando [Universidade do Norte do Paraná, UNOPAR, Londrina, PR (Brazil); Pacagnelli, Francis Lopes [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil)

2016-01-15

Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca{sup 2+} transport.

Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress.

Science.gov (United States)

André, Lucas; Gouzi, Fares; Thireau, Jérôme; Meyer, Gregory; Boissiere, Julien; Delage, Martine; Abdellaoui, Aldja; Feillet-Coudray, Christine; Fouret, Gilles; Cristol, Jean-Paul; Lacampagne, Alain; Obert, Philippe; Reboul, Cyril; Fauconnier, Jérémy; Hayot, Maurice; Richard, Sylvain; Cazorla, Olivier

2011-11-01

Arrhythmias following cardiac stress are a key predictor of death in healthy population. Carbon monoxide (CO) is a ubiquitous pollutant promoting oxidative stress and associated with hospitalization for cardiovascular disease and cardiac mortality. We investigated the effect of chronic CO exposure on the occurrence of arrhythmic events after a cardiac stress test and the possible involvement of related oxidative stress. Wistar rats exposed chronically (4 weeks) to sustained urban CO pollution presented more arrhythmic events than controls during recovery after cardiac challenge with isoprenaline in vivo. Sudden death occurred in 22% of CO-exposed rats versus 0% for controls. Malondialdehyde (MDA), an end-product of lipid peroxidation, was increased in left ventricular tissue of CO-exposed rats. Cardiomyocytes isolated from CO-exposed rats showed higher reactive oxygen species (ROS) production (measured with MitoSox Red dye), higher diastolic Ca(2+) resulting from SR calcium leak and an higher occurrence of irregular Ca(2+) transients (measured with Indo-1) in comparison to control cells after a high pacing sequence. Acute treatment with a ROS scavenger (N-acetylcysteine, 20 mmol/L, 1 h) prevented this sequence of alterations and decreased the number of arrhythmic cells following high pacing. Chronic CO exposure promotes oxidative stress that alters Ca(2+) homeostasis (through RYR2 and SERCA defects) and thereby mediates the triggering of ventricular arrhythmia after cardiac stress that can lead to sudden death.

Inhibition of galectin-3 ameliorates the consequences of cardiac lipotoxicity in a rat model of diet-induced obesity

Directory of Open Access Journals (Sweden)

Gema Marín-Royo

2018-02-01

Full Text Available Obesity is accompanied by metabolic alterations characterized by insulin resistance and cardiac lipotoxicity. Galectin-3 (Gal-3 induces cardiac inflammation and fibrosis in the context of obesity; however, its role in the metabolic consequences of obesity is not totally established. We have investigated the potential role of Gal-3 in the cardiac metabolic disturbances associated with obesity. In addition, we have explored whether this participation is, at least partially, acting on mitochondrial damage. Gal-3 inhibition in rats that were fed a high-fat diet (HFD for 6 weeks with modified citrus pectin (MCP; 100 mg/kg/day attenuated the increase in cardiac levels of total triglyceride (TG. MCP treatment also prevented the increase in cardiac protein levels of carnitine palmitoyl transferase IA, mitofusin 1, and mitochondrial complexes I and II, reactive oxygen species accumulation and decrease in those of complex V but did not affect the reduction in 18F-fluorodeoxyglucose uptake observed in HFD rats. The exposure of cardiac myoblasts (H9c2 to palmitic acid increased the rate of respiration, mainly due to an increase in the proton leak, glycolysis, oxidative stress, β-oxidation and reduced mitochondrial membrane potential. Inhibition of Gal-3 activity was unable to affect these changes. Our findings indicate that Gal-3 inhibition attenuates some of the consequences of cardiac lipotoxicity induced by a HFD since it reduced TG and lysophosphatidyl choline (LPC levels. These reductions were accompanied by amelioration of the mitochondrial damage observed in HFD rats, although no improvement was observed regarding insulin resistance. These findings increase the interest for Gal-3 as a potential new target for therapeutic intervention to prevent obesity-associated cardiac lipotoxicity and subsequent mitochondrial dysfunction.

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

Science.gov (United States)

Finosh, G.T.; Jayabalan, Muthu

2012-01-01

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

Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats

International Nuclear Information System (INIS)

Minor, Robin K.; Smith, Daniel L.; Sossong, Alex M.; Kaushik, Susmita; Poosala, Suresh; Spangler, Edward L.; Roth, George S.; Lane, Mark; Allison, David B.; Cabo, Rafael de; Ingram, Donald K.; Mattison, Julie A.

2010-01-01

Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolarization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.

Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

Science.gov (United States)

Liu, Qian; Zhang, Qi; Wang, Kai; Wang, Shengchan; Lu, Dasheng; Li, Zhenzhen; Geng, Jie; Fang, Ping; Wang, Ying; Shan, Qijun

2015-12-01

Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.

Empagliflozin lessened cardiac injury and reduced visceral adipocyte hypertrophy in prediabetic rats with metabolic syndrome.

Science.gov (United States)

Kusaka, Hiroaki; Koibuchi, Nobutaka; Hasegawa, Yu; Ogawa, Hisao; Kim-Mitsuyama, Shokei

2016-11-11

The potential benefit of SGLT2 inhibitors in metabolic syndrome is with prediabetic stage unclear. This work was undertaken to investigate the non-glycemic effect of empagliflozin on metabolic syndrome rats with prediabetes. SHR/NDmcr-cp(+/+) rats (SHRcp), a model of metabolic syndrome with prediabetes, were given empagliflozin for 10 weeks to examine the effects on urinary sodium and water balance, visceral and subcutaneous adipocyte, and cardiac injury. Further, the effect of empagliflozin on blood pressure and autonomic nervous system was continuously investigated by using radiotelemetry system. Empagliflozin significantly reduced urinary sodium and water balance of SHRcp only within 1 week of the treatment, but later than 1 week did not alter them throughout the treatment. Empagliflozin significantly reduced body weight of SHRcp, which was mainly attributed to the significant reduction of subcutaneous fat mass. Empagliflozin significantly reduced the size of visceral adipocytes and increased the number of smaller size of adipocytes, which was associated with the attenuation of oxidative stress. Empagliflozin ameliorated cardiac hypertrophy and fibrosis of SHRcp, in association with the attenuation of cardiac oxidative stress and inflammation. However, empagliflozin did not significantly change blood pressure, heart rate, sympathetic activity, or baroreceptor function, as evidenced by radiotelemetry analysis. Our present work provided the evidence that SGLT2 inhibition reduced visceral adipocytes hypertrophy and ameliorated cardiac injury in prediabetic metabolic syndrome rat, independently of diuretic effect or blood pressure lowering effect. Thus, SGLT2 inhibition seems to be a promising therapeutic strategy for prediabetic metabolic syndrome.

Optimal iodine staining of cardiac tissue for X-ray computed tomography.

Science.gov (United States)

Butters, Timothy D; Castro, Simon J; Lowe, Tristan; Zhang, Yanmin; Lei, Ming; Withers, Philip J; Zhang, Henggui

2014-01-01

X-ray computed tomography (XCT) has been shown to be an effective imaging technique for a variety of materials. Due to the relatively low differential attenuation of X-rays in biological tissue, a high density contrast agent is often required to obtain optimal contrast. The contrast agent, iodine potassium iodide ([Formula: see text]), has been used in several biological studies to augment the use of XCT scanning. Recently I2KI was used in XCT scans of animal hearts to study cardiac structure and to generate 3D anatomical computer models. However, to date there has been no thorough study into the optimal use of I2KI as a contrast agent in cardiac muscle with respect to the staining times required, which has been shown to impact significantly upon the quality of results. In this study we address this issue by systematically scanning samples at various stages of the staining process. To achieve this, mouse hearts were stained for up to 58 hours and scanned at regular intervals of 6-7 hours throughout this process. Optimal staining was found to depend upon the thickness of the tissue; a simple empirical exponential relationship was derived to allow calculation of the required staining time for cardiac samples of an arbitrary size.

Downregulation of Plzf Gene Ameliorates Metabolic and Cardiac Traits in the Spontaneously Hypertensive Rat

Czech Academy of Sciences Publication Activity Database

Liška, F.; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Strnad, Hynek; Trnovská, J.; Škop, V.; Kazdová, L.; Starker, C.G.; Voytas, D.F.; Izsvák, Z.; Mancini, M.; Šeda, O.; Křen, V.; Pravenec, Michal

2017-01-01

Roč. 69, č. 6 (2017), s. 1084-1091 ISSN 0194-911X R&D Projects: GA ČR(CZ) GB14-36804G; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : fibrosis * hypertension * hypertrophy * left ventricular rats * inbred * SHR * transcriptome Subject RIV: EB - Genetics ; Molecular Biology; EB - Genetics ; Molecular Biology (UMG-J) OBOR OECD: Cardiac and Cardiovascular systems; Cardiac and Cardiovascular systems (UMG-J) Impact factor: 6.857, year: 2016

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

OpenAIRE

Hasan, Wohaib; Smith, Peter G

2013-01-01

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

Thicker three-dimensional tissue from a “symbiotic recycling system” combining mammalian cells and algae

Science.gov (United States)

Haraguchi, Yuji; Kagawa, Yuki; Sakaguchi, Katsuhisa; Matsuura, Katsuhisa; Shimizu, Tatsuya; Okano, Teruo

2017-01-01

In this paper, we report an in vitro co-culture system that combines mammalian cells and algae, Chlorococcum littorale, to create a three-dimensional (3-D) tissue. While the C2C12 mouse myoblasts and rat cardiac cells consumed oxygen actively, intense oxygen production was accounted for by the algae even in the co-culture system. Although cell metabolism within thicker cardiac cell-layered tissues showed anaerobic respiration, the introduction of innovative co-cultivation partially changed the metabolism to aerobic respiration. Moreover, the amount of glucose consumption and lactate production in the cardiac tissues and the amount of ammonia in the culture media decreased significantly when co-cultivated with algae. In the cardiac tissues devoid of algae, delamination was observed histologically, and the release of creatine kinase (CK) from the tissues showed severe cardiac cell damage. On the other hand, the layered cell tissues with algae were observed to be in a good histological condition, with less than one-fifth decline in CK release. The co-cultivation with algae improved the culture condition of the thicker tissues, resulting in the formation of 160 μm-thick cardiac tissues. Thus, the present study proposes the possibility of creating an in vitro “symbiotic recycling system” composed of mammalian cells and algae. PMID:28139713

Aldosterone Blockade Reduces Mortality without Changing Cardiac Remodeling in Spontaneously Hypertensive Rats

Directory of Open Access Journals (Sweden)

Marcelo D.M. Cezar

2013-11-01

Full Text Available Background: The role of aldosterone blockers during transition from long-term compensated hypertrophy to dilated failure is not completely understood. In this study we evaluated the effects of early administration of spironolactone on cardiac remodeling, myocardial function, and mortality in spontaneously hypertensive rats (SHR. Methods: Sixteen-month-old SHR received no treatment (SHR-C, n=72 or spironolactone (SHR-SPR, 20 mg/kg/day, n=34 for six months. Echocardiogram was performed before and after treatment. Myocardial function was analyzed in left ventricular (LV papillary muscle preparations. Myocardial collagen and hydroxyproline concentration were evaluated by morphometry and spectrophotometry, respectively. LV gene expression was assessed by real time RT-PCR. Statistics: Student's t test; Log rank test (Kaplan Meyer. Results: SHR-C and SHR-SPR presented mortality rates of 71 and 38%, respectively (p=0.004. Systolic arterial pressure did not differ between groups (SHR-C 199±43; SHR-SPR 200±35 mmHg. Initial and final echocardiograms did not show significant differences in cardiac structures or LV function between groups. Myocardial function was similar between groups at basal and after inotropic stimulation. Collagen fractional area, hydroxyproline concentration, gene expression for α- and β-myosin heavy chain, atrial natriuretic peptide, and Serca2a were not different between groups. Conclusion: Early spironolactone administration reduces mortality without changing cardiac remodeling in spontaneous hypertensive rats.

A gold nanoparticle coated porcine cholecyst-derived bioscaffold for cardiac tissue engineering.

Science.gov (United States)

Nair, Reshma S; Ameer, Jimna Mohamed; Alison, Malcolm R; Anilkumar, Thapasimuthu V

2017-09-01

Extracellular matrices of xenogeneic origin have been extensively used for biomedical applications, despite the possibility of heterogeneity in structure. Surface modification of biologically derived biomaterials using nanoparticles is an emerging strategy for improving topographical homogeneity when employing these scaffolds for sophisticated tissue engineering applications. Recently, as a tissue engineering scaffold, cholecyst derived extracellular matrix (C-ECM) has been shown to have several advantages over extracellular matrices derived from other organs such as jejunum and urinary bladder. This study explored the possibility of adding gold nanoparticles, which have a large surface area to volume ratio on C-ECM for achieving homogeneity in surface architecture, a requirement for cardiac tissue engineering. In the current study, gold nanoparticles (AuNPs) were synthesized and functionalised for conjugating with a porcine cholecystic extracellular matrix scaffold. The conjugation of nanoparticles to C-ECM was achieved by 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide/N-hydroxysuccinimide chemistry and further characterized by Fourier transform infrared spectroscopy, environmental scanning electron microscopy, energy dispersive X-ray spectroscopy and thermogravimetric analysis. The physical properties of the modified scaffold were similar to the original C-ECM. Biological properties were evaluated by using H9c2 cells, a cardiomyoblast cell line commonly used for cellular and molecular studies of cardiac cells. The modified scaffold was found to be a suitable substrate for the growth and proliferation of the cardiomyoblasts. Further, the non-cytotoxic nature of the modified scaffold was established by direct contact cytotoxicity testing and live/dead staining. Thus, the modified C-ECM appears to be a potential biomaterial for cardiac tissue engineering. Copyright © 2017 Elsevier B.V. All rights reserved.

Squalene Modulates Radiation-Induced Structural, Ultrastructural And Biochemical Changes In Cardiac Muscles Of Male Albino Rats

International Nuclear Information System (INIS)

REZK, R.G.; YACOUB, S.F.; ABDEL AZIZ, N.

2009-01-01

The failing heart represents an enormous clinical problem and is a major cause of death throughout the world. Hyperlipidemia and oxidative stress have been shown to contribute to heart failure. Squalene is a remarkable bioactive substance that belongs to a class of antioxidants called isoprenoids, which neutralize the harmful effect of excessive free radicals production in the body.The present study was designed to determine the possible protective effect of squalene against oxidative cardiac muscle damage induced by gamma irradiation.Rats were treated daily by gavage with 0.4 ml/kg squalene for 42 days before whole body gamma irradiation at a dose of 4 Gy and continued until animals were sacrificed 3 days post irradiation.Histological examination of cardiac muscles sections by using light and electron microscopes showed that exposure of rats to ionizing radiation has provoked a severe architecture damage such as necrotic nuclei, nuclei located at the periphery, alteration in chromatin distribution, ruptured cell and mitochondrial membranes, cristae of mitochondria disappeared, sticking mitochondria and ruptured myofibers. Structural and ultra-structural changes were associated with severe oxidative stress. Significant increase of lipid peroxidation products (malondialdehyde) (MDA) along with reduction in the activity of the antioxidant enzymes; superoxide dismutase (SOD) and catalse (CAT), and glutathione content (GSH), were recorded.Treatment of rats with squalene has significantly attenuated the radiation-induced oxidative damage and histopathological changes in cardiac muscle which was substantiated by a significant amelioration in the activity of plasma lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and aspartate transaminase (AST). Furthermore, administration of squalene to rats has adjusted the radiation-induced increase in plasma triglycerides (TG), total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). Based on these results, it

Towards optical spectroscopic anatomical mapping (OSAM) for lesion validation in cardiac tissue (Conference Presentation)

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Singh-Moon, Rajinder P.; Zaryab, Mohammad; Hendon, Christine P.

2017-02-01

Electroanatomical mapping (EAM) is an invaluable tool for guiding cardiac radiofrequency ablation (RFA) therapy. The principle roles of EAM is the identification of candidate ablation sites by detecting regions of abnormal electrogram activity and lesion validation subsequent to RF energy delivery. However, incomplete lesions may present interim electrical inactivity similar to effective treatment in the acute setting, despite efforts to reveal them with pacing or drugs, such as adenosine. Studies report that the misidentification and recovery of such lesions is a leading cause of arrhythmia recurrence and repeat procedures. In previous work, we demonstrated spectroscopic characterization of cardiac tissues using a fiber optic-integrated RF ablation catheter. In this work, we introduce OSAM (optical spectroscopic anatomical mapping), the application of this spectroscopic technique to obtain 2-dimensional biodistribution maps. We demonstrate its diagnostic potential as an auxiliary method for lesion validation in treated swine preparations. Endocardial lesion sets were created on fresh swine cardiac samples using a commercial RFA system. An optically-integrated catheter console fabricated in-house was used for measurement of tissue optical spectra between 600-1000nm. Three dimensional, Spatio-spectral datasets were generated by raster scanning of the optical catheter across the treated sample surface in the presence of whole blood. Tissue optical parameters were recovered at each spatial position using an inverse Monte Carlo method. OSAM biodistribution maps showed stark correspondence with gross examination of tetrazolium chloride stained tissue specimens. Specifically, we demonstrate the ability of OSAM to readily distinguish between shallow and deeper lesions, a limitation faced by current EAM techniques. These results showcase the OSAMs potential for lesion validation strategies for the treatment of cardiac arrhythmias.

Tissue disposition of bifenthrin in the rat

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U.S. Environmental Protection Agency — Tissue disposition of bifenthrin in the rat and oral and intravenous administration. This dataset is associated with the following publication: Hughes , M., D. Ross...

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

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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

Micro and Nano-mediated 3D Cardiac Tissue Engineering

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2010-10-01

dilated cardiomyopathy . Critical Care Medicine. 2009;37:1197-1205 21. Leor J. Bioengineered cardiac grafts: A new approach to repair the infarcted...chamber and while the atrium “helps” during inner flow. Since increase of amplitude as response to synchronism is a measure of contraction and dilation ...optimal pump function in canine hearts. Journal of the American College of Cardiology. 2003;41:1218-1226 4. Storaa C. Tissue motion imaging of the left

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism.

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Kobori, H; Ichihara, A; Suzuki, H; Takenaka, T; Miyashita, Y; Hayashi, M; Saruta, T

1997-08-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

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Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya

2017-09-01

The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

Protective Effect of Momordica charantia Fruit Extract on Hyperglycaemia-Induced Cardiac Fibrosis

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Razif Abas

2014-01-01

Full Text Available In diabetes mellitus, cardiac fibrosis is characterized by increase in the deposition of collagen fibers. The present study aimed to observe the effect of Momordica charantia (MC fruit extract on hyperglycaemia-induced cardiac fibrosis. Diabetes was induced in the male Sprague-Dawley rats with a single intravenous injection of streptozotocin (STZ. Following 4 weeks of STZ induction, the rats were subdivided (n = 6 into control group (Ctrl, control group treated with MC (Ctrl-MC, diabetic untreated group (DM-Ctrl, diabetic group treated with MC (DM-MC, and diabetic group treated with 150 mg/kg of metformin (DM-Met. Administration of MC fruit extract (1.5 g/kg body weight in diabetic rats for 28 days showed significant increase in the body weight and decrease in the fasting blood glucose level. Significant increase in cardiac tissues superoxide dismutase (SOD, glutathione contents (GSH, and catalase (CAT was observed following MC treatment. Hydroxyproline content was significantly reduced and associated morphological damages reverted to normal. The decreased expression of type III and type IV collagens was observed under immunohistochemical staining. It is concluded that MC fruit extract possesses antihyperglycemic, antioxidative, and cardioprotective properties which may be beneficial in the treatment of diabetic cardiac fibrosis.

Transcapillary permeability and subendothelial distribution of endothelial and amniotic fluid insulin-like growth factor binding proteins in the rat heart

International Nuclear Information System (INIS)

Bar, R.S.; Clemmons, D.R.; Boes, M.; Busby, W.H.; Booth, B.A.; Dake, B.L.; Sandra, A.

1990-01-01

Insulin-like growth factor (IGF) binding proteins (IGFBP) were purified from conditioned media of cultured bovine endothelial cells (ECBP) and from human amniotic fluid (IGFBP-1), and then labeled by radioiodination. 125I-ECBP and 125I-IGFBP-1 were perfused through isolated beating rat hearts for 1 and 5 min, and the hearts fixed and analyzed for 125I-BP content and distribution. One to 4% of the perfused 125I-ECBP and 125I-IGFBP-1 crossed the capillary boundary. The ECBPs predominantly localized as intact 125I-BP in connective tissue elements of the heart with less 125I-BP in cardiac muscle. The ratio of 125I-ECBP in connective tissue: muscle (normalized to percent vol of these compartments) was greater than or equal to 10:1. In contrast, the IGFBP-1 had a greater affinity for cardiac muscle with ratios of 125I-IGFBP-1 in connective tissue:muscle of approximately 1:2. When 125I-IGF-I, in the absence of any BPs, was perfused through the hearts approximately 3-5% left the microcirculation and was found in subendothelial tissues. 125I-IGF-I localized primarily to cardiac muscle with a distribution of connective tissue:cardiac muscle of about 1:3. The findings in the isolated perfused heart were confirmed in intact animals. After 125I-IGFBP-1 was injected into anesthetized rats and allowed to circulate for 5 min, substantial radioactivity was associated with the heart. As in the isolated heart, the IGFBP-1 preferentially localized to cardiac muscle with a connective tissue:cardiac muscle ratio of 1:3. We conclude that IGFBPs produced by endothelial cells and the IGFBP-1 contained in amniotic fluid can cross the capillary boundaries of the rat heart, and that the ECBPs preferentially localize in connective tissue elements of the myocardium, whereas IGFBP-1 predominantly localizes in cardiac muscle

Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations.

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Wang, Bo; Wang, Guangjun; To, Filip; Butler, J Ryan; Claude, Andrew; McLaughlin, Ronald M; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

2013-09-03

Recently, we developed an optimal decellularization protocol to generate 3D porcine myocardial scaffolds, which preserve the natural extracellular matrix structure, mechanical anisotropy, and vasculature templates and also show good cell recellularization and differentiation potential. In this study, a multistimulation bioreactor was built to provide coordinated mechanical and electrical stimulation for facilitating stem cell differentiation and cardiac construct development. The acellular myocardial scaffolds were seeded with mesenchymal stem cells (10(6) cells/mL) by needle injection and subjected to 5-azacytidine treatment (3 μmol/L, 24 h) and various bioreactor conditioning protocols. We found that after 2 days of culturing with mechanical (20% strain) and electrical stimulation (5 V, 1 Hz), high cell density and good cell viability were observed in the reseeded scaffold. Immunofluorescence staining demonstrated that the differentiated cells showed a cardiomyocyte-like phenotype by expressing sarcomeric α-actinin, myosin heavy chain, cardiac troponin T, connexin-43, and N-cadherin. Biaxial mechanical testing demonstrated that positive tissue remodeling took place after 2 days of bioreactor conditioning (20% strain + 5 V, 1 Hz); passive mechanical properties of the 2 day and 4 day tissue constructs were comparable to those of the tissue constructs produced by stirring reseeding followed by 2 weeks of static culturing, implying the effectiveness and efficiency of the coordinated simulations in promoting tissue remodeling. In short, the synergistic stimulations might be beneficial not only for the quality of cardiac construct development but also for patients by reducing the waiting time in future clinical scenarios.

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

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

2018-06-05

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

Blockade of TGF-β 1 Signalling Inhibits Cardiac NADPH Oxidase Overactivity in Hypertensive Rats

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José Luis Miguel-Carrasco

2012-01-01

Full Text Available NADPH oxidases constitute a major source of superoxide anion (⋅O2 - in hypertension. Several studies suggest an important role of NADPH oxidases in different effects mediated by TGF-β 1. In this study we show that chronic administration of P144, a peptide synthesized from type III TGF-β 1 receptor, significantly reduced the cardiac NADPH oxidase expression and activity as well as in the nitrotyrosine levels observed in control spontaneously hypertensive rats (V-SHR to levels similar to control normotensive Wistar Kyoto rats. In addition, P144 was also able to reduce the significant increases in the expression of collagen type I protein and mRNA observed in hearts from V-SHR. In addition, positive correlations between collagen expression, NADPH oxidase activity, and nitrotyrosine levels were found in all animals. Finally, TGF-β 1-stimulated Rat-2 exhibited significant increases in NADPH oxidase activity that was inhibited in the presence of P144. It could be concluded that the blockade of TGF-β 1 with P144 inhibited cardiac NADPH oxidase in SHR, thus adding new data to elucidate the involvement of this enzyme in the profibrotic actions of TGF-β 1.

Living cardiac patch: the elixir for cardiac regeneration.

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Lakshmanan, Rajesh; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

2012-12-01

A thorough understanding of the cellular and muscle fiber orientation in left ventricular cardiac tissue is of paramount importance for the generation of artificial cardiac patches to treat the ischemic myocardium. The major challenge faced during cardiac patch engineering is to choose a perfect combination of three entities; cells, scaffolds and signaling molecules comprising the tissue engineering triad for repair and regeneration. This review provides an overview of various scaffold materials, their mechanical properties and fabrication methods utilized in cardiac patch engineering. Stem cell therapies in clinical trials and the commercially available cardiac patch materials were summarized in an attempt to provide a recent perspective in the treatment of heart failure. Various tissue engineering strategies employed thus far to construct viable thick cardiac patches is schematically illustrated. Though many strategies have been proposed for fabrication of various cardiac scaffold materials, the stage and severity of the disease condition demands the incorporation of additional cues in a suitable scaffold material. The scaffold may be nanofibrous patch, hydrogel or custom designed films. Integration of stem cells and biomolecular cues along with the scaffold may provide the right microenvironment for the repair of unhealthy left ventricular tissue as well as promote its regeneration.

Low Intensity Physical Exercise Attenuates Cardiac Remodeling and Myocardial Oxidative Stress and Dysfunction in Diabetic Rats

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C. Gimenes

2015-01-01

Full Text Available We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control (C-Sed, exercised control (C-Ex, sedentary diabetes (DM-Sed, and exercised diabetes (DM-Ex. Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed: 5.73±0.49; C-Ex: 5.67±0.53; DM-Sed: 6.41±0.54; DM-Ex: 5.81±0.50 mm; P<0.05 DM-Sed vs C-Sed and DM-Ex. Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex. Conclusion. Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats.

Cardioprotective effect of magnetic hydrogel nanocomposite loaded N,α-L-rhamnopyranosyl vincosamide isolated from Moringa oleifera leaves against doxorubicin-induced cardiac toxicity in rats: in vitro and in vivo studies.

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Cheraghi, Mostafa; Namdari, Mehrdad; Daraee, Hadis; Negahdari, Babak

2017-06-01

Cardioprotective effect of N, α-L-rhamnopyranosyl vincosamide (VR), isolated from the leaves of Moringa oleifera plant in doxorubicin (Dox)-induced cardiac toxicity rats was evaluated. Twelve (12) rats were randomly selected into three groups; two rats received distilled water in the control group, five rats in group I received varying concentration of VR treatment, and group II containing five rats received varying concentration of VR-loaded magnetic hydrogel nanocomposite. Malondialdehyde (MDA), glutathione peroxidase (GSH) and superoxide dismutase (SOD) enzymes activities level were analysed after two weeks. In addition, the expression of three heart failure markers; beta major histocompatibility complex (β-MHC), atrial natriuretic peptide (ANP), and B type natriuretic peptide (BNP) were also evaluated. It was observed that the level of these markers expression decreases with an increase in VR concentration (p < 0.05). The reduced GSH and SOD level were increased after VR administration, this extract also reduced the initially increased MDA level in cardiac tissue. Pharmacokinetic parameters evaluation showed that nanogel treated rats possesses a significantly increased VR plasma concentration, C max , K el , t ½(a), t ½(el), K a and AUC. The result of this study indicated that VR may help to lower the dosage level, and reduces the treatment course in cardiovascular diseases (CVD). Our conclusion proposes the cardio-protective ability of the isolated VR and its beneficial effect via free radical scavenging properties.

Genistein induces estrogen-like effects in ovariectomized rats but fails to increase cardiac GLUT4 and oxidative stress.

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Al-Nakkash, Layla; Markus, Brandon; Batia, Lyn; Prozialeck, Walter C; Broderick, Tom L

2010-12-01

This study aimed to determine whether a 2-week genistein treatment induced estrogen-like effects in ovariectomized (OVX) Sprague-Dawley rats, after 2 weeks of subcutaneous genistein injections (250 mg/kg of body weight/day). Uterine weight, uterine-to-body weight ratio, femur weight, and femur-to-body weight ratio were all significantly increased with genistein in OVX rats. Body weight was significantly decreased with genistein in OVX rats. Genistein had no effect on the weights of heart, heart-to-body ratio, and fat pad but significantly decreased heart rate and pulse pressure. Genistein had no effect on cardiac GLUT4 protein, oxidative stress, plasma glucose, nonesterified fatty acids, or low-density lipoprotein levels; however, plasma insulin levels were significantly increased. Our results show that a 2-week genistein treatment produced favorable estrogen-like effects on some physical and physiological characteristics in OVX rats. However, based on our experimental conditions, the effects of genistein were not associated with changes in cardiac GLUT4 or oxidative stress.

Cardiac Time Intervals Measured by Tissue Doppler Imaging M-mode

DEFF Research Database (Denmark)

Biering-Sørensen, Tor; Møgelvang, Rasmus; Schnohr, Peter

2016-01-01

function was evaluated in 1915 participants by using both conventional echocardiography and tissue Doppler imaging (TDI). The cardiac time intervals, including the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET), were obtained by TDI M-mode through the mitral......). Additionally, they displayed a significant dose-response relationship, between increasing severity of elevated blood pressure and increasing left ventricular mass index (P

Corticosterone binding to tissues of adrenalectomized lean and obese Zucker rats.

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Grasa, M M; Cabot, C; Balada, F; Virgili, J; Sanchis, D; Monserrat, C; Fernández-López, J A; Remesar, X; Alemany, M

1998-12-01

The binding of corticosterone, dexamethasone and aldosterone was investigated in plasma and in homogenates of liver, kidney, brain, brown adipose tissue and visceral (periovaric) and subcutaneous white adipose tissues of Zucker lean and obese rats: intact controls, adrenalectomized and sham-operated. Corticosterone-binding globulin (CBG) accounted for most of the binding, whereas that of glucocorticoid and mineralocorticoid receptors was much lower. Plasma corticosterone levels increased in sham-operated and obviously decreased in the adrenalectomized animals. Sham-operated and adrenalectomized lean rats showed decreased plasma CBG; in the obese, CBG levels were lower than in controls and were not affected by either surgery. No variation with obesity or surgery was observed either in dexamethasone or aldosterone binding, the latter being practically zero in most samples. When expressed per unit of tissue protein, CBG activity was maximal in adipose tissues, with lowest values in brain and liver. In lean rats, tissue CBG activity decreased with either surgical treatment; no changes were observed in the obese, which also had lower CBG tissue levels. The relative lack of changes in CBG of obese rats suggests that they have lost -- at least in part -- the ability to counter-modulate the changes in glucocorticoid levels through CBG modulation, thus relying only on the control of corticosterone levels. This interpretation agrees with the postulated role of CBG modulating the availability of glucocorticoids to target cells.

Valsartan attenuates cardiac and renal hypertrophy in rats with experimental cardiorenal syndrome possibly through down-regulating galectin-3 signaling.

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Zhang, M-J; Gu, Y; Wang, H; Zhu, P-F; Liu, X-Y; Wu, J

2016-01-01

Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a β-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model. Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal. Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment. Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway.

Exercise training starting at weaning age preserves cardiac pacemaker function in adulthood of diet-induced obese rats.

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Carvalho de Lima, Daniel; Guimarães, Juliana Bohnen; Rodovalho, Gisele Vieira; Silveira, Simonton Andrade; Haibara, Andrea Siqueira; Coimbra, Cândido Celso

2014-08-01

Peripheral sympathetic overdrive in young obese subjects contributes to further aggravation of insulin resistance, diabetes, and hypertension, thus inducing worsening clinical conditions in adulthood. Exercise training has been considered a strategy to repair obesity autonomic dysfunction, thereby reducing the cardiometabolic risk. Therefore, the aim of this study was to assess the effect of early exercise training, starting immediately after weaning, on cardiac autonomic control in diet-induced obese rats. Male Wistar rats (weaning) were divided into four groups: (i) a control group (n = 6); (ii) an exercise-trained control group (n = 6); (iii) a diet-induced obesity group (n = 6); and (iv) an exercise-trained diet-induced obesity group (n = 6). The development of obesity was induced by 9 weeks of palatable diet intake, and the training program was implemented in a motor-driven treadmill (5 times per week) during the same period. After this period, animals were submitted to vein and artery catheter implantation to assess cardiac autonomic balance by methylatropine (3 mg/kg) and propranolol (4 mg/kg) administration. Exercise training increased running performance in both groups (p Exercise training also prevented the increased resting heart rate in obese rats, which seemed to be related to cardiac pacemaker activity preservation (p exercise program beginning at weaning age prevents cardiovascular dysfunction in obese rats, indicating that exercise training may be used as a nonpharmacological therapeutic strategy for the treatment of cardiometabolic diseases.

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

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Peter Nordbeck

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

Effects of growth hormone on morphology of cardiac muscle and skeletal muscle and hormone levels in rats

International Nuclear Information System (INIS)

Yang Ping; Liu Cong; Meng Fanbo; Zhu Jinming; Ni Jinsong; Zhou Hong; Tang Yubo

2005-01-01

Objective: To study the effects of growth hormone (GH) on morphology of cardiac muscle and skeletal muscle and hormone levels in Wistar rats. Methods: The GH was given with subcutaneous injection for 15 days, the level of serum GH was determined by radiation-immune method; the body weight and the ratio of organ weight to body weight were determined; the cell appearances of cardiac muscle and skeletal muscle were observed under microscope. the control group was set up. Results; The level of serum GH and rat body weight in experimental group were obviously higher than that in the control group, but the ratio of organ weight to body weight was not obviously different in two groups; musculature hypertrophy and cell nucleolus increasing were observed under microscopy, there were no capillary vessel hyperplasia and inflammatory soakage. Conclusion: GH can induce hypertrophy of cardiac muscle cells and skeletal muscle cells but not interstitial proliferation. (authors)

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

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Richard A Lasher

2012-12-01

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

Three-Dimensional Elastomeric Scaffolds Designed with Cardiac-Mimetic Structural and Mechanical Features

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Neal, Rebekah A.; Jean, Aurélie; Park, Hyoungshin; Wu, Patrick B.; Hsiao, James; Engelmayr, George C.; Langer, Robert

2013-01-01

Tissue-engineered constructs, at the interface of material science, biology, engineering, and medicine, have the capacity to improve outcomes for cardiac patients by providing living cells and degradable biomaterials that can regenerate the native myocardium. With an ultimate goal of both delivering cells and providing mechanical support to the healing heart, we designed three-dimensional (3D) elastomeric scaffolds with (1) stiffnesses and anisotropy mimicking explanted myocardial specimens as predicted by finite-element (FE) modeling, (2) systematically varied combinations of rectangular pore pattern, pore aspect ratio, and strut width, and (3) structural features approaching tissue scale. Based on predicted mechanical properties, three scaffold designs were selected from eight candidates for fabrication from poly(glycerol sebacate) by micromolding from silicon wafers. Large 20×20 mm scaffolds with high aspect ratio features (5:1 strut height:strut width) were reproducibly cast, cured, and demolded at a relatively high throughput. Empirically measured mechanical properties demonstrated that scaffolds were cardiac mimetic and validated FE model predictions. Two-layered scaffolds providing fully interconnected pore networks were fabricated by layer-by-layer assembly. C2C12 myoblasts cultured on one-layered scaffolds exhibited specific patterns of cell elongation and interconnectivity that appeared to be guided by the scaffold pore pattern. Neonatal rat heart cells cultured on two-layered scaffolds for 1 week were contractile, both spontaneously and in response to electrical stimulation, and expressed sarcomeric α-actinin, a cardiac biomarker. This work not only demonstrated several scaffold designs that promoted functional assembly of rat heart cells, but also provided the foundation for further computational and empirical investigations of 3D elastomeric scaffolds for cardiac tissue engineering. PMID:23190320

Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy.

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Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

1999-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

Pharmacokinetics of warfarin in rats: role of serum protein binding and tissue distribution

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Cheung, W.K.

1985-01-01

The purpose of this study was to explore the role of serum protein binding and tissue distribution in the non-linear pharmacokinetics of warfarin in rats. The first phase of the research was an attempt to elucidate the causes of intersubject differences in serum protein binding of warfarin in rats. It was found that the distribution of S-warfarin between blood and liver, kidneys, muscle, or fatty tissue was non-linear. Based on the tissue distribution data obtained, a physiologically-based pharmacokinetic model was developed to describe the time course of S-warfarin concentrations in the serum and tissues of rats. The proposed model was able to display the dose-dependent pharmacokinetics of warfarin in rats. Namely a lower clearance and a smaller apparent volume of distribution with increasing dose, which appear to be due to the presence of capacity-limited, high-affinity binding sites for warfarin in various tissues. To determine if the binding of warfarin to the high-affinity binding sites in the liver of rats is reversible, concentrations of S-warfarin in the liver and serum of rats were monitored for a very long time after an intravenous injection of a 1 mg/kg dose. In another study in rats, non-radioactive warfarin was found to be able to displace tissue-bound C 14 -warfarin which was administered about 200 hours before the i.v. injection of the non-radioactive warfarin, showing that the binding of warfarin to the high-affinity binding sites in the body is persistent and reversible

Cardiac effects of MDMA on the metabolic profile determined with 1H-magnetic resonance spectroscopy in the rat†

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Perrine, Shane A.; Michaels, Mark S.; Ghoddoussi, Farhad; Hyde, Elisabeth M.; Tancer, Manuel E.; Galloway, Matthew P.

2010-01-01

Despite the potential for deleterious (even fatal) effects on cardiac physiology, 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) abuse abounds driven mainly by its euphoric effects. Acute exposure to MDMA has profound cardiovascular effects on blood pressure and heart rate in humans and animals. To determine the effects of MDMA on cardiac metabolites in rats, MDMA (0, 5, or 10 mg/kg) was injected every 2 h for a total of four injections; animals were sacrificed 2 h after the last injection (8 h drug exposure), and their hearts removed and tissue samples from left ventricular wall dissected. High resolution magic angle spinning proton magnetic resonance spectroscopy (1H-MRS) at 11.7 T, a specialized version of MRS aptly suited for analysis of semi-solid materials such as intact tissue samples, was used to measure the cardiac metabolomic profile, including alanine, lactate, succinate, creatine, and carnitine, in heart tissue from rats treated with MDMA. MDMA effects on MR-visible choline, glutamate, glutamine, and taurine were also determined. Body temperature was measured following each MDMA administration and serotonin and norepinephrine (NE) levels were measured by high pressure liquid chromatography (HPLC) in heart tissue from treated animals. MDMA significantly and dose-dependently increased body temperature, a hallmark of amphetamines. Serotonin, but not NE, levels were significantly and dose-dependently decreased by MDMA in the heart wall. MDMA significantly altered the MR-visible profile with an increase in carnitine and no change in other key compounds involved in cardiomyocyte energy metabolomics. Finally, choline levels were significantly decreased by MDMA in heart. The results are consistent with the notion that MDMA has significant effects on cardiovascular serotonergic tone and disrupts the metabolic homeostasis of energy regulation in cardiac tissue, potentially increasing utilization of fatty acid metabolism. The contributions of serotonergic

Long-term increase in coherence between the basal ganglia and motor cortex after asphyxial cardiac arrest and resuscitation in developing rats.

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Aravamuthan, Bhooma R; Shoykhet, Michael

2015-10-01

The basal ganglia are vulnerable to injury during cardiac arrest. Movement disorders are a common morbidity in survivors. Yet, neuronal motor network changes post-arrest remain poorly understood. We compared function of the motor network in adult rats that, during postnatal week 3, underwent 9.5 min of asphyxial cardiac arrest (n = 9) or sham intervention (n = 8). Six months after injury, we simultaneously recorded local field potentials (LFP) from the primary motor cortex (MCx) and single neuron firing and LFP from the rat entopeduncular nucleus (EPN), which corresponds to the primate globus pallidus pars interna. Data were analyzed for firing rates, power, and coherence between MCx and EPN spike and LFP activity. Cardiac arrest survivors display chronic motor deficits. EPN firing rate is lower in cardiac arrest survivors (19.5 ± 2.4 Hz) compared with controls (27.4 ± 2.7 Hz; P motor network after cardiac arrest. Increased motor network synchrony is thought to be antikinetic in primary movement disorders. Characterization of motor network synchrony after cardiac arrest may help guide management of post-hypoxic movement disorders.

Dioxin-induced acute cardiac mitochondrial oxidative damage and increased activity of ATP-sensitive potassium channels in Wistar rats

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Pereira, Susana P.; Pereira, Gonçalo C.; Pereira, Cláudia V.; Carvalho, Filipa S.; Cordeiro, Marília H.; Mota, Paula C.; Ramalho-Santos, João; Moreno, António J.; Oliveira, Paulo J.

2013-01-01

The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent. We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats with TCDD (50 μg/kg i.p.) and measured the regulation of cardiac mitoKATP. While the function of cardiac mitochondria was slightly depressed, mitoKATP activity was 52% higher in animals treated with TCDD. The same effects were not observed in liver mitochondria isolated from the same animals. Our data also shows that regulation of mitochondrial ROS production by mitoKATP activity is different in both groups. To our knowledge, this is the first report to show that TCDD increases mitoKATP activity in the heart, which may counteract the increased oxidative stress caused by the dioxin during acute exposure. -- Highlights: •Acute TCDD treatment of Wistar rats causes cardiac oxidative stress. •Acute TCDD treatment causes cardiac mitochondrial alterations. •Mitochondrial liver vs. heart alterations are distinct. •TCDD treatment resulted in altered activity of cardiac mitochondrial K-ATP channels. -- Dioxin alters the regulation of cardiac mitochondrial ATP-sensitive potassium channels and disturbs mitochondrial physiology

Rosemary supplementation (Rosmarinus oficinallis L. attenuates cardiac remodeling after myocardial infarction in rats.

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Bruna Paola Murino Rafacho

Full Text Available Myocardial infarction (MI is one of the leading causes of morbidity and mortality worldwide. Dietary intervention on adverse cardiac remodeling after MI has significant clinical relevance. Rosemary leaves are a natural product with antioxidant/anti-inflammatory properties, but its effect on morphology and ventricular function after MI is unknown.To determine the effect of the dietary supplementation of rosemary leaves on cardiac remodeling after MI, male Wistar rats were divided into 6 groups after sham procedure or experimental induced MI: 1 Sham group fed standard chow (SR0, n = 23; 2 Sham group fed standard chow supplemented with 0.02% rosemary (R002 (SR002, n = 23; 3 Sham group fed standard chow supplemented with 0.2% rosemary (R02 (SR02, n = 22; 4 group submitted to MI and fed standard chow (IR0, n = 13; 5 group submitted to MI and fed standard chow supplemented with R002 (IR002, n = 8; and 6 group submitted to MI and fed standard chow supplemented with R02 (IR02, n = 9. After 3 months of the treatment, systolic pressure evaluation, echocardiography and euthanasia were performed. Left ventricular samples were evaluated for: fibrosis, cytokine levels, apoptosis, energy metabolism enzymes, and oxidative stress. Rosemary dietary supplementation attenuated cardiac remodeling by improving energy metabolism and decreasing oxidative stress. Rosemary supplementation of 0.02% improved diastolic function and reduced hypertrophy after MI. Regarding rosemary dose, 0.02% and 0.2% for rats are equivalent to 11 mg and 110 mg for humans, respectively.Our findings support further investigations of the rosemary use as adjuvant therapy in adverse cardiac remodeling.

Autophagic signaling and proteolytic enzyme activity in cardiac and skeletal muscle of spontaneously hypertensive rats following chronic aerobic exercise.

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Elliott M McMillan

Full Text Available Hypertension is a cardiovascular disease associated with deleterious effects in skeletal and cardiac muscle. Autophagy is a degradative process essential to muscle health. Acute exercise can alter autophagic signaling. Therefore, we aimed to characterize the effects of chronic endurance exercise on autophagy in skeletal and cardiac muscle of normotensive and hypertensive rats. Male Wistar Kyoto (WKY and spontaneously hypertensive rats (SHR were assigned to a sedentary condition or 6 weeks of treadmill running. White gastrocnemius (WG of hypertensive rats had higher (p<0.05 caspase-3 and proteasome activity, as well as elevated calpain activity. In addition, skeletal muscle of hypertensive animals had elevated (p<0.05 ATG7 and LC3I protein, LAMP2 mRNA, and cathepsin activity, indicative of enhanced autophagic signaling. Interestingly, chronic exercise training increased (p<0.05 Beclin-1, LC3, and p62 mRNA as well as proteasome activity, but reduced (p<0.05 Beclin-1 and ATG7 protein, as well as decreased (p<0.05 caspase-3, calpain, and cathepsin activity. Left ventricle (LV of hypertensive rats had reduced (p<0.05 AMPKα and LC3II protein, as well as elevated (p<0.05 p-AKT, p-p70S6K, LC3I and p62 protein, which collectively suggest reduced autophagic signaling. Exercise training had little effect on autophagy-related signaling factors in LV; however, exercise training increased (p<0.05 proteasome activity but reduced (p<0.05 caspase-3 and calpain activity. Our results suggest that autophagic signaling is altered in skeletal and cardiac muscle of hypertensive animals. Regular aerobic exercise can effectively alter the proteolytic environment in both cardiac and skeletal muscle, as well as influence several autophagy-related factors in skeletal muscle of normotensive and hypertensive rats.

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

LENUS (Irish Health Repository)

O'Donnell, David H

2012-02-01

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

PHYTOTHERAPEUTIC EFFECT OF AVOCADOS AND SOYA AS DRUG ON HEART OF RATS EXPOSED TO GAMMA RADIATION

International Nuclear Information System (INIS)

OMRAN, M.F.; IBRAHIM, N.K.; ABU-ZIED, N.M.

2008-01-01

This study was planed to determine the role of single oral dose of avocados and soya in irradiated rats exposed to gamma radiation. the experimental animals were randomly divided into four groups; 12 rats for each. Group 1: kept as control. Group 2: rats received piascledine for 14 consecutive days. Group 3: rats submitted to whole body gamma rays (4 Gy). Group 4: rats received the same piascledine 14 days post-exposure to 4 Gy gamma radiation. The animals were weighed then dissected after one and fourteen days post-administration and the cardiac tissue and plasma were stored at 12 oC till used for biochemical analysis and kept in ice. The following parameters were determined: plasma total cholesterol, triacylglycerol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, LDH, phospholipids, ALT, CPK and TBARS. In cardiac tissue, determinations of total cholesterol, triacylglycerol, phospholipids and TBARS were conducted.It can be concluded that administration of avocados and soy as natural drug (piascledine) post-irradiation in rats is a favorable modificator against the impaired physiological processes in animal body due to gamma irradiation

Transient gestational and neonatal hypothyroidism-induced specific changes in androgen receptor expression in skeletal and cardiac muscles of adult rat.

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Annapoorna, K; Anbalagan, J; Neelamohan, R; Vengatesh, G; Stanley, J; Amudha, G; Aruldhas, M M

2013-03-01

The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V). Serum was collected for hormone assay. Androgen receptor status, Glu-4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles. Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control. Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism (group II-V). Glut-4 expression remained normal in skeletal and cardiac muscle of experimental rats. Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone. It is concluded that transient gestational/lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood. Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood. © Georg Thieme Verlag KG Stuttgart · New York.

Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress.

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Ozel Turkcu, Ummuhani; Bilgihan, Ayşe; Biberoglu, Gursel; Mertoglu Caglar, Oznur

2010-06-01

Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.

The Effect of Aerobic Training and Arbotin on Cardiac Nitric Oxide, Tumor Necrosis Factor alpha, and Vascular Endothelial Growth Factor in Male Diabetic Rats

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Rahemeh Jahangiri Jahangiri

2017-07-01

Full Text Available Background and Objectives: Diabetes is one of the most important metabolic diseases, which its incidence rate has increased in recent years. In this disease, the insulin function is impaired, leading to several complications. Physical exercise and medicinal plants are considered as a way to control diabetes along with nutrition and medicine. The present study was conducted with the purpose of determining the effect of aerobic training and use of arbutin on cardiac nitric oxide, tumor necrosis factor-α and vessel endothelial growth factor in male diabetic rats. Methods: In this experimental study, 42 male adult Wistar rats (age, 8 weeks; weight, 190-220g, were randomly divided into 6 groups of 7 each (control, arbutin, diabetic, diabetic+training, diabetic+arbutin, and diabetic+training+arbutin. Training programs included 5 days of swimming per week for 6 weeks. Sampling from the heart was performed 72 hours after the last training session and arbutin consumption to analyze NO, TNF-α and VEGF. Data were analyzed using one-way ANOVA at the significance level p≤0.05. Results: Aerobic training along with use of arbutin led to increased levels of NO and VEGF and decreased level of TNF-α in cardiac tissue of diabetic rats (p<0.001. Conclusion: The results indicated that a period of regular aerobic training and use of arbutin can be considered as an appropriate non-medicinal method to control diabetes mellitus type 2 through decrease in inflammatory factors.

Noninvasive detection of cardiac repair after acute myocardial infarction in rats by 111In fab fragment of monoclonal antibody specific for tenascin-C

International Nuclear Information System (INIS)

Okada, Kenichi; Uehara, Tomoya; Arano, Yasushi

2008-01-01

Left ventricular (LV) remodeling after acute myocardial infarction (MI) causes heart failure, and thus it is important to evaluate cardiac repair as the early stage of LV remodeling. Tenascin-C (TNC), an extracellular matrix glycoprotein, is transiently and abundantly expressed in the heart during the early stage of tissue remodeling after MI. However, it is not expressed in healthy adult heart. This study was undertaken to develop a new noninvasive diagnostic technique to detect cardiac repair after acute MI using 111 In Fab fragment of a monoclonal antibody specific for TNC. 111 In-anti-TNC-Fab was injected intravenously in 13 rats at 1 (D1, n=3), 3 (D3, n=5), and 5 (D5, n=5) days after producing MI and in 5 sham-operated rats (S). We performed autoradiography and dual-isotope single-photon emission computed tomography imaging (SPECT) of 111 In-anti-TNC-Fab and 99m Tc methoxyisobutyl isonitrile (MIBI). The radioactivity in the heart was significantly higher in D (D1, 0.45±0.06% injected-dose/g; D3, 0.64±0.12; D5, 0.38±0.07) than S (0.27±0.06, P 111 In-anti-TNC-Fab, which was complementary to the perfusion image. The results of the present study indicated that we can localize the infarcted region in the heart by ex vivo and in vivo imaging methods using 111 In-anti-TNC-Fab, and suggested the potential usefulness of noninvasive detection of cardiac repair. (author)

Milrinone ameliorates cardiac mechanical dysfunction after hypothermia in an intact rat model.

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Dietrichs, Erik Sveberg; Kondratiev, Timofei; Tveita, Torkjel

2014-12-01

Rewarming from hypothermia is often complicated by cardiac dysfunction, characterized by substantial reduction in stroke volume. Previously we have reported that inotropic agents, working via cardiac β-receptor agonism may exert serious side effects when applied to treat cardiac contractile dysfunction during rewarming. In this study we tested whether Milrinone, a phosphodiesterase III inhibitor, is able to ameliorate such dysfunction when given during rewarming. A rat model designed for circulatory studies during experimental hypothermia with cooling to a core temperature of 15°C, stable hypothermia at this temperature for 3h and subsequent rewarming was used, with a total of 3 groups: (1) a normothermic group receiving Milrinone, (2) a hypothermic group receiving Milrinone the last hour of hypothermia and during rewarming, and (3) a hypothermic saline control group. Hemodynamic function was monitored using a conductance catheter introduced to the left ventricle. After rewarming from 15°C, stroke volume and cardiac output returned to within baseline values in Milrinone treated animals, while these variables were significantly reduced in saline controls. Milrinone ameliorated cardiac dysfunction during rewarming from 15°C. The present results suggest that at low core temperatures and during rewarming from such temperatures, pharmacologic efforts to support cardiovascular function is better achieved by substances preventing cyclic AMP breakdown rather than increasing its formation via β-receptor stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy.

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Huang, Chao; Sachse, Frank B; Hitchcock, Robert W; Kaza, Aditya K

2016-01-01

Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 ± 0.3% and 98.0 ± 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 ± 0.3% and 94.0 ± 2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease.

Cardiac Insulin Resistance and MicroRNA Modulators

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Lakshmi Pulakat

2012-01-01

Full Text Available Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS, and this disorder may be accentuated by chronic alcohol consumption. In conditions of over-nutrition, increased insulin (INS and angiotensin II (Ang II activate mammalian target for rapamycin (mTOR/p70 S6 kinase (S6K1 signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activation of mTOR/S6K1 induces cardiac INS resistance via serine phosphorylation of INS receptor substrates (IRS-1/2, it also renders cardioprotection via increased Ang II receptor 2 (AT2R upregulation and adaptive hypertrophy. In the INS-resistant and hyperinsulinemic Zucker obese (ZO rat, a rodent model for CRS, activation of mTOR/S6K1signaling in cardiac tissue is regulated by protective feed-back mechanisms involving mTOR↔AT2R signaling loop and profile changes of microRNA that target S6K1. Such regulation may play a role in attenuating progressive heart failure. Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy.

Dihydrotestosterone induces pro-angiogenic factors and assists homing of MSC into the cardiac tissue.

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Popa, Mirel-Adrian; Mihai, Maria-Cristina; Constantin, Alina; Şuică, Viorel; Ţucureanu, Cătălin; Costache, Raluca; Antohe, Felicia; Dubey, Raghvendra K; Simionescu, Maya

2018-01-01

The use of mesenchymal stem cells (MSC) as a therapeutic tool in cardiovascular diseases is promising. Since androgens exert some beneficial actions on the cardiovascular system, we tested our hypothesis that this hormone could promote MSC-mediated repair processes, also. Cultured MSCs isolated from Wharton's jelly were exposed to 30 nM dihydrotestosterone (DHT) for 1 or 4 days and the effects of the hormone on their growth/migration/adhesion and the underlying mechanisms were assessed. Results were obtained by real-time cell impedance measurements, and DNA quantification showed that DHT increased MSC proliferation by ~30%. As determined by xCELLigence system, DHT augmented (~2 folds) the migration of MSC toward cardiac tissue slices (at 12 h), and this effect was blocked by flutamide, an androgen receptor (AR) antagonist. Exposure of cells to DHT, upregulated the gene and protein expression of AR , EMMPRIN and MMP-9 and downregulated the expression of MMP-2 DHT significantly induced the release of nitric oxide by MSC (≥2-fold) and flutamide blocked this effect. When MSCs were co-cultured with cardiac slices, immunohistochemical analysis and qRT-PCR showed that the integration of DHT-stimulated MSC was significantly higher than that of in controls. In conclusion, our findings provide the first evidence that DHT promotes MSC growth, migration and integration into the cardiac slices. The modulating effects of DHT were associated with upregulation of ARs and of key molecules known to promote tissue remodeling and angiogenesis. Our findings suggest that priming of MSC with DHT may potentially increase their capability to regenerate cardiac tissue; in vivo studies are needed to confirm our in vitro findings. © 2018 Society for Endocrinology.

Impact of organic hydroperoxides on rat testicular tissue and ...

African Journals Online (AJOL)

The effects of hydroperoxides on testicular tissue and epididymal sperm were investigated. Male Wistar rats aged 10 - 12 weeks were randomly placed in groups and received standard rat chow and water ad libitum. Animals were injected intraperitoneally with saline (0.5 ml), t-butyl hydroperoxide (5, 10, 20 and 40 ìM; 0.5 ...

Cardiac tissue Doppler imaging in sports medicine.

Science.gov (United States)

Krieg, Anne; Scharhag, Jürgen; Kindermann, Wilfried; Urhausen, Axel

2007-01-01

The differentiation of training-induced cardiac adaptations from pathological conditions is a key issue in sports cardiology. As morphological features do not allow for a clear delineation of early stages of relevant pathologies, the echocardiographic evaluation of left ventricular function is the technique of first choice in this regard. Tissue Doppler imaging (TDI) is a relatively recent method for the assessment of cardiac function that provides direct, local measurements of myocardial velocities throughout the cardiac cycle. Although it has shown a superior sensitivity in the detection of ventricular dysfunction in clinical and experimental studies, its application in sports medicine is still rare. Besides technical factors, this may be due to a lack in consensus on the characteristics of ventricular function in relevant conditions. For more than two decades there has been an ongoing debate on the existence of a supernormal left ventricular function in athlete's heart. While results from traditional echocardiography are conflicting, TDI studies established an improved diastolic function in endurance-trained athletes with athlete's heart compared with controls.The influence of anabolic steroids on cardiac function also has been investigated by standard echocardiographic techniques with inconsistent results. The only TDI study dealing with this topic demonstrated a significantly impaired diastolic function in bodybuilders with long-term abuse of anabolic steroids compared with strength-trained athletes without abuse of anabolic steroids and controls, respectively.Hypertrophic cardiomyopathy is the most frequent cause of sudden death in young athletes. However, in its early stages, it is difficult to distinguish from athlete's heart. By means of TDI, ventricular dysfunction in hypertrophic cardiomyopathy can be disclosed even before the development of left ventricular hypertrophy. Also, a differentiation of left ventricular hypertrophy due to hypertrophic

Effect of irradiation on the dental pulp tissues in streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Kang, Ho Duk; Hwang, Eui Hwan; Lee, Sang Rae

2005-01-01

To observe the histological changes in the pulp tissues of mandibular molars in streptozotocin-induced diabetic rats after irradiation. The male Sprague-Dawley rats weighing approximately 250 gm were divided into four groups : control, diabetes, irradiation, and diabetes-irradiation groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in control and irradiation groups were injected with citrate buffer only. After 5 days, the head and neck region of the rats in irradiation and diabetes-irradiation groups were irradiated with a single absorbed dose of 10 Gy. All the rats were sacrificed at 3, 7, 14, 21, and 28 days after irradiation. The specimen including the mandibular molars were sectioned and observed using a histopathological method. In the diabetes group, capillary dilatation was observed. However, there was no obvious morphologic alteration of the odontoblasts. In the irradiation group, generalized necrosis of the dental pulp tissues was observed. Vacuolation of the odontoblasts and dilatation of the capillaries were noted in the early experimental phases. In the diabetes-irradiation group, generalized degeneration of the dental pulp tissues was observed. Vacuolation of the dental pulp cells and the odontoblasts was noted in the late experimental phases. This experiment suggest that dilatation of the capillaries in the dental pulp tissue is induced by diabetic state, and generalized degeneration of the dental pulp tissues is induced by irradiation of the diabetic group.

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

Science.gov (United States)

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

2014-01-01

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

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

Science.gov (United States)

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

2017-10-01

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

Effects of Intracerebroventricularly (ICV) Injected Ghrelin on Cardiac Inducible Nitric Oxide Synthase Activity/Expression in Obese Rats.

Science.gov (United States)

Sudar Milovanovic, E; Jovanovic, A; Misirkic-Marjanovic, M; Vucicevic, Lj; Janjetovic, K; Isenovic, E R

2015-11-01

The aim of this study was to examine the effects of ghrelin on regulation of cardiac inducible nitric oxide synthase (iNOS) activity/expression in high fat (HF), obese rats.For this study, male Wistar rats fed with HF diet (30% fat) for 4 weeks were injected every 24 h for 5 days intracerebroventricularly (ICV) with ghrelin (0.3 nmol/5 µl) or with an equal volume of phosphate buffered saline (PBS). Control rats were ICV injected with an equal volume of PBS. Glucose, insulin and nitric oxide (NO) concentrations were measured in serum, while arginase activity and citrulline concentrations were measured in heart lysate. Protein iNOS and regulatory subunit of nuclear factor-κB (NFκB-p65), phosphorylation of enzymes protein kinase B (Akt) at Ser(473), and extracellular signal-regulated kinases 1/2 (ERK1/2) at Tyr(202)/Tyr(204) were determined in heart lysate by Western blot. For gene expression of iNOS qRT-PCR was used.Results show significantly (parginase activity (pactivity of cardiac iNOS via Akt phosphorylation followed by NFκB activation in HF rats. © Georg Thieme Verlag KG Stuttgart · New York.

Leonurine (SCM-198) improves cardiac recovery in rat during chronic infarction.

Science.gov (United States)

Liu, XinHua; Pan, LiLong; Gong, QiHai; Zhu, YiZhun

2010-12-15

Leonurine, an alkaloid typically found in Herba leonuri, is known to have both antioxidant and cardioprotective properties. In the present study, we investigated the cardioprotective mechanism of leonurine the in vivo rat model of chronic myocardial ischemia and in vitro H9c2 cardiac myocyte model of oxidative stress. Myocardial ischemia was induced by ligating the left anterior descending coronary artery. Rats were divided into sham, myocardial ischemia+saline, and myocardial ischemia+leonurine (15 mg/kg/day). Cardiac function was recorded by catheterization. Apoptosis-related factor vascular endothelial growth factor (VEGF), survivin, Bcl-2 and Bax and pro-survival signaling pathways Akt, hypoxia inducible factor (HIF)-1α were measured by Western blotting or RT-PCR. Our results showed leonurine significantly improved myocardial function as evidenced by the decreased left ventricle end-diastolic pressure and the increased +dP/dt. Interestingly, leonurine increased the phosphorylation of Akt, the protein and gene expression of Bcl-2, but it reduced the protein and gene expression of Bax in vivo. Meanwhile leonurine significantly increased Akt phosphorylation in a concentration-dependent manner in H9c2 cardiac myocyte induced by oxidative stress in vitro, which was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. Furthermore, leonurine not only increased the expression of HIF-1α but also the expression of survivin and VEGF. The results of present study demonstrated, for the first time that leonurine has potent anti-apoptotic effects after chronic myocardial ischemia mediated by activating the PI3K/Akt signaling pathway. Angiogenic mechanisms may be partially responsible for such an effect, which needs to be studied further. Copyright © 2010 Elsevier B.V. All rights reserved.

PROPOSED CARDIAC STEM CELLS DERIVED FROM “CARDIOSPHERES” LACK CARDIOMYOGENIC POTENTIAL

DEFF Research Database (Denmark)

Andersen, Ditte Caroline

   Recent studies have reported that clinical relevant numbers of cardiac stem cells (CSCs) with cardiomyogenic potential can be obtained from small heart tissue biopsies, by an intrinsic ability of CSCs to form beating cardiospheres (CSs) during ex vivo culture. Such data have provided optimism...... that injuried heart tissue may be repaired by stem cell therapy using autologous CS derived cells, and pre-clinical studies have already been described in literature.    Herein, we established CSs from neonatal rats, and by immunofluorescence, qRT-PCR, and microscopic examination we demonstrated...... to form CSs by themselves. Phenotypically, CS cells largely resembled fibroblasts, and they lacked cardiomyogenic as well as endothelial differentiation potential.    Our data imply that at least the murine cardiosphere model seems unsuitable for enrichment of cardiac stem cells with cardiomyogenic...

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...

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

Energy Technology Data Exchange (ETDEWEB)

Baei, Payam [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Jalili-Firoozinezhad, Sasan [Department of Biomedicine and Surgery, University Hospital Basel, University of Basel, Hebelstrasse 20, CH-4031 Basel (Switzerland); Department of Bioengineeringand IBB - Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa (Portugal); Rajabi-Zeleti, Sareh [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad [Cardiovascular Engineering Laboratory, Faculty of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran (Iran, Islamic Republic of); Baharvand, Hossein, E-mail: Baharvand@royaninstitute.org [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of); Department of Developmental Biology, University of Science and Culture, ACECR, Tehran (Iran, Islamic Republic of); Aghdami, Nasser, E-mail: Nasser.Aghdami@royaninstitute.org [Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran (Iran, Islamic Republic of)

2016-06-01

Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14 days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues. - Highlights: • Thermosensitive electro-conductive hydrogels were prepared from CS and GNPs. • Gelation time and conductivity were tuned by varying concentration of GNPs. • CS-2GNP with gelation time of 25.7 min and conductivity of 0.13 S·m{sup −1} was selected for in vitro studies. • CS-2GNP supported active metabolism, migration and proliferation of MSCs. • Expression of cardiac markers increased about two-fold in CS-2GNP compared to CS.

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

International Nuclear Information System (INIS)

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

2016-01-01

Injectable hydrogels that resemble electromechanical properties of the myocardium are crucial for cardiac tissue engineering prospects. We have developed a facile approach that uses chitosan (CS) to generate a thermosensitive conductive hydrogel with a highly porous network of interconnected pores. Gold nanoparticles (GNPs) were evenly dispersed throughout the CS matrix in order to provide electrical cues. The gelation response and electrical conductivity of the hydrogel were controlled by different concentrations of GNPs. The CS-GNP hydrogels were seeded with mesenchymal stem cells (MSCs) and cultivated for up to 14 days in the absence of electrical stimulations. CS-GNP scaffolds supported viability, metabolism, migration and proliferation of MSCs along with the development of uniform cellular constructs. Immunohistochemistry for early and mature cardiac markers showed enhanced cardiomyogenic differentiation of MSCs within the CS-GNP compared to the CS matrix alone. The results of this study demonstrate that incorporation of nanoscale electro-conductive GNPs into CS hydrogels enhances the properties of myocardial constructs. These constructs could find utilization for regeneration of other electroactive tissues. - Highlights: • Thermosensitive electro-conductive hydrogels were prepared from CS and GNPs. • Gelation time and conductivity were tuned by varying concentration of GNPs. • CS-2GNP with gelation time of 25.7 min and conductivity of 0.13 S·m"−"1 was selected for in vitro studies. • CS-2GNP supported active metabolism, migration and proliferation of MSCs. • Expression of cardiac markers increased about two-fold in CS-2GNP compared to CS.

Transient receptor potential vanilloid-3 (TRPV3) activation plays a central role in cardiac fibrosis induced by pressure overload in rats via TGF-β1 pathway.

Science.gov (United States)

Liu, Yan; Qi, Hanping; E, Mingyao; Shi, Pilong; Zhang, Qianhui; Li, Shuzhi; Wang, Ye; Cao, Yonggang; Chen, Yunping; Ba, Lina; Gao, Jingquan; Huang, Wei; Sun, Hongli

2018-02-01

Cardiac fibrosis is a common pathologic change along with pressure overload. Recent studies indicated that transient receptor potential (TRP) channels played multiple roles in heart. However, the functional role of transient receptor potential vanilloid-3 (TRPV3) in cardiac fibrosis remained unclear. The present study was designed to investigate the relationship between TRPV3 activation and pressure overload-induced cardiac fibrosis. Pressure overload rats were successfully established by abdominal aortic constriction (AAC), and cardiac fibrosis was simulated by 100 nM angiotensin II (Ang II) in neonatal cardiac fibroblasts. Echocardiographic parameters, cardiac fibroblast proliferation, cell cycle, intracellular calcium concentration ([Ca 2+ ] i ), and the protein expressions of collagen I, collagen III, transforming growth factor beta 1 (TGF-β 1 ), cyclin E, and cyclin-dependent kinase 2 (CDK2) were measured. Echocardiographic and histological measurements suggested that the activation of TRPV3 exacerbated the cardiac dysfunction and increased interstitial fibrosis in pressure overload rats. Further results showed that TRPV3 activation upregulated the expressions of collagen I, collagen III, TGF-β 1 , cyclin E, and CDK2 in vivo and in vitro. At the same time, blocking TGF-β 1 pathway could partially reverse the effect of TRPV3 activation. These results suggested that TRPV3 activation exacerbated cardiac fibrosis by promoting cardiac fibroblast proliferation through TGF-β 1 /CDK2/cyclin E pathway in the pressure-overloaded rat hearts.

Reduced CGP12177 binding to cardiac β-adrenoceptors in hyperglycemic high-fat-diet-fed, streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Thackeray, James T.; Parsa-Nezhad, Maryam; Kenk, Miran; Thorn, Stephanie L.; Kolajova, Maria; Beanlands, Rob S.B.; DaSilva, Jean N.

2011-01-01

Introduction: Abnormal sympathetic nervous system and β-adrenoceptor (β-AR) signaling is associated with diabetes. [ 3 H]CGP12177 is a nonselective β-AR antagonist that can be labeled with carbon-11 for positron emission tomography. The aim of this study was to examine the suitability of this tracer for evaluation of altered β-AR expression in diabetic rat hearts. Methods: Ex vivo biodistribution with [ 3 H]CGP12177 was carried out in normal Sprague-Dawley rats for evaluation of specific binding and response to continuous β-AR stimulation by isoproterenol. In a separate group, high-fat-diet feeding imparted insulin resistance and a single intraperitoneal injection of streptozotocin (STZ) or vehicle evoked hyperglycemia (blood glucose >11 mM). [ 3 H]CGP12177 biodistribution was assessed at 2 and 8 weeks post-STZ to measure β-AR binding in heart, 30 min following tracer injection. Western blotting of β-AR subtypes was completed in parallel. Results: Infusion of isoproterenol over 14 days did not affect cardiac binding of [ 3 H]CGP12177. Approximately half of rats treated with STZ exhibited sustained hyperglycemia and progressive hypoinsulinemia. Myocardial [ 3 H]CGP12177 specific binding was unchanged at 2 weeks post-STZ but significantly reduced by 30%-40% at 8 weeks in hyperglycemic but not euglycemic STZ-treated rats compared with vehicle-treated controls. Western blots supported a significant decrease in β 1 -AR in hyperglycemic rats. Conclusions: Reduced cardiac [ 3 H]CGP12177 specific binding in the presence of sustained hyperglycemia corresponds to a decrease in relative β 1 -AR expression. These data indirectly support the use of [ 11 C]CGP12177 for assessment of cardiac dysfunction in diabetes.

Glutamine reduces myocardial cell apoptosis in a rat model of sepsis by promoting expression of heat shock protein 90.

Science.gov (United States)

Li, Wanxia; Tao, Shaoyu; Wu, Qinghua; Wu, Tao; Tao, Ran; Fan, Jun

2017-12-01

Myocardial cell injury and cardiac myocyte apoptosis are associated with sepsis. Glutamine (Gln) has been reported to repair myocardial cell injury. The aim of this study was to explore the role of Gln on cardiac myocytes in a cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Following induction of sepsis in a CLP rat model, viral encoding heat shock protein 90 (Hsp90) gene and Hsp90dsDNA were designed to express and knockdown Hsp90, respectively. Rat cardiac tissues were examined histologically, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, Hsp90, p53 upregulated modulator of apoptosis, and p53 was measured by western blotting and real-time polymerase chain reaction. Caspase-3, caspase-8, and caspase-9 were detected by enzyme-linked immunosorbent assay. Rat cardiac myocyte damage induced by CLP was reduced by Gln treatment and Hsp90 overexpression, and these changes were reversed by Hsp90 knockdown. Bcl-2 expression, Bcl-2-associated X protein, p53, p53 upregulated modulator of apoptosis, caspase-8, caspase-9, and caspase-3 activities were significantly upregulated in the CLP model, which were reduced by Gln treatment and Hsp90 overexpression. Gln reduced apoptosis of cardiac myocytes in a rat model of sepsis, by promoting Hsp90 expression. Further studies are needed to determine the possible therapeutic action of Gln in sepsis in human tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions.

Directory of Open Access Journals (Sweden)

Jitender P Dubey

Full Text Available The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse.Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i. to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25% of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle.This study reevaluated

Effects of Gallic Acid and Cyclosporine A on Antioxidant Capacity and Cardiac Markers of Rat Isolated Heart After Ischemia/Reperfusion

Science.gov (United States)

Badavi, Mohammad; Sadeghi, Najmeh; Dianat, Mahin; Samarbafzadeh, Alireza

2014-01-01

Background: Myocardial infarction is one of the important causes of death during old ages. Gallic acid as an antioxidant or cyclosporine A (CsA) as inhibitor of mitochondrial permeability transition pore (mPTP) alone could prevent these complications to some extent, but their combination effect has not been investigated. Objectives: The aim of this study was to determine the combined effect of gallic acid and CsA on antioxidant capacity of isolated heart tissues during ischemia reperfusion. Materials and Methods: Eighty male Wistar rats were randomly assigned to different groups: sham, control (Ca, received saline, 1 mL/kg); 3 groups were pretreated with gallic acid (G1a: 7.5, G2a: 15, G3a: 30 mg/kg) for 10 days, and the other 3 groups were pretreated with gallic acid and received CsA (0.2 µM) for 10 minutes before induction of ischemia and during the first 10 minutes of reperfusion (G1b, G2b and G3b) and the last group received CsA alone (Cb). After 10 days of pretreatment, the heart was isolated and transferred to the Langendorff apparatus and exposed to 30 minutes ischemia followed by 60 minutes of reperfusion. After that cardiac markers and antioxidant enzymes were assessed in cardiac tissues. Results: Lactate dehydrogenase (LDH), Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activity increased and malondialdehyde (MDA) decreased in animals pretreated with gallic acid significantly. However, pretreatment with gallic acid followed by CsA during reperfusion improved the antioxidant capacity and cardiac marker enzymes and restored the lipid peroxidation more effective than gallic acid or CsA alone. Nevertheless, CsA did not change the cardiac marker enzymes significantly. Conclusions: Gallic acid and CsA combination improved antioxidant capacity and cell membrane integrity more than each one alone. Therefore, it can be a therapeutic approach to reduce the I/R injury. PMID:25068044

Hibiscus sabdariffa (Roselle) Polyphenol-rich Extract Averts Cardiac Functional and Structural Abnormalities in Type 1 Diabetic Rats.

Science.gov (United States)

Mohammed Yusof, Nur Liyana; Zainalabidin, Satirah; Mohd Fauzi, Norsyahida; Budin, Siti Balkis

2018-05-04

Diabetes mellitus is often associated with cardiac functional and structural alteration, an initial event leading to cardiovascular complications. Hibiscus sabdariffa or roselle has been widely proven as an antioxidant and recently has incited research interest for its potential in treating cardiovascular disease. Therefore, this study aimed to determine the cardioprotective effects of H. sabdariffa (roselle) polyphenol-rich extract (HPE) in type-1 induced diabetic rats. Twenty-four male Sprague-Dawley rats were randomized into four groups (n=6/group): non-diabetic (NDM), diabetic alone (DM), diabetic supplemented with HPE (DM+HPE) and metformin (DM+MET). Type-1 diabetes was induced with streptozotocin (55 mg/kg/i.p). Rats were forced-fed HPE (100 mg/kg) and metformin (150 mg/kg) daily for eight weeks. Results showed that HPE supplementation improved hyperglycemia and dyslipidemia significantly (p<0.05) in DM+HPE compared to DM group. HPE supplementation attenuated cardiac oxidative damage in DM group, indicated by low malondialdehyde and advanced oxidation protein product. As for the antioxidant status, HPE significantly (p<0.05) increased glutathione level, as well as catalase and superoxide dismutase 1 and 2 activities. These findings correlate with cardiac function, whereby HPE supplementation improved left ventricle developed pressure, coronary flow, cardiac contractility and relaxation rate significantly (p<0.05). Histological analysis showed a marked decrease in cardiomyocyte hypertrophy and fibrosis in DM+HPE compared to DM group. Ultrastructural changes and impairment of mitochondria induced by diabetes were minimized by HPE supplementation. Collectively, these findings suggest that HPE is a potential cardioprotective agent in a diabetic setting through its hypoglycemic, anti-hyperlipidemia and antioxidant properties.

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

Science.gov (United States)

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

2017-11-01

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

MRI-based morphological modeling, synthesis and characterization of cardiac tissue-mimicking materials.

Science.gov (United States)

Kossivas, Fotis; Angeli, S; Kafouris, D; Patrickios, C S; Tzagarakis, V; Constantinides, C

2012-06-01

This study uses standard synthetic methodologies to produce tissue-mimicking materials that match the morphology and emulate the in vivo murine and human cardiac mechanical and imaging characteristics, with dynamic mechanical analysis, atomic force microscopy (AFM), scanning electron microscopy (SEM) and magnetic resonance imaging. In accordance with such aims, poly(glycerol sebacate) (PGS) elastomeric materials were synthesized (at two different glycerol (G)-sebacic (S) acid molar ratios; the first was synthesized using a G:S molar ratio of 2:2, while the second from a 2:5 G:S molar ratio, resulting in PGS2:2 and PGS2:5 elastomers, respectively). Unlike the synthesized PGS2:2 elastomers, the PGS2:5 materials were characterized by an overall mechanical instability in their loading behavior under the three successive loading conditions tested. An oscillatory response in the mechanical properties of the synthesized elastomers was observed throughout the loading cycles, with measured increased storage modulus values at the first loading cycle, stabilizing to lower values at subsequent cycles. These elastomers were characterized at 4 °C and were found to have storage modulus values of 850 and 1430 kPa at the third loading cycle, respectively, in agreement with previously reported values of the rat and human myocardium. SEM of surface topology indicated minor degradation of synthesized materials at 10 and 20 d post-immersion in the PBS buffer solution, with a noted cluster formation on the PGS2:5 elastomers. AFM nanoindentation experiments were also conducted for the measurement of the Young modulus of the sample surface (no bulk contribution). Correspondingly, the PGS2:2 elastomer indicated significantly decreased surface Young's modulus values 20 d post-PBS immersion, compared to dry conditions (Young's modulus = 1160 ± 290 kPa (dry) and 200 ± 120 kPa (20 d)). In addition to the two-dimensional (2D) elastomers, an integrative platform for accurate construction of

MRI-based morphological modeling, synthesis and characterization of cardiac tissue-mimicking materials

International Nuclear Information System (INIS)

Kossivas, Fotis; Angeli, S; Constantinides, C; Kafouris, D; Patrickios, C S; Tzagarakis, V

2012-01-01

This study uses standard synthetic methodologies to produce tissue-mimicking materials that match the morphology and emulate the in vivo murine and human cardiac mechanical and imaging characteristics, with dynamic mechanical analysis, atomic force microscopy (AFM), scanning electron microscopy (SEM) and magnetic resonance imaging. In accordance with such aims, poly(glycerol sebacate) (PGS) elastomeric materials were synthesized (at two different glycerol (G)–sebacic (S) acid molar ratios; the first was synthesized using a G:S molar ratio of 2:2, while the second from a 2:5 G:S molar ratio, resulting in PGS2:2 and PGS2:5 elastomers, respectively). Unlike the synthesized PGS2:2 elastomers, the PGS2:5 materials were characterized by an overall mechanical instability in their loading behavior under the three successive loading conditions tested. An oscillatory response in the mechanical properties of the synthesized elastomers was observed throughout the loading cycles, with measured increased storage modulus values at the first loading cycle, stabilizing to lower values at subsequent cycles. These elastomers were characterized at 4 °C and were found to have storage modulus values of 850 and 1430 kPa at the third loading cycle, respectively, in agreement with previously reported values of the rat and human myocardium. SEM of surface topology indicated minor degradation of synthesized materials at 10 and 20 d post-immersion in the PBS buffer solution, with a noted cluster formation on the PGS2:5 elastomers. AFM nanoindentation experiments were also conducted for the measurement of the Young modulus of the sample surface (no bulk contribution). Correspondingly, the PGS2:2 elastomer indicated significantly decreased surface Young's modulus values 20 d post-PBS immersion, compared to dry conditions (Young's modulus = 1160 ± 290 kPa (dry) and 200 ± 120 kPa (20 d)). In addition to the two-dimensional (2D) elastomers, an integrative platform for accurate construction of

Plasma transthyretin. Tissue sites of degradation and turnover in the rat

International Nuclear Information System (INIS)

Makover, A.; Moriwaki, H.; Ramakrishnan, R.; Saraiva, M.J.; Blaner, W.S.; Goodman, D.S.

1988-01-01

Transthyretin (TTR) is involved in the plasma transport of both retinol and thyroid hormones. TTR is synthesized in the liver and choroid plexus, and in small amounts in several other tissues. A study was conducted to determine the tissue sites of degradation and turnover of TTR in the rat. The study employed TTR labeled with tyramine cellobiose (TC) and the trapped ligand method. Samples of purified rat TTR were labeled either with 125I-TC or directly with 131I. A mixture of the two labeled TTRs was injected intravenously into six rats. Blood samples were collected via a venous catheter for kinetic (turnover) analysis. After 24 or 48 h, the rats were killed, and 23 different tissues/organs were assayed as possible sites of TTR degradation. Derivatization of TTR with TC did not appreciably alter TTR plasma kinetics. Plasma turnover data were best fit by a three-pool model. The mean fractional turnover of plasma TTR was 0.15/h, and of total body TTR 0.04/h. The major sites of TTR degradation were the liver (36-38% of total body TTR degradation, almost all in hepatocytes), muscle (12-15%), and skin (8-10%). Tissues that were sites of 1-8% of body TTR degradation included kidneys, adipose tissue, testes, and the gastrointestinal tract. Less than 1% of total TTR degradation occurred in the other tissues examined. A second study was conducted in which labeled TTR was injected intraventricularly into the cerebrospinal fluid in order to explore the degradation of TTR of choroid plexus origin. The kinetics of the appearance and disappearance of such labeled TTR in plasma were physiologically reasonable, with an estimated turnover of cerebrospinal fluid TTR of the order of 0.33/h. The major tissue sites of degradation of labeled TTR injected into cerebrospinal fluid and into plasma were approximately the same

Distribution of /sup 125/I-thyroxine in different organs and tissues of dietically obese rats

Energy Technology Data Exchange (ETDEWEB)

Hartmann, K.; Voss, C.; Huebner, G. (Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic)); Weber, A. (Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic). Radiologische Klinik)

1985-04-01

The distribution of /sup 125/I-thyroxine (% dose/g tissue; tissue/plasma radioactivity ratio) was investigated in different tissues of 28-week-old obese Wistar rats. Obesity was induced by high-fat diet (HFD) and confirmed by carcass analysis; in heavy obese animals the relative and absolute fat content is increased twofold and threefold, respectively, compared to control rats fed on a low-fat diet (LFD). Heavy HFD rats exhibit diminished /sup 125/I-T/sub 4/ distribution in the 'slow pool' (fat tissue, muscle) and unchanged values in the 'fast pool' (liver, kidneys) in comparison with LFD rats with low body weight. The differences in distribution presented here are not caused by the diet per se, but they are the consequence of the obesity of the animal, because no differences in the /sup 125/I-T/sub 4/ distribution were found in the /sup 125/I-T/sub 4/ between HFD and LFD rats with relatively equal body weight and body composition. The reduced T/sub 4/ distribution in the fat tissue of obese rats is discussed in connection with possibly decreased lipolysis in this tissue and possible causal participation in the beginning of obesity.

Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

Science.gov (United States)

Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

2010-04-01

This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p <0.05. Obese group on grain-based diet showed significant increase in MDA levels only in the duodenum, p <0.05. We conclude that dietary intervention differentially affects the oxidative markers in obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

The profound effects of microcystin on cardiac antioxidant enzymes, mitochondrial function and cardiac toxicity in rat

International Nuclear Information System (INIS)

Qiu Tong; Xie Ping; Liu Ying; Li Guangyu; Xiong Qian; Hao Le; Li Huiying

2009-01-01

Deaths from microcystin toxication have widely been attributed to hypovolemic shock due to hepatic interstitial hemorrhage, while some recent studies suggest that cardiogenic complication is also involved. So far, information on cardiotoxic effects of MC has been rare and the underlying mechanism is still puzzling. The present study examined toxic effects of microcystins on heart muscle of rats intravenously injected with extracted MC at two doses, 0.16LD 50 (14 μg MC-LReq kg -1 body weight) and 1LD 50 (87 μg MC-LReq kg -1 body weight). In the dead rats, both TTC staining and maximum elevations of troponin I levels confirmed myocardial infarction after MC exposure, besides a serious interstitial hemorrhage in liver. In the 1LD 50 dose group, the coincident falls in heart rate and blood pressure were related to mitochondria dysfunction in heart, while increases in creatine kinase and troponin I levels indicated cardiac cell injury. The corresponding pathological alterations were mainly characterized as loss of adherence between cardiac myocytes and swollen or ruptured mitochondria at the ultrastructural level. MC administration at a dose of 1LD 50 not only enhanced activities and up-regulated mRNA transcription levels of antioxidant enzymes, but also increased GSH content. At both doses, level of lipid peroxides increased obviously, suggesting serious oxidative stress in mitochondria. Simultaneously, complex I and III were significantly inhibited, indicating blocks in electron flow along the mitochondrial respiratory chain in heart. In conclusion, the findings of this study implicate a role for MC-induced cardiotoxicity as a potential factor that should be considered when evaluating the mechanisms of death associated with microcystin intoxication in Brazil

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

International Nuclear Information System (INIS)

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

2016-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-08-15

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

Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

Energy Technology Data Exchange (ETDEWEB)

Faddah, L. M.; Baky, Nayira A. Abdel [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia); Mohamed, Azza M., E-mail: azzamohamed99@yahoo.com [King Abdulaziz University, Biochemistry Department, Faculty of Science for Girls (Saudi Arabia); Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M. [King Saud University, Pharmacology Department, Faculty of Pharmacy (Saudi Arabia)

2013-04-15

The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-{alpha}, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

Science.gov (United States)

Faddah, L. M.; Baky, Nayira A. Abdel; Mohamed, Azza M.; Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M.

2013-04-01

The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-α, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

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

NARCIS (Netherlands)

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

1995-01-01

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

Calcium and magnesium content in hard tissues of rats under condition of subchronic lead intoxication.

Science.gov (United States)

Todorovic, Tatjana; Vujanovic, Dragana; Dozic, Ivan; Petkovic-Curcin, Aleksandra

2008-03-01

Lead manifests toxic effects in almost all organs and tissues, especially in: the nervous system, hematopoietic system, kidney and liver. This metal has a special affinity for deposition in hard tissue, i.e., bones and teeth. It is generally believed that the main mechanism of its toxicity relies on its interaction with bioelements, especially with Ca and Mg. This article analyses the influence of Pb poisoning on Ca and Mg content in hard tissues, (mandible, femur, teeth and skull) of female and young rats. Experiments were carried out on 60 female rats, AO breed, and on 80 of their young rats (offspring). Female rats were divided into three groups: the first one was a control group, the second one received 100 mg/kg Pb2+ kg b.wt. per day in drinking water, the third one received 30 mg/kg Pb(2+) kg b.wt. per day in drinking water. Young rats (offspring) were divided into the same respective three groups. Lead, calcium and magnesium content in hard tissues (mandible, femur, teeth-incisors and skull) was determined by flame atomic absorption spectrophotometry in mineralized samples. There was a statistically significant Pb deposition in all analyzed female and young rat hard tissues. Ca and Mg contents were significantly reduced in all female and young rat hard tissues. These results show that Pb poisoning causes a significant reduction in Ca and Mg content in animal hard tissues, which is probably the consequence of competitive antagonism between Pb and Ca and Mg.

Activity and immunohistochemical localization of porphobilinogen deaminase in rat tissues

DEFF Research Database (Denmark)

Jørgensen, P E; Erlandsen, E J; Poulsen, Steen Seier

2000-01-01

the activity and the immunohistochemical localization of PBGD in the following tissues of wistar female rats: brain, heart, submandibular gland, liver, kidney, pancreas, ovary, stomach, duodenum, jejunum, ileum, colon and musculature. The PBGD activity varied considerably among the tissues. It was highest...

Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF-α and TGF-β1/ERK1/2 signaling pathways

Science.gov (United States)

Zhang, Changyi; Zhou, Guichi; Chen, Yezeng; Liu, Sizheng; Chen, Fen; Xie, Lichun; Wang, Wei; Zhang, Yonggang; Wang, Tianyou; Lai, Xiulan; Ma, Lian

2018-01-01

Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord-derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin-induced rat model of DCM. Male Lewis rats (aged 8-weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1×106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle-injected and negative control rats. Myosin injections in rats (vehicle group and experimental group) for 28 days led to severe fibrosis and significant deterioration of cardiac function indicative of DCM. HuMSC treatment reduced fibrosis as determined by Masson's staining of collagen deposits, as well as quantification of molecular markers of myocardial fibrosis such as collagen I/III, profibrotic factors transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and connective tissue growth factor (CTGF). HuMSC treatment restored cardiac function as observed using echocardiography. In addition, western blot analysis indicated that HuMSC injections in DCM rats inhibited the expression of TNF-α, extracellular-signal regulated kinase 1/2 (ERK1/2) and TGF-β1, which is a master switch for inducing myocardial fibrosis. These findings suggested that HuMSC injections attenuated myocardial fibrosis and dysfunction in a rat model of DCM, likely by inhibiting TNF-α and the TGF-β1/ERK1/2 fibrosis pathways. Therefore, HuMSC treatment may represent a potential therapeutic method for treatment of DCM. PMID:29115435

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

Directory of Open Access Journals (Sweden)

Jingchao Lu

2016-06-01

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

The cardioprotective efficacy of TVP1022 against ischemia/reperfusion injury and cardiac remodeling in rats.

Science.gov (United States)

Malka, Assaf; Ertracht, Offir; Bachner-Hinenzon, Noa; Reiter, Irina; Binah, Ofer

2016-12-01

Following acute myocardial infarction (MI), early and successful reperfusion is the most effective strategy for reducing infarct size and improving the clinical outcome. However, immediate restoration of blood flow to the ischemic zone results in myocardial damage, defined as "reperfusion-injury". Whereas we previously reported that TVP1022 (the S-isomer of rasagiline, FDA-approved anti-Parkinson drug) decreased infarct size 24 h post ischemia reperfusion (I/R) in rats, in this study we investigated the chronic cardioprotective efficacy of TVP1022 14 days post-I/R. To simulate the clinical settings of acute MI followed by reperfusion therapy, we employed a rat model of left anterior descending artery occlusion for 30 min followed by reperfusion and a follow-up for 14 days. TVP1022 was initially administered postocclusion-prereperfusion, followed by chronic daily administrations. Cardiac performance and remodeling were evaluated using customary and advanced echocardiographic methods, hemodynamic measurements by Millar Mikro-Tip ® catheter, and histopathological techniques. TVP1022 administration markedly decreased the remodeling process as illustrated by attenuation of left ventricular enlargement and cardiac hypertrophy (both at the whole heart and the cellular level). Furthermore, TVP1022 inhibited cardiac fibrosis and reduced ventricular BNP levels. Functionally, TVP1022 treatment preserved cardiac wall motion. Specifically, the echocardiographic and most of the direct hemodynamic measures were pronouncedly improved by TVP1022. Collectively, these findings indicate that TVP1022 provides prominent cardioprotection against I/R injury and post-MI remodeling in this I/R model.

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

Directory of Open Access Journals (Sweden)

Żebrowska Aleksandra

2017-04-01

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

Transmission electron microscopy of heart and liver tissues from rats fed with gums arabic and tragacanth.

Science.gov (United States)

Anderson, D M; Ashby, P; Busuttil, A; Kempson, S A; Lawson, M E

1984-04-01

Transmission electron microscopy has been used to examine the ultrastructure of rat hearts and livers after diet supplementation with (a) 0, 0.5, 1.5, 2.5 and 3.5% (w/w) gum tragacanth (GT) for 91 days, (b) 0 and 1% GT for 5 days (c) 0, 1, 4 and 8% (w/w) gum arabic (GA) for 28 days. The preparation and scrutiny of the electron micrographs was undertaken by two independent teams of specialists. There were no detectable abnormalities in any of the organelles in the heart and liver specimens from any of the test animals and no inclusions nor other pathological changes were observed. All micrographs showed normal, healthy tissues; particular attention was given to the mitochondria in hepatocytes as they serve as sensitive indicators of the health and state of activity of cells. In addition, the data obtained from assays of the microsomal protein and cytochrome P-450 content of the livers showed that GA and GT did not cause inductive effects. These results do not support earlier suggestions, based on in vitro assays, that GA and GT cause changes in the function of rat heart and liver mitochondria and liver microsomes; however, they confirm a report by Zbinden that the ingestion of GT does not produce abnormalities in the cardiac function of rats.

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-07-11

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

Reduced CGP12177 binding to cardiac {beta}-adrenoceptors in hyperglycemic high-fat-diet-fed, streptozotocin-induced diabetic rats

Energy Technology Data Exchange (ETDEWEB)

Thackeray, James T.; Parsa-Nezhad, Maryam; Kenk, Miran; Thorn, Stephanie L. [Molecular Function and Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Roger Guindon Hall, Ottawa, Ontario, K1H8M5 (Canada); Kolajova, Maria [Molecular Function and Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y4W7 (Canada); Beanlands, Rob S.B. [Molecular Function and Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Roger Guindon Hall, Ottawa, Ontario, K1H8M5 (Canada); DaSilva, Jean N., E-mail: jdasilva@ottawaheart.ca [Molecular Function and Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, K1Y4W7 (Canada); Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Roger Guindon Hall, Ottawa, Ontario, K1H8M5 (Canada)

2011-10-15

Introduction: Abnormal sympathetic nervous system and {beta}-adrenoceptor ({beta}-AR) signaling is associated with diabetes. [{sup 3}H]CGP12177 is a nonselective {beta}-AR antagonist that can be labeled with carbon-11 for positron emission tomography. The aim of this study was to examine the suitability of this tracer for evaluation of altered {beta}-AR expression in diabetic rat hearts. Methods: Ex vivo biodistribution with [{sup 3}H]CGP12177 was carried out in normal Sprague-Dawley rats for evaluation of specific binding and response to continuous {beta}-AR stimulation by isoproterenol. In a separate group, high-fat-diet feeding imparted insulin resistance and a single intraperitoneal injection of streptozotocin (STZ) or vehicle evoked hyperglycemia (blood glucose >11 mM). [{sup 3}H]CGP12177 biodistribution was assessed at 2 and 8 weeks post-STZ to measure {beta}-AR binding in heart, 30 min following tracer injection. Western blotting of {beta}-AR subtypes was completed in parallel. Results: Infusion of isoproterenol over 14 days did not affect cardiac binding of [{sup 3}H]CGP12177. Approximately half of rats treated with STZ exhibited sustained hyperglycemia and progressive hypoinsulinemia. Myocardial [{sup 3}H]CGP12177 specific binding was unchanged at 2 weeks post-STZ but significantly reduced by 30%-40% at 8 weeks in hyperglycemic but not euglycemic STZ-treated rats compared with vehicle-treated controls. Western blots supported a significant decrease in {beta}{sub 1}-AR in hyperglycemic rats. Conclusions: Reduced cardiac [{sup 3}H]CGP12177 specific binding in the presence of sustained hyperglycemia corresponds to a decrease in relative {beta}{sub 1}-AR expression. These data indirectly support the use of [{sup 11}C]CGP12177 for assessment of cardiac dysfunction in diabetes.

Determination of trace elements in tissues of diabetic rats by INAA

International Nuclear Information System (INIS)

Tan Mingguang; Wang Yinsong; Qian Yine; Zhang Guilin

2000-01-01

By using streptozotocin (STZ) injection to induce model diabetic rats, instrumental neutron activation analysis was applied to analyze elemental; concentrations in liver, kidney and pancreas tissues in diabetes and control rats. Results obtained for As, Br, Ca, Co, Cl, Cu, Fe, Hg, Mg, Mn, Na, Rb, S, Se and Zn in those tissues show that some elemental contents in diabetic group change obviously when compared with those of the controls. The changes of elemental contents and their significance are discussed

Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart.

Science.gov (United States)

Granata, Riccarda; Trovato, Letizia; Gallo, Maria Pia; Destefanis, Silvia; Settanni, Fabio; Scarlatti, Francesca; Brero, Alessia; Ramella, Roberta; Volante, Marco; Isgaard, Jorgen; Levi, Renzo; Papotti, Mauro; Alloatti, Giuseppe; Ghigo, Ezio

2009-07-15

The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH) stimulates GH synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signalling mechanisms. Reverse transcriptase-polymerase chain reaction analysis showed GHRH receptor (GHRH-R) mRNA in adult rat ventricular myocytes (ARVMs) and in rat heart H9c2 cells. In ARVMs, GHRH prevented cell death and caspase-3 activation induced by serum starvation and by the beta-adrenergic receptor agonist isoproterenol. The GHRH-R antagonist JV-1-36 abolished GHRH survival action under both experimental conditions. GHRH-induced cardiac cell protection required extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide-3 kinase (PI3K)/Akt activation and adenylyl cyclase/cAMP/protein kinase A signalling. Isoproterenol strongly upregulated the mRNA and protein of the pro-apoptotic inducible cAMP early repressor, whereas GHRH completely blocked this effect. Similar to ARVMs, in H9c2 cardiac cells, GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signalling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischaemia-reperfusion (I/R) injury. These effects involved PI3K/Akt signalling and were inhibited by JV-1-36. Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signalling mechanisms and protects against I/R injury in isolated rat heart, indicating a novel cardioprotective role of this hormone.

Increased activities of mitochondrial enzymes in white adipose tissue in trained rats

DEFF Research Database (Denmark)

Stallknecht, B; Vinten, J; Ploug, T

1991-01-01

of 8-12 rats were swim trained for 10 wk or served as either sedentary, sham swim-trained, or cold-stressed controls. White adipose tissue was removed, and the activities of the respiratory chain enzyme cytochrome-c oxidase (CCO) and of the enzyme malate dehydrogenase (MDH), which participates...... 0.05). In female rats the CCO activity expressed per milligram protein was increased 4.5-fold in the trained compared with the sedentary control rats (P less than 0.01). Neither cold stress nor sham swim training increased CCO or MDH activities in white adipose tissue (P greater than 0...

Dietary arginine silicate inositol complex inhibits periodontal tissue loss in rats with ligature-induced periodontitis.

Science.gov (United States)

Dundar, Serkan; Eltas, Abubekir; Hakki, Sema S; Malkoc, Sıddık; Uslu, M Ozay; Tuzcu, Mehmet; Komorowski, James; Ozercan, I Hanifi; Akdemir, Fatih; Sahin, Kazim

2016-01-01

The purpose of this study was to induce experimental periodontitis in rats previously fed diets containing arginine silicate inositol (ASI) complex and examine the biochemical, immunological, and radiological effects. Fifty two 8-week-old female Sprague Dawley rats were equally divided into four groups. The control group included those fed a standard rat diet with no operation performed during the experiment. The periodontitis, ASI I, and ASI II groups were subjected to experimental periodontitis induction for 11 days after being fed a standard rat diet alone, a diet containing 1.81 g/kg ASI complex, or a diet containing 3.62 g/kg ASI complex, respectively, for 8 weeks. Throughout the 11-day duration of periodontitis induction, all rats were fed standard feed. The rats were euthanized on the eleventh day, and their tissue and blood samples were collected. In the periodontitis group, elevated tissue destruction parameters and reduced tissue formation parameters were found, as compared to the ASI groups. Levels of enzymes, cytokines, and mediators associated with periodontal tissue destruction were lower in rats fed a diet containing ASI complex after experimental periodontitis. These results indicate that ASI complex could be an alternative agent for host modulation.

Effect of Piper sarmentosum Extract on the Cardiovascular System of Diabetic Sprague-Dawley Rats: Electron Microscopic Study

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Zar Chi Thent

2012-01-01

Full Text Available Although Piper sarmentosum (PS is known to possess the antidiabetic properties, its efficacy towards diabetic cardiovascular tissues is still obscured. The present study aimed to observe the electron microscopic changes on the cardiac tissue and proximal aorta of experimental rats treated with PS extract. Thirty-two male Sprague-Dawley rats were divided into four groups: untreated control group (C, PS-treated control group (CTx, untreated diabetic group (D, and PS-treated diabetic group (DTx. Intramuscular injection of streptozotocin (STZ, 50 mg/kg body weight was given to induce diabetes. Following 28 days of diabetes induction, PS extract (0.125 g/kg body weight was administered orally for 28 days. Body weight, fasting blood glucose, and urine glucose levels were measured at 4-week interval. At the end of the study, cardiac tissues and the aorta were viewed under transmission electron microscope (TEM. DTx group showed increase in body weight and decrease in fasting blood glucose and urine glucose level compared to the D group. Under TEM study, DTx group showed lesser ultrastructural degenerative changes in the cardiac tissues and the proximal aorta compared to the D group. The results indicate that PS restores ultrastructural integrity in the diabetic cardiovascular tissues.

Local renin–angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

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Kobori, H; Ichihara, A; Miyashita, Y; Hayashi, M; Saruta, T

2008-01-01

We have reported previously that thyroid hormone activates the circulating and tissue renin–angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin–angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin–angiotensin system in Sprague–Dawley rats was fixed by chronic angiotensin II infusion (40 ng/ min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0·1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0·12 ± 0·03 and 0·15 ± 0·03 μg/h per liter, 126 ± 5 and 130 ± 5 ng/l respectively) (means ± s.e.m.). Despite stabilization of the circulating renin–angiotensin system, thyroid hormone induced cardiac hypertrophy (5·0 ± 0·5 vs 3·5 ± 0·1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74 ± 2 vs 48 ± 2%, 6·5 ± 0·8 vs 3·8 ± 0·4 ng/h per g, 231 ± 30 vs 149 ± 2 pg/g respectively). These results indicate that the local renin–angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy. PMID:9854175

Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

Science.gov (United States)

Roy, Abhro Jyoti; Stanely Mainzen Prince, P

2013-10-01

The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Pretransplant portal venous administration of donor antigen and portal venous allograft drainage synergistically prolong rat cardiac allograft survival

International Nuclear Information System (INIS)

Kamei, T.; Callery, M.P.; Flye, M.W.

1990-01-01

The effect of antigen given through the portal vein (PV) before transplantation or continuous drainage of a graft into the PV results in moderate prolongation of allograft survival. This study examines these treatment modalities further. Pretransplant donor antigen as 25 x 10(6) ultraviolet B-irradiated (12,000 joules/m2) donor spleen cells was given 7 days before heart transplantation through either the PV or systemic venous (IV) routes. On day 0, Lewis-to-Buffalo rat cardiac allografts were drained either into the PV or IV. Pretransplant PV donor antigen administration (p less than 0.005), but not by IV administration, significantly prolonged cardiac allograft survival across the strong RT 1 rat histoincompatibility barrier. Similarly PV, but not IV, drainage of the graft prolonged graft survival (p less than 0.005). Pretransplant IV antigen administration had no additive effect on PV drainage graft survival. In contrast, when pretransplant PV donor antigen was combined with PV drainage, 11 of 14 allografts (p less than 0.001) continued to function, free of rejection, after 150 days. Therefore for rat cardiac transplants a clearly synergistic graft-prolonging effect results when pretransplant PV donor antigen is combined with PV drainage of the allografts. These data clarify the potent tolerogenic effects of alloantigen not only administered into the PV but also continuously shed intraportally so that it is first processed by the liver

Targeted NGF siRNA delivery attenuates sympathetic nerve sprouting and deteriorates cardiac dysfunction in rats with myocardial infarction.

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Hesheng Hu

Full Text Available Nerve growth factor (NGF is involved in nerve sprouting, hyper-innervation, angiogenesis, anti-apoptosis, and preservation of cardiac function after myocardial infarction (MI. Positively modulating NGF expression may represent a novel pharmacological strategy to improve post-infarction prognosis. In this study, lentivirus encoding NGF short interfering RNA (siRNA was prepared, and MI was modeled in the rat using left anterior descending coronary artery ligation. Rats were randomly grouped to receive intramyocardial injection of lentiviral solution containing NGF-siRNA (n = 19, MI-SiNGF group, lentiviral solution containing empty vector (n = 18, MI-GFP group or 0.9% NaCl solution (n = 18, MI-control group, or to receive thoracotomy and pericardiotomy (n = 17, sham-operated group. At 1, 2, 4, and 8 wk after transduction, rats in the MI-control group had higher levels of NGF mRNA and protein than those in the sham-operated group, rats in the MI-GFP group showed similar levels as the MI-control group, and rats in the MI-SiNGF group had lower levels compared to the MI-GFP group, indicating that MI model was successfully established and NGF siRNA effectively inhibited the expression of NGF. At 8 wk, echocardiographic and hemodynamic studies revealed a more severe cardiac dysfunction in the MI-siRNA group compared to the MI-GFP group. Moreover, rats in the MI-siRNA group had lower mRNA and protein expression levels of tyrosine hydroxylase (TH and growth-associated protein 43-positive nerve fibers (GAP-43 at both the infarcted border and within the non-infarcted left ventricles (LV. NGF silencing also reduced the vascular endothelial growth factor (VEGF expression and decreased the arteriolar and capillary densities at the infarcted border compared to the MI-GFP group. Histological analysis indicated a large infarcted size in the MI-SiNGF group. These findings suggested that endogenous NGF silencing attenuated sympathetic nerve sprouting

Effects of fermented Cordyceps sinensis on oxidative stress in doxorubicin treated rats.

Science.gov (United States)

Wu, Rong; Gao, Jian-Ping; Wang, Hui-Lin; Gao, Yan; Wu, Qian; Cui, Xiao-Hua

2015-01-01

Cordyceps sinensis (CS) is one of the rare traditional Chinese herbs, only a very limited amount of natural CS is produced. Fermented CS, as a substitute for natural CS, is widely used in the field of supplementary medical treatment and health products. Its antagonistic effect on oxidative stress (OS) in vivo has not been investigated. Our aim was to investigate the antagonistic effect of fermented CS on OS in doxorubicin (DOX) treated rats and to compare the anti-OS effects in heart and liver tissues. OS rats were induced by tail-intravenous injection of DOX (total of 7.5 mg/kg), and then administered intragastrically with fermented CS (1.5 g/kg) for 4 weeks. At the end of the experiment, heart, liver and serum samples were taken for and biochemical analyses. Fermented CS significantly increased the activities of glutathione peroxidase and catalase and the scavenging activity of O2 (-) in serum, and the total superoxide dismutase activity in cardiac tissue; reduced the malondialdehyde content in liver and cardiac tissues. Fermented CS can inhibit DOX-induced OS reactions, and the anti-OS effects have high selectivity to heart and liver, especially to heart. Thus, fermented CS may be a candidate used for the prevention against various cardiac diseases induced by OS.

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

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Akira Nakayama

2002-10-01

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

Effect of rana galamensis–based diet on the activities of some enzymes and histopathology of selected tissues of albino rats

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Basiru Olaitan Ajiboye

2016-10-01

Full Text Available The effect of Rana galamensis-based diet on the activities of some enzymes and histopathology of selected tissues of albino rats was investigated for eight weeks. A total of sixteen albino rats weighing between 29.15 and 26.01g (21 days old were divided into two groups. The first group contains animals fed on casein-based diet (control; the second group was fed on Rana galamensis-based diet. The animals were fed with their appropriate diet on daily basis and on the eight weeks of the experiment the animals were sacrificed using diethyl ether as anesthesia, blood was collected by cardiac puncture and organs of interest were harvested. Thereafter, organ to body weight ratio, some biochemical parameters and histopathology examination were carried out. There was no significant difference (p >0.05 in the organ to body weight ratio of the animals fed on control and Rana galamensis-based diets. Also, there was no significant different (p >0.05 in the activities of all the enzymes (ALP [alkaline phosphatase], AST [asparate transaminase], ALT [alanine transaminase], and γGT [gamma glutamyl transferase] investigated in the selected tissues and serum of rats fed on Rana galamensis- based diet when compared with the control. In addition, histological examinations of hepatocyte's rats fed on Rana galamensis- based diet show normal architecture structure when compared with the control. The insignificant different in the activities of all the enzymes studies (ALP, AST, ALT and γGT indicated no organ damage, supported by the normal histology studies. The obtained results may imply that Rana galamensis is safe for consumption.  Normal 0 false false false EN-US X-NONE X-NONE

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

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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.

Simulation of a plane wavefront propagating in cardiac tissue using a cellular automata model

International Nuclear Information System (INIS)

Barbosa, Carlos R Hall

2003-01-01

We present a detailed description of a cellular automata model for the propagation of action potential in a planar cardiac tissue, which is very fast and easy to use. The model incorporates anisotropy in the electrical conductivity and a spatial variation of the refractory time. The transmembrane potential distribution is directly derived from the cell states, and the intracellular and extracellular potential distributions are calculated for the particular case of a plane wavefront. Once the potential distributions are known, the associated current densities are calculated by Ohm's law, and the magnetic field is determined at a plane parallel to the cardiac tissue by applying the law of Biot and Savart. The results obtained for propagation speed and for magnetic field amplitude with the cellular automata model are compared with values predicted by the bidomain formulation, for various angles between wavefront propagation and fibre direction, characterizing excellent agreement between the models

Biofabrication enables efficient interrogation and optimization of sequential culture of endothelial cells, fibroblasts and cardiomyocytes for formation of vascular cords in cardiac tissue engineering

International Nuclear Information System (INIS)

Iyer, Rohin K; Radisic, Milica; Chiu, Loraine L Y; Vunjak-Novakovic, Gordana

2012-01-01

We previously reported that preculture of fibroblasts (FBs) and endothelial cells (ECs) prior to cardiomyocytes (CMs) improved the structural and functional properties of engineered cardiac tissue compared to culture of CMs alone or co-culture of all three cell types. However, these approaches did not result in formation of capillary-like cords, which are precursors to vascularization in vivo. Here we hypothesized that seeding the ECs first on Matrigel and then FBs 24 h later to stabilize the endothelial network (sequential preculture) would enhance cord formation in engineered cardiac organoids. Three sequential preculture groups were tested by seeding ECs (D4T line) at 8%, 15% and 31% of the total cell number on Matrigel-coated microchannels and incubating for 24 h. Cardiac FBs were then seeded (32%, 25% and 9% of the total cell number, respectively) and incubated an additional 24 h. Finally, neonatal rat CMs (60% of the total cell number) were added and the organoids were cultivated for seven days. Within 24 h, the 8% EC group formed elongated cords which eventually developed into beating cylindrical organoids, while the 15% and 31% EC groups proliferated into flat EC monolayers with poor viability. Excitation threshold (ET) in the 8% EC group (3.4 ± 1.2 V cm −1 ) was comparable to that of the CM group (3.3 ± 1.4 V cm −1 ). The ET worsened with increasing EC seeding density (15% EC: 4.4 ± 1.5 V cm −1 ; 31% EC: 4.9 ± 1.5 V cm −1 ). Thus, sequential preculture promoted vascular cord formation and enhanced architecture and function of engineered heart tissues. (paper)

Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-β1 improves cardiac function in heart failure rats

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Lv, Y. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China); Liu, B. [Department of Pathology, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei (China); Wang, H.P. [Department of Histology and Embryology, Hebei North University, Zhangjiakou, Hebei (China); Zhang, L. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China)

2016-05-31

The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats.

Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-β1 improves cardiac function in heart failure rats

International Nuclear Information System (INIS)

Lv, Y.; Liu, B.; Wang, H.P.; Zhang, L.

2016-01-01

The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats

A combination of methylprednisolone and quercetin is effective for the treatment of cardiac contusion following blunt chest trauma in rats

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Demir, F. [Department of Pediatric Cardiology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Güzel, A. [Department of Pediatrics, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Katı, C. [Department of Emergency Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Karadeniz, C. [Pediatric Cardiology Services, Behçet Uz Children' s Hospital, İzmir (Turkey); Akdemir, U. [Department of Emergency Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Okuyucu, A. [Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Gacar, A. [Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayıs University, Samsun (Turkey); Özdemir, S. [Department of Pediatrics, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Güvenç, T. [Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayıs University, Samsun (Turkey)

2014-08-01

Cardiac contusion is a potentially fatal complication of blunt chest trauma. The effects of a combination of quercetin and methylprednisolone against trauma-induced cardiac contusion were studied. Thirty-five female Sprague-Dawley rats were divided into five groups (n=7) as follows: sham, cardiac contusion with no therapy, treated with methylprednisolone (30 mg/kg on the first day, and 3 mg/kg on the following days), treated with quercetin (50 mg·kg{sup −1}·day{sup −1}), and treated with a combination of methylprednisolone and quercetin. Serum troponin I (Tn-I) and tumor necrosis factor-alpha (TNF-α) levels and cardiac histopathological findings were evaluated. Tn-I and TNF-α levels were elevated after contusion (P=0.001 and P=0.001). Seven days later, Tn-I and TNF-α levels decreased in the rats treated with methylprednisolone, quercetin, and the combination of methylprednisolone and quercetin compared to the rats without therapy, but a statistical significance was found only with the combination therapy (P=0.001 and P=0.011, respectively). Histopathological degeneration and necrosis scores were statistically lower in the methylprednisolone and quercetin combination group compared to the group treated only with methylprednisolone (P=0.017 and P=0.007, respectively). However, only degeneration scores were lower in the combination therapy group compared to the group treated only with quercetin (P=0.017). Inducible nitric oxide synthase positivity scores were decreased in all treatment groups compared to the untreated groups (P=0.097, P=0.026, and P=0.004, respectively). We conclude that a combination of quercetin and methylprednisolone can be used for the specific treatment of cardiac contusion.

Genomic and metabolic disposition of non-obese type 2 diabetic rats to increased myocardial fatty acid metabolism.

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Sriram Devanathan

Full Text Available Lipotoxicity of the heart has been implicated as a leading cause of morbidity in Type 2 Diabetes Mellitus (T2DM. While numerous reports have demonstrated increased myocardial fatty acid (FA utilization in obese T2DM animal models, this diabetic phenotype has yet to be demonstrated in non-obese animal models of T2DM. Therefore, the present study investigates functional, metabolic, and genomic differences in myocardial FA metabolism in non-obese type 2 diabetic rats. The study utilized Goto-Kakizaki (GK rats at the age of 24 weeks. Each rat was imaged with small animal positron emission tomography (PET to estimate myocardial blood flow (MBF and myocardial FA metabolism. Echocardiograms (ECHOs were performed to assess cardiac function. Levels of triglycerides (TG and non-esterified fatty acids (NEFA were measured in both plasma and cardiac tissues. Finally, expression profiles for 168 genes that have been implicated in diabetes and FA metabolism were measured using quantitative PCR (qPCR arrays. GK rats exhibited increased NEFA and TG in both plasma and cardiac tissue. Quantitative PET imaging suggests that GK rats have increased FA metabolism. ECHO data indicates that GK rats have a significant increase in left ventricle mass index (LVMI and decrease in peak early diastolic mitral annular velocity (E' compared to Wistar rats, suggesting structural remodeling and impaired diastolic function. Of the 84 genes in each the diabetes and FA metabolism arrays, 17 genes in the diabetes array and 41 genes in the FA metabolism array were significantly up-regulated in GK rats. Our data suggest that GK rats' exhibit increased genomic disposition to FA and TG metabolism independent of obesity.

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

Science.gov (United States)

Finosh, G T; Jayabalan, Muthu

2012-01-01

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

Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123

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Reske, S.N.; Schoen, S.; Schmitt, W.; Knopp, R.; Winkler, C.; Machulla, H.J.

1986-08-01

The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid /sup 14/C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides.

Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) I 123

International Nuclear Information System (INIS)

Reske, S.N.; Schoen, S.; Schmitt, W.; Knopp, R.; Winkler, C.; Machulla, H.J.

1986-01-01

The effect of regional myocardial perfusion and flow-independent adrenergic stimulation, as well as lactate-mediated inhibition of cardiac lipolysis, on cardiac IPPA uptake and metabolism was examined in canine hearts (flow studies) and in the isolated perfused Langendorff rat heart (metabolic interventions). In both normal and ischaemic myocardium, local perfusion is a major determinant of cardiac IPPA uptake. In pacing-induced hyperaemia, the strict flow-dependence of cardiac IPPA uptake is not preserved. Adrenergic stimulation raises the rate of oxidation of both palmitic acid 14 C and IPPA. This change is reflected by increased metabolite production released into the perfusate and radioactivity clearance recorded externally. Lactate in high concentrations exerts the opposite effect on cardiac free fatty acid oxidation. IPPA is stored in this condition preferentially in tissue phospholipids and triglycerides. (orig.)

Early Treatment of radiation-Induced Heart Damage in Rats by Caffeic acid phenethyl Ester

International Nuclear Information System (INIS)

Tawfik, S.S.; Mansour, H. H.

2012-12-01

The study designed to determine the therapeutic effect of caffeic acid phenethyl ester (CAPE) in minimising radiation-induced injuries in rats. Rats were exposed to 7 Gy γ-rays, 30 minutes later; rats were injected with CAPE (10μmol/ kg body, i.p.) for 7 consecutive days. Rats were sacrificed at 8 and 15 days after starting the experiment. Gamma-irradiation induced significant increase in malonaldehyde (MDA) level and xanthine oxidase (XO) and adenosine deaminase (ADA) activities, and significant decrease in total nitrate/nitrate (NO (x)) level and glutathione peroxidise (Gpx), superoxide dismutase (SOD)and catalase (CAT) activities in heart tissue and augmented activities of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and aspartate transaminase (AST) in serum. Irradiated rats early treated with CAPE showed significant decrease in MDA, XO and ADA and significant increase in group. Cardiac enzymes were restored. Conclusion, CAPE could exhibits curable effect on gamma irradiation-induced cardiac-oxidative impairment in rats. (Author)

Glutathione turnover in 14 rat tissues

International Nuclear Information System (INIS)

Potter, D.W.; Tran, T.

1990-01-01

GSH is a tripeptide found in all tissues and is important in maintaining cellular redox status. First-order rate constants for GSH turnover were determined for various tissues of Fischer male rats. Animals were administered [ 35 S]Cys by tail vein injection and GSH turnover was estimated by the decrease in GSH specific activity following incorporation of Cys, 1-102 hr after administration. Tissue nonprotein sulfhydryls (NPSH) were detected by Ellman's assay and compared with GSH and Cys concentrations determined by HPLC with electrochemical detection. [ 35 S]GSH was analyzed by HPLC equipped with a flow-through radioactivity detector. Although total GSH and Cys were usually slightly lower than NPSH concentrations for the tissues examined, both assay systems gave comparable results. An exception was the glandular stomach which had approximately 2-fold higher NPSH. Liver and kidney had rapid turnover rates with GSH half-lives between 2-5 hr, while heart and skeletal muscle tissue had half-lives of 80-90 hr. Turnover in the blood was slowest, with a half-life of 170 hr. Gastrointestinal tract tissues were shown to have intermediate turnover rates of the following order: glandular stomach > duodenum = small intestine = caecum = large intestine = colon > forestomach. GSH half-life in lung and skin was approximately 45 hr. These studies indicate that tissues utilize GSH at markedly different rates

Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats.

Science.gov (United States)

Huang, Rong; Xue, Xinli; Li, Shengxian; Wang, Yuying; Sun, Yun; Liu, Wei; Yin, Huiyong; Tao, Tao

2018-03-30

The metabolism of polyunsaturated fatty acids (PUFAs) remains poorly characterized in ovarian tissues of patients with polycystic ovary syndrome (PCOS). This study aimed to explore alterations in the levels of PUFAs and their metabolites in serum and ovarian tissues in a PCOS rat model treated with a high-fat diet and andronate. Levels of PUFAs and their metabolites were measured using gas/liquid chromatography-mass spectrometry after the establishment of a PCOS rat model. Only 3 kinds of PUFAs [linoleic acid, arachidonic acid (AA) and docosahexaenoic acid] were detected in both the circulation and ovarian tissues of the rats, and their concentrations were lower in ovarian tissues than in serum. Moreover, significant differences in the ovarian levels of AA were observed between control, high-fat diet-fed and PCOS rats. The levels of prostaglandins, AA metabolites via the cyclooxygenase (COX) pathway, in ovarian tissues of the PCOS group were significantly increased compared to those in the controls. Further studies on the mechanism underlying this phenomenon showed a correlation between decreased expression of phosphorylated cytosolic phospholipase A2 (p-cPLA2) and increased mRNA and protein expression of COX2, potentially leading to a deeper understanding of altered AA and prostaglandin levels in ovarian tissues of PCOS rats. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Measuring cardiac efficiency using PET/MRI

International Nuclear Information System (INIS)

Gullberg, Grand; Aparici, Carina Mari; Brooks, Gabriel; Liu, Jing; Guccione, Julius; Saloner, David; Seo, Adam Youngho; Ordovas, Karen Gomes

2015-01-01

Heart failure (HF) is a complex syndrome that is projected by the American Heart Association to cost $160 billion by 2030. In HF, significant metabolic changes and structural remodeling lead to reduced cardiac efficiency. A normal heart is approximately 20-25% efficient measured by the ratio of work to oxygen utilization (1 ml oxygen = 21 joules). The heart requires rapid production of ATP where there is complete turnover of ATP every 10 seconds with 90% of ATP produced by mitochondrial oxidative metabolism requiring substrates of approximately 30% glucose and 65% fatty acids. In our preclinical PET/MRI studies in normal rats, we showed a negative correlation between work and the influx rate constant for 18FDG, confirming that glucose is not the preferred substrate at rest. However, even though fatty acid provides 9 kcal/gram compared to 4 kcal/gram for glucose, in HF the preferred energy source is glucose. PET/MRI offers the potential to study this maladapted mechanism of metabolism by measuring work in a region of myocardial tissue simultaneously with the measure of oxygen utilization, glucose, and fatty acid metabolism and to study cardiac efficiency in the etiology of and therapies for HF. MRI is used to measure strain and a finite element mechanical model using pressure measurements is used to estimate myofiber stress. The integral of strain times stress provides a measure of work which divided by energy utilization, estimated by the production of 11CO2 from intravenous injection of 11C-acetate, provides a measure of cardiac efficiency. Our project involves translating our preclinical research to the clinical application of measuring cardiac efficiency in patients. Using PET/MRI to develop technologies for studying myocardial efficiency in patients, provides an opportunity to relate cardiac work of specific tissue regions to metabolic substrates, and measure the heterogeneity of LV efficiency.

Measuring cardiac efficiency using PET/MRI

Energy Technology Data Exchange (ETDEWEB)

Gullberg, Grand [Lawrence Berkeley National Laboratory (United States); Aparici, Carina Mari; Brooks, Gabriel [University of California San Francisco (United States); Liu, Jing; Guccione, Julius; Saloner, David; Seo, Adam Youngho; Ordovas, Karen Gomes [Lawrence Berkeley National Laboratory (United States)

2015-05-18

Heart failure (HF) is a complex syndrome that is projected by the American Heart Association to cost $160 billion by 2030. In HF, significant metabolic changes and structural remodeling lead to reduced cardiac efficiency. A normal heart is approximately 20-25% efficient measured by the ratio of work to oxygen utilization (1 ml oxygen = 21 joules). The heart requires rapid production of ATP where there is complete turnover of ATP every 10 seconds with 90% of ATP produced by mitochondrial oxidative metabolism requiring substrates of approximately 30% glucose and 65% fatty acids. In our preclinical PET/MRI studies in normal rats, we showed a negative correlation between work and the influx rate constant for 18FDG, confirming that glucose is not the preferred substrate at rest. However, even though fatty acid provides 9 kcal/gram compared to 4 kcal/gram for glucose, in HF the preferred energy source is glucose. PET/MRI offers the potential to study this maladapted mechanism of metabolism by measuring work in a region of myocardial tissue simultaneously with the measure of oxygen utilization, glucose, and fatty acid metabolism and to study cardiac efficiency in the etiology of and therapies for HF. MRI is used to measure strain and a finite element mechanical model using pressure measurements is used to estimate myofiber stress. The integral of strain times stress provides a measure of work which divided by energy utilization, estimated by the production of 11CO2 from intravenous injection of 11C-acetate, provides a measure of cardiac efficiency. Our project involves translating our preclinical research to the clinical application of measuring cardiac efficiency in patients. Using PET/MRI to develop technologies for studying myocardial efficiency in patients, provides an opportunity to relate cardiac work of specific tissue regions to metabolic substrates, and measure the heterogeneity of LV efficiency.

Possible Ameliorative Effect of Chicory Extract (Cichorium Intybus) on Radiation-Induced Oxidative Damage in Rats Heart

International Nuclear Information System (INIS)

Osman, N. N; Farag, M. F. S.; Darwish, M. M

2011-01-01

The radioprotective effect of aqueous leaf extract of Chicorium intybus (Chicory) against radiation induced-oxidative stress and changes in the levels of 150-180 g were divided into four groups. Group 1: control animals, group 2: animals orally administrated with chicory extract at a daily dose of 250 mg/kg b.wt/day for four weeks, group 3: animals exposed to whole body gamma irradiation (6.5 Gy), group 4: animals orally administrated with chicory extract two weeks before and two weeks after irradiation. Serum level of creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lipid profile was measured.also concentration of superoxide dismutase (SOD), glutathione (GSH), Catalase (CAT) and TBARS level was estimated in the cardiac tissue. The results showed decreased body weight and heart weight in irradiated animals. Compared to the control normal rats, irradiated rats had higher total cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), serum creatinine phosphokinase(CPK), lactate dehydrogenase (LDH), serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lower high-density lipoprotein-cholesterol (HDL-C) levels. Moreover, cardiac tissue TBARS was markedly increased while SOD, GSH and CAT were significantly decreased. Oral and heart weights, serum cardiac enzymes and lipid profile. Cardiac GSH, SOD and CAT were significantly increased while TBARS was markedly reduced, membrane bound enzymes in rats' heart was investigated. Rats weighing about administration of chicory extract at doses of 250 mg/kg b.wt. improved the body compared to irradiated rats. These results may suggest a strong antioxidant effect of chicory, which was effective in mitigating adverse effect of γ irradiation on animals

The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover.

Science.gov (United States)

Jugdaohsingh, Ravin; Watson, Abigail I E; Pedro, Liliana D; Powell, Jonathan J

2015-06-01

Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague-Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n=8-10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2-6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague-Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than

The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover☆

Science.gov (United States)

Jugdaohsingh, Ravin; Watson, Abigail I.E.; Pedro, Liliana D.; Powell, Jonathan J.

2015-01-01

Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague–Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n = 8–10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2–6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague–Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially

Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice

Directory of Open Access Journals (Sweden)

Hsu Cheng-chin

2009-08-01

Full Text Available Abstract Background Caffeic acid (CA and ellagic acid (EA are phenolic acids naturally occurring in many plant foods. Cardiac protective effects of these compounds against dyslipidemia, hypercoagulability, oxidative stress and inflammation in diabetic mice were examined. Methods Diabetic mice were divided into three groups (15 mice per group: diabetic mice with normal diet, 2% CA treatment, or 2% EA treatment. One group of non-diabetic mice with normal diet was used for comparison. After 12 weeks supplement, mice were sacrificed, and the variation of biomarkers for hypercoagulability, oxidative stress and inflammation in cardiac tissue of diabetic mice were measured. Results The intake of CA or EA significantly increased cardiac content of these compounds, alleviated body weight loss, elevated plasma insulin and decreased plasma glucose levels in diabetic mice (p p p p p p p Conclusion These results support that CA and EA could provide triglyceride-lowering, anti-coagulatory, anti-oxidative, and anti-inflammatory protection in cardiac tissue of diabetic mice. Thus, the supplement of these agents might be helpful for the prevention or attenuation of diabetic cardiomyopathy.

Plasma disappearance, urine excretion, and tissue distribution of ribavirin in rats and rhesus monkeys

International Nuclear Information System (INIS)

Ferrara, E.A.; Oishi, J.S.; Wannemacher, R.W. Jr.; Stephen, E.L.

1981-01-01

Ribavirin has been shown to have broad-spectrum antiviral. To study its tissue distribution and disappearance rate, a single dose of 10 mg/kg which contained 10 microCi of [14C]ribavirin was injected intravenously into rhesus monkeys and intramuscularly into monkeys and rats. Except for peak plasma concentrations and the initial phases of the plasma disappearance and urine excretion curves, no significant difference was observed between plasma, tissue, or urine values for intramuscularly or intravenously injected monkeys. Plasma disappearance curves were triphasic; plasma concentrations of ribavirin were similar for both monkeys and rats. Rats excreted ribavirin in the urine more rapidly and to a greater extent (82% excreted in 24 h) than did monkeys (60% excreted in 72 h). In the rat, only 3% of the injected [14C]ribavirin was detected in expired CO2. Therefore, for both species, urine was the major route for the elimination of labeled ribavirin and its metabolites from the body. In monkeys, the amount of parent drug in blood cells increased through 48 h and remained stable for 72 h, whereas in rats, ribavirin decreased at a rate similar to the plasma disappearance curve. Concentrations of ribavirin at 8 h were consistently higher in monkeys than in rats for all tissues except the brain. Thus, these differences in blood cellular components and organ content and in urine excretion suggested that there was greater tissue retention of ribavirin in monkeys than in rats

Prophylactic Properties Of Licorice Roots (GLYCYRRHIZA Gabbler) And / Or Aspirin (Acetylsalicylic Acid) Against GAMMA Radiation-Induced Oxidative Stress And Metabolic Disorders In Rats

International Nuclear Information System (INIS)

FAHIM, TH.M.; ABDEL FATTAH, S.M.

2009-01-01

Oxidative stress with subsequent production of reactive oxygen species (ROS) has been postulated as one of the mechanism of cardiac and renal toxicity. The aim of the present study is to investigate the possible protective effects of licorice and/or aspirin on gamma irradiation-induced cardiac and renal damage in rats. Licorice and/or aspirin was supplemented daily to rats (100 mg licorice/kg body wt and 50 mg aspirin/kg body wt) orally, 15 days before and after whole body gamma irradiation at a dose of 6 Gy (applied as a shot dose). Gamma irradiation caused significant drop in haemoglobin, erythrocytes, haematocrit values, platelets count, prothrombin time (PT) and leukocytes with their differential counts with elevation in C-reactive protein (CRP) and activated partial thromboplastin time (aPTT).The results obtained showed that whole body gamma irradiation of rats induced biochemical alteration in the levels of serum lipid profile (total lipids, total cholesterol, triglycerides, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol), creatinine and urea. Furthermore, some markers of cardiac injury enzymes such as serum aspartate transaminase (AST), creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities showed significant increase associated with decrease in the glutathione content (GSH) of cardiac and renal tissues. Significant increase of lipid peroxidation end products malondialdehyde (MDA) and nitric oxide (NO) in the cardiac and renal tissues was observed.Licorice and/or aspirin treatment prior and post gamma irradiation of rats has attenuated the renal and cardiac toxic effects of radiation manifested by reduction in the levels of MDA and NO, rescued the depletion of endogenous GSH, haematologial parameters and diminished the increase of cardiac and renal injury markers .

Increased in vivo glucose utilization in 30-day-old obese Zucker rat: Role of white adipose tissue

International Nuclear Information System (INIS)

Krief, S.; Bazin, R.; Dupuy, F.; Lavau, M.

1988-01-01

In vivo whole-body glucose utilization and uptake in multiple individual tissues were investigated in conscious 30-day-old Zucker rats, which when obese are hyperphagic, hyperinsulinemic, and normoglycemic. Whole-body glucose metabolism (assessed by [3- 3 H]glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia. In obese compared with lean rats, tissue glucose uptake was increased by 15, 12, and 6 times in dorsal, inguinal, perigonadal white depots, respectively; multiplied by 2.5 in brown adipose tissue; increased by 50% in skin from inguinal region but not in that from cranial, thoracic, or dorsal area; and increased twofold in diaphragm but similar in heart in proximal intestine, and in total muscular mass of limbs. The data establish that in young obese rats the hypertrophied white adipose tissue was a major glucose-utilizing tissue whose capacity for glucose disposal compared with that of half the muscular mass. Adipose tissue could therefore play an important role in the homeostasis of glucose in obese rats in the face of their increased carbohydrate intake

Species difference between rat and hamster in tissue accumulation of mercury after administration of methylmercury

International Nuclear Information System (INIS)

Omata, Saburo; Kasama, Hidetaka; Hasegawa, Hiroshi; Hasegawa, Kazuhiro; Sugano, Hiroshi; Ozaki, Kunio

1986-01-01

The accumulation of mercury in tissues of the rat and hamster was determined after the administration of a single dose of 203 Hg-methylmercury chloride (10 mg/kg body weight). (1) On day 2, the mercury contents of hamster tissues were higher than those of rat tissues, except for red blood cells, in which the mercury content was about 6-fold higher in the rat than in the hamster. (2) After that time, the mercury content of hamster tissues decreased rather steeply and on day 16 it had reached 14-25% in nervous tissues and 7-15% in other tissues, of the levels on day 2. (3) In the rat, on the other hand, the mercury content of nervous tissues on day 16 was higher than that on day 2 (106-220%), except for dorsal roots and dorsal root ganglia, which showed slight decreases (75-94% of the levels on day 2). In non-neural tissues, the decreases up to day 16 were also small (71-92% of the levels on day 2). (4) Thus, both the uptake and elimination of mercury seem to be more rapid in the tissues of hamster compared with those of the rat. Similar trends of mercury accumulation and elimination were observed when animals received multiple injections of methylmercury that induced acute methylmercury intoxication. (5) Significant biotransmormation of the injected methylmercury to inorganic mercury was detected in the liver, kidney and spleen of both animal species. Although the percentages of inorganic mercury in these tissues wer not so different between the two species on day 2, they became exceedingly high in the tissues of hamster at the later stage, except in the kidney cytosol, in which the values were close in both animal species between day 2 and day 16. (orig.)

Effect of Kombucha, a fermented black tea in attenuating oxidative stress mediated tissue damage in alloxan induced diabetic rats.

Science.gov (United States)

Bhattacharya, Semantee; Gachhui, Ratan; Sil, Parames C

2013-10-01

Diabetic complications associated with increased oxidative stress can be suppressed by antioxidants. In the present study we investigated the antidiabetic and antioxidant effects of Kombucha (KT), a fermented black tea, in comparison to that of unfermented black tea (BT), in ALX-induced diabetic rats. ALX exposure lowered the body weight and plasma insulin by about 28.12% and 61.34% respectively and elevated blood glucose level and glycated Hb by about 3.79 and 3.73 folds respectively. The oxidative stress related parameters like lipid peroxidation end products (increased by 3.38, 1.7, 1.65, 1.94 folds respectively), protein carbonyl content (increased by 2.5, 2.35, 1.8, 3.26 folds respectively), glutathione content (decreased by 59.8%, 47.27%, 53.69%, 74.03% respectively), antioxidant enzyme activities were also altered in the pancreatic, hepatic, renal and cardiac tissues of diabetic animals. Results showed significant antidiabetic potential of the fermented beverage (150 mg lyophilized extract/kg bw for 14 days) as it effectively restored ALX-induced pathophysiological changes. Moreover, it could ameliorate DNA fragmentation and caspase-3 activation in the pancreatic tissue of diabetic rats. Although unfermented black tea is effective in the above pathophysiology, KT was found to be more efficient. This might be due to the formation of some antioxidant molecules during fermentation period. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

OpenAIRE

KOBORI, HIROYUKI; ICHIHARA, ATSUHIRO; SUZUKI, HIROMICHI; TAKENAKA, TSUNEO; MIYASHITA, YUTAKA; HAYASHI, MATSUHIKO; SARUTA, TAKAO

1997-01-01

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was onl...

The application of lesion sterilization and tissue repair 3Mix-MP for treating rat's dental pulp tissue

Directory of Open Access Journals (Sweden)

Raditya Nugroho

2015-03-01

Full Text Available Background: Lesion sterilization and tissue repair (LSTR 3Mix-MP are three broad-spectrum antibiotics, including metronidazole, ciprofloxacin and minocycline are mixed with propylene glycol or macrogol. There is the possibility ofthe healing process that marked proliferation ofnew blood vessels and proliferation offibroblasts in the treatment ofirreversible pulpitis by pulp capping LSTR 3MixMP because of  the principle of the method LSTR 3Mix-MP is to kill bacteria. Purpose: The purpose of this study to prove the effect of LSTR 3Mix-MP on chronic inflammation and the healing process in rat dental pulp tissue in vivo. Methods: Rattus norvegicus anaesthetized by using ketamine and xylazine dissolved in sterile isotonic saline solution (0.2 ml/50gr mm on the upper right thigh. Cavity preparation class I to perforation by using a low speed tapered diamond round bur. In the treatment group, rats were treated 3Mix-MP at a dose of10 mg and then covered with glass ionomer cement for 7 days on the pulp that has been opened for 3 days. The control group treated with saline irrigation on the pulp that has been opened for 3 days. Rats were killed after seven days, and then made preparations pulp tissue to count the number oflymphocytes, macrophages, plasma cells, blood vessels, and fibroblasts Results: There is an increase in the average number ofmacrophage cells, plasma, and fibroblasts; and decreased lymphocytes and blood vessels in the treated group exposure LSTR 3Mix-MP. Conclusion:LSTR 3Mix-MP can reduce chronic inflammation process and enhance the healing process in rat dental pulp tissue.

Tissue distribution of 14C-diazepam and its metabolites in rats

International Nuclear Information System (INIS)

Igari, Y.; Sugiyama, Y.; Sawada, Y.; Iga, T.; Hanano, M.

1982-01-01

We have kinetically investigated the tissue distribution of 14 C-diazepam and described the appearance and disappearance of its metabolites (3-hydroxydiazepam, desmethyldiazepam, and oxazepam) following a single iv injection of 14 C-diazepam into rats. Significant amounts of oxazepam were detected in plasma and various tissues in the rat, contrary to previous reports. Concentration-time profiles of diazepam in the main disposing organs (liver, kidney, and lung) and the other organs (brain, heart, and small intestine) indicated that diazepam was distributed rapidly to these organs. Concentration-time profiles of diazepam in the main tissues for drug distribution (skin and adipose) indicated that diazepam was slowly distributed to these tissues, whereas that in muscle, which is also responsible for drug distribution, indicated that diazepam was less rapidly distributed to this tissue. Metabolites appeared in plasma and various tissues or organs immediately after iv injection of diazepam. Metabolites levels in plasma and various tissues or organs were significantly lower than that of diazepam except for liver and small intestine, where metabolites levels were higher compared to that of diazepam and metabolites exhibited a considerable persistence

Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy

DEFF Research Database (Denmark)

Christoffersen, Tue E.H.; Aplin, Mark; Strom, Claes C.

2006-01-01

also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg.kg(-1).day(-1)) to investigate a possible role of the renin-angiotensin system......RNAs for the natriuretic peptides or their receptors. Although increased gene expression does not necessarily convey a higher concentration of the protein, the data suggest that pressure overload is accompanied by upregulation of not only ANP and BNP but also their receptors NPR-A and NPR-C in the left ventricle....

Cardiac remodeling and myocardial dysfunction in obese spontaneously hypertensive rats

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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.

The expression and significance of tyrosine hydroxylase in the brain tissue of Parkinsons disease rats

OpenAIRE

Chen, Yuan; Lian, Yajun; Ma, Yunqing; Wu, Chuanjie; Zheng, Yake; Xie, Nanchang

2017-01-01

The expression and significance of tyrosine hydroxylase (TH) in brain tissue of rats with Parkinson's disease (PD) were explored and analyzed. A total of 120 clean-grade and healthy adult Wistar rats weighing 180–240 g were randomly divided equally into four groups according to the random number table method. Rats were sacrificed before and after the model establishment for 3, 6 or 8 weeks. The number of revolutions in rats was observed and the relative expression of TH mRNA in brain tissue w...

Metabolic disposition of ivermectin in tissues of cattle, sheep, and rats

International Nuclear Information System (INIS)

Chiu, S.H.; Sestokas, E.; Taub, R.; Buhs, R.P.; Green, M.; Sestokas, R.; Vandenheuvel, W.J.; Arison, B.H.; Jacob, T.A.

1986-01-01

The metabolic disposition of ivermectin, a new antiparasitic drug, has been studied in cattle, sheep, and also in rats dosed with the drug labeled with tritium in the C-22,23 positions. In the edible tissues of these animals, the unaltered drug was the major tissue residue component and was quantitated by HPLC-reverse isotope dilution assay. The depletion half-lives of the drug ranged between 1 and 6 days, similar to those of the total tissue residue in these species. Most metabolites present in the liver tissues were more polar than the parent drug. Based on spectral (NMR, mass spectrometric) analysis and chromatographic comparison with authentic compounds prepared by in vitro rat or steer microsomal incubations, three of these metabolites have been isolated and identified as the hydroxylation derivatives of ivermectin, i.e. 24-hydroxymethyl-H 2 B1a, its monosaccharide, and 24-hydroxymethyl-H 2 B1b

Nesfatin-1 activates cardiac vagal neurons of nucleus ambiguus and elicits bradycardia in conscious rats.

Science.gov (United States)

Brailoiu, G Cristina; Deliu, Elena; Tica, Andrei A; Rabinowitz, Joseph E; Tilley, Douglas G; Benamar, Khalid; Koch, Walter J; Brailoiu, Eugen

2013-09-01

Nesfatin-1, a peptide whose receptor is yet to be identified, has been involved in the modulation of feeding, stress, and metabolic responses. More recently, increasing evidence supports a modulatory role for nesfatin-1 in autonomic and cardiovascular activity. This study was undertaken to test if the expression of nesfatin-1 in the nucleus ambiguus, a key site for parasympathetic cardiac control, may be correlated with a functional role. As we have previously demonstrated that nesfatin-1 elicits Ca²⁺ signaling in hypothalamic neurons, we first assessed the effect of this peptide on cytosolic Ca²⁺ in cardiac pre-ganglionic neurons of nucleus ambiguus. We provide evidence that nesfatin-1 increases cytosolic Ca²⁺ concentration via a Gi/o-coupled mechanism. The nesfatin-1-induced Ca²⁺ rise is critically dependent on Ca²⁺ influx via P/Q-type voltage-activated Ca²⁺ channels. Repeated administration of nesfatin-1 leads to tachyphylaxis. Furthermore, nesfatin-1 produces a dose-dependent depolarization of cardiac vagal neurons via a Gi/o-coupled mechanism. In vivo studies, using telemetric and tail-cuff monitoring of heart rate and blood pressure, indicate that microinjection of nesfatin-1 into the nucleus ambiguus produces bradycardia not accompanied by a change in blood pressure in conscious rats. Taken together, our results identify for the first time that nesfatin-1 decreases heart rate by activating cardiac vagal neurons of nucleus ambiguus. Our results indicate that nesfatin-1, one of the most potent feeding peptides, increases cytosolic Ca²⁺ by promoting Ca²⁺ influx via P/Q channels and depolarizes nucleus ambiguus neurons; both effects are Gi/o-mediated. In vivo studies indicate that microinjection of nesfatin-1 into nucleus ambiguus produces bradycardia in conscious rats. This is the first report that nesfatin-1 increases the parasympathetic cardiac tone. © 2013 International Society for Neurochemistry.

Effects of acupuncture on tissue oxygenation of the rat brain.

Science.gov (United States)

Chen, G S; Erdmann, W

1978-04-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by smypathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture points (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible and was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase in inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes increased brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients.

Effect of Twisted Fiber Anisotropy in Cardiac Tissue on Ablation with Pulsed Electric Fields.

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Fei Xie

Full Text Available Ablation of cardiac tissue with pulsed electric fields is a promising alternative to current thermal ablation methods, and it critically depends on the electric field distribution in the heart.We developed a model that incorporates the twisted anisotropy of cardiac tissue and computed the electric field distribution in the tissue. We also performed experiments in rabbit ventricles to validate our model. We find that the model agrees well with the experimentally determined ablation volume if we assume that all tissue that is exposed to a field greater than 3 kV/cm is ablated. In our numerical analysis, we considered how tissue thickness, degree of anisotropy, and electrode configuration affect the geometry of the ablated volume. We considered two electrode configurations: two parallel needles inserted into the myocardium ("penetrating needles" configuration and one circular electrode each on epi- and endocardium, opposing each other ("epi-endo" configuration.For thick tissues (10 mm and moderate anisotropy ratio (a = 2, we find that the geometry of the ablated volume is almost unaffected by twisted anisotropy, i.e. it is approximately translationally symmetric from epi- to endocardium, for both electrode configurations. Higher anisotropy ratio (a = 10 leads to substantial variation in ablation width across the wall; these variations were more pronounced for the penetrating needle configuration than for the epi-endo configuration. For thinner tissues (4 mm, typical for human atria and higher anisotropy ratio (a = 10, the epi-endo configuration yielded approximately translationally symmetric ablation volumes, while the penetrating electrodes configuration was much more sensitive to fiber twist.These results suggest that the epi-endo configuration will be reliable for ablation of atrial fibrillation, independently of fiber orientation, while the penetrating electrode configuration may experience problems when the fiber orientation is not consistent

Effect of Twisted Fiber Anisotropy in Cardiac Tissue on Ablation with Pulsed Electric Fields.

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Xie, Fei; Zemlin, Christian W

2016-01-01

Ablation of cardiac tissue with pulsed electric fields is a promising alternative to current thermal ablation methods, and it critically depends on the electric field distribution in the heart. We developed a model that incorporates the twisted anisotropy of cardiac tissue and computed the electric field distribution in the tissue. We also performed experiments in rabbit ventricles to validate our model. We find that the model agrees well with the experimentally determined ablation volume if we assume that all tissue that is exposed to a field greater than 3 kV/cm is ablated. In our numerical analysis, we considered how tissue thickness, degree of anisotropy, and electrode configuration affect the geometry of the ablated volume. We considered two electrode configurations: two parallel needles inserted into the myocardium ("penetrating needles" configuration) and one circular electrode each on epi- and endocardium, opposing each other ("epi-endo" configuration). For thick tissues (10 mm) and moderate anisotropy ratio (a = 2), we find that the geometry of the ablated volume is almost unaffected by twisted anisotropy, i.e. it is approximately translationally symmetric from epi- to endocardium, for both electrode configurations. Higher anisotropy ratio (a = 10) leads to substantial variation in ablation width across the wall; these variations were more pronounced for the penetrating needle configuration than for the epi-endo configuration. For thinner tissues (4 mm, typical for human atria) and higher anisotropy ratio (a = 10), the epi-endo configuration yielded approximately translationally symmetric ablation volumes, while the penetrating electrodes configuration was much more sensitive to fiber twist. These results suggest that the epi-endo configuration will be reliable for ablation of atrial fibrillation, independently of fiber orientation, while the penetrating electrode configuration may experience problems when the fiber orientation is not consistent across the

Influence of lead injection on calcium-45 distribution in hard tissues of rats

International Nuclear Information System (INIS)

Sato, Makoto

1978-01-01

This study determines the relationship between calcium distribution in hard tissues and age. The distribution of calcium was examined by using calcium-45 as tracer. Further, influences of such environmental toxic heavy metals as lead, cadmium and mercury upon calcium metabolism were determined. According to checks performed on 3-week-old rats, calcium-45 distributions in hard tissues from 6 hours to 6 days after injection were greater in the following tissues in the order listed: femurs, incisors, molars. In 2-week-old rats, the calcium distributions throughout the body were about the same. In 3-week-old rats, however, they were graded in descending order from femur to incisors, and then to molars. In rats of 18 weeks or more, the distribution of calcium-45 in the femur decreased. A slow increase was noted in calcium-45 deposits in the incisors of rats of four or more weeks; this increase remained constant at a very low level in rats of more than eight weeks. Calcium-45 distribution in rats of 61 weeks of age was graded in this descending order: incisors, femurs, and molars. In the group injected with calcium-45 and lead acetate, calcium-45 distribution was significantly less in 3-week-old than in 3-month-old rats. The following are percentages of calcium-45 distribution in rats to which 100 mg/kg of lead (equivalent of 1/3 of LD 50 were injected, when 100-percent distribution is assumed for controls; 3-week-old rats: femur 48 percent, incisors 49 percent, and molars 40 percent, 3-month-old rats: femurs 73 percent, incisors 67 percent, and molars 71 percent. No difference was observed in calcium-45 uptake between rats to whom injections of cadmium and mercury equivalent to 1/3 of a dose of LD 50 had been administered and rats who received only a single injection of calcium-45. (auth.)

Different sources of omega-3 polyunsaturated fatty acids affects apparent digestibility, tissue deposition, and tissue oxidative stability in growing female rats

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Benedito Vagner A

2011-10-01

Full Text Available Abstract Background Numerous health benefits associated with increased omega-3 polyunsaturated fatty acid (n-3 PUFA consumption has lead to an increasing variety of available n-3 PUFA sources. However, sources differ in the type, amount, and structural form of the n-3 PUFAs. Therefore, the objective of this study was to determine the effect of different sources of ω-3 PUFAs on digestibility, tissue deposition, eicosanoid metabolism, and oxidative stability. Methods Female Sprague-Dawley rats (age 28 d were randomly assigned (n = 10/group to be fed a high fat 12% (wt diet consisting of either corn oil (CO or n-3 PUFA rich flaxseed (FO, krill (KO, menhaden (MO, salmon (SO or tuna (TO oil for 8 weeks. Rats were individually housed in metabolic cages to determine fatty acid digestibility. Diet and tissue fatty acid composition was analyzed by gas chromatography and lipid classes using thin layer chromatography. Eicosanoid metabolism was determined by measuring urinary metabolites of 2-series prostaglandins (PGs and thromoboxanes (TXBs using enzyme immunoassays. Oxidative stability was assessed by measuring thiobarbituric acid reactive substances (TBARS and total antioxidant capacity (TAC using colorimetric assays. Gene expression of antioxidant defense enzymes was determined by real time quantitative polymerase chain reaction (RT-qPCR. Results Rats fed KO had significantly lower DHA digestibility and brain DHA incorporation than SO and TO-fed rats. Of the n-3 PUFA sources, rats fed SO and TO had the highest n-3 PUFAs digestibility and in turn, tissue accretion. Higher tissue n-3 LC-PUFAs had no significant effect on 2-series PG and TXB metabolites. Despite higher tissue n-3 LC-PUFA deposition, there was no increase in oxidation susceptibility indicated by no significant increase in TBARS or decrease in TAC and gene expression of antioxidant defense enzymes, in SO or TO-fed rats. Conclusions On the basis that the optimal n-3 PUFA sources should

Fruit vinegars attenuate cardiac injury via anti-inflammatory and anti-adiposity actions in high-fat diet-induced obese rats.

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Bounihi, Abdenour; Bitam, Arezki; Bouazza, Asma; Yargui, Lyece; Koceir, Elhadj Ahmed

2017-12-01

Fruit vinegars (FVs) are used in Mediterranean folk medicine for their hypolipidemic and weight-reducing properties. To investigate the preventive effects of three types of FV, commonly available in Algeria, namely prickly pear [Opuntia ficus-indica (L.) Mill (Cectaceae)], pomegranate [Punica granatum L. (Punicaceae)], and apple [Malus domestica Borkh. (Rosaceae)], against obesity-induced cardiomyopathy and its underlying mechanisms. Seventy-two male Wistar rats were equally divided into 12 groups. The first group served as normal control (distilled water, 7 mL/kg bw), and the remaining groups were respectively treated with distilled water (7 mL/kg bw), acetic acid (0.5% w/v, 7 mL/kg bw) and vinegars of pomegranate, apple or prickly pear (at doses of 3.5, 7 and 14 mL/kg bw, acetic acid content as mentioned above) along with a high-fat diet (HFD). The effects of the oral administration of FV for 18 weeks on the body and visceral adipose tissue (VAT) weights, plasma inflammatory and cardiac enzymes biomarkers, and in heart tissue were evaluated. Vinegars treatments significantly (p inflammatory and anti-adiposity properties of these vinegars.

MiR-34a/miR-93 target c-Ski to modulate the proliferaton of rat cardiac fibroblasts and extracellular matrix deposition in vivo and in vitro.

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Zhang, Chengliang; Zhang, Yanfeng; Zhu, Hong; Hu, Jiajia; Xie, Zhongshang

2018-06-01

Cardiac fibrosis is associated with diverse heart diseases. In response to different pathological irritants, cardiac fibroblasts may be induced to proliferate and differentiate into cardiac myofibroblasts, thus contributing to cardiac fibrosis. TGF-β signaling is implicated in the development of heart failure through the induction of cardiac fibrosis. C-Ski, an inhibitory regulator of TGF-β signaling, has been reported to suppress TGF-β1-induced human cardiac fibroblasts' proliferation and ECM protein increase; however, the underlying molecular mechanism needs further investigation. In the present study, we demonstrated that c-Ski could ameliorate isoproterenol (ISO)-induced rat myocardial fibrosis model and TGF-β1-induced primary rat cardiac fibroblasts' proliferation, as well as extracellular matrix (ECM) deposition. The protein level of c-Ski was dramatically decreased in cardiac fibrosis and TGF-β1-stimulated primary rat cardiac fibroblasts. In recent decades, a family of small non-coding RNA, namely miRNAs, has been reported to regulate gene expression by interacting with diverse mRNAs and inducing either translational suppression or mRNA degradation. Herein, we selected miR-34a and miR-93 as candidate miRNAs that might target to regulate c-Ski expression. After confirming that miR-34a/miR-93 targeted c-Ski to inhibit its expression, we also revealed that miR-34a/miR-93 affected TGF-β1-induced fibroblasts' proliferation and ECM deposition through c-Ski. Taken together, we demonstrated a miR-34a/miR-93-c-Ski axis which modulates TGF-β1- and ISO-induced cardiac fibrosis in vitro and in vivo; targeting the inhibitory factors of c-Ski to rescue its expression may be a promising strategy for the treatment of cardiac fibrosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Influence of glutamine on the effect of resistance exercise on cardiac ANP in rats

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Romeu Rodrigues de Souza

2015-03-01

Full Text Available Various nutritional supplements (herbs, vitamins, and micronutrients improve responses and adaptations to resistance exercise. ANP is a heart hormone that contributes to fluid, electrolyte and blood pressure homeostasis through its natriuretic and vasodilative actions. In the present study, the adaptation of ANP in response to resistance exercise was investigated in rats supplemented with glutamine for five weeks. The results showed that supplementation with glutamine did not influence the number of ANP granules per atrial cardiocyte in sedentary animals. In exercised-trained rats, the number and diameter of the granules was significantly higher in comparison with the control group and in exercised animals supplemented with glutamine there was significant increase in the number and diameter of ANP granules compared with controls. Altogether, these data indicated that in resistance exercise rats, glutamine significantly enhances cardiac ANP thus implicating the beneficial effects of glutamine supplementation to the ANP system.

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

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

2004-09-01

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

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

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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.

Effect of irradiation on the periodontal tissues in streptozotocin-induced diabetic rats

International Nuclear Information System (INIS)

Park, Dong Sin; Hwang, Eui Hwan; Lee, Sang Rae

2005-01-01

To observe the histopathological changes in the periodontal tissues of mandibular molars in streptozotocin-induced diabetic rats after irradiation. The male Sprague-Dawley rats weighing approximately 250 gm were divided into four groups; control, diabetes, irradiation, and diabetes - irradiation groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control and irradiation groups were injected with citrate buffer only. After 5 days, the head and neck region of the rats in irradiation and diabetes - irradiation groups were irradiated with a single absorbed dose of 10 Gy. All the rats were sacrificed at 3, 7, 14, 21, and 28 days after irradiation. The specimen including the mandibular molars were sectioned and observed using a histopathological method. In the diabetes group, osteoclastic activity was observed in the alveolar bone and the root throughout the period of experiment. Also, osteoblastic and fibroblastic activities were markedly decreased. In the irradiation group, the osteoclasts were observed in the alveolar bone and the dilated capillaries were increased in the early experimental phases. However, vigorous osteoblastic activity was noted in the late experimental phases. In the diabetes- irradiation group, osteoblastic activity in the alveolar bone and the root was observed in the early experimental phases. However, there were no resorption and osteoblastic activity in the alveolar bone and the root in the late experimental phases, and obvious atrophic change of fibrous tissues was noted. This experiment suggests that osteoblastic activity was caused by irradiation in the late experimental phases, but atrophic change of the periodontal ligament tissues was induced after irradiation in diabetic state.

Extreme hypoxia tolerance of naked mole-rat brain.

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Larson, John; Park, Thomas J

2009-12-09

Mammalian brains have extremely high levels of aerobic metabolism and typically suffer irreversible damage after brief periods of oxygen deprivation such as occur during stroke or cardiac arrest. Here we report that brain tissue from naked mole-rats, rodents that live in a chronically low-oxygen environment, is remarkably resistant to hypoxia: naked mole-rat neurons maintain synaptic transmission much longer than mouse neurons and can recover from periods of anoxia exceeding 30 min. We suggest that brain tolerance to hypoxia may result from slowed or arrested brain development in these extremely long-lived animals.

Autoradiographic localization of 131I-labelled thyroxine in the tissues of rat

International Nuclear Information System (INIS)

Prakash, P.; Romack, F.E.

1977-01-01

An attempt was made to visualize the sites of localization of 131 I-labelled thyroxine in the tissues of the rat by autoradiographic dipping techniques. The maximal uptake of 131 I-thyroxine in rats occured at 12 hours in all the tissues examined. The radioactivity continued to decrease from 12 to 36 hours after the injection. In the liver and kidney, the decline after 12 hours was rather marked. The radioactivity decreased only slightly from 12 to 36 hours in the spleen. After 3 hours of injection, the radioactivity was consistently higher in the thyroid follicular epithelial cells than in the interfollicular connective tissue. A high concentration of radioactivity was found at the periphery of the colloid areas. (author)

Metabolism of 15(p123I iodophenyl-)pentadecanoic acid in heart muscle and noncardiac tissues

International Nuclear Information System (INIS)

Reske, S.N.; Sauer, W.; Winkler, C.; Machulla, H.J.; Knust, J.

1985-01-01

The uptake and turnover of W(p 123 I iodophenyl-)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in the heart, lung, liver, kidneys, spleen, and skeletal muscle of rats. At 2 min post injection, a high cardiac uptake of 4.4% dose per gram had already been achieved; this was followed by a rapid, two-component, tracer clearance. The kinetics of tissue concentrations of labeled hydrophilic catabolites indicated a rapid oxidation of I-PPA and the subsequent washout of I-PPA catabolites from heart-muscle tissue. The fractional distribution of the labeled cardiac lipids compared favorably with previously reported values for 3 H-oleic- or 14 C-palmitic-acid-labeled myocardial lipids. Typical patterns of I-PPA metabolism were observed in tissues; dedpending on primary fatty-acid oxidation, lipid metabolism regulation, or I-PPA-catabolite excretion. The tissue concentrations and kinetics of I-PPA and its metabolites in the heart muscle indicated that general pathways of cardiac-lipid metabolism are traced by this new γ-emitting isotope-labeled radiopharmaceutical. (orig.)

Vitamins C and E attenuate lipid dystrophy in tissues of rats ...

African Journals Online (AJOL)

To investigate the effects of aluminum chloride (AlCl3) in the deviation of tissue lipid profiles and ways to reduce its effect using antioxidant vitamins C and E, thirty-six male albino rats (120-150g) were divided into six groups with six rats each. Group (1) received normal saline and served as control, Group (2) was ...

Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells.

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Yao, Takako; Fujimura, Tsutomu; Murayama, Kimie; Okumura, Ko; Seko, Yoshinori

2017-10-18

We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo. In this study, to investigate the mechanism of cell injury of cardiac myocytes and pancreatic β-cells involved in diabetes mellitus (DM), we analyzed plasma ORAIP levels in DM model rats and the role of ORAIP in high glucose-induced apoptosis of cardiac myocytes in vitro. We also examined whether recombinant-ORAIP induces apoptosis in pancreatic β-cells. Plasma ORAIP levels in DM rats during diabetic phase were about 18 times elevated as compared with non-diabetic phase. High glucose induced massive apoptosis in cardiac myocytes (66.2 ± 2.2%), which was 78% suppressed by neutralizing anti-ORAIP mAb in vitro. Furthermore, recombinant-ORAIP clearly induced apoptosis in pancreatic β-cells in vitro. These findings strongly suggested that ORAIP plays a pivotal role in hyperglycemia-induced myocardial injury and pancreatic β-cell injury in DM. ORAIP will be a biomarker and a critical therapeutic target for cardiac injury and progression of DM itself.

Identification and characterization of novel gut-associated lymphoid tissues in rat small intestine.

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Hitotsumatsu, Osamu; Hamada, Hiromasa; Naganuma, Makoto; Inoue, Nagamu; Ishii, Hiromasa; Hibi, Toshifumi; Ishikawa, Hiromichi

2005-10-01

The crypt lamina propria of the mouse small intestine has been shown to harbor multiple tiny clusters filled with c-kit- and interleukin 7 receptor (IL-7R)-positive lympho-hemopoietic cells (cryptopatches; CPs). However, it has remained an open question whether similar lymphoid tissue are present in the gastrointesitinal tract in other animals. In the present study, we investigated whether the small intestine of rats harbored lymphoid tissues similar to mouse CPs. Immunohistochemical and flow cytometric analyses were carried out using various antibodies, including those to c-kit and IL-7R molecules. Lymphocyte-filled villi (LFVs), populated predominantly with c-kit- and IL-7 receptor (IL-7R)-positive cells and less with T cell receptor (TCR)-alphabeta T cells were found throughout the small intestine of young adult rats. Although LFVs were absent from fetal rat intestine, they were first detected at around 2 weeks after birth. Notably, in most LFVs that settled in the antimesenteric wall of the small intestine in young adult rats, immunoglobulin M-positive B cells were also detectable at the bottom of the LFVs. In aged rats, lymphocytes in some LFVs displayed a different phenotype, comprising a large B-cell area that included a germinal center. Thus, these clusters represent the first description of isolated lymphoid follicles (ILFs) in the rat small intestine. The present study provides the first evidence for c-kit- and IL-7R-positive lymphocyte clusters in the rat small intestine. Our data also indicating that LFVs and ILFs may constitute novel organized gut-associated lymphoid tissues in lamina propria of the rat small intestine.