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Sample records for adult rat hearts

  1. Adult Congenital Heart Association

    MedlinePlus

    ... survivable, manageable, yet in the routine years between infancy and adulthood, sometimes forgettable. The Adult Congenital Heart ... understand the continuum of the disease from its infancy. The Adult Congential Heart Association brings together valuable ...

  2. Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart.

    PubMed

    Chouabe, C; Amsellem, J; Espinosa, L; Ribaux, P; Blaineau, S; Mégas, P; Bonvallet, R

    2002-04-01

    Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities. PMID:11893582

  3. Nuclear β-adrenergic receptors modulate gene expression in adult rat heart

    PubMed Central

    Vaniotis, George; Del Duca, Danny; Trieu, Phan; Rohlicek, Charles V.; Hébert, Terence E.; Allen, Bruce G.

    2016-01-01

    Both β1- and β3-adrenergic receptors (β1ARs and β3ARs) are present on nuclear membranes in adult ventricular myocytes. These nuclear-localized receptors are functional with respect to ligand binding and effector activation. In isolated cardiac nuclei, the non-selective βAR agonist isoproterenol stimulated de novo RNA synthesis measured using assays of transcription initiation (Boivin et al., 2006 Cardiovasc Res. 71:69–78). In contrast, stimulation of endothelin receptors, another G protein-coupled receptor (GPCR) that localizes to the nuclear membrane, resulted in decreased RNA synthesis. To investigate the signalling pathway(s) involved in GPCR-mediated regulation of RNA synthesis, nuclei were isolated from intact adult rat hearts and treated with receptor agonists in the presence or absence of inhibitors of different mitogen-activated protein kinase (MAPK) and PI3K/PKB pathways. Components of p38, JNK, and ERK1/2 MAP kinase cascades as well as PKB were detected in nuclear preparations. Inhibition of PKB with triciribine, in the presence of isoproterenol, converted the activation of the βAR from stimulatory to inhibitory with regards to RNA synthesis, while ERK1/2, JNK and p38 inhibition reduced both basal and isoproterenol-stimulated activity. Analysis by qPCR indicated an increase in the expression of 18 S rRNA following isoproterenol treatment and a decrease in NFκB mRNA. Further qPCR experiments revealed that isoproterenol treatment also reduced the expression of several other genes involved in the activation of NFκB, while ERK1/2 and PKB inhibition substantially reversed this effect. Our results suggest that GPCRs on the nuclear membrane regulate nuclear functions such as gene expression and this process is modulated by activation/inhibition of downstream protein kinases within the nucleus. PMID:20732414

  4. Adults with Congenital Heart Defects

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Web Booklet: Adults With Congenital Heart Defects Updated:Apr ... topic from the list below to learn more. Web Booklet: Adults With Congenital Heart Defects Introduction Introduction: ...

  5. Episodic ozone exposure in adult and senescent Brown Norway rats: acute and delayed effect on heart rate, core temperature and motor activity.

    PubMed

    Gordon, C J; Johnstone, A F; Aydin, C; Phillips, P M; MacPhail, R C; Kodavanti, U P; Ledbetter, A D; Jarema, K A

    2014-06-01

    Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O₃) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T(c)) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O₃ (6 h/day of 1 ppm O₃ for 2 consecutive days/week for 13 weeks). Acute O₃ initially led to marked drops in HR and T(c). As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O₃. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O₃ exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O₃, adult and senescent rats exhibited an elevated T(c) and HR during the day but not at night, an effect that persisted for at least 48 h after O₃ exposure. MA was elevated in adults but not senescent rats during recovery from O₃. Overall, acute effects of O₃, including reductions in HR and T(c), were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T(c) with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O₃ in senescent rats may explain the relatively heightened physiological response to O₃ in younger rats. PMID:24779854

  6. IN VITRO SENSITIVITY OF CHOLINESTERASES AND [3H]OXOTREMORINE-M BINDING IN HEART AND BRAIN OF ADULT AND AGING RATS TO ORGANOPHOSPHORUS ANTICHOLINESTERASES

    PubMed Central

    Mirajkar, Nikita; Pope, Carey N.

    2008-01-01

    Organophosphorus (OP) insecticides elicit toxicity via acetylcholinesterase inhibition, allowing acetylcholine accumulation and excessive stimulation of cholinergic receptors. Some OP insecticides bind to additional macromolecules including butyrylcholinesterase and cholinergic receptors. While neurotoxicity from OP anticholinesterases has been extensively studied, effects on cardiac function have received less attention. We compared the in vitro sensitivity of acetylcholinesterase, butyrylcholinesterase and [3H]oxotremorine-M binding to muscarinic receptors in the cortex and heart of adult (3 months) and aging (18 months) rats to chlorpyrifos, methyl parathion and their active metabolites chlorpyrifos oxon and methyl paraoxon. Using selective inhibitors, the great majority of cholinesterase in brain was defined as acetylcholinesterase, while butyrylcholinesterase was the major cholinesterase in heart, regardless of age. In the heart, butyrylcholinesterase was markedly more sensitive than acetylcholinesterase to inhibition by chlorpyrifos oxon, and butyrylcholinesterase in tissues from aging rats was more sensitive than enzyme from adults, possibly due to differences in A-esterase mediated detoxification. Relatively similar differences were noted in brain. In contrast, acetylcholinesterase was more sensitive than butyrylcholinesterase to methyl paraoxon in both heart and brain, but no age-related differences were noted. Both oxons displaced [3H]oxotremorine-M binding in heart and brain of both age groups in a concentration-dependent manner. Chlorpyrifos had no effect but methyl parathion was a potent displacer of binding in heart and brain of both age groups. Such OP and age-related differences in interactions with cholinergic macromolecules may be important because of potential for environmental exposures to insecticides as well as the use of anticholinesterases in age-related neurological disorders. PMID:18761328

  7. Immunocytochemical localization of the nuclear 3,5,3'-triiodothyronine receptor in the adult rat: liver, kidney, heart, lung and spleen.

    PubMed

    Luo, M; Faure, R; Tong, Y A; Dussault, J H

    1989-04-01

    A monoclonal antibody was used for the localization of the nuclear T3 receptor in different tissues of the adult rat: the liver, kidney, heart, lung, spleen, testis, and pituitary. In the liver, the immunoreactivity was found uniformly distributed in the nuclei of hepatocytes. Sections incubated with a control ascitic fluid or with the same ascitic fluid pre-adsorbed with purified receptor showed no specific staining. In the kidney, the immunoreactivity was higher in the epithelial cell of the proximal convoluted tubes and juxtaglomerular cells. In the heart, only the myocardial cells were stained. In the lung, the immunoreactivity was confined to type II pneumocytes and alveolar macrophages. In the spleen, only a few mature lymphocyte and macrophage cell nuclei were stained. These results show that: 1) the abundance of the nuclear T3 correlates with previous studies using hormone binding techniques; 2) the nuclear T3 receptor is selectively located in certain cell types, which possess a precise local function.

  8. Radiation induced heart disease in hypertensive rats

    SciTech Connect

    Lauk, S.; Trott, K.R.

    1988-01-01

    Spontaneously hypertensive Wistar rats were given single doses of X rays to their heart. Irradiation decreased the blood pressure before any myocardial radiation damage was apparent. Male rats, which were more hypertensive than female rats, had a shorter survival time after local heart irradiation than female rats. Antihypertensive treatment with hydralazine did not increase the survival time. It is considered that myocardial hypertrophy is the cause of the increased susceptibility of spontaneously hypertensive rats to local heart irradiation.

  9. Histone methylations in heart development, congenital and adult heart diseases.

    PubMed

    Zhang, Qing-Jun; Liu, Zhi-Ping

    2015-01-01

    Heart development comprises myocyte specification, differentiation and cardiac morphogenesis. These processes are regulated by a group of core cardiac transcription factors in a coordinated temporal and spatial manner. Histone methylation is an emerging epigenetic mechanism for regulating gene transcription. Interplay among cardiac transcription factors and histone lysine modifiers plays important role in heart development. Aberrant expression and mutation of the histone lysine modifiers during development and in adult life can cause either embryonic lethality or congenital heart diseases, and influences the response of adult hearts to pathological stresses. In this review, we describe current body of literature on the role of several common histone methylations and their modifying enzymes in heart development, congenital and adult heart diseases.

  10. Histone methylations in heart development, congenital and adult heart diseases

    PubMed Central

    Zhang, Qing-Jun; Liu, Zhi-Ping

    2015-01-01

    Heart development comprises myocyte specification, differentiation and cardiac morphogenesis. These processes are regulated by a group of core cardiac transcription factors in a coordinated temporal and spatial manner. Histone methylation is an emerging epigenetic mechanism for regulating gene transcription. Interplay among cardiac transcription factors and histone lysine modifiers plays important role in heart development. Aberrant expression and mutation of the histone lysine modifiers during development and in adult life can cause either embryonic lethality or congenital heart diseases, and influences the response of adult hearts to pathological stresses. In this review, we describe current body of literature on the role of several common histone methylations and their modifying enzymes in heart development, congenital and adult heart diseases. PMID:25942538

  11. [Evaluation of congenital heart disease in adults].

    PubMed

    Oliver Ruiz, José María; Mateos García, Marta; Bret Zurita, Montserrat

    2003-06-01

    Improvements in the diagnosis and surgical treatment of congenital heart disease during infancy and childhood have resulted in an outstanding increase in the prevalence of these entities during adulthood. Congenital heart disease in the adult represents a new diagnostic challenge to the consultant cardiologist, unfamiliar with the anatomical and functional complexities of cardiac malformations. Assessment of adult congenital heart disease with imaging techniques can be as accurate as in children. However, these techniques cannot substitute for a detailed clinical assessment. Physical examination, electrocardiography and chest x-rays remain the three main pillars of bedside diagnosis. Transthoracic echocardiography is undoubtedly the imaging technique which provides most information, and in many situations no additional studies are needed. Nevertheless, ultrasound imaging properties in adults are not as favorable as in children, and prior surgical procedures further impair image quality. Despite recent advances in ultrasound technologies such as harmonic or contrast imaging, other diagnostic procedures are sometimes required. Fortunately, transesophageal echocardiography and magnetic resonance imaging are easily performed in the adult, and do not require anaesthetic support, in contrast to pediatric patients. These techniques, together with nuclear cardiology and cardiac catheterization, complete the second tier of diagnostic techniques for congenital heart disease. To avoid unnecessary repetition of diagnostic procedures, the attending cardiologist should choose the sequence of diagnostic techniques carefully; although the information this yields is often redundant, it is also frequently complementary. This article aims to compare the diagnostic utility of different imaging techniques in adult patients with congenital heart disease, both with and without prior surgical repair.

  12. Physiologic consequences of local heart irradiation in rats

    SciTech Connect

    Geist, B.J.; Lauk, S.; Bornhausen, M.; Trott, K.R. )

    1990-05-01

    Noninvasive methods have been used to study the long-term cardiovascular and pulmonary functional changes at rest and after exercise in adult rats following local heart irradiation with single x-ray doses of 15, 17.5 or 20 Gy, and in non-irradiated control animals. Rats that had undergone a chronic exercise program were compared with untrained cohorts. The earliest dysfunction detected was an increased respiratory rate (f) at 10 weeks after irradiation in the highest dose group. In contrast, both telemetric heart-rate (HR) and rhythm and indirect systolic blood pressure measurements performed at rest only revealed changes starting at 43 weeks after irradiation with 20 Gy, up to which point the rats showed no clinical signs of heart failure. However, the number of minutes required for the recovery of the HR to pre-exercise levels following the implementation of a standardized exercise challenge was elevated in untrained rats compared with their trained cohorts at 18 weeks after irradiation with 20 Gy. Increases in recovery times were required in the two lowest dose groups, starting at 26 weeks after irradiation. It was concluded that the reserve capacity of the cardiopulmonary system masks functional decrements at rest for many months following local heart irradiation, necessitating the use of techniques which reveal reductions in reserve capacities. Further, the influence of local irradiation to the heart and lungs deserves closer scrutiny due to mutual interactions.

  13. Pregnancy and adult congenital heart disease.

    PubMed

    Karamermer, Yusuf; Roos-Hesselink, Jolien W

    2007-09-01

    Increasing numbers of women with complex congenital heart disease are reaching childbearing age. Pregnancy is a major issue in the management of adult congenital heart disease. Cardiac disease is one of the most common causes of maternal morbidity and mortality. Complications, such as growth retardation, preterm and premature birth and even fetal and neonatal mortality, are more frequent among children of women with congenital heart disease. The risk of complications is determined by the severity of the cardiac lesion, the presence of cyanosis, the maternal functional class and the use of anticoagulation. However, the pathophysiology of these complications is not completely understood and may be related to a diminished increase in cardiac output and/or endothelial dysfunction. The management of pregnant cardiac patients is based on limited clinical information. This article reviews pre-pregnancy counseling and management during pregnancy in patients with congenital heart disease.

  14. Origin of Cardiomyocytes in the Adult Heart

    PubMed Central

    Leri, Annarosa; Rota, Marcello; Pasqualini, Francesco S.; Goichberg, Polina; Anversa, Piero

    2014-01-01

    This review article discusses the mechanisms of cardiomyogenesis in the adult heart. They include the reentry of cardiomyocytes into the cell cycle; dedifferentiation of preexisting cardiomyocytes which assume an immature replicating cell phenotype; transdifferentiation of hematopoietic stem cells into cardiomyocytes; and cardiomyocytes derived from activation and lineage specification of resident cardiac stem cells. The recognition of the origin of cardiomyocytes is of critical importance for the development of strategies capable of enhancing the growth response of the myocardium; in fact, cell therapy for the decompensated heart has to be based on the acquisition of this fundamental biological knowledge. PMID:25552694

  15. Sex Suffers for Younger Adults After Heart Attack

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160722.html Sex Suffers for Younger Adults After Heart Attack Lack ... who don't talk to their doctors about sex in the first few weeks after a heart ...

  16. An ontogenic study of adrenomedullin gene expression in the rat lung, adrenal, kidney, and heart.

    PubMed

    Wong, P F; O, W S; Tang, F

    2012-04-01

    In this study, the gene expression of adrenomedullin (Adm) in the peripheral tissues which include lung, adrenal, kidney, and heart during development was investigated in the rat. The preproadrenomedullin (preproAdm) mRNA and mRNAs of its related receptor components, calcitonin receptor-like receptor (Crlr), and receptor activity-modifying proteins (Ramp1, 2 and 3) of the lung, adrenal, kidney, and heart were measured by real-time RT-PCR and the ADM peptide measured by radioimmunoassay in 1-, 7-, 21-day-old rats and the adult rats. From day 1 to 21, preproAdm mRNA levels increased with age in the lung, the kidney, and the heart but decreased with age in the adrenal. ADM levels, however, increased with age in the lung but decreased with age in the kidney, the adrenal, and the heart. The preproAdm levels in the lung, in the kidney, and in the adrenal all increased in the adult rat. ADM peptide levels, however, decreased in the adult rat. Crlr and Ramp2 gene expression increased with age in the lung, in the kidney, and in the heart but decreased with age in the adrenal in the prepubertal rats. The results indicate that the levels of preproAdm mRNA, ADM peptide and its receptor component mRNAs in different tissues followed different patterns of changes during development.

  17. [Approach to congenital heart disease in adults].

    PubMed

    Alva Espinosa, Carlos

    2006-01-01

    After a few decades treating patients with congenital heart disease during childhood, we now face the problem of dealing with many of them as adults and few cases with disorders detected in adult life. The number of patients, with and without surgery is growing up rapidly. Conservatively speaking, there are in Mexico approximately 300 thousands patients with this condition, increasing by 15 thousands patients per year. In addition to the complexity of the congenital pathology, the knowledge of acquired diseases should be incorporated as well as the genetic advise, pregnancy care and specialized psychological support. The approach to these patients begins with stratification; diagnosis and treatment requiring a multidisciplinary, well informed and an capable to perform together medical team.

  18. Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts.

    PubMed

    Rorabaugh, Boyd R; Seeley, Sarah L; Bui, Albert D; Sprague, Lisanne; D'Souza, Manoranjan S

    2016-02-15

    Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg(-1)·day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart.

  19. Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination

    MedlinePlus

    ... Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

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

    SciTech Connect

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

    2014-01-15

    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

  1. Caloric restriction restores the cardioprotective effect of preconditioning in the rat heart.

    PubMed

    Long, Paige; Nguyen, Quang; Thurow, Chantelle; Broderick, Tom L

    2002-07-01

    Preconditioning (PC) describes the observation that brief periods of ischemia paradoxically protect the heart and limit necrosis caused by a subsequent more prolonged period of ischemia. However, the PC response is attenuated in hearts from 9- to 12-month-old Sprague-Dawley rats, as compared to young adults. This study determined whether long-term caloric restriction (CR) could preserve the PC response, since CR increases ischemic tolerance in these hearts. Following 6 months of CR, isolated hearts underwent PC followed by ischemia and reperfusion. In contrast to control hearts in which PC response was attenuated, PC in CR hearts was clearly of benefit. In these hearts, aortic flow was increased resulting in a dramatic improvement of cardiac output. Our study suggests that CR is effective in preserving the PC response.

  2. A Novel Technique for Image-Guided Local Heart Irradiation in the Rat

    PubMed Central

    Sharma, Sunil; Moros, Eduardo G.; Boerma, Marjan; Sridharan, Vijayalakshmi; Han, Eun Young; Clarkson, Richard; Hauer-Jensen, Martin; Corry, Peter M.

    2014-01-01

    In radiotherapy treatment of thoracic, breast and chest wall tumors, the heart may be included (partially or fully) in the radiation field. As a result, patients may develop radiation-induced heart disease (RIHD) several years after exposure to radiation. There are few methods available to prevent or reverse RIHD and the biological mechanisms remain poorly understood. In order to further study the effects of radiation on the heart, we developed a model of local heart irradiation in rats using an image-guided small animal conformal radiation therapy device (SACRTD) developed at our institution. First, Monte Carlo based simulations were used to design an appropriate collimator. EBT-2 films were used to measure relative dosimetry, and the absolute dose rate at the isocenter was measured using the AAPM protocol TG-61. The hearts of adult male Sprague-Dawley rats were irradiated with a total dose of 21 Gy. For this purpose, rats were anesthetized with isoflurane and placed in a custom-made vertical rat holder. Each heart was irradiated with a 3-beam technique (one AP field and 2 lateral fields), with each beam delivering 7 Gy. For each field, the heart was visualized with a digital flat panel X-ray imager and placed at the isocenter of the 1.8 cm diameter beam. In biological analysis of radiation exposure, immunohistochemistry showed γH2Ax foci and nitrotyrosine throughout the irradiated hearts but not in the lungs. Long-term follow-up of animals revealed histopathological manifestations of RIHD, including myocardial degeneration and fibrosis. The results demonstrate that the rat heart irradiation technique using the SACRTD was successful and that surrounding untargeted tissues were spared, making this approach a powerful tool for in vivo radiobiological studies of RIHD. Functional and structural changes in the rat heart after local irradiation are ongoing. PMID:24000983

  3. Manganese depresses rat heart muscle respiration.

    PubMed

    Miller, Kevin B; Caton, Joel S; Finley, John W

    2006-01-01

    It has previously been reported that moderately high dietary manganese (Mn) in combination with marginal magnesium (Mg) resulted in ultrastructural damage to heart mitochondria. Manganese may replace Mg in biological functions, including the role of enzyme cofactor. Manganese may accumulate and substitute for Mg during the condition of Mg-deficiency. The objective of the current study was to determine whether high Mn alters heart muscle respiration and Mg-enzyme activity as well as whole body Mn retention under marginal Mg. An additional objective was to determine whether high Mn results in increased oxidative stress. In experiment 1: forty-eight rats were fed a 2 x 3 factorial arrangement of Mn (10, 100, or 1000 mg/kg) and Mg (200 or 500 mg/kg). In experiment 2: thirty-two rats were fed one of four diets in a 2 x 2 factorial arrangement of Mn (10 or 250 mg/kg) and Mg (200 or 500 mg/kg). In experiment 3: thirty-two rats were fed one of four diets in a 2 x 2 factorial arrangement of Mn (10 or 650 mg/kg) and Mg (200 or 500 mg/kg). In experiment 2, high Mn and marginal Mg reduced (P<0.05) oxygen consumption of left ventricle muscle. Marginal Mg, but not Mn, reduced (P<0.05) activity of sarcoplasmic reticulum calcium-ATPase enzyme. Dietary Mg had no affect on (54)Mn kinetics, but high dietary Mn decreased (P<0.01) absorption, retention, and rate of excretion of (54)Mn. Neither cellular stress, measured by Comet assay, nor antioxidant activities were increased by high Mn. A strong interaction (P<0.001) between increasing Mn and adequate Mg on hematology was observed. These results confirm previous research in swine that high Mn alters myocardial integrity as well as function, but not as a result of altered calcium transport or oxidative stress.

  4. Prevention of anemia alleviates heart hypertrophy in copper deficient rats

    SciTech Connect

    Lure, M.D.; Fields, M.; Lewis, C.G. Univ. of Maryland, College Park Georgetown Univ., Washington, DC )

    1991-03-11

    The present investigation was designed to examine the role of anemia in the cardiomegaly and myocardial pathology of copper deficiency. Weanling rats were fed a copper deficient diet containing either starch (ST) or fructose (FRU) for five weeks. Six rats consuming the FRU diet were intraperitoneally injected once a week with 1.0 ml/100g bw of packed red blood cells (RBC) obtained from copper deficient rats fed ST. FRU rats injected with RBC did not develop anemia. Additionally, none of the injected rats exhibited heart hypertrophy or gross pathology and all survived. In contrast, non-injected FRU rats were anemic, exhibited severe signs of copper deficiency which include heart hypertrophy with gross pathology, and 44% died. Maintaining the hematocrit with RBC injections resulted in normal heart histology and prevented the mortality associated with the fructose x copper interaction. The finding suggest that the anemia associated with copper deficiency contributes to heart pathology.

  5. Acquired heart conditions in adults with congenital heart disease: a growing problem.

    PubMed

    Tutarel, Oktay

    2014-09-01

    The number of adults with congenital heart disease is increasing due to the great achievements in the field of paediatric cardiology, congenital heart surgery and intensive care medicine over the last decades. Mortality has shifted away from the infant and childhood period towards adulthood. As congenital heart disease patients get older, a high prevalence of cardiovascular risk factors is encountered similar to the general population. Consequently, the contribution of acquired morbidities, especially acquired heart conditions to patient outcome, is becoming increasingly important. Therefore, to continue the success story of the last decades in the treatment of congenital heart disease and to further improve the outcome of these patients, more attention has to be given to the prevention, detection and adequate therapy of acquired heart conditions. The aim of this review is to give an overview about acquired heart conditions that may be encountered in adults with congenital heart disease.

  6. A review of the economics of adult congenital heart disease.

    PubMed

    Seckeler, Michael D; Thomas, Ian D; Andrews, Jennifer; Joiner, Keith; Klewer, Scott E

    2016-01-01

    Adults living with congenital heart disease (CHD) now outnumber children with the disease. Thanks to medical advances over the past 75 years, many of these fatal childhood heart problems have changed to chronic medical conditions. As the population of adults with CHD increases, they will require increasingly complex medical, surgical and catheter-based therapies. In addition, social burdens including education, employment and insurability, which increase the societal costs of adult CHD, are now being recognized for adults living with CHD. This review summarizes the available literature on the economics of adult CHD.

  7. Studies on proteolytic activities in heart muscle of diabetic rats.

    PubMed

    Dahlmann, B; Metzinger, H; Reinauer, H

    1982-06-01

    Induction of diabetes mellitus in rats following injection of streptozotocin caused reduction in rate of gain of heart weight, of protein and of DNA content in the first two weeks. During the same time interval the overall activity of acid proteinases (cathepsin D), of alkaline proteinases and of proteinase inhibitors was measured in heart muscle homogenates. No statistically significant differences were detected compared with the proteinase activities in control rats. In contrast, total aminopeptidase activity in diabetic hearts was consistently lower than in control hearts. Earlier studies on rat skeletal muscles have shown that induction of diabetes mellitus is followed by a substantial increase of alkaline proteinase as well as aminopeptidase activities. These findings are contrasted by present data obtained with heart muscle of diabetic rats, suggesting that this tissue responds differently to insulin deficiency.

  8. Characterization of apela, a novel endogenous ligand of apelin receptor, in the adult heart.

    PubMed

    Perjés, Ábel; Kilpiö, Teemu; Ulvila, Johanna; Magga, Johanna; Alakoski, Tarja; Szabó, Zoltán; Vainio, Laura; Halmetoja, Eveliina; Vuolteenaho, Olli; Petäjä-Repo, Ulla; Szokodi, István; Kerkelä, Risto

    2016-01-01

    The G protein-coupled apelin receptor regulates important processes of the cardiovascular homeostasis, including cardiac development, cardiac contractility, and vascular tone. Most recently, a novel endogenous peptide ligand for the apelin receptor was identified in zebrafish, and it was named apela/elabela/toddler. The peptide was originally considered as an exclusively embryonic regulator, and so far its function in the adult organism remains elusive. We show here that apela is predominantly expressed in the non-cardiomyocyte fraction in the adult rodent heart. We also provide evidence that apela binds to apelin receptors in the heart. Using isolated adult rat hearts, we demonstrate, that just like the fellow receptor agonist apelin, apela increases cardiac contractility and induces coronary vasodilation already in the nanomolar level. The inotropic effect, as revealed by Western blot analysis, is accompanied by a significant increase in extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. Pharmacological inhibition of ERK1/2 activation markedly attenuates the apela-induced inotropy. Analysis of samples from infarcted mouse hearts showed that expression of both apela and apelin receptor is induced in failing mouse hearts and correlate with left ventricular ejection fraction. Hence, we conclude that apela is present in the adult heart, is upregulated in post-infarction cardiac remodeling, and increases cardiac contractility in an ERK1/2-dependent manner.

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

    PubMed

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

    2014-01-15

    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 100μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24h. In this in vivo rat study (0.5mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48h. 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 70kD 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.

  10. More Than Just the Heart: Transition and Psychosocial Issues in Adult Congenital Heart Disease.

    PubMed

    Kovacs, Adrienne H; Utens, Elisabeth M

    2015-11-01

    Most infants born with congenital heart disease (CHD) are now expected to reach adulthood. However, adults with CHD of moderate or great complexity remain at elevated risk of heart failure, arrhythmias, additional surgeries and interventional procedures, and premature mortality. This creates a need for lifelong specialized cardiac care and leads to 2 sets of potential challenges: (1) the transition from pediatric to adult care and (2) the psychosocial implications of coping with a chronic and often life-shortening medical condition. Many adolescents struggle with the transition to adult care, and mood and anxiety disorders are not uncommon in the adult setting.

  11. [Average values of electrocardiograph parameters in healthy, adult Wistar rats].

    PubMed

    Zaciragić, Asija; Nakas-ićindić, Emina; Hadzović, Almira; Avdagić, Nesina

    2004-01-01

    Average values of heart rate (HR) and the average duration of electrocardiograph parameters were investigated (RR interval, P wave, PQ interval, QRS complex and QT interval) in healthy, adult Wistar rats of both sexes (n=86). Electrocardiogram (ECG) was recorded by Shiller Resting ECG, and for analysis of recordings SEMA-200 Vet computer program was used. Prior to registration animals were exposed to light ether anesthesia. Mean value of HR was 203.03+/-3.09 beats/min in whole sample. Observed differences in mean values of heart rate and duration of followed ECG parameters between sexes were not statistically significant. Results gathered in our study could serve as standard values for electrocardiograph parameters in future research where will be used Wistar rats in conditions of registration and analysis of ECG that are described in our paper.

  12. Complete inhibition of creatine kinase in isolated perfused rat hearts

    SciTech Connect

    Fossel, E.T.; Hoefeler, H.

    1987-01-01

    Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts are able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. /sup 31/P-NMR of the heart was carried out.

  13. Molecular cloning of rat cardiac troponin I and analysis of troponin I isoform expression in developing rat heart.

    PubMed

    Murphy, A M; Jones, L; Sims, H F; Strauss, A W

    1991-01-22

    We have isolated and sequenced a cDNA encoding rat cardiac troponin I. The predicted amino acid sequence was highly identical with previously reported chemically derived amino acid sequences for rabbit and bovine cardiac troponin I. Clones for slow skeletal muscle troponin I were also obtained from neonatal rat cardiac ventricle by the polymerase chain reaction. The nucleotide sequences of these clones were determined to be more than 99% identical with a previously reported rat slow skeletal troponin I cDNA [Koppe et al. (1989) J. Biol. Chem. 264, 14327-14333]. The troponin I clones hybridized to RNA from the appropriate muscle from adult animals. However, RNA from fetal and neonatal rat heart also hybridized with the slow skeletal troponin I cDNA, demonstrating its expression in fetal and neonatal rat heart. Slow skeletal troponin I steady-state mRNA levels decreased with increasing age, but cardiac troponin I mRNA levels increased through fetal and early neonatal cardiac development. Thus, during fetal and neonatal development, slow skeletal and cardiac troponin I isoforms are coexpressed in the rat heart and regulated in opposite directions. The degree of primary sequence differences in these isoforms, especially at phosphorylation sites, may result in important functional differences in the neonatal myocardium.

  14. Pregnancy and Adult Congenital Heart Disease.

    PubMed

    Bhatt, Ami B; DeFaria Yeh, Doreen

    2015-11-01

    Most women with known congenital heart disease can have successful pregnancy, labor, and delivery. Preconception assessment is essential in understanding anatomy, repairs, and current physiology, all of which can influence risk in pregnancy. With that foundation, a multidisciplinary cardio-obstetric team can predict and prepare for complications that may occur with superimposed hemodynamic changes of pregnancy. Individuals with Eisenmenger syndrome, pulmonary hypertension, cyanosis, significant left heart obstruction, ventricular dysfunction, or prior major cardiac event are among the highest risk for complications.

  15. Constant magnetic field influence on a heart beat in rats

    SciTech Connect

    Lazetic, B.; Pekaric-Nadj, N.; Kasas-Lazetic, K.

    1991-03-11

    The authors used uretan narcose to implant constant magnets of 50 mT under the skin of rats in head region. The ECG was registrated in the next 6 hours. From it they found much slower heart beat which culminated in the first 105 minutes. After 6 weeks of continual exposure the heart beat of the exposed rats was still slower then in the controls. It is concluded that a chronical exposition to the constant magnetic field affected rats organisms and no regulatory mechanism could prevent it.

  16. Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair

    PubMed Central

    Xin, Mei; Olson, Eric N.; Bassel-Duby, Rhonda

    2013-01-01

    As the adult mammalian heart has limited potential for regeneration and repair, the loss of cardiomyocytes during injury and disease can result in heart failure and death. The cellular processes and regulatory mechanisms involved in heart growth and development can be exploited to repair the injured adult heart through ‘reawakening’ pathways that are active during embryogenesis. Heart function has been restored in rodents by reprogramming non-myocytes into cardiomyocytes, by expressing transcription factors (GATA4, HAND2, myocyte-specific enhancer factor 2C (MEF2C) and T-box 5 (TBX5)) and microRNAs (miR-1, miR-133, miR-208 and miR-499) that control cardiomyocyte identity. Stimulating cardiomyocyte dedifferentiation and proliferation by activating mitotic signalling pathways involved in embryonic heart growth represents a complementary approach for heart regeneration and repair. Recent advances in understanding the mechanistic basis of heart development offer exciting opportunities for effective therapies for heart failure. PMID:23839576

  17. Nicotine and carbon monoxide: effects on the isolated rat heart.

    PubMed

    McGrath, J J

    1986-01-01

    We studied the combined effects of carbon monoxide (CO) and nicotine on the performance of the isolated rat heart. Hearts were removed from laboratory rats and perfused through the aorta with 95% O2-5% CO2 (oxygenated) Krebs-Henseleit solution (KHs). After 30 min, the perfusate was switched rapidly to one of three solutions: KHs containing 10% CO-85% O2-5% CO2 (CO), 10 micrograms/ml nicotine (Nic), or CO combined with nicotine (CO + Nic). KHs containing CO increased coronary flow by 41% without affecting heart rate or pulse pressure. Coronary flow returned to control values during recovery in oxygenated KHs. KHs containing Nic decreased heart rate by 20% and coronary flow by 28%. Pulse pressure was unaffected. Both heart rate and coronary flow returned towards control values during recovery in oxygenated KHs. KHs containing CO + Nic decreased heart rate 16% but stimulated coronary flow 13%. Heart rate returned towards control values during recovery; however, coronary flow, which declined to control values after 8 min, continued to decrease during recovery. These results indicate that the separate effects of CO and Nic on coronary flow in the isolated rat heart are opposing and reversible, but that the decrease they produce in combination is irreversible.

  18. Hope in elderly adults with chronic heart failure. Concept analysis

    PubMed Central

    Caboral, Meriam F.; Evangelista, Lorraine S.; Whetsell, Martha V.

    2015-01-01

    This topic review employed Walker and Avant’s method of concept analysis to explore the construct of hope in elderly adults with chronic heart failure. The articles analyzed revealed that hope, as the belief of the occurrence of a positive result without any guarantee that it will be produced, is necessary for the survival and wellbeing of the elderly adults enduring this disease. PMID:26321777

  19. Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury

    PubMed Central

    Melo, Dirceu S.; Costa-Pereira, Liliane V.; Santos, Carina S.; Mendes, Bruno F.; Costa, Karine B.; Santos, Cynthia Fernandes F.; Rocha-Vieira, Etel; Magalhães, Flávio C.; Esteves, Elizabethe A.; Ferreira, Anderson J.; Guatimosim, Sílvia; Dias-Peixoto, Marco F.

    2016-01-01

    Background and Aims: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. Methods and Results: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. Conclusion: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS. PMID:27092082

  20. Advances in the Care of Adults With Congenital Heart Disease.

    PubMed

    Nasr, Viviane G; Kussman, Barry D

    2015-09-01

    The significant decline in mortality among children and adolescents with congenital heart disease (CHD) is associated with an increasing prevalence of CHD in adults, particularly those with moderate to severe defects. As a significant percentage of adolescents and young adults are lost to follow-up in the transition from pediatric to adult care, they may present for elective procedures with substantial CHD-associated morbidity. In addition to the specific cardiac defect, the procedures performed, and the current pathophysiological status, several factors should be considered when managing the adult with CHD. These include the type of setting (adult vs pediatric institution); surgeon (pediatric vs adult cardiac surgeon); coexisting diseases associated with CHD, such as coronary artery disease, hepatic dysfunction, renal dysfunction, cerebrovascular accidents, myopathy, and coagulation disorders; acquired diseases of aging; pregnancy; and psychosocial functioning. The current status of the management of common and important congenital cardiac defects is also described. PMID:25542866

  1. Ventricular repolarization in a rat model of global heart failure.

    PubMed

    Krandycheva, Valeria; Kharin, Sergey; Strelkova, Marina; Shumikhin, Konstantin; Sobolev, Aleksey; Shmakov, Dmitry

    2013-07-01

    Isoproterenol in high doses induces infarction-like myocardial damage and structural and functional remodelling of the ventricular myocardium. The purpose of the present study was to investigate ventricular repolarization in a rat model of isoproterenol-induced heart failure. Isoproterenol was administered twice to female Wistar rats (170 mg/kg, s.c., 24 h apart). Four weeks after the injections, cardiac output was measured and unipolar epicardial ventricular electrograms were recorded in situ. Activation-recovery intervals were calculated to assess repolarization. Histological examination of the heart ventricles was also performed. Heart failure in rats treated with isoproterenol was indicated by myocardial histopathological damage and reduced cardiac output. In rats with heart failure, the regional differences in activation-recovery interval prolongation over the ventricular epicardium resulted in increasing heterogeneity in the activation-recovery interval distribution and increasing repolarization heterogeneity of the ventricular subepicardium. Myocardial damage and haemodynamic changes in heart failure induced by isoproterenol were accompanied by significant changes in ventricular repolarization, which were not associated with myocardial hypertrophy.

  2. Measurement of rat heart fatty acid binding protein by ELISA. Tissue distribution, developmental changes and subcellular distribution.

    PubMed

    Crisman, T S; Claffey, K P; Saouaf, R; Hanspal, J; Brecher, P

    1987-05-01

    A class of soluble, low molecular weight proteins collectively called fatty acid binding proteins (FABP) are thought to function in the intracellular movement of fatty acids. To understand more clearly the role of FABP in cardiac metabolism, we used ELISA and immunoblotting techniques to study the distribution of heart FABP in several rat tissues, compare male and female rat heart content, quantitate developmental changes, and determine its subcellular distribution. Immunoreactive protein was found in appreciable amounts in rat heart, red skeletal muscle and kidney. Adult rat heart contained about 1.5 mg FABP/g tissue wet weight with the atrial content being approximately 50% of the ventricular concentration. No significant difference was detected between the sexes. The amount of FABP increased progressively during development from fetal to adult animals, and measureable amounts were found in 17-day-old fetal tissue. Comparisons between myoglobin and FABP showed that FABP appeared earlier than myoglobin in development, but myoglobin was more abundant than FABP at birth. Using immunoblots it was determined that rat heart FABP was localized in the cytosol with no detectable intramitochondrial material. PMID:3625779

  3. Mesenchymal Stem Cells Improve Heart Rate Variability and Baroreflex Sensitivity in Rats with Chronic Heart Failure

    PubMed Central

    de Morais, Sharon Del Bem Velloso; da Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Silva, Carlos Alberto Aguiar; de Oliveira, Luciano Fonseca Lemos; de Carvalho, Eduardo Elias Vieira; Simões, Marcus Vinicius; da Silva Meirelles, Lindolfo; Fazan, Rubens

    2015-01-01

    Heart failure induced by myocardial infarct (MI) attenuates the heart rate variability (HRV) and baroreflex sensitivity, which are important risk factors for life-threatening cardiovascular events. Therapies with mesenchymal stem cells (MSCs) have shown promising results after MI. However, the effects of MSCs on hemodynamic (heart rate and arterial pressure) variability and baroreflex sensitivity in chronic heart failure (CHF) following MI have not been evaluated thus far. Male Wistar rats received MSCs or saline solution intravenously 1 week after ligation of the left coronary artery. Control (noninfarcted) rats were also evaluated. MI size was assessed using single-photon emission computed tomography (SPECT). The left ventricular ejection fraction (LVEF) was evaluated using radionuclide ventriculography. Four weeks after MSC injection, the animals were anesthetized and instrumented for chronic ECG recording and catheters were implanted in the femoral artery to record arterial pressure. Arterial pressure and HRVs were determined in time and frequency domain (spectral analysis) while HRV was also examined using nonlinear methods: DFA (detrended fluctuation analysis) and sample entropy. The initial MI size was the same among all infarcted rats but was reduced by MSCs. CHF rats exhibited increased myocardial interstitial collagen and sample entropy combined with the attenuation of the following cardiocirculatory parameters: DFA indices, LVEF, baroreflex sensitivity, and HRV. Nevertheless, MSCs hampered all these alterations, except the LVEF reduction. Therefore, 4 weeks after MSC therapy was applied to CHF rats, MI size and myocardial interstitial fibrosis decreased, while baroreflex sensitivity and HRV improved. PMID:26059001

  4. Responses of the working rat heart to carbon monoxide.

    PubMed

    Lin, H; McGrath, J J

    1989-07-01

    The effects of carbon monoxide (CO) were studied in the isolated working rat heart. Hearts removed from male laboratory rats were perfused via the left atrium with Krebs-Henseleit solution (KH) oxygenated with 95% O2-5% CO2 (O2). Heart rate and arterial pressures were measured by a transducer inserted in the aortic outflow line and connected to a data logger. Aortic flow was determined by collecting the effluent from the aortic bubble trap in a graduated cylinder. Coronary flow through the pulmonary cannula was collected and measured in a graduated cylinder. After 30 min, the hearts were challenged with solutions containing either CO (5% CO-90% O2-5% CO2) or N2 (5% N2-90% O2-5% CO2) for 10 min (Challenge I). After recovery in O2, the hearts were challenged with the alternate test solution (Challenge II). CO increased coronary flow (CF) and coronary flow as a percent of cardiac output (CF%) 13 and 16% respectively. N2 had no significant effect on CF or CF%. CO and N2 had no significant effect on heart rate, cardiac output, oxygen consumption or on aortic flow or pressure. These results indicate that vasodilation is the major response of the working heart to CO, and this response is not mediated by simple hypoxia. PMID:2813558

  5. The effect of Ligustrum delavayanum on isolated perfused rat heart

    PubMed Central

    Stankovičová, Tatiana; Frýdl, Miroslav; Kubicová, Mária; Baróniková, Slávka; Nagy, Milan; Grančai, Daniel; Švec, Pavel

    2001-01-01

    BACKGROUND: Extract of ligustrum leaves (Ligustrum delavayanum Hariot [Oleaceae]) is well known in traditional Chinese medicine. One of the active components, oleuropein, displays vasodilating and hypotensive effects. OBJECTIVE: To analyze the effect of 0.008% lyophilized extract of ligustrum dissolved in 0.5% ethanol on heart function. ANIMALS AND METHODS: Experiments were done on isolated rat hearts perfused by the Langendorff method in control conditions and during ischemic-reperfusion injury. RESULTS: Application of ligustrum induced positive inotropic and vasodilating effects in spontaneously beating hearts. Pretreatment of the hearts with ligustrum reduced left ventricular diastolic pressure measured during reperfusion and improved left ventricular contraction compared with hearts without any pretreatment. Ligustrum significantly suppressed the incidence and duration of cardiac reperfusion arrhythmias, expressed as G-score, from 7.40±0.58 in nontreated rats to 1.97±0.50. DISCUSSION: Application of ligustrum or ethanol alone induced changes in coordination between atria and ventricles during ischemia-reperfusion injury. The ‘g-score’, a new parameter summing the incidence and duration of atrioventricular blocks, atrioventricular dissociation and cardiac arrest, is introduced. The g-scores with ligustrum pretreatment were higher during ischemia than during reperfusion. Ethanol significantly depressed myocardial contractility and coronary flow, and nonsignificantly decreased heart rate of isolated rat hearts. Electrical changes observed during coronary reperfusion in the presence of ethanol were accompanied by deterioration of contractile function. CONCLUSIONS: Ligustrum had a significant protective effect on rat myocardium against ischemic-reperfusion injury. Ethanol partially attenuated the protective effect of ligustrum. PMID:20428448

  6. [Pediatric cardiology and congenital heart disease: from fetus to adult].

    PubMed

    Subirana, M Teresa; Oliver, José M; Sáez, José M; Zunzunegui, José L

    2012-01-01

    This article contains a review of some of the most important publications on congenital heart disease and pediatric cardiology that appeared in 2010 and up until September 2011. Of particular interest were studies on demographic changes reported in this patient population and on the need to manage the patients' transition from the pediatric to the adult cardiology department. This transition has given rise to the appearance of new areas of interest: for example, pregnancy in women with congenital heart disease, and the effect of genetic factors on the etiology and transmission of particular anomalies. In addition, this review considers some publications on fetal cardiology from the perspective of early diagnosis and, if possible, treatment. There follows a discussion on new contributions to Eisenmenger's syndrome and arrhythmias, as well as on imaging techniques, interventional catheterization and heart transplantation. Finally, there is an overview of the new version of clinical practice guidelines on the management of adult patients with congenital heart disease and of recently published guidelines on pregnancy in women with heart disease, both produced by the European Society of Cardiology.

  7. Panax ginseng reduces adriamycin-induced heart failure in rats.

    PubMed

    You, Jyh-Sheng; Huang, Hui-Feng; Chang, Ying-Ling

    2005-12-01

    The purpose of this study was to investigate the protective effects of Panax ginseng on adriamycin-induced heart failure. Wistar rats were divided into four groups: control, adriamycin, ginseng and adriamycin with ginseng. Adriamycin (cumulative dose, 15 mg/kg) was administered to rats in six equal intraperitoneal injections over a period of 2 weeks. Ginseng was administered via an oral feeding tube once a day for 30 days (cumulative dose, 150 g/kg). At the end of the 5 week post-treatment period, the hearts of the rats were used to study the synthesis rates of DNA, RNA and protein, myocardial antioxidants and lipid peroxidation. At the end of 3 weeks treatment, heart failure was characterized by ascites, congested liver and depressed cardiac function. Nucleic acid as well as protein synthesis was inhibited, lipid peroxidation was increased and myocardial glutathione peroxidase activity was decreased indicating adriamycin-induced heart failure. In contrast, the administration of ginseng, before and concurrent with adriamycin, significantly attenuated the myocardial effects, lowered the mortality as well as the amount of ascites, increased in myocardial glutathione peroxidase, macromolecular biosynthesis and superoxide dismutase activities, with a concomitant decrease in lipid peroxidation. These findings indicated that ginseng may be partially protective against adriamycin-induced heart failure.

  8. The Protection of Salidroside of the Heart against Acute Exhaustive Injury and Molecular Mechanism in Rat

    PubMed Central

    Wang, Yunru; Xu, Peng; Wang, Yang; Liu, Haiyan; Zhou, Yuwen; Cao, Xuebin

    2013-01-01

    Objective. To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction. Method. Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique. Results. Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dtmax under the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats. Conclusion. Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside. PMID:24454984

  9. Manganese depresses rat heart muscle respiration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has previously been reported that moderately high dietary manganese (Mn) in combination with marginal magnesium (Mg) resulted in ultrastructural damage to heart mitochondria. Manganese may replace Mg in biological functions, including the role of enzyme cofactor. Manganese may accumulate and subs...

  10. Endurance training in early life results in long-term programming of heart mass in rats.

    PubMed

    Wadley, Glenn D; Laker, Rhianna C; McConell, Glenn K; Wlodek, Mary E

    2016-02-01

    Being born small for gestational age increases the risk of developing adult cardiovascular and metabolic diseases. This study aimed to examine if early-life exercise could increase heart mass in the adult hearts from growth restricted rats. Bilateral uterine vessel ligation to induce uteroplacental insufficiency and fetal growth restriction in the offspring (Restricted) or sham surgery (Control) was performed on day 18 of gestation in WKY rats. A separate group of sham litters had litter size reduced to five pups at birth (Reduced litter), which restricted postnatal growth. Male offspring remained sedentary or underwent treadmill running from 5 to 9 weeks (early exercise) or 20 to 24 weeks of age (later exercise). Remarkably, in Control, Restricted, and Reduced litter groups, early exercise increased (P < 0.05) absolute and relative (to body mass) heart mass in adulthood. This was despite the animals being sedentary for ~4 months after exercise. Later exercise also increased adult absolute and relative heart mass (P < 0.05). Blood pressure was not significantly altered between groups or by early or later exercise. Phosphorylation of Akt Ser(473) in adulthood was increased in the early exercise groups but not the later exercise groups. Microarray gene analysis and validation by real-time PCR did not reveal any long-term effects of early exercise on the expression of any individual genes. In summary, early exercise programs the heart for increased mass into adulthood, perhaps by an upregulation of protein synthesis based on greater phosphorylation of Akt Ser(473).

  11. Protective effects of drag-reducing polymers on ischemic reperfusion injury of isolated rat heart.

    PubMed

    Hu, Feng; Wang, Yali; Gong, Kaizheng; Ge, Gaoyuan; Cao, Mingqiang; Zhao, Pei; Sun, Xiaoning; Zhang, Zhengang

    2016-01-01

    Drag-reducing polymers (DRPs) are blood-soluble macromolecules that can increase blood flow and reduce vascular resistance. The purpose of the present study was to observe the effect of DRPs on ischemic reperfusion (I/R) injury of isolated rat hearts. Experiments were performed on isolated rat hearts subjected to 30 min of ischemia followed by 90 min of reperfusion in Langendorff preparations. Adult Wistar rats were divided into the following five groups: control group, I/R group, group III (I/R and 2×10(-7)  g/ml PEO reperfusion), group IV (I/R and 1×10(-6)  g/ml PEO reperfusion), and group V (I/R and 5×10(-6)  g/ml PEO reperfusion). Left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximum rate of ventricular pressure increase and decrease ( ± dp/dtmax), heart rate (HR) and coronary flow were measured. Lactate dehydrogenase (LDH) and creatine kinase (CK) activity and coronary flow, myocardial infarction size and cardiomyocytes apoptosis were also assayed. Our results showed that PEO decreased LVEDP and increased LVSP, ± dP/dtmax in group IV and group V compared with the I/R group (all P <  0.05). The coronary flow significantly increased and the activities of LDH and CK in the coronary flow significantly decreased in group IV and group V compared with those in the I/R group (all P <  0.05). Cell apoptosis and myocardial infarction size were reduced in group IV and group V compared with the I/R group (all P <  0.05). Collectively, these results suggested that DRPs had a protective effect on cardiac I/R injury of isolated rat hearts and it may offer a new potential approach for the treatment of acute ischemic heart diseases.

  12. Angiopoietin-2 in Adults with Congenital Heart Disease and Heart Failure

    PubMed Central

    Kümpers, Philipp; Denecke, Agnieszka; Westhoff-Bleck, Mechthild; Schieffer, Bernhard; Bauersachs, Johann; Kielstein, Jan T.; Tutarel, Oktay

    2013-01-01

    Background Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an established biomarker for heart failure of non-congenital origin, its application in ACHD has limitations. The angiogenic factors Angiopoietin-1 and -2 (Ang-1, Ang-2), vascular endothelial growth factor (VEGF), and soluble receptor tyrosine kinase of the Tie family (sTie2) correlate with disease severity in heart failure of non-congenital origin. Their role in ACHD has not been studied. Methods In 91 patients Ang-2 and NT-proBNP were measured and related to New York Heart Association class, systemic ventricular function and parameters of cardiopulmonary exercise testing. Ang-1, VEGF, and sTie2 were also measured. Results Ang-2 correlates with NYHA class and ventricular dysfunction comparable to NT-proBNP. Further, Ang-2 showed a good correlation with parameters of cardiopulmonary exercise testing. Both, Ang-2 and NT-proBNP identified patients with severely limited cardiopulmonary exercise capacity. Additionally, Ang-2 is elevated in patients with a single ventricle physiology in contrast to NT-proBNP. VEGF, Ang-1, and sTie2 were not correlated with any clinical parameter. Conclusion The performance of Ang-2 as a biomarker for heart failure in ACHD is comparable to NT-proBNP. Its significant elevation in patients with single ventricle physiology indicates potential in this patient group and warrants further studies. PMID:23826161

  13. Heart Rate Changes in Electroacupuncture Treated Polycystic Ovary in Rats

    PubMed Central

    Ramadoss, Mukilan; Subbiah, Angelie Jessica; Natrajan, Chidambaranathan

    2016-01-01

    Introduction Polycystic Ovary Syndrome (PCOS) is a common metabolic disorder, it affects both humans and animals. It may induce coronary heart disease, obesity and hyperandrogenism. Previous studies show that Low frequency Electroacupuncture (EA) have an effect on PCOS, however the exact pathway is unclear. Aim To find the effect of EA on autonomic activity of the heart in Estradiol Valerate (EV) induced PCOS rats. Materials and Methods Heart rate variability (HRV) was assessed in 3 groups: 1) Control; 2) PCOS rats; and 3) PCOS rats after EA treatment (n=8 in each group). From the time domain analysis and frequency domain analysis (linear measures) HRV analysis was done. EA stimulation was given at low frequency of 2Hz for 15 min on alternate days for 4-5 weeks. Collected data were statistically analysed using One-Way Analysis of Variance with the application of multiple comparisons of Tukey test. Results EA treatment group shows significant reduction in Heart Rate (HR) and low frequency, high frequency ratio (LF/HF); and increase in RR interval, Total Power (TP) when compared to PCOS group. Conclusion The study concludes that EA treatment has a significant effect on reducing sympathetic tone and decreasing HR in PCOS. PMID:27134868

  14. Transfer to Adult Care--Experiences of Young Adults with Congenital Heart Disease.

    PubMed

    Asp, Ann; Bratt, Ewa-Lena; Bramhagen, Ann-Cathrine

    2015-01-01

    More than 90% of children born with congenital heart disease survive into adulthood due to successes of cardiac surgery and medical management. Interviews with 16 young adults with congenital heart disease to explore their experiences of transfer from pediatric to adult care were performed. The analysis identified five themes; Feeling secure during the transfer process, Experiencing trust in the care, Expecting to be involved, Assuming responsibility for one's health is a process and Lack of knowledge leads to uncertainty. In conclusion; a structured and gradual transfer process was necessary to enable the informants to shoulder the responsibility for self-care.

  15. Skeletal muscle electrical stimulation improves baroreflex sensitivity and heart rate variability in heart failure rats.

    PubMed

    Lazzarotto Rucatti, Ananda; Jaenisch, Rodrigo Boemo; Rossato, Douglas Dalcin; Bonetto, Jéssica Hellen Poletto; Ferreira, Janaína; Xavier, Leder Leal; Sonza, Anelise; Dal Lago, Pedro

    2015-12-01

    The goal of the current study was to evaluate the effects of electrical stimulation (ES) on the arterial baroreflex sensitivity (BRS) and cardiovascular autonomic control in rats with chronic heart failure (CHF). Male Wistar rats were designated to one of four groups: placebo sham (P-Sham, n=9), ES sham (ES-Sham, n=9), placebo CHF (P-CHF, n=9) or ES CHF (ES-CHF, n=9). The ES was adjusted at a low frequency (30 Hz), duration of 250 μs, with hold and rest time of 8s (4 weeks, 30 min/day, 5 times/week). It was applied on the gastrocnemius muscle with intensity to produce a visible muscle contraction. The rats assigned to the placebo groups performed the same procedures with the equipment turned off. The two-way ANOVA and the post hoc Student-Newman-Keuls tests (P<0.05) were used to data comparison. The BRS was higher in ES-Sham group compared to the P-Sham group and the ES-CHF group compared to the P-CHF group. ES was able to decrease heart rate sympatho-vagal modulation and peripheral sympathetic modulation in ES-CHF compared to P-CHF group. Interestingly, heart rate sympatho-vagal modulation was similar between ES-CHF and P-Sham groups. Thus, ES enhances heart rate parasympathetic modulation on heart failure (ES-CHF) compared to placebo (P-CHF), with consequent decrease of sympatho-vagal balance in the ES-CHF group compared to the P-CHF. The results show that a 4 week ES protocol in CHF rats enhances arterial BRS and cardiovascular autonomic control.

  16. Preconditioning boosts regenerative programmes in the adult zebrafish heart

    PubMed Central

    de Preux Charles, Anne-Sophie; Bise, Thomas; Baier, Felix; Sallin, Pauline; Jaźwińska, Anna

    2016-01-01

    During preconditioning, exposure to a non-lethal harmful stimulus triggers a body-wide increase of survival and pro-regenerative programmes that enable the organism to better withstand the deleterious effects of subsequent injuries. This phenomenon has first been described in the mammalian heart, where it leads to a reduction of infarct size and limits the dysfunction of the injured organ. Despite its important clinical outcome, the actual mechanisms underlying preconditioning-induced cardioprotection remain unclear. Here, we describe two independent models of cardiac preconditioning in the adult zebrafish. As noxious stimuli, we used either a thoracotomy procedure or an induction of sterile inflammation by intraperitoneal injection of immunogenic particles. Similar to mammalian preconditioning, the zebrafish heart displayed increased expression of cardioprotective genes in response to these stimuli. As zebrafish cardiomyocytes have an endogenous proliferative capacity, preconditioning further elevated the re-entry into the cell cycle in the intact heart. This enhanced cycling activity led to a long-term modification of the myocardium architecture. Importantly, the protected phenotype brought beneficial effects for heart regeneration within one week after cryoinjury, such as a more effective cell-cycle reentry, enhanced reactivation of embryonic gene expression at the injury border, and improved cell survival shortly after injury. This study reveals that exposure to antecedent stimuli induces adaptive responses that render the fish more efficient in the activation of the regenerative programmes following heart damage. Our results open a new field of research by providing the adult zebrafish as a model system to study remote cardiac preconditioning. PMID:27440423

  17. Upper thermal limits of the hearts of Arctic cod Boreogadus saida: adults compared with larvae.

    PubMed

    Drost, H E; Fisher, J; Randall, F; Kent, D; Carmack, E C; Farrell, A P

    2016-02-01

    Wild adult and reared larval Boreogadus saida were acclimated to 3·5° C before testing their cardiac response to acute warming. Heart rate transition temperatures during warming were similar for adult and larval hearts, except that the maximum temperature for heart rate was 3° C warmer for adults. Thus, in a rapidly warming Arctic Ocean, the upper temperature limit for larval rather than adult B. saida appears more likely to dictate the southern range of the species. PMID:26608719

  18. Upper thermal limits of the hearts of Arctic cod Boreogadus saida: adults compared with larvae.

    PubMed

    Drost, H E; Fisher, J; Randall, F; Kent, D; Carmack, E C; Farrell, A P

    2016-02-01

    Wild adult and reared larval Boreogadus saida were acclimated to 3·5° C before testing their cardiac response to acute warming. Heart rate transition temperatures during warming were similar for adult and larval hearts, except that the maximum temperature for heart rate was 3° C warmer for adults. Thus, in a rapidly warming Arctic Ocean, the upper temperature limit for larval rather than adult B. saida appears more likely to dictate the southern range of the species.

  19. Micro-CT analysis of myocardial blood supply in young and adult rats

    NASA Astrophysics Data System (ADS)

    Schaefer, Heather M.; Beighley, Patricia E.; Eaker, Diane R.; Vercnocke, Andrew J.; Ritman, Erik L.

    2009-02-01

    This study addresses whether the vasculature grows in proportion to the myocardium as the rat heart develops. The volume of myocardium and coronary vessels were estimated from micro-CT images of the hearts injected with Microfil(R) contrast agent. Young (n=5) and adult (n=5) hearts were scanned, resulting in 3D images comprised of 20μm on-a-side cubic voxels. The myocardial muscle and vessel lumen volumes were measured for all vessels 40 to 320μm in diameter by an erosion and dilation method applied to the binary images in which the contrast in the vessels were assigned "1" and all non-opacified entities were assigned "0". The average total muscle volume increases by 50%, 129.4 to 237.4mm3, from young to adult rats, while the luminal volume increases by 10%, 16.6 to 18.6mm3. The vessel volume is 12% of the total muscle volume in young and 8% in adults. For a given vessel volume, the muscle volume in the young is 82% of the muscle volume in adults. We conclude that as the heart matures, the myocardium grows more rapidly than the vasculature. This may result in greater angles of separation between vessel branches, and the increase in myocardial coronary volume. The ratio suggests either higher blood flow velocity or a lower metabolic rate in adults.

  20. Antithetical regulation of α-myosin heavy chain between fetal and adult heart failure though shuttling of HDAC5 regulating YY-1 function.

    PubMed

    Fang, Jie; Li, Yifei; Zhou, Kaiyu; Hua, Yimin; Wang, Chuan; Mu, Dezhi

    2015-04-01

    Molecular switches of myosin isoforms are known to occur in various conditions. Here, we demonstrated the result from fetal heart failure and its potential mechanisms. Fetal and adult heart failure rat models were induced by injections of isoproterenol as previously described, and Go6976 was given to heart failing fetuses. Real-time PCR and Western blot were adopted to measure the expressions of α-MHC, β-MHC and YY-1. Co-immunoprecipitation was performed to analysis whether YY-1 interacts with HDAC5. Besides, histological immunofluorescence assessment was carried out to identify the location of HDAC5. α-MHC was recorded elevated in fetal heart failure which was decreased in adult heart failure. Besides, YY-1 was observed elevated both in fetal and adult failing hearts, but YY-1 could co-immunoprecipitation with HDAC5 only in adult hearts. Nuclear localization of HDAC5 was identified in adult cardiomyocytes, while cytoplasmic localization was identified in fetuses. After Go6976 supplied, HDAC5 shuttled into nucleuses interacted with YY-1. The myosin molecular switches were reversed with worsening cardiac functions and higher mortalities. Regulation of MHC in fetal heart failure was different from adult which provided a better compensation with increased α-MHC. This kind of transition was involved with shuttling of HDAC5 regulating YY-1 function.

  1. Mitochondrial and Metabolic Gene Expression in the Aged Rat Heart

    PubMed Central

    Barton, Gregory P.; Sepe, Joseph J.; McKiernan, Susan H.; Aiken, Judd M.; Diffee, Gary M.

    2016-01-01

    Aging is associated with a decline in cardiac function. Exercise intervention has been suggested as a way to improve this decrement. Age-related decline in cardiac function is associated with decreases in fatty acid oxidation, mitochondrial function, and AMP-activated protein kinase (AMPK) activity. The molecular mechanisms involved with age-related changes in mitochondrial function and substrate metabolism are poorly understood. We determined gene expression differences in hearts of Young (6 mo), Old (33 mo), and old exercise trained (Old + EXE) (34 mo) FBN rats, using Qiagen PCR arrays for Glucose, Fatty acid, and Mitochondrial metabolism. Old rats demonstrated decreased (p < 0.05) expression for key genes in fatty acid oxidation, mitochondrial function, and AMPK signaling. There were no differences in the expression of genes involved in glucose metabolism with age. These gene expression changes occurred prior to altered protein translation as we found no differences in the protein content of peroxisome proliferator activated receptor gamma, coactivators 1 alpha (PGC-1α), peroxisome proliferator activated receptor alpha (PPARα), and AMPKα2 between young and old hearts. Four months of exercise training did not attenuate the decline in the gene expression in aged hearts. Despite this lack of change in gene expression, exercise-trained rats demonstrated increased exercise capacity compared to their sedentary counterparts. Taken together, our results show that differential expression of genes associated with fatty acid metabolism, AMPK signaling and mitochondrial function decrease in the aging heart which may play a role in age-related declines in fatty acid oxidation, AMPK activity, and mitochondrial function in the heart. PMID:27601998

  2. Mitochondrial and Metabolic Gene Expression in the Aged Rat Heart

    PubMed Central

    Barton, Gregory P.; Sepe, Joseph J.; McKiernan, Susan H.; Aiken, Judd M.; Diffee, Gary M.

    2016-01-01

    Aging is associated with a decline in cardiac function. Exercise intervention has been suggested as a way to improve this decrement. Age-related decline in cardiac function is associated with decreases in fatty acid oxidation, mitochondrial function, and AMP-activated protein kinase (AMPK) activity. The molecular mechanisms involved with age-related changes in mitochondrial function and substrate metabolism are poorly understood. We determined gene expression differences in hearts of Young (6 mo), Old (33 mo), and old exercise trained (Old + EXE) (34 mo) FBN rats, using Qiagen PCR arrays for Glucose, Fatty acid, and Mitochondrial metabolism. Old rats demonstrated decreased (p < 0.05) expression for key genes in fatty acid oxidation, mitochondrial function, and AMPK signaling. There were no differences in the expression of genes involved in glucose metabolism with age. These gene expression changes occurred prior to altered protein translation as we found no differences in the protein content of peroxisome proliferator activated receptor gamma, coactivators 1 alpha (PGC-1α), peroxisome proliferator activated receptor alpha (PPARα), and AMPKα2 between young and old hearts. Four months of exercise training did not attenuate the decline in the gene expression in aged hearts. Despite this lack of change in gene expression, exercise-trained rats demonstrated increased exercise capacity compared to their sedentary counterparts. Taken together, our results show that differential expression of genes associated with fatty acid metabolism, AMPK signaling and mitochondrial function decrease in the aging heart which may play a role in age-related declines in fatty acid oxidation, AMPK activity, and mitochondrial function in the heart.

  3. Mitochondrial and Metabolic Gene Expression in the Aged Rat Heart.

    PubMed

    Barton, Gregory P; Sepe, Joseph J; McKiernan, Susan H; Aiken, Judd M; Diffee, Gary M

    2016-01-01

    Aging is associated with a decline in cardiac function. Exercise intervention has been suggested as a way to improve this decrement. Age-related decline in cardiac function is associated with decreases in fatty acid oxidation, mitochondrial function, and AMP-activated protein kinase (AMPK) activity. The molecular mechanisms involved with age-related changes in mitochondrial function and substrate metabolism are poorly understood. We determined gene expression differences in hearts of Young (6 mo), Old (33 mo), and old exercise trained (Old + EXE) (34 mo) FBN rats, using Qiagen PCR arrays for Glucose, Fatty acid, and Mitochondrial metabolism. Old rats demonstrated decreased (p < 0.05) expression for key genes in fatty acid oxidation, mitochondrial function, and AMPK signaling. There were no differences in the expression of genes involved in glucose metabolism with age. These gene expression changes occurred prior to altered protein translation as we found no differences in the protein content of peroxisome proliferator activated receptor gamma, coactivators 1 alpha (PGC-1α), peroxisome proliferator activated receptor alpha (PPARα), and AMPKα2 between young and old hearts. Four months of exercise training did not attenuate the decline in the gene expression in aged hearts. Despite this lack of change in gene expression, exercise-trained rats demonstrated increased exercise capacity compared to their sedentary counterparts. Taken together, our results show that differential expression of genes associated with fatty acid metabolism, AMPK signaling and mitochondrial function decrease in the aging heart which may play a role in age-related declines in fatty acid oxidation, AMPK activity, and mitochondrial function in the heart. PMID:27601998

  4. Sodium alterations in isolated rat heart during cardioplegic arrest

    SciTech Connect

    Schepkin, V.D.; Choy, I.O.; Budinger, T.F.

    1996-12-01

    Triple-quantum-filtered (TQF) Na nuclear magnetic resonance (NMR) without chemical shift reagent is used to investigate Na derangement in isolated crystalloid perfused rat hearts during St. Thomas cardioplegic (CP) arrest. The extracellular Na contribution to the NMR TQF signal of a rat heart is found to be 73 {+-} 5%, as determined by wash-out experiments at different moments of ischemia and reperfusion. With the use of this contribution factor, the estimated intracellular Na ([Na{sup +}]{sub i}) TQF signal is 222 {+-} 13% of preischemic level after 40 min of CP arrest and 30 min of reperfusion, and the heart rate pressure product recovery is 71 {+-} 8%. These parameters are significantly better than for stop-flow ischemia: 340 {+-} 20% and 6 {+-} 3%, respectively. At 37{degrees}C, the initial delay of 15 min in [Na{sup +}]{sub i} growth occurs during CP arrest along with reduced growth later ({approximately}4.0%/min) in comparison with stop-flow ischemia ({approximately}6.7%/min). The hypothermia (21{degrees}C, 40 min) for the stop-flow ischemia and CP dramatically decreases the [Na{sup +}]{sub i} gain with the highest heart recovery for CP ({approximately}100%). These studies confirm the enhanced sensitivity of TQF NMR to [Na{sup +}]{sub i} and demonstrate the potential of NMR without chemical shift reagent to monitor [Na{sup +}]{sub i} derangements. 48 refs., 7 figs., 1 tab.

  5. Protective effects of remote ischemic preconditioning in isolated rat hearts

    PubMed Central

    Teng, Xiao; Yuan, Xin; Tang, Yue; Shi, Jingqian

    2015-01-01

    To use Langendorff model to investigate whether remote ischemic preconditioning (RIPC) attenuates post-ischemic mechanical dysfunction on isolated rat heart and to explore possible mechanisms. SD rats were randomly divided into RIPC group, RIPC + norepinephrine (NE) depletion group, RIPC + pertussis toxin (PTX) pretreatment group, ischemia/reperfusion group without treatment (ischemia group) and time control (TC) group. RIPC was achieved through interrupted occlusion of anterior mesenteric artery. Then, Langendorff model was established using routine methods. Heart function was tested; immunohistochemistry and ELISA methods were used to detect various indices related to myocardial injury. Compared with ischemia group in which the hemodynamic parameters deteriorated significantly, heart function recovered to a certain degree among the RIPC, RIPC + NE depletion, and RIPC + PTX groups (P<0.05). More apoptotic nuclei were observed in ischemia group than in the other three groups (P<0.05); more apoptotic nuclei were detected in NE depletion and PTX groups than in RIPC group (P<0.05). While, there was no significant difference between NE depletion and PTX groups. In conclusion, RIPC protection on I/R myocardium extends to the period after hearts are isolated. NE and PTX-sensitive inhibitory G protein might have a role in the protection process. PMID:26550168

  6. Clinical Research Priorities in Adult Congenital Heart Disease

    PubMed Central

    Cotts, Timothy; Khairy, Paul; Opotowsky, Alexander R.; John, Anitha S.; Valente, Anne Marie; Zaidi, Ali N.; Cook, Stephen C.; Aboulhosn, Jamil; Ting, Jennifer Grando; Gurvitz, Michelle; Landzberg, Michael J.; Verstappen, Amy; Kay, Joseph; Earing, Michael; Franklin, Wayne; Kogon, Brian; Broberg, Craig S.

    2014-01-01

    Background Adult congenital heart disease (ACHD) clinicians are hampered by the paucity of data to inform clinical decision-making. The objective of this study was to identify priorities for clinical research in ACHD. Methods A list of 45 research questions was developed by the Alliance for Adult Research in Congenital Cardiology (AARCC), compiled into a survey, and administered to ACHD providers. Patient input was sought via the Adult Congenital Heart Association at community meetings and online forums. The 25 top questions were sent to ACHD providers worldwide via an online survey. Each question was ranked based on perceived priority and weighted based on time spent in ACHD care. The top 10 topics identified are presented and discussed. Results The final online survey yielded 139 responses. Top priority questions related to tetralogy of Fallot (timing of pulmonary valve replacement and criteria for primary prevention ICDs), patients with systemic right ventricles (determining the optimal echocardiographic techniques for measuring right ventricular function, and indications for tricuspid valve replacement and primary prevention ICDs), and single ventricle/Fontan patients (role of pulmonary vasodilators, optimal anticoagulation, medical therapy for preservation of ventricular function, treatment for protein losing enteropathy). In addition, establishing criteria to refer ACHD patients for cardiac transplantation was deemed a priority. Conclusions The ACHD field is in need of prospective research to address fundamental clinical questions. It is hoped that this methodical consultation process will inform researchers and funding organizations about clinical research topics deemed to be of high priority. PMID:24411207

  7. Cardioprotective Effects of Astragalin against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart.

    PubMed

    Qu, Daoxu; Han, Jichun; Ren, Huanhuan; Yang, Wenxiao; Zhang, Xinjie; Zheng, Qiusheng; Wang, Dong

    2016-01-01

    This study aims to evaluate the cardioprotective effects of astragalin against myocardial ischemia/reperfusion (I/R) injury in isolated rat heart. The cardioprotective effects of astragalin on myocardial I/R injury were investigated on Langendorff apparatus. Adult male Sprague-Dawley rats were randomly divided into five groups. The results showed that astragalin pretreatment improved myocardial function. Compared with I/R group, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in coronary flow decreased in astragalin pretreatment groups, whereas superoxide dismutase (SOD) activity and glutathione/glutathione disulfide (GSH/GSSG) ratio significantly increased. The levels of malondialdehyde (MDA), intracellular reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) decreased in astragalin-treated groups. The infarct size (IS) and apoptosis rate in hearts from astragalin-treated groups were lower than those in hearts from the I/R group. Western blot analysis also revealed that astragalin preconditioning significantly reduced Bax level, whereas Bcl-2 was increased in the myocardium. Therefore, astragalin exhibited cardioprotective effects via its antioxidative, antiapoptotic, and anti-inflammatory activities.

  8. Cardioprotective Effects of Astragalin against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart

    PubMed Central

    Qu, Daoxu; Ren, Huanhuan; Yang, Wenxiao; Zhang, Xinjie; Zheng, Qiusheng; Wang, Dong

    2016-01-01

    This study aims to evaluate the cardioprotective effects of astragalin against myocardial ischemia/reperfusion (I/R) injury in isolated rat heart. The cardioprotective effects of astragalin on myocardial I/R injury were investigated on Langendorff apparatus. Adult male Sprague-Dawley rats were randomly divided into five groups. The results showed that astragalin pretreatment improved myocardial function. Compared with I/R group, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in coronary flow decreased in astragalin pretreatment groups, whereas superoxide dismutase (SOD) activity and glutathione/glutathione disulfide (GSH/GSSG) ratio significantly increased. The levels of malondialdehyde (MDA), intracellular reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) decreased in astragalin-treated groups. The infarct size (IS) and apoptosis rate in hearts from astragalin-treated groups were lower than those in hearts from the I/R group. Western blot analysis also revealed that astragalin preconditioning significantly reduced Bax level, whereas Bcl-2 was increased in the myocardium. Therefore, astragalin exhibited cardioprotective effects via its antioxidative, antiapoptotic, and anti-inflammatory activities. PMID:26788251

  9. Changes in expression of a functional G sub i protein in cultured rat heart cells

    SciTech Connect

    Allen, I.S.; Gaa, S.T.; Rogers, T.B. )

    1988-07-01

    The muscarinic cholinergic agonist, carbachol, and pertussis toxin were used to examine the functional status of the guanine nucleotide-binding protein that inhibits adenylate cyclase (G{sub i}) in cultured neonatal rat heart myocytes. The isoproterenol stimulation of adenylate cyclase activity in myocyte membranes and adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) accumulation in intact cells (4 days in culture) were insensitive to carbachol. However, in cells cultured for 11 days, carbachol inhibited isoproterenol-stimulated cAMP accumulation by 30%. Angiotensin II (ANG II) was also found to inhibit isoproterenol-stimulated cAMP accumulation in day 11 cells in a dose-dependent manner. Pertussis toxin treatment reversed the inhibitory effects of both ANG II and carbachol, suggesting a role for G{sub i} in the process. Carbachol binding to membranes from day 4 cells was relatively insensitive to guanine nucleotides when compared with binding to membranes from day 11 or adult cells. Furthermore, pertussis toxin-mediated {sup 32}P incorporation into a 39- to 41-kDa substrate in day 11 membranes was increased 3.2-fold over that measured in day 4 membranes. These findings support the view that, although G{sub i} is expressed, it is nonfunctional in 4-day-old cultured neonatal rat heart myocytes and acquisition of functional G{sub i} is dependent on culture conditions. Furthermore, the ANG II receptor can couple to G{sub i} in heart.

  10. Hypertrophic response of the Association of Thyroid Hormone and Exercise in the Heart of Rats

    PubMed Central

    de Souza, Fernanda Rodrigues; Resende, Elmiro Santos; Lopes, Leandro; Gonçalves, Alexandre; Chagas, Rafaella; Fidale, Thiago; Rodrigues, Poliana

    2014-01-01

    Background Cardiac hypertrophy is a component of cardiac remodeling occurring in response to an increase of the activity or functional overload of the heart. Objective Assess hypertrophic response of the association of thyroid hormone and exercise in the rat heart. Methods We used 37 Wistar rats, male, adults were randomly divided into four groups: control, hormone (TH), exercise (E), thyroid hormone and exercise (H + E); the group received daily hormone levothyroxine sodium by gavage at a dose of 20 μg thyroid hormone/100g body weight, the exercise group took swimming five times a week, with additional weight corresponding to 20% of body weight for six weeks; in group H + E were applied simultaneously TH treatment groups and E. The statistics used was analysis of variance, where appropriate, by Tukey test and Pearson correlation test. Results The T4 was greater in groups TH and H + E. The total weight of the heart was greater in patients who received thyroid hormone and left ventricular weight was greater in the TH group. The transverse diameter of cardiomyocytes increased in groups TH, E and H + E. The percentage of collagen was greater in groups E and H + E Correlation analysis between variables showed distinct responses. Conclusion The association of thyroid hormone with high-intensity exercise produced cardiac hypertrophy, and generated a standard hypertrophy not directly correlated to the degree of fibrosis. PMID:24676374

  11. Protective effect of oxymatrine on chronic rat heart failure.

    PubMed

    Hu, Shu-Ting; Tang, Ying; Shen, Ya-Feng; Ao, Hai-Hang; Bai, Jie; Wang, Yong-Liang; Yang, Yong-Ji

    2011-09-01

    Oxymatrine is one of the alkaloids extracted from the Chinese herb Sophora japonica (Sophora flavescens Ait.) with anti-inflammatory, immune reaction inhibiting, antiviral, and hepatocyte and antihepatic fibrosis protective activities. However, the effect of oxymatrine on heart failure is not yet known. In this study, the effect of oxymatrine on heart failure was investigated using a Sprague-Dawley rat model of chronic heart failure. Morphological findings showed that in the group treated with 50 and 100 mg/kg of oxymatrine; intermyofibrillar lysis disappeared, myofilaments were orderly, closely and evenly arranged; and mitochondria contained tightly packed cristae compared with the heart failure group. We investigated the cytosolic Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) content, and assessed the expression of ryanodine receptor (RyR2), SR-Ca(2+) ATPase (SERCA2a), and L-type Ca(2+) channel (dihydropyridine receptor, DHPR). We found that the cytosolic Ca(2+) transients were markedly increased in amplitude in the medium- (ΔF/F (0) = 26.22 ± 2.01) and high-dose groups (ΔF/F (0) = 29.49 ± 1.17) compared to the heart failure group (ΔF/F (0) = 12.12 ± 1.35, P < 0.01), with changes paralleled by a significant increase in the SR Ca(2+) content (medium-dose group: ΔF/F (0) = 32.20 ± 1.67, high-dose group: ΔF/F (0) = 32.57 ± 1.29, HF: ΔF/F (0) = 17.26 ± 1.05, P < 0.01). Moreover, we demonstrated that the expression of SERCA2a and cardiac DHPR was significantly increased in the medium- and high-dose group compared with the heart failure rats. These findings suggest that oxymatrine could improve heart failure by improving the cardiac function and that this amelioration is associated with upregulation of SERCA2a and DHPR. PMID:21691940

  12. Exogenous oxytocin reduces signs of sickness behavior and modifies heart rate fluctuations of endotoxemic rats.

    PubMed

    Reyes-Lagos, José Javier; Hadamitzky, Martin; Peña-Castillo, Miguel Ángel; Echeverría, Juan Carlos; Bösche, Katharina; Lückemann, Laura; Schedlowski, Manfred; Pacheco-López, Gustavo

    2016-10-15

    Besides the well-known roles of oxytocin on birth, maternal bonding, and lactation, recent evidence shows that this hypothalamic hormone possesses cardioprotective, anti-inflammatory and parasympathetic neuromodulation properties. In this study, we explore the heart rate fluctuations (HRF) in an endotoxemic rodent model that was accompanied by the administration of exogenous oxytocin. The assessment of HRF has been widely used as an indirect measure of the cardiac autonomic function. In this context, adult male Dark Agouti rats were equipped with a telemetric transmitter to continuously and remotely measure the electrocardiogram, temperature, and locomotion. In a between-subjects experimental design, rats received the following peripheral treatment: saline solution as a vehicle (V); lipopolysaccharide (LPS); oxytocin (Ox); lipopolysaccharide + oxytocin (LPS+Ox). Linear and non-linear parameters of HRF were estimated starting 3h before to 24h after treatments. Our results showed that exogenous oxytocin does not modify by itself the HRF of oxytocin-treated rats in comparison to vehicle-treated rats. However, in animals undergoing endotoxemia it: a) provokes a less anticorrelated pattern in HRF, b) decreased mean heart rate, c) moderated the magnitude and duration of the LPS-induced hyperthermia, and d) increased locomotion, up to 6h after the LPS injection. The less anticorrelated pattern in the HRF and decreased mean heart rate may reflect a cardiac pacemaker coupling with cholinergic influences mediated by oxytocin during LPS-induced endotoxemia. Finally, the anti-lethargic and long-term temperature moderating effects of the administration of oxytocin during endotoxemia could be a consequence of the systemic anti-inflammatory properties of oxytocin.

  13. Reduced high-energy phosphate levels in rat hearts. II. Effects of sodium cyanate.

    PubMed

    Allison, T B; Pieper, G M; Clayton, F C; Eliot, R S

    1976-06-01

    The effects of increased blood-oxygen affinity, due to carbamylation of hemoglobin in vivo, on aerobic metabolism in the heart were studied in rats. Adult male rats were injected intraperitoneally 3 times weekly for 10 wk with sodium cyanate (60 mg/kg). Significant derangement of blood-oxygen interaction was observed. Oxygen-dissociation curves were left shifted by 13 mmHg (35.1-21.8), and the overall deoxygenation rate (k) was reduced 41% (6.142-3.624; s(-1)); P is less than 0.001 for each parameter. Heart ATP and PCr levels were reduced (ATP: 19.4-16.7; PCr: 15.0-11.0, mum/g dry wt; P is less than 0.001 for each). In addition, glycogen levels fell (161.4-112.9, mum C6/g dry wt; P is less than 0.001). Myocardial lactate levels increased 54% (2.6-4.0, mum/g dry wt; P is less than 0.01) in the cyanate-treated group. These findings strongly suggest a hypoxia-induced activation of glycolysis as a consequence of altered oxidative metabolism in rats treated with sodium cyanate. PMID:937561

  14. Heart Alterations after Domoic Acid Administration in Rats.

    PubMed

    Vieira, Andres C; Cifuentes, José Manuel; Bermúdez, Roberto; Ferreiro, Sara F; Castro, Albina Román; Botana, Luis M

    2016-03-10

    Domoic acid (DA) is one of the best known marine toxins, causative of important neurotoxic alterations. DA effects are documented both in wildlife and experimental assays, showing that this toxin causes severe injuries principally in the hippocampal area. In the present study we have addressed the long-term toxicological effects (30 days) of DA intraperitoneal administration in rats. Different histological techniques were employed in order to study DA toxicity in heart, an organ which has not been thoroughly studied after DA intoxication to date. The presence of DA was detected by immunohistochemical assays, and cellular alterations were observed both by optical and transmission electron microscopy. Although histological staining methods did not provide any observable tissue damage, transmission electron microscopy showed several injuries: a moderate lysis of myofibrils and loss of mitochondrial conformation. This is the first time the association between heart damage and the presence of the toxin has been observed.

  15. Heart Alterations after Domoic Acid Administration in Rats

    PubMed Central

    Vieira, Andres C.; Cifuentes, José Manuel; Bermúdez, Roberto; Ferreiro, Sara F.; Castro, Albina Román; Botana, Luis M.

    2016-01-01

    Domoic acid (DA) is one of the best known marine toxins, causative of important neurotoxic alterations. DA effects are documented both in wildlife and experimental assays, showing that this toxin causes severe injuries principally in the hippocampal area. In the present study we have addressed the long-term toxicological effects (30 days) of DA intraperitoneal administration in rats. Different histological techniques were employed in order to study DA toxicity in heart, an organ which has not been thoroughly studied after DA intoxication to date. The presence of DA was detected by immunohistochemical assays, and cellular alterations were observed both by optical and transmission electron microscopy. Although histological staining methods did not provide any observable tissue damage, transmission electron microscopy showed several injuries: a moderate lysis of myofibrils and loss of mitochondrial conformation. This is the first time the association between heart damage and the presence of the toxin has been observed. PMID:26978401

  16. Effect of suprachiasmatic lesions on diurnal heart rate rhythm in the rat

    NASA Technical Reports Server (NTRS)

    Saleh, M. A.; Winget, C. M.

    1977-01-01

    Heart rate and locomotor activity of rats kept under 12L/12D illumination regimen were recorded every six minutes for ten days using implantable radio transmitters. Some of the rats then received bilateral RF lesions into the suprachiasmatic nucleus (SCN). Control sham operations were performed on the rest of the animals. After recovery from surgery, recording of heart rate and locomotor activity was continued for ten days. SCN-lesioned rats showed no significant diurnal fluctuation in heart rate, while normal and sham-operated rats showed the normal diurnal rhythm in that function. The arrhythmic diurnal heart-rate pattern of SCN rats appeared to be correlated with their sporadic activity pattern. The integrity of the suprachiasmatic nucleus is therefore necessary for the generation and/or expression of diurnal rhythmicity in heart rate in the rat.

  17. A STUDY OF THE T SYSTEM IN RAT HEART

    PubMed Central

    Forssmann, W. G.; Girardier, L.

    1970-01-01

    The technique of extracellular space tracing with horseradish peroxidase is adapted for labeling the transverse tubular system (T system) in rat heart. In rat ventricular muscle the T system shows extensive branching and remarkable tortuosity. The T system can only be defined operationally, since it does not display specific morphological features throughout its entire structure. Owing to branching of the T system, a sizable proportion of the apposition between the T system and L system (or closed system) occurs at the level of longitudinal branches of the T system and is not restricted to the Z line region. The regions of apposition between the T system and L system are analyzed in rat ventricular muscle and skeletal muscle (diaphragm) and compared with the intercellular tight junctions (nexuses) of heart muscle by the use of a photometric method. The over-all thickness of the nexus is significantly smaller than that of T-L junctions in both cardiac and skeletal muscles. The thickness of the membranes of the T and L systems are not significantly different in the two muscles, but the gap between both membranes is larger in the heart. In atrial muscle the following two types of cells are found: (a) those cells with a well-developed T system in which the tubular diameter is quite uniform and the orientation predominantly longitudinal and, (b) cells with no T system, but with a well-developed L system. Atrial cells possessing a T system are richly provided with specific granules and show little micropinocytotic activity, whereas cells devoid of T system show intense micropinocytotic activity and few specific granules. The possible functional implications of these findings are discussed. PMID:4901374

  18. Interactions between respiratory oscillators in adult rats

    PubMed Central

    Huckstepp, Robert TR; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. DOI: http://dx.doi.org/10.7554/eLife.14203.001 PMID:27300271

  19. Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

    PubMed Central

    Baran, Halina; Staniek, Katrin; Bertignol-Spörr, Melanie; Attam, Martin; Kronsteiner, Carina; Kepplinger, Berthold

    2016-01-01

    Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3), respiratory control index (RC) and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochondria were incubated with glutamate/malate (5 mM) or succinate (10 mM) and in the presence of L-tryptophan metabolites (1 mM) or in the absence, as control. Kynurenic and anthranilic acids significantly reduced RC values of heart mitochondria in the presence of glutamate/malate. Xanthurenic acid significantly reduced RC values of brain mitochondria in the presence of glutamate/malate. Furthermore, 3-hydroxykynurenine and 3-hydroxyanthranilic acid decreased RC values of brain, liver and heart mitochondria using glutamate/malate. In the presence of succinate, 3-hydroxykynurenine and 3-hydroxyanthranilic acid affected RC values of brain mitochondria, whereas in liver and heart mitochondria only 3-hydroxykynurenine lowered RC values significantly. Furthermore, lowered ADP/oxygen ratios were observed in brain mitochondria in the presence of succinate with 3-hydroxykynurenine and 3-hydroxyanthranilic acid, and to a lesser extent with glutamate/malate. In addition, 3-hydroxyanthranilic acid significantly lowered the ADP/oxygen ratio in heart mitochondria exposed to glutamate/malate, while in the liver mitochondria only a mild reduction was found. Tests of the influence of L-tryptophan and its metabolites on complex I in liver mitochondria showed that only 3-hydroxykynurenine, 3-hydroxyanthranilic acid and L-kynurenine led to a significant acceleration of NADH-driven complex I activities. The data indicate that L-tryptophan metabolites had different effects on brain, liver and heart

  20. Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria.

    PubMed

    Baran, Halina; Staniek, Katrin; Bertignol-Spörr, Melanie; Attam, Martin; Kronsteiner, Carina; Kepplinger, Berthold

    2016-01-01

    Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3), respiratory control index (RC) and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochondria were incubated with glutamate/malate (5 mM) or succinate (10 mM) and in the presence of L-tryptophan metabolites (1 mM) or in the absence, as control. Kynurenic and anthranilic acids significantly reduced RC values of heart mitochondria in the presence of glutamate/malate. Xanthurenic acid significantly reduced RC values of brain mitochondria in the presence of glutamate/malate. Furthermore, 3-hydroxykynurenine and 3-hydroxyanthranilic acid decreased RC values of brain, liver and heart mitochondria using glutamate/malate. In the presence of succinate, 3-hydroxykynurenine and 3-hydroxyanthranilic acid affected RC values of brain mitochondria, whereas in liver and heart mitochondria only 3-hydroxykynurenine lowered RC values significantly. Furthermore, lowered ADP/oxygen ratios were observed in brain mitochondria in the presence of succinate with 3-hydroxykynurenine and 3-hydroxyanthranilic acid, and to a lesser extent with glutamate/malate. In addition, 3-hydroxyanthranilic acid significantly lowered the ADP/oxygen ratio in heart mitochondria exposed to glutamate/malate, while in the liver mitochondria only a mild reduction was found. Tests of the influence of L-tryptophan and its metabolites on complex I in liver mitochondria showed that only 3-hydroxykynurenine, 3-hydroxyanthranilic acid and L-kynurenine led to a significant acceleration of NADH-driven complex I activities. The data indicate that L-tryptophan metabolites had different effects on brain, liver and heart

  1. Antiapoptotic effect of exercise training on ovariectomized rat hearts.

    PubMed

    Huang, Chih-Yang; Lin, Yi-Yuan; Hsu, Chih-Chao; Cheng, Shiu-Min; Shyu, Woei-Cherng; Ting, Hua; Yang, Ai-Lun; Ho, Tsung-Jung; Lee, Shin-Da

    2016-08-01

    The purpose of this study was to evaluate the effects of exercise training on cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways in ovariectomized rats. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from three groups of Sprague-Dawley rats, which were divided into a sham-operated group, a bilaterally ovariectomized group (OVX), and a bilaterally ovariectomized group that underwent treadmill running exercise for 60 min/day, 5 sessions/wk, for 10 wk (OVX-EX). The abnormal myocardial architecture, cardiac trichome-stained fibrosis and cardiac TUNEL-positive apoptotic cells in ovariectomized rats improved after exercise training. The protein levels of tumor necrosis factor-α, tumor necrosis factor receptor 1, Fas ligand, Fas receptors, Fas-associated death domain, activated caspase-8 and activated caspase-3 (Fas receptor-dependent apoptotic pathways), as well as t-Bid, Bad, Bak, Bax, cytosolic cytochrome c, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) were decreased in the OVX-EX group compared with the OVX group. Exercise training suppressed ovariectomy-induced cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways in ovariectomized rat models. These findings might indicate a new therapeutic effect for exercise training to prevent cardiac apoptosis in menopausal or bilaterally oophorectomized women. PMID:27339185

  2. 3D Printing to Guide Ventricular Assist Device Placement in Adults With Congenital Heart Disease and Heart Failure.

    PubMed

    Farooqi, Kanwal M; Saeed, Omar; Zaidi, Ali; Sanz, Javier; Nielsen, James C; Hsu, Daphne T; Jorde, Ulrich P

    2016-04-01

    As the population of adults with congenital heart disease continues to grow, so does the number of these patients with heart failure. Ventricular assist devices are underutilized in adults with congenital heart disease due to their complex anatomic arrangements and physiology. Advanced imaging techniques that may increase the utilization of mechanical circulatory support in this population must be explored. Three-dimensional printing offers individualized structural models that would enable pre-surgical planning of cannula and device placement in adults with congenital cardiac disease and heart failure who are candidates for such therapies. We present a review of relevant cardiac anomalies, cases in which such models could be utilized, and some background on the cost and procedure associated with this process. PMID:27033018

  3. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart

    PubMed Central

    Wei, Ke; Serpooshan, Vahid; Hurtado, Cecilia; Diez-Cuñado, Marta; Zhao, Mingming; Maruyama, Sonomi; Zhu, Wenhong; Fajardo, Giovanni; Noseda, Michela; Nakamura, Kazuto; Tian, Xueying; Liu, Qiaozhen; Wang, Andrew; Matsuura, Yuka; Bushway, Paul; Cai, Wenqing; Savchenko, Alex; Mahmoudi, Morteza; Schneider, Michael D.; van den Hoff, Maurice J. B.; Butte, Manish J.; Yang, Phillip C.; Walsh, Kenneth; Zhou, Bin; Bernstein, Daniel; Mercola, Mark; Ruiz-Lozano, Pilar

    2016-01-01

    The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans. PMID:26375005

  4. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart.

    PubMed

    Wei, Ke; Serpooshan, Vahid; Hurtado, Cecilia; Diez-Cuñado, Marta; Zhao, Mingming; Maruyama, Sonomi; Zhu, Wenhong; Fajardo, Giovanni; Noseda, Michela; Nakamura, Kazuto; Tian, Xueying; Liu, Qiaozhen; Wang, Andrew; Matsuura, Yuka; Bushway, Paul; Cai, Wenqing; Savchenko, Alex; Mahmoudi, Morteza; Schneider, Michael D; van den Hoff, Maurice J B; Butte, Manish J; Yang, Phillip C; Walsh, Kenneth; Zhou, Bin; Bernstein, Daniel; Mercola, Mark; Ruiz-Lozano, Pilar

    2015-09-24

    The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans.

  5. Social burden and lifestyle in adults with congenital heart disease.

    PubMed

    Zomer, A Carla; Vaartjes, Ilonca; Uiterwaal, Cuno S P; van der Velde, Enno T; Sieswerda, Gert-Jan T; Wajon, Elly M C; Plomp, Koos; van Bergen, Paul F M; Verheugt, Carianne L; Krivka, Eva; de Vries, Cees J; Lok, Dirk J A; Grobbee, Diederick E; Mulder, Barbara J M

    2012-06-01

    We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group. PMID:22444325

  6. The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure

    EPA Science Inventory

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4 weeks) isoproterenol (ISO) infusion exacerbated cardiomyopathy in Spontaneously Hypertensive Heart Failure (SHHF) rats. Others have shown...

  7. Perspectives of Puerto Rican Adults about Heart Health and a Potential Community Program

    ERIC Educational Resources Information Center

    Todorova, Irina L. G.; Tejada, Shirley; Castaneda-Sceppa, Carmen

    2014-01-01

    Background: Puerto Ricans are the second largest Hispanic group in the United States, and older adults have significant health disparities. Educational programs that address heart disease risk for this population have rarely been developed and implemented. Purpose: To address this gap, the Heart Healthy Initiative for Puerto Rican adults is being…

  8. Interaction between caffeine intake and heart zinc concentrations in the rat.

    PubMed

    Rossowska, M J; Dinh, C; Gottschalk, S B; Yazdani, M; Sutton, F S; Nakamoto, T

    1990-09-01

    The purpose of the present study was to determine the levels of zinc in the hearts of growing post-weaning offspring, fetuses and their dams chronically fed caffeine. A further study was conducted to determine the distribution of Zn in subcellular heart fractions affected by acutely injecting caffeine into the veins of the adult rats. After delivery pups were raised on a 200 g protein/kg diet until day 22 of weaning. On day 22 randomly selected male offspring from each litter were divided into two groups. Group 1 was fed continuously on the same diet as a control, whereas in the experimental group offspring were fed on a 200 g protein/kg diet supplemented with caffeine (20 mg/kg). On day 49 the animals were killed and Zn, calcium and magnesium concentrations of the hearts were measured. In the second series of studies pregnant dams were randomly divided into two groups. Group 1 was fed on a 200 g protein/kg diet from day 3 of gestation, whereas in the experimental group dams were fed on the diet supplemented with caffeine. On day 22 of gestation the fetuses were surgically removed. The Zn, Ca and Mg concentrations of hearts of fetuses and dams were determined. In the third phase a caffeine solution was injected into the vein. After 45 min the hearts were removed and Zn levels in the subcellular fractions determined. The hearts of the growing offspring fed on a caffeine-supplemented diet consistently showed decreased Zn and Ca levels compared with the non-caffeine group.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Adolescents and Adults with Congenital Heart Diseases in Oman

    PubMed Central

    Al-Balushi, Asim; Al-Kindi, Hamood; Al-Shuaili, Hamood; Kumar, Suresh; Al-Maskari, Salim

    2015-01-01

    Objectives The aim of our study was to examine the spectrum, demographics, and mortality rate among adolescents and adults with congenital heart diseases (CHD) in Oman. Methods Data was collected retrospectively from the Royal Hospital, Muscat, electronic health records for all patients with a diagnosis of CHD aged 13 years and above. Data was analyzed according to the type of CHD and in-hospital mortality was assessed using Kaplan-Meier survival analysis. Results A total of 600 patients with CHD were identified, among them 145 (24%) were aged 18 years or below. The median age was 24 years. The majority of patients had a simple form of CHD. Atrial and ventricular septal defects together constituted 62.8% of congenital heart diseases. Most patients were clustered in Muscat (32%) and the Batinah regions (31.1%) of Oman. Patients with tetralogy of Fallot and Fontan had shorter survival time than recorded in the published literature. Conclusion Mostly simple forms of CHD in younger patients was observed. The survival rate was significantly shortened in more complex lesions compared to simple lesions. A national data registry for CHD is needed to address the morbidities and mortality associated with the disease. PMID:25829997

  10. A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET

    EPA Science Inventory

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4wk) isoproterenol (ISO) infusion in Spontaneously Hypertensive Heart Failure (SHHF) rats caused cardiac injury with minimal hypertrophy. O...

  11. Metabolic fate of rat heart endothelial lipoprotein lipase

    SciTech Connect

    Chajek-Shaul, T.; Bengtsson-Olivecrona, G.; Peterson, J.; Olivecrona, T.

    1988-09-01

    When isolated rat hearts were perfused with medium containing 125I-labeled bovine lipoprotein lipase (LPL), they bound both lipase activity and radioactivity. More than 80% of the bound lipase could be rapidly released by heparin. Low concentrations of bovine LPL displaced 50-60% of the endogeneous, endothelial-bound LPL. Higher concentrations caused additional binding. Both binding and exchange were rapid processes. The hearts continuously released endogenous LPL into the medium. An antiserum that inhibited bovine but not rat LPL was used to differentiate endogeneous and exogeneous LPL activity. When the pool of endothelial LPL was labeled with bovine 125I-labeled LPL and then chased with unlabeled bovine LPL, approximately 50% of the labeled lipase was rapidly displaced. During chase perfusion with medium only, catalytically active bovine LPL appeared in the perfusate. The rate of release was similar to that observed for endogeneous LPL activity and amounted to 10-13% of the heparin-releasable fraction in the first 5 min of perfusion. There was little or no degradation of bovine 125I-labeled LPL to fragments or acid-soluble products. These results indicate that endothelial LPL is accessible for exchange with exogeneous LPL and that detachment rather than degradation may be the pathway for catabolism of endothelial LPL.

  12. Modulation of AMP deaminase in rat hearts subjected to ischemia and reperfusion by purine riboside.

    PubMed

    Borkowski, T; Lipinski, M; Kaminski, R; Krzyminska-Stasiuk, E; Langowska, M; Raczak, G; Slominska, E M; Smolenski, R T

    2008-06-01

    Changes in AMP deaminase (AMPD) activity influence heart function and progression of heart disease, but the underlying mechanism is unknown. We evaluated the effect of purine riboside (Purr) on the activity of AMPD in perfused rat hearts and in isolated rat cardiomyocytes. Brief perfusion of the pre-ischemic heart with 200 micro M Purr resulted in activation of AMPD, more pronounced degradation of the adenine nucleotides, and reduced recovery of the adenine nucleotide pool during reperfusion. Brief incubation of rat cardiomyocytes with 200 micro M Purr also activated AMPD, while prolonged exposure resulted in enzyme inhibition. We conclude that Purr activates AMPD, whereas metabolites of this compound may inhibit the enzyme.

  13. Nickel chloride inhibits metabolic coronary vasodilatation in isolated rat hearts

    SciTech Connect

    Edoute, Y.; Rubanyi, G.M.; Vanhoutte, P.M.

    1986-03-01

    Nickel is a potent coronary vasoconstrictor and it is released from ischemic myocardium. To determine whether or not nickel ions cause coronary vasoconstriction when local vasodilator mechanisms are stimulated the authors studied the inter-relation between exogenous nickel chloride (NiCl/sub 2/) and metabolic coronary vasodilatation in isolated rat hearts perfused by a modified Langendorff technique. NiCl/sub 2/ induced dose-dependent (10/sup -7/-10/sup -5/M) increases in coronary vascular resistance in spontaneously beating hearts. Pacing of the hearts (380/min) and infusing adenosine (10/sup -6/M) evoked comparable increases in coronary flow but did not affect the coronary vasoconstriction caused by NiCl/sub 2/. At concentrations (> 10/sup -7/M) which evoked vasoconstriction, NiCl/sub 2/ significantly reduced vasodilator responses evoked by pacing, transient coronary occlusion and adenosine. Lower concentrations, which did not cause vasoconstriction, had no effect on these vasodilator responses. Thus, at relative low concentrations NiCl/sub 2/ inhibits metabolic dilatation of the coronary vessels which may contribute to the increased vascular resistance caused by the trace metal under ischemic/hypoxic conditions.

  14. Selective lymphoid irradiation and cyclosporin A in rat heart allografts

    SciTech Connect

    Kuromoto, N.; Hardy, M.A.; Fawwaz, R.; Reemtsma, K.; Nowygrod, R.

    1984-05-01

    Short-term peritransplant treatment utilizing 2-dose ALG and 1-dose Palladium-109-hematoporphyrin (PD-H) for selective lymphoid irradiation (SLI) leads to donor-specific permanent acceptance of heart allografts in the Fisher to Lewis rat model. The same treatment significantly prolongs survival of hearts transplanted to strongly histoincompatable , presensitized, and xenogeneic recipients. The purpose of this study was to evaluate synergistic effects of short-term, low-dose cyclosporin treatment and SLI in an attempt to develop a nontoxic protocol utilizing peritransplant treatment for immune preconditioning with minimal subsequent immunosuppression. Single-agent treatment alone with cyclosporin, ALG, or Pd-H resulted in a maximal mean graft survival time (MST) of 33 days. Immunosuppression with 1-dose Pd-H, 2-dose ALG, and low-dose cyclosporin (5 mg/kg) for 14 days doubled the MST to 78 days. Use of therapeutic-dose cyclosporin (20 mg/kg), given for just 3 days, was also quite effective, MST of 57 days with SLI and 43 days with ALG, but toxic; 3 of 12 recipients died of infection with functioning grafts. These results demonstrate that the use of low-dose cyclosporin over a short interval, when combined with peritransplant SLI, is a highly effective and safe method for prolonging heart allograft survival.

  15. 24-h Langendorff-perfused neonatal rat heart used to study the impact of adenoviral gene transfer.

    PubMed

    Wiechert, S; El-Armouche, A; Rau, T; Zimmermann, W-H; Eschenhagen, T

    2003-08-01

    The human genome project has increased the demand for simple experimental systems that allow the impact of gene manipulations to be studied under controlled ex vivo conditions. We hypothesized that, in contrast to adult hearts, neonatal hearts allow long-term perfusion and efficient gene transfer ex vivo. A Langendorff perfusion system was modified to allow perfusion for >24 h with particular emphasis on uncompromised contractile activity, sterility, online measurement of force of contraction, inotropic response to beta-adrenergic stimulation, and efficient gene transfer. The hearts were perfused with serum-free medium (DMEM + medium 199, 4 + 1) supplemented with hydrocortisone, triiodothyronine, ascorbic acid, insulin, pyruvate, l-carnitine, creatine, taurine, l-glutamine, mannitol, and antibiotics recirculating (500 ml/2 hearts) at 1 ml/min. Hearts from 2 day-old rats beat constantly at 135-155 beats/min and developed active force of 1-2 mN. During 24 h of perfusion, twitch tension increased to approximately 165% of initial values (P < 0.05), whereas the inotropic response to isoprenaline remained constant. A decrease in total protein content of 10% and histological examination indicated moderate edema, but actin and calsequestrin concentration remained unchanged and perfusion pressure remained constant at 7-11 mmHg. Perfusion with a LacZ-encoding adenovirus at 3 x 108 active virus particles yielded homogeneous transfection of approximately 80% throughout the heart and did not affect heart rate, force of contraction, or response to isoprenaline compared with uninfected controls (n = 7 each). Taken together, the 24-h Langendorff-perfused neonatal rat heart is a relatively simple, inexpensive, and robust new heart model that appears feasible as a test bed for functional genomics.

  16. Differences between brainstem gliomas in juvenile and adult rats

    PubMed Central

    WANG, YU; TIAN, YONGJI; WAN, HONG; LI, DEZHI; WU, WENHAO; YIN, LUXIN; JIANG, JIAN; WAN, WEIQING; ZHANG, LIWEI

    2013-01-01

    Clinical studies have shown that gliomas of the brainstem behave differently in children and adults. The aim of the present study was to compare and analyze the differences between these gliomas in juvenile and adult rats with regard to tumor growth, survival, pathology and magnetic resonance imaging (MRI). A total of 25 juvenile and 25 adult Wistar rats were divided into groups A (15 juvenile rats), B (10 juvenile rats), C (15 adult rats) and D (10 adult rats). The rats of groups A and C (experimental) were injected with glioma cells, while groups B and D (control) were injected with a physiological saline solution. Rat neurological signs, survival time, tumor size, hematoxylin and eosin (HE) staining and immunohistochemical staining for MMP-2, MMP-9 and β-catenin were compared. The survival time of group A was 19.47±2.232 days, whereas that of group C was 21.47±2.232 days (P<0.05). The tumor sizes were 4.55 and 4.62 mm (P>0.05) in groups A and C, respectively. HE and immunohistochemical staining revealed no differences between the groups. The results suggest that the growth patterns and invasiveness of brainstem gliomas may vary in children compared with adults due to the varied biological behaviors of the tumor cells. PMID:23946812

  17. Curcumin ameliorates streptozotocin-induced heart injury in rats.

    PubMed

    Abo-Salem, Osama M; Harisa, Gamaleldin I; Ali, Tarek M; El-Sayed, El-Sayed M; Abou-Elnour, Fatma M

    2014-06-01

    Heart failure (HF) is one of diabetic complications. This work was designed to investigate the possible modulatory effect of curcumin against streptozotocin-induced diabetes and consequently HF in rats. Rats were divided into control, vehicle-treated, curcumin-treated, diabetic-untreated, diabetic curcumin-treated, and diabetic glibenclamide-treated groups. Animal treatment was started 5 days after induction of diabetes and extended for 6 weeks. Diabetic rats showed significant increase in serum glucose, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, nitric oxide, lactate dehydrogenase, cardiac malondialdehyde, plasma levels of interleukin-6, and tumor necrosis factor-alpha, and also showed marked decrease in serum high-density lipoprotein-cholesterol, cardiac reduced glutathione, and cardiac antioxidant enzymes (catalase, superoxide dismutase, and glutathione-S-transferase). However, curcumin or glibenclamide treatment significantly mitigated such changes. In conclusion, curcumin has a beneficial therapeutic effect in diabetes-induced HF, an effect that might be attributable to its antioxidant and suppressive activity on cytokines.

  18. The efficiency coefficient of the rat heart and muscular system after physical training and hypokinesia

    NASA Technical Reports Server (NTRS)

    Alyukhin, Y. S.; Davydov, A. F.

    1982-01-01

    The efficiency of an isolated heart did not change after prolonged physical training of rats for an extreme load. The increase in oxygen consumption by the entire organism in 'uphill' running as compared to the resting level in the trained rats was 14% lower than in the control animals. Prolonged hypokinesia of the rats did not elicit a change in the efficiency of the isolated heart.

  19. Chronic heart failure modifies respiratory mechanics in rats: a randomized controlled trial

    PubMed Central

    Pacheco, Deise M.; Silveira, Viviane D.; Thomaz, Alex; Nunes, Ramiro B.; Elsner, Viviane R.; Dal Lago, Pedro

    2016-01-01

    ABSTRACT Objective To analyze respiratory mechanics and hemodynamic alterations in an experimental model of chronic heart failure (CHF) following myocardial infarction. Method Twenty-seven male adult Wistar rats were randomized to CHF group (n=12) or Sham group (n=15). Ten weeks after coronary ligation or sham surgery, the animals were anesthetized and submitted to respiratory mechanics and hemodynamic measurements. Pulmonary edema as well as cardiac remodeling were measured. Results The CHF rats showed pulmonary edema 26% higher than the Sham group. The respiratory system compliance (Crs) and the total lung capacity (TLC) were lower (40% and 27%, respectively) in the CHF rats when compared to the Sham group (P<0.01). There was also an increase in tissue resistance (Gti) and elastance (Hti) (28% and 45%, respectively) in the CHF group. Moreover, left ventricular end-diastolic pressure was higher (32 mmHg vs 4 mmHg, P<0.01), while the left ventricular systolic pressure was lower (118 mmHg vs 130 mmHg, P=0.02) in the CHF group when compared to the control. Pearson’s correlation coefficient showed a negative association between pulmonary edema and Crs (r=–0.70, P=0.0001) and between pulmonary edema and TLC (r=–0.67, P=0.0034). Pulmonary edema correlated positively with Gti (r=0.68, P=0.001) and Hti (r=0.68, P=0.001). Finally, there was a strong positive relationship between pulmonary edema and heart weight (r=0.80, P=0.001). Conclusion Rats with CHF present important changes in hemodynamic and respiratory mechanics, which may be associated with alterations in cardiopulmonary interactions. PMID:27556388

  20. Dose-dependent immunohistochemical and ultrastructural changes after oral methylphenidate administration in rat heart tissue.

    PubMed

    Take, G; Bahcelioglu, M; Oktem, H; Tunc, E; Gözil, R; Erdogan, D; Calguner, E; Helvacioglu, F; Giray, S G; Elmas, C

    2008-08-01

    Methylphenidate, more commonly known as Ritalin, is a piperidine derivative and is the drug most often used to treat attention deficit/hyperactivity disorder, one of the most common behavioural disorders of children and young adults. Our aims were to investigate dose-dependent immunohistochemical D2 expression and ultrastructural changes of the rat heart tissue, and to demonstrate possible toxicity of the long-term and high dose use of the methylphenidate. In this study, 27 female pre-pubertal Wistar albino rats, divided into three different dose groups (5, 10 and 20 mg/kg) and their control groups, were used. They were treated orally with methylphenidate dissolved in saline solution for 5 days/week during 3 months. At the end of the third month, after perfusion fixation, left ventricle of cardiac tissue was removed. Paraffin, semi-thin and thin sections were collected and immunohistochemical, terminal deoxynucleotidyl transferase-mediated Dig-dUTP nick end labelling assay and ultrastructural studies were performed. In conclusion, we believe that Ritalin is dose-related affecting dopaminergic system to increase heart rhythm and contraction. Thus, this drug may cause degenerative ultrastructural changes in mitochondrial path.

  1. Hypoalbuminaemia predicts outcome in adult patients with congenital heart disease

    PubMed Central

    Kempny, Aleksander; Diller, Gerhard-Paul; Alonso-Gonzalez, Rafael; Uebing, Anselm; Rafiq, Isma; Li, Wei; Swan, Lorna; Hooper, James; Donovan, Jackie; Wort, Stephen J; Gatzoulis, Michael A; Dimopoulos, Konstantinos

    2015-01-01

    Background In patients with acquired heart failure, hypoalbuminaemia is associated with increased risk of death. The prevalence of hypoproteinaemia and hypoalbuminaemia and their relation to outcome in adult patients with congenital heart disease (ACHD) remains, however, unknown. Methods Data on patients with ACHD who underwent blood testing in our centre within the last 14 years were collected. The relation between laboratory, clinical or demographic parameters at baseline and mortality was assessed using Cox proportional hazards regression analysis. Results A total of 2886 patients with ACHD were included. Mean age was 33.3 years (23.6–44.7) and 50.1% patients were men. Median plasma albumin concentration was 41.0 g/L (38.0–44.0), whereas hypoalbuminaemia (<35 g/L) was present in 13.9% of patients. The prevalence of hypoalbuminaemia was significantly higher in patients with great complexity ACHD (18.2%) compared with patients with moderate (11.3%) or simple ACHD lesions (12.1%, p<0.001). During a median follow-up of 5.7 years (3.3–9.6), 327 (11.3%) patients died. On univariable Cox regression analysis, hypoalbuminaemia was a strong predictor of outcome (HR 3.37, 95% CI 2.67 to 4.25, p<0.0001). On multivariable Cox regression, after adjusting for age, sodium and creatinine concentration, liver dysfunction, functional class and disease complexity, hypoalbuminaemia remained a significant predictor of death. Conclusions Hypoalbuminaemia is common in patients with ACHD and is associated with a threefold increased risk of risk of death. Hypoalbuminaemia, therefore, should be included in risk-stratification algorithms as it may assist management decisions and timing of interventions in the growing ACHD population. PMID:25736048

  2. Use of fluorescent antimyosin and DNA labeling for the estimation of the myoblast and myocyte population of primary rat heart cell cultures

    SciTech Connect

    Masse, M.J.O.; Harary, I.

    1981-01-01

    Cell division in heart muscle cells progressively ceases during the development of the rat heart, leading to an adult stage with muscle cells incapable of cell division. We have quantitatively determined the number of dividing and nondividing heart muscle cells in cultures derived from different stages of the developing rat heart with the use of /sup 3/HTdR continuous labeling and fluorescent antimyosin staining. The cultures were derived from 14 and 17 day postcoital (dPC) rat embryos and from 1 and 4 day postnatal (dPN) rats. The percent nondividing cells increased with development and the age of the postnatal rat. The percent nondividing cells in 14 dPC equalled 21%, 17 dPC equalled 25%, 1 dPN equalled 44%, and 4 dPN equalled 60%. This method for the quantitative determination of dividing and nondividing cells in the developing rat heart provides a model that is useful for the study of the mechanism of the loss of cell division capacity.

  3. 31P-NMR studies of isolated adult heart cells: effect of myoglobin inactivation.

    PubMed

    Gupta, R K; Wittenberg, B A

    1991-10-01

    31P nuclear magnetic resonance (NMR) studies of isolated adult rat heart cells revealed that the cells maintained high-energy phosphates for up to 6 h in polyamide hollow fibers perfused with well-oxygenated nutrient medium. Glucose plus pyruvate superfused heart cells maintained [phosphocreatine]/[ATP] at 1.4 +/- 0.1, internal pH at 7.09 +/- 0.04 (external pH = 7.25), and intracellular free Mg2+ at 0.51 +/- 0.04 mM. In glucose-containing media, hypoxia was accompanied by a reversible decrease in intracellular ATP and phosphocreatine of approximately 50% and 80%, respectively, while the intracellular free Mg2+ was reversibly increased by 40%. However, inhibition of glycolysis by iodoacetate in aerobic pyruvate-containing medium did not significantly alter high-energy phosphate content. Inactivation of intracellular myoglobin with 1-2 mM sodium nitrite, which reduces the steady-state respiratory oxygen consumption rate by 30%, caused a significant (30%) decrease in intracellular phosphocreatine peak, which was reversed upon removal of sodium nitrite. The nitrite-induced decrease in phosphocreatine was also observed in iodoacetate-treated myocytes but not in oligomycin-treated cells. These results indicate that functional myoglobin enhances high-energy phosphate synthesis in well-oxygenated myocytes. PMID:1928397

  4. Merit of Ginseng in the Treatment of Heart Failure in Type 1-Like Diabetic Rats

    PubMed Central

    Tsai, Cheng-Chia; Chan, Paul; Chen, Li-Jen; Chang, Chen Kuei; Liu, Zhongmin

    2014-01-01

    The present study investigated the merit of ginseng in the improvement of heart failure in diabetic rats and the role of peroxisome proliferator-activated receptors δ (PPARδ). We used streptozotocin-induced diabetic rat (STZ-rat) to screen the effects of ginseng on cardiac performance and PPARδ expression. Changes of body weight, water intake, and food intake were compared in three groups of age-matched rats; the normal control (Wistar rats) received vehicle, STZ-rats received vehicle and ginseng-treated STZ-rats. We also determined cardiac performances in addition to blood glucose level in these animals. The protein levels of PPARδ in hearts were identified using Western blotting analysis. In STZ-rats, cardiac performances were decreased but the food intake, water intake, and blood glucose were higher than the vehicle-treated control. After a 7-day treatment of ginseng in STZ-rats, cardiac output was markedly enhanced without changes in diabetic parameters. This treatment with ginseng also increased the PPARδ expression in hearts of STZ-rats. The related signal of cardiac contractility, troponin I phosphorylation, was also raised. Ginseng-induced increasing of cardiac output was reversed by the cotreatment with PPARδ antagonist GSK0660. Thus, we suggest that ginseng could improve heart failure through the increased PPARδ expression in STZ-rats. PMID:24745017

  5. Risks and Benefits of Exercise Training in Adults With Congenital Heart Disease.

    PubMed

    Chaix, Marie-A; Marcotte, François; Dore, Annie; Mongeon, François-Pierre; Mondésert, Blandine; Mercier, Lise-Andrée; Khairy, Paul

    2016-04-01

    Exercise capacity in adults with various forms of congenital heart disease is substantially lower than that of the general population. Although the underlying congenital heart defect, and its sequelae, certainly contribute to observed exercise limitations, there is evidence suggesting that deconditioning and a sedentary lifestyle are important implicated factors. The prevalence of acquired cardiovascular comorbidities is on the increase in the aging population with congenital heart disease, such that obesity and a sedentary lifestyle confer increased risk. Health fears and misconceptions are common barriers to regular physical activity in adults with congenital heart disease, despite evidence linking lower functional capacity to poor outcomes, and data supporting the safety and efficacy of exercise in bestowing numerous physical and psychosocial rewards. With few exceptions, adults with congenital heart disease should be counselled to exercise regularly. In this contemporary review, we provide a practical approach to assessing adults with congenital heart disease before exercise training. We examine available evidence supporting the safety and benefits of exercise training. Risks associated with exercise training in adults with congenital heart disease are discussed, particularly with regard to sudden cardiac death. Finally, recommendations for exercise training are provided, with consideration for the type of congenital heart disease, the nature (ie, static vs dynamic) and intensity (ie, low, medium, high) of the physical activity, and associated factors such as systemic ventricular dysfunction and residual defects. Further research is required to determine optimal exercise regimens and to identify effective strategies to implement exercise training as a key determinant of healthy living. PMID:26868839

  6. Leucocyte responses to fighting in the adult male bandicoot rat.

    PubMed

    Ghosh, P R; Sahu, A; Maiti, B R

    1983-01-01

    The effect of fighting stress on blood leucocyte count was studied in the adult male bandicoot rat. Exposure to fighting stress for 3 h induced neutrophilia, eosinopenia, lymphopenia and monocytopenia. The changes were more significant in the subordinate rat than in the dominant animal. It is suggested that leucocyte responses to fighting are perhaps mediated by the adrenal gland in these animals.

  7. Placing Advocacy at the Heart of Adult Education

    ERIC Educational Resources Information Center

    Taylor, Jackie

    2016-01-01

    Adult educators know that adults and families change their lives through adult education. Adult education also positively impacts a host of social and economic issues. Yet this fact is largely unknown or misunderstood by the general public. Resources have become increasingly scarce, while at the same time adult educators are asked to do more with…

  8. Myocardial infarction induces cognitive impairment by increasing the production of hydrogen peroxide in adult rat hippocampus.

    PubMed

    Liu, Chunhua; Liu, Ye; Yang, Zhuo

    2014-02-01

    Accumulating clinical evidence has shown a causal relationship between heart diseases and cognitive impairment in clinical, but the underlying mechanism remains unclear. In this study, rats with myocardial infarction (MI) were used to investigate cognition-related synaptic function and proteins. Adult male Wistar rats were subjected to MI by ligating of left anterior descending artery (LAD) and the infarct size of rat heart was measured by 2,3,5-triphenyltetrazoium chloride (TTC) staining. In this study, results showed that compared with control group, long-term potentiation was suppressed in dentate gyrus area, the contents of hydrogen peroxide (H2O2) and malondialdehyde were significantly increased, whereas the Cu/Zn-superoxide dismutase activity and N-methyl-d-aspartate receptor subunit 2B were attenuated in hippocampus of MI rats. Interestingly, it was observed that the PI3K/Akt pathway was activated in MI rats. Therefore, this study suggests that H2O2 plays an important role in cognitive dysfunction induced by MI.

  9. Effects of thyroid state on respiration of perfused rat and guinea pig hearts

    SciTech Connect

    Read, L.C.; Wallace, P.G.; Berry, M.N. )

    1987-09-01

    The effects of thyroid state on the respiration of the isolated heart were investigated using retrograde perfused rat and guinea pig hearts. In both species, hypothyroidism caused a marked depression in circulating thyroid hormone concentrations and in the respiration of the isolated, retrograde perfused heart. Hypothyroidism was caused by injecting animals with Na{sup 131}I. The effects on myocardial respiration could be attributed to changes in the contraction frequency and in the oxygen consumption per beat, with little contribution from basal respiration. Treatment of animals with thyroxine elevated plasma thyroid hormones to a similar extent in rats and guinea pigs. In the latter, thyroxine treatment was associated with substantial increases in the contraction frequency and the oxygen consumption per beat of the isolated heart. In contrast, only small changes were apparent in the retrograde perfused rat heart, observations that were confirmed in rat hearts perfused at near physiological work loads. It was concluded that rat hearts isolated from normal animals function at near maximal thyroid state, in contrast to the guinea pig heart, which requires higher circulating concentrations of thyroid hormones to attain maximal responses.

  10. [Activity of aldehyde scavenger enzymes in the heart of rats of different age during immobilized stress].

    PubMed

    Grabovetskaia, E R; Davydov, V V

    2009-01-01

    This study was made to determine the activity of aldehyde scavenger enzymes in the heart's postmitochondrial fraction of rats of different age during immobilization stress. Our study demonstrated, that immobilization of 1.5-, 2- and 12-month rats was accompanied by inhibiting activity of aldehyde dehydrogenase and aldehyde reductase. At the same time we observed an increase in glutathione transferase activity in immobilized 1.5-month-old rats and that in reductase activity in 24-month-old rats. The revealed changes can lead to a decrease in the rate of endogenous aldehyde utilization in the heart during stress at puberty.

  11. Anticoagulation in adults with congenital heart disease: The who, the when and the how?

    PubMed

    Jensen, A S; Idorn, L; Nørager, B; Vejlstrup, N; Sondergaard, L

    2015-03-01

    Adults with congenital heart disease are a growing population. One of the major challenges in the care of these patients is to prevent thromboembolic episodes. Despite relative young age and no typical cardiovascular risk factors, this cohort has a high prevalence of thrombotic events. It is difficult to use treatment algorithms from the general adult population with acquired heart disease in this heterogeneous population due to special conditions such as myocardial scarring after previous surgery, atypical atrial flutter, prothrombotic conditions and the presence of interatrial shunts. Furthermore, there is a lack of scientific evidence regarding how to prevent thromboembolic events with anticoagulation in adults with congenital heart disease. The aim of this paper is to review the current literature pertaining to anticoagulation in adults with congenital heart disease and hence enable recommendations for which patients are likely to benefit from which anticoagulation treatments, when they should be considered and how these would be carried out.

  12. Precursors of Hypertensive Heart Phenotype Develop in Healthy Adults

    PubMed Central

    de Marvao, Antonio; Dawes, Timothy J.W.; Shi, Wenzhe; Durighel, Giuliana; Rueckert, Daniel; Cook, Stuart A.; O’Regan, Declan P.

    2015-01-01

    Objectives This study used high-resolution 3-dimensional cardiac magnetic resonance to define the anatomical and functional left ventricular (LV) properties associated with increasing systolic blood pressure (SBP) in a drug-naïve cohort. Background LV hypertrophy and remodeling occur in response to hemodynamic stress but little is known about how these phenotypic changes are initiated in the general population. Methods In this study, 1,258 volunteers (54% women, mean age 40.6 ± 12.8 years) without self-reported cardiovascular disease underwent 3-dimensional cardiac magnetic resonance combined with computational modeling. The relationship between SBP and wall thickness (WT), relative WT, end-systolic wall stress (WS), and fractional wall thickening were analyzed using 3-dimensional regression models adjusted for body surface area, sex, race, age, and multiple testing. Significantly associated points in the LV model (p < 0.05) were identified and the relationship with SBP reported as mean β coefficients. Results There was a continuous relationship between SBP and asymmetric concentric hypertrophic adaptation of the septum and anterior wall that was associated with normalization of wall stress. In the lateral wall an increase in wall stress with rising SBP was not balanced by a commensurate hypertrophic relationship. In normotensives, SBP was positively associated with WT (β = 0.09) and relative WT (β = 0.07) in the septal and anterior walls, and this regional hypertrophic relationship was progressively stronger among pre-hypertensives (β = 0.10) and hypertensives (β = 0.30). Conclusions These findings show that the precursors of the hypertensive heart phenotype can be traced to healthy normotensive adults and that an independent and continuous relationship exists between adverse LV remodeling and SBP in a low-risk population. These adaptations show distinct regional variations with concentric hypertrophy of the septum and eccentric hypertrophy of the

  13. Novel Insights into the Cardio-Protective Effects of FGF21 in Lean and Obese Rat Hearts

    PubMed Central

    Chen, Jing; Ramanjaneya, Manjunath; Bari, Muhammad F.; Bhudia, Sunil K.; Hillhouse, Edward W.; Tan, Bee K.; Randeva, Harpal S.

    2014-01-01

    Aims Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia. PMID:24498293

  14. Effects of increased heart work on glycolysis and adenine nucleotides in the perfused heart of normal and diabetic rats

    PubMed Central

    Opie, L. H.; Mansford, K. R. L.; Owen, Patricia

    1971-01-01

    1. In the isolated perfused rat heart, the contractile activity and the oxygen uptake were varied by altering the aortic perfusion pressure, or by the atrial perfusion technique (`working heart'). 2. The maximum increase in the contractile activity brought about an eightfold increase in the oxygen uptake. The rate of glycolytic flux rose, while tissue contents of hexose monophosphates, citrate, ATP and creatine phosphate decreased, and contents of ADP and AMP rose. 3. The changes in tissue contents of adenine nucleotides during increased heart work were time-dependent. The ATP content fell temporarily (30s and 2min) after the start of left-atrial perfusion; at 5 and 10min values were normal; and at 30 and 60min values were decreased. ADP and AMP values were increased in the first 15min, but were at control values 30 or 60min after the onset of increased heart work. 4. During increased heart work changes in the tissue contents of adenine nucleotide and of citrate appeared to play a role in altered regulation of glycolysis at the level of phosphofructokinase activity. 5. In recirculation experiments increased heart work for 30min was associated with increased entry of [14C]glucose (11.1mm) and glycogen into glycolysis and a comparable increase in formation of products of glycolysis (lactate, pyruvate and 14CO2). There was no major accumulation of intermediates. Glycogen was not a major fuel for respiration. 6. Increased glycolytic flux in Langendorff perfused and working hearts was obtained by the addition of insulin to the perfusion medium. The concomitant increases in the tissue values of hexose phosphates and of citrate contrasted with the decreased values of hexose monophosphates and of citrate during increased glycolytic flux obtained by increased heart work. 7. Decreased glycolytic flux in Langendorff perfused hearts was obtained by using acute alloxan-diabetic and chronic streptozotocin-diabetic rats; in the latter condition there were decreased tissue

  15. Manganese protects against heart mitochondrial lipid peroxidation in rats fed high levels of polyunsaturated fatty acids.

    PubMed

    Malecki, E A; Greger, J L

    1996-01-01

    We demonstrated previously that dietary manganese (Mn) deficiency depressed Mn concentrations in most tissues and consistently depressed Mn superoxide dismutase (MnSOD) levels in heart. To examine the functional consequences of these effects, we fed weanling male Sprague-Dawley rats (n = 12/diet) diets containing 20% (wt/wt) corn oil or 19% menhaden oil + 1% corn oil by weight and 0.75 or 82 mg Mn/kg diet for 2 mo (the fish oil mixture was supplemented with (+)-(mixed)-alpha-tocopherol to the level in corn oil). Heart and liver Mn concentrations in the Mn-deficient rats were 56% of those in Mn-adequate rats (P < 0.0001), confirming Mn deficiency. The Mn-deficient rats had more conjugated dienes in heart mitochondria than Mn-adequate rats (P < 0.001); rats fed fish oil had more conjugated dienes than those fed corn oil (P < 0.001). The MnSOD activity was inversely correlated with conjugated dienes (r = -0.71, P < 0.005), and Mn-deficient rats had 37% less MnSOD activity in the heart than did Mn-adequate rats (P < 0.0001). The dietary treatments did not affect heart microsomal conjugated diene formation, possibly because of compensation by copper-zinc (CuZn) SOD activity; CuZnSOD activities were 35% greater in the hearts of Mn-deficient animals (P < 0.01). Liver was less sensitive to Mn deficiency than was the heart as judged by MnSOD activity and conjugated diene formation. This work is the first to demonstrate that dietary Mn protects against in vivo oxidation of heart mitochondrial membranes. PMID:8558311

  16. Characterization of a fatty acid-binding protein from rat heart.

    PubMed

    Offner, G D; Troxler, R F; Brecher, P

    1986-04-25

    A fatty acid-binding protein has been isolated from rat heart and purified by gel filtration chromatography on Sephadex G-75 and anion-exchange chromatography on DE52. The circular dichroic spectrum of this protein was not affected by protein concentration, suggesting that it does not aggregate into multimers. Computer analyses of the circular dichroic spectrum predicted that rat heart fatty acid-binding protein contains approximately 22% alpha-helix, 45% beta-form and 33% unordered structure. Immunological studies showed that the fatty acid-binding proteins from rat heart and rat liver are immunochemically unrelated. The amino acid composition and partial amino acid sequence of the heart protein indicated that it is structurally related to, but distinct from, other fatty acid-binding proteins from liver, intestine, and 3T3 adipocytes. Using a binding assay which measures the transfer of fatty acids between donor liposomes and protein (Brecher, P., Saouaf, R., Sugarman, J. M., Eisenberg, D., and LaRosa, K. (1984) J. Biol. Chem. 259, 13395-13401), it was shown that both rat heart and liver fatty acid-binding proteins bind 2 mol of oleic acid or palmitic acid/mol of protein. The structural and functional relationship of rat heart fatty acid-binding protein to fatty acid-binding proteins from other tissues is discussed. PMID:3957934

  17. Neurotensin stimulates histamine release from the isolated, spontaneously beating heart of rats.

    PubMed

    Rioux, F; Kérouac, R; St-Pierre, S

    1984-07-23

    Neurotensin (NT) evoked a transient, dose-dependent histamine release (ED50 170 ng ml-1) from the rat perfused heart. Histamine release by NT occurred within seconds and lasted less than 2 min. The histamine releasing effect of NT was followed by a dose-dependent increase of the perfusion pressure and a slight tachycardia. The histamine releasing effect of NT was completely abolished in hearts derived from rats pretreated for 3 days with high doses of compound 48/80. The coronary vasoconstrictor effect of NT was increased in hearts derived from compound 48/80-pretreated rats. The mast cell inhibitor cromoglycate markedly inhibited NT-induced histamine release without affecting the coronary vasoconstrictor effect of NT. The histamine releasing effect of NT was inhibited, while its coronary vasoconstrictor effect was markedly potentiated, in hearts derived from rats pretreated with the antiallergic and antiinflammatory steroid dexamethasone. The increase of perfusion pressure evoked by NT was not modified by antihistamine drugs. Infusions of exogenous histamine (10(-6)-10(-5) g ml-1) caused a dose-dependent coronary vasodilation in the rat perfused heart. The results suggest that NT stimulates histamine release from cardiac mast cells. These results together with those obtained in previous studies suggest that mast cell mediators (particularly histamine and serotonin) are unlikely to be responsible for the coronary vasoconstrictor effect of NT in the rat perfused heart.

  18. Prevalence and correlates of heart disease among adults in Singapore.

    PubMed

    Picco, Louisa; Subramaniam, Mythily; Abdin, Edimansyah; Vaingankar, Janhavi Ajit; Chong, Siow Ann

    2016-02-01

    Heart disease is one of the leading causes of morbidity and mortality worldwide and it has been well established that it is associated with both mental and physical conditions. This paper describes the prevalence of heart disease with mental disorders and other chronic physical conditions among the Singapore resident population. Data were from the Singapore Mental Health Study which was a representative, cross-sectional epidemiological survey undertaken with 6616 Singapore residents, between December 2009 and December 2010. The Composite International Diagnostic Interview Version 3.0 was used to establish the diagnosis of mental disorders, while a chronic medical conditions checklist was used to gather information on 15 physical conditions, including various forms of heart disease. Health-related quality of life was measured using the Euro-Quality of Life Scale (EQ-5D). The lifetime prevalence of heart disease was 2.8%. Socio-demographic correlates of heart disease included older age, Indian ethnicity, secondary education (vs. tertiary) and being economically inactive. After adjusting for socio-demographic variables and other comorbid physical and mental disorders, the prevalence of major depressive disorder and bipolar disorder were significantly higher among those with heart disease, as were diabetes, arthritis, kidney failure and lung disease. These findings highlight important associations between heart disease and various socio-demographic correlates, mental disorders and physical conditions. Given the high prevalence of mood disorders among heart disease patients, timely and appropriate screening and treatment of mental disorders among this group is essential.

  19. Asymmetrical Dimethylarginine - More Sensitive than NT-proBNP to Diagnose Heart Failure in Adults with Congenital Heart Disease

    PubMed Central

    Bode-Böger, Stefanie M.; Martens-Lobenhoffer, Jens; Lovric, Svjetlana; Bauersachs, Johann; Schieffer, Bernhard; Westhoff-Bleck, Mechthild; Kielstein, Jan T.

    2012-01-01

    Background Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an established biomarker for heart failure of non-congenital origin, its value in ACHD has limitations. Asymmetrical dimethylarginine (ADMA) correlates with disease severity and independently predicts adverse clinical events in heart failure of non-congenital origin. Its role in ACHD has not been investigated. Methods In 102 patients ADMA and NT-proBNP were measured and related to NYHA class, systemic ventricular function and parameters of cardiopulmonary exercise testing. Results In contrast to NT-proBNP ADMA differentiated between NYHA classes I-III. Both, ADMA and NT-proBNP showed a good correlation with parameters of cardiopulmonary exercise testing with comparable receiver-operating characteristic curves for identifying patients with severely limited cardiopulmonary exercise capacity. Conclusion ADMA seems to be a better biomarker than NT-proBNP for the assessment of NYHA class and as a good as NT-proBNP for the estimation of maximum exercise capacity in adults with congenital heart disease. Its use in clinical routine should be evaluated. PMID:22470476

  20. A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis123

    PubMed Central

    Grigereit, Laura; Pickel, James

    2016-01-01

    Abstract The growth of research on adult neurogenesis and the development of new models and tools have greatly advanced our understanding of the function of newborn neurons in recent years. However, there are still significant limitations in the ability to identify the functions of adult neurogenesis in available models. Here we report a transgenic rat (TK rat) that expresses herpes simplex virus thymidine kinase in GFAP+ cells. Upon treating TK rats with the antiviral drug valganciclovir, granule cell neurogenesis can be completely inhibited in adulthood, in both the hippocampus and olfactory bulb. Interestingly, neurogenesis in the glomerular and external plexiform layers of the olfactory bulb was only partially inhibited, suggesting that some adult-born neurons in these regions derive from a distinct precursor population that does not express GFAP. Within the hippocampus, blockade of neurogenesis was rapid and nearly complete within 1 week of starting treatment. Preliminary behavioral analyses indicate that general anxiety levels and patterns of exploration are generally unaffected in neurogenesis-deficient rats. However, neurogenesis-deficient TK rats showed reduced sucrose preference, suggesting deficits in reward-related behaviors. We expect that TK rats will facilitate structural, physiological, and behavioral studies that complement those possible in existing models, broadly enhancing understanding of the function of adult neurogenesis. PMID:27257630

  1. Influence of microwaves on the beating rate of isolated rat hearts.

    PubMed

    Yee, K C; Chou, C K; Guy, A W

    1988-01-01

    Previous reports have shown that microwave exposure can decrease the beating rate of isolated rat hearts. These experiments were conducted at room temperature and with the hearts exposed to air. We observed arrhythmia frequently at room temperature, and the variation of heart beat was so large that it makes the results difficult to reproduce. Therefore, we employed a double-circulating system to provide perfusion through the coronary artery and around the outside of the heart to maintain the rat hearts at 37.7 degrees C. No arrhythmias were observed in our experiments, and the hearts were beating for at least 1 h. The effects of 16-Hz modulated 2,450-MHz pulsed microwaves (10 microseconds, 100 pps) on the beating rate of 50 isolated rat hearts were studied. Results showed no statistically significant changes of heart rate in exposed groups at SARs of 2 and 10 W/kg compared with the control group. The effect seen at 200 W/kg was shown to be similar to that resulting from heating the heart.

  2. Influence of microwaves on the beating rate of isolated rat hearts

    SciTech Connect

    Yee, K.C.; Chou, C.K.; Guy, A.W.

    1988-01-01

    Previous reports have shown that microwave exposure can decrease the beating rate of isolated rat hearts. These experiments were conducted at room temperature and with the hearts exposed to air. We observed arrhythmia frequently at room temperature, and the variation of heart beat was so large that it makes the results difficult to reproduce. Therefore, we employed a double-circulating system to provide perfusion through the coronary artery and around the outside of the heart to maintain the rat hearts at 37.7 degrees C. No arrhythmias were observed in our experiments, and the hearts were beating for at least 1 h. The effects of 16-Hz modulated 2,450-MHz pulsed microwaves (10 microseconds, 100 pps) on the beating rate of 50 isolated rat hearts were studied. Results showed no statistically significant changes of heart rate in exposed groups at SARs of 2 and 10 W/kg compared with the control group. The effect seen at 200 W/kg was shown to be similar to that resulting from heating the heart.

  3. Activity of cholinesterases of blood and heart in rats of different sex and age during muscular loads and hypokinesia

    NASA Technical Reports Server (NTRS)

    Rozanova, V. D.; Antonova, G. A.

    1979-01-01

    The activity of acetylcholinesterase (Ache) and butyrilcholinesterase (Bche) in the blood and the heart of 3 and 13 month old control male rats is considerably lower than in female rats. In 25 month old rats, no sex differences in the Ache and Bche were revealed in the heart. In 3 and 13 month old male and female rats, under conditions of muscular exercises, the Ache and Bche activity is lower, and in hypokinetic male rats -- higher than that in respective control animals. In all the rats, irrespective of sex, age, and motor conditions, Ache and Bche activity tended to decrease from the sinoatrial node to the heart apex.

  4. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    PubMed

    Liao, Song-Yan; Tse, Hung-Fat

    2013-12-24

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed.

  5. Regulation of atriopeptin release from the isolated rat heart

    SciTech Connect

    Currie, M.G.; Newman, W.H.

    1986-03-05

    Recent studies have demonstrated that the mammalian atria possess an endocrine function which appears to play a role in the regulation of systemic arterial pressure, fluid balance, and electrolyte homeostasis. They have begun to study the regulation of atriopeptin (atrial natriuretic factor) release into the coronary effluent of the isolated perfused rat heart. Characterization by high pressure liquid chromatography of the form of the hormone released indicates that the predominant form is the active low MW circulating hormone not the pro-hormone. The release of immunoreactive atriopeptin (iAP) was stimulated by infusion of norepinephrine (1 ..mu..M) or epinephrine (1 ..mu..M) 3.0 and 2.6-fold, respectively. The ..beta..-adrenergic agonist isoproterenol and the ..cap alpha..-2 adrenergic agonist BHT-920 lacked effects on iAP release. On the other hand, the ..cap alpha..-1 adrenergic agonist phenylephrine caused a dose-dependent increase in release of iAP. Release of iAP stimulated by phenylephrine was inhibited by the ..cap alpha.. antagonist phentolamine. Further, iAP release was stimulated 4.2-fold by phorbol ester (1 ..mu..M) but was not affected by 4-..beta.. phorbol (1 ..mu..M). From these collective data they conclude that the release of atriopeptin is stimulated by ..cap alpha..-1 receptor activation and that protein kinase C participates in the regulation of secretion. The data suggests that the sympathetic nervous system may play a physiologic role in the regulation of atriopeptin secretion.

  6. Effects of ethanol on rat heart and skeletal muscles

    SciTech Connect

    Pagala, M.; Ravindran, K.; Namba, T.; Grob, D. State Univ. of New York, Brooklyn )

    1991-03-11

    Chronic alcoholism causes myopathy of both cardiac and skeletal muscles. In order to evaluate acute effects, the authors infused ethanol intravenously in anesthetized rats, and, 10 min later, monitored the electrocardiogram, and the compound action potential and isometric tension of the anterior tibialis evoked by sciatic nerve stimulation. Ethanol at 0.1, 0.2 and 0.5 g/kg decreased the heart rate by 12%, 22% and 69%, increased the P-R interval by 5%, 25%, and 116%, and reduced the QRS amplitude by 1% , 2% and 10%, respectively. Within 5 min after infusing 0.5 g/kg ethanol, breathing was stopped. Ethanol increased the amplitude of the compound action potential and tension of the anterior tibialis by 25% at 0.1 and 0.2 g/kg, while it decreased the compound action potential by 5% and tension by 35% at 0.5 g/kg. At this dose, ethanol caused 70% decrement in amplitude of the compound action potentials and 50% fade of tetanic tensions evoked by a train of nerve stimulations at 100 Hz for 0.5 sec. When ethanol was injected intraperitoneally, about 10 times greater doses were required to produce effects equivalent to intravenous administration. These results indicate that ethanol reduces cardiac output dose-dependently, and potentiates skeletal muscle function at subintoxication doses and reduces it at higher doses.

  7. Overweight Status, Obesity, and Risk Factors for Coronary Heart Disease in Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Henderson, C. Michael; Robinson, Laura M.; Davidson, Philip W.; Haveman, Meindert; Janicki, Matthew P.; Albertini, Giorgio

    2008-01-01

    Research indicates that adults with intellectual disabilities (ID) have high rates of overweight status/obesity (OSO). OSO is associated with several important risk factors for coronary heart disease (CHD). This study focused on assessing whether such risk factors are being identified in adults with ID who are receiving their healthcare in…

  8. Myocardial kinetics of carbon-11-epinephrine in the isolated working rat heart

    SciTech Connect

    Nguyen, N.T.B.; DeGrado, T.R.; Chakraborty, P.

    1997-05-01

    The kinetics of EPI were studied in the isolated rat heart model to evaluate {sup 11}C-epinephrine (EPI) as a radiotracer for the assessment of sympathetic neuronal function in the heart. Isolated rat hearts were perfused in a working mode. Carbon-11-EPI was added to the perfusate during wash-in period of 20 min, followed by a washout period of 40 min. Radioactivity in the heart was externally monitored and time-activity curves were recorded as a function of time. Effluent samples were collected throughout each study to determine the fraction of {sup 11}C radioactivity as intact tracer. Time-activity curves of control hearts showed that {sup 11}C-EPI is taken up and retained by the myocardium. Desipramine inhibition (DMI) of uptake-1 resulted in a significant decrease in myocardial uptake and retention of {sup 11}C-EPI by 91% compared to controls. Addition of DMI to the perfusion medium during washout did not affect kinetics of {sup 11}C-EPI compared to control hearts. Reserpine pretreated rat hearts also showed significant decrease in tracer retention of 95% compared to controls. The metabolic data showed that, in control conditions, about 61% of {sup 11}C-EPI taken up by the rat heart is rapidly metabolized and released. Carbon-11-EPI traces sympathetic nerve terminals in the isolated rat heart. Uptake blockade by DMI and reserpine suggest that uptake and storage of {sup 11}C-EPI appear to be similar to that of norepinephrine. However, the prominent metabolic pathway warrants further consideration. These results suggest that {sup 11}C-EPI may be a suitable radiolabeled tracer for the evaluation of sympathetic vesicular function of the heart by PET. 23 refs., 3 figs., 3 tabs.

  9. Association between Functional Variables and Heart Failure after Myocardial Infarction in Rats

    PubMed Central

    Polegato, Bertha F.; Minicucci, Marcos F.; Azevedo, Paula S.; Gonçalves, Andréa F.; Lima, Aline F.; Martinez, Paula F.; Okoshi, Marina P.; Okoshi, Katashi; Paiva, Sergio A. R.; Zornoff, Leonardo A. M.

    2016-01-01

    Background Heart failure prediction after acute myocardial infarction may have important clinical implications. Objective To analyze the functional echocardiographic variables associated with heart failure in an infarction model in rats. Methods The animals were divided into two groups: control and infarction. Subsequently, the infarcted animals were divided into groups: with and without heart failure. The predictive values were assessed by logistic regression. The cutoff values predictive of heart failure were determined using ROC curves. Results Six months after surgery, 88 infarcted animals and 43 control animals were included in the study. Myocardial infarction increased left cavity diameters and the mass and wall thickness of the left ventricle. Additionally, myocardial infarction resulted in systolic and diastolic dysfunction, characterized by lower area variation fraction values, posterior wall shortening velocity, E-wave deceleration time, associated with higher values of E / A ratio and isovolumic relaxation time adjusted by heart rate. Among the infarcted animals, 54 (61%) developed heart failure. Rats with heart failure have higher left cavity mass index and diameter, associated with worsening of functional variables. The area variation fraction, the E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate were functional variables predictors of heart failure. The cutoff values of functional variables associated with heart failure were: area variation fraction < 31.18%; E / A > 3.077; E-wave deceleration time < 42.11 and isovolumic relaxation time adjusted by heart rate < 69.08. Conclusion In rats followed for 6 months after myocardial infarction, the area variation fraction, E/A ratio, E-wave deceleration time and isovolumic relaxation time adjusted by heart rate are predictors of heart failure onset. PMID:26815462

  10. Heart rate variability and electrocardiogram waveform as predictors of morbidity during hypothermia and rewarming in rats.

    PubMed

    Matthew, C B; Bastille, A M; Gonzalez, R R; Sils, I V

    2002-09-01

    This study examined electrocardiogram (ECG) waveform, heart rate (HR), mean blood pressure (BP), and HR variability as potential autonomic signatures of hypothermia and rewarming. Adult male Sprague-Dawley rats had telemetry transmitters surgically implanted, and 2 weeks were allowed for recovery prior to induction of hypothermia. Rats were lightly anesthetized (sodium pentobarbital, 35 mg/kg i.p.) and placed in a coil of copper tubing through which temperature-controlled water was circulated. Animals were cooled to a core temperature (Tc) of 20 degrees C, maintained there for 30 min, and then rewarmed. Data (Tc, BP, HR from ECG, and 10-s strips of ECG waveforms) were collected every 5 min throughout hypothermia and rewarming. Both HR and BP declined after initial increases with the drop in HR starting at a higher Tc than the drop in BP (29.6 +/- 2.4 degrees C vs. 27.1 +/- 3.3 degrees C, p < 0.05). Animals that were not successfully rewarmed exhibited a significant (p < 0.05) increase in the normalized standard deviation of interbeat intervals (IBI) throughout cooling compared with animals that were successfully rewarmed. The T wave of the ECG increased in amplitude and area with decreasing Tc. T-wave amplitude and IBI variability show potential as predictors of survival in hypothermic victims.

  11. Endurance Training and Glutathione-Dependent Antioxidant Defense Mechanism in Heart of the Diabetic Rats

    PubMed Central

    Gül, Mustafa; Atalay, Mustafa; Hänninen, Osmo

    2003-01-01

    Regular physical exercise beneficially influences cardiac antioxidant defenses in normal rats. The aim of this study was to test whether endurance training can strengthen glutathione-dependent antioxidant defense mechanism and decrease lipid peroxidation in heart of the streptozotocin-induced diabetic rats. Redox status of glutathione in blood of diabetic rats in response to training and acute exercise was also examined. Eight weeks of treadmill training increased the endurance in streptozotocin-induced diabetic rats. It did not affect glutathione level in heart tissue at rest and also after exercise. On the other hand, endurance training decreased glutathione peroxidase activity in heart, while glutathione reductase and glutathione S-transferase activities were not affected either by acute exhaustive exercise or endurance training. Reduced and oxidized glutathione levels in blood were not affected by either training or acute exercise. Conjugated dienes levels in heart tissue were increased by acute exhaustive exercise and also 8 weeks treadmill training. Longer duration of exhaustion in trained group may have contributed to the increased conjugated dienes levels in heart after acute exercise. Our results suggest that endurance type exercise may make heart more susceptible to oxidative stress. Therefore it may be wise to combine aerobic exercise with insulin treatment to prevent its adverse effects on antioxidant defense in heart in patients with diabetes mellitus. PMID:24616611

  12. Effect of ethanol of heart rate and blood pressure in nonstressed and stressed rats

    SciTech Connect

    Sparrow, M.G.; Roggendorf, H.; Vogel, W.H.

    1987-06-29

    The effect of ethanol on the cardiovascular system (ECG, heart rate, blood pressure) was studied in anesthetized, nonstressed or stressed rats. In anesthetized rats, ethanol showed no effect on heart rate or ECG. In nonstressed rats, ethanol sedated the animals but increased heart rate significantly. This ethanol induced tachycardia seemed the result of a direct stimulation of the sympathetic nerves to the heart. Blood pressure was not significantly affected by ethanol in these nonstressed rats. In stressed rats, marked behavioral excitation and significant increases in heart rate and blood pressure were noted. Ethanol pretreatment calmed the animals considerably during restraint. Ethanol did reduce slightly the stress-induced tachycardia but markedly reduced or antagonized stress-induced blood pressure increases. No major changes in the ECG were noted during these studies with the exception of a few individual animals which showed pathologic ECG responses to ethanol. These data show that ethanol affects cardiovascular functions differently in anesthetized, non stressed or stressed rats, and that ethanol can significantly reduce or antagonize stress-induced behavioral excitation, tachycardia and hypertension. 32 references, 4 tables.

  13. Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation.

    PubMed

    Hirt, Marc N; Boeddinghaus, Jasper; Mitchell, Alice; Schaaf, Sebastian; Börnchen, Christian; Müller, Christian; Schulz, Herbert; Hubner, Norbert; Stenzig, Justus; Stoehr, Andrea; Neuber, Christiane; Eder, Alexandra; Luther, Pradeep K; Hansen, Arne; Eschenhagen, Thomas

    2014-09-01

    Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2× higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca(2+)-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2Hz in the first week and 1.5Hz thereafter developed 1.5× higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT.

  14. Physiological responses during whole body suspension of adult rats

    NASA Technical Reports Server (NTRS)

    Steffen, J. M.; Fell, R. D.; Musacchia, X. J.

    1987-01-01

    The objective of this study was to characterize responses of adult rats to one and two weeks of whole body suspension. Body weights and food and water intakes were initially reduced during suspension, but, while intake of food and water returned to presuspension levels, body weight remained depressed. Diuresis was evident, but only during week two. Hindlimb muscle responses were differential, with the soleus exhibiting the greatest atrophy and the EDL a relative hypertrophy. These findings suggest that adult rats respond qualitatively in a manner similar to juveniles during suspension.

  15. Long-term physiological T3 supplementation in hypertensive heart disease in rats.

    PubMed

    Weltman, Nathan Y; Pol, Christine J; Zhang, Youhua; Wang, Yibo; Koder, Adrienne; Raza, Sarah; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Gerdes, A Martin

    2015-09-15

    Animal studies suggest that hypertension leads to cardiac tissue hypothyroidism, a condition that can by itself lead to heart failure. We have previously shown that short-term thyroid hormone treatment in Spontaneously Hypertensive Heart Failure (SHHF) rats near heart failure is beneficial. This study tested the hypothesis that therapeutic, long-term T3 treatment in SHHF rats can prevent or attenuate cardiac dysfunction. Female SHHF rats were treated orally with a physiological T3 dose (0.04 μg/ml) from 12 to 24 mo of age. Age-matched female SHHF and Wistar-Kyoto rats served as hypertensive and normotensive controls, respectively. SHHF rats had reduced serum free thyroid hormone levels and cardiac tissue T3 levels, LV dysfunction, and elevated LV collagen content compared with normotensive controls. Restoration of serum and cardiac tissue thyroid hormone levels in T3-treated rats was associated with no change in heart rate, but strong trends for improvement in LV systolic function and collagen levels. For instance, end-systolic diameter, fractional shortening, systolic wall stress, and LV collagen levels were no longer significantly different from controls. In conclusion, longstanding hypertension in rats led to chronic low serum and cardiac tissue thyroid hormone levels. Long-term treatment with low-dose T3 was safe. While cardiac dysfunction could not be completely prevented in the absence of antihypertensive treatment, T3 may offer additional benefits as an adjunct therapy with possible improvement in diastolic function.

  16. Long-term physiological T3 supplementation in hypertensive heart disease in rats.

    PubMed

    Weltman, Nathan Y; Pol, Christine J; Zhang, Youhua; Wang, Yibo; Koder, Adrienne; Raza, Sarah; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Gerdes, A Martin

    2015-09-15

    Animal studies suggest that hypertension leads to cardiac tissue hypothyroidism, a condition that can by itself lead to heart failure. We have previously shown that short-term thyroid hormone treatment in Spontaneously Hypertensive Heart Failure (SHHF) rats near heart failure is beneficial. This study tested the hypothesis that therapeutic, long-term T3 treatment in SHHF rats can prevent or attenuate cardiac dysfunction. Female SHHF rats were treated orally with a physiological T3 dose (0.04 μg/ml) from 12 to 24 mo of age. Age-matched female SHHF and Wistar-Kyoto rats served as hypertensive and normotensive controls, respectively. SHHF rats had reduced serum free thyroid hormone levels and cardiac tissue T3 levels, LV dysfunction, and elevated LV collagen content compared with normotensive controls. Restoration of serum and cardiac tissue thyroid hormone levels in T3-treated rats was associated with no change in heart rate, but strong trends for improvement in LV systolic function and collagen levels. For instance, end-systolic diameter, fractional shortening, systolic wall stress, and LV collagen levels were no longer significantly different from controls. In conclusion, longstanding hypertension in rats led to chronic low serum and cardiac tissue thyroid hormone levels. Long-term treatment with low-dose T3 was safe. While cardiac dysfunction could not be completely prevented in the absence of antihypertensive treatment, T3 may offer additional benefits as an adjunct therapy with possible improvement in diastolic function. PMID:26254335

  17. Natriuretic Peptides as Cardiovascular Safety Biomarkers in Rats: Comparison With Blood Pressure, Heart Rate, and Heart Weight.

    PubMed

    Engle, Steven K; Watson, David E

    2016-02-01

    Cardiovascular (CV) toxicity is an important cause of failure during drug development. Blood-based biomarkers can be used to detect CV toxicity during preclinical development and prioritize compounds at lower risk of causing such toxicities. Evidence of myocardial degeneration can be detected by measuring concentrations of biomarkers such as cardiac troponin I and creatine kinase in blood; however, detection of functional changes in the CV system, such as blood pressure, generally requires studies in animals with surgically implanted pressure transducers. This is a significant limitation because sustained changes in blood pressure are often accompanied by changes in heart rate and together can lead to cardiac hypertrophy and myocardial degeneration in animals, and major adverse cardiovascular events (MACE) in humans. Increased concentrations of NPs in blood correlate with higher risk of cardiac mortality, all-cause mortality, and MACE in humans. Their utility as biomarkers of CV function and toxicity in rodents was investigated by exploring the relationships between plasma concentrations of NTproANP and NTproBNP, blood pressure, heart rate, and heart weight in Sprague Dawley rats administered compounds that caused hypotension or hypertension, including nifedipine, fluprostenol, minoxidil, L-NAME, L-thyroxine, or sunitinib for 1-2 weeks. Changes in NTproANP and/or NTproBNP concentrations were inversely correlated with changes in blood pressure. NTproANP and NTproBNP concentrations were inconsistently correlated with relative heart weights. In addition, increased heart rate was associated with increased heart weights. These studies support the use of natriuretic peptides and heart rate to detect changes in blood pressure and cardiac hypertrophy in short-duration rat studies. PMID:26609138

  18. Collagen remodeling after myocardial infarction in the rat heart.

    PubMed Central

    Cleutjens, J. P.; Verluyten, M. J.; Smiths, J. F.; Daemen, M. J.

    1995-01-01

    In this study changes in the amount and distribution of types I and III collagen mRNA and protein were investigated in the rat heart after induction of a left ventricular myocardial infarction (MI). Sham operated rats served as controls. The animals were sacrificed at different time intervals after operation. Northern blotting of cardiac RNA and hybridization with cDNA probes for types I and III procollagen revealed a 5- to 15-fold increase in the infarcted left ventricle. Type III procollagen mRNA levels were already increased at day 2 after MI, whereas type I procollagen mRNA followed this response at day 4 after MI. This increase was sustained for at least 21 days in the infarcted left ventricle for type III procollagen mRNA, whereas type 1 procollagen mRNA levels were still elevated at 90 days after MI. In the noninfarcted right ventricle a 5- to 7-fold increase was observed for both type I and type III procollagen mRNA levels, but only at day 4 after MI. In the non-infarcted septum a transient increase was observed for type I procollagen mRNA from day 7-21 (4- to 5-fold increase) and a decline to sham levels thereafter. In the septum type III procollagen mRNA levels were only elevated at 7 days after MI (4- to 5-fold increase) compared with sham operated controls. In situ hybridization with the same types I and III procollagen probes showed procollagen mRNA-producing cells in the infarcted area around necrotic cardiomyocytes, and in the interstitial cells in the non-infarcted part of the myocardium. No labeling was detected above cardiomyocytes. Combined in situ hybridization and immunohistochemistry showed that the collagen mRNA producing cells have a myofibroblast-like phenotype in the infarcted myocardium and are fibroblasts in the noninfarcted septum and right ventricle. The increase in types I and III procollagen mRNA in both infarcted and non-infarcted myocardium was followed by an increased collagen deposition, measured by computerized morphometry on

  19. Enhanced arrhythmogenicity of Freon 113 by hypoxia in the perfused rat heart

    SciTech Connect

    Kawakami, T.; Takano, T.; Araki, R. )

    1990-05-01

    The interaction of Freon 113 (1,1,2-trichloro-1,2,2-trifluoroethane) and hypoxia on the heart conduction system was studied using electrocardiogram monitoring of isolated perfused rat hearts. Freon 113 (0.2 mM) alone elicited significant atrioventricular conduction delay (p less than 0.05) and heart rate decrease (p less than 0.01), which were significantly enhanced by hypoxia (75% oxygen decrease), for instance, resulting in 2:1 AV block. The data suggest that arrhythmogenicity of Freon 113 on the heart conduction system may be enhanced synergistically by hypoxia.

  20. Notch-independent RBPJ controls angiogenesis in the adult heart

    PubMed Central

    Díaz-Trelles, Ramón; Scimia, Maria Cecilia; Bushway, Paul; Tran, Danh; Monosov, Anna; Monosov, Edward; Peterson, Kirk; Rentschler, Stacey; Cabrales, Pedro; Ruiz-Lozano, Pilar; Mercola, Mark

    2016-01-01

    Increasing angiogenesis has long been considered a therapeutic target for improving heart function after injury such as acute myocardial infarction. However, gene, protein and cell therapies to increase microvascularization have not been successful, most likely because the studies failed to achieve regulated and concerted expression of pro-angiogenic and angiostatic factors needed to produce functional microvasculature. Here, we report that the transcription factor RBPJ is a homoeostatic repressor of multiple pro-angiogenic and angiostatic factor genes in cardiomyocytes. RBPJ controls angiogenic factor gene expression independently of Notch by antagonizing the activity of hypoxia-inducible factors (HIFs). In contrast to previous strategies, the cardiomyocyte-specific deletion of Rbpj increased microvascularization of the heart without adversely affecting cardiac structure or function even into old age. Furthermore, the loss of RBPJ in cardiomyocytes increased hypoxia tolerance, improved heart function and decreased pathological remodelling after myocardial infarction, suggesting that inhibiting RBPJ might be therapeutic for ischaemic injury. PMID:27357444

  1. Perinatal taurine exposure programs patterns of autonomic nerve activity responses to tooth pulp stimulation in adult male rats

    PubMed Central

    Khimsuksri, Sawita; Wyss, J. Michael; Thaeomor, Atcharaporn; Paphangkorakit, Jarin; Jirakulsomchok, Dusit; Roysommuti, Sanya

    2016-01-01

    Perinatal taurine excess or deficit influences adult health and disease, especially relative to the autonomic nervous system. This study tests the hypothesis that perinatal taurine exposure influences adult autonomic nervous system control of arterial pressure in response to acute electrical tooth pulp stimulation. Female Sprague-Dawley rats were fed normal rat chow with 3% β-alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS) or water alone (control, C) from conception to weaning. Their male offspring were fed normal rat chow and tap water throughout the experiment. At 8–10 weeks of age, blood chemistry, arterial pressure, heart rate and renal sympathetic nerve activity were measured in anesthetized rats. Age, body weight, mean arterial pressure, heart rate, plasma electrolytes, blood urea nitrogen, plasma creatinine and plasma cortisol were not significantly different among the three groups. Before tooth pulp stimulation, low (0.3–0.5 Hz) and high frequency (0.5–4.0 Hz) power spectral densities of arterial pressure were not significantly different among groups, while the power spectral densities of renal sympathetic nerve activity were significantly decreased in TD compared to control rats. Tooth pulp stimulation did not change arterial pressure, heart rate, renal sympathetic nerve and arterial pressure power spectral densities in the 0.3–4.0 Hz spectrum or renal sympathetic nerve firing rate in any group. In contrast, perinatal taurine imbalance disturbed very low frequency power spectral densities of both arterial pressure and renal sympathetic nerve activity (below 0.1 Hz), both before and after the tooth pulp stimulation. The power densities of TS were most sensitive to ganglionic blockade and central adrenergic inhibition, while those of TD were sensitive to both central and peripheral adrenergic inhibition. The present data indicate that perinatal taurine imbalance can lead to aberrant autonomic nervous system responses in

  2. Congenital Heart Diseases in Adults: A Review of Echocardiogram Records in Enugu, South-East Nigeria

    PubMed Central

    Ejim, EC; Anisiuba, BC; Oguanobi, NI; Ubani-Ukoma, BC; Nwaneli, UC; Ugwu, C; Ike, SO

    2014-01-01

    Background: Congenital abnormalities of the heart and cardiovascular system are reported in almost 1% of live births, and about half of these children need medical or surgical help in infancy. In the first decade, a further 25% require surgery to maintain or improve their life. Only 10% survive to adolescence without treatment. Of these 10%, however, many live a normal life for years before their abnormality is discovered. Aim: The aim of this study was to find the most common congenital heart diseases in adults presenting for echocardiographic examination in Enugu, and to determine whether there are any gender differences in frequency. Materials and Methods: The consecutive echocardiogram reports of 5058 adults done over a period of 9 years (2003-2012) were retrospectively reviewed. All adults who had congenital anomaly on transthoracic echocardiography were included in the study. Results: Congenital heart diseases were found in 115 adults representing 2.5% of the adult population (115/4539). The most common congenital anomalies were ventricular septal defects (VSD) - 31.3%, (36/115), atrial septal defects - 28.7% (33/115) and tetralogy of fallot - 10.4% (12/115). Conclusion: VSD are the most common congenital heart diseases in adults presenting for echocardiographic examination in Enugu, Nigeria. PMID:25221697

  3. Theory of mind deficit in adult patients with congenital heart disease.

    PubMed

    Chiavarino, Claudia; Bianchino, Claudia; Brach-Prever, Silvia; Riggi, Chiara; Palumbo, Luigi; Bara, Bruno G; Bosco, Francesca M

    2015-10-01

    This article provides the first assessment of theory of mind, that is, the ability to reason about mental states, in adult patients with congenital heart disease. Patients with congenital heart disease and matched healthy controls were administered classical theory of mind tasks and a semi-structured interview which provides a multidimensional evaluation of theory of mind (Theory of Mind Assessment Scale). The patients with congenital heart disease performed worse than the controls on the Theory of Mind Assessment Scale, whereas they did as well as the control group on the classical theory-of-mind tasks. These findings provide the first evidence that adults with congenital heart disease may display specific impairments in theory of mind.

  4. 31P NMR spectroscopy of hypertrophied rat heart: effect of graded global ischemia.

    PubMed

    Clarke, K; Sunn, N; Willis, R J

    1989-12-01

    To investigate the cause for the greater susceptibility of hypertrophied hearts to ischemic injury, we determined the interrelations of total work output, contractile function and energy metabolism in isolated, perfused normal and hypertrophied rat hearts subjected to graded global ischemia. Cardiac hypertrophy was induced by giving rats seven daily injections of either triiodothyronine (0.2 mg/kg) or isoproterenol (5 mg/kg). All hearts were perfused at an aortic pressure of 100 mmHg in the isovolumic mode in an NMR spectrometer (7.05 Tesla). Heart rate, developed pressure, and coronary flow were monitored simultaneously with changes in pH, creatine phosphate, ATP and inorganic phosphate. During pre-ischemic perfusion, the total work output (rate-pressure product) of hyperthyroid hearts was 28% higher than that of control hearts, whereas hearts from isoproterenol-treated animals showed no difference. However, when related to unit muscle mass, work was normal in hyperthyroid hearts and 26% lower after isoproterenol. Contractile function per unit myocardium (developed pressure/g wet weight) was lower in the hypertrophied hearts. ATP content was the same in all groups. Creatine phosphate decreased 41% after triiodothyronine and 25% after isoproterenol. Inorganic phosphate levels and intracellular pH were similar in control and isoproterenol-treated rat hearts, but were higher in the hyperthyroid rat hearts. The phosphorylation potential and the free energy change of ATP hydrolysis were lowered by hypertrophy, the levels correlating with the depressed contractile function. At each ischemic flow rate, both work and contractile function per unit myocardium were the same for all hearts, but the relations between flow and phosphorylation potential were different for each type of heart. Thus, at low flow rates, hypertrophied hearts perform the same amount of work and have the same contractile function as control hearts, but with abnormal changes in energy metabolism

  5. The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats

    PubMed Central

    Morimoto, Tatsuya; Sunagawa, Yoichi; Kawamura, Teruhisa; Takaya, Tomohide; Wada, Hiromichi; Nagasawa, Atsushi; Komeda, Masashi; Fujita, Masatoshi; Shimatsu, Akira; Kita, Toru; Hasegawa, Koji

    2008-01-01

    Hemodynamic overload in the heart can trigger maladaptive hypertrophy of cardiomyocytes. A key signaling event in this process is nuclear acetylation by histone deacetylases and p300, an intrinsic histone acetyltransferase (HAT). It has been previously shown that curcumin, a polyphenol responsible for the yellow color of the spice turmeric, possesses HAT inhibitory activity with specificity for the p300/CREB-binding protein. We found that curcumin inhibited the hypertrophy-induced acetylation and DNA-binding abilities of GATA4, a hypertrophy-responsive transcription factor, in rat cardiomyocytes. Curcumin also disrupted the p300/GATA4 complex and repressed agonist- and p300-induced hypertrophic responses in these cells. Both the acetylated form of GATA4 and the relative levels of the p300/GATA4 complex markedly increased in rat hypertensive hearts in vivo. The effects of curcumin were examined in vivo in 2 different heart failure models: hypertensive heart disease in salt-sensitive Dahl rats and surgically induced myocardial infarction in rats. In both models, curcumin prevented deterioration of systolic function and heart failure–induced increases in both myocardial wall thickness and diameter. From these results, we conclude that inhibition of p300 HAT activity by the nontoxic dietary compound curcumin may provide a novel therapeutic strategy for heart failure in humans. PMID:18292809

  6. Combined effects of niacin and chromium treatment on heart of hyperlipidemic rats.

    PubMed

    Döger, M Mutluhan; Sokmen, Bahar B; Yanardag, Refiye

    2011-10-01

    The present study was undertaken to investigate the effects of the combination of niacin and chromium(III)-chloride on heart glutathione (GSH), lipid peroxidation (LPO) levels, serum paraoxonase (PON), gamma-glutamyl transferase (GGT) activities and protein carbonyl contents (PCC) of hyperlipidemic rats. In this study, female Swiss albino rats were used. They were divided into four groups. The animals of the first group (group I) were fed with pellet chow. The rats (group II) were fed with a lipogenic diet consisting of 2% cholesterol, 0.5% cholic acid and 20% sunflower oil added to the pellet chow, and given 3% alcoholic water for 60 days. The rats (group III) were fed with the same lipogenic diet and treated by gavage technique with CrCl(3) 6H(2)O to a dose of 250 µg/kg and 100 mg/kg niacin for 45 days, 15 days after experimental animals were done hyperlipidemic. Group IV was fed with pellet chow and treated with 250 µg/kg CrCl(3) 6H(2)O and 100 mg/kg niacin for 45 days. On the 60th day, the heart tissue and blood samples were taken from animals. As a result, heart LPO, serum GGT activity and serum PCC were increased; serum PON activity and heart GSH levels were decreased in hyperlipidemic rats. Treatment with combined niacin and chromium reversed these effects. In conclusion, the combined treatment with niacin and chromium might induce a protective effect on heart tissue.

  7. Analysis of proteome changes in doxorubicin-treated adult rat cardiomyocyte

    PubMed Central

    Kumar, Suresh N.; Konorev, Eugene A.; Aggarwal, Deepika; Kalyanaraman, Balaraman

    2011-01-01

    Doxorubicin-induced cardiomyopathy in cancer patients is well established. The proposed mechanism of cardiac damage includes generation of reactive oxygen species, mitochondrial dysfunction and cardiomyocyte apoptosis. Exposure of adult rat cardiomyocytes to low levels of DOX for 48 h induced apoptosis. Analysis of protein expression showed a differential regulation of several key proteins including the voltage dependent anion selective channel protein 2 and methylmalonate semialdehyde dehydrogenase. In comparison, proteomic evaluation of DOX-treated rat heart showed a slightly different set of protein changes that suggests nuclear accumulation of DOX. Using a new solubilization technique, changes in low abundant protein profiles were monitored. Altered protein expression, modification and function related to oxidative stress response may play an important role in DOX cardiotoxicity. PMID:21338723

  8. Hypothyroidism and oxidative stress: differential effect on the heart of virgin and pregnant rats.

    PubMed

    Carmona, Y V; Coria, M J; Oliveros, L B; Gimenez, M S

    2014-01-01

    The present study investigates the effects of hypothyroidism on both the redox state and the thyroid hormone receptors expression in the heart ventricle of virgin and pregnant rats.Hypothyroid state was induced by 6-n-propyl-2-thiouracil in drinking water given to Wistar rats starting 8 days before mating until day 21 of pregnancy or for 30 days in virgin rats. Serum paraoxonase-1 (PON-1) activity, serum and heart nitrites, and thiobarbituric acid-reactive substances (TBARS) were analyzed. Heart protein oxidation, as carbonyls, and copper-zinc superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx), and catalase (CAT) activities, were determined. In addition, heart expressions of NADPH oxidase (NOX-2), CAT, SOD, GPx, and thyroid receptors (TRα and TRβ) mRNA were assessed by RT-PCR. Inducible and endothelial Nitric Oxide Synthase (iNOS and eNOS) were determined by Western blot. Hypothyroidism in the heart of virgin rats decreased TRα and TRβ expressions, and induced oxidative stress, leading to a decrease of nitrites and an increase of carbonyls, NOX-2 mRNA, and GPx activity. A decreased PON-1 activity suggested low protection against oxidative stress in blood circulation. Pregnancy reduced TRα and TRβ mRNA expressions and induced oxidative stress by increasing nitrite and TBARS levels, SOD and CAT activities and NOX-2, eNOS and iNOS expressions, while hypothyroidism, emphasized the decreases of TRα mRNA levels and did not alter the redox state in the heart. TR expressions and redox balance of rat hearts depend on the physiological state. Pregnancy per se seems to protect the heart against oxidative stress induced by hypothyroidism. Supporting Information for this article is available online at http://www.thieme-connect.de/ejournals/toc/hmr.

  9. Effect of restraint and copper deficiency on blood pressure and mortality of adult rats

    SciTech Connect

    Klevay, L.M.; Halas, E.S. )

    1989-02-01

    The etiology of most hypertension is unknown; stress is thought to elevate blood pressure. Male, weanling Sprague-Dawley rats were fed a purified diet plus a drinking solution containing 10{mu}g Zn and 2{mu}g Cu/ml (acetate sulfate, respectively). Systolic blood pressure was measured without anesthesia. After being matched by mean weight (280g) and blood pressure into 4 groups of 15, groups 1 and 2 received a drinking solution without copper. After 24 days rats in groups 2 and 4 were restrained for 45 min. daily (A.M.) for 23 days in a small plastic cage (19{times}6{times}6 cm). Final pressures were affected both by stress and dietary Cu: group 1, 119; group 2, 131; group 3, 114; group 4, 123 mm Hg. One rat in each of groups 1, 3, 4 and 10 rats in group 2, died. Among these latter hemorrhage was prominent, blood being found in bladder (2), gut (2), peritoneum (2) and scrotum (1). Copper deficiency decreased cooper in both adrenal gland and liver by 58% and in heart by 29% restraint was without effect. Cardiac sodium was increased 6% only by deficiency. Results confirm the hypertensive effect of copper deficiency in adult rats and reveal that the stress of restraint increases blood pressure. Copper deficiency plus stress is harmful.

  10. Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

    SciTech Connect

    Weinberger, Florian Mehrkens, Dennis Starbatty, Jutta Nicol, Philipp Eschenhagen, Thomas

    2015-01-02

    Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.

  11. Dietary nitrate supplementation: impact on skeletal muscle vascular control in exercising rats with chronic heart failure.

    PubMed

    Ferguson, Scott K; Holdsworth, Clark T; Colburn, Trenton D; Wright, Jennifer L; Craig, Jesse C; Fees, Alex; Jones, Andrew M; Allen, Jason D; Musch, Timothy I; Poole, David C

    2016-09-01

    Chronic heart failure (CHF) results in central and peripheral derangements that ultimately reduce skeletal muscle O2 delivery and impair exercise tolerance. Dietary nitrate (NO3 (-)) supplementation improves skeletal muscle vascular function and tolerance to exercise. We tested the hypothesis that NO3 (-) supplementation would elevate exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats. Myocardial infarction (MI) was induced (coronary artery ligation) in young adult male rats. After 21 days of recovery, rats randomly received 5 days of NO3 (-)-rich beetroot juice (CHF + BR, n = 10) or a placebo (CHF, n = 10). Mean arterial pressure (carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% grade). CHF-induced dysfunction, as determined by myocardial infarction size (29 ± 3% and 33 ± 4% in CHF and CHF + BR, respectively) and left ventricular end-diastolic pressure (18 ± 2 and 18 ± 2 mmHg in CHF and CHF + BR, respectively), and exercising mean arterial pressure (131 ± 3 and 128 ± 4 mmHg in CHF and CHF + BR, respectively) were not different (P > 0.05) between groups. Total exercising hindlimb skeletal muscle BF (95 ± 5 and 116 ± 9 ml·min(-1)·100 g(-1) in CHF and CHF + BR, respectively) and VC (0.75 ± 0.05 and 0.90 ± 0.05 ml·min(-1)·100 g(-1)·mmHg(-1) in CHF and CHF + BR, respectively) were 22% and 20% greater in BR-supplemented rats, respectively (P < 0.05). During exercise, BF in 9 and VC in 10 hindlimb muscles and muscle portions were significantly greater in the CHF + BR group. These results provide strong evidence that dietary NO3 (-) supplementation improves skeletal muscle vascular function during exercise in rats with CHF and, thus, support the use of BR as a novel therapeutic modality for the treatment of CHF.

  12. The role of calcium-independent phospholipase A2 in cardiolipin remodeling in the spontaneously hypertensive heart failure rat heart.

    PubMed

    Zachman, Derek K; Chicco, Adam J; McCune, Sylvia A; Murphy, Robert C; Moore, Russell L; Sparagna, Genevieve C

    2010-03-01

    Cardiolipin (CL) is an essential phospholipid component of the inner mitochondrial membrane. In the mammalian heart, the functional form of CL is tetralinoleoyl CL [(18:2)(4)CL]. A decrease in (18:2)(4)CL content, which is believed to negatively impact mitochondrial energetics, occurs in heart failure (HF) and other mitochondrial diseases. Presumably, (18:2)(4)CL is generated by remodeling nascent CL in a series of deacylation-reacylation cycles; however, our overall understanding of CL remodeling is not yet complete. Herein, we present a novel cell culture method for investigating CL remodeling in myocytes isolated from Spontaneously Hypertensive HF rat hearts. Further, we use this method to examine the role of calcium-independent phospholipase A(2) (iPLA(2)) in CL remodeling in both HF and nonHF cardiomyocytes. Our results show that 18:2 incorporation into (18:2)(4)CL is: a) performed singly with respect to each fatty acyl moiety, b) attenuated in HF relative to nonHF, and c) partially sensitive to iPLA(2) inhibition by bromoenol lactone. These results suggest that CL remodeling occurs in a step-wise manner, that compromised 18:2 incorporation contributes to a reduction in (18:2)(4)CL in the failing rat heart, and that mitochondrial iPLA(2) plays a role in the remodeling of CL's acyl composition. PMID:19741254

  13. The role of calcium-independent phospholipase A2 in cardiolipin remodeling in the spontaneously hypertensive heart failure rat heart

    PubMed Central

    Zachman, Derek K.; Chicco, Adam J.; McCune, Sylvia A.; Murphy, Robert C.; Moore, Russell L.; Sparagna, Genevieve C.

    2010-01-01

    Cardiolipin (CL) is an essential phospholipid component of the inner mitochondrial membrane. In the mammalian heart, the functional form of CL is tetralinoleoyl CL [(18:2)4CL]. A decrease in (18:2)4CL content, which is believed to negatively impact mitochondrial energetics, occurs in heart failure (HF) and other mitochondrial diseases. Presumably, (18:2)4CL is generated by remodeling nascent CL in a series of deacylation-reacylation cycles; however, our overall understanding of CL remodeling is not yet complete. Herein, we present a novel cell culture method for investigating CL remodeling in myocytes isolated from Spontaneously Hypertensive HF rat hearts. Further, we use this method to examine the role of calcium-independent phospholipase A2 (iPLA2) in CL remodeling in both HF and nonHF cardiomyocytes. Our results show that 18:2 incorporation into (18:2)4CL is: a) performed singly with respect to each fatty acyl moiety, b) attenuated in HF relative to nonHF, and c) partially sensitive to iPLA2 inhibition by bromoenol lactone. These results suggest that CL remodeling occurs in a step-wise manner, that compromised 18:2 incorporation contributes to a reduction in (18:2)4CL in the failing rat heart, and that mitochondrial iPLA2 plays a role in the remodeling of CL's acyl composition. PMID:19741254

  14. Alteration of Na,K-ATPase subunit mRNA and protein levels in hypertrophied rat heart.

    PubMed

    Charlemagne, D; Orlowski, J; Oliviero, P; Rannou, F; Sainte Beuve, C; Swynghedauw, B; Lane, L K

    1994-01-14

    To determine if an altered expression of the Na,K-ATPase alpha isoform genes is responsible for an observed increase in cardiac glycoside sensitivity in compensatory hypertrophy, we performed Northern and slot blot analyses of RNA and specific immunological detection of Na,K-ATPase isoforms in rat hearts from normal and pressure overload-treated animals induced by abdominal aortic constriction. During the early phase of hypertrophy, the only alteration is a decrease in the alpha 2 mRNA isoform. In the compensated hypertrophied heart, the levels of the predominant alpha 1 isoform (mRNA and protein) and the beta 1 subunit mRNA are unchanged. In contrast, the alpha 2 isoform (mRNA and protein) is decreased by 35% and up to 61-64% in mild (< 55%) and severe (> 55%) hypertrophy, respectively. The alpha 3 isoform (mRNA and protein), which is extremely low in adult heart, is increased up to 2-fold during hypertrophy but accounts for only approximately equal to 5% of the total alpha isoform mRNA. These findings demonstrate that, in cardiac hypertrophy, the three alpha isoforms of the Na,K-ATPase are independently regulated and that regulation occurs at a pretranslational level. The pattern of expression in hypertrophied adult heart is similar to that of the neonatal heart where the inverse regulation between the alpha 2 and alpha 3 ouabain high affinity isoforms has been reported. This suggests that distinct regulatory mechanisms controlling Na,K-ATPase isoform expression may, at least in part, be involved in the sensitivity to cardiac glycosides. PMID:8288620

  15. Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

    SciTech Connect

    Montaigne, David; Marechal, Xavier; Baccouch, Riadh; Modine, Thomas; Preau, Sebastien; Zannis, Konstantinos; Marchetti, Philippe; Lancel, Steve; Neviere, Remi

    2010-05-01

    The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 muM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt{sub max} of 105 +- 8 mN/s in control hearts vs. 49 +- 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 +- 0.2 in control hearts vs. 2.2 +- 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 +- 1 muM cytochrome c/min/mg in control hearts vs. 14 +- 3 muM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.

  16. Orthotopic Heart Transplantation in an Adult Patient with Heterotaxy Syndrome: Surgical Implications.

    PubMed

    González-López, María-Teresa; Pérez-Caballero-Martínez, Ramón; Amoros-Rivera, Carlos; Zamorano-Serrano, José; Pita-Fernández, Ana-María; Gil-Jaurena, Juan-Miguel

    2015-12-01

    Modified techniques for orthotopic heart transplantation are mandatory when complex congenital anomalies are associated in adult patients. An unusual case of a heterotaxy syndrome and dilated cardiomyopathy following mitral ring annuloplasty is presented in a 62-year-old male. Orthotopic cardiac transplantation was performed by using a modified operative strategy: selective peripheral and central venous cannulation according to the thoraco-abdominal venous challenges, biatrial technique, and preservation of venous drainage via the native coronary sinus. We discuss the anatomical features of heterotaxy in adult patients and surgical approaches when heart transplantation is needed. PMID:26450654

  17. The Regulatory Role of Nuclear Factor Kappa B in the Heart of Hereditary Hypertriglyceridemic Rat

    PubMed Central

    Vranková, Stanislava; Barta, Andrej; Klimentová, Jana; Dovinová, Ima; Líšková, Silvia; Dobešová, Zdenka; Pecháňová, Oľga; Kuneš, Jaroslav; Zicha, Josef

    2016-01-01

    Activation of nuclear factor-κB (NF-κB) by increased production of reactive oxygen species (ROS) might induce transcription and expression of different antioxidant enzymes and also of nitric oxide synthase (NOS) isoforms. Thus, we aimed at studying the effect of NF-κB inhibition, caused by JSH-23 (4-methyl-N1-(3-phenyl-propyl)-benzene-1,2-diamine) injection, on ROS and NO generation in hereditary hypertriglyceridemic (HTG) rats. 12-week-old, male Wistar and HTG rats were treated with JSH-23 (bolus, 10 μmol, i.v.). After one week, blood pressure (BP), superoxide dismutase (SOD) activity, SOD1, endothelial NOS (eNOS), and NF-κB (p65) protein expressions were higher in the heart of HTG rats compared to control rats. On the other hand, NOS activity was decreased. In HTG rats, JSH-23 treatment increased BP and heart conjugated dienes (CD) concentration (measured as the marker of tissue oxidative damage). Concomitantly, SOD activity together with SOD1 expression was decreased, while NOS activity and eNOS protein expression were increased significantly. In conclusion, NF-κB inhibition in HTG rats led to decreased ROS degradation by SOD followed by increased oxidative damage in the heart and BP elevation. In these conditions, increased NO generation may represent rather a counterregulatory mechanism activated by ROS. Nevertheless, this mechanism was not sufficient enough to compensate BP increase in HTG rats. PMID:27148433

  18. Alternative Splicing Generates a Novel Truncated Cav1.2 Channel in Neonatal Rat Heart*

    PubMed Central

    Liao, Ping; Yu, Dejie; Hu, Zhenyu; Liang, Mui Cheng; Wang, Jue Jin; Yu, Chye Yun; Ng, Gandi; Yong, Tan Fong; Soon, Jia Lin; Chua, Yeow Leng; Soong, Tuck Wah

    2015-01-01

    L-type Cav1.2 Ca2+ channel undergoes extensive alternative splicing, generating functionally different channels. Alternatively spliced Cav1.2 Ca2+ channels have been found to be expressed in a tissue-specific manner or under pathological conditions. To provide a more comprehensive understanding of alternative splicing in Cav1.2 channel, we systematically investigated the splicing patterns in the neonatal and adult rat hearts. The neonatal heart expresses a novel 104-bp exon 33L at the IVS3-4 linker that is generated by the use of an alternative acceptor site. Inclusion of exon 33L causes frameshift and C-terminal truncation. Whole-cell electrophysiological recordings of Cav1.233L channels expressed in HEK 293 cells did not detect any current. However, when co-expressed with wild type Cav1.2 channels, Cav1.233L channels reduced the current density and altered the electrophysiological properties of the wild type Cav1.2 channels. Interestingly, the truncated 3.5-domain Cav1.233L channels also yielded a dominant negative effect on Cav1.3 channels, but not on Cav3.2 channels, suggesting that Cavβ subunits is required for Cav1.233L regulation. A biochemical study provided evidence that Cav1.233L channels enhanced protein degradation of wild type channels via the ubiquitin-proteasome system. Although the physiological significance of the Cav1.233L channels in neonatal heart is still unknown, our report demonstrates the ability of this novel truncated channel to modulate the activity of the functional Cav1.2 channels. Moreover, the human Cav1.2 channel also contains exon 33L that is developmentally regulated in heart. Unexpectedly, human exon 33L has a one-nucleotide insertion that allowed in-frame translation of a full Cav1.2 channel. An electrophysiological study showed that human Cav1.233L channel is a functional channel but conducts Ca2+ ions at a much lower level. PMID:25694430

  19. Characterization of the histamine releasing effect of neurotensin in the rat heart.

    PubMed

    Rioux, F; Kérouac, R; St-Pierre, S

    1985-01-01

    Bolus injections of neurotensin (NT) in the rat perfused heart elicited a transient, dose-dependent histamine release. The histamine releasing effect of NT appears to be independent of the heart rate and coronary perfusion pressure and it was not influenced by atropine, propanolol, prazosin, methysergide, ketanserin, indomethacin, morphine, lidocaine or by removal of the atria. However, it was potentiated by adenosine, inhibited by sub-stimulatory concentrations of NT and the mast cell membrane stabilizing drug cromoglycate but was unaltered by the calcium antagonist verapamil. The absence of calcium in the heart perfusate suppressed the histamine releasing effect of NT. These results suggest that the histamine releasing effect of NT in the rat heart results from a direct effect on ventricular mast cells and is calcium-dependent.

  20. Endoplasmic reticulum stress involved in heart and liver injury in iron-loaded rats.

    PubMed

    Lou, Li-Xia; Geng, Bin; Chen, Yu; Yu, Fang; Zhao, Jing; Tang, Chao-Shu

    2009-07-01

    1. Iron overload contributes to the pathogenesis of various diseases and directly induces tissue injury. In the present study, we investigated the relationship between heart and liver injury induced by iron overload and cellular endoplasmic reticulum (ER) stress to explore the molecular mechanism of iron overload-induced cellular injury. 2. Iron overload in rats was generated by intraperitoneal injection of iron-dextran chronically (30 mg/kg per day for 9 weeks) or acutely (300 mg/kg once). Tissue injury was assessed by determining serum lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, as well as malondialdehyde (MDA) content in the heart and liver. The ER stress response was analysed by expression of glucose-response protein 78 (GRP78) and activation of caspase 12. 3. In chronic iron-loaded rats, iron levels in the heart and liver were higher, by approximately 2- and 7.8-fold, respectively (P < 0.01), compared with control. Serum LDH, ALT and AST activity, as well as MDA content, GRP78 expression and caspase 12 activity in the heart and liver, were upregulated in chronically iron-loaded rats. In acute iron-loaded rats, iron content in the heart and liver was 51% and 63% higher than in controls (both P < 0.01). Serum LDH, ALT and AST activity, MDA content in the heart and liver and levels of ER stress markers were all increased in acute iron-loaded rats. N-Acetylcysteine (150 mg/kg, s.c.) lowered the levels of these parameters in acute iron-loaded rats. 4. The results of the present study indicate that ER stress may play an important role in iron-induced tissue injury and that reactive oxygen species may mediate the ER stress response in the pathogenesis of iron-overload cellular injury. PMID:19594550

  1. Juniperus communis Linn oil decreases oxidative stress and increases antioxidant enzymes in the heart of rats administered a diet rich in cholesterol.

    PubMed

    Gumral, Nurhan; Kumbul, Duygu Doguc; Aylak, Firdevs; Saygin, Mustafa; Savik, Emin

    2015-01-01

    It has been asserted that consumption of dietary cholesterol (Chol) raises atherosclerotic cardiovascular diseases and that Chol causes an increase in free radical production. Hypercholesterolemic diet has also been reported to cause changes in the antioxidant system. In our study, different doses of Juniperus communis Linn (JCL) oil, a tree species growing in Mediterranean and Isparta regions and having aromatic characteristics, were administered to rats; and the levels of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and thiobarbituric acid reactive substances assay (TBARS) were examined in the heart tissue of rats. In this study, 35 Wistar Albino male adult rats weighing approximately 250-300 g were used. The rats were divided into five groups of seven each. The control group was administered normal pellet chow, and the Chol group was administered pellet chow including 2% Chol, while 50 JCL, 100 JCL, and 200 JCL groups were administered 50, 100, and 200 mg/kg JCL oil dissolved in 0.5% sodium carboxy methyl cellulose, respectively, in addition to the pellet chow containing 2% Chol, by gavage. After 30 days, the experiment was terminated and the antioxidant enzyme activities were examined in the heart tissue of rats. While consumption of dietary Chol decreases the activities of SOD, GSH-Px, and CAT in heart tissue of rats (not significant), administeration of 200 mg/kg JCL oil in addition to Chol led to a significant increase in the activity of antioxidant enzymes. Administering Chol led to a significant increase in TBARS level. Administering 100 and 200 mg/kg JCL oil together with Chol prevented significantly the increase in lipid peroxides. As a result of the study, JCL oil showed oxidant-antioxidant effect in the heart tissue of rats.

  2. Leptin inhibits testosterone secretion from adult rat testis in vitro.

    PubMed

    Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

    1999-05-01

    Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed

  3. Leptin inhibits testosterone secretion from adult rat testis in vitro.

    PubMed

    Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

    1999-05-01

    Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed

  4. Ex vivo intracoronary gene transfer of adeno-associated virus 2 leads to superior transduction over serotypes 8 and 9 in rat heart transplants.

    PubMed

    Raissadati, Alireza; Jokinen, Janne J; Syrjälä, Simo O; Keränen, Mikko A I; Krebs, Rainer; Tuuminen, Raimo; Arnaudova, Ralica; Rouvinen, Eeva; Anisimov, Andrey; Soronen, Jarkko; Pajusola, Katri; Alitalo, Kari; Nykänen, Antti I; Lemström, Karl

    2013-11-01

    Heart transplant gene therapy requires vectors with long-lasting gene expression, high cardiotropism, and minimal pathological effects. Here, we examined transduction properties of ex vivo intracoronary delivery of adeno-associated virus (AAV) serotype 2, 8, and 9 in rat syngenic and allogenic heart transplants. Adult Dark Agouti (DA) rat hearts were intracoronarily perfused ex vivo with AAV2, AAV8, or AAV9 encoding firefly luciferase and transplanted heterotopically into the abdomen of syngenic DA or allogenic Wistar-Furth (WF) recipients. Serial in vivo bioluminescent imaging of syngraft and allograft recipients was performed for 6 months and 4 weeks, respectively. Grafts were removed for PCR-, RT-PCR, and luminometer analysis. In vivo bioluminescent imaging of recipients showed that AAV9 induced a prominent and stable luciferase activity in the abdomen, when compared with AAV2 and AAV8. However, ex vivo analyses revealed that intracoronary perfusion with AAV2 resulted in the highest heart transplant transduction levels in syngrafts and allografts. Ex vivo intracoronary delivery of AAV2 resulted in efficient transgene expression in heart transplants, whereas intracoronary AAV9 escapes into adjacent tissues. In terms of cardiac transduction, these results suggest AAV2 as a potential vector for gene therapy in preclinical heart transplants studies, and highlight the importance of delivery route in gene transfer studies.

  5. Effects of middle cerebral artery occlusion on baroreceptor reflex control of heart rate in the rat.

    PubMed

    Saad, M A; Huerta, F; Trancard, J; Elghozi, J L

    1989-07-01

    Neurons in the insular cortex have recently been shown to innervate medullary autonomic nuclei such as the nucleus tractus solitarii (NTS). The present study examines the effect of lesioning the insular cortex on baroreceptor-heart rate reflex in conscious rats. We did this by occluding the stem of the left proximal middle cerebral artery which causes a lesion of the insular and adjacent lateral frontoparietal cortices. Nine and 10 days after lesioning or sham operation, reflex heart rate responses were recorded following i.v. doses of the pressor agent phenylephrine and the depressor agent sodium nitroprusside. Baroreceptor reflex parameters were determined by computerized sigmoidal curve-fitting. The overall contribution of the sympathetic and the cardiac vagus were assessed by using peripherally acting muscarinic and beta-adrenoceptor antagonists, respectively. Lesioned rats were compared to sham-operated rats. Lesioning the insular cortex did not affect mean blood pressure and heart rate. However, the lesion selectively enhanced reflex vagal bradycardia that occurred when mean blood pressure was artificially elevated. A greater vagal bradycardia with no change in the upper plateau indicated that ischemia was acting entirely on the baroreflex-dependent vagal cardiac motoneurons. There was no effect on the sympathetic heart rate range but the normalized gain of the sympathetic component was increased in those lesioned rats. These observations suggest that the unilateral cortical lesion chronically affected the baroreceptor control of heart rate through mechanisms differentially affecting the vagus and the cardiac sympathetic nerves. PMID:2778268

  6. Myocardial pharmacokinetics of ebastine, a substrate for cytochrome P450 2J, in rat isolated heart

    PubMed Central

    Kang, W; Elitzer, S; Noh, K; Bednarek, T; Weiss, M

    2011-01-01

    BACKGROUND AND PURPOSE It is well established that cytochrome P450 2J (CYP2J) enzymes are expressed preferentially in the heart, and that ebastine is a substrate for CYP2J, but it is not known whether ebastine is metabolized in myocardium. Therefore, we investigated its pharmacokinetics in the rat isolated perfused heart. EXPERIMENTAL APPROACH Rat isolated hearts were perfused in the recirculating mode with ebastine for 130 min. The concentrations of ebastine and its metabolites, hydroxyebastine and carebastine, were measured using liquid chromatography with a tandem mass spectrometry. The data were analysed by a compartmental model. The time course of negative inotropic response was linked to ebastine concentration to determine the concentration–effect relationship. KEY RESULTS Ebastine was metabolized to an intermediate compound, hydroxyebastine, which was subsequently further metabolized to carebastine. No desalkylebastine was found. The kinetics of the sequential metabolism of ebastine was well described by the compartmental model. The EC50 of the negative inotropic effect of ebastine in rat isolated heart was much higher than free plasma concentrations in humans after clinical doses. CONCLUSIONS AND IMPLICATIONS The kinetics of ebastine conversion to carebastine via hydroxyebastine resembled that observed in human liver microsomes. The results may be of interest for functional characterization of CYP2J activity in rat heart. PMID:21410688

  7. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    SciTech Connect

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-03-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  8. Heart Rate Variability in Nonlinear Rats with Different Orientation and Exploratory Activity in the Open Field.

    PubMed

    Kur'yanova, E V; Teplyi, D L; Zhukova, Yu D; Zhukovina, N V

    2015-12-01

    The basic behavioral activity of nonlinear rats was evaluated from the sum of crossed peripheral and central squares and peripheral and central rearing postures in the open fi eld test. This index was low (<20 episodes), intermediate (20-29 episodes), or high (>30 episodes). Male rats with high score of orientation and exploratory activity were characterized by higher indexes of total heart rate variability than rats with low or intermediate activity. Specimens with a greater contribution of VLF waves into the total power spectrum of heart rate variability were shown to dominate among the rats with high behavioral activity. Our results are consistent with the notions of a suprasegmental nature of VLF waves.

  9. Distinct effects of inflammation on preconditioning and regeneration of the adult zebrafish heart

    PubMed Central

    de Preux Charles, Anne-Sophie; Bise, Thomas; Baier, Felix; Marro, Jan; Jaźwińska, Anna

    2016-01-01

    The adult heart is able to activate cardioprotective programmes and modifies its architecture in response to physiological or pathological changes. While mammalian cardiac remodelling often involves hypertrophic expansion, the adult zebrafish heart exploits hyperplastic growth. This capacity depends on the responsiveness of zebrafish cardiomyocytes to mitogenic signals throughout their entire life. Here, we have examined the role of inflammation on the stimulation of cell cycle activity in the context of heart preconditioning and regeneration. We used thoracotomy as a cardiac preconditioning model and cryoinjury as a model of cardiac infarction in the adult zebrafish. First, we performed a spatio-temporal characterization of leucocytes and cycling cardiac cells after thoracotomy. This analysis revealed a concomitance between the infiltration of inflammatory cells and the stimulation of the mitotic activity. However, decreasing the immune response using clodronate liposome injection, PLX3397 treatment or anti-inflammatory drugs surprisingly had no effect on the re-entry of cardiac cells into the cell cycle. In contrast, reducing inflammation using the same strategies after cryoinjury strongly impaired cardiac cell mitotic activity and the regenerative process. Taken together, our results show that, while the immune response is not necessary to induce cell-cycle activity in intact preconditioned hearts, inflammation is required for the regeneration of injured hearts in zebrafish. PMID:27440424

  10. Exercise prescription in adults with congenital heart disease: a long way to go

    PubMed Central

    Swan, L; Hillis, W

    2000-01-01

    OBJECTIVE—To determine if appropriate advice had been given to adults with congenital heart disease regarding safe and effective exercise, and to assess pre-existing misconceptions of the potential benefits and dangers of exercise.
DESIGN—An anonymous self assessment questionnaire.
SETTING—A tertiary referral clinic.
PATIENTS—99 adults (57 men, 42 women) with congenital heart disease, mean age 25.6 years.
MAIN OUTCOME MEASURES—The extent and nature of exercise advice given over previous years; a measure of current activity level compared with the American Heart Association recommendations; and an assessment of exercise limiting symptoms and a description of barriers to further exercise.
RESULTS—44% of the cohort assumed all exercise was safe despite their cardiac disease. A health care professional had only raised the issue of specific exercise advice in 28 cases. Of those given instruction it was more common to receive prohibitive advice (30%) than to be encouraged to take more exercise (19%). Despite this 61% were involved in some form of at least light exercise. The most prevalent barriers to exercise were current symptoms (32.3%), lack of interest in exercise (24.2%), and health fears (16.1%).
CONCLUSIONS—The education of adults with congenital heart disease regarding exercise and its potential benefits and limitations is suboptimal even in a specialist clinic.


Keywords: congenital heart defects; exercise prescription PMID:10814630

  11. Hydrogen-containing saline attenuates doxorubicin-induced heart failure in rats.

    PubMed

    Wu, Shujing; Zhu, Liqun; Yang, Jing; Fan, Zhixin; Dong, Yanli; Luan, Rui; Cai, Jingjing; Fu, Lu

    2014-08-01

    Interactions between doxorubicin (DOX) and iron generate reactive oxygen species and contribute to DOX-induced heart failure. Hydrogen, as a selective antioxidant, is a promising potential therapeutic option for the treatment of a variety of diseases. Therefore, we investigated the preventive effects of hydrogen treatment on DOX-induced heart failure in rats. We found that cardiac function was significantly improved and that the plasma levels of oxidative-stress markers and myocardial autophagic activity were decreased in animals treated with hydrogen-containing saline. Therefore, we conclude that hydrogen-containing saline may have beneficial effects for doxorubicin-induced heart failure.

  12. Metabolic Syndrome and Short-Term Heart Rate Variability in Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Chang, Yaw-Wen; Lin, Jin-Ding; Chen, Wei-Liang; Yen, Chia-Feng; Loh, Ching-Hui; Fang, Wen-Hui; Wu, Li-Wei

    2012-01-01

    Metabolic syndrome (MetS) increases the risk of cardiovascular events. Heart rate variability (HRV) represents autonomic functioning, and reduced HRV significantly increases cardiovascular mortality. The aims of the present paper are to assess the prevalence of MetS in adults with intellectual disabilities (ID), the difference in short-term HRV…

  13. Understanding age-based transition needs: Perspectives from adolescents and adults with congenital heart disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to explore the transition process in congenital heart disease (CHD) care through the perceived needs and concerns of adolescents (pretransition) and the experiential insight from adults (post-transition), in order to inform future transition initiatives and information ...

  14. Experience of decortication for restrictive hemodynamics in adults with congenital heart disease.

    PubMed

    Mizuno, Masanori; Ohuchi, Hideo; Kagisaki, Koji; Miyazaki, Aya; Ishibashi-Ueda, Hatsue; Yamada, Osamu

    2014-08-01

    We treated four postoperative adults with congenital heart disease with severe restrictive hemodynamics (RH), and performed decortication (DC) with the anticipation of some relief of the RH. The catheterizations before DC showed high central venous, and right and left ventricular end-diastolic pressures with "dip-and-plateau" pressure waveforms in the right and left ventricles. Upon myocardial histopathologic examination, moderate myocardial fibrotic change was demonstrated in two of three cases. DC led to decrease in type B natriuretic peptide levels in all cases, resulting in a decline in the central venous, right and left ventricular end-diastolic pressures in three cases. Successful DC-related relief of RH, dilatation of the ventricles with decline in central and end-diastolic pressures, was observed in only one case. Our limited DC-related hemodynamic improvement indicates a complexity of the severe RH, which may represent a unique intractable heart failure pathophysiology in intractable postoperative adult congenital heart disease.

  15. Attributing heart attack and stroke to "Old Age": Implications for subsequent health outcomes among older adults.

    PubMed

    Stewart, Tara L; Chipperfield, Judith G; Perry, Raymond P; Hamm, Jeremy M

    2016-01-01

    This study assessed the extent to which older adults attribute a recent heart attack/stroke to "old age," and examined consequences for subsequent lifestyle behavior and health-care service utilization. Community-dwelling adults (N = 57, ages 73-98 years) were interviewed about their heart attack/stroke, and an objective health registry provided data on health-care utilization over a 3-year period. Endorsement of "old age" as a cause of heart attack/stroke negatively predicted lifestyle behavior change, and positively predicted frequency of physician visits and likelihood of hospitalization over the subsequent 3 years. Findings suggest the importance of considering "old age" attributions in the context of cardiovascular health events.

  16. Transitioning the young adult with congenital heart disease for life-long medical care.

    PubMed

    Fernandes, Susan M; Landzberg, Michael J

    2004-12-01

    Guidelines for the successful orchestration of transitioning of the adolescent and young and older adult patient with congenital heart disease to a health care system appropriate for their long-term congenital heart disease care and counseling appear necessary to improve patient and family confidence, education, therapy, life quality, and survival outcomes. Schema for care organization and delivery for adult patients with congenital heart disease remain primitive and largely unimplemented. The presence of a strong central care oversight organization and the establishment of a multi-institutional database to assist in assessment of care outcomes and guidelines appears requisite to these needs and for the establishment of transitioning guidelines for these patients as they assume a greater and deeper shared control of their futures with their caregivers.

  17. Direct cardiac effects of dobutamine, dopamine, epinephrine, and levosimendan in isolated septic rat hearts.

    PubMed

    Zausig, York A; Geilfus, Diana; Missler, Goetz; Sinner, Barbara; Graf, Bernhard M; Zink, Wolfgang

    2010-09-01

    In septic patients, myocardial depression-the so-called septic cardiomyopathy-needing inotropic support is common. The aim of this study was to compare the dose-responsive electrophysiological and mechanical properties concerning metabolic effects of clinically available inotropic agents in an isolated septic rat heart model. After 20 h of incubation, both sham-operated and septic (cecal ligation and single puncture) hearts from male Wistar rats (n = 64) were isolated and received dobutamine, dopamine, epinephrine, or levosimendan at concentrations of 10 to 10 M. Electrophysiological, mechanical, and metabolic properties were measured, and the myocardial oxygen supply-demand ratio and cardiac efficiency were calculated. With the exception of levosimendan, all of the drugs tested showed dose-dependent, significantly positive changes in chronotropy, inotropy, and lusitropy in all hearts. Maximum increases in septic hearts were dose-dependent and were ordered as follows: epinephrine > dopamine > dobutamine > levosimendan. These increases in cardiac performance were accompanied by a decrease in the myocardial oxygen supply-demand ratio. However, cardiac efficiency was significantly improved in the epinephrine-treated septic hearts. With the drug-induced increase in cardiac performance, the myocardial oxygen supply-demand ratio decreased proportionally in the epinephrine-, dobutamine-, and dopamine-treated septic hearts. However, epinephrine showed the most favorable results with regard to cardiac efficiency, and levosimendan showed no beneficial effect in septic hearts with regard to efficiency in this study.

  18. Multiscale entropy analysis of heart rate variability in heart failure, hypertensive, and sinoaortic-denervated rats: classical and refined approaches.

    PubMed

    Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Castania, Jaci Airton; da Silva, Carlos Alberto Aguiar; Valencia, Jose Fernando; Murta, Luiz Otavio; Salgado, Helio Cesar; Fazan, Rubens; Porta, Alberto

    2016-07-01

    The analysis of heart rate variability (HRV) by nonlinear methods has been gaining increasing interest due to their ability to quantify the complexity of cardiovascular regulation. In this study, multiscale entropy (MSE) and refined MSE (RMSE) were applied to track the complexity of HRV as a function of time scale in three pathological conscious animal models: rats with heart failure (HF), spontaneously hypertensive rats (SHR), and rats with sinoaortic denervation (SAD). Results showed that HF did not change HRV complexity, although there was a tendency to decrease the entropy in HF animals. On the other hand, SHR group was characterized by reduced complexity at long time scales, whereas SAD animals exhibited a smaller short- and long-term irregularity. We propose that short time scales (1 to 4), accounting for fast oscillations, are more related to vagal and respiratory control, whereas long time scales (5 to 20), accounting for slow oscillations, are more related to sympathetic control. The increased sympathetic modulation is probably the main reason for the lower entropy observed at high scales for both SHR and SAD groups, acting as a negative factor for the cardiovascular complexity. This study highlights the contribution of the multiscale complexity analysis of HRV for understanding the physiological mechanisms involved in cardiovascular regulation.

  19. Cardiac and renal distribution of ACE and ACE-2 in rats with heart failure.

    PubMed

    Cohen-Segev, Ravit; Francis, Bahaa; Abu-Saleh, Niroz; Awad, Hoda; Lazarovich, Aviva; Kabala, Aviva; Aronson, Doron; Abassi, Zaid

    2014-10-01

    Congestive heart failure is often associated with impaired kidney function. Over-activation of the renin-angiotensin-aldosterone system (RAAS) contributes to avid salt and water retention in heart failure. While the expression of angiotensin converting enzyme (ACE), a key enzyme in the synthesis of angiotensin II (Ang II), is well established, the expression of angiotensin converting enzyme-2 (ACE-2), an enzyme responsible for angiotensin 1-7 generation, is largely unknown. This issue is of a special interest since angiotensin 1-7 counteracts many of the proliferative and hypertensive effects of angiotensin II. Therefore, the present study was designed to investigate the expression of both enzymes in the kidney and heart of rats with heart failure. Heart failure (CHF) was induced in male Sprague Dawley rats (n=9) by the creation of a surgical aorto-caval fistula. Sham-operated rats served as controls (n=8). Two weeks after surgery, the animals were sacrificed and their hearts and kidneys were harvested for assessment of cardiac remodeling and ACE and ACE-2 immunoreactivity by immunohistochemical staining. ACE immunostaining was significantly increased in the kidneys (4.34 ± 0.39% vs. 2.96 ± 0.40%, P<0.05) and hearts (4.57 ± 0.54% vs. 2.19 ± 0.37%, P<0.01) of CHF rats as compared with their sham controls. In a similar manner, ACE-2 immunoreactivity was also elevated in the kidneys (4.65 ± 1.17% vs. 1.75 ± 0.29%, P<0.05) and hearts (5.48 ± 1.11% vs. 1.13 ± 0.26%, P<0.01) of CHF rats as compared with their healthy controls. This study showed that both ACE and ACE-2 are overexpressed in the cardiac and renal tissues of animals with heart failure as compared with their sham controls. The increased expression of the beneficial ACE-2 in heart failure may serve as a compensatory response to the over-activity of the deleterious isoform, namely, angiotensin converting enzyme 1(ACE-1).

  20. Home Health Care With Telemonitoring Improves Health Status for Older Adults with Heart Failure

    PubMed Central

    Madigan, Elizabeth; Schmotzer, Brian J.; Struk, Cynthia J.; DiCarlo, Christina M.; Kikano, George; Piña, Ileana L.; Boxer, Rebecca S.

    2014-01-01

    Home telemonitoring can augment home health care services during a patient's transition from hospital to home. Home health care agencies commonly use telemonitors for patients with heart failure although studies have shown mixed results in the use of telemonitors to reduce rehospitalizations. This randomized trial investigated if older patients with heart failure admitted to home health care following a hospitalization would have a reduction in rehospitalizations and improved health status if they received telemonitoring. Patients were followed up to 180 days post-discharge from home health care services. Results showed no difference in the time to rehospitalizations or emergency visits between those who received a telemonitoring vs. usual care. Older heart failure patients who received telemonitoring had better health status by home health care discharge than those who received usual care. Therefore for older adults with heart failure telemonitoring may be important adjunct to home health care services to improve health status. PMID:23438509

  1. Effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart.

    PubMed

    Kansal, Sunil Kumar; Jyoti, Uma; Sharma, Samridhi; Kaura, Arun; Deshmukh, Rahul; Goyal, Sandeep

    2015-06-01

    Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 μM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 μM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion. PMID:25743572

  2. Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

    PubMed

    Ferreira, Gabriela Kozuchovski; Cardoso, Eria; Vuolo, Francieli Silva; Michels, Monique; Zanoni, Elton Torres; Carvalho-Silva, Milena; Gomes, Lara Mezari; Dal-Pizzol, Felipe; Rezin, Gislaine Tezza; Streck, Emilio L; Paula, Marcos Marques da Silva

    2015-12-01

    This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism. PMID:26583437

  3. Gold nanoparticles alter parameters of oxidative stress and energy metabolism in organs of adult rats.

    PubMed

    Ferreira, Gabriela Kozuchovski; Cardoso, Eria; Vuolo, Francieli Silva; Michels, Monique; Zanoni, Elton Torres; Carvalho-Silva, Milena; Gomes, Lara Mezari; Dal-Pizzol, Felipe; Rezin, Gislaine Tezza; Streck, Emilio L; Paula, Marcos Marques da Silva

    2015-12-01

    This study evaluated the parameters of oxidative stress and energy metabolism after the acute and long-term administration of gold nanoparticles (GNPs, 10 and 30 nm in diameter) in different organs of rats. Adult male Wistar rats received a single intraperitoneal injection or repeated injections (once daily for 28 days) of saline solution, GNPs-10 or GNPs-30. Twenty-four hours after the last administration, the animals were killed, and the liver, kidney, and heart were isolated for biochemical analysis. We demonstrated that acute administration of GNPs-30 increased the TBARS levels, and that GNPs-10 increased the carbonyl protein levels. The long-term administration of GNPs-10 increased the TBARS levels, and the carbonyl protein levels were increased by GNPs-30. Acute administration of GNPs-10 and GNPs-30 increased SOD activity. Long-term administration of GNPs-30 increased SOD activity. Acute administration of GNPs-10 decreased the activity of CAT, whereas long-term administration of GNP-10 and GNP-30 altered CAT activity randomly. Our results also demonstrated that acute GNPs-30 administration decreased energy metabolism, especially in the liver and heart. Long-term GNPs-10 administration increased energy metabolism in the liver and decreased energy metabolism in the kidney and heart, whereas long-term GNPs-30 administration increased energy metabolism in the heart. The results of our study are consistent with other studies conducted in our research group and reinforce the fact that GNPs can lead to oxidative damage, which is responsible for DNA damage and alterations in energy metabolism.

  4. Effects of Melatonin and Epiphyseal Proteins on Fluoride-Induced Adverse Changes in Antioxidant Status of Heart, Liver, and Kidney of Rats

    PubMed Central

    Bharti, Vijay K.; Srivastava, R. S.; Kumar, H.; Bag, S.; Majumdar, A. C.; Singh, G.; Pandi-Perumal, S. R.; Brown, Gregory M.

    2014-01-01

    Several experimental and clinical reports indicated the oxidative stress-mediated adverse changes in vital organs of human and animal in fluoride (F) toxicity. Therefore, the present study was undertaken to evaluate the therapeutic effect of buffalo (Bubalus bubalis) epiphyseal (pineal) proteins (BEP) and melatonin (MEL) against F-induced oxidative stress in heart, liver, and kidney of experimental adult female rats. To accomplish this experimental objective, twenty-four adult female Wistar rats (123–143 g body weights) were divided into four groups, namely, control, F, F + BEP, and F + MEL and were administered sodium fluoride (NaF, 150 ppm elemental F in drinking water), MEL (10 mg/kg BW, i.p.), and BEP (100 µg/kg BW, i.p.) for 28 days. There were significantly (P < 0.05) high levels of lipid peroxidation and catalase and low levels of reduced glutathione, superoxide dismutase, glutathione reductase, and glutathione peroxidase in cardiac, hepatic, and renal tissues of F-treated rats. Administration of BEP and MEL in F-treated rats, however, significantly (P < 0.05) attenuated these adverse changes in all the target components of antioxidant defense system of cardiac, hepatic, and renal tissues. The present data suggest that F can induce oxidative stress in liver, heart, and kidney of female rats which may be a mechanism in F toxicity and these adverse effects can be ameliorated by buffalo (Bubalus bubalis) epiphyseal proteins and melatonin by upregulation of antioxidant defense system of heart, liver, and kidney of rats. PMID:24790596

  5. Effects of melatonin and epiphyseal proteins on fluoride-induced adverse changes in antioxidant status of heart, liver, and kidney of rats.

    PubMed

    Bharti, Vijay K; Srivastava, R S; Kumar, H; Bag, S; Majumdar, A C; Singh, G; Pandi-Perumal, S R; Brown, Gregory M

    2014-01-01

    Several experimental and clinical reports indicated the oxidative stress-mediated adverse changes in vital organs of human and animal in fluoride (F) toxicity. Therefore, the present study was undertaken to evaluate the therapeutic effect of buffalo (Bubalus bubalis) epiphyseal (pineal) proteins (BEP) and melatonin (MEL) against F-induced oxidative stress in heart, liver, and kidney of experimental adult female rats. To accomplish this experimental objective, twenty-four adult female Wistar rats (123-143 g body weights) were divided into four groups, namely, control, F, F + BEP, and F + MEL and were administered sodium fluoride (NaF, 150 ppm elemental F in drinking water), MEL (10 mg/kg BW, i.p.), and BEP (100 µg/kg BW, i.p.) for 28 days. There were significantly (P < 0.05) high levels of lipid peroxidation and catalase and low levels of reduced glutathione, superoxide dismutase, glutathione reductase, and glutathione peroxidase in cardiac, hepatic, and renal tissues of F-treated rats. Administration of BEP and MEL in F-treated rats, however, significantly (P < 0.05) attenuated these adverse changes in all the target components of antioxidant defense system of cardiac, hepatic, and renal tissues. The present data suggest that F can induce oxidative stress in liver, heart, and kidney of female rats which may be a mechanism in F toxicity and these adverse effects can be ameliorated by buffalo (Bubalus bubalis) epiphyseal proteins and melatonin by upregulation of antioxidant defense system of heart, liver, and kidney of rats.

  6. Enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with heart failure induced by adriamycin.

    PubMed

    Zhang, Shujuan; Zhang, Feng; Sun, Haijian; Zhou, Yebo; Han, Ying

    2012-11-01

    Our previous studies have shown that the cardiac sympathetic afferent reflex is enhanced in rats with chronic heart failure (CHF) induced by coronary artery ligation and contributes to the over-excitation of sympathetic activity. We sought to determine whether sympathetic activity and cardiac sympathetic afferent reflex were enhanced in adriamycin-induced CHF and whether angiotensin II (Ang II) in the paraventricular nucleus (PVN) was involved in enhancing sympathetic activity and cardiac sympathetic afferent reflex. Heart failure was induced by intraperitoneal injection of adriamycin for six times during 2 weeks (15 mg/kg). Six weeks after the first injection, the rats underwent anesthesia with urethane and α-chloralose. After vagotomy and baroreceptor denervation, cardiac sympathetic afferent reflex was evaluated by renal sympathetic nerve activity and mean arterial pressure (MAP) response to epicardial application of capsaicin (1.0 nmol). The response of MAP to ganglionic blockade with hexamethonium in conscious rats was performed to evaluate sympathetic activity. The renal sympathetic nerve activity and cardiac sympathetic afferent reflex were enhanced in adriamycin rats and the maximum depressor response of MAP induced by hexamethonium was significantly greater in adriamycin rats than that in control rats. Bilateral PVN microinjection of angiotensin II (Ang II) caused larger responses of the cardiac sympathetic afferent reflex, baseline renal sympathetic nerve activity and MAP in adriamycin rats than control rats. These results indicated that both sympathetic activity and cardiac sympathetic afferent reflex were enhanced and Ang II in the PVN was involved in the enhanced sympathetic activity and cardiac sympathetic afferent reflex in rats with adriamycin-induced heart failure. PMID:23554781

  7. Morphological features of adult rats of IS/Kyo and IS-Tlk/Kyo strains with lumbar and caudal vertebral anomalies.

    PubMed

    Takano, Masao; Ogawa, Emi; Saitou, Tsubasa; Yamaguchi, Yuko; Asano, Yuzo; Serikawa, Tadao; Kuramoto, Takashi

    2014-01-01

    IS-Tlk/Kyo, a mutant derived from IS/Kyo strain, exhibits a kinked and/or short tail, in addition to the congenital lumbar vertebral anomaly. Homozygotes of Tlk dominant gene are known to die during embryonic development. We previously reported the morphological features of the skeleton in IS/Kyo and IS-Tlk/Kyo fetuses and of the heart in IS/Kyo fetuses [19]. This study was conducted to clarify the morphological features of the skeleton in both adult rats and of the heart in adult IS/Kyo rats. Ventricular septal defect (VSD) was observed in 3 out of 10 IS/Kyo rats. Neither splitting of lumbar vertebra and supernumerary rib (in both strains) nor fused or absent caudal cartilage (in IS-Tlk/Kyo strain) was detected in adult rats. Fusion of lumbar vertebrae was observed in almost all specimens together with lumbarization of sacral vertebrae in a few specimens in both adult rats as well as fusion of sacral and caudal vertebrae only in adult IS-Tlk/Kyo rats. In addition, a severe reduction in the ossified sacral and caudal vertebrae was noted in adult IS-Tlk/Kyo rats (mean number: 20.6) and IS/Kyo rats (31.8), and the difference was similar to that in the length of sacral and caudal vertebrae. These results suggest that the Tlk gene may be involved in both the congenital and acquired abnormal formation of the lower vertebral centra as well as the persistent occurrence of VSD by the background gene in IS/Kyo strain.

  8. Differential rate responses to nicotine in rat heart: evidence for two classes of nicotinic receptors.

    PubMed

    Ji, Susan; Tosaka, Toshimasa; Whitfield, Bernard H; Katchman, Alexander N; Kandil, Abdurrahman; Knollmann, Bjoern C; Ebert, Steven N

    2002-06-01

    Nicotinic acetylcholine receptors are pentameric, typically being composed of two or more different subunits. To investigate which receptor subtypes are active in the heart, we initiated a series of experiments using an isolated perfused rat heart (Langendorff) preparation. Nicotine administration (100 microM) caused a brief decrease (-7 +/- 2%) followed by a much larger increase (17 +/- 5%) in heart rate that slowly returned to baseline within 10 to 15 min. The nicotine-induced decrease in heart rate could be abolished by an alpha7-specific antagonist, alpha-bungarotoxin (100 nM). In contrast, the nicotine-induced increase in heart rate persisted in the presence of alpha-bungarotoxin. These results suggest that the nicotinic acetylcholine receptors (nAChRs) that mediate the initial decrease in heart rate probably contain alpha7 subunits, whereas those that mediate the increase in heart rate probably do not contain alpha7 subunits. To investigate which subunits may contribute to the nicotine-induced increase in heart rate, we repeated our experiments with cytisine, an agonist at nAChRs that contain beta4 subunits. The cytisine results were similar to those obtained with nicotine, thereby suggesting that the nAChRs on sympathetic nerve terminals in the heart probably contain beta4 subunits. Thus, the results of this study show that pharmacologically distinct nAChRs are responsible for the differential effects of nicotine on heart rate. More specifically, our results suggest that alpha7 subunits participate in the initial nicotine-induced heart rate decrease, whereas beta4 subunits help to mediate the subsequent nicotine-induced rise in heart rate.

  9. The respiration and calcium content of heart mitochondria from rats with vitamin D-induced cardionecrosis.

    PubMed Central

    Zydowo, M M; Swierczyński, J; Nagel, G; Wrzołkowa, T

    1985-01-01

    Mitochondria were isolated from the heart and skeletal muscle of rats treated with three consecutive daily doses of 100 000 i.u. of calciol (cholecalciferol; 'vitamin D3'). On the fourth day after the last dose, cardiac necrosis developed. At that time mitochondria isolated from heart displayed a 10-fold higher Ca2+ content and a 6-fold lower respiratory rate with pyruvate-plus-malate as substrate as well as with other NAD-dependent substrates. No decrease in respiratory rate with succinate as substrate was observed. EDTA (5 mM) added to the medium during the isolation procedure restored both the high respiratory rate with pyruvate + malate and the low Ca2+ content of the heart mitochondria. The addition of 1 mM-CaCl2 to the medium in which a healthy (control) rat heart had been homogenized caused the same impairment of the mitochondria as did calciol treatment of the animals. No changes of mitochondria isolated from skeletal muscle were observed in rats treated with calciol. It is concluded that the heart mitochondria in vivo fail to accumulate Ca2+ from the cardiac cell overloaded with Ca2+ as the consequence of calciol treatment. Mitochondrial Ca2+ accumulation occurs during the isolation procedure unless an appropriate amount of chelating agent is added to the homogenization medium. The implication of these findings for the biochemical sequence of events in the calciol-induced cardiac necrosis is discussed. Images Fig. 1. PMID:2983684

  10. Reproductive toxicity of DDT in adult male rats.

    PubMed

    Ben Rhouma, K; Tébourbi, O; Krichah, R; Sakly, M

    2001-08-01

    The reproductive toxicity of DDT was investigated in adult male rats exposed to 50 and 100 mg/kg body weight (b.wt) day(-1) for 10 successive days. Compared with control animals, administration of DDT led to a dose-dependent reduction of testicular weight and the number as well as the percentage of motile spermatozoa in the epididymis. Testicular histological observations revealed also a marked loss of gametes in the lumen of seminiferous tubules. In DDT-treated rats, the seminal vesicles weights dropped significantly, resulting from a decrease of testosterone production by testes, whereas serum LH and FSH increased after pesticide exposure. This increase of gonadotrophin levels may be related to an impairment of the negative feedback exerted by the steroid on the hypothalamic--pituitary axis. It is concluded that DDT induced adverse effects on male rat fertility by acting directly on the testes and altering the neuroendocrine function.

  11. Toxicity of zinc oxide nanoparticles on adult male Wistar rats.

    PubMed

    Abbasalipourkabir, Roghayeh; Moradi, Hemen; Zarei, Sadegh; Asadi, Soheila; Salehzadeh, Aref; Ghafourikhosroshahi, Abolfazl; Mortazavi, Motahareh; Ziamajidi, Nasrin

    2015-10-01

    The purpose of this study was to investigate the effects of zinc oxide nanoparticles (nZnO) on adult male Wistar rats. Thirty male Wistar rats divided into five groups of six animals each were used for this study. For ten days, Groups one to four continuously received 50, 100, 150 and 200 mg/kg nZnO, respectively. Group five served as the control group. At the end of the study, the rats were sacrificed and histopathological study of the liver and renal tissue, sperm analysis, serum oxidative stress parameters and some liver enzymes were done. The results of this study showed that nZnO at concentration more than 50 mg/kg lead to significant changes in liver enzymes, oxidative stress, liver and renal tissue and sperm quality and quantity. In conclusion, the toxicity of nZnO is more significant when the concentration is increased; however, the use of low doses requires further investigation.

  12. Arrhythmias in Adult Congenital Heart Disease: Diagnosis and Management.

    PubMed

    Kumar, Saurabh; Tedrow, Usha B; Triedman, John K

    2015-11-01

    Cardiac arrhythmias are a major source of morbidity and mortality in adults with CHD. A multidisciplinary approach in a center specializing in the care of ACHD is most likely to have the expertise needed provide this care. Knowledge of the underlying anatomy, mechanism of arrhythmia, and potential management strategies is critical, as well as access and expertise in the use of advanced imaging and ablative technologies. Future challenges in management include refining the underlying mechanism and putative ablation targets for catheter ablation of AF, an arrhythmia rapidly rising in prevalence in this population.

  13. Protection of isolated perfused working rat heart from oxidative stress by exogenous L-propionyl carnitine.

    PubMed

    Ronca, G; Ronca, F; Yu, G; Zucchi, R; Bertelli, A

    1992-01-01

    The effect of exogenous L-propionyl carnitine on peroxidative injury was investigated on isolated working rat hearts. The addition of 190 microM hydrogen peroxide to the perfusion buffer caused a marked decrease in aortic flow, minute work and peak aortic pressure, and a release of intracellular enzymes. In the presence of L-propionyl carnitine the haemodynamic damage was significantly lower and enzyme leakage remarkably decreased. The protection was concentration-dependent and the whole structure of the molecule was required, since carnitine alone was found less effective and propionate had no effect. In the absence of hydrogen peroxide L-propionyl carnitine increased heart performance. The effect of L-propionyl carnitine on oxidative stress could account for the beneficial effect of this substance in different models of ischaemic injury. L-propionyl carnitine increases the cardiac performance and protects the rat heart from peroxidation through metabolic and antiperoxidative mechanisms. PMID:1308473

  14. Histomorphometric evaluation of renal glomeruli exposed to sustained delivery of estrogen using adult ovariectomized rats.

    PubMed

    Hafez, Naiel A; Benghuzzi, Hamed; Tucci, Michelle

    2003-01-01

    Hormonal replacement therapy (HRT) has shown to be efficacious in treatment and preventing of heart disease, osteoporosis and reducing mortality in postmenopausal and ovariectomized females. Several attempts to utilize the native estrogen and its analogs such as Depo-Provera, conjugated estrogen and estrogen benzoate have shown different physiological responses. In addition, the route of administration and its mode of action is lacking in the literature. The specific objective of this study was to investigate the role of sustained delivery of estrogen on the functional and structural capacity of the kidney using adult female rats as a model. A total of 24 adult female rats were subdivided into four equal groups. Groups I and II were ovariectomized (OVX) by following standard laboratory surgical procedures. Each rat in groups II and III (intact) were implanted with tricalcium phosphate lysine (TCPL) drug delivery system loaded with 40 mg of estrogen. Rats in group IV were unimplanted and untreated to be served as a control group. At the end of 45 days post treatment the animals were sacrificed by using overdose of Halothane and assured by cervical dislocation. Vital and reproductive organs were retrieved, weighed and subjected to H&E staining procedure. The results of this investigation suggest: (i) TCPL delivery system released estrogen at a sustained level for 45 days without any untoward response, (ii) the wet weights of kidneys (normalized to body weight) were increased (p < 0.05) in intact rats treated with estrogen compared to control, (iii) sustained delivery of estrogen resulted in a maintenance of kidney weights compared to the control level, however, the lack of estrogen treatment resulted in a remarkable regression in the kidney weights of OVX rats, (iv) the ratio of renal arteries-diameter (normalized to arterial wall thickness) was significantly increased in intact rats treated with estrogen compared to the control and other experimental groups, (v

  15. Renal and cardiac neuropeptide Y and NPY receptors in a rat model of congestive heart failure.

    PubMed

    Callanan, Ean Y; Lee, Edward W; Tilan, Jason U; Winaver, Joseph; Haramati, Aviad; Mulroney, Susan E; Zukowska, Zofia

    2007-12-01

    Neuropeptide Y (NPY) is coreleased with norepinephrine and stimulates vasoconstriction, vascular and cardiomyocyte hypertrophy via Y1 receptors (R) and angiogenesis via Y2R. Although circulating NPY is elevated in heart failure, NPY's role remains unclear. Activation of the NPY system was determined in Wistar rats with the aortocaval (A-V) fistula model of high-output heart failure. Plasma NPY levels were elevated in A-V fistula animals (115.7 +/- 15.3 vs. 63.1 +/- 17.4 pM in sham, P < 0.04). Animals either compensated [urinary Na(+) excretion returning to normal with moderate disease (COMP)] or remained decompensated with severe cardiac and renal failure (urinary Na(+) excretion <0.5 meq/day), increased heart weight, decreased mean arterial pressure and renal blood flow (RBF), and death within 5-7 days (DECOMP). Cardiac and renal tissue NPY decreased with heart failure, proportionate to the severity of renal complications. Cardiac and renal Y1R mRNA expression also decreased (1.5-fold, P < 0.005) in rats with heart failure. In contrast, Y2R expression increased up to 72-fold in the heart and 5.7-fold in the kidney (P < 0.001) proportionate to severity of heart failure and cardiac hypertrophy. Changes in receptor expression were confirmed since the Y1R agonist, [Leu31, Pro34]-NPY, had no effect on RBF, whereas the Y2R agonist (13-36)-NPY increased RBF to compensate for disease. Thus, in this model of heart failure, cardiac and renal NPY Y1 receptors decrease and Y2 receptors increase, suggesting an increased effect of NPY on the receptors involved in cardiac remodeling and angiogenesis, and highlighting an important regulatory role of NPY in congestive heart failure.

  16. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  17. Exercise training upregulates nitric oxide synthases in the kidney of rats with chronic heart failure.

    PubMed

    Ito, Daisuke; Ito, Osamu; Mori, Nobuyoshi; Cao, Pengyu; Suda, Chihiro; Muroya, Yoshikazu; Hao, Kiyotaka; Shimokawa, Hiroaki; Kohzuki, Masahiro

    2013-09-01

    There is an interaction between heart and kidney diseases, which is a condition termed cardiorenal syndrome. Exercise training has cardioprotective effects, involving upregulation of endothelial (e) nitric oxide synthase (NOS) in the cardiovascular system. However, the effects of exercise training on NOS in the kidney with heart disease are unknown. The aim of the present study was to investigate whether exercise training upregulates NOS in the kidney, left ventricle and aorta of rats with chronic heart failure (CHF). Male Sprague-Dawley rats underwent left coronary artery ligation (LCAL) to induce CHF and were randomly assigned to sedentary or treadmill exercise groups 4 weeks after LCAL. Three days after exercising for 4 weeks, urine samples were collected for 24 h and blood samples were collected following decapitation. Nitric oxide synthase activity and protein expression were examined. Significant interactions between CHF and exercise training were observed on parameters of cardiac and renal function. Exercise training improved cardiac function, decreased plasma B-type natriuretic peptide levels, decreased urinary albumin excretion and increased creatinine clearance in CHF rats. Nitric oxide synthase activity, eNOS expression and neuronal (n) NOS expression were significantly decreased in the left ventricle and kidney of CHF rats. Exercise training significantly increased NOS activity and eNOS and nNOS expression. Upregulation of NOS in the kidney and left ventricle may contribute, in part, to the renal and cardiac protective effects of exercise training in cardiorenal syndrome in CHF rats.

  18. Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure

    PubMed Central

    Wu, San-Pin; Kao, Chung-Yang; Wang, Leiming; Creighton, Chad J.; Yang, Jin; Donti, Taraka R.; Harmancey, Romain; Vasquez, Hernan G.; Graham, Brett H.; Bellen, Hugo J.; Taegtmeyer, Heinrich; Chang, Ching-Pin; Tsai, Ming-Jer; Tsai, Sophia Y.

    2015-01-01

    Mitochondrial dysfunction and metabolic remodelling are pivotal in the development of cardiomyopathy. Here, we show that myocardial COUP-TFII overexpression causes heart failure in mice, suggesting a causal effect of elevated COUP-TFII levels on development of dilated cardiomyopathy. COUP-TFII represses genes critical for mitochondrial electron transport chain enzyme activity, oxidative stress detoxification and mitochondrial dynamics, resulting in increased levels of reactive oxygen species and lower rates of oxygen consumption in mitochondria. COUP-TFII also suppresses the metabolic regulator PGC-1 network and decreases the expression of key glucose and lipid utilization genes, leading to a reduction in both glucose and oleate oxidation in the hearts. These data suggest that COUP-TFII affects mitochondrial function, impairs metabolic remodelling and has a key role in dilated cardiomyopathy. Last, COUP-TFII haploinsufficiency attenuates the progression of cardiac dilation and improves survival in a calcineurin transgenic mouse model, indicating that COUP-TFII may serve as a therapeutic target for the treatment of dilated cardiomyopathy. PMID:26356605

  19. Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure.

    PubMed

    Wu, San-Pin; Kao, Chung-Yang; Wang, Leiming; Creighton, Chad J; Yang, Jin; Donti, Taraka R; Harmancey, Romain; Vasquez, Hernan G; Graham, Brett H; Bellen, Hugo J; Taegtmeyer, Heinrich; Chang, Ching-Pin; Tsai, Ming-Jer; Tsai, Sophia Y

    2015-01-01

    Mitochondrial dysfunction and metabolic remodelling are pivotal in the development of cardiomyopathy. Here, we show that myocardial COUP-TFII overexpression causes heart failure in mice, suggesting a causal effect of elevated COUP-TFII levels on development of dilated cardiomyopathy. COUP-TFII represses genes critical for mitochondrial electron transport chain enzyme activity, oxidative stress detoxification and mitochondrial dynamics, resulting in increased levels of reactive oxygen species and lower rates of oxygen consumption in mitochondria. COUP-TFII also suppresses the metabolic regulator PGC-1 network and decreases the expression of key glucose and lipid utilization genes, leading to a reduction in both glucose and oleate oxidation in the hearts. These data suggest that COUP-TFII affects mitochondrial function, impairs metabolic remodelling and has a key role in dilated cardiomyopathy. Last, COUP-TFII haploinsufficiency attenuates the progression of cardiac dilation and improves survival in a calcineurin transgenic mouse model, indicating that COUP-TFII may serve as a therapeutic target for the treatment of dilated cardiomyopathy. PMID:26356605

  20. Awareness of heart attack and stroke symptoms among Hispanic male adults living in the United States.

    PubMed

    Lutfiyya, May Nawal; Bardales, Ricardo; Bales, Robert; Aguero, Carlos; Brady, Shelly; Tobar, Adriana; McGrath, Cynthia; Zaiser, Julia; Lipsky, Martin S

    2010-10-01

    There is evidence that Hispanic men are a high risk group for treatment delay for both heart attack and stroke. More targeted research is needed to elucidate this specific population's knowledge of warning signs for these acute events. This study sought to describe within-group disparities in Hispanic men's knowledge of heart attack and stroke symptomology. Multivariate techniques were used to analyze a multi-year Behavioral Risk Factor Surveillance Heart and Stroke module database. The data were cross-sectional and focused on health risk factors and behaviors. The research participants were U.S. male Hispanic adults aged 18-99. The main outcome measure for the study was heart attack and stroke symptom knowledge score. Multivariate logistic regression analysis yielded that Hispanic men aged >or=18 years who earned low scores on the composite heart attack and stroke knowledge questions (range 0-8 points) were more likely to: have less than a high school education, have deferred medical care because of cost, not have an identified health care provider, and be uninsured. There were significant within-group differences. Targeting educational efforts toward older (>or=55 years) Hispanic men with less than high school education, those who do not have an identified health care provider or health insurance, and who defer health care because of cost could be ways to improve the outcome of acute vascular events among the U.S. Hispanic adult male population.

  1. Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages.

    PubMed

    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Kodama, Itsuo

    2010-12-01

    Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal rat hearts and superior cervical ganglia, and were co-cultured, either in a random or localized way. Neurite growth from SNs toward CMs was assessed by immunohistochemistry for neurofilament M and α-actinin in response to neurotrophic factors-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and a chemical repellent, semaphorin 3A. As a result, GDNF as well as NGF and BDNF stimulated neurite growth. GDNF enhanced neurite outgrowth even under the NGF-depleted culture condition, excluding an indirect effect of GDNF via NGF. Quantification of mRNA and protein by real-time PCR and immunohistochemistry at different developmental stages revealed that GDNF is abundantly expressed in the hearts of embryos and neonates, but not in adult hearts. GDNF plays an important role in inducing cardiac sympathetic innervation at the early developmental stages. A possible role in (re)innervation of injured or transplanted or cultured and transplanted myocardium may deserve investigation.

  2. Prenatal exposure to PFOS caused mitochondia-mediated apoptosis in heart of weaned rat.

    PubMed

    Zeng, Huai-Cai; He, Qing-Zhi; Li, Yuan-Yuan; Wu, Cheng-Qiu; Wu, Yi-Mou; Xu, Shun-Qing

    2015-09-01

    Perfluorooctanyl sulfonate (PFOS), a cardiac toxicity compound, has been widely detected in the environment and in organisms. However, the toxic mechanism is not clear. Our previous study indicated that prenatal PFOS exposure led to swollen mitochondrial with vacuolar structure and loss of cristae in offsping's heart. The purpose of this study was to investigate the effect of PFOS on the apoptosis in developing heart and mitochondria-mediated apoptosis pathway. Pregnant Sprague-Dawley (SD) rats were exposed to PFOS at doses of 0.1, 0.6, and 2.0 mg/kg-d and 0.05% Tween 80 as control by gavage from gestation day 2 (GD 2) to GD 21. Apoptosis, as well as expression of apoptosis related genes associated with mitochondrial-mediated apoptosis pathway, including p53, bcl-2, bax, cytochrome c, caspase-9, and caspase-3 were analyzed in heart tissues from weaned (postnatal day 21, PND 21) offspring. The results showed that prenatal PFOS exposure resulted in apoptosis in the offspring's heart. The mRNA and protein expression levels of p53, bax, cytochrome c, caspase-9, and caspase-3 in the offspring's heart were enhanced in various PFOS-treated groups, meanwhile, the bcl-2 expression levels were decreased. Our results indicated that prenatal PFOS exposure induced the apoptosis of weaned offspring rat heart tissue via mitochondria-mediated apoptotic pathway. PMID:24616003

  3. Prenatal exposure to PFOS caused mitochondia-mediated apoptosis in heart of weaned rat.

    PubMed

    Zeng, Huai-Cai; He, Qing-Zhi; Li, Yuan-Yuan; Wu, Cheng-Qiu; Wu, Yi-Mou; Xu, Shun-Qing

    2015-09-01

    Perfluorooctanyl sulfonate (PFOS), a cardiac toxicity compound, has been widely detected in the environment and in organisms. However, the toxic mechanism is not clear. Our previous study indicated that prenatal PFOS exposure led to swollen mitochondrial with vacuolar structure and loss of cristae in offsping's heart. The purpose of this study was to investigate the effect of PFOS on the apoptosis in developing heart and mitochondria-mediated apoptosis pathway. Pregnant Sprague-Dawley (SD) rats were exposed to PFOS at doses of 0.1, 0.6, and 2.0 mg/kg-d and 0.05% Tween 80 as control by gavage from gestation day 2 (GD 2) to GD 21. Apoptosis, as well as expression of apoptosis related genes associated with mitochondrial-mediated apoptosis pathway, including p53, bcl-2, bax, cytochrome c, caspase-9, and caspase-3 were analyzed in heart tissues from weaned (postnatal day 21, PND 21) offspring. The results showed that prenatal PFOS exposure resulted in apoptosis in the offspring's heart. The mRNA and protein expression levels of p53, bax, cytochrome c, caspase-9, and caspase-3 in the offspring's heart were enhanced in various PFOS-treated groups, meanwhile, the bcl-2 expression levels were decreased. Our results indicated that prenatal PFOS exposure induced the apoptosis of weaned offspring rat heart tissue via mitochondria-mediated apoptotic pathway.

  4. Estimation of Early Postmortem Interval Through Biochemical and Pathological Changes in Rat Heart and Kidney.

    PubMed

    Abo El-Noor, Mona Mohamed; Elhosary, Naema Mahmoud; Khedr, Naglaa Fathi; El-Desouky, Kareema Ibraheem

    2016-03-01

    Accurate estimation of time passed since death is a complicated task in forensic medicine especially in homicide or unwitnessed death investigations. Changes in oxidant/antioxidant parameters were investigated if it can be relied upon in estimating the early postmortem interval (EPI) in rat heart and kidney, and whether these changes were correlated with histopathological findings in these tissues. Heart and kidney tissues of 84 male albino rats were divided into 2 parts. One part used for estimation of levels of malondialdehyde (MDA), nitric oxide (NO), and total thiol as well as the activity of glutathione reductase (GR), glutathione S transferase, and catalase. The second part was examined histopathologically. It was found that MDA and NO were significantly increased earlier in the heart than kidney tissues. Meanwhile, total thiol, catalase, glutathione S transferase, and GR were commenced to be significantly decreased in the heart before kidney tissues. Linear regression analysis of independent variables of heart was found to be of a high predictive value of 97.2% (EPI = 8.607 - 0.240 GR + 0.002 MDA + 0.014 NO). Structural deterioration of heart started 3 to 4 hours compared with renal sections that began 5 to 6 hours after death. The relationship between oxidant and antioxidant parameters is crucial in determining the EPI. The kidney was found to be more resistible to oxidative damage. Further research on humans is needed.

  5. Emerging Research Directions in Adult Congenital Heart Disease: A Report From an NHLBI/ACHA Working Group.

    PubMed

    Gurvitz, Michelle; Burns, Kristin M; Brindis, Ralph; Broberg, Craig S; Daniels, Curt J; Fuller, Stephanie M P N; Honein, Margaret A; Khairy, Paul; Kuehl, Karen S; Landzberg, Michael J; Mahle, William T; Mann, Douglas L; Marelli, Ariane; Newburger, Jane W; Pearson, Gail D; Starling, Randall C; Tringali, Glenn R; Valente, Anne Marie; Wu, Joseph C; Califf, Robert M

    2016-04-26

    Congenital heart disease (CHD) is the most common birth defect, affecting about 0.8% of live births. Advances in recent decades have allowed >85% of children with CHD to survive to adulthood, creating a growing population of adults with CHD. Little information exists regarding survival, demographics, late outcomes, and comorbidities in this emerging group, and multiple barriers impede research in adult CHD. The National Heart, Lung, and Blood Institute and the Adult Congenital Heart Association convened a multidisciplinary working group to identify high-impact research questions in adult CHD. This report summarizes the meeting discussions in the broad areas of CHD-related heart failure, vascular disease, and multisystem complications. High-priority subtopics identified included heart failure in tetralogy of Fallot, mechanical circulatory support/transplantation, sudden cardiac death, vascular outcomes in coarctation of the aorta, late outcomes in single-ventricle disease, cognitive and psychiatric issues, and pregnancy.

  6. Exercise training improves renal excretory responses to acute volume expansion in rats with heart failure.

    PubMed

    Zheng, Hong; Li, Yi-Fan; Zucker, Irving H; Patel, Kaushik P

    2006-12-01

    Experiments were performed to test the postulate that exercise training (ExT) improves the blunted renal excretory response to acute volume expansion (VE), in part, by normalizing the neural component of the volume reflex typically observed in chronic heart failure (HF). Diuretic and natriuretic responses to acute VE were examined in sedentary and ExT groups of rats with either HF or sham-operated controls. Experiments were performed in anesthetized (Inactin) rats 6 wk after coronary ligation surgery. Histological data indicated that there was a 34.9 +/- 3.0% outer and 42.5 +/- 3.2% inner infarct of the myocardium in the HF group. Sham rats had no observable damage to the myocardium. In sedentary rats with HF, VE produced a blunted diuresis (46% of sham) and natriuresis (35% of sham) compared with sham-operated control rats. However, acute VE-induced diuresis and natriuresis in ExT rats with HF were comparable to sham rats and significantly higher than sedentary HF rats. Renal denervation abolished the salutary effects of ExT on renal excretory response to acute VE in HF. Since glomerular filtration rates were not significantly different between the groups, renal hemodynamic changes may not account for the blunted renal responses in rats with HF. Additional experiments confirmed that renal sympathetic nerve activity responses to acute VE were blunted in sedentary HF rats; however, ExT normalized the renal sympathoinhibition in HF rats. These results confirm an impairment of neurally mediated excretory responses to acute VE in rats with HF. ExT restored the blunted excretory responses as well as the renal sympathoinhibitory response to acute VE in HF rats. Thus the beneficial effects of ExT on cardiovascular regulation in HF may be partly due to improvement of the neural component of volume reflex.

  7. Psychosocial issues affecting adults with congenital heart disease: one patient's perspective.

    PubMed

    Livecchi, Tracy A

    2004-12-01

    This article addresses a number of psychosocial issues that advance practice nurses and other health care providers should be aware of when working with patients who have congenital heart disease. If not properly addressed, particularly during adolescence, these issues can have a strong impact on a person's medical care and over-all quality of life. This article includes information from medical literature, conversations with adult patients, and my own experiences as both a patient with congenital heart disease and as a clinical social worker.

  8. Somatostatin in the human heart and comparison with guinea pig and rat heart.

    PubMed Central

    Day, S M; Gu, J; Polak, J M; Bloom, S R

    1985-01-01

    Somatostatin has been shown to have negative inotropic and chronotopic effects and to restore sinus rhythm in some cases of cardiac arrhythmia. Using acid extracts, regions of human heart were examined by radioimmunoassay to determine their somatostatin content. Mean (SD) concentrations of 4.1 (0.8) pmol/g and 2.9 (0.8) pmol/g were found in atrioventricular node and right atria respectively and were significantly higher than in other heart regions. Using fresh heart tissue from guinea pigs, somatostatin was localised to cardiac nerves by immunocytochemistry. Nerves containing somatostatin were most abundant in the atria, where the concentrations measured by radioimmunoassay were 7.6 (1.0) and 2.6 (0.4) pmol/g for right and left atria respectively. Somatostatin contained in cardiac nerves may have a physiological role in the cardiac conduction system. Images PMID:2857086

  9. De novo cardiomyocytes from within the activated adult heart after injury

    PubMed Central

    Smart, Nicola; Bollini, Sveva; Dubé, Karina N.; Vieira, Joaquim M.; Zhou, Bin; Davidson, Sean; Yellon, Derek; Riegler, Johannes; Price, Anthony N.; Lythgoe, Mark F.; Pu, William T.; Riley, Paul R.

    2013-01-01

    A significant bottleneck in cardiovascular regenerative medicine is the identification of a viable source of stem/progenitor cells that could contribute new muscle after ischaemic heart disease and acute myocardial infarction1. A therapeutic ideal—relative to cell transplantation—would be to stimulate a resident source, thus avoiding the caveats of limited graft survival, restricted homing to the site of injury and host immune rejection. Here we demonstrate in mice that the adult heart contains a resident stem or progenitor cell population, which has the potential to contribute bona fide terminally differentiated cardiomyocytes after myocardial infarction. We reveal a novel genetic label of the activated adult progenitors via re-expression of a key embryonic epicardial gene, Wilm’s tumour 1 (Wt1), through priming by thymosin β4, a peptide previously shown to restore vascular potential to adult epicardium-derived progenitor cells2 with injury. Cumulative evidence indicates an epicardial origin of the progenitor population, and embryonic reprogramming results in the mobilization of this population and concomitant differentiation to give rise to de novo cardiomyocytes. Cell transplantation confirmed a progenitor source and chromosome painting of labelled donor cells revealed transdifferentiation to a myocyte fate in the absence of cell fusion. Derived cardiomyocytes are shown here to structurally and functionally integrate with resident muscle; as such, stimulation of this adult progenitor pool represents a significant step towards residentcell-based therapy in human ischaemic heart disease. PMID:21654746

  10. Contextual fear conditioning differs for infant, adolescent, and adult rats.

    PubMed

    Esmorís-Arranz, Francisco J; Méndez, Cástor; Spear, Norman E

    2008-07-01

    Contextual fear conditioning was tested in infant, adolescent, and adult rats in terms of Pavlovian-conditioned suppression. When a discrete auditory-conditioned stimulus (CS) was paired with footshock (unconditioned stimulus, US) within the largely olfactory context, infants and adolescents conditioned to the context with substantial effectiveness, but adult rats did not. When unpaired presentations of the CS and US occurred within the context, contextual fear conditioning was strong for adults, weak for infants, but about as strong for adolescents as when pairings of CS and US occurred in the context. Nonreinforced presentations of either the CS or context markedly reduced contextual fear conditioning in infants, but, in adolescents, CS extinction had no effect on contextual fear conditioning, although context extinction significantly reduced it. Neither CS extinction nor context extinction affected responding to the CS-context compound in infants, suggesting striking discrimination between the compound and its components. Female adolescents showed the same lack of effect of component extinction on response to the compound as infants, but CS extinction reduced responding to the compound in adolescent males, a sex difference seen also in adults. Theoretical implications are discussed for the development of perceptual-cognitive processing and hippocampus role.

  11. Nutritional strategy in the management of heart failure in adults.

    PubMed

    Bourdel-Marchasson, I; Emeriau, J P

    2001-01-01

    The incidence of congestive heart failure (CHF) is increasing in Westernized countries, and patients with CHF experience poor quality of life (functional impairment, high hospitalization rate and high mortality). Malnutrition occurring during the course of CHF is referred to as cardiac cachexia and is associated with higher mortality independent of the severity of CHF. Cardiac cachexia involving a loss of more than 10% of lean body mass can clinically be defined as a bodyweight loss of 7.5% of previous dry bodyweight in a period longer than 6 months. The energy requirements of patients with CHF, whether cachectic or not, are not noticeably modified since the increase in resting energy expenditure is compensated by a decrease in physical activity energy expenditure. Malnutrition in CHF has been ascribed to neurohormonal alterations, i.e. anabolic/catabolic imbalance and increased cytokine release. Anorexia may occur, particularly during acute decompensation of CHF. Function is impaired in CHF, because of exertional dyspnea and changes in skeletal muscle. Decreased exercise endurance seems to be related to decreased mitochondrial oxidative capacities and atrophy of type 1 fibers, which are attributed to alteration in muscle perfusion and are partially reversible by training. Malnutrition could also impair muscle function, because of decreased muscle mass and strength associated with decreased glycolytic capacities and atrophy of type 2a and 2b fibres. With respect to the putative mechanisms of cardiac cachexia, anabolic therapy (hormones or nutrients) and anticytokine therapy have been proposed, but trials are scarce and often inconclusive. In surgical patients with CHF, perioperative (pre- and postoperative) nutritional support has been shown to be effective in reducing the mortality rate. Long term nutritional supplementation trials in patients with CHF and cachexia are thus required to establish recommendations for the nutritional management of patients with CHF.

  12. Intestinal absorption of aspartame decomposition products in adult rats.

    PubMed

    Lipton, W E; Li, Y N; Younoszai, M K; Stegink, L D

    1991-12-01

    The dipeptide sweetener aspartame (N-L-alpha-aspartyl-L-phenylalanine, 1-methyl ester; alpha-APM) is relatively stable in dry powder form. However, when exposed to elevated temperature, extremes of pH and/or moisture, alpha-APM is converted into a variety of products. In aqueous solution alpha-APM decomposes to yield methanol, two isomeric forms of L-aspartyl-L-phenylalanine (Asp-Phe) [alpha-Asp-Phe and beta-Asp-Phe], and APM's diketopiperazine cyclo-Asp-Phe. Depending on beverage storage conditions, individuals drinking alpha-APM-sweetened beverages may consume small quantities of these three compounds. Relatively little has been published about the metabolism of beta-Asp-Phe and cyclo-Asp-Phe. We compared the absorption and metabolism of alpha-Asp-Phe, beta-Asp-Phe, and cyclo-Asp-Phe with that of L-phenylalanine (Phe) in adult rats. Steady-state perfusion studies of rat jejunum indicated rapid carrier-assisted uptake of Phe and alpha-Asp-Phe, but only slow passive diffusion of beta-Asp-Phe and cyclo-Asp-Phe from the lumen. Homogenates of rat intestinal mucosa, liver, and cecal contents, as well as homogenates of pure cultures of Escherichia coli B, catalyzed the hydrolysis of alpha-Asp-Phe, but not cyclo-Asp-Phe. Homogenates of E coli and rat cecal contents, but not homogenates of rat liver or intestinal mucosa catalyzed the hydrolysis of beta-Asp-Phe.

  13. Myocardial Factor Revisited: The Importance of Myocardial Fibrosis in Adults with Congenital Heart Disease

    PubMed Central

    Broberg, Craig S.; Burchill, Luke J.

    2015-01-01

    Pioneers in congenital heart surgery observed that exercise capacity did not return to normal levels despite successful surgical repair, leading some to cite a “myocardial factor” playing a role. They conjectured that residual alterations in myocardial function would be significant for patients’ long-term outlook. In fulfillment of their early observations, today’s adult congenital heart disease (ACHD) population shows well-recognized features of heart failure, even among patients without clear residual anatomic or hemodynamic abnormalities, demonstrating the vital role of the myocardium in their morbidity and mortality. Whereas the ‘myocardial factor’ was an elusive concept in the early history of congenital heart care, we now have imaging techniques to detect and quantify one such factor – myocardial fibrosis. Understanding the importance of myocardial fibrosis as a final common pathway in a variety of congenital lesions provides a framework for both the study and treatment of clinical heart failure in this context. While typical heart failure pharmacology should reduce or attenuate fibrogenesis, efforts to show meaningful improvements with standard pharmacotherapy in ACHD repeatedly fall short. This paper considers the importance of myocardial fibrosis and function, the current body of evidence for myocardial fibrosis in ACHD, and its implications for research and treatment. PMID:25897907

  14. Plexin a4 expression in adult rat cranial nerves.

    PubMed

    Gutekunst, Claire-Anne; Gross, Robert E

    2014-11-01

    PlexinsA1-A4 participate in class 3 semaphorin signaling as co-receptors to neuropilin 1 and 2. PlexinA4 is the latest member of the PlexinA subfamily to be identified. In previous studies, we described the expression of PlexinA4 in the brain and spinal cord of the adult rat. Here, antibodies to PlexinA4 were used to reveal immunolabeling in most of the cranial nerve surveyed. Labeling was found in the olfactory, optic, oculomotor, trochlear, trigeminal, abducens, facial, vestibulocochlear, glossopharyngeal, vagus, and hypoglossal nerves. This is the first detailed description of the cellular and subcellular distribution of PlexinA4 in the adult cranial nerves. The findings will set the basis for future studies on the potential role of PlexinA4 in regeneration and repair of the adult central and peripheral nervous system.

  15. 5'-Adenosine monophosphate and adenosine metabolism, and adenosine responses in mouse, rat and guinea pig heart.

    PubMed

    Headrick, J P; Peart, J; Hack, B; Garnham, B; Matherne, G P

    2001-11-01

    We examined myocardial 5'-adenosine monophosphate (5'-AMP) catabolism, adenosine salvage and adenosine responses in perfused guinea pig, rat and mouse heart. MVO(2) increased from 71+/-8 microl O(2)/min per g in guinea pig to 138+/-17 and 221+/-15 microl O(2)/min per g in rat and mouse. VO(2)/beat was 0.42+/-0.03, 0.50+/-0.03 and 0.55+/-0.04 microl O(2)/g in guinea pig, rat and mouse, respectively. Resting and peak coronary flows were highest in mouse vs. rat and guinea pig, and peak ventricular pressures and Ca(2+) sensitivity declined as heart mass increased. Net myocardial 5'-AMP dephosphorylation increased significantly as mass declined (3.8+/-0.5, 9.0+/-1.4 and 11.0+/-1.6 nmol/min per g in guinea pig, rat and mouse, respectively). Despite increased 5'-AMP catabolism, coronary venous [adenosine] was similar in guinea pig, rat and mouse (45+/-8, 69+/-10 and 57+/-14 nM, respectively). Comparable venous [adenosine] was achieved by increased salvage vs. deamination: 64%, 41% and 39% of adenosine formed was rephosphorylated while 23%, 46%, and 50% was deaminated in mouse, rat and guinea pig, respectively. Moreover, only 35-45% of inosine and its catabolites derive from 5'-AMP (vs. IMP) dephosphorylation in all species. Although post-ischemic purine loss was low in mouse (due to these adaptations), functional tolerance to ischemia decreased with heart mass. Cardiovascular sensitivity to adenosine also differed between species, with A(1) receptor sensitivity being greatest in mouse while A(2) sensitivity was greatest in guinea pig. In summary: (i) cardiac 5'-AMP dephosphorylation, VO(2), contractility and Ca(2+) sensitivity all increase as heart mass falls; (ii) adaptations in adenosine salvage vs. deamination limit purine loss and yield similar adenosine levels across species; (iii) ischemic tolerance declines with heart mass; and (iv) cardiovascular sensitivity to adenosine varies, with increasing A(2) sensitivity relative to A(1) sensitivity in larger hearts.

  16. Is rate–pressure product of any use in the isolated rat heart? Assessing cardiac ‘effort’ and oxygen consumption in the Langendorff‐perfused heart

    PubMed Central

    Aksentijević, Dunja; Lewis, Hannah R.

    2016-01-01

    New Findings What is the central question of this study? Rate–pressure product (RPP) is commonly used as an index of cardiac ‘effort’. In canine and human hearts (which have a positive force–frequency relationship), RPP is linearly correlated with oxygen consumption and has therefore been widely adopted as a species‐independent index of cardiac work. However, given that isolated rodent hearts demonstrate a negative force–frequency relationship, its use in this model requires validation. What is the main finding and its importance? Despite its widespread use, RPP is not correlated with oxygen consumption (or cardiac ‘effort’) in the Langendorff‐perfused isolated rat heart. This lack of correlation was also evident when perfusions included a range of metabolic substrates, insulin or β‐adrenoceptor stimulation. Langendorff perfusion of hearts isolated from rats and mice has been used extensively for physiological, pharmacological and biochemical studies. The ability to phenotype these hearts reliably is, therefore, essential. One of the commonly used indices of function is rate–pressure product (RPP); a rather ill‐defined index of ‘work’ or, more correctly, ‘effort’. Rate–pressure product, as originally described in dog or human hearts, was shown to be correlated with myocardial oxygen consumption (MV˙O2). Despite its widespread use, the application of this index to rat or mouse hearts (which, unlike the dog or human, have a negative force–frequency relationship) has not been characterized. The aim of this study was to examine the relationship between RPP and MV˙O2 in Langendorff‐perfused rat hearts. Paced hearts (300–750 beats min−1) were perfused either with Krebs–Henseleit (KH) buffer (11 mm glucose) or with buffer supplemented with metabolic substrates and insulin. The arteriovenous oxygen consumption (MV˙O2) was recorded. Metabolic status was assessed using 31P magnetic resonance spectroscopy and lactate efflux

  17. The effect of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart.

    PubMed

    Khedun, S M; Maharaj, B; Leary, W P; Lockett, C J

    1992-01-01

    This investigation was conducted to determine the influence of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart and myocardial electrolyte levels. Ventricular fibrillation threshold was measured using the Langendorff perfusion apparatus. Heart rate was measured by a universal digital counter and the cardiac flow by collecting the outflow of the heating chamber below the heart into a graduated measuring cylinder. Magnesium and zinc were measured by atomic absorption spectrophotometry and potassium by flame photometry. Two groups of rats were studied; those in the experimental group were given 0.2 ml of hexane and the control group 0.2 ml olive oil subcutaneously for 90 days. Their hearts were removed under anaesthesia. Half of the experimental and control hearts were mounted on the Langendorff perfusion apparatus and the heart rate, coronary flow and ventricular fibrillation threshold were measured. The hearts of the other half were used to measure myocardial electrolyte levels. In the experimental group the ventricular fibrillation threshold decreased (4.72 (S.D. +/- 1.87) vs 9.48 (S.D. +/- 2.98); P less than 0.001). There was no change in the coronary flow and heart rate in between the groups. The mean myocardial potassium levels (2586 (S.D. +/- 162) vs 2968 (S.D. +/- 218) micrograms/g; P less than 0.001), magnesium levels (164 (S.D. +/- 28) vs 208 (S.D. +/- 18) micrograms/g; P less than 0.001) and zinc levels (19.6 (S.D. +/- 4) vs 33.8 (S.D. +/- 6.8) micrograms/g; P less than 0.001) were significantly lower in the hexane-treated group compared to controls. Hexane, a constituent of glue and benzine, is cardiotoxic; marked derangement in myocardial electrolytes and a reduced ventricular fibrillation threshold, indicating an increased myocardial vulnerability to arrhythmias, was noted in the experimental animals. PMID:1729763

  18. Cardioprotection by remote ischemic preconditioning of the rat heart is mediated by extracellular vesicles.

    PubMed

    Giricz, Zoltán; Varga, Zoltán V; Baranyai, Tamás; Sipos, Péter; Pálóczi, Krisztina; Kittel, Ágnes; Buzás, Edit I; Ferdinandy, Péter

    2014-03-01

    Remote ischemic preconditioning (RIPC) of the heart is exerted by brief ischemic insults affected on a remote organ or a remote area of the heart before a sustained cardiac ischemia. To date, little is known about the inter-organ transfer mechanisms of cardioprotection by RIPC. Exosomes and microvesicles/microparticles are vesicles of 30-100 nm and 100-1000 nm in diameter, respectively (collectively termed extracellular vesicles [EVs]). Their content of proteins, mRNAs and microRNAs, renders EV ideal conveyors of inter-organ communication. However, whether EVs are involved in RIPC, is unknown. Therefore, here we investigated whether (1) IPC induces release of EVs from the heart, and (2) EVs are necessary for cardioprotection by RIPC. Hearts of male Wistar rats were isolated and perfused in Langendorff mode. A group of donor hearts was exposed to 3 × 5-5 min global ischemia and reperfusion (IPC) or 30 min aerobic perfusion, while coronary perfusates were collected. Coronary perfusates of these hearts were given to another set of recipient isolated hearts. A group of recipient hearts received IPC effluent depleted of EVs by differential ultracentrifugation. Infarct size was determined after 30 min global ischemia and 120 min reperfusion. The presence or absence of EVs in perfusates was confirmed by dynamic light scattering, the EV marker HSP60 Western blot, and electron microscopy. IPC markedly increased EV release from the heart as assessed by HSP60. Administration of coronary perfusate from IPC donor hearts attenuated infarct size in non-preconditioned recipient hearts (12.9 ± 1.6% vs. 25.0 ± 2.7%), similarly to cardioprotection afforded by IPC (7.3 ± 2.7% vs. 22.1 ± 2.9%) on the donor hearts. Perfusates of IPC hearts depleted of EVs failed to exert cardioprotection in recipient hearts (22.0 ± 2.3%). This is the first demonstration that EVs released from the heart after IPC are necessary for cardioprotection by RIPC, evidencing the importance of vesicular

  19. Adult Rats Treated with Risperidone during Development Are Hyperactive

    PubMed Central

    Bardgett, Mark E.; Franks-Henry, Julie M.; Colemire, Kristin R.; Juneau, Kathleen R.; Stevens, Rachel M.; Marczinski, Cecile A.; Griffith, Molly S.

    2014-01-01

    Risperidone is an antipsychotic drug approved for use in children, but little is known about the long-term effects of early-life risperidone treatment. In animals, prolonged risperidone administration during development increases forebrain dopamine receptor expression immediately upon the cessation of treatment. A series of experiments was performed to ascertain whether early-life risperidone administration altered locomotor activity, a behavior sensitive to dopamine receptor function, in adult rats. One additional behavior modulated by forebrain dopamine function, spatial reversal learning, was also measured during adulthood. In each study, Long-Evans rats received daily subcutaneous injections of vehicle or one of two doses of risperidone (1.0 and 3.0 mg/kg per day) from postnatal days 14 – 42. Weight gain during development was slightly yet significantly reduced in risperidone-treated rats. In the first two experiments, early-life risperidone administration was associated with increased locomotor activity at one week post-administration through approximately nine months of age, independent of changes in weight gain. In a separate experiment, it was found that the enhancing effect of early-life risperidone on locomotor activity occurred in males and female rats. A final experiment indicated that spatial reversal learning was unaffected in adult rats administered risperidone early in life. These results indicate that locomotor activity during adulthood is permanently modified by early-life risperidone treatment. The findings suggest that chronic antipsychotic drug use in pediatric populations (e.g., treatment for the symptoms of autism) could modify brain development and alter neural set-points for specific behaviors during adulthood. PMID:23750695

  20. Caffeine-induced myocardial injury in calcium-free perfused rat hearts.

    PubMed

    Vander Heide, R S; Ganote, C E

    1985-01-01

    Hearts depleted of extracellular calcium become susceptible to injury caused by repletion of extracellular calcium (calcium paradox). It has been suggested that calcium-free perfusion causes weakening of intercalated disks and that the physical stress of contracture may cause sarcolemmal membrane rupture and creatine kinase (CK) release. To further investigate this hypothesis, the effects of caffeine on contracture, cellular morphology, and CK release were studied in control and calcium-free perfused isolated rat hearts. Control hearts perfused with 2.5 mM calcium retained normal ultrastructure for long periods of perfusion. Calcium-free hearts perfused for 12 minutes developed separations of fascia adherens portions of intercalated disks but retained intact nexus junctions. Hearts subjected to 5-minute calcium-free perfusion, followed by calcium repletion, developed a massive CK release and extensive contraction band necrosis (calcium paradox). Ten millimolar caffeine, which causes rapid calcium release from sarcoplasmic reticulum (SR), produced contracture, but not CK release, from control hearts perfused with medium containing 2.5 mM calcium. In calcium-free perfused hearts, caffeine caused sudden CK release accompanied by contracture, development of contraction bands, wide separations of cells at intercalated disks, and sarcolemmal membrane injury. Caffeine-induced injury occurred despite 3 mM amobarbital inhibition of mitochondrial respiration. Hearts perfused with caffeine in the presence of calcium relaxed when made calcium-free and did not release CK. Addition of caffeine following calcium-free perfusion at 22 C, which protects the heart from the calcium paradox, produced a rapid, transient contracture. These results are compatible with the hypothesis that myocardial cell injury in calcium-free hearts is not dependent on repletion of extracellular calcium or mitochondrial function, but can result from contracture following caffeine-induced release of

  1. Protective effect of apigenin on ischemia/reperfusion injury of the isolated rat heart.

    PubMed

    Hu, Jing; Li, Zilin; Xu, Li-ting; Sun, Ai-jun; Fu, Xiao-yan; Zhang, Li; Jing, Lin-lin; Lu, An-dong; Dong, Yi-fei; Jia, Zheng-ping

    2015-07-01

    Apigenin (Api), a mainly bioactive component of Apium graveolens L. var. dulce DC. (a traditional Chinese medicinal herb), possesses a wide range of biological activities, including antioxidant effects. It also has been shown to associate with lower prevalence of cardiovascular diseases, but its mechanisms of action remain unclear. The aim of the present study is to investigate the role of Api in isolated rat heart model of ischemia/reperfusion (I/R). Langendorff-perfused isolated rat hearts were used in our study. Api was added to the perfusate before ischemia and during reperfusion in the isolated pulsed rat heart exposed to 30-min ischemia followed by 50-min reperfusion. The treatment with Api conferred a cardioprotective effect, and the treated hearts demonstrated an improved ischemic cardiac functional recovery, a decreased myocardial infarct size, a reduced activities of creatine kinase isoenzyme and lactate dehydrogenase in the coronary flow, a reduced number of apoptotic cardiomyocytes, a reduced activity of caspase-3, up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the pro-apoptotic protein Bax. In addition, Api inhibited the phosphorylation of p38 MAPKS during I/R. In conclusion, these observations provide preliminary evidence that Api can protect cardiomyocytes from I-/R-induced injury, at least partially, through the inhibition of p38 MAPKS signaling pathway. PMID:25377428

  2. Hydrogen sulfide post-conditioning preserves interfibrillar mitochondria of rat heart during ischemia reperfusion injury.

    PubMed

    Banu, Shakila A; Ravindran, Sriram; Kurian, Gino A

    2016-07-01

    Cardiac mitochondrial dysfunction is considered to be the main manifestation in the pathology of ischemia reperfusion injury, and by restoring its functional activity, hydrogen sulfide (H2S), a novel endogenous gaseotransmitter renders cardioprotection. Given that interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria are the two main types in the heart, the present study investigates the specific H2S-mediated action on IFM and SSM during ischemic reperfusion in the Langendorff rat heart model. Rats were randomly divided into five groups, namely normal, ischemic control, reperfusion control (I/R), ischemic post-conditioning (POC), and H2S post-conditioning (POC_H2S). In reperfusion control, cardiac contractility decreased, and lactate dehydrogenase, creatine kinase, and infracted size increased compared to both normal and ischemic group. In hearts post-conditioned with H2S and the classical method improved cardiac mechanical function and decreased cardiac markers in the perfusate and infarct size significantly. Both POC and POC_H2S exerts its cardioprotective effect of preserving the IFM, as evident by significant improvement in electron transport chain enzyme activities and mitochondrial respiration. The in vitro action of H2S on IFM and SSM from normal and I/R rat heart supports H2S and mediates cardioprotection via IFM preservation. Our study indicates that IFM play an important role in POC_H2S mediated cardioprotection from reperfusion injury. PMID:26951457

  3. Cardioprotective properties of citicoline against hyperthyroidism-induced reperfusion damage in rat hearts.

    PubMed

    Hernández-Esquivel, Luz; Pavón, Natalia; Buelna-Chontal, Mabel; González-Pacheco, Héctor; Belmont, Javier; Chávez, Edmundo

    2015-06-01

    Hyperthyroidism represents an increased risk factor for cardiovascular morbidity, especially when the heart is subjected to an ischemia/reperfusion process. The aim of this study was to explore the possible protective effect of the nucleotide citicoline on the susceptibility of hyperthyroid rat hearts to undergo reperfusion-induced damage, which is associated with mitochondrial dysfunction. Hence, we analyzed the protective effect of citicoline on the electrical behavior and on the mitochondrial function in rat hearts. Hyperthyroidism was established after a daily i.p. injection of triiodothyronine (at 2 mg/kg of body weight) during 5 days. Thereafter, citicoline was administered i.p. (at 125 mg/kg of body weight) for 5 days. In hyperthyroid rat hearts, citicoline protected against reperfusion-induced ventricular arrhythmias. Moreover, citicoline maintained the accumulation of mitochondrial Ca(2+), allowing mitochondria to reach a high transmembrane electric gradient that protected against the release of cytochrome c. It also preserved the activity of the enzyme aconitase that inhibited the release of cytokines. The protection also included the inhibition of oxidative stress-induced mDNA disruption. We conclude that citicoline protects against the reperfusion damage that is found in the hyperthyroid myocardium. This effect might be due to its inhibitory action on the permeability transition in mitochondria. PMID:25589288

  4. Accumulation of amino acids in muscle of perfused rat heart. Effect of insulin

    PubMed Central

    Scharff, R.; Wool, I. G.

    1965-01-01

    1. Rat heart perfused with Krebs–Henseleit bicarbonate buffer released material containing ninhydrin-positive nitrogen, but the amount was less than that reported to be released by diaphragm; glucose, but not insulin, decreased the release of ninhydrin-positive nitrogen and increased the concentration of the same material in the intracellular water of heart. 2. When heart was perfused with a mixture of amino acids and glucose, there was actually a net uptake, and an increase in intracellular concentration, of ninhydrin-positive nitrogen. Changes in the concentration of ninhydrin-positive nitrogen did not accurately reflect changes in concentration of amino acids. 3. The effect of insulin on the actual concentration of individual amino acids in heart muscle was examined by perfusing the heart with a mixture of amino acids and other ninhydrin-positive substances in the same concentration as they are found in plasma. 4. The effect of insulin on the concentrations of amino acids in the medium and in the intracellular water of the heart was determined after perfusion for different periods of time. No clear or meaningful effect of insulin was observed, despite the fact that insulin significantly increased the accumulation, in each of the same hearts, of radioactivity from amino[14C]isobutyric acid. PMID:16749112

  5. Interventional and surgical treatment of cardiac arrhythmias in adults with congenital heart disease.

    PubMed

    Koyak, Zeliha; de Groot, Joris R; Mulder, Barbara J M

    2010-12-01

    Arrhythmias are a major cause of morbidity, mortality and hospital admission in adults with congenital heart disease (CHD). The etiology of arrhythmias in this population is often multifactorial and includes electrical disturbances as part of the underlying defect, surgical intervention or hemodynamic abnormalities. Despite the numerous existing arrhythmia management tools including drug therapy, pacing and ablation, management of arrhythmias in adults with CHD remains difficult and challenging. Owing to improvement in mapping and ablation techniques, ablation and arrhythmia surgery are being performed more frequently in adults with CHD. However, there is little information on the long-term results of these treatment strategies. The purpose of this article is therefore to review the available data on nonpharmacological treatment of cardiac arrhythmias in adult patients with CHD and to give an overview of the available data on the early and late outcomes of these treatment strategies.

  6. Recent advancements in understanding endogenous heart regeneration-insights from adult zebrafish and neonatal mice.

    PubMed

    Rubin, Nicole; Harrison, Michael R; Krainock, Michael; Kim, Richard; Lien, Ching-Ling

    2016-10-01

    Enhancing the endogenous regenerative capacity of the mammalian heart is a promising strategy that can lead to potential treatment of injured cardiac tissues. Studies on heart regeneration in zebrafish and neonatal mice have shown that cardiomyocyte proliferation is essential for replenishing myocardium. We will review recent advancements that have demonstrated the importance of Neuregulin 1/ErbB2 and innervation in regulating cardiomyocyte proliferation using both adult zebrafish and neonatal mouse heart regeneration models. Emerging findings suggest that different populations of macrophages and inflammation might contribute to regenerative versus fibrotic responses. Finally, we will discuss variation in the severity of the cardiac injury and size of the wound, which may explain the range of outcomes observed in different injury models.

  7. Anti-dopamine beta-hydroxylase immunotoxin-induced sympathectomy in adult rats

    NASA Technical Reports Server (NTRS)

    Picklo, M. J.; Wiley, R. G.; Lonce, S.; Lappi, D. A.; Robertson, D.

    1995-01-01

    Anti-dopamine beta-hydroxylase immunotoxin (DHIT) is an antibody-targeted noradrenergic lesioning tool comprised of a monoclonal antibody against the noradrenergic enzyme, dopamine beta-hydroxylase, conjugated to saporin, a ribosome-inactivating protein. Noradrenergic-neuron specificity and completeness and functionality of sympathectomy were assessed. Adult, male Sprague-Dawley rats were given 28.5, 85.7, 142 or 285 micrograms/kg DHIT i.v. Three days after injection, a 6% to 73% decrease in the neurons was found in the superior cervical ganglia of the animals. No loss of sensory, nodose and dorsal root ganglia, neurons was observed at the highest dose of DHIT. In contrast, the immunotoxin, 192-saporin (142 micrograms/kg), lesioned all three ganglia. To assess the sympathectomy, 2 wk after treatment (285 micrograms/kg), rats were anesthetized with urethane (1 g/kg) and cannulated in the femoral artery and vein. DHIT-treated animals' basal systolic blood pressure and heart rate were significantly lower than controls. Basal plasma norepinephrine levels were 41% lower in DHIT-treated animals than controls. Tyramine-stimulated release of norepinephrine in DHIT-treated rats was 27% of controls. Plasma epinephrine levels of DHIT animals were not reduced. DHIT-treated animals exhibited a 2-fold hypersensitivity to the alpha-adrenergic agonist phenylephrine. We conclude that DHIT selectively delivered saporin to noradrenergic neurons resulting in destruction of these neurons. Anti-dopamine beta-hydroxylase immunotoxin administration produces a rapid, irreversible sympathectomy.

  8. Histopathological evaluation of liver, pancreas, spleen, and heart from iron-overloaded Sprague-Dawley rats.

    PubMed

    Whittaker, P; Hines, F A; Robl, M G; Dunkel, V C

    1996-01-01

    The effects of increasing dietary levels of Fe on the histopathology of liver, pancreas, spleen, and heart were examined in a rat model for iron overload. Sprague-Dawley rats were fed diets containing 35, 350, 3,500, or 20,000 micrograms Fe/g, and, after 12 wk, there was a direct correlation between increased liver nonheme Fe and lipid peroxidation measured by the lipid-conjugated diene assay. Histopathological examination of tissues revealed the following: (a) hepatocellular hemosiderosis in all groups of rats, with a dose-related accumulation of cytoplasmic Fe-positive material predominantly in hepatocytes located in the periportal region (Zone 1), (b) myocardial degeneration and necrosis (cardiomyopathy) with hemosiderin in interstitial macrophages or in myocardial fibers of animals with heart damage, (c) splenic lymphoid atrophy affecting the marginal zone of the white pulp and hemosiderin deposition in the sinusoidal macrophages, and (d) pancreatic atrophy with loss of both the endocrine and exocrine pancreatic tissue in those animals receiving 3,500 and 20,000 micrograms Fe/g of diet. The toxic effects of Fe overload in this rat model include cellular apoptosis or necrosis in heart, spleen, and pancreas and, when coupled with the findings on lipid peroxidation, suggests that oxidative stress is involved in the pathogenesis of the lesions.

  9. Role of the bradykinin B2 receptor in a rat model of local heart irradiation

    PubMed Central

    Lieblong, Benjamin J.; Sridharan, Vijayalakshmi; Srivastava, Anup K.; Moros, Eduardo G.; Sharma, Sunil K.; Boerma, Marjan

    2016-01-01

    Purpose Radiation-induced heart disease (RIHD) is a delayed effect of radiotherapy for cancers of the chest, such as breast, esophageal, and lung. Kinins are small peptides with cardioprotective properties. We previously used a rat model that lacks the precursor kininogen to demonstrate that kinins are involved in RIHD. Here, we examined the role of the kinin B2 receptor (B2R) in early radiation-induced signaling in the heart. Materials and methods Male Brown Norway rats received the B2R-selective antagonist HOE-140 (icatibant) via osmotic minipump from 5 days before until 4 weeks after 21 Gy local heart irradiation. At 4 weeks, signaling events were measured in left ventricular homogenates and nuclear extracts using western blotting and real-time polymerase chain reaction. Numbers of CD68-positive (monocytes/macrophages), CD2-positive (T-lymphocytes), and mast cells were measured using immunohistochemistry. Results Radiation-induced c-Jun phosphorylation and nuclear translocation were enhanced by HOE-140. HOE-140 did not modify endothelial nitric oxide synthase (eNOS) phosphorylation or alter numbers of CD2-positive or mast cells, but enhanced CD68-positive cell counts in irradiated hearts. Conclusions B2R signaling may regulate monocyte/macrophage infiltration and c-Jun signals in the irradiated heart. Although eNOS is a main target for kinins, the B2R may not regulate eNOS phosphorylation in response to radiation. PMID:25955317

  10. Prenatal Ethanol Exposure Increases Brain Cholesterol Content in Adult Rats

    PubMed Central

    Barceló-Coblijn, Gwendolyn; Wold, Loren E.; Ren, Jun; Murphy, Eric J.

    2013-01-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content is known to change in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43%, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total PUFA, in the n-3/n-6 ratio, and in the 22:6 n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of post-natal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats. PMID:23996454

  11. Studies on Pentoxifylline and Tocopherol Combination for Radiation-Induced Heart Disease in Rats

    SciTech Connect

    Liu Hui; Xiong Mai; Xia Yunfei; Cui Nianji; Lu Rubiao; Deng Ling; Lin Yuehao; Rong Tiehua

    2009-04-01

    Purpose: To investigate whether the application of pentoxifylline (PTX) and tocopherol l (Vit. E) could modify the development of radiation-induced heart disease and downregulate the expression of transforming growth factor (TGF)-{beta}1mRNA in rats. Methods and Materials: A total of 120 Sprague-Dawley rats were separated into four groups: control group, irradiated group, experimental group 1, and experiment group 2. Supplementation was started 3 days before irradiation; in experimental group 1, injection of PTX (15 mg/kg/d) and Vit. E (5.5 mg/kg/d) continued till the 12th week postirradiation, whereas in experimental group 2 it was continued until the 24th week postirradiation. All rats were administrated a single dose of 20 Gy irradiation to the heart except the control group. Histopathologic evaluation was performed at various time points (Days 1, 2, 4, 8, and 12 and 24th week) up to 24 weeks after irradiation. Changes of levels of TGF-{beta}1 mRNA expression were also investigated at the same time points using competitive polymerase chain reaction. Results: Compared with the irradiated group, levels of TGF-{beta}1 mRNA of the rat hearts were relatively low in the two experimental groups on the 12th week postirradiation. In experimental group 1, there was a rebound expression of TGF-{beta}1 mRNA on the 24th week postirradiation, whereas that of the experimental group 2 remained low (p < 0.05). The proportions of collagen fibers of the two experimental groups were lower than that of irradiated group (p < 0.05). A rebound could be observed in the experimental group 1. Conclusion: PTX and Vit. E downregulated the expression of TGF-{beta}1 mRNA. The irradiated rat hearts showed a marked pathologic response to the drugs. The withdrawal of drugs in the 12th week postirradiation could cause rebound effects of the development of fibrosis.

  12. Heart Rate Response During Underwater Treadmill Training in Adults with Incomplete Spinal Cord Injury

    PubMed Central

    Morgan, Don W.

    2015-01-01

    Background: Walking on a submerged treadmill can improve mobility in persons displaying lower limb muscle weakness and balance deficits. Little is known, however, regarding the effect of water treadmill exercise on cardiac performance in persons with incomplete spinal cord injury (iSCI). Objective: To assess heart rate response during underwater treadmill training (UTT) in adults with iSCI. Methods: Seven males and 4 females with iSCI (age = 48 ± 13 years; 5 ± 8 years after injury) completed 8 weeks of UTT (3 sessions per week; 3 walks per session) incorporating individually determined walking speeds, personalized levels of body weight unloading, and gradual, alternating increases in speed and duration. Heart rate was monitored during the last 15 seconds of the final 2 minutes of each walk. Results: Over the course of 3 biweekly periods in which walking speed remained constant, heart rate fell by 7% (7 ± 1 b•min-1; P < .001) in weeks 2 and 3, 14% (17 ± 6 b•min-1; P < .001) in weeks 4 and 5, and 17% (21 ± 11 b•min-1; P < .001) in weeks 6 and 7. Conclusion: In adults with iSCI, progressively greater absolute and relative reductions in submaximal exercise heart rate occurred after 2 months of UTT featuring a systematic increase in training volume. PMID:25762859

  13. Electron microscopy examination of ventricles from hypertrophied hearts of copper deficient rats

    SciTech Connect

    Medeiros, D.M.; Bagby, D.; Ovecka, G.; McCormick, R.J. )

    1989-02-15

    Male Long Evans rats were fed AIN-76 diets that were either copper adequate (8 mg/kg diet, n=6) or copper deficient (0.4 mg/Kg diet, n=6) from weaning until 8 weeks, thereafter. Copper deficiency was verified by decreased hematocrit and liver copper levels and increased heart weight in the copper deficient group. Left ventricular cardiac muscle was removed and processed from histological examination by transmission electron microscopy. In copper adequate rats the myocytes were usually separated by single rows of mitochondria with cristae in densely packed parallel arrays. In copper deficient rats, pockets of greatly proliferated mitochondria were observed between the muscle fibers. These mitochondria were enlarged vacuolized and contained fragmented cristae. Areas of poorly organized myofilaments were detected in the ventricles of copper deficient animals. Accumulation of glycogen and lipid droplets was apparent in these rats.

  14. Effects of Adolescent Ethanol Exposure on Sleep in Adults Rats

    PubMed Central

    Criado, José R.; Wills, Derek N.; Walker, Brendan M.; Ehlers, Cindy L.

    2010-01-01

    Although adolescent ethanol (EtOH) exposure has been associated with long-lasting changes in brain function, little is known as to whether EtOH exposure during adolescence alters sleep and cortical arousal. This study examined protracted alterations in sleep in adult rats exposed to EtOH during adolescence. Adolescent male Wistar rats were exposed to EtOH vapor for 12 hr/day for five weeks. Cortical electroencephalograms (EEGs) were obtained during 4-hr recording sessions after five weeks of withdrawal from EtOH. Adolescent EtOH exposure significantly reduced the mean duration of slow-wave sleep (SWS) episodes and the total amount of time spent in SWS in EtOH-exposed rats, compared to controls. Spectral analysis revealed that adolescent EtOH exposure significantly increased cortical peak frequencies during SWS in the 2-4 Hz, 4-6 Hz and 6-8 Hz bands. Taken together, our findings suggest that chronic EtOH exposure in adolescent rats reduces measures of SWS, an effect also seen as part of normal aging. Although the cellular and molecular mechanisms mediating the consequences of EtOH exposure on the aging process are not known, the similarities between adolescent EtOH exposure and aging merits further investigation. PMID:18922666

  15. Preproglucagon mRNA expression in adult rat submandibular glands.

    PubMed

    Egéa, J C; Hirtz, C; Deville de Périère, D

    2003-04-01

    Salivary glands of various animal species have been reported to contain and suggested to produce glucagon or glucagon-like material, but the origin and the nature of this salivary peptide are still doubtful. The present study was undertaken to ascertain whether the glucagon gene is expressed in rat submandibular glands and in an immortalized murine cell line derived from salivary glands (SCA-9 cell line). For this purpose, total RNA was isolated from submandibular glands or cultured cells and submitted to reverse transcription. The cDNAs obtained were amplified by a nested polymerase chain reaction using preproglucagon primers. The results showed that the preproglucagon mRNA was expressed in adult rat submandibular glands but not in the SCA-9 cell line. Determination of cyclic DNA (cDNA) sequence established identity with the coding regions of rat pancreatic pre-proglucagon gene. In conclusion, these results strongly support the idea that rat submandibular glands could represent a source of extrapancreatic glucagon or of its precursor's peptide.

  16. Maternal hyperthyroidism in rats impairs stress coping of adult offspring.

    PubMed

    Zhang, Limei; Hernández, Vito S; Medina-Pizarro, Mauricio; Valle-Leija, Pablo; Vega-González, Arturo; Morales, Teresa

    2008-05-01

    Given the evidence that maternal hyperthyroidism (MH) compromises expression of neuronal cytoskeletal proteins in the late fetal brain by accelerated neuronal differentiation, we investigated possible consequences of MH for the emotional and cognitive functions of adult offspring during acute and subchronic stress coping. Experimental groups consisted of male rat offspring from mothers implanted with osmotic minipumps infusing either thyroxine (MH) or vehicle (Ctrl) during pregnancy. Body weight and T4 level were monitored during the first 3 postnatal months, and no differences were found with the controls. We analyzed hippocampal CA3 pyramidal neurons and dentate granular cell morphology during several postnatal stages and found increased dendritic arborization. On postnatal day 90 a modified subchronic mild stress (SCMS) protocol was applied to experimental subjects for 10 days. The Morris water maze was used before, during, and after application of the SCMS protocol to measure spatial learning. The tail suspension test (TST) and forced-swimming test (FST) were used to evaluate behavioral despair. The MH rats displayed normal locomotor activity and spatial memory prior to SCMS, but impaired spatial learning after acute and chronic stress. In both the FST and TST we found that MH rats spent significantly more time immobile than did controls. Serum corticosterone level was found to increase after 30 min of restraint stress, and corticotropin-releasing factor immunoreactivity was found to be increased in the central nucleus of the amygdala. Our results suggest that MH in rats leads to the offspring being more vulnerable to stress in adulthood.

  17. Furosemide modifies heart hypertrophy and glycosaminoglycan myocardium content in a rat model of neurogenic hypertension.

    PubMed

    Pourzitaki, Chryssa; Tsaousi, Georgia; Manthou, Maria Eleni; Karakiulakis, Georgios; Kouvelas, Dimitrios; Papakonstantinou, Eleni

    2016-08-01

    Hypertension is a major risk factor for atherogenesis and heart hypertrophy, both of which are associated with specific morphological and functional changes of the myocardium. Glycosaminoglycans (GAGs) are complex molecules involved both in tissue morphology and function. In the present study, we investigated the effects of neurogenic hypertension and subsequent antihypertensive treatment with furosemide, on heart hypertrophy and the content of GAGs in the myocardium. Neurogenic hypertension was achieved in male Wistar rats by bilateral aortic denervation (bAD). At days 2, 7 and 15 after surgery, animals were sacrificed and the hearts were dissected away, weighted, and homogenized. Total GAGs were assessed by measuring the uronic acid content colorimetrically and individual GAGs were isolated and characterized by enzymatic treatment, with GAG-degrading enzymes, using electrophoresis on polyacrylamide gradient gels and cellulose acetate membranes. In bAD-animals blood pressure, blood pressure lability, heart rate and heart weight were significantly increased 15 days postoperatively. These effects were prevented by treatment with furosemide. Major GAGs identified in the heart were chondroitin sulphates, heparin (H), heparan sulphate (HS) and hyaluronic acid. The content of uronic and the relative content of H and HS in the heart in bAD animals significantly decreased from day 2 to day 15 postoperatively. Furosemide prevented the bAD induced decrease in GAG content. Considering that H and HS are potent inhibitors of cardiomyocyte hypertrophy, our results indicate that heart hypertrophy induced by neurogenic hypertension may be associated with decreases in the relative content of heparin and heparan sulphate in the heart. PMID:27221775

  18. Monolayer co-culture of rat heart cells and bovine adrenal chromaffin paraneurons.

    PubMed

    Trifaró, J M; Tang, R; Novas, M L

    1990-04-01

    This paper describes a method for the preparation of co-cultures of rat heart cells and bovine adrenal chromaffin paraneurons. The most suitable condition for heart cell isolation was when a combination of trypsin-DNAse I in Locke's solution was used for digestion. The best co-culture conditions were obtained when 10(6) heart cells were plated on 7- to 8-d-old adrenal chromaffin paraneuron cultures containing 0.5 x 10(6) cells per 35-mm diameter culture dishes. Measurements of DNA (heart cells and chromaffin paraneurons), monitoring of beating frequency (heart cells), and catecholamine (chromaffin paraneurons) levels and release indicated that both cell types remain viable and functional for several weeks. Heart cells started their characteristic contractile activity 24 h earlier when plated either on viable or lysed chromaffin paraneurons, an effect apparently due to faster surface adhesion of heart cells. The beating frequency of heart cells increased after treatment of co-cultures with either noradrenaline or nicotine, with the latter agent acting indirectly through the release of chromaffin paraneuron catecholamines. Propranolol produced a dose-related inhibition of the responses to either noradrenaline or nicotine, thus suggesting that the increase in myocyte's beating activity was mediated through beta-receptors. Anti-myosin and anti-dopamine-beta-hydroxylase immunostaining was used for cell type identification and for the demonstration of body-to-body and process-to-process contacts between adrenal chromaffin paraneurons and heart cells. This co-culture system will serve as a starting point of further studies directed to understand a) the influence of a cell type on the development and on the phenotypic characteristics of a second cell type and b) the interaction of cells derived from different organs and species.

  19. The Mr 28,000 gap junction proteins from rat heart and liver are different but related.

    PubMed

    Nicholson, B J; Gros, D B; Kent, S B; Hood, L E; Revel, J P

    1985-06-10

    The sequence of the amino-terminal 32 residues of the rat heart Mr 28,000 gap junction protein presented here allows, for the first time, a sequence comparison of gap junctional proteins from different tissues (heart and liver). Comparison of the rat heart gap junction protein sequence and that available from rat liver reveals 43% sequence identity and conservative changes at an additional 25% of the positions. Both proteins exhibit a hydrophobic domain which could represent a transmembrane span of the junction. This result unequivocally demonstrates the existence of at least two forms of the gap junction protein. As yet, no homology is evident between the gap junctional proteins of either heart or liver and main intrinsic protein from rat eye lens. PMID:2987225

  20. Improving Medication Knowledge among Older Adults with Heart Failure: A Patient-Centered Approach to Instruction Design

    ERIC Educational Resources Information Center

    Morrow, Daniel G.; Weiner, Michael; Young, James; Steinley, Douglas; Deer, Melissa; Murray, Michael D.

    2005-01-01

    Purpose: We investigated whether patient-centered instructions for chronic heart failure medications increase comprehension and memory for medication information in older adults diagnosed with chronic heart failure. Design and Methods: Patient-centered instructions for familiar and unfamiliar medications were compared with instructions for the…

  1. Protein remodeling of the heart ventricles in hereditary hypertriglyceridemic rat: effect of ACE-inhibition.

    PubMed

    Simko, Fedor; Pelouch, Václav; Torok, Jozef; Luptak, Ivan; Matuskova, Jana; Pechanova, Olga; Babal, Pavel

    2005-01-01

    The aim of this study was to determine whether protein remodeling of the heart ventricles and remodeling of the aorta were present in hereditary hypertriglyceridemic (hHTG) rats and whether treatment with the angiotensin-converting enzyme inhibitor, captopril could prevent these alterations. Three groups of rats were investigated in a four week experiment control Wistar /C/rats, hHTg rats, hHTg rats given captopril (100 mg/kg/day) (hHTg + CAP). In the hHTg group, the increased systolic blood pressure (SBP) was associated with hypertrophy of the LV and RV. Protein profile analysis revealed an enhancement of metabolic protein concentration in both ventricles. The concentration of total collagenous proteins was not changed in either ventricles. However, alterations in composition of cardiac collagen were detected, characterized by higher concentration of hydroxyproline in pepsin-insoluble fraction and lower concentration of hydroxyproline in pepsin soluble faction in the LV. Hypertrophy of aorta, associated with the reduction of nitric oxide dependent relaxation, was also present in hHTG rats. Captopril normalized SBP, reduced left ventricular hypertrophy (LVH), diminished metabolic protein concentration in both ventricles, and improved NO-dependent relaxation of the aorta. Furthermore, captopril partially reversed alterations in hydroxyproline concentration in soluble and insoluble collagenous fractions of the LV. We conclude that hypertrophy of both ventricles and the aorta are present in hHTG rats, along with protein remodeling of both ventricles. Captopril partially prevented left ventricular hypertrophy development and protein remodeling of the myocardium.

  2. Functional evaluation of rat hearts transplanted after preservation in a high-pressure gaseous mixture of carbon monoxide and oxygen

    PubMed Central

    Hatayama, Naoyuki; Inubushi, Masayuki; Naito, Munekazu; Hirai, Shuichi; Jin, Yong-Nan; Tsuji, Atsushi B.; Seki, Kunihiro; Itoh, Masahiro; Saga, Tsuneo; Li, Xiao-Kang

    2016-01-01

    We recently succeeded in resuscitating an extracted rat heart following 24–48 hours of preservation in a high-pressure gaseous mixture of carbon monoxide (CO) and oxygen (O2). This study aimed to examine the function of rat hearts transplanted after being preserved in the high-pressure CO and O2 gas mixture. The hearts of donor rats were preserved in a chamber filled with CO and O2 under high pressure for 24 h (CO24h) or 48 h at 4 °C. For the positive control (PC) group, hearts immediately extracted from donor rats were used for transplantation. The preserved hearts were transplanted into recipient rats by heterotopic cervical heart transplantation. CO toxicity does not affect the grafts or the recipients. Light microscopy and [18F]-fluorodeoxyglucose positron emission tomography revealed that there were no significant differences in the size of the myocardial infarction or apoptosis of myocardial cells in post-transplant hearts between the PC and CO24h groups. Furthermore, at 100 days after the transplantation, the heart rate, weight and histological staining of the post-transplanted hearts did not differ significantly between the PC and CO24h groups. These results indicate that the function of rat hearts is well preserved after 24 hours of high-pressure preservation in a CO and O2 gas mixture. Therefore, high-pressure preservation in a gas mixture can be a useful method for organ preservation. PMID:27562456

  3. Effects of two newly synthesized analogues of lidocaine on rat arterial blood pressure and heart rate.

    PubMed

    Al Rasheed, N M; Al Sayed, M I; Al Zuhair, H H; Al Obaid, A R; Fatani, A J

    2001-04-01

    Two new analogues of lidocaine were synthesized at the College of Pharmacy, King Saud University: compound I (Methyl-2-[2-(N,N-diethylamino) acetamido]-3-cyano-4,5-dimethylbenzoate) and compound II (Methyl-2-[2-(piperidino) acetamido]-3-cyano-4,5-dimethylbenzoate). Their influence on the arterial blood pressure and the heart rate of urethane-anaesthetized rats was studied and compared with the actions of lidocaine. Compounds I, II and lidocaine induced significant dose-dependent decreases in the arterial blood pressure and heart rate, which usually returned to basal values within 3-5 min. There were significant differences in the potency of the three compounds in producing their effects on blood pressure and heart rate (P< 0.0001, ANOVA). Compound II was 14 and 6 times more potent in reducing blood pressure and 8 and 2 times more capable of reducing the heart rate than lidocaine and compound I, respectively. The results of this study also indicated the ineffectiveness of antagonists of autonomic, histaminergic and 5-HT receptor, and various vasodilators in blocking the actions of the three compounds on blood pressure and heart rate. Pretreatment with CaCl(2)significantly reduced the hypotension and bradycardia induced by the three compounds, suggesting the involvement of calcium channels, probably of the L type. Several possible mechanisms are postulated. In conclusion, the results direct attention to the capability of the two new compounds to decrease blood pressure and heart rate; affects that may have clinical potential.

  4. Acute Effects of Vagotomy on Baroreflex Equilibrium Diagram in Rats with Chronic Heart Failure.

    PubMed

    Kawada, Toru; Li, Meihua; Zheng, Can; Sugimachi, Masaru

    2016-01-01

    The arterial baroreflex system can be divided into the neural arc, from pressure input to efferent sympathetic nerve activity (SNA), and the peripheral arc, from SNA to arterial pressure (AP). Plotting the neural and peripheral arcs on a pressure-SNA plane yields a baroreflex equilibrium diagram. We examined the effects of vagotomy on the open-loop static characteristics of the carotid sinus baroreflex in normal control rats (NC, n = 10) and rats with heart failure after myocardial infarction (MI, n = 10). In the NC group, vagotomy shifted the neural arc toward higher SNA and decreased the slope of the peripheral arc. Consequently, the operating-point SNA increased without a significant change in the operating-point AP on the baroreflex equilibrium diagram. These vagotomy-induced effects were not observed in the MI group, suggesting a loss of vagal modulation of the carotid sinus baroreflex function in heart failure. PMID:27594790

  5. Acute Effects of Vagotomy on Baroreflex Equilibrium Diagram in Rats with Chronic Heart Failure

    PubMed Central

    Kawada, Toru; Li, Meihua; Zheng, Can; Sugimachi, Masaru

    2016-01-01

    The arterial baroreflex system can be divided into the neural arc, from pressure input to efferent sympathetic nerve activity (SNA), and the peripheral arc, from SNA to arterial pressure (AP). Plotting the neural and peripheral arcs on a pressure–SNA plane yields a baroreflex equilibrium diagram. We examined the effects of vagotomy on the open-loop static characteristics of the carotid sinus baroreflex in normal control rats (NC, n = 10) and rats with heart failure after myocardial infarction (MI, n = 10). In the NC group, vagotomy shifted the neural arc toward higher SNA and decreased the slope of the peripheral arc. Consequently, the operating-point SNA increased without a significant change in the operating-point AP on the baroreflex equilibrium diagram. These vagotomy-induced effects were not observed in the MI group, suggesting a loss of vagal modulation of the carotid sinus baroreflex function in heart failure.

  6. Acute Effects of Vagotomy on Baroreflex Equilibrium Diagram in Rats with Chronic Heart Failure

    PubMed Central

    Kawada, Toru; Li, Meihua; Zheng, Can; Sugimachi, Masaru

    2016-01-01

    The arterial baroreflex system can be divided into the neural arc, from pressure input to efferent sympathetic nerve activity (SNA), and the peripheral arc, from SNA to arterial pressure (AP). Plotting the neural and peripheral arcs on a pressure–SNA plane yields a baroreflex equilibrium diagram. We examined the effects of vagotomy on the open-loop static characteristics of the carotid sinus baroreflex in normal control rats (NC, n = 10) and rats with heart failure after myocardial infarction (MI, n = 10). In the NC group, vagotomy shifted the neural arc toward higher SNA and decreased the slope of the peripheral arc. Consequently, the operating-point SNA increased without a significant change in the operating-point AP on the baroreflex equilibrium diagram. These vagotomy-induced effects were not observed in the MI group, suggesting a loss of vagal modulation of the carotid sinus baroreflex function in heart failure. PMID:27594790

  7. Mechanically induced orientation of adult rat cardiac myocytes in vitro

    NASA Technical Reports Server (NTRS)

    Samuel, J.-L.; Vandenburgh, H. H.

    1990-01-01

    The present study describes the spatial orientation of a population of freshly isolated adult rat cardiac myocytes using a computerized mechanical cell stimulator device for tissue cultured cells. A continuous unidirectional stretch of the substratum at 60 to 400 microns/min for 120 to 30 min, respectively, during the cell attachment period in a serum-free medium was found to induce a significant threefold increase in the number of rod-shaped myocytes oriented parallel to the direction of movement. The myocytes orient less well with unidirectional substratum stretching after their adhesion to the substratum. Adult myocytes plated onto a substratum undergoing continuous 10-percent stretch-relaxation cycling show no significant change in the myocyte orientation or cytoskeletal organization. In addition to the type of mechanical activity, orientation of rod-shaped myocytes is dependent on the speed of the substratum, the final stretch amplitude, and the timing between initiation of substratum stretching and adhesion of myocytes to the substratum.

  8. X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography

    SciTech Connect

    Umetani, K.; Fukushima, K.

    2013-03-15

    An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 {mu}m, yielding sharp images of small arteries. The exposure time has been shortened to around 2 ms using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 {mu}m diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 {mu}m was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct

  9. X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography

    NASA Astrophysics Data System (ADS)

    Umetani, K.; Fukushima, K.

    2013-03-01

    An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 μm, yielding sharp images of small arteries. The exposure time has been shortened to around 2 ms using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 μm diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 μm was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct

  10. Alcohol exposure in utero perturbs retinoid homeostasis in adult rats

    PubMed Central

    Kim, Youn-Kyung; Zuccaro, Michael V.; Zhang, Changqing; Sarkar, Dipak

    2015-01-01

    Background Maternal alcohol exposure and adult alcohol intake have been shown to perturb the metabolism of various micro- and macro-nutrients, including vitamin A and its derivatives (retinoids). Therefore, it has been hypothesized that the well-known detrimental consequences of alcohol consumption may be due to deregulations of the metabolism of such nutrients rather than to a direct effect of alcohol. Alcohol exposure in utero also has long-term harmful consequences on the health of the offspring with mechanisms that have not been fully clarified. Disruption of tissue retinoid homeostasis has been linked not only to abnormal embryonic development, but also to various adult pathological conditions, including cancer, metabolic disorders and abnormal lung function. We hypothesized that prenatal alcohol exposure may permanently perturb tissue retinoid metabolism, predisposing the offspring to adult chronic diseases. Methods Serum and tissues (liver, lung and prostate from males; liver and lung from females) were collected from 60-75 day-old sprague dawley rats born from dams that were: (I) fed a liquid diet containing 6.7% alcohol between gestational day 7 and 21; or (II) pair-fed with isocaloric liquid diet during the same gestational window; or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum and tissue retinoid levels were analyzed by reverse-phase high-performance liquid chromatography (HPLC). Serum retinol-binding protein (RBP) levels were measured by western blot analysis, and liver, lung and prostate mRNA levels of lecithin-retinol acyltransferase (LRAT) were measured by qPCR. Results Retinyl ester levels were significantly reduced in the lung of both males and females, as well as in the liver and ventral prostate of males born from alcohol-fed dams. Tissue LRAT mRNA levels remained unchanged upon maternal alcohol treatment. Conclusions Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a tissue- and sex

  11. Human fetal cardiac progenitors: The role of stem cells and progenitors in the fetal and adult heart.

    PubMed

    Bulatovic, Ivana; Månsson-Broberg, Agneta; Sylvén, Christer; Grinnemo, Karl-Henrik

    2016-02-01

    The human fetal heart is formed early during embryogenesis as a result of cell migrations, differentiation, and formative blood flow. It begins to beat around gestation day 22. Progenitor cells are derived from mesoderm (endocardium and myocardium), proepicardium (epicardium and coronary vessels), and neural crest (heart valves, outflow tract septation, and parasympathetic innervation). A variety of molecular disturbances in the factors regulating the specification and differentiation of these cells can cause congenital heart disease. This review explores the contribution of different cardiac progenitors to the embryonic heart development; the pathways and transcription factors guiding their expansion, migration, and functional differentiation; and the endogenous regenerative capacity of the adult heart including the plasticity of cardiomyocytes. Unfolding these mechanisms will become the basis for understanding the dynamics of specific congenital heart disease as well as a means to develop therapy for fetal as well as postnatal cardiac defects and heart failure.

  12. Dietary Interventions for Heart Failure in Older Adults: Re-emergence of the Hedonic Shift

    PubMed Central

    Wessler, Jeffrey D.; Hummel, Scott L.; Maurer, Mathew S.

    2014-01-01

    Dietary non-adherence to sodium restriction is an important contribution to heart failure (HF) symptom burden, particularly in older adults. While knowledge, skills, and attitudes towards sodium restriction are important, sodium intake is closely linked to the ability to taste salt. The ‘hedonic shift’ occurs when sodium restriction induces changes in an individual’s salt taste that lower subsequent salt affinity. Older adults often have compromised salt taste and higher dietary salt affinity due to age-related changes. Older HF patients may have additional loss of salt taste and elevated salt appetite due to comorbid conditions, medication use, and micronutrient or electrolyte abnormalities, creating a significant barrier to dietary adherence. Induction of the hedonic shift has the potential to improve long-term dietary sodium restriction and significantly impact HF outcomes in older adults. PMID:25216615

  13. Dietary interventions for heart failure in older adults: re-emergence of the hedonic shift.

    PubMed

    Wessler, Jeffrey D; Hummel, Scott L; Maurer, Mathew S

    2014-01-01

    Dietary non-adherence to sodium restriction is an important contribution to heart failure (HF) symptom burden, particularly in older adults. While knowledge, skills, and attitudes toward sodium restriction are important, sodium intake is closely linked to the ability to taste salt. The 'hedonic shift' occurs when sodium restriction induces changes in an individual's salt taste that lower subsequent salt affinity. Older adults often have compromised salt taste and higher dietary salt affinity due to age-related changes. Older HF patients may have additional loss of salt taste and elevated salt appetite due to comorbid conditions, medication use, and micronutrient or electrolyte abnormalities, creating a significant barrier to dietary adherence. Induction of the hedonic shift has the potential to improve long-term dietary sodium restriction and significantly impact HF outcomes in older adults.

  14. Exposure of rats to ozone: evidence of damage to heart and brain

    SciTech Connect

    Rahman, I.; Massaro, G.D.; Massaro, D. )

    1992-01-01

    Ozone is a strong oxidizing agent, and in many locations it is a major atmospheric pollutant. It is phytotoxic and an important cause of lung dysfunction in humans. Recently, a significant association has been established between total atmospheric oxidants, of which ozone is one, and daily cardiovascular mortality rates. In this article, we show that exposure of rats to ozone for 5 days, in a concentration found in major urban centers, results in an increased concentration of thiobarbituric acid-reactive material (an indicator of lipid peroxidation) in heart and brain tissue as well as elevated activity of catalase and glutathione peroxidase (enzymic scavengers of peroxides) in these tissues. We examined the heart anatomically and found evidence of extracellular and intracellular edema. These findings indicate that the heart and brain are damaged by a concentration of ozone present in major urban centers; they may have important implications for chronic illness and degenerative processes in humans.

  15. Motion compensation of optical mapping signals from isolated beating rat hearts

    NASA Astrophysics Data System (ADS)

    Stender, B.; Ernst, F.; Wang, B.; Zhang, Z. X.; Schlaefer, A.

    2013-09-01

    Optical mapping is a well established technique for recording monophasic action potential traces on the epicardial surface of isolated hearts. This measuring technique offers a high spatial resolution but it is sensitive towards myocardial motion. Motion artifacts occur because the mapping between a certain tissue portion sending out fluorescent light and a pixel of the photo detector changes over time. So far this problem has been addressed by suppressing the motion or ratiometric imaging. We developed a different approach to compensate the motion artifacts based on image registration. We could demonstrate how an image deformation field temporally changing with the heart motion could be determined. Using these deformation field time series for image transformation motion signals could be generated for each image pixel which were then successfully applied to remove baseline shift and compensate motion artifacts potentially leading to errors within maps of the first arrival time. The investigation was based on five different rat hearts stained with Di-4-ANEPPS.

  16. Oxidative Stress in the Heart of Rats Infected with Trypanosoma evansi

    PubMed Central

    Baldissera, Matheus D.; Souza, Carine de F.; Bertoncheli, Cláudia M.; da Silveira, Karine L.; Grando, Thirssa H.; Porto, Bianca C. Z.; Leal, Daniela B. R.; Silva, Aleksandro S. Da; Mendes, Ricardo E.; Stefani, Lenita M.; Monteiro, Silvia G.

    2016-01-01

    This study was conducted to investigate the occurrence of oxidative stress in the heart tissue of rats infected with Trypanosoma evansi. Rats were divided into 2 groups (A and B) with 12 animals each, and further subdivided into 4 subgroups (A1 and A2, 6 animals/each; and B1 and B2, 6 animals/each). Animals in the groups B1 and B2 were subcutaneously inoculated with T. evansi. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase activity (SOD), glutathione S-transferase activity (GST), reduced glutathione activity (GSH), and non-protein thiols (NPSH) in the heart tissue were evaluated. At day 5 and 15 post-infection (PI), an increase in the TBARS levels and a decrease in the SOD activity (P<0.05) were observed. GSH and GST activities were decreased in infected animals at day 15 PI (P<0.05). Considering the proper functioning of the heart, it is possible that the changes in the activity of these enzymes involved in the oxidative stress may be related, at least in part, in the pathophysiology of rats infected with T. evansi. PMID:27417077

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

    PubMed

    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.

  18. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats

    PubMed Central

    Mansouri, Esrafil; Khorsandi, Layasadat; Abdollahzade Fard, Amin

    2015-01-01

    Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg-1 body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes. PMID:26261706

  19. Simultaneous gene expression signature of heart and peripheral blood mononuclear cells in astemizole-treated rats.

    PubMed

    Lee, Eun-Hee; Oh, Jung-Hwa; Park, Han-Jin; Kim, Do-Geun; Lee, Jong-Hwa; Kim, Choong-Yong; Kwon, Myung-Sang; Yoon, Seokjoo

    2010-08-01

    We investigated the effects of astemizole, a second-generation antihistamine, on the heart and peripheral blood mononuclear cells (PBMCs) and identified the early markers of its cardiotoxicity using gene expression profiling. Astemizole causes torsades de pointes, which is a type of ventricular tachycardia. We administered astemizole (dosage: 20, 60 mg/kg) to male Sprague-Dawley rats, using an oral gavage. Cardiac tissue and PBMCs were collected from the rats 4 h after treatment. Gene expression profiles were obtained using an Affymetrix GeneChip. The most deregulated genes were associated with energy metabolism pathways and calcium ion homeostasis in the heart of astemizole-treated rats. The most altered genes in the PBMCs were those involved in developmental processes and cardiotoxicity. Genes related to the response to oxidative stress, reactive oxygen species, heat shock proteins, hypoxia, immunity, and inflammation were also deregulated in the heart and PBMCs. These data provide further insight into the genetic pathways affected by astemizole. In addition, the simultaneously deregulated genes identified herein may be further studied. It will be interesting to find out whether single genes or certain sets of these genes could finally serve as biomarkers for cardiotoxicity of astemizole or other similar antihistamine drugs. PMID:20221588

  20. Modification of caffeine-induced injury in Ca2+-free perfused rat hearts. Relationship to the calcium paradox.

    PubMed Central

    Vander Heide, R. S.; Altschuld, R. A.; Lamka, K. G.; Ganote, C. E.

    1986-01-01

    The pathogenesis of the calcium paradox has not been established. In calcium-free perfused hearts, caffeine, which releases calcium from the sarcoplasmic reticulum, causes severe myocardial injury, with creatine kinase (CK) release and contraction band necrosis similar in many respects to the calcium paradox. It has been postulated that contracture, initiated by a small rise in intracellular calcium, may cause sarcolemmal injury in both the calcium paradox and caffeine-induced myocardial injury. The present study was initiated to determine whether interventions which modulate caffeine-induced contracture will also correspondingly alter cellular injury. The effects of caffeine dose, procaine, extended calcium-free perfusion, elevated potassium, temperature, and increasing intracellular sodium on caffeine-induced contracture were examined in Langendorff-perfused adult rat hearts. Caffeine-induced contracture at 22 C increased over a dose range of 5-40 mM caffeine. Procaine, which inhibits caffeine-induced calcium release at doses between 5 and 20 mM, progressively reduced contracture caused by addition of 20 mM caffeine at 22 C. Hearts perfused with calcium-free solution containing 16 mM K+ showed a reduction in caffeine-induced contracture. Extended calcium-free perfusion (20 minutes) at temperatures from 18 to 37 C resulted in a progressive reduction of caffeine-induced contracture. Each of these interventions was also found to inhibit caffeine-induced injury at 37 C. Low temperature was found to have complex effects. Hypothermia enhanced caffeine contractures but also protected hearts from cell separations and CK release. Increasing intracellular sodium was found to enhance caffeine-induced contracture at 37 C. There was a direct correlation between measured intracellular sodium levels and the magnitude and duration of caffeine-induced contracture. These results demonstrate a direct correlation between the magnitude of contracture and myocardial injury in calcium

  1. Blood Pressure and Heart Rate During Continuous Experimental Sleep Fragmentation in Healthy Adults

    PubMed Central

    Carrington, Melinda J.; Trinder, John

    2008-01-01

    Study Objectives: This paper aims to determine whether experimental arousals from sleep delay the sleep related fall in cardiovascular activity in healthy adults. Design: We report the results of 2 studies. The first experiment manipulated arousals from sleep in young adults. The second compared the effect of frequent arousals on young and middle-aged adults. The influence of arousals were assessed in 2 ways; (1) the fall in cardiovascular activity over sleep onset and the early sleep period, and (2) the underlying sleep levels during the sleep periods in between arousals. Setting: Both experiments were conducted in the sleep laboratory of the Department of Psychology, The University of Melbourne, Australia. Participants: There were 5 male and 5 female healthy individuals in each experiment between the ages of 18–25 years (Experiment 1) and 38–55 years (Experiment 2). Interventions: Participants in Experiment 1 were aroused by auditory stimuli every (i) 2 min, (ii) 1 min, and (iii) 30 sec of sleep for 90 min after the first indication of sleep. In a control condition, participants slept undisturbed for one NREM sleep cycle. Experiment 2 compared the control with the 30-sec condition in the young adults and in an additional group of middle-aged adults. Measurements and Results: The dependent variables were blood pressure (BP) and heart rate (HR). In Experiment 1, sleep fragmentation at higher frequencies retarded the fall in BP over sleep onset but did not affect the underlying sleep levels. Experiment 2 showed that there were no age differences on the effect of arousals on changes in BP and HR during sleep. Conclusions: This paper supports the hypothesis that repetitive arousals from sleep independently contribute to elevations in BP at night. Citation: Carrington MJ; Trinder J. Blood pressure and heart rate during continuous experimental sleep fragmentation in healthy adults. SLEEP 2008;31(12):1701–1712. PMID:19090326

  2. Propagation of the cardiac impulse in the diabetic rat heart: reduced conduction reserve

    PubMed Central

    Nygren, A; Olson, M L; Chen, K Y; Emmett, T; Kargacin, G; Shimoni, Y

    2007-01-01

    Diabetes mellitus is a growing epidemic with severe cardiovascular complications. Although much is known about mechanical and electrical cardiac dysfunction in diabetes, few studies have investigated propagation of the electrical signal in the diabetic heart and the associated changes in intercellular gap junctions. This study was designed to investigate these issues, using hearts from control and diabetic rats. Diabetic conditions were induced by streptozotocin (STZ), given i.v. 7–14 days before experiments. Optical mapping with the voltage-sensitive dye di-4-ANEPPS, using hearts perfused on a Langendorff apparatus, showed little change in baseline conduction velocity in diabetic hearts, reflecting the large reserve of function. However, both the gap junction uncoupler heptanol (0.5–1 mm) and elevated potassium (9 mm, to reduce cell excitability) produced a significantly greater slowing of impulse propagation in diabetic hearts than in controls. The maximal action potential upstroke velocity (an index of the sodium current) and resting potential was similar in single ventricular myocytes from control and diabetic rats, suggesting similar electrical excitability. Immunoblotting of connexin 43 (Cx43), a major gap junction component, showed no change in total expression. However, immunofluorescence labelling of Cx43 showed a significant redistribution, apparent as enhanced Cx43 lateralization. This was quantified and found to be significantly larger than in control myocytes. Labelling of two other gap junction proteins, N-cadherin and β-catenin, showed a (partial) loss of co-localization with Cx43, indicating that enhancement of lateralized Cx43 is associated with non-functional gap junctions. In conclusion, conduction reserve is smaller in the diabetic heart, priming it for impaired conduction upon further challenges. This can desynchronize contraction and contribute to arrhythmogenesis. PMID:17185336

  3. Phosphorylation and hydrolysis of 7-deazaadenine nucleotides by rat liver and beef heart mitochondria.

    PubMed

    Petrescu, I; Lascu, I; Goia, I; Markert, M; Schmidt, F H; Deaciuc, I V; Kezdi, M; Bârzu, O

    1982-03-01

    Tubercidin nucleotides [tubercidin 5'-mono-phosphate (TuMP), 5'-diphosphate (TuDP), and 5'-triphosphate (TuTP)] were tested as potential substrates for the mitochondrial phosphotransferases from rat liver and beef heart. TuDP is recognized by the mitochondrial translocase and phosphorylated by the respiratory chain enzymes in both mitochondria and submitochondrial particles from rat liver and beef heart; the low transport rate of the analogue into the matrix space of the intact organelles seems to be not a limiting step in the formation of TuTP. The phosphorylation of TuDP is significantly lower in beef heart mitochondria because of a higher specificity for ADP of the heart oxidative phosphorylation system. On the basis of the kinetic parameters of the partially purified liver mitochondrial adenylate kinase, one can conclude that the liver mitochondria are able to phosphorylate in vivo TuMP at a rate practically equal to the rate of AMP phosphorylation. The liver mitochondrial NDP kinase ensures a further fast phosphorylation of TuDP without the direct involvement of respiratory chain enzymes. In the case of heart mitochondria, two factors limit the rate of TuMP phosphorylation to TuTP: the lower acceptor activity of adenylate kinase with TuMP as compared with AMP and the different localization of heart NDP kinase situated on the inner face of the inner mitochondrial membrane. TuDP and TuTP preserve the ability of the natural nucleotides to interact with the "tight" nucleotide binding sites of isolated or membrane-bound F1. The low hydrolytic rate of TuTP with F1 may be related to the unusual flexibility of the glycosyl bond of tubercidin nucleotides in aqueous solution, with a high accessibility to syn conformation.

  4. Affecting Rhomboid-3 Function Causes a Dilated Heart in Adult Drosophila

    PubMed Central

    Yu, Lin; Lee, Teresa; Lin, Na; Wolf, Matthew J.

    2010-01-01

    Drosophila is a well recognized model of several human diseases, and recent investigations have demonstrated that Drosophila can be used as a model of human heart failure. Previously, we described that optical coherence tomography (OCT) can be used to rapidly examine the cardiac function in adult, awake flies. This technique provides images that are similar to echocardiography in humans, and therefore we postulated that this approach could be combined with the vast resources that are available in the fly community to identify new mutants that have abnormal heart function, a hallmark of certain cardiovascular diseases. Using OCT to examine the cardiac function in adult Drosophila from a set of molecularly-defined genomic deficiencies from the DrosDel and Exelixis collections, we identified an abnormally enlarged cardiac chamber in a series of deficiency mutants spanning the rhomboid 3 locus. Rhomboid 3 is a member of a highly conserved family of intramembrane serine proteases and processes Spitz, an epidermal growth factor (EGF)–like ligand. Using multiple approaches based on the examination of deficiency stocks, a series of mutants in the rhomboid-Spitz–EGF receptor pathway, and cardiac-specific transgenic rescue or dominant-negative repression of EGFR, we demonstrate that rhomboid 3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac function. The importance of EGF receptor signaling in the adult Drosophila heart underscores the concept that evolutionarily conserved signaling mechanisms are required to maintain normal myocardial function. Interestingly, prior work showing the inhibition of ErbB2, a member of the EGF receptor family, in transgenic knock-out mice or individuals that received herceptin chemotherapy is associated with the development of dilated cardiomyopathy. Our results, in conjunction with the demonstration that altered ErbB2 signaling underlies certain forms of mammalian cardiomyopathy, suggest that an

  5. The establishment of regular beating in populations of pacemaker heart cells. A study with tissue-cultured rat heart cells.

    PubMed

    Jongsma, H J; Tsjernina, L; de Bruijne, J

    1983-02-01

    Single isolated neonatal rat heart cells beat slowly (mean beating interval duration in the range of seconds) and irregularly (coefficient of variation greater than 40%). It is shown that slowness and irregularity of beating are intrinsic properties of the cells and are not caused by dissociation damage or lack of conditioning factors in the culture medium. When cell contacts are established either by letting the cultures grow for given amounts of time or by plating cells at increasing densities both interval duration and irregularity decrease. The beating regularity of small groups of interconnected cells (3 to 35 cells) and larger groups (200 to 15000 cells) is comparable. There is no clear cut proportionality between number of interconnected cells and beating regularity. Confluent monolayers beat fast (mean interval duration ranging between 200 and 400 ms and regular (coefficient of variation less than 5%). The hypothesis is discussed that this clock-like behavior of monolayers of heart cells is caused by the interaction of several pacemaker centers which are by themselves less regular and beat more slowly. PMID:6854658

  6. Comparison of carbon dioxide and argon euthanasia: effects on behavior, heart rate, and respiratory lesions in rats.

    PubMed

    Burkholder, Tanya H; Niel, Lee; Weed, James L; Brinster, Lauren R; Bacher, John D; Foltz, Charmaine J

    2010-07-01

    In this study we compared rat (n = 16) responses to euthanasia with either gradual-fill CO(2) or rapid induction argon gas by evaluating the animals' heart rate via radiotelemetry, behavior, and vocalizations. We also evaluated the histologic effects of the gases. Rats were placed in an open test chamber 24 h before the start of the experiment. During baseline tests, rats were exposed to oxygen to evaluate the effects of the noise and movement of gas entering the chamber; 1 wk later, rats were euthanized by gas displacement with either 10%/min CO(2) or 50%/min argon gas. Rats tended to have higher heart rats and were more active during the baseline test, but these parameters were normal before the euthanasia experiment, suggesting that the rats had acclimated to the equipment. Heart rate, behavior, and ultrasonic vocalizations were recorded for 2 min after gas introduction in both groups. All rats appeared conscious throughout the test interval. The heart rates of rats exposed to argon did not change, whereas those of rats exposed to CO(2) declined significantly. Unlike those exposed to CO(2), rats euthanized with argon gas gasped and demonstrated seizure-like activity. There were no differences in the pulmonary lesions resulting from death by either gas. Our results suggest that argon as a sole euthanasia agent is aversive to rats. CO(2) using a 10%/min displacement may be less aversive than more rapid displacements. Future research investigating methods of euthanasia should allow sufficient time for the rats to acclimate to the test apparatus.

  7. Comparison of carbon dioxide and argon euthanasia: effects on behavior, heart rate, and respiratory lesions in rats.

    PubMed

    Burkholder, Tanya H; Niel, Lee; Weed, James L; Brinster, Lauren R; Bacher, John D; Foltz, Charmaine J

    2010-07-01

    In this study we compared rat (n = 16) responses to euthanasia with either gradual-fill CO(2) or rapid induction argon gas by evaluating the animals' heart rate via radiotelemetry, behavior, and vocalizations. We also evaluated the histologic effects of the gases. Rats were placed in an open test chamber 24 h before the start of the experiment. During baseline tests, rats were exposed to oxygen to evaluate the effects of the noise and movement of gas entering the chamber; 1 wk later, rats were euthanized by gas displacement with either 10%/min CO(2) or 50%/min argon gas. Rats tended to have higher heart rats and were more active during the baseline test, but these parameters were normal before the euthanasia experiment, suggesting that the rats had acclimated to the equipment. Heart rate, behavior, and ultrasonic vocalizations were recorded for 2 min after gas introduction in both groups. All rats appeared conscious throughout the test interval. The heart rates of rats exposed to argon did not change, whereas those of rats exposed to CO(2) declined significantly. Unlike those exposed to CO(2), rats euthanized with argon gas gasped and demonstrated seizure-like activity. There were no differences in the pulmonary lesions resulting from death by either gas. Our results suggest that argon as a sole euthanasia agent is aversive to rats. CO(2) using a 10%/min displacement may be less aversive than more rapid displacements. Future research investigating methods of euthanasia should allow sufficient time for the rats to acclimate to the test apparatus. PMID:20819391

  8. Myogenic regulatory factors during regeneration of skeletal muscle in young, adult, and old rats

    NASA Technical Reports Server (NTRS)

    Marsh, D. R.; Criswell, D. S.; Carson, J. A.; Booth, F. W.

    1997-01-01

    Myogenic factor mRNA expression was examined during muscle regeneration after bupivacaine injection in Fischer 344/Brown Norway F1 rats aged 3, 18, and 31 mo of age (young, adult, and old, respectively). Mass of the tibialis anterior muscle in the young rats had recovered to control values by 21 days postbupivacaine injection but in adult and old rats remained 40% less than that of contralateral controls at 21 and 28 days of recovery. During muscle regeneration, myogenin mRNA was significantly increased in muscles of young, adult, and old rats 5 days after bupivacaine injection. Subsequently, myogenin mRNA levels in young rat muscle decreased to postinjection control values by day 21 but did not return to control values in 28-day regenerating muscles of adult and old rats. The expression of MyoD mRNA was also increased in muscles at day 5 of regeneration in young, adult, and old rats, decreased to control levels by day 14 in young and adult rats, and remained elevated in the old rats for 28 days. In summary, either a diminished ability to downregulate myogenin and MyoD mRNAs in regenerating muscle occurs in old rat muscles, or the continuing myogenic effort includes elevated expression of these mRNAs.

  9. Developmental Vitamin D3 deficiency alters the adult rat brain.

    PubMed

    Féron, F; Burne, T H J; Brown, J; Smith, E; McGrath, J J; Mackay-Sim, A; Eyles, D W

    2005-03-15

    There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention. PMID:15763180

  10. Decline of taste sensitivity in protein deficient adult rats.

    PubMed

    Ohara, I; Tabuchi, R; Kimura, M; Itokawa, Y

    1995-05-01

    The influence of dietary protein levels on taste sensitivity was studied in adult rats. Low protein diets of 0.0, 2.5, or 5.0% purified egg protein (PEP) were fed to animals for 28 days. Two bottle choice preference tests between aqueous solutions of either 2, 9, 17, or 86 mM sodium chloride and deionized water were conducted in an ascending order on days 14, 16, 18, and 20. Urine samples were collected for zinc and creatinine analysis. Blood samples were also collected for measuring serum zinc and creatinine concentrations. Scanning electron microscopy was performed to observe rats' tongue epithelia. Protein free diet group showed significantly lower taste sensitivity and renal reabsorption rate than other protein containing diet groups, while serum zinc and creatinine concentrations, and creatinine clearance were not affected by dietary protein level. Degeneration of filiform papillae and imperforation of taste pore of fungiform papillae were observed in protein free diet group. This experiment implies at least 2.5% dietary protein is required to manifest normal taste function in the adult. PMID:7610145

  11. Decline of taste sensitivity in protein deficient adult rats.

    PubMed

    Ohara, I; Tabuchi, R; Kimura, M; Itokawa, Y

    1995-05-01

    The influence of dietary protein levels on taste sensitivity was studied in adult rats. Low protein diets of 0.0, 2.5, or 5.0% purified egg protein (PEP) were fed to animals for 28 days. Two bottle choice preference tests between aqueous solutions of either 2, 9, 17, or 86 mM sodium chloride and deionized water were conducted in an ascending order on days 14, 16, 18, and 20. Urine samples were collected for zinc and creatinine analysis. Blood samples were also collected for measuring serum zinc and creatinine concentrations. Scanning electron microscopy was performed to observe rats' tongue epithelia. Protein free diet group showed significantly lower taste sensitivity and renal reabsorption rate than other protein containing diet groups, while serum zinc and creatinine concentrations, and creatinine clearance were not affected by dietary protein level. Degeneration of filiform papillae and imperforation of taste pore of fungiform papillae were observed in protein free diet group. This experiment implies at least 2.5% dietary protein is required to manifest normal taste function in the adult.

  12. Effect of acute exposure to ozone on heart rate and blood pressure of the conscious rat

    SciTech Connect

    Uchiyama, I.; Simomura, Y.; Yokoyama, E.

    1985-12-01

    Electrocardiogram and arterial blood pressure in conscious and unrestrained rats of various ages were recorded during a 3-hr exposure to filtered air or 1 ppm ozone (O/sub 3/). In general, heart rate and mean arterial blood pressure of rats significantly decreased during exposure to O/sub 3/, whereas these functional parameters remained almost stable during exposure to filtered air. Heart rate usually reached a plateau during the exposure to O/sub 3/. Additionally, PR interval and QRS complex significantly increased and premature atrial contraction and incomplete A-V block were frequently observed during the exposure to O/sub 3/. These circulatory effects of O/sub 3/ were more markedly manifested by rats 11 weeks old than either those 8 or 4 weeks old. On the other hand, no significant difference in the circulatory responses was observed between male and female rats. These circulatory effects of O/sub 3/ may be significant from the viewpoint of health effects, although its mechanisms remain unsolved.

  13. Acute behavioral toxicity of carbaryl and propoxur in adult rats.

    PubMed

    Ruppert, P H; Cook, L L; Dean, K F; Reiter, L W

    1983-04-01

    Motor activity and neuromotor function were examined in adult CD rats exposed to either carbaryl or propoxur, and behavioral effects were compared with the time course of cholinesterase inhibition. Rats received an IP injection of either 0, 2, 4, 6 or 8 mg/kg propoxur or 0, 4, 8, 16 or 28 mg/kg carbaryl in corn oil 20 min before testing. All doses of propoxur reduced 2 hr activity in a figure-eight maze, and crossovers and rears in an open field. For carbaryl, dosages of 8, 16 and 28 mg/kg decreased maze activity whereas 16 and 28 mg/kg reduced open field activity. In order to determine the time course of effects, rats received a single IP injection of either corn oil, 2 mg/kg propoxur or 16 mg/kg carbaryl, and were tested for 5 min in a figure-eight maze either 15, 30, 60, 120 or 240 min post-injection. Immediately after testing, animals were sacrificed and total cholinesterase was measured. Maximum effects of propoxur and carbaryl on blood and brain cholinesterase and motor activity were seen within 15 min. Maze activity had returned to control levels within 30 and 60 min whereas cholinesterase levels remained depressed for 120 and 240 min for propoxur and carbaryl, respectively. These results indicate that both carbamates decrease motor activity, but behavioral recovery occurs prior to that of cholinesterase following acute exposure.

  14. Effect of exposure to diazinon on adult rat's brain.

    PubMed

    Rashedinia, Marzieh; Hosseinzadeh, Hossein; Imenshahidi, Mohsen; Lari, Parisa; Razavi, Bibi Marjan; Abnous, Khalil

    2016-04-01

    Diazinon (DZN), a commonly used agricultural organophosphate insecticide, is one of the major concerns for human health. This study was planned to investigate neurotoxic effects of subacute exposure to DZN in adult male Wistar rats. Animals received corn oil as control and 15 and 30 mg/kg DZN orally by gastric gavage for 4 weeks. The cerebrum malondialdehyde and glutathione (GSH) contents were assessed as biomarkers of lipid peroxidation and nonenzyme antioxidants, respectively. Moreover, activated forms of caspase 3, -9, and Bax/Bcl-2 ratios were evaluated as key apoptotic proteins. Results of this study suggested that chronic administration of DZN did not change lipid peroxidation and GSH levels significantly in comparison with control. Also, the active forms of caspase 3 and caspase 9 were not significantly altered in DZN-treated rat groups. Moreover, no significant changes were observed in Bax and Bcl-2 ratios. This study indicated that generation of reactive oxygen species was probably modulated by intracellular antioxidant system. In conclusion, subacute oral administration of DZN did not alter lipid peroxidation. Moreover, apoptosis induction was not observed in rat brain.

  15. Life experiences and coping strategies in adults with congenital heart disease.

    PubMed

    Callus, E; Quadri, E; Compare, A; Tovo, A; Giamberti, A; Chessa, M

    2013-01-01

    Many adults with congenital heart disease (ACHD) have to face considerable psychosocial difficulties. The aim of this study was to explore the life experiences of ACHD patients, from when they become aware of having a condition, till after the open heart surgery they underwent. The study was conducted with the use of unstructured, in-depth interviews, performed on 11 patients (age ranging: 20 - 56 y) after they recovered from open heart surgery and a focus group, which included 16 participants (age ranging: 22 - 46 y). Both the interviews and the focus group were recorded, transcribed and analyzed according to Grounded Theory procedures. Our findings show that the condition of diversity is the core of the emotional experiences connected to ACHD. Feeling different and being perceived as being different are clearly interlinked and coping strategies adopted resulted as being influenced by this perception. This study also clearly outlines the importance of having an adequate perception of one's condition and the link between maladaptive coping strategies and an incorrect perception of one's heart condition. Results are discussed in order to promote psychosocial interventions within and outside of the hospital setting in order to improve the patients' emotional wellbeing. PMID:24516946

  16. Exercise training attenuates the pressor response evoked by peripheral chemoreflex in rats with heart failure.

    PubMed

    Calegari, Leonardo; Mozzaquattro, Bruna B; Rossato, Douglas D; Quagliotto, Edson; Ferreira, Janaina B; Rasia-Filho, Alberto; Dal Lago, Pedro

    2016-09-01

    The effects of exercise training (ExT) on the pressor response elicited by potassium cyanide (KCN) in the rat model of ischemia-induced heart failure (HF) are unknown. We evaluated the effects of ExT on chemoreflex sensitivity and its interaction with baroreflex in rats with HF. Wistar rats were divided into four groups: trained HF (Tr-HF), sedentary HF (Sed-HF), trained sham (Tr-Sham), and sedentary sham (Sed-Sham). Trained animals underwent to a treadmill running protocol for 8 weeks (60 m/day, 5 days/week, 16 m/min). After ExT, arterial pressure (AP), baroreflex sensitivity (BRS), peripheral chemoreflex (KCN: 100 μg/kg body mass), and cardiac function were evaluated. The results demonstrate that ExT induces an improvement in BRS and attenuates the pressor response to KCN relative to the Sed-HF group (P < 0.05). The improvement in BRS was associated with a reduction in the pressor response following ExT in HF rats (P < 0.05). Moreover, ExT induced a reduction in left ventricular end-diastolic pressure and pulmonary congestion compared with the Sed-HF group (P < 0.05). The pressor response to KCN in the hypotensive state is decreased in sedentary HF rats. These results suggest that ExT improves cardiac function and BRS and attenuates the pressor response evoked by KCN in HF rats. PMID:27295522

  17. Effect of ethanol on function of the rat heart and skeletal muscles.

    PubMed

    Pagala, M; Ravindran, K; Amaladevi, B; Namba, T; Grob, D

    1995-06-01

    The present study was undertaken to evaluate the acute effects of ethanol on responses of the rat heart and skeletal muscles both in vivo and in vitro. In the anesthetized rat, intravenous infusion of ethanol at 0.1-0.5 g/kg body weight (33-167 mM) decreased the breathing rate by 8-83%, heart rate by 4-52%, and QRS amplitude by 5-27%, and increased the P-R interval by 1-49%. In the anterior tibialis muscle subjected to repetitive nerve stimulation at 100 Hz for 0.5 sec, ethanol at 0.1 g/kg increased the amplitude of the muscle action potential (AP) by 7%, whereas at 0.5 g/kg it decreased the muscle AP by 32%. The nerve-evoked tetanic tension was reduced by 7-34% at 0.1-0.5 g/kg ethanol. In the isolated rat heart, perfusion of ethanol at 0.1-3.0% (22-651 mM) decreased the heart rate by 8-48% and QRS amplitude by 10-39%, and increased the P-R interval by 5-61%. Left ventricular pressure was increased by 10% at 0.1% ethanol, and decreased by 80% at 3.0% ethanol. In the isolated rat phrenic nerve-diaphragm muscle preparation subjected to repetitive nerve stimulation at 100 Hz for 0.5 sec, 0.1-3.0% ethanol decreased the amplitude of the nerve AP by 5-89%, nerve-evoked muscle AP by 2-96%, and peak tetanic tension by 1-87%. On repetitive direct muscle stimulation at 100 Hz for 0.5 sec, 0.1-3.0% ethanol decreased the amplitude of the muscle-evoked muscle AP by 8-65%, and muscle-evoked tetanic tension by 2-65%. These studies indicate that ethanol causes smaller reduction in responses of the heart and skeletal muscles at clinical concentrations, but marked reduction in these responses at higher concentrations due to direct action on excitability of these tissues. At higher concentrations, ethanol causes greater reduction in excitability of the skeletal muscle than of the heart. PMID:7573793

  18. [Role of the general practitioner or primary care physician in the management of adult congenital heart disease].

    PubMed

    Thambo, Jean-Benoît

    2013-03-01

    Congenital heart diseases are the most common inborn defect, occurring approximately 0.8% according to the last European Union count. This rate is stable for decades. Nowadays, up to 90% of children born with congenital heart diseases underwent surgical correction and reach adulthood, gratefully to the surgery and interventional cardiology advances, in conjunction to the post-surgery and following cares improvement. Both of this facts results to a growing population of adults with congenital heart diseases, actually exceeding the infant population. This arising population will lead general practitioners and primary care physicians to face more often this kind of patient. The needed cares are specifics, regarding the typical evolutions of this pathologies, as well as because congenital heart diseases wil impact other pathologies or usual cares. The need of an extended knowledge of the adult patients with congenital heart diseases is clearly emerging, and should lead the whole medical corps to work in close network. PMID:23687765

  19. Early life exposures and the occurrence and timing of heart disease among the older adult Puerto Rican population.

    PubMed

    McEnry, Mry; Palloni, Alberto

    2010-02-01

    Few studies have examined the effects of early life conditions on the timing of the onset of heart disease. We use the remarkable example of a representative sample of the population of older Puerto Ricans aged 60-74 who lived in the countryside during childhood (n = 1,438) to examine the effects ofseasonal exposures to poor nutrition and infectious diseases during late gestation on the timing of the onset and the probability of ever experiencing adult heart disease. Cox and log logistic hazard models controlling for childhood conditions (self-reported childhood health status and socioeconomic status [SES], rheumatic fever, and knee height) and adult risk factors (adult SES, obesity, smoking, exercise, and self-reported diabetes) showed that the risk of onset of heart disease was 65% higher among those born during high-exposure periods compared with unexposed individuals. However, there were no significant differences in median time of onset for those ever experiencing heart disease. As a comparison, we found that there were no significant seasonality effects for those who lived in urban areas during childhood. We conclude that early exposures in utero have important ramifications for adult heart disease among the older Puerto Rican population. We show, however, that while exposure is associated with the probability of ever experiencing adult heart disease, it is not associated with the timing of onset among those who do experience it.

  20. Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts.

    PubMed

    Yao, Yuan-yuan; Zhu, Man-hua; Zhang, Feng-jiang; Wen, Chuan-yun; Ma, Lei-lei; Wang, Wen-na; Wang, Can-can; Liu, Xian-bao; Yu, Li-na; Qian, Ling-bo; Wang, Jian-an; Yan, Min

    2013-06-01

    It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in vivo. Our aim was to investigate the duration of effective sevoflurane administration and its underlying mechanism in isolated rat hearts exposed to global ischemia/reperfusion (I/R) injury. Adult male Sprague-Dawley rats were randomly divided into six groups (n=12): a sham-operation group, an I/R group, and four sevoflurane postconditioning groups (S2, S5, S10, and S15). In the S2, S5, S10, and S15 groups, the duration times of sevoflurane administration were 2, 5, 10, and 15 min after the onset of reperfusion, respectively. The isolated rat hearts were mounted on the Langendorff system, and after a period of equilibrium were subjected to 40 min global ischemia and 120 min reperfusion. Left ventricular (LV) hemodynamic parameters were monitored throughout each experiment and the data at 30 min of equilibrium and 30, 60, 90, and 120 min of reperfusion were analyzed. Myocardial infarct size at the end of reperfusion (n=7 in each group) and the expression of myocardial phosphorylated Akt (p-Akt) after 15-min reperfusion were determined in a duplicate set of six groups of rat hearts (n=5 in each group). Compared with the I/R group, the S5, S10, and S15 groups had significantly improved left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), and the maximal rate of rise or fall of the LV pressure (±dP/dtmax), and decreased myocardial infarct size (P<0.05), but not the S2 group. After 15 min of reperfusion, the expression of p-Akt was markedly up-regulated in the S5, S10, and S15 groups compared with that in the I/R group (P<0.05), but not in the S2 group. Sevoflurane postconditioning for 5 min was sufficient to activate Akt and exert maximal cardioprotection against I/R injury in isolated rat hearts.

  1. Effect of MPEP in Morris water maze in adult and old rats.

    PubMed

    Car, Halina; Stefaniuk, Radosław; Wiśniewska, Róza J

    2007-01-01

    The present investigation assessed the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on acquisition and reference memory in the Morris water maze in young adult rats aged 3-month and old rats aged 26-month. MPEP reduced the swim speed of the young adult rats during acquisition, shortened the distance they covered and reduced their swim speed in the probe trial. The untreated old rats had impaired acquisition of spatial learning, shortened distance and a lower swim speed in the probe trial in comparison with young rats. MPEP did not influence the activity of the old rats in the water maze. In summary, MPEP did not influence acquisition of spatial learning and reference memory in the young adult and old rats.

  2. Metabolic imaging of acute and chronic infarction in the perfused rat heart using hyperpolarised [1-13C]pyruvate.

    PubMed

    Ball, Daniel R; Cruickshank, Rachel; Carr, Carolyn A; Stuckey, Daniel J; Lee, Philip; Clarke, Kieran; Tyler, Damian J

    2013-11-01

    Hyperpolarised (13)C MRI can be used to generate metabolic images of the heart in vivo. However, there have been no similar studies performed in the isolated perfused heart. Therefore, the aim of this study was to develop a method for the creation of (13)C metabolite maps of the perfused rat heart and to demonstrate the technique in a study of acute and chronic myocardial infarction. Male Wistar rat hearts were isolated, perfused and imaged before and after occlusion of the left anterior descending (LAD) coronary artery, creating an acute infarct group. In addition, a chronic infarct group was generated from hearts which had their LAD coronary artery occluded in vivo. Four weeks later, hearts were excised, perfused and imaged to generate metabolic maps of infused pyruvate and its metabolites lactate and bicarbonate. Myocardial perfusion and energetics were assessed by first-pass perfusion imaging and (31)P MRS, respectively. In both acute and chronically infarcted hearts, perfusion was reduced to the infarct region, as revealed by reduced gadolinium influx and lower signal intensity in the hyperpolarised pyruvate images. In the acute infarct region, there were significant alterations in the lactate (increased) and bicarbonate (decreased) signal ratios. In the chronically infarcted region, there was a significant reduction in both bicarbonate and lactate signals. (31)P-derived energetics revealed a significant decrease between control and chronic infarcted hearts. Significant decreases in contractile function between control and both acute and chronic infracted hearts were also seen. In conclusion, we have demonstrated that hyperpolarised pyruvate can detect reduced perfusion in the rat heart following both acute and chronic infarction. Changes in lactate and bicarbonate ratios indicate increased anaerobic metabolism in the acute infarct, which is not observed in the chronic infarct. Thus, this study has successfully demonstrated a novel imaging approach to assess

  3. The influx of amino acids into the heart of the rat.

    PubMed Central

    Baños, G; Daniel, P M; Moorhouse, S R; Pratt, O E; Wilson, P A

    1978-01-01

    1. The influx of nineteen amino acids into the heart of the living rat was studied by a method specially devised for experiments under controlled conditions in vivo. 2. When, in separate experiments, the concentration of each amino acid in turn was artificially raised in the circulation, the influx of that amino acid into the heart increased. 3. Our data indicate that at least ten of these amino acids enter the heart in vivo by means of saturable carrier-mediated transport systems. The transport rates conform, at least approximately, to Michaelis kinetics and the transport systems are clearly, in the cases of many amino acids, active, i.e. energy-dependent. 4. The amino acids which were studied had rates of influx into the heart which differed from each other over a range of more than 10 to 1, even when allowances were made for the difference in their concentration in the circulating blood. These differences in influx were not related to such factors as the molecular size of the individual amino acids. 5. The amino acids which have a high influx into the heart are mainly those which are needed either to re-synthesize contractile protein or as oxidizable substrates. PMID:690905

  4. Ouabain triggers preconditioning through activation of the Na+,K+-ATPase signaling cascade in rat hearts

    PubMed Central

    Pierre, Sandrine V.; Yang, Changjun; Yuan, Zhaokan; Seminerio, Jennifer; Mouas, Christian; Garlid, Keith D.; Dos-Santos, Pierre; Xie, Zijian

    2007-01-01

    Objective Because ouabain activates several pathways that are critical to cardioprotective mechanisms such as ischemic preconditioning, we tested if this digitalis compound could protect the heart against ischemia-reperfusion injury through activation of the Na+,K+-ATPase/c-Src receptor complex. Methods and Results In Langendorff-perfused rat hearts, a short (4 min) administration of ouabain 10 μM followed by an 8-minute washout before 30 minutes of global ischemia and reperfusion improved cardiac function, decreased lactate dehydrogenase release and reduced infarct size by 40%. Western blot analysis revealed that ouabain activated the cardioprotective phospholipase Cγ1/protein kinase Cε (PLC-γ1/PKCε) pathway. Pre-treatment of the hearts with the Src kinase family inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine (PP2) blocked not only ouabain-induced activation of PLC-γ1/PKCε pathway, but also cardiac protection. This protection was also blocked by a PKCε translocation inhibitor peptide (PKCε TIP). Conclusion Short exposure to a low concentration of ouabain protects the heart against ischemia/reperfusion injury. This effect of ouabain on the heart is most likely due to the activation of the Na+,K+-ATPase/c-Src receptor complex and subsequent stimulation of key mediators of preconditioning, namely PLC-γ1 and PKCε. PMID:17157283

  5. Long-term evaluation of myoblast seeded patches implanted on infarcted rat hearts.

    PubMed

    Giraud, Marie-Noëlle; Flueckiger, Remy; Cook, Stéphane; Ayuni, Erick; Siepe, Matthias; Carrel, Thierry; Tevaearai, Hendrik

    2010-06-01

    Cell transplantation presents great potential for treatment of patients with severe heart failure. However, its clinical application was revealed to be more challenging than initially expected in experimental studies. Further investigations need to be undertaken to define the optimal treatment conditions. We previously reported on the epicardial implantation of a bio-engineered construct of skeletal myoblast-seeded polyurethane and its preventive effect on progression toward heart failure. In the present study, we present a long-term evaluation of this functional outcome. Left anterior descending coronary ligation was performed in female Lewis rats. Two weeks later, animals were treated with either epicardial implantation of biograft, acellular scaffold, sham operation, or direct intramyocardial skeletal myoblast injection. Functional assessments were performed with serial echocardiographies every 3 months and end point left ventricle pressure was assessed. Hearts were then harvested for histological examinations. Myocardial infarction induced a slow and progressive reduction in fractional shortening after 3 months. Progression toward heart failure was significantly prevented for up to 6 months after injection of myoblasts and for up to 9 months following biograft implantation. Nevertheless, this effect vanished after 12 months, with immunohistological examinations revealing an absence of the transplanted myoblasts within the scaffold. We demonstrated that tissue therapy is superior to cell therapy for stabilization of heart function. However, beneficial effects are transient.

  6. Purification and culture of adult rat dorsal root ganglia neurons.

    PubMed

    Delree, P; Leprince, P; Schoenen, J; Moonen, G

    1989-06-01

    To study the trophic requirements of adult rat dorsal root ganglia neurons (DRG) in vitro, we developed a purification procedure that yields highly enriched neuronal cultures. Forty to fifty ganglia are dissected from the spinal column of an adult rat. After enzymatic and mechanical dissociation of the ganglia, myelin debris are eliminated by centrifugation on a Percoll gradient. The resulting cell suspension is layered onto a nylon mesh with a pore size of 10 microns. Most of the neurons, the diameter of which ranged from 17 microns to greater than 100 microns, are retained on the upper surface of the sieve; most of the non-neuronal cells with a caliber of less than 10 microns after trypsinization go through it. Recovery of neurons is achieved by reversing the mesh onto a Petri dish containing culture medium. Neurons to non-neurons ratio is 1 to 10 in the initial cell suspension and 1 to 1 after separation. When these purified neurons are seeded at a density of 3,000 neurons/cm2 in 6 mm polyornithine-laminin (PORN-LAM) coated wells, neuronal survival (assessed by the ability to extend neurites), measured after 48 hr of culture, is very low (from 0 to 16%). Addition of nerve growth factor (NGF) does not improve neuronal survival. However, when neurons are cultured in the presence of medium conditioned (CM) by astrocytes or Schwann cells, 60-80% of the seeded, dye-excluding neurons survive. So, purified adult DRG neurons require for their short-term survival and regeneration in culture, a trophic support that is present in conditioned medium from PNS or CNS glia.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Immature rat Leydig cells are intrinsically less sensitive than adult Leydig cells to ethane dimethanesulfonate.

    PubMed

    Kelce, W R; Zirkin, B R; Ewing, L L

    1991-11-01

    Leydig cells from immature rat testes appear to be insensitive to doses of ethane-1,2-dimethanesulfonate (EDS) which eliminate Leydig cells from adult rat testes. We sought to determine whether this differential response to EDS is intrinsic to the Leydig cell or mediated by other intra- or extratesticular differences between adult and immature rats. To differentiate among these possibilities, Leydig cells were exposed to EDS (1) in vivo, (2) through in vitro testicular perfusion, or (3) in highly purified Leydig cell primary cultures. Four days after ip injections of 85 mg EDS/kg body wt Leydig cells were eliminated from testes of adult, but not immature rats. Total androgen production by testes perfused in vitro with 94 micrograms EDS/ml was dramatically reduced in adult, but not immature rats. Highly purified adult, but not immature, rat Leydig cells were far more sensitive to the effects of EDS on luteinizing hormone-stimulated androgen production (functional effects; apparent EC50 = 94 for adult and 407 micrograms/ml for immature rat Leydig cells) and on [35S]methionine incorporation (cytotoxic effects; apparent EC50 = 140 for adult and 1000 micrograms/ml for immature rat Leydig cells). Finally, the in vitro effects of EDS were both cell type and chemical specific. Since the differential response of adult and immature rat Leydig cells to EDS was manifest in vivo, during in vitro testicular perfusion, and in highly purified Leydig cell primary cultures, we conclude that immature rat Leydig cells are intrinsically less sensitive to the specific cytotoxic effects of EDS than adult rat Leydig cells.

  8. Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

    PubMed

    Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

    2015-09-01

    Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease.

  9. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts

    PubMed Central

    Gerbin, Kaytlyn A.; Yang, Xiulan; Murry, Charles E.; Coulombe, Kareen L. K.

    2015-01-01

    Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC)-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle) delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300–390 beats per minute (5–6.5 Hz). Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart’s pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they identify lack of

  10. Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension

    PubMed Central

    Benoist, David; Stones, Rachel; Drinkhill, Mark J.; Benson, Alan P.; Yang, Zhaokang; Cassan, Cecile; Gilbert, Stephen H.; Saint, David A.; Cazorla, Olivier; Steele, Derek S.; Bernus, Olivier

    2012-01-01

    Pulmonary hypertension provokes right heart failure and arrhythmias. Better understanding of the mechanisms underlying these arrhythmias is needed to facilitate new therapeutic approaches for the hypertensive, failing right ventricle (RV). The aim of our study was to identify the mechanisms generating arrhythmias in a model of RV failure induced by pulmonary hypertension. Rats were injected with monocrotaline to induce either RV hypertrophy or failure or with saline (control). ECGs were measured in conscious, unrestrained animals by telemetry. In isolated hearts, electrical activity was measured by optical mapping and myofiber orientation by diffusion tensor-MRI. Sarcoplasmic reticular Ca2+ handling was studied in single myocytes. Compared with control animals, the T-wave of the ECG was prolonged and in three of seven heart failure animals, prominent T-wave alternans occurred. Discordant action potential (AP) alternans occurred in isolated failing hearts and Ca2+ transient alternans in failing myocytes. In failing hearts, AP duration and dispersion were increased; conduction velocity and AP restitution were steeper. The latter was intrinsic to failing single myocytes. Failing hearts had greater fiber angle disarray; this correlated with AP duration. Failing myocytes had reduced sarco(endo)plasmic reticular Ca2+-ATPase activity, increased sarcoplasmic reticular Ca2+-release fraction, and increased Ca2+ spark leak. In hypertrophied hearts and myocytes, dysfunctional adaptation had begun, but alternans did not develop. We conclude that increased electrical and structural heterogeneity and dysfunctional sarcoplasmic reticular Ca2+ handling increased the probability of alternans, a proarrhythmic predictor of sudden cardiac death. These mechanisms are potential therapeutic targets for the correction of arrhythmias in hypertensive, failing RVs. PMID:22427523

  11. CARBONYLATION OF MYOSIN HEAVY CHAINS IN RAT HEARTS DURING DIABETES

    PubMed Central

    Shao, Chun-Hong; Rozanski, George J.; Nagai, Ryoji; Stockdale, Frank E.; Patel, Kaushik P.; Wang, Mu; Singh, Jaipaul; Mayhan, William G.; Bidasee, Keshore R.

    2010-01-01

    Cardiac inotropy progressively declines during diabetes mellitus. To date, the molecular mechanisms underlying this defect remain incompletely characterized. This study tests the hypothesis that ventricular myosin heavy chains (MHC) undergo carbonylation by reactive carbonyl species (RCS) during diabetes and these modifications contribute to the inotropic decline. Male Sprague-Dawley rats were injected with streptozotocin (STZ). Fourteen days later animals were divided into two groups: one group was treated with the RCS blocker aminoguanidine for six weeks, while the other group received no treatment. After eight weeks of diabetes, cardiac ejection fraction, fractional shortening, left ventricular pressure development (+dP/dt) and myocyte shortening were decreased by 9%, 16%, 34% and 18%, respectively. Ca2+- and Mg2+-actomyosin ATPase activities and peak actomyosin syneresis were also reduced by 35%, 28%, and 72%. MHC-α to MHC-β ratio was 12:88. Mass spectrometry and Western blots revealed the presence of carbonyl adducts on MHC-α and MHC-β. Aminoguandine treatment did not alter MHC composition, but it blunted formation of carbonyl adducts and decreases in actomyosin Ca2+-sensitive ATPase activity, syneresis, myocyte shortening, cardiac ejection fraction, fractional shortening and +dP/dt induced by diabetes. From these new data it can be concluded that in addition to isozyme switching, modification of MHC by RCS also contributes to the inotropic decline seen during diabetes. PMID:20359464

  12. Carbonylation of myosin heavy chains in rat heart during diabetes.

    PubMed

    Shao, Chun-Hong; Rozanski, George J; Nagai, Ryoji; Stockdale, Frank E; Patel, Kaushik P; Wang, Mu; Singh, Jaipaul; Mayhan, William G; Bidasee, Keshore R

    2010-07-15

    Cardiac inotropy progressively declines during diabetes mellitus. To date, the molecular mechanisms underlying this defect remain incompletely characterized. This study tests the hypothesis that ventricular myosin heavy chains (MHC) undergo carbonylation by reactive carbonyl species (RCS) during diabetes and these modifications contribute to the inotropic decline. Male Sprague-Dawley rats were injected with streptozotocin (STZ). Fourteen days later the animals were divided into two groups: one group was treated with the RCS blocker aminoguanidine for 6 weeks, while the other group received no treatment. After 8 weeks of diabetes, cardiac ejection fraction, fractional shortening, left ventricular pressure development (+dP/dt) and myocyte shortening were decreased by 9%, 16%, 34% and 18%, respectively. Ca(2+)- and Mg(2+)-actomyosin ATPase activities and peak actomyosin syneresis were also reduced by 35%, 28%, and 72%. MHC-alpha to MHC-beta ratio was 12:88. Mass spectrometry and Western blots revealed the presence of carbonyl adducts on MHC-alpha and MHC-beta. Aminoguanidine treatment did not alter MHC composition, but it blunted formation of carbonyl adducts and decreases in actomyosin Ca(2+)-sensitive ATPase activity, syneresis, myocyte shortening, cardiac ejection fraction, fractional shortening and +dP/dt induced by diabetes. From these new data it can be concluded that in addition to isozyme switching, modification of MHC by RCS also contributes to the inotropic decline seen during diabetes.

  13. Persistent effects after trigeminal nerve proprioceptive stimulation by mandibular extension on rat blood pressure, heart rate and pial microcirculation.

    PubMed

    Lapi, D; Colantuoni, A; Del Seppia, C; Ghione, S; Tonlorenzi, D; Brunelli, M; Scuri, R

    2013-03-01

    The trigemino-cardiac reflex is a brainstem reflex known to lead to a decrement in heart rate and blood pressure, whereas few data have been collected about its effects on the cerebral hemodynamic. In this study we assess the in vivo effects of trigeminal nerve peripheral stimulation by mandibular extension on pial microcirculation and systemic arterial blood pressure in rats. Experiments were performed in male Wistar rats subjected to mandibular extension obtained inserting an ad hoc developed retractor between the dental arches. Mean arterial blood pressure and heart rate were recorded and the pial arterioles were visualized by fluorescence microscopy to measure the vessel diameters before (15 minutes) during (5-15 minutes) and after (80 minutes) mandibular extension. While in control rats (sham-operated rats) and in rats subjected to the dissection of the trigeminal peripheral branches mean arterial blood pressure, heart rate and pial microcirculation did not change during the whole observation period (110 minutes), in rats submitted to mandibular extension, mean arterial blood pressure, heart rate and arteriolar diameter significantly decreased during stimulation. Afterward mean arterial blood pressure remained reduced as well as heart rate, while arteriolar diameter significantly increased evidencing a vasodilatation persisting for the whole remaining observation time. Therefore, trigeminal nerve proprioceptive stimulation appears to trigger specific mechanisms regulating systemic arterial blood pressure and pial microcirculation.

  14. Advanced Echocardiography in Adult Zebrafish Reveals Delayed Recovery of Heart Function after Myocardial Cryoinjury

    PubMed Central

    Kossack, Mandy; Juergensen, Lonny; Fuchs, Dieter; Katus, Hugo A.; Hassel, David

    2015-01-01

    Translucent zebrafish larvae represent an established model to analyze genetics of cardiac development and human cardiac disease. More recently adult zebrafish are utilized to evaluate mechanisms of cardiac regeneration and by benefiting from recent genome editing technologies, including TALEN and CRISPR, adult zebrafish are emerging as a valuable in vivo model to evaluate novel disease genes and specifically validate disease causing mutations and their underlying pathomechanisms. However, methods to sensitively and non-invasively assess cardiac morphology and performance in adult zebrafish are still limited. We here present a standardized examination protocol to broadly assess cardiac performance in adult zebrafish by advancing conventional echocardiography with modern speckle-tracking analyses. This allows accurate detection of changes in cardiac performance and further enables highly sensitive assessment of regional myocardial motion and deformation in high spatio-temporal resolution. Combining conventional echocardiography measurements with radial and longitudinal velocity, displacement, strain, strain rate and myocardial wall delay rates after myocardial cryoinjury permitted to non-invasively determine injury dimensions and to longitudinally follow functional recovery during cardiac regeneration. We show that functional recovery of cryoinjured hearts occurs in three distinct phases. Importantly, the regeneration process after cryoinjury extends far beyond the proposed 45 days described for ventricular resection with reconstitution of myocardial performance up to 180 days post-injury (dpi). The imaging modalities evaluated here allow sensitive cardiac phenotyping and contribute to further establish adult zebrafish as valuable cardiac disease model beyond the larval developmental stage. PMID:25853735

  15. Drosophila as a model for the identification of genes causing adult human heart disease

    PubMed Central

    Wolf, Matthew J.; Amrein, Hubert; Izatt, Joseph A.; Choma, Michael A.; Reedy, Mary C.; Rockman, Howard A.

    2006-01-01

    Drosophila melanogaster genetics provides the advantage of molecularly defined P-element insertions and deletions that span the entire genome. Although Drosophila has been extensively used as a model system to study heart development, it has not been used to dissect the genetics of adult human heart disease because of an inability to phenotype the adult fly heart in vivo. Here we report the development of a strategy to measure cardiac function in awake adult Drosophila that opens the field of Drosophila genetics to the study of human dilated cardiomyopathies. Through the application of optical coherence tomography, we accurately distinguish between normal and abnormal cardiac function based on measurements of internal cardiac chamber dimensions in vivo. Normal Drosophila have a fractional shortening of 87 ± 4%, whereas cardiomyopathic flies that contain a mutation in troponin I or tropomyosin show severe impairment of systolic function. To determine whether the fly can be used as a model system to recapitulate human dilated cardiomyopathy, we generated transgenic Drosophila with inducible cardiac expression of a mutant of human δ-sarcoglycan (δsgS151A), which has previously been associated with familial dilated cardiomyopathy. Compared to transgenic flies overexpressing wild-type δsg, or the standard laboratory strain w1118, Drosophila expressing δsgS151A developed marked impairment of systolic function and significantly enlarged cardiac chambers. These data illustrate the utility of Drosophila as a model system to study dilated cardiomyopathy and the applicability of the vast genetic resources available in Drosophila to systematically study the genetic mechanisms responsible for human cardiac disease. PMID:16432241

  16. Rat Heterotopic Heart Transplantation Model to Investigate Unloading-Induced Myocardial Remodeling

    PubMed Central

    Fu, Xuebin; Segiser, Adrian; Carrel, Thierry P.; Tevaearai Stahel, Hendrik T.; Most, Henriette

    2016-01-01

    Unloading of the failing left ventricle in order to achieve myocardial reverse remodeling and improvement of contractile function has been developed as a strategy with the increasing frequency of implantation of left ventricular assist devices in clinical practice. But, reverse remodeling remains an elusive target, with high variability and exact mechanisms still largely unclear. The small animal model of heterotopic heart transplantation (hHTX) in rodents has been widely implemented to study the effects of complete and partial unloading on cardiac failing and non-failing tissue to better understand the structural and molecular changes that underlie myocardial recovery. We herein review the current knowledge on the effects of volume unloading the left ventricle via different methods of hHTX in rats, differentiating between changes that contribute to functional recovery and adverse effects observed in unloaded myocardium. We focus on methodological aspects of heterotopic transplantation, which increase the correlation between the animal model and the setting of the failing unloaded human heart. Last, but not least, we describe the late use of sophisticated techniques to acquire data, such as small animal MRI and catheterization, as well as ways to assess unloaded hearts under “reloaded” conditions. While giving regard to certain limitations, heterotopic rat heart transplantation certainly represents the crucial model to mimic unloading-induced changes in the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further improve our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients. PMID:27807535

  17. Oxidative state and oxidative metabolism of the heart from rats with adjuvant-induced arthritis.

    PubMed

    Schubert, Amanda Caroline; Wendt, Mariana Marques Nogueira; de Sá-Nakanishi, Anacharis Babeto; Amado, Ciomar Aparecida Bersani; Peralta, Rosane Marina; Comar, Jurandir Fernando; Bracht, Adelar

    2016-06-01

    The aim of the present work was to investigate, in a more extensive way, the oxidative state and parameters related to energy metabolism of the heart tissue of rats using the model of adjuvant-induced arthritis. The latter is a model for the human arthritic disease. Measurements were done in the total tissue homogenate, isolated mitochondria and cytosolic fraction. The adjuvant-induced arthritis caused several modifications in the oxidative state of the heart which, in general, indicate an increased oxidative stress (+80% reactive oxygen species), protein damage (+53% protein carbonyls) and lipid damage (+63% peroxidation) in the whole tissue. The distribution of these changes over the various cell compartments was frequently unequal. For example, protein carbonyls were increased in the whole tissue and in the cytosol, but not in the mitochondria. No changes in GSH content of the whole tissue were found, but it was increased in the mitochondria (+33%) and decreased in the cytosol (-19%). The activity of succinate dehydrogenase was 77% stimulated by arthritis; the activities of glutamate dehydrogenase, isocitrate dehydrogenase and cytochrome c oxidase were diminished by 31, 25 and 35.3%, respectively. In spite of these alterations, no changes in the mitochondrial respiratory activity and in the efficiency of energy transduction were found. It can be concluded that the adjuvant-induced arthritis in rats causes oxidative damage to the heart with an unequal intracellular distribution. Compared to the liver and brain the modifications caused by arthritis in the heart are less pronounced on variables such as GSH levels and protein integrity. Possibly this occurs because the antioxidant system of the heart is less impaired by arthritis than that reported for the former tissues. Even so, the modifications caused by arthritis represent an imbalanced situation that probably contributes to the cardiac symptoms of the arthritis disease. PMID:27032477

  18. Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

    PubMed

    Carnevali, Luca; Trombini, Mimosa; Graiani, Gallia; Madeddu, Denise; Quaini, Federico; Landgraf, Rainer; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

    2014-04-10

    In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease.

  19. Elements of Psychocardiology in the Psychosocial Handling of Adults with Congenital Heart Disease

    PubMed Central

    Callus, Edward; Quadri, Emilia; Chessa, Massimo

    2010-01-01

    When it comes to the role of the clinical psychology in the cardiac settings, or psychocardiology, there is often a focus on acquired cardiac illnesses in the rehabilitation settings. However, the increase of adults with congenital heart disease due to technological advances in cardiology and cardiac surgery have created a new emergency. It is thus necessary to reflect upon the elements of psychocardiology adapting them to this new population, also when it comes to interventional hospital settings of cardiology and cardiac surgery. This perspective article is an effort in this direction. PMID:21833204

  20. Heart failure and obesity in adults: pathophysiology, clinical manifestations and management.

    PubMed

    Alpert, Martin A; Agrawal, Harsh; Aggarwal, Kul; Kumar, Senthil A; Kumar, Arun

    2014-06-01

    Obesity is both a risk factor and a direct cause of heart failure (HF) in adults. Severe obesity produces hemodynamic alterations that predispose to changes in left ventricular morphology and function, which, over time, may lend to the development of HF (obesity cardiomyopathy). Certain neurohormonal and metabolic abnormalities as well as cardiovascular co-morbidities may facilitate this process. Substantial purposeful weight loss is capable of reversing most of the alterations in cardiac performance and morphology and may improve functional capacity and quality of life in patents with obesity cardiomyopathy.

  1. Neonatal rat heart cells cultured in simulated microgravity

    NASA Technical Reports Server (NTRS)

    Akins, Robert E.; Schroedl, Nancy A.; Gonda, Steve R.; Hartzell, Charles R.

    1994-01-01

    In vitro characteristics of cardiac cells cultured in simulated microgravity are reported. Tissue culture methods performed at unit gravity constrain cells to propagate, differentiate, and interact in a two dimensional (2D) plane. Neonatal rat cardiac cells in 2D culture organize predominantly as bundles of cardiomyocytes with the intervening areas filled by non-myocyte cell types. Such cardiac cell cultures respond predictably to the addition of exogenous compounds, and in many ways they represent an excellent in vitro model system. The gravity-induced 2D organization of the cells, however, does not accurately reflect the distribution of cells in the intact tissue. We have begun characterizations of a three-dimensional (3D) culturing system designed to mimic microgravity. The NASA designed High-Aspect-Ratio-Vessel (HARV) bioreactors provide a low shear environment which allows cells to be cultured in static suspension. HARV-3D cultures were prepared on microcarrier beads and compared to control-2D cultures using a combination of microscopic and biochemical techniques. Both systems were uniformly inoculated and medium exchanged at standard intervals. Cells in control cultures adhered to the polystyrene surface of the tissue culture dishes and exhibited typical 2D organization. Cells in cultured in HARV's adhered to microcarrier beads, the beads aggregated into defined clusters containing 8 to 15 beads per cluster, and the clusters exhibited distinct 3D layers: myocytes and fibroblasts appeared attached to the surfaces of beads and were overlaid by an outer cell type. In addition, cultures prepared in HARV's using alternative support matrices also displayed morphological formations not seen in control cultures. Generally, the cells prepared in HARV and control cultures were similar, however, the dramatic alterations in 3D organization recommend the HARV as an ideal vessel for the generation of tissue-like organizations of cardiac cells in simulated microgravity.

  2. Neonatal rat heart cells cultured in simulated microgravity

    NASA Technical Reports Server (NTRS)

    Akins, R. E.; Schroedl, N. A.; Gonda, S. R.; Hartzell, C. R.

    1997-01-01

    In vitro characteristics of cardiac cells cultured in simulated microgravity are reported. Tissue culture methods performed at unit gravity constrain cells to propagate, differentiate, and interact in a two-dimensional (2D) plane. Neonatal rat cardiac cells in 2D culture organize predominantly as bundles of cardiomyocytes with the intervening areas filled by nonmyocyte cell types. Such cardiac cell cultures respond predictably to the addition of exogenous compounds, and in many ways they represent an excellent in vitro model system. The gravity-induced 2D organization of the cells, however, does not accurately reflect the distribution of cells in the intact tissue. We have begun characterizations of a three-dimensional (3D) culturing system designed to mimic microgravity. The NASA-designed High-Aspect Ratio Vessel (HARV) bioreactors provide a low shear environment that allows cells to be cultured in static suspension. HARV-3D cultures were prepared on microcarrier beads and compared to control-2D cultures using a combination of microscopic and biochemical techniques. Both systems were uniformly inoculated and medium exchanged at standard intervals. Cells in control cultures adhered to the polystyrene surface of the tissue culture dishes and exhibited typical 2D organization. Cells cultured in HARVs adhered to microcarrier beads, the beads aggregated into defined clusters containing 8 to 15 beads per cluster, and the clusters exhibited distinct 3D layers: myocytes and fibroblasts appeared attached to the surfaces of beads and were overlaid by an outer cell type. In addition, cultures prepared in HARVs using alternative support matrices also displayed morphological formations not seen in control cultures. Generally, the cells prepared in HARV and control cultures were similar; however, the dramatic alterations in 3D organization recommend the HARV as an ideal vessel for the generation of tissuelike organization of cardiac cells in vitro.

  3. Ranolazine attenuated heightened plasma norepinephrine and B-Type natriuretic peptide-45 in improving cardiac function in rats with chronic ischemic heart failure.

    PubMed

    Feng, Guangqiu; Yang, Yu; Chen, Juan; Wu, Zhiyong; Zheng, Yin; Li, Wei; Dai, Wenxin; Guan, Pin; Zhong, Chunrong

    2016-01-01

    As a new anti-anginal agent, ranolazinehas been shown to play a cardioprotective role in regulating myocardial ischemic injury. Given that plasma norepinephrine (NE) and brain natriuretic peptide (BNP, also termed B-type natriuretic peptide-45 in rats) are considered neuron-hormones to indicate heart failure progression. This study aims to examine effects of ranolazine on plasma NE and BNP-45 of rats with chronic ischemic heart failure (CHF). CHF was induced by myocardial infarction following ligation of a left anterior descending artery in adult Sprague-Dawley rats. We hypothesized that ranolazine attenuates the elevated levels of NE and BNP-45 observed in CHF rats thereby leading to improvement of the left ventricular function. Results showed that levels of plasma NE and BNP-45 were increased in CHF rats 6-8 weeks after ligation of the coronary artery. Our data demonstrate for the first time that ranolazine significantly attenuated the augmented NE and BNP-45 induced by CHF (P<0.05 vs. saline control). In addition, a liner relation was observed between NE/BNP-45levels and left ventricular fractional shortening as indication of left ventricular function (r=0.91 and P<0.01 for NE; and r=0.93 and P<0.01 for BNP-45) after administration of ranolazine. In conclusion, CHF increases the expression of NE and BNP-45 in peripheral circulation and these changes are related to the left ventricular function. Ranolazine improves the left ventricular function likely by decreasing heightened NE and BNP-45 induced by CHF. Therefore, our data indicate the role played by ranolazine in improving cardiac function in rats with CHF. PMID:27158417

  4. Ranolazine attenuated heightened plasma norepinephrine and B-Type natriuretic peptide-45 in improving cardiac function in rats with chronic ischemic heart failure

    PubMed Central

    Feng, Guangqiu; Yang, Yu; Chen, Juan; Wu, Zhiyong; Zheng, Yin; Li, Wei; Dai, Wenxin; Guan, Pin; Zhong, Chunrong

    2016-01-01

    As a new anti-anginal agent, ranolazinehas been shown to play a cardioprotective role in regulating myocardial ischemic injury. Given that plasma norepinephrine (NE) and brain natriuretic peptide (BNP, also termed B-type natriuretic peptide-45 in rats) are considered neuron-hormones to indicate heart failure progression. This study aims to examine effects of ranolazine on plasma NE and BNP-45 of rats with chronic ischemic heart failure (CHF). CHF was induced by myocardial infarction following ligation of a left anterior descending artery in adult Sprague-Dawley rats. We hypothesized that ranolazine attenuates the elevated levels of NE and BNP-45 observed in CHF rats thereby leading to improvement of the left ventricular function. Results showed that levels of plasma NE and BNP-45 were increased in CHF rats 6-8 weeks after ligation of the coronary artery. Our data demonstrate for the first time that ranolazine significantly attenuated the augmented NE and BNP-45 induced by CHF (P<0.05 vs. saline control). In addition, a liner relation was observed between NE/BNP-45levels and left ventricular fractional shortening as indication of left ventricular function (r=0.91 and P<0.01 for NE; and r=0.93 and P<0.01 for BNP-45) after administration of ranolazine. In conclusion, CHF increases the expression of NE and BNP-45 in peripheral circulation and these changes are related to the left ventricular function. Ranolazine improves the left ventricular function likely by decreasing heightened NE and BNP-45 induced by CHF. Therefore, our data indicate the role played by ranolazine in improving cardiac function in rats with CHF. PMID:27158417

  5. Expression of Lymphatic Markers in the Adult Rat Spinal Cord

    PubMed Central

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A.; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  6. Expression of Lymphatic Markers in the Adult Rat Spinal Cord.

    PubMed

    Kaser-Eichberger, Alexandra; Schroedl, Falk; Bieler, Lara; Trost, Andrea; Bogner, Barbara; Runge, Christian; Tempfer, Herbert; Zaunmair, Pia; Kreutzer, Christina; Traweger, Andreas; Reitsamer, Herbert A; Couillard-Despres, Sebastien

    2016-01-01

    Under physiological conditions, lymphatic vessels are thought to be absent from the central nervous system (CNS), although they are widely distributed within the rest of the body. Recent work in the eye, i.e., another organ regarded as alymphatic, revealed numerous cells expressing lymphatic markers. As the latter can be involved in the response to pathological conditions, we addressed the presence of cells expressing lymphatic markers within the spinal cord by immunohistochemistry. Spinal cord of young adult Fisher rats was scrutinized for the co-expression of the lymphatic markers PROX1 and LYVE-1 with the cell type markers Iba1, CD68, PGP9.5, OLIG2. Rat skin served as positive control for the lymphatic markers. PROX1-immunoreactivity was detected in many nuclei throughout the spinal cord white and gray matter. These nuclei showed no association with LYVE-1. Expression of LYVE-1 could only be detected in cells at the spinal cord surface and in cells closely associated with blood vessels. These cells were found to co-express Iba1, a macrophage and microglia marker. Further, double labeling experiments using CD68, another marker found in microglia and macrophages, also displayed co-localization in the Iba1+ cells located at the spinal cord surface and those apposed to blood vessels. On the other hand, PROX1-expressing cells found in the parenchyma were lacking Iba1 or PGP9.5, but a significant fraction of those cells showed co-expression of the oligodendrocyte lineage marker OLIG2. Intriguingly, following spinal cord injury, LYVE-1-expressing cells assembled and reorganized into putative pre-vessel structures. As expected, the rat skin used as positive controls revealed classical lymphatic vessels, displaying PROX1+ nuclei surrounded by LYVE-1-immunoreactivity. Classical lymphatics were not detected in adult rat spinal cord. Nevertheless, numerous cells expressing either LYVE-1 or PROX1 were identified. Based on their localization and overlapping expression with

  7. Protective effects of Salvia miltiorrhizae on the hearts of rats with severe acute pancreatits or obstructive jaundice*

    PubMed Central

    Zhang, Xi-ping; Feng, Guang-hua; Zhang, Jie; Cai, Yang; Tian, Hua; Zhang, Xiao-feng; Zhou, Yi-feng; Wang, Zhi-wei; Wang, Ke-yi

    2009-01-01

    Objective: To investigate the therapeutic effects and mechanisms of Salvia miltiorrhizae (Danshen) in the treatment of severe acute pancreatitis (SAP)- or obstructive jaundice (OJ)-induced heart injury. Methods: A total of 288 rats were used for SAP- (n=108) and OJ-associated (n=180) experiments. The rats were randomly divided into sham-operated, model control, and Salvia miltiorrhizae-treated groups. According to the difference of time points after operation, SAP rats in each group were subdivided into 3, 6 and 12 h subgroups (n=12), whereas OJ rats were subdivided into 7, 14, 21, and 28 d subgroups (n=15). At the corresponding time points after operation, the mortality rates of the rats, the contents of endotoxin and phospholipase A2 (PLA2) in blood, and pathological changes of the hearts were investigated. Results: The numbers of dead SAP and OJ rats in the treated groups declined as compared with those in the model control group, but not significantly (P>0.05). The contents of endotoxin (at 6 and 12 h in SAP rats and on 7, 14, 21, and 28 d in OJ rats, respectively) and PLA2 (at 6 and 12 h in SAP rats and on 28 d in OJ rats, respectively) in the treated group were significantly lower than those in the model control group (P<0.01 and P<0.001, respectively). Besides, myocardial pathological injuries were mitigated in SAP and OJ rats. Conclusion: In this study, we found that Salvia miltiorrhizae improved myocardial pathological changes, reduced the content of PLA2 in blood, and decreased the mortality rates of SAP and OJ rats, exerting protective effects on the hearts of the rats. PMID:19283874

  8. Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels

    SciTech Connect

    Temma, K.; Akera, T.; Ng, Y.C.

    1985-03-01

    The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. The specific (/sup 3/H)phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca/sup 2 +/ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K/sup +/ currents.

  9. Cardiac Sympathetic Afferent Denervation Attenuates Cardiac Remodeling and Improves Cardiovascular Dysfunction in Rats with Heart Failure

    PubMed Central

    Wang, Han-Jun; Wang, Wei; Cornish, Kurtis G.; Rozanski, George J.; Zucker, Irving H.

    2014-01-01

    The enhanced cardiac sympathetic afferent reflex (CSAR) contributes to the exaggerated sympatho-excitation in chronic heart failure (CHF). Increased sympatho-excitation is positively related to mortality in CHF patients. However, the potential beneficial effects of chronic CSAR deletion on cardiac and autonomic function in CHF have not been previously explored. Here we determined the effects of chronic CSAR deletion on cardiac remodeling and autonomic dysfunction in CHF. In order to selectively delete the transient receptor potential vanilloid 1 receptor (TRPV1) -expressing CSAR afferents, epicardial application of resiniferatoxin (RTX, 50 μg/ml), an ultrapotent analogue of capsaicin, was performed during myocardium infarction (MI) surgery in rats. This procedure largely abolished the enhanced CSAR, prevented the exaggerated renal and cardiac sympathetic nerve activity and improved baroreflex sensitivity in CHF rats. Most importantly, we found that epicardial application of RTX largely prevented the elevated LVEDP, lung edema and cardiac hypertrophy, partially reduced left ventricular dimensions in the failing heart and increased cardiac contractile reserve in response to β-adrenergic receptor stimulation with isoproterenol in CHF rats. Molecular evidence showed that RTX attenuated cardiac fibrosis and apoptosis and reduced expression of fibrotic markers and TGF β-receptor I in CHF rats. Pressure - volume loop analysis showed that RTX reduced the end diastolic pressure volume relations in CHF rats indicating improved cardiac compliance. In summary, cardiac sympathetic afferent deletion exhibits protective effects against deleterious cardiac remodeling and autonomic dysfunction in CHF. These data suggest a potential new paradigm and therapeutic potential in the management of CHF. PMID:24980663

  10. Metformin Prevents the Development of Chronic Heart Failure in the SHHF Rat Model

    PubMed Central

    Cittadini, Antonio; Napoli, Raffaele; Monti, Maria Gaia; Rea, Domenica; Longobardi, Salvatore; Netti, Paolo Antonio; Walser, Marion; Samà, Mariateresa; Aimaretti, Gianluca; Isgaard, Jörgen; Saccà, Luigi

    2012-01-01

    Insulin resistance is a recently identified mechanism involved in the pathophysiology of chronic heart failure (CHF). We investigated the effects of two insulin-sensitizing drugs (metformin and rosiglitazone) in a genetic model of spontaneously hypertensive, insulin-resistant rats (SHHF). Thirty SHHF rats were randomized into three treatment groups as follows: 1) metformin (100 mg/kg per day), 2) rosiglitazone (2 mg/kg per day), and 3) no drug. Ten Sprague-Dawley rats served as normal controls. At the end of the treatment period (12 months), the cardiac phenotype was characterized by histology, echocardiography, and isolated perfused heart studies. Metformin attenuated left ventricular (LV) remodeling, as shown by reduced LV volumes, wall stress, perivascular fibrosis, and cardiac lipid accumulation. Metformin improved both systolic and diastolic indices as well as myocardial mechanical efficiency, as shown by improved ability to convert metabolic energy into mechanical work. Metformin induced a marked activation of AMP-activated protein kinase, endothelial nitric oxide synthase, and vascular endothelial growth factor and reduced tumor necrosis factor-α expression and myocyte apoptosis. Rosiglitazone did not affect LV remodeling, increased perivascular fibrosis, and promoted further cardiac lipid accumulation. In conclusion, long-term treatment with metformin, but not with rosiglitazone, prevents the development of severe CHF in the SHHF model by a wide-spectrum interaction that involves molecular, structural, functional, and metabolic-energetic mechanisms. PMID:22344560

  11. Acetyl-L-carnitine increases mitochondrial protein acetylation in the aged rat heart.

    PubMed

    Kerner, Janos; Yohannes, Elizabeth; Lee, Kwangwon; Virmani, Ashraf; Koverech, Aleardo; Cavazza, Claudio; Chance, Mark R; Hoppel, Charles

    2015-01-01

    Previously we showed that in vivo treatment of elderly Fisher 344 rats with acetylcarnitine abolished the age-associated defect in respiratory chain complex III in interfibrillar mitochondria and improved the functional recovery of the ischemic/reperfused heart. Herein, we explored mitochondrial protein acetylation as a possible mechanism for acetylcarnitine's effect. In vivo treatment of elderly rats with acetylcarnitine restored cardiac acetylcarnitine content and increased mitochondrial protein lysine acetylation and increased the number of lysine-acetylated proteins in cardiac subsarcolemmal and interfibrillar mitochondria. Enzymes of the tricarboxylic acid cycle, mitochondrial β-oxidation, and ATP synthase of the respiratory chain showed the greatest acetylation. Acetylation of isocitrate dehydrogenase, long-chain acyl-CoA dehydrogenase, complex V, and aspartate aminotransferase was accompanied by decreased catalytic activity. Several proteins were found to be acetylated only after treatment with acetylcarnitine, suggesting that exogenous acetylcarnitine served as the acetyl-donor. Two-dimensional fluorescence difference gel electrophoresis analysis revealed that acetylcarnitine treatment also induced changes in mitochondrial protein amount; a two-fold or greater increase/decrease in abundance was observed for thirty one proteins. Collectively, our data provide evidence for the first time that in the aged rat heart in vivo administration of acetylcarnitine provides acetyl groups for protein acetylation and affects the amount of mitochondrial proteins. PMID:25660059

  12. Pretreatment with Assafoetida exerts dose-dependent dual effects on rat hearts

    PubMed Central

    Esmailidehaj, Mansour; Kakoo, Mohadeseh; Rezvani, Mohammad Ebrahim; Mosaddeghmehrjardi, Mohammad Hossein

    2014-01-01

    Context: Although many studies displayed the favorable effects of Assafoetida, some of them reported that high doses of Assafoetida could lead to harmful effects. Aims: In this study, the effect of pretreatment with Assafoetida investigated on ischemic–reperfusion injury in isolated rat heart model. Materials and Methods: Thirty two male Wistar rats were divided into 4 groups of eight. Group 1 as the control (Con) group and three other groups as the treatment groups that given Assafoetida by gavage at levels of 25, 50 and 100 mg/kg, once a day for four weeks (T25, T50 and T100 groups). Then their hearts were subjected to 30 min global ischemia and 90 min reperfusion under langendorff apparatus. Results: The data shown that hemodynamic parameters including left ventricular developed pressure (LVDP) and maximum and minimum of pressure changes (±dp/dt) were increased in T25 and decreased in T50 and T100 groups during reperfusion in comparison with Con group. There was not any significant difference in the incidence of irreversible ventricular fibrillation between T25 and Con group, while it was increased in T50 and T100 groups significantly. There was not any significant difference in infarct size between all groups. Conclusion: These data indicate that pretreatment of rats with Assafoetida have cardioprotective effects in low doses and cardiotoxic effects in higher doses. Therefore, it needs more investigation in the future. PMID:24914280

  13. Polygonal networks, "geodomes", of adult rat hepatocytes in primary culture.

    PubMed

    Mochizuki, Y; Furukawa, K; Mitaka, T; Yokoi, T; Kodama, T

    1988-01-01

    Polygonal networks, "geodomes", in cultured hepatocytes of adult rats were examined by both light and electron microscopy. On light microscopical examinations of specimens stained with Coomassie blue after the treatment with Triton X-100, the networks were detected 5 days after culture, which consisted of triangles arranged mainly in hexagonal patterns. They surrounded main cell body, looking like a headband, or were occasionally situated over nuclei, looking like a geodesic dome. Scanning electron microscopical observations after Triton treatment revealed that these structures were located underneath surface membrane. Transmission electron microscopical investigations revealed that the connecting fibers of networks consisted of microfilaments which radiated in a compact bundle from electron-dense vertices. PMID:3396075

  14. Cysteamine reduces serum gonadotropin concentrations in adult male rats.

    PubMed

    Badger, T M; Sagar, S M; Millard, W J; Martin, J B; Rosenblum, P

    1982-01-18

    We have examined the effects of cysteamine on the hypothalamic-pituitary-gonadal axis of the adult male rat. A single subcutaneous injection of cysteamine (300 mg/kg) reduces significantly (p less than or equal to 0.05 serum concentrations of LH, FSH and T. Cysteamine blocked LH secretion induced by castration and administration of naloxone and LHRH. Neither acute nor chronic treatment (7 days) altered the hypothalamic LHRH content. These results suggest that cysteamine acts to reduce pituitary responsiveness to LHRH, resulting in lower mean serum gonadotropin and testosterone concentrations. It is possible, however, that cysteamine acts also at the hypothalamus to reduce LHRH secretion and/or at the testes to reduce testosterone release.

  15. Morphological and functional changes in the rat heart after X irradiation: Strain differences

    SciTech Connect

    Yeung, T.K.; Lauk, S.; Simmonds, R.H.; Hopewell, J.W.; Trott, K.R. )

    1989-09-01

    The hearts of mature male rats of the Wistar and Sprague-Dawley strains were locally irradiated with single doses of 17.5 and 20.0 Gy of X rays, respectively. These two dose levels had previously been shown to result in a comparable latent period between irradiation and the death of rats of these two strains from cardiac failure. Morphological changes in the myocardium and modifications in cardiac function were assessed in the animals at 28, 70, and 100 days after irradiation. The first radiation-induced change which was observed in the myocardium was a rapid decline in capillary density and a loss of alkaline phosphatase activity by the capillary endothelial cells. The capillary density was reduced to approximately 50% of that of unirradiated control values at 28 days and to approximately 40% of the control values between 70 and 100 days after irradiation. The loss of enzyme activity was also detected at 28 days. Examination of histological sections showed an increase by 70 days in the areas with negative enzyme activity up to approximately 70% of the myocardium. The reduction in capillary density and the loss of enzyme activity occurred before any marked pathological changes were seen in the myocardium. The pathological lesions seen in the myocardium at 100 days after irradiation were qualitatively and quantitatively the same in the two strains of rat. Measurements of cardiac output in Sprague-Dawley rats showed a gradual decline in output after irradiation; however, measurements in Wistar rats showed a progressive increase in cardiac output over the same period of time. It was shown by rubidium extraction that there was an increase in the percentage of the total cardiac output distributed to the ventricular muscle of Sprague-Dawley rats, while similar measurements in Wistar rats showed no significant change.

  16. The Impact of Heart Irradiation on Dose-Volume Effects in the Rat Lung

    SciTech Connect

    Luijk, Peter van Faber, Hette; Meertens, Harm; Schippers, Jacobus M.; Langendijk, Johannes A.; Brandenburg, Sytze; Kampinga, Harm H.; Coppes, Robert P. Ph.D.

    2007-10-01

    Purpose: To test the hypothesis that heart irradiation increases the risk of a symptomatic radiation-induced loss of lung function (SRILF) and that this can be well-described as a modulation of the functional reserve of the lung. Methods and Materials: Rats were irradiated with 150-MeV protons. Dose-response curves were obtained for a significant increase in breathing frequency after irradiation of 100%, 75%, 50%, or 25% of the total lung volume, either including or excluding the heart from the irradiation field. A significant increase in the mean respiratory rate after 6-12 weeks compared with 0-4 weeks was defined as SRILF, based on biweekly measurements of the respiratory rate. The critical volume (CV) model was used to describe the risk of SRILF. Fits were done using a maximum likelihood method. Consistency between model and data was tested using a previously developed goodness-of-fit test. Results: The CV model could be fitted consistently to the data for lung irradiation only. However, this fitted model failed to predict the data that also included heart irradiation. Even refitting the model to all data resulted in a significant difference between model and data. These results imply that, although the CV model describes the risk of SRILF when the heart is spared, the model needs to be modified to account for the impact of dose to the heart on the risk of SRILF. Finally, a modified CV model is described that is consistent to all data. Conclusions: The detrimental effect of dose to the heart on the incidence of SRILF can be described by a dose dependent decrease in functional reserve of the lung.

  17. Respiratory autoresuscitation following severe acute hypoxemia in anesthetized adult rats.

    PubMed

    Krause, A; Nowak, Z; Srbu, R; Bell, H J

    2016-10-01

    In the present study we investigated the pattern and efficacy of respiratory autoresuscitation in spontaneously breathing adult male rats across three separate anesthetic backgrounds. Each animal was administered one of three injectable anesthetics to achieve a surgical plane of anesthesia: ketamine-xylazine (KET, n=10), pentobarbital (PEN, n=10), or urethane (URE, n=10). Animals were tracheostomized and equipped with a femoral artery catheter to record airflow and arterial pressures. In response to a bout of breathing anoxic air, none of the 10 URE animals were able to mount a successful autoresuscitation response. In contrast, all KET and PEN animals survived all four consecutive anoxic exposures, restoring eupneic breathing in all cases. Moreover, only 4/10 URE animals expressed gasping breaths following the onset of respiratory arrest, and these were temporally delayed (p<0.001) and much smaller in volume (P≤0.012) compared to KET and PEN animals. URE animals showed no clear aberrations in their cardiovascular responses to anoxia, with the exception of lower arterial pulse pressures compared to either KET or PEN animals at specific points following RA. Ketamine-xylazine and pentobarbital anesthesia can be reliably and effectively used to create models for the study of autoresuscitation in adult rats. In contrast, urethane causes catastrophic failure of respiratory autoresuscitation, by delaying or outright preventing the elaboration of gasping breaths following anoxia-induced respiratory arrest. The neuronal and synaptic alterations accompanying urethane anesthesia may therefore provide a means of understanding potential pathological alterations in rhythm generation that can predispose the respiratory control system to failed autoresuscitation following an episode of acute severe hypoxemia. PMID:27378495

  18. Fate of undifferentiated mouse embryonic stem cells within the rat heart: role of myocardial infarction and immune suppression

    PubMed Central

    He, Qing; Trindade, Pedro T; Stumm, Michael; Li, Jian; Zammaretti, Prisca; Bettiol, Esther; Dubois-Dauphin, Michel; Herrmann, François; Kalangos, Afksendyios; Morel, Denis; Jaconi, Marisa E

    2009-01-01

    Abstract It has recently been suggested that the infarcted rat heart microenvironment could direct pluripotent mouse embryonic stem cells to differentiate into cardiomyocytes through an in situ paracrine action. To investigate whether the heart can function as a cardiogenic niche and confer an immune privilege to embryonic stem cells, we assessed the cardiac differentiation potential of undifferentiated mouse embryonic stem cells (mESC) injected into normal, acutely or chronically infarcted rat hearts. We found that mESC survival depended on immunosuppression both in normal and infarcted hearts. However, upon Cyclosporin A treatment, both normal and infarcted rat hearts failed to induce selective cardiac differentiation of implanted mESC. Instead, teratomas developed in normal and infarcted rat hearts 1 week and 4 weeks (50% and 100%, respectively) after cell injection. Tight control of ESC commitment into a specific cardiac lineage is mandatory to avoid the risk of uncontrolled growth and tumourigenesis following transplantation of highly plastic cells into a diseased myocardium. PMID:18373734

  19. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

  20. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.

  1. Characteristic subcellular distribution, in brain, heart and lung, of biperiden, trihexyphenidyl, and (-)-quinuclidinyl benzylate in rats.

    PubMed

    Ishizaki, J; Yokogawa, K; Nakashima, E; Ohkuma, S; Ichimura, F

    1998-01-01

    The subcellular distribution of biperiden (BP), trihexyphenidyl (TP) and (-)-quinuclidinyl benzylate (QNB) in brain, heart and lung following high dose (3.2 mg/kg) i.v. administration was investigated in rats. The subcellular distribution of BP or TP used clinically conformed with that of QNB, a typical potent central muscarinic antagonist. The concentration-time courses of the brain subcellular fractions for these drugs were of two types which decreased slowly and in parallel to the plasma concentration. The subcellular distribution in the brain and heart was dependent on the protein amount of each fraction. The percent post-nuclear fraction (P2) of the total concentration in the lung was characteristically about 3-5 times larger than that in the heart. It was elucidated that the distribution in the lung differs from that in the brain and heart, with high affinity which is not dependent on the protein amount in the P2 fraction containing lysosomes. On the other hand, at a low dose (650 ng/kg) of 3H-QNB, each fraction as a percentage of the total concentration in the brain increased in synaptic membrane and synaptic vesicles and decreased in nuclei and cytosol as compared with the high dose. These results show that although the tissue concentration-time courses of anticholinergic drugs appear to decrease simply in parallel to plasma concentration, the subcellular distribution exhibits a variety of patterns among various tissues.

  2. Comparison of electroretinographic responses between two different age groups of adult Dark Agouti rats

    PubMed Central

    Fu, Lin; Lo, Amy Cheuk Yin; Lai, Jimmy Shiu Ming; Shih, Kendrick Co

    2015-01-01

    AIM To describe and compare the differences in electroretinographic responses between two different age groups of adult Dark Agouti (DA) rats and to better understand the effect of age on retinal histology and function. METHODS The electroretinographic responses of two different age groups of adult DA rats were compared. Animals were divided into younger adult DA rats 10-12wk (n=8) and older adult DA rats 17-19wk (n=8). Full field electroretinography (ERG) was recorded simultaneously from both eyes after dark adaption and light adaption and parameters including the positive scotopic threshold response (pSTR), negative scotopic threshold response (nSTR), scotopic a-wave, b-wave, photopic a-wave, b-wave and photopic negative response (PhNR) were compared between groups. RESULTS The older adult rats displayed lower stimulation thresholds of the STRs (pSTR and nSTR) and higher amplitudes of pSTR, scotopic a-wave and b-wave, photopic b-wave and PhNR amplitudes, with shorter implicit times. Photopic a-wave amplitudes were however higher in the younger adult rats. CONCLUSION In summary, for the rod system, photoreceptor, bipolar cell and RGC activity was enhanced in the older adult rats. For the cone system, RGC and bipolar cell activity was enhanced, while photoreceptor activity was depressed in the older adult rats. Such age-related selective modification of retinal cell function needs to be considered when conducting ophthalmic research in adult rats. PMID:26558198

  3. Correlates of carotid artery stiffness in young adults: The Bogalusa Heart Study.

    PubMed

    Urbina, E M; Srinivasan, S R; Kieltyka, R L; Tang, R; Bond, M G; Chen, W; Berenson, G S

    2004-09-01

    Decreased arterial elasticity, an independent risk factor for cardiovascular (C-V) disease, is associated with C-V risk factors in middle-aged and older individuals. However, information is limited in this regard in young adults. This aspect was examined in a community-based sample of 516 black and white subjects aged 25-38 years (71% white, 39% male). The common carotid artery elasticity was measured from M-mode ultrasonography as Peterson's elastic modulus (Ep) and relative wall thickness-adjusted Young's elastic modulus (YEM). Blacks and males had higher Ep (P < 0.05); males had higher YEM (P < 0.0001); and blacks had higher wall thickness (P < 0.01). For the entire sample adjusted for race and gender both Ep and YEM correlated significantly (P < 0.05-0.0001) with age, BMI, waist, systolic and diastolic blood pressures, heart rate, product of heart rate and pulse pressure, triglycerides, total cholesterol to HDL cholesterol ratio, insulin and glucose. In a multivariate regression model that included hemodynamic variables, systolic blood pressure, product of heart rate and pulse pressure, age, triglycerides, BMI, and male gender (for YEM only) were independent correlates of Ep (R2 = 0.38) and YEM (R2 = 0.25). When the hemodynamic variables were excluded from the model, age, triglycerides, BMI, black race (Ep only), male gender, parental history of hypertension, HDL cholesterol (inverse association), and insulin (marginal significance) remained independent correlates of Ep (R2 = 0.20) and YEM (R2 = 16). Both Ep and YEM increased (P for trend P < 0.0001) with increasing number of independent continuous risk factors (defined as values above or below the age, race, and gender-specific extreme quintiles) that were retained in the regression models. The observed increasing arterial stiffness (or decreased elasticity) with increasing number of risk factors related to insulin resistance syndrome in free-living, asymptomatic young adults has important implications for

  4. Neonatal injections of methoxychlor decrease adult rat female reproductive behavior.

    PubMed

    Bertolasio, Jennifer; Fyfe, Susanne; Snyder, Ben W; Davis, Aline M

    2011-12-01

    Methoxychlor (MXC), a commonly used pesticide, has been labeled as an endocrine disruptor. To evaluate the impact of neonatal exposure to MXC on female reproduction, female Sprague-Dawley rats were given subcutaneous injections on postnatal days 1, 3, and 5. The injections contained 1.0mg MXC, 2.0mg MXC, 10 μg 17β-estradiol benzoate (positive control), or sesame oil (vehicle). The injections of MXC had no effect on anogenital distance or day of vaginal opening. Treatment with either 2.0mg MXC or estradiol significantly increased the total number of days with vaginal keratinization. Treatment with MXC had no effect on ability to exhibit a mating response as an adult female, although the high dose MXC (2.0) and the positive control (estradiol) animals demonstrated a decrease in degree of receptivity, a decrease in proceptive behavior and an increase in rejection behavior. These data suggest that higher doses of MXC given directly to pups during the neonatal period can act as an estrogen and alter aspects of the nervous system, impacting adult reproductive characteristics.

  5. An ultrastructural study of sinuatrial node cells in the embryonic rat heart.

    PubMed Central

    Domenech-Mateu, J M; Boya-Vegué, J

    1975-01-01

    Sinuatrial nodal tissue, obtained from rat embryos of 15, 16 and 17 days, was examined with the electron microscope. Embryonic nodal cells were generally similar to adult cells except that (1) they showed thick prolongations of the cytoplasm which insinuated themselves between neighbouring cells; (2) they possessed osmiophilic granules with a predeliction for the region of the Golgi complex; (3) they exhibited a lesser and variable degree of pinocytosis. Images Fig. 1 Fig. 2 Fig. 3 PMID:1133091

  6. [Nonspecific effect of Na+/K(+)-ATPase inhibition with strophanthin or under hypothermia in rat heart].

    PubMed

    Pogorelova, V N; Panait, A I; Pogorelov, A G

    2014-01-01

    Electron probe microanalysis was applied to study the kinetics of changes in potassium and sodium concentration in muscle cells of isolated heart from Wistar rat during experimental ischemia. Hypoxic perfusion without glucose was shown to evoke the potassium deficiency and sodium accumulation in cardiac myocells. Short-term action (10 min) of strophanthin (0.1 mM/l) recovered Na/K balance in ischemic myocells. Hypothermic perfusion exhibited the opportunity to conserve the cytoplasmic elemental contents in the state corresponding to the beginning of low temperature (4 degrees C) operation. PMID:25730978

  7. The effects of interferon-alpha/beta in a model of rat heart transplantation

    NASA Technical Reports Server (NTRS)

    Slater, A. D.; Klein, J. B.; Sonnenfeld, G.; Ogden, L. L. 2nd; Gray, L. A. Jr

    1992-01-01

    Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.

  8. Effects of long-term caffeine consumption on renal function in spontaneously hypertensive heart failure prone rats.

    PubMed

    Tofovic, S P; Jackson, E K

    1999-03-01

    Our previous studies supported the hypothesis that prolonged administration of caffeine to animals with high-renin hypertension causes progressive deterioration of renal function. However, thus far this hypothesis has been tested with only a few animal models of hypertension. The aim of this study was to test this hypothesis further by investigating the effects of long-term caffeine consumption on renal function in adult spontaneously hypertensive heart failure (SHHF/Mcc-fa(cp)) rats, another model of high-renin hypertension. Lean, male, 9-month-old SHHF/Mcc-fa(cp) rats were randomized to receive either normal drinking water (control group) or drinking water containing 0.1% caffeine (caffeine group) for 20 weeks. No changes in body weight, food and fluid intake, urine volume, and sodium and potassium excretion were found in conscious SHHF/Mcc-fa(cp) rats after 10 or 20 weeks of caffeine treatment. However, caffeine treatment accelerated the time-related decline in renal function and augmented urinary protein excretion. Ten weeks into the protocol, creatinine clearance was 3.6+/-0.4 and 5.7+/-0.9 L/kg/day in the caffeine group and control group, respectively (p<0.02), whereas 20 weeks into the study, creatinine clearance was similarly diminished in both groups. Proteinuria was greater in the caffeine group compared with the control group at both 10 (928+/-131 vs. 439+/-21 mg/kg/day, respectively; p<0.02) and 20 weeks (1,202+/-196 vs. 603+/-30 mg/kg/day, respectively; p<0.01) into the protocol. After 20 weeks, all animals were anesthetized and instrumented. Caffeine treatment for 20 weeks had no effects on blood pressure, heart rate, or vascular resistance in four examined vascular beds (abdominal aorta and renal, carotid, and mesenteric arteries). No changes in renal hemodynamics and electrolyte excretion were found, whereas significantly lower glomerular filtration rate (GFR; inulin clearance) and creatinine clearance (p<0.05) were observed in caffeine

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

    PubMed Central

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

    2013-01-01

    Background Autonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy. Methods and Results Somal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm2; P<0.01) and canine hearts (767.80±18.37 versus 650.23±9.84 μm2; P<0.01) failing secondary to ischemia and neurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm2; P<0.01) failing secondary to hypertension reveal significant hypertrophy of neurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures. Conclusions Hypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia. PMID:23959444

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

    PubMed Central

    Nagai-Okatani, Chiaki; Minamino, Naoto

    2016-01-01

    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. PMID:27281159

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

    PubMed

    Nagai-Okatani, Chiaki; Minamino, Naoto

    2016-01-01

    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. PMID:27281159

  12. Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats.

    PubMed

    Ramos, Linnet; Hicks, Callum; Caminer, Alex; McGregor, Iain S

    2014-08-01

    The neuropeptides vasopressin (AVP) and oxytocin (OT) have therapeutic potential across a range of psychiatric disorders. However, there is uncertainty about the effectiveness of the intranasal route of administration that is often used to deliver these neuropeptides. Recent preclinical studies, typically involving anesthetized or restrained animals, have assessed intranasal AVP or OT effects, and have obtained somewhat inconsistent results. Here we obtained intranasal administration of AVP in rats by nebulizing the peptide (1ml of 5 or 10mg/ml solution) into a small enclosed chamber over a 2min period in which well-habituated, unanesthetized, unrestrained, rats were placed. Rats were immediately removed from the chamber and tested in the social interaction test, or assessed for changes in heart rate and body temperature using biotelemetry. Results showed that rats exposed to nebulized AVP (5 or 10mg/ml) showed increased social proximity (adjacent lying) and decreased anogenital sniffing in the social interaction test. Biotelemetry showed substantial and long lasting (>1h) hypothermic and bradycardic effects of nebulized AVP. These behavioral and physiological effects of nebulized AVP mimic those observed in recent studies with peripherally injected AVP. Plasma AVP concentrations were substantially increased 10min after nebulized AVP, producing levels above those seen with a behaviorally effective injected dose of AVP (0.005mg/kg intraperitoneal). This study thus provides a novel and effective method for neuropeptide administration to rodents. PMID:24882157

  13. Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats.

    PubMed

    Ramos, Linnet; Hicks, Callum; Caminer, Alex; McGregor, Iain S

    2014-08-01

    The neuropeptides vasopressin (AVP) and oxytocin (OT) have therapeutic potential across a range of psychiatric disorders. However, there is uncertainty about the effectiveness of the intranasal route of administration that is often used to deliver these neuropeptides. Recent preclinical studies, typically involving anesthetized or restrained animals, have assessed intranasal AVP or OT effects, and have obtained somewhat inconsistent results. Here we obtained intranasal administration of AVP in rats by nebulizing the peptide (1ml of 5 or 10mg/ml solution) into a small enclosed chamber over a 2min period in which well-habituated, unanesthetized, unrestrained, rats were placed. Rats were immediately removed from the chamber and tested in the social interaction test, or assessed for changes in heart rate and body temperature using biotelemetry. Results showed that rats exposed to nebulized AVP (5 or 10mg/ml) showed increased social proximity (adjacent lying) and decreased anogenital sniffing in the social interaction test. Biotelemetry showed substantial and long lasting (>1h) hypothermic and bradycardic effects of nebulized AVP. These behavioral and physiological effects of nebulized AVP mimic those observed in recent studies with peripherally injected AVP. Plasma AVP concentrations were substantially increased 10min after nebulized AVP, producing levels above those seen with a behaviorally effective injected dose of AVP (0.005mg/kg intraperitoneal). This study thus provides a novel and effective method for neuropeptide administration to rodents.

  14. Effect of MDMA (ecstasy) on activity and cocaine conditioned place preference in adult and adolescent rats.

    PubMed

    Aberg, Maria; Wade, Dean; Wall, Erin; Izenwasser, Sari

    2007-01-01

    MDMA (ecstasy) is a drug commonly used in adolescence, and many users of MDMA also use other illicit drugs. It is not known whether MDMA during adolescence alters subsequent responses to cocaine differently than in adults. This study examined the effects of MDMA in adolescent and adult rats on cocaine conditioned reward. At the start of these experiments, adolescent rats were at postnatal day (PND) 33 and adult rats at PND 60. Each rat was treated for 7 days with MDMA (2 or 5 mg/kg/day or vehicle) and locomotor activity was measured. Five days later cocaine conditioned place preference (CPP) was begun. Rats were trained for 3 days, in the morning with saline and in the afternoon with 10 mg/kg cocaine in 30 min sessions, and tested on the fourth day. MDMA stimulated activity in both age groups, but with a greater effect in the adult rats. Sensitization to the locomotor-stimulant effects of the lower dose of MDMA occurred in adult rats and in both groups to the higher dose. Cocaine did not produce a CPP in vehicle-treated adolescent rats, but a significant CPP was observed subsequent to treatment with MDMA. In contrast, cocaine-induced CPP was diminished after MDMA in adult rats. These effects were still evident 2 weeks later upon retest. Thus, under the present conditions, MDMA increased cocaine conditioned reward in adolescent and decreased it in adult rats. These findings suggest that exposure to MDMA during this critical developmental period may carry a greater risk than during adulthood and that male adolescents may be particularly vulnerable to the risk of stimulant abuse after use of MDMA.

  15. HAND1 and HAND2 are expressed in the adult-rodent heart and are modulated during cardiac hypertrophy.

    PubMed

    Thattaliyath, Bijoy D; Livi, Carolina B; Steinhelper, Mark E; Toney, Glenn M; Firulli, Anthony B

    2002-10-01

    The HAND basic Helix-Loop-Helix (bHLH) transcription factors are essential for normal cardiac and extraembryonic development. Although highly evolutionarily conserved genes, HAND cardiac expression patterns differ across species. Mouse expression of HAND1 and HAND2 was reported absent in the adult heart. Human HAND genes are expressed in the adult heart and HAND1 expression is downregulated in cardiomyopathies. As rodent and human expression profiles are inconsistent, we re-examined expression of HAND1 and HAND2 in adult-rodent hearts. HAND1 and HAND2 are expressed in adult-rodent hearts and HAND2 is expressed in the atria. Induction of cardiac hypertrophy shows modulation of HAND expression, corresponding with observations in human cardiomyopathy. The downregulation of HAND expression observed in rodent hypertrophy and human cardiomyopathy may reflect a permissive role allowing, cardiomyocytes to reinitiate the fetal gene program and initiate the adaptive physiological changes that allow the heart to compensate (hypertrophy) for the increase in afterload.

  16. Forskolin- and dihydroalprenolol (DHA) binding sites and adenylate cyclase activity in heart of rats fed diets containing different oils

    SciTech Connect

    Alam, S.Q.; Ren, Y.F.; Alam, B.S.

    1987-05-01

    The purpose of the present investigation was to determine if dietary lipids can induce changes in the adenylate cyclase system in rat heart. Three groups of male young Sprague-Dawley rats were fed for 6 weeks diets containing 10% corn oil (I), 8% coconut oil + 2% corn oil (II) or 10% menhaden oil (III). Adenylate cyclase activity (basal, fluoride-, isoproterenol-, and forskolin-stimulated) was higher in heart homogenates of rats in group III than in the other two groups. Concentration of the (/sup 3/H)-forskolin binding sites in the cardiac membranes were significantly higher in rats fed menhaden oil. The values (pmol/mg protein) were 4.8 +/- 0.2 (I), 4.5 +/- 0.7 (II) and 8.4 +/- 0.5 (III). There was no significant difference in the affinity of the forskolin binding sites among the 3 dietary groups. When measured at different concentrations of forskolin, the adenylate cyclase activity in cardiac membranes of rats fed menhaden oil was higher than in the other 2 groups. Concentrations of the (/sup 3/H)DHA binding sites were slightly higher but their affinity was lower in cardiac membranes of rats fed menhaden oil. The results suggest that diets containing fish oil increase the concentration of the forskolin binding sites and may also affect the characteristics of the ..beta..-adrenergic receptor in rat heart.

  17. Trends in Heart Disease Mortality among Mississippi Adults over Three Decades, 1980-2013

    PubMed Central

    2016-01-01

    Heart disease (HD) remains the leading cause of death among Mississippians; however, despite the importance of the condition, trends in HD mortality in Mississippi have not been adequately explored. This study examined trends in HD mortality among adults in Mississippi from 1980 through 2013 and further examined these trends by race and sex. We used data from Mississippi Vital Statistics (1980–2013) to calculate age-adjusted HD mortality rates for Mississippians age 25 or older. Cases were identified using underlying cause of death codes from the International Classification of Diseases, Ninth Revision (ICD-9: 390–398, 402, 404–429) and Tenth Revision (ICD-10), including I00-I09, I11, I13, and I20-I51. Joinpoint software was used to calculate the average annual percent change in HD mortality rates for the overall population and by race and sex. Overall, the age-adjusted HD mortality rate among Mississippi adults decreased by 36.5% between 1980 and 2013, with an average annual percent change of -1.60% (95% CI -2.00 to -1.30). This trend varied across subgroups: HD mortality rates experienced an average annual change of -1.34% (95% CI -1.98 to -0.69) for black adults; -1.60% (95% CI -1.74 to -1.46) for white adults; -1.30% (95% CI -1.50 to -1.10) for all women, and -1.90% (95% -2.20 to -1.50) for all men. From 1980 to 2013, there was a continuous decrease in HD mortality among adult Mississippians. However, the magnitude of this reduction differed by race and sex. PMID:27518895

  18. Trends in Heart Disease Mortality among Mississippi Adults over Three Decades, 1980-2013.

    PubMed

    Mendy, Vincent L; Vargas, Rodolfo; El-Sadek, Lamees

    2016-01-01

    Heart disease (HD) remains the leading cause of death among Mississippians; however, despite the importance of the condition, trends in HD mortality in Mississippi have not been adequately explored. This study examined trends in HD mortality among adults in Mississippi from 1980 through 2013 and further examined these trends by race and sex. We used data from Mississippi Vital Statistics (1980-2013) to calculate age-adjusted HD mortality rates for Mississippians age 25 or older. Cases were identified using underlying cause of death codes from the International Classification of Diseases, Ninth Revision (ICD-9: 390-398, 402, 404-429) and Tenth Revision (ICD-10), including I00-I09, I11, I13, and I20-I51. Joinpoint software was used to calculate the average annual percent change in HD mortality rates for the overall population and by race and sex. Overall, the age-adjusted HD mortality rate among Mississippi adults decreased by 36.5% between 1980 and 2013, with an average annual percent change of -1.60% (95% CI -2.00 to -1.30). This trend varied across subgroups: HD mortality rates experienced an average annual change of -1.34% (95% CI -1.98 to -0.69) for black adults; -1.60% (95% CI -1.74 to -1.46) for white adults; -1.30% (95% CI -1.50 to -1.10) for all women, and -1.90% (95% -2.20 to -1.50) for all men. From 1980 to 2013, there was a continuous decrease in HD mortality among adult Mississippians. However, the magnitude of this reduction differed by race and sex.

  19. Effects of short- and long-term exposure to ozone on heart rate and blood pressure of emphysematous rats

    SciTech Connect

    Uchiyama, I.; Yokoyama, E.

    1989-02-01

    Electrocardiogram and arterial blood pressure of elastase-treated emphysematous rats (E rats) and saline-treated control rats (S rats) were recorded continuously during exposure to either 1 ppm ozone (O/sub 3/) for 3 hr or 0.5 ppm O/sub 3/ for 6 hr. The heart rates (HRs) of both groups decreased to about 50 and 65% of the initial levels at the end of 1 ppm and 0.5 ppm O/sub 3/ exposure, respectively. Mean arterial blood pressures (MAPs) also decreased to about 76 and 82%, respectively. There was no significant difference in these responses between E and S rats, although the levels of HRs and MAPs of the E rats were always a little lower than those of the S rats. Another group of E and S rats was continuously exposed to 0.2 ppm O/sub 3/ for 4 weeks. The HRs of both E and S groups decreased to about 81 and 88% of the initial levels on the first day, respectively, although they recovered completely by the third day. No significant difference in the variation of HRs during exposure was noted between E and S rats. However, the HR responses of these rats to a challenge exposure of 0.8 ppm O/sub 3/ for 1.5 hr appeared to be different. That is, S rats were more tolerant of the challenge exposure to O/sub 3/ for 1.5 hr than the E rats.

  20. Dipeptidyl Peptidase IV Inhibition Exerts Renoprotective Effects in Rats with Established Heart Failure.

    PubMed

    Arruda-Junior, Daniel F; Martins, Flavia L; Dariolli, Rafael; Jensen, Leonardo; Antonio, Ednei L; Dos Santos, Leonardo; Tucci, Paulo J F; Girardi, Adriana C C

    2016-01-01

    Circulating dipeptidyl peptidase IV (DPPIV) activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF) models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for 4 weeks with vildagliptin (120 mg/kg/day) or vehicle by oral gavage. Echocardiography was performed before (pretreatment) and at the end of treatment (post-treatment) to evaluate cardiac function. The fractional area change (FAC) increased (34 ± 5 vs. 45 ± 3%, p < 0.05), and the isovolumic relaxation time decreased (33 ± 2 vs. 27 ± 1 ms; p < 0.05) in HF rats treated with vildagliptin (post-treatment vs. pretreatment). On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR) and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow, GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1) serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with

  1. Dipeptidyl Peptidase IV Inhibition Exerts Renoprotective Effects in Rats with Established Heart Failure

    PubMed Central

    Arruda-Junior, Daniel F.; Martins, Flavia L.; Dariolli, Rafael; Jensen, Leonardo; Antonio, Ednei L.; dos Santos, Leonardo; Tucci, Paulo J. F.; Girardi, Adriana C. C.

    2016-01-01

    Circulating dipeptidyl peptidase IV (DPPIV) activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF) models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for 4 weeks with vildagliptin (120 mg/kg/day) or vehicle by oral gavage. Echocardiography was performed before (pretreatment) and at the end of treatment (post-treatment) to evaluate cardiac function. The fractional area change (FAC) increased (34 ± 5 vs. 45 ± 3%, p < 0.05), and the isovolumic relaxation time decreased (33 ± 2 vs. 27 ± 1 ms; p < 0.05) in HF rats treated with vildagliptin (post-treatment vs. pretreatment). On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR) and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow, GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1) serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with

  2. Measurement of Technetium-99m Sestamibi Signals in Rats Administered a Mitochondrial Uncoupler and in a Rat Model of Heart Failure

    PubMed Central

    Kawamoto, Akira; Kato, Takao; Shioi, Tetsuo; Okuda, Junji; Kawashima, Tsuneaki; Tamaki, Yodo; Niizuma, Shinichiro; Tanada, Yohei; Takemura, Genzou; Narazaki, Michiko; Matsuda, Tetsuya; Kimura, Takeshi

    2015-01-01

    Background Many methods have been used to assess mitochondrial function. Technetium-99m sestamibi (99mTc-MIBI), a lipophilic cation, is rapidly incorporated into myocardial cells by diffusion and mainly localizes to the mitochondria. The purpose of this study was to investigate whether measurement of 99mTc-MIBI signals in animal models could be used as a tool to quantify mitochondrial membrane potential at the organ level. Methods and Results We analyzed 99mTc-MIBI signals in Sprague-Dawley (SD) rat hearts perfused with carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler known to reduce the mitochondrial membrane potential. 99mTc-MIBI signals could be used to detect changes in the mitochondrial membrane potential with sensitivity comparable to that obtained by two-photon laser microscopy with the cationic probe tetramethylrhodamine ethyl ester (TMRE). We also measured 99mTc-MIBI signals in the hearts of SD rats administered CCCP (4 mg/kg intraperitoneally) or vehicle. 99mTc-MIBI signals decreased in rat hearts administered CCCP, and the ATP content, as measured by 31P magnetic resonance spectroscopy, decreased simultaneously. Next, we administered 99mTc-MIBI to Dahl salt-sensitive rats fed a high-salt diet, which leads to hypertension and heart failure. The 99mTc-MIBI signal per heart tissue weight was inversely correlated with heart weight, cardiac function, and the expression of atrial natriuretic factor, a marker of heart failure, and positively correlated with the accumulation of labeled fatty acid analog. The 99mTc-MIBI signal per liver tissue weight was lower than that per heart tissue weight. Conclusion Measurement of 99mTc-MIBI signals can be an effective tool for semiquantitative investigation of cardiac mitochondrial membrane potential in the SD rat model by using a chemical to decrease the mitochondrial membrane potential. The 99mTc-MIBI signal per heart tissue weight was inversely correlated with the severity of heart failure in

  3. Radiologic evaluation of coronary artery disease in adults with congenital heart disease.

    PubMed

    Valenzuela, David M; Ordovas, Karen G

    2016-01-01

    Improved surgical and medical therapy have prolonged survival in patients with congenital heart disease (CHD) such that general medical conditions like coronary artery disease (CAD) are now the main determinants of mortality. A summary of the association of CAD with CHD, as well as a discussion of the radiologic evaluation of the coronary arteries in adults with CHD is described herein. Cross sectional imaging to evaluate CAD in adults with CHD should follow the same appropriateness criteria as gender and aged matched patients without CHD. Coronary CT imaging may be particularly valuable in evaluating the coronary arteries in this patient population as invasive coronary angiography may prove challenging secondary to complicated or unconventional anatomy of the coronary arteries. Further, typical methods for evaluating CAD such as stress or echocardiography may be impractical in adults with CHD. Finally, delineating the anatomic relationship of the coronary arteries and their relationship with the sternum, chest wall, conduits, grafts, and valves is highly recommended in patients with CHD prior to reintervention to avoid iatrogenic complications.

  4. In Utero Caffeine Exposure Induces Transgenerational Effects on the Adult Heart

    PubMed Central

    Fang, Xiefan; Poulsen, Ryan R.; Rivkees, Scott A.; Wendler, Christopher C.

    2016-01-01

    Each year millions of pregnant woman are exposed to caffeine, which acts to antagonize adenosine action. The long-term consequences of this exposure on the developing fetus are largely unknown, although in animal models we have found adverse effects on cardiac function. To assess if these effects are transmitted transgenerationally, we exposed pregnant mice to caffeine equivalent to 2–4 cups of coffee at two embryonic stages. Embryos (F1 generation) exposed to caffeine early from embryonic (E) day 6.5–9.5 developed a phenotype similar to dilated cardiomyopathy by 1 year of age. Embryos exposed to caffeine later (E10.5–13.5) were not affected. We next examined the F2 generation and F3 generation of mice exposed to caffeine from E10.5–13.5, as this coincides with germ cell development. These F2 generation adult mice developed a cardiac phenotype similar to hypertrophic cardiomyopathy. The F3 generation exhibited morphological changes in adult hearts, including increased mass. This report shows that in utero caffeine exposure has long-term effects into adulthood and that prenatal caffeine exposure can exert adverse transgenerational effects on adult cardiac function. PMID:27677355

  5. The small-molecule fast skeletal troponin activator, CK-2127107, improves exercise tolerance in a rat model of heart failure.

    PubMed

    Hwee, Darren T; Kennedy, Adam R; Hartman, James J; Ryans, Julie; Durham, Nickie; Malik, Fady I; Jasper, Jeffrey R

    2015-04-01

    Heart failure-mediated skeletal myopathy, which is characterized by muscle atrophy and muscle metabolism dysfunction, often manifests as dyspnea and limb muscle fatigue. We have previously demonstrated that increasing Ca(2+) sensitivity of the sarcomere by a small-molecule fast skeletal troponin activator improves skeletal muscle force and exercise performance in healthy rats and models of neuromuscular disease. The objective of this study was to investigate the effect of a novel fast skeletal troponin activator, CK-2127107 (2-aminoalkyl-5-N-heteroarylpyrimidine), on skeletal muscle function and exercise performance in rats exhibiting heart failure-mediated skeletal myopathy. Rats underwent a left anterior descending coronary artery ligation, resulting in myocardial infarction and a progressive decline in cardiac function [left anterior descending coronary artery heart failure (LAD-HF)]. Compared with sham-operated control rats, LAD-HF rat hindlimb and diaphragm muscles exhibited significant muscle atrophy. Fatigability was increased during repeated in situ isokinetic plantar flexor muscle contractions. CK-2127107 produced a leftward shift in the force-Ca(2+) relationship of skinned, single diaphragm, and extensor digitorum longus fibers. Exercise performance, which was assessed by rotarod running, was lower in vehicle-treated LAD-HF rats than in sham controls (116 ± 22 versus 193 ± 31 seconds, respectively; mean ± S.E.M.; P = 0.04). In the LAD-HF rats, a single oral dose of CK-2127107 (10 mg/kg p.o.) increased running time compared with vehicle treatment (283 ± 47 versus 116 ± 22 seconds; P = 0.0004). In summary, CK-2127107 substantially increases exercise performance in this heart failure model, suggesting that modulation of skeletal muscle function by a fast skeletal troponin activator may be a useful therapeutic in heart failure-associated exercise intolerance. PMID:25678535

  6. The small-molecule fast skeletal troponin activator, CK-2127107, improves exercise tolerance in a rat model of heart failure.

    PubMed

    Hwee, Darren T; Kennedy, Adam R; Hartman, James J; Ryans, Julie; Durham, Nickie; Malik, Fady I; Jasper, Jeffrey R

    2015-04-01

    Heart failure-mediated skeletal myopathy, which is characterized by muscle atrophy and muscle metabolism dysfunction, often manifests as dyspnea and limb muscle fatigue. We have previously demonstrated that increasing Ca(2+) sensitivity of the sarcomere by a small-molecule fast skeletal troponin activator improves skeletal muscle force and exercise performance in healthy rats and models of neuromuscular disease. The objective of this study was to investigate the effect of a novel fast skeletal troponin activator, CK-2127107 (2-aminoalkyl-5-N-heteroarylpyrimidine), on skeletal muscle function and exercise performance in rats exhibiting heart failure-mediated skeletal myopathy. Rats underwent a left anterior descending coronary artery ligation, resulting in myocardial infarction and a progressive decline in cardiac function [left anterior descending coronary artery heart failure (LAD-HF)]. Compared with sham-operated control rats, LAD-HF rat hindlimb and diaphragm muscles exhibited significant muscle atrophy. Fatigability was increased during repeated in situ isokinetic plantar flexor muscle contractions. CK-2127107 produced a leftward shift in the force-Ca(2+) relationship of skinned, single diaphragm, and extensor digitorum longus fibers. Exercise performance, which was assessed by rotarod running, was lower in vehicle-treated LAD-HF rats than in sham controls (116 ± 22 versus 193 ± 31 seconds, respectively; mean ± S.E.M.; P = 0.04). In the LAD-HF rats, a single oral dose of CK-2127107 (10 mg/kg p.o.) increased running time compared with vehicle treatment (283 ± 47 versus 116 ± 22 seconds; P = 0.0004). In summary, CK-2127107 substantially increases exercise performance in this heart failure model, suggesting that modulation of skeletal muscle function by a fast skeletal troponin activator may be a useful therapeutic in heart failure-associated exercise intolerance.

  7. [Changes in adrenergic nerve plexuses of the heart during immobilization stress in the rat].

    PubMed

    Mar'ian, K L; Buniatian, A M

    1984-03-01

    Luminescent microscopical analysis on the state of the cardiac adrenergic neural apparatus under immobilization stress has been performed in 48 rats of August and Wistar strains. The rats of August strain demonstrate a high sensitivity to the stress: 40% of the animals died during the first 4-17 h of immobilization. Cryostate sections are treated in 2% glyoxylic acid and studied in the luminescent microscope. Quantitative analysis of density distribution of the adrenergic neural terminals is performed by means of dot nets. Decreasing luminescent brightness and decreasing density by 10-15% are noted in the right auricle, and by 30-34%--in the left ventricle, comparing to that of the control. In the animals died a sudden death these parameters are even stronger (28% and 54%, respectively). The data obtained correlate to the functional disturbances of the heart activity (fluctuations of the arterial pressure, disturbances of the rhythm, ECG changes). A suggestion is made that catecholamines content in the neural terminals of the heart is of certain importance in development of the cardiovascular disturbances under immobilization stress.

  8. Cyclic AMP-receptor proteins in heart muscle of rats flown on Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Mednieks, Maija I.; Popova, Irina A.; Grindeland, Richard E.

    1991-01-01

    The cellular compartmentalization of the cyclic AMP-receptor proteins in heart ventricular tissue obtained from rats flown on the Cosmos 1887 is determined. Photoaffinity labeling of soluble and particular cell fractions with a (32P)-8-azido analog of cyclic AMP is followed by electrophoretic separation of the proteins and by autoradiographic identification of the labeled isoforms of cAPK R subunits. It is shown that RII in the particulate subcellular fraction was significantly decreased in heart cells from rats in the flight group when compared to controls. Protein banding patterns in both the cytoplasmic fraction and in a fraction enriched in chromatin-bound proteins exhibited some variability in tissues of individual animals, but showed no changes that could be directly attributed to flight conditions. No significant change was apparent in the distribution of RI or RII cyclic AMP binding in the soluble fractions. It is inferred that the cardiac cell integrity or its protein content is not compromised under flight conditions.

  9. Enzyme activities and adenine nucleotide content in aorta, heart muscle and skeletal muscle from uraemic rats.

    PubMed Central

    Krog, M.; Ejerblad, S.; Agren, A.

    1986-01-01

    A prominent feature of arterial and myocardial lesions in uraemia is necrosis of the smooth muscle cells. In this study the possibility of detecting metabolic disturbances before necroses appear was investigated. The investigation was made on rats with moderate uraemia (mean serum creatinine 165 mumol/l) of 12 weeks duration. Enzyme activities and concentrations of adenine nucleotides were measured in aorta, heart and skeletal muscles. Histological examination disclosed no changes in these organs. Hexokinase, an important glycolytic enzyme, showed decreased activity in the skeletal muscle and aorta, whereas the hexosemonophosphate shunt enzyme glucose-6-phosphate dehydrogenase remained unchanged. The aspartate aminotransferase was increased in the skeletal muscle. Fat metabolism was not disturbed as reflected by unchanged activity of hydroxyacyl-CoA-dehydrogenase. Adenylatekinase which is important for the energy supply showed markedly increased activities in all tissues examined from the uraemic rats. Decreased ATP levels were found in the heart muscle and the aorta of the uraemic animals, whereas the total pool of adenosine phosphates remained unchanged in all tissues. The animal model described offers a useful means of detecting early changes in uraemia and should be useful for studying the effects of different treatments of uraemic complications. PMID:3718844

  10. The effects of compensated cardiac hypertrophy on dihydropyridine and ryanodine receptors in rat, ferret and guinea-pig hearts.

    PubMed

    Rannou, F; Sainte-Beuve, C; Oliviero, P; Do, E; Trouvé, P; Charlemagne, D

    1995-05-01

    The number of dihydropyridine and ryanodine receptors (DHP-R and RyR) has been measured in control and hypertrophied ventricles from rats, guinea pigs and ferrets to determine whether these two channels contribute to the alterations in excitation-contraction coupling (ECC), and in Ca2+ transient during compensated cardiac hypertrophy. We found that ventricular hypertrophy did not change the density of DHP-R. Mild hypertrophy did not alter the density of RyR in the rat but decreased it in the guinea-pig and in the ferret (30% and 36%, respectively). Severe hypertrophy decreased the density of RyR by 20% in the rat and by 34% in the guinea-pig. Therefore, the decrease is greater in ferret and guinea-pig hearts than in rat heart. We conclude that the sarcoplasmic reticulum (SR) Ca2+ release channels but not the L-type Ca2+ channels could contribute to the slowing of intracellular Ca2+ movements and to the reduced velocity of shortening of the hypertrophied hearts. We suggest that, in the guinea pig and ferret hearts which express only the beta myosin heavy chain (MHC) isoform, the reduced velocity of shortening during hypertrophy is related to the decrease in RyR density, whereas in the rat, it is regulated primarily via a shift in the MHC isoform, except in severe hypertrophy in which the moderate decrease in RyR would also be involved. PMID:7473781

  11. Effects of lowering barometric pressure on guarding behavior, heart rate and blood pressure in a rat model of neuropathic pain.

    PubMed

    Sato, J; Takanari, K; Omura, S; Mizumura, K

    2001-02-16

    We investigated whether lowering barometric pressure by 20 mmHg (LP) aggravates the guarding behavior suggestive of spontaneous pain following sciatic nerve chronic constriction injury (CCI) in rats. Systemic blood pressure (BP) and heart rate (HR) of unrestrained rats were recorded telemetrically during LP both before and after the CCI surgery. CCI rats showed guarding posture in normopressure conditions, and LP increased the cumulative time of this behavior. Baseline BP but not HR was increased following CCI. LP increased BP and HR of the rats only before the CCI surgery. Animals after CCI surgery showed variable (BP, HR) and transient (HR) responses to LP. These results indicate that (1) LP aggravated spontaneous pain and increased BP and HR in the CCI rats, and (2) CCI surgery influenced BP and HR of rats.

  12. Co-administration of trientine and flaxseed oil on oxidative stress, serum lipids and heart structure in diabetic rats.

    PubMed

    Rezaei, Ali; Heidarian, Esfandiar

    2013-08-01

    The administration of flaxseed oil or flaxseed oil plus trientine in diabetic rats reduced triglyceride, very low density lipoprotein, and total cholesterol. Furthermore, the combined treatment significantly increased superoxide dismutase activity and attenuated serum Cu2+. The results suggest that the administration of flaxseed oil plus trientine is useful in controlling serum lipid abnormalities, oxidative stress, restoring heart structure, and reducing serum Cu2+ in diabetic rats.

  13. Morphological and biochemical examination of Cosmos 1887 rat heart tissue. Part 1: Ultrastructure

    NASA Technical Reports Server (NTRS)

    Philpott, D. E.; Popova, I. A.; Kato, K.; Stevenson, J.; Miquel, J.; Sapp, W.

    1990-01-01

    Morphological changes were observed in the left ventricle of rat heart tissue from animals flown on the Cosmos 1887 biosatellite for 12.5 days. These tissues were compared to the synchronous and vivarium control hearts. While many normal myofibrils were observed, others exhibited ultrastructural alterations, i.e., damaged and irregular-shaped mitochondria and generalized myofibrillar edema. Analysis of variance (ANOVA) of the volume density data revealed a statistically significant increase in glycogen and a significant decrease in mitochondria compared to the synchronous and vivarium controls. Point counting indicated an increase in lipid and myeloid bodies and a decrease in microtubules, but these changes were not statistically significant. In addition, the flight animals exhibited some patchy loss of protofibrils (actin and myosin filaments) and some abnormal supercontracted myofibrils that were not seen in the controls. This study was undertaken to gain insight into the mechanistic aspects of cardiac changes in both animals and human beings as a consequence of space travel. Cardiac hypotrophy and fluid shifts have been observed after actual or simulated weightlessness and raise concerns about the functioning of the heart and circulatory system during and after travel in space.

  14. Multiple Mass Isotopomer Tracing of Acetyl-CoA Metabolism in Langendorff-perfused Rat Hearts

    PubMed Central

    Li, Qingling; Deng, Shuang; Ibarra, Rafael A.; Anderson, Vernon E.; Brunengraber, Henri; Zhang, Guo-Fang

    2015-01-01

    We developed an isotopic technique to assess mitochondrial acetyl-CoA turnover (≈citric acid flux) in perfused rat hearts. Hearts are perfused with buffer containing tracer [13C2,2H3]acetate, which forms M5 + M4 + M3 acetyl-CoA. The buffer may also contain one or two labeled substrates, which generate M2 acetyl-CoA (e.g. [13C6]glucose or [1,2-13C2]palmitate) or/and M1 acetyl-CoA (e.g. [1-13C]octanoate). The total acetyl-CoA turnover and the contributions of fuels to acetyl-CoA are calculated from the uptake of the acetate tracer and the mass isotopomer distribution of acetyl-CoA. The method was applied to measurements of acetyl-CoA turnover under different conditions (glucose ± palmitate ± insulin ± dichloroacetate). The data revealed (i) substrate cycling between glycogen and glucose-6-P and between glucose-6-P and triose phosphates, (ii) the release of small excess acetyl groups as acetylcarnitine and ketone bodies, and (iii) the channeling of mitochondrial acetyl-CoA from pyruvate dehydrogenase to carnitine acetyltransferase. Because of this channeling, the labeling of acetylcarnitine and ketone bodies released by the heart are not proxies of the labeling of mitochondrial acetyl-CoA. PMID:25645937

  15. Diosmin pretreatment improves cardiac function and suppresses oxidative stress in rat heart after ischemia/reperfusion.

    PubMed

    Senthamizhselvan, Oomaidurai; Manivannan, Jeganathan; Silambarasan, Thangarasu; Raja, Boobalan

    2014-08-01

    Reperfusion of ischemic tissue leads to the generation of oxygen derived free radicals which plays an important role in cellular damage. Objective of the current study is to evaluate the cardio-protective and antioxidant effect of diosmin on ischemia-reperfusion related cardiac dysfunction, oxidative stress and apoptosis. Diosmin (50 and 100 mg/kg body weight (bw)) was given every day to the rats orally throughout the experimental period. Ischemia/reperfusion protocol was carried out ex vivo using langendorff perfusion method and the cardiac functional recovery was assessed in terms of percentage rate pressure product. Coronary effluents of LDH and CK-MB activities, antioxidant enzyme activities, lipid peroxidation products, activity of TCA cycle enzymes were evaluated. Moreover, in vitro superoxide anion and hydroxyl radical scavenging potential of diosmin was also quantified. Finally, quantitative real-time PCR was used for assessing Bcl-2 mRNA expression in heart. Cardiac functional recovery was impaired after reperfusion compared with continuously perfused heart. It was significantly prevented by diosmin treatment. Impaired antioxidant enzyme activities and elevated lipid peroxidation products level were also significantly suppressed. The activity of TCA cycle enzymes was protected against reperfusion stress. Down regulated Bcl-2 was also significantly increased. This study concluded that diosmin pretreatment prevents all the impaired patterns including cardiac function, oxidative stress and apoptosis associated with reperfusion in control heart by its antioxidant role.

  16. Morphological and biochemical examination of Cosmos 1887 rat heart tissue: Part I--Ultrastructure.

    PubMed

    Philpott, D E; Popova, I A; Kato, K; Stevenson, J; Miquel, J; Sapp, W

    1990-01-01

    Morphological changes were observed in the left ventricle of rat heart tissue from animals flown on the Cosmos 1887 biosatellite for 12.5 days. These tissues were compared to the synchronous and vivarium control hearts. While many normal myofibrils were observed, others exhibited ultrastructural alterations, i.e., damaged and irregular-shaped mitochondria and generalized myofibrillar edema. Analysis of variance (ANOVA) of the volume density data revealed a statistically significant increase in glycogen and a significant decrease in mitochondria compared to the synchronous and vivarium controls. Point counting indicated an increase in lipid and myeloid bodies and a decrease in microtubules, but these changes were not statistically significant. In addition, the flight animals exhibited some patchy loss of protofibrils (actin and myosin filaments) and some abnormal supercontracted myofibrils that were not seen in the controls. This study was undertaken to gain insight into the mechanistic aspects of cardiac changes in both animals and human beings as a consequence of space travel (1). Cardiac hypotrophy and fluid shifts have been observed after actual or simulated weightlessness and raise concerns about the functioning of the heart and circulatory system during and after travel in space (2-4).

  17. In situ Raman study of redox state changes of mitochondrial cytochromes in a perfused rat heart.

    PubMed

    Brazhe, Nadezda A; Treiman, Marek; Faricelli, Barbara; Vestergaard, Jakob H; Sosnovtseva, Olga

    2013-01-01

    We developed a Raman spectroscopy-based approach for simultaneous study of redox changes in c-and b-type cytochromes and for a semiquantitative estimation of the amount of oxygenated myoglobin in a perfused rat heart. Excitation at 532 nm was used to obtain Raman scattering of the myocardial surface of the isolated heart at normal and hypoxic conditions. Raman spectra of the heart under normal pO2 demonstrate unique peaks attributable to reduced c-and b-type cytochromes and oxymyoglobin (oMb). The cytochrome peaks decreased in intensity upon FCCP treatment, as predicted from uncoupling mitochondrial respiration. Conversely, transient hypoxia causes the reversible increase in the intensity of peaks assigned to cytochromes c and c1, reflecting electron stacking proximal to cytochrome oxidase due to the lack of terminal electron acceptor O2. Intensities of peaks assigned to oxy- and deoxyhemoglobin were used for the semiquantitative estimation of oMb deoxygenation that was found to be of approximately 50[Formula: see text] under hypoxia conditions.

  18. Ischemic postconditioning influences electron transport chain protein turnover in Langendorff-perfused rat hearts

    PubMed Central

    Cao, Song; Liu, Yun; Wang, Haiying; Mao, Xiaowen; Chen, Jincong; Liu, Jiming; Xia, Zhengyuan; Zhang, Lin; Liu, Xingkui

    2016-01-01

    Ischemia postconditioning (IPo) is a promising strategy in reducing myocardial ischemia reperfusion (I/R) injury (MIRI), but its specific molecular mechanism is incompletely understood. Langendorff-perfused isolated rat hearts were subjected to global I/R and received IPo in the absence or presence of the mitochondrial ATP-sensitive potassium channel (mitoKATP) blocker 5-hydroxydecanoate (5-HD). Myocardial mitochondria were extracted and mitochondrial comparative proteomics was analyzed. IPo significantly reduces post-ischemic myocardial infarction and improved cardiac function in I/R rat hearts, while 5-HD basically cancelled IPo’s myocardial protective effect. Joint application of two-dimensional polyacrylamide gel electrophoresis (2DE) and MALDI-TOF MS identified eight differentially expressed proteins between groups. Expression of cardiac succinate dehydrogenase (ubiquinone) flavoprotein subunit (SDHA) increased more than two-fold after I/R, while IPo led to overexpression of dihydrolipoyl dehydrogenase (DLD), NADH dehydrogenase (ubiquinone) flavoprotein 1 and isoform CRA_b (NDUFV1). When the mitoKATP was blocked, MICOS complex subunit Mic60 (IMMT) and Stress-70 protein (Grp75) were over expressed, while DLDH, ATPase subunit A (ATPA) and rCG44606 were decreased. Seven of the differential proteins belong to electron transport chain (ETC) or metabolism regulating proteins, and five of them were induced by closing mitoKATP in I/R hearts. We thus conclude that IPo’s myocardial protective effect relies on energy homeostasis regulation. DLD, SDHA, NDUFV1, Grp75, ATPA and rCG44606 may contribute to IPo’s cardial protective effect. PMID:26925330

  19. Influence of starvation on heart contractility and corticosterone level in rats.

    PubMed

    Lee, Sung Ryul; Ko, Tae Hee; Kim, Hyoung Kyu; Marquez, Jubert; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

    2015-11-01

    The physiological changes, including cardiac modification, that occur during starvation are not yet completely understood. The purpose of this study is to examine the effects of a 2-week starvation period on heart contractility, muscle mass, and irisin and corticosterone levels in rats. Rats in the starved group showed a significant reduction in the body, heart, kidney, and muscle weight (n = 23, p < 0.05). Blood glucose, total protein, and albumin showed a 44, 17.5, and 10.3 % reduction, respectively (p < 0.05). Lipid reserves, such as total lipid, triglyceride, and free fatty acid, were also comparably reduced (p < 0.05). However, the bilirubin, creatinine, blood urea nitrogen, and creatine kinase levels were higher than in the control group (p < 0.05). The blood irisin level was unchanged, but the stress-related corticosterone level was significantly higher in the starved group. The differences observed in M-mode echocardiography were further compared with the body-weight-matched control group. Starvation reduced the left ventricle mass; however, this difference was not significant compared with the body-weight-matched group (p > 0.05). In the starvation group, the impairment of cardiac output was dependent on the reduction in stroke volume and heart rate. Starvation induced a severe reduction in ejection fraction and fractional shortening when compared with the body-weight-matched control group (p < 0.05). In summary, prolonged starvation, which leads to a deficiency of available nutrition, increases the stress-related corticosterone level, impairs the cardiac output, and is associated with changes in cardiac morphogeometry.

  20. Influence of starvation on heart contractility and corticosterone level in rats.

    PubMed

    Lee, Sung Ryul; Ko, Tae Hee; Kim, Hyoung Kyu; Marquez, Jubert; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

    2015-11-01

    The physiological changes, including cardiac modification, that occur during starvation are not yet completely understood. The purpose of this study is to examine the effects of a 2-week starvation period on heart contractility, muscle mass, and irisin and corticosterone levels in rats. Rats in the starved group showed a significant reduction in the body, heart, kidney, and muscle weight (n = 23, p < 0.05). Blood glucose, total protein, and albumin showed a 44, 17.5, and 10.3 % reduction, respectively (p < 0.05). Lipid reserves, such as total lipid, triglyceride, and free fatty acid, were also comparably reduced (p < 0.05). However, the bilirubin, creatinine, blood urea nitrogen, and creatine kinase levels were higher than in the control group (p < 0.05). The blood irisin level was unchanged, but the stress-related corticosterone level was significantly higher in the starved group. The differences observed in M-mode echocardiography were further compared with the body-weight-matched control group. Starvation reduced the left ventricle mass; however, this difference was not significant compared with the body-weight-matched group (p > 0.05). In the starvation group, the impairment of cardiac output was dependent on the reduction in stroke volume and heart rate. Starvation induced a severe reduction in ejection fraction and fractional shortening when compared with the body-weight-matched control group (p < 0.05). In summary, prolonged starvation, which leads to a deficiency of available nutrition, increases the stress-related corticosterone level, impairs the cardiac output, and is associated with changes in cardiac morphogeometry. PMID:25784619

  1. Effect of ozone on body temperature and heart rate in the unanesthetized, unrestrained rats

    SciTech Connect

    Watkinson, W.P.; Aileru, A.A.; Dowd, S.M.; Tepper, J.T.; Gordon, C.J. )

    1990-02-26

    Previous studies from this laboratory have demonstrated the importance of changes in body core temperature (T{sub co}) as both an index and modulator of toxicity. This study examined the effects of ambient temperature (T{sub a}) on the toxicant-induced changes in T{sub co}, heart rate (HR), and other toxicological endpoints following exposure to 1 ppm ozone (O{sub 3}). Two groups of male Fischer 334 rats (n = 6/group) were implanted with radiotelemetry transmitters and allowed to recover overnight. The transmitters permitted monitoring of T{sub co} and electrocardiogram (ECG); HR was derived from the ECG signal. All animals were continually monitored according to the following protocol: control (filtered air; .25 hours); exposure (1 ppm O{sub 3}; 2 hours); recovery (filtered air; 18 hours). The first group of rats, maintained at an T{sub a} of 18-20 C, exhibited a 4-5 C drop in T{sub co} accompanied by an average 250 bpm decrease in HR. The decrease and subsequent recovery of HR appeared to precede the T{sub co} response. The second group of rats was subjected to the same experimental protocol but maintained at an T{sub a} of 30-32 C. These rats also showed decreases in T{sub co} and HR; however, these decreases only averaged {approximately}1 C and 100 bpm, respectively. These experiments demonstrate the profound impact of T{sub a} on T{sub co} and the subsequent toxic response in the conscious rat and may have important implications for the study of toxicology.

  2. Change in heart rate variability after the adult attachment interview in dissociative patients.

    PubMed

    Farina, Benedetto; Speranza, Anna Maria; Imperatori, Claudio; Quintiliani, Maria Isabella; Della Marca, Giacomo

    2015-01-01

    The aim of this study was to assess heart rate variability (HRV) in individuals with dissociative disorders (DD) before and after the Adult Attachment Interview (AAI). Electrocardiograms were recorded before, during, and after the AAI in 13 individuals with DD and 13 healthy participants matched for age and gender. Significant change in HRV was observed only in the DD group. After the AAI, those with DD showed significant increases in the low frequency/high frequency ratio (pre-AAI = 1.91 ± 1.19; post-AAI = 4.03 ± 2.40; Wilcoxon test = -2.76, p = .005). Our results suggest that the retrieval of childhood attachment experiences in individuals with DD is associated with a change in HRV patterns that could reflect the emotion dysregulation of dissociative psychopathological processes.

  3. Endothelial alkaline phosphatase activity loss as an early stage in the development of radiation-induced heart disease in rats

    SciTech Connect

    Lauk, S.

    1987-04-01

    Alkaline phosphatase activity of capillary endothelial cells in the heart of Wistar and Sprague-Dawley rats was studied sequentially after single doses of 10, 15, 20, or 25 Gy. Following irradiation capillary density and alkaline phosphatase activity were focally lost before myocardial degeneration or clinical symptoms of heart disease developed. Recovery from both changes took place after doses of 10 or 15 Gy. The decrease in capillary density and enzyme activity showed the same strain difference in latency times and in the extent of the lesions as previously described for pathological and clinical signs of heart disease.

  4. Contribution of Major Lifestyle Risk Factors for Incident Heart Failure in Older Adults

    PubMed Central

    Del Gobbo, Liana C.; Kalantarian, Shadi; Imamura, Fumiaki; Lemaitre, Rozenn; Siscovick, David S.; Psaty, Bruce M.; Mozaffarian, Dariush

    2015-01-01

    Objectives The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults. Background HF incurs high morbidity, mortality, and health care costs among adults ≥65 years of age, which is the most rapidly growing segment of the U.S. population. Methods We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity. Results No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26% and 22% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.63 to 0.86; leisure activity ≥845 kcal/week vs. <845 kcal/week; HR: 0.78; 95% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m2, and not smoking were also independently associated with a lower risk of HF. Participants with ≥4 healthy lifestyle factors had a 45% (HR: 0.55; 95% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed. Conclusions Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF. PMID:26160366

  5. Exercise Performance in Children and Young Adults After Complete and Incomplete Repair of Congenital Heart Disease.

    PubMed

    Rosenblum, Omer; Katz, Uriel; Reuveny, Ronen; Williams, Craig A; Dubnov-Raz, Gal

    2015-12-01

    Few previous studies have addressed exercise capacity in patients with corrected congenital heart disease (CHD) and significant anatomical residua. The aim of this study was to determine the aerobic fitness and peak cardiac function of patients with corrected CHD with complete or incomplete repairs, as determined by resting echocardiography. Children, adolescents and young adults (<40 years) with CHD from both sexes, who had previously undergone biventricular corrective therapeutic interventions (n = 73), and non-CHD control participants (n = 76) underwent cardiopulmonary exercise testing. The CHD group was further divided according to the absence/presence of significant anatomical residua on a resting echocardiogram ("complete"/"incomplete" repair groups). Aerobic fitness and cardiac function were compared between groups using linear regression and analysis of covariance. Peak oxygen consumption, O2 pulse and ventilatory threshold were significantly lower in CHD patients compared with controls (all p < 0.01). Compared with the complete repair group, the incomplete repair group had a significantly lower mean peak work rate, age-adjusted O2 pulse (expressed as % predicted) and a higher VE/VCO2 ratio (all p ≤ 0.05). Peak oxygen consumption was comparable between the subgroups. Patients after corrected CHD have lower peak and submaximal exercise parameters. Patients with incomplete repair of their heart defect had decreased aerobic fitness, with evidence of impaired peak cardiac function and lower pulmonary perfusion. Patients that had undergone a complete repair had decreased aerobic fitness attributed only to deconditioning. These newly identified differences explain why in previous studies, the lowest fitness was seen in patients with the most hemodynamically significant heart malformations.

  6. Knowledge Management in Cardiac Surgery: The Second Tehran Heart Center Adult Cardiac Surgery Database Report

    PubMed Central

    Abbasi, Kyomars; Karimi, Abbasali; Abbasi, Seyed Hesameddin; Ahmadi, Seyed Hossein; Davoodi, Saeed; Babamahmoodi, Abdolreza; Movahedi, Namdar; Salehiomran, Abbas; Shirzad, Mahmood; Bina, Peyvand

    2012-01-01

    Background: The Adult Cardiac Surgery Databank (ACSD) of Tehran Heart Center was established in 2002 with a view to providing clinical prediction rules for outcomes of cardiac procedures, developing risk score systems, and devising clinical guidelines. This is a general analysis of the collected data. Methods: All the patients referred to Tehran Heart Center for any kind of heart surgery between 2002 and 2008 were included, and their demographic, medical, clinical, operative, and postoperative data were gathered. This report presents general information as well as in-hospital mortality rates regarding all the cardiac procedures performed in the above time period. Results: There were 24959 procedures performed: 19663 (78.8%) isolated coronary artery bypass grafting surgeries (CABGs); 1492 (6.0%) isolated valve surgeries; 1437 (5.8%) CABGs concomitant with other procedures; 832 (3.3%) CABGs combined with valve surgeries; 722 (2.9%) valve surgeries concomitant with other procedures; 545 (2.2%) surgeries other than CABG or valve surgery; and 267 (1.1%) CABGs concomitant with valve and other types of surgery. The overall mortality was 205 (1.04%), with the lowest mortality rate (0.47%) in the isolated CABGs and the highest (4.49%) in the CABGs concomitant with valve surgeries and other types of surgery. Meanwhile, the overall mortality rate was higher in the female patients than in the males (1.90% vs. 0.74%, respectively). Conclusion: Isolated CABG was the most prevalent procedure at our center with the lowest mortality rate. However, the overall mortality was more prevalent in our female patients. This database can serve as a platform for the participation of the other countries in the region in the creation of a regional ACSD. PMID:23304179

  7. Prevalence and Correlates of Post-traumatic Stress Disorder in Adults With Congenital Heart Disease.

    PubMed

    Deng, Lisa X; Khan, Abigail May; Drajpuch, David; Fuller, Stephanie; Ludmir, Jonathan; Mascio, Christopher E; Partington, Sara L; Qadeer, Ayesha; Tobin, Lynda; Kovacs, Adrienne H; Kim, Yuli Y

    2016-03-01

    Post-traumatic stress disorder (PTSD) is associated with adverse outcomes and increased mortality in cardiac patients. No studies have examined PTSD in the adult congenital heart disease (ACHD) population. The objectives of this study were to assess the prevalence of self-reported symptoms of PTSD in patients with ACHD and explore potential associated factors. Patients were enrolled from an outpatient ACHD clinic and completed several validated measures including the Impact of Event Scale-Revised, PTSD Checklist-Civilian Version, and the Hospital Anxiety and Depression Scale. Clinical data were abstracted through medical data review. A total of 134 participants (mean age 34.6 ± 10.6; 46% men) were enrolled. Of the 127 participants who completed the Impact of Event Scale-Revised, 14 (11%) met criteria for elevated PTSD symptoms specifically related to their congenital heart disease or treatment. Of the 134 patients who completed PTSD Checklist-Civilian Version, 27 (21%) met criteria for global PTSD symptoms. In univariate analyses, patients with congenital heart disease-specific PTSD had their most recent cardiac surgery at an earlier year (p = 0.008), were less likely to have attended college (p = 0.04), had higher rates of stroke or transient ischemic attack (p = 0.03), and reported greater depressive symptoms on the Hospital Anxiety and Depression Scale (7 vs 2, p <0.001). In multivariable analysis, the 2 factors most strongly associated with PTSD were depressive symptoms (p <0.001) and year of most recent cardiac surgery (p <0.03). In conclusion, PTSD is present in 11% to 21% of subjects seen at a tertiary referral center for ACHD. The high prevalence of PTSD in this complex group of patients has important implications for the medical and psychosocial management of this growing population.

  8. Enhanced sympathetic nerve activity induced by neonatal colon inflammation induces gastric hypersensitivity and anxiety-like behavior in adult rats.

    PubMed

    Winston, John H; Sarna, Sushil K

    2016-07-01

    Gastric hypersensitivity (GHS) and anxiety are prevalent in functional dyspepsia patients; their underlying mechanisms remain unknown largely because of lack of availability of live visceral tissues from human subjects. Recently, we demonstrated in a preclinical model that rats subjected to neonatal colon inflammation show increased basal plasma norepinephrine (NE), which contributes to GHS through the upregulation of nerve growth factor (NGF) expression in the gastric fundus. We tested the hypothesis that neonatal colon inflammation increases anxiety-like behavior and sympathetic nervous system activity, which upregulates the expression of NGF to induce GHS in adult life. Chemical sympathectomy, but not adrenalectomy, suppressed the elevated NGF expression in the fundus muscularis externa and GHS. The measurement of heart rate variability showed a significant increase in the low frequency-to-high frequency ratio in GHS vs. the control rats. Stimulus-evoked release of NE from the fundus muscularis externa strips was significantly greater in GHS than in the control rats. Tyrosine hydroxylase expression was increased in the celiac ganglia of the GHS vs. the control rats. We found an increase in trait but not stress-induced anxiety-like behavior in GHS rats in an elevated plus maze. We concluded that neonatal programming triggered by colon inflammation upregulates tyrosine hydroxylase in the celiac ganglia, which upregulates the release of NE in the gastric fundus muscularis externa. The increase of NE release from the sympathetic nerve terminals concentration dependently upregulates NGF, which proportionately increases the visceromotor response to gastric distention. Neonatal programming concurrently increases anxiety-like behavior in GHS rats. PMID:27151940

  9. Cardioprotection Resulting from Glucagon-Like Peptide-1 Administration Involves Shifting Metabolic Substrate Utilization to Increase Energy Efficiency in the Rat Heart

    PubMed Central

    Aravindhan, Karpagam; Bao, Weike; Harpel, Mark R.; Willette, Robert N.; Lepore, John J.; Jucker, Beat M.

    2015-01-01

    Previous studies have shown that glucagon-like peptide-1 (GLP-1) provides cardiovascular benefits independent of its role on peripheral glycemic control. However, the precise mechanism(s) by which GLP-1 treatment renders cardioprotection during myocardial ischemia remain unresolved. Here we examined the role for GLP-1 treatment on glucose and fatty acid metabolism in normal and ischemic rat hearts following a 30 min ischemia and 24 h reperfusion injury, and in isolated cardiomyocytes (CM). Relative carbohydrate and fat oxidation levels were measured in both normal and ischemic hearts using a 1-13C glucose clamp coupled with NMR-based isotopomer analysis, as well as in adult rat CMs by monitoring pH and O2 consumption in the presence of glucose or palmitate. In normal heart, GLP-1 increased glucose uptake (↑64%, p<0.05) without affecting glycogen levels. In ischemic hearts, GLP-1 induced metabolic substrate switching by increasing the ratio of carbohydrate versus fat oxidation (↑14%, p<0.01) in the LV area not at risk, without affecting cAMP levels. Interestingly, no substrate switching occurred in the LV area at risk, despite an increase in cAMP (↑106%, p<0.05) and lactate (↑121%, p<0.01) levels. Furthermore, in isolated CMs GLP-1 treatment increased glucose utilization (↑14%, p<0.05) and decreased fatty acid oxidation (↓15%, p<0.05) consistent with in vivo finding. Our results show that this benefit may derive from distinct and complementary roles of GLP-1 treatment on metabolism in myocardial sub-regions in response to this injury. In particular, a switch to anaerobic glycolysis in the ischemic area provides a compensatory substrate switch to overcome the energetic deficit in this region in the face of reduced tissue oxygenation, whereas a switch to more energetically favorable carbohydrate oxidation in more highly oxygenated remote regions supports maintaining cardiac contractility in a complementary manner. PMID:26098939

  10. Cardioprotection Resulting from Glucagon-Like Peptide-1 Administration Involves Shifting Metabolic Substrate Utilization to Increase Energy Efficiency in the Rat Heart.

    PubMed

    Aravindhan, Karpagam; Bao, Weike; Harpel, Mark R; Willette, Robert N; Lepore, John J; Jucker, Beat M

    2015-01-01

    Previous studies have shown that glucagon-like peptide-1 (GLP-1) provides cardiovascular benefits independent of its role on peripheral glycemic control. However, the precise mechanism(s) by which GLP-1 treatment renders cardioprotection during myocardial ischemia remain unresolved. Here we examined the role for GLP-1 treatment on glucose and fatty acid metabolism in normal and ischemic rat hearts following a 30 min ischemia and 24 h reperfusion injury, and in isolated cardiomyocytes (CM). Relative carbohydrate and fat oxidation levels were measured in both normal and ischemic hearts using a 1-13C glucose clamp coupled with NMR-based isotopomer analysis, as well as in adult rat CMs by monitoring pH and O2 consumption in the presence of glucose or palmitate. In normal heart, GLP-1 increased glucose uptake (↑64%, p<0.05) without affecting glycogen levels. In ischemic hearts, GLP-1 induced metabolic substrate switching by increasing the ratio of carbohydrate versus fat oxidation (↑14%, p<0.01) in the LV area not at risk, without affecting cAMP levels. Interestingly, no substrate switching occurred in the LV area at risk, despite an increase in cAMP (↑106%, p<0.05) and lactate (↑121%, p<0.01) levels. Furthermore, in isolated CMs GLP-1 treatment increased glucose utilization (↑14%, p<0.05) and decreased fatty acid oxidation (↓15%, p<0.05) consistent with in vivo finding. Our results show that this benefit may derive from distinct and complementary roles of GLP-1 treatment on metabolism in myocardial sub-regions in response to this injury. In particular, a switch to anaerobic glycolysis in the ischemic area provides a compensatory substrate switch to overcome the energetic deficit in this region in the face of reduced tissue oxygenation, whereas a switch to more energetically favorable carbohydrate oxidation in more highly oxygenated remote regions supports maintaining cardiac contractility in a complementary manner.

  11. Successful cord blood transplantation in an adult acute lymphoblastic leukemia patient with congenital heart disease.

    PubMed

    Kowata, Shugo; Fujishima, Yukiteru; Suzuki, Yuzo; Tsukushi, Yasuhiko; Oyake, Tatsuo; Togawa, Ryou; Oyama, Kotaro; Ikai, Akio; Ito, Shigeki; Ishida, Yoji

    2016-08-01

    Recent advances in surgical corrections and supportive care for congenital heart disease have resulted in increasing numbers of adult survivors who may develop hematological malignancies. Treatments including chemotherapy for such patients may cause serious hemodynamic or cardiac complications, especially in those receiving stem cell transplantation. We present a 29-year-old woman with acute lymphoblastic leukemia and congenital heart disease. She had been diagnosed with pulmonary atresia with an intact ventricular septum at birth, and the anomaly was surgically corrected according to the Fontan technique at age 9 years. Her induction chemotherapy required modifications due to poor cardiac status with Fontan circulation. However, after surgical procedures including total cavopulmonary connection and aortic valve replacement at first complete remission, her cardiac status was significantly improved. Subsequently, she underwent cord blood stem cell transplantation at the third complete remission. She required intensive supportive care for circulatory failure as a pre-engraftment immune reaction and stage III acute graft versus host disease of the gut, but recovered from these complications. She was discharged on day 239, and remained in complete remission at 1-year post-transplantation. PMID:27599417

  12. Place of birth and adult cardiovascular disease: the British Regional Heart Study.

    PubMed

    Shaper, A G; Elford, J

    1991-01-01

    Coronary heart disease (CHD) is almost certainly a nutritional disorder related to the quality and quantity of dietary fats and mediated by blood and tissue lipid concentrations. There is current controversy as to when the underlying process of atherosclerosis is initiated and whether the critical susceptibility to CHD may be established in utero or infancy. Blood pressure and hypertension may also be nutritionally based, and the age at which the rate of rise in blood pressure with age is determined is also controversial. The British Regional Heart Study (BRHS) involves 7,735 middle-aged men from 24 towns in England, Wales and Scotland and reveals that average blood cholesterol levels in these towns show no relationship to CHD mortality but all are high by international standards. Blood pressure levels vary markedly between the 24 towns and relate strongly to CHD mortality patterns, which are highest in Scotland and lowest in the South of England. The hypothesis relating adult blood pressures and CHD mortality to foetal and infant life circumstances has been examined using the data on birthplace and place of examination of the BRHS men. Regardless of where they were born, men living and examined in the South had lower mean blood pressures than men living in Scotland. The highest mean blood pressures were observed in Scotland, irrespective of where the men had been born. For CHD, regardless of their place of birth, men living in the South had a lower risk of CHD than men living elsewhere. The geographic zone of examination appeared to be more important than the zone of birth in determining the risk of CHD and the level of blood pressure. While patterns of nutrition during pregnancy, in infancy and childhood may be of importance for some outcomes, such as height, it seems that exposure to risk factors during adult life predominantly determine the outcome in cardiovascular disease.

  13. Optimal Cutoff Points of Anthropometric Parameters to Identify High Coronary Heart Disease Risk in Korean Adults

    PubMed Central

    2016-01-01

    Several published studies have reported the need to change the cutoff points of anthropometric indices for obesity. We therefore conducted a cross-sectional study to estimate anthropometric cutoff points predicting high coronary heart disease (CHD) risk in Korean adults. We analyzed the Korean National Health and Nutrition Examination Survey data from 2007 to 2010. A total of 21,399 subjects aged 20 to 79 yr were included in this study (9,204 men and 12,195 women). We calculated the 10-yr Framingham coronary heart disease risk score for all individuals. We then estimated receiver-operating characteristic (ROC) curves for body mass index (BMI), waist circumference, and waist-to-height ratio to predict a 10-yr CHD risk of 20% or more. For sensitivity analysis, we conducted the same analysis for a 10-yr CHD risk of 10% or more. For a CHD risk of 20% or more, the area under the curve of waist-to-height ratio was the highest, followed by waist circumference and BMI. The optimal cutoff points in men and women were 22.7 kg/m2 and 23.3 kg/m2 for BMI, 83.2 cm and 79.7 cm for waist circumference, and 0.50 and 0.52 for waist-to-height ratio, respectively. In sensitivity analysis, the results were the same as those reported above except for BMI in women. Our results support the re-classification of anthropometric indices and suggest the clinical use of waist-to-height ratio as a marker for obesity in Korean adults. PMID:26770039

  14. Optimal Cutoff Points of Anthropometric Parameters to Identify High Coronary Heart Disease Risk in Korean Adults.

    PubMed

    Kim, Sang Hyuck; Choi, Hyunrim; Won, Chang Won; Kim, Byung-Sung

    2016-01-01

    Several published studies have reported the need to change the cutoff points of anthropometric indices for obesity. We therefore conducted a cross-sectional study to estimate anthropometric cutoff points predicting high coronary heart disease (CHD) risk in Korean adults. We analyzed the Korean National Health and Nutrition Examination Survey data from 2007 to 2010. A total of 21,399 subjects aged 20 to 79 yr were included in this study (9,204 men and 12,195 women). We calculated the 10-yr Framingham coronary heart disease risk score for all individuals. We then estimated receiver-operating characteristic (ROC) curves for body mass index (BMI), waist circumference, and waist-to-height ratio to predict a 10-yr CHD risk of 20% or more. For sensitivity analysis, we conducted the same analysis for a 10-yr CHD risk of 10% or more. For a CHD risk of 20% or more, the area under the curve of waist-to-height ratio was the highest, followed by waist circumference and BMI. The optimal cutoff points in men and women were 22.7 kg/m(2) and 23.3 kg/m(2) for BMI, 83.2 cm and 79.7 cm for waist circumference, and 0.50 and 0.52 for waist-to-height ratio, respectively. In sensitivity analysis, the results were the same as those reported above except for BMI in women. Our results support the re-classification of anthropometric indices and suggest the clinical use of waist-to-height ratio as a marker for obesity in Korean adults.

  15. Blood risk factor metabolites associated with heart disease and myocardial fatty acids in copper-deficient male and female rats

    SciTech Connect

    Fields, M.; Lewis, C.; Beal, T. ); Berlin, E.; Kliman, P.G.; Peters, R.C. )

    1989-07-01

    Intact and castrated males and intact and ovariectomized female rats were fed a copper-deficient diet in order to establish whether the protection provided in females against cardiovascular pathology and mortality is due to endogenous sex hormones, and different levels of blood lipids and/or myocardial fatty acids. Seventy-three male and female rats were assigned to a copper-deficient diet (0.6 {mu}g of copper/g diet) containing 62% fructose for 8 weeks. Twelve of the male rats underwent castration and 12 of the females were ovariectomized. All animals exhibited high levels of plasma cholesterol, triglycerides, and uric acid, which were neither affected by the sex of the rat nor by the surgical treatment. The composition of fatty acids of the myocardium was similar in males and females. Except for those animals that were sacrificed by us, all other male rats died of heart pathology. In contrast, none of the female rats exhibited heart pathology and none died of the deficiency. It is suggested that heart pathology and mortality in copper deficiency are sex related and not due to high levels of plasma cholesterol, triglycerides, and uric acid or to differences in myocardial fatty acid composition.

  16. Voluntary and involuntary running in the rat show different patterns of theta rhythm, physical activity, and heart rate.

    PubMed

    Li, Jia-Yi; Kuo, Terry B J; Yen, Jiin-Cherng; Tsai, Shih-Chih; Yang, Cheryl C H

    2014-05-01

    Involuntarily exercising rats undergo more physical and mental stress than voluntarily exercising rats; however, these findings still lack electrophysiological evidence. Many studies have reported that theta rhythm appears when there is mental stress and that it is affected by emotional status. Thus we hypothesized that the differences between voluntary and involuntary movement should also exist in the hippocampal theta rhythm. Using the wheel and treadmill exercise models as voluntary and involuntary exercise models, respectively, this study wirelessly recorded the hippocampal electroencephalogram, electrocardiogram, and three-dimensional accelerations of young male rats. Treadmill and wheel exercise produced different theta patterns in the rats before and during running. Even though the waking baselines for the two exercise types were recorded in different environments, there did not exist any significant difference after distinguishing the rats' sleep/wake status. When the same movement-related parameters are considered, the treadmill running group showed more changes in their theta frequency (4-12 Hz), in their theta power between 9.5-12 Hz, and in their heart rate than the wheel running group. A positive correlation between the changes in high-frequency (9.5-12 Hz) theta power and heart rate was identified. Our results reveal various voluntary and involuntary changes in hippocampal theta rhythm as well as divergences in heart rate and high-frequency theta activity that may represent the effects of an additional emotional state or the sensory interaction during involuntary running by rats. PMID:24623507

  17. Vitamin E and Hippophea rhamnoides L. extract reduce nicotine-induced oxidative stress in rat heart.

    PubMed

    Gumustekin, Kenan; Taysi, Seyithan; Alp, Hamit Hakan; Aktas, Omer; Oztasan, Nuray; Akcay, Fatih; Suleyman, Halis; Akar, Sedat; Dane, Senol; Gul, Mustafa

    2010-06-01

    The effects of vitamin E and Hippophea rhamnoides L. extract (HRe-1) on nicotine-induced oxidative stress in rat heart were investigated. There were eight rats per group and supplementation period was 3 weeks. The groups were: nicotine [0.5 mg kg(-1)day(-1), intraperitoneal (i.p.)]; nicotine plus vitamin E [75 mg kg(-1)day(-1), intragastric (i.g.)]; nicotine plus HRe-1 (250 mg kg(-1)day(-1), i.g.); and the control group (receiving only vehicles). Nicotine increased the malondialdehyde level, which was prevented by both vitamin E and HRe-1. Glutathione peroxidase (GPx) activity in nicotine plus vitamin E supplemented group was higher than the others. Glutathione S-transferase (GST) activity in nicotine plus HRe-1 supplemented group was increased compared with the control group. Catalase activity was higher in nicotine group compared with others. GPx activity in nicotine plus vitamin E supplemented group was elevated compared with the others. Total and non-enzymatic superoxide scavenger activities in nicotine plus vitamin E supplemented group were lower than nicotine plus HRe-1 supplemented group. Superoxide dismutase (SOD) activity was higher in nicotine plus HRe-1 supplemented group compared with others. Glutathione reductase activity and nitric oxide level were not affected. Increased SOD and GST activities might have taken part in the prevention of nicotine-induced oxidative stress in HRe-1 supplemented group in rat heart. Flavonols such as quercetin, and isorahmnetin, tocopherols such as alpha-tocopherol and beta-tocopherol and carotenoids such as alpha-carotene and beta-carotene, reported to be present in H. rhamnoides L. extracts may be responsible for the antioxidant effects of this plant extract. PMID:20517898

  18. Implementation of the American College of Cardiology/American Heart Association 2008 Guidelines for the Management of Adults With Congenital Heart Disease.

    PubMed

    Goossens, Eva; Fernandes, Susan M; Landzberg, Michael J; Moons, Philip

    2015-08-01

    Although different guidelines on adult congenital heart disease (ACHD) care advocate for lifetime cardiac follow-up, a critical appraisal of the guideline implementation is lacking. We investigated the implementation of the American College of Cardiology/American Heart Association 2008 guidelines for ACHD follow-up by investigating the type of health care professional, care setting, and frequency of outpatient visits in young adults with CHD. Furthermore, correlates for care in line with the recommendations or untraceability were investigated. A cross-sectional observational study was conducted, including 306 patients with CHD who had a documented outpatient visit at pediatric cardiology before age 18 years. In all, 210 patients (68.6%) were in cardiac follow-up; 20 (6.5%) withdrew from follow-up and 76 (24.9%) were untraceable. Overall, 198 patients were followed up in tertiary care, 1/4 (n = 52) of which were seen at a formalized ACHD care program and 3/4 (n = 146) remained at pediatric cardiology. Of those followed in formalized ACHD and pediatric cardiology care, the recommended frequency was implemented in 94.2% and 89%, respectively (p = 0.412). No predictors for the implementation of the guidelines were identified. Risk factors for becoming untraceable were none or lower number of heart surgeries, health insurance issues, and nonwhite ethnicity. In conclusion, a significant number of adults continue to be cared for by pediatric cardiologists, indicating that transfer to adult-oriented care was not standard practice. Frequency of follow-up for most patients was in line with the ACC/AHA 2008 guidelines. A considerable proportion of young adults were untraceable in the system, which makes them vulnerable for discontinuation of care.

  19. Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

    PubMed

    Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

    2015-09-01

    Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease

  20. Paleolithic nutrition improves plasma lipid concentrations of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations.

    PubMed

    Pastore, Robert L; Brooks, Judith T; Carbone, John W

    2015-06-01

    Recent research suggests that traditional grain-based heart-healthy diet recommendations, which replace dietary saturated fat with carbohydrate and reduce total fat intake, may result in unfavorable plasma lipid ratios, with reduced high-density lipoprotein (HDL) and an elevation of low-density lipoprotein (LDL) and triacylglycerols (TG). The current study tested the hypothesis that a grain-free Paleolithic diet would induce weight loss and improve plasma total cholesterol, HDL, LDL, and TG concentrations in nondiabetic adults with hyperlipidemia to a greater extent than a grain-based heart-healthy diet, based on the recommendations of the American Heart Association. Twenty volunteers (10 male and 10 female) aged 40 to 62 years were selected based on diagnosis of hypercholesterolemia. Volunteers were not taking any cholesterol-lowering medications and adhered to a traditional heart-healthy diet for 4 months, followed by a Paleolithic diet for 4 months. Regression analysis was used to determine whether change in body weight contributed to observed changes in plasma lipid concentrations. Differences in dietary intakes and plasma lipid measures were assessed using repeated-measures analysis of variance. Four months of Paleolithic nutrition significantly lowered (P < .001) mean total cholesterol, LDL, and TG and increased (P < .001) HDL, independent of changes in body weight, relative to both baseline and the traditional heart-healthy diet. Paleolithic nutrition offers promising potential for nutritional management of hyperlipidemia in adults whose lipid profiles have not improved after following more traditional heart-healthy dietary recommendations. PMID:26003334

  1. Blue 405 nm laser light mediates heart rate – investigations at the acupoint Neiguan (Pe.6) in Chinese adults

    PubMed Central

    Litscher, Gerhard; Xie, Zheng; Wang, Lu; Gaischek, Ingrid

    2009-01-01

    Background: In previous studies, we showed that laser needle acupuncture with red and infrared light has specific effects on bio-signals of the brain and heart. Aims: In this publication we report the effect of blue laser light on heart rate and heart rate variability (HRV) before, during and after acupuncture at the acupoint Neiguan (Pe.6) in Chinese adults. These are the first data published concerning heart rate and HRV, obtained with blue laser acupuncture equipment. Patients and Methods: The investigations were carried out in 13 healthy Chinese volunteers with a mean age of 31.2 ± 7.5 years within a randomized, controlled study. Stimulation was performed with painless blue laser light (wavelength: 405 nm; activation: 10 minutes) bilaterally at Pe.6. In a second session, for control reasons the laser was not activated. Results: Heart rate showed a significant (p=0.008) decrease during blue laser light stimulation. In contrast, no significant changes were found when the laser was deactivated. The evaluation parameter LF/HF ratio (low frequency/high frequency ratio) from the HRV spectral analysis showed a very slight increase during stimulation, however it was not significant. Conclusions: Our main conclusion is that continuous blue laser light stimulation on Neiguan significantly reduces heart rate of Chinese adults. PMID:22666700

  2. Nocturnal food-related hyperdipsia in the adult spontaneously hypertensive rat.

    PubMed

    Kraly, F S; Moore, A F; Miller, L A; Drexler, A

    1982-05-01

    Male adult spontaneously hypertensive rats (SHR) ate the same but drank more and had a higher water to food ratio (W:F) than did Wistar-Kyoto (WKY) rats in 24-hr when they had continuous access to standard laboratory pellets and tap water. When rats ate in the day phase of a 12:12 light/dark cycle after 24-hr food deprivation, SHR rats ate and drank the same ad did WKY rats in a 60-min test. When the same rats ate at night after 24-hr food deprivation, however, SHR rats were hyperdipsic: They ate the same as did WKY rats, but SHR rats drank more and had a higher W:F. This relative hyperdipsia reflected the increased ability of ingestion of food to stimulate drinking in SHR, because when food was absent for a 60-min test at night SHR drank the same as did WKY rats. Three dipsogens which are candidate components for eating-elicited drinking in the rat, cellular dehydration, histamine and angiotensin II, elicited drinking differentially in SHR and WKY rats: SHR drank more than did WKY rats in response to (1) cellular dehydration produced by IP hypertonic saline, (2) large doses of SC histamine, and (3) SC angiotensin II. These results demonstrate that SHR exhibit a nocturnal food-related hyperdipsia which may reflect differential sensitivity to stimuli important for eating-elicited drinking such as increased osmolality and endogenous histamine or angiotensin.

  3. Adenosine monophosphate-activated protein kinase activation, substrate transporter translocation, and metabolism in the contracting hyperthyroid rat heart.

    PubMed

    Heather, Lisa C; Cole, Mark A; Atherton, Helen J; Coumans, Will A; Evans, Rhys D; Tyler, Damian J; Glatz, Jan F C; Luiken, Joost J F P; Clarke, Kieran

    2010-01-01

    Thyroid hormones can modify cardiac metabolism via multiple molecular mechanisms, yet their integrated effect on overall substrate metabolism is poorly understood. Here we determined the effect of hyperthyroidism on substrate metabolism in the isolated, perfused, contracting rat heart. Male Wistar rats were injected for 7 d with T(3) (0.2 mg/kg x d ip). Plasma free fatty acids increased by 97%, heart weights increased by 33%, and cardiac rate pressure product, an indicator of contractile function, increased by 33% in hyperthyroid rats. Insulin-stimulated glycolytic rates and lactate efflux rates were increased by 33% in hyperthyroid rat hearts, mediated by an increased insulin-stimulated translocation of the glucose transporter GLUT4 to the sarcolemma. This was accompanied by a 70% increase in phosphorylated AMP-activated protein kinase (AMPK) and a 100% increase in phosphorylated acetyl CoA carboxylase, confirming downstream signaling from AMPK. Fatty acid oxidation rates increased in direct proportion to the increased heart weight and rate pressure product in the hyperthyroid heart, mediated by synchronized changes in mitochondrial enzymes and respiration. Protein levels of the fatty acid transporter, fatty acid translocase (FAT/CD36), were reduced by 24% but were accompanied by a 19% increase in the sarcolemmal content of fatty acid transport protein 1 (FATP1). Thus, the relationship between fatty acid metabolism, cardiac mass, and contractile function was maintained in the hyperthyroid heart, associated with a sarcolemmal reorganization of fatty acid transporters. The combined effects of T(3)-induced AMPK activation and insulin stimulation were associated with increased sarcolemmal GLUT4 localization and glycolytic flux in the hyperthyroid heart. PMID:19940039

  4. Sex differences in the mechano-energetic effects of genistein on stunned rat and guinea pig hearts.

    PubMed

    Colareda, Germán A; Ragone, María I; Consolini, Alicia E

    2016-01-01

    Although the phytoestrogen genistein (Gen) is considered protective in cardiovascular diseases, its direct effects on stunned hearts after transient ischemia-reperfusion (I/R) are unknown. This report studied the effects of 20 μmol/L Gen on the mechano-calorimetric behaviour during I/R of rat and guinea pig hearts to evaluate the energetics of Ca(2+) homeostasis. Isolated beating hearts were perfused with control Krebs solution inside a calorimeter with or without perfusion of Gen before a transient period of I/R. Left ventricular pressure development (P) and total heat rate (Ht) were continuously measured. At 37°C, Gen did not change post-ischemic contractile recovery (PICR), but it increased the relaxation rate. However, PICR was reduced in hearts of male rats and guinea pigs at 30°C. Total muscle economy (P/Ht) showed the same behaviour as P at each temperature. Inhibition of phosphatases with orthovanadate during Gen perfusion prevented a decrease in PICR in male rat hearts, suggesting that this effect is due to tyrosine kinase inhibition. Reperfusing ischemic hearts with 10 mmol/L caffeine-36 mmol/L Na(+)-Krebs induced contracture dependent on the sarcoreticular Ca(2+) content. Contracture relaxation depends on mitochondrial Ca(2+) uptake and Gen reduced the relaxation rate. Moreover, Gen prevented the increase in Rhod-2 fluorescence (free [Ca(2+)]m) of rat cardiomyocytes. In guinea pig hearts, Gen maintained ischemic preconditioning, but was reduced by 5-hydroxydecanoate, suggesting the participation of mitochondrial adenosine triphosphate (ATP)-dependent K channels. Results suggest that Gen acts on several mechanisms that regulate myocardial calcium homeostasis and energetics during I/R, which differ in a temperature- and sex-dependent manner. PMID:26452245

  5. Sex differences in the mechano-energetic effects of genistein on stunned rat and guinea pig hearts.

    PubMed

    Colareda, Germán A; Ragone, María I; Consolini, Alicia E

    2016-01-01

    Although the phytoestrogen genistein (Gen) is considered protective in cardiovascular diseases, its direct effects on stunned hearts after transient ischemia-reperfusion (I/R) are unknown. This report studied the effects of 20 μmol/L Gen on the mechano-calorimetric behaviour during I/R of rat and guinea pig hearts to evaluate the energetics of Ca(2+) homeostasis. Isolated beating hearts were perfused with control Krebs solution inside a calorimeter with or without perfusion of Gen before a transient period of I/R. Left ventricular pressure development (P) and total heat rate (Ht) were continuously measured. At 37°C, Gen did not change post-ischemic contractile recovery (PICR), but it increased the relaxation rate. However, PICR was reduced in hearts of male rats and guinea pigs at 30°C. Total muscle economy (P/Ht) showed the same behaviour as P at each temperature. Inhibition of phosphatases with orthovanadate during Gen perfusion prevented a decrease in PICR in male rat hearts, suggesting that this effect is due to tyrosine kinase inhibition. Reperfusing ischemic hearts with 10 mmol/L caffeine-36 mmol/L Na(+)-Krebs induced contracture dependent on the sarcoreticular Ca(2+) content. Contracture relaxation depends on mitochondrial Ca(2+) uptake and Gen reduced the relaxation rate. Moreover, Gen prevented the increase in Rhod-2 fluorescence (free [Ca(2+)]m) of rat cardiomyocytes. In guinea pig hearts, Gen maintained ischemic preconditioning, but was reduced by 5-hydroxydecanoate, suggesting the participation of mitochondrial adenosine triphosphate (ATP)-dependent K channels. Results suggest that Gen acts on several mechanisms that regulate myocardial calcium homeostasis and energetics during I/R, which differ in a temperature- and sex-dependent manner.

  6. Differences in Response Initiation and Behavioral Flexibility Between Adolescent and Adult Rats

    PubMed Central

    Simon, Nicholas W.; Gregory, Timothy A.; Wood, Jesse; Moghaddam, Bita

    2014-01-01

    Adolescence is a period of increased vulnerability to psychiatric illnesses such as addiction, mood disorders, and schizophrenia. Rats provide a useful animal model for investigating the differences in behavior and biology between adults and adolescents that stem from ongoing brain development. We developed the Cued Response Inhibition Task, or CRIT, to assess response inhibition and initiation processes by measuring the ability of rodents to withhold a response during an inhibitory cue and then to respond promptly after cue termination. We found no difference between adult and adolescent rats in the ability to appropriately inhibit a response during cue presentation. Adolescents, however, were unable to initiate a response as quickly as adults after cue termination. Further, we observed that this difference in responding was abolished after adolescent rats aged to adulthood with no additional training. In a separate experiment, adult and adolescent rats were trained in CRIT and then trained in another protocol in which the response inhibitory cue from CRIT was used as a Pavlovian cue predictive of reward. Adolescents demonstrated more reward-seeking behavior during the previously inhibitory Pavlovian cue than adults, indicative of greater behavioral flexibility. Taken together, these data suggest that, compared with adults, adolescent rats (a) are less able to initiate a response after response inhibition, (b) equally inhibit behavioral responses, and (c) are more adept at flexibly switching behavioral patterns. Furthermore, this study characterizes a task that is well suited for future pharmacological and electrophysiological investigations for assessing neuronal processing differences between adolescents and adults. PMID:23398439

  7. Chronic hypoxia-induced alterations in mitochondrial energy metabolism are not reversible in rat heart ventricles.

    PubMed

    Nouette-Gaulain, Karine; Biais, Matthieu; Savineau, Jean-Pierre; Marthan, Roger; Mazat, Jean-Pierre; Letellier, Thierry; Sztark, François

    2011-01-01

    Chronic hypoxia alters mitochondrial energy metabolism. In the heart, oxidative capacity of both ventricles is decreased after 3 weeks of chronic hypoxia. The aim of this study was to evaluate the reversal of these metabolic changes upon normoxia recovery. Rats were exposed to a hypobaric environment for 3 weeks and then subjected to a normoxic environment for 3 weeks (normoxia-recovery group) and compared with rats maintained in a normoxic environment (control group). Mitochondrial energy metabolism was differentially examined in both left and right ventricles. Oxidative capacity (oxygen consumption and ATP synthesis) was measured in saponin-skinned fibers. Activities of mitochondrial respiratory chain complexes and antioxidant enzymes were measured on ventricle homogenates. Morphometric analysis of mitochondria was performed on electron micrographs. In normoxia-recovery rats, oxidative capacities of right ventricles were decreased in the presence of glutamate or palmitoyl carnitine as substrates. In contrast, oxidation of palmitoyl carnitine was maintained in the left ventricle. Enzyme activities of complexes III and IV were significantly decreased in both ventricles. These functional alterations were associated with a decrease in numerical density and an increase in size of mitochondria. Finally, in the normoxia-recovery group, the antioxidant enzyme activities (catalase and glutathione peroxidase) increased. In conclusion, alterations of mitochondrial energy metabolism induced by chronic hypoxia are not totally reversible. Reactive oxygen species could be involved and should be investigated under such conditions, since they may represent a therapeutic target.

  8. Effect of antihypertensive agents - captopril and nifedipine - on the functional properties of rat heart mitochondria

    PubMed Central

    Kancirová, Ivana; Jašová, Magdaléna; Waczulíková, Iveta; Ravingerová, Táňa; Ziegelhöffer, Attila; Ferko, Miroslav

    2016-01-01

    Objective(s): Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment. Materials and Methods: Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro) were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril + nifedipine added to the incubation medium (in vitro) or administered per os to rat (in vivo) on mitochondrial ATP synthase activity and membrane fluidity were monitored. Results: In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P<0.05) with nonsignificant differences in membrane fluidity. Decrease in the value of maximum reaction rate Vmax (P<0.05) without any change in the value of Michaelis-Menten constant Km, indicative of a noncompetitive inhibition, was presented. At the in vivo level, we did not demonstrate any significant changes in the ATP synthase activity and the membrane fluidity in rats receiving captopril, nifedipine, and combined therapy. Conclusion: In vitro kinetics study revealed that antihypertensive drugs (captopril and nifedipine) directly interact with mitochondrial ATP synthase. In vivo experiment did not prove any acute effect on myocardial bioenergetics and suggest that drugs do not enter cardiomyocyte and have no direct effect on mitochondria. PMID:27482342

  9. Defective stretch-induced release of atrial natriuretic peptide from aging hypertensive rat heart: possible role of phosphatidylinositol pathway.

    PubMed

    Brunner, F; Mouton, R; Lochner, A; Opie, L H

    1995-01-01

    Because the phosphatidylinositol pathway may be part of the signaling system associated with stretch-induced release of atrial natriuretic peptide (ANP), we tested the hypothesis that formation of the intermediate inositol-1,4,5-trisphosphate (IP3) is impaired when ANP release is decreased in response to atrial stretch in hearts from aging genetically hypertensive (GH) rats. Immunoreactive ANP release into the coronary effluent and IP3 levels were studied in cardiac tissues of isolated perfused hearts from normotensive control (WAG) or GH rats aged 4, 11, or 16 months. Left atria were repeatedly distended and released with a latex balloon. ANP was measured in coronary effluent, and IP3 was measured in cardiac tissues. In all age groups, stretch and relief of stretch evoked considerably less ANP release in spontaneously beating hearts from GH than from WAG rats. Hearts from GH rats aged 16 months released no ANP, but electrical pacing restored some stretch-induced ANP secretion. With repeated stretch and release of stretch of the left atrium for 2 min, IP3 levels increased in left atrial tissue in WAG but not in GH hearts of all age groups. IP3 levels in (unstretched) left ventricles were much lower than in left atria and were unaltered by atrial stretch. In aging GH rats, the capacity to release ANP on atrial stretch is largely lost, in association with complete suppression of stimulus-induced increase in IP3 levels. These data support a role for IP3 in stretch-mediated atrial ANP secretion and suggest a progressive uncoupling of this signaling pathway in aging hypertensive rats. PMID:7723347

  10. Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart

    PubMed Central

    Ashmore, Tom; Fernandez, Bernadette O; Branco-Price, Cristina; West, James A; Cowburn, Andrew S; Heather, Lisa C; Griffin, Julian L; Johnson, Randall S; Feelisch, Martin; Murray, Andrew J

    2014-01-01

    Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n = 40) were given water supplemented with 0.7 mmol l−1 NaCl (as control) or 0.7 mmol l−1 NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n = 10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac l-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics. PMID:25172947

  11. Chronic Aerobic Exercise Decreases Lectin-Like Low Density Lipoprotein (LOX-1) Receptor Expression in Heart of Diabetic Rat

    PubMed Central

    Riahi, Simin; Mohammadi, Mohammad Taghi; Sobhani, Vahid; Ababzadeh, Shima

    2016-01-01

    Background: Overexpression of lectin-like low density lipoprotein (LOX-1) receptor plays an important role in hyperglycemia-induced vascular complications such as atherosclerosis. Based on the beneficial effects of exercise on preventing cardiovascular complications of diabetes, we aimed to examine the protective effects of aerobic exercise on expression of LOX-1 receptor and production of free radicals in the heart of diabetic rats. Methods: Four groups of rats were used: (n = 5 per group): sedentary normal, trained normal, sedentary diabetes and trained diabetes. Diabetes was induced by a single intraperitoneal injection of streptozotocin (50 mg/kg). The exercise protocol was consisted of swimming 30 min/day, 5 days/week for eight weeks. Plasma glucose was evaluated at initiation, weeks 4 and 8 of experiment. At the end of experiment, rats were sacrificed and the heart was removed for determination of nitrate, malondialdehyde, and LOX-1 gene expression. Results: In normal non-diabetic rats, the blood glucose level was <150 mg/dl; however, the induction of diabetes resulted in levels more than >400 mg/dl. Gene expression of LOX-1 was increased in the heart of diabetic rats. Exercise reduced the gene expression of this protein in diabetic states without reducing the blood glucose. Finally, swimming exercise decreased the malondialdehyde and nitrate levels in heart tissue both in control and diabetic rats. Conclusion: Swimming exercise reduces heart expression of the LOX-1 receptor in accompany with reduction of free radicals production. Since these parameters are important in generation of diabetic complications, swimming exercise is a good candidate for reducing these complications. PMID:26432573

  12. Accumulation of glycogen in axotomized adult rat facial motoneurons.

    PubMed

    Takezawa, Yosuke; Baba, Otto; Kohsaka, Shinichi; Nakajima, Kazuyuki

    2015-06-01

    This study biochemically determined glycogen content in the axotomized facial nucleus of adult rats up to 35 days postinsult. The amounts of glycogen in the transected facial nucleus were significantly increased at 5 days postinsult, peaked at 7 days postinsult, and declined to the control levels at 21-35 days postinsult. Immunohistochemical analysis with antiglycogen antibody revealed that the quantity of glycogen granules in the axotomized facial nucleus was greater than that in the control nucleus at 7 days postinjury. Dual staining methods with antiglycogen antibody and a motoneuron marker clarified that the glycogen was localized mainly in motoneurons. Immunoblotting and quantification analysis revealed that the ratio of inactive glycogen synthase (GS) to total GS was significantly decreased in the injured nucleus at about 1-3 days postinsult and significantly increased from 7 to 14 days postinsult, suggesting that glycogen is actively synthesized in the early period postinjury but suppressed after 7 days postinsult. The enhanced glycogen at about 5-7 days postinsult is suggested to be responsible for the decrease in inactive GS levels, and the decrease of glycogen after 7 days postinsult is considered to be caused by increased inactive GS levels and possibly the increase in active glycogen phosphorylase.

  13. Outcomes of a Telehealth Intervention for Homebound Older Adults with Heart or Chronic Respiratory Failure: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Gellis, Zvi D.; Kenaley, Bonnie; McGinty, Jean; Bardelli, Ellen; Davitt, Joan; Ten Have, Thomas

    2012-01-01

    Purpose: Telehealth care is emerging as a viable intervention model to treat complex chronic conditions, such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), and to engage older adults in self-care disease management. Design and Methods: We report on a randomized controlled trial examining the impact of a multifaceted…

  14. No increases in biomarkers of genetic damage or pathological changes in heart and brain tissues in male rats administered methylphenidate hydrochloride (Ritalin) for 28 days.

    PubMed

    Witt, Kristine L; Malarkey, David E; Hobbs, Cheryl A; Davis, Jeffrey P; Kissling, Grace E; Caspary, William; Travlos, Gregory; Recio, Leslie

    2010-01-01

    Following a 2005 report of chromosomal damage in children with attention deficit/hyperactivity disorder (ADHD) who were treated with the commonly prescribed medication methylphenidate (MPH), numerous studies have been conducted to clarify the risk for MPH-induced genetic damage. Although most of these studies reported no changes in genetic damage endpoints associated with exposure to MPH, one recent study (Andreazza et al. [2007]: Prog Neuropsychopharmacol Biol Psychiatry 31:1282-1288) reported an increase in DNA damage detected by the Comet assay in blood and brain cells of Wistar rats treated by intraperitoneal injection with 1, 2, or 10 mg/kg MPH; no increases in micronucleated lymphocyte frequencies were observed in these rats. To clarify these findings, we treated adult male Wistar Han rats with 0, 2, 10, or 25 mg/kg MPH by gavage once daily for 28 consecutive days and measured micronucleated reticulocyte (MN-RET) frequencies in blood, and DNA damage in blood, brain, and liver cells 4 hr after final dosing. Flow cytometric evaluation of blood revealed no significant increases in MN-RET. Comet assay evaluations of blood leukocytes and cells of the liver, as well as of the striatum, hippocampus, and frontal cortex of the brain showed no increases in DNA damage in MPH-treated rats in any of the three treatment groups. Thus, the previously reported observations of DNA damage in blood and brain tissue of rats exposed to MPH for 28 days were not confirmed in this study. Additionally, no histopathological changes in brain or heart, or elevated serum biomarkers of cardiac injury were observed in these MPH-exposed rats.

  15. Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats

    EPA Science Inventory

    Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

  16. Influence of doxazosin on biosynthesis of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats.

    PubMed

    Kasacka, Irena; Piotrowska, Żaneta; Filipek, Anna; Majewski, Mariusz

    2016-02-01

    Hypertension frequently results in severe complications in cardiovascular system and histopathological changes in the heart. To better understand the cellular processes and signaling pathways responsible for the proper functioning of the heart, we decided to check whether doxazosin affects the density of structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats. The aim of this study is to find differences in the density of the structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats treated with doxazosin compared to untreated animals. Fragments of heart were collected from five spontaneously hypertensive rats and five spontaneously hypertensive rats receiving doxazosin for six weeks (dose 0.1 mg per 1 kg of body weight). On the paraffin sections S100A6 and atrial natriuretic factor peptides were localized in the heart using immunohistochemistry. Positive immunohistochemical reaction for S100A6 was observed in atrial and ventricular cardiomyocytes and in the coronary vasculature. In the heart of hypertensive rats treated with doxazosin the S100A6 immunoreactivity was significantly lower compared to untreated animals. Immunodetection of atrial natriuretic factor in the heart of rats confirmed presence of peptide in atrial myocardium. Delicate atrial natriuretic factor-immunoreactivity was observed also in few ventricular cardiomyocytes. The atrial natriuretic factor-immunosignal was significantly weaker in hearts of hypertensive rats receiving doxazosin compared to spontaneously hypertensive rats untreated. Since we found that doxazosin reduces the levels of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats, it can be assumed that cardiovascular disorders that occur in hypertension may be associated with disturbances of cellular processes and signaling pathways.

  17. Influence of doxazosin on biosynthesis of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats

    PubMed Central

    Piotrowska, Żaneta; Filipek, Anna; Majewski, Mariusz

    2016-01-01

    Hypertension frequently results in severe complications in cardiovascular system and histopathological changes in the heart. To better understand the cellular processes and signaling pathways responsible for the proper functioning of the heart, we decided to check whether doxazosin affects the density of structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats. The aim of this study is to find differences in the density of the structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats treated with doxazosin compared to untreated animals. Fragments of heart were collected from five spontaneously hypertensive rats and five spontaneously hypertensive rats receiving doxazosin for six weeks (dose 0.1 mg per 1 kg of body weight). On the paraffin sections S100A6 and atrial natriuretic factor peptides were localized in the heart using immunohistochemistry. Positive immunohistochemical reaction for S100A6 was observed in atrial and ventricular cardiomyocytes and in the coronary vasculature. In the heart of hypertensive rats treated with doxazosin the S100A6 immunoreactivity was significantly lower compared to untreated animals. Immunodetection of atrial natriuretic factor in the heart of rats confirmed presence of peptide in atrial myocardium. Delicate atrial natriuretic factor-immunoreactivity was observed also in few ventricular cardiomyocytes. The atrial natriuretic factor-immunosignal was significantly weaker in hearts of hypertensive rats receiving doxazosin compared to spontaneously hypertensive rats untreated. Since we found that doxazosin reduces the levels of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats, it can be assumed that cardiovascular disorders that occur in hypertension may be associated with disturbances of cellular processes and signaling pathways. PMID:26515144

  18. Early development of intracellular calcium cycling defects in intact hearts of spontaneously hypertensive rats

    PubMed Central

    Kapur, Sunil; Aistrup, Gary L.; Sharma, Rohan; Kelly, James E.; Arora, Rishi; Zheng, Jiabo; Veramasuneni, Mitra; Kadish, Alan H.; Balke, C. William

    2010-01-01

    Defects in excitation-contraction coupling have been reported in failing hearts, but little is known about the relationship between these defects and the development of heart failure (HF). We compared the early changes in intracellular Ca2+ cycling to those that underlie overt pump dysfunction and arrhythmogenesis found later in HF. Laser-scanning confocal microscopy was used to measure Ca2+ transients in myocytes of intact hearts in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) at different ages. Early compensatory mechanisms include a positive inotropic effect in SHRs at 7.5–9 mo compared with 6 mo. Ca2+ transient duration increased at 9 mo in SHRs, indicating changes in Ca2+ reuptake during decompensation. Cell-to-cell variability in Ca2+ transient duration increased at 7.5 mo, decreased at 9 mo, and increased again at 22 mo (overt HF), indicating extensive intercellular variability in Ca2+ transient kinetics during disease progression. Vulnerability to intercellular concordant Ca2+ alternans increased at 9–22 mo in SHRs and was mirrored by a slowing in Ca2+ transient restitution, suggesting that repolarization alternans and the resulting repolarization gradients might promote reentrant arrhythmias early in disease development. Intercellular discordant and subcellular Ca2+ alternans increased as early as 7.5 mo in SHRs and may also promote arrhythmias during the compensated phase. The incidence of spontaneous and triggered Ca2+ waves was increased in SHRs at all ages, suggesting a higher likelihood of triggered arrhythmias in SHRs compared with WKY rats well before HF develops. Thus serious and progressive defects in Ca2+ cycling develop in SHRs long before symptoms of HF occur. Defective Ca2+ cycling develops early and affects a small number of myocytes, and this number grows with age and causes the transition from asymptomatic to overt HF. These defects may also underlie the progressive susceptibility to Ca2+ alternans and Ca2+ wave

  19. Fatty Acid Chain Elongation in Palmitate-perfused Working Rat Heart

    PubMed Central

    Kerner, Janos; Minkler, Paul E.; Lesnefsky, Edward J.; Hoppel, Charles L.

    2014-01-01

    Rat hearts were perfused with [1,2,3,4-13C4]palmitic acid (M+4), and the isotopic patterns of myocardial acylcarnitines and acyl-CoAs were analyzed using ultra-HPLC-MS/MS. The 91.2% 13C enrichment in palmitoylcarnitine shows that little endogenous (M+0) palmitate contributed to its formation. The presence of M+2 myristoylcarnitine (95.7%) and M+2 acetylcarnitine (19.4%) is evidence for β-oxidation of perfused M+4 palmitic acid. Identical enrichment data were obtained in the respective acyl-CoAs. The relative 13C enrichment in M+4 (84.7%, 69.9%) and M+6 (16.2%, 17.8%) stearoyl- and arachidylcarnitine, respectively, clearly shows that the perfused palmitate is chain-elongated. The observed enrichment of 13C in acetylcarnitine (19%), M+6 stearoylcarnitine (16.2%), and M+6 arachidylcarnitine (17.8%) suggests that the majority of two-carbon units for chain elongation are derived from β-oxidation of [1,2,3,4-13C4]palmitic acid. These data are explained by conversion of the M+2 acetyl-CoA to M+2 malonyl-CoA, which serves as the acceptor for M+4 palmitoyl-CoA in chain elongation. Indeed, the 13C enrichment in mitochondrial acetyl-CoA (18.9%) and malonyl-CoA (19.9%) are identical. No 13C enrichment was found in acylcarnitine species with carbon chain lengths between 4 and 12, arguing against the simple reversal of fatty acid β-oxidation. Furthermore, isolated, intact rat heart mitochondria 1) synthesize malonyl-CoA with simultaneous inhibition of carnitine palmitoyltransferase 1b and 2) catalyze the palmitoyl-CoA-dependent incorporation of 14C from [2-14C]malonyl-CoA into lipid-soluble products. In conclusion, rat heart has the capability to chain-elongate fatty acids using mitochondria-derived two-carbon chain extenders. The data suggest that the chain elongation process is localized on the outer surface of the mitochondrial outer membrane. PMID:24558043

  20. Visualization and quantification of whole rat heart laminar structure using high-spatial resolution contrast-enhanced MRI.

    PubMed

    Gilbert, Stephen H; Benoist, David; Benson, Alan P; White, Ed; Tanner, Steven F; Holden, Arun V; Dobrzynski, Halina; Bernus, Olivier; Radjenovic, Aleksandra

    2012-01-01

    It has been shown by histology that cardiac myocytes are organized into laminae and this structure is important in function, both influencing the spread of electrical activation and enabling myocardial thickening in systole by laminar sliding. We have carried out high-spatial resolution three-dimensional MRI of the ventricular myolaminae of the entire volume of the isolated rat heart after contrast perfusion [dimeglumine gadopentate (Gd-DTPA)]. Four ex vivo rat hearts were perfused with Gd-DTPA and fixative and high-spatial resolution MRI was performed on a 9.4T MRI system. After MRI, cryosectioning followed by histology was performed. Images from MRI and histology were aligned, described, and quantitatively compared. In the three-dimensional MR images we directly show the presence of laminae and demonstrate that these are highly branching and are absent from much of the subepicardium. We visualized these MRI volumes to demonstrate laminar architecture and quantitatively demonstrated that the structural features observed are similar to those imaged in histology. We showed qualitatively and quantitatively that laminar architecture is similar in the four hearts. MRI can be used to image the laminar architecture of ex vivo hearts in three dimensions, and the images produced are qualitatively and quantitatively comparable with histology. We have demonstrated in the rat that: 1) laminar architecture is consistent between hearts; 2) myolaminae are absent from much of the subepicardium; and 3) although localized orthotropy is present throughout the myocardium, tracked myolaminae are branching structures and do not have a discrete identity.

  1. [CA²⁺ ACCUMULATION IN ISOLATED RAT HEART MITOCHONDRIA UNDER MAINTENANCE OF MITOCHONDRIAL POTENTIAL].

    PubMed

    Budko, A Yu; Strutynska, N A; Okhay, I Yu; Semenykhina, O M; Sagach, V F

    2015-01-01

    It is known that mitochondria can accumulate calcium, which regulates energy metabolism and cell death. About 90% of energy of cardiomyocytes is synthesized in mitochondria. Heart cells are also affected by the rapid changes in the Ca²⁺ concentration in the cytoplasm. Therefore, mitochondrial Ca²⁺-accumulation ability is crucial. The aim of our work was to study the accumulation of Ca²⁺ in isolated rat heart mitochondria in the presence of mitochondrial potential and different extramitochondrial Ca²⁺ concentrations. Isolated organelles were loaded with fluorescent dye Fluo-4 AM (2.5 μmol/l) at a temperature of 26°C for 30 min. It has been revealed that under these conditions high mitochondrial potential was maintained sufficiently, which is necessary for the functioning of the calcium transporting system in organelles. We established that mitochondria have a limited ability to store ionized calcium, as addition of Ca²⁺ ion in concentrations of 10, 20, 50 µmol/l ensures a certain level of accumulation in organelles with further fluorescent signal growth cessation. Addition of 100 µmol/Ca²⁺ to isolated mitochondria resulted in a significant increase in fluorescence intensity (46% in the fifth minute, compared to the fluorescence when 20 µmol/l Ca²⁺ was added) and likely to activation of cation release. It was shown that ruthenium red (10⁻⁵ mol/l), an inhibitor of Ca²⁺-uniporter, prevented accumulation of calcium ions in organelles by 89%, in the presence of 100 µmol/ Ca²⁺. It was clearly seen that heart mitochondria require Mg²⁺-ATP complex (3 mmol/l) to accumulate Ca²⁺, likely to maintain the inner membrane potential, activity of Ca²⁺ uniporter and energetic processes in organelles. Thus, the process of Ca²⁺ accumulation in rat heart mitochondria requires the maintenance of mitochondrial potential, activity of Ca²⁺-uniporter, depends on extramitochondrial Ca²⁺ concentration and presence of Mg²⁺-ATP complex.

  2. Adolescent and adult male spontaneous hyperactive rats (SHR) respond differently to acute and chronic methylphenidate (Ritalin).

    PubMed

    Barron, Elyssa; Yang, Pamela B; Swann, Alan C; Dafny, Nachum

    2009-01-01

    Eight groups of male adolescent and adult spontaneous hyperactive rats (SHR) were used in a dose response (saline, 0.6, 2.5, and 10 mg/kg) experiment of methylphenidate (MPD). Four different locomotor indices were recorded for 2 hours postinjection using a computerized monitoring system. Acutely, the 0.6 mg/kg dose of MPD did not elicit an increase in locomotor activity in either the adolescent or in the adult male SHR. The 2.5 and the 10.0 mg/kg doses increased activity in the adolescent and the adult rats. Chronically, MPD treatment when comparing adolescent and adult gave the following results: the 0.6 mg/kg dose of MPD failed to cause sensitization in the adolescent group but caused sensitization in the adult group, while the 2.5 and 10 mg/kg both caused sensitization in the adolescent and adult groups.

  3. Light-emitting diode therapy (LEDT) improves functional capacity in rats with heart failure.

    PubMed

    Capalonga, Lucas; Karsten, Marlus; Hentschke, Vítor Scotta; Rossato, Douglas Dalcin; Dornelles, Maurício Pinto; Sonza, Anelise; Bagnato, Vanderlei Salvador; Ferraresi, Cleber; Parizotto, Nivaldo Antonio; Dal Lago, Pedro

    2016-07-01

    The syndrome of heart failure (HF) promotes central and peripheral dysfunctions that result in functional capacity decrease, leading to fatigue, dyspnea, and exercise intolerance. The use of light-emitting diode therapy (LEDT) has shown good results reducing fatigue and exercise intolerance, when applied on skeletal muscles before or after exercises. Thereby, the aim of this study was to compare the effects of LEDT on functional capacity, aerobic power, and hemodynamic function in HF rats. Male Wistar rats (230-260 g) were randomly allocated into three experimental groups: Sham (n = 6), Control-HF (n = 4), and LEDT-HF (n = 6). The animals were subjected to an exercise performance test (ET) with gas analysis coupled in a metabolic chamber for rats performed two times (6 and 14 weeks after myocardial infarction). On the day after the baseline aerobic capacity test, the animals were submitted during 8 weeks to the phototherapy protocol, five times/week, 60 s of irradiation, 6 J delivered per muscle group. Statistical analysis was performed by one- and two-way ANOVAs with repeated measures and Student-Newman-Keuls post hoc tests (p ≤ 0.05). Comparing the percentage difference (Δ) between baseline and the final ET, there was no significant difference for the VO2max variable considering all groups. However, Sham and LEDT-HF groups showed higher relative values than the Control-HF group, respectively, for distance covered (27.7 and 32.5 %), time of exercise test (17.7 and 20.5 %), and speed (13.6 and 12.2 %). In conclusion, LEDT was able to increase the functional capacity evaluated by distance covered, time, and speed of exercise in rats with HF. PMID:27059227

  4. Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells

    PubMed Central

    Wang, Hua; Lau, Benson Wui-Man; Wang, Ning-li; Wang, Si-ying; Lu, Qing-jun; Chang, Raymond Chuen-Chung; So, Kwok-fai

    2015-01-01

    Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve. However, it remains unclear regarding the effects of Lycium barbarum polysaccharides, the main component of Lycium barbarum, on in vivo proliferation of adult ciliary body cells. In this study, adult rats were intragastrically administered low- and high-dose Lycium barbarum polysaccharides (1 and 10 mg/kg) for 35 days and those intragastrically administered phosphate buffered saline served as controls. The number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups, in particular low-dose Lycium barbarum polysaccharides group, was significantly greater than that in the phosphate buffered saline group. Ki-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic protein. These findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype. PMID:26889185

  5. Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate.

    PubMed

    Li, Ping; Luo, Shike; Pan, Chunji; Cheng, Xiaoshu

    2015-12-01

    Heart failure is a disease predominantly caused by an energy metabolic disorder in cardiomyocytes. The present study investigated the inhibitory effects of fenofibrate (FF) on isoproterenol (ISO)‑induced hear failure in rats, and examined the underlying mechanisms. The rats were divided into CON, ISO (HF model), FF and FF+ISO (HF animals pretreated with FF) groups. The cardiac structure and function of the rats were assessed, and contents of free fatty acids and glucose metabolic products were determined. In addition, myocardial cells were isolated from neonatal rats and used in vitro to investigate the mechanisms by which FF relieves heart failure. Western blot analysis was performed to quantify the expression levels of peroxisome proliferator‑activated receptor (PPAR)α and uncoupling protein 2 (UCP2). FF effectively alleviated the ISO‑induced cardiac structural damage, functional decline, and fatty acid and carbohydrate metabolic abnormalities. Compared with the ISO group, the serum levels of brain natriuretic peptide (BNP), free fatty acids, lactic acid and pyruvic acid were decreased in the FF animals. In the cultured myocardial cells, lactic acid and pyruvic acid contents were lower in the supernatants obtained from the FF animals, with lower levels of mitochondrial ROS production and cell necrosis, compared with the ISO group, whereas PPARα upregulation and UCP2 downregulation occurred in the FF+ISO group. The results demonstrated that FF efficiently alleviated heart failure in the ISO‑induced rat model, possibly via promoting fatty acid oxidation. PMID:26497978

  6. Training differentially regulates elastin level and proteolysis in skeletal and heart muscles and aorta in healthy rats

    PubMed Central

    Gilbert, Anna; Wyczalkowska-Tomasik, Aleksandra; Zendzian-Piotrowska, Malgorzata; Czarkowska-Paczek, Bozena

    2016-01-01

    ABSTRACT Exercise induces changes in muscle fibers and the extracellular matrix that may depend on elastin content and the activity of proteolytic enzymes. We investigated the influence of endurance training on the gene expression and protein content and/or activity of elastin, elastase, cathepsin K, and plasmin in skeletal and heart muscles and in the aorta. Healthy rats were randomly divided into untrained (n=10) and trained (n=10; 6 weeks of endurance training with increasing load) groups. Gene expression was evaluated via qRT-PCR. Elastin content was measured via enzyme-linked immunosorbent assay and enzyme activity was measured fluorometrically. Elastin content was significantly higher in skeletal (P=0.0014) and heart muscle (P=0.000022) from trained rats versus untrained rats, but not in the aorta. Although mRNA levels in skeletal muscle did not differ between groups, the activities of elastase (P=0.0434), cathepsin K (P=0.0343) and plasmin (P=0.000046) were higher in trained rats. The levels of cathepsin K (P=0.0288) and plasminogen (P=0.0005) mRNA were higher in heart muscle from trained rats, but enzyme activity was not. Enzyme activity in the aorta did not differ between groups. Increased elastin content in muscles may result in better adaption to exercise, as may remodeling of the extracellular matrix in skeletal muscle. PMID:27069251

  7. Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate

    PubMed Central

    LI, PING; LUO, SHIKE; PAN, CHUNJI; CHENG, XIAOSHU

    2015-01-01

    Heart failure is a disease predominantly caused by an energy metabolic disorder in cardiomyocytes. The present study investigated the inhibitory effects of fenofibrate (FF) on isoproterenol (ISO)-induced hear failure in rats, and examined the underlying mechanisms. The rats were divided into CON, ISO (HF model), FF and FF+ISO (HF animals pretreated with FF) groups. The cardiac structure and function of the rats were assessed, and contents of free fatty acids and glucose metabolic products were determined. In addition, myocardial cells were isolated from neonatal rats and used in vitro to investigate the mechanisms by which FF relieves heart failure. Western blot analysis was performed to quantify the expression levels of peroxisome proliferator-activated receptor (PPAR)α and uncoupling protein 2 (UCP2). FF effectively alleviated the ISO-induced cardiac structural damage, functional decline, and fatty acid and carbohydrate metabolic abnormalities. Compared with the ISO group, the serum levels of brain natriuretic peptide (BNP), free fatty acids, lactic acid and pyruvic acid were decreased in the FF animals. In the cultured myocardial cells, lactic acid and pyruvic acid contents were lower in the supernatants obtained from the FF animals, with lower levels of mitochondrial ROS production and cell necrosis, compared with the ISO group, whereas PPARα upregulation and UCP2 downregulation occurred in the FF+ISO group. The results demonstrated that FF efficiently alleviated heart failure in the ISO-induced rat model, possibly via promoting fatty acid oxidation. PMID:26497978

  8. Effects of long-term methylphenidate treatment in adolescent and adult rats on hippocampal shape, functional connectivity and adult neurogenesis.

    PubMed

    van der Marel, K; Bouet, V; Meerhoff, G F; Freret, T; Boulouard, M; Dauphin, F; Klomp, A; Lucassen, P J; Homberg, J R; Dijkhuizen, R M; Reneman, L

    2015-11-19

    Methylphenidate (MPH) is a widely prescribed stimulant drug for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents. Its use in this age group raises concerns regarding the potential interference with ongoing neurodevelopmental processes. Particularly the hippocampus is a highly plastic brain region that continues to develop postnatally and is involved in cognition and emotional behavior, functions known to be affected by MPH. In this study, we assessed whether hippocampal structure and function were affected by chronic oral MPH treatment and whether its effects were different in adolescent or adult rats. Using behavioral testing, resting-state functional MRI, post-mortem structural magnetic resonance imaging (MRI), and immunohistochemistry, we assessed MPH's effects on recognition memory, depressive-like behavior, topological features of functional connectivity networks, hippocampal shape and markers for hippocampal neurogenesis and proliferation. Object recognition memory was transiently impaired in adolescent treated rats, while in animals treated during adulthood, increased depressive-like behavior was observed. Neurogenesis was increased in adolescent treated rats, whereas cell proliferation was decreased following adult treatment. Adolescent treated rats showed inward shape deformations adjacent to ventral parahippocampal regions known to be involved in recognition memory, whereas such deformations were not observed in adult treated animals. Irrespective of the age of treatment, MPH affected topological features of ventral hippocampal functional networks. Thus, chronic oral treatment with a therapeutically relevant dose of MPH preferentially affected the ventral part of the hippocampus and induced contrasting effects in adolescent and adult rats. The differences in behavior were paralleled by opposite effects on adult neurogenesis and granule cell proliferation.

  9. Quantitative proteomic analysis reveals novel mitochondrial targets of estrogen deficiency in the aged female rat heart

    PubMed Central

    Lancaster, T. S.; Jefferson, S. J.; Hunter, J. Craig; Lopez, Veronica; Van Eyk, J. E.; Lakatta, E. G.

    2012-01-01

    The incidence of myocardial infarction rises sharply at menopause, implicating a potential role for estrogen (E2) loss in age-related increases in ischemic injury. We aimed to identify quantitative changes to the cardiac mitochondrial proteome of aging females, based on the hypothesis that E2 deficiency exacerbates age-dependent disruptions in mitochondrial proteins. Mitochondria isolated from left ventricles of adult (6 mo) and aged (24 mo) F344 ovary-intact or ovariectomized (OVX) rats were labeled with 8plex isobaric tags for relative and absolute quantification (iTRAQ; n = 5–6/group). Groups studied were adult, adult OVX, aged, and aged OVX. In vivo coronary artery ligation and in vitro mitochondrial respiration studies were also performed in a subset of rats. We identified 965 proteins across groups and significant directional changes in 67 proteins of aged and/or aged OVX; 32 proteins were unique to aged OVX. Notably, only six proteins were similarly altered in adult OVX (voltage-dependent ion channel 1, adenine nucleotide translocator 1, cytochrome c oxidase subunits VIIc and VIc, catalase, and myosin binding protein C). Proteins affected by aging were primarily related to cellular metabolism, oxidative stress, and cell death. The largest change occurred in monoamine oxidase-A (MAO-A), a source of oxidative stress. While acute MAO-A inhibition induced mild uncoupling in aged mitochondria, reductions in infarct size were not observed. Age-dependent alterations in mitochondrial signaling indicate a highly selective myocardial response to E2 deficiency. The combined proteomic and functional approaches described here offer possibility of new protein targets for experimentation and therapeutic intervention in the aged female population. PMID:22930739

  10. Reactivation of peroxisome proliferator-activated receptor alpha is associated with contractile dysfunction in hypertrophied rat heart.

    PubMed

    Young, M E; Laws, F A; Goodwin, G W; Taegtmeyer, H

    2001-11-30

    In pressure overload-induced hypertrophy, the heart increases its reliance on glucose as a fuel while decreasing fatty acid oxidation. A key regulator of this substrate switching in the hypertrophied heart is peroxisome proliferator-activated receptor alpha (PPARalpha). We tested the hypothesis that down-regulation of PPARalpha is an essential component of cardiac hypertrophy at the levels of increased mass, gene expression, and metabolism by pharmacologically reactivating PPARalpha. Pressure overload (induced by constriction of the ascending aorta for 7 days in rats) resulted in cardiac hypertrophy, increased expression of fetal genes (atrial natriuretic factor and skeletal alpha-actin), decreased expression of PPARalpha and PPARalpha-regulated genes (medium chain acyl-CoA dehydrogenase and pyruvate dehydrogenase kinase 4), and caused substrate switching (measured ex vivo in the isolated working heart preparation). Treatment of rats with the specific PPARalpha agonist WY-14,643 (8 days) did not affect the trophic response or atrial natriuretic factor induction to pressure overload. However, PPARalpha activation blocked skeletal alpha-actin induction, reversed the down-regulation of measured PPARalpha-regulated genes in the hypertrophied heart, and prevented substrate switching. This PPARalpha reactivation concomitantly resulted in severe depression of cardiac power and efficiency in the hypertrophied heart (measured ex vivo). Thus, PPARalpha down-regulation is essential for the maintenance of contractile function of the hypertrophied heart. PMID:11574533

  11. Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses

    PubMed Central

    Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

    2015-01-01

    Objective To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Methods Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85–90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Results Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Conclusions Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated. PMID:26566220

  12. The care of adults with congenital heart disease across the globe: Current assessment and future perspective: A position statement from the International Society for Adult Congenital Heart Disease (ISACHD).

    PubMed

    Webb, Gary; Mulder, Barbara J; Aboulhosn, Jamil; Daniels, Curt J; Elizari, Maria Amalia; Hong, Gu; Horlick, Eric; Landzberg, Michael J; Marelli, Ariane J; O'Donnell, Clare P; Oechslin, Erwin N; Pearson, Dorothy D; Pieper, Els P G; Saxena, Anita; Schwerzmann, Markus; Stout, Karen K; Warnes, Carole A; Khairy, Paul

    2015-09-15

    The number of adults with congenital heart disease (CHD) has increased markedly over the past few decades as a result of astounding successes in pediatric cardiac care. Nevertheless, it is now well understood that CHD is not cured but palliated, such that life-long expert care is required to optimize outcomes. All countries in the world that experience improved survival in CHD must face new challenges inherent to the emergence of a growing and aging CHD population with changing needs and medical and psychosocial issues. Founded in 1992, the International Society for Adult Congenital Heart Disease (ISACHD) is the leading global organization of professionals dedicated to pursuing excellence in the care of adults with CHD worldwide. Recognizing the unique and varied issues involved in caring for adults with CHD, ISACHD established a task force to assess the current status of care for adults with CHD across the globe, highlight major challenges and priorities, and provide future direction. The writing committee consisted of experts from North America, South America, Europe, South Asia, East Asia, and Oceania. The committee was divided into subgroups to review key aspects of adult CHD (ACHD) care. Regional representatives were tasked with investigating and reporting on relevant local issues as accurately as possible, within the constraints of available data. The resulting ISACHD position statement addresses changing patterns of worldwide epidemiology, models of care and organization of care, education and training, and the global research landscape in ACHD.

  13. Cardiac effects of the extract and active components of radix stephaniae tetrandrae. II. Myocardial infarct, arrhythmias, coronary arterial flow and heart rate in the isolated perfused rat heart.

    PubMed

    Yu, X C; Wu, S; Wang, G Y; Shan, J; Wong, T M; Chen, C F; Pang, K T

    2001-05-11

    The primary purpose of the present study was to compare the cardioprotective effects of the extract from radix stephaniae tetrandrae (RST) and its individual compounds, tetrandrine (Tet) and fanchinoline (Fan). Secondly, we also compared the cardiac effects of the individual compounds and the RST extract with those of verapamil, a classical Ca2+ channel blocker. The Langendorff isolated perfused rat heart preparation was used. Regional ischaemia and reperfusion was employed to induce myocardial infarct and arrhythmia. Infarct, arrhythmia, heart rate and coronary artery flow were determined in hearts treated with vehicle, RST extract, Tet, Fan, or verapamil. It was found that RST extract, of which only 9% was Tet, and Tet alone produced equally potent ameliorating effects on arrhythmia and infarct induced by ischaemia and reperfusion without further inhibiting ischaemia-reduced heart rate and coronary artery flow. Fan had no effects on arrhythmia and infarct induced by ischaemia and reperfusion; but it induced S-T segment elevation and further reduced heart rate and coronary artery flow during ischaemia. Verapamil also ameliorated the effects of ischaemia and reperfusion on arrhythmia and infarct. It should be noted that 1 microM verapamil, that produced comparable effects on infarct and arrhythmia to the RST extract and Tet, further inhibited heart rate during ischaemia. The results indicate that the RST extract produces equally potent cardioprotective and anti-arrhythmic effects as Tet alone. Both RST extract and Tet may be better choices for the treatment of arrhythmia and infarct induced by myocardial ischaemia and reperfusion than the classical Ca2+ channel blocker, verapamil as they do not further reduce heart rate during ischaemia. PMID:11432452

  14. Cumulative rate and distribution of Cd and Pb in the organs of adult male Wistar rats during oral exposure.

    PubMed

    Winiarska-Mieczan, Anna

    2014-11-01

    The degree of accumulation of Cd and Pb in the brains, spleens, lungs, hearts, livers and kidneys of adult Wistar rats was compared both for separate (Cd or Pb) and combined (Cd+Pb) oral exposure. In addition, the metals were administered either with liquids or with solid feed. Rats were exposed to low doses of metals (7mg Cd and 50mg Pb/kg feed or L of distilled water) over 6 or 12 weeks. In total the organs of rats accumulated about 0.3-0.5% Cd and 0.4-0.6% Pb supplied with food or drink. The presented studies demonstrated that the distribution of Cd and Pb in the organs is affected by: the type of exposure (separate or combined), the source of metals (feed or drinks) and the duration of exposure. It was found that simultaneous exposure to low doses of Cd and Pb supplied with food is much more hazardous than exposure to such metals supplied with water.

  15. Mass isotopomer study of anaplerosis from propionate in the perfused rat heart

    PubMed Central

    Kasumov, Takhar; Cendrowski, Andrea V.; David, France; Jobbins, Kathryn A.; Anderson, Vernon E.; Brunengraber, Henri

    2007-01-01

    Anaplerosis from propionate was investigated in rat hearts perfused with 0–2 mM [13C3]propionate and physiological concentrations of glucose, lactate and pyruvate. The data show that when the concentration of [13C3]propionate was raised from 0 to 2 mM, total anaplerosis increases from 5 to 16% of the turnover of citric acid cycle intermediates. Then, [13C3]propionate abolished anaplerosis from endogenous substrates, glucose, lactate and pyruvate. Also, while the contents of propionyl-CoA and methylmalonyl-CoA increased with [13C3]propionate concentration, the content of succinyl-CoA decreased, presumably via activation of succinyl-CoA hydrolysis by a decrease in free CoA. Under our conditions, [13C3]propionate was a purely anaplerotic substrate since there was no labeling of mitochondrial acetyl-CoA, reflected by the labeling of the acetyl moiety of citrate. PMID:17418801

  16. Protective effects of amlodipine on mitochondrial injury in ischemic reperfused rat heart.

    PubMed

    Khan, Najam Ali; Chattopadhyay, Pronobesh; Abid, Mohammad; Pawdey, Abhijeet; Kishore, Kamal; Wahi, Arun Kumar

    2012-05-01

    The most significant finding of the present study was the release of nitric oxide (NO). The effect of amlodipine on NO production associated with ischemic reperfused (IR) injury was investigated in rat heart model. Cardiac tissues from animal groups were processed for biochemical, histopathological and electron microscopic studies. There was a significant increase in myocardial catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) enzymes in amlodipine treated group (1.37, 10.27, 6.39) when compared to IR injured group (0.81, 6.87, 4.53). Histopathology studies showed amlodipine reduce cardiocyte damage in cardiac injury during the cardiac IR. Transmission electron microscopic (TEM) study confirmed the cardioprotective role of amlodipine against IR induced cardiac injury. On the basis of findings, it is hypothesized that a portion of the beneficial actions of amlodipine may involve the release or action of NO and probably by its antioxidant properties.

  17. Matrine improved the function of heart failure in rats via inhibiting apoptosis and blocking β3‑adrenoreceptor/endothelial nitric oxide synthase pathway.

    PubMed

    Yu, Jiangbo; Yang, Shusen; Wang, Xu; Gan, Runtao

    2014-12-01

    Matrine, an alkaloid isolated from the traditional Chinese medicine Sophora flavescens AIT has exhibited a number of therapeutic effects on cardiovascular and liver diseases. The purpose of the present study was to investigate whether matrine has a protective effect on heart failure in rats. Coronary artery ligation was used to induce a heart failure (CHF) model in rats. Four weeks following the procedure, the rats were treated with different doses of matrine for one month. Histopathological examination demonstrated that matrine treatment alleviated myocardial hypertrophy and cardiac fibrosis in failing hearts. Furthermore, matrine administration also inhibited the increase of plasma aspartate amino transferase, creatine phosphokinase and lactate dehydrogenase levels in CHF rats. The rats with heart failure exhibited a significant reduction in ejection fraction and fractional shortening, as well as an increase in the left ventricular end systolic dimension, and matrine attenuated this decline in heart function. Further investigation demonstrated that matrine treatment also inhibited the upregulation of Bax and increase in the Bcl‑2 expression in the failing hearts. Furthermore, the upregulation of β3-adrenoreceptor (AR) and endothelial nitric oxide synthase proteins following heart failure were also attenuated by matrine. In conclusion, matrine had a preventive role in heart failure in rats at least in part by inhibiting myocardial apoptosis and the β3-AR pathway.

  18. Differential Effects of Acute Alcohol on EEG and Sedative Responses in Adolescent and Adult Wistar Rats

    PubMed Central

    Pian, Jerry P.; Criado, Jose R.; Walker, Brendan M.; Ehlers, Cindy L.

    2008-01-01

    Age-related developmental differences in sensitivity to the acute effects of alcohol may play an important role in the development of alcoholism. The present study was designed to evaluate the acute effects of alcohol on cortical electroencephalogram (EEG) in adolescent (P36) and adult (P78) Wistar rats. Five minutes of EEG was recorded after administration of 0, 0.75 or 1.5 g/kg alcohol. The righting reflex was performed to measure the sedative effects of alcohol (3.5 g/kg) and total sleeping time for each rat. Our results showed that alcohol (1.5 g/kg) increased power in the 1–2 Hz band and decreased the power in the 32–50 Hz band in the parietal cortical region of adolescent rats. Alcohol (1.5 g/kg) also increased stability of the EEG power in the slow-wave frequency bands (2–4 Hz, 4–6 Hz, and 6–8 Hz) of adolescent rats. In the frontal cortex of adult rats, but not in adolescent rats, alcohol (1.5 or 0.75 g/kg) decreased the power in the 16–32 Hz frequency band. Alcohol (1.5 g/kg) differentially increased power in a multiple of slow-wave frequency bands (2–4 Hz and 4–6 Hz) in the parietal cortex of adult rats as compared to adolescent rats. Adolescent rats were shown significantly shorter sleeping time and higher blood alcohol levels after regaining reflex than adult rats. Our results provide additional evidence of age-related differences in the effects of acute alcohol on cortical EEG, sedation and tolerance. PMID:18191821

  19. Daily patterns of ethanol drinking in peri-adolescent and adult alcohol-preferring (P) rats.

    PubMed

    Bell, Richard L; Rodd, Zachary A; Sable, Helen J K; Schultz, Jonathon A; Hsu, Cathleen C; Lumeng, Lawrence; Murphy, James M; McBride, William J

    2006-01-01

    Alcohol abuse among adolescents continues to be a major health problem for our society. Our laboratory has used the peri-adolescent alcohol-preferring, P, rat as an animal model of adolescent alcohol abuse. Even though peri-adolescent P rats consume more alcohol (g/kg/day) than their adult counterparts, it is uncertain whether their drinking is sufficiently aggregated to result in measurable blood ethanol concentrations (BECs). The objectives of this study were to examine daily alcohol drinking patterns of adolescent and adult, male and female P rats, and to determine whether alcohol drinking episodes were sufficiently aggregated to result in meaningful BECs. Male and female P rats were given 30 days of 24 h free-choice access to alcohol (15%, v/v) and water, with ad lib access to food, starting at the beginning of adolescence (PND 30) or adulthood (PND 90). Water and alcohol drinking patterns were monitored 22 h/day with a "lickometer" set-up. The results indicated that (a) peri-adolescent P rats consumed more water and total fluids than adult P rats, (b) female P rats consumed more water and total fluids than male P rats, (c) there were differences in alcohol, and water, licking patterns between peri-adolescent and adult and female and male P rats, (d) individual licking patterns revealed that alcohol was consumed in bouts often exceeding the amount required to self-administer 1 g/kg of alcohol, and (e) BECs at the end of the dark cycle, on the 30th day of alcohol access, averaged 50 mg%, with alcohol intakes during the last 1 to 2 h averaging 1.2 g/kg. Overall, these findings indicate that alcohol drinking patterns differ across the age and sex of P rats. This suggests that the effectiveness of treatments for reducing excessive alcohol intake may vary depending upon the age and/or sex of the subjects being tested.

  20. Beneficial effect of zinc chloride and zinc ionophore pyrithione on attenuated cardioprotective potential of preconditioning phenomenon in STZ-induced diabetic rat heart.

    PubMed

    Jamwal, Sumit; Kumar, Kushal; Reddy, B V Krishna

    2016-05-01

    Ischemic preconditioning (IPC) is well demonstrated to produce cardioprotection by phosphorylation and subsequent inactivation of glycogen synthase kinase-3β (GSk-3β) in the normal rat heart, but its effect is attenuated in the diabetic rat heart. This study was designed to investigate the effect of zinc chloride and zinc ionophore pyrithione (ZIP) on the attenuated cardioprotective potential of IPC in the diabetic rat heart. Diabetes mellitus (DM) was induced by a single intraperitoneal administration of streptozotocin (STZ) (50 mg/kg; i.p). The isolated perfused rat heart was subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and cardiac injury was measured by estimating lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the coronary effluent. Also, GSK-3β was measured and neutrophil accumulation was measured by estimating myeloperoxidase (MPO) levels. IPC significantly decreased the myocardial infarct size, the release of LDH and CK-MB, the GSK-3β levels and the MPO levels in the normal rat heart. Pre- and post-ischemic treatment with zinc chloride and zinc ionophore pyrithione (ZIP) in the normal and diabetic rat hearts significantly decreased the myocardial infarct size, the level of CK-MB and LDH in the coronary effluent and GSK-3β and MPO levels. Our results suggest that pharmacological preconditioning with zinc chloride and ZIP significantly restored the attenuated cardioprotective potential of IPC in the diabetic rat heart. PMID:26423303

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

    PubMed Central

    Farraj, Aimen K.

    2013-01-01

    Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel engine exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance of normal cardiac function. To explore this putative mechanism, we examined cardiophysiologic responses to DE inhalation in a model of aged heart failure–prone rats without signs or symptoms of overt heart failure. We hypothesized that acute DE exposure would alter heart rhythm, cardiac electrophysiology, and ventricular performance and dimensions consistent with autonomic imbalance while increasing biochemical markers of toxicity. Spontaneously hypertensive heart failure rats (16 months) were exposed once to whole DE (4h, target PM2.5 concentration: 500 µg/m3) or filtered air. DE increased multiple heart rate variability (HRV) parameters during exposure. In the 4h after exposure, DE increased cardiac output, left ventricular volume (end diastolic and systolic), stroke volume, HRV, and atrioventricular block arrhythmias while increasing electrocardiographic measures of ventricular repolarization (i.e., ST and T amplitudes, ST area, T-peak to T-end duration). DE did not affect heart rate relative to air. Changes in HRV positively correlated with postexposure changes in bradyarrhythmia frequency, repolarization, and echocardiographic parameters. At 24h postexposure, DE-exposed rats had increased serum C-reactive protein and pulmonary eosinophils. This study demonstrates that cardiac effects of DE inhalation are likely to occur through changes in autonomic balance associated with modulation of cardiac electrophysiology and mechanical function and may offer insights into the adverse health effects of traffic-related air pollutants. PMID:23047911

  2. Cyclic AMP-receptor proteins in heart muscle of rats flown on Cosmos 1887.

    PubMed

    Mednieks, M I; Popova, I A; Grindeland, R E

    1991-10-01

    A frequent cellular response to organismal stress is the increase in ligand binding by beta-adrenergic receptors. The extracellular signal is amplified by intracellular increases in cyclic AMP and the ensuing activation of cyclic AMP-dependent protein kinase (cAPK). The molecular mechanisms involve the binding of cyclic AMP to regulatory (R) subunits of cAPK, thus freeing the catalytic subunit for protein phosphorylation. This study was carried out to determine the cellular compartmentalization of the cyclic AMP-receptor proteins in heart ventricular tissue obtained from rats flown on the Cosmos 1887 mission. Photoaffinity labeling of soluble and particulate cell fractions with an [32P]-8-azido analog of cyclic AMP was followed by electrophoretic separation of the proteins and by autoradiographic identification of the labeled isoforms of cAPK R subunits. The results showed that RII in the particulate subcellular fraction was significantly decreased in heart cells from rats in the flight group when compared to controls. Protein banding patterns in both the cytoplasmic fraction and in a fraction enriched in chromatin-bound proteins showed some variability in tissues of individual animals, but exhibited no changes that could be directly attributed to flight conditions. No significant change was apparent in the distribution of RI or RII cyclic AMP binding in the soluble fractions. These findings indicate that the cardiac cell integrity or its protein content is not compromised under flight conditions. There is, however, what appears to be an adaptive molecular response which can be detected using microanalytical methods, indicating that a major hormone regulated mechanism may be affected during some phase of travel in space.

  3. Inhibition of KV7 Channels Protects the Rat Heart against Myocardial Ischemia and Reperfusion Injury.

    PubMed

    Hedegaard, Elise R; Johnsen, Jacob; Povlsen, Jonas A; Jespersen, Nichlas R; Shanmuganathan, Jeffrey A; Laursen, Mia R; Kristiansen, Steen B; Simonsen, Ulf; Bøtker, Hans Erik

    2016-04-01

    The voltage-gated KV7 (KCNQ) potassium channels are activated by ischemia and involved in hypoxic vasodilatation. We investigated the effect of KV7 channel modulation on cardiac ischemia and reperfusion injury and its interaction with cardioprotection by ischemic preconditioning (IPC). Reverse-transcription polymerase chain reaction revealed expression of KV7.1, KV7.4, and KV7.5 in the left anterior descending rat coronary artery and all KV7 subtypes (KV7.1-KV7.5) in the left and right ventricles of the heart. Isolated hearts were subjected to no-flow global ischemia and reperfusion with and without IPC. Infarct size was quantified by 2,3,5-triphenyltetrazolium chloride staining. Two blockers of KV7 channels, XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone] (10 µM) and linopirdine (10 µM), reduced infarct size and exerted additive infarct reduction to IPC. An opener of KV7 channels, flupirtine (10 µM) abolished infarct size reduction by IPC. Hemodynamics were measured using a catheter inserted in the left ventricle and postischemic left ventricular recovery improved in accordance with reduction of infarct size and deteriorated with increased infarct size. XE991 (10 µM) reduced coronary flow in the reperfusion phase and inhibited vasodilatation in isolated small branches of the left anterior descending coronary artery during both simulated ischemia and reoxygenation. KV7 channels are expressed in rat coronary arteries and myocardium. Inhibition of KV7 channels exerts cardioprotection and opening of KV7 channels abrogates cardioprotection by IPC. Although safety issues should be further addressed, our findings suggest a potential role for KV7 blockers in the treatment of ischemia-reperfusion injury. PMID:26869667

  4. Non-steady-state calcium handling in failing hearts from the spontaneously hypertensive rat.

    PubMed

    Ward, Marie-Louise; Crossman, David J; Loiselle, Denis S; Cannell, Mark B

    2010-11-01

    It is generally agreed that changes in Ca(2+) cycling are often associated with heart failure, yet the impact of these changes on a beat-to-beat basis remains unclear. Measurements of isometric force and [Ca(2+)](i) were made at 37°C in left ventricular trabeculae from failing spontaneously hypertensive rat (SHR) hearts, and their normotensive Wistar-Kyoto (WKY) controls. At 1 Hz, peak stress was reduced in SHR (14.5 ± 2.4 mN mm(-2) versus 22.5 ± 6.7 mN mm⁻² for WKY), although the Ca(2+) transients were bigger (peak [Ca(2+)](i) 0.60 ± 0.08 μM versus 0.38 ± 0.03 μM for WKY) with a slower decay of fluorescence (time constant 0.105 ± 0.005 s versus 0.093 ± 0.002 s for WKY). To probe dynamic Ca(2+) cycling, two experimental protocols were used to potentiate force: (1) an interval of 30 s rest, and (2) a 30-s train of paired-pulses, and the recirculation fraction (RF) calculated for recovery to steady-state. No difference was found between rat strains for RF calculated from either peak force or Ca(2+), although the RF was dependent on potentiation protocol. Since SR uptake is slower in SHR, the lack of change in RF must be due to a parallel decrease in trans-sarcolemmal Ca(2+) extrusion. This view was supported by a slower decay of caffeine-induced Ca(2+) transients in SHR trabeculae. Confocal analysis of LV free wall showed t-tubules were distorted in SHR myocytes, with reduced intensity of NCX and SERCA2a labelling in comparison to WKY.

  5. Cyclic AMP-receptor proteins in heart muscle of rats flown on Cosmos 1887.

    PubMed

    Mednieks, M I; Popova, I A; Grindeland, R E

    1991-10-01

    A frequent cellular response to organismal stress is the increase in ligand binding by beta-adrenergic receptors. The extracellular signal is amplified by intracellular increases in cyclic AMP and the ensuing activation of cyclic AMP-dependent protein kinase (cAPK). The molecular mechanisms involve the binding of cyclic AMP to regulatory (R) subunits of cAPK, thus freeing the catalytic subunit for protein phosphorylation. This study was carried out to determine the cellular compartmentalization of the cyclic AMP-receptor proteins in heart ventricular tissue obtained from rats flown on the Cosmos 1887 mission. Photoaffinity labeling of soluble and particulate cell fractions with an [32P]-8-azido analog of cyclic AMP was followed by electrophoretic separation of the proteins and by autoradiographic identification of the labeled isoforms of cAPK R subunits. The results showed that RII in the particulate subcellular fraction was significantly decreased in heart cells from rats in the flight group when compared to controls. Protein banding patterns in both the cytoplasmic fraction and in a fraction enriched in chromatin-bound proteins showed some variability in tissues of individual animals, but exhibited no changes that could be directly attributed to flight conditions. No significant change was apparent in the distribution of RI or RII cyclic AMP binding in the soluble fractions. These findings indicate that the cardiac cell integrity or its protein content is not compromised under flight conditions. There is, however, what appears to be an adaptive molecular response which can be detected using microanalytical methods, indicating that a major hormone regulated mechanism may be affected during some phase of travel in space. PMID:1662483

  6. Strategies to Enhance the Effectiveness of Adult Stem Cell Therapy for Ischemic Heart Diseases Affecting the Elderly Patients

    PubMed Central

    Khatiwala, Roshni

    2016-01-01

    Myocardial infarctions and chronic ischemic heart disease both commonly and disproportionately affect elderly patients more than any other patient population. Despite available treatments, heart tissue is often permanently damaged as a result of cardiac injury. This review aims to summarize recent literature proposing the use of modified autologous adult stem cells to promote healing of post-infarct cardiac tissue. This novel cellular treatment involves isolation of adult stem cells from the patient, in vitro manipulation of these stem cells, and subsequent transplantation back into the patient’s own heart to accelerate healing. One of the hindrances affecting this process is that cardiac issues are increasingly common in elderly patients, and stem cells recovered from their tissues tend to be pre-senescent or already in senescence. As a result, harsh in vitro manipulations can cause the aged stem cells to undergo massive in vivo apoptosis after transplantation. The consensus in literature is that inhibition or reversal of senescence onset in adult stem cells would be of utmost benefit. In fact, it is believed that this strategy may lower stem cell mortality and coerce aged stem cells into adopting more resilient phenotypes similar to that of their younger counterparts. This review will discuss a selection of the most efficient and most-recent strategies used experimentally to enhance the effectiveness of current stem cell therapies for ischemic heart diseases. PMID:26779896

  7. Alternatively activated macrophages determine repair of the infarcted adult murine heart

    PubMed Central

    Shiraishi, Manabu; Shintani, Yasunori; Shintani, Yusuke; Ishida, Hidekazu; Saba, Rie; Yamaguchi, Atsushi; Adachi, Hideo; Yashiro, Kenta

    2016-01-01

    Alternatively activated (also known as M2) macrophages are involved in the repair of various types of organs. However, the contribution of M2 macrophages to cardiac repair after myocardial infarction (MI) remains to be fully characterized. Here, we identified CD206+F4/80+CD11b+ M2-like macrophages in the murine heart and demonstrated that this cell population predominantly increases in the infarct area and exhibits strengthened reparative abilities after MI. We evaluated mice lacking the kinase TRIB1 (Trib1–/–), which exhibit a selective depletion of M2 macrophages after MI. Compared with control animals, Trib1–/– mice had a catastrophic prognosis, with frequent cardiac rupture, as the result of markedly reduced collagen fibril formation in the infarct area due to impaired fibroblast activation. The decreased tissue repair observed in Trib1–/– mice was entirely rescued by an external supply of M2-like macrophages. Furthermore, IL-1α and osteopontin were suggested to be mediators of M2-like macrophage–induced fibroblast activation. In addition, IL-4 administration achieved a targeted increase in the number of M2-like macrophages and enhanced the post-MI prognosis of WT mice, corresponding with amplified fibroblast activation and formation of more supportive fibrous tissues in the infarcts. Together, these data demonstrate that M2-like macrophages critically determine the repair of infarcted adult murine heart by regulating fibroblast activation and suggest that IL-4 is a potential biological drug for treating MI. PMID:27140396

  8. Effect of diesel emissions and coal dust inhalation on heart and pulmonary arteries of rats

    SciTech Connect

    Vallyathan, V.; Virmani, R.; Rochlani, S.; Green, F.H.; Lewis, T.

    1986-01-01

    Fischer 344 (SPF) rats were exposed by inhalation to respirable particulate levels of 2 mg/m3 diesel emissions, diesel emissions plus coal dust, coal dust, or air for 7 h/d, 5 d/wk for 24 mo. The effects of treatment on body and heart weights, right and left ventricular wall thickness, severity of cardiomyopathy, and changes in the small pulmonary arteries were evaluated after 24 mo of exposure. In all dust-exposed animals, light microscopic examination of the lungs revealed dust-laden macrophages in alveolar spaces and focal accumulations of dust-laden macrophages near the respiratory bronchioles associated with hyperplasia of type II cells. This response was more prominent in animals exposed to diesel emissions alone. Age-related myocardial fibrosis and inflammatory infiltrates were common in all four groups. No statistically significant differences were detected between the groups for heart weights, ventricular wall thickness, and pulmonary arterial wall thickness. However, animals exposed to diesel emissions did show a consistent trend toward increased pulmonary arterial wall thickness, for all size categories of artery, compared to controls.

  9. Direct effects of (-)-epicatechin and procyanidin B2 on the respiration of rat heart mitochondria.

    PubMed

    Kopustinskiene, Dalia M; Savickas, Arunas; Vetchý, David; Masteikova, Ruta; Kasauskas, Arturas; Bernatoniene, Jurga

    2015-01-01

    Flavonol (-)-epicatechin and its derived dimer procyanidin B2, present in high amounts in cocoa products, have been shown to exert beneficial effects on the heart and cardiovascular system; however, their mechanism of action has not been fully elucidated. We studied effects of (-)-epicatechin and procyanidin B2 on the oxidative phosphorylation of isolated rat heart mitochondria. (-)-Epicatechin and procyanidin B2 had stimulating effect (up to 30% compared to control) on substrate-driven (State 2) mitochondrial respiration. Their effect was dependent on the respiratory substrates used. (-)-Epicatechin at higher concentrations (from 0.27 µg/mL) significantly decreased (up to 15%) substrate- and ADP-driven (State 3) mitochondrial respiration in case of pyruvate and malate oxidation only. Procyanidin B2 (0.7-17.9 ng/mL) inhibited State 3 respiration rate up to 19%, the most profound effect being expressed with succinate as the substrate. (-)-Epicatechin at concentrations of 0.23 µg/mL and 0.46 µg/mL prevented loss of the cytochrome c from mitochondria when substrate was succinate, supporting the evidence of membrane stabilizing properties of this flavonol. Thus, both (-)-epicatechin and procyanidin B2 directly influenced mitochondrial functions and the observed effects could help to explain cardiometabolic risk reduction ascribed to the consumption of modest amounts of cocoa products.

  10. Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue

    PubMed Central

    Cuello, Friederike; Luther, Pradeep; Schulze, Thomas; Eder, Alexandra; Streichert, Thomas; Mannhardt, Ingra; Hirt, Marc N.; Schaaf, Sebastian; Stenzig, Justus; Force, Thomas

    2016-01-01

    Introduction Left ventricular dysfunction is a frequent and potentially severe side effect of many tyrosine kinase inhibitors (TKI). The mode of toxicity is not identified, but may include impairment of mitochondrial or sarcomeric function, autophagy or angiogenesis, either as an on-target or off-target mechanism. Methods and Results We studied concentration-response curves and time courses for nine TKIs in three-dimensional, force generating engineered heart tissue (EHT) from neonatal rat heart cells. We detected a concentration- and time-dependent decline in contractile force for gefitinib, lapatinib, sunitinib, imatinib, sorafenib, vandetanib and lestaurtinib and no decline in contractile force for erlotinib and dasatinib after 96 hours of incubation. The decline in contractile force was associated with an impairment of autophagy (LC3 Western blot) and appearance of autophagolysosomes (transmission electron microscopy). Conclusion This study demonstrates the feasibility to study TKI-mediated force effects in EHTs and identifies an association between a decline in contractility and inhibition of autophagic flux. PMID:26840448

  11. Differential hemodynamic effects of ethanol on rat heart: Beneficial vs. detrimental actions

    SciTech Connect

    Zou, L.Y.; Alture, B.T.; Wu, F.; Barbour, R.L.; Altura, B.M. )

    1991-03-11

    Epidemiologic studies suggest that daily ingestion of small amounts of alcohol may protect the heart, whereas higher intake may be detrimental. The authors therefore studied cardiac performance of isolated working rat hearts during perfusion with Krebs-Nenseleit medium containing three different concentrations (conc) of ethanol (ET). ET produced a biphasic hemodynamic change depending upon conc. 45 mM ET was stimulatory; higher ET were depressive. 45 mM ET increased coronary flow (CF) by 45%, cardiac output (CO) 29%, stroke volume (SV) 30%, oxygen consumption (MVO{sub 2}) 29% at 25 min, respectively. However, higher conc of ET, e.g. 90 mM, depressed most parameters. CF was reduced by 62%, CO 56%, SV 57%, peak systolic pressure (PSP) 80%, and MVO{sub 2} 77%, respectively. Lactic acid (LA) fended to increase with decline of CF. 135 mM ET decreased all cardiac parameters and MVO{sub 2} rapidly and significantly from the first 5 min. LA, LDH and CPK levels tended to be elevated, and pH tended to be reduced. These data indicate that a low conc of ET is beneficial on cardiac performance; higher concentrations of ET are detrimental. High conc of ET decrease CF leading to hypoxia, metabolic acidosis of myocardium, and cell membrane damage.

  12. Interventricular comparison of the energetics of contraction of trabeculae carneae isolated from the rat heart

    PubMed Central

    Han, June-Chiew; Taberner, Andrew J; Nielsen, Poul M F; Loiselle, Denis S

    2013-01-01

    We compare the energetics of right ventricular and left ventricular trabeculae carneae isolated from rat hearts. Using our work-loop calorimeter, we subjected trabeculae to stress-length work (W), designed to mimic the pressure–volume work of the heart. Simultaneous measurement of heat production (Q) allowed calculation of the accompanying change of enthalpy (ΔH=W+Q). From the mechanical measurements (i.e. stress and change of length), we calculated work, shortening velocity and power. In combination with heat measurements, we calculated activation heat (QA), crossbridge heat (Qxb) and two measures of cardiac efficiency: ‘mechanical efficiency’ (ɛmech=W/ΔH) and ‘crossbridge efficiency’ (ɛxb=W/(ΔH–QA)). With respect to their left ventricular counterparts, right venticular trabeculae have higher peak shortening velocity, and higher peak mechanical efficiency, but with no difference of stress development, twitch duration, work performance, shortening power or crossbridge efficiency. That is, the 35% greater maximum mechanical efficiency of right venticular than left ventricular trabeculae (13.6 vs. 10.2%) is offset by the greater metabolic cost of activation (QA) in the latter. When corrected for this difference, crossbridge efficiency does not differ between the ventricles. PMID:23184511

  13. Effects of prolonged application of isoprenaline on intracellular free magnesium concentration in isolated heart of rat.

    PubMed Central

    Nishimura, H.; Matsubara, T.; Ikoma, Y.; Nakayama, S.; Sakamoto, N.

    1993-01-01

    1. The effect of prolonged application of isoprenaline on intracellular free-Mg2+ concentration ([Mg2+]i) was examined by use of 31P-nuclear magnetic resonance (31P-n.m.r.) in rat isolated hearts. Left ventricular pressure (LVP) was simultaneously measured. 2. [Mg2+]i was estimated from the separation of the alpha- and beta-ATP peaks, using the dissociation constant of MgATP 38 microM (established previously). In normal (phosphate-free, Krebs-Henseleit) solution, [Mg2+]i was approximately 0.4 mM. 3. When isoprenaline was applied for 100 min, a transient increase in [Mg2+]i was observed during the initial 25 min, whilst concentrations of ATP ([ATP]) and phosphocreatine ([PCr]) decreased and [Pi] correspondingly increased. During the subsequent 75 min of isoprenaline application, [Mg2+]i decreased below its resting levels. Washout of isoprenaline restored [Mg2+]i and [PCr], but [ATP] remained low. These changes elicited by isoprenaline were not observed in the presence of propranolol, a typical alpha-adrenoceptor blocker. 4. Isoprenaline increased both LVP and heart rate. The increased LVP and heart rate slowly returned to lower values during prolonged application of isoprenaline, but remained higher than those before application. 5. The transient rise in [Mg2+]i elicited by isoprenaline could be attributed to the decrease in [ATP] resulting in a release of Mg2+. The subsequent decrease in [Mg2+]i during the prolonged applications suggests that beta-adrenoceptor stimulation itself facilitates Mg(2+)-extruding mechanism(s). PMID:8358545

  14. Differential effects of furnidipine and its active metabolites in rat isolated working heart.

    PubMed

    Krzemiński, Tadeusz F; Hudziak, Damian; Sielańczyk, Andrzej W; Porc, Maurycy; Kedzia, Agnieszka

    2008-01-01

    1,4,-dihydropyridines, belonging to the class of "privileged structures", are known to protect the heart from stunning, ischemia and ventricular arrhythmias and mainly used in hypertension. The aim of this study was to compare the continuous infusion of parent drug, furnidipine, with its two active metabolites (M-2; M-3) in rat isolated working heart model, where the following parameters were measured and calculated: heart rate, preload pressure, aortic systolic and diastolic pressures (AoD), as well as +/-dP/dt, aortic (AF) and coronary flow (CF), oxygen and carbon dioxide partial pressures and pH values in pulmonary effluent, myocardial oxygen consumption. At first, the optimal vasodilatatory dose of M-2 was estimated and afterwards it was compared with equivalent doses of both remaining substances. The strongest vasodilatatory effects were observed after the lowest dose of M-2 was used (10(-7) M), at the same time being without marked influence on pressure parameters. The pro-drug evoked significantly weaker influence on both flows. Furthermore, furnidipine significantly reduced AoD and AF in comparison to control as well as +dP/dt in comparison to the initial values, while M-2 did not. Both metabolites caused a significant CF increase, but M-3 additionally the AoS and AoD decrease in comparison to the control. Regarding clear differences in the measured parameters between the pro-drug and its metabolites found, the obtained results allow to claim that the metabolites vs. furnidipine possess a beneficial influence. The distinct flow shift from aorta into the coronaries was observed only after M-2 and to a lesser extent--M-3. The cardio-depressant potency of both metabolites is overcome by advantageous vasodilatatory effect. M-2, being a final product, easier to control and at the same time a precursor of the new chemical class of therapeutics, is promising as a cardio-protective agent.

  15. The effects of acute alcohol on motor impairments in adolescent, adult, and aged rats.

    PubMed

    Ornelas, Laura C; Novier, Adelle; Van Skike, Candice E; Diaz-Granados, Jaime L; Matthews, Douglas B

    2015-03-01

    Acute alcohol exposure has been shown to produce differential motor impairments between aged and adult rats and between adolescent and adult rats. However, the effects of acute alcohol exposure among adolescent, adult, and aged rats have yet to be systematically investigated within the same project using a dose-dependent analysis. We sought to determine the age- and dose-dependent effects of acute alcohol exposure on gross and coordinated motor performance across the rodent lifespan. Adolescent (PD 30), adult (PD 70), and aged (approximately 18 months) male Sprague-Dawley rats were tested on 3 separate motor tasks: aerial righting reflex (ARR), accelerating rotarod (RR), and loss of righting reflex (LORR). In a separate group of animals, blood ethanol concentrations (BEC) were determined at multiple time points following a 3.0 g/kg ethanol injection. Behavioral tests were conducted with a Latin square repeated-measures design in which all animals received the following doses: 1.0 g/kg or 2.0 g/kg alcohol or saline over 3 separate sessions via intraperitoneal (i.p.) injection. During testing, motor impairments were assessed on the RR 10 min post-injection and on ARR 20 min post-injection. Aged animals spent significantly less time on the RR when administered 1.0 g/kg alcohol compared to adult rats. In addition, motor performance impairments significantly increased with age after 2.0 g/kg alcohol administration. On the ARR test, aged rats were more sensitive to the effects of 1.0 g/kg and 2.0 g/kg alcohol compared to adolescents and adults. Seven days after the last testing session, animals were given 3.0 g/kg alcohol and LORR was examined. During LORR, aged animals slept longer compared to adult and adolescent rats. This effect cannot be explained solely by BEC levels in aged rats. The present study suggests that acute alcohol exposure produces greater motor impairments in older rats when compared to adolescent and adult rats and begins to establish a

  16. The Efficiency of Barley (Hordeum vulgare) Bran in Ameliorating Blood and Treating Fatty Heart and Liver of Male Rats

    PubMed Central

    Abulnaja, Khalid O.; El Rabey, Haddad A.

    2015-01-01

    The current study focused on testing the hypolipidemic activity of two doses of barley bran on hypercholesterolemic male rats. Twenty-four male albino rats weighing 180–200 gm were divided into four groups. The first group (G1) was the negative control, the second group (G2) was the positive control group fed 2% cholesterol in the diet, and rats of the third and the fourth groups were fed 2% cholesterol and were cosupplemented with 5% and 10% barley bran, respectively, for 8 weeks. The hypercholesterolemic rats of (G2) showed an increase in lipid profile, liver enzymes, lactate dehydrogenase, creatine kinase-MB, and lipid peroxide and a decrease in antioxidant enzymes, whereas kidney function, fasting blood sugar, glycated hemoglobin total protein, and total bilirubin were not significantly affected compared with the negative control group in G1. Moreover, histology of heart, liver, and kidney of G2 rats showed histopathological changes compared with the negative control. Administration of the two doses of barley bran in G3 and G4 to the hypercholesterolemic rats ameliorated the level of lipids, liver enzymes, lactate dehydrogenase, and creatine kinase-MB. In addition, the histology of heart, liver, and kidney tissues nearly restored the normal state as in G1. PMID:25866539

  17. Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult.

    PubMed

    Silva, A C; Rodrigues, S C; Caldeira, J; Nunes, A M; Sampaio-Pinto, V; Resende, T P; Oliveira, M J; Barbosa, M A; Thorsteinsdóttir, S; Nascimento, D S; Pinto-do-Ó, P

    2016-10-01

    A main challenge in cardiac tissue engineering is the limited data on microenvironmental cues that sustain survival, proliferation and functional proficiency of cardiac cells. The aim of our study was to evaluate the potential of fetal (E18) and adult myocardial extracellular matrix (ECM) to support cardiac cells. Acellular three-dimensional (3D) bioscaffolds were obtained by parallel decellularization of fetal- and adult-heart explants thereby ensuring reliable comparison. Acellular scaffolds retained main constituents of the cardiac ECM including distinctive biochemical and structural meshwork features of the native equivalents. In vitro, fetal and adult ECM-matrices supported 3D culture of heart-derived Sca-1(+) progenitors and of neonatal cardiomyocytes, which migrated toward the center of the scaffold and displayed elongated morphology and excellent viability. At the culture end-point, more Sca-1(+) cells and cardiomyocytes were found adhered and inside fetal bioscaffolds, compared to the adult. Higher repopulation yields of Sca-1(+) cells on fetal ECM relied on β1-integrin independent mitogenic signals. Sca-1(+) cells on fetal bioscaffolds showed a gene expression profile that anticipates the synthesis of a permissive microenvironment for cardiomyogenesis. Our findings demonstrate the superior potential of the 3D fetal microenvironment to support and instruct cardiac cells. This knowledge should be integrated in the design of next-generation biomimetic materials for heart repair.

  18. cap alpha. -skeletal and. cap alpha. -cardiac actin genes are coexpressed in adult human skeletal muscle and heart

    SciTech Connect

    Gunning, P.; Ponte, P.; Blau, H.; Kedes, L.

    1983-11-01

    The authors determined the actin isotypes encoded by 30 actin cDNA clones previously isolated from an adult human muscle cDNA library. Using 3' untranslated region probes, derived from ..cap alpha.. skeletal, ..beta..- and ..gamma..-actin cDNAs and from an ..cap alpha..-cardiac actin genomic clone, they showed that 28 of the cDNAs correspond to ..cap alpha..-skeletal actin transcripts. Unexpectedly, however, the remaining two cDNA clones proved to derive from ..cap alpha..-cardiac actin mRNA. Sequence analysis confirmed that the two skeletal muscle ..cap alpha..-cardiac actin cDNAs are derived from transcripts of the cloned ..cap alpha..-cardiac actin gene. Comparison of total actin mRNA levels in adult skeletal muscle and adult heart revealed that the steady-state levels in skeletal muscle are about twofold greater, per microgram of total cellular RNA, than those in heart. Thus, in skeletal muscle and in heart, both of the sarcomeric actin mRNA isotypes are quite abundant transcripts. They conclude that ..cap alpha..-skeletal and ..cap alpha..-cardiac actin genes are coexpressed as an actin pair in human adult striated muscles. Since the smooth-muscle actins (aortic and stomach) and the cytoplasmic actins (..beta.. and ..gamma..) are known to be coexpressed in smooth muscle and nonmuscle cells, respectively, they postulate that coexpression of actin pairs may be a common feature of mammalian actin gene expression in all tissues.

  19. Autonomic control of heart rate and blood pressure in spontaneously hypertensive rats during aversive classical conditioning.

    PubMed

    Hatton, D C; Buchholz, R A; Fitzgerald, R D

    1981-12-01

    An examination was made of the heart rate (HR) and blood pressure (BP) responses of 7-9-wk-old spontaneously hypertensive rats (SHR) and genetical control Wistar/Kyoto (WKY) rats during aversive classical conditioning. Subsequent to the development of conditioned responding (CRs), assessments were made of the effects of selective autonomic blockade by methyl atropine (10 mg/kg), phentolamine (2 mg/kg), and propranolol (2 mg/kg). The CR complex in the two strains consisted of pressor BP CRs in conjunction with vagally mediated decelerative HR CRs in the SHR strain and sympathetically mediated accelerative HR CRs in the WKY strain. The decelerative SHR HR CR did not appear to be secondary to baroreceptor reflex activity, although such activity did appear to be involved in the pressor BP and decelerative HR orienting response (OR) and unconditioned response (UR) complex of the SHRs on the initial application of the CS and the US, respectively. Augmented pressor BP ORs, CRs, and URs in the SHRs relative to the WKYs and differential drug effects on BP and HR baselines of the two strains suggested the presence of enhanced sympathetic activity in the SHRs that was not reflected in the SHR decelerative HR CR. Phentolamine unmasked evidence of reflex beta 2-vasodilation deficiency in the SHRs that could have contributed to the enhancement of their BP OR and CR.

  20. Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart.

    PubMed Central

    Bani, D.; Masini, E.; Bello, M. G.; Bigazzi, M.; Sacchi, T. B.

    1998-01-01

    Myocardial injury caused by ischemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, platelet and mast cell activation, and peroxidation of cell membrane lipids, which are followed by myocardial cell alterations resulting eventually in cell necrosis. The current study was designed to test the possible cardioprotective effect of the hormone relaxin, which has been found to cause coronary vessel dilation and to inhibit platelet and mast cell activation. Ischemia (for 30 minutes) was induced in rat hearts in vivo by ligature of the left anterior descending coronary artery; reperfusion (for 60 minutes or less if the rats died before this predetermined time) was induced by removal of the ligature. Relaxin (100 ng) was given intravenously 30 minutes before ischemia. The results obtained showed that relaxin strongly reduces 1) the extension of the myocardial areas affected by ischemia-reperfusion-induced damage, 2) ventricular arrhythmias, 3) mortality, 4) myocardial neutrophil number, 5) myeloperoxidase activity, a marker of neutrophil accumulation, 6) production of malonyldialdehyde, an end product of lipid peroxidation, 7) mast cell granule release, 8) calcium overload, and 9) morphological signs of myocardial cell injury. This study shows that relaxin can be regarded as an agent with a marked cardioprotective action against ischemia-reperfusion-induced myocardial injury. Images Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:9588905

  1. Altered profile of gene expression in rat hearts induced by chronic nicotine consumption.

    PubMed

    Hu, Dahai; Cao, Kun; Peterson-Wakeman, Robert; Wang, Rui

    2002-10-01

    Using a cDNA microarray technique, we analyzed the expression profile of 1081 genes in the whole heart tissue of rats. The expressions of three classes of genes encoding cellular energy metabolism enzymes, transmembrane receptors, and intracellular kinase network members were reduced by more than 2.5-fold in cardiac tissues from the rats fed with nicotine (3mg/kg/day) for 3 months. The down-regulated 11 genes included mitochondrial ATP synthase beta subunit, mitochondrial H(+) transporting ATP synthase F1 complex alpha subunit isoform 1, liver mitochondrial aldehyde dehydrogenase 2, glutathione-S-transferase mu type 2, corticotropin-releasing factor receptor 2, metabotropic glutamate receptor 2, N-methyl-D-aspartate receptor subtype 2B, muscarinic acetylcholine receptor M3, transmembrane receptor Unc5H1, glycogen synthase kinase 3alpha, and Ca(2+)/calmodulin-dependent protein kinase II beta subunit. It appears that chronic nicotine treatment affects cardiac function by modulating the expressions of genes involved in energy metabolism and signal transduction.

  2. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    PubMed

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF. PMID:22028869

  3. Testosterone differentially alters cocaine-induced ambulatory and rearing behavioral responses in adult and adolescent rats

    PubMed Central

    Minerly, AnaChristina E.; Wu, Hui Bing K.; Weierstall, Karen M.; Niyomchai, Tipyamol; Kemen, Lynne; Jenab, Shirzad; Quinones-Jenab, Vanya

    2016-01-01

    Little is known about the physiological and behavioral effects of testosterone when co-administered with cocaine during adolescence. The present study aimed to determine whether exogenous testosterone administration differentially alters psychomotor responses to cocaine in adolescent and adult male rats. To this end, intact adolescent (30-days-old) and adult (60-day-old) male Fisher rats were pretreated with vehicle (sesame oil) or testosterone (5 or 10 mg/kg) 45 minutes prior to saline or cocaine (20 mg/kg) administration. Behavioral responses were monitored 1 hour after drug treatment, and serum testosterone levels were determined. Serum testosterone levels were affected by age: saline- and cocaine-treated adults in the vehicle groups had higher serum testosterone levels than adolescents rats, but after co-administration of testosterone the adolescent rats had higher serum testosterone levels than the adults. Pretreatment with testosterone affected baseline activity in adolescent rats: 5 mg/kg of testosterone increased both rearing and ambulatory behaviors in saline-treated adolescent rats. After normalizing data to % saline, an interaction between hormone administration and cocaine-induced behavioral responses was observed; 5 mg/kg of testosterone decreased both ambulatory and rearing behaviors among adolescents whereas 10 mg/kg of testosterone decreased only rearing behaviors. Testosterone pretreatment did not alter cocaine-induced behavioral responses in adult rats. These findings suggest that adolescents are more sensitive than adults to an interaction between testosterone and cocaine, and, indirectly, suggest that androgen abuse may lessen cocaine-induced behavioral responses in younger cocaine users. PMID:19822170

  4. Low Cardiac Output Leads Hepatic Fibrosis in Right Heart Failure Model Rats

    PubMed Central

    Fujimoto, Yoshitaka; Urashima, Takashi; Shimura, Daisuke; Ito, Reiji; Kawachi, Sadataka; Kajimura, Ichige; Akaike, Toru; Kusakari, Yoichiro; Fujiwara, Masako; Ogawa, Kiyoshi; Goda, Nobuhito; Ida, Hiroyuki; Minamisawa, Susumu

    2016-01-01

    Background Hepatic fibrosis progresses with right heart failure, and becomes cardiac cirrhosis in a severe case. Although its causal factor still remains unclear. Here we evaluated the progression of hepatic fibrosis using a pulmonary artery banding (PAB)-induced right heart failure model and investigated whether cardiac output (CO) is responsible for the progression of hepatic fibrosis. Methods and Results Five-week-old Sprague-Dawley rats divided into the PAB and sham-operated control groups. After 4 weeks from operation, we measured CO by echocardiography, and hepatic fibrosis ratio by pathological examination using a color analyzer. In the PAB group, CO was significantly lower by 48% than that in the control group (78.2±27.6 and 150.1±31.2 ml/min, P<0.01). Hepatic fibrosis ratio and serum hyaluronic acid, an index of hepatic fibrosis, were significantly increased in the PAB group than those in the control group (7.8±1.7 and 1.0±0.2%, P<0.01, 76.2±27.5 and 32.7±7.5 ng/ml, P<0.01). Notably, the degree of hepatic fibrosis significantly correlated a decrease in CO. Immunohistological analysis revealed that hepatic stellate cells were markedly activated in hypoxic areas, and HIF-1α positive hepatic cells were increased in the PAB group. Furthermore, by real-time PCR analyses, transcripts of profibrotic and fibrotic factors (TGF-β1, CTGF, procollargen I, procollargen III, MMP 2, MMP 9, TIMP 1, TIMP 2) were significantly increased in the PAB group. In addition, western blot analyses revealed that the protein level of HIF-1α was significantly increased in the PAB group than that in the control group (2.31±0.84 and 1.0±0.18 arbitrary units, P<0.05). Conclusions Our study demonstrated that low CO and tissue hypoxia were responsible for hepatic fibrosis in right failure heart model rats. PMID:26863419

  5. An Autonomic Link Between Inhaled Diesel Exhaust and Impaired Cardiac Performance: Insight From Treadmill and Dobutamine Challenges in Heart Failure–Prone Rats

    PubMed Central

    Farraj, Aimen K.

    2013-01-01

    Cardiac disease exacerbation is associated with short-term exposure to vehicular emissions. Diesel exhaust (DE) might impair cardiac performance in part through perturbing efferent sympathetic and parasympathetic autonomic nervous system (ANS) input to the heart. We hypothesized that acute changes in ANS balance mediate decreased cardiac performance upon DE inhalation. Young adult heart failure–prone rats were implanted with radiotelemeters to measure heart rate (HR), HR variability (HRV), blood pressure (BP), core body temperature, and pre-ejection period (PEP, a contractility index). Animals pretreated with sympathetic antagonist (atenolol), parasympathetic antagonist (atropine), or saline were exposed to DE (500 µg/m3 fine particulate matter, 4h) or filtered air and then treadmill exercise challenged. At 1 day postexposure, separate rats were catheterized for left ventricular pressure (LVP), contractility, and lusitropy and assessed for autonomic influence using the sympathoagonist dobutamine and surgical vagotomy. During DE exposure, atenolol inhibited increases in HR, BP, and contractility, but not body temperature, suggesting a role for sympathetic dominance. During treadmill recovery at 4h post-DE exposure, HR and HRV indicated parasympathetic dominance in saline- and atenolol-pretreated groups that atropine inhibited. Conversely, at treadmill recovery 21h post-DE exposure, HRV and PEP indicated sympathetic dominance and subsequently diminished contractility that only atenolol inhibited. LVP at 1 day postexposure indicated that DE impaired contractility and lusitropy while abolishing parasympathetic-regulated cardiac responses to dobutamine. This is the first evidence that air pollutant inhalation both causes time-dependent oscillations between sympathetic and parasympathetic dominance and decreases cardiac performance via aberrant sympathetic dominance. PMID:23872579

  6. Unpredictable chronic stress in juvenile or adult rats has opposite effects, respectively, promoting and impairing resilience.

    PubMed

    Ricon, T; Toth, E; Leshem, M; Braun, K; Richter-Levin, G

    2012-01-01

    We evaluated the effects of early maternal deprivation (MD; age 7-14 days) alone or in combination with unpredictable chronic stress (UCS; MDUN; 28-84 days) on anxiety and learning in 90 days old adult rats. We hypothesized that exposure to both stressors (MDUN) would be more detrimental than exposure to one or neither. Unexpectedly, adult rats from the MDUN group did not differ from control animals, whereas adult MD animals exhibited impaired avoidance learning. We next investigated the effect of juvenile-onset (30-90 days) versus adult-onset (60-90 days) stress on avoidance learning in adulthood (90 days). We found that adult-onset chronic stress impaired avoidance learning and memory whereas juvenile-onset stress did not. Thus, the results again indicate that juvenile exposure to UCS induces resilience rather than impairment.

  7. Exergaming in older adults: A scoping review and implementation potential for patients with heart failure

    PubMed Central

    Jaarsma, Tiny; Strömberg, Anna

    2014-01-01

    Background: Physical activity can improve exercise capacity, quality of life and reduce mortality and hospitalization in patients with heart failure (HF). Adherence to exercise recommendations in patients with HF is low. The use of exercise games (exergames) might be a way to encourage patients with HF to exercise especially those who may be reluctant to more traditional forms of exercise. No studies have been conducted on patients with HF and exergames. Aim: This scoping review focuses on the feasibility and influence of exergames on physical activity in older adults, aiming to target certain characteristics that are important for patients with HF to become more physically active. Methods: A literature search was undertaken in August 2012 in the databases PsychInfo, PUBMED, Scopus, Web of Science and CINAHL. Included studies evaluated the influence of exergaming on physical activity in older adults. Articles were excluded if they focused on rehabilitation of specific limbs, improving specific tasks or describing no intervention. Fifty articles were found, 11 were included in the analysis. Results: Exergaming was described as safe and feasible, and resulted in more energy expenditure compared to rest. Participants experienced improved balance and reported improved cognitive function after exergaming. Participants enjoyed playing the exergames, their depressive symptoms decreased, and they reported improved quality of life and empowerment. Exergames made them feel more connected with their family members, especially their grandchildren. Conclusion: Although this research field is small and under development, exergaming might be promising in order to enhance physical activity in patients with HF. However, further testing is needed. PMID:24198306

  8. Adoption of American Heart Association 2020 ideal healthy diet recommendations prevents weight gain in young adults.

    PubMed

    Forget, Geneviève; Doyon, Myriam; Lacerte, Guillaume; Labonté, Mélissa; Brown, Christine; Carpentier, André C; Langlois, Marie-France; Hivert, Marie-France

    2013-11-01

    In 2010, the American Heart Association established the concept of ideal cardiovascular health. Nationally representative data estimated that <1% of Americans meet the seven health metrics required for achieving ideal cardiovascular health, with the main challenge residing in meeting the criteria for an ideal Healthy Diet Score. In a cohort of young adults (N=196), we aimed to investigate the prevalence of ideal cardiovascular health and ideal Healthy Diet Score and its association to weight gain over a 4-year follow-up period. Anthropometric measures, blood pressure, and blood samples were taken according to standardized procedures. Dietary intake was measured by a 3-day food diary and verified by a registered dietitian. We observed that only 0.5% of our sample met the criteria for ideal cardiovascular health and only 4.1% met the criteria for an ideal Healthy Diet Score. The components of the Healthy Diet Score with the lowest observance were consumption of fruits and vegetables (9.7%) and whole grains (14.8%). Meeting zero or one out of five of the Healthy Diet Score components was associated with increased risk of weight gain over 4 years compared with meeting at least two components (P=0.03). With the exception of dietary criteria, prevalence was high for achieving ideal levels of the remaining six cardiovascular health metrics. In conclusion, in this sample