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Sample records for reperfusion cardiac function

  1. Protective function of tocilizumab in human cardiac myocytes ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Hai-Feng Cheng; Yan Feng; Da-Ming Jiang; Kai-Yu Tao; Min-Jian Kong

    2015-01-01

    Objective:To investigate the protective function of tocilizumab in human cardiac myocytes ischemia-reperfusion injury.Methods:The human cardiac myocytes were treated by tocilizumab with different concentrations(1.0 mg/mL, 3.0 mg/mL, 5.0 mg/mL) for 24 h,then cells were cultured in ischemia environment for 24 h and reperfusion environment for 1 h. The MTT and flow cytometry were used to detect the proliferation and apoptosis of human cardiac myocytes, respectively. The mRNA and protein expressions of Bcl-2 and Bax were measured by qRT-PCR and western blot, respectively.Results:Compared to the negative group, pretreated by tocilizumab could significantly enhance the proliferation viability and suppress apoptosis of human cardiac myocytes after suffering ischemia reperfusion injury(P<0.05).The expression of Bcl-2 in tocilizumab treated group were higher thanNC group(P<0.05), while theBax expression were lower(P<0.05).Conclusions:Tocilizumab could significantly inhibit apoptosis and keep the proliferation viability of human cardiac myocytes after suffering ischemia reperfusion injury. Tocilizumab may obtain a widely application in the protection of ischemia reperfusion injury.

  2. Preserved recovery of cardiac function following ischemia-reperfusion in mice lacking SIRT3.

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    Koentges, Christoph; Pfeil, Katharina; Meyer-Steenbuck, Maximilian; Lother, Achim; Hoffmann, Michael M; Odening, Katja E; Hein, Lutz; Bode, Christoph; Bugger, Heiko

    2016-01-01

    Lack of the mitochondrial deacetylase sirtuin 3 (SIRT3) impairs mitochondrial function and increases the susceptibility to induction of the mitochondrial permeability transition pore. Because these alterations contribute to myocardial ischemia-reperfusion (IR) injury, we hypothesized that SIRT3 deficiency may increase cardiac injury following myocardial IR. Hearts of 10-week-old mice were perfused in the isolated working mode and subjected to 17.5 min of global no-flow ischemia, followed by 30 min of reperfusion. Measurements before ischemia revealed a decrease in cardiac power (-20%) and rate pressure product (-15%) in SIRT3(-/-) mice. Mitochondrial state 3 respiration (-15%), ATP synthesis (-39%), and ATP/O ratios (-29%) were decreased in hearts of SIRT3(-/-) mice. However, percent recovery of cardiac power (WT 94% ± 9%; SIRT3(-/-) 89% ± 9%) and rate pressure product (WT 89% ± 16%; SIRT3(-/-) 96% ± 3%) following IR was similar in both groups. Myocardial infarct size was not increased in SIRT3(-/-) mice following permanent ligation of the left anterior descending coronary artery (LAD). Left ventricular pressure and dP/dtmax, and mitochondrial respiration and ATP synthesis were not different between groups following LAD ligation. Thus, despite pre-existing defects in cardiac function and mitochondrial respiratory capacity in SIRT3(-/-) mice, SIRT3 deficiency does not additionally impair cardiac function following IR or following myocardial infarction.

  3. Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion.

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    Li, Tingting; Xu, Jie; Qin, Xinghua; Hou, Zuoxu; Guo, Yongzheng; Liu, Zhenhua; Wu, Jianjiang; Zheng, Hong; Zhang, Xing; Gao, Feng

    2017-03-21

    Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia/reperfusion injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. Here we found that glucose uptake was remarkably diminished in myocardium following reperfusion in Sprague-Dawley rats as detected by 18F-labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by 3 folds and GLUT4 translocation remained unchanged compared with those of sham rats. The decreased glucose uptake was accompanied by suppressed glucose oxidation. Interestingly, stimulating glucose oxidation by inhibition of pyruvate dehydrogenase kinase 4 (PDK4), a rate-limiting enzyme for glucose oxidation, increased glucose uptake and alleviated ischemia/reperfusion injury. In vitro data in neonatal myocytes showed that PDK4 overexpression decreased glucose uptake, while its knockdown increased glucose uptake, suggesting a role of PDK4 in regulating glucose uptake. Moreover, inhibition of PDK4 increased myocardial glucose uptake with concomitant enhancement of cardiac insulin sensitivity following myocardial ischemia/reperfusion. These results showed that the suppressed glucose oxidation mediated by PDK4 contributes to the reduced glucose uptake in myocardium following reperfusion, and enhancement of glucose uptake exerts cardioprotection. The findings suggest that stimulating glucose oxidation via PDK4 could be an efficient approach to improve recovery from myocardial ischemia/reperfusion injury. Copyright © 2017, American Journal of Physiology-Endocrinology and Metabolism.

  4. Propofol improves cardiac functional recovery after ischemia-reperfusion by upregulating nitric oxide synthase activity in the isolated rat hearts

    Institute of Scientific and Technical Information of China (English)

    SUN Hai-yan; XUE Fu-shan; XU Ya-chao; LI Cheng-wen; XIONG Jun; LIAO Xu; ZHANG Yan-ming

    2009-01-01

    Background There are few studies to assess whether propofol attenuates myocardial ischemia-reperfusion injury via a mechanism related to nitric oxide (NO) route, so we designed this randomized blinded experiment to observe the changes of NO contents, nitric oxide synthase (NOS) activity, NOS contents in the myocardium, and cardiac function in ischemic reperfused isolated rat hearts, and to assess the relation between myocardial NO system and cardioprotection of propofol.Methods The hearts of 30 Sprague-Dawley male rats were removed, mounted on a Langendorff apparatus, and randomly assigned to one of three groups (n=10 each group) to be treated with the following treatments in a blinded manner: Group 1, control group, after perfusion with pure Krebs Henseleit bicarbonate (K-HBB) buffer solution for 15 minutes, hearts were subjected to 20 minutes global ischemia followed by 60 minutes reperfusion with pure K-HBB buffer; Group 2, after perfusion with K-HBB buffer solution containing propofol (10 μg/ml) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution; Group 3, after perfusion with K-HBB buffer solution containing propofol (10 μg/ml) and L-NAME (100 μmol/L) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution. The cardiac function was continuously monitored throughout the experiment.The coronary flow was also measured. An ISO-NO electrode was placed into the right atrium close to the coronary sinus to continuously measure NO concentration in the coronary effluent. The tissue samples from apex of hearts in Groups 1 and 2 were obtained to measure the NOS activity by spectrophotometry and the NOS contents by immunohistochemistry, respectively.Results The cardiac function was significantly inhibited after ischemia and then gradually improved with reperfusion in all three groups. As compared with Group 1

  5. Diverse Effects of L-arginine on Cardiac Function of Rats Subjected to Myocardial Ischemia and Reperfusion in vivo

    Institute of Scientific and Technical Information of China (English)

    Xiaoliang WANG; Feng LIANG; Xiangying JIAO; Lei LIU; Xiaojie BAI; Meixia LI; Jianmin ZHI; Huirong LIU

    2007-01-01

    In vivo administration of L-arginine at different time points during the course of myocardial ischemia and reperfusion (MI/R) has been shown to differentially regulate postischemic apoptosis.Cardiac function is one of the most important indexes used to judge the degree of myocardial injury.The present study attempted to determine whether in vivo administration of L-arginine at different stages of MI/R has a diverse influence on cardiac function of ischemic reperfused hearts and,if So,to investigate the mechanisms involved.Male adult rats were subjected to 30 min myocardial ischemia followed by 5 h reperfusion.An intravenous L-arginine bolus was given either 10 min before and 50 min after reperfusion (early treatment) or 3 h and 4 h after reperfusion (late treatment).Early treatment with L-arginine markedly increased the left ventricular systolic pressure (LVSP) and dP/dtmax,and decreased myocardial nitrotyrosine content.In strict contrast,late treatment with L-arginine resulted in a significant decrease in LVSP and dP/dtmx from 4 h to 5h after reperfusion,and increase in toxic peroxynitrite formation as measured by nitrotyrosine.These results suggest that the administration of L-arginine at different time points during the course of MI/R leads to diverse effects on cardiac dysfunction.Early supplementation decreased the nitrative stress and improved left ventricular function.However,late treatment with L-arginine increased the formation of peroxynitrite and aggravated cardiac functional injury.

  6. Physiologically tolerable insulin reduces myocardial injury and improves cardiac functional recovery in myocardial ischemic/reperfused dogs.

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    Zhang, Hang-Xiang; Zang, Yi-Min; Huo, Jian-Hua; Liang, Shao-Jun; Zhang, Hai-Feng; Wang, Yue-Min; Fan, Qian; Guo, Wen-Yi; Wang, Hai-Chang; Gao, Feng

    2006-12-01

    This study was designed to examine whether physiologically tolerable insulin, which maintains lower blood glucose, can protect the myocardium against ischemia/reperfusion (I/R) injury in a preclinical large animal model. Adult dogs were subjected to 50 minutes of myocardial ischemia (80% reduction in coronary blood flow) followed by 4 hours of reperfusion and treated with vehicle, glucose-insulin-potassium (GIK; glucose, 250 g/L; insulin, 60 U/L; potassium, 80 mmol/L), GK, or low-dose insulin (30 U/L) 10 minutes before reperfusion. Treatment with GIK exerted significant cardioprotective effects as evidenced by improved cardiac function, improved coronary blood flow, reduced infarct size, and myocardial apoptosis. In contrast, treatment with GK increased blood glucose level and aggravated myocardial I/R injury. It is interesting that treatment with insulin alone at the dose that reduced blood glucose to a clinically tolerable level exerted significant cardioprotective effects that were comparable to that seen in the GIK-treated group. This low-dose insulin had no effect on coronary blood flow after reperfusion but markedly reduced coronary reactive hyperemia and switched myocardial substrate uptake from fat to carbohydrate. Our results suggest that lower glucose supply to the ischemic myocardium at early reperfusion may create a "metabolic postconditioning" and thus reduce myocardial ischemia/reperfusion injury after prolonged reperfusion.

  7. Insulin improves cardiac myocytes contractile function recovery in simulated ischemia-reperfusion: Key role of Akt

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bo; ZHANG Haifeng; FAN Qian; MA Xinliang; GAO Feng

    2003-01-01

    The present study examined cardiac myocyte contractile and Ca2+ transient responses to insulin during simulated ischemia/reperfusion (I/R) and furtherinvestigated the role of protein kinase B (Akt) in the insulin- induced inotropic effect. Ventricular myocytes were enzymatically isolated from adult Sprague-Dawley rats and perfused with Tyrode solution while electrically field-stimulated. Simulated I/R was induced by perfusing the cells with chemical anoxic solution including sodium cyanide-sodium lactate for 15 min followed by reperfusion with normal oxygenated Tyrode solution with or without insulin. It is found that insulin only at concentration as high as 10 IU/L could increase cell shortening (16±5%, P < 0.05) in normal myocytes, whereas it concentration-dependently (0.01-10 IU/L) increased the contraction,the velocity of shortening/releng- theningand Ca2+ transient in I/R myocytes. In addition, insulin treatment (1 IU/L) increased Akt phosphorylation of I/R cardiomyocytes by 2.4-fold compared with that of the control (P < 0.01). Most importantly, pretreatment with LY 294002, a specific inhibitor of phosphatidylinositol 3′-kinase (PI3-kinase), significantly inhibited both Akt phosphorylation and the positive inotropic response to insulin in the I/R cardiomyocytes. These results suggest that insulin exerts direct positive inotropic effect by increasing Ca2+ transient of cardiomyocytes, which is enhanced in the pathological condition of I/R. Akt activation plays an important role in the insulin-induced improvement of myocyte contractile function following I/R.

  8. Nanosecond pulsed platelet-rich plasma (nsPRP) improves mechanical and electrical cardiac function following myocardial reperfusion injury.

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    Hargrave, Barbara; Varghese, Frency; Barabutis, Nektarios; Catravas, John; Zemlin, Christian

    2016-02-01

    Ischemia and reperfusion (I/R) of the heart is associated with biochemical and ionic changes that result in cardiac contractile and electrical dysfunction. In rabbits, platelet-rich plasma activated using nanosecond pulsed electric fields (nsPRP) has been shown to improve left ventricular pumping. Here, we demonstrate that nsPRP causes a similar improvement in mouse left ventricular function. We also show that nsPRP injection recovers electrical activity even before reperfusion begins. To uncover the mechanism of nsPRP action, we studied whether the enhanced left ventricular function in nsPRP rabbit and mouse hearts was associated with increased expression of heat-shock proteins and altered mitochondrial function under conditions of oxidative stress. Mouse hearts underwent 30 min of global ischemia and 1 h of reperfusion in situ. Rabbit hearts underwent 30 min of ischemia in vivo and were reperfused for 14 days. Hearts treated with nsPRP expressed significantly higher levels of Hsp27 and Hsp70 compared to hearts treated with vehicle. Also, pretreatment of cultured H9c2 cells with nsPRP significantly enhanced the "spare respiratory capacity (SRC)" also referred to as "respiratory reserve capacity" and ATP production in response to the uncoupler FCCP. These results suggest a cardioprotective effect of nsPRP on the ischemic heart during reperfusion.

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

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    Laila Elsherif

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

  10. Superior Cardiac Function Via Anaplerotic Pyruvate in the Immature Swine Heart After Cardiopulmonary Bypass and Reperfusion

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    Olson, Aaron; Hyyti, Outi M.; Cohen, Gordon A.; Ning, Xue-Han; Sadilek, Martin; Isern, Nancy G.; Portman, Michael A.

    2008-12-01

    Pyruvate produces inotropic responses in the adult reperfused heart. Pyruvate oxidation and anaplerotic entry into the citric acid cycle (CAC) via carboxylation are linked to stimulation of contractile function. The goals of this study were to determine if these metabolic pathways operate and are maintained in the developing myocardium after reperfusion. Immature male swine (age 10-18 days) were subjected to cardiopulmonary bypass (CPB). Intracoronary infusion of [2]-13C-pyruvate (to achieve a final concentration of 8 mM) was given for 35 minutes starting either during weaning (Group I), after discontinuation (Group II) or without (Control) CPB. Hemodynamic data was collected. 13C NMR spectroscopy was used to determine the fraction of pyruvate entering the CAC via pyruvate carboxylation (PC) to total CAC entry (PC plus decarboxlyation via pyruvate dehydrogenase). Liquid chromatography-mass spectrometry was used to determine total glutamate enrichment.

  11. Protective effects of sitagliptin on myocardial injury and cardiac function in an ischemia/reperfusion rat model.

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    Chang, Guanglei; Zhang, Peng; Ye, Lin; Lu, Kai; Wang, Ying; Duan, Qin; Zheng, Aihua; Qin, Shu; Zhang, Dongying

    2013-10-15

    The purpose of this study is to investigate the effects and the underlying mechanisms of sitagliptin pretreatment on myocardial injury and cardiac function in myocardial ischemia/reperfusion (I/R) rat model. The rat model of myocardial I/R was constructed by coronary occlusion. Rats were pretreated with sitagliptin (300 mg/kg/day) for 2 weeks, and then subjected to 30 min ischemia and 2h reperfusion. The release of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB), cardiac function and cardiomyocyte apoptosis were evaluated. The levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in heart and glucagon-like peptide-1 (GLP-1) level in plasma were measured. Western blot analysis was performed to detect the target proteins of sitagliptin. Our results showed that sitagliptin pretreatment decreased LDH and CK-MB release, and MDA level in I/R rats. More importantly, we revealed for the first time that sitagliptin pretreatment decreased cardiomyocyte apoptosis while increased the levels of GSH-Px and SOD in heart. Sitagliptin also increased GLP-1 level and enhanced cardiac function in I/R rats. Furthermore, sitagliptin pretreatment up-regulated Akt(serine473) and Bad(serine136) phosphorylation, reduced the ratio of Bax/Bcl-2, and decreased expression levels of cleaved caspase-3 and caspase-3. Interestingly, the above observed effects of sitagliptin were all abolished when co-administered with GLP-1 receptor antagonist exendin-(9-39) or PI3K inhibitor LY294002. Taken together, our data indicate that sitagliptin pretreatment could reduce myocardial injury and improve cardiac function in I/R rats by reducing apoptosis and oxidative damage. The underlying mechanism might be the activation of PI3K/Akt signaling pathway by GLP-1/GLP-1 receptor. Crown Copyright © 2013 Published by Elsevier B.V. All rights reserved.

  12. The Effect of Sleep Deprivation on Cardiac Function and Tolerance to Ischemia-Reperfusion Injury in Male Rats.

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    Jeddi, Sajad; Asl, Amir Nezami; Asgari, Alireza; Ghasemi, Asghar

    2016-01-01

    Sleep deprivation (SD) is strongly associated with elevated risk for cardiovascular disease. To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR) injury in male rats. SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP); heart rate (HR); and the maximum rate of increase and decrease of left ventricular pressure (± dp/dt). Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP) was measured at start and end of study. In the SD group, the baseline levels of LVDP (19%), +dp/dt (18%), and -dp/dt (21%) were significantly (p function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days. Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR.

  13. The Effect of Sleep Deprivation on Cardiac Function and Tolerance to Ischemia-Reperfusion Injury in Male Rats

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    Sajad Jeddi

    2015-01-01

    Full Text Available AbstractBackground:Sleep deprivation (SD is strongly associated with elevated risk for cardiovascular disease.Objective:To determine the effect of SD on basal hemodynamic functions and tolerance to myocardial ischemia-reperfusion (IR injury in male rats.Method:SD was induced by using the flowerpot method for 4 days. Isolated hearts were perfused with Langendorff setup, and the following parameters were measured at baseline and after IR: left ventricular developed pressure (LVDP; heart rate (HR; and the maximum rate of increase and decrease of left ventricular pressure (±dp/dt. Heart NOx level, infarct size and coronary flow CK-MB and LDH were measured after IR. Systolic blood pressure (SBP was measured at start and end of study.Results:In the SD group, the baseline levels of LVDP (19%, +dp/dt (18%, and -dp/dt (21% were significantly (p < 0.05 lower, and HR (32% was significantly higher compared to the controls. After ischemia, hearts from SD group displayed a significant increase in HR together with a low hemodynamic function recovery compared to the controls. In the SD group, NOx level in heart, coronary flow CK-MB and LDH and infarct size significantly increased after IR; also SD rats had higher SBP after 4 days.Conclusion:Hearts from SD rats had lower basal cardiac function and less tolerance to IR injury, which may be linked to an increase in NO production following IR.

  14. Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

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    Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

    2016-05-01

    Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.

  15. High-fat, low-carbohydrate diet alters myocardial oxidative stress and impairs recovery of cardiac function after ischemia and reperfusion in obese rats.

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    Liu, Jian; Lloyd, Steven G

    2013-04-01

    Obesity is associated with elevated risk of heart disease. A solid understanding of the safety and potential adverse effects of high-fat, low-carbohydrate diet (HFLCD) similar to that used by humans for weight loss on the heart is crucial. High fat intake is known to promote increases in reactive oxygen species and mitochondrial damage. We hypothesized that there would be adverse effects of HFLCD on myocardial ischemia/reperfusion injury through enhancing oxidative stress injury and impairing mitochondrial biogenesis in a nongenetic, diet-induced rat model of obesity. To test the hypothesis, 250-g male Sprague-Dawley rats were fed an obesity-promoting diet for 7 weeks to induce obesity, then switched to HFLCD or a low-fat control diet for 2 weeks. Isolated hearts underwent global low flow ischemia for 60 minutes and reperfusion for 60 minutes. High-fat, low-carbohydrate diet resulted in greater weight gain and lower myocardial glycogen, plasma adiponectin, and insulin. Myocardial antioxidant gene transcript and protein expression of superoxide dismutase and catalase were reduced in HFLCD, along with increased oxidative gene NADPH oxidase-4 transcript and xanthine oxidase activity, and a 37% increase in nitrated protein (nitrotyrosine) in HFLCD hearts. The cardiac expression of key mitochondrial regulatory factors such as nuclear respiratory factor-1 and transcription factor A-mitochondrial were inhibited and myocardial mitochondrial DNA copy number decreased. The cardiac expression of adiponectin and its receptors was down-regulated in HFLCD. High-fat, low-carbohydrate diet impaired recovery of left ventricular rate-pressure product after ischemia/reperfusion and led to 3.5-fold increased injury as measured by lactate dehydrogenase release. In conclusion, HFLCD leads to increased ischemic myocardial injury and impaired recovery of function after reperfusion and was associated with attenuation of mitochondrial biogenesis and enhanced oxidative stress in obese rats

  16. ACID-FUNCTIONALIZED SINGLE-WALLED CARBON NANOTUBES ENHANCE CARDIAC ISCHEMIC/REPERFUSION INJURY

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    Engineered nanotubes are being intensively developed for biomedical applications such as gene and drug delivery. Because of their unique properties, nanotubes can impose some potentially toxic effects, particularly if they have been modified to express functionally reactive chem...

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

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

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

  18. 舒芬太尼对家兔心肌缺血再灌注后心功能的影响%The Effects Sufentanil on Myocardial Ischemia Reperfusion Cardiac Function in Rabbits

    Institute of Scientific and Technical Information of China (English)

    刘金波; 张好华

    2012-01-01

      Objective To observe the effects sufentanil on myocardial ischemia reperfusion cardiac function in rabbits and discuss the mechanism for clinical rational drug use, to provide the basis. Methods 24 rabbits were divided into three groups: control, sufentanil group, ketone, winding sufentanil group, each period in ischemia-reperfusion determination cardiac index. Results LVDP and LVSP, ±dp/dt ischemia period LVEDP reduced significantly, and increased significantly. And LVDP and LVSP, ± dp/dt in myocardial reperfusion not drops further, and after recovery started the trend. Conclusion Myocardial ischemia reperfusion to the rabbit cardiac had significant inhibitory, sufentanil can significantly improve cardiac function, as partial cancellation collaterals ketone of sufentanil myocardial protection.%  目的观察舒芬太尼对家兔心肌缺血再灌注后心功能的影响并探讨其作用机制,为临床合理用药提供实验依据。方法24只家兔随机分为3组:对照组、舒芬太尼组、纳络酮-舒芬太尼组,于缺血再灌注各个时期测定心功能指标。结果左室收缩峰压(LVSP)、左室发展压(LVDP)和心室收缩的最大速率(±dp/dt)缺血期明显降低,左室舒张末压(LVEDP)明显升高。而 LVSP、 LVDP 和±dp/dt 于心肌再灌注后未再进一步下降。而是随时间延长逐渐恢复并明显好转。结论心肌缺血再灌注对兔心功能有明显抑制,舒芬太尼能明显改善心脏功能,纳络酮可部分取消舒芬太尼的心肌保护作用。

  19. Ischemia-reperfusion injury leads to distinct temporal cardiac remodeling in normal versus diabetic mice.

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    Megumi Eguchi

    Full Text Available Diabetes is associated with higher incidence of myocardial infarction (MI and increased propensity for subsequent events post-MI. Here we conducted a temporal analysis of the influence of diabetes on cardiac dysfunction and remodeling after ischemia reperfusion (IR injury in mice. Diabetes was induced using streptozotocin and IR performed by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for up to 42 days. We first evaluated changes in cardiac function using echocardiography after 24 hours reperfusion and observed IR injury significantly decreased the systolic function, such as ejection fraction, fractional shortening and end systolic left ventricular volume (LVESV in both control and diabetic mice. The longitudinal systolic and diastolic strain rate were altered after IR, but there were no significant differences between diabetic mice and controls. However, a reduced ability to metabolize glucose was observed in the diabetic animals as determined by PET-CT scanning using 2-deoxy-2-((18Ffluoro-D-glucose. Interestingly, after 24 hours reperfusion diabetic mice showed a reduced infarct size and less apoptosis indicated by TUNEL analysis in heart sections. This may be explained by increased levels of autophagy detected in diabetic mice hearts. Similar increases in IR-induced macrophage infiltration detected by CD68 staining indicated no change in inflammation between control and diabetic mice. Over time, control mice subjected to IR developed mild left ventricular dilation whereas diabetic mice exhibited a decrease in both end diastolic left ventricular volume and LVESV with a decreased intraventricular space and thicker left ventricular wall, indicating concentric hypertrophy. This was associated with marked increases in fibrosis, indicted by Masson trichrome staining, of heart sections in diabetic IR group. In summary, we demonstrate that diabetes principally influences distinct IR-induced chronic changes

  20. α-Lipoic acid reduces infarct size and preserves cardiac function in rat myocardial ischemia/reperfusion injury through activation of PI3K/Akt/Nrf2 pathway.

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    Chao Deng

    Full Text Available BACKGROUND: The present study investigates the effects and mechanisms of α-Lipoic acid (LA on myocardial infarct size, cardiac function and cardiomyocyte apoptosis in rat hearts subjected to in vivo myocardial ischemia/reperfusion (MI/R injury. METHODOLOGY/PRINCIPAL FINDINGS: Male adult rats underwent 30 minutes of ischemia followed by 3, 24, or 72 h of reperfusion. Animals were pretreated with LA or vehicle before coronary artery ligation. The level of MI/R- induced LDH and CK release, infarct size, cardiomyocyte apoptosis and cardiac functional impairment were examined and compared. Western blot analysis was performed to elucidate the mechanism of LA pretreatment. The level of inflammatory cytokine TNF-α released to serum and accumulated in injured myocardium as well as neutrophil accumulation in injured myocardium were also examined after MI/R injury. Our results reveal that LA administration significantly reduced LDH and CK release, attenuated myocardial infarct size, decreased cardiomyocytes apoptosis, and partially preserved heart function. Western blot analysis showed that LA pretreatment up-regulated Akt phosphorylation and Nrf2 nuclear translocation while producing no impact on p38MAPK activation or nitric oxide (NO production. LA pretreatment also increased expression of HO-1, a major target of Nrf2. LA treatment inhibited neutrophil accumulation and release of TNF-α. Moreover, PI3K inhibition abolished the beneficial effects of LA. CONCLUSIONS/SIGNIFICANCE: This study indicates that LA attenuates cardiac dysfunction by reducing cardiomyoctyes necrosis, apoptosis and inflammation after MI/R. LA exerts its action by activating the PI3K/Akt pathway as well as subsequent Nrf2 nuclear translocation and induction of cytoprotective genes such as HO-1.

  1. [The effect of argan oil on heart function during ischemia and reperfusion].

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    Benajiba, N; Morel, S; De Leiris, J; Boucher, F; Charrouf, Z; Mokhtar, N; Aguenaou, H

    2002-01-01

    The aim of this study was to evaluate the effect of organ oil on isolated heart function before and after ischemia and on the activity of cardiac antioxidant enzymes. 16 Wistar rats were divided into 2 groups; control group and treated group receiving 5 mL/kg/day of organ oil. After 8 weeks of treatment, hearts were perfused and subjected to a global ischemia followed by reperfusion. Activity of cardiac antioxidant enzymes was assessed in freeze-clamped hearts at the end of reperfusion. Results showed that organ oil induces: 1--damage to heart function during the preischemic period, 2--decreased functional recovery during reperfusion and 3--significant increase in catalase activity. It seems that, in our experimental conditions, organ oil increases heart sensitivity to ischemia and reperfusion. However, the mechanism involved has yet to be understood.

  2. Roles of Calcium Regulating MicroRNAs in Cardiac Ischemia-Reperfusion Injury

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    Eunhyun Choi

    2014-09-01

    Full Text Available Cardiac Ca2+ cycling and signaling are closely associated with cardiac function. Changes in cellular Ca2+ homeostasis may lead to aberrant cardiac rhythm and may play a critical role in the pathogenesis of cardiac diseases, due to their exacerbation of heart failure. MicroRNAs (miRNAs play a key role in the regulation of gene expression at the post-transcriptional level and participate in regulating diverse biological processes. The emerging evidence indicates that the expression profiles of miRNAs vary among human diseases, including cardiovascular diseases. Cardiac Ca2+-handling and signaling proteins are also regulated by miRNAs. Given the relationship between cardiac Ca2+ homeostasis and signaling and miRNA, Ca2+-related miRNAs may serve as therapeutic targets during the treatment of heart failure. In this review, we summarize the knowledge currently available regarding the role of Ca2+ in cardiac function, as well as changes in Ca2+ cycling and homeostasis and the handling of these processes by miRNAs during cardiac ischemia-reperfusion injury.

  3. Renal ischemia/reperfusion-induced cardiac hypertrophy in mice: Cardiac morphological and morphometric characterization

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    Cirino-Silva, Rogério; Kmit, Fernanda V; Trentin-Sonoda, Mayra; Nakama, Karina K; Panico, Karine; Alvim, Juliana M; Dreyer, Thiago R; Martinho-Silva, Herculano

    2017-01-01

    Background Tissue remodeling is usually dependent on the deposition of extracellular matrix that may result in tissue stiffness and impaired myocardium contraction. Objectives We had previously demonstrated that renal ischemia/reperfusion (I/R) is able to induce development of cardiac hypertrophy in mice. Therefore, we aimed to characterize renal I/R-induced cardiac hypertrophy. Design C57BL/6 J mice were subjected to 60 minutes’ unilateral renal pedicle occlusion, followed by reperfusion (I/R) for 5, 8, 12 or 15 days. Gene expression, protein abundance and morphometric analyses were performed in all time points. Results Left ventricle wall thickening was increased after eight days of reperfusion (p < 0.05). An increase in the number of heart ventricle capillaries and diameter after 12 days of reperfusion (p < 0.05) was observed; an increase in the density of capillaries starting at 5 days of reperfusion (p < 0.05) was also observed. Analyses of MMP2 protein levels showed an increase at 15 days compared to sham (p < 0.05). Moreover, TGF-β gene expression was downregulated at 12 days as well TIMP 1 and 2 (p < 0.05). The Fourier-transform infrared spectroscopy analysis showed that collagen content was altered only in the internal section of the heart (p < 0.05); such data were supported by collagen mRNA levels. Conclusions Renal I/R leads to impactful changes in heart morphology, accompanied by an increase in microvasculature. Although it is clear that I/R is able to induce cardiac remodeling, such morphological changes is present in only a section of the heart tissue.

  4. Cardiac lymphatic dynamics after ischemia and reperfusion - experimental model

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    Santos, A.C. E-mail: cristina@imagem.ibili.uc.pt; Lima, J.J.P. de; Botelho, M.F.; Pacheco, M.F.; Sousa, P.; Bernardo, J.; Ferreira, N.; Goncalves, L.; Aguiar, J.; Providencia, L.A.; Pauwels, E.K.J

    1998-10-01

    The aim of the present study was to investigate the lymphatic cardiac circulation in an experimental model of ischemia plus reperfusion in mongrel dogs (Canis familiaris L). As radiotracer we used 0.2-0.25 ml (111 MBq) of {sup 99m}Tc-Re{sub 2}S{sub 7} colloid ({+-}10 {mu}m), injected subcapsullary below the second diagonal of the descending anterior ligated coronary artery with a special needle. A {gamma}-camera/Starport + DecStation were used for data acquisition. Four experimental groups with five animals each were established: G I = controls; G II = immediately after acute myocardial infarction (AMI); G III = late infarction (5 days after AMI); G IV = ischemia (90 min) + reperfusion. Four regions of interest (ROIs) were chosen: injection area (ZA), above (ZB), near right (ZD), and far right (ZC) from ZA. Mean disappearance times in ZA and dynamic parameters in the other ROIs were determined from activity/time curves drawn in each area, using homemade software. The results obtained seem to indicate that the methodology is appropriate to a detailed study of lymphatic drainage in pathological situations in animal models.

  5. Protective role of fibrates in cardiac ischemia/reperfusion

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    G Singh

    2012-01-01

    Full Text Available Prevention of myocardial injury has been considered as the most important therapeutic challenge of today. Fibrates, the agonists of the peroxisome proliferator-activated receptor (PPAR-a receptor, have been regarded as potent therapeutic agents in this context. Hence, the present study has been designed to investigate the effect of fibrates, i.e., Clofibrate and Fenofibrate, the potent agonists PPAR-a, on ischemia-reperfusion (I/R-induced myocardial injury. The isolated Langendorff-perfused rat hearts were subjected to global ischemia for 30 minutes followed by reperfusion for 120 minutes. Myocardial infarct size and the release of lactate dehydrogenase (LDH and creatine kinase (CK in coronary effluent have been conducted to assess the degree of cardiac injury. Moreover, the oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation, and reduced glutathione. Clofibrate and Fenofibrate showed cardioprotection against I/R-induced myocardial injury in rat hearts as assessed in terms of reductions in myocardial infarct size, LDH, and CK levels in coronary effluent along with reduction in I/R-induced oxidative stress. It may be concluded that the observed cardioprotective potential of Clofibrate and Fenofibrate against I/R-induced myocardial injury was due to the reductions in infarct size and oxidative stress.

  6. The effect of Allium sativum on ischemic preconditioning and ischemia reperfusion induced cardiac injury

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    Bhatti Rajbir

    2008-01-01

    Full Text Available In the present study, the effect of garlic (Allium sativum extract on ischemic preconditioning and ischemia-reperfusion induced cardiac injury has been studied. Hearts from adult albino rats of Wistar strain were isolated and immediately mounted on Langendorff′s apparatus for retrograde perfusion. After 15 minutes of stabilization, the hearts were subjected to four episodes of 5 min ischemia, interspersed with 5 min reperfusion (to complete the protocol of ischemic preconditioning, 30 min global ischemia, followed by 120 min of reperfusion. In the control and treated groups, respective interventions were given instead of ischemic preconditioning. The magnitude of cardiac injury was quantified by measuring Lactate Dehydrogenase and creatine kinase concentration in the coronary effluent and myocardial infarct size by macroscopic volume method. Our study demonstrates that garlic extract exaggerates the cardio protection offered by ischemic preconditioning and per se treatment with garlic extract also protects the myocardium against ischemia reperfusion induced cardiac injury.

  7. Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia-reperfusion.

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    Li, Ting-Ting; Zhang, Yi-Shuai; He, Lan; Liu, Bin; Shi, Rui-Zheng; Zhang, Guo-Gang; Peng, Jun

    2012-07-01

    Myeloperoxidase (MPO) is involved in myocardial ischemia-reperfusion (IR) injury and vascular peroxidase (VPO) is a newly identified isoform of MPO. This study was conducted to explore whether VPO is involved in IR-induced cardiac dysfunction and apoptosis. In a rat Langendorff model of myocardial IR, the cardiac function parameters (left ventricular pressure and the maximum derivatives of left ventricular pressure and coronary flow), creatine kinase (CK) activity, apoptosis, VPO1 activity were measured. In a cell (rat-heart-derived H9c2 cells) model of hypoxia-reoxygenation (HR), apoptosis, VPO activity, and VPO1 mRNA expression were examined. In isolated heart, IR caused a marked decrease in cardiac function and a significant increase in apoptosis, CK, and VPO activity. These effects were attenuated by pharmacologic inhibition of VPO. In vitro, pharmacologic inhibition of VPO activity or silencing of VPO1 expression significantly suppressed HR-induced cellular apoptosis. Our results suggest that increased VPO activity contributes to IR-induced cardiac dysfunction and inhibition of VPO activity may have the potential clinical value in protecting the myocardium against IR injury.

  8. A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo.

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    Tang, Yao Liang; Qian, Keping; Zhang, Y Clare; Shen, Leping; Phillips, M Ian

    2005-12-01

    The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector'' system that amplifies cardioprotective gene expression. Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.

  9. miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models.

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    Zhenwei Pan

    Full Text Available Recent studies have revealed the critical role of microRNAs (miRNAs in regulating cardiac injury. Among them, the cardiac enriched microRNA-1(miR-1 has been extensively investigated and proven to be detrimental to cardiac myocytes. However, solid in vivo evidence for the role of miR-1 in cardiac injury is still missing and the potential therapeutic advantages of systemic knockdown of miR-1 expression remained unexplored. In this study, miR-1 transgenic (miR-1 Tg mice and locked nucleic acid modified oligonucleotide against miR-1 (LNA-antimiR-1 were used to explore the effects of miR-1 on cardiac ischemia/reperfusion injury (30 min ischemia followed by 24 h reperfusion. The cardiac miR-1 level was significantly increased in miR-1 Tg mice, and suppressed in LNA-antimiR-1 treated mice. When subjected to ischemia/reperfusion injury, miR-1 overexpression exacerbated cardiac injury, manifested by increased LDH, CK levels, caspase-3 expression, apoptosis and cardiac infarct area. On the contrary, LNA-antimiR-1 treatment significantly attenuated cardiac ischemia/reperfusion injury. The expression of PKCε and HSP60 was significantly repressed by miR-1 and enhanced by miR-1 knockdown, which may be a molecular mechanism for the role miR-1 in cardiac injury. Moreover, luciferase assay confirmed the direct regulation of miR-1 on protein kinase C epsilon (PKCε and heat shock protein 60 (HSP60. In summary, this study demonstrated that miR-1 is a causal factor for cardiac injury and systemic LNA-antimiR-1 therapy is effective in ameliorating the problem.

  10. Protective effects of hypovolemic hypotension preconditioning on cardiopulmonary function after myocardium ischemia/reperfusion injury

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    陈雪君; 王昕; 夏中元; 罗涛; 涂仲凡

    2004-01-01

    Objective: To identify the protective effects of hypovolemic hypotension preconditioning on cardiopulmonary function after myocardial ischemia/reperfusion injury and to explore the possible mechanism.Methods: Twenty-four male white rabbits were randomly assigned to two groups. In the control group, ischemia/reperfusion animals(Group I/R, n=10) were subjected to thirty-minute occlusion of left anterior descending coronary artery and two-hour reperfusion. Animals in hypovolemic hypotension preconditioning group (Group HHP, n=14) experienced brief systemic ischemia preconditioning through blood withdrawl to lower blood pressure to 40%-50% of the baseline before myocardial ischemia/reperfusion. Hemodynamic parameters were recorded. Blood sample was taken to measure superoxide dismutase (SOD), malondialdehyde (MDA) and nitrogen monoxide (NO) changes with blood gas analysis. Myocardium specimens were sampled to examine apoptosis-related gene interleukin-1 beta converting enzyme (ICE) mRNA. Results: Cardiac mechanical function and lung gas exchange remained stable in Group HHP with a significant increase in NO level; while in Group I/R without preconditioning, cardiopulmonary dysfunction was present after 2 h reperfusion associated with a significant reduction in NO formation and an increase in MDA (P<0.001). There was negative expression of ICE mRNA in the two groups.Conclusions: Hypovolemic hypotension preconditioning significantly improves cardiopulmonary function and increases NO formation and the protective benefit associated with hypovolemic hypotension preconditioning of the heart may be regulated through NO mediated mechanism.

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

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

    2016-07-01

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

  12. Arginase induction and activation during ischemia and reperfusion and functional consequences for the heart

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    Klaus-Dieter eSchlüter

    2015-03-01

    Full Text Available Induction and activation of arginase is among the fastest responses of the heart to ischemic events. Induction of arginase expression and enzyme activation under ischemic conditions shifts arginine consumption from nitric oxide formation (NO to the formation of ornithine and urea. In the heart such a switch in substrate utilisation reduces the impact of the NO/cGMP-pathway on cardiac function that requires intact electromechanical coupling but at the same time it induces ornithine-dependent pathways such as the polyamine metabolism. Both effects significantly reduce the recovery of heart function during reperfusion and thereby limits the success of reperfusion strategies. In this context, changes in arginine consumption trigger cardiac remodelling in an unfavourable way and increases the risk of arrhythmia, specifically in the initial post-ischemic period in which arginase activity is dominating. However, during the entire ischemic period arginase activation might be a meaningful adaptation that is specifically relevant for reperfusion following prolonged ischemic periods. Therefore, a precise understanding about the underlying mechanism that leads to arginase induction as well as of it’s mechanistic impact on post-ischemic hearts is required for optimizing reperfusion strategies. In this review we will summarize our current understanding of these processes and give an outlook about possible treatment options for the future.

  13. Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology.

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    Feng, Yuanbo; Chen, Feng; Yin, Ting; Xia, Qian; Liu, Yewei; Huang, Gang; Zhang, Jian; Oyen, Raymond; Ni, Yicheng

    2015-10-01

    Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P < 0.05), significantly increased blood flow in the AAR (P < 0.05), significantly decreased microvascular obstruction (P < 0.05), increased the perfusion density rate by 1.7-fold, lowered the AMI core/AAR ratio (P < 0.05), and increased the myocardial salvage index (P < 0.05). These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis (P < 0.05). Thus, CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility.

  14. Phosphomimetic modulation of eNOS improves myocardial reperfusion and mimics cardiac postconditioning in mice.

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    Terrence Pong

    Full Text Available OBJECTIVE: Myocardial infarction resulting from ischemia-reperfusion injury can be reduced by cardiac postconditioning, in which blood flow is restored intermittently prior to full reperfusion. Although key molecular mechanisms and prosurvival pathways involved in postconditioning have been identified, a direct role for eNOS-derived NO in improving regional myocardial perfusion has not been shown. The objective of this study is to measure, with high temporal and spatial resolution, regional myocardial perfusion during ischemia-reperfusion and postconditioning, in order to determine the contribution of regional blood flow effects of NO to infarct size and protection. METHODS AND RESULTS: We used myocardial contrast echocardiography to measure regional myocardial blood flow in mice over time. Reperfusion after myocardial ischemia-reperfusion injury is improved by postconditioning, as well as by phosphomimetic eNOS modulation. Knock-in mice expressing a phosphomimetic S1176D form of eNOS showed improved myocardial reperfusion and significantly reduced infarct size. eNOS knock-out mice failed to show cardioprotection from postconditioning. The size of the no-reflow zone following ischemia-reperfusion is substantially reduced by postconditioning and by the phosphomimetic eNOS mutation. CONCLUSIONS AND SIGNIFICANCE: Using myocardial contrast echocardiography, we show that temporal dynamics of regional myocardial perfusion restoration contribute to reduced infarct size after postconditioning. eNOS has direct effects on myocardial blood flow following ischemia-reperfusion, with reduction in the size of the no-reflow zone. These results have important implications for ongoing clinical trials on cardioprotection, because the degree of protective benefit may be significantly influenced by the regional hemodynamic effects of eNOS-derived NO.

  15. Cardiac Sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion.

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    Yamamoto, Tsunehisa; Tamaki, Kayoko; Shirakawa, Kohsuke; Ito, Kentaro; Yan, Xiaoxiang; Katsumata, Yoshinori; Anzai, Atsushi; Matsuhashi, Tomohiro; Endo, Jin; Inaba, Takaaki; Tsubota, Kazuo; Sano, Motoaki; Fukuda, Keiichi; Shinmura, Ken

    2016-04-15

    Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury.Am J Physiol Heart Circ Physiol 308: H894-H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (CM-Sirt1(-/-)) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (-40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM-Sirt1(-/-)mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM-Sirt1(-/-)mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventional C3 knockout (C3(-/-)) mice treated with CR was similar to that in the ad libitum-fed C3(-/-)mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting

  16. Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes.

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    Huang, Zhouqing; Han, Zhihua; Ye, Bozhi; Dai, Zhenyu; Shan, Peiren; Lu, Zhongqiu; Dai, Kezhi; Wang, Changqian; Huang, Weijian

    2015-09-05

    Ischemia/reperfusion (I/R)-induced autophagy increases the severity of cardiomyocyte injury. The aim of this study was to investigate the effects of berberine, a natural extract from Rhizoma coptidis, on the I/R-induced excessive autophagy in in vitro and in vivo models. Autophagy was increased both in H9c2 myocytes during hypoxia/reoxygenation (H/R) injury and in mouse hearts exposed to I/R. And the expression level of p-AMPK and p-mTORC2 (Ser2481) were increased during H/R period. In addition, the increased autophagy level was correlated with reduced cell survival in H9c2 myocytes and increased infarct size in mouse hearts. However, berberine treatment significantly enhanced the H/R-induced cell viability and reduced I/R-induced myocardial infarct size, which was accompanied by improved cardiac function. The beneficial effect of berberine is associated with inhibiting the cellular autophagy level, due to decreasing the expression level of autophagy-related proteins such as SIRT1, BNIP3, and Beclin-1. Furthermore, both the level of p-AMPK and p-mTORC2 (Ser2481) in H9c2 myocytes exposed to H/R were decreased by berberine. In summary, berberine protects myocytes during I/R injury through suppressing autophagy activation. Therefore, berberine may be a promising agent for treating I/R-induced cardiac myocyte injury.

  17. Chronic testosterone replacement exerts cardioprotection against cardiac ischemia-reperfusion injury by attenuating mitochondrial dysfunction in testosterone-deprived rats.

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    Wanpitak Pongkan

    Full Text Available Although testosterone deficiency is associated with increased risks of heart disease, the benefits of testosterone therapy are controversial. Moreover, current understanding on the cardiac effect of testosterone during cardiac ischemia-reperfusion (I/R periods is unclear. We tested the hypothesis that testosterone replacement attenuates the impairment of left ventricular (LV function and heart rate variability (HRV, and reduces the infarct size and arrhythmias caused by I/R injury in orchiectomized (ORX rats.ORX or sham-operated male Wistar rats (n = 24 were randomly divided and received either testosterone (2 mg/kg, subcutaneously administered or the vehicle for 8 weeks. The ejection fraction (EF and HRV were determined at baseline and the 4th and 8th week. I/R was performed by left anterior descending coronary artery ligation for 30 minutes, followed by a 120-minute reperfusion. LV pressure, arrhythmia scores, infarct size and cardiac mitochondrial function were determined.Prior to I/R, EF and HRV were impaired in the ORX group, but were restored in the testosterone-treated group. During I/R, arrhythmia scores and the infarct size were greater, and cardiac mitochondrial function was impaired, whereas the time to 1st VT/VF onset and the LV end-systolic pressure were decreased in the ORX group when compared to the sham group. Testosterone replacement attenuated the impairment of these parameters in ORX rats during I/R injury, but did not show any benefit or adverse effect in non-ORX rats.Testosterone replacement restores cardiac function and autonomic regulation, and exerts cardioprotective effects during the I/R period via mitochondrial protection in ORX rats.

  18. Chronic Testosterone Replacement Exerts Cardioprotection against Cardiac Ischemia-Reperfusion Injury by Attenuating Mitochondrial Dysfunction in Testosterone-Deprived Rats

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    Pongkan, Wanpitak; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2015-01-01

    Background Although testosterone deficiency is associated with increased risks of heart disease, the benefits of testosterone therapy are controversial. Moreover, current understanding on the cardiac effect of testosterone during cardiac ischemia-reperfusion (I/R) periods is unclear. We tested the hypothesis that testosterone replacement attenuates the impairment of left ventricular (LV) function and heart rate variability (HRV), and reduces the infarct size and arrhythmias caused by I/R injury in orchiectomized (ORX) rats. Methodology ORX or sham-operated male Wistar rats (n = 24) were randomly divided and received either testosterone (2 mg/kg, subcutaneously administered) or the vehicle for 8 weeks. The ejection fraction (EF) and HRV were determined at baseline and the 4th and 8th week. I/R was performed by left anterior descending coronary artery ligation for 30 minutes, followed by a 120-minute reperfusion. LV pressure, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. Results Prior to I/R, EF and HRV were impaired in the ORX group, but were restored in the testosterone-treated group. During I/R, arrhythmia scores and the infarct size were greater, and cardiac mitochondrial function was impaired, whereas the time to 1st VT/VF onset and the LV end-systolic pressure were decreased in the ORX group when compared to the sham group. Testosterone replacement attenuated the impairment of these parameters in ORX rats during I/R injury, but did not show any benefit or adverse effect in non-ORX rats. Conclusions Testosterone replacement restores cardiac function and autonomic regulation, and exerts cardioprotective effects during the I/R period via mitochondrial protection in ORX rats. PMID:25822979

  19. Dynamic mechanisms of cardiac oxygenation during brief ischemia and reperfusion

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    Parsons, W.J.; Rembert, J.C.; Bauman, R.P.; Greenfield, J.C. Jr.; Piantadosi, C.A. (Duke Univ., Durham (USA))

    1990-11-01

    Myocardial oxygenation may be altered markedly by changes in tissue blood flow. During brief ischemia and reperfusion produced by transient occlusion of the left anterior descending artery in 10 open-chest dogs, changes in the oxygenation of tissue hemoglobin (Hb) plus myoglobin (Mb) and the oxidation-reduction (redox) state of mitochondrial cytochrome aa3 were monitored continuously using near-infrared spectroscopy. The nondestructive optical technique indicated that coronary occlusion produced an abrupt drop in tissue oxygen stores (tHb02 + Mb02), tissue blood volume (tBV), and the oxidation level of cytochrome aa3. Changes in the cytochrome oxidation state were related inversely to transmural collateral blood flow within the ischemic region (r = 0.77) measured with radiolabeled microspheres. Furthermore, there was a direct relationship (r = 0.91) between collateral blood flow and the tissue level of desaturated Hb and Mb (tHb + Mb). Reperfusion after 2 min of ischemia led to a synchronous overshoot of baseline in coronary flow and tBV followed by supranormal increases in tHb + Mb02 and the oxidation level of cytochrome aa3. The tHb + Mb level increased transiently during reperfusion. This response correlated inversely with collateral flow during ischemia (r = 0.91). Accordingly, the time required to reach peak tHb + Mb levels was shortest in dogs with high collateral flows (r = 0.75). Thus collateral blood flow partially sustains myocardial oxygenation during coronary artery occlusion and influences tissue reoxygenation early during reperfusion.

  20. Sulforaphane improves oxidative status without attenuating the inflammatory response or cardiac impairment induced by ischemia-reperfusion in rats.

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    Bonetto, Jéssica Hellen Poletto; Fernandes, Rafael Oliveira; Seolin, Bruna Gazzi de Lima; Müller, Dalvana Daneliza; Teixeira, Rayane Brinck; Araujo, Alex Sander; Vassallo, Dalton; Schenkel, Paulo Cavalheiro; Belló-Klein, Adriane

    2016-05-01

    Sulforaphane, a natural isothiocyanate, demonstrates cardioprotection associated with its capacity to stimulate endogenous antioxidants and to inhibit inflammation. The aim of this study was to investigate whether sulforaphane is capable of attenuating oxidative stress and inflammatory responses through the TLR4/MyD88/NFκB pathway, and thereby could modulate post-ischemic ventricular function in isolated rat hearts submitted to ischemia and reperfusion. Male Wistar rats received sulforaphane (10 mg·kg(-1)·day(-1)) or vehicle i.p. for 3 days. Global ischemia was performed using isolated hearts, 24 h after the last injection, by interruption of the perfusion flow. The protocol included a 20 min pre-ischemic period followed by 20 min of ischemia and a 20 min reperfusion. Although no changes in mechanical function were observed, sulforaphane induced a significant increase in superoxide dismutase and heme oxygenase-1 expression (both 66%) and significantly reduced reactive oxygen species levels (7%). No differences were observed for catalase and glutathione peroxidase expression or their activities, nor for thioredoxin reductase, glutaredoxin reductase and glutathione-S-transferase. No differences were found in lipid peroxidation or TLR4, MyD88, and NF-κB expression. In conclusion, although sulforaphane was able to stimulate endogenous antioxidants modestly, this result did not impact inflammatory signaling or cardiac function of hearts submitted to ischemia and reperfusion.

  1. Postconditioning's Protection of THSG on Cardiac Ischemia-reperfusion Injury and Mechanism

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    2,3,5,4'-tetra-hydroxystilbene-2-O-glucoside (THSG), the water-soluble active components extracted from dried tuber root of Polygonum multiflorum (Polygonaceae), can promote the release of nitric oxide (NO) from vascular endothelial cells and has strong antioxidation. The postconditioning's protection of THSG on cardiac ischemia-reperfusion injury and the mechanism were investigated. After reperfusion for 3 h following occlusion of rat left anterior descending coronary artery (LAD) for 30 min, SαT recovery speed, arrhythmia and cardiac infarct size were observed.The ischemic size and infarct size was identified by using Evans blue and TTC staining methods respectively. The results showed that the infarct size in THSG 7. 5 mg/kg postconditioning group was significantly decreased from 43.6 %±9.1 % in mode group to 16.5 %±6.5 % (P<0.01).SαT recovery was quicker and the incidence of arrhythmia (55.6 % vs 100 %, P<0.05) was significantly lower than in control group. The infarct size in THSG+glybenclamide group was greater than in THSG group, but equivalent to that in control group (46.8 %±9.8 % vs 43.6 %±9. 1 %, P >0. 05), SαT recovery speed slower and the incidence of arrhythmia also lower (33. 3 % vs 100 %, P<0. 01), suggesting that glybenclamide could abolish the effects of THSG postconditioning reducing the cardiac infart size. It was concluded that THSG administration before reperfusion could effectively alleviate the cardiac reperfusion injury and possessed the postconditioning effects of reducing cardiac infarct size, which might be related with the KATP channel opening.

  2. Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

    Directory of Open Access Journals (Sweden)

    J.G.P. Tavares

    2015-02-01

    Full Text Available The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12 and epilepsy (n=14. It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01. During the ischemia period, there was an increase in the QRS interval (P<0.05 and a reduction in the P wave and QT intervals (P<0.05 for both in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01 was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode.

  3. Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, J.G.P. [Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Universidade Iguaçu, Campos V, Itaperuna, RJ (Brazil); Faculdade de Minas, Muriaé, MG (Brazil); Vasques, E.R. [Departamento de Gastroenterologia, LIM 37, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Arida, R.M. [Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cavalheiro, E.A. [Departamento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cabral, F.R.; Torres, L.B. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Menezes-Rodrigues, F.S.; Jurkiewicz, A.; Caricati-Neto, A. [Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Godoy, C.M.G. [Departamento de Ciência e Tecnologia, Universidade Federal de São Paulo, São José dos Campos, SP (Brazil); Gomes da Silva, S. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Núcleo de Pesquisas Tecnológicas, Programa Integrado em Engenharia Biomédica, Universidade de Mogi das Cruzes, Mogi das Cruzes, SP (Brazil)

    2015-01-13

    The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI) model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12) and epilepsy (n=14). It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01). During the ischemia period, there was an increase in the QRS interval (P<0.05) and a reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01) was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode.

  4. Protective effect of hyperoside on cardiac ischemia reperfusion injury through inhibition of ER stress and activation of Nrf2 signaling

    Institute of Scientific and Technical Information of China (English)

    Jia-Yin Hou; Ying Liu; Liang Liu; Xin-Ming Li

    2016-01-01

    Objective: To study the protective effect of hyperoside (Hyp) on cardiac ischemia reperfusion injury and its potential mechanism. Methods: Rats were divided into two groups for the evaluation, the Hyp (50 μM Hyp; n=8) and the control group (n=8). Rat hearts were isolated and perfused with Krebs-Henseleit buffer (KHB) for 30 min. After being inhibited with cardioplegic solution, they were stored for 4 h in B21 solution at 4 ℃. Afterwards, rat hearts were perfused with KHB again for 45 min. In this period, Hyp was added into solutions of cardioplegia for storage and KHB. Parameters of cardiac functions, including heart rate, the systolic pressure of the left ventricle, the end-diastolic pressure of the left ventricle, the developed pressure of the left ventricle, the left-ventricular systolic pressure and the peak rise rate of the pressure of the left ventricle were recorded. The levels of adenosine triphosphate (ATP), the content of malondialdehyde and apoptotic cells were determined to evaluate the protective effect of Hyp on hearts suffered from ischemia reperfusion injury. Moreover, cultured cardiac myocytes were subjected to the process simulating ischemia/reperfusion. What were analyzed included the endoplasmic reticulum (ER) stress hallmarks expressions, such as binding immunoglobulin protein and C/EBP homologous protein, using the western blot and real-time PCR. Besides, the NF-E2-related factor 2 (Nrf2) expression was measured to explore the potential mechanism. Results: Compared with the control group, the Hyp group had better cardiac functional parameters and higher ATP levels; pretreatment of Hyp greatly relieved the apoptosis of myocyte, decreased oxidative stress as well as ER stress and activated the signaling pathway of anti-oxidative Nrf2 to a further extent. Conclusions: Hyp plays an important role in preserving cardiac function by improving ATP levels of tissue, easing oxidative injury of myocardium and reducing apoptosis following IRI

  5. Glycyrrhiza glabra protects from myocardial ischemia-reperfusion injury by improving hemodynamic, biochemical, histopathological and ventricular function.

    Science.gov (United States)

    Ojha, Shreesh; Golechha, Mahaveer; Kumari, Santosh; Bhatia, Jagriti; Arya, Dharamvir S

    2013-01-01

    Present study evaluated the cardioprotective effect of Glycyrrhiza glabra against ischemia-reperfusion injury (I-R) induced by ligation of left anterior descending coronary artery (LADCA) in rats. Ligation of LADCA for 45 min followed by 60 min of reperfusion has induced significant (pglabra significantly (pglabra also prevented GSH depletion and inhibited lipid peroxidation in heart. In addition to improving biochemical indices of myocardial function, G. glabra also significantly (pglabra. Taken together, results of the present study clearly suggest the cardioprotective potential of G. glabra against myocardial infarction by amelioration of oxidative stress and favorable modulation of cardiac function.

  6. Ultrafine ambient particulate matter enhances cardiac ischemia and reperfusion injury

    Science.gov (United States)

    Epidemiological studies have demonstrated a consistent link between exposure to ambient particulate air pollutant (PM) and the incidence of cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of ambient PM. Mice were exposed to 1...

  7. DPP-4 Inhibitor and Estrogen Share Similar Efficacy Against Cardiac Ischemic-Reperfusion Injury in Obese-Insulin Resistant and Estrogen-Deprived Female Rats

    Science.gov (United States)

    Sivasinprasasn, Sivaporn; Tanajak, Pongpan; Pongkan, Wanpitak; Pratchayasakul, Wasana; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2017-01-01

    Estrogen deprivation aggravates cardiac injury after myocardial ischemia and reperfusion (I/R) injury. Although either estrogen or the dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin, reduces myocardial damage following cardiac I/R, their effects on the heart in obese-insulin resistant and estrogen deprived conditions remain unknown. Ovariectomized (O) rats (n = 36) were divided to receive either normal diet (NDO) or high-fat diet (HFO) for 12 weeks, followed by treatment with a vehicle, estrogen or vildagliptin for 4 weeks. The setting of in vivo cardiac I/R injury, 30-min ischemia and 120-min reperfusion, was performed. At 12 weeks after ovariectomy, both NDO and HFO rats exhibited an obese-insulin resistant condition. Both NDO and HFO rats treated with estrogen and vildagliptin showed reduced fasting plasma glucose, insulin and HOMA index. Both treatments improved cardiac function indicated by restoration of heart rate variability and increased %left ventricular ejection fraction (%LVEF). The treatments similarly protected cardiac mitochondrial function against I/R injury, leading to a reduction in the infarct size, oxidative stress and apoptosis in the ischemic myocardium. These findings demonstrate that vildagliptin effectively improves metabolic status, and shares similar efficacy to estrogen in reducing myocardial infarction and protecting cardiac mitochondrial function against I/R injury in estrogen-deprived obese-insulin resistant rats. PMID:28281660

  8. Low T3 State Is Correlated with Cardiac Mitochondrial Impairments after Ischemia Reperfusion Injury: Evidence from a Proteomic Approach

    Directory of Open Access Journals (Sweden)

    Francesca Forini

    2015-11-01

    Full Text Available Mitochondria are major determinants of cell fate in ischemia/reperfusion injury (IR and common effectors of cardio-protective strategies in cardiac ischemic disease. Thyroid hormone homeostasis critically affects mitochondrial function and energy production. Since a low T3 state (LT3S is frequently observed in the post infarction setting, the study was aimed to investigate the relationship between 72 h post IR T3 levels and both the cardiac function and the mitochondrial proteome in a rat model of IR. The low T3 group exhibits the most compromised cardiac performance along with the worst mitochondrial activity. Accordingly, our results show a different remodeling of the mitochondrial proteome in the presence or absence of a LT3S, with alterations in groups of proteins that play a key role in energy metabolism, quality control and regulation of cell death pathways. Overall, our findings highlight a relationship between LT3S in the early post IR and poor cardiac and mitochondrial outcomes, and suggest a potential implication of thyroid hormone in the cardio-protection and tissue remodeling in ischemic disease.

  9. Conditioning techniques and ischemic reperfusion injury in relation to on-pump cardiac surgery

    DEFF Research Database (Denmark)

    Holmberg, Fredrik Eric Olof; Ottas, Konstantin Alex; Andreasen, Charlotte

    2014-01-01

    OBJECTIVES: The objective was to investigate the potential protective effects of two conditioning methods, on myocardial ischemic and reperfusion injury in relation to cardiac surgery. DESIGN: Totally 68 patients were randomly assigned to either a control group (n = 23), a remote ischemic....... The other secondary endpoints were metabolic parameters related to myocardial ischemia, measured using microdialysis technique, as well as other operative- and postoperative data. RESULTS: Postoperative cardiac enzyme release indicated a possible beneficial effect of the interventions, but the difference......, unable to show distinct protective effects of the studied conditioning methods. However, this trial can hopefully contribute to generate a productive discussion concerning limitations and future use of cardiac conditioning as well as microdialysis technique....

  10. Calpains and proteasomes mediate degradation of ryanodine receptors in a model of cardiac ischemic reperfusion.

    Science.gov (United States)

    Pedrozo, Zully; Sánchez, Gina; Torrealba, Natalia; Valenzuela, Rodrigo; Fernández, Carolina; Hidalgo, Cecilia; Lavandero, Sergio; Donoso, Paulina

    2010-03-01

    Type-2 ryanodine receptors (RyR2)--the calcium release channels of cardiac sarcoplasmic reticulum--have a central role in cardiac excitation-contraction coupling. In the heart, ischemia/reperfusion causes a rapid and significant decrease in RyR2 content but the mechanisms responsible for this effect are not fully understood. We have studied the involvement of three proteolytic systems--calpains, the proteasome and autophagy--on the degradation of RyR2 in rat neonatal cardiomyocyte cultures subjected to simulated ischemia/reperfusion (sI/R). We found that 8h of ischemia followed by 16h of reperfusion decreased RyR2 content by 50% without any changes in RyR2 mRNA. Specific inhibitors of calpains and the proteasome prevented the decrease of RyR2 caused by sI/R, implicating both pathways in its degradation. Proteasome inhibitors also prevented the degradation of calpastatin, the endogenous calpain inhibitor, hindering the activation of calpain induced by calpastatin degradation. Autophagy was activated during sI/R as evidenced by the increase in LC3-II and beclin-1, two proteins involved in autophagosome generation, and in the emergence of GFP-LC3 containing vacuoles in adenovirus GFP-LC3 transduced cardiomyocytes. Selective autophagy inhibition, however, induced even further RyR2 degradation, making unlikely the participation of autophagy in sI/R-induced RyR2 degradation. Our results suggest that calpain activation as a result of proteasome-induced degradation of calpastatin initiates RyR2 proteolysis, which is followed by proteasome-dependent degradation of the resulting RyR2 fragments. The decrease in RyR2 content during ischemia/reperfusion may be relevant to the decrease of heart contractility after ischemia.

  11. Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes

    Directory of Open Access Journals (Sweden)

    Urankar Rakhee N

    2012-10-01

    Full Text Available Abstract Background The exceptional physical-chemical properties of carbon nanotubes have lead to their use in diverse commercial and biomedical applications. However, their utilization has raised concerns about human exposure that may predispose individuals to adverse health risks. The present study investigated the susceptibility to cardiac ischemic injury following a single exposure to various forms of multi-walled carbon nanotubes (MWCNTs. It was hypothesized that oropharyngeal aspiration of MWCNTs exacerbates myocardial ischemia and reperfusion injury (I/R injury. Methods Oropharyngeal aspiration was performed on male C57BL/6J mice with a single amount of MWCNT (0.01 - 100 μg suspended in 100 μL of a surfactant saline (SS solution. Three forms of MWCNTs were used in this study: unmodified, commercial grade (C-grade, and functionalized forms that were modified either by acid treatment (carboxylated, COOH or nitrogenation (N-doped and a SS vehicle. The pulmonary inflammation, serum cytokine profile and cardiac ischemic/reperfusion (I/R injury were assessed at 1, 7 and 28 days post-aspiration. Results Pulmonary response to MWCNT oropharyngeal aspiration assessed by bronchoalveolar lavage fluid (BALF revealed modest increases in protein and inflammatory cell recruitment. Lung histology showed modest tissue inflammation as compared to the SS group. Serum levels of eotaxin were significantly elevated in the carboxylated MWCNT aspirated mice 1 day post exposure. Oropharyngeal aspiration of all three forms of MWCNTs resulted in a time and/or dose-dependent exacerbation of myocardial infarction. The severity of myocardial injury varied with the form of MWCNTs used. The N-doped MWCNT produced the greatest expansion of the infarct at any time point and required a log concentration lower to establish a no effect level. The expansion of the I/R injury remained significantly elevated at 28 days following aspiration of the COOH and N-doped forms, but

  12. Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion

    Directory of Open Access Journals (Sweden)

    Shinpei Kadowaki

    2016-04-01

    Full Text Available Early myocardial reperfusion is an effective therapy but ischemia/reperfusion (I/R causes lethal myocardial injury. The aging heart was reported to show greater cardiac damage after I/R injury than that observed in young hearts. Senescence marker protein 30 (SMP30, whose expression decreases with age, plays a role in reducing oxidative stress and apoptosis. However, the impact of SMP30 on myocardial I/R injury remains to be determined. In this study, the left anterior descending coronary artery was occluded for 30 min, followed by reperfusion in wild-type (WT and SMP30 knockout (KO mice. After I/R, cardiomyocyte apoptosis and the ratio of infarct area/area at risk were higher, left ventricular fractional shortening was lower, and reactive oxygen species (ROS generation was enhanced in SMP30 KO mice. Moreover, the previously increased phosphorylation of GSK-3β and Akt was lower in SMP30 KO mice than in WT mice. In cardiomyocytes, silencing of SMP30 expression attenuated Akt and GSK-3β phosphorylation, and increased Bax to Bcl-2 ratio and cardiomyocyte apoptosis induced by hydrogen peroxide. These results suggested that SMP30 deficiency augments myocardial I/R injury through ROS generation and attenuation of Akt activation.

  13. Effects of coronary artery occlusion and reperfusion on cardiac cycle-dependent variation of myocardial ultrasonic backscatter

    Energy Technology Data Exchange (ETDEWEB)

    Glueck, R.M.; Mottley, J.G.; Miller, J.G.; Sobel, B.E.; Perez, J.E.

    1985-05-01

    We have recently reported a systematic variation in integrated ultrasonic backscatter throughout the cardiac cycle in canine hearts. This study was performed to determine whether the pattern of such variation is modified systematically by ischemia. Measurements of integrated ultrasonic backscatter in selected regions of normal, ischemic, and reperfused hearts were compared in view of known differences in systolic function of myocardium in each of these regions. Integrated ultrasonic backscatter (3-7 MHz) gated to the first derivative of left ventricular pressure was measured at the apex, midwall, and base in 10 dogs and at the apex before and during transient ischemia and reperfusion in four dogs. Quantitative integrated ultrasonic backscatter was referenced to a steel reflector. Cyclic variation of integrated ultrasonic backscatter was greatest at the apex (peak to trough variation 5.5 +/- 0.9 dB (mean +/- SE)) with the maximum near end diastole (-52.9 +/- 0.9 dB) and minimum near end systole (-58.4 +/- 1.0 dB). Variation at the apex (5.5 +/- 0.9 dB) and the midwall (4.3 +/- 0.8 dB) was greater than at the base (0.5 +/- 1.0 dB) (P less than 0.01 for either region compared with base). Left anterior descending coronary occlusion for 10 minutes in four of 10 dogs reduced variation at the apex to 0.4 +/- 1.5 dB (P less than 0.02 compared with preocclusion). Reperfusion for 2 hours restored apical cyclic variation to 3.9 +/- 1.7 dB, i.e., to values not significantly different from those before occlusion.

  14. Mitochondrial approaches to protect against cardiac ischemia and reperfusion injury

    Directory of Open Access Journals (Sweden)

    Amadou K.S. Camara

    2011-04-01

    Full Text Available The mitochondrion is a vital component in cellular energy metabolism and intracellular signaling processes. Mitochondria are involved in a myriad of complex signaling cascades regulating cell death vs. survival. Importantly, mitochondrial dysfunction and the resulting oxidative and nitrosative stress are central in the pathogenesis of numerous human maladies including cardiovascular diseases, neurodegenerative diseases, diabetes, and retinal diseases, many of which are related. This review will examine the emerging understanding of the role of mitochondria in the etiology and progression of cardiovascular diseases and will explore potential therapeutic benefits of targeting the organelle in attenuating the disease process. Indeed, recent advances in mitochondrial biology have led to selective targeting of drugs designed to modulate or manipulate mitochondrial function, to the use of light therapy directed to the mitochondrial function, and to modification of the mitochondrial genome for potential therapeutic benefit. The approach to rationally treat mitochondrial dysfunction could lead to more effective interventions in cardiovascular diseases that to date have remained elusive. The central premise of this review is that if mitochondrial abnormalities contribute to the etiology of cardiovascular diseases (e.g. ischemic heart disease, alleviating the mitochondrial dysfunction will contribute to mitigating the severity or progression of the disease. To this end, this review will provide an overview of our current understanding of mitochondria function in cardiovascular diseases as well as the potential role for targeting mitochondria with potential drugs or other interventions that lead to protection against cell injury.

  15. Passive targeting of lipid-based nanoparticles to mouse cardiac ischemia-reperfusion injury

    NARCIS (Netherlands)

    Geelen, T.; Paulis, L.E.M.; Coolen, B.F.; Nicolay, K.; Strijkers, G.J.

    2013-01-01

    Reperfusion therapy is commonly applied after a myocardial infarction. Reperfusion, however, causes secondary damage. An emerging approach for treatment of ischemia-reperfusion (IR) injury involves the delivery of therapeutic nanoparticles to the myocardium to promote cell survival and constructivel

  16. The fibrin-derived peptide Bbeta(15-42) significantly attenuates ischemia-reperfusion injury in a cardiac transplant model.

    NARCIS (Netherlands)

    Wiedemann, D.; Schneeberger, S.; Friedl, P.H.A.; Zacharowski, K.; Wick, N.; Boesch, F.; Margreiter, R.; Laufer, G.; Petzelbauer, P.; Semsroth, S.

    2010-01-01

    BACKGROUND: The inflammatory response after prolonged ischemia and subsequent reperfusion leads to increased risk of primary organ dysfunction after cardiac transplantation. It has been demonstrated that the fibrin-derived peptide Bbeta(15-42) (also called FX06) reduces infarct size in coronary arte

  17. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lijuan [Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Wang, Yingjie [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Internal Medicine of Traditional Chinese Medicine, Shuguang Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Pan, Yaohua; Zhang, Lan [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Shen, Chengxing [Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai (China); Qin, Gangjian [Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States); Ashraf, Muhammad [Pathology and Lab Med, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Weintraub, Neal [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Ma, Genshan, E-mail: magenshan@hotmail.com [Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Tang, Yaoliang, E-mail: tangyg@ucmail.uc.edu [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States)

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  18. Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation

    Science.gov (United States)

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2016-01-01

    There is strong evidence to suggest that angiotensin-converting enzyme inhibitors (ACEIs) protect against local myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore whether ACEIs exert cardioprotective effects in a swine model of cardiac arrest (CA) and resuscitation. Male pigs were randomly assigned to three groups: sham-operated group, saline treatment group and enalapril treatment group. Thirty minutes after drug infusion, the animals in the saline and enalapril groups were subjected to ventricular fibrillation (8 min) followed by cardiopulmonary resuscitation (up to 30 min). Cardiac function was monitored, and myocardial tissue and blood were collected for analysis. Enalapril pre-treatment did not improve cardiac function or the 6-h survival rate after CA and resuscitation; however, this intervention ameliorated myocardial ultrastructural damage, reduced the level of plasma cardiac troponin I and decreased myocardial apoptosis. Plasma angiotensin (Ang) II and Ang-(1–7) levels were enhanced in the model of CA and resuscitation. Enalapril reduced the plasma Ang II level at 4 and 6 h after the return of spontaneous circulation whereas enalapril did not affect the plasma Ang-(1–7) level. Enalapril pre-treatment decreased the myocardial mRNA and protein expression of angiotensin-converting enzyme (ACE). Enalapril treatment also reduced the myocardial ACE/ACE2 ratio, both at the mRNA and the protein level. Enalapril pre-treatment did not affect the upregulation of ACE2, Ang II type 1 receptor (AT1R) and MAS after CA and resuscitation. Taken together, these findings suggest that enalapril protects against ischemic injury through the attenuation of the ACE/Ang II/AT1R axis after CA and resuscitation in pigs. These results suggest the potential therapeutic value of ACEIs in patients with CA. PMID:27633002

  19. Insulin improves cardiomyocyte contractile function through enhancement of SERCA2a activity in simulated ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Jie YU; Hai-feng ZHANG; Feng WU; Qiu-xia LI; Heng MA; Wen-yi GUO; Hai-chang WANG; Feng GAO

    2006-01-01

    Aim: Insulin exerts anti-apoptotic effects in both cardiomyocytes and coronary endothelial cells following ischemia/reperfusion (I/R) via the Akt-endothelial nitric oxide synthase survival signal pathway. This important insulin signaling might further contribute to the improvement of cardiac function after reperfusion. In this study, we tested the hypothesis that sarcoplasmic reticulum calcium-AT-Pase (SERCA2a) is involved in the insulin-induced improvement of cardiac contractile function following I/R. Methods: Ventricular myocytes were enzymatically isolated from adult SD rats. Simulated I/R was induced by perfusing cells with chemical anoxic solution for 15 min followed by reperfusion with Tyrode's solution with or without insulin for 30 min. Myocyte shortening and intracellular calcium transients were assessed and underlying mechanisms were investigated. Results: Reperfusion with insulin (10-7 mol/L) significantly improved the recovery of contractile function (n=15-20 myocytes from 6-8 hearts, P<0.05), and increased calcium transients, as evidenced by the increased calcium (Ca2+) fluorescence ratio, shortened time to peak Ca2+ and time to 50% diastolic Ca2+, compared with those in cells reperfused with vehicle (P<0.05). In addition, Akt phosphorylation and SERCA2a activity were both increased in insulin-treated I/R cardiomyocytes, which were markedly inhibited by pretreatment of cells with a specific Akt inhibitor. Moreover, inhibition of Akt activity abolished insulin-induced positive contractile and calcium transients responses in I/R cardiomyocytes. Conclusion: These data demonstrated for the first time that insulin improves the recovery of contractile function in simulated I/R cardiomyocytes in an Akt-dependent and SERCA2a-mediated fashion.

  20. Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-Induced Cardiac Hypertrophy in Mice.

    Science.gov (United States)

    Trentin-Sonoda, Mayra; da Silva, Rogério Cirino; Kmit, Fernanda Vieira; Abrahão, Mariana Vieira; Monnerat Cahli, Gustavo; Brasil, Guilherme Visconde; Muzi-Filho, Humberto; Silva, Paulo André; Tovar-Moll, Fernanda Freire; Vieyra, Adalberto; Medei, Emiliano; Carneiro-Ramos, Marcela Sorelli

    2015-01-01

    We investigated whether the pathways linked to Toll-like receptors 2 and 4 (TLRs) are involved in renal ischemia-reperfusion (I/R)-induced cardiac hypertrophy. Wild type (WT) C57BL/6J, TLR2-/- and TLR4-/- mice were subjected to left kidney ischemia for 60 min followed by reperfusion for 5, 8, 12 and 15 days. Proton density magnetic resonance showed alterations in the injured kidney from WT mice, together with signs of parenchymal edema and higher levels of vimentin mRNA, accompanied by: (i) small, but significant, increase in serum urea after 24 h, (ii) 100% increase in serum creatinine at 24 h. A serum peak of inflammatory cytokines occurred after 5 days of reperfusion. Heart weight/body weight and heart weight/tibia length ratios increased after 12 and 15 days of reperfusion, respectively. Cardiac hypertrophy markers, B-type natriuretic peptide (BNP) and α-actin, left ventricle mass, cardiac wall thickness and myocyte width increased after 15 days of reperfusion, together with longer QTc and action potential duration. Cardiac TLRs, MyD88, HSP60 and HSP70 mRNA levels also increased. After 15 days of reperfusion, absence of TLRs prevented cardiac hypertrophy, as reflected by similar values of left ventricular cardiac mass and heart weight/body weight ratio compared to the transgenic Sham. Renal tissular injury also ameliorated in both knockout mice, as revealed by the comparison of their vimentin mRNA levels with those found in the WT on the same day after I/R. The I/R TLR2-/- group had TNF-α, IFN-γ and IL-1β levels similar to the non-I/R group, whereas the TLR4-/- group conserved the p-NF-κB/NF- κB ratio contrasting with that found in TLR2-/-. We conclude: (i) TLRs are involved in renal I/R-induced cardiac hypertrophy; (ii) absence of TLRs prevents I/R-induced cardiac hypertrophy, despite renal lesions seeming to evolve towards those of chronic disease; (iii) TLR2 and TLR4 selectively regulate the systemic inflammatory profile and NF- κB activation.

  1. 芬太尼预处理对兔心肌缺血再灌注后心肌梗死范围及心功能的影响%Effects of pretreatment with fentanyl on myocardial infarction size and cardiac function in rabbits with acute myocardial ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    郑向明; 孟凡民; 王春亭

    2012-01-01

    by limiting infarction size effectively and improving cardiac function.%目的 探讨芬太尼预处理对免心肌缺血再灌注后的心肌保护效应.方法 将24只雄性新西兰白兔随机分为C组(心肌缺血再灌注组)、F组(芬太尼组)和N-F组(纳络酮-芬太尼组)三组,每组8只.C组仅做心肌缺血再灌注损伤模型,不行任何治疗;F组于缺血前15 min静脉注射芬太尼0.15 mg/kg,余同C组;N-F组于缺血前20 min静脉射注纳络酮3 mg/kg,继而以70 μg/(kg·min)的速度持续静脉滴注至再灌注前;缺血前15 min仍静脉注射芬太尼0.15 mg/kg,余同C组.记录基础状态(T0)、缺血后再灌注前即刻(T1)、再灌注10 min(T2)、再灌注30 min (T3)、再灌注120 min(T4)的心率(HR)、左心室收缩内压峰值(LVSP)、左心室舒张末压(LVEDP)、左心室收缩及舒张最大压力变化速率(±dp/dt).再灌注后切取心脏,测定心肌缺血范围及心肌梗死范围.结果 与基础值比较,T1 4时各组LVSP和±dp/dt下降(P<0.05),LVEDP升高(P<0.05).C组与N-F组比较,各时段血流动力学指标比较差异无统计学意义(P>0.05);与C组、N-F组比较,F组T2-4时LVSP,+ dp/dt升高(P<0.05),梗死心肌重量和梗死心肌范围缩小(P<0.01).结论 芬太尼预处理可限制兔心肌缺血再灌注损伤后心肌梗死范围,具有心肌保护效应.

  2. Inhibition of neutrophil activity improves cardiac function after cardiopulmonary bypass

    Directory of Open Access Journals (Sweden)

    Grünwald Frank

    2007-10-01

    Full Text Available Abstract Background The arterial in line application of the leukocyte inhibition module (LIM in the cardiopulmonary bypass (CPB limits overshooting leukocyte activity during cardiac surgery. We studied in a porcine model whether LIM may have beneficial effects on cardiac function after CPB. Methods German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min reperfusion without (group I; n = 6 or with LIM (group II; n = 6. The cardiac indices (CI and cardiac function were analyzed pre and post CPB with a Swan-Ganz catheter and the cardiac function analyzer. Neutrophil labeling with technetium, scintigraphy, and histological analyses were done to track activated neutrophils within the organs. Results LIM prevented CPB-associated increase of neutrophil counts in peripheral blood. In group I, the CI significantly declined post CPB (post: 3.26 ± 0.31; pre: 4.05 ± 0.45 l/min/m2; p 2; p = 0.23. Post CPB, the intergroup difference showed significantly higher CI values in the LIM group (p Conclusion Our data provides strong evidence that LIM improves perioperative hemodynamics and cardiac function after CPB by limiting neutrophil activity and inducing accelerated sequestration of neutrophils in the spleen.

  3. SUV39H1 mediated SIRT1 trans-repression contributes to cardiac ischemia-reperfusion injury.

    Science.gov (United States)

    Yang, Guang; Zhang, Xinjian; Weng, Xinyu; Liang, Peng; Dai, Xin; Zeng, Sheng; Xu, Huihui; Huan, Hailin; Fang, Mingming; Li, Yuehua; Xu, Dachun; Xu, Yong

    2017-05-01

    Ischemic reperfusion (I/R) contributes to deleterious cardiac remodeling and heart failure. The deacetylase SIRT1 has been shown to protect the heart from I/R injury. We examined the mechanism whereby I/R injury represses SIRT1 transcription in the myocardium. There was accumulation of trimethylated histone H3K9 on the proximal SIRT1 promoter in the myocardium in mice following I/R injury and in cultured cardiomyocytes exposed to hypoxia-reoxygenation (H/R). In accordance, the H3K9 trimethyltransferase SUV39H1 bound to the SIRT1 promoter and repressed SIRT1 transcription. SUV39H1 expression was up-regulated in the myocardium in mice following I/R insults and in H/R-treated cardiomyocytes paralleling SIRT1 down-regulation. Silencing SUV39H1 expression or suppression of SUV39H1 activity erased H3K9Me3 from the SIRT1 promoter and normalized SIRT1 levels in cardiomyocytes. Meanwhile, SUV39H1 deficiency or inhibition attenuated I/R-induced infarction and improved heart function in mice likely through influencing ROS levels in a SIRT1-dependent manner. Therefore, our data uncover a novel mechanism for SIRT1 trans-repression during cardiac I/R injury and present SUV39H1 as a druggable target for the development of therapeutic strategies against ischemic heart disease.

  4. Surfactant treatment before reperfusion improves the immediate function of lung transplants in rats

    NARCIS (Netherlands)

    Erasmus, ME; Petersen, AH; Hofstede, G; Haagsman, HP; Oetomo, SB; Prop, J

    1996-01-01

    An impaired function of alveolar surfactant can cause lung transplant dysfunction early after reperfusion. In this study it was investigated whether treatment with surfactant before reperfusion improves the immediate function of lung transplants and whether an improved transplant function was associ

  5. Metabolic aspects of cardiac and skeletal muscle tissues in the condition of hypoxia, ischaemia and reperfusion induced by extracorporeal circulation.

    Science.gov (United States)

    Corbucci, G G; Menichetti, A; Cogliati, A; Ruvolo, C

    1995-01-01

    Extracorporeal circulation (ECC) during aortopulmonary bypass surgery allows the investigation of the metabolic and biochemical effects of hypoxia (skeletal muscle), ischaemia (cardiac muscle) and reperfusion (skeletal and cardiac muscle) in homogeneous groups of patients. In this study we examined the mitochondrial enzymic response to oxidative stress in 40 subjects, and analysis was carried out on heart and skeletal-muscle biopsies taken before, during and after aortic clamping and 115 min of ECC. The results obtained constitute a clinical and biochemical picture characterized by some peculiar adaptive changes of enzymic activities which thus antagonize the oxidative damage due to acute hypoxia, ischaemia and reperfusion. Consequently it seems that this cellular protective mechanism plays a crucial role in the reversibility of oxidative damage in hypoxic and ischaemic tissues.

  6. Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury

    DEFF Research Database (Denmark)

    Hostrup, Anders; Christensen, Gitte Lund; Bentzen, Bo Hjort;

    2012-01-01

    of the physiological functions of AngII. The AT(1)R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the ß-arrestin biased agonist [SII]AngII on ischemia......-reperfusion injury in rat hearts. Isolated hearts mounted in a Langendorff perfused rat heart preparations showed that preconditioning with [SII]AngII reduced the infarct size induced by global ischemia from 46±8.4% to 22±3.4%. In contrast, neither preconditioning with AngII nor postconditioning with AngII or [SII...

  7. Caveolin-3 expression and caveolae are required for isoflurane-induced cardiac protection from hypoxia and ischemia/reperfusion injury.

    Science.gov (United States)

    Horikawa, Yousuke T; Patel, Hemal H; Tsutsumi, Yasuo M; Jennings, Michelle M; Kidd, Michael W; Hagiwara, Yasuko; Ishikawa, Yoshihiro; Insel, Paul A; Roth, David M

    2008-01-01

    Volatile anesthetics protect the heart from ischemia/reperfusion injury but the mechanisms for this protection are poorly understood. Caveolae, sarcolemmal invaginations, and caveolins, scaffolding proteins in caveolae, localize molecules involved in cardiac protection. We tested the hypothesis that caveolae and caveolins are essential for volatile anesthetic-induced cardiac protection using cardiac myocytes (CMs) from adult rats and in vivo studies in caveolin-3 knockout mice (Cav-3(-/-)). We incubated CM with methyl-beta-cyclodextrin (MbetaCD) or colchicine to disrupt caveolae formation, and then exposed the myocytes to the volatile anesthetic isoflurane (30 min, 1.4%), followed by simulated ischemia/reperfusion (SI/R). Isoflurane protected CM from SI/R [23.2+/-1.6% vs. 71.0+/-5.8% cell death (assessed by trypan blue exclusion), Pprotection was abolished by MbetaCD or colchicine (84.9+/-5.5% and 64.5+/-6.1% cell death, Pprotection in vivo was assessed by measurement of infarct size relative to the area at risk and cardiac troponin levels. Isoflurane-induced a reduction in infarct size and cardiac troponin relative to control (infarct size: 26.5%+/-2.6% vs. 45.3%+/-5.4%, Pprotection was abolished in Cav-3(-/-) mice (infarct size: 53.4%+/-6.1% vs. 53.2%+/-3.5%, Pprotection is thus dependent on the presence of caveolae and the expression of caveolin-3. We conclude that caveolae and caveolin-3 are critical for volatile anesthetic-induced protection of the heart from ischemia/reperfusion injury.

  8. Effects of Acetyl-L-Carnitine on Cardiac Arrhythmias and Infarct Size in Ischemic-Reperfused Isolated Rat Heart

    Directory of Open Access Journals (Sweden)

    Moslem Najafi

    2010-01-01

    Full Text Available This study aimed to examine whether acetyl-L-carnitine (ALC was able to reduce cardiac arrhythmias and infarct size in the ischemic-reperfused isolated rat heart.Materials and MethodsThe isolated hearts were mounted on a Langendorff apparatus then perfused by a modified Krebs-Henseleit solution during 30 min regional ischemia and 120 min reperfusion (control or by enriched Krebs solution with 0.375, 0.75, 1.5 and 3 mM of ALC (treatment groups. The ECGs were recorded and analyzed to determine cardiac arrhythmias. The infarct size was determined by using a computerized planimetry package.ResultsDuring ischemia, all used concentrations of ALC decreased number and duration of ventricular tachycardia (VT, total number of ventricular ectopic beats (VEBs (P<0.01, incidence of total ventricular fibrillation (VF and the time spent for reversible VF (P<0.05. At the reperfusion phase, duration of VT, incidence of total VF and reversible VF were significantly lowered by ALC (P<0.05. In addition, infarct size significantly was decreased in all treated groups. In the control group, the infarct size was 23±3.1%, however, ALC (0.375, 0.75 and 3 mM reduced it to 8.7±2.3, 5.3±1.4, and 8±2.9%, respectively (P<0.01. ConclusionConsidering the results, it may be concluded that ALC has protective effects against cardiac ischemia-reperfusion (I/R injuries by reduction of infarct size and arrhythmias in isolated rat heart. Among the potential cardioprotective mechanisms for ALC, increase in glucose oxidation and resulting reduced lactate production, reduction of toxic fatty acid metabolites and removing free radicals from the myocytes are more relevant.

  9. Cardiac Ischemia Reperfusion Injury Following Instillation of 20 nm Citrate-capped Nanosilver

    Energy Technology Data Exchange (ETDEWEB)

    Becak DP, Holland NA; Shannahan, Jonathan H.

    2015-10-01

    Background: Silver nanoparticles (AgNP) have garnered much interest due to their antimicrobial properties, becoming one of the most utilized nano scale materials. However, any potential evocable cardiovascular injury associated with exposure has not been previously reported. We have previously demonstrated expansion of myocardial infarction after intratracheal (IT) instillation of other nanomaterials. We hypothesized that pulmonary exposure to Ag core AgNP induces persistent increase in circulating cytokines, expansion of cardiac ischemia-reperfusion (I/R) injury and associated with altered coronary vessel reactivity. Methods: Male Sprague-Dawley rats were exposed to 200 µg of 20 nm citrate capped Ag core AgNP, or a citrate vehicle intratracheally (IT). One and 7 days following IT instillation lungs were evaluated for inflammation and silver presence, serum was analyzed for concentrations of selected cytokines, and cardiac I/R injury and coronary artery reactivity was assessed. Results: AgNP instillation resulted in modest pulmonary injury with detection of silver in lung tissue and infiltrating cells, elevation of serum cytokines: G-CSF, MIP-1α, IL-1β, IL-2, IL-6, IL-13, IL-10, IL-18, IL-17, TNFα, and RANTES, expansion of I/R injury and depression of the coronary vessel reactivity at 1 day post IT compared to vehicle treated rats. Seven days post IT instillation was associated with persistent detection of silver in lungs, elevation in cytokines: IL-2, IL-13, and TNFα and expansion of I/R injury. Conclusions: Based on these data, IT instillation of AgNP increases circulating levels of several cytokines, which may contribute to persistent expansion of I/R injury possibly through an impaired vascular responsiveness.

  10. Triiodothyronine increases myocardial function and pyruvate entry into the citric acid cycle after reperfusion in a model of infant cardiopulmonary bypass.

    Science.gov (United States)

    Olson, Aaron K; Bouchard, Bertrand; Ning, Xue-Han; Isern, Nancy; Rosiers, Christine Des; Portman, Michael A

    2012-03-01

    Triiodothyronine (T3) supplementation improves clinical outcomes in infants after cardiac surgery using cardiopulmonary bypass by unknown mechanisms. We utilized a translational model of infant cardiopulmonary bypass to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC), thereby providing the energy support for improved cardiac function after ischemia-reperfusion (I/R). Neonatal piglets received intracoronary [2-(13)Carbon((13)C)]pyruvate for 40 min (8 mM) during control aerobic conditions (control) or immediately after reperfusion (I/R) from global hypothermic ischemia. A third group (I/R-Tr) received T3 (1.2 μg/kg) during reperfusion. We assessed absolute CAC intermediate levels and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC) and anaplerotic carboxylation (PC) using [2-(13)C]pyruvate and isotopomer analysis by gas and liquid chromatography-mass spectrometry and (13)C-nuclear magnetic resonance spectroscopy. When compared with I/R, T3 (group I/R-Tr) increased cardiac power and oxygen consumption after I/R while elevating flux of both PDC and PC (∼4-fold). Although neither I/R nor I/R-Tr modified absolute CAC levels, T3 inhibited I/R-induced reductions in their molar percent enrichment. Furthermore, (13)C-labeling of CAC intermediates suggests that T3 may decrease entry of unlabeled carbons at the level of oxaloacetate through anaplerosis or exchange reaction with asparate. T3 markedly enhances PC and PDC fluxes, thereby providing potential substrate for elevated cardiac function after reperfusion. This T3-induced increase in pyruvate fluxes occurs with preservation of the CAC intermediate pool. Our labeling data raise the possibility that T3 reduces reliance on amino acids for anaplerosis after reperfusion.

  11. KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Ewa Soltysinska

    Full Text Available Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/reperfusion injury. Recently, mitochondrial BK channels (mitoBKs in cardiomyocytes were implicated as infarct-limiting factors that derive directly from the KCNMA1 gene encoding for canonical BKs usually present at the plasma membrane of cells. However, some studies challenged these cardio-protective roles of mitoBKs. Herein, we present electrophysiological evidence for paxilline- and NS11021-sensitive BK-mediated currents of 190 pS conductance in mitoplasts from wild-type but not BK-/- cardiomyocytes. Transmission electron microscopy of BK-/- ventricular muscles fibres showed normal ultra-structures and matrix dimension, but oxidative phosphorylation capacities at normoxia and upon re-oxygenation after anoxia were significantly attenuated in BK-/- permeabilized cardiomyocytes. In the absence of BK, post-anoxic reactive oxygen species (ROS production from cardiomyocyte mitochondria was elevated indicating that mitoBK fine-tune the oxidative state at hypoxia and re-oxygenation. Because ROS and the capacity of the myocardium for oxidative metabolism are important determinants of cellular survival, we tested BK-/- hearts for their response in an ex-vivo model of ischemia/reperfusion (I/R injury. Infarct areas, coronary flow and heart rates were not different between wild-type and BK-/- hearts upon I/R injury in the absence of ischemic pre-conditioning (IP, but differed upon IP. While the area of infarction comprised 28±3% of the area at risk in wild-type, it was increased to 58±5% in BK-/- hearts suggesting that BK mediates the beneficial effects of IP. These findings suggest that cardiac BK channels are important for proper oxidative energy supply of

  12. KCNMA1 encoded cardiac BK channels afford protection against ischemia-reperfusion injury.

    Science.gov (United States)

    Soltysinska, Ewa; Bentzen, Bo Hjorth; Barthmes, Maria; Hattel, Helle; Thrush, A Brianne; Harper, Mary-Ellen; Qvortrup, Klaus; Larsen, Filip J; Schiffer, Tomas A; Losa-Reyna, Jose; Straubinger, Julia; Kniess, Angelina; Thomsen, Morten Bækgaard; Brüggemann, Andrea; Fenske, Stefanie; Biel, Martin; Ruth, Peter; Wahl-Schott, Christian; Boushel, Robert Christopher; Olesen, Søren-Peter; Lukowski, Robert

    2014-01-01

    Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated potassium channel of big-conductance (BK) have a pre-conditioning-like effect on survival of cardiomyocytes after ischemia/reperfusion injury. Recently, mitochondrial BK channels (mitoBKs) in cardiomyocytes were implicated as infarct-limiting factors that derive directly from the KCNMA1 gene encoding for canonical BKs usually present at the plasma membrane of cells. However, some studies challenged these cardio-protective roles of mitoBKs. Herein, we present electrophysiological evidence for paxilline- and NS11021-sensitive BK-mediated currents of 190 pS conductance in mitoplasts from wild-type but not BK-/- cardiomyocytes. Transmission electron microscopy of BK-/- ventricular muscles fibres showed normal ultra-structures and matrix dimension, but oxidative phosphorylation capacities at normoxia and upon re-oxygenation after anoxia were significantly attenuated in BK-/- permeabilized cardiomyocytes. In the absence of BK, post-anoxic reactive oxygen species (ROS) production from cardiomyocyte mitochondria was elevated indicating that mitoBK fine-tune the oxidative state at hypoxia and re-oxygenation. Because ROS and the capacity of the myocardium for oxidative metabolism are important determinants of cellular survival, we tested BK-/- hearts for their response in an ex-vivo model of ischemia/reperfusion (I/R) injury. Infarct areas, coronary flow and heart rates were not different between wild-type and BK-/- hearts upon I/R injury in the absence of ischemic pre-conditioning (IP), but differed upon IP. While the area of infarction comprised 28±3% of the area at risk in wild-type, it was increased to 58±5% in BK-/- hearts suggesting that BK mediates the beneficial effects of IP. These findings suggest that cardiac BK channels are important for proper oxidative energy supply of cardiomyocytes at

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

    Science.gov (United States)

    González-Pacheco, Héctor; Méndez-Domínguez, Aurelio; Hernández, Salomón; López-Marure, Rebeca; Vazquez-Mellado, Maria J.; Aguilar, Cecilia; Rocha-Zavaleta, Leticia

    2014-01-01

    Background. CDP-choline is a key intermediate in the biosynthesis of phosphatidylcholine, which is an essential component of cellular membranes, and a cell signalling mediator. CDP-choline has been used for the treatment of cerebral ischaemia, showing beneficial effects. However, its potential benefit for the treatment of myocardial ischaemia has not been explored yet. Aim. In the present work, we aimed to evaluate the potential use of CDP-choline as a cardioprotector in an in vitro model of ischaemia/reperfusion injury. Methods. Neonatal rat cardiac myocytes were isolated and subjected to hypoxia/reperfusion using the coverslip hypoxia model. To evaluate the effect of CDP-choline on oxidative stress-induced reperfusion injury, the cells were incubated with H2O2 during reperfusion. The effect of CDP-choline pre- and postconditioning was evaluated using the cell viability MTT assay, and the proportion of apoptotic and necrotic cells was analyzed using the Annexin V determination by flow cytometry. Results. Pre- and postconditioning with 50 mg/mL of CDP-choline induced a significant reduction of cells undergoing apoptosis after hypoxia/reperfusion. Preconditioning with CDP-choline attenuated postreperfusion cell death induced by oxidative stress. Conclusion. CDP-choline administration reduces cell apoptosis induced by oxidative stress after hypoxia/reperfusion of cardiac myocytes. Thus, it has a potential as cardioprotector in ischaemia/reperfusion-injured cardiomyocytes. PMID:24578622

  14. TRIIODOTHYRONINE INCREASES MYOCARDIAL FUNCTION AND PYRUVATE ENTRY INTO THE CITRIC ACID CYCLE AFTER REPERFUSION IN A MODEL OF INFANT CARDIOPULMONARY BYPASS

    Energy Technology Data Exchange (ETDEWEB)

    Olson, Aaron; Bouchard, Bertrand; Ning, Xue-Han; Isern, Nancy G.; Des Rosiers, Christine; Portman, Michael A.

    2012-03-01

    We utilized a translational model of infant CPB to test the hypothesis that T3 modulates pyruvate entry into the citric acid cycle (CAC) thereby providing the energy support for improved cardiac function after ischemia-reperfusion. Methods and Results: Neonatal piglets received intracoronary [2-13Carbon(13C)]-pyruvate for 40 minutes (8 mM) during control aerobic conditions (Cont) or immediately after reperfusion (IR) from global hypothermic ischemia. A third group (IR-Tr) received T3 (1.2 ug/kg) during reperfusion. We assessed absolute CAC intermediate levels (aCAC) and flux parameters into the CAC through oxidative pyruvate decarboxylation (PDC ) and anaplerotic carboxylation (PC; ) using 13C-labeled pyruvate and isotopomer analysis by gas and liquid chromatography-mass spectrometry and 13C NMR. Neither IR nor IR-Tr modified aCAC. However, compared to IR, T3 (group IR-Tr) increased cardiac power and oxygen consumption after CPB while elevating both PDC and PC (~ four-fold). T3 inhibited IR induced reductions in CAC intermediate molar percent enrichment (MPE) and oxaloacetate(citrate)/malate MPE ratio; an index of aspartate entry into the CAC. Conclusions: T3 markedly enhances PC and PDC thereby providing substrate for elevated cardiac function and work after reperfusion. The increases in pyruvate flux occur with preservation of the CAC intermediate pool. Additionally, T3 inhibition of reductions in CAC intermediate MPEs indicates that T3 reduces the reliance on amino acids (AA) for anaplerosis after reperfusion. Thus, AA should be more available for other functions such as protein synthesis.

  15. Protein levels of heme oxygenase-1 during reperfusion in human kidney transplants with delayed graft function.

    Science.gov (United States)

    Ollinger, Robert; Kogler, Pamela; Biebl, Matthias; Sieb, Michael; Sucher, Robert; Bösmüller, Claudia; Troppmair, Jakob; Mark, Walter; Weiss, Helmut; Margreiter, Raimund

    2008-01-01

    Delayed graft function (DGF) as a consequence of ischemia reperfusion injury (IRI) is associated with a decrease in long-term allograft survival. Heme oxygenase-1 (HO-1) is a stress responsive gene that is highly expressed in multiple pathological processes. The aim of our study was to analyze whether HO-1 protein levels in human kidney transplants during IRI correlate with the incidence of DGF. Kidney biopsies were obtained from 27 kidney allografts at two time points: at the end of cold storage and shortly after reperfusion. Samples were analyzed for HO-1 protein levels by Western blot. Heme oxygenase-1 protein levels were significantly higher in post-reperfusion biopsies (39.4 vs. 13.7 arbitrary units, p = 0.001). In pre-reperfusion biopsies no association was observed between HO-1 protein levels and DGF. In post-reperfusion biopsies, higher levels of HO-1 protein were measured in kidneys with DGF (53.7 vs. 36.2 arbitrary units, p = 0.064). DGF kidneys showed a significantly higher increase from pre- to post-reperfusion in HO-1 protein (42.0 vs. 18.7 arbitrary units, p = 0.025). Heme oxygenase-1 protein levels shortly after allograft reperfusion are closely related with initial graft function. Assessment thereof may be considered a valuable tool to predict DGF.

  16. Gene control of acupuncture and moxibustion preconditioning on apoptosis in ischemic cardiac muscle of rats with re-perfusion

    Institute of Scientific and Technical Information of China (English)

    SUN Zhong-ren; LI Xiao-ning; ZHAO Yu-hui; TIAN Yan-yan; XU Li

    2008-01-01

    In order to explore the effect of acupuncture preconditioning on rats' cell apoptosis with cardiac muscle re-perfusion damage and bcl-2mRNA genes, we used differentiating acupuncture and moxibustion preconditioning among groups, then compared acupuncture and moxibustion preconditioning with ischemic preconditioning. The experimental results show that acupuncture and moxibustion preconditioning makes more bcl-2mRNA genes expressed and produces less cell apeptosis, furthermore, groups of acupuncture and moxibustion preconditioning for twice a day are more effective than those of ischemic preconditioning.

  17. Switching Back to Normal Diet Following High-Fat Diet Feeding Reduces Cardiac Vulnerability to Ischaemia and Reperfusion Injury

    OpenAIRE

    Ben Littlejohns; Hua Lin; Gianni D Angelini; Halestrap, Andrew P.; M. Saadeh Suleiman

    2014-01-01

    Background: We have recently shown that hearts of mice fed high-fat diet exhibit increased vulnerability to ischaemia and reperfusion (I/R) in parallel to changes in catalase protein expression, mitochondrial morphology and intracellular diastolic Ca2+. Aims: To determine whether switching from high-fat back to normal diet alters vulnerability to I/R and to investigate cardiac cellular remodelling in relation to the mechanism(s) underlying I/R injury. Methods and Results: Male C57BL/6J mice w...

  18. A novel cardioprotective agent in cardiac transplantation: metformin activation of AMP-activated protein kinase decreases acute ischemia-reperfusion injury and chronic rejection.

    Science.gov (United States)

    Chin, Jocelyn T; Troke, Joshua J; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P; Robbins, Robert C; Fischbein, Michael P

    2011-12-01

    The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury.

  19. Forebrain Ischemia-Reperfusion Simulating Cardiac Arrest in Mice Induces Edema and DNA Fragmentation in the Brain

    Directory of Open Access Journals (Sweden)

    Christina H. Liu

    2007-05-01

    Full Text Available Brain injury affects one-third of persons who survive after heart attack, even with restoration of spontaneous circulation by cardiopulmonary resuscitation. We studied brain injury resulting from transient bilateral carotid artery occlusion (BCAO and reperfusion by simulating heart attack and restoration of circulation, respectively, in live C57Black6 mice. This model is known to induce neuronal death in the hippocampus, striatum, and cortex. We report the appearance of edema after transient BCAO of 60 minutes and 1 day of reperfusion. Hyperintensity in diffusion-weighted magnetic resonance imaging (MRI was detectable in the striatum, thalamus, and cortex but not in the hippocampus. To determine whether damage to the hippocampus can be detected in live animals, we infused a T2 susceptibility magnetic resonance contrast agent (superparamagnetic iron oxide nanoparticles [SPIONs] that was linked to single-stranded deoxyribonucleic acid (DNA complementary in sequence to c-fos messenger ribonucleic acid (SPION-cfos; we acquired in vivo T2*-weighted MRI 3 days later. SPION retention was measured as T2* (milliseconds signal reduction or R2* value (s−1 elevation. We found that animals treated with 60-minute BCAO and 7-day reperfusion exhibited significantly less SPION retention in the hippocampus and cortex than sham-operated animals. These findings suggest that brain injury induced by cardiac arrest can be detected in live animals.

  20. Degradation of cardiac myosin light chain kinase by matrix metalloproteinase-2 contributes to myocardial contractile dysfunction during ischemia/reperfusion.

    Science.gov (United States)

    Gao, Ling; Zheng, Yan-Jun; Gu, Shan-Shan; Tan, Ji-Liang; Paul, Christian; Wang, Yi-Gang; Yang, Huang-Tian

    2014-12-01

    Although ischemia/reperfusion (I/R)-induced myocardial contractile dysfunction is associated with a prominent decrease in myofilament Ca(2+) sensitivity, the underlying mechanisms have not yet been fully clarified. Phosphorylation of ventricular myosin light chain 2 (MLC-2v) facilitates actin-myosin interactions and enhances contractility, however, its level and regulation by cardiac MLC kinase (cMLCK) and cMLC phosphatase (cMLCP) in I/R hearts are debatable. In this study, the levels and/or effects of MLC-2v phosphorylation, cMLCK, cMLCP, and proteases during I/R were determined. Global myocardial I/R-suppressed cardiac performance in isolated rat hearts was concomitant with decreases of MLC-2v phosphorylation, myofibrillar Ca(2+)-stimulated ATPase activity, and cMLCK content, but not cMLCP proteins. Consistently, simulated I/R in isolated cardiomyocytes inhibited cell shortening, Ca(2+) transients, MLC-2v phosphorylation, and myofilament sensitivity to Ca(2+). These observations were reversed by cMLCK overexpression, while the specific cMLCK knockdown by short hairpin RNA (shRNA) had the opposite effect. Moreover, the inhibition of matrix metalloproteinase-2 (MMP-2, a zinc-dependent endopeptidase) reversed IR-decreased cMLCK, MLC-2v phosphorylation, myofibrillar Ca(2+)-stimulated ATPase activity, myocardial contractile function, and myofilament sensitivity to Ca(2+), while the inhibition or knockdown of cMLCK by ML-9 or specific shRNA abolished MMP-2 inhibition-induced cardioprotection. Finally, the co-localization in cardiomyocytes and interaction in vivo of MMP-2 and cMLCK were observed. Purified recombinant rat cMLCK was concentration- and time-dependently degraded by rat MMP-2 in vitro, and this was prevented by the inhibition of MMP-2. These findings reveal that the I/R-activated MMP-2 leads to the degradation of cMLCK, resulting in a reduction of MLC-2v phosphorylation, and myofibrillar Ca(2+)-stimulated ATPase activity, which subsequently suppresses

  1. Pre-ischemic mitochondrial substrate constraint by inhibition of malate-aspartate shuttle preserves mitochondrial function after ischemia-reperfusion

    DEFF Research Database (Denmark)

    Jespersen, Nichlas Riise; Yokota, Takashi; Støttrup, Nicolaj Brejnholt

    2017-01-01

    and early reperfusion by AOA treatment could prevent mitochondrial damage at later reperfusion. The AOA treatment preserved mitochondrial respiratory capacity with reduced mitochondrial oxidative stress during late reperfusion to the same extent as ischaemic preconditioning (IPC). However, AOA treatment...... of mitochondrial function during late reperfusion in an IR-injured heart. ABSTRACT: Mitochondrial dysfunction plays a central role in ischaemia-reperfusion (IR) injury. Pre-ischaemic administration of aminooxyacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against IR...... injury, although the underlying mechanism remains unknown. We hypothesized that a transient inhibition of the MAS during ischaemia and early reperfusion could preserve mitochondrial function at later phase of reperfusion in the IR-injured heart to the same extent as ischaemic preconditioning (IPC), which...

  2. Effect of hypertensive reperfusion on the changes between cerebral oxygen delivery and uptake after cardiac arrest and resuscitation in dogs

    Institute of Scientific and Technical Information of China (English)

    杜权; 马永达; 葛衡江; 刘怀琼; 李阳

    2004-01-01

    Objective: To study the changes between cerebral oxygen (O2) delivery and uptake in dogs resuscitated under normotension or hypertension for 4 h. Methods: The model of ventricular fibrillation of 8 min in 12 dogs was made,followed by open cardiopulmonary resuscitation, reperfnsion with normal or high mean arterial pressure (MAP), and controlled ventilation to 4 h. Animals were randomly assigned into Group NT (normotensive reperfusion, n = 6) and Group HT(hypertensive reperfusion, n = 6). Cerebral arteriovenous (sagittal sinus) O2 content difference (Ca-ssO2) and venous(sagittal sinus) PO2(PssO2) were determined before cardiac arrest (CA) and 30, 60, 120, and 240 min after CA. Results: In Group NT, Ca-ssO2 was lower at 30 min ( P < 0.05) but higher at 240 min ( P < 0.01 ) after CA than that before CA. In Group HT, Ca-ssO2 was not significantly different from that in Group NT before CA but was lower than that in Group NT at 30 min after CA ( P < 0.01 ). Ca-ssO2 was not significantly different in Group NT and HT thereafter. In both groups,PssO2 was both higher at 30 min after reperfnsion ( P < 0.01 ) and at 240 min after reperfnsion lower ( P < 0.05) than those before CA .At 30 min after reperfusion, PssO2 was higher (P<0.01) in Group HT than that in Group NT, with insignificant difference between two groups. Conclusion: Cerebral O2 delivery and uptake are mismatched after CA and resuscitation. Hypertensive reperfusion improves oxygen delivery to the brain early after CA.

  3. Normal cardiac function in mice with supraphysiological cardiac creatine levels.

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    Santacruz, Lucia; Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A; Jacobs, Danny O

    2014-02-01

    Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies.

  4. Reversible blockade of complex I or inhibition of PKCβ reduces activation and mitochondria translocation of p66Shc to preserve cardiac function after ischemia.

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    Meiying Yang

    Full Text Available AIM: Excess mitochondrial reactive oxygen species (mROS play a vital role in cardiac ischemia reperfusion (IR injury. P66Shc, a splice variant of the ShcA adaptor protein family, enhances mROS production by oxidizing reduced cytochrome c to yield H2O2. Ablation of p66Shc protects against IR injury, but it is unknown if and when p66Shc is activated during cardiac ischemia and/or reperfusion and if attenuating complex I electron transfer or deactivating PKCβ alters p66Shc activation during IR is associated with cardioprotection. METHODS: Isolated guinea pig hearts were perfused and subjected to increasing periods of ischemia and reperfusion with or without amobarbital, a complex I blocker, or hispidin, a PKCβ inhibitor. Phosphorylation of p66Shc at serine 36 and levels of p66Shc in mitochondria and cytosol were measured. Cardiac functional variables and redox states were monitored online before, during and after ischemia. Infarct size was assessed in some hearts after 120 min reperfusion. RESULTS: Phosphorylation of p66Shc and its translocation into mitochondria increased during reperfusion after 20 and 30 min ischemia, but not during ischemia only, or during 5 or 10 min ischemia followed by 20 min reperfusion. Correspondingly, cytosolic p66Shc levels decreased during these ischemia and reperfusion periods. Amobarbital or hispidin reduced phosphorylation of p66Shc and its mitochondrial translocation induced by 30 min ischemia and 20 min reperfusion. Decreased phosphorylation of p66Shc by amobarbital or hispidin led to better functional recovery and less infarction during reperfusion. CONCLUSION: Our results show that IR activates p66Shc and that reversible blockade of electron transfer from complex I, or inhibition of PKCβ activation, decreases p66Shc activation and translocation and reduces IR damage. These observations support a novel potential therapeutic intervention against cardiac IR injury.

  5. New perspectives on the role of cardiac magnetic resonance imaging to evaluate myocardial salvage and myocardial hemorrhage after acute reperfused ST-elevation myocardial infarction.

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    Mangion, Kenneth; Corcoran, David; Carrick, David; Berry, Colin

    2016-07-01

    Cardiac magnetic resonance (CMR) imaging enables the assessment of left ventricular function and pathology. In addition to established contrast-enhanced methods for the assessment of infarct size and microvascular obstruction, other infarct pathologies, such as myocardial edema and myocardial hemorrhage, can be identified using innovative CMR techniques. The initial extent of myocardial edema revealed by T2-weighted CMR has to be stable for edema to be taken as a retrospective marker of the area-at-risk, which is used to calculate myocardial salvage. The timing of edema assessment is important and should be focused within 2 - 7 days post-reperfusion. Some recent investigations have called into question the diagnostic validity of edema imaging after acute STEMI. Considering the results of these studies, as well as results from our own laboratory, we conclude that the time-course of edema post-STEMI is unimodal, not bimodal. Myocardial hemorrhage is the final consequence of severe vascular injury and a progressive and prognostically important complication early post-MI. Myocardial hemorrhage is a therapeutic target to limit reperfusion injury and infarct size post-STEMI.

  6. Quantitative cardiac phosphoproteomics profiling during ischemia-reperfusion in an immature swine model

    Energy Technology Data Exchange (ETDEWEB)

    Ledee, Dolena R.; Kang, Min A.; Kajimoto, Masaki; Purvine, Samuel O.; Brewer, Heather M.; Pasa Tolic, Ljiljana; Portman, Michael A.

    2017-07-01

    Ischemia-reperfusion (I/R) results in altered metabolic and molecular responses, and phosphorylation is one of the most noted regulatory mechanisms mediating signaling mechanisms during physiological stresses. To expand our knowledge of the potential phosphoproteomic changes in the myocardium during I/R, we used Isobaric Tags for Relative and Absolute Quantitation-based analyses in left ventricular samples obtained from porcine hearts under control or I/R conditions. The data are available via ProteomeXchange with identifier PXD006066. We identified 1,896 phosphopeptides within left ventricular control and I/R porcine samples. Significant differential phosphorylation between control and I/R groups was discovered in 111 phosphopeptides from 86 proteins. Analysis of the phosphopeptides using Motif-x identified five motifs: (..R..S..), (..SP..), (..S.S..), (..S…S..), and (..S.T..). Semiquantitative immunoblots confirmed site location and directional changes in phosphorylation for phospholamban and pyruvate dehydrogenase E1, two proteins known to be altered by I/R and identified by this study. Novel phosphorylation sites associated with I/R were also identified. Functional characterization of the phosphopeptides identified by our methodology could expand our understanding of the signaling mechanisms involved during I/R damage in the heart as well as identify new areas to target therapeutic strategies.

  7. Lin28a protects against cardiac ischaemia/reperfusion injury in diabetic mice through the insulin-PI3K-mTOR pathway.

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    Zhang, Mingming; Sun, Dongdong; Li, Shuang; Pan, Xietian; Zhang, Xiaotian; Zhu, Di; Li, Congye; Zhang, Rongqing; Gao, Erhe; Wang, Haichang

    2015-06-01

    The insulin-PI3K-mTOR pathway exhibits a variety of cardiovascular activities including protection against I/R injury. Lin28a enhanced glucose uptake and insulin-sensitivity via insulin-PI3K-mTOR signalling pathway. However, the role of lin28a on experimental cardiac I/R injury in diabetic mice are not well understood. Diabetic mice underwent 30 min. of ischaemia followed by 3 hrs of reperfusion. Animals were randomized to be treated with lentivirus carrying lin28a siRNA (siLin28a) or lin28a cDNA (Lin28a) 72 hrs before coronary artery ligation. Myocardial infarct size (IS), cardiac function, cardiomyocyte apoptosis and mitochondria morphology in diabetic mice who underwent cardiac I/R injury were compared between groups. The target proteins of lin28a were examined by western blot analysis. Lin28a overexpression significantly reduced myocardial IS, improved LV ejection fraction (LVEF), decreased myocardial apoptotic index and alleviated mitochondria cristae destruction in diabetic mice underwent cardiac I/R injury. Lin28a knockdown exacerbated cardiac I/R injury as demonstrated by increased IS, decreased LVEF, increased apoptotic index and aggravated mitochondria cristae destruction. Interestingly, pre-treatment with rapamycin abolished the beneficial effects of lin28a overexpression. Lin28a overexpression increased, while Lin28a knockdown decreased the expression of IGF1R, p-Akt, p-mTOR and p-p70s6k after cardiac I/R injury in diabetic mice. Rapamycin pre-treatment abolished the effects of increased p-mTOR and p-p70s6k expression exerted by lin28a overexpression. This study indicates that lin28a overexpression reduces IS, improves cardiac function, decreases cardiomyocyte apoptosis index and alleviates cardiomyocyte mitochondria impairment after cardiac I/R injury in diabetic mice. The mechanism responsible for the effects of lin28a is associated with the insulin-PI3K-mTOR dependent pathway. © 2015 The Authors. Journal of Cellular and Molecular Medicine

  8. Effect of terminal warm reperfusion (hot shot and remote ischemic preconditioning, either separately or combined, on myocardial recovery in adult cardiac surgery

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    Mohamed Elgariah

    2017-09-01

    Conclusions: Both remote ischemic preconditioning and terminal hot shot reperfusion before removal of the aortic cross clamping improved outcome of on-pump adult cardiac surgery patients. There was a significant effect on the in-hospital mortality and there were fewer incidences of arrhythmias and less requirement for postoperative inotropic support with this technique.

  9. The Impact of Ischemia/Reperfusion Injury on Liver Allografts from Deceased after Cardiac Death versus Deceased after Brain Death Donors.

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    Jin Xu

    Full Text Available The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD. The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD, we aimed to understand how ischemia/reperfusion (I/R injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration.Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13 and DBD (n = 10 livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22 and DBD (n = 13 livers.When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05 and C22 ceramide (p<0.05 were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST of DCD allografts had significantly increased.These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation.

  10. Playing with cardiac "redox switches": the "HNO way" to modulate cardiac function.

    Science.gov (United States)

    Tocchetti, Carlo G; Stanley, Brian A; Murray, Christopher I; Sivakumaran, Vidhya; Donzelli, Sonia; Mancardi, Daniele; Pagliaro, Pasquale; Gao, Wei Dong; van Eyk, Jennifer; Kass, David A; Wink, David A; Paolocci, Nazareno

    2011-05-01

    The nitric oxide (NO(•)) sibling, nitroxyl or nitrosyl hydride (HNO), is emerging as a molecule whose pharmacological properties include providing functional support to failing hearts. HNO also preconditions myocardial tissue, protecting it against ischemia-reperfusion injury while exerting vascular antiproliferative actions. In this review, HNO's peculiar cardiovascular assets are discussed in light of its unique chemistry that distinguish HNO from NO(•) as well as from reactive oxygen and nitrogen species such as the hydroxyl radical and peroxynitrite. Included here is a discussion of the possible routes of HNO formation in the myocardium and its chemical targets in the heart. HNO has been shown to have positive inotropic/lusitropic effects under normal and congestive heart failure conditions in animal models. The mechanistic intricacies of the beneficial cardiac effects of HNO are examined in cellular models. In contrast to β-receptor/cyclic adenosine monophosphate/protein kinase A-dependent enhancers of myocardial performance, HNO uses its "thiophylic" nature as a vehicle to interact with redox switches such as cysteines, which are located in key components of the cardiac electromechanical machinery ruling myocardial function. Here, we will briefly review new features of HNO's cardiovascular effects that when combined with its positive inotropic/lusitropic action may render HNO donors an attractive addition to the current therapeutic armamentarium for treating patients with acutely decompensated congestive heart failure.

  11. Autophagy: an adaptive physiological countermeasure to cellular senescence and ischaemia/reperfusion-associated cardiac arrhythmias.

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    Lekli, Istvan; Haines, David Donald; Balla, Gyorgy; Tosaki, Arpad

    2017-06-01

    Oxidative stress placed on tissues that involved in pathogenesis of a disease activates compensatory metabolic changes, such as DNA damage repair that in turn causes intracellular accumulation of detritus and 'proteotoxic stress', leading to emergence of 'senescent' cellular phenotypes, which express high levels of inflammatory mediators, resulting in degradation of tissue function. Proteotoxic stress resulting from hyperactive inflammation following reperfusion of ischaemic tissue causes accumulation of proteinaceous debris in cells of the heart in ways that cause potentially fatal arrhythmias, in particular ventricular fibrillation (VF). An adaptive response to VF is occurrence of autophagy, an intracellular bulk degradation of damaged macromolecules and organelles that may restore cellular and tissue homoeostasis, improving chances for recovery. Nevertheless, depending on the type and intensity of stressors and inflammatory responses, autophagy may become pathological, resulting in excessive cell death. The present review examines the multilayered defences that cells have evolved to reduce proteotoxic stress by degradation of potentially toxic material beginning with endoplasmic reticulum-associated degradation, and the unfolded protein response, which are mechanisms for removal from the endoplasmic reticulum of misfolded proteins, and then progressing through the stages of autophagy, including descriptions of autophagosomes and related vesicular structures which process material for degradation and autophagy-associated proteins including Beclin-1 and regulatory complexes. The physiological roles of each mode of proteotoxic defence will be examined along with consideration of how emerging understanding of autophagy, along with a newly discovered regulatory cell type called telocytes, may be used to augment existing strategies for the prevention and management of cardiovascular disease. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by

  12. Sustained protective effects of 7-monohydroxyethylrutoside in an in vivo model of cardiac ischemia-reperfusion

    NARCIS (Netherlands)

    De Celle, T; Heeringa, P; Strzelecka, AE; Bast, A; Smits, JF; Janssen, BJ

    2004-01-01

    Earlier studies have shown that 7-monohydroxyethylrutoside (monoHER), an antioxidant flavonoid, protects against doxorubicin-induced cardiotoxicity. In this study, we investigated potential sustained cardioprotective effects of monoHER in a model of ischemia-reperfusion (I/R) in mice. Ischemia was i

  13. O2 free radicals: cause of ischemia-reperfusion injury to cardiac Na+-K+-ATPase

    Energy Technology Data Exchange (ETDEWEB)

    Kim, M.S.; Akera, T.

    1987-02-01

    The role of O2 free radicals in the reduction of sarcolemmal Na+-K+-ATPase, which occurs during reperfusion of ischemic heart, was examined in isolated guinea pig heart using exogenous scavengers of O2 radicals and an inhibitor of xanthine oxidase. Ischemia and reperfusion reduced Na+-K+-ATPase activity and specific (3H)ouabain binding to the enzyme in ventricular muscle homogenates and also markedly lowered sodium pump activity estimated from ouabain-sensitive 86Rb+ uptake by ventricular muscle slices. These effects of ischemia and reperfusion were prevented to various degrees by O2-radical scavengers, such as superoxide dismutase, catalase, dimethyl-sulfoxide, histidine, or vitamin E or by the xanthine oxidase inhibitor, allopurinol. The degree of protection afforded by these agents paralleled that of reduction in enhanced lipid peroxidation of myocardial tissue as estimated from malondialdehyde production. These results strongly suggest that O2 radicals play a crucial role in the injury to sarcolemmal Na+-K+-ATPase during reperfusion of ischemic heart.

  14. Protection of Coronary Endothelial Function during Cardiac Surgery: Potential of Targeting Endothelial Ion Channels in Cardioprotection

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    Qin Yang

    2014-01-01

    Full Text Available Vascular endothelium plays a critical role in the control of blood flow by producing vasoactive factors to regulate vascular tone. Ion channels, in particular, K+ channels and Ca2+-permeable channels in endothelial cells, are essential to the production and function of endothelium-derived vasoactive factors. Impairment of coronary endothelial function occurs in open heart surgery that may result in reduction of coronary blood flow and thus in an inadequate myocardial perfusion. Hyperkalemic exposure and concurrent ischemia-reperfusion during cardioplegic intervention compromise NO and EDHF-mediated function and the impairment involves alterations of K+ channels, that is, KATP and KCa, and Ca2+-permeable TRP channels in endothelial cells. Pharmacological modulation of these channels during ischemia-reperfusion and hyperkalemic exposure show promising results on the preservation of NO and EDHF-mediated endothelial function, which suggests the potential of targeting endothelial K+ and TRP channels for myocardial protection during cardiac surgery.

  15. Effects of Acupuncture Pretreatment on Ischemic Cardiac Muscle Cell Apoptosis and Gene Expression in Ischemia-reperfusion Rats

    Institute of Scientific and Technical Information of China (English)

    赵宇辉; 孙忠人; 崔学军

    2009-01-01

    目的:针灸预处理对缺血心肌具有保护作用.通过观察针刺预处理对心肌缺血再灌注损伤大鼠心肌细胞凋亡及HSP70mPNA表达的影响,探讨针刺预处理的心肌保护机制.方法:64只Wistar大鼠随机分为8组,即正常对照组,假手术组,缺血再灌注组,缺血预处理组,手捻针预处理日1次组,电针预处理日1次组,手捻针预处理日2次组,电针预处理日2次组.建立大鼠心肌缺血再灌注模型,采用原位杂交法测定心肌HSP70mRNA的表达,TUNEL法检测细胞凋亡.结果:与正常对照组、假手术组比较,缺血再灌注组细胞凋亡增加,HSP70 mRNA表达增加;与缺血再灌注组比较,针刺预处理使心肌细胞凋亡减少、HSP70mRNA表达增加,且针刺预处理日2次组作用强于针刺预处理日1次组和缺血预处理组.结论:针刺预处理能够抑制心肌缺血再灌注损伤大鼠心肌细胞凋亡,上调心肌HSP70mRNA的表达.针刺预处理每日2次的作用强于针剌预处理每日1次.%Objective:To investigate the protective effects of acupuncture pretreatment on ischemic myocardium,the protective mechanism of acupuncture pretreatment on ischemic myocardium was explored by observing the cardiac muscle cell apoptosis and the expression of HSP70 mRNA of ischemia-reperfusion injury rats treated with acupuncture pretreatment.Methods:Sixty-four Wistar rats were randomly divided into eight groups:control group,sham surgery group,ischemia-repertusion group,ischemia pretreatment group,manual acupuncture pretreatment group(once a day),electroacupuncture pretreatment group(once a day),manual acupuncture pretreatment group(twice a day),and electroacupuncture pretreatment group(twice a day).The reperfusion model of rat myocardial ischemia was made.Expression of HSP70 mRNA was assayed by in situ hyrbridization,and cell apoptosis by TUNEL.Results:Compared with those in the control group and the sham surgery group,the apoptosis and the expression of HSP70 m

  16. N-acetylcysteine and allopurinol synergistically enhance cardiac adiponectin content and reduce myocardial reperfusion injury in diabetic rats.

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    Tingting Wang

    Full Text Available BACKGROUND: Hyperglycemia-induced oxidative stress plays a central role in the development of diabetic myocardial complications. Adiponectin (APN, an adipokine with anti-diabetic and anti-ischemic effects, is decreased in diabetes. It is unknown whether or not antioxidant treatment with N-acetylcysteine (NAC and/or allopurinol (ALP can attenuate APN deficiency and myocardial ischemia reperfusion (MI/R injury in the early stage of diabetes. METHODOLOGY/PRINCIPAL FINDINGS: Control or streptozotocin (STZ-induced diabetic rats were either untreated (C, D or treated with NAC (1.5 g/kg/day or ALP (100 mg/kg/day or their combination for four weeks starting one week after STZ injection. Plasma and cardiac biochemical parameters were measured after the completion of treatment, and the rats were subjected to MI/R by occluding the left anterior descending artery for 30 min followed by 2 h reperfusion. Plasma and cardiac APN levels were decreased in diabetic rats accompanied by decreased cardiac APN receptor 2 (AdipoR2, reduced phosphorylation of Akt, signal transducer and activator of transcription 3 (STAT3 and endothelial nitric oxide synthase (eNOS but increased IL-6 and TNF-α (all P<0.05 vs. C. NAC but not ALP increased cardiac APN concentrations and AdipoR2 expression in diabetic rats. ALP enhanced the effects of NAC in restoring cardiac AdipoR2 and phosphorylation of Akt, STAT3 and eNOS in diabetic rats. Further, NAC and ALP, respectively, decreased postischemic myocardial infarct size and creatinine kinase-MB (CK-MB release in diabetic rats, while their combination conferred synergistic protective effects. In addition, exposure of cultured rat cardiomyocytes to high glucose resulted in significant reduction of cardiomyocyte APN concentration and AdipoR2 protein expression. APN supplementation restored high glucose induced AdipoR2 reduction in cardiomyocytes. CONCLUSIONS/SIGNIFICANCE: NAC and ALP synergistically restore myocardial APN and AdipoR2

  17. Early reperfusion hemodynamics predict recovery in rat hearts: a potential approach towards evaluating cardiac grafts from non-heart-beating donors.

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    Monika Dornbierer

    Full Text Available AIMS: Cardiac grafts from non-heartbeating donors (NHBDs could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs. METHODS AND RESULTS: Hearts (n = 31 isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001. Coronary flow and the production of lactate and lactate dehydrogenase (LDH also correlated significantly with outcomes after 60 min reperfusion (p<0.05. Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR, developed pressure (DP and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *10(3 mmHg*beats*min(-1 (p<0.01. CONCLUSION: Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation.

  18. Early Reperfusion Hemodynamics Predict Recovery in Rat Hearts: A Potential Approach towards Evaluating Cardiac Grafts from Non-Heart-Beating Donors

    Science.gov (United States)

    Dornbierer, Monika; Stadelmann, Mathieu; Sourdon, Joevin; Gahl, Brigitta; Cook, Stéphane; Carrel, Thierry P.; Tevaearai, Hendrik T.; Longnus, Sarah L.

    2012-01-01

    Aims Cardiac grafts from non-heartbeating donors (NHBDs) could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs. Methods and Results Hearts (n = 31) isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C) for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV) pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001). Coronary flow and the production of lactate and lactate dehydrogenase (LDH) also correlated significantly with outcomes after 60 min reperfusion (p<0.05). Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR), developed pressure (DP) and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *103 mmHg*beats*min−1 (p<0.01). Conclusion Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation. PMID:22928009

  19. Protective Effect of Sevoflurane Postconditioning against Cardiac Ischemia/Reperfusion Injury via Ameliorating Mitochondrial Impairment, Oxidative Stress and Rescuing Autophagic Clearance.

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    Peng Yu

    Full Text Available Myocardial infarction leads to heart failure. Autophagy is excessively activated in myocardial ischemia/reperfusion (I/R in rats. The aim of this study is to investigate whether the protection of sevoflurane postconditioning (SPC in myocardial I/R is through restored impaired autophagic flux.Except for the sham control (SHAM group, each rat underwent 30 min occlusion of the left anterior descending coronary (LAD followed by 2 h reperfusion. Cardiac infarction was determined by 2,3,5-triphenyltetrazolium chloride triazole (TTC staining. Cardiac function was examined by hemodynamics and echocardiography. The activation of autophagy was evaluated by autophagosome accumulation, LC3 conversion and p62 degradation. Potential molecular mechanisms were investigated by immunoblotting, real-time PCR and immunofluorescence staining.SPC improved the hemodynamic parameters, cardiac dysfunction, histopathological and ultrastructural damages, and decreased myocardial infarction size after myocardial I/R injury (P < 0.05 vs. I/R group. Compared with the cases in I/R group, myocardial ATP and NAD+ content, mitochondrial function related genes and proteins, and the expressions of SOD2 and HO-1 were increased, while the expressions of ROS and Vimentin were decreased in the SPC group (P < 0.05 vs. I/R group. SPC significantly activated Akt/mTOR signaling, and inhibited the formation of Vps34/Beclin1 complex via increasing expression of Bcl2 protein (P < 0.05 vs. I/R group. SPC suppressed elevated expressions of LC3 II/I ratio, Beclin1, Atg5 and Atg7 in I/R rat, which indicated that SPC inhibited over-activation of autophagy, and promoted autophagosome clearance. Meanwhile, SPC significantly suppressed the decline of Opa1 and increases of Drp1 and Parkin induced by I/R injury (P < 0.05 vs. I/R group. Moreover, SPC maintained the contents of ATP by reducing impaired mitochondria.SPC protects rat hearts against I/R injury via ameliorating mitochondrial impairment

  20. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System.

    Science.gov (United States)

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2015-11-12

    Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1-7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1-7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafil further boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  1. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

    Directory of Open Access Journals (Sweden)

    Guoxing Wang

    2015-11-01

    Full Text Available Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg group. Thirty min after drug infusion, ventricular fibrillation (8 min and cardiopulmonary resuscitation (up to 30 min was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II and Ang (1–7 levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE, ACE2, Ang II type 1 receptor (AT1R, and the Ang (1–7 receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS, cyclic guanosine monophosphate (cGMP and inducible nitric oxide synthase(iNOS. Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  2. TIR/BB-loop mimetic AS-1 attenuates cardiac ischemia/reperfusion injury via a caveolae and caveolin-3-dependent mechanism

    Science.gov (United States)

    Hu, Yuanping; Zhang, Meiling; Shen, Xin; Dai, Guoliang; Ren, Danyang; Que, Linli; Ha, Tuanzhu; Li, Chuanfu; Xu, Yong; Ju, Wenzheng; Li, Yuehua

    2017-01-01

    AS-1, the TIR/BB loop mimetic, plays a protective role in cardiac ischemia/reperfusion (I/R) but the molecular mechanism remains unclear. The muscle specific caveolin3 (Cav-3) and the caveolae have been found to be critical for cardioprotection. This study aimed to evaluate our hypothesis that caveolae and Cav-3 are essential for AS-1-induced cardioprotection against myocardial I/R injury. To address these issues, we analyzed the involvement of Cav-3 in AS-1 mediated cardioprotection both in vivo and in vitro. We demonstrate that AS-1 administration significantly decreased infarct size, improved cardiac function after myocardial I/R and modulated membrane caveolae and Cav-3 expression in the myocardium. For in vitro studies, AS-1 treatment prevented Cav-3 re-distribution induced by H/R injury. In contrast, disruption of caveolae by MCD treatment or Cav-3 knockdown abolished the protection against H/R-induced myocytes injury by AS-1. Our findings reveal that AS-1 attenuates myocardial I/R injury through caveolae and Cav-3 dependent mechanism. PMID:28291255

  3. Ultrasound assessment of fetal cardiac function

    Science.gov (United States)

    Crispi, Fàtima; Valenzuela‐Alcaraz, Brenda; Cruz‐Lemini, Monica

    2015-01-01

    Abstract Introduction: Fetal heart evaluation with US is feasible and reproducible, although challenging due to the smallness of the heart, the high heart rate and limited access to the fetus. However, some cardiac parameters have already shown a strong correlation with outcomes and may soon be incorporated into clinical practice. Materials and Methods: Cardiac function assessment has proven utility in the differential diagnosis of cardiomyopathies or prediction of perinatal mortality in congenital heart disease. In addition, some cardiac parameters with high sensitivity such as MPI or annular peak velocities have shown promising results in monitoring and predicting outcome in intrauterine growth restriction or congenital diaphragmatic hernia. Conclusion: Cardiac function can be adequately evaluated in most fetuses when appropriate expertise, equipment and time are available. Fetal cardiac function assessment is a promising tool that may soon be incorporated into clinical practice to diagnose, monitor or predict outcome in some fetal conditions. Thus, more research is warranted to further define specific protocols for each fetal condition that may affect cardiac function. PMID:28191192

  4. Whole blood transcriptomics in cardiac surgery identifies a gene regulatory network connecting ischemia reperfusion with systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Orfeas Liangos

    Full Text Available BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CS/CPB is associated with increased risk for postoperative complications causing substantial morbidity and mortality. To identify the molecular mechanisms underlying CS/CPB-induced pathophysiology we employed an integrative systems biology approach using the whole blood transcriptome as the sentinel organ. METHODOLOGY/PRINCIPAL FINDINGS: Total RNA was isolated and globin mRNA depleted from whole blood samples prospectively collected from 10 patients at time points prior (0, 2 and 24 hours following CS/CPB. Genome-wide transcriptional analysis revealed differential expression of 610 genes after CS/CPB (p<0.01. Among the 375 CS/CPB-upregulated genes, we found a gene-regulatory network consisting of 50 genes, reminiscent of activation of a coordinated genetic program triggered by CS/CPB. Intriguingly, the highly connected hub nodes of the identified network included key sensors of ischemia-reperfusion (HIF-1alpha and C/EBPbeta. Activation of this network initiated a concerted inflammatory response via upregulation of TLR-4/5, IL1R2/IL1RAP, IL6, IL18/IL18R1/IL18RAP, MMP9, HGF/HGFR, CalgranulinA/B, and coagulation factors F5/F12 among others. Differential regulation of 13 candidate genes including novel, not hitherto CS/CBP-associated genes, such as PTX3, PGK1 and Resistin, was confirmed using real-time quantitative RT-PCR. In support of the mRNA data, differential expression of MMP9, MIP1alpha and MIP1beta plasma proteins was further confirmed in 34 additional patients. CONCLUSIONS: Analysis of blood transcriptome uncovered critical signaling pathways governing the CS/CPB-induced pathophysiology. The molecular signaling underlying ischemia reperfusion and inflammatory response is highly intertwined and includes pro-inflammatory as well as cardioprotective elements. The herein identified candidate genes and pathways may provide promising prognostic biomarker and therapeutic targets.

  5. Protective Effect of Peroxisome Proliferator-Activated Receptor α Activation against Cardiac Ischemia-Reperfusion Injury Is Related to Upregulation of Uncoupling Protein-3

    OpenAIRE

    2016-01-01

    Activation of peroxisome proliferator-activated receptor α (PPARα) confers cardioprotection, while its mechanism remains elusive. We investigated the protective effect of PPARα activation against cardiac ischemia-reperfusion injury in terms of the expression of uncoupling protein (UCP). Myocardial infarct size and UCP expression were measured in rats treated with WY-14643 20 mg/kg, a PPARα ligand, or vehicle. WY-14643 increased UCP3 expression in vivo. Myocardial infarct size was decreased in...

  6. Reperfusion therapy in out-of-hospital cardiac arrest: current insights.

    NARCIS (Netherlands)

    Keuper, W.; Dieker, H.J.; Brouwer, M.A.; Verheugt, F.W.A.

    2007-01-01

    Although early care in out-of-hospital cardiac arrest has been improved over the past decades, survival remains poor and neurological performance after survival is often impaired. Consequently, new therapies are needed to improve outcome. As thrombotic processes such as acute myocardial infarction o

  7. Epicardial measurement of alterations in extracellular pH and electrolytes during ischemia and reperfusion in cardiac surgery.

    Science.gov (United States)

    Vogt, Sebastian; Troitzsch, Dirk; Moosdorf, Rainer

    2009-12-01

    Simultaneous measurements of extracellular pH, potassium (K(+)), and calcium (Ca(2+)) activity might be indicative of myocardium vitality or ischemia. Ten consecutive patients undergoing elective coronary artery bypass grafting were studied. Epicardial extracellular pH, potassium, and calcium were measured by a miniaturized disposable multi-sensor probe. Blood gases and electrolytes were derived with measurements of arterial and mixed venous blood samples at intervals during surgery. The mean epicardial baseline levels for pH in all patients were 8.04+/-0.22 arbitrary units (AU) for the right ventricle (RV) and 8.03+/-0.21 AU for the left ventricle (LV); for Ca(2+) 0.23+/-0.07 mmol/l (RV) and 0.20+/-0.10 mmol/l (LV); and for K(+) 4.54+/-1.51 mmol/l (RV) and 4.38+/-0.57 mmol/l (LV). Before ischemia, epicardial pH was moderately (ppH, venous K(+) and Ca(2+), but moderately correlated with arterial K(+) and Ca(2+) (pischemia and reperfusion with reproducible trends of extracellular pH, K(+), and Ca(2+), which results in electrolyte patterns applicable for detecting inadequate myocardial protection during cardiac surgery in patients.

  8. Protective effect of olmesartan against cardiac ischemia/reperfusion injury in spontaneously hypertensive rats.

    Science.gov (United States)

    Lu, Xin; Bi, Yan-Wen; Chen, Ke-Biao; Wang, Hong-Yue

    2015-06-01

    Olmesartan, as a new angiotensin II receptor blocker, has shown beneficial effects on cardiovascular diseases. Nevertheless, the effect of olmesartan on ischemia/reperfusion (I/R) injury in the hypertensive heart has not been investigated. Therefore, the present study aimed to investigate the effect of olmesartan on I/R injury in spontaneously hypertensive rats (SHRs). Experimental groups were designed with a 2×2 factorial design for olmesartan and I/R effects. In the I/R group, the left anterior descending coronary artery (LAD) was ligated for 40 min followed by a 180-min reperfusion. In the sham group, SHRs underwent the same surgical procedure as the I/R group, with the exception that the suture passed under the LAD without being tightened. In the Olm-I/R group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the I/R group. In the Olm-sham group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the sham group. Infarct size was measured for the I/R and Olm-I/R groups. Blood pressure (BP), serum creatine kinase (CK), left ventricular mass index (LVMI), high mobility group box 1 (HMGB1) protein expression levels and hypoxia-inducible factor-1α (HIF-1α) mRNA expression levels were measured for all four groups. Olmesartan significantly reduced BP and LVMI in the olmesartan-treated SHRs compared with those in the SHRs that were not treated with olmesartan. HMGB1 and HIF-1α expression levels were significantly decreased in the Olm-sham and Olm-I/R groups compared with those in the sham and I/R groups, respectively. The proportional increase in HIF-1α expression due to I/R was greater in the olmesartan-treated rats than in the untreated rats. Serum CK levels were significantly reduced in the Olm-I/R group compared with those in the I/R group. In conclusion, olmesartan ameliorates left ventricular hypotrophy and protects the heart against I

  9. Cardiac mitochondria exhibit dynamic functional clustering

    Directory of Open Access Journals (Sweden)

    Felix Tobias Kurz

    2014-09-01

    Full Text Available Multi-oscillatory behavior of mitochondrial inner membrane potential ΔΨm in self-organized cardiac mitochondrial networks can be triggered by metabolic or oxidative stress. Spatio-temporal analyses of cardiac mitochondrial networks have shown that mitochondria are heterogeneously organized in synchronously oscillating clusters in which the mean cluster frequency and size are inversely correlated, thus suggesting a modulation of cluster frequency through local inter-mitochondrial coupling. In this study, we propose a method to examine the mitochondrial network's topology through quantification of its dynamic local clustering coefficients. Individual mitochondrial ΔΨm oscillation signals were identified for each cardiac myocyte and cross-correlated with all network mitochondria using previously described methods (Kurz et al., 2010. Time-varying inter-mitochondrial connectivity, defined for mitochondria in the whole network whose signals are at least 90% correlated at any given time point, allowed considering functional local clustering coefficients. It is shown that mitochondrial clustering in isolated cardiac myocytes changes dynamically and is significantly higher than for random mitochondrial networks that are constructed using the Erdös-Rényi model based on the same sets of vertices. The network's time-averaged clustering coefficient for cardiac myocytes was found to be 0.500 ± 0.051 (N=9 versus 0.061 ± 0.020 for random networks, respectively. Our results demonstrate that cardiac mitochondria constitute a network with dynamically connected constituents whose topological organization is prone to clustering. Cluster partitioning in networks of coupled oscillators has been observed in scale-free and chaotic systems and is therefore in good agreement with previous models of cardiac mitochondrial networks (Aon et al., 2008.

  10. A polysaccharide (PNPA) from Pleurotus nebrodensis offers cardiac protection against ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Yan, Bingju; Jing, Liying; Wang, Jun

    2015-11-20

    In this study, we isolated a polysaccharide (PNPA), with a molecular weight of 105kDa, from the fruiting bodies of Pleurotus nebrodensis. It had a backbone consisting of 1,3-linked-d-glucpyranosyl and 1,3,6-linked-d-galactopyranosyl residues, which was terminated with 1-linked-d-mannopyranosyl terminal at O-3 position of 1,3,6-linked-d-galactopyranosyl unit along the main chain in the ratio of 4:1:1. We further examined the effect of PNPA on myocardial ischemia-reperfusion (I/R) injury in rats and elucidated the underlying mechanism. Pretreatment with PNPA (100 and 400mg/kg) for 30 days significantly attenuated myocardial infarct size as compared to I/R model group. A decrease in superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels, as well as an increased malondialdehyde (MDA) content were observed in both myocardial serum and tissues of control I/R group, whereas pretreatment with PNPA markedly restored these change, and also relieved myocardial cell apoptosis. These results suggested that PNPA achieved protective effect on myocardial I/R injury in part through improving endogenous antioxidants and suppressing myocardial cell apoptosis.

  11. Relation between Tc-99m-PYP and Tl-201 scintigraphic findings and left ventricular function in acute myocardial infarction with early reperfusion

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Takao; Fukuzaki, Hisashi; Igarashi, Yuuichirou; Minamiji, Katsumi; Takarada, Akira; Imai, Naoaki; Fujino, Motohiro; Kurogane, Hiroyuki; Yoshida, Yutaka.

    1988-07-01

    The purpose of this study was to examine the significance of Tc-99m PYP uptake in the evaluation of myocardial salvage and reperfusion injury during early reperfusion in acute myocardial infarction. The subjects were 54 patients with initial myocardial infarction attributable to left anterior descending branch lesion in whom early reperfusion was attained by spontaneous recanalization (SR), intracoronary thrombolysis (ICT), and percutaneous transluminal angioplasty (PTCA). The radionuclide imaging appearances of the myocardium fell into four categories : I) small Tl-201 defect and faint Tc-99m PYP uptake ; II) small Tl-201 defect and intense Tc-99m PYP uptake ; III) large Tl-201 defect and faint Tc-99m PYP uptake ; and IV) large Tl-201 defect and intense Tc-99m PYP uptake. The incidences of I and II were higher in the group of SR patients than the group of ICT and PTCA patients. Features of left ventricular ejection fraction (LVEF) from the acute through the chronic stages were as follows : Category I - favorable LVEF through the stages ; Category II - improvement at chronic stage ; Category III - no consistent tendency for LVEF ; and Category IV - aggravation at chronic stage. In cases of early recanalization of acute myocardial infarction, Tc-99m PYP images combined with Tl-201 images may provide useful information on changes of cardiac function and salvage of the ischemic myocardium. (Namekawa, K.).

  12. Effects of vagus nerve stimulation on cognitive functioning in rats with cerebral ischemia reperfusion

    OpenAIRE

    Liu, Ai-Fen; Zhao, Feng-bo; Wang, Jing; Lu, Yi-Fan; Tian, Jian; Zhao, Yin; Gao, Yan; Hu, Xia-jun; LIU, XIAO-YAN; Tan, Jie; Tian, Yun-li; Shi, Jing

    2016-01-01

    Background Vagus nerve stimulation (VNS) has become the most common non-pharmacological treatment for intractable drug-resistant epilepsy. However, the contribution of VNS to neurological rehabilitation following stroke has not been thoroughly examined. Therefore, we investigated the specific role of acute VNS in the recovery of cognitive functioning and the possible mechanisms involved using a cerebral ischemia/reperfusion (I/R) injury model in rats. Methods The I/R-related injury was modele...

  13. Effect of Thermal Stress on Cardiac Function

    OpenAIRE

    Wilson, Thad E.; Crandall, Craig G.

    2011-01-01

    Whole-body heating decreases pulmonary capillary wedge pressure and cerebral vascular conductance, and causes an inotropic shift in the Frank-Starling curve. Whole-body cooling increases pulmonary capillary wedge pressure and cerebral vascular conductance without changing systolic function. These and other data indicate factors affecting cardiac function may mechanistically contribute to syncope during heat stress and improvements in orthostatic tolerance during cold stress.

  14. Protection of the ischaemic myocardium by L-propionylcarnitine: effects on the recovery of cardiac output after ischaemia and reperfusion, carnitine transport, and fatty acid oxidation.

    Science.gov (United States)

    Paulson, D J; Traxler, J; Schmidt, M; Noonan, J; Shug, A L

    1986-07-01

    The effects of L-propionylcarnitine on the recovery of cardiac contractile performance after global ischaemia and reperfusion were studied in isolated perfused rat hearts. The addition of either 5.5 or 11 mmol X litre-1 L-propionylcarnitine significantly improved the recovery of cardiac output, left ventricular pressure, and dP/dt after 90 min of ischaemia and 15 min of reperfusion. Myocardial adenosine triphosphate and creatine phosphate concentrations were significantly higher in the L-propionylcarnitine treated hearts than in controls, but the concentrations of long chain acyl carnitine and coenzyme A were unaffected. The protecting effects of L-propionylcarnitine were compared with those of L-carnitine and L-acetylcarnitine. A 11 mmol X litre-1 dose of L-propionylcarnitine and L-acetylcarnitine significantly improved the recovery of cardiac output after 90 min of ischaemia and 15 min of reperfusion, but L-carnitine did not. L-Propionylcarnitine was the most protective agent. The effects of these derivatives on L-3H-carnitine transport and 14C-palmitate oxidation were also measured. All of these derivatives competitively inhibited L-3H-carnitine transport in isolated cardiac myocytes, but L-propionylcarnitine was the most potent. Carnitine and L-propionylcarnitine stimulated palmitate oxidation in the homogenate, whereas L-acetylcarnitine inhibited it. In myocytes only L-propionylcarnitine affected palmitate oxidation. These data show that L-propionylcarnitine protects the ischaemic myocardium. Its protection is greater than that for L-carnitine or L-acetylcarnitine, and the difference in effectiveness may relate to the rate of transport into the cells and the effects on fatty acid utilisation.

  15. Effects of chromium picolinate on vascular reactivity and cardiac ischemia-reperfusion injury in spontaneously hypertensive rats.

    Science.gov (United States)

    Abebe, Worku; Liu, Jun Yao; Wimborne, Hereward; Mozaffari, Mahmood S

    2010-01-01

    Chromium picolinate [Cr(pic)(3)] is a nutritional supplement widely promoted to exert beneficial metabolic effects in patients with type 2 diabetes/impaired glucose tolerance. Frequent comorbidities in these individuals include systemic hypertension, abnormal vascular function and ischemic heart disease, but information on the effects of the supplement on these aspects is sparse. Utilizing male spontaneously hypertensive rats (SHR), we examined the potential impact of Cr(pic)(3) on blood pressure, vascular reactivity and myocardial ischemia-reperfusion injury (IRI). Dietary Cr(pic)(3) supplementation (as 10 mg chromium/kg diet for six weeks) did not affect blood pressure of the SHR. Also, neither norepinephrine (NE) and potassium chloride (KCl)-induced contractility nor sodium nitroprusside (SNP)-induced relaxation of aortic smooth muscle from the SHR was altered by Cr(pic)(3) treatment. However, Cr(pic)(3) augmented endothelium-dependent relaxation of aortas, produced by acetylcholine (ACh), and this effect was abolished by N-nitro-L-arginine methyl ester (L-NAME), suggesting induction of nitric oxide (NO) production/release. Treatment with Cr(pic)(3) did not affect baseline coronary flow rate and rate-pressure-product (RPP) or infarct size following regional IRI. Nonetheless, Cr(pic)(3) treatment was associated with improved coronary flow and recovery of myocardial contractility and relaxation following ischemia-reperfusion insult. In conclusion, dietary Cr(pic)(3) treatment of SHR alters neither blood pressure nor vascular smooth muscle reactivity but causes enhancement of endothelium-dependent vasorelaxation associated with NO production/release. Additionally, while the treatment does not affect infarct size, it improves functional recovery of the viable portion of the myocardium following IRI.

  16. Far red/near infrared light-induced protection against cardiac ischemia and reperfusion injury remains intact under diabetic conditions and is independent of nitric oxide synthase

    Directory of Open Access Journals (Sweden)

    Agnes eKeszler

    2014-08-01

    Full Text Available Far red/near-infrared light (NIR promotes a wide range of biological effects including tissue protection but whether and how NIR is capable of acutely protecting myocardium against ischemia and reperfusion injury in vivo is not fully elucidated. Our previous work indicates that NIR exposure immediately before and during early reperfusion protects the myocardium against infarction through mechanisms that are nitric oxide (NO-dependent. Here we tested the hypothesis that NIR elicits protection in a diabetic mouse model where other cardioprotective interventions such as pre- and postconditioning fail, and that the protection is independent of nitric oxide synthase (NOS. NIR reduced infarct size dose dependently. Importantly, NIR-induced protection was preserved in a diabetic mouse model (db/db and during acute hyperglycemia, as well as in endothelial NOS-/- mice and in wild type mice treated with NOS inhibitor L-NAME. In in vitro experiments NIR light liberates NO from nitrosyl hemoglobin (HbNO and nitrosyl myoglobin (MbNO in a wavelength (660-830 nm and dose-dependent manner. Irradiation at 660 nm yields the highest release of NO, while at longer wavelengths a dramatic decrease of NO release can be observed. Similar wavelength dependence was observed for the protection of mice against cardiac ischemia and reperfusion injury in vivo. NIR-induced NO release from deoxymyoglobin in the presence of nitrite mildly inhibits respiration of isolated mitochondria after hypoxia. In summary, NIR applied during reperfusion protects the myocardium against infarction in an NO dependent, but NOS-independent mechanisms, whereby mitochondria may be a target of NO released by NIR, leading to reduced reactive oxygen species generation during reperfusion. This unique mechanism preserves protection even during diabetes where other protective strategies fail.

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

    Science.gov (United States)

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

    2011-01-01

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

  18. Effects of interleukin-1 on cardiac fibroblast function: relevance to post-myocardial infarction remodelling.

    Science.gov (United States)

    Turner, Neil A

    2014-01-01

    The cardiac fibroblast (CF) is a multifunctional and heterogeneous cell type that plays an essential role in regulating cardiac development, structure and function. Following myocardial infarction (MI), the myocardium undergoes complex structural remodelling in an attempt to repair the damaged tissue and overcome the loss of function induced by ischemia/reperfusion injury. Evidence is emerging that CF play critical roles in all stages of post-MI remodelling, including the initial inflammatory phase that is triggered in response to myocardial damage. CF are particularly responsive to the proinflammatory cytokine interleukin-1 (IL-1) whose levels are rapidly induced in the myocardium after MI. Studies from our laboratory in recent years have sought to evaluate the functional effects of IL-1 on human CF function and to determine the underlying molecular mechanisms. This review summarises these data and sets it in the context of post-MI cardiac remodelling, identifying the fibroblast as a potential therapeutic target for reducing adverse cardiac remodelling and its devastating consequences. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Noninvasive MR characterization of structural and functional components of reperfused infarct

    Energy Technology Data Exchange (ETDEWEB)

    Saeed, Maythem; Martin, Alastair J.; Saloner, David; Loi Do; Wilson, Mark (Dept. of Radiology and Biomedical Imaging, Univ. of California San Francisco, San Francisco, CA (United States)), e-mail: Maythem.Saeed@radiology.ucsf.edu

    2010-12-15

    Background: Left ventricular (LV) remodeling is a highly complex phenomenon that starts soon after infarction and progresses to extensive regional and global architectural changes over time. Purpose: To noninvasively comprehensively characterize transient (edema, hemorrhage, microvascular obstruction (MO)) and persistent structural (infarct size) components of reperfused infarct up to 10 weeks and to determine their relation to LV function. Material and Methods: Farm pigs were used for the study. Under fluoroscopy the left anterior descending (LAD) coronary artery was occluded for 90 min. MR imaging was performed at 3 days (n=14 pigs), 5 weeks (n=10), and 10 weeks (n=6) after reperfusion. The following MR imaging sequences were used: (i) cine; (ii) T2-weighted turbo spin echo; (iii) T2-weighted turbo spin echo; (iv) tagged; (v) phase-contrast velocity-encoded; (vi) first-pass perfusion; and (vii) delayed contrast-enhanced (DE-MR imaging). After imaging, animals were euthanized at 3 days (n=4), 5 weeks (n=4), and 10 weeks (n=6) and hearts were stained with triphenyltetrazolium chloride to define acute, subacute, and scar infarct and interstitial hemorrhage. Results: T2, T2, and DE-MR imaging demonstrated transient interstitial edema, interstitial hemorrhage, and MO, respectively. MO was observed in 85% of animals and 60% of these showed hemorrhages. Cine, tagged, and phase-contrast velocity-encoded images documented the persistent impairment in 3D strain of infarcted segments, which on first-pass perfusion showed persistent perfusion deficit. MR imaging demonstrated the progressive increase in LV volumes and decreased ejection fraction over time. The changes in LV between 5 and 10 weeks were not related to the presence of interstitial edema, interstitial hemorrhage, MO or increase in infarct size. Conclusion: The various MR sequences described in this study allowed the demonstration of transient and persistent components of reperfused infarct. The progressive

  20. Interplay between cardiac function and heart development.

    Science.gov (United States)

    Andrés-Delgado, Laura; Mercader, Nadia

    2016-07-01

    Mechanotransduction refers to the conversion of mechanical forces into biochemical or electrical signals that initiate structural and functional remodeling in cells and tissues. The heart is a kinetic organ whose form changes considerably during development and disease. This requires cardiomyocytes to be mechanically durable and able to mount coordinated responses to a variety of environmental signals on different time scales, including cardiac pressure loading and electrical and hemodynamic forces. During physiological growth, myocytes, endocardial and epicardial cells have to adaptively remodel to these mechanical forces. Here we review some of the recent advances in the understanding of how mechanical forces influence cardiac development, with a focus on fluid flow forces. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  1. Gene transfer strategies for augmenting cardiac function.

    Science.gov (United States)

    Peppel, K; Koch, W J; Lefkowitz, R J

    1997-07-01

    Recent transgenic as well as gene-targeted animal models have greatly increased our understanding of the molecular mechanisms of normal and compromised heart function. These studies have raised the possibility of using somatic gene transfer as a means for improving cardiac function. DNA transfer to a significant portion of the myocardium has thus far been difficult to accomplish. This review describes current efforts to achieve myocardial gene transfer in several model systems, with particular emphasis placed on adenovirus-mediated gene delivery, its possibilities, and current limitations. (Trend Cardiovasc Med 1997;7:145-150). © 1997, Elsevier Science Inc.

  2. Protective Effect of Peroxisome Proliferator-Activated Receptor α Activation against Cardiac Ischemia-Reperfusion Injury Is Related to Upregulation of Uncoupling Protein-3

    Directory of Open Access Journals (Sweden)

    Jong Wook Song

    2016-01-01

    Full Text Available Activation of peroxisome proliferator-activated receptor α (PPARα confers cardioprotection, while its mechanism remains elusive. We investigated the protective effect of PPARα activation against cardiac ischemia-reperfusion injury in terms of the expression of uncoupling protein (UCP. Myocardial infarct size and UCP expression were measured in rats treated with WY-14643 20 mg/kg, a PPARα ligand, or vehicle. WY-14643 increased UCP3 expression in vivo. Myocardial infarct size was decreased in the WY-14643 group (76 ± 8% versus 42 ± 12%, P<0.05. During reperfusion, the incidence of arrhythmia was higher in the control group compared with the WY-14643 group (9/10 versus 3/10, P<0.05. H9c2 cells were incubated for 24 h with WY-14643 or vehicle. WY-14643 increased UCP3 expression in H9c2 cells. WY-14643 decreased hypoxia-stimulated ROS production. Cells treated with WY-14643 were more resistant to hypoxia-reoxygenation than the untreated cells. Knocking-down UCP3 by siRNA prevented WY-14643 from attenuating the production of ROS. UCP3 siRNA abolished the effect of WY-14643 on cell viability against hypoxia-reoxygenation. In summary, administration of PPARα agonist WY-14643 mitigated the extent of myocardial infarction and incidence of reperfusion-induced arrhythmia. PPARα activation conferred cytoprotective effect against hypoxia-reoxygenation. Associated mechanisms involved increased UCP3 expression and resultant attenuation of ROS production.

  3. Chronic Intermittent Hypobaric Hypoxia Improves Cardiac Function through Inhibition of Endoplasmic Reticulum Stress.

    Science.gov (United States)

    Yuan, Fang; Zhang, Li; Li, Yan-Qing; Teng, Xu; Tian, Si-Yu; Wang, Xiao-Ran; Zhang, Yi

    2017-08-11

    We investigated the role of endoplasmic reticulum stress (ERS) in chronic intermittent hypobaric hypoxia (CIHH)-induced cardiac protection. Adult male Sprague-Dawley rats were exposed to CIHH treatment simulating 5000 m altitude for 28 days, 6 hours per day. The heart was isolated and perfused with Langendorff apparatus and subjected to 30-min ischemia followed by 60-min reperfusion. Cardiac function, infarct size, and lactate dehydrogenase (LDH) activity were assessed. Expression of ERS molecular chaperones (GRP78, CHOP and caspase-12) was assayed by western blot analysis. CIHH treatment improved the recovery of left ventricular function and decreased cardiac infarct size and activity of LDH after I/R compared to control rats. Furthermore, CIHH treatment inhibited over-expression of ERS-related factors including GRP78, CHOP and caspase-12. CIHH-induced cardioprotection and inhibition of ERS were eliminated by application of dithiothreitol, an ERS inducer, and chelerythrine, a protein kinase C (PKC) inhibitor. In conclusion CIHH treatment exerts cardiac protection against I/R injury through inhibition of ERS via PKC signaling pathway.

  4. Advanced glycation end products accelerate ischemia/reperfusion injury through receptor of advanced end product/nitrative thioredoxin inactivation in cardiac microvascular endothelial cells.

    Science.gov (United States)

    Liu, Yi; Ma, Yanzhuo; Wang, Rutao; Xia, Chenhai; Zhang, Rongqing; Lian, Kun; Luan, Ronghua; Sun, Lu; Yang, Lu; Lau, Wayne B; Wang, Haichang; Tao, Ling

    2011-10-01

    The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured by increased inducible nitric oxide synthase expression, total nitric oxide production, superoxide generation, and peroxynitrite formation) and increased SI/R-induced nitrative inactivation of thioredoxin-1 (Trx-1), an essential cytoprotective molecule. Supplementation of EUK134 (peroxynitrite decomposition catalyst), human Trx-1, or soluble receptor of advanced end product (sRAGE) (a RAGE decoy) in AGE-BSA precultured cells attenuated SI/R-induced oxidative/nitrative stress, reduced SI/R-induced Trx-1 nitration, preserved Trx-1 activity, and reduced SI/R injury. Our results demonstrated that AGEs may increase SI/R-induced endothelial injury by increasing oxidative/nitrative injury and subsequent nitrative inactivation of Trx-1. Interventions blocking RAGE signaling or restoring Trx activity may be novel therapies to mitigate endothelial ischemia/reperfusion injury in the diabetic population.

  5. Insulin Preconditioning Elevates p-Akt and Cardiac Contractility after Reperfusion in the Isolated Ischemic Rat Heart

    Directory of Open Access Journals (Sweden)

    Tamaki Sato

    2014-01-01

    Full Text Available Insulin induces cardioprotection partly via an antiapoptotic effect. However, the optimal timing of insulin administration for the best quality cardioprotection remains unclear. We tested the hypothesis that insulin administered prior to ischemia provides better cardioprotection than insulin administration after ischemia. Isolated rat hearts were prepared using Langendorff method and divided into three groups. The Pre-Ins group (Pre-Ins received 0.5 U/L insulin prior to 15 min no-flow ischemia for 20 min followed by 20 min of reperfusion. The Post-Ins group (Post-Ins received 0.5 U/L insulin during the reperfusion period only. The control group (Control was perfused with KH buffer throughout. The maximum of left ventricular derivative of pressure development (dP/dt(max was recorded continuously. Measurements of TNF-α and p-Akt in each time point were assayed by ELISA. After reperfusion, dP/dt(max in Pre-Ins was elevated, compared with Post-Ins at 10 minutes after reperfusion and Control at all-time points. TNF-α levels at 5 minutes after reperfusion in the Pre-Ins were lower than the others. After 5 minutes of reperfusion, p-Akt was elevated in Pre-Ins compared with the other groups. Insulin administration prior to ischemia provides better cardioprotection than insulin administration only at reperfusion. TNF-α suppression is possibly mediated via p-Akt leading to a reduction in contractile myocardial dysfunction.

  6. Exendin-4 improves cardiac function in mice overexpressing monocyte chemoattractant protein-1 in cardiomyocytes.

    Science.gov (United States)

    Younce, Craig W; Niu, Jianli; Ayala, Jennifer; Burmeister, Melissa A; Smith, Layton H; Kolattukudy, Pappachan; Ayala, Julio E

    2014-11-01

    The incretin hormone glucagon-like peptide-1 (Glp1) is cardioprotective in models of ischemia-reperfusion injury, myocardial infarction and gluco/lipotoxicity. Inflammation is a factor in these models, yet it is unknown whether Glp1 receptor (Glp1r) agonists are protective against cardiac inflammation. We tested the hypothesis that the Glp1r agonist Exendin-4 (Ex4) is cardioprotective in mice with cardiac-specific monocyte chemoattractant protein-1 overexpression. These MHC-MCP1 mice exhibit increased cardiac monocyte infiltration, endoplasmic reticulum (ER) stress, apoptosis, fibrosis and left ventricular dysfunction. Ex4 treatment for 8 weeks improved cardiac function and reduced monocyte infiltration, fibrosis and apoptosis in MHC-MCP1 mice. Ex4 enhanced expression of the ER chaperone glucose-regulated protein-78 (GRP78), decreased expression of the pro-apoptotic ER stress marker CCAAT/-enhancer-binding protein homologous protein (CHOP) and increased expression of the ER calcium regulator Sarco/Endoplasmic Reticulum Calcium ATPase-2a (SERCA2a). These findings suggest that the Glp1r is a viable target for treating cardiomyopathies associated with stimulation of pro-inflammatory factors.

  7. Cardiac function and cognition in older community-dwelling cardiac patients.

    Science.gov (United States)

    Eggermont, Laura H P; Aly, Mohamed F A; Vuijk, Pieter J; de Boer, Karin; Kamp, Otto; van Rossum, Albert C; Scherder, Erik J A

    2017-04-17

    Cognitive deficits have been reported in older cardiac patients. An underlying mechanism for these findings may be reduced cardiac function. The relationship between cardiac function as represented by different echocardiographic measures and different cognitive function domains in older cardiac patients remains unknown. An older (≥70 years) heterogeneous group of 117 community-dwelling cardiac patients under medical supervision by a cardiologist underwent thorough echocardiographic assessment including left ventricular ejection fraction, cardiac index, left atrial volume index, left ventricular mass index, left ventricular diastolic function, and valvular calcification. During a home visit, a neuropsychological assessment was performed within 7.1 ± 3.8 months after echocardiographic assessment; the neuropsychological assessment included three subtests of a word-learning test (encoding, recall, recognition) to examine one memory function domain and three executive function tests, including digit span backwards, Trail Making Test B minus A, and the Stroop colour-word test. Regression analyses showed no significant linear or quadratic associations between any of the echocardiographic functions and the cognitive function measures. None of the echocardiographic measures as representative of cardiac function was correlated with memory or executive function in this group of community-dwelling older cardiac patients. These findings contrast with those of previous studies. © 2017 Japanese Psychogeriatric Society.

  8. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    Science.gov (United States)

    Gotzhein, Frauke; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk

    2017-01-01

    Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice. PMID:28352641

  9. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Peter Moritz Becher

    2017-01-01

    Full Text Available Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice.

  10. Traditional Chinese Medicine Shuang Shen Ning Xin Attenuates Myocardial Ischemia/Reperfusion Injury by Preserving of Mitochondrial Function

    Directory of Open Access Journals (Sweden)

    Xueli Li

    2014-01-01

    Full Text Available To investigate the potential cardioprotective effects of Shuang Shen Ning Xin on myocardial ischemia/reperfusion injury. Wistar rats were treated with trimetazidine (10 mg/kg/day, ig, Shuang Shen Ning Xin (22.5, 45 mg/kg/day, ig, or saline for 5 consecutive days. Myocardial ischemia/reperfusion injury was induced by ligation of the left anterior descending coronary artery for 40 min and reperfusion for 120 min on the last day of administration. It is found that Shuang Shen Ning Xin pretreatment markedly decreased infarct size and serum LDH levels, and this observed protection was associated with reduced myocardial oxidative stress and cardiomyocyte apoptosis after myocardial ischemia/reperfusion injury. In addition, further studies on mitochondrial function showed that rats treated with Shuang Shen Ning Xin displayed decreased mitochondrial swelling and cytosolic cytochrome c levels, which were accompanied by a preservation of complex I activities and inhibition of mitochondrial permeability transition. In conclusion, the mitochondrial protective effect of Shuang Shen Ning Xin could be a new mechanism, by which Shuang Shen Ning Xin attenuates myocardial ischemia/reperfusion injury.

  11. Functional cardiac imaging by random access microscopy

    Directory of Open Access Journals (Sweden)

    Claudia eCrocini

    2014-10-01

    Full Text Available Advances in the development of voltage sensitive dyes and Ca2+ sensors in combination with innovative microscopy techniques allowed researchers to perform functional measurements with an unprecedented spatial and temporal resolution. At the moment, one of the shortcomings of available technologies is their incapability of imaging multiple fast phenomena while controlling the biological determinants involved. In the near future, ultrafast deflectors can be used to rapidly scan laser beams across the sample, performing optical measurements of action potential and Ca2+ release from multiple sites within cardiac cells and tissues. The same scanning modality could also be used to control local Ca2+ release and membrane electrical activity by activation of caged compounds and light-gated ion channels. With this approach, local Ca2+ or voltage perturbations could be induced, simulating arrhythmogenic events, and their impact on physiological cell activity could be explored. The development of this optical methodology will provide fundamental insights in cardiac disease, boosting new therapeutic strategies, and, more generally, it will represent a new approach for the investigation of the physiology of excitable cells.

  12. MicroRNAs regulate mitochondrial apoptotic pathway in myocardial ischemia-reperfusion-injury.

    Science.gov (United States)

    Makhdoumi, Pouran; Roohbakhsh, Ali; Karimi, Gholamreza

    2016-12-01

    MicroRNAs (miRNAs) are small non-coding RNAs that act as post-transcriptional gene regulators. They are involved in the pathogenesis of different disorders including heart diseases. MiRNAs contribute to ischemia/reperfusion injury (I/RI) by altering numerous key signaling elements. Together with alterations in the various potential signaling pathways, modification in miRNA expression has been suggested as a part of the response network following ischemia/reperfusion (I/R). In addition, cardiac mitochondrial homeostasis is closely associated with cardiac function and impairment of mitochondrial activity occurred after ischemia/reperfusion injury. MiRNAs play a key role in the regulation of mitochondrial apoptotic pathway and signaling proteins. In this review, we summarize the knowledge currently available regarding the molecular mechanisms of miRNA-regulated mitochondrial functions during ischemia/reperfusion injury. This regulation occurs in different stages of mitochondrial apoptosis pathway.

  13. Effects of melatonin on liver function and lipid peroxidation in a rat model of hepatic ischemia/reperfusion injury.

    Science.gov (United States)

    Deng, Wen-Sheng; Xu, Qing; Liu, Y E; Jiang, Chun-Hui; Zhou, Hong; Gu, Lei

    2016-05-01

    The present study aimed to investigate the effects of melatonin (MT) on liver function and lipid peroxidation following hepatic ischemia-reperfusion injury (IRI). A total of 66 male Sprague-Dawley rats were randomly assigned into three groups: Normal control (N) group, ischemia-reperfusion (IR) group and the MT-treated group. A hepatic IRI model was developed by blocking the first porta hepatis, and subsequently restoring hepatic blood inflow after 35 min. Following reperfusion, changes in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were detected by a chemical method at various time points. In the MT group, the MDA levels were significantly reduced (PLDH were significantly reduced in the MT group at each time point, as compared with that of the IR group (Pfunction following IRI.

  14. Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury

    NARCIS (Netherlands)

    Olthof, Pim B.; Golen, van Rowan F.; Meijer, Ben; Beek, van Adriaan A.; Bennink, Roelof J.; Verheij, Joanne; Gulik, van Thomas M.; Heger, Michal

    2017-01-01

    Background

    Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse

  15. Abcc6 deficiency causes increased infarct size and apoptosis in a mouse cardiac ischemia-reperfusion model

    NARCIS (Netherlands)

    I.N. Mungrue; P. Zhao; Y. Yao; H. Meng; C. Rau; J.V. Havel; T.G.M.F. Gorgels; A.A.B. Bergen; W.R. Maclellan; T.A. Drake; K.I. Boström; A.J. Lusis

    2011-01-01

    ABCC6 genetic deficiency underlies pseudoxanthoma elasticum (PXE) in humans, characterized by ectopic calcification, and early cardiac disease. The spectrum of PXE has been noted in Abcc6-deficient mice, including dystrophic cardiac calcification. We tested the role of Abcc6 in response to cardiac i

  16. Nebivolol: impact on cardiac and endothelial function and clinical utility

    Directory of Open Access Journals (Sweden)

    Toblli JE

    2012-03-01

    Full Text Available Jorge Eduardo Toblli1, Federico DiGennaro1, Jorge Fernando Giani2, Fernando Pablo Dominici21Hospital Aleman, 2Instituto de Química y Fisicoquímica Biológicas (IQUIFIB, Facultad de Farmacia y Bioquímica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, ArgentinaAbstract: Endothelial dysfunction is a systemic pathological state of the endothelium characterized by a reduction in the bioavailability of vasodilators, essentially nitric oxide, leading to impaired endothelium-dependent vasodilation, as well as disarrangement in vascular wall metabolism and function. One of the key factors in endothelial dysfunction is overproduction of reactive oxygen species which participate in the development of hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, ischemia-reperfusion injury, and stroke. Because impaired endothelial activity is believed to have a major causal role in the pathophysiology of vascular disease, hypertension, and heart failure, therapeutic agents which modify this condition are of clinical interest. Nebivolol is a third-generation β-blocker with high selectivity for β1-adrenergic receptors and causes vasodilation by interaction with the endothelial L-arginine/nitric oxide pathway. This dual mechanism of action underscores several hemodynamic qualities of nebivolol, which include reductions in heart rate and blood pressure and improvements in systolic and diastolic function. Although nebivolol reduces blood pressure to a degree similar to that of conventional β-blockers and other types of antihypertensive drugs, it may have advantages in populations with difficult-to-treat hypertension, such as patients with heart failure along with other comorbidities, like diabetes and obesity, and elderly patients in whom nitric oxide-mediated endothelial dysfunction may be more pronounced. Furthermore, recent data indicate that nebivolol appears to be a cost-effective treatment for elderly patients with

  17. DISSOCIATION OF STRUCTURE AND FUNCTION AFTER ISCHAEMIA-REPERFUSION INJURY IN THE ISOLATED PERFUSED RAT KIDNEYS

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    M. Kadkhodaee

    1999-08-01

    Full Text Available Oxygen-derived free radical* (OFR involvement in ischacmia-rcpcrfusion (IR injury was investigated in a rat isolated kidney model, using 20 minutes iscliaemia followed by 15 or 60 minutes reperfusion. Two antioxidants, the xanthine oxidase inhibitor allopurinol and the hydroxyl radical scavenger dimcthylthiourca (DMTU, were uscit to try and prevent OFR-relatcd damage. Renal function was estimated from the inulin clearance, fractional soiiium excretion and renal vascular resistance, location and extent of tubular damage, and type of cell death (apoptosis vs necrosis were used as morphological parameters of IR-iiuluced change. Cell damage was most extensive in the nephron segments of the outer zone of the outer medulla (straight proximal tubule and thick ascending limb (TAL. I're-treatment with allopttrinol or DMTU did not Improve renal function. Less structural damage was observed in the TAL of allopuriol - or DMTU - treated kidneys compared with IR alone. In allopurinol - treated kidneys, luminal debris was less extensive than that seen in IR kidneys. Most cell death was necrotic in type and morphological features of apoptosis were seen infrequently. Tlic beneficial effects of allopurinol and DMTU on structural change did not correlate with functional improvement during the reperfusion period, litis may require longer repcrfusion or multiple treatments. Tlie results suggest that OFR ■ injury is of limited significance in this model of renal IR injury. Targeting OFR injury may only be useful after very brief periods of iscliaemia where necrosis is minimal ami the potential for recover}- is greater, Tiie results confirm the different susccptibilitcs of individual nephron segments to injury within the intact kidney. Understanding the molecular response to injury in each segment should facilitate development of methods to accelerate repair after [R injury.

  18. Transplantation of 5-azacytidine treated cardiac fibroblasts improves cardiac function of infarct hearts in rats

    Institute of Scientific and Technical Information of China (English)

    TANG Cheng-chun; MA Gan-shan; CHEN Ji-yuan

    2010-01-01

    Background Cellular cardiomyoplasty by transplantation of various cell types has been investigated as potential treatments for the improvement of cardiac function after myocardial injury. A major barrier for the clinical application of cell transplantation is obtaining sufficiently large quantities of suitable cells. AIIogeneic cellular cardiomyoplasty may provide an alternative source of abundant, transplantable, myogenic cells by in vitro manipulation of cardiac fibroblasts using chemicals including 5-azacytidine. This study evaluated cardiomyogenic differentiation of cardiac fibroblasts, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.Methods Primary cardiac fibroblasts from neonatal rats were treated with 5-azacytidine (10 μmol/L) or control.Treatment of 5-azacytidine caused myogenic differentiation of cultured cardiac fibroblasts, as defined by elongation and fusion into multinucleated myotubes with sarcomeric structures as identified by electron microscopy, and positive immunostaining for cardiac specific proteins, troponin I and β-myosin heavy chain (β-MHC) and the gap junction protein connexin 43. The myogenic cells (1.0x106) were transplanted into the infarcted myocardium 2 weeks after coronary artery occlusion.Results By 1 month after transplantation, the converted fibroblasts gave rise to a cluster of cardiac-like muscle cells that in the hearts occupied a large part of the scar with positive immunostaining for the myogenic proteins troponin I and β-MHC. Engrafted cells also expressed the gap junction protein connexin 43 in a disorganized manner. There was no positive staining in the control hearts treated with injections of culture medium. Heart function was evaluated at 6 weeks after myocardial injury with echocardiographic and hemodynamic measurements. Improvement in cardiac function was seen in the hearts transplanted with the 5-azacytidine-treated cardiac fibroblasts which was absent in the

  19. Relationship between cardiac function and resting cerebral blood flow

    DEFF Research Database (Denmark)

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

    2014-01-01

    Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF...... and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1......) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P...

  20. The relation between hypointense core, microvascular obstruction and intramyocardial haemorrhage in acute reperfused myocardial infarction assessed by cardiac magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kandler, Diana; Luecke, Christian; Grothoff, Matthias; Andres, Claudia; Lehmkuhl, Lukas; Nitzsche, Stefan; Riese, Franziska; Gutberlet, Matthias [University Leipzig - Heart Centre, Department of Diagnostic and Interventional Radiology, Leipzig (Germany); Mende, Meinhard [University Leipzig, Coordination Centre for Clinical Trials, Leipzig (Germany); Waha, Suzanne de; Desch, Steffen; Lurz, Philipp; Eitel, Ingo [University Leipzig - Heart Centre, Department of Internal Medicine/ Cardiology, Leipzig (Germany)

    2014-12-15

    Intramyocardial haemorrhage (IMH) and microvascular obstruction (MVO) represent reperfusion injury after reperfused ST-elevation myocardial infarction (STEMI) with prognostic impact and ''hypointense core'' (HIC) appearance in T{sub 2}-weighted images. We aimed to distinguish between IMH and MVO by using T{sub 2}{sup *}-weighted cardiovascular magnetic resonance imaging (CMR) and analysed influencing factors for IMH development. A total of 151 patients with acute STEMI underwent CMR after primary angioplasty. T{sub 2}-STIR sequences were used to identify HIC, late gadolinium enhancement to visualise MVO and T{sub 2}{sup *}-weighted sequences to detect IMH. IMH{sup +}/IMH{sup -} patients were compared considering infarct size, myocardial salvage, thrombolysis in myocardial infarction (TIMI) flow, reperfusion time, ventricular volumes, function and pre-interventional medication. Seventy-six patients (50 %) were IMH{sup +}, 82 (54 %) demonstrated HIC and 100 (66 %) MVO. IMH was detectable without HIC in 16 %, without MVO in 5 % and HIC without MVO in 6 %. Multivariable analyses revealed that IMH was associated with significant lower left ventricular ejection fraction and myocardial salvage index, larger left ventricular volume and infarct size. Patients with TIMI flow grade ≤1 before angioplasty demonstrated IMH significantly more often. IMH is associated with impaired left ventricular function and higher infarct size. T{sub 2} and HIC imaging showed moderate agreement for IMH detection. T{sub 2}{sup *} imaging might be the preferred CMR imaging method for comprehensive IMH assessment. (orig.)

  1. Angiogenesis and cardiac hypertrophy: maintenance of cardiac function and causative roles in heart failure.

    Science.gov (United States)

    Oka, Toru; Akazawa, Hiroshi; Naito, Atsuhiko T; Komuro, Issei

    2014-01-31

    Cardiac hypertrophy is an adaptive response to physiological and pathological overload. In response to the overload, individual cardiac myocytes become mechanically stretched and activate intracellular hypertrophic signaling pathways to re-use embryonic transcription factors and to increase the synthesis of various proteins, such as structural and contractile proteins. These hypertrophic responses increase oxygen demand and promote myocardial angiogenesis to dissolve the hypoxic situation and to maintain cardiac contractile function; thus, these responses suggest crosstalk between cardiac myocytes and microvasculature. However, sustained pathological overload induces maladaptation and cardiac remodeling, resulting in heart failure. In recent years, specific understanding has increased with regard to the molecular processes and cell-cell interactions that coordinate myocardial growth and angiogenesis. In this review, we summarize recent advances in understanding the regulatory mechanisms of coordinated myocardial growth and angiogenesis in the pathophysiology of cardiac hypertrophy and heart failure.

  2. Protection of the reperfused heart by L-propionylcarnitine.

    Science.gov (United States)

    Leipälä, J A; Bhatnagar, R; Pineda, E; Najibi, S; Massoumi, K; Packer, L

    1991-10-01

    The effects of L-propionylcarnitine on mechanical function, creatine phosphate and ATP content, and lactate dehydrogenase leakage were studied in isolated perfused rat hearts exposed to global no-flow ischemia for 30 min followed by reperfusion for 20 min. Five and 10 mM L-propionylcarnitine resulted in a 100% recovery of left ventricular-developed pressure, whereas the recovery was only 40% in the hearts perfused without this agent. Ischemia-reperfusion caused a 85% loss of creatine phosphate and a 77% loss of ATP, which was prevented by 10 mM L-propionylcarnitine. Five millimolar L-propionylcarnitine protected the heart from the loss of creatine phosphate but not from the loss of ATP. Ten millimolar L-propionylcarnitine failed to improve the postischemic left ventricular-developed pressure, when it was added to the perfusate only after ischemia. L-propionylcarnitine alleviated the decrease of coronary flow in the reperfused hearts. Lactate dehydrogenase leakage was aggravated in the beginning of the reperfusion period by 10 mM L-propionylcarnitine. This adverse effect was, however, transient. L-Propionylcarnitine provides protection for the postischemic reperfused heart in a dose-dependent manner. The optimal time for administration is before the ischemic insult. High doses of this compound may perturb cell membrane integrity. Moreover, the present data point to an intracellular, metabolic, and perhaps anaplerotic mechanism of action of L-propionylcarnitine in cardiac ischemia-reperfusion injury.

  3. Comparison of regional and global left ventricular function by serial echocardiograms after reperfusion in acute myocardial infarction.

    Science.gov (United States)

    Broderick, T M; Bourdillon, P D; Ryan, T; Feigenbaum, H; Dillon, J C; Armstrong, W F

    1989-01-01

    Fifty patients undergoing successful reperfusion therapy (percutaneous transluminal coronary angioplasty 20, thrombolysis 10, combined 20) for acute myocardial infarction were evaluated with serial two-dimensional echocardiograms performed early (less than 24 hours, mean 8 hours) and late (greater than 3 days, mean 6 days) after presentation. Treatment occurred within 12 hours of the onset of symptoms with most patients achieving reperfusion in less than 6 hours (mean 4.7 hours) from the onset of pain. Reperfusion was demonstrated short-term by angiography in 42 of 50 patients (84%). Four patients had clinical signs of reperfusion and subsequent angiographic confirmation. An additional four patients with "stuttering" infarct courses were treated late by percutaneous transluminal coronary angioplasty. Echocardiograms were analyzed for global performance by calculation of fractional area change at the papillary muscle level and ejection fraction (biplane Simpson's rule) in 18 patients in whom this analysis could be performed. Measurements of regional function included fractional shortening at the base (n = 37), regional wall motion index (n = 50) and percent of normal functioning myocardium (n = 50). Overall there was a significant improvement in regional wall scores and percent of functioning myocardium (regional wall motion index 1.73 to 1.43, p less than 0.001 and percent of functioning myocardium 0.61 to 0.70, p less than 0.001) but only a trend toward improvement when global function was assessed by ejection fraction (0.42 to 0.48, p less than 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

  4. MG132 Inhibits Myocardial Ischemia-reperfusion Injury by Regulating Apoptotic Pathway

    Institute of Scientific and Technical Information of China (English)

    Dai Cuilian; Luo Kailiang; Chen Zhangrong

    2007-01-01

    Objectives To administrated proteasome inhibitor-MG-132 prior to reperfusion in rat myocardial ischemia-reperfusion model to determine whether MG-132 could reduce myocytic apoptosis. Methods and results MG-132 (0.75 mg/kg in 2 ml DMSO) injection 5 min prior to reperfusion resulted significant reduction of myocardial reperfusion injury. This effect was accompanied by reduced polymorphonuclear neutrophils(PMN) infiltration in myocardial region surrounding the myocardial infarct, reduced apoptosis in cardiac myocytes, reduced NF-κB activation, as determined by electron microscopy, histology, immunohistochemistry, the terminal deoxynucleotidyl transferase-mediated nick endlabeling (TUNEL) method, reverse transcription-polymerase chain reaction. Functional effects of MG-132 on PMN accumulation, activation of nuclear factor kappa B(p65 mRNA and protein levels ), and apoptosis were characterized in rat myocardial tissue. MG132 time-dependently inhibited myocardial p65 mRNA expression and reduced myocardial apoptotic index (AI) after reperfusion for 2 h, 6 h and 24 h ( P<0.01 ). Moreover, MG-132 time-dependently decreased Bax protein levels, while increased Bcl-2 protein levels in ischemic and reperfused myocardium ( P<0.05 ), its effect peaked after reperfusion for 24 h. Conclusions Our results demonstrate that MG-132 reduced myocardial reperfusion injury by inhibiting myosytic apoptotic cell death and blocking activation of NF-κB, down-regulating Bax expression and up-regulating Bcl-2 expression as well as elevating Bcl-2/Bax ratio.

  5. Function of Heat Shock Protein 70 in Myocardial Ischemia-Reperfusion Injury%热休克蛋白70在心肌缺血/再灌注损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    高奎乐

    2012-01-01

    Ischemia-reperfusion injury is an important cause of myocardial injury during cardiac surgery under cardiopulmonary bypass. Heat shock protein 70 is an important endogenous protective factor,which enhances cell damage tolerance of ischemia-reperfusion injury,maintaining the normal function of the cell metabolism,and improving cell survival. It also plays an important role in the anti-arrhythmia and myocardial anti-oxidative process. Heat shock protein 70 has an endogenous protective effect on myocardial in ischemia-reperfusion injury.%缺血/再灌注损伤是体外循环下心脏手术中心肌损伤的重要原因.热休克蛋白70是一种重要的内源性保护因子,它在缺血/再灌注损伤过程中增强细胞对损害的耐受程度,维持细胞的正常功能代谢,提高细胞生存率,在抗心律失常及心肌抗氧化过程中也起到重要作用.热休克蛋白70对缺血/再灌注损伤心肌具有内源性保护作用.

  6. Echocardiographic assessment of cardiac morphology and function in Xenopus.

    Science.gov (United States)

    Bartlett, Heather L; Escalera, Robert B; Patel, Sonali S; Wedemeyer, Elesa W; Volk, Kenneth A; Lohr, Jamie L; Reinking, Benjamin E

    2010-04-01

    Advances using Xenopus as a model permit valuable inquiries into cardiac development from embryo to adult. Noninvasive methods are needed to study cardiac function longitudinally. The objective of this study was to evaluate the feasibility of echocardiographic studies in Xenopus and establish normative data of adult cardiac structure and function. Doppler and 2D echocardiograms and electrocardiograms were acquired from adult Xenopus laevis and X. tropicalis. Frogs were exposed to either isoflurane or tricaine to discern the effect of sedating agents on cardiac function. Cardiac dimensions, morphology, flow velocities, and electrophysiologic intervals were measured and evaluated by using bivariate and regression analyses. Normal cardiac dimensions relative to body weight and species were established by echocardiography. Normal conduction intervals were determined by electrocardiography and did not vary by body weight or species. Anesthetic agent did not affect ejection fraction or flow velocity but did alter the QRS duration and QT interval. Echocardiographic and electrocardiographic studies in Xenopus provide information about cardiac anatomy and physiology and can readily be used for longitudinal analyses of developmental inquiries. Body weight, species, and anesthetic agent are factors that should be considered in experimental design and analyses.

  7. Cardiac function in trisomy 21 fetuses

    NARCIS (Netherlands)

    Clur, S. A. B.; Rengerink, K. Oude; Ottenkamp, J.; Bilardo, C. M.

    2011-01-01

    Objectives Trisomy 21 is associated with an increased nuchal translucency thickness (NT), abnormal ductus venosus (DV) flow at 11-14 weeks' gestation and congenital heart defects (CHD), and cardiac dysfunction has been hypothesized as the link between them. We therefore aimed to investigate whether

  8. Cardiac function in trisomy 21 fetuses

    NARCIS (Netherlands)

    Clur, S. A. B.; Rengerink, K. Oude; Ottenkamp, J.; Bilardo, C. M.

    2011-01-01

    Objectives Trisomy 21 is associated with an increased nuchal translucency thickness (NT), abnormal ductus venosus (DV) flow at 11-14 weeks' gestation and congenital heart defects (CHD), and cardiac dysfunction has been hypothesized as the link between them. We therefore aimed to investigate whether

  9. Cold preservation with hyperbranched polyglycerol-based solution improves kidney functional recovery with less injury at reperfusion in rats

    Science.gov (United States)

    Li, Shadan; Liu, Bin; Guan, Qiunong; Chafeeva, Irina; Brooks, Donald E; Nguan, Christopher YC; Kizhakkedathu, Jayachandran N; Du, Caigan

    2017-01-01

    Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation. PMID:28337272

  10. Correlation of CT-based regional cardiac function (SQUEEZ) with myocardial strain calculated from tagged MRI: an experimental study.

    Science.gov (United States)

    Pourmorteza, Amir; Chen, Marcus Y; van der Pals, Jesper; Arai, Andrew E; McVeigh, Elliot R

    2016-05-01

    The objective of this study was to investigate the correlation between local myocardial function estimates from CT and myocardial strain from tagged MRI in the same heart. Accurate detection of regional myocardial dysfunction can be an important finding in the diagnosis of functionally significant coronary artery disease. Tagged MRI is currently a reference standard for noninvasive regional myocardial function analysis; however, it has practical drawbacks. We have developed a CT imaging protocol and automated image analysis algorithm for estimating regional cardiac function from a few heartbeats. This method tracks the motion of the left ventricular (LV) endocardial surface to produce local function maps: we call the method Stretch Quantification of Endocardial Engraved Zones (SQUEEZ). Myocardial infarction was created by ligation of the left anterior descending coronary artery for 2 h followed by reperfusion in canine models. Tagged and cine MRI scans were performed during the reperfusion phase and first-pass contrast enhanced CT scans were acquired. The average delay between the CT and MRI scans was myocardial strain (Ecc) was calculated from the tagged MRI data. The agreement between peak systolic Ecc and SQUEEZ was investigated in 162 segments in the 9 hearts. Linear regression and Bland-Altman analysis was used to assess the correlation between the two metrics of local LV function. The results show good agreement between SQUEEZ and Ecc: (r = 0.71, slope = 0.78, p function. The good agreement between the estimates of local myocardial function obtained from CT SQUEEZ and tagged MRI provides encouragement to investigate the use of SQUEEZ for measuring regional cardiac function at a low clinical dose in humans.

  11. Prognostic value and determinants of a hypointense infarct core in T2-weighted cardiac magnetic resonance in acute reperfused ST-elevation-myocardial infarction.

    Science.gov (United States)

    Eitel, Ingo; Kubusch, Konrad; Strohm, Oliver; Desch, Steffen; Mikami, Yoko; de Waha, Suzanne; Gutberlet, Matthias; Schuler, Gerhard; Friedrich, Matthias G; Thiele, Holger

    2011-07-01

    A hypointense core of infarcted myocardium in T2-weighted cardiovascular MRI (CMR) has been used as a noninvasive marker for intramyocardial hemorrhage. However, the clinical significance of such findings not yet been established. The aim of this study was to evaluate determinants and prognostic impact of a hypointense infarct core in T2-weighted CMR images, studied in patients after acute, reperfused ST-elevation-myocardial infarction. We analyzed 346 patients with ST-elevation-myocardial infarction undergoing primary angioplasty core in T2-weighted images, and late microvascular obstruction. Patients were categorized into 2 groups defined by the presence or absence of a hypointense core. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and congestive heart failure within 6 months after infarction. A hypointense core was present in 122 (35%) patients and was associated with larger infarcts, greater amount of microvascular obstruction, less myocardial salvage, and impaired left ventricular function (P core was a strong univariable predictor of major adverse cardiovascular events (hazard ratio, 2.59; confidence interval, 1.27 to 5.27) and was significantly associated with an increased major adverse cardiovascular events rate (16.4% versus 7.0%, P = 0.006) 6 months after infarction. A hypointense infarct core within the area at risk of reperfused infarcted myocardium in T2-weighted CMR is closely related to infarct size, microvascular obstruction, and impaired left ventricular function, with subsequent adverse clinical outcome.

  12. Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling

    Science.gov (United States)

    Yu, Liming; Gong, Bing; Duan, Weixun; Fan, Chongxi; Zhang, Jian; Li, Zhi; Xue, Xiaodong; Xu, Yinli; Meng, Dandan; Li, Buying; Zhang, Meng; Bin Zhang; Jin, Zhenxiao; Yu, Shiqiang; Yang, Yang; Wang, Huishan

    2017-01-01

    Enhancing mitochondrial biogenesis and reducing mitochondrial oxidative stress have emerged as crucial therapeutic strategies to ameliorate diabetic myocardial ischemia/reperfusion (MI/R) injury. Melatonin has been reported to be a safe and potent cardioprotective agent. However, its role on mitochondrial biogenesis or reactive oxygen species (ROS) production in type 1 diabetic myocardium and the underlying mechanisms remain unknown. We hypothesize that melatonin ameliorates MI/R injury in type 1 diabetic rats by preserving mitochondrial function via AMPK-PGC-1α-SIRT3 signaling pathway. Both our in vivo and in vitro data showed that melatonin reduced MI/R injury by improving cardiac function, enhancing mitochondrial SOD activity, ATP production and oxidative phosphorylation complex (II, III and IV), reducing myocardial apoptosis and mitochondrial MDA, H2O2 generation. Importantly, melatonin also activated AMPK-PGC-1α-SIRT3 signaling and increased SOD2, NRF1 and TFAM expressions. However, these effects were abolished by Compound C (a specific AMPK signaling blocker) administration. Additionally, our cellular experiment showed that SIRT3 siRNA inhibited the cytoprotective effect of melatonin without affecting p-AMPK/AMPK ratio and PGC-1α expression. Taken together, we concluded that melatonin preserves mitochondrial function by reducing mitochondrial oxidative stress and enhancing its biogenesis, thus ameliorating MI/R injury in type 1 diabetic state. AMPK-PGC1α-SIRT3 axis plays an essential role in this process. PMID:28120943

  13. Low dose prospective ECG-gated delayed enhanced dual-source computed tomography in reperfused acute myocardial infarction comparison with cardiac magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Wang Rui, E-mail: rui_wang1979@yahoo.cn [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Zhang Zhaoqi, E-mail: zhaoqi5000@vip.sohu.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Xu Lei, E-mail: leixu2001@hotmail.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Ma Qin, E-mail: tel1367@gmail.com [Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); He Yi, E-mail: heyi139@sina.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Lu Dongxu, E-mail: larry.hi@163.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Yu Wei, E-mail: yuwei02@gmail.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China); Fan Zhanming, E-mail: fanzm120@tom.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing (China)

    2011-11-15

    Purpose: To determine whether prospective electrocardiogram (ECG)-gated delayed contrast-enhanced dual-source computed tomography (DCE-DSCT) can accurately delineate the extension of myocardial infarction (MI) compared with delayed enhanced cardiac MR (DE-MR). Material and methods: Eleven patients were examined using dual-source CT and cardiac MR in 2 weeks after a first reperfused MI. DCE-DSCT scan protocol was performed with prospective ECG-gating sequential scan model 7 min after contrast administration. In a 17-model, infarcted myocardium detected by DE-MR was categorized as transmural and subendocardial extension. Segment of infarcted location and graded transmurality were compared between DCE-MDCT and DE-MR. Results: In all eleven patients, diagnostic quality was obtained for depicting delayed enhanced myocardium. Agreement between DCE-DSCT and MR was good on myocardial segment based comparison (kappa = 0.85, p < 0.001), and on transmural and subendocardial infarction type comparison (kappa = 0.82, p < 0.001, kappa = 0.52, p < 0.001, respectively). CT value was higher on infarcted region than that of normal region (100.02 {+-} 9.57 HU vs. 72.63 {+-} 7.32 HU, p < 0.001). Radiation dose of prospectively ECG-gating protocol were 0.99 {+-} 0.08 mSv (0.82-1.19 mSv). Conclusions: Prospective ECG-gated DCE-DSCT can accurately assess the extension and the patterns of myocardial infarction with low radiation dose.

  14. Effects of Lead on Systolic and Diastolic Cardiac Functions

    Institute of Scientific and Technical Information of China (English)

    ZOUHE-JIAN; DINGYUE; 等

    1995-01-01

    In this paper,both systolic and diastolic cardiac functions were evaluated in 54 lead exposed and 24 non-exposed workers by Doppler echocardiography.With regard to systolic cardiac function,the results suggested that cardiac systolic function increased in exposed groups as a compensatory response for the effect of lead on myocardium.To study left ventricular diastolic function,2.5MHz pulsed Doppler analyses of transmitral flow velocity were performed from apical four-chamber view.The results showed that timerelated parameters were comparable among all groups,but blood flow velocity through the mitral valve and Doppler area fractions changed significantly in lead-exposed groups as evidenced by increased value A,decreased value E and E/A ratio.The decrease of diastolic cardiac function was more significant in lead intoxication group.It was also observed in this study that the activity in serum of the MB isoenzyme of creatine phosphokinase(CPK-MB),one of the indices of myocardial damage,was significantly higher in exposed group than that in control(P<0.05),and a positive correlation was found between CPK-MB activity and Pb-B.It denoted that the increasing of lead burden leads to more relase of CPK-MB from the myocardial cells and suggested the existence of slight myocardial damage,which conceivably,might cause harm to diastolic cardiac function.

  15. Hemoperfusion with polymyxin B-immobilized fiber column improves liver function after ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Hiroaki Sato; Kiyohiro Oshima; Katsumi Kobayashi; Hodaka Yamazaki; Yujin Suto; Izumi Takeyoshi

    2009-01-01

    AIM: To investigate the usefulness of direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX therapy) for warm hepatic ischemia-reperfusion (I/R) injury after total hepatic vascular exclusion (THVE) using a porcine model.METHODS: Eleven Mexican hairless pigs weighing 22-38 kg were subjected to THVE for 120 min and then observed for 360 min. The animals were divided into two groups randomly: the DHP-PMX group (n = 5) underwent DHP-PMX at a flow rate of 80 mL/min for 120 min (beginning 10 min before reperfusion), while the control group did not (n = 6). The rate pressure product (RPP): heart rate × end-systolic arterial blood pressure,hepatic tissue blood flow (HTBF), portal vein blood flow (PVBF), and serum aspartate aminotransferase (AST) levels were compared between the two groups. RESULTS: RPP and HTBF were significantly (P < 0.05) higher in the DHP-PMX group than in the control group 240 and 360 min after reperfusion. PVBF in the DHP-PMX group was maintained at about 70% of the flow before ischemia and differed significantly (P < 0.05) compared to the control group 360 min after reperfusion. The serum AST increased gradually after reperfusion in both groups, but the AST was significantly (P < 0.05) lower in the DHP-PMX group 360 min after reperfusion. CONCLUSION: DHP-PMX therapy reduced the hepatic warm I/R injury caused by THVE in a porcine model.

  16. 心脏死亡捐献供肝热缺血再灌注损伤及MRI评价的研究进展%Study progress of hepatic warm ischemia-reperfusion injury in donation after cardiac death liver graft and its MRI evaluation

    Institute of Scientific and Technical Information of China (English)

    季倩; 沈文

    2016-01-01

    供体严重短缺是制约我国肝移植事业发展的瓶颈,而心脏死亡捐献(DCD)将有效扩大供体来源,但肝脏热缺血再灌注损伤一直困扰着DCD供肝的利用效果。功能MR成像能够无创、准确评价活体肝组织的微观信息变化,并获得动态的定量资料,对进一步认识肝脏热缺血再灌注损伤的机制及其预后评估提供有价值的信息。现就我国DCD供肝现状、肝脏热缺血再灌注损伤及MRI评价予以综述。%Donor shortage has hampered the development of liver transplantation in China. Donation after Cardiac Death (DCD) will effectively expand the donor source, while hepatic warm ischemia-reperfusion injury has severe influence on the prognosis of DCD liver graft. Functional MR imaging can evaluate microscopic information changes of liver tissue in vivo non-invasively, accurately and quantitatively, the results are expected to provide valuable information on further understanding the mechanism and prognosis of hepatic warm ischemia-reperfusion injury. The aims of the present review were as follows: (a) to present the state of DCD donor liver in China, (b) to present the hepatic warm ischemia-reperfusion injury, and (c) to review the MRI evaluation of hepatic warm ischemia-reperfusion injury.

  17. Effects of preconditioning on reperfusion arrhythmias, myocardial functions, formation of free radicals, and ion shifts in isolated ischemic/reperfused rat hearts.

    Science.gov (United States)

    Tosaki, A; Cordis, G A; Szerdahelyi, P; Engelman, R M; Das, D K

    1994-03-01

    The effects of preconditioning on development of reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT), free radical formation, and ion shifts, particularly those of Na, K, Ca, and Mg, were studied in isolated rat heart. Hearts were randomly divided into four groups: group I, aerobically perfused time-matched controls with no preconditioning or ischemia; group II, hearts subjected to 30-min global ischemia followed by 30-min reperfusion; group III, hearts subjected to one cycle of preconditioning, consisting of 5-min global ischemia plus 10-min reperfusion, followed by 30-min global ischemia plus 30-min reperfusion; and group IV, hearts subjected to four cycles of preconditioning (5-min ischemia plus 10-min reperfusion) followed by 30-min ischemia plus 30-min reperfusion. The incidences of VF and VT were reduced from their nonpreconditioned ischemic values of 100 and 100% in group II to 83 and 92% in group III and to 33% (p < 0.05) and 41% (p < 0.05) in group IV, respectively. Maximum malondialdehyde formation, as an indirect marker of free radicals, was observed after 30-min ischemia followed by 10-min reperfusion (0.72 +/- 0.1 nmol/ml) in the nonpreconditioned ischemic group (protocol II). One and four cycles of preconditioning reduced formation of malondialdehyde from the nonpreconditioned ischemic value of 0.72 +/- 0.1 to 0.35 +/- 0.02 and 0.26 +/- 0.02 nmol/ml (p < 0.05), respectively. The same trend was observed when free radical formation was directly detected by salicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Value of carnitine therapy in kidney dialysis patients and effects on cardiac function from human and animal studies.

    Science.gov (United States)

    Molyneux, Rebekah; Seymour, A-M; Bhandari, Sunil

    2012-02-01

    Cardiovascular complications are the leading cause of mortality, accounting for 50% of all deaths among patients with end-stage renal disease (ESRD). The majority of these deaths are from cardiac causes. The mechanisms underlying the enhanced susceptibility to myocardial ischaemia and subsequent morbidity in ESRD remain ill-defined. Numerous metabolic derangements accompany myocardial ischaemia and reperfusion and play a pivotal role in the development of concurrent myocardial dysfunction. Carnitine plays a critical role in myocardial energy metabolism, as the transporter of long chain fatty acyl intermediates across the inner mitochondrial membrane for β oxidation and as a central regulator of carbohydrate metabolism. Myocardial carnitine is significantly depleted during ischaemia and more particularly in uraemic patients and those on dialysis therapy. Carnitine treatment has cardiovascular benefits including modulation of myocardial metabolism, reduction in necrotic cell death and infarct size, decrease in the incidence of arrhythmias and preservation of mechanical function. This review details the profile of substrate metabolism in the uraemic heart and the impact of carnitine supplementation on metabolism and function of the reperfused heart and finally the experimental and clinical evidence for carnitine replacement therapy, in particular its impact on the uraemic heart via modulation of function and energetics.

  19. Antioxidant effects of xanthohumol and functional impact on hepatic ischemia-reperfusion injury.

    Science.gov (United States)

    Hartkorn, Andreas; Hoffmann, Florian; Ajamieh, Hussam; Vogel, Susanne; Heilmann, Jörg; Gerbes, Alexander L; Vollmar, Angelika M; Zahler, Stefan

    2009-10-01

    Therapeutic effects of dietary flavonoids have been attributed mainly to their antioxidant capacity. Xanthohumol (1), a prominent flavonoid of the hop plant, Humulus lupulus, was investigated for its antioxidant potential and for its effect on NF-kappaB activation. To examine the biological relevance of 1, a hepatic ischemia/reperfusion model was chosen as a widely accepted model of oxidative stress generation. The impact of 1 on endogenous antioxidant systems, on the NF-kappaB signal transduction pathway as well as on apoptotic parameters, and on hepatic tissue damage was evaluated. Compound 1 markedly decreased the level of reactive oxygen species in vitro. Furthermore, levels of enzymatic and nonenzymatic antioxidants were restored after pretreatment in postischemic hepatic tissue, and lipid peroxidation was attenuated. NF-kappaB activity was reduced in vitro as well as in hepatic tissue after ischemia/reperfusion upon pretreatment with 1. In addition, the phosphorylation of Akt was markedly inhibited. Surprisingly, 1 decreased the expression of the antiapoptotic protein Bcl-X and increased caspase-3 like-activity, a proapoptotic parameter. Moreover, hepatic tissue damage as well as TNF-alpha levels increased in xanthohumol-pretreated liver tissue after ischemia/reperfusion. In summary, xanthohumol did not protect against ischemia/reperfusion injury in rat liver, despite its antioxidant and NF-kappaB inhibitory properties.

  20. MRI of renal oxygenation and function after normothermic ischemia-reperfusion injury

    NARCIS (Netherlands)

    Oostendorp, M. van; Vries, E.E. de; Slenter, J.M.; Peutz-Kootstra, C.J.; Snoeijs, M.G.; Post, M.J.; Heurn, L.W. van; Backes, W.H.

    2011-01-01

    The in vivo assessment of renal damage after ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, is a major challenge. This injury often results in temporary or permanent nonfunction. In order to improve the clinical outcome of the kidneys, novel therapies are

  1. Ischemia-Reperfusion Injury : Maintaining skeletal muscle function and vasomotor control

    NARCIS (Netherlands)

    With, M.C.J. de

    2009-01-01

    In reconstructive surgery, ischemia-reperfusion (I-R) injury of skeletal muscle tissue occurs during replantations, free vascularized transfers of muscle flaps and following composite tissue allograft (CTA) transplantations. The latter is a newly emerging field and involves the allotransplantation o

  2. MRI of renal oxygenation and function after normothermic ischemia-reperfusion injury

    NARCIS (Netherlands)

    Oostendorp, M. van; Vries, E.E. de; Slenter, J.M.; Peutz-Kootstra, C.J.; Snoeijs, M.G.; Post, M.J.; Heurn, L.W. van; Backes, W.H.

    2011-01-01

    The in vivo assessment of renal damage after ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, is a major challenge. This injury often results in temporary or permanent nonfunction. In order to improve the clinical outcome of the kidneys, novel therapies are

  3. Luoyutong Treatment Promotes Functional Recovery and Neuronal Plasticity after Cerebral Ischemia-Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Ning-qun Wang

    2015-01-01

    Full Text Available Luoyutong (LYT capsule has been used to treat cerebrovascular diseases clinically in China and is now patented and approved by the State Food and Drug Administration. In this retrospective validation study we investigated the ability of LYT to protect against cerebral ischemia-reperfusion injury in rats. Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion followed by reperfusion. Capsule containing LYT (high dose and medium dose as treatment group and Citicoline Sodium as positive control treatment group were administered daily to rats 30 min after reperfusion. Treatment was continued for either 3 days or 14 days. A saline solution was administered to control animals. Behavior tests were performed after 3 and 14 days of treatment. Our findings revealed that LYT treatment improved the neurological outcome, decreased cerebral infarction volume, and reduced apoptosis. Additionally, LYT improved neural plasticity, as the expression of synaptophysin, microtubule associated protein, and myelin basic protein was upregulated by LYT treatment, while neurofilament 200 expression was reduced. Moreover, levels of brain derived neurotrophic factor and basic fibroblast growth factor were increased. Our results suggest that LYT treatment may protect against ischemic injury and improve neural plasticity.

  4. SUMO-1 gene transfer improves cardiac function in a large-animal model of heart failure.

    Science.gov (United States)

    Tilemann, Lisa; Lee, Ahyoung; Ishikawa, Kiyotake; Aguero, Jaume; Rapti, Kleopatra; Santos-Gallego, Carlos; Kohlbrenner, Erik; Fish, Kenneth M; Kho, Changwon; Hajjar, Roger J

    2013-11-13

    Recently, the impact of small ubiquitin-related modifier 1 (SUMO-1) on the regulation and preservation of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2a) function was discovered. The amount of myocardial SUMO-1 is decreased in failing hearts, and its knockdown results in severe heart failure (HF) in mice. In a previous study, we showed that SUMO-1 gene transfer substantially improved cardiac function in a murine model of pressure overload-induced HF. Toward clinical translation, we evaluated in this study the effects of SUMO-1 gene transfer in a swine model of ischemic HF. One month after balloon occlusion of the proximal left anterior descending artery followed by reperfusion, the animals were randomized to receive either SUMO-1 at two doses, SERCA2a, or both by adeno-associated vector type 1 (AAV1) gene transfer via antegrade coronary infusion. Control animals received saline infusions. After gene delivery, there was a significant increase in the maximum rate of pressure rise [dP/dt(max)] that was most pronounced in the group that received both SUMO-1 and SERCA2a. The left ventricular ejection fraction (LVEF) improved after high-dose SUMO-1 with or without SERCA2a gene delivery, whereas there was a decline in LVEF in the animals receiving saline. Furthermore, the dilatation of LV volumes was prevented in the treatment groups. SUMO-1 gene transfer therefore improved cardiac function and stabilized LV volumes in a large-animal model of HF. These results support the critical role of SUMO-1 in SERCA2a function and underline the therapeutic potential of SUMO-1 for HF patients.

  5. The Role of Tetrahydrobiopterin and Dihydrobiopterin in Ischemia/Reperfusion Injury When Given at Reperfusion

    Directory of Open Access Journals (Sweden)

    Qian Chen

    2010-01-01

    Full Text Available Reduced nitric oxide (NO bioavailability and increased oxidative stress are major factors mediating ischemia/reperfusion (I/R injury. Tetrahydrobiopterin (BH4 is an essential cofactor of endothelial NO synthase (eNOS to produce NO, whereas dihydrobiopterin (BH2 can shift the eNOS product profile from NO to superoxide, which is further converted to hydrogen peroxide (H2O2 and cause I/R injury. The effects of BH4 and BH2 on oxidative stress and postreperfused cardiac functions were examined in ex vivo myocardial and in vivo femoral I (20 min/R (45 min models. In femoral I/R, BH4 increased NO and decreased H2O2 releases relative to saline control, and these effects correlated with improved postreperfused cardiac function. By contrast, BH2 decreased NO release relative to the saline control, but increased H2O2 release similar to the saline control, and these effects correlated with compromised postreperfused cardiac function. In conclusion, these results suggest that promoting eNOS coupling to produce NO and decrease H2O2 may be a key mechanism to restore postreperfused organ function during early reperfusion.

  6. Cardiac sympathetic nerve terminal function in congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    Chang-seng LIANG

    2007-01-01

    Increased cardiac release of norepinephrine (NE) and depleted cardiac stores of NE are two salient features of the human failing heart. Researches from my labo-ratory have shown that these changes are accompanied by a functional defect of NE uptake in the cardiac sympathetic nerve terminals. Our studies have shown that the decrease of NE uptake is caused by reduction of NE transporter density in the sympathetic nerve endings, and this change is responsible, at least in part, for the increased myocardial interstitial NE, decreased myocardial adrenoceptor density, and increased myocyte apoptosis in experimental cardiomyopathies. We have also provided evidence in both intact animals and cultured PC12 cells that the decrease of NE transporter is induced by the actions of oxidative metabolites of exogenous NE, involving endoplasmic reticulum stress and impaired N-glycosylation of the NE transporter. This change in the cardiac sympathetic NE uptake function, as demonstrated by [123I] metaiodobenzylguanidine in human studies, may not only serve as an important prognostic variable in patients with congestive heart failure, but also be used as a surrogate for the efficacies of various therapeutic interventions for heart failure. Finally, increasing evidence suggests and further studies are needed to show that the cardiac sympathetic nerve terminal function may be a direct target for pharmacologic treatment of congestive heart failure.

  7. Systolic and diastolic cardiac function in acromegaly. An echocardiographic study.

    Science.gov (United States)

    Galanti, G; Cappelli, B; Diricatti, G; Mininni, S; Vono, M C; Gensini, G F

    1996-01-01

    The aim of this study was to establish the existence of primary acromegalic cardiomyopathy different from the cardiovascular complications often associated with acromegaly. Thirty-four acromegalic patients, referred to our non-invasive laboratory and divided into two groups on the basis of the presence of hypertension, underwent echocardiographic studies. A control group of 34 subjects individually matched with the patients for age, sex, and blood pressure values was also studied. To evaluate cardiac function during exercise, the normotensive acromegalics, the control group, and a group of 9 athletes with left ventricular mass comparable to that of the acromegalic subjects underwent a handgrip test. Cardiac mass was increased in all patients; hypertensive patients had a greater increase than normotensive patients (144.9 +/- 38 vs 120.9 +/- 20.8 g/m, p cardiac hypertrophy caused by GH hyperincretion does not improve acromegalic heart activity: diastolic function, although normal at rest, appears deficient during isometric exercise.

  8. Cardiac Function in Long-Term Survivors of Childhood Lymphoma

    Directory of Open Access Journals (Sweden)

    Mark K. Friedberg

    2011-01-01

    Full Text Available Objectives. We studied long-term effects of therapy for childhood lymphoma on cardiac function. Design and patients. We prospectively evaluated 45 survivors of childhood lymphoma, using clinical parameters, electrocardiography and echocardiography. Further comparisons were made between lymphoma subgroups and between males and females. Results. Mean age at diagnosis was 9.1 years. Mean followup duration was 10.9 years. The NYHA functional class was I in 43 patients and II in 2 patients. A prolonged QTc interval (>0.44 msec was found in 8 patients. Left ventricular (LV systolic function and compliance were normal (LV shortening fraction 40±5.6%; cardiac index 2.84±1.13 L/min/m2; E/A wave ratio 2.5±1.3; mean ± S.D., LV mass was normal (97±40 grams/m2, mean ± S.D.. Mitral regurgitation was observed in 7/45 patients (16%. Asymptomatic pericardial effusions were found in 3/45 (7% patients. Conclusions. Long-term follow-up shows that most parameters of cardiac function are normal in survivors of childhood lymphoma. This is likely due to relatively low doses of anthracyclines in modern protocol modalities. Abnormalities in mitral valve flow, QTc prolongation and in a small proportion of survivors, and functional capacity necessitate long-term cardiac follow-up of these patients.

  9. EPAC expression and function in cardiac fibroblasts and myofibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Olmedo, Ivonne; Muñoz, Claudia; Guzmán, Nancy; Catalán, Mabel; Vivar, Raúl; Ayala, Pedro; Humeres, Claudio; Aránguiz, Pablo [Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); García, Lorena [Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile); Velarde, Victoria [Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile (Chile); Díaz-Araya, Guillermo, E-mail: gadiaz@ciq.uchile.cl [Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (Chile)

    2013-10-15

    In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF were treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in cardiac

  10. Acupuncture Effects on Cardiac Functions Measured by Cardiac Magnetic Resonance Imaging in a Feline Model

    Directory of Open Access Journals (Sweden)

    Jen-Hsou Lin

    2010-01-01

    Full Text Available The usefulness of acupuncture (AP as a complementary and/or alternative therapy in animals is well established but more research is needed on its clinical efficacy relative to conventional therapy, and on the underlying mechanisms of the effects of AP. Cardiac magnetic resonance imaging (CMRI, an important tool in monitoring cardiovascular diseases, provides a reliable method to monitor the effects of AP on the cardiovascular system. This controlled experiment monitored the effect electro-acupuncture (EA at bilateral acupoint Neiguan (PC6 on recovery time after ketamine/xylazine cocktail anesthesia in healthy cats. The CMRI data established the basic feline cardiac function index (CFI, including cardiac output and major vessel velocity. To evaluate the effect of EA on the functions of the autonomic nervous and cardiovascular systems, heart rate, respiration rate, electrocardiogram and pulse rate were also measured. Ketamine/xylazine cocktail anesthesia caused a transient hypertension in the cats; EA inhibited this anesthetic-induced hypertension and shortened the post-anesthesia recovery time. Our data support existing knowledge on the cardiovascular benefits of EA at PC6, and also provide strong evidence for the combination of anesthesia and EA to shorten post-anesthesia recovery time and counter the negative effects of anesthetics on cardiac physiology.

  11. [Effect of different concentrations liposomal emoxipine on coronary flow, contractive and pump function of the isolated rat heart after normotermic ischema and further reperfusion].

    Science.gov (United States)

    Toropova, Ia G; Mukhamadiiarov, R A; Golovkin, A S

    2013-07-01

    In the experiments on the isolated perfused rat heart we studied the effects of liposomes containing different concentrations (0.25 and 0.1 mg/ml) of emoxipine on coronary flow, contractive and pump function of the isolated heart, which was effected by total normothermical ischemia and reperfusion. The parameters of the contractile activity of hearts, coronary flow and pump function of the hearts were assessed. It was detected that the introduction of the liposomal emoxipine during ischemia provides a protective effect against ischemic and reperfusion myocardial damage and smaller concentration of the emoxipin (0.1 mg/ml) in composition with the liposomes promote the best recovery of contractile activity and the pumping function of the ischemic heart in the period of the reperfusion.

  12. Reviewing EKGs in Thalassemia Patients to Evaluate Their Cardiac Function

    Directory of Open Access Journals (Sweden)

    Abdolhamid Bagheri

    2016-03-01

    Full Text Available Introduction: There are more than 18000 thalassemia patients in Iran. In a current study, a high rate of mortality in these patients due to heart failure, is shown. Main factors for evaluating this disorder in thalassemia patients were their electrocardiograms (EKGs and Serum Ferritin Levels (SFLs.Methods: We studied the cardiac function in 91 patients (73 major and 18 intermediate thalassemia patients treated in Zafar Thalassemia Center, of whom 35 (38.45% were male and 56 (61.55% were female. The Factors in this study contains: EKGs, mean annual serum ferritin (at least, three SFL had been recorded in each patient treatment file in 2009, mean annual hemoglobin (Hb levels and mean annual hematocrit (Hct levels (average, 12 recorded hematocrit levels during 2009.Results: Our findings have shown that Q-T interval did not correlate with ferritin (r = 0.05, P > 0.05. In both patients with LVH and without LVH, there was no significant difference in SFL (P > 0.05. Although, the mean rate among the thalassemia patients was 85.34 ± 12.91, it did not correlate significantly with QRS duration and P-R Interval (r = -0.08, P > 0.05. In addition, ferritin did not correlate significantly with QRS duration and P-R Interval (r = 0.1, r = 0.05 and P > 0.05, P > 0.05. Furthermore, there was no difference in SFL in patients with normal cardiac axis and those with cardiac axis deviation.Conclusion: There is no correlation between SFL and variations in EKG. Although EKG is an available method for checking cardiac function in thalassemic patients, especially in developing countries, physicians cannot rely on it for diagnosis or prognosis of cardiac failure in thalassemia patients. Therefore, other methods such as MRIT2* and Echocardiography are suggested to be used periodically in order to check the cardiac function in thalassemia patients.

  13. Visualization and analysis of functional cardiac MRI data

    Science.gov (United States)

    McVeigh, Elliot R.; Guttman, Michael A.; Poon, Eric; Pisupati, Chandrasekhar; Moore, Christopher C.; Zerhouni, Elias A.; Solaiyappan, Meiyappan; Heng, PhengAnn

    1994-05-01

    Rapid analysis of large multi-dimensional data sets is critical for the successful implementation of a comprehensive MR cardiac exam. We have developed a software package for the analysis and visualization of cardiac MR data. The program allows interactive visualization of time and space stacks of MRI data, automatic segmentation of myocardial borders and myocardial tagging patterns, and visualization of functional parameters such a motion, strain, and blood flow, mapped as colors in an interactive dynamic 3D volume rendering of the beating heart.

  14. Radionuclide assessment of left ventricular function following cardiac surgery

    Energy Technology Data Exchange (ETDEWEB)

    Howe, W.R.; Jones, R.H.; Sabiston, D.C. Jr.

    1976-01-01

    Use of a high count-rate gamma scintillation camera permits the noninvasive assessment of left ventricular function by nuclear angiocardiography. Counts recorded from the region of the left ventricle at 50- or 100-msec intervals during the first transit of an intravenously administered bolus of radioisotope produce a high-fidelity indicator-dilution curve. Count fluctuations reflect left ventricular volume changes during the cardiac cycle and permit measurement of dv/dt, ejection fraction, mean transit time, and wall motion of this chamber. The present study evaluates (1) the accuracy of this technique compared to standard biplane cineangiography and (2) its usefulness in evaluating patients after cardiac surgery.

  15. Cardiac nuclear receptors: architects of mitochondrial structure and function.

    Science.gov (United States)

    Vega, Rick B; Kelly, Daniel P

    2017-04-03

    The adult heart is uniquely designed and equipped to provide a continuous supply of energy in the form of ATP to support persistent contractile function. This high-capacity energy transduction system is the result of a remarkable surge in mitochondrial biogenesis and maturation during the fetal-to-adult transition in cardiac development. Substantial evidence indicates that nuclear receptor signaling is integral to dynamic changes in the cardiac mitochondrial phenotype in response to developmental cues, in response to diverse postnatal physiologic conditions, and in disease states such as heart failure. A subset of cardiac-enriched nuclear receptors serve to match mitochondrial fuel preferences and capacity for ATP production with changing energy demands of the heart. In this Review, we describe the role of specific nuclear receptors and their coregulators in the dynamic control of mitochondrial biogenesis and energy metabolism in the normal and diseased heart.

  16. PET Demonstrates Functional Recovery after Treatment by Danhong Injection in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

    Science.gov (United States)

    Wang, Zefeng; Song, Fahuan; Li, Jinhui; Zhang, Yuyan; He, Yu; Yang, Jiehong; Zhou, Huifen; Zhao, Tao; Fu, Wei; Xing, Panke; Wan, Haitong; Tian, Mei; Zhang, Hong

    2014-01-01

    This study aimed to investigate neuroprotection of Danhong injection (DHI) in a rat model of cerebral ischemia using (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). Method. Rats were divided into 5 groups: sham group, ischemia-reperfusion untreated (IRU) group, DHI-1 group (DHI 1 mL/kg/d), DHI-2 group (DHI 2 mL/kg/d), and DHI-4 group (DHI 4 mL/kg/d). AII the treated groups were intraperitoneally injected with DHI daily for 14 days. The therapeutic effects in terms of cerebral infarct volume, neurological function, and cerebral glucose metabolism were evaluated. Expression of TNF-α and IL-1β was detected with enzyme-linked immunosorbent assay (ELISA). Levels of mature neuronal marker (NeuN), glial marker (GFAP), vascular density factor (vWF), and glucose transporter 1 (GLUT1) were assessed by immunohistochemistry. Results. Compared with the IRU group, rats treated with DHI showed dose dependent reductions in cerebral infarct volume and levels of proinflammatory cytokines, improvement of neurological function, and recovery of cerebral glucose metabolism. Meanwhile, the significantly increased numbers of neurons, gliocytes, and vessels and the recovery of glucose utilization were found in the peri-infarct region after DHI treatment using immunohistochemical analysis. Conclusion. This study demonstrated the metabolic recovery after DHI treatment by micro-PET imaging with (18)F-FDG and the neuroprotective effects of DHI in a rat model of cerebral ischemic-reperfusion injury.

  17. PET Demonstrates Functional Recovery after Treatment by Danhong Injection in a Rat Model of Cerebral Ischemic-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Zefeng Wang

    2014-01-01

    Full Text Available This study aimed to investigate neuroprotection of Danhong injection (DHI in a rat model of cerebral ischemia using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET. Method. Rats were divided into 5 groups: sham group, ischemia-reperfusion untreated (IRU group, DHI-1 group (DHI 1 mL/kg/d, DHI-2 group (DHI 2 mL/kg/d, and DHI-4 group (DHI 4 mL/kg/d. AII the treated groups were intraperitoneally injected with DHI daily for 14 days. The therapeutic effects in terms of cerebral infarct volume, neurological function, and cerebral glucose metabolism were evaluated. Expression of TNF-α and IL-1β was detected with enzyme-linked immunosorbent assay (ELISA. Levels of mature neuronal marker (NeuN, glial marker (GFAP, vascular density factor (vWF, and glucose transporter 1 (GLUT1 were assessed by immunohistochemistry. Results. Compared with the IRU group, rats treated with DHI showed dose dependent reductions in cerebral infarct volume and levels of proinflammatory cytokines, improvement of neurological function, and recovery of cerebral glucose metabolism. Meanwhile, the significantly increased numbers of neurons, gliocytes, and vessels and the recovery of glucose utilization were found in the peri-infarct region after DHI treatment using immunohistochemical analysis. Conclusion. This study demonstrated the metabolic recovery after DHI treatment by micro-PET imaging with 18F-FDG and the neuroprotective effects of DHI in a rat model of cerebral ischemic-reperfusion injury.

  18. EANM/ESC guidelines for radionuclide imaging of cardiac function

    DEFF Research Database (Denmark)

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

    2008-01-01

    radionuclide ventriculography, gated myocardial perfusion scintigraphy, gated PET, and studies with non-imaging devices for the evaluation of cardiac function. The items covered are presented in 11 sections: clinical indications, radiopharmaceuticals and dosimetry, study acquisition, RV EF, LV EF, LV volumes......Radionuclide imaging of cardiac function represents a number of well-validated techniques for accurate determination of right (RV) and left ventricular (LV) ejection fraction (EF) and LV volumes. These first European guidelines give recommendations for how and when to use first-pass and equilibrium......, LV regional function, LV diastolic function, reports and image display and reference values from the literature of RVEF, LVEF and LV volumes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "prevailing or general consensus...

  19. Functional protection of pentoxifylline against spinal cord ischemia/reperfusion injury in rabbits: necrosis and apoptosis effects

    Institute of Scientific and Technical Information of China (English)

    ZHU Dan-jie; XIA Bing; BI Qing; ZHANG Shui-jun; QIU Bin-song; ZHAO Chen

    2008-01-01

    Background Little is known about neuronal death mechanisms following spinal cord ischemia.The present study aimed to investigate the protective effect of pentoxifylline (PIX) against spinal cord ischemia/reperfusion (I/R) injury.Methods Rabbits sustained spinal cord ischemia following 45 minutes cress-clamping of the infrarenal aorta.Experimental groups were as follows: the first group of animals (sham,n=8) underwent laparotomy alone and served as the sham group; the second group (I/R,n=20) received carrier (3 ml saline solution) and served as the control group; the third group (PTX-A,n=20) received PTX intravenously 10 minutes prior to ischemia; and the fourth group (PTX-B,n=20)received PTX intravenously at the onset of reperfusion.Rabbits were evaluated for hind-limb motor function with the Tarlov scoring system at 48 hours.Serum was assayed with enzyme-linked immunosorbent assay for tumor necrosis factor α (TNF-α) and spinal cords were harvested for myeloperoxidase (MPO) activity,histopathological analysis,terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling staining,platelet/endothelial cell adhesion molecule-1 (PECAM-1) and caspase-3 immunohistochemistry,and the number of necrotic and apoptotic neuron were counted and data analyzed at 12,24,48 and 72 hours of reperfusion.Spinal cords were studied by electron microscopy.Results Improved Tarlov scores were seen in PTX-treated rabbits as compared with ischemic control rabbits at 48 hours.A significant reduction was found in TNF-α in serum,activity of MPO and immunoreactivity of the PECAM-1 and caspase-3 in PTX-treated rabbits.There were fewer apoptotic neurons than necrotic neurons (P<0.05).A significant decrease in both necrotic and apoptotic neurons was observed in the PTX-treated groups (PTX-A and PTX-B) compared with the I/R group (P<0.05).Both necrotic and apoptotic neurons were found with the electron microscope.Conclusions PTX may induce protection against ischemia injury in the

  20. The role of different concentrations of nitroglycerin on cardiac ischemia and reperfusion injury in isolated perfused rat hearts%不同浓度硝酸甘油对大鼠离体心脏缺血/再灌注损伤的作用

    Institute of Scientific and Technical Information of China (English)

    姜翠荣; 高琴; 王晓梅; 李正红

    2011-01-01

    目的:探讨不同浓度硝酸甘油(nitroglycerin,GTN)对大鼠离体心脏缺血/再灌注损伤的作用.方法:采用离体大鼠心脏Langendorff灌流方法,结扎冠状动脉左前降支30 min和再灌注120 min复制局部缺血/再灌注损伤模型,测定各项心室动力学指标、冠状动脉流出液中乳酸脱氢酶(lactatede hydrogenase,LDH)含量及心肌梗死面积.结果:与单纯缺血/再灌注组相比,GTN高浓度组(2×10-6 mol/L)抑制了再灌注后心功能的恢复(P<0.05~P<0.01),增大了心肌梗死面积(P<0.01),再灌注时冠状动脉流出液中LDH释放增加(P<0.05);GTN中浓度组(1×10-7 mol/L)与单纯缺血/再灌注组相比,对心功能的恢复、心肌梗死面积和LDH含量改变不明显;GTN低浓度组(1×10-8 mol/L)明显促进了再灌注后心功能的恢复,减小了心肌梗死面积,冠状动脉流出液中LDH释放减少(P<0.05~P<0.01).结论:高浓度GTN加重心肌缺血/再灌注损伤,中浓度GTN对缺血/再灌注心肌作用不明显,低浓度GTN可保护缺血/再灌注心肌.%Objective:To examine the effects of different concentrations of nitroglycerin(GTN) on cardiac ischemia and reperfusion injury in isolated perfused rat hearts. Methods: Male Sprague-Dawley rats were used for Langendoff isolated heart perfusion. The hearts were subjected to 30 min regional ischemia( occlusion of left anterior descending artery) and 120 min reperfusion. The ventricular hemodynamic parameters,lactate dehydrogenase (LDH) release during reperfusion and myocardial infarct size were measured. Results: Administration of GTN at high concentration(2 x 10-6 mol/L) significantly aggravated post-ischemic myocardial injury characterized by depressed cardiac function recovery( P < 0.05 - P < 0.01 ), enlarged myocardial infarct size ( P < 0.01 ) and increased LDH release (P < 0. 05 ). GTN at middle concentration( 1 × 10 -7 mol/L) did not change the cardiac function recovery, myocardial infarct size and LDH release

  1. Functional role of anion channels in cardiac diseases

    Institute of Scientific and Technical Information of China (English)

    Da-yue DUAN; Luis LH LIU; Nathan BOZEAT; Z Maggie HUANG; Sunny Y XIANG; Guan-lei WANG; Linda YE; Joseph R HUME

    2005-01-01

    In comparison to cation (K+, Na+, and Ca2+) channels, much less is currently known about the functional role of anion (Cl-) channels in cardiovascular physiology and pathophysiology. Over the past 15 years, various types of Cl- currents have been recorded in cardiac cells from different species including humans. All cardiac Cl- channels described to date may be encoded by five different Cl- channel genes: the PKA- and PKC-activated cystic fibrosis tansmembrane conductance regulator (CFTR), the volume-regulated ClC-2 and ClC-3, and the Ca2+-activated CLCA or Bestrophin. Recent studies using multiple approaches to examine the functional role of Cl- channels in the context of health and disease have demonstrated that Cl- channels might contribute to: 1) arrhythmogenesis in myocardial injury; 2) cardiac ischemic preconditioning; and 3) the adaptive remodeling of the heart during myocardial hypertrophy and heart failure. Therefore,anion channels represent very attractive novel targets for therapeutic approaches to the treatment of heart diseases. Recent evidence suggests that Cl- channels,like cation channels, might function as a multiprotein complex or functional module.In the post-genome era, the emergence of functional proteomics has necessitated a new paradigm shift to the structural and functional assessment of integrated Cl- channel multiprotein complexes in the heart, which could provide new insight into our understanding of the underlying mechanisms responsible for heart disease and protection.

  2. Autoimmune Response Confers Decreased Cardiac Function in ...

    African Journals Online (AJOL)

    ... interleukin-6 (IL-6), high –sensitivity C-reactive protein (hs-CRP) and echocardiographic indices of heart function in the two .... patients were classified as NYHA class II, fifteen as class III, and ... group were excluded if they had a history of.

  3. Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

    NARCIS (Netherlands)

    Wild, Philipp S.; Felix, Janine F.; Schillert, Arne; Teumer, Alexander; Chen, Ming-Huei; Leening, Maarten J. G.; Voelker, Uwe; Grossmann, Vera; Brody, Jennifer A.; Irvin, Marguerite R.; Shah, Sanjiv J.; Pramana, Setia; Lieb, Wolfgang; Schmidt, Reinhold; Stanton, Alice V.; Malzahn, Doerthe; Smith, Albert Vernon; Sundstrom, Johan; Minelli, Cosetta; Ruggiero, Daniela; Lyytikainen, Leo-Pekka; Tiller, Daniel; Smith, J. Gustav; Monnereau, Claire; Di Tullio, Marco R.; Musani, Solomon K.; Morrison, Alanna C.; Pers, Tune H.; Morley, Michael; Kleber, Marcus E.; Aragam, Jayashri; Benjamin, Emelia J.; Bis, Joshua C.; Bisping, Egbert; Broeckel, Ulrich; Cheng, Susan; Deckers, Jaap W.; Del Greco, Fabiola; Edelmann, Frank; Fornage, Myriam; Franke, Lude; Friedrich, Nele; Harris, Tamara B.; Hofer, Edith; Hofman, Albert; Huang, Jie; Hughes, Alun D.; Kahonen, Mika; Kruppa, Jochen; Lackner, Karl J.; Lannfelt, Lars; Laskowski, Rafael; Launer, Lenore J.; Leosdottir, Margret; Lin, Honghuang; Lindgren, Cecilia M.; Loley, Christina; MacRae, Calum A.; Mascalzoni, Deborah; Mayet, Jamil; Medenwald, Daniel; Morris, Andrew P.; Mueller, Christian; Mueller-Nurasyid, Martina; Nappo, Stefania; Nilsson, Peter M.; Nuding, Sebastian; Nutile, Teresa; Peters, Annette; Pfeufer, Arne; Pietzner, Diana; Pramstaller, Peter P.; Raitakari, Olli T.; Rice, Kenneth M.; Rivadeneira, Fernando; Rotter, Jerome I.; Ruohonen, Saku T.; Sacco, Ralph L.; Samdarshi, Tandaw E.; Schmidt, Helena; Sharp, Andrew S. P.; Shields, Denis C.; Sorice, Rossella; Sotoodehnia, Nona; Stricker, Bruno H.; Surendran, Praveen; Thom, Simon; Toeglhofer, Anna M.; Uitterlinden, Andre G.; Wachter, Rolf; Voelzke, Henry; Ziegler, Andreas; Muenzel, Thomas; Maerz, Winfried; Cappola, Thomas P.; Hirschhorn, Joel N.; Mitchell, Gary F.; Smith, Nicholas L.; Fox, Ervin R.; Dueker, Nicole D.; Jaddoe, Vincent W. V.; Melander, Olle; Russ, Martin; Lehtimaki, Terho; Ciullo, Marina; Hicks, Andrew A.; Lind, Lars; Gudnason, Vilmundur; Pieske, Burkert; Barron, Anthony J.; Zweiker, Robert; Schunkert, Heribert; Ingelsson, Erik; Liu, Kiang; Arnett, Donna K.; Psaty, Bruce M.; Blankenberg, Stefan; Larson, Martin G.; Felix, Stephan B.; Franco, Oscar H.; Zeller, Tanja; Vasan, Ramachandran S.; Doerr, Marcus

    2017-01-01

    BACKGROUND. Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS. A GWAS

  4. Small molecule cardiogenol C upregulates cardiac markers and induces cardiac functional properties in lineage-committed progenitor cells.

    Science.gov (United States)

    Mike, Agnes K; Koenig, Xaver; Koley, Moumita; Heher, Philipp; Wahl, Gerald; Rubi, Lena; Schnürch, Michael; Mihovilovic, Marko D; Weitzer, Georg; Hilber, Karlheinz

    2014-01-01

    Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited transdifferentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules. Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC), and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays. Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies. CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy.

  5. Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Suzuki, Tadashi; Kurabayashi, Masahiko [Gunma University School of Medicine, Department of Cardiovascular Medicine, Maebashi (Japan); Kumakura, Hisao; Takayama, Yoshiaki; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan, Gunma (Japan)

    2005-03-01

    Ischaemic preconditioning (PC) is a cardioprotective phenomenon in which short periods of myocardial ischaemia result in resistance to decreased contractile dysfunction during a subsequent period of sustained ischaemia. Nicorandil, an ATP-sensitive potassium channel opener, can induce PC effects on sympathetic nerves during myocardial ischaemia. However, its effects on cardiac sympathetic nerve activity (CSNA) and left ventricular remodelling have not been determined. In this study, we sought to determine whether nicorandil administration improves CSNA in patients with acute myocardial infarction (AMI). We studied 58 patients with first anterior AMI, who were randomly assigned to receive nicorandil (group A) or isosorbide dinitrate (group B) after primary coronary angioplasty. The nicorandil or isosorbide dinitrate was continuously infused for >48 h. The extent score (ES) was determined from {sup 99m}Tc-pyrophosphate scintigraphy, and the total defect score (TDS) was determined from {sup 201}Tl scintigraphy 3-5 days after primary angioplasty. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed TDS and washout rate (WR) were determined from {sup 123}I-meta-iodobenzylguanidine (MIBG) images 3 weeks later. The left ventriculography results were re-examined 6 months after treatment. Fifty patients originally enrolled in the trial completed the entire protocol. After treatment, no significant differences were observed in ES or left ventricular parameters between the two groups. However, in group A (n=25), the TDSs determined from {sup 201}Tl and {sup 123}I-MIBG were significantly lower (26{+-}6 vs 30{+-}5, P<0.01, and 32{+-}8 vs 40{+-}6, P<0.0001, respectively), the H/M ratio significantly higher (1.99{+-}0.16 vs 1.77{+-}0.30, P<0.005) and the WR significantly lower (36%{+-}8% vs 44%{+-}12%, P<0.005) than in group B

  6. Control of the cardiac consequences of myocardial ischemia and reperfusion by L-propionylcarnitine: age-response and dose-response studies in the rat heart.

    Science.gov (United States)

    Riva, E; Leopaldi, D

    1993-10-01

    We assessed the protective effects of L-propionylcarnitine, a liposoluble analogue of carnitine, in the isolated heart from rats of different ages subjected to global ischemia and reperfusion. Hearts from neonatal (3- to 7-d-old), immature (2- to 3-wk-old), and adult rats were retrogradely perfused with a modified Krebs bicarbonate buffer and subjected to ischemia and reperfusion. L-Pro-pionylcarnitine was given either before ischemia and throughout reperfusion (protocol 1) or during reperfusion only (protocol 2). Coronary flow, heart rate, left ventricular developed pressure, and left ventricular end-diastolic pressure were measured throughout the perfusion period. Ventricular arrhythmias and creatine kinase leakage were measured at the time of reperfusion. Postischemic recovery of coronary flow and left ventricular developed pressure were age dependent and were not affected by L-propionylcarnitine, but recovery of heart rate was decreased in neonatal and immature hearts by 10(-4) M and 10(-5) M (p Propionylcarnitine always reduced creatine kinase leakage in the adult (p propionylcarnitine. However, in the adult rat hearts, L-propionylcarnitine given before ischemia and throughout reperfusion was protective by reducing creatine kinase leakage.

  7. Effects of glycyl-glutamine dipeptide supplementation on myocardial damage and cardiac function in rats after severe burn injury.

    Science.gov (United States)

    Zhang, Yong; Yan, Hong; Lv, Shang-Gun; Wang, Lin; Liang, Guang-Ping; Wan, Qian-Xue; Peng, Xi

    2013-01-01

    Glutamine decreases myocardial damage in ischemia/reperfusion injury. However, the cardioprotective effect of glutamine after burn injury remains unclear. Present study was to explore the protective effect of glycyl-glutamine dipeptide on myocardial damage in severe burn rats. Seventy-two Wistar rats were randomly divided into three groups: normal control (C), burned control (B) and glycyl-glutamine dipeptide-treated (GG) groups. B and GG groups were inflicted with 30% total body surface area of full thickness burn. The GG group was given 1.5 g/kg glycyl-glutamine dipeptide per day and the B group was given the same dose of alanine via intraperitoneal injection for 3 days. The serum CK, LDH, AST, and, blood lactic acid levels, as well as the myocardium ATP and GSH contents, were measured. The indices of cardiac contractile function and histopathological change were analyzed at 12, 24, 48, and 72 post-burn hours (PBH). The serum CK, LDH, AST and blood lactic acid levels increased, and the myocardium ATP and GSH content decreased in both burned groups. Compared with B group, the CK, LDH, AST and blood lactic acid levels reduced, myocardium ATP and GSH content increased in GG group. Moreover, the inhibition of cardiac contractile function and myocardial histopathological damage were reduced significantly in GG group. We conclude that myocardial histological structure and function were damaged significantly after burn injury, glycyl-glutamine dipeptide supplementation is beneficial to myocardial preservation by improving cardiocyte energy metabolism, increasing ATP and glutathione synthesis.

  8. Exercise improves cardiac autonomic function in obesity and diabetes.

    Science.gov (United States)

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

    2013-05-01

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

  9. Improvement of cardiac function after kidney transplantation with dilated cardiomyopathy and long dialysis vintage.

    Science.gov (United States)

    Mimura, Imari; Kawarazaki, Hiroo; Momose, Toshimitsu; Shibagaki, Yugo; Fujita, Toshiro

    2009-12-01

    Patients with long dialysis vintage have low cardiac output for various reasons. Although kidney transplantation is known to improve cardiac mortality, patients are sometimes evaluated as contraindicated for transplantation because of cardiac risk. We successfully performed kidney transplantation for a patient with a long dialysis vintage and dilated cardiomyopathy. Sequential (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy suggested that amelioration of uraemia improved cardiac function. Kidney transplantation for patients with severely impaired cardiac function is safe and effective under careful perioperative monitoring irrespective of dialysis vintage. Sequential (123)I-MIBG scintigraphy can be used as an evaluation tool for the improvement in cardiac function.

  10. Osteoprotegerin Levels Change During STEMI and Reflect Cardiac Function

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan S; Hoffmann, Søren

    2014-01-01

    of OPG levels during STEMI treated with percutaneous coronary intervention (PCI) and additionally, the effect of OPG levels on cardiac function. METHODS: We prospectively included 42 patients with STEMI treated with primary PCI. Four consecutive blood samples were obtained before and after PCI treatment......BACKGROUND: High levels of circulating osteoprotegerin (OPG) predicts long-term outcome in patients with ST-elevation myocardial infarction (STEMI), possibly because of increased vascular inflammation resulting in myocardial damage. In the present study we aimed at elucidating the dynamic progress....... Plasma OPG levels were determined using an in-house immunoassay. Cardiac function was increased according to echocardiography, estimating left ventricular ejection fraction (LVEF) 1-3 days after STEMI. RESULTS: During STEMI, OPG levels peaked after PCI and then decreased; mean concentrations (95...

  11. Effect of Mixed Anesthesia on Cardiac Function by Phonocardiogram

    Institute of Scientific and Technical Information of China (English)

    Fei Han; Hong-Mei Yan; Xin-Chuan Wei; Qing Yan

    2008-01-01

    Objective of this investigation is to further analyze the cardiac function status change by phonocar diogram during mixed anesthesia which is conducted by midazolam, skelaxin, fentanyi and propofoL The results show that blood pressure, heart rate, amplitude of R wave and T wave, amplitude of first heart sound (Si) and second heart sound (52) about 37 subjects after anesthesia decrease compared with baseline, while the. ratio of first heart sound and second heart sound (Si/S2) and the ratio of diastole duration and systole duration (DIS) increase. Our study demonstrates that phonocardiogram as a noninvasive, high benefit/cost ratio, objective, repeatable and portable method can be used for the monitoring and evaluation of cardiac function status during anesthesia and operations.

  12. Ginkgolide B Reduces the Degradation of Membrane Phospholipids to Prevent Ischemia/Reperfusion Myocardial Injury in Rats.

    Science.gov (United States)

    Pei, Hong-Xia; Hua, Rong; Guan, Cha-Xiang; Fang, Xiang

    2015-01-01

    Platelet-activating factor (PAF), a bioactive phospholipid, plays an important role in the integrity of the cellular membrane structure, and is involved in the pathogenesis of myocardial ischemia/reperfusion (IR) injuries. In this study, we tested the hypothesis that blockage of PAF receptor by BN 52021 (Ginkgolide B) can prevent IR-induced degradation of the myocardial membrane phospholipid, and deterioration of the cardiac function. Rat hearts in situ were subjected to 5 min ischemia and followed by 10 min reperfusion. Cardiac performances during periods of ischemia and reperfusion were monitored, and the amount of membrane phospholipids was analyzed. Myocardial total phospholipids, phosphatidylcholine, and phosphatidylethanolamine were decreased significantly in ischemia-reperfusion rat hearts compared with those of sham-operated rat hearts. Degradation of the membrane phospholipid was accompanied by the deterioration of cardiac functions and increase in serum lactate dehydrogenase (LDH) activity. BN 52021 (15 mg/kg), given by intravenous infusion 10 min prior to the left anterior descending coronary artery occlusion, reduced IR-related degradation of the myocardial phospholipids, the activity of serum LDH, and was concomitant with improvement of cardiac function. Furthermore, we demonstrated that the production of PAF was increased and BN 52021 decreased cellular damage in cultured anoxic cardiomyocytes. These results indicated that PAF antagonist BN 52021 has a protective effect against IR-induced myocardial dysfunction and degradation of the membrane phospholipids.

  13. Overhydration, Cardiac Function and Survival in Hemodialysis Patients

    OpenAIRE

    Mihai Onofriescu; Dimitrie Siriopol; Luminita Voroneanu; Simona Hogas; Ionut Nistor; Mugurel Apetrii; Laura Florea; Gabriel Veisa; Irina Mititiuc; Mehmet Kanbay; Radu Sascau; Adrian Covic

    2015-01-01

    RESEARCH ARTICLE Overhydration, Cardiac Function and Survival in Hemodialysis Patients Mihai Onofriescu1☯, Dimitrie Siriopol1☯, Luminita Voroneanu1, Simona Hogas1, Ionut Nistor1, Mugurel Apetrii1, Laura Florea1, Gabriel Veisa1, Irina Mititiuc1, Mehmet Kanbay3, Radu Sascau2, Adrian Covic1* 1 Department of Nephrology, University of Medicine and Pharmacy “Gr. T. Popa”, Iasi, Romania, 2 Department of Cardiology, University of Medicine and Pharmacy “Gr. T. Popa”, Iasi, Romania...

  14. Lovastatin protects mithochondrial and renal function in kidney ischemia-reperfusion in rats Lovastatina protege a função renal e mitocondrial na isquemia/reperfusão renal em ratos

    Directory of Open Access Journals (Sweden)

    Silvio Tucci Junior

    2012-07-01

    Full Text Available PURPOSE: To investigate the effect of lovastatin on renal ischemia followed by reperfusion. METHODS: Thirty one Wistar rats submitted to left renal ischemia for 60 minutes followed by contralateral nephrectomy were divided into two groups: A (n =17, control, no treatment, and B (n=14, lovastatin 15 mg/kg/day p.o. ten days before ischemia. The animals were sacrificed at the end of ischemia, after 24 hours and at seven days after reperfusion. Survival, serum urea and creatinine levels and renal mitochondrial function were evaluated. RESULTS: Mortality was 29.4% in group A and 0.7% in group B. Urea and creatinine levels were increased in both groups, but the values were significantly lower in group B. Mitochondrial function showed decoupling in 83.4% of group A, as opposed to 38.4/% of group B. CONCLUSIONS: The result shows a protective action of renal function by lovastatin administered before ischemia/reperfusion. Since most of the mitochondrial fraction presented membranes with the ability to maintain ATP production in group B, stabilization of the mitochondrial membrane should be considered as part of the protective action of lovastatin on renal function in ischemia/reperfusion.OBJETIVO: Investigar a ação da lovastatina na isquemia renal seguida de reperfusão. MÉTODOS: Trinta e um ratos Wistar submetidos à isquemia renal esquerda durante 60 minutos, seguida da nefrectomia contralateral, foram distribuídos em dois grupos: A (n=17, controle, sem tratamento e B (n=14, recebendo 15 mg/Kg/dia de lovastatina via oral, durante os dez dias que antecederam a isquemia. Os animais foram mortos ao final da isquemia, e com 24 horas e sete dias após a reperfusão. Foram avaliadas a sobrevida, os valores séricos de uréia e creatinina e a função mitocondrial renal. RESULTADOS: A mortalidade foi 29,4% no grupo A e 0,7% no grupo B. Os níveis de uréia e creatinina elevaram-se nos dois grupos, mas foram significativamente menores no grupo B. No grupo

  15. Erythropoietin improves left ventricular function and coronary flow in an experimental model of ischemia-reperfusion injury

    NARCIS (Netherlands)

    van der Meer, P; Lipsic, E; Henning, RH; de Boer, RA; Suurmeijer, AJH; van Veldhuisen, DJ; van Gilst, WH

    2004-01-01

    Recent studies show that erythropoietin (EPO) plays a protective role in brain ischemia. In this condition, administration of EPO protects neurons from ischemic damage. Recently, it has been shown that in patients with chronic heart failure (CHF), EPO treatment improved cardiac function. In the pres

  16. Identification and functional characterization of cardiac pacemaker cells in zebrafish.

    Directory of Open Access Journals (Sweden)

    Federico Tessadori

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

  17. Renal function changes after elective cardiac surgery with cardiopulmonary bypass.

    Science.gov (United States)

    de Moraes Lobo, E M; Burdmann, E A; Abdulkader, R C

    2000-01-01

    Cardiac surgery can either induce acute renal failure or improve GFR by improving the cardiac performance. In order to study renal function changes after elective cardiac surgery (CS) with cardiopulmonary bypass (CPBP), 21 patients undergoing valvular CS (VCS) or coronary artery bypass (CAB) were prospectively evaluated in three time periods: before, 24 hours after surgery and 48 hours after surgery. Patients were divided in 2 groups according to the GFR percent change in comparison to the baseline value found 24 hours after CS (deltaGFR24): Group 1, deltaGFR24 decrease higher than 20% (n = 11) and Group 2, deltaGFR24 decrease UpH) in both groups. The deltaGFR24 showed positive correlation with baseline FENa (r = 0.44 p = 0.04) and negative correlation with volume balance during the first 24h after CS (r = -0.63, p = 0.007). More patients in Group 1 required nitroprusside than in Group 2 (66% vs. 14%, p = 0.04). Anesthesia time was shorter in Group 1 as compared to Group 2: 323+/-21 vs. 395+/-26 min, p = 0.04. No significant hemolysis occurred during CS in either group. There were no differences in age, gender, CPBP time, need for dopamine and/or dobutamine between the two groups. In conclusion, patients who presented GFR decrease after CS underwent VCS more frequently, had more prevalence of previous CS, presented lower baseline FENa, required more volume infusion and more nitroprusside use. On the other hand, no tubular dysfunction was detected in the early follow-up of CS. These results suggest that the observed renal function changes should be the result of an appropriated renal response to a low effective blood volume. In fact, a low baseline FENa anticipated a GFR decrease in these patients. Consistently, CAB patients that usually improve their cardiac output after surgery showed a clear GFR improvement.

  18. Glaucocalyxin A Ameliorates Myocardial Ischemia-Reperfusion Injury in Mice by Suppression of Microvascular Thrombosis

    Science.gov (United States)

    Liu, Xiaohui; Xu, Dongzhou; Wang, Yuxin; Chen, Ting; Wang, Qi; Zhang, Jian; You, Tao; Zhu, Li

    2016-01-01

    Background The aim of this study was to evaluate the cardio-protective roles of glaucocalyxin A (GLA) in myocardial ischemia-reperfusion injury and to explore the underlying mechanism. Material/Methods Myocardial ischemia-reperfusion in wild-type C57BL/6J mice was induced by transient ligation of the left anterior descending artery. GLA or vehicle (solvent) was administrated intraperitoneally to the mice before reperfusion started. After 24 h of myocardial reperfusion, ischemic size was revealed by Evans blue/TTC staining. Cardiac function was evaluated by echocardiography and microvascular thrombosis was assessed by immunofluorescence staining of affected heart tissue. We also measured the phosphorylation of AKT, ERK, P-GSK-3β, and cleaved caspase 3 in the myocardium. Results Compared to the solvent-treated control group, GLA administration significantly reduced infarct size (GLA 13.85±2.08% vs. Control 18.95±0.97%, p<0.05) and improved left ventricular ejection fraction (LVEF) (GLA 53.13±1.11% vs. Control 49.99±1.25%, p<0.05) and left ventricular fractional shortening (LVFS) (28.34±0.71% vs. Control 25.11±0.74%, p<0.05) in mice subjected to myocardial ischemia-reperfusion. GLA also attenuated microvascular thrombosis (P<0.05) and increased the phosphorylation of pro-survival kinase AKT (P<0.05) and GSK-3β (P<0.05) in the myocardium upon reperfusion injury. Conclusions Administration of GLA before reperfusion ameliorates myocardial ischemia-reperfusion injury in mice. The cardio-protective roles of GLA may be mediated through the attenuation of microvascular thrombosis. PMID:27716735

  19. On the mechanics of cardiac function of Drosophila embryo.

    Science.gov (United States)

    Wu, Mingming; Sato, Thomas N

    2008-01-01

    The heart is a vital organ that provides essential circulation throughout the body. Malfunction of cardiac pumping, thus, leads to serious and most of the times, to fatal diseases. Mechanics of cardiac pumping is a complex process, and many experimental and theoretical approaches have been undertaken to understand this process. We have taken advantage of the simplicity of the embryonic heart of an invertebrate, Drosophila melanogaster, to understand the fundamental mechanics of the beating heart. We applied a live imaging technique to the beating embryonic heart combined with analytical imaging tools to study the dynamic mechanics of the pumping. Furthermore, we have identified one mutant line that exhibits aberrant pumping mechanics. The Drosophila embryonic heart consists of only 104 cardiac cells forming a simple straight tube that can be easily accessed for real-time imaging. Therefore, combined with the wealth of available genetic tools, the embryonic Drosophila heart may serve as a powerful model system for studies of human heart diseases, such as arrhythmia and congenital heart diseases. We, furthermore, believe our mechanistic data provides important information that is useful for our further understanding of the design of biological structure and function and for engineering the pumps for medical uses.

  20. Evaluation of Chronic Physical and Psychological Stress Induction on Cardiac Ischemia / Reperfusion Injuries in Isolated Male Rat Heart: The Role of Sympathetic Nervous System.

    Science.gov (United States)

    Rakhshan, Kamran; Imani, Alireza; Faghihi, Mahdieh; Nabavizadeh, Fatemeh; Golnazari, Masoumeh; Karimian, SeyedMorteza

    2015-08-01

    Exposure to stress leads to physiological changes called "stress response" which are the result of the changes in the adrenomedullary hormone system, hypothalamus-pituitary-adrenal (HPA) and sympathetic nervous system (SNS) activity. In the present study, the effects of chronic physical and psychological stress and also the role of sympathetic system effects in stress on ischemia/reperfusion (I/R) injuries have been studied in isolated rat heart. Rat heart was isolated and subjected to 30 min regional ischemia and 120 min reperfusion. The daily stress was induced for one week prior to I/R induction. Sympathectomy was done chemically by injection of hydroxyl-dopamine prior to stress induction. There were no significant changes in heart rate and Coronary Flow between groups. Left ventricular developed pressure (LVDP) and rate product pressure (RPP) in both physical and psychological stress groups decreased significantly compared to those in control group (Pphysical and psychological stress groups. Infarct size significantly increased in both physical and psychological stress groups and control group(Pstress led to the elimination of the deleterious effects of stress as compared with stress groups (Presults show that induction of chronic physical and psychological stress prior to ischemia/reperfusion causes enhancement of myocardial injuries and it seems that increased sympathetic activity in response to stress is responsible for these adverse effects of stress on ischemic/reperfused heart.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2007-05-01

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

  3. Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion.

    Science.gov (United States)

    Okere, Isidore C; McElfresh, Tracy A; Brunengraber, Daniel Z; Martini, Wenjun; Sterk, Joseph P; Huang, Hazel; Chandler, Margaret P; Brunengraber, Henri; Stanley, William C

    2006-01-01

    In the normal heart, there is loss of citric acid cycle (CAC) intermediates that is matched by the entry of intermediates from outside the cycle, a process termed anaplerosis. Previous in vitro studies suggest that supplementation with anaplerotic substrates improves cardiac function during myocardial ischemia and/or reperfusion. The present investigation assessed whether treatment with the anaplerotic medium-chain fatty acid heptanoate improves contractile function during ischemia and reperfusion. The left anterior descending coronary artery of anesthetized pigs was subjected to 60 min of 60% flow reduction and 30 min of reperfusion. Three treatment groups were studied: saline control, heptanoate (0.4 mM), or hexanoate as a negative control (0.4 mM). Treatment was initiated after 30 min of ischemia and continued through reperfusion. Myocardial CAC intermediate content was not affected by ischemia-reperfusion; however, treatment with heptanoate resulted in a more than twofold increase in fumarate and malate, with no change in citrate and succinate, while treatment with hexanoate did not increase fumarate or malate but increased succinate by 1.8-fold. There were no differences among groups in lactate exchange, glucose oxidation, oxygen consumption, and contractile power. In conclusion, despite a significant increase in the content of carbon-4 CAC intermediates, treatment with heptanoate did not result in improved mechanical function of the heart in this model of reversible ischemia-reperfusion. This suggests that reduced anaplerosis and CAC dysfunction do not play a major role in contractile and metabolic derangements observed with a 60% decrease in coronary flow followed by reperfusion.

  4. Cardiac autonomic functions in children with familial Mediterranean fever.

    Science.gov (United States)

    Şahin, Murat; Kır, Mustafa; Makay, Balahan; Keskinoğlu, Pembe; Bora, Elçin; Ünsal, Erbil; Ünal, Nurettin

    2016-05-01

    Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. The long-term effects of subclinical inflammation in FMF are not well recognized. Some studies have suggested that FMF is associated with cardiac autonomic dysfunction in adult FMF patients. The objective of this study was to investigate the cardiac autonomic functions in pediatric FMF patients by using several autonomic tests. Thirty-five patients with FMF and 35 healthy controls were enrolled in this cross-sectional study. Demographic data, disease-specific data, and orthostatic symptoms were recorded. In all participants, 12-lead electrocardiography (ECG), 24 h ambulatory electrocardiographic monitoring, transthoracic echocardiography, treadmill exercise test, and head upright tilt-table (HUTT) test were performed. The heart rate recovery (HRR) indices of the two groups were similar. Also, chronotropic response was similar in both groups. The time-domain parameters of heart rate variability (HRV) were similar in both groups, except mean RR (p = 0.024). Frequencies of ventricular and supraventricular ectopic stimuli were similar in both groups. There were no statistically significant differences between the groups in average QT and average corrected QT interval length, average QT interval dispersion, and average QT corrected dispersion. There was no significant difference between the two groups regarding the ratio of clinical dysautonomic reactions on HUTT. However, we observed a significantly higher rate of dysautonomic reactions on HUTT in patients with exertional leg pain than that in patients without (p = 0.013). When the fractal dimension of time curves were compared, FMF patients exhibited significantly lower diastolic blood pressure parameters than controls in response to HUTT. Cardiovascular autonomic dysfunction in children with FMF is not prominent. Particularly, patients with exertional leg pain are more prone to have dysautonomic features

  5. 心脏肥大细胞在心肌缺血/再灌注损伤中的研究进展%Cardiac mast cells in myocardial ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    张江玲; 陈杰; 王祥瑞

    2010-01-01

    Mast cells are multifunctional effector cells and originate from stem cells in the bone marrow. After being activated, it degranulates and releases several kind of inflammation mediators, (eg. cytokines and proteases) participating in inflammatory reaction and IgE-dependent histamine-mediated hypersusceptibility reaction. This article discusses the relationship between cardiac mast cells and the pathological progress such as inflammatory reaction、cell apoptosis and infarct recovery in myocardial ischemia-reperfusion injury.%肥大细胞是一种多效应细胞,起源于骨髓多分化细胞,激活后脱颗粒释放多种炎症介质、细胞因子及蛋白酶,参与炎症反应及IgE依赖的组胺介导的高敏反应.现讨论心脏肥大细胞与心肌缺血/再灌注(ischemia/reperfusion,I/R)损伤中炎症反应、细胞凋亡及梗死修复等病理过程的相关关系.

  6. Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury

    Science.gov (United States)

    Sharma, Ashish Kumar; Munajjam, Arshee; Vaishnav, Bhawna; Sharma, Richa; Sharma, Ashok; Kishore, Kunal; Sharma, Akash; Sharma, Divya; Kumari, Rita; Tiwari, Ashish; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh; Srinivasan, Barthu Parthi; Agarwal, Shyam Sunder

    2012-01-01

    The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide. PMID:23554727

  7. Protective effects of garlic extract on cardiac function, heart rate variability, and cardiac mitochondria in obese insulin-resistant rats.

    Science.gov (United States)

    Supakul, Luerat; Pintana, Hiranya; Apaijai, Nattayaporn; Chattipakorn, Siriporn; Shinlapawittayatorn, Krekwit; Chattipakorn, Nipon

    2014-04-01

    Garlic has been shown to exhibit antioxidant effects and cardioprotective properties. However, the effects of garlic extract on the heart in insulin resistance induced by long-term high-fat-diet consumption are not well defined. Therefore, we sought to determine the effects of garlic extract in the obese insulin-resistant rats. Male Wistar rats (180-200 g) were divided into two groups: normal-diet or high-fat-diet (n = 24/group) fed for 12 weeks. Rats in each groups were divided into three subgroups (n = 8 each): vehicle or garlic extract (250 or 500 mg/kg/day, respectively) treated for 28 days. At the end of the treatment, the metabolic parameters, heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined. Rats that received a high-fat-diet for 12 weeks had increased body weight, visceral fat, plasma insulin levels, total cholesterol, oxidative stress levels, depressed HRV, and cardiac mitochondrial dysfunction. Garlic extract at both concentrations significantly decreased the plasma insulin, total cholesterol, homeostasis model assessment index, and oxidative stress levels. Furthermore, garlic extract at both doses restored the HRV, cardiac function, and cardiac mitochondrial function. We concluded that garlic extract at both concentrations exerted cardioprotective effects against cardiac dysfunction and mitochondrial dysfunction in obese insulin-resistant rats.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Cardiac autonomic dysfunction and cardiac microvascular dysfunction are diabetic complications associated with increased mortality, but the association between these has been difficult to assess. We applied new and sensitive methods to assess this in patients with type 2 diabetes mellitus (T2DM...... (123)I-metaiodobenzylguanidine scintigraphy was conducted in a subgroup of 29 patients and 14 control subjects and evaluated as the late heart-to-mediastinum ratio and washout rate. Impaired function of all the cardiac autonomic measures (except the washout rate) was associated with reduced CFR....... A heart rate variability index, reflecting sympathetic and parasympathetic function (low-frequency power), and the late heart-to-mediastinum ratio, reflecting the function of adrenergic receptors and sympathetic activity, were positively correlated with CFR after adjustment for age and heart rate...

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

    Directory of Open Access Journals (Sweden)

    Nathan Y Weltman

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

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

    Science.gov (United States)

    Redetzke, Rebecca A.; Gerdes, A. Martin

    2012-01-01

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

  11. Regular Football Practice Improves Autonomic Cardiac Function in Male Children

    Science.gov (United States)

    Fernandes, Luis; Oliveira, Jose; Soares-Miranda, Luisa; Rebelo, Antonio; Brito, Joao

    2015-01-01

    Background: The role of the autonomic nervous system (ANS) in the cardiovascular regulation is of primal importance. Since it has been associated with adverse conditions such as cardiac arrhythmias, sudden death, sleep disorders, hypertension and obesity. Objectives: The present study aimed to investigate the impact of recreational football practice on the autonomic cardiac function of male children, as measured by heart rate variability. Patients and Methods: Forty-seven male children aged 9 - 12 years were selected according to their engagement with football oriented practice outside school context. The children were divided into a football group (FG; n = 22) and a control group (CG; n = 25). The FG had regular football practices, with 2 weekly training sessions and occasional weekend matches. The CG was not engaged with any physical activity other than complementary school-based physical education classes. Data from physical activity, physical fitness, and heart rate variability measured in time and frequency domains were obtained. Results: The anthropometric and body composition characteristics were similar in both groups (P > 0.05). The groups were also similar in time spent daily on moderate-to-vigorous physical activities (FG vs. CG: 114 ± 64 vs. 87 ± 55 minutes; P > 0.05). However, the FG performed better (P football practice presented enhanced physical fitness and autonomic function, by increasing vagal tone at rest. PMID:26448848

  12. Altering Cardiac Function via Transgenesis A Nuts and Bolts Approach.

    Science.gov (United States)

    Robbins, J

    1997-08-01

    Transgenesis provides a means to modify the mammalian genome. By directing expression of a engineered protein to the heart, one now is able to remodel effectively the cardiac protein profile and study the consequences of a single genetic manipulation at the molecular, biochemical, cytological, and physiologic levels. Often, a particular pathology or even a global remodeling process such as hypertrophy is accompanied by the upregulation or downregulation of a gene or set(s) of genes. What is not known is whether these changes represent a beneficial compensatory response or contribute to the continued degeneration of normal heart function. The ability to perform genetic manipulations on cardiac gene expression via transgenesis offers one a rapid and effective means of extending the correlations noted to the mechanistic level. Now, one can, in theory, express a candidate protein at a particular developmental time and determine the direct consequences of its appearance. Similarly, one can explore structure-function relationships, both between different forms of a protein family and in terms of active domains within a protein, by expressing a transgene that encodes a suitable mutation or ectopic protein isoform. This review explores the practical considerations of the transgenic approach in terms of what is important for a successful experiment from the necessary animal husbandry to designing constructs that will express at appropriate levels in the heart. (Trends Cardiovasc Med 1997;7:185-191). © 1997, Elsevier Science Inc.

  13. Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction

    OpenAIRE

    Anne-Laure Leblond; Kerstin Klinkert; Kenneth Martin; Turner, Elizebeth C.; Arun H Kumar; Tara Browne; Caplice, Noel M.

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1...

  14. Evaluation of platelet function in dogs with cardiac disease using the PFA-100 platelet function analyzer.

    Science.gov (United States)

    Clancey, Noel; Burton, Shelley; Horney, Barbara; Mackenzie, Allan; Nicastro, Andrea; Côté, Etienne

    2009-09-01

    Cardiac disease has the potential to alter platelet function in dogs. Evaluation of platelet function using the PFA-100 analyzer in dogs of multiple breeds and with a broad range of cardiac conditions would help clarify the effect of cardiac disease on platelets. The objective of this study was to assess differences in closure time (CT) in dogs with cardiac disease associated with murmurs, when compared with that of healthy dogs. Thirty-nine dogs with cardiac murmurs and turbulent blood flow as determined echocardiographically were included in the study. The dogs represented 23 different breeds. Dogs with murmurs were further divided into those with atrioventricular valvular insufficiency (n=23) and subaortic stenosis (n=9). Fifty-eight clinically healthy dogs were used as controls. CTs were determined in duplicate on a PFA-100 analyzer using collagen/ADP cartridges. Compared with CTs in the control group (mean+/-SD, 57.6+/-5.9 seconds; median, 56.5 seconds; reference interval, 48.0-77.0 seconds), dogs with valvular insufficiency (mean+/-SD, 81.9+/-26.3 seconds; median, 78.0 seconds; range, 52.5-187 seconds), subaortic stenosis (71.4+/-16.5 seconds; median, 66.0 seconds; range, 51.5-95.0 seconds), and all dogs with murmurs combined (79.6+/-24.1 seconds; median, 74.0 seconds; range, 48.0-187 seconds) had significantly prolonged CTs (P<.01). The PFA-100 analyzer is useful in detecting platelet function defects in dogs with cardiac murmurs, most notably those caused by mitral and/or tricuspid valvular insufficiency or subaortic stenosis. The form of turbulent blood flow does not appear to be an important factor in platelet hypofunction in these forms of cardiac disease.

  15. Effects of Lipoteichoic Acid induced Delayed Preconditioning on Ischemia-reperfusion Injury in Isolated Rat Hearts

    Institute of Scientific and Technical Information of China (English)

    马世玉; 向继洲; 吴基良; 胡本容

    2003-01-01

    To explore the potential of lipoteichoic acid (LTA) induced cardioprotection against is-chemia-reperfusion (I/R) injury in isolated rat hearts and whether endogenous nitric oxide (NO)participates-in the protection, the rats were pretreated with LTA (1 mg/kg, i. p. ) 24 h before theexperiment, and the isolated hearts were subjected to 30 min no-flow normothermic global ischemiaand 60 min reperfusion after a 20-min stabilization period by the langendorff method. Cardiac func-tions were evaluated at the end of stabilization, and at 30 min, 60 min of reperfusion. The amountsof MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase(LDH) and total NO oxidationproducts in the coronary effluent were measured spectrophotometrically at the end of reperfusion. Itwas revealed that pretreatment with LTA could significantly improve the recovery of cardiac func-tion, reduce the release of CK-MB and LDH, and increase the concentrations of NO in coronary ef-fluent. The protective effects were abrogated by pretreatment of the rats with L-NAME. It wasconcluded that LTA could induce the delayed cardioprotection against I/R injury, and endogenousNO may be involved in the mechanisms.

  16. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury

    Science.gov (United States)

    Masuzawa, Akihiro; Black, Kendra M.; Pacak, Christina A.; Ericsson, Maria; Barnett, Reanne J.; Drumm, Ciara; Seth, Pankaj; Bloch, Donald B.; Levitsky, Sidney; Cowan, Douglas B.

    2013-01-01

    Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 106/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2–8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury. PMID:23355340

  17. Myocardial ischemia/reperfusion impairs neurogenesis and hippocampal-dependent learning and memory.

    Science.gov (United States)

    Evonuk, Kirsten S; Prabhu, Sumanth D; Young, Martin E; DeSilva, Tara M

    2017-03-01

    The incidence of cognitive impairment in cardiovascular disease (CVD) patients has increased, adversely impacting quality of life and imposing a significant economic burden. Brain imaging of CVD patients has detected changes in the hippocampus, a brain region critical for normal learning and memory. However, it is not clear whether adverse cardiac events or other associated co-morbidities impair cognition. Here, using a murine model of acute myocardial ischemia/reperfusion (I/R), where the coronary artery was occluded for 30min followed by reperfusion, we tested the hypothesis that acute myocardial infarction triggers impairment in cognitive function. Two months following cardiac I/R, behavioral assessments specific for hippocampal cognitive function were performed. Mice subjected to cardiac I/R performed worse in the fear-conditioning paradigm as well as the object location memory behavioral test compared to sham-operated mice. Reactive gliosis was apparent in the hippocampal subregions CA1, CA3, and dentate gyrus 72h post-cardiac I/R as compared with sham, which was sustained two months post-cardiac I/R. Consistent with the inflammatory response, the abundance of doublecortin positive newborn neurons was decreased in the dentate gyrus 72h and 2months post-cardiac I/R as compared with sham. Therefore, we conclude that following acute myocardial infarction, rapid inflammatory responses negatively affect neurogenesis, which may underlie long-term changes in learning and memory.

  18. Critical role of bicarbonate and bicarbonate transporters in cardiac function

    Institute of Scientific and Technical Information of China (English)

    Hong-Sheng; Wang; Yamei; Chen; Kanimozhi; Vairamani; Gary; E; Shull

    2014-01-01

    Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2 O, either spontaneously or via the catalytic activity of carbonic anhydrase. It serves as a component of the major buffer system, thereby playing a critical role in pH homeostasis. Bicarbonate can also be utilized by a variety of ion transporters, often working in coupled systems, to transport other ions and organic substrates across cell membranes. The functions of HCO3- and HCO3--transporters in epithelial tissues have been studied extensively, but their functions in heart are less well understood. Here we review studies of the identities and physiological functions of Cl-/HCO3- exchangers and Na+/HCO3-cotransporters of the SLC4 A and SLC26 A families in heart. We also present RNA Seq analysis of their cardiac mRNA expression levels. These studies indicate that slc4a3(AE3) is the major Cl-/HCO3- exchanger and plays a protective role in heart failure, and that Slc4a4(NBCe1) is the major Na+/HCO3- cotransporter and affects action potential duration. In addition, previous studies show that HCO3- has a positive inotropic effect in the perfused heart that is largely independent of effects on intracellular Ca2+. The importance of HCO3- in the regulation of contractility is supported by experiments showing that isolated cardiomyocytes exhibit sharply enhanced contractility, with no change in Ca2+ transients, when switched from Hepes-buffered to HCO3-- buffered solutions. These studies demonstrate that HCO3- and HCO3--handling proteins play important roles in the regulation of cardiac function.

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

    Science.gov (United States)

    Nelson, O Lynne; Robbins, Charles T

    2010-03-01

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

  20. Role of Mitochondrial Enzymes and Sarcoplasmic ATPase in Cardioprotection Mediated by Aqueous Extract of Desmodium gangeticum (L) DC Root on Ischemic Reperfusion Injury.

    Science.gov (United States)

    Kurian, G A; Paddikkala, J

    2010-11-01

    The present study investigate the protective effect of aqueous root extract of Desmodium gangeticum in preserving mitochondrial and sarcoplasmic ATPase during ischemia reperfusion injury. The isolated rat hearts in both drug and control group were subjected to warm ischemia (37°), followed by reperfusion with the Langendorff perfusion system. The aqueous root extract of Desmodium gangeticum (L) at a dose of 50 mg/kg body weight was found to be effective in the rat heart for the management of ischemic reperfusion injury. Physiological parameters were significantly (PDesmodium gangeticum treated rat heart. These results suggest that Desmodium gangeticum aqueous root extract can preserve the mitochondrial and sarcoplasmic ATPase in the myocardium, resulting in the improvement of cardiac function after ischemia reperfusion injury.

  1. Evaluation of Chronic Physical and Psychological Stress Induction on Cardiac Ischemia / Reperfusion Injuries in Isolated Male Rat Heart: The Role of Sympathetic Nervous System

    Directory of Open Access Journals (Sweden)

    Kamran Rakhshan

    2015-10-01

    Full Text Available Exposure to stress leads to physiological changes called “stress response” which are the result ofthe changes in the adrenomedullary hormone system, hypothalamus-pituitary-adrenal (HPA and sympatheticnervous system (SNS activity. In the present study, the effects of chronic physical and psychological stressand also the role of sympathetic system effects in stress on ischemia/reperfusion (I/R injuries have beenstudied in isolated rat heart. Rat heart was isolated and subjected to 30 min regional ischemia and 120 minreperfusion. The daily stress was induced for one week prior to I/R induction. Sympathectomy was donechemically by injection of hydroxyl-dopamine prior to stress induction. There were no significant changes inheart rate and Coronary Flow between groups. Left ventricular developed pressure (LVDP and rate productpressure (RPP in both physical and psychological stress groups decreased significantly compared to those incontrol group (Pgroups. Infarct size significantly increased in both physical and psychological stress groups and control group(Pas compared with stress groups (Ppsychological stress prior to ischemia/reperfusion causes enhancement of myocardial injuries and it seemsthat increased sympathetic activity in response to stress is responsible for these adverse effects of stress onischemic/reperfused heart.

  2. Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery

    OpenAIRE

    André Luiz Lisboa Cordeiro; Thiago Araújo de Melo; Daniela Neves; Julianne Luna; Mateus Souza Esquivel; André Raimundo França Guimarães; Daniel Lago Borges; Jefferson Petto

    2016-01-01

    Abstract Introduction: Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. Objective: To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. Methods: This is a clinical randomized controlled tri...

  3. Does machine perfusion decrease ischemia reperfusion injury?

    Science.gov (United States)

    Bon, D; Delpech, P-O; Chatauret, N; Hauet, T; Badet, L; Barrou, B

    2014-06-01

    In 1990's, use of machine perfusion for organ preservation has been abandoned because of improvement of preservation solutions, efficient without perfusion, easy to use and cheaper. Since the last 15 years, a renewed interest for machine perfusion emerged based on studies performed on preclinical model and seems to make consensus in case of expanded criteria donors or deceased after cardiac death donations. We present relevant studies highlighted the efficiency of preservation with hypothermic machine perfusion compared to static cold storage. Machines for organ preservation being in constant evolution, we also summarized recent developments included direct oxygenation of the perfusat. Machine perfusion technology also enables organ reconditioning during the last hours of preservation through a short period of perfusion on hypothermia, subnormothermia or normothermia. We present significant or low advantages for machine perfusion against ischemia reperfusion injuries regarding at least one primary parameter: risk of DFG, organ function or graft survival. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  4. Cardioprotection by modulation of mitochondrial respiration during ischemia–reperfusion: Role of apoptosis-inducing factor

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Aijun [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030 (China); Szczepanek, Karol; Hu, Ying [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Lesnefsky, Edward J. [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298 (United States); McGuire Department of Veterans Affairs Medical Center, Richmond, VA 23249 (United States); Chen, Qun, E-mail: qchen8@vcu.edu [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States)

    2013-06-14

    Highlights: •Blockade of electron transport prevents the loss of AIF from mitochondria during IR. •Blockade of electron transport decreases caspase-independent cell death during IR. •Mitochondrial AIF content is down-regulated in Harlequin mice. •Blockade of electron transport protects Harlequin mouse hearts during IR. •Amobarbital protection is partially dependent on mitochondrial AIF content. -- Abstract: The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia–reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia–reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in

  5. Small Molecule Cardiogenol C Upregulates Cardiac Markers and Induces Cardiac Functional Properties in Lineage-Committed Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Agnes K. Mike

    2014-01-01

    Full Text Available Background/Aims: Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited transdifferentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules. Methods: Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC, and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays. Results: Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies. Conclusion: CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy.

  6. Targeted inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis and Preserves Heart Function in Adverse Cardiac Remodeling

    Science.gov (United States)

    Zhang, Jie; Fan, Guangpu; Zhao, Hui; Wang, Zhiwei; Li, Fei; Zhang, Peide; Zhang, Jing; Wang, Xu; Wang, Wei

    2017-01-01

    Cardiac fibrosis in post-myocardial infarction (MI), seen in both infarcted and non-infarcted myocardium, is beneficial to the recovery of heart function. But progressively pathological fibrosis impairs ventricular function and leads to poor prognosis. FAK has recently received attention as a potential mediator of fibrosis, our previous study reported that pharmacological inhibition of FAK can attenuate cardiac fibrosis in post MI models. However, the long-term effects on cardiac function and adverse cardiac remodelling were not clearly investigated. In this study, we tried to determine the preliminary mechanisms in regulating CF transformation to myofibroblasts and ECM synthesis relevant to the development of adverse cardiac remolding in vivo and in vitro. Our study provides even more evidence that FAK is directly related to the activation of CF in hypoxia condition in a dose-dependent and time-dependent manner. Pharmacological inhibition of FAK significantly reduces myofibroblast differentiation; our in vivo data demonstrated that a FAK inhibitor significantly decreases fibrotic score, and preserves partial left ventricular function. Both PI3K/AKT signalling and ERK1/2 are necessary for hypoxia-induced CF differentiation and ECM synthesis; this process also involves lysyl oxidase (LOX). These findings suggest that pharmacological inhibition of FAK may become an effective therapeutic strategy against adverse fibrosis. PMID:28225063

  7. Novel O-palmitolylated beta-E1 subunit of pyruvate dehydrogenase is phosphorylated during ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Barr Amy J

    2010-07-01

    Full Text Available Abstract Background During and following myocardial ischemia, glucose oxidation rates are low and fatty acids dominate as a source of oxidative metabolism. This metabolic phenotype is associated with contractile dysfunction during reperfusion. To determine the mechanism of this reliance on fatty acid oxidation as a source of ATP generation, a functional proteomics approach was utilized. Results 2-D gel electrophoresis of mitochondria from working rat hearts subjected to 25 minutes of global no flow ischemia followed by 40 minutes of aerobic reperfusion identified 32 changes in protein abundance compared to aerobic controls. Of the five proteins with the greatest change in abundance, two were increased (long chain acyl-coenzyme A dehydrogenase (48 ± 1 versus 39 ± 3 arbitrary units, n = 3, P In silico analysis identified the putative kinases as the insulin receptor kinase for the more basic form and protein kinase Cζ or protein kinase A for the more acidic form. These modifications of pyruvate dehydrogenase are associated with a 35% decrease in glucose oxidation during reperfusion. Conclusions Cardiac ischemia/reperfusion induces significant changes to a number of metabolic proteins of the mitochondrial proteome. In particular, ischemia/reperfusion induced the post-translational modification of pyruvate dehydrogenase, the rate-limiting step of glucose oxidation, which is associated with a 35% decrease in glucose oxidation during reperfusion. Therefore these post-translational modifications may have important implications in the regulation of myocardial energy metabolism.

  8. Cardioprotective effect of aqueous extract of Chichorium intybus on ischemia-reperfusion injury in isolated rat heart.

    Science.gov (United States)

    Sadeghi, Najmeh; Dianat, Mahin; Badavi, Mohammad; Malekzadeh, Ahad

    2015-01-01

    Several studies have shown that Chichorium intybus (C. intybus) which possesses flavonoid compounds has an effective role in treatment of cardiovascular diseases. Contractile dysfunction mostly occurs after acute myocardial infarction, cardiac bypass surgery, heart transplantation and coronary angioplasty. The aim of the present study was to investigate the effect of aqueous extract of C. intybus on ischemia- reperfusion injury in isolated rat heart. The animals were divided into four groups (Sham, Control, 1 mg/ml and 3 mg/ml of extract) of 8 rats. The aorta was cannulated, and then the heart was mounted on a Langendorff apparatus. Next, a balloon was inserted into the left ventricle (LV) and peak positive value of time derivate of LV pressure (+dp/dt), coronary flow (CF), and left ventricular systolic pressure (LVSP) in pre-ischemia and reperfusion period were calculated by a Power Lab system. All groups underwent a 30-minute global ischemia followed by a 60-minute reperfusion. The results showed that heart rate (HR), coronary flow, and left ventricular developed pressure (LVDP) and rate of pressure product (RPP) significantly decreased in the control group during reperfusion, while these values in the groups receiving the extract (3mg/ml) improved significantly during reperfusion (p<0.001). It seems that flavonoid compounds of aqueous extract of C. intybus reduce ischemia - reperfusion injuries, suggesting its protective effect on heart function after ischemia.

  9. Comparison of Cardiac Autonomic Functions in Glucometabolic Disturbances

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    Seda Elçim Yıldırım

    2016-12-01

    Full Text Available INTRODUCTION: Autonomic neuropathy is a common complication of diabetes mellitus. The aim of the present study was to compare heart rate recovery time and heart rate variation among the indicators of cardiac autonomic function between patients with glucometabolic abnormalities in various levels and normal glucose homeostasis. METHODS: A total of 90 patients were enrolled in the study. The patients were divided into four groups: impaired fasting glucose (IFG (n=18, impaired glucose tolerance (IGT (n=25, type 2 diabetes mellitus (DM (n=21, and the control group (n=26. Cardiac autonomic neuropathy (CAN was evaluated by the maximum exercise stress test and Holter electrocardiography. RESULTS: The baseline heart rate in the DM group was higher than the IFG, IGT, and control groups, but the difference was not statistically significant (93.5±15.5, 87.8±9.4, 84.3±10.8, and 84.3±14.2, respectively; p=0.06. In multiple regression analysis FPG level was an independent variable, increased baseline heart rate was correlated with an elevated FPG level (constant: 71.35, p: 0.004. The metabolic equivalent of task (MET value was lower in the DM group compared to the IFG, IGT, and control groups (9.9±1.2, 9.0±1.6, 9.78±1.46, 8.77±1.74 p=0.06. DISCUSSION AND CONCLUSION: When compared to patients with normal glucose homeostasis heart rate at rest was higher in the IGT, IFG, and DM groups. Elevated fasting glucose levels were correlated with an increased baseline heart rate. A negative correlation was found between HbA1c levels and HRRT, and HR index. These finding indicate autonomic functions are impaired in patients with DM, IGT and IFG groups.

  10. Iloprost reduces myocardial edema in a rat model of myocardial ischemia reperfusion.

    Science.gov (United States)

    Caliskan, A; Yavuz, C; Karahan, O; Yazici, S; Guclu, O; Demirtas, S; Mavitas, B

    2014-05-01

    Myocardial ischemia severely reduces myocyte longevity and function. Extensive interstitial edema and cell damage occur as a result of myocardial reperfusion injury. Current therapies are directed at prevention of ischemia-induced damage to cardiac tissue. Iloprost is a novel pharmaceutical agent for the treatment of ischemia. Twenty rats were segregated into four experimental groups. The procedure control group consisted of four rats undergoing a sham operation. The remaining 16 rats were divided into two equal groups. The first group (control group) received a continuous intravenous infusion of physiological serum immediately prior to the procedure. Iloprost was administered by a continuous intravenous infusion into the right jugular vein at an infusion rate of 100 ng/kg/min for 30 minutes prior to reperfusion in the experimental group (study group). Following the infusion treatments, ligation of the left coronary artery was conducted for 30 minutes to induce myocardial ischemia. The rats were euthanized 24 hours after reperfusion and cardiac tissue was harvested from all specimens for analysis. Histological examination revealed three myocardial tissue specimens with grade II damage and five myocardial tissue specimens with grade III reperfusion injury in the control group. However, the study group consisted of two grade III myocardial tissue specimens, five grade II myocardial tissue specimens and one grade I myocardial tissue specimen. Moreover, a statistically significant reduction in myocardial edema was observed in the study group (p=0.022). Our results support the hypothesis that iloprost enhances protection against cardiac ischemia reperfusion injury. This protective effect may be associated with vasodilation, antioxidant or anti-edema mechanisms.

  11. The protective activity of noscapine on renal ischemia–reperfusion injury in male Wistar rat

    Science.gov (United States)

    Khanmoradi, Mehrangiz; Ali Mard, Seyyed; Aboutaleb, Nahid; Nobakht, Malihe; Mahmoudian, Masoud

    2014-01-01

    Objective(s): Bradykinin is a part of the kinin-kallikrein system which is involved in ischemia-reperfusion injury via B1 and B2 receptors. Noscapine is a non-competitive antagonist of bradykinin receptors. Noscapine has been reported to to be able to protect some organs against ischemia-reperfusion injury but its effect on renal ischemia-reperfusion injury (RIR) in rats is unknown. Therefore, the present study was designed to evaluate the effect of noscapine on renal ischemia-reperfusion injury in rats. Materials and Methods: Twenty four rats were randomly assigned to four groups; sham, RIR control, pre-and post-treatment with noscapine. To induce RIR injury, 20 days after right nephrectomy, animals underwent a midline laparotomy and the renal artery was clamped for 40 min to induce ischemia, and the clamp was then removed to allow reperfusion for 48 hr. Animals received noscapine or vehicle 1 hr before RIR or just prior to reperfusion. At the end of the experiment, animals were killed by cardiac exsanguination. Blood samples were collected to assess blood urea nitrogen (BUN) and creatinine. The kidneys were also removed for histopathlogical and western-blot analysis. Results: Noscapine treatment 1 hr before RIR or just prior to reperfusion protects the renal tissue structure as compared with the control. The expression levels of the studied inflammatory mediators, TNF-α and MCP-1in pretreated-, and treated-noscapine groups decreased as compared with the control group. The levels of BUN and creatinine in pre-, and post-treated noscapine groups were significantly lower than in control animals. Conclusion: Noscapine protects renal tissue structure and function against RIR through down-regulation of the inflammatory mediators. PMID:24904716

  12. HL-1 mouse cardiomyocyte injury and death after simulated ischemia and reperfusion: roles of pH, Ca2+-independent phospholipase A2, and Na+/H+ exchange

    DEFF Research Database (Denmark)

    Andersen, Ann-Dorit; Poulsen, Kristian Arild; Lambert, Ian H;

    2009-01-01

    The Ca(2+)-independent phospholipase A(2) VI (iPLA(2)-VI) and the Na(+)/H(+) exchanger isoform 1 (NHE1) are highly pH-sensitive proteins that exert both protective and detrimental effects in cardiac ischemia-reperfusion. Here, we investigated the role of extracellular pH (pH(o)) in ischemia-reperfusion...... injury and death and in regulation and function of iPLA(2)-VI and NHE1 under these conditions. HL-1 cardiomyocytes were exposed to simulated ischemia (SI; 0.5% O(2), 8 mM K(+), and 20 mM lactate) at pH(o) 6.0 and 7.4, with or without 4 or 8 h of reperfusion (SI/R). Cytochrome c release and caspase-3...... previous studies of iPLA(2)-VIA and NHE1 during cardiac I/R....

  13. Metabolism of eicosanoids and their action on renal function during ischaemia and reperfusion: the effect of alprostadil.

    Science.gov (United States)

    Dołegowska, B; Pikuła, E; Safranow, K; Olszewska, M; Jakubowska, K; Chlubek, D; Gutowski, P

    2006-12-01

    Eicosanoids, active metabolites of arachidonic acid (AA), play an important role in the regulation of renal haemodynamics and glomerular filtration. Our study verified the hypothesis on the positive action of exogenously administered PGE(1) on renal function during an operation with temporary ischaemia of the lower half of the body. Also the effect of alprostadil (prostaglandin E(1) analogue) administered during the operation of an abdominal aorta aneurysm on the postoperative systemic metabolism of AA and the glomerular filtration rate (GFR) was investigated. The study included 42 patients with a diagnosed abdominal aorta aneurysm who have been qualified for the operation of implantation of the aortic prosthesis. The patients were randomly assigned to two groups: the study group (I) receiving alprostadil and the control group (II) without alprostadil. The levels of hydroxyeicosatetraenoic acids (15-HETE, 12-HETE, 5-HETE) were determined by RP-HPLC and the level of thromboxane B(2) (TxB(2)) was determined by ELISA in the plasma of the blood drawn from vena cava superior immediately before aortic clamping (A) and 5 min after aortic declamping (B). The administration of PGE(1) affects the metabolism of 15-HETE in a manner dependent on the baseline value of GFR but does not significantly change the postoperative renal function. The metabolism of 15-HETE is affected by the baseline value of GFR1 and a longer period of ischaemia is correlated with lower concentrations of 5-HETE during reperfusion. The results of our studies indicate that TxB(2) influences the postoperative function of kidneys.

  14. Behavior of cholinesterase and liver mitochondrial function in dogs submitted to normothermic ischemia and reperfusion Colinesterase e função mitocondrial hepática em cães submetidos a isquemia normotérmica e reperfusão do fígado

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    Luis Pinto Fernandes

    2003-01-01

    Full Text Available PURPOSE: The plasmatic activity of the cholinesterase (CHE and the liver mitochondrial function, expressed by the ratio of respiratory control (RCR, were studied during normothermic ischemia. METHODS: Sixteen adult mongrels, eight females and eight males were submitted to ischemia by clamping of the hepatic artery, portal vein and infrahepatic inferior vena cava, infra-hepatic, for two h, follwed by reperfusion for 1 h. The CHE and the mitochondrial function were evaluated at 60 and 120 min. of ischemia and at 15 and 60 minutes of reperfusion. RESULTS: The CHE decreased, significantly, during ischemia and in reperfusion. The RCR was decreased at 120 min. of ischemia, returning to the initial values on reperfusion. CONCLUSION: In this study, the CHE was a sensitive indicator of ischemic injury , suggesting irreversibility of ischemia injury. The RCR, by other side, showed a greater sensibility than the CHE in detection sense, during the studied period, the reversibility of the hepatic ischemic injury.OBJETIVO: A atividade plasmática da colinesterase (CHE e a função mitocondrial do fígado expressa pela RCR- razão de controle respiratório mitocondrial foram estudadas durante a isquemia/reperfusão hepáticas. MÉTODOS: Dezesseis cães adultos sem raça definida (oito machos e oito fêmeas foram submetidos a isquemia normotérmica por pinçamento do pedículo hepático e da veia cava inferior infra-hepática por 2 horas, seguida de 15 e 60 minutos de reperfusão.A CHE e a RCR foram avaliadas após 60 e 120 minutos de isquemia e após 15 e 60 minutos de reperfusão. RESULTADOS: Os níveis de CHE diminuíram significativamente na isquemia e reperfusão.A RCR diminuiu após 120 minutos de isquemia retornando a níveis semelhantes ao controle após a reperfusão. CONCLUSÃO: A CHE foi sensível para indicar a lesão isquêmica, sugerindo irreversibilidade da lesão. Já a RCR foi mais sensível no sentido de detectar a reversibilidade da les

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

    Science.gov (United States)

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

    2009-01-01

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

  16. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats

    Science.gov (United States)

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

    2016-01-01

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

  17. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats

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    Fabricio Furtado Vieira

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

  18. 67. Do prenatal intracardiac echogenic foci affect postnatal cardiac function?

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    R. Bader

    2016-07-01

    Full Text Available Echogenic foci in the prenatal hear is not an uncommon finding. To determine whether prenatally diagnosed intracardiac echogenic foci are associated with neonatal cardiac dysfunction and persistence. Fetuses in which intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center from (September 2009 to December 2013 underwent postnatal echocardiography at ages 1 month to1 year. A single pediatric cardiologist assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid valve regurgitation was also sought. Prenatally 60 fetuses had intracardiac echogenic foci mean age ± SD at diagnosis (23 ± 3.1. 53 (88.3% had left ventricular intracardiac echogenic foci, and 7 (11.6% had right ventricular intracardiac echogenic foci. 12 preganant ladies were lost for follow up (2 fetuses of 7 (28.5% with right ventricular intracardiac echogenic foci., and 10 fetuses of 53 (18.8% with LV intracardiac echogenic foci %. Post natally, those infants, 32 (66.6% males and 16 (33.3% females were examined. At a mean age ± SD of 7.4 ± 3.1 months. Prenatally, all infants had a normal left ventricular shortening fraction. The overall mean left ventricular myocardial performance index (reference value, 0.36 ± 0.06, was normal for both infants with left ventricular intracardiac echogenic foci (0.32 ± 0.01 and those with right ventricular intracardiac echogenic foci (0.33 ± 0.05. Trace tricuspid valve regurgitation were noted in 15 (31% of the infants. Left ventricular intracardiac echogenic foci persisted in 15 infants (34.8%, whereas right ventricular intracardiac echogenic foci persisted in 1 infant (20%. Prenatally diagnosed intracardiac echogenic foci can be persistent but is not associated with myocardial dysfunction in the first year of life.

  19. Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model

    Science.gov (United States)

    Keller, Anna K.; Hansen, Rie Schultz; Nørregaard, Rikke; Krag, Søren Palmelund; Møldrup, Ulla; Pedersen, Michael; Jespersen, Bente; Birn, Henrik

    2016-01-01

    Introduction Ischemia/reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) and is associated with increased mortality. Danegaptide is a selective modifier of the gap junction protein connexion 43. It has cytoprotective as well as anti-arrhythmic properties and has been shown to reduce the size of myocardial infarct in pigs. The aim of this study was to investigate the ischemia-protective effect of Danegaptide in a porcine renal I/R-I model with two weeks follow up. Methods Unilateral renal I/R-I was induced in pigs by clamping the left renal artery over a two hour period. The model allowed examination of renal blood flow by magnetic resonance imaging (MRI) and the measurement of single kidney GFR two weeks after injury. Eleven animals were randomized to Danegaptide-infusion while nine animals received placebo. Kidney histology and urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion were included as markers of AKI. Results Unilateral kidney I/R-I resulted in an immediate ~50% GFR reduction, associated with a four-fold increase in urinary NGAL-excretion. Fourteen days after I/R-I, the total GFR was ~75% of baseline with a significantly lower GFR in the injured left kidney compared to the right kidney. No differences in GFR were observed between the treated and non-treated animals immediately after I/R-I or at Day 14. Furthermore, no differences were observed in the urinary excretion of NGAL, renal blood flow or other markers of renal function. Conclusions As expected this porcine renal I/R-I model was associated with reduced GFR two weeks after injury. Danegaptide did not improve renal function after I/R-I. PMID:27760220

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

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    Beate M Herbert

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

  1. Regular Football Practice Improves Autonomic Cardiac Function in Male Children

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    Fernandes

    2015-09-01

    Full Text Available Background The role of the autonomic nervous system (ANS in the cardiovascular regulation is of primal importance. Since it has been associated with adverse conditions such as cardiac arrhythmias, sudden death, sleep disorders, hypertension and obesity. Objectives The present study aimed to investigate the impact of recreational football practice on the autonomic cardiac function of male children, as measured by heart rate variability. Patients and Methods Forty-seven male children aged 9 - 12 years were selected according to their engagement with football oriented practice outside school context. The children were divided into a football group (FG; n = 22 and a control group (CG; n = 25. The FG had regular football practices, with 2 weekly training sessions and occasional weekend matches. The CG was not engaged with any physical activity other than complementary school-based physical education classes. Data from physical activity, physical fitness, and heart rate variability measured in time and frequency domains were obtained. Results The anthropometric and body composition characteristics were similar in both groups (P > 0.05. The groups were also similar in time spent daily on moderate-to-vigorous physical activities (FG vs. CG: 114 ± 64 vs. 87 ± 55 minutes; P > 0.05. However, the FG performed better (P < 0.05 in Yo-Yo intermittent endurance test (1394 ± 558 vs. 778 ± 408 m and 15-m sprint test (3.06 ± 0.17 vs. 3.20 ± 0.23 s. Also, the FG presented enhanced autonomic function. Significant differences were detected (P < 0.05 between groups for low frequency normalized units (38.0 ± 15.2 vs. 47.3 ± 14.2 n.u (normalized units, high frequency normalized units (62.1 ± 15.2 vs. 52.8 ± 14.2 n.u., and LF:HF ratio (0.7 ± 0.4 vs. 1.1 ± 0.6 ms2. Conclusions Children engaged with regular football practice presented enhanced physical fitness and autonomic function, by increasing vagal tone at rest.

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

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    Leela K Lella

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

  3. Compensatory up-regulation of cardiac SR Ca2+-pump by heat-shock counteracts SR Ca2+-channel activation by ischemia/reperfusion.

    Science.gov (United States)

    O'Brien, P J; Li, G O; Locke, M; Klabunde, R E; Ianuzzo, C D

    1997-08-01

    We tested the hypothesis that heat-shock protected myocardial Ca2+-cycling by sarcoplasmic reticulum from ischemia and reperfusion (I/R) injury. Twenty-four hours after increasing body temperature to 42 degrees C for 15 min, rat hearts were isolated, Langendorff-perfused, and subjected to 30 min ischemia then 30 min reperfusion. Left ventricles were homogenized and their ionized Ca2+ concentration monitored with indo- during Ca2+-uptake in the presence and absence of the Ca2+-release channel (CRC) modulator ryanodine. Tissue content of heat-shock protein 72 (HSP 72) was analyzed. Exposure to I/R resulted in a 37% enhancement of CRC activity but no effect on Ca2+-pumping activity, resulting in 25% decreased net Ca2+-uptake activity. Pre-exposure to heat-shock resulted in a 10-fold increase in HSP 72, and a 25% enhancement of maximal Ca2+-pumping activity which counteracted the effect of I/R on CRC and net Ca2+-uptake activities. This protection of SR Ca2+-cycling was associated with partial protection of myocardial physiological performance. Net Ca2+-uptake activity was correlated with the left ventricular developed pressure and its rate of change. We conclude that one of the mechanisms by which heat-shock protects myocardium from I/R injury is to upregulate SR Ca2+-pumping activity to counteract the enhanced SR Ca2+-release produced by I/R.

  4. Sodium Channel (Dys)Function and Cardiac Arrhythmias

    NARCIS (Netherlands)

    C.A. Remme; C.R. Bezzina

    2010-01-01

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

  5. Renal replacement therapy after cardiac surgery; renal function recovers

    DEFF Research Database (Denmark)

    Steinthorsdottir, Kristin Julia; Kandler, Kristian; Agerlin Windeløv, Nis

    2013-01-01

    To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy.......To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy....

  6. Measurement of Cardiac Angiotensin II by Immunoassays, HPLC-Chip/Mass Spectrometry, and Functional Assays.

    Science.gov (United States)

    De Mello, Walmor C; Gerena, Yamil

    2017-01-01

    The molecular mechanisms related to the effect of angiotensin II, its level on cardiac tissues, as well as its overexpression represent an important aspect of cardiovascular pharmacology and pathology. Severe alterations of cardiac functions are induced by hypertension including activation of circulating and local cardiac renin angiotensin systems. In this chapter, we are providing the methods and materials necessary for further investigation of this important topic.

  7. The mucus layer is critical in protecting against ischemia-reperfusion-mediated gut injury and in the restitution of gut barrier function.

    Science.gov (United States)

    Qin, Xiaofa; Sheth, Sharvil U; Sharpe, Susan M; Dong, Wei; Lu, Qi; Xu, Dazhong; Deitch, Edwin A

    2011-03-01

    It is well documented that the gut injury plays a critical role in the development of systemic inflammation and distant organ injury in conditions associated with splanchnic ischemia. Consequently, understanding the mechanisms leading to gut injury is important. In this context, recent work suggests a protective role for the intestinal mucus layer and an injury-inducing role for luminal pancreatic proteases. Thus, we explored the role of the mucus layer in gut barrier function by observing how the removal of the mucus layer affects ischemia-reperfusion-mediated gut injury in rats as well as the potential role of luminal pancreatic proteases in the pathogenesis of gut injury. Ischemia was induced by the ligation of blood vessels to segments of the ileum for 45 min, followed by up to 3 h of reperfusion. The ileal segments were divided into five groups. These included a nonischemic control, ischemic segments exposed to saline, the mucolytic N-acetylcysteine (NAC), pancreatic proteases, or NAC + pancreatic proteases. Changes in gut barrier function were assessed by the permeation of fluorescein isothiocyanate dextran (molecular weight, 4,000 d) in ileal everted sacs. Gut injury was measured morphologically and by the luminal content of protein, DNA, and hemoglobin. The mucus layer was assessed functionally by measuring its hydrophobicity and morphologically. Gut barrier function was promptly and effectively reestablished during reperfusion, which was accompanied by the restoration of the mucus layer. In contrast, treatment of the gut with the mucolytic NAC for 10 min during ischemia resulted in a failure of mucus restitution and further increases in gut permeability and injury. The presence of digestive proteases by themselves did not exacerbate gut injury, but in combination with NAC, they caused an even greater increase in gut injury and permeability. These results suggest that the mucus layer not only serves as a barrier between the luminal contents and gut surface

  8. Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

    Science.gov (United States)

    O’Connell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.

    2014-01-01

    Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha1-ARs signal through Gαq, and signaling through Gq, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha1-ARs mediate important protective and adaptive functions in the heart, although alpha1-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha1-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha1-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate “inside-out” signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha1-AR expression is similar to that in the mouse, where alpha1-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha1-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha1-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha1-AR function and suggest that activation of cardiac alpha1-AR might be a viable therapeutic strategy in heart failure. PMID:24368739

  9. PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3.

    Science.gov (United States)

    Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

    2014-02-01

    Determination of renal plasma flow (RPF) by para-aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigated this phenomenon in a rat model of renal ischemia and reperfusion by determining PAH clearance, PAH extraction, PAH net secretion, and the expression of rOat1 and rOat3. PAH extraction was seriously impaired after ischemia and reperfusion which led to a threefold underestimation of RPF when PAH extraction ratio was not considered. PAH extraction directly correlated with the expression of basolateral Oat1 and Oat3. Tubular PAH secretion directly correlated with PAH extraction. Consequently, our data offer an explanation for impaired renal PAH extraction by reduced expression of the rate limiting basolateral organic anion transporters Oat1 and Oat3. Moreover, we show that determination of PAH net secretion is suitable to correct PAH clearance for impaired extraction after ischemia and reperfusion in order to get valid results for RPF.

  10. The role of muscarinic receptors in the beneficial effects of adenosine against myocardial reperfusion injury in rats.

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    Lei Sun

    Full Text Available Adenosine, a catabolite of ATP, displays a wide variety of effects in the heart including regulation of cardiac response to myocardial ischemia and reperfusion injury. Nonetheless, the precise mechanism of adenosine-induced cardioprotection is still elusive. Isolated Sprague-Dawley rat hearts underwent 30 min global ischemia and 120 min reperfusion using a Langendorff apparatus. Both adenosine and acetylcholine treatment recovered the post-reperfusion cardiac function associated with adenosine and muscarinic receptors activation. Simultaneous administration of adenosine and acetylcholine failed to exert any additive protective effect, suggesting a shared mechanism between the two. Our data further revealed a cross-talk between the adenosine and acetylcholine receptor signaling in reperfused rat hearts. Interestingly, the selective M(2 muscarinic acetylcholine receptor antagonist methoctramine significantly attenuated the cardioprotective effect of adenosine. In addition, treatment with adenosine upregulated the expression and the maximal binding capacity of muscarinic acetylcholine receptor, which were inhibited by the selective A(1 adenosine receptor antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX and the nitric oxide synthase inhibitor N(ω-nitro-L-arginine methyl ester (L-NAME. These data suggested a possible functional coupling between the adenosine and muscarinic receptors behind the observed cardioprotection. Furthermore, nitric oxide was found involved in triggering the response to each of the two receptor agonist. In summary, there may be a cross-talk between the adenosine and muscarinic receptors in ischemic/reperfused myocardium with nitric oxide synthase might serve as the distal converging point. In addition, adenosine contributes to the invigorating effect of adenosine on muscarinic receptor thereby prompting to regulation of cardiac function. These findings argue for a potentially novel mechanism behind the adenosine

  11. ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism

    Science.gov (United States)

    Tian, Zhe; Miyata, Keishi; Kadomatsu, Tsuyoshi; Horiguchi, Haruki; Fukushima, Hiroyuki; Tohyama, Shugo; Ujihara, Yoshihiro; Okumura, Takahiro; Yamaguchi, Satoshi; Zhao, Jiabin; Endo, Motoyoshi; Morinaga, Jun; Sato, Michio; Sugizaki, Taichi; Zhu, Shunshun; Terada, Kazutoyo; Sakaguchi, Hisashi; Komohara, Yoshihiro; Takeya, Motohiro; Takeda, Naoki; Araki, Kimi; Manabe, Ichiro; Fukuda, Keiichi; Otsu, Kinya; Wada, Jun; Murohara, Toyoaki; Mohri, Satoshi; Yamashita, Jun K.; Sano, Motoaki; Oike, Yuichi

    2016-01-01

    A cardioprotective response that alters ventricular contractility or promotes cardiomyocyte enlargement occurs with increased workload in conditions such as hypertension. When that response is excessive, pathological cardiac remodelling occurs, which can progress to heart failure, a leading cause of death worldwide. Mechanisms underlying this response are not fully understood. Here, we report that expression of angiopoietin-like protein 2 (ANGPTL2) increases in pathologically-remodeled hearts of mice and humans, while decreased cardiac ANGPTL2 expression occurs in physiological cardiac remodelling induced by endurance training in mice. Mice overexpressing ANGPTL2 in heart show cardiac dysfunction caused by both inactivation of AKT and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a signalling and decreased myocardial energy metabolism. Conversely, Angptl2 knockout mice exhibit increased left ventricular contractility and upregulated AKT-SERCA2a signalling and energy metabolism. Finally, ANGPTL2-knockdown in mice subjected to pressure overload ameliorates cardiac dysfunction. Overall, these studies suggest that therapeutic ANGPTL2 suppression could antagonize development of heart failure. PMID:27677409

  12. Evaluation of cardiac functions in patients with thalassemia major

    Energy Technology Data Exchange (ETDEWEB)

    Kucuk, N.O.; Aras, G.; Sipahi, T.; Ibis, E.; Akar, N.; Soylu, A.; Erbay, G. [Ankara Univ. (Turkey). Medical School

    1999-06-01

    It is known that a blood transfusion is necessary for survival in patients with thalassemia, but it may cause myocardial dysfunction due to myocardial siderosis as in other organs. The aim of this study was to evaluate myocardial perfusion by means of stress thallium scanning (MPS) and left ventricular functions by rest radionuclide ventriculography (RNV). Twenty-one patients at ages 9-16 (mean 12.1{+-}3.2) who have been diagnosed with thalassemia for 4-15 years mean 12.7{+-}4.8) were included in the study. They had blood transfusion 78-318 times (mean 162.1{+-}71). MPS and RNV was performed within two days after the any transfusion. MPS showed ischemia in 3 patients and normal perfusion in 18 patients. RNV revealed normal systolic parameters (wall motion, EF, PER, TPE) but diminished diastolic parameters (TPF, PFR) compared with normal values (p<0.05). We conclude that ischemia or fixed defects may be seen in stress MPS as results of cardiac involvement in patients with thalassemia. But, RNV is an important and preferable test for the early detection of subclinic cardiomyopathy. RNV may therefore show diastolic abnormalities before the systolic abnormalities show up. (author)

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

    Directory of Open Access Journals (Sweden)

    Maarten Rijpert

    2011-01-01

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

  14. Effects of Obesity on Cardiovascular Hemodynamics, Cardiac Morphology, and Ventricular Function.

    Science.gov (United States)

    Alpert, Martin A; Omran, Jad; Bostick, Brian P

    2016-12-01

    Obesity produces a variety of hemodynamic alterations that may cause changes in cardiac morphology which predispose to left and right ventricular dysfunction. Various neurohormonal and metabolic alterations commonly associated with obesity may contribute to these abnormalities of cardiac structure and function. These changes in cardiovascular hemodynamics, cardiac morphology, and ventricular function may, in severely obese patients, predispose to heart failure, even in the absence of other forms of heart disease (obesity cardiomyopathy). In normotensive obese patients, cardiac involvement is commonly characterized by elevated cardiac output, low peripheral vascular resistance, and increased left ventricular (LV) end-diastolic pressure. Sleep-disordered breathing may lead to pulmonary arterial hypertension and, in association with left heart failure, may contribute to elevation of right heart pressures. These alterations, in association with various neurohormonal and metabolic abnormalities, may produce LV hypertrophy; impaired LV diastolic function; and less commonly, LV systolic dysfunction. Many of these alterations are reversible with substantial voluntary weight loss.

  15. Functional and Hemodynamic Cardiac Determinants of Exercise Capacity in Patients With Systolic Heart Failure

    NARCIS (Netherlands)

    Hummel, Yoran M.; Bugatti, Silvia; Damman, Kevin; Willemsen, Suzan; Hartog, Jasper W. L.; Metra, Marco; Sipkens, Johannes S.; van Veldhuisen, Dirk J.; Voors, Adriaan A.

    2012-01-01

    Decreased exercise capacity is the main symptom in patients with heart failure (HF). We assessed the association among noninvasively determined maximal cardiac output at exercise, systolic and diastolic cardiac functions at rest, and peak oxygen uptake (pVO(2)) exercise capacity in patients with con

  16. 24-Hour motor activity and autonomic cardiac functioning in major depressive disorder

    NARCIS (Netherlands)

    A.C. Volkers (Anita)

    2002-01-01

    textabstractThe studies of this thesis concern the spontaneous pattern of motor activity and autonomic cardiac functioning in major depressive disorder. The main purpose of the studies was to obtain insight in the psychomotor and autonomic cardiac dysfunction in depression by investigating the 24-ho

  17. Olmesartan attenuates cardiac hypertrophy and improves cardiac diastolic function in spontaneously hypertensive rats through inhibition of calcineurin pathway.

    Science.gov (United States)

    Fu, Mingqiang; Zhou, Jingmin; Xu, Jianfeng; Zhu, Hongmin; Liao, Jianquan; Cui, Xiaotong; Sun, Aijun; Fu, Michael; Zou, Yunzeng; Hu, Kai; Ge, Junbo

    2014-03-01

    To test whether olmesartan ameliorates cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs) through calcineurin pathway. Twenty-four male SHRs of 6 months were divided into saline- (n = 12) and olmesartan-treated (n = 12) groups. Age-matched WKY (n = 12) rats served as controls. Saline (10 mL·kg·d) or the same volume of olmesartan liquor (2.5 mg·kg·d) was administered by gavage for 3 months. Heart rate, systolic blood pressure, cardiac structure, and function and histological studies were determined. Expression of calcineurin and downstream NFAT3 were also detected. Compared with age-matched Wistar Kyoto rats, SHRs of 6 months exhibited evident cardiac hypertrophy and diastolic dysfunction as demonstrated by elevated systolic blood pressure and E/E', decreased E/A and E'/A', while F, left ventricular ejection fraction and fractional shortening remained unimpaired. Treatment with olmesartan significantly decreased systolic blood pressure and ventricular hypertrophy, attenuated fibrosis, and improved diastolic function (all P olmesartan group compared with the other 2 groups (both P olmesartan on cardiac structure and diastolic dysfunction, and it may be mediated through calcineurin pathway. This indicates a new therapeutic target for diastolic dysfunction.

  18. Cardiac function and hypertension in patients with obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Bertolami A

    2014-08-01

    Full Text Available Adriana Bertolami, Carolina Gonzaga, Celso AmodeoSleep Laboratory of Dante Pazzanese Institute of Cardiology, Sao Paulo, BrazilAbstract: Cardiovascular disease is one of the major causes of death worldwide. Among its risk factors, obstructive sleep apnea (OSA is a common but still underestimated condition. OSA often coexists and interacts with obesity, sharing multiple pathophysiological mechanisms and subsequent cardiovascular risk factors, such as type 2 diabetes, dyslipidemia, systemic inflammation, and in particular hypertension. There is also evidence suggesting an increased risk of arrhythmia, heart failure, renal failure, acute myocardial infarction, stroke, and death. OSA is characterized by recurrent episodes of partial (hypopnea or complete interruption (apnea of breathing during sleep due to airway collapse in the pharyngeal region. The main mechanisms linking OSA to impaired cardiovascular function are secondary to hypoxemia and reoxygenation, arousals, and negative intrathoracic pressure. Consequently, the sympathetic nervous and the renin-angiotensin-aldosterone systems may be overestimulated, and blood pressure increased. Resistance to treatment for hypertension represents a growing issue, and given that OSA has been recognized as the major secondary cause of resistant hypertension, clinical investigation for apnea is mandatory in this population. Standard diagnosis includes polysomnography, and treatment for OSA should include control of risk factors for cardiovascular disease, including obesity. So far, continuous positive airway pressure is the treatment of choice for OSA, impacting positively on blood pressure goals; however, the impact on long-term follow-up and on cardiovascular disease should be better assessed.Keywords: obstructive sleep apnea, hypertension, cardiac function

  19. Increasing Cycles of Intermittent Ischemia Can Effectively Maintain Liver Function during the Acute Phase of Ischemia Reperfusion Injury by Promotion of Bile Flow and Reduction in Bile Salt Toxicity

    NARCIS (Netherlands)

    Peters, J.; Nieuwenhuijs, V. B.; Morphett, A.; Porte, R. J.; Padbury, R. T. A.; Barritt, G. J.

    2009-01-01

    Background/Aims: Intermittent ischemia (INT) can improve liver function following inflow occlusion. The aim was to test whether the number of cycles of INT can be increased without impairing liver function. Methods: Liver function in the acute phase of ischemia reperfusion injury was assessed by mea

  20. Pulmonary function and adverse cardiovascular outcomes: Can cardiac function explain the link?

    Science.gov (United States)

    Burroughs Peña, Melissa S; Dunning, Allison; Schulte, Phillip J; Durheim, Michael T; Kussin, Peter; Checkley, William; Velazquez, Eric J

    2016-12-01

    The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization. A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97). In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Compensatory renal growth and mitochondrial function: the influence of warm ischemia and reperfusion Hipertrofia renal compensatória e função mitocondrial: influência da isquemia quente e reperfusão

    Directory of Open Access Journals (Sweden)

    Silvio Tucci Jr

    2008-01-01

    Full Text Available PURPOSE: To evaluate the influence of ischemia/reperfusion injury on renal compensatory growth (CGR and mitochondrial function. METHODS: Forty five Wistar rats were divided in 3 groups: Control Group (GC - 21 rats were submitted to a sham laparotomy and sacrificed at 1st (6 rats and 7th (15 rats postoperative days to evaluate the dry weight of both kidneys and their growth during 1 week (6 rats and to quantify mitochondrial respiration (9 rats; Group 1 (G1 - 12 rats underwent right nephrectomy and were sacrificed 7 days later for analysis of renal mitochondrial function (6 rats and dry weight (6 rats. Group 2 (G2 - renal warm ischemia for 60 minutes followed by right nephrectomy was performed in 12 rats; they were sacrificed 7 days later to evaluate renal mitochondrial function (6 rats and dry weight (6 rats. RESULTS: Dry weight (mg of left kidneys at 7th day: GC - 219±18, G1 - 281±23 and G2 - 338±39 (GCxG1 p0.05. State 3 respirations (mM/min/mg in GC, G1 and G2 was respectively: 99±23, 132±22 and 82±44 (pOBJETIVO: Avaliar a influência da lesão de isquemia/reperfusão na hipertrofia renal compensatória (HRC e na função mitocondrial. MÉTODOS: 45 ratos Wistar foram divididos em três grupos: Grupo Controle (GC - 21 ratos submetidos apenas à laparotomia e sacrificados no 1º dia (6 ratos e 7º dia pós-operatório (15 ratos para avaliar o peso seco de ambos os rins e seu crescimento durante uma semana (6 ratos e quantificar a função mitocondrial (9 ratos; Grupo 1 (G1 - 12 ratos submetidos à nefrectomia direita e sacrificados após 7 dias para análise da função mitocondrial renal (6 ratos e peso renal seco (6 ratos; Grupo 2 (G2 - isquemia renal quente durante 60 minutos no rim esquerdo seguida da nefrectomia direita foi realizada em 12 ratos, que foram sacrificados após 7 dias para avaliação da função mitocondrial (6 ratos e peso seco (6 ratos. RESULTADOS: peso seco (mg do rim esquerdo no 7º dia: GC= 219±18; G1=281±23 e G2

  2. Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression.

    Science.gov (United States)

    Byrne, Nikole J; Levasseur, Jody; Sung, Miranda M; Masson, Grant; Boisvenue, Jamie; Young, Martin E; Dyck, Jason R B

    2016-05-15

    Impaired cardiac substrate metabolism plays an important role in heart failure (HF) pathogenesis. Since many of these metabolic changes occur at the transcriptional level of metabolic enzymes, it is possible that this loss of metabolic flexibility is permanent and thus contributes to worsening cardiac function and/or prevents the full regression of HF upon treatment. However, despite the importance of cardiac energetics in HF, it remains unclear whether these metabolic changes can be normalized. In the current study, we investigated whether a reversal of an elevated aortic afterload in mice with severe HF would result in the recovery of cardiac function, substrate metabolism, and transcriptional reprogramming as well as determined the temporal relationship of these changes. Male C57Bl/6 mice were subjected to either Sham or transverse aortic constriction (TAC) surgery to induce HF. After HF development, mice with severe HF (% ejection fraction hypertrophy/HF were returned to values observed in healthy controls. Interestingly, pressure-overload-induced left ventricular hypertrophy (LVH) and cardiac substrate metabolism were restored at 1-week post-DB, which preceded functional recovery. The regression of severe HF is associated with early and dramatic improvements in cardiac energy metabolism and LVH normalization that precede restored cardiac function, suggesting that metabolic and structural improvements may be critical determinants for functional recovery. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Gianluca Pontone

    2015-01-01

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

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

    Science.gov (United States)

    Andreini, Daniele; Bertella, Erika; Mushtaq, Saima; Guaricci, Andrea Igoren; Pepi, Mauro

    2015-01-01

    Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality and it is responsible for an increasing resource burden. The identification of patients at high risk for adverse events is crucial to select those who will receive the greatest benefit from revascularization. To this aim, several non-invasive functional imaging modalities are usually used as gatekeeper to invasive coronary angiography, but the diagnostic yield of elective invasive coronary angiography remains unfortunately low. Stress myocardial perfusion imaging by cardiac magnetic resonance (stress-CMR) has emerged as an accurate technique for diagnosis and prognostic stratification of the patients with known or suspected CAD thanks to high spatial and temporal resolution, absence of ionizing radiation, and the multiparametric value including the assessment of cardiac anatomy, function, and viability. On the other side, cardiac computed tomography (CCT) has emerged as unique technique providing coronary arteries anatomy and more recently, due to the introduction of stress-CCT and noninvasive fractional flow reserve (FFR-CT), functional relevance of CAD in a single shot scan. The current review evaluates the technical aspects and clinical experience of stress-CMR and CCT in the evaluation of functional relevance of CAD discussing the strength and weakness of each approach. PMID:25692133

  5. PAH clearance after renal ischemia and reperfusion is a function of impaired expression of basolateral Oat1 and Oat3

    OpenAIRE

    Bischoff, Ariane; Bucher, Michael; Gekle, Michael; Sauvant, Christoph

    2014-01-01

    Abstract Determination of renal plasma flow (RPF) by para‐aminohippurate (PAH) clearance leads to gross underestimation of this respective parameter due to impaired renal extraction of PAH after renal ischemia and reperfusion injury. However, no mechanistic explanation for this phenomenon is available. Based on our own previous studies we hypothesized that this may be due to impairment of expression of the basolateral rate limiting organic anion transporters Oat1 and Oat3. Thus, we investigat...

  6. Metallothionein-II Inhibits Lipid Peroxidation and Improves Functional Recovery after Transient Brain Ischemia and Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Araceli Diaz-Ruiz

    2014-01-01

    Full Text Available After transient cerebral ischemia and reperfusion (I/R, damaging mechanisms, such as excitotoxicity and oxidative stress, lead to irreversible neurological deficits. The induction of metallothionein-II (MT-II protein is an endogenous mechanism after I/R. Our aim was to evaluate the neuroprotective effect of MT-II after I/R in rats. Male Wistar rats were transiently occluded at the middle cerebral artery for 2 h, followed by reperfusion. Rats received either MT (10 μg per rat i.p. or vehicle after ischemia. Lipid peroxidation (LP was measured 22 h after reperfusion in frontal cortex and hippocampus; also, neurological deficit was evaluated after ischemia, using the Longa scoring scale. Infarction area was analyzed 72 hours after ischemia. Results showed increased LP in frontal cortex (30.7% and hippocampus (26.4%, as compared to control group; this effect was fully reversed by MT treatment. Likewise, we also observed a diminished neurological deficit assessed by the Longa scale in those animals treated with MT compared to control group values. The MT-treated group showed a significant (P<0.05 reduction of 39.9% in the infarction area, only at the level of hippocampus, as compared to control group. Results suggest that MT-II may be a novel neuroprotective treatment to prevent ischemia injury.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  8. Cardiac baroreflex function and dynamic cerebral autoregulation in elderly Masters athletes

    NARCIS (Netherlands)

    Aengevaeren, V.L.; Claassen, J.A.H.R.; Levine, B.D.; Zhang, R.

    2013-01-01

    Cerebral blood flow (CBF) is stably maintained through the combined effects of blood pressure (BP) regulation and cerebral autoregulation. Previous studies suggest that aerobic exercise training improves cardiac baroreflex function and beneficially affects BP regulation, but may negatively affect ce

  9. EFFECT OF OBESITY ON CARDIAC FUNCTION IN CHILDREN AND ADOLESCENTS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Thomas W. Rowland

    2007-09-01

    Full Text Available Increases in cardiac mass, ventricular dimensions, and stroke volume are typically observed in obese adults, accompanied by evidence of diminished ventricular systolic and diastolic function. Given sufficient severity and duration of excessive body fat, signs of overt congestive heart failure may ensue (cardiomyopathy of obesity. This review of cardiac findings in obese children and adolescents indicates similar anatomic features as well as early subclinical findings of ventricular dysfunction. However, cardiac functional reserve (cardiovascular fitness appears to be preserved even in those with morbid levels of obesity

  10. Beneficial properties of selenium incorporated guar gum nanoparticles against ischemia/reperfusion in cardiomyoblasts (H9c2).

    Science.gov (United States)

    Soumya, R S; Vineetha, V P; Salin Raj, P; Raghu, K G

    2014-11-01

    Nanotechnology for the treatment and diagnosis has been emerging recently as a potential area of research and development. In the present study, selenium incorporated guar gum nanoparticles have been prepared by nanoprecipitation and characterized by transmission electron microscopy and particle size analysis. The nanoparticles were screened for antioxidant potential (metal chelation, total reducing power and hydroxyl radical scavenging activity) and were evaluated against the cell line based cardiac ischemia/reperfusion model with special emphasis on oxidative stress and mitochondrial parameters. The cell based cardiac ischemia model was employed using H9c2 cell lines. Investigations revealed that there was a significant alteration (P ≤ 0.05) in the innate antioxidant status (glutathione↓, glutathione peroxidase↓, thioredoxin reductase↓, superoxide dismutase↓, catalase↓, lipid peroxidation↑, protein carbonyl↑, xanthine oxidase↑ and caspase 3 activity↑), mitochondrial functions (reactive oxygen species generation, membrane potential, and pore opening) and calcium homeostasis (calcium ATPase and intracellular calcium overload) during both ischemia and reperfusion. For comparative evaluation, selenium, guar gum and selenium incorporated guar gum nanoparticles were evaluated for their protective properties against ischemia/reperfusion. The study reveals that selenium incorporated guar gum nanoparticles were better at protecting the cells from ischemia/reperfusion compared to selenium and guar gum nanoparticles. The potent antioxidant capability shown by the sample in in vitro assays may be the biochemical basis of its better biological activity. Further, the nanodimensions of the particle may be the additional factor responsible for its better effect.

  11. The Effects of Prenatal Protein Restriction on β-Adrenergic Signalling of the Adult Rat Heart during Ischaemia Reperfusion

    Directory of Open Access Journals (Sweden)

    Kevin J. P. Ryan

    2012-01-01

    Full Text Available A maternal low-protein diet (MLP fed during pregnancy leads to hypertension in adult rat offspring. Hypertension is a major risk factor for ischaemic heart disease. This study examined the capacity of hearts from MLP-exposed offspring to recover from myocardial ischaemia-reperfusion (IR and related this to cardiac expression of β-adrenergic receptors (β-AR and their associated G proteins. Pregnant rats were fed control (CON or MLP diets (n=12 each group throughout pregnancy. When aged 6 months, hearts from offspring underwent Langendorff cannulation to assess contractile function during baseline perfusion, 30 min ischemia and 60 min reperfusion. CON male hearts demonstrated impaired recovery in left ventricular pressure (LVP and dP/dtmax (P<0.01 during reperfusion when compared to MLP male hearts. Maternal diet had no effect on female hearts to recover from IR. MLP males exhibited greater membrane expression of β2-AR following reperfusion and urinary excretion of noradrenaline and dopamine was lower in MLP and CON female rats versus CON males. In conclusion, the improved cardiac recovery in MLP male offspring following IR was attributed to greater membrane expression of β2-AR and reduced noradrenaline and dopamine levels. In contrast, females exhibiting both decreased membrane expression of β2-AR and catecholamine levels were protected from IR injury.

  12. Effects of Long-term Right Ventricular Apical Pacing on Left Ventricular Remodeling and Cardiac Function

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective: To investigate the impacts of long-term right ventricular apical pacing on the ventricular remodeling and cardiac functions of patients with high-grade and third-degree atrioventricular blockage with normal heart structures and cardiac functions. In addition, we provide many evidences for choosing an optimal electrode implantation site.Methods: Study participants included patients who were admitted for pacemaker replacements and revisited for examinations of implanted pacemakers at outpatient. Pa...

  13. Echocardiographic Evaluation of Cardiac Function in Ischemic Rats: Value of M-Mode Echocardiography

    OpenAIRE

    Darbandi Azar, Amir; Tavakoli, Fatemeh; Moladoust, Hassan; Zare, Asghar; Sadeghpour, Anita

    2014-01-01

    Background: Echocardiography is a well-established diagnostic tool for a safe, reproducible and accurate evaluation of cardiac anatomy, hemodynamics and function in clinical practice. Objectives: We sought to demonstrate the efficacy and feasibility of M-mode echocardiography to evaluate cardiac structure and function in normal and MI-induced adult rats. Materials and Methods: All animal procedures were approved by the ethics committee of Tehran University of Medical Sciences and the investig...

  14. Tyrosol prevents ischemia/reperfusion-induced cardiac injury in H9c2 cells: involvement of ROS, Hsp70, JNK and ERK, and apoptosis.

    Science.gov (United States)

    Sun, Liwei; Fan, Hang; Yang, Lingguang; Shi, Lingling; Liu, Yujun

    2015-02-25

    Ischemia-Reperfusion (I/R) injury causes ROS overproduction, creating oxidative stress, and can trigger myocyte death, resulting in heart failure. Tyrosol is an antioxidant abounded in diets and medicine. Our objective was to investigate the protective effect of tyrosol on I/R-caused mortality in H9c2 cardiomyocytes through its influence on ROS, Hsp70, ERK, JNK, Bcl-2, Bax and caspase-8. A simulated I/R model was used, myocytes loss was examined by MTT, and ROS levels were measured using DCFH-DA. Nuclear condensation and caspase-3 activity were assessed by DAPI staining and fluorometric assay. Phosphorylated ERK and JNK were determined by electrochemiluminescent ELISA, and Hsp70, Bcl-2, Bax and caspase-8 were examined by Western blotting. Results show that tyrosol salvaged myocyte loss, inhibited nuclear condensation and caspase-3 activity dose-dependently, indicating its protection against I/R-caused myocyte loss. Furthermore, tyrosol significantly inhibited ROS accumulation and activation of ERK and JNK, augmenting Hsp70 expression. Besides, tyrosol inhibited I/R-induced apoptosis, associated with retained anti-apoptotic Bcl-2 protein, and attenuated pro-apoptotic Bax protein, resulting in a preservation of Bcl-2/Bax ratio. Finally, tyrosol notably decreased cleaved caspase-8 levels. In conclusion, cytoprotection of tyrosol in I/R-caused myocyte mortality was involved with the mitigation of ROS, prohibition of the activation of ERK, JNK and caspase-8, and elevation of Hsp70 and Bcl-2/Bax ratio.

  15. Tyrosol Prevents Ischemia/Reperfusion-Induced Cardiac Injury in H9c2 Cells: Involvement of ROS, Hsp70, JNK and ERK, and Apoptosis

    Directory of Open Access Journals (Sweden)

    Liwei Sun

    2015-02-01

    Full Text Available Ischemia-Reperfusion (I/R injury causes ROS overproduction, creating oxidative stress, and can trigger myocyte death, resulting in heart failure. Tyrosol is an antioxidant abounded in diets and medicine. Our objective was to investigate the protective effect of tyrosol on I/R-caused mortality in H9c2 cardiomyocytes through its influence on ROS, Hsp70, ERK, JNK, Bcl-2, Bax and caspase-8. A simulated I/R model was used, myocytes loss was examined by MTT, and ROS levels were measured using DCFH-DA. Nuclear condensation and caspase-3 activity were assessed by DAPI staining and fluorometric assay. Phosphorylated ERK and JNK were determined by electrochemiluminescent ELISA, and Hsp70, Bcl-2, Bax and caspase-8 were examined by Western blotting. Results show that tyrosol salvaged myocyte loss, inhibited nuclear condensation and caspase-3 activity dose-dependently, indicating its protection against I/R-caused myocyte loss. Furthermore, tyrosol significantly inhibited ROS accumulation and activation of ERK and JNK, augmenting Hsp70 expression. Besides, tyrosol inhibited I/R-induced apoptosis, associated with retained anti-apoptotic Bcl-2 protein, and attenuated pro-apoptotic Bax protein, resulting in a preservation of Bcl-2/Bax ratio. Finally, tyrosol notably decreased cleaved caspase-8 levels. In conclusion, cytoprotection of tyrosol in I/R-caused myocyte mortality was involved with the mitigation of ROS, prohibition of the activation of ERK, JNK and caspase-8, and elevation of Hsp70 and Bcl-2/Bax ratio.

  16. Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction.

    Science.gov (United States)

    Leblond, Anne-Laure; Klinkert, Kerstin; Martin, Kenneth; Turner, Elizebeth C; Kumar, Arun H; Browne, Tara; Caplice, Noel M

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1lo and F4/80hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function.

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

    Directory of Open Access Journals (Sweden)

    Zhendong Zhang

    2014-12-01

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

  18. Near death experiences, cognitive function and psychological outcomes of surviving cardiac arrest.

    Science.gov (United States)

    Parnia, S; Spearpoint, K; Fenwick, P B

    2007-08-01

    Cardiac arrest is associated with a number of cognitive processes as well as long term psychological outcomes. Recent studies have indicated that approximately 10-20% of cardiac arrest survivors report cognitive processes, including the ability to recall specific details of their resuscitation from the period of cardiac arrest. In addition it has been demonstrated that these cognitive processes are consistent with the previously described near death experience and that those who have these experiences are left with long term positive life enhancing effects. There have also been numerous studies that have indicated that although the quality of life for cardiac arrest survivors is generally good, some are left with long term cognitive impairments as well as psychological sequelae such as post-traumatic stress disorder. This paper will review near death experiences, cognitive function and psychological outcomes in survivors of cardiac arrest.

  19. Nanowires and Electrical Stimulation Synergistically Improve Functions of hiPSC Cardiac Spheroids.

    Science.gov (United States)

    Richards, Dylan J; Tan, Yu; Coyle, Robert; Li, Yang; Xu, Ruoyu; Yeung, Nelson; Parker, Arran; Menick, Donald R; Tian, Bozhi; Mei, Ying

    2016-07-13

    The advancement of human induced pluripotent stem-cell-derived cardiomyocyte (hiPSC-CM) technology has shown promising potential to provide a patient-specific, regenerative cell therapy strategy to treat cardiovascular disease. Despite the progress, the unspecific, underdeveloped phenotype of hiPSC-CMs has shown arrhythmogenic risk and limited functional improvements after transplantation. To address this, tissue engineering strategies have utilized both exogenous and endogenous stimuli to accelerate the development of hiPSC-CMs. Exogenous electrical stimulation provides a biomimetic pacemaker-like stimuli that has been shown to advance the electrical properties of tissue engineered cardiac constructs. Recently, we demonstrated that the incorporation of electrically conductive silicon nanowires to hiPSC cardiac spheroids led to advanced structural and functional development of hiPSC-CMs by improving the endogenous electrical microenvironment. Here, we reasoned that the enhanced endogenous electrical microenvironment of nanowired hiPSC cardiac spheroids would synergize with exogenous electrical stimulation to further advance the functional development of nanowired hiPSC cardiac spheroids. For the first time, we report that the combination of nanowires and electrical stimulation enhanced cell-cell junction formation, improved development of contractile machinery, and led to a significant decrease in the spontaneous beat rate of hiPSC cardiac spheroids. The advancements made here address critical challenges for the use of hiPSC-CMs in cardiac developmental and translational research and provide an advanced cell delivery vehicle for the next generation of cardiac repair.

  20. Cardioprotective properties of Crataegus oxycantha extract against ischemia-reperfusion injury

    Science.gov (United States)

    Swaminathan, Jayachandran Kesavan; Khan, Mahmood; Mohan, Iyappu K; Selvendiran, Karuppaiyah; Devaraj, S. Niranjali; Rivera, Brian K.; Kuppusamy, Periannan

    2010-01-01

    The aim of the study was to investigate the cardioprotective effect and mechanism of Crataegus oxycantha (COC) extract, a well-known natural antioxidant-based cardiotonic, against ischemia/reperfusion (I/R) injury. Electron paramagnetic resonance studies showed that COC extract was capable of scavenging superoxide, hydroxyl, and peroxyl radicals, in vitro. The cardioprotective efficacy of the extract was studied in a crystalloid perfused heart model of I/R injury. Hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. During reperfusion, COC extract was infused at a dose rate of 1 mg/ml/min for 10 min. Hearts treated with COC extract showed a significant recovery in cardiac contractile function, reduction in infarct size, and decrease in creatine kinase and lactate dehydrogenase activities. The expressions of xanthine oxidase and NADPH oxidase were significantly reduced in the treated group. A significant upregulation of the anti-apoptotic proteins Bcl-2 and Hsp70 with simultaneous downregulation of the pro-apoptotic proteins cytochrome c and cleaved caspase-3 was observed. The molecular signaling cascade including phospho-Akt (ser-473) and HIF-1α that lead to the activation or suppression of apoptotic pathway also showed a significant protective role in the treatment group. No significant change in phospho-p38 levels was observed. The results suggested that the COC extract may reduce the oxidative stress in the reperfused myocardium, and play a significant role in the inhibition of apoptotic pathways leading to cardioprotection. PMID:20171068

  1. Analysis of temporal dynamics in imagery during acute limb ischemia and reperfusion

    Science.gov (United States)

    Irvine, John M.; Regan, John; Spain, Tammy A.; Caruso, Joseph D.; Rodriquez, Maricela; Luthra, Rajiv; Forsberg, Jonathon; Crane, Nicole J.; Elster, Eric

    2014-03-01

    Ischemia and reperfusion injuries present major challenges for both military and civilian medicine. Improved methods for assessing the effects and predicting outcome could guide treatment decisions. Specific issues related to ischemia and reperfusion injury can include complications arising from tourniquet use, such as microvascular leakage in the limb, loss of muscle strength and systemic failures leading to hypotension and cardiac failure. Better methods for assessing the viability of limbs/tissues during ischemia and reducing complications arising from reperfusion are critical to improving clinical outcomes for at-risk patients. The purpose of this research is to develop and assess possible prediction models of outcome for acute limb ischemia using a pre-clinical model. Our model relies only on non-invasive imaging data acquired from an animal study. Outcome is measured by pathology and functional scores. We explore color, texture, and temporal features derived from both color and thermal motion imagery acquired during ischemia and reperfusion. The imagery features form the explanatory variables in a model for predicting outcome. Comparing model performance to outcome prediction based on direct observation of blood chemistry, blood gas, urinalysis, and physiological measurements provides a reference standard. Initial results show excellent performance for the imagery-base model, compared to predictions based direct measurements. This paper will present the models and supporting analysis, followed by recommendations for future investigations.

  2. Blockage of transient receptor potential vanilloid 4 alleviates myocardial ischemia/reperfusion injury in mice

    Science.gov (United States)

    Dong, Qian; Li, Jing; Wu, Qiong-feng; Zhao, Ning; Qian, Cheng; Ding, Dan; Wang, Bin-bin; Chen, Lei; Guo, Ke-Fang; Fu, Dehao; Han, Bing; Liao, Yu-Hua; Du, Yi-Mei

    2017-01-01

    Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable nonselective cation channel and can be activated during ischemia/reperfusion (I/R). This study tested whether blockade of TRPV4 can alleviate myocardial I/R injury in mice. TRPV4 expression began to increase at 1 h, reached statistically at 4 h, and peaked at 24–72 h. Treatment with the selective TRPV4 antagonist HC-067047 or TRPV4 knockout markedly ameliorated myocardial I/R injury as demonstrated by reduced infarct size, decreased troponin T levels and improved cardiac function at 24 h after reperfusion. Importantly, the therapeutic window for HC-067047 lasts for at least 12 h following reperfusion. Furthermore, treatment with HC-067047 reduced apoptosis, as evidenced by the decrease in TUNEL-positive myocytes, Bax/Bcl-2 ratio, and caspase-3 activation. Meanwhile, treatment with HC-067047 attenuated the decrease in the activation of reperfusion injury salvage kinase (RISK) pathway (phosphorylation of Akt, ERK1/2, and GSK-3β), while the activation of survival activating factor enhancement (SAFE) pathway (phosphorylation of STAT3) remained unchanged. In addition, the anti-apoptotic effects of HC-067047 were abolished by the RISK pathway inhibitors. We conclude that blockade of TRPV4 reduces apoptosis via the activation of RISK pathway, and therefore might be a promising strategy to prevent myocardial I/R injury. PMID:28205608

  3. Effects of exercise training on myocardial fatty acid metabolism in rats with depressed cardiac function induced by transient ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liguang; Nohara, Ryuji; Hirai, Taku [Kyoto Univ. (Japan). Graduate School of Medicine] (and others)

    2001-06-01

    The effects of exercise training on metabolic and functional recovery after myocardial transient ischemia were investigated in a rat model. Male Wistar Kyoto rats were subjected either to a 30-min left coronary artery occlusion followed by reperfusion or to a sham operation. At 4 weeks after operation, the rats were randomly assigned either to sedentary conditions or to exercise training for 6 weeks. In the ischemic rats, pinhole SPECT (single photon emission computed tomography) imaging with thallium-201 ({sup 201}Tl) and {sup 123}I-({rho}-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) showed a reduction of both myocardial perfusion and fatty acid metabolism in the risk zone of the left ventricle (LV). The LV was dilated and the ejection fraction was decreased after ischemic injury. The severity score showed a significant decrease on both {sup 201}Tl and BMIPP ({sup 201}Tl, from 19.9{+-}2.7 to 17.0{+-}2.2, p<0.05; BMIPP, from 21.5{+-}2.4 to 18.6{+-}1.9, p<0.05) after exercise training in the ischemic trained rats, but did not change significantly in their sedentary counterparts. Plasma levels of free fatty acids normalized in the ischemic trained rats, but elevated in the ischemic sedentary rats (0.53{+-}0.05 vs 0.73{+-}0.06 mmol/L, p<0.05). Furthermore, the trained rats had a significant increase in LV stroke volume (0.25{+-}0.02 vs 0.21{+-}0.01 ml/beat, p<0.05) and adaptive cardiac hypertrophy. These findings demonstrate that adaptive improvements in myocardial perfusion, fatty-acid metabolism and LV function were induced by exercise training after transient ischemia. (author)

  4. Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

    Directory of Open Access Journals (Sweden)

    Mihai Onofriescu

    .67, 95%CI = 2.29-5.89 for RFO >17.4% and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4% Cox regression analysis.The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

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

    Directory of Open Access Journals (Sweden)

    Zuheng Liu

    2017-09-01

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

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

    OpenAIRE

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

    2013-01-01

    The carboxyl terminus of HSP70-interacting protein (CHIP) is a ubiquitin ligase/co-chaperone critical for the maintenance of cardiac function. Mice lacking CHIP (CHIP −/−) suffer decreased survival, enhanced myocardial injury, and increased arrhythmias compared to wild type controls following challenge with cardiac ischemia reperfusion injury. Recent evidence implicates a role for CHIP in chaperone-assisted selective autophagy, a process that is associated with exercise-induced cardioprotecti...

  7. Cell therapy in reperfused acute myocardial infarction does not improve the recovery of perfusion in the infarcted myocardium: a cardiac MR imaging study.

    Science.gov (United States)

    Robbers, Lourens F H J; Nijveldt, Robin; Beek, Aernout M; Hirsch, Alexander; van der Laan, Anja M; Delewi, Ronak; van der Vleuten, Pieter A; Tio, René A; Tijssen, Jan G P; Hofman, Mark B M; Piek, Jan J; Zijlstra, Felix; van Rossum, Albert C

    2014-07-01

    To investigate the effects of cell therapy on myocardial perfusion recovery after treatment of acute myocardial infarction (MI) with primary percutaneous coronary intervention (PCI). In this HEBE trial substudy, which was approved by the institutional review board (trial registry number ISRCTN95796863), the authors assessed the effects of intracoronary infusion with bone marrow-derived mononuclear cells (BMMCs) or peripheral blood-derived mononuclear cells (PBMCs) on myocardial perfusion recovery by using cardiac magnetic resonance (MR) imaging after revascularization. In 152 patients with acute MI treated with PCI, cardiac MR imaging was performed after obtaining informed consent-before randomization to BMMC, PBMC, or standard therapy (control group)-and repeated at 4-month follow-up. Cardiac MR imaging consisted of cine, rest first-pass perfusion, and late gadolinium enhancement imaging. Perfusion was evaluated semiquantitatively with signal intensity-time curves by calculating the relative upslope (percentage signal intensity change). The relative upslope was calculated for the MI core, adjacent border zone, and remote myocardium. Perfusion differences among treatment groups or between baseline and follow-up were assessed with the Wilcoxon signed rank or Mann-Whitney U test. At baseline, myocardial perfusion differed between the MI core (median, 6.0%; interquartile range [IQR], 4.1%-8.0%), border zone (median, 8.4%; IQR, 6.4%-10.2%), and remote myocardium (median, 12.2%; IQR, 10.5%-15.9%) (P < .001 for all), with equal distribution among treatment groups. These interregional differences persisted at follow-up (P < .001 for all). No difference in perfusion recovery was found between the three treatment groups for any region. After revascularization of ST-elevation MI, cell therapy does not augment the recovery of resting perfusion in either the MI core or border zone. © RSNA, 2014.

  8. The mucus layer is critical in protecting against ischemia/reperfusion-mediated gut injury and in the restitution of gut barrier function

    Science.gov (United States)

    Qin, Xiaofa; Sheth, Sharvil U.; Sharpe, Susan M.; Dong, Wei; Lu, Qi; Xu, Dazhong; Deitch, Edwin A.

    2011-01-01

    It is well documented that the gut injury plays a critical role in the development of systemic inflammation and distant organ injury in conditions associated with splanchnic ischemia. Consequently understanding the mechanisms leading to gut injury is important. In this context, recent work suggests a protective role for the intestinal mucus layer and an injury-inducing role for luminal pancreatic proteases. Thus, we explored the role of the mucus layer in gut barrier function by observing how the removal of the mucus layer affects ischemia/reperfusion-mediated gut injury in rats as well as the potential role of luminal pancreatic proteases in the pathogenesis of gut injury. Ischemia was induced by the ligation of blood vessels to segments of the ileum for 45 min, followed by up to three hours of reperfusion. The ileal segments were divided into 5 groups. These included a non-ischemic control, ischemic segments exposed to saline, the mucolytic N-acetylcholine (NAC), pancreatic proteases or NAC plus pancreatic proteases. Changes in gut barrier function were assessed by the permeation of fluorescein isothiocyanate dextran (MW 4000 Da; FD4) in ileal everted sacs. Gut injury was measured morphologically and by the luminal content of protein, DNA and hemoglobin. The mucus layer was assessed functionally by measuring its hydrophobicity and morphologically. Gut barrier function was promptly and effectively re-established during reperfusion, which was accompanied by the restoration of the mucus layer. In contrast, treatment of the gut with the mucolytic NAC for 10 min during ischemia resulted in a failure of mucus restitution and further increases in gut permeability and injury. The presence of digestive proteases by themselves did not exacerbate gut injury but in combination with NAC, they caused an even greater increase in gut injury and permeability. These results suggest that the mucus layer not only serves as a barrier between the luminal contents and gut surface

  9. Recovery of brain function after cardiac arrest, case report and review.

    Science.gov (United States)

    Nekoui, A; Tresierra, del Carmen Escalante; Abdolmohammadi, S; Charbonneau, S; Blaise, G

    2016-01-01

    Cerebral hypoxia during cardiac arrest is the leading cause of mortality and morbidity in survival victims. To reduce cerebral damage, studies focus on finding effective treatments during the resuscitation period. Our report focuses on a 36-year-old police officer who had had two cardiac arrests (one at home and one at the hospital). After acute treatment, his cardiac and brain functions recovered impressively. Neuropsychological results were normal except for mild anomia. He also reported some retrograde memory loss. Surprisingly, he also reported an improvement in a very specific capacity, his episodic memory. We here review the possible causes and mechanisms that may have affected his memory abilities.

  10. Translational Medicine Study on Cardiac Microvascular Endothelial Barrier Function and Myocardial Ischemia/Re-perfusion Injury

    Institute of Scientific and Technical Information of China (English)

    Yeong Yeh Lee

    2015-01-01

    Vascular endothelial barrier is defined as the ability of endothelial cells and their components that make up the microvascular wall structure in controlling the cellular components and marco-molecular substances in blood from penetrating vascular walls. It is the place for the selective exchange of oxygen, nutrients and metabolites, and has kernel effect in maintaining myocardial micro-environmental homeostasis. In clinic, microvascular permeability is commonly used as the index for evaluating endothelial barrier function. Myocardial microvascular endothelial cells, inter-endothelial connexin and basilar membrane (BM) interact synergically to constitute the basis for barrier function, which has a selective permeability effect on interaction between nutrient substances and other myocardial cell molecules. Increase of microvascular permeability is closely associated with cardiovascular events like coronary heart disease (CHD) and myocardial ischemia, and is the risk factor for CHD attack. And deep exploration of the mechanism of endothelial permeability and positive selection of new-type re-perfusion complementary drugs for alleviating endothelial permeability can be beneifcial in improving the prognosis of patients with acute myocardial infarction (AMI). Therefore, from the view of translational medicine, this study mainly summarized the increase of microvascular permeability and its pathological signiifcance after AMI, physiological and pathological mechanisms of regulating microvascular permeability and complementary therapies for AMI re-perfusion as well as microvascular endothelial barrier function, hoping to provide a basis for improving the prognosis of patients with AMI.

  11. Translational Medicine Study on Cardiac Microvascular Endothelial Barrier Function and Myocardial Ischemia/Re-perfusion Injury

    Directory of Open Access Journals (Sweden)

    Yeong Yeh Lee

    2015-09-01

    Full Text Available Vascular endothelial barrier is defined as the ability of endothelial cells and their components that make up the microvascular wall structure in controlling the cellular components and marco-molecular substances in blood from penetrating vascular walls. It is the place for the selective exchange of oxygen, nutrients and metabolites, and has kernel effect in maintaining myocardial micro-environmental homeostasis. In clinic, microvascular permeability is commonly used as the index for evaluating endothelial barrier function. Myocardial microvascular endothelial cells, inter-endothelial connexin and basilar membrane (BM interact synergically to constitute the basis for barrier function, which has a selective permeability effect on interaction between nutrient substances and other myocardial cell molecules. Increase of microvascular permeability is closely associated with cardiovascular events like coronary heart disease (CHD and myocardial ischemia, and is the risk factor for CHD attack. And deep exploration of the mechanism of endothelial permeability and positive selection of new-type re-perfusion complementary drugs for alleviating endothelial permeability can be beneficial in improving the prognosis of patients with acute myocardial infarction (AMI. Therefore, from the view of translational medicine, this study mainly summarized the increase of microvascular permeability and its pathological significance after AMI, physiological and pathological mechanisms of regulating microvascular permeability and complementary therapies for AMI re-perfusion as well as microvascular endothelial barrier function, hoping to provide a basis for improving the prognosis of patients with AMI.

  12. [Cardioprotective effect of heme oxygenase-1 induction by hemin on the isolated rat heart during ischemia--reperfusion].

    Science.gov (United States)

    Kukoba, T V; Moĭbenko, O O; Kotsioruba, A V

    2003-01-01

    The aim of the study was to determine the role of both an inducible isoform of heme oxygenase (HO-1) and products of heme catabolism (carbon monoxide (CO), cardiac bilirubin and Fe2+) in protecting myocardium against post-ischemic myocardial dysfunction. Rat hearts were isolated and perfused according to the Langendorff technique to evaluate the recovery of myocardial function after total ischemia (20 min) and reperfusion (40 min) and production of reactive oxygen forms at a reperfusion phase. Ischemia/reperfusion caused impairment in myocardial function: left ventricular developing pressure (LVDP) was shown to be decreased, while end-diastolic pressure (EDP) and both coronary perfusion pressure and coronary resistance increased. Free oxygen radicals were generated at the reperfusion phase which led to injuries to cardiomyocytes and creatine kinase efflux into perfusate. We have found that upregulation of HO-1 by preliminary (24 h before ischemia) injections of 25 mg/kg hemin (i.p.) resulted in improving the myocardial function due to increasing the enzyme activity and forming the cardial bilirubine, while generation of reactive oxygen forms was inhibited, as well as the contents of creatine kinase reduced. As a result, impairment in cardiomyocytes diminished, and coronary vessels dilated to improve the functional parametres of the heart work.

  13. Cardiac function and rejection following transplantation of the heart

    Energy Technology Data Exchange (ETDEWEB)

    Schober, O.; Schuler, S.; Gratz, K.; Warnecke, H.; Lang, W.; Hetzer, R.; Creutzig, H.

    1985-05-01

    It was the purpose of the study to evaluate the noninvasive detection of rejection following cardiac transplantation. Multigated cardiac blood pool imaging (MUGA) at rest with assessment of ejection fraction (EF) and regional wall motion was determined prospectively in 14 patients with 180 studies (follow up 5.1 +- 3.2 months) following orthotopic cardiac transplantation. The results were compared with histological examination of a percutaneous endocardial biopsy specimen (EMB) from the right ventricle. Diagnosis of rejection by EF measurement was defined by a decrease of 10% if EF < 70%, and 15% if EF > 70%. In 152 studies a normal MUGA study correlated with none rejection as defined by EMB. In 14 of 22 studies with moderate or severe rejection decrease of EF followed the rejection with a delay of 5 days. Septal wall motion abnormalities were typical. In 6 studies an abnormal temporal course of EF was not related to a similar finding in EMB. A sensitivity of 69% and a specifity of 96% can be estimated in the investigated group, in which all patients survived during the period of the study. It is concluded that rejection can be excluded by noninvasive MUGA (specifity 96%) and that MUGA is predictive of rejection (sensitivity 67%) mostly with a delay of 5 days.

  14. Endomorphins and β-Endorphin Do Not Affect Heart Tolerance to the Pathogenic Effect of Reperfusion.

    Science.gov (United States)

    Mukhomedzyanov, A V; Maslov, L N; Tsibulnikov, S Yu; Pei, J M

    2016-11-01

    Selective agonists of μ1- and μ2-opioid receptors endomorphin-2 and endomorphin-1 injected intravenously in a dose of 4500 nmol/kg in 5 min before coronary blood flow resumption had no effect on cardiac reperfusion damage. Consequently, μ1- and μ2-opioid receptors are not involved in the regulation of heart tolerance to reperfusion injury. Nonselective opioid receptor agonist β-endorphin (100 nmol/kg) also did not affect heart tolerance to the pathogenic effect of reperfusion.

  15. Inhibition of KV7 channels protects against myocardial ischemia and reperfusion injury

    DEFF Research Database (Denmark)

    Hedegaard, Elise Røge; Johnsen, Jacob; Povlsen, Jonas Agerlund;

    2015-01-01

    Aims: KV7 channel are activated by ischemia and mediate hypoxic vasodilatation. We investigated the effect of KV7 channel modulation on cardiac ischemia and reperfusion (IR) injury and the interaction with cardioprotection by ischemic preconditioning (IPC). Methods and Results: We investigated......-flow, global ischemia and reperfusion with and without IPC. Infarct size (IS) was quantified by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hemodynamics were measured using a catheter inserted in the left ventricle. Functional studies on isolated coronary arteries were performed in a wire myograph. KV7.......1, KV7.4 and KV7.5 were expressed in rat coronary arteries and all KV7 subtypes (KV7.1-5) in the left and right ventricles of the heart. KV7 channel blockade by XE991 and linopirdine reduced infarct size additive to infarct reduction by IPC. Flupirtine abolished infarct size reduction by IPC...

  16. Proteasome inhibition slightly improves cardiac function in mice with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Schlossarek, Saskia; Singh, Sonia R; Geertz, Birgit; Schulz, Herbert; Reischmann, Silke; Hübner, Norbert; Carrier, Lucie

    2014-01-01

    A growing line of evidence indicates a dysfunctional ubiquitin-proteasome system (UPS) in cardiac diseases. Anti-hypertrophic effects and improved cardiac function have been reported after treatment with proteasome inhibitors in experimental models of cardiac hypertrophy. Here we tested whether proteasome inhibition could also reverse the disease phenotype in a genetically-modified mouse model of hypertrophic cardiomyopathy (HCM), which carries a mutation in Mybpc3, encoding the myofilament protein cardiac myosin-binding protein C. At 7 weeks of age, homozygous mutant mice (KI) have 39% higher left ventricular mass-to-body-weight ratio and 29% lower fractional area shortening (FAS) than wild-type (WT) mice. Both groups were treated with epoxomicin (0.5 mg/kg/day) or vehicle for 1 week via osmotic minipumps. Epoxomicin inhibited the chymotrypsin-like activity by ~50% in both groups. All parameters of cardiac hypertrophy (including the fetal gene program) were not affected by epoxomicin treatment in both groups. In contrast, FAS was 12% and 35% higher in epoxomicin-treated than vehicle-treated WT and KI mice, respectively. To identify which genes or pathways could be involved in this positive effect, we performed a transcriptome analysis in KI and WT neonatal cardiac myocytes, treated or not with the proteasome inhibitor MG132 (1 μM, 24 h). This revealed 103 genes (four-fold difference; 5% FDR) which are commonly regulated in both KI and WT cardiac myocytes. Thus, even in genetically-modified mice with manifest HCM, proteasome inhibition showed beneficial effects, at least with regard to cardiac function. Targeting the UPS in cardiac diseases remains therefore a therapeutic option.

  17. 无创性延迟肢体缺血预适应保护糖尿病大鼠缺血/再灌注心肌%Cardiac protective effects of noninvasive delayed limb ischemic preconditioning against ischemia-reperfusion injury in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    朱学慧; 娄建石; 李玉梅; 袁恒杰; 吴艳娜; 康毅; 焦建杰

    2009-01-01

    AIM: To study the effects of noninvasive delayed limb ischemic preconditioning (NDLIP) on myocardium ischemia-reperfusion injury in diabetic rats. METHODS: The acute diabetic rat models were induced by injecting streptozotocin (STZ) through vena caudalis. The diabetic rats were randomly divided into ischemia-reperfusion (I/R) group, cardiac ischemic preconditioning (CIP) group and NDLIP group. Rats in NDLIP group subjected to NDLIP left hind limb for 3 days, and at the fourth day, all rats were subjected to myocardial ischemia/reperfusion injury. Rats in CIP group were myocardial ischemic preconditioning before ischemia. Blood pressure and electrocardiogram were monitored continuously. The effects of myocardial electrophysiology function, myocardial infarction size and myocardial enzyme were observed in the diabetic rats with NDLIP after myocardium ischemia-reperfusion injury, and the superoxide dismutase(SOD), the activities of glutathion peroxidase(GSH-Px), the content of mal-onaldehyde in rats muscular tissues were detected. RESULTS: The levels of blood glucose were increased and the body weights were decreased in diabetic model rats(P < 0.01). Compared with I/R group, the elevation extent of ST segment in NDLIP and CIP group were degraded, the emergence time of ventricular premature contraction and ventricular tachycardia were delayed and the duration of both was shortened, and the incidence of ventricular arrhythmia was decreased (P < 0.05), the myocardial infarct size was reduced(P < 0.01), the releases of cadiocyte lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase isozyme were decreased (P<0.05, P < 0.01), the activities of SOD and GSH-Px in rats muscular tissues were increased (P < 0.01) and the content of MDA was decreased in CIP and NDLIP groups(P < 0.05, P <0.01). CONCLUSION: NDLIP can relieve cadiocyte damage induced by I/R injury in the diabetic rats and the leakage of cardiac muscle enzyme is decreased, and the physiologic

  18. Qiliqiangxin Enhances Cardiac Glucose Metabolism and Improves Diastolic Function in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Jingfeng Wang

    2017-01-01

    Full Text Available Cardiac diastolic dysfunction has emerged as a growing type of heart failure. The present study aims to explore whether Qiliqiangxin (QL can benefit cardiac diastolic function in spontaneously hypertensive rat (SHR through enhancement of cardiac glucose metabolism. Fifteen 12-month-old male SHRs were randomly divided into QL-treated, olmesartan-treated, and saline-treated groups. Age-matched WKY rats served as normal controls. Echocardiography and histological analysis were performed. Myocardial glucose uptake was determined by 18F-FDG using small-animal PET imaging. Expressions of several crucial proteins and key enzymes related to glucose metabolism were also evaluated. As a result, QL improved cardiac diastolic function in SHRs, as evidenced by increased E′/A′and decreased E/E′ (P<0.01. Meanwhile, QL alleviated myocardial hypertrophy, collagen deposits, and apoptosis (P<0.01. An even higher myocardial glucose uptake was illustrated in QL-treated SHR group (P<0.01. Moreover, an increased CS activity and ATP production was observed in QL-treated SHRs (P<0.05. QL enhanced cardiac glucose utilization and oxidative phosphorylation in SHRs by upregulating AMPK/PGC-1α axis, promoting GLUT-4 expression, and regulating key enzymes related to glucose aerobic oxidation such as HK2, PDK4, and CS (P<0.01. Our data suggests that QL improves cardiac diastolic function in SHRs, which may be associated with enhancement of myocardial glucose metabolism.

  19. Functional Alterations of Ion Channels From Cardiac Fibroblasts in Heart Diseases

    Directory of Open Access Journals (Sweden)

    Gracious R. Ross

    2016-11-01

    Full Text Available In an aged population, cardiovascular disease is the leading cause of fatality and morbidity. Age-related fibrotic remodeling of the heart contributes to progressive myocardial dysfunction. Cardiac fibroblasts (CF, responsible for the maintenance of extracellular matrix and fibrosis process, play an important role in cardiac health and disease. CFs influence myocardial function by their chemical, electrical and mechanical interactions with cardiomyocytes through extracellular matrix deposition or secretion of cytokines and growth factors. These, in turn, are modulated by ion channels, macromolecular pores in the plasma membrane that allow selective ionic fluxes of major ions like K+, Ca2+, Na+ or Cl-, which affect membrane potential and cellular signal transduction. The importance of ion channels in modulating various functions of CFs, including proliferation, differentiation, secretion and apoptosis, is being recognized from recent studies of CFs from animal models and tissue from patients with various cardiac pathologies. Understanding the role of ion channels in CFs under physiological conditions and their alterations in age-related cardiac diseases may help facilitate development of novel therapeutic strategies to limit cardiac fibrosis and its adverse effect on myocardial function. This narrative review summarizes the knowledge gained thus far on ion channels in CFs and their relationship with cardiac diseases in human and experimental animal models.

  20. Functional Status, Anxiety, Cardiac Self-Efficacy, and Health Beliefs of Patients with Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Hamid Allahverdipour

    2013-12-01

    Full Text Available Background: Beliefs and emotions could effect on functional status, quality of life, and mortality amongst patients who are suffering coronary heart disease (CHD. Current study examined the role of anxiety: trait/ state, self-efficacy, health beliefs, and functional status among patient with history of CHD. Method: In this correlational study, 105 hospitalized and outpatients patients suffering CHD in Tehran Heart Center Hospital participated by using convenience sampling method in 2012. Cardiac self-efficacy, Seattle Angina, and research- designed health beliefs questionnaires were used to gather data. Results: The functional status in CHD patients showed significant relationships with gender, job, and type of medical insurance of the participants (All ps<0.05. In addition , perceived vulnerability to face again cardiac attack in the future, perceived severity of next cardiac attack, anxiety, state anxiety and trait anxiety (All ps<0.05 had significant and negative relationships with functional status. Conversely, the cardiac self-efficacy had a positive and significant relationship (P<0.001 with functional status. Conclusion: Psychological factors have important role in functional status and quality of life of patients who suffering CHD. Therefore, it is necessary to emphasize on supportive and complementary programs to promote Cardiac Rehabilitation Programs.

  1. Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Schwaiger, M.; Schelbert, H.R.; Keen, R.; Vinten-Johansen, J.; Hansen, H.; Selin, C.; Barrio, J.; Huang, S.C.; Phelps, M.E.

    1985-08-01

    Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored. Using intracoronary carbon-11 palmitic acid as a tracer of myocardial fatty acid metabolism in an open chest dog model, retention and clearance of tracer in myocardium were evaluated at control, during ischemia and after reperfusion following a 20 minute occlusion of the left anterior descending coronary artery. Myocardial C-11 time-activity curves were analyzed with biexponential curve-fitting routines yielding fractional distribution and clearance half-times of C-11 palmitic acid in myocardial tissue. In animals with permanent occlusion and intracoronary injection of C-11 palmitic acid distal to the occlusion site, the relative size and half-time of the early clearance curve component differed markedly from control values and did not change with ongoing ischemia. Conversely, in animals with only 20 minutes of coronary occlusion, the relative size of the early C-11 clearance phase was still significantly depressed at 20 and 90 minutes of reperfusion but returned to control level at 180 minutes. Tissue C-11 clearance half-times remained significantly prolonged throughout the reperfusion period. Regional function in reperfused myocardium monitored with ultrasonic crystals recovered slowly and was still less than control after 3 hours of reperfusion. The data indicate that after transient ischemia, myocardial fatty acid metabolism fails to recover immediately. Because the metabolic recovery occurs in parallel with recovery of regional function, C-11 palmitic acid in conjunction with positron tomography may be useful for studying regional fatty acid metabolism noninvasively after an ischemic injury, and may be helpful in identifying reversible tissue injury.

  2. Detection and evaluation of renal biomarkers in a swine model of acute myocardial infarction and reperfusion.

    Science.gov (United States)

    Duan, Su-Yan; Xing, Chang-Ying; Zhang, Bo; Chen, Yan

    2015-01-01

    The prevalence of type 1 cardiorenal syndrome (CRS) is increasing and strongly associated with long-term mortality. However, lack of reliable animal models and well-defined measures of renoprotection, made early diagnosis and therapy difficult. We previously successfully established the swine acute myocardial infarction (AMI) model of ischemia-reperfusion by blocking left anterior descending branch (LAD). Reperfusion was performed after 90-minute occlusion of the LAD. AMI was confirmed by ECG and left ventricular angiography (LVG). Then those 52 survived AMI reperfusion swine, including ventricular fibrillation-cardiac arrest after restoration of blood flow, were randomly divided into four groups (four/group) according to different interventions: resuscitation in room temperature, resuscitation with 500 ml saline in room temperature, resuscitation with 4°C 500 ml saline and normal control (with no intervention of resuscitation). Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias: 1, 3, 5, 10-minute reperfusion after ventricular arrhythmias. Plasma and random urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury (AKI). Our swine AMI model of ischemia-reperfusion provoked subclinical AKI with the elevation of the tubular damage biomarker, NGAL, IL-18 and L-FABP. Renal damage rapidly observed after hemodynamic instability, rather than observation after several hours as previously reported. The increasing rate of biological markers declined after interventions, however, its impact on the long-term prognosis remains to be further studied. These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS.

  3. Assessment of microembolization associated with revascularization in acute myocardial infarction: MDCT cardiac perfusion and function study.

    Science.gov (United States)

    Saeed, Maythem; Hetts, Steven W; Do, Loi; Wilson, Mark W

    2013-12-01

    To use multi-detector computed tomography (MDCT) for assessing the effects of coronary microemboli on pre-existing acute myocardial infarct (AMI) and to compare this pathology to LAD microembolization and occlusion/reperfusion. An angioplasty balloon catheter was placed in the LAD coronary artery of pigs under X-ray guidance. Four animals served as controls without intervention (group A) and an additional 24 animals (8/group) were subjected to microembolization (group B), occlusion/reperfusion (group C) or combination of the two insults (group D). MDCT was used to assess perfusion, LV function and viability. At postmortem, the LV sections were stained with hematoxylin/eosin and triphenyltetrazolium chloride (TTC). Dynamic perfusion and helical cine MDCT demonstrated decline in regional LV perfusion and function, respectively, after all interventions. MDCT showed significant differences in ejection fraction between groups: A = 57.5 ± 4.7%, B = 40.3 ± 0.5% P 0.7). Microscopic examination confirmed the presence of patchy and contiguous necrosis, MVO, edema and calcium deposits. Dynamic and helical cine MDCT imaging can grade LV dysfunction and perfusion deficit, respectively. DE-MDCT demonstrated a large and persistent MVO zone after microembolization of pre-existing AMI. Furthermore, it has the potential to visualize patchy microinfarct, detect perfusion deficits and dysfunction at the border zone after microembolization of pre-existing AMI.

  4. The effect of marine n-3 polyunsaturated fatty acids on cardiac autonomic and hemodynamic function in patients with psoriatic arthritis

    DEFF Research Database (Denmark)

    Kristensen, Salome; Schmidt, Erik Berg; Schlemmer, Annette;

    2016-01-01

    The aim of this study was to investigate the effect of marine n-3 polyunsaturated fatty acids (PUFA) on cardiac autonomic function and vascular function in patients with psoriatic arthritis.......The aim of this study was to investigate the effect of marine n-3 polyunsaturated fatty acids (PUFA) on cardiac autonomic function and vascular function in patients with psoriatic arthritis....

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

    Directory of Open Access Journals (Sweden)

    Viveka P Jyotsna

    2013-01-01

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

  6. COMPARATIVE STUDY OF CARDIOPROTECTIVE EFFECT OF VARIOUS DIAMETER AND COMPOSITION LIPOSOMES DURING REPERFUSION OF THE ISOLATED RAT HEARTS AFTER NORMOTHERMIC ISCHEMIA

    Directory of Open Access Journals (Sweden)

    Ya. G. Toropova

    2013-01-01

    Full Text Available The wide application of cardiac surgery using the aorto-pulmonary bypass technique needs the development of new drugs, capable to minimize the heart damaging during ischemia and reperfusion. But the direct delivery of drugs into the damaged tissues and cells is a big problem. The liposomes as unique transport system can be used to solve this problem.The aim of the study was to evaluate the influence of "empty" liposomes of various diameter and the liposomes of different composition on the myocardium contractile function which has underwent the ischemia and the subsequent reperfusion. The obtained results allowed us to make the conclusion that liposomes of 50 nanometers in diameter are most effective to cardiac protection versus liposomes of 100 nanometers.Inclusion the emoxipine into the composition of liposomes provide the best results on contractile function of an ischemic myocardium.

  7. Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter.

    Science.gov (United States)

    Holmström, Kira M; Pan, Xin; Liu, Julia C; Menazza, Sara; Liu, Jie; Nguyen, Tiffany T; Pan, Haihui; Parks, Randi J; Anderson, Stasia; Noguchi, Audrey; Springer, Danielle; Murphy, Elizabeth; Finkel, Toren

    2015-08-01

    Mitochondrial calcium is thought to play an important role in the regulation of cardiac bioenergetics and function. The entry of calcium into the mitochondrial matrix requires that the divalent cation pass through the inner mitochondrial membrane via a specialized pore known as the mitochondrial calcium uniporter (MCU). Here, we use mice deficient of MCU expression to rigorously assess the role of mitochondrial calcium in cardiac function. Mitochondria isolated from MCU(-/-) mice have reduced matrix calcium levels, impaired calcium uptake and a defect in calcium-stimulated respiration. Nonetheless, we find that the absence of MCU expression does not affect basal cardiac function at either 12 or 20months of age. Moreover, the physiological response of MCU(-/-) mice to isoproterenol challenge or transverse aortic constriction appears similar to control mice. Thus, while mitochondria derived from MCU(-/-) mice have markedly impaired mitochondrial calcium handling, the hearts of these animals surprisingly appear to function relatively normally under basal conditions and during stress.

  8. Dapsone improves functional deficit and diminishes brain damage evaluated by 3-Tesla magnetic resonance image after transient cerebral ischemia and reperfusion in rats.

    Science.gov (United States)

    Diaz-Ruiz, Araceli; Roldan-Valadez, Ernesto; Ortiz-Plata, Alma; Mondragón-Lozano, Rodrigo; Heras-Romero, Yessica; Mendez-Armenta, Marisela; Osorio-Rico, Laura; Nava-Ruiz, Concepción; Ríos, Camilo

    2016-09-01

    Stroke is a frequent cause of death and the first of disability in the world population. We have shown that dapsone acts as an antioxidant, antiinflammatory and antiapoptotic agent after brain Ischemia reperfusion (I/R) in rats; however, its therapeutic efficacy, measured by imaging has not been characterized. In this context, the aim of this study was to evaluate the neuroprotective effect of dapsone by magnetic resonance imaging (MRI) and to correlate imaging markers with motor function and oxidative stress after transient cerebral ischemia and reperfusion (I/R). We used male rats throughout the experiment. Functional deficit after I/R was assessed by using Longa scale. The area of brain tissue damage was measured by histology. The nuclear factor erythroid 2-related factor 2 (Nrf-2) and the amount of reactive oxygen species (ROS) were measured as biomarkers of oxidative stress. Finally, difussion tensor MRI was employed to measure the fractional anisotropy (FA), as a MRI marker of the pathophysiologic brain status. Results showed a better functional recovery and less damaged tissue in animals treated with dapsone vs control group. The values of FA were higher in animals receiving treatment, indicating a better preservation of brain structure. At early stages of the damage, dapsone was able to reduce both oxidative markers (Nrf-2 and ROS). Our findings provide new evidence for the efficacy of dapsone when administered during the acute phase after I/R and that quantitative sequences of MRI are useful for characterizing its potential therapeutic benefits after stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Metabolic effects of propionate, hexanoate and propionylcarnitine in normoxia, ischaemia and reperfusion. Does an anaplerotic substrate protect the ischaemic myocardium?

    Science.gov (United States)

    Sundqvist, K E; Vuorinen, K H; Peuhkurinen, K J; Hassinen, I E

    1994-04-01

    It has been suggested that propionyl-L-carnitine administration to ischaemic hearts facilitates the restoration of cardiac function upon reperfusion, but it is still a matter of dispute whether its effect is conveyed via the metabolic effect of the propionyl moiety, the carnitine moiety or other mechanisms involving membrane receptor interactions. The metabolism of propionylcarnitine involves the formation of succinyl-CoA, which causes an increase in the total amount of tricarboxylic acid cycle intermediates. According to the current paradigm, anaplerosis ensures rapid restoration of tricarboxylic acid cycle activity during reperfusion. To evaluate the contribution of anaplerosis to the protective effect of propionylcarnitine during ischaemia and reperfusion, isolated rat hearts were perfused with Krebs-Henseleit bicarbonate buffer containing 5 mM glucose+insulin (12 IU per litre), to which 1 mM propionate, 0.8 mM hexanoate or 1 mM propionylcarnitine were added. Global 20 or 24 min no-flow ischaemia was followed by 10 min reperfusion. The flavoprotein redox state, myoglobin oxygenation, oxygen consumption and mechanical functioning of the heart were recorded and metabolites determined in freeze-trapped tissue. In parallel experiments, the cellular energy state was studied with phosphorus nuclear magnetic resonance spectrometry. The addition of 1 mM propionylcarnitine failed to cause an anaplerotic effect, but did bring about an oxidation of flavins, probably due to citrate synthase inhibition. Propionate showed similar but stronger effects and a marked anaplerosis, but still failed to improve the recovery of the heart upon reperfusion. The addition of hexanoate caused marked anaplerosis upon reperfusion and flavin reduction. The results failed to demonstrate that propionylcarnitine had any beneficial effect on the ischaemic myocardium.

  10. ICF-based approach to evaluating functionality in cardiac rehabilitation patients after heart surgery.

    Science.gov (United States)

    Racca, V; Di Rienzo, M; Mazzini, P; Ripamonti, V; Gasti, G; Spezzaferri, R; Modica, M; Ferratini, M

    2015-08-01

    Heart surgery is a frequent reason for admission to in-patient cardiac rehabilitation programmes. ICF approach has never been used to evaluate cardiac patients after major heart surgery. The aim was to evaluate and measure functionality in cardiac patients who have undergone heart surgery, using for the first time the ICF-based approach and to assess whether such approach can be feasible and useful in cardiac rehabilitation. Observational study. In-patients cardiac Rehabilitation Unit in Milan. Fifty consecutively admitted patients who had undergone heart surgery (34 males, 16 females; mean age 65.7±12.5 years). We prepared a ICF-core set short enough to be feasible and practical. Patients were individually interviewed by different healthcare professionals (randomly selected from a group of two physicians, two physiotherapists and two psychologists) at the beginning (T1) and end of cardiac rehabilitation (T2) RESULTS: The sum of the scores of each ICF body function, body structure, activity and participation code significantly decreased between T1 and T2 (PICF body function scores and Barthel's index (ρ=0.381; P=0.006), NYHA class (ρ=0.404; P=0.004) and plasma Cr-P levels (r=0.31; P=0.03), between the ICF body structure codes and the Conley scale (ρ=0.306; P=0.02), and between the activity/participation codes and SpO2 (ρ=0.319; P=0.04). There were no correlations between the ICF environmental codes and clinical parameters. The ICF-based data provided functional information that was consistent with the patients' clinical course. The core set used allowed to quantify important body functions and activities, including some areas that are generally insufficiently considered by healthcare professionals during cardiac rehabilitation, and document their improvement.

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

    Directory of Open Access Journals (Sweden)

    Bonpei Takase

    2009-01-01

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

  12. A Role for Photobiomodulation in the Prevention of Myocardial Ischemic Reperfusion Injury: A Systematic Review and Potential Molecular Mechanisms.

    Science.gov (United States)

    Liebert, Ann; Krause, Andrew; Goonetilleke, Neil; Bicknell, Brian; Kiat, Hosen

    2017-02-09

    Myocardial ischemia reperfusion injury is a negative pathophysiological event that may result in cardiac cell apoptosis and is a result of coronary revascularization and cardiac intervention procedures. The resulting loss of cardiomyocyte cells and the formation of scar tissue, leads to impaired heart function, a major prognostic determinant of long-term cardiac outcomes. Photobiomodulation is a novel cardiac intervention that has displayed therapeutic effects in reducing myocardial ischemia reperfusion related myocardial injury in animal models. A growing body of evidence supporting the use of photobiomodulation in myocardial infarct models has implicated multiple molecular interactions. A systematic review was conducted to identify the strength of the evidence for the therapeutic effect of photobiomodulation and to summarise the current evidence as to its mechanisms. Photobiomodulation in animal models showed consistently positive effects over a range of wavelengths and application parameters, with reductions in total infarct size (up to 76%), decreases in inflammation and scarring, and increases in tissue repair. Multiple molecular pathways were identified, including modulation of inflammatory cytokines, signalling molecules, transcription factors, enzymes and antioxidants. Current evidence regarding the use of photobiomodulation in acute and planned cardiac intervention is at an early stage but is sufficient to inform on clinical trials.

  13. A Role for Photobiomodulation in the Prevention of Myocardial Ischemic Reperfusion Injury: A Systematic Review and Potential Molecular Mechanisms

    Science.gov (United States)

    Liebert, Ann; Krause, Andrew; Goonetilleke, Neil; Bicknell, Brian; Kiat, Hosen

    2017-01-01

    Myocardial ischemia reperfusion injury is a negative pathophysiological event that may result in cardiac cell apoptosis and is a result of coronary revascularization and cardiac intervention procedures. The resulting loss of cardiomyocyte cells and the formation of scar tissue, leads to impaired heart function, a major prognostic determinant of long-term cardiac outcomes. Photobiomodulation is a novel cardiac intervention that has displayed therapeutic effects in reducing myocardial ischemia reperfusion related myocardial injury in animal models. A growing body of evidence supporting the use of photobiomodulation in myocardial infarct models has implicated multiple molecular interactions. A systematic review was conducted to identify the strength of the evidence for the therapeutic effect of photobiomodulation and to summarise the current evidence as to its mechanisms. Photobiomodulation in animal models showed consistently positive effects over a range of wavelengths and application parameters, with reductions in total infarct size (up to 76%), decreases in inflammation and scarring, and increases in tissue repair. Multiple molecular pathways were identified, including modulation of inflammatory cytokines, signalling molecules, transcription factors, enzymes and antioxidants. Current evidence regarding the use of photobiomodulation in acute and planned cardiac intervention is at an early stage but is sufficient to inform on clinical trials. PMID:28181487

  14. False dyssynchrony: problem with image-based cardiac functional analysis using x-ray computed tomography

    Science.gov (United States)

    Kidoh, Masafumi; Shen, Zeyang; Suzuki, Yuki; Ciuffo, Luisa; Ashikaga, Hiroshi; Fung, George S. K.; Otake, Yoshito; Zimmerman, Stefan L.; Lima, Joao A. C.; Higuchi, Takahiro; Lee, Okkyun; Sato, Yoshinobu; Becker, Lewis C.; Fishman, Elliot K.; Taguchi, Katsuyuki

    2017-03-01

    We have developed a digitally synthesized patient which we call "Zach" (Zero millisecond Adjustable Clinical Heart) phantom, which allows for an access to the ground truth and assessment of image-based cardiac functional analysis (CFA) using CT images with clinically realistic settings. The study using Zach phantom revealed a major problem with image-based CFA: "False dyssynchrony." Even though the true motion of wall segments is in synchrony, it may appear to be dyssynchrony with the reconstructed cardiac CT images. It is attributed to how cardiac images are reconstructed and how wall locations are updated over cardiac phases. The presence and the degree of false dyssynchrony may vary from scan-to-scan, which could degrade the accuracy and the repeatability (or precision) of image-based CT-CFA exams.

  15. The ET axis mediates arrhythmogenesis and compromised cardiac function in two cardiomyopathy models

    Institute of Scientific and Technical Information of China (English)

    YuFENG; De-zaiDAI; YuanZHANG; Hai-boHE; Min-youQI; YinDAI; FengYU

    2005-01-01

    AIM Endothelin 1(ET-1), a potent vasoconstrictor peptide, is also regarded as an important etiological factor involved in many cardiac diseases like heart failure and cardiac hypertrophy. It mediates pathologic changes by forming an """"ET axis"""" at the upstream to ion channels, such as stimulating oxidant stress, eliciting cardiac remodeling by proliferation of cardiomyocytes, inducing apoptosis, affecting signal transduction pathway, and modulating intranuclear gene transcription. The purpose of this study was to investigate the pivotal role by ET axis in worsening arrhythmias and cardiac function in experimental hypertrophic cardiomyopathy (HCM) and heart failure (HF) models. METHODS The rat HCM model was induced by s.c L-thyroxin (L-thy, 0.2mg/Kg/d) for 10d,

  16. Protective Effects of HDL Against Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Gomaraschi, Monica; Calabresi, Laura; Franceschini, Guido

    2016-01-01

    Several lines of evidence suggest that, besides being a strong independent predictor of the occurrence of primary coronary events, a low plasma high density lipoprotein (HDL) cholesterol level is also associated with short- and long-term unfavorable prognosis in patients, who have recovered from a myocardial infarction, suggesting a direct detrimental effect of low HDL on post-ischemic myocardial function. Experiments performed in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury have clearly shown that HDL are able to preserve cardiac function when given before ischemia or at reperfusion; the protective effects of HDL against I/R injury have been also confirmed in other tissues and organs, as brain and hind limb. HDL were shown to act on coronary endothelial cells, by limiting the increase of endothelium permeability and promoting vasodilation and neoangiogenesis, on white blood cells, by reducing their infiltration into the ischemic tissue and the release of pro-inflammatory and matrix-degrading molecules, and on cardiomyocytes, by preventing the activation of the apoptotic cascade. Synthetic HDL retains the cardioprotective activity of plasma-derived HDL and may become a useful adjunctive therapy to improve clinical outcomes in patients with acute coronary syndromes or undergoing coronary procedures.

  17. Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Gorsuch, W Brian; Guikema, Benjamin J; Fritzinger, David C; Vogel, Carl-Wilhelm; Stahl, Gregory L

    2009-12-01

    Cobra venom factor (CVF) is a complement activating protein in cobra venom, which functionally resembles C3b, and has been used for decades for decomplementation of serum to investigate the role of complement in many model systems of disease. The use of CVF for clinical practice is considered impractical because of immunogenicity issues. Humanization of CVF was recently demonstrated to yield a potent CVF-like molecule. In the present study, we demonstrate that mice treated with recombinant humanized CVF (HC3-1496) are protected from myocardial ischemia-reperfusion (MI/R) injuries with resultant preservation of cardiac function. Also, C3 deposition in the myocardium following MI/R was not observed following treatment with HC3-1496. HC3-1496 led to complement activation and depletion of C3, but preserved C5 titers. These data suggest, unlike CVF, HC3-1496 does not form a C5 convertase in the mouse, similar to recent studies in human sera/plasma. These results suggest that humanized CVF (HC3-1496) protects the ischemic myocardium from reperfusion injuries induced by complement activation and represents a novel anti-complement therapy for potential clinical use.

  18. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct

    Science.gov (United States)

    Valarmathi, Mani T.; Fuseler, John W.; Davis, Jeffrey M.; Price, Robert L.

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty. PMID:28194397

  19. Cardiac Structure and Function in Weight Trainers Runners, and Runner/Weight Trainers.

    Science.gov (United States)

    Elias, Barbara A.; And Others

    1991-01-01

    Study compared cardiac structure and function in adult male weight trainers, runners, and those who did both. Results indicate men who run or weight train and run have similar heart structural and functional characteristics and greater relative internal diameter and left ventricular wall thickness than men who only weight train. (SM)

  20. SHEAR-INDUCED PATHWAY OF PLATELET-FUNCTION IN CARDIAC-SURGERY

    NARCIS (Netherlands)

    TABUCHI, N; TIGCHELAAR, [No Value; VANOEVEREN, W

    1995-01-01

    The contribution of platelet dysfunction to the impaired hemostasis after cardiac surgery remains to be established, because there is no sensitive method to assess platelet function. Measurement of the shear-induced pathway of platelet function, an important mechanism in inducing hemostasis, became

  1. SHEAR-INDUCED PATHWAY OF PLATELET-FUNCTION IN CARDIAC-SURGERY

    NARCIS (Netherlands)

    TABUCHI, N; TIGCHELAAR, [No Value; VANOEVEREN, W

    1995-01-01

    The contribution of platelet dysfunction to the impaired hemostasis after cardiac surgery remains to be established, because there is no sensitive method to assess platelet function. Measurement of the shear-induced pathway of platelet function, an important mechanism in inducing hemostasis, became

  2. Older Adults in Cardiac Rehabilitation: A New Strategy for Enhancing Physical Function.

    Science.gov (United States)

    Rejeski, W. Jack; Foy, Capri Gabrielle; Brawley, Lawrence R.; Brubaker, Peter H.; Focht, Brian C.; Norris, James L., III; Smith, Marci L.

    2002-01-01

    Contrasted the effect of a group-mediated cognitive- behavioral intervention (GMCB) versus traditional cardiac rehabilitation (CRP) upon changes in objective and self-reported physical function of older adults after 3 months of exercise therapy. Both groups improved significantly. Adults with lower function at the outset of the intervention…

  3. L-propionylcarnitine effects on cardiac carnitine content and function in secondary carnitine deficiency.

    Science.gov (United States)

    Broderick, T L; DiDomenico, D; Shug, A L; Paulson, D J

    1995-04-01

    Long-term treatment with sodium pivalate, a compound conjugated to carnitine and excreted in the urine, results in carnitine deficiency and cardiac dysfunction. Since L-propionylcarnitine (LPC) is generally of benefit to cardiac function, it was of interest to determine whether it is effective in preventing the reductions in both heart carnitine content and function from occurring in carnitine deficiency. Secondary carnitine deficiency was induced in male Sprague-Dawley rats by supplementing the drinking water with 20 mM sodium pivalate for 26 weeks. Control animals received an equimolar concentration of sodium bicarbonate. At 13 weeks into treatment, a subgroup of control and sodium pivalate animals were given 80 mg/kg of LPC in their drinking water. Following treatment, isolated working hearts were perfused with buffer containing 11 mM glucose and 0.4 mM palmitate. Hearts from sodium pivalate treated animals demonstrated a severe reduction in tissue carnitine. When mechanical function was measured in these hearts, heart rate, rate-pressure product, and aortic flow were significantly depressed. Treatment with LPC, however, prevented the depletion in cardiac carnitine content and improved these cardiac parameters. Our results demonstrate that LPC treatment is beneficial in preventing the depression in cardiac function from occurring in this model of secondary carnitine deficiency.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-11-01

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

  5. Evaluation of cardiac structures and function in hypertrophic cardiomyopathy with magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To assess the capability of magnetic resonance imaging(MRI)in evaluating the cardiac structures and function in the hypertrophic cardiomyopathy(HCM).Methods:Fourteen healthy volunteers and eighteen cases with HCM verified by history,clinical presentation,electrocardiogram and echocardiography(ECG)were performed with MRI.The myocardial thickness of interventricular septum at the basal segment and that of posterolateral free wall of the left ventricle(LV)were measured.Some indexes for evaluating cardiac function were measured using ARGUS auto-quantitative program.Resuits:The myocardial thickness of septum at the basal segment had significant difference between the HCM patients and the healthy volunteers.There was no significant difference between MRI and ECG in examining end-diastolic volume,ejection fraction of the LV.Conclusion:MRI can fully provide more information on the abnormalities of cardiac anatomy and function;thus,it is of great value in clinical application.

  6. Transient receptor potential vanilloid 2 function regulates cardiac hypertrophy via stretch-induced activation.

    Science.gov (United States)

    Koch, Sheryl E; Mann, Adrien; Jones, Shannon; Robbins, Nathan; Alkhattabi, Abdullah; Worley, Mariah C; Gao, Xu; Lasko-Roiniotis, Valerie M; Karani, Rajiv; Fulford, Logan; Jiang, Min; Nieman, Michelle; Lorenz, John N; Rubinstein, Jack

    2017-03-01

    Hypertension (increased afterload) results in cardiomyocyte hypertrophy leading to left ventricular hypertrophy and subsequently, heart failure with preserved ejection fraction. This study was performed to test the hypothesis that transient receptor potential vanilloid 2 subtype (TRPV2) function regulates hypertrophy under increased afterload conditions. We used functional (pore specific) TRPV2 knockout mice to evaluate the effects of increased afterload-induced stretch on cardiac size and function via transverse aortic constriction (TAC) as well as hypertrophic stimuli including adrenergic and angiotensin stimulation via subcutaneous pumps. Wild-type animals served as control for all experiments. Expression and localization of TRPV2 was investigated in wild-type cardiac samples. Changes in cardiac function were measured in vivo via echocardiography and invasive catheterization. Molecular changes, including protein and real-time PCR markers of hypertrophy, were measured in addition to myocyte size. TRPV2 is significantly upregulated in wild-type mice after TAC, though not in response to beta-adrenergic or angiotensin stimulation. TAC-induced stretch stimulus caused an upregulation of TRPV2 in the sarcolemmal membrane. The absence of functional TRPV2 resulted in significantly reduced left ventricular hypertrophy after TAC, though not in response to beta-adrenergic or angiotensin stimulation. The decreased development of hypertrophy was not associated with significant deterioration of cardiac function. We conclude that TRPV2 function, as a stretch-activated channel, regulates the development of cardiomyocyte hypertrophy in response to increased afterload.

  7. Assembly of a functional 3D primary cardiac construct using magnetic levitation

    Directory of Open Access Journals (Sweden)

    Glauco Souza

    2016-07-01

    Full Text Available Easily assembled organotypic co-cultures have long been sought in medical research. In vitro tissue constructs with faithful representation of in vivo tissue characteristics are highly desirable for screening and characteristic assessment of a variety of tissue types. Cardiac tissue analogs are particularly sought after due to the phenotypic degradation and difficulty of culture of primary cardiac myocytes. This study utilized magnetic nanoparticles and primary cardiac myocytes in order to levitate and culture multicellular cardiac aggregates (MCAs. Cells were isolated from 2 day old Sprague Dawley rat hearts and subsequently two groups were incubated with either C1: 33 µL nanoshell/million cells or C2: 50 µL nanoshell/million cells. Varying numbers of cells for each concentration were cultured in a magnetic field in a 24 well plate and observed over a period of 12 days. Constructs generally formed spherical structures. Masson’s trichrome staining of a construct shows the presence of extracellular matrix protein, indicating the presence of functional fibroblasts. Many constructs exhibited noticeable contraction after 4 days of culture and continued contracting noticeably past day 9 of culture. Noticeable contractility indicates the presence of functional primary cardiac myocytes in culture. Phenotypic conservation of cardiac cells was ascertained using IHC staining by α-actinin and collagen. CD31 and fibrinogen were probed in order to assess localization of fibroblasts and endothelial cells. The study verifies a protocol for the use of magnetic levitation in order to rapidly assemble 3D cardiac like tissue with phenotypic and functional stability.

  8. Galnt1 is required for normal heart valve development and cardiac function.

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    E Tian

    Full Text Available Congenital heart valve defects in humans occur in approximately 2% of live births and are a major source of compromised cardiac function. In this study we demonstrate that normal heart valve development and cardiac function are dependent upon Galnt1, the gene that encodes a member of the family of glycosyltransferases (GalNAc-Ts responsible for the initiation of mucin-type O-glycosylation. In the adult mouse, compromised cardiac function that mimics human congenital heart disease, including aortic and pulmonary valve stenosis and regurgitation; altered ejection fraction; and cardiac dilation, was observed in Galnt1 null animals. The underlying phenotype is aberrant valve formation caused by increased cell proliferation within the outflow tract cushion of developing hearts, which is first detected at developmental stage E11.5. Developing valves from Galnt1 deficient animals displayed reduced levels of the proteases ADAMTS1 and ADAMTS5, decreased cleavage of the proteoglycan versican and increased levels of other extracellular matrix proteins. We also observed increased BMP and MAPK signaling. Taken together, the ablation of Galnt1 appears to disrupt the formation/remodeling of the extracellular matrix and alters conserved signaling pathways that regulate cell proliferation. Our study provides insight into the role of this conserved protein modification in cardiac valve development and may represent a new model for idiopathic valve disease.

  9. CHIP Enhances Angiogenesis and Restores Cardiac Function After Infarction in Transgenic Mice

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    Cheng-Wei Xu

    2013-02-01

    Full Text Available Background: Carboxyl terminus of Hsp70-interacting protein (CHIP is a chaperone/ubiquitin ligase that plays an important role in stress-induced apoptosis. However, the effect of CHIP on angiogenesis, cardiac function and survival 4 weeks after myocardial infarction (MI remain to be explored. Methods: Wild-type (WT and transgenic mice (TG with cardiac-specific overexpression of CHIP were used for coronary artery ligation. The cardiac function, cardiomyocyte apoptosis, inflammation and angiogenesis were examined by echocardiography, histological analysis, real-time PCR and Western blot analysis. Results: At 4 weeks of after coronary artery ligation, echocardiography demonstrated that cardiac remodeling and dysfunction were prevented in TG mice compared with WT mice. The infarct size, cardiomyocyte apoptosis and inflammation were significantly reduced in TG mice than in WT mice. The survival rate after MI in TG mice was higher than that of WT mice. Furthermore, the levels of p53 protein was markedly decreased, but the expression of HIF-1α and VEGF, and the formation of capillary and arteriole after MI were significantly enhanced in TG mice compared with WT mice. Conclusion: We report the first in vivo evidence that CHIP enhances angiogenesis, inhibits inflammation, restores cardiac function, and improves survival at 4 weeks after MI. The present study expands on previous results and defines a novel mechanism. Thus, increased CHIP level may provide a novel therapeutic approach for left ventricular dysfunction after MI.

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

    DEFF Research Database (Denmark)

    Krag, Aleksander; Bendtsen, Flemming; Mortensen, Christian

    2010-01-01

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

  11. Influence of transposed stomach on cardiac function in patients with resected esophageal cancer.

    Science.gov (United States)

    Coral, R P; Constant-Neto, M; Silva, I S; Barros, S; Jawetz, J

    2004-01-01

    Although the use of the posterior mediastinum and the stomach as a reconstruction option after esophagectomy has wide acceptance, there are concerns about the potential cardiac impairment it could cause. We prospectively studied 27 patients regarding the function and the systolic diameter, diastolic diameter, shortening fraction, ejection fraction and the presence of extrinsic compression. The patients were studied preoperatively and between the 45th and 60th postoperative days. The parameters were still within normal clinical ranges. We concluded that this type of reconstruction does not harm the patients in terms of their cardiac function.

  12. Renal ischemia and reperfusion injury: influence of chorpromazine on renal function and lipid peroxidation Lesão de isquemia e reperfusão renal: influência da clorpromazina na função renal e na peroxidação lipídica

    Directory of Open Access Journals (Sweden)

    Silvio Tucci Junior

    2008-01-01

    Full Text Available PURPOSE: To evaluate the influence of chlorpromazine (CPZ on renal function and lipid peroxidation in a rat model of kidney ischemia/reperfusion injury. METHODS: Forty eight Wistar rats underwent a laparotomy for hilar clamping of left kidney with a bulldog clamp for 60 minutes followed by organ reperfusion and contralateral nephrectomy. Of these, 26 received 3mg/kg of CPZ intravenously 15 minutes before renal ischemia (G-E while the remaining 22 were used as ischemic control group (G-C. Eleven rats of G-E and 8 of G-C were followed for blood urea nitrogen and creatinine determinations before renal ischemia and at 1st, 4th and 7th postoperative days. Samplings of left renal tissue were obtained at 5 minutes (5 rats from each group and 24 hours (9 G-C and 10 of G-E of reperfusion for malondialdehy (MDA content determination. Controls of renal MDA content were determined in kidneys harvested from 6 additional normal rats. RESULTS: Acute renal failure occurred in all animals but levels of BUN and creatinine were significantly lower in G-E (p0.05 and returned near to normal levels 24 hours later. CONCLUSION: CPZ conferred partial protection of renal function to kidneys submitted to ischemia/reperfusion injury that seems to be not dependent on inhibition of lipid peroxidation.OBJETIVO: avaliar a influência da clorpromazina (CPZ na função renal e na peroxidação lipídica num modelo de lesão de isquemia/reperfusão renal em ratos. MÉTODOS: 48 ratos Wistar foram submetidos à laparotomia para clampamento da artéria renal esquerda durante 60 minutos, seguido da reperfusão e nefrectomia contralateral. Destes animais, 26 receberam 3 mg/kg de CPZ intravenosa 15 minutos antes da isquemia renal (G-E, sendo os 22 animais restantes utilizados como grupo controle isquêmico (G-C. Em 11 ratos do G-E e 8 do G-C foi feita a dosagem de uréia e creatinina sérica antes da isquemia renal e no 1º, 4º e 7º dia pós-operatório. Amostras de tecido do rim

  13. Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

    Science.gov (United States)

    Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2017-01-01

    Intracellular calcium [Ca2+]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca2+]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca2+]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca2+]i homeostasis, only DFP + NAC restored cardiac [Ca2+]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca2+]i homeostasis, leading to restored myocardial contractility in iron-overloaded rats. PMID:28287621

  14. Influence of granulocyte colony-stimulating factor on cardiac function in patients with acute myocardial infarction and leukopenia after revascularization

    Institute of Scientific and Technical Information of China (English)

    GUO Shi-zun; WANG Ning-fu; ZHOU Liang; YE Xian-hua; PAN Hao; TONG Guo-xin; YANG Jian-min; XU Jian

    2010-01-01

    Background Granulocyte colony-stimulating factor (G-CSF) seems to improve cardiac function and perfusion when used systemically through mobilization of stem cells into peripheral blood, but results of previous clinical trials remain controversial. This study was designed to investigate safety and efficacy of subcutaneous injection of G-CSF on left ventricular function in patients with impaired left ventricular function after ST-segment elevation myocardial infarction (STEMI).Methods Thirty-three patients (22 men; age, (68.5±6.1) years) with STEMI and with comorbidity of leukopenia were included after successful primary percutaneous coronary intervention within 12 hours after symptom onset. Patients were randomized into G-CSF group who received G-CSF (10 μg/kg of body weight, daily) for continuous 7 days and control group. Results of blood analyses, echocardiography and angiography were documented as well as possibly occurred adverse events.Results No severe adverse events occurred in both groups. Mean segmental wall thickening in infract segments increased significantly at 6-month follow up compared with baseline in both groups, but the longitudinal variation between two groups had no significant difference (P >0.05). The same change could also be found in longitudinal variation of wall motion score index of infarct segments (P >0.05). At 6-month follow-up, left ventricular end-diastolic volume of both groups increased to a greater extent, but there were no significant differences between the two groups when comparing the longitudinal variations (P >0.05). In both groups, left ventricular ejection fraction measured by echocardiography ameliorated significantly at 6-month follow-up (P 0.05). When pay attention to left ventricular ejection fraction measured by angiocardiography,difference of the longitudinal variation between groups was significant (P=0.046). Early diastolic mitral flow velocity deceleration time changed significantly at 6-month follow-up in both

  15. Time Course of Atrophic Remodeling: Effects of Exercise on Cardiac Morpology and Function

    Science.gov (United States)

    Scott, J. M.; Martin, D.; Caine, T.; Matz, T.; Ploutz-Snyder, L. L.

    2014-01-01

    Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. Exercise training is one intervention that has been shown to confer favorable improvements in LV mass and function during unloading. However, the format and intensity of exercise required to induce optimal cardiac improvements has not been investigated. PURPOSE: This randomized, controlled trial was designed to 1) comprehensively characterize the time course of unloading-induced morpho-functional remodeling, and 2) examine the effects of high intensity exercise training on cardiac structural and functional parameters during unloading. METHODS: Twenty six subjects completed 70 days of head down tilt bed rest (HDBR): 17 were randomized to exercise training (ExBR) and 9 remained sedentary. Exercise consisted of integrated high intensity, continuous, and resistance exercise. We assessed cardiac morphology (left ventricular mass; LVM) and function (speckle-tracking assessment of longitudinal, radial, and circumferential strain and twist) before (BR-2), during (BR7,21,31,70), and following (BR+0, +3) HDBR. Cardiorespiratory fitness (VO2max) was evaluated before (BR- 3), during (BR4,25,46,68) and following (BR+0) HDBR. RESULTS: Sedentary HDBR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain, and an increase in twist. ExBR mitigated decreases in LVM and function. Change in twist was significantly related to change in VO2max (R=0.68, premodeling.

  16. [Progress of studies on mechanisms of acupuncture underlying regulation of cardiac function via autonomic nervous system].

    Science.gov (United States)

    Wang, Ya-Li; Yu, Zhi; Xu, Bin

    2014-02-01

    Acupuncture therapy has been confirmed to be effective in treating cardiovascular diseases in clinical practice. Acupuncture-induced balance of the autonomic nervous system activities is one of its key mechanisms. In the present paper, the authors review progress of studies on acupuncture treatment of cardiovascular diseases from 1) regulating cardiac sympathetic-beta-adrenergic receptor activity and myocardial intracellular GTP-binding protein (Gs)-adenylylcyclase (AC)-cyclic adenosine monophosphate (cAMP)-protein kinase (PKA) signaling, and 2) balancing cardiac sympathetic and vagal nerve activities. Due to limited experimental conditions, in-depth studies about the mechanisms of acupuncture intervention underlying improvement of cardiovascular functions are relatively fewer up to now. Along with the further development of modern biology, the mechanism of acupuncture intervention underlying regulation of cardiac function via autonomic nerve system will be revealed in detail.

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Effects of interval and continuous exercise training on autonomic cardiac function in COPD patients.

    Science.gov (United States)

    Rodríguez, Diego A; Arbillaga, Ane; Barberan-Garcia, Anael; Ramirez-Sarmiento, Alba; Torralba, Yolanda; Vilaró, Jordi; Gimeno-Santos, Elena; Gea, Joaquim; Orozco-Levi, Mauricio; Roca, Josep; Marco, Ester

    2016-01-01

    Both interval (IT) and continuous (CT) exercise training results in an improvement of aerobic capacity in patients with chronic obstructive pulmonary disease (COPD); however, their effects on cardiac autonomic function remains unclear. The aim of our study was to evaluate the effect of a supervised CT vs IT on autonomic cardiac function in COPD patients. COPD patients were divided into two different groups according to training modality (IT or CT). Autonomic cardiac dysfunction (ACD) was defined as a heart rate recovery lower than 12 bpm heart rate after the first minute of maximal exercise (HRR1 ) and an abnormal chronotropic response (CR) to exercise (exercise training improve heart rate recovery and CR in COPD patients. These benefits could help to individualize exercise training. © 2014 John Wiley & Sons Ltd.

  19. Cardiac tamponade as an independent condition affecting the relationship between the plasma B-type natriuretic peptide levels and cardiac function.

    Science.gov (United States)

    Minai, Kosuke; Komukai, Kimiaki; Arase, Satoshi; Nagoshi, Tomohisa; Matsuo, Seiichiro; Ogawa, Kazuo; Kayama, Yosuke; Inada, Keiichi; Tanigawa, Shin-Ichi; Takemoto, Tomoyuki; Sekiyama, Hiroshi; Date, Taro; Ogawa, Takayuki; Taniguchi, Ikuo; Yoshimura, Michihiro

    2013-07-01

    Plasma B-type natriuretic peptide (BNP) is finely regulated by the cardiac function and several extracardiac factors. Therefore, the relationship between the plasma BNP levels and the severity of heart failure sometimes seems inconsistent. The purpose of the present study was to investigate the plasma BNP levels in patients with cardiac tamponade and their changes after pericardial drainage. This study included 14 patients with cardiac tamponade who underwent pericardiocentesis. The cardiac tamponade was due to malignant diseases in 13 patients and uremia in 1 patient. The plasma BNP levels were measured before and 24-48 h after drainage. Although the patients reported severe symptoms of heart failure, their plasma BNP levels were only 71.2 ± 11.1 pg/ml before drainage. After appropriate drainage, the plasma BNP levels increased to 186.0 ± 22.5 pg/ml, which was significantly higher than that before drainage (P = 0.0002). In patients with cardiac tamponade, the plasma BNP levels were low, probably because of impaired ventricular stretching, and the levels significantly increased in response to the primary condition after drainage. This study demonstrates an additional condition that affects the relationship between the plasma BNP levels and cardiac function. If inconsistency is seen in the relationship between the plasma BNP levels and clinical signs of heart failure, the presence of cardiac tamponade should therefore be considered.

  20. STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.

    Directory of Open Access Journals (Sweden)

    Nelson W Chong

    Full Text Available BACKGROUND: STARS (STriated muscle Activator of Rho Signaling is a sarcomeric protein expressed early in cardiac development that acts as an acute stress sensor for pathological remodeling. However the role of STARS in cardiac development and function is incompletely understood. Here, we investigated the role of STARS in heart development and function in the zebrafish model and in vitro. METHODOLOGY AND PRINCIPAL FINDINGS: Expression of zebrafish STARS (zSTARS first occurs in the somites by the 16 somite stage [17 hours post fertilization (hpf]. zSTARS is expressed in both chambers of the heart by 48 hpf, and also in the developing brain, jaw structures and pectoral fins. Morpholino-induced knockdown of zSTARS alters atrial and ventricular dimensions and decreases ventricular fractional shortening (measured by high-speed video microscopy, with pericardial edema and decreased or absent circulation [abnormal cardiac phenotypes in 126/164 (77% of morpholino-injected embryos vs. 0/152 (0% of control morpholino embryos]. Co-injection of zsrf (serum response factor mRNA rescues the cardiac phenotype of zSTARS knockdown, resulting in improved fractional shortening and ventricular end-diastolic dimensions. Ectopic over-expression of STARS in vitro activates the STARS proximal promoter, which contains a conserved SRF site. Chromatin immunoprecipitation demonstrates that SRF binds to this site in vivo and the SRF inhibitor CCG-1423 completely blocks STARS proximal reporter activity in H9c2 cells. CONCLUSIONS/SIGNIFICANCE: This study demonstrates for the first time that STARS deficiency severely disrupts cardiac development and function in vivo and revealed a novel STARS-SRF feed-forward autoregulatory loop that could play an essential role in STARS regulation and cardiac function.

  1. Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects?

    Science.gov (United States)

    Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Peterson, Lindsy M; Mai, Katherine; McHale, Quinn; Jenkins, Michael W; Linask, Kersti K; Rollins, Andrew M; Watanabe, Michiko

    2014-02-01

    Alcohol-induced congenital heart defects are frequently among the most life threatening and require surgical correction in newborns. The etiology of these defects, collectively known as fetal alcohol syndrome, has been the focus of much study, particularly involving cellular and molecular mechanisms. Few studies have addressed the influential role of altered cardiac function in early embryogenesis because of a lack of tools with the capability to assay tiny beating hearts. To overcome this gap in our understanding, we used optical coherence tomography (OCT), a nondestructive imaging modality capable of micrometer-scale resolution imaging, to rapidly and accurately map cardiovascular structure and hemodynamics in real time under physiological conditions. In this study, we exposed avian embryos to a single dose of alcohol/ethanol at gastrulation when the embryo is sensitive to the induction of birth defects. Late-stage hearts were analyzed using standard histological analysis with a focus on the atrio-ventricular valves. Early cardiac function was assayed using Doppler OCT, and structural analysis of the cardiac cushions was performed using OCT imaging. Our results indicated that ethanol-exposed embryos developed late-stage valvuloseptal defects. At early stages, they exhibited increased regurgitant flow and developed smaller atrio-ventricular cardiac cushions, compared with controls (uninjected and saline-injected embryos). The embryos also exhibited abnormal flexion/torsion of the body. Our evidence suggests that ethanol-induced alterations in early cardiac function have the potential to contribute to late-stage valve and septal defects, thus demonstrating that functional parameters may serve as early and sensitive gauges of cardiac normalcy and abnormalities.

  2. Cardiac mass and function decrease in bronchiolitis obliterans syndrome after lung transplantation: relationship to physical activity?

    Directory of Open Access Journals (Sweden)

    Jan B Hinrichs

    Full Text Available RATIONALE: There is a need to expand knowledge on cardio-pulmonary pathophysiology of bronchiolitis obliterans syndrome (BOS following lung transplantation (LTx. OBJECTIVES: The purpose of this study was to assess MRI-derived biventricular cardiac mass and function parameters as well as flow hemodynamics in patients with and without BOS after LTx. METHODS: Using 1.5T cardiac MRI, measurements of myocardial structure and function as well as measurements of flow in the main pulmonary artery and ascending aorta were performed in 56 lung transplant patients. The patients were dichotomized into two gender matched groups of comparable age range: one with BOS (BOS stages 1-3 and one without BOS (BOS 0/0p. MEASUREMENTS AND MAIN RESULTS: Significantly lower biventricular cardiac mass, right and left ventricular end-diastolic volume, biventricular stroke volume, flow hemodynamics and significant higher heart rate but preserved cardiac output were observed in patients with BOS 1-3 compared to the BOS 0/0p group (p < 0.05. In a stepwise logistic regression analysis global cardiac mass (p = 0.046 and days after LTx (p = 0.0001 remained independent parameters to predict BOS. In a second model an indicator for the physical fitness level - walking number of stairs - was added to the logistic regression model. In this second model, time after LTx (p = 0.005 and physical fitness (p = 0.01 remained independent predictors for BOS. CONCLUSION: The observed changes in biventricular cardiac mass and function as well as changes in hemodynamic flow parameters in the pulmonary trunk and ascending aorta are likely attributed to the physical fitness level of patients after lung transplantation, which in turn is strongly related to lung function.

  3. Changes to both cardiac metabolism and performance accompany acute reductions in functional capillary supply.

    Science.gov (United States)

    Hauton, David; Winter, James; Al-Shammari, Abdullah A; Gaffney, Eamonn A; Evans, Rhys D; Egginton, Stuart

    2015-04-01

    The relative importance of arteriole supply or ability to switch between substrates to preserve cardiac performance is currently unclear, but may be critically important in conditions such as diabetes. Metabolism of substrates was measured before and after infusion of polystyrene microspheres in the perfused working heart to mimic random capillary loss due to microvascular disease. The effect of acute loss of functional capillary supply on palmitate and glucose metabolism together with function was quantified, and theoretical tissue oxygen distribution calculated from histological samples and ventricular VO(2) estimated. Microsphere infusion led to a dose-dependent decrease in rate-pressure product (RPP) and oxygen consumption (Ppatent capillaries (P<0.001) and correspondingly increased the average capillary supply area by 40% (P<0.01). Calculated rates of oxygen consumption declined from 16.6±7.2 ml/100 ml/min to 12.4±9 ml/100 ml/min following arteriole occlusion, coupled with increases in size of regions of myocardial hypoxia (Control=22.0% vs. Microspheres=42.2%). Cardiac mechanical performance is very sensitive to arteriolar blockade, but metabolite switching from fatty acid to glucose utilisation may also support cardiac function in regions of declining PO(2). Preserving functional capillary supply may be critical for maintenance of cardiac function when metabolic flexibility is lost, as in diabetes. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

    Science.gov (United States)

    Luck, Christian; DeMarco, Vincent G.; Mahmood, Abuzar; Gavini, Madhavi P.

    2017-01-01

    Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes. PMID:28408970

  5. A review of heart chamber segmentation for structural and functional analysis using cardiac magnetic resonance imaging.

    Science.gov (United States)

    Peng, Peng; Lekadir, Karim; Gooya, Ali; Shao, Ling; Petersen, Steffen E; Frangi, Alejandro F

    2016-04-01

    Cardiovascular magnetic resonance (CMR) has become a key imaging modality in clinical cardiology practice due to its unique capabilities for non-invasive imaging of the cardiac chambers and great vessels. A wide range of CMR sequences have been developed to assess various aspects of cardiac structure and function, and significant advances have also been made in terms of imaging quality and acquisition times. A lot of research has been dedicated to the development of global and regional quantitative CMR indices that help the distinction between health and pathology. The goal of this review paper is to discuss the structural and functional CMR indices that have been proposed thus far for clinical assessment of the cardiac chambers. We include indices definitions, the requirements for the calculations, exemplar applications in cardiovascular diseases, and the corresponding normal ranges. Furthermore, we review the most recent state-of-the art techniques for the automatic segmentation of the cardiac boundaries, which are necessary for the calculation of the CMR indices. Finally, we provide a detailed discussion of the existing literature and of the future challenges that need to be addressed to enable a more robust and comprehensive assessment of the cardiac chambers in clinical practice.

  6. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Christian Luck

    2017-01-01

    Full Text Available Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1. However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL and diabetic obese Zucker (ZO rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes.

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

    Science.gov (United States)

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

    2013-11-15

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

  8. The alpha1-adrenergic receptors in cardiac hypertrophy: signaling mechanisms and functional implications.

    Science.gov (United States)

    Cotecchia, Susanna; Del Vescovo, Cosmo Damiano; Colella, Matilde; Caso, Stefania; Diviani, Dario

    2015-10-01

    Cardiac hypertrophy is a complex remodeling process of the heart induced by physiological or pathological stimuli resulting in increased cardiomyocyte size and myocardial mass. Whereas cardiac hypertrophy can be an adaptive mechanism to stressful conditions of the heart, prolonged hypertrophy can lead to heart failure which represents the primary cause of human morbidity and mortality. Among G protein-coupled receptors, the α1-adrenergic receptors (α1-ARs) play an important role in the development of cardiac hypertrophy as demonstrated by numerous studies in the past decades, both in primary cardiomyocyte cultures and genetically modified mice. The results of these studies have provided evidence of a large variety of α1-AR-induced signaling events contributing to the defining molecular and cellular features of cardiac hypertrophy. Recently, novel signaling mechanisms have been identified and new hypotheses have emerged concerning the functional role of the α1-adrenergic receptors in the heart. This review will summarize the main signaling pathways activated by the α1-AR in the heart and their functional implications in cardiac hypertrophy. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. ASSESSMENT OF SELECTED CARDIAC FUNCTIONS OF SPORTSPERSON OF VADODARA CITY

    Directory of Open Access Journals (Sweden)

    Rachit Joshi

    2012-02-01

    Full Text Available Aims and objective: Sports activity had always been an epitome of physical fitness activities. Multiple studies have shown that people, who maintain appropriate body fitness, using judicious regimens of exercise and weight control, have the additional benefit of prolonged life. The aim of this study was to find out and confirm the fact that regular exercise or sports activity have a beneficial effect on the various system of our body especially the cardiovascular system. Methodology: A comparative study was carried out at IPCL sports complex of Vadodara city in between the sportsperson and control persons using unpaired ‘t’ test for resting heart rate and blood pressure. They were subjected to hopping test: following which the maximum heart rate achieved and time taken for recovery to resting heart rate was measured. Results: As a result of our study we came to know that sportsperson have a significantly lower resting heart rate; lower maximum heart rate achieved and a reduced recovery time after hopping test than sedentary individuals. Conclusion: Our study reaffirms the fact that regular physical activity in any form slows the rate of decline with age of most of the physiological parameters that we associate with health and fitness especially by decline in basal heart rate and increased cardiac reserves. [National J of Med Res 2012; 2(1.000: 47-50

  10. A portable cadmium telluride multidetector probe for cardiac function monitoring

    CERN Document Server

    Arntz, Y; Dumitresco, B; Eclancher, B; Prat, V

    1999-01-01

    A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5x5x2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) wh...

  11. Dipropionylcysteine ethyl ester compensates for loss of citric acid cycle intermediates during post ischemia reperfusion in the pig heart.

    Science.gov (United States)

    Kasumov, Takhar; Sharma, Naveen; Huang, Hazel; Kombu, Rajan S; Cendrowski, Andrea; Stanley, William C; Brunengraber, Henri

    2009-12-01

    During reperfusion, following myocardial ischemia, uncompensated loss of citric acid cycle (CAC) intermediates may impair CAC flux and energy transduction. Propionate has an anaplerotic effect when converted to the CAC intermediate succinyl-CoA, and may improve contractile recovery during reperfusion. Antioxidant therapy with N-acetylcysteine decreases reperfusion injury. To synergize the antioxidant effects of cysteine with the anaplerotic effects of propionate, we synthesized a novel bi-functional compound, N,S-dipropionyl cysteine ethyl ester (DPNCE) and tested its anaplerotic and anti-oxidative capacity in anesthetized pigs. Ischemia was induced by a 70% reduction in left anterior descending coronary artery flow for one hour, followed by 1 h of reperfusion. After 30 min of ischemia and throughout reperfusion animals were treated with saline or intravenous DPNCE (1.5 mg x kg(-1) x min(-1), n = 8/group). Arterial concentrations and myocardial propionate, cysteine, free fatty acids, glucose and lactate uptakes, cardiac mechanical functions, myocardial content of CAC intermediates and oxidative stress were assessed. Ischemia resulted in reduction in myocardial tissue concentration of CAC intermediates. DPNCE treatment elevated arterial propionate and cysteine concentrations and myocardial propionate uptake, and increased myocardial concentrations of citrate, succinate, fumarate, and malate compared to saline treated animals. DPNCE treatment did not affect blood pressure or myocardial contractile function, but increased arterial free fatty acid concentration and myocardial fatty acid uptake. Arterial cysteine concentration was elevated by DPNCE, but there was negligible myocardial cysteine uptake, and no change in markers of oxidative stress. DPNCE elevated arterial cysteine and propionate, and increased myocardial concentration of CAC intermediates, but did not affect mechanical function or oxidative stress.

  12. Cleavage of serum response factor mediated by enteroviral protease 2A contributes to impaired cardiac function

    Institute of Scientific and Technical Information of China (English)

    Jerry Wong; Jingchun Zhang; Bobby Yanagawa; Zongshu Luo; Xiangsheng Yang; Jiang Chang; Bruce McManus; Honglin Luo

    2012-01-01

    Enteroviral infection can lead to dilated cardiomyopathy (DCM),which is a major cause of cardiovascular mortality worldwide.However,the pathogenetic mechanisms have not been fully elucidated.Serum response factor (SRF) is a cardiac-enriched transcription regulator controlling the expression of a variety of target genes,including those involved in the contractile apparatus and immediate early response,as well as microRNAs that silence the expression of cardiac regulatory factors.Knockout of SRF in the heart results in downregulation of cardiac contractile gene expression and development of DCM.The goal of this study is to understand the role of SRF in enterovirus-induced cardiac dysfunction and progression to DCM.Here we report that SRF is cleaved following enteroviral infection of mouse heart and cultured cardiomyocytes.This cleavage is accompanied by impaired cardiac function and downregulation of cardiac-specific contractile and regulatory genes.Further investigation by antibody epitope mapping and site-directed mutagenesis demonstrates that SRF cleavage occurs at the region of its transactivation domain through the action of virus-encoded protease 2A.Moreover,we demonstrate that cleavage of SRF dissociates its transactivation domain from DNA-binding domain,resulting in the disruption of SRF-mediated gene transactivation.In addition to loss of functional SRF,finally we report that the N-terminal fragment of SRF cleavage products can also act as a dominant-negative transcription factor,which likely competes with the native SRF for DNA binding.Our results suggest a mechanism by which virus infection impairs heart function and may offer a new therapeutic strategy to ameliorate myocardial damage and progression to DCM.

  13. Engineering a growth factor embedded nanofiber matrix niche to promote vascularization for functional cardiac regeneration.

    Science.gov (United States)

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

    2016-08-01

    The major loss of tissue extracellular matrix (ECM) after myocardial ischemia is a serious burden that gradually leads to heart failure. Due to lack of available treatment methods to restore the cardiac function, various research strategies have come up to treat the ischemic myocardium. However these have met with limited success due to the complexity of the cardiac tissue, which exhibits a nanofibrous collagenous matrix with spatio-temporal localization of a combination of growth factors. To mimic the topographical and chemical cues of the natural cardiac tissue, we have fabricated a growth factor embedded nanofibrous scaffold through electrospinning. In our previous work, we have reported a nanofibrous matrix made of PLCL and PEOz with an average diameter of 500 nm. The scaffold properties were specifically characterized in vitro for cardio-compatibility. In the present study, we have loaded dual growth factors VEGF and bFGF in the nanofiber matrix and investigated its suitability for cardiac tissue engineering. The encapsulation and release of dual growth factors from the matrix were studied using XPS and ELISA. Bioactivity of the loaded growth factors towards proliferation and migration of endothelial cells (HUVECs) was evaluated through MTS and Boyden chamber assays respectively. The efficiency of growth factors on the nanofibrous matrix to activate signaling molecules was studied in HUVECs through gene expression analysis. Preclinical evaluation of the growth factor embedded nanofibrous patch in a rabbit acute myocardial infarction (AMI) model was studied and cardiac function assessment was made through ECG and echocardiography. The evidence for angiogenesis in the patch secured regions was analyzed through histopathology and immunohistochemistry. Our results confirm the effectiveness of growth factor embedded nanofiber matrix in restoration of cardiac function after ischemia when compared to conventional patch material thereby exhibiting promise as a

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  15. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure

    NARCIS (Netherlands)

    Yin, Meimei; van der Horst, Iwan C. C.; van Melle, Joost P.; Qian, Cheng; van Gilst, Wiek H.; Sillje, Herman H. W.; de Boer, Rudolf A.

    2011-01-01

    Yin M, van der Horst IC, van Melle JP, Qian C, van Gilst WH, Sillje HH, de Boer RA. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol 301: H459-H468, 2011. First published May 13, 2011; doi:10.1152/ajpheart.00054.2011.-Metformin

  16. Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization

    NARCIS (Netherlands)

    Westenbrink, B. Daan; Lipsic, Erik; van der Meer, Peter; van der Harst, Pirn; Oeseburg, Hisko; Sarvaas, Gideon J. Du Marchie; Koster, Johan; Voors, Adriaan A.; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Schoemaker, Regien G.

    2007-01-01

    Aims Erythropoietin (EPO) improves cardiac function and induces neovascutarization in chronic heart failure (CHF), although the exact mechanism has not been elucidated. We studied the effects of EPO on homing and incorporation of endothelial progenitor cells (EPC) into the myocardial microvasculatur

  17. Sinus node function after cardiac surgery : is impairment specific for the maze procedure?

    NARCIS (Netherlands)

    Tuinenburg, AE; Van Gelder, IC; Van Den Berg, MP; Grandjean, JG; Tieleman, RG; Smit, AJ; Huet, RCG; Van Der Maaten, JMAA; Volkers, CP; Ebels, T; Crijns, HJGM

    2004-01-01

    Background: Maze surgery is a final solution for intractable atrial fibrillation (AF), but an adverse effect on postoperative sinus node function has been reported. Whether this also applies to other types of cardiac surgery is unclear. Methods: We assessed postoperative rhythm by means of repeated

  18. Early association of electrocardiogram alteration with infarct size and cardiac function after myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    陶则伟; 黄元伟; 夏强; 傅军; 赵志宏; 陆贤; BRUCEI.C.

    2004-01-01

    Objective:Myocardial infarction (MI) is the main cause of heart failure, but the relationship between the extent of MI and cardiac function has not been clearly determined.The present study was undertaken to investigate early changes in the electrocardiogram associated with infarct size and cardiac function after MI. Methods: MI was induced by ligating the left anterior descending coronary artery in rats. Electrocardiograms, echocardiographs and hemodynamic parameters were assessed and myocardial infarct size was measured from mid-transverse sections stained with Masson's trichrome. Results:The sum of pathological Q wave amplitudes was strongly correlated with myocardial infarct size (r=0.920, P<0.0001), left ventricular ejection fraction (r=-0.868, P<0.0001) and left ventricular end diastolic pressure (r=0.835, P<0.0004).Furthermore, there was close relationship between MI size and cardiac function as assessed by left ventricular ejection fraction (r=-0.913, P<0.0001) and left ventricular end diastolic pressure (r=0.893, P<0.0001).Conclusion: The sum of pathological Q wave amplitudes after MI can be used to estimate the extent of MI as well as cardiac function.

  19. Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    André Luiz Lisboa Cordeiro

    Full Text Available Abstract Introduction: Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. Objective: To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. Methods: This is a clinical randomized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia. Patients were divided into two groups: control group and training. Preoperatively, were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test. From the third postoperative day, the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge. Results: 50 patients, 27 (54% males were included, with a mean age of 56.7±13.9 years. After the analysis, the training group had significant increase in maximum inspiratory pressure (69.5±14.9 vs. 83.1±19.1 cmH2O, P=0.0073 and 6-minute walk test (422.4±102.8 vs. 502.4±112.8 m, P=0.0031. Conclusion: We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery.

  20. Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery

    Science.gov (United States)

    Cordeiro, André Luiz Lisboa; de Melo, Thiago Araújo; Neves, Daniela; Luna, Julianne; Esquivel, Mateus Souza; Guimarães, André Raimundo França; Borges, Daniel Lago; Petto, Jefferson

    2016-01-01

    Introduction Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. Objective To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. Methods This is a clinical randomized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia. Patients were divided into two groups: control group and training. Preoperatively, were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test. From the third postoperative day, the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge. Results 50 patients, 27 (54%) males were included, with a mean age of 56.7±13.9 years. After the analysis, the training group had significant increase in maximum inspiratory pressure (69.5±14.9 vs. 83.1±19.1 cmH2O, P=0.0073) and 6-minute walk test (422.4±102.8 vs. 502.4±112.8 m, P=0.0031). Conclusion We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery. PMID:27556313

  1. Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

    Science.gov (United States)

    Junqueira, Luiz Fernando, Jr.

    2008-01-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

  2. An Exploratory Study of Functional Status in Post Cardiac Arrest Survivors Discharged To Home

    Science.gov (United States)

    2005-08-01

    arrest. The physical functioning (PF) and mental health (MH) scales were relatively wholesome, being specific to medical or psychiatric disorders ...cardiac rehabilitation post myocardial infarction. Exclusion criteria for this sample included 1. The existence of cognitive inability, delusional ...illness, and monitor response to treatment. The MMSE has also been used as a research tool to screen for cognitive disorders in epidemiological studies

  3. Early association of electrocardiogram alteration with infarct size and cardiac function after myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    TAO Ze-wei (陶则伟); HUANG Yuan-wei (黄元伟); XIA Qiang (夏强); FU Jun (傅军); ZHAO Zhi-hong (赵志宏); LU Xian (陆贤); BRUCE I.C.

    2004-01-01

    Objective: Myocardial infarction (MI) is the main cause of heart failure, but the relationship between the extent of MI and cardiac function has not been clearly determined. The present study was undertaken to investigate early changes in the electrocardiogram associated with infarct size and cardiac function after MI. Methods: MI was induced by ligating the left anterior descending coronary artery in rats. Electrocardiograms, echocardiographs and hemodynamic parameters were assessed and myocardial infarct size was measured from mid-transverse sections stained with Masson's trichrome. Results: The sum of pathological Q wave amplitudes was strongly correlated with myocardial infarct size (r = 0.920, P < 0.0001), left ventricular ejection fraction (r = (0.868, P < 0.0001) and left ventricular end diastolic pressure (r = 0.835, P < 0.0004). Furthermore, there was close relationship between MI size and cardiac function as assessed by left ventricular ejection fraction (r = (0.913, P < 0.0001) and left ventricular end diastolic pressure (r = 0.893, P < 0.0001). Conclusion: The sum of pathological Q wave amplitudes after MI can be used to estimate the extent of MI as well as cardiac function.

  4. In utero dimethadione exposure causes postnatal disruption in cardiac structure and function in the rat.

    Science.gov (United States)

    Aasa, Kristiina L; Purssell, Elizabeth; Adams, Michael A; Ozolinš, Terence R S

    2014-12-01

    In utero exposure of rat embryos to dimethadione (DMO), the N-demethylated teratogenic metabolite of the anticonvulsant trimethadione, induces a high incidence of cardiac heart defects including ventricular septal defects (VSDs). The same exposure regimen also leads to in utero cardiac functional deficits, including bradycardia, dysrhythmia, and a reduction in cardiac output (CO) and ejection fraction that persist until parturition (10 days after the final dose). Despite a high rate of spontaneous postnatal VSD closure, we hypothesize that functional sequelae will persist into adulthood. Pregnant Sprague Dawley rats were administered six 300 mg/kg doses of DMO, one every 12 h in mid-pregnancy beginning on the evening of gestation day 8. Postnatal cardiac function was assessed in control (CTL) and DMO-exposed offspring using radiotelemetry and ultrasound at 3 and 11 months of age, respectively. Adult rats exposed to DMO in utero had an increased incidence of arrhythmia, elevated blood pressure and CO, greater left ventricular volume and elevated locomotor activity versus CTL. The mean arterial pressure of DMO-exposed rats was more sensitive to changes in dietary salt load compared with CTL. Importantly, most treated rats had functional deficits in the absence of a persistent structural defect. It was concluded that in utero DMO exposure causes cardiovascular deficits that persist into postnatal life in the rat, despite absence of visible structural anomalies. We speculate this is not unique to DMO, suggesting possible health implications for infants with unrecognized gestational chemical exposures.

  5. Value of plasma ADMA in predicting cardiac structure and function of patients with chronic kidney diseases

    Institute of Scientific and Technical Information of China (English)

    叶建华

    2012-01-01

    Objective To explore the predicting value of plasma asymmetric dimethylarginine (ADMA) in cardiac structure and function of patients with chronic kidney diseases(CKD). Methods A total of 100 CKD patients were enrolled in this cross-sectional study. According to staging of the

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing...

  7. Novel Measures of Volume Status and Cardiac Function in Traumatic Shock

    Science.gov (United States)

    2016-06-01

    Focused rapid echocardiographic evaluation versus vascular catheter-based assessment of cardiac output and function in critically ill trauma ...adequacy of resuscitation in patients with traumatic shock and (2) to determine the incidence, time course, and clinical relevance of trauma ...evaluation serially over time in a civilian model of military trauma . Upon closure of the study, only six patients were enrolled, so no association

  8. Effect of weight support exercise therapy on the cardiac function in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    Dong-Dong Jiao; Wen-Yu Zhang; Jing Xu; Guang-Jian Zhu; Jia Chen

    2016-01-01

    Objective:To explore the effect of weight support exercise therapy on the cardiac function and living quality in patients with chronic heart failure.Methods: A total of 75 patients with CHF were included in the study and randomized into the observation group (n=38) and the control group (n=37). the patients in the control group were given routine drug therapy. on the above basis, the patients in the observation group were given weight support exercise therapy for rehabilitation. six-month treatment was regarded as one course. the plasma BNP and aldosterone levels before and after treatment in the two groups were detected. the related cardiac function indicators in the two groups were compared. 6mwt and MHL were used to evaluate the exercise tolerance and living quality, respectively.Results:The comparison of plasma BNP and aldosterone levels, various cardiac function indicators, 6 min walking distance, and MHL score before treatment between the two groups was not statistically significant. BNP and aldosterone levels after treatment in the two groups were significantly reduced, and the reduced degree in the observation group was significantly greater than that in the control group. after treatment, HR, LVEDD, and MHL score were significantly reduced, LVEF, FS, and 6 min walking distance were significantly increased, and the comparison between the two groups was statistically significant.Conclusions:Weight support exercise therapy can significantly reduce the plasma BNP and aldosterone levels in CHF patients, improve the cardiac function, and enhance the exercise tolerance and living quality.

  9. Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

    Science.gov (United States)

    Junqueira, Luiz Fernando, Jr.

    2008-01-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

  10. Exercise improves cardiac function and attenuates insulin resistance in Dahl salt-sensitive rats.

    Science.gov (United States)

    Stevens, An L M; Ferferieva, Vesselina; Bito, Virginie; Wens, Inez; Verboven, Kenneth; Deluyker, Dorien; Voet, Annemie; Vanhoof, Joke; Dendale, Paul; Eijnde, Bert O

    2015-01-01

    The development of heart failure (HF) secondary to hypertension is a complex process related to a series of physiological and molecular factors including glucose dysregulation. The overall objective of this study was to investigate whether exercise training could improve cardiac function and insulin resistance in a rat model of hypertensive HF. Seven week old Dahl salt-sensitive rats received either 8% NaCl (n = 30) or 0.3% NaCl (n = 18) diet. After a 5-week diet, animals were randomly assigned to exercise training (treadmill running at 18 m/min, 5% inclination for 60 min, 5 days/week) or kept sedentary for 6 additional weeks. 2D echocardiography was used to calculate left ventricular (LV) dimensions, volumes and global functional parameters. LV global deformation parameters were measured with speckle tracking echocardiography. Insulin resistance was assessed using 1h oral glucose tolerance testing. High salt diet led to cardiac hypertrophy and HF, characterized by increased wall thicknesses and LV volumes as well as reduced deformation parameters. In addition, high salt diet was associated with the development of insulin resistance. Exercise training improved cardiac function, reduced the extent of interstitial fibrosis and reduced insulin levels 60 min post-glucose administration. Even if not fully reversed, exercise training in HF animals improved cardiac function and insulin resistance. Adjusted modalities of exercise training might offer new insights not only as a preventive strategy, but also as a treatment for HF patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Association of renal function with cardiac calcifications in older adults : the cardiovascular health study

    NARCIS (Netherlands)

    Asselbergs, Folkert W.; Mozaffarian, Dariush; Katz, Ronit; Kestenbaum, Bryan; Fried, Linda F.; Gottdiener, John S.; Shlipak, Michael G.; Siscovick, David S.

    2009-01-01

    Background. Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are highly prevalent in patients with end-stage renal disease. It is less well established whether milder kidney disease is associated with cardiac calcifications. We evaluated the relationships between renal function an

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

    Institute of Scientific and Technical Information of China (English)

    Guo-Dong Li; Jia-Yuan Yi; Shu-Yu Gao; Hong-Ping Liang; Yan-Qing Liu

    2016-01-01

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

  13. The impact of therapeutic hypothermia on neurological function and quality of life after cardiac arrest

    DEFF Research Database (Denmark)

    Bro-Jeppesen, John; Kjaergaard, Jesper; Horsted, Tina I;

    2008-01-01

    AIMS: To assess the impact of therapeutic hypothermia on cognitive function and quality of life in comatose survivors of out of Hospital Cardiac arrest (OHCA). METHODS: We prospectively studied comatose survivors of OHCA consecutively admitted in a 4-year period. Therapeutic hypothermia was imple...

  14. Effect of contractile protein alterations on cardiac myofilament function in human heart failure

    NARCIS (Netherlands)

    Narolska, N.A.

    2006-01-01

    The main objective of this thesis was to elucidate the effect of translational and post-translational alterations in contractile proteins occurring during heart failure on contractile function in human cardiac tissue. Isometric force and ATPase activity measurements were performed in skinned human

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

    NARCIS (Netherlands)

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

    2012-01-01

    BACKGROUND Loss-of-function sodium channelopathies manifest as a spectrum of diseases including Brugada syndrome (BrS) and cardiac conduction disease. OBJECTIVE To analyze the diagnostic and therapeutic aspects of these disorders in children. METHODS Patients aged 98th percentile for age). RESULTS:

  16. Cardiac and pulmonary function variability in Duchenne/Becker muscular dystrophy: an initial report.

    Science.gov (United States)

    Birnkrant, David J; Ashwath, Mahi Lakshmi; Noritz, Garey H; Merrill, Michelle C; Shah, Tushar A; Crowe, Carol A; Bahler, Robert C

    2010-09-01

    The Duchenne and Becker forms of muscular dystrophy are associated with dilated cardiomyopathy and are diseases in which pulmonary function peaks and then progressively declines. In this report, the authors quantify cardiopulmonary function variability among brothers. Brothers in 3 of 7 eligible sibships had discordant pulmonary function, with significant differences between the brothers' peak forced vital capacities and their vital capacities at last comparable age. There was no relationship between pulmonary and cardiac function among the siblings. The authors concluded that despite identical genetic mutations, cardiac and pulmonary function variability was common among brothers in their clinic with Duchenne or Becker muscular dystrophy. If confirmed by larger studies, these results have negative implications for the use of genetic testing to predict cardiopulmonary course and response to therapies in Duchenne or Becker muscular dystrophy.

  17. Performance of automated software in the assessment of segmental left ventricular function in cardiac CT: Comparison with cardiac magnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Rui [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Capital Medical University, Department of Radiology, Beijing Anzhen Hospital, Beijing (China); Meinel, Felix G. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Ludwig-Maximilians-University Hospital, Institute for Clinical Radiology, Munich (Germany); Schoepf, U.J. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Medical University of South Carolina, Division of Cardiology, Department of Medicine, Charleston, SC (United States); Canstein, Christian [Siemens Medical Solutions USA, Malvern, PA (United States); Spearman, James V. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); De Cecco, Carlo N. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); University of Rome ' ' Sapienza' ' , Departments of Radiological Sciences, Oncology and Pathology, Latina (Italy)

    2015-12-15

    To evaluate the accuracy, reliability and time saving potential of a novel cardiac CT (CCT)-based, automated software for the assessment of segmental left ventricular function compared to visual and manual quantitative assessment of CCT and cardiac magnetic resonance (CMR). Forty-seven patients with suspected or known coronary artery disease (CAD) were enrolled in the study. Wall thickening was calculated. Segmental LV wall motion was automatically calculated and shown as a colour-coded polar map. Processing time for each method was recorded. Mean wall thickness in both systolic and diastolic phases on polar map, CCT, and CMR was 9.2 ± 0.1 mm and 14.9 ± 0.2 mm, 8.9 ± 0.1 mm and 14.5 ± 0.1 mm, 8.3 ± 0.1 mm and 13.6 ± 0.1 mm, respectively. Mean wall thickening was 68.4 ± 1.5 %, 64.8 ± 1.4 % and 67.1 ± 1.4 %, respectively. Agreement for the assessment of LV wall motion between CCT, CMR and polar maps was good. Bland-Altman plots and ICC indicated good agreement between CCT, CMR and automated polar maps of the diastolic and systolic segmental wall thickness and thickening. The processing time using polar map was significantly decreased compared with CCT and CMR. Automated evaluation of segmental LV function with polar maps provides similar measurements to manual CCT and CMR evaluation, albeit with substantially reduced analysis time. (orig.)

  18. Healthy aging does not compromise the augmentation of cardiac function during heat stress.

    Science.gov (United States)

    Gagnon, Daniel; Romero, Steven A; Ngo, Hai; Sarma, Satyam; Cornwell, William K; Poh, Paula Y S; Stoller, Douglas; Levine, Benjamin D; Crandall, Craig G

    2016-10-01

    During heat stress, stroke volume is maintained in young adults despite reductions in cardiac filling pressures. This is achieved by a general augmentation of cardiac function, highlighted by a left and upward shift of the Frank-Starling relation. In contrast, healthy aged adults are unable to maintain stroke volume during heat stress. We hypothesized that this would be associated with a lack of shift in the Frank-Starling relation. Frank-Starling relations were examined in 11 aged [69 ± 4 (SD) yr, 4 men/7 women] and 12 young (26 ± 5 yr, 6 men/6 women) adults during normothermic and heat stress (1.5°C increase in core temperature) conditions. During heat stress, increases in cardiac output were attenuated in aged adults (+2.5 ± 0.3 (95% CI) vs. young: +4.5 ± 0.5 l/min, P < 0.01) because of an attenuated chronotropic response (+30 ± 4 vs. young: +42 ± 5 beats/min, P < 0.01). In contrast to our hypothesis, a leftward shift of the Frank-Starling relation maintained stroke volume during heat stress in aged adults (76 ± 8 vs. normothermic: 74 ± 8 ml, P = 0.38) despite reductions in cardiac filling pressure (6.6 ± 1.0 vs. normothermic: 8.9 ± 1.1 mmHg, P < 0.01). In a subset of participants, volume loading was used to return cardiac filling pressure during heat stress to normothermic values, which resulted in a greater stroke volume for a given cardiac filling pressure in both groups. These results demonstrate that the Frank-Starling relation shifts during heat stress in healthy young and aged adults, thereby preserving stroke volume despite reductions in cardiac filling pressures. Copyright © 2016 the American Physiological Society.

  19. Analysis of 2-d ultrasound cardiac strain imaging using joint probability density functions.

    Science.gov (United States)

    Ma, Chi; Varghese, Tomy

    2014-06-01

    Ultrasound frame rates play a key role for accurate cardiac deformation tracking. Insufficient frame rates lead to an increase in signal de-correlation artifacts resulting in erroneous displacement and strain estimation. Joint probability density distributions generated from estimated axial strain and its associated signal-to-noise ratio provide a useful approach to assess the minimum frame rate requirements. Previous reports have demonstrated that bi-modal distributions in the joint probability density indicate inaccurate strain estimation over a cardiac cycle. In this study, we utilize similar analysis to evaluate a 2-D multi-level displacement tracking and strain estimation algorithm for cardiac strain imaging. The effect of different frame rates, final kernel dimensions and a comparison of radio frequency and envelope based processing are evaluated using echo signals derived from a 3-D finite element cardiac model and five healthy volunteers. Cardiac simulation model analysis demonstrates that the minimum frame rates required to obtain accurate joint probability distributions for the signal-to-noise ratio and strain, for a final kernel dimension of 1 λ by 3 A-lines, was around 42 Hz for radio frequency signals. On the other hand, even a frame rate of 250 Hz with envelope signals did not replicate the ideal joint probability distribution. For the volunteer study, clinical data was acquired only at a 34 Hz frame rate, which appears to be sufficient for radio frequency analysis. We also show that an increase in the final kernel dimensions significantly affect the strain probability distribution and joint probability density function generated, with a smaller effect on the variation in the accumulated mean strain estimated over a cardiac cycle. Our results demonstrate that radio frequency frame rates currently achievable on clinical cardiac ultrasound systems are sufficient for accurate analysis of the strain probability distribution, when a multi-level 2-D

  20. Improved cardiac function and exercise capacity following correction of pectus excavatum

    DEFF Research Database (Denmark)

    Sørensen, Marie Maagaard; Heiberg, Johan

    2016-01-01

    no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions......, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac function should be integrated in the clinical assessment of patients with PE....

  1. Fusion of structural and functional cardiac magnetic resonance imaging data for studying ventricular fibrillation.

    Science.gov (United States)

    Magtibay, K; Beheshti, M; Foomany, F H; Balasundaram, K; Masse, S; Lai, P; Asta, J; Zamiri, N; Jaffray, D A; Nanthakumar, K; Krishnan, S; Umapathy, K

    2014-01-01

    Magnetic Resonance Imaging (MRI) techniques such as Current Density Imaging (CDI) and Diffusion Tensor Imaging (DTI) provide a complementing set of imaging data that can describe both the functional and structural states of biological tissues. This paper presents a Joint Independent Component Analysis (jICA) based fusion approach which can be utilized to fuse CDI and DTI data to quantify the differences between two cardiac states: Ventricular Fibrillation (VF) and Asystolic/Normal (AS/NM). Such an approach could lead to a better insight on the mechanism of VF. Fusing CDI and DTI data from 8 data sets from 6 beating porcine hearts, in effect, detects the differences between two cardiac states, qualitatively and quantitatively. This initial study demonstrates the applicability of MRI-based imaging techniques and jICA-based fusion approach in studying cardiac arrhythmias.

  2. Maturation status of sarcomere structure and function in human iPSC-derived cardiac myocytes.

    Science.gov (United States)

    Bedada, Fikru B; Wheelwright, Matthew; Metzger, Joseph M

    2016-07-01

    Human heart failure due to myocardial infarction is a major health concern. The paucity of organs for transplantation limits curative approaches for the diseased and failing adult heart. Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) have the potential to provide a long-term, viable, regenerative-medicine alternative. Significant progress has been made with regard to efficient cardiac myocyte generation from hiPSCs. However, directing hiPSC-CMs to acquire the physiological structure, gene expression profile and function akin to mature cardiac tissue remains a major obstacle. Thus, hiPSC-CMs have several hurdles to overcome before they find their way into translational medicine. In this review, we address the progress that has been made, the void in knowledge and the challenges that remain. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  3. MT1-MMP-dependent remodeling of cardiac extracellular matrix structure and function following myocardial infarction.

    Science.gov (United States)

    Koenig, Gerald C; Rowe, R Grant; Day, Sharlene M; Sabeh, Farideh; Atkinson, Jeffrey J; Cooke, Kenneth R; Weiss, Stephen J

    2012-05-01

    The myocardial extracellular matrix (ECM), an interwoven meshwork of proteins, glycoproteins, proteoglycans, and glycosaminoglycans that is dominated by polymeric fibrils of type I collagen, serves as the mechanical scaffold on which myocytes are arrayed for coordinated and synergistic force transduction. Following ischemic injury, cardiac ECM remodeling is initiated via localized proteolysis, the bulk of which has been assigned to matrix metalloproteinase (MMP) family members. Nevertheless, the key effector(s) of myocardial type I collagenolysis both in vitro and in vivo have remained unidentified. In this study, using cardiac explants from mice deficient in each of the major type I collagenolytic MMPs, including MMP-13, MMP-8, MMP-2, MMP-9, or MT1-MMP, we identify the membrane-anchored MMP, MT1-MMP, as the dominant collagenase that is operative within myocardial tissues in vitro. Extending these observations to an in vivo setting, mice heterozygous for an MT1-MMP-null allele display a distinct survival advantage and retain myocardial function relative to wild-type littermates in an experimental model of myocardial infarction, effects associated with preservation of the myocardial type I collagen network as a consequence of the decreased collagenolytic potential of cardiac fibroblasts. This study identifies MT1-MMP as a key MMP responsible for effecting postinfarction cardiac ECM remodeling and cardiac dysfunction.

  4. The role of sirtuins in mitochondrial function and doxorubicin-induced cardiac dysfunction.

    Science.gov (United States)

    Dolinsky, Vernon W

    2017-08-28

    Anthracycline chemotherapeutics such as doxorubicin continue to be important treatments for many cancers. Through improved screening and therapy, more patients are surviving and living longer after the diagnosis of their cancer. However, anthracyclines are associated with both short- and long-term cardiotoxic effects. Doxorubicin-induced mitochondrial dysfunction is a central mechanism in the cardiotoxic effects of doxorubicin that contributes to impaired cardiac energy levels, increased reactive oxygen species production, cardiomyocyte apoptosis and the decline in cardiac function. Sirtuins are protein deacetylases that are activated by low energy levels and stimulate energy production through their activation of transcription factors and enzymatic regulators of cardiac energy metabolism. In addition, sirtuins activate oxidative stress resistance pathways. SIRT1 and SIRT3 are expressed at high levels in the cardiomyocyte. This review examines the function of sirtuins in the regulation of cardiac mitochondrial function, with a focus on their role in heart failure and an emphasis on their effects on doxorubicin-induced cardiotoxicity. We discuss the potential for sirtuin activation in combination with anthracycline chemotherapy in order to mitigate its cardiotoxic side-effects without reducing the antineoplastic activity of anthracyclines.

  5. RNA splicing regulated by RBFOX1 is essential for cardiac function in zebrafish.

    Science.gov (United States)

    Frese, Karen S; Meder, Benjamin; Keller, Andreas; Just, Steffen; Haas, Jan; Vogel, Britta; Fischer, Simon; Backes, Christina; Matzas, Mark; Köhler, Doreen; Benes, Vladimir; Katus, Hugo A; Rottbauer, Wolfgang

    2015-08-15

    Alternative splicing is one of the major mechanisms through which the proteomic and functional diversity of eukaryotes is achieved. However, the complex nature of the splicing machinery, its associated splicing regulators and the functional implications of alternatively spliced transcripts are only poorly understood. Here, we investigated the functional role of the splicing regulator rbfox1 in vivo using the zebrafish as a model system. We found that loss of rbfox1 led to progressive cardiac contractile dysfunction and heart failure. By using deep-transcriptome sequencing and quantitative real-time PCR, we show that depletion of rbfox1 in zebrafish results in an altered isoform expression of several crucial target genes, such as actn3a and hug. This study underlines that tightly regulated splicing is necessary for unconstrained cardiac function and renders the splicing regulator rbfox1 an interesting target for investigation in human heart failure and cardiomyopathy.

  6. Proteção da recuperação funcional do miocárdio pelo omeprazol após isquemia-reperfusão em corações isolados de ratos Myocardium functional recovery protection by omeprazole after ischemia-reperfusion in isolated rat hearts

    Directory of Open Access Journals (Sweden)

    Otoni Moreira Gomes

    2010-09-01

    ischemia period induction. The following parameters were registered after the stabilization period (t0, and after the reperfusion period (t30: heart rate (HR, coronary flow (CoF, systolic pressure (SP, +dP/dt and -dP/dt. The Kruskal-Wallis test (P0.05 between groups among HR and CoF values. Differences (P<0.05 occurred between groups, I e II after the reperfusion period (t30 regarding systolic pressure reduced for 28.0±3.6% in the control group GI and for 79.0±5.9% in GII; The +dP/dtmax declined to be only 31.0±5.6% in GI, preserving 99.4±11.2% values in GII (P<0.05. The t30 -dP/dtmax values were GI 26.0±7.3% and GII 82.0±2.2% (P<0.05. CONCLUSION: The omeprazole administration before ischemia induction significantly protected the myocardium function recovery.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui; Wang, Lin; Song, Li; Zhang, Yan-Wan; Ye, Jue; Xu, Rui-Xia; Shi, Na; Meng, Xian-Min [Core Laboratory, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

    2013-02-01

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

  8. [PHARMACOLOGICAL CARDIOPROTECTION DURING REPERFUSION OF ISOLATED HEART].

    Science.gov (United States)

    Grigor'ev, E V; Toropova, Ya G; Plotnikov, G P; Krutitskiy, S S; Shukevich, D L; Salmin, V V; Golovkin, A S

    2015-01-01

    To study the contractile function, the degree of damage and regional myocardial metabolism in the isolated rat heart model subjected to cardioplegic stop and reperfusion under the protection of levosimendan. The study was performed on isolated rat hearts Wistar (group using "Custodiol" vs group using "Custodiol" + "Levosimendan". We assessed the extent of myocardial damage (in terms of markers of myocardial necrosis), the contractile function of the myocardium (coronary flow, heart rate, left ventricular pressure), the dynamics of redox processes during reperfusion with a parallel study of histology of the myocardium. We found a presence of cardioprotective effect of levosimendan in respect of the isolated heart in the reperfusion period of cardioplegic ischemia. The effect related to reducing the emission of reperfusion enzyme markers of myocardial damage, reducing the severity of pathological changes in the myocardium and reducing the intensity of free radical reactions in the myocardium. Cardioprotection with levosimendan reduces the severity of free radical attack the isolated heart, reduces the severity of damage to cardiomyocytes and preserves the contractile activity of the myocardium during reperfusion due to the effect of postconditioning.

  9. Sildenafil citrate (viagra) induces cardioprotective effects after ischemia/reperfusion injury in infant rabbits.

    Science.gov (United States)

    Bremer, Yvonne A; Salloum, Fadi; Ockaili, Ramzi; Chou, Eric; Moskowitz, William B; Kukreja, Rakesh C

    2005-01-01

    Infants undergoing surgery for congenital heart disease are at risk for myocardial ischemia during cardiopulmonary bypass, circulatory arrest, or low-flow states. The purpose of this study was to demonstrate the effects of sildenafil, a selective phosphodiesterase-5 (PDE-5) inhibitor on myocardial functional improvement and infarct size reduction during ischemia/reperfusion injury in infant rabbits. Infant rabbits (aged 8 wk) were treated with sildenafil citrate (0.7 mg/kg i.v.) or normal saline 30 min before sustained ischemia for 30 min and reperfusion for 3 h. Transesophageal echocardiography (TEE) was used to assess left ventricular cardiac output (LVCO) and aortic velocity time integral (VTI). After ischemia/reperfusion, risk area was demarcated by Evan's blue dye and infarct size determined by computer morphometry of triphenyltetrazolium chloride-stained sections. The sildenafil-treated group had preservation and elevation in LVCO (143% of baseline, p sildenafil group compared with controls (n = 6/group, p sildenafil-treated group had significant reduction in infarct size (15.5 +/- 1.2 versus 33 +/- 2.3 in the saline group, % risk area, mean +/- SEM, n = 10-15/group, p sildenafil citrate promotes myocardial protection in infant rabbits as evidenced by postischemic preservation and elevation in LVCO and aortic VTI and reduction in infarct size.

  10. Cardiac Function Evaluation Analyzing Spectral Components due to the Consumption of Energy Drinks

    Directory of Open Access Journals (Sweden)

    Md. Bashir Uddin

    2014-05-01

    Full Text Available The aim of this study is to investigate the effect of energy drinks consumption on cardiac function of human being by analyzing the spectral components of pulse and ECG of several healthy people. Using pulse transducer connected with MP36 (Biopac, USA data acquisition unit, pulse recordings were performed. With electrode lead set connected to the same MP36 data acquisition unit, ECG recordings were also performed. At before and after the consumption of energy drinks available in Bangladesh, pulse and ECG recordings as well as analysis were performed with Biopac software. After having energy drinks, the spectral components such as power of spectral density and amplitude of fast Fourier transform of pulse signal decreased about 47.5 and 37%, respectively. In case of ECG signal, the spectral components such as power of spectral density and amplitude of fast Fourier transform increased about 17 and 7.5% within a short interval about 0-20 min, then effective decrements about 10 and 18.5%, respectively started for long duration. Analyzing spectral parameters, the findings highlight the adverse impacts on cardiac function which may cause cardiac abnormality as well as severe cardiac disease due to the regular consumption of energy drinks.

  11. Docetaxel does not impair cardiac autonomic function in breast cancer patients previously treated with anthracyclines.

    Science.gov (United States)

    Ekholm, Eeva; Rantanen, Virpi; Syvänen, Kari; Jalonen, Jarmo; Antila, Kari; Salminen, Eeva

    2002-04-01

    The effects of docetaxel treatment on autonomic cardiac function was studied with 24-h ECG recordings in breast cancer patients pretreated with anthracyclines. Twenty-four women were evaluated before docetaxel treatment and after 3-4 courses of docetaxel 100 mg/m(2). The heart rate, cardiac extrasystoles and heart rate variability (HRV) in both the time and frequency domain were assessed from 24-h ECG recordings. The acute effects of docetaxel were calculated from 1-h recordings immediately prior to, during and after infusion. Long-term effects were evaluated from 24-h recordings performed before treatment and after 3-4 courses of docetaxel. There was no increase in the number of cardiac extrasystoles during docetaxel infusion. The number of ventricular extrasystoles decreased from 14 (23) to 7 (14) during and 5 (10) after the first infusion (p=0.02). The heart rate, HRV and extrasystoles were similar before and after 3-4 courses of docetaxel. The treatment did not abolish circadian variability of the heart rate. Docetaxel did not deteriorate autonomic cardiac function. In conclusion, our findings suggest that docetaxel does not have harmful cumulative effects on autonomic control of the heart and is therefore unlikely to be cardiotoxic.

  12. Cardiac contraction and calcium transport function aftersevere burn injury in rats

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To examine the function change of myocardial calcium transports and determined what role the change plays in cardiac dysfunction after severe burn injury in rats. Methods: The contraction and relaxation properties of the left ventricle (LV) were studied in the isolated hearts preparations of Wistar rats at 3, 8, and 24 h after a 30%TBSA (total body surface area) full-thickness burn. The calcium transport function of the sarcoplasmic reticulum (SR) was measured by the millipore filtration technique. Results: The maximal rate of LV pressure (± dp/dtmax) of the burn group was significantly lower than that of the control group (P < 0.01). In addition, the calciumdependent ATPase activity and the coupling ratio of SR were also markedly depressed. Conclusions: It indicates that the decrease in the SR calcium transport function is one of the important mechanisms for the cardiac contractile dysfunction after severe burn injury.

  13. Improved cardiac function and exercise capacity following correction of pectus excavatum: a review of current literature.

    Science.gov (United States)

    Maagaard, Marie; Heiberg, Johan

    2016-09-01

    Patients with pectus excavatum (PE) often describe improvements in exercise stamina following corrective surgery. Studies have investigated the surgical effect on physiological parameters; still, no consensus has yet been reached. Therefore, the aim of this literature review was to describe the cardiac outcome after surgical correction, both at rest and during exercise. In February 2016, a detailed search of the databases PubMed, Medline, and EMBASE was performed. We assessed clinical studies that described cardiac outcomes both before and after surgical correction of PE. We only included studies reporting either pre-defined echocardiographic or exercise test parameters. No exclusion criteria or statistical analyses were applied. Twenty-one full-text articles, published between 1972 and 2016, were selected, with cohort-ranges of 3-168 patients, mean age-ranges of 5-33 years, and mean follow-up-ranges from immediately to 4 years after surgery. Twelve studies described resting cardiac parameters. Four studies measured cardiac output, where one described 36% immediate increase after surgery, one reported 15% increase after Nuss-bar removal and two found no difference. Three studies demonstrated improvement in mean stroke volume ranges of 22-34% and two studies found no difference. Fifteen studies investigated exercise capacity, with 11 considering peak O2 pr. kg, where five studies demonstrated improvements with the mean ranging from 8% to 15% after surgery, five studies demonstrated no difference, and one saw a decrease of 19% 3 months after Nuss-bar implantation. A measurable increase in exercise capacity exists following surgery, which may be caused by multiple factors. This may be owed to the relief of compressed cardiac chambers with the increased anterior-posterior thoracic dimensions, which could facilitate an improved filling of the heart. With these results, the positive physiological impact of the surgery is emphasized and the potential gain in cardiac

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

    Science.gov (United States)

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

    2012-12-01

    Loss-of-function sodium channelopathies manifest as a spectrum of diseases including Brugada syndrome (BrS) and cardiac conduction disease. To analyze the diagnostic and therapeutic aspects of these disorders in children. Patients aged ≤ 16 years with genetically confirmed loss-of-function sodium channelopathies (SCN5A mutation), presenting with cardiac symptoms, positive family history, and/or abnormal electrocardiogram (ECG), were included. Abnormal ECG consisted of type 1 BrS ECG and/or prolonged conduction intervals (PR interval/QRS duration > 98th percentile for age). Among the cohort (n = 33, age 6 ± 5 years, 58% male subjects, 30% probands), 14 (42%) patients were symptomatic, presenting with syncope (n = 5), palpitations (n = 1), supraventricular arrhythmias (n = 3), aborted cardiac arrest (n = 3), and sudden cardiac death (n = 2). Heart rate was 91 ± 26 beats/min, PR interval 168 ± 35 ms, QRS duration 112 ± 20 ms, and heart-rate corrected QT interval 409 ± 26 ms. Conduction intervals were prolonged in 28 (85%) patients; 6 of these patients also had spontaneous type 1 BrS ECG. Eight fever-associated events occurred in 6 patients; 2 of these were vaccination-related fever episodes. Treatment included aggressive antipyretics during fever in all patients; antiarrhythmic treatment included implantable cardioverter-defibrillator (n = 4), pacemaker (n = 2), and beta-blockers, either alone (n = 3) or in combination with device (n = 2). During follow-up (4 ± 4 years), 2 previously symptomatic patients had monomorphic ventricular tachycardia; there were no deaths. Diagnosis of loss-of-function sodium channelopathies in children relies on cardiac symptoms, family history, and ECG. Fever and vaccination are potential arrhythmia triggers; conduction delay is the commonest finding on ECG. Beta-blockers have a role in preventing tachycardia-induced arrhythmias; implantable cardioverter-defibrillator should probably be reserved for severe cases. Copyright © 2012

  15. Sexually dimorphic adaptation of cardiac function: roles of epoxyeicosatrienoic acid and peroxisome proliferator-activated receptors.

    Science.gov (United States)

    Qin, Jun; Le, Yicong; Froogh, Ghezal; Kandhi, Sharath; Jiang, Houli; Luo, Meng; Sun, Dong; Huang, An

    2016-06-01

    Epoxyeicosatrienoic acids (EETs) are cardioprotective mediators metabolized by soluble epoxide hydrolase (sEH) to form corresponding diols (DHETs). As a sex-susceptible target, sEH is involved in the sexually dimorphic regulation of cardiovascular function. Thus, we hypothesized that the female sex favors EET-mediated potentiation of cardiac function via downregulation of sEH expression, followed by upregulation of peroxisome proliferator-activated receptors (PPARs). Hearts were isolated from male (M) and female (F) wild-type (WT) and sEH-KO mice, and perfused with constant flow at different preloads. Basal coronary flow required to maintain the perfusion pressure at 100 mmHg was significantly greater in females than males, and sEH-KO than WT mice. All hearts displayed a dose-dependent decrease in coronary resistance and increase in cardiac contractility, represented as developed tension in response to increases in preload. These responses were also significantly greater in females than males, and sEH-KO than WT 14,15-EEZE abolished the sex-induced (F vs. M) and transgenic model-dependent (KO vs. WT) differences in the cardiac contractility, confirming an EET-driven response. Compared with M-WT controls, F-WT hearts expressed downregulation of sEH, associated with increased EETs and reduced DHETs, a pattern comparable to that observed in sEH-KO hearts. Coincidentally, F-WT and sEH-KO hearts exhibited increased PPARα expression, but comparable expression of eNOS, PPARβ, and EET synthases. In conclusion, female-specific downregulation of sEH initiates an EET-dependent adaptation of cardiac function, characterized by increased coronary flow via reduction in vascular resistance, and promotion of cardiac contractility, a response that could be further intensified by PPARα. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. Acidic infusion in early reperfusion affects the activity of antioxidant enzymes in postischemic isolated rat heart.

    Science.gov (United States)

    Penna, Claudia; Perrelli, Maria-Giulia; Tullio, Francesca; Angotti, Carmelina; Pagliaro, Pasquale

    2013-07-01

    Acidic perfusion (AP) performed at the onset of reperfusion (i.e., acid postconditioning) is cardioprotective. We investigated the effect of AP on postischemic cardiac function and on the activity of endogenous superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase. The role of exogenous CAT or SOD on AP cardioprotection was also investigated. Phosphorylation of redox-sensitive survival kinases (protein kinase C [PKC] ε and extracellular signal-regulated kinase [ERK] 1/2) was also checked. Isolated rat hearts underwent ischemia and reperfusion (I/R) for 30 and 120 min, respectively. AP was obtained by lowering [HCO3(-)] in the perfusion buffer. Infarct size and left ventricular pressure were measured. Protocols include I/R only, I/R plus acidic perfusion in early reperfusion (I/R + AP), and I/R plus AP and CAT (I/R + AP + CAT) or SOD (I/R + AP + SOD). I/R + SOD and I/R + CAT additional hearts served as controls. AP and/or antioxidants were given in the initial 3 min of reperfusion. Enzyme activities were studied in postischemic phase (seventh minute of reperfusion) in I/R or I/R + AP and Sham (buffer-perfused) hearts. AP with (I/R + AP + CAT or I/R + AP + SOD) or without (I/R + AP) antioxidant enzymes resulted in a larger reduction of infarct size compared with I/R, I/R + SOD, or I/R + CAT. Compared with I/R, the postischemic systolic and diastolic recoveries of the cardiac function were markedly improved by the addition of AP and a lesser extent by AP + SOD or AP + CAT. AP increased the postischemic activity of CAT and lowered that of SOD and glutathione peroxidase compared with I/R only. Also, the phosphorylation and activity of ERK1/2 and PKCε were increased by AP. Acid postconditioning affects the activity of endogenous antioxidant enzymes, activates ERK1/2-PKCε pathways, and protects against myocardial I/R injury. The combination of AP and exogenous SOD or CAT still provides cardioprotection. It is likely that intracellular (not

  17. Subject specific BOLD fMRI respiratory and cardiac response functions obtained from global signal.

    Science.gov (United States)

    Falahpour, Maryam; Refai, Hazem; Bodurka, Jerzy

    2013-05-15

    Subtle changes in either breathing pattern or cardiac pulse rate alter blood oxygen level dependent functional magnetic resonance imaging signal (BOLD fMRI). This is problematic because such fluctuations could possibly not be related to underlying neuronal activations of interest but instead the source of physiological noise. Several methods have been proposed to eliminate physiological noise in BOLD fMRI data. One such method is to derive a template based on average multi-subject data for respiratory response function (RRF) and cardiac response function (CRF) by simultaneously utilizing an external recording of cardiac and respiratory waveforms with the fMRI. Standard templates can then be used to model, map, and remove respiration and cardiac fluctuations from fMRI data. Utilizing these does not, however, account for intra-subject variations in physiological response. Thus, performing a more individualized approach for single subject physiological noise correction becomes more desirable, especially for clinical purposes. Here we propose a novel approach that employs subject-specific RRF and CRF response functions obtained from the whole brain or brain tissue-specific global signals (GS). Averaging multiple voxels in global signal computation ensures physiological noise dominance over thermal and system noise in even high-spatial-resolution fMRI data, making the GS suitable for deriving robust estimations of both RRF and CRF for individual subjects. Using these individualized response functions instead of standard templates based on multi-subject averages judiciously removes physiological noise from the data, assuming that there is minimal neuronal contribution in the derived individualized filters. Subject-specific physiological response functions obtained from the GS better maps individuals' physiological characteristics.

  18. The cardioprotective effect of brief acidic reperfusion after ischemia in perfused rat hearts is not mimicked by inhibition of the Na+/H+ exchanger NHE1

    DEFF Research Database (Denmark)

    Andersen, Ann-Dorit; Bentzen, Bo Hjorth; Salling, H.

    2011-01-01

    Ischemic postconditioning (PostC), i.e. brief ischemia-reperfusion cycles before full reperfusion, is protective against cardiac ischemia/reperfusion (I/R) injury. Inhibition of the Na(+)/H(+) exchanger NHE1 and delayed intracellular pH-normalization have been proposed to underlie protection...

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

    Science.gov (United States)

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

    2013-02-01

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

  20. Ultrasonographic and histological evaluation of the effects of long-term carotid catheterization on cardiac function in NMRI mice

    DEFF Research Database (Denmark)

    Teilmann, Anne C; Thomsen, Morten B; Ihms, Elizabeth A

    2017-01-01

    weights were compared between groups. No effects on echocardiography parameters, histology, body weights or cardiac weights could be found between groups. In the present study, implantation of a carotid catheter with catheter tip placement in the proximal brachiocephalic trunk had minimal influence...... to the small body size of the mouse, a catheter tends to occupy a great part of even the larger vessel lumens, and this may increase vascular resistance with potential pathophysiological impacts on the heart. The present study compared cardiac function of catheterized mice, with catheter tip placement...... on cardiac and aortic physiology and did not induce significant cardiac changes....

  1. Clinical characteristics and vital and functional prognosis of out-of-hospital cardiac arrest survivors admitted to five cardiac intensive care units.

    Science.gov (United States)

    Loma-Osorio, Pablo; Aboal, Jaime; Sanz, Maria; Caballero, Ángel; Vila, Montserrat; Lorente, Victoria; Sánchez-Salado, José Carlos; Sionis, Alessandro; Curós, Antoni; Lidón, Rosa-Maria

    2013-08-01

    Survivors of out-of-hospital cardiac arrest constitute an increasing patient population in cardiac intensive care units. Our aim was to characterize these patients and determine their vital and functional prognosis in accordance with the latest evidence. A multicenter, prospective register was constructed with information from patients admitted to 5 cardiac intensive care units from January 2010 through January 2012 with a diagnosis of resuscitated out-of-hospital cardiac arrest. The information included clinical status, cardiac arrest characteristics, in-hospital course, and vital and neurologic status at discharge and at 6 months. A total of 204 patients were included. In 64% of cases, a first shockable rhythm was identified. The time to return of spontaneous circulation was 29 (18) min. An etiologic diagnosis was made in 86% of patients; 44% were discharged with no neurologic sequelae; 40% died in the hospital. At 6 months, 79% of survivors at discharge were still alive and neurologically intact with minimal sequelae. Short resuscitation time, first recorded rhythm, pH on admission >7.1, absence of shock, and use of hypothermia were the independent variables associated with a good neurologic prognosis. Half the patients who recovered from out-of-hospital cardiac arrest had good neurologic prognosis at discharge, and 79% of survivors were alive and neurologically intact after 6 months of follow-up. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  2. Gadolinium decreases inflammation related to myocardial ischemia and reperfusion injury

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    Nicolosi Alfred C

    2009-12-01

    Full Text Available Abstract Background The lanthanide cation, gadolinium (GdCl3 protects the myocardium against infarction following ischemia and reperfusion. Neutrophils and macrophages are the main leukocytes responsible for infarct expansion after reperfusion. GdCl3 interferes with macrophage and neutrophil function in the liver by decreasing macrophage secretion of inflammatory cytokines and neutrophil infiltration. We hypothesized that GdCl3 protects against ischemia and reperfusion injury by decreasing inflammation. We determined the impact of GdCl3 treatment for reperfusion injury on 1 circulating monoctye and neutrophil counts, 2 secretion of inflammatory cytokines, and 3 influx of monocytes and neutrophils into the myocardium. Methods Rats (n = 3-6/gp were treated with saline or GdCl3 (20 μmol/kg 15 min prior to a 30 min period of regional ischemia and 120 min reperfusion. Sham rats were not subject to ischemia. Blood was collected either after 30 min ischemia or 120 min reperfusion and hearts were harvested at 120 min reperfusion for tissue analysis. Blood was analyzed for leukocytes counts and cytokines. Tissue was analyzed for cytokines and markers of neutrophil and monocyte infiltration by measuring myeloperoxidase (MPO and α-naphthyl acetate esterase (ANAE. Results GdCl3 did not affect the number of circulating neutrophils prior to ischemia. Two hours reperfusion resulted in a 2- and 3- fold increase in circulating monocytes and neutrophils, respectively. GdCl3 decreased the number of circulating monocytes and neutrophils during reperfusion to levels below those present prior to ischemia. Furthermore, after 120 min of reperfusion, GdCl3 decreased ANAE and MPO activity in the myocardium by 1.9-fold and 6.5-fold respectively. GdCl3 decreased MPO activity to levels below those measured in the Sham group. Serum levels of the major neutrophil chemoattractant cytokine, IL-8 were increased from pre-ischemic levels during ischemia and reperfusion in both

  3. Effects of Obstructive Sleep Apnea on Cardiac Function and Clinical Outcomes in Chinese Patients with ST-Elevation Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Baoxin Liu

    2014-01-01

    Full Text Available Aim. The objective of this study was to investigate the influence of OSA on cardiac function in Chinese patients with ST-elevation myocardial infarction (STEMI and determine the prognostic impact of OSA among these patients. Methods. In this retrospective study, 198 STEMI patients were enrolled. Doppler echocardiography was performed to detect the effect of OSA on cardiac function. Major adverse cardiac events (MACE and cardiac mortality were analyzed to determine whether OSA was a clinical prognostic factor; its prognostic impact was then assessed adjusting for other covariates. Results. The echocardiographic results showed that the myocardium of STEMI patients with OSA appeared to be more hypertrophic and with a poorer cardiac function compared with non-OSA STEMI patients. A Kaplan-Meier survival analysis revealed significantly higher cumulative incidence of MACE and cardiac mortality in the OSA group compared with that in the non-OSA group during a mean follow-up of 24 months. Multivariate Cox regression analysis revealed that OSA was an independent risk factor for MACE and cardiac mortality. Conclusion. These results indicate that the OSA is a powerful predictor of decreased survival and exerts negative prognostic impact on cardiac function in STEMI patients.

  4. Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models

    Science.gov (United States)

    Wang, Louis W.; Huttner, Inken G.; Santiago, Celine F.; Kesteven, Scott H.; Yu, Ze-Yan; Feneley, Michael P.

    2017-01-01

    ABSTRACT The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l−1 having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high

  5. Preserved cardiac function despite marked impairment of cAMP generation.

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    Mei Hua Gao

    Full Text Available OBJECTIVES: So many clinical trials of positive inotropes have failed, that it is now axiomatic that agents that increase cAMP are deleterious to the failing heart. An alternative strategy is to alter myocardial Ca(2+ handling or myofilament response to Ca(2+ using agents that do not affect cAMP. Although left ventricular (LV function is tightly linked to adenylyl cyclase (AC activity, the beneficial effects of AC may be independent of cAMP and instead stem from effects on Ca(2+ handling. Here we ask whether an AC mutant molecule that reduces LV cAMP production would have favorable effects on LV function through its effects on Ca(2+ handling alone. METHODS AND RESULTS: We generated transgenic mice with cardiac-directed expression of an AC6 mutant (AC6mut. Cardiac myocytes showed impaired cAMP production in response to isoproterenol (74% reduction; p<0.001, but LV size and function were normal. Isolated hearts showed preserved LV function in response to isoproterenol stimulation. AC6mut expression was associated with increased sarcoplasmic reticulum Ca(2+ uptake and the EC50 for SERCA2a activation was reduced. Cardiac myocytes isolated from AC6mut mice showed increased amplitude of Ca(2+ transients in response to isoproterenol (p = 0.0001. AC6mut expression also was associated with increased expression of LV S100A1 (p = 0.03 and reduced expression of phospholamban protein (p = 0.01. CONCLUSION: LV AC mutant expression is associated with normal cardiac function despite impaired cAMP generation. The mechanism appears to be through effects on Ca(2+ handling - effects that occur despite diminished cAMP.

  6. Haemodynamics and cardiac function during robotic-assisted laparoscopic prostatectomy in steep Trendelenburg position.

    Science.gov (United States)

    Haas, Sebastian; Haese, Alexander; Goetz, Alwin E; Kubitz, Jens C

    2011-12-01

    Robotic-assisted laparoscopic prostatectomy (RALP) is usually performed in steep Trendelenburg position, which can be associated with cardiac impairment due to positioning and capnoperitoneum. This study investigated haemodynamic consequences and cardiac function in this type of surgery and evaluated the hypothesis that steep Trendelenburg position and capnoperitoneum results in haemodynamic and ventricular impairment. 10 patients (ASA I-III) scheduled for RALP in steep Trendelenburg position with capnoperitoneum were prospectively studied. Heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP) were recorded. Stroke volume variation (SVV) and cardiac output (CO) were measured using pulse-contour analysis. Further, cardiac function was assessed using trans-oesophageal echocardiography before positioning (T1) and 10 min (T2) and 60 min (T3) after implementation of steep Trendelenburg position and capnoperitoneum. HR did not change statistically. MAP (T1, 69.7 ± 1.55; T2, 82.9 ± 3.05; T3, 79.4 ± 2.18 mmHg), CVP (T1, 7.7 ± 1.3; T2, 17.3 ± 2.01; T3, 16.9 ± 1.66 mmHg) and CO (T1, 4.0 ± 0.15; T2, 4.9 ± 0.26; T3, 4.9 ± 0.36 l/min) increased significantly at T2 and T3. Echocardiography showed no deterioration of left or right ventricular function. In one patient with pre-existing mitral valve insufficiency (I°) an aggravation of the insufficiency (III°) was observed. No other valve dysfunctions were observed. The steep Trendelenburg position may improve haemodynamic function and does not deteriorate left or right ventricular function during RALP. However, mitral valve insufficiency may be aggravated by positioning and capnoperitoneum. Copyright © 2011 John Wiley & Sons, Ltd.

  7. Hydroxyfasudil-mediated inhibition of ROCK1 and ROCK2 improves kidney function in rat renal acute ischemia-reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Dominik Kentrup

    Full Text Available Renal ischemia-reperfusion (IR injury (IRI is a common and important trigger of acute renal injury (AKI. It is inevitably linked to transplantation. Involving both, the innate and the adaptive immune response, IRI causes subsequent sterile inflammation. Attraction to and transmigration of immune cells into the interstitium is associated with increased vascular permeability and loss of endothelial and tubular epithelial cell integrity. Considering the important role of cytoskeletal reorganization, mainly regulated by RhoGTPases, in the development of IRI we hypothesized that a preventive, selective inhibition of the Rho effector Rho-associated coiled coil containing protein kinase (ROCK by hydroxyfasudil may improve renal IRI outcome. Using an IRI-based animal model of AKI in male Sprague Dawley rats, animals treated with hydroxyfasudil showed reduced proteinuria and polyuria as well as increased urine osmolarity when compared with sham-treated animals. In addition, renal perfusion (as assessed by (18F-fluoride Positron Emission Tomography (PET, creatinine- and urea-clearances improved significantly. Moreover, endothelial leakage and renal inflammation was significantly reduced as determined by histology, (18F-fluordesoxyglucose-microautoradiography, Evans Blue, and real-time PCR analysis. We conclude from our study that ROCK-inhibition by hydroxyfasudil significantly improves kidney function in a rat model of acute renal IRI and is therefore a potential new therapeutic option in humans.

  8. Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues.

    Science.gov (United States)

    Marsano, Anna; Conficconi, Chiara; Lemme, Marta; Occhetta, Paola; Gaudiello, Emanuele; Votta, Emiliano; Cerino, Giulia; Redaelli, Alberto; Rasponi, Marco

    2016-02-07

    In the past few years, microfluidic-based technology has developed microscale models recapitulating key physical and biological cues typical of the native myocardium. However, the application of controlled physiological uniaxial cyclic strains on a defined three-dimension cellular environment is not yet possible. Two-dimension mechanical stimulation was particularly investigated, neglecting the complex three-dimensional cell-cell and cell-matrix interactions. For this purpose, we developed a heart-on-a-chip platform, which recapitulates the physiologic mechanical environment experienced by cells in the native myocardium. The device includes an array of hanging posts to confine cell-laden gels, and a pneumatic actuation system to induce homogeneous uniaxial cyclic strains to the 3D cell constructs during culture. The device was used to generate mature and highly functional micro-engineered cardiac tissues (μECTs), from both neonatal rat and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), strongly suggesting the robustness of our engineered cardiac micro-niche. Our results demonstrated that the cyclic strain was effectively highly uniaxial and uniformly transferred to cells in culture. As compared to control, stimulated μECTs showed superior cardiac differentiation, as well as electrical and mechanical coupling, owing to a remarkable increase in junction complexes. Mechanical stimulation also promoted early spontaneous synchronous beating and better contractile capability in response to electric pacing. Pacing analyses of hiPSC-CM constructs upon controlled administration of isoprenaline showed further promising applications of our platform in drug discovery, delivery and toxicology fields. The proposed heart-on-a-chip device represents a relevant step forward in the field, providing a standard functional three-dimensional cardiac model to possibly predict signs of hypertrophic changes in cardiac phenotype by mechanical and biochemical co-stimulation.

  9. Altered right ventricular contractile pattern after cardiac surgery: monitoring of septal function is essential.

    Science.gov (United States)

    Nguyen, Tin; Cao, Long; Movahed, Assad

    2014-10-01

    Assessment of right ventricular (RV) function is important in the management of various forms of cardiovascular disease. Accurately assessing RV volume and systolic function is a challenge in day-to-day clinical practice due to its complex geometry. Tricuspid annular plane systolic excursion (TAPSE) and systolic excursion velocity (S') have been reviewed to further assess their suitability and objectivity in evaluating RV function. Multiple studies have validated their diagnostic and prognostic values in numerous pathologic conditions. Diminished longitudinal contraction after cardiothoracic surgery is a well-known phenomenon, but it is not well validated. Despite significant reduction in RV performance along the long-axis assessed by TAPSE and S' after cardiac surgery, RV ejection fractions did not change as well as the left ventricular parameters and exercise capacity. RV contractile patterns were markedly altered with decreased longitudinal shortening and increased transverse shortening, which are likely resulted from the septal damage during cardiac surgery. The septum is essential for RV performance due to its oblique fiber orientation. This allows ventricular twisting, which is a vital mechanism against increased pulmonary vascular resistance. The septum function along with TAPSE and S' should be adequately assessed during cardiac surgery, and evidence of septal dysfunction should lead to reevaluation of myocardial protection methods.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-11-01

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

  11. Systems analysis of the mechanisms of cardiac diastolic function changes after microgravity exposure

    Science.gov (United States)

    Summers, Richard; Coleman, Thomas; Steven, Platts; Martin, David

    Detailed information concerning cardiac function was collected by two-dimensional and M-mode echocardiography at 10 days before flight and 3h after landing in astronauts returning from shuttle missions. A comparative analysis of this data suggests that cardiac diastolic function is reduced after microgravity exposure with little or no change in systolic function as measured by ejection fraction However, the mechanisms responsible for these adaptations have not been determined. In this study, an integrative computer model of human physiology that forms the framework for the Digital Astronaut Project (Guyton/Coleman/Summers Model) was used in a systems analysis of the echocardiographic data in the context of general cardiovascular physiologic functioning. The physiologic mechanisms involved in the observed changes were then determined by a dissection of model interrelationships. The systems analysis of possible physiologic mechanisms involved reveals that a loss of fluid from the myocardial interstitial space may lead to a stiffening of the myocardium and could potentially result in some of the cardiac diastolic dysfunction seen postflight. The cardiovascular dynamics may be different during spaceflight.

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

    Directory of Open Access Journals (Sweden)

    Hermans Mieke CE

    2012-07-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  14. Berberine Attenuates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Inflammation Response: Role of Silent Information Regulator 1

    Directory of Open Access Journals (Sweden)

    Liming Yu

    2016-01-01

    Full Text Available Berberine (BBR exerts potential protective effect against myocardial ischemia/reperfusion (MI/R injury. Activation of silent information regulator 1 (SIRT1 signaling attenuates MI/R injury by reducing oxidative damage and inflammation response. This study investigated the antioxidative and anti-inflammatory effects of BBR treatment in MI/R condition and elucidated its potential mechanisms. Sprague-Dawley rats were treated with BBR in the absence or presence of the SIRT1 inhibitor sirtinol (Stnl and then subjected to MI/R injury. BBR conferred cardioprotective effects by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase levels, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Stnl attenuated these effects by inhibiting SIRT1 signaling. BBR treatment also reduced myocardium superoxide generation, gp91phox expression, malondialdehyde (MDA level, and cardiac inflammatory markers and increased myocardium superoxide dismutase (SOD level. However, these effects were also inhibited by Stnl. Consistently, BBR conferred similar antioxidative and anti-inflammatory effects against simulated ischemia reperfusion injury in cultured H9C2 cardiomyocytes. SIRT1 siRNA administration also abolished these effects. In summary, our results demonstrate that BBR significantly improves post-MI/R cardiac function recovery and reduces infarct size against MI/R injury possibly due to its strong antioxidative and anti-inflammatory activity. Additionally, SIRT1 signaling plays a key role in this process.

  15. Functional and morphological cardiac magnetic resonance imaging of mice using a cryogenic quadrature radiofrequency coil.

    Directory of Open Access Journals (Sweden)

    Babette Wagenhaus

    Full Text Available Cardiac morphology and function assessment by magnetic resonance imaging is of increasing interest for a variety of mouse models in pre-clinical cardiac research, such as myocardial infarction models or myocardial injury/remodeling in genetically or pharmacologically induced hypertension. Signal-to-noise ratio (SNR constraints, however, limit image quality and blood myocardium delineation, which crucially depend on high spatial resolution. Significant gains in SNR with a cryogenically cooled RF probe have been shown for mouse brain MRI, yet the potential of applying cryogenic RF coils for cardiac MR (CMR in mice is, as of yet, untapped. This study examines the feasibility and potential benefits of CMR in mice employing a 400 MHz cryogenic RF surface coil, compared with a conventional mouse heart coil array operating at room temperature. The cryogenic RF coil affords SNR gains of 3.0 to 5.0 versus the conventional approach and hence enables an enhanced spatial resolution. This markedly improved image quality--by better deliniation of myocardial borders and enhanced depiction of papillary muscles and trabeculae--and facilitated a more accurate cardiac chamber quantification, due to reduced intraobserver variability. In summary the use of a cryogenically cooled RF probe represents a valuable means of enhancing the capabilities of CMR of mice.

  16. Cardiac function in muscular dystrophy associates with abdominal muscle pathology

    Science.gov (United States)

    Gardner, Brandon B.; Swaggart, Kayleigh A.; Kim, Gene; Watson, Sydeaka; McNally, Elizabeth M.

    2015-01-01

    Background The muscular dystrophies target muscle groups differentially. In mouse models of muscular dystrophy, notably the mdx model of Duchenne Muscular Dystrophy, the diaphragm muscle shows marked fibrosis and at an earlier age than other muscle groups, more reflective of the histopathology seen in human muscular dystrophy. Methods Using a mouse model of limb girdle muscular dystrophy, the Sgcg mouse, we compared muscle pathology across different muscle groups and heart. A cohort of nearly 200 Sgcg mice were studied using multiple measures of pathology including echocardiography, Evans blue dye uptake and hydroxyproline content in multiple muscle groups. Spearman rank correlations were determined among echocardiographic and pathological parameters. Findings The abdominal muscles were found to have more fibrosis than other muscle groups, including the diaphragm muscle. The abdominal muscles also had more Evans blue dye uptake than other muscle groups. The amount of diaphragm fibrosis was found to correlate positively with fibrosis in the left ventricle, and abdominal muscle fibrosis correlated with impaired left ventricular function. Fibrosis in the abdominal muscles negatively correlated with fibrosis in the diaphragm and right ventricles. Together these data reflect the recruitment of abdominal muscles as respiratory muscles in muscular dystrophy, a finding consistent with data from human patients. PMID:26029630

  17. The cycle of form and function in cardiac valvulogenesis

    Directory of Open Access Journals (Sweden)

    Stephanie E. Lindsey

    2011-12-01

    Full Text Available The formation and remodeling of the embryonic valves is a complex and dynamic process that occurs within a constantly changing hemodynamic environment. Defects in embryonic and fetal valve remodeling are the leading cause of congenital heart defects, yet very little is known about how fibrous leaflet tissue is created from amorphous gelatinous masses called cushions. Microenvironmental cues such as mechanical forces and extracellular matrix composition play major roles in cell differentiation, but almost all research efforts in valvulogenesis center around genetics and molecular approaches. This review summarizes what is known about the dynamic mechanical and extracellular matrix microenvironment of the atrioventricular and semilunar valves during embryonic development and their possible guidance roles. A variety of new computational tools and sophisticated experimental techniques are progressing that enable precise microenvironmental alterations that are critical to complement genetic gain and loss of function approaches. Studies at the interface of mechanical and genetic signaling in embryonic valvulogenesis will likely pay significant dividends, not only in terms of increasing our mechanistic understanding, but also lead to the development of novel therapeutic strategies for patients with congenital valve abnormalities.

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

    Directory of Open Access Journals (Sweden)

    Margaret E McCormick

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

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

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    A. O. Shevchenko

    2015-01-01

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

  20. Efficacy of angiotensin II type 1 receptor blockade on reperfusion-induced arrhythmias and mortality early after myocardial infarction is increased in transgenic rats with cardiac angiotensin II type 1 overexpression

    NARCIS (Netherlands)

    de Boer, RA; van Geel, PP; Pinto, YM; Suurmeijer, AJH; Crijns, HJGM; van Gilst, WH; van Veldhuisen, DJ

    2002-01-01

    Angiotensin II induces ischemia/reperfusion (I/R)-induced arrhythmias and blockade of the angiotensin II type I receptor (AT1R) may therefore be beneficial in preventing arrhythmias and decreasing mortality after myocardial infarction (MI). Because the AT1R is upregulated after myocardial ischemia,

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-15

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

  2. Hypertensive Disorders of Pregnancy and Offspring Cardiac Structure and Function in Adolescence

    OpenAIRE

    Timpka, Simon; Macdonald-Wallis, Corrie; Hughes, Alun D.; Chaturvedi, Nish; Franks, Paul; Lawlor, Debbie; Fraser, Abigail

    2016-01-01

    BACKGROUND: Fetal exposure to preeclampsia is associated with higher blood pressure and later risk of stroke. We aimed to investigate the associations of maternal preeclampsia, gestational hypertension, and maternal blood pressure change in pregnancy with offspring cardiac structure and function in adolescence. METHODS AND RESULTS: Using data from a prospective birth cohort study, we included offspring who underwent echocardiography (mean age, 17.7 years; SD, 0.3; N=1592). We examined whether...

  3. Doxorubicin Cardiotoxicity and Cardiac Function Improvement After Stem Cell Therapy Diagnosed by Strain Echocardiography

    OpenAIRE

    Oliveira, Maira S.; Melo, Marcos B; Carvalho, Juliana L; Melo, Isabela M; Lavor, Mario SL; Gomes, Dawidson A.; Goes, Alfredo M.; Melo, Marilia M

    2013-01-01

    Doxorubicin (Dox) is one of the most effective chemotherapeutic agents; however, it causes dose-dependent cardiotoxicity. Evaluation of left ventricular function relies on measurements based on M-mode echocardiography. A new technique based on quantification of myocardial motion and deformation, strain echocardiography, has been showed promising profile for early detection of cardiac dysfunction. Different therapy strategies, such as flavonoid plant extracts and stem cells, have been investig...

  4. Effects of right atrial and ventricular DDD pacing on cardiac function and ventricular contraction synchrony

    Institute of Scientific and Technical Information of China (English)

    支力大; 华伟; 张澍; 史蓉芳; 王方正; 陈新

    2004-01-01

    Background Right ventricular apical pacing has been reported to reduce cardiac performance. But there are few reports on the effects of dual chamber (DDD) pacing on cardiac function compared to sinus rhythm. In this study, we evaluated the effects of right atrial and ventricular DDD pacing on cardiac function and ventricular contraction synchrony using equilibrium radionuclide angiography.Methods Ten patients implanted with a right atrial and ventricular DDD pacemaker underwent equilibrium radionuclide angiography. The scintigraphic data were obtained during sinus rhythm and pacing rhythm. Cardiac function parameters were obtained semimanually. Phase analysis was used to study the ventricular activation sequence and ventricular synchrony.Results The left ventricular 1/3 ejection fraction decreased significantly during pacing compared with that during sinus rhythm[(23.4 ±6.1)% vs(27.7 ±4.5)%, P =0.01]. Regional ejection fraction also decreased during pacing, although the difference was not statistically significant. Phase analysis showed that the right ventricle was activated earlier than the left ventricle during pacing, and that the phase shift was significantly greater during pacing than that during sinus rhythm[64.13°±16.80° vs 52.88°± 9.26°, P =0.007]. The activation of both ventricles occurred simultaneously during sinus rhythm, with the activation sequence from proximal septum or base of left ventricle to apex. The earliest activation during pacing occurred at the right ventricular apex, and subsequently spread to the base and left ventricle.Conclusion Right atrial and ventricular DDD pacing impairs left ventricular systolic function and ventricular synchrony.

  5. Muscarinic 2 Receptors Modulate Cardiac Proteasome Function in a Protein Kinase G-dependent Manner

    OpenAIRE

    Ranek, Mark J.; Kost, Curtis K.; Hu, Chengjun; Martin, Douglas S.; Wang, Xuejun

    2014-01-01

    Proteasome function insufficiency and inadequate protein quality control are strongly implicated in a large subset of cardiovascular disease and may play an important role in their pathogenesis. Protein degradation by the ubiquitin proteasome system can be physiologically regulated. Cardiac muscarinic 2 (M2) receptors were pharmacologically interrogated in intact mice and cultured neonatal rat ventricular myocytes (NRVMs). Proteasome-mediated proteolysis was measured with a surrogate misfolde...

  6. Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.

    Science.gov (United States)

    Wyrwoll, Caitlin S; Noble, June; Thomson, Adrian; Tesic, Dijana; Miller, Mark R; Rog-Zielinska, Eva A; Moran, Carmel M; Seckl, Jonathan R; Chapman, Karen E; Holmes, Megan C

    2016-05-31

    Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction.

  7. Health-Related Quality of Life, Functional Status, and Cardiac Event-Free Survival in Patients With Heart Failure.

    Science.gov (United States)

    Wu, Jia-Rong; Lennie, Terry A; Frazier, Susan K; Moser, Debra K

    2016-01-01

    Health-related quality of life (HRQOL), functional status, and cardiac event-free survival are outcomes used to assess the effectiveness of interventions in patients with heart failure (HF). However, the nature of the relationships among HRQOL, functional status, and cardiac event-free survival remains unclear. The purpose of this study is to examine the nature of the relationships among HRQOL, functional status, and cardiac event-free survival in patients with HF. This was a prospective, observational study of 313 patients with HF that was a secondary analysis from a registry. At baseline, patient demographic and clinical data were collected. Health-related quality of life was assessed using the Minnesota Living With Heart Failure Questionnaire and functional status was measured using the Duke Activity Status Index. Cardiac event-free survival data were obtained by patient interview, hospital database, and death certificate review. Multiple linear and Cox regressions were used to explore the relationships among HRQOL, functional status, and cardiac event-free survival while adjusting for demographic and clinical factors. Participants (n = 313) were men (69%), white (79%), and aged 62 ± 11 years. Mean left ventricular ejection fraction was 35% ± 14%. The mean HRQOL score of 32.3 ± 20.6 indicated poor HRQOL. The mean Duke Activity Status Index score of 16.2 ± 12.9 indicated poor functional status. Cardiac event-free survival was significantly worse in patients who had worse HRQOL or poorer functional status. Patients who had better functional status had better HRQOL (P quality of life was not a significant predictor of cardiac event-free survival after entering functional status in the model (P = .54), demonstrating that it was a mediator of the relationship between HRQOL and outcome. Functional status was a mediator between HRQOL and cardiac event-free survival. These data suggest that intervention studies to improve functional status are needed.

  8. [Successful mitral valve replacement in a patient with functional mitral regurgitation induced by cardiac sarcoidosis;report of a case].

    Science.gov (United States)

    Sato, Ken; Takazawa, Ippei; Aizawa, Kei; Misawa, Yoshio

    2015-03-01

    We report a case of cardiac sarcoidosis associated with mitral valve regurgitation. A 62-year-old woman with cardiac sarcoidosis was admitted for the treatment of an intractable mitral regurgitation. She had been treated for cardiac sarcoidosis with prednisolone, and she had undergone pacemaker implantation because of advanced complete A-V block 5 years before. However, her hemodynamics deteriorated, and echocardiography revealed severe functional mitral regurgitation, thinning of the ventricular septum, and left ventricular dysfunction. The patient underwent mitral valve replacement with a mechanical prosthetic valve, and her postoperative course was uneventful. She is currently well without exacerbation of heart failure at 2 years after operation. Functional mitral regurgitation is a relatively common complication in patients with cardiac sarcoidosis. Mitral valve replacement should be considered in patients with medically intractable mitral valve dysfunction due to cardiac sarcoidosis.

  9. Influence of fluvastatin on cardiac function and baroreflex sensitivity in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Fang XIE; Chao SUN; Li-hua SUN; Jing-yuan LI; Xin CHEN; Hui CHE; Guan-yi LU; Bao-feng YANG; Jing AI

    2011-01-01

    Aim: To investigate whether fluvastatin is able to ameliorate the impaired cardiac function or baroreflex sensitivity (BRS) in rats with type 1 diabetes.Methods: Type 1 diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) and then administered fluvastatin (1.5,cardiac function and BRS were measured in diabetic rats after fluvastatin treatment for 30 d.Results: The polydipsia, polyphagia and abnormal biochemical indexes of blood were significantly ameliorated by the the 3.0- and 6.0-mg doses of fluvastatin in STZ-induced diabetic rats. FBG was decreased in diabetic rats after fluvastatin treatment for 30 d. The left ventricular systolic pressure (LVSP) and the maximum rate of change of left ventricular pressure in the isovolumic contraction and relaxation period (±dp/dtmax) were elevated, and left ventricular diastolic pressure (LVEDP) was decreased by fluvastatin. The attenuated heart rate responses to arterial blood pressure (ABP) increase induced by phenylephrine (PE) and ABP decrease induced by sodium nitroprusside (SNP) were reversed by the 3.0-mg dose of fluvastatin.Conclusion: Fluvastatin regulates blood lipid levels and decreases the FBG level in diabetic rats. These responses can protect the diabetic heart from complications by improving cardiac function and BRS.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-01-01

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

  11. Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade.

    Science.gov (United States)

    Hathaway, Catherine K; Grant, Ruriko; Hagaman, John R; Hiller, Sylvia; Li, Feng; Xu, Longquan; Chang, Albert S; Madden, Victoria J; Bagnell, C Robert; Rojas, Mauricio; Kim, Hyung-Suk; Wu, Bingruo; Zhou, Bin; Smithies, Oliver; Kakoki, Masao

    2015-04-21

    We have generated low-expressing and high-expressing endothelin-1 genes (L and H) and have bred mice with four levels of expression: L/L, ∼20%; L/+, ∼65%; +/+ (wild type), 100%; and H/+, ∼350%. The hypomorphic L allele can be spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination. Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and increased plasma volumes, together with increased ventricular superoxide levels, increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular stiffness. H/+ mice have decreased plasma volumes and significantly heavy stiff hearts. Global or cardiomyocyte-specific switching expression from L to H normalized the abnormalities already present in young adult L/L mice. An epithelial sodium channel antagonist normalized plasma volume and blood pressure, but only partially corrected the cardiomyopathy. A superoxide dismutase mimetic made superoxide levels subnormal, reduced Mmp9 overexpression, and substantially improved cardiac function. Genetic absence of Mmp9 also improved cardiac function, but increased superoxide remained. We conclude that endothelin-1 is critical for maintaining normal contractile function, for controlling superoxide and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to prevent overstretching. Even a modest (∼35%) decrease in endothelin-1 gene (Edn1) expression is sufficient to cause cardiac dysfunction.

  12. Exercise training and cardiac autonomic function in type 2 diabetes mellitus: A systematic review.

    Science.gov (United States)

    Bhati, Pooja; Shenoy, Shweta; Hussain, M Ejaz

    2017-09-06

    Cardiac autonomic neuropathy (CAN) is a common complication of type 2 diabetes mellitus (T2DM). It has been found to independently predict all cause and cardiovascular disease (CVD) mortality. It remains unclear whether exercise training could improve autonomic control in T2DM patients. The purpose of this study was to systematically review the effects of exercise training on cardiac autonomic function in T2DM patients. Electronic databases (MEDLINE, CENTRAL, PEDro, Scopus and Web of science) were systematically searched to retrieve relevant evidence. Clinical trials administering exercise training for at least 4 weeks and examining either heart rate variability (HRV), baroreflex sensitivity (BRS), heart rate recovery (HRR) as outcome measures were eligible. Eighteen articles were found to be relevant and were then assessed for characteristics and quality. Fifteen studies out of 18 found that exercise training leads to positive improvements in autonomic function of T2DM patients. Exercise participation enhances cardiac autonomic function of type 2 diabetics and therefore should be implemented in their management programs. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  13. A role for matrix stiffness in the regulation of cardiac side population cell function.

    Science.gov (United States)

    Qiu, Yiling; Bayomy, Ahmad F; Gomez, Marcus V; Bauer, Michael; Du, Ping; Yang, Yanfei; Zhang, Xin; Liao, Ronglih

    2015-05-01

    The mechanical properties of the local microenvironment may have important influence on the fate and function of adult tissue progenitor cells, altering the regenerative process. This is particularly critical following a myocardial infarction, in which the normal, compliant myocardial tissue is replaced with fibrotic, stiff scar tissue. In this study, we examined the effects of matrix stiffness on adult cardiac side population (CSP) progenitor cell behavior. Ovine and murine CSP cells were isolated and cultured on polydimethylsiloxane substrates, replicating the elastic moduli of normal and fibrotic myocardium. Proliferation capacity and cell cycling were increased in CSP cells cultured on the stiff substrate with an associated reduction in cardiomyogeneic differentiation and accelerated cell ageing. In addition, culture on stiff substrate stimulated upregulation of extracellular matrix and adhesion proteins gene expression in CSP cells. Collectively, we demonstrate that microenvironment properties, including matrix stiffness, play a critical role in regulating progenitor cell functions of endogenous resident CSP cells. Understanding the effects of the tissue microenvironment on resident cardiac progenitor cells is a critical step toward achieving functional cardiac regeneration.

  14. Echocardiographic evaluation of female centrifuge subjects for chronic changes in cardiac function.

    Science.gov (United States)

    Albery, W B

    1999-06-01

    High sustained G exposure as experienced in flying high performance aircraft can affect cardiac function. Numerous studies, mostly on male pilots, have evaluated the chronic effects of exposure to high G. To date, none of these studies has revealed significant positive findings in cardiac function as a result of long-term high G exposure. A longitudinal study was conducted on six female centrifuge panel members who did not have a history of significant high +Gz exposure. Baseline echocardiographic studies were conducted prior to any +Gz exposure on the Dynamic Environment Simulator (DES) centrifuge. The echocardiograms were repeated after each panel member completed approximately 100 3-min high G (up to 9 G) exposures over the period of 7 mo. These follow-up echos were performed after all six subjects had been exposed to at least 6 h (cumulative) of sustained acceleration > 3 G. The women were protected with the COMBAT EDGE positive pressure breathing G protection ensemble. Each subject served as her own control. All studies were evaluated independently by a cardiologist who was blinded to the order in which the echos were performed. Although complete echocardiographic studies were performed, only the parameters identified as significant in prior studies were evaluated. No significant differences were found between the initial and follow-up echo parameters. We found no significant differences in cardiac function after at least 6 and up to 17 h (cumulative) of exposure to G > 3 in women. These subjects will be monitored during a longitudinal study throughout their centrifuge subject career.

  15. Treatment with hESC-Derived Myocardial Precursors Improves Cardiac Function after a Myocardial Infarction.

    Directory of Open Access Journals (Sweden)

    Jianqin Ye

    Full Text Available We previously reported the generation of a reporter line of human embryonic stem cells (hESCs with enhanced green fluorescent protein (eGFP expression driven by the α-myosin heavy chain (αMHC promoter. The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs in vitro. In this study, we evaluated the therapeutic effects of GFP+/αMHC+ cells isolated from the reporter line in a mouse model of myocardial infarction (MI.MI was generated in immunodeficient mice. hMPs were injected into murine infarcted hearts under ultrasound guidance at 3 days post-MI. Human fetal skin fibroblasts (hFFs were injected as control. Cardiac function was evaluated by echocardiography. Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining.Compared with control, hMPs resulted in improvement of cardiac function post-MI with smaller infarct size, induced endogenous angiogenesis, and reduced apoptosis of host cardiomyocytes at the peri-infarct zone at 28 days post-MI.Intramyocardial injection of hMPs improved cardiac function post-MI. The engraftment rate of these cells in the myocardium post-MI was low, suggesting that the majority of effect occurs via paracrine mechanisms.

  16. SIRT3 in cardiac physiology and disease

    Directory of Open Access Journals (Sweden)

    Christoph Koentges

    2016-10-01

    Full Text Available Functional defects in mitochondrial biology causally contribute to various human diseases, including cardiovascular disease. Impairment in oxidative phosphorylation, mitochondrial oxidative stress and increased opening of the mitochondrial permeability transition pore add to the underlying mechanisms of heart failure or myocardial ischemia reperfusion (IR injury. Recent evidence demonstrated that the mitochondrial NAD+-dependent deacetylase sirtuin 3 (SIRT3 may regulate these mitochondrial functions by reversible protein lysine deacetylation. Loss of function studies demonstrated a role of impaired SIRT3 activity in the pathogenesis of myocardial IR injury as well as in the development of cardiac hypertrophy and the transition into heart failure. Gain of function studies and treatment approaches increasing mitochondrial NAD+ availability that ameliorate these cardiac pathologies have led to the proposal that activation of SIRT3 may represent a promising therapeutic strategy to improve mitochondrial derangements in various cardiac pathologies. In the current review, we will present and discuss the available literature on the role of SIRT3 in cardiac physiology and disease.

  17. Oral delivery of insulin withDesmodium gangeticum root aqueous extract protects rat hearts against ischemia reperfusion injury in streptozotocin induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Gino A Kurian; Jose Paddikkala

    2010-01-01

    Objective:To evaluate the effect of insulin administered via oral route with the help of aqueous extract ofDesmodium gangeticum (DG) root in rendering cardio protection against ischemia reperfusion injury in diabetic rats.Methods: Diabetes mellitus was induced in rats by theβ-cell toxin, streptozotocin (STZ, 60 mg/kg). Isolated rat (IR) heart was used to investigate the effect of insulin mixed DG pretreatment on ischemia reperfusion injury. Mitochondrial respiratory enzymes and microsomal enzymes were used to assess the metabolic recovery of myocardium. Cardiac marker enzymes were used to find the functional recovery, which were compared with that of the STZ treated IR rats.Results: Compared with IR control group, rat treated with insulin mixed DG showed a significant functional and metabolic recovery of myocardium from the insult of ischemia reperfusion. Even though orally administered insulin mixed DG displayed a slow but prolonged hypoglycemic effect, the cardio protection it provided was more significant than when it was given intra peritoneal. Furthermore the above result indicates that insulin mixed DG can overcome the barriers in the gastrointestinal tract and be absorbed.Conclusions: The above results indicate the efficacy of insulin mixed DG in protecting the heart from ischemia reperfusion induced injury in diabetic rats. Furthermore the study gives additional information that herbal extracts can be used to transport insulin across the membrane and found to be a feasible approach for developing the oral delivery of insulin, as well as other peptide drugs.

  18. Cardiac resynchronization therapy modulation of exercise left ventricular function and pulmonary O₂ uptake in heart failure.

    Science.gov (United States)

    Tomczak, Corey R; Paterson, Ian; Haykowsky, Mark J; Lawrance, Richard; Martellotto, Andres; Pantano, Alfredo; Gulamhusein, Sajad; Haennel, Robert G

    2012-06-15

    To better understand the mechanisms contributing to improved exercise capacity with cardiac resynchronization therapy (CRT), we studied the effects of 6 mo of CRT on pulmonary O(2) uptake (Vo(2)) kinetics, exercise left ventricular (LV) function, and peak Vo(2) in 12 subjects (age: 56 ± 15 yr, peak Vo(2): 12.9 ± 3.2 ml·kg(-1)·min(-1), ejection fraction: 18 ± 3%) with heart failure. We hypothesized that CRT would speed Vo(2) kinetics due to an increase in stroke volume secondary to a reduction in LV end-systolic volume (ESV) and that the increase in peak Vo(2) would be related to an increase in cardiac output reserve. We found that Vo(2) kinetics were faster during the transition to moderate-intensity exercise after CRT (pre-CRT: 69 ± 21 s vs. post-CRT: 54 ± 17 s, P exercise, LV ESV reserve (exercise - resting) increased 9 ± 7 ml (vs. a 3 ± 9-ml decrease pre-CRT, P increased (pre-CRT: 42 ± 8 ml vs. post-CRT: 61 ± 12 ml, P exercise post-CRT (P > 0.05). CRT improved heart rate, measured as a lower resting and steady-state exercise heart rate and as faster heart rate kinetics after CRT (pre-CRT: 89 ± 12 s vs. post-CRT: 69 ± 21 s, P exercise, cardiac output reserve increased significantly post-CRT and was 22% higher at peak exercise post-CRT (both P increase in cardiac output was due to both a significant increase in peak and reserve stroke volume and to a nonsignificant increase in heart rate reserve. Similar patterns in LV volumes as moderate-intensity exercise were observed at peak exercise. Cardiac output reserve was related to peak Vo(2) (r = 0.48, P increase in peak Vo(2) in clinically stable heart failure patients.

  19. Radiographic and electrocardiographic evaluation of cardiac morphology and function in captive cheetahs (Acinonyx jubatus).

    Science.gov (United States)

    Schumacher, Juergen; Snyder, Patti; Citino, Scott B; Bennett, R Avery; Dvorak, Laura D

    2003-12-01

    In a prospective study, eight (four males and four females) healthy, adult captive cheetahs (Acinonyx jubatus) were immobilized with a combination of tiletamine-zolazepam (4 mg/kg, i.m.), administered with a remote drug delivery system, to define normal cardiac morphology and function. Standard lateral and ventrodorsal (VD) radiographs were then taken to measure heart and thorax using a metric and vertebral scale system. Standard six-lead electrocardiograms were obtained with the animals in right lateral recumbency under isoflurane anesthesia. Mean chest depth and width was 18.7 +/- 1.3 cm and 13.0 +/- 0.6 cm, respectively. The mean lateral cardiac short axis (X) was 9.1 +/- 0.6 cm. the mean cardiac long axis (Y) was 13.6 +/- 0.7 cm, and the mean lateral heart sum (X + Y) was 22.6 +/- 1.2 cm. In the VD projection, mean cardiac short axis (V) was 10.1 +/- 0.7 cm, mean cardiac long axis (W) was 14.9 +/- 1.2 cm, and the heart sum (V + W) was 24.9 +/- 1.8 cm. The vertebral heart size was 8.2 +/- 0.9. All cheetahs had sinus rhythm, and no arrhythmias were noted. Mean heart rate was 126 +/- 15 beats/min, and the mean electrical axis was 82 + 5 degrees. P waves were always positive on lead II and had a width of 0.04 +/- 0.01 sec and a height between 0.1 and 0.3 mV. PR intervals were 0.11 +/- 0.01 sec. The height of the QRS complex was 1.25 +/- 0.24 mV and the width 0.06 +/- 0.01 sec. The ST segment was 0.04 sec, and the T wave (height: 0.25 +/- 0.05 mV) was positive in all cheetahs examined. Although these cardiac and thoracic measurements were larger than those of domestic cats (Felis catus), ratios of cardiac parameters were similar in both species. Electrocardiographic findings were similar to those reported from domestic cats.

  20. Reperfusion pulmonary edema

    Energy Technology Data Exchange (ETDEWEB)

    Klausner, J.M.; Paterson, I.S.; Mannick, J.A.; Valeri, C.R.; Shepro, D.; Hechtman, H.B. (Harvard Medical School, Boston, MA (USA))

    1989-02-17

    Reperfusion following lower-torso ischemia in humans leads to respiratory failure manifest by pulmonary hypertension, hypoxemia, and noncardiogenic pulmonary edema. The mechanism of injury has been studied in the sheep lung lymph preparation, where it has been demonstrated that the reperfusion resulting in pulmonary edema is due to an increase in microvascular permeability of the lung to protein. This respiratory failure caused by reperfusion appears to be an inflammatory reaction associated with intravascular release of the chemoattractants leukotriene B{sub 4} and thromboxane. Histological studies of the lung in experimental animals revealed significant accumulation of neutrophils but not platelets in alveolar capillaries. The authors conclude that thromboxane generated and released from the ischemic tissue is responsible for the transient pulmonary hypertension. Second, it is likely that the chemoattractants are responsible for leukosequestration, and third, neutrophils, oxygen-derived free radicals, and thromboxane moderate the altered lung permeability.

  1. Cardiac structure and function in relation to cardiovascular risk factors in Chinese

    Directory of Open Access Journals (Sweden)

    Zhang Yi

    2012-10-01

    Full Text Available Abstract Background Cardiac structure and function are well-studied in Western countries. However, epidemiological data is still scarce in China. Methods Our study was conducted in the framework of cardiovascular health examinations for the current and retired employees of a factory and their family members. According to the American Society of Echocardiography recommendations, we performed echocardiography to evaluate cardiac structure and function, including left atrial volume, left ventricular hypertrophy and diastolic dysfunction. Results The 843 participants (43.0 years included 288 (34.2% women, and 191 (22.7% hypertensive patients, of whom 82 (42.9% took antihypertensive drugs. The prevalence of left atrial enlargement, left ventricular hypertrophy and concentric remodeling was 2.4%, 5.0% and 12.7%, respectively. The prevalence of mild and moderate-to-severe left ventricular diastolic dysfunction was 14.2% and 3.3%, respectively. The prevalence of these cardiac abnormalities significantly (P ≤ 0.002 increased with age, except for the moderate-to-severe left ventricular diastolic dysfunction. After adjustment for age, gender, body height and body weight, left atrial enlargement was associated with plasma glucose (P = 0.009, and left ventricular hypertrophy and diastolic dysfunction were significantly associated with systolic and diastolic blood pressure (P ≤ 0.03, respectively. Conclusions The prevalence of cardiac structural and functional abnormalities increased with age in this Chinese population. Current drinking and plasma glucose had an impact on left atrial enlargement, whereas systolic and diastolic blood pressures were major correlates for left ventricular hypertrophy and diastolic dysfunction, respectively.

  2. PPARα augments heart function and cardiac fatty acid oxidation in early experimental polymicrobial sepsis.

    Science.gov (United States)

    Standage, Stephen W; Bennion, Brock G; Knowles, Taft O; Ledee, Dolena R; Portman, Michael A; McGuire, John K; Liles, W Conrad; Olson, Aaron K

    2017-02-01

    Children with sepsis and multisystem organ failure have downregulated leukocyte gene expression of peroxisome proliferator-activated receptor-α (PPARα), a nuclear hormone receptor transcription factor that regulates inflammation and lipid metabolism. Mouse models of sepsis have likewise demonstrated that the absence of PPARα is associated with decreased survival and organ injury, specifically of the heart. Using a clinically relevant mouse model of early sepsis, we found that heart function increases in wild-type (WT) mice over the first 24 h of sepsis, but that mice lacking PPARα (Ppar